Transplant international : official journal of the European Society for Organ Transplantation, Jan 20, 2015
We congratulate Weissenbacher and colleagues on their retrospective study examining the influence... more We congratulate Weissenbacher and colleagues on their retrospective study examining the influence of anastomosis time (AT) on outcomes after deceased donor kidney transplant, provocatively entitled "The Faster the Better" (1). The authors conclude that AT is independently associated with patient survival, but not overall graft survival, and suggest that AT is "one of the most important modifiable transplant factors [and] should be considered a major risk factor for long term outcome". This article is protected by copyright. All rights reserved.
Emergency abdominal surgery outcomes represent an internationally important marker of healthcare ... more Emergency abdominal surgery outcomes represent an internationally important marker of healthcare quality and capacity. In this study, a novel approach to investigating global surgical outcomes is proposed, involving collaborative methodology using 'snapshot' clinical data collection over a 2-week period. The primary aim is to identify internationally relevant, modifiable surgical practices (in terms of modifiable process, equipment and clinical management) associated with best care for emergency abdominal surgery. This is a multicentre, international, prospective cohort study. Any hospital in the world performing acute surgery can participate, and any patient undergoing emergency intraperitoneal surgery is eligible to enter the study. Centres will collect observational data on patients for a 14-day period during a 5-month window and required data points will be limited to ensure practicality for collaborators collecting data. The primary outcome measure is the 24 h periopera...
Enhanced recovery after surgery (ERAS) is a well-established pathway of perioperative care in sur... more Enhanced recovery after surgery (ERAS) is a well-established pathway of perioperative care in surgery in an increasing number of specialties. To implement protocols and maintain high levels of compliance, continued support from care providers and patients is vital. This survey aimed to assess the perceptions of care providers and patients of the relevance and importance of the ERAS targets and strategies. Pre- and post-operative surveys were completed by patients who underwent major hepatic, colorectal, or oesophagogastric surgery in three major centers in Scotland, Norway, and The Netherlands. Anonymous web-based and article surveys were also sent to surgeons, anesthetists, and nurses experienced in delivering enhanced recovery protocols. Each questionnaire asked the responder to rate a selection of enhanced recovery targets and strategies in terms of perceived importance. One hundred nine patients and 57 care providers completed the preoperative survey. Overall, both patients and ...
Social media use has become common for organisations in surgery, however the nature and reach of ... more Social media use has become common for organisations in surgery, however the nature and reach of these communications is unknown. This study aimed to characterise and compare the use of "Twitter" by five prominent organisations in surgery. Data were collected from Twitter and the scale, reach, nature and sentiment of messages analysed. Message influence was determined and content analysed by frequency and association using hierarchical clustering and network analysis. Poisson regression was used to compare institutional message and "re-tweet" counts. 7712 messages were analysed from a four-year period up to 13th April 2013. The American College of Surgeons (ACS) had tweeted most and posted the greatest number of messages per day (3.3/day). The number of followers reflects social reach and the Royal College of Surgeons of England (RCSEng) had the greatest number (11,600) followed by the ACS (7320). The number of "retweets" a message receives is a measure of influence with the RCSEng (2.0) demonstrating a significantly greater count than the Royal College of Surgeons of Ireland (RCSI; 0.8, p < 0.001) and the ACS (1.3, p < 0.001). Followers of the RCSEng and ACS appeared most influential. Terms relating to education feature prominently in messages posted by the RCSEng and RCSEd, but less so in those from the RCSI and ACS. Education and training terms were highly correlated with "events". Surgical colleges have significant international reach through social media. UK colleges frequently communicate about education/training opportunities while the ACS focuses on patient-related matters. Only one organisation was found to have an explicit social media policy, which would be considered best practice and can focus on-line activity.
Intermittent clamping of the porta hepatis (PHC) is commonly performed during liver surgery to re... more Intermittent clamping of the porta hepatis (PHC) is commonly performed during liver surgery to reduce blood loss and has been reported to precondition livers resulting in improved outcome after liver surgery (humans) and transplantation (animals). This study investigated the early expression of cytoprotective stress proteins during ischemia-reperfusion induced by PHC. Liver samples were taken before and after each event in a two-cycle ischemia-reperfusion protocol using 15 minutes of PHC followed by 5 minutes of reperfusion. Liver tissue was analyzed by real-time polymerase chain reaction for heme oxygenase (HO)-1 and heat shock protein (HSP)-70 mRNA expression. Extracted protein was analyzed by Western blot for HO-1, and HSP-70 and nuclear extracts were analyzed by DNA mobility shift assay for hypoxia inducible factor (HIF)-1alpha and heat shock factor (HSF)-1. Within minutes of PHC, significant increases in HO-1 mRNA expression were detected, and these were maintained throughout the protocol (P < 0.01). Protein expression of HO-1 (P < 0.03) and HO-1 activity (P < 0.05) were similarly increased between the start and end of ischemia- reperfusion (40 minutes). Binding of active HIF-1alpha to its consensus sequence was increased within 15 minutes of the start of the ischemia-reperfusion cycle. Although evidence of the transcriptionally active form of HSF-1 was detected at the same time point, this was not reflected in measurable changes in HSP-70 mRNA or protein. In conclusion, expression of the cytoprotective protein HO-1 is significantly up-regulated in the liver within minutes of PHC. It is likely that HO-1 contributes to the early protective effects of ischemic preconditioning.
Preconditioning treatments hold significant potential for improving outcomes in solid organ trans... more Preconditioning treatments hold significant potential for improving outcomes in solid organ transplantation. Protective phenotypes can be induced using certain drugs. Curcumin is a biologically active component of turmeric and has been reported to induce stress proteins in certain cell lines, leading to cell protection. This study investigates in detail the effect of curcumin on the stress-response in human hepatocytes, in particular its effect on heme oxygenase 1 (HO-1) and its cytoprotective effect. Pretreatment with curcumin protected hepatocytes in a model of oxidative injury and this protection was mediated through HO-1. In a model of cold preservation injury, curcumin pretreatment resulted in elevation of HO-1 throughout the cold storage and rewarming period, and was cytoprotective against oxidative injury. This is the first study to demonstrate that curcumin induces HO-1 in human hepatocytes, and that the protective effects of curcumin pretreatment may have clinical potential in hepatic transplantation.
Gender disparities in live kidney donation are well documented, but little is known about differe... more Gender disparities in live kidney donation are well documented, but little is known about differences that may exist in the moral reasoning of potential donors prior to donation. American psychologist Carol Gilligan hypothesized that men are more likely to consider moral dilemmas ...
The optimal analgesic technique following open abdominal surgery within an enhanced recovery prot... more The optimal analgesic technique following open abdominal surgery within an enhanced recovery protocol remains controversial. Thoracic epidural is often recommended; however, its role is increasingly being challenged and alternative techniques are being suggested as suitable replacements. To determine by meta-analysis whether epidurals are superior to alternative analgesic techniques following open abdominal surgery within an enhanced recovery setting in terms of postoperative morbidity and other markers of recovery. A literature search was performed of EMBASE, Medline, PubMed, and the Cochrane databases from 1966 through May 2013. All randomized clinical trials comparing epidurals with an alternative analgesic technique following open abdominal surgery within an enhanced recovery protocol were included. All studies were assessed by 2 independent reviewers. Study quality was assessed using the Cochrane bias assessment tool and the Jadad and Chalmers modified bias risk assessment tools. Dichotomous data were analyzed by random or fixed-effects odds ratios. Qualitative analysis was performed where appropriate. Seven trials with a total of 378 patients were identified. No significant difference in complication rate was detected between epidurals and alternative analgesic methods (odds ratio, 1.14; 95% CI, 0.49-2.64; P = .76). Subgroup analysis showed fewer complications in the patient-controlled analgesia group compared with epidural analgesia (odds ratio, 1.97; 95% CI, 1.10-3.53; P = .02). Following qualitative assessment, epidural analgesia was associated with faster return of gut function and reduced pain scores; however, no difference was observed in length of stay. Epidurals may be associated with superior pain control but this does not translate into improved recovery or reduced morbidity when compared with alternative analgesic techniques when used within an enhanced recovery protocol.
Donation after cardiac death (DCD) liver transplantation is increasingly common but concerns exis... more Donation after cardiac death (DCD) liver transplantation is increasingly common but concerns exist over the development of biliary complications and ischemic cholangiopathy (IC). This study aimed to compare outcomes between DCD and donation after brain death (DBD) liver grafts. Studies reporting on post-transplantation outcomes after Maastricht category III DCD liver transplantation were screened for inclusion. Odds ratios (OR) with 95% confidence intervals were produced using random-effects models for the incidence of biliary complications, IC, graft and recipient survival. Meta-regression was undertaken to identify between-study predictors of effect size for biliary complications and IC. PROSPERO Record: CRD42012002113. Twenty-five studies with 62 184 liver transplant recipients (DCD = 2478 and DBD = 59 706) were included. In comparison with DBD, there was a significant increase in biliary complications [OR = 2.4 (1.9, 3.1); P < 0.00001] and IC [OR = 10.5 (5.7, 19.5); P < 0.00001] following DCD liver transplantation. In comparison with DBD, at 1 year [OR = 0.7 (0.5, 0.8); P = 0.0002] and 3 years [OR = 0.6 (0.5, 0.8); P = 0.001], there was a significant decrease in graft survival following DCD liver transplantation. At 1 year, there was also a nonsignificant decrease [OR = 0.8 (0.6, 1.0); P = 0.08] and by 3 years a significant decrease [OR = 0.7 (0.5, 1.0); P = 0.04] found in recipient survival following DCD liver transplantation. Eleven factors were entered into meta-regression models, but none explained the variability in effect size between studies. DCD liver transplantation is associated with an increase in biliary complications, IC, graft loss and mortality. Significant unexplained differences in effect size exist between centers.
The incidence of acute kidney injury due to ischaemia-reperfusion injury (IRI) is rising but effe... more The incidence of acute kidney injury due to ischaemia-reperfusion injury (IRI) is rising but effective treatments and preventative approaches are currently lacking. IRI is also an inevitable consequence of kidney transplantation and significantly contributes to delayed graft function. Heat-shock proteins (Hsps) are highly conserved and ubiquitously expressed molecular chaperones that help maintain and restore normal cellular function in the kidney following IRI. Hsp70 is one of the most frequently studied Hsps because of potential cytoprotective properties and attractiveness as a therapeutic target. However, the protective properties of Hsp70 in renal IRI are not fully understood and putative modes of protection include correction of protein conformation, cytoskeletal stabilisation, anti-inflammatory effects, requirement in autophagy, anti-apoptotic properties, influence over macrophage phenotype and stimulation of regulatory T cells. Significant clinical interest has been generated about the possibility of applying pharmacological agents to induce Hsp70 and prevent renal IRI, but prior to this, an increased mechanistic understanding of the protective nature of Hsp70 is needed. In particular, further investigation of Hsp expression on inflammatory cell behaviour is required as this could lead to the development of new therapeutic strategies for enhancing recovery following renal IRI and broaden the range of these therapies to a wider group of patients.
Targeted deletion of c-jun amino terminal kinase-2 (jnk-2) upregulates the activator protein-1 tr... more Targeted deletion of c-jun amino terminal kinase-2 (jnk-2) upregulates the activator protein-1 transcription factor system. We hypothesized that this would lead to induction of hemeoxygenase-1 (HO-1) and confer protection from hepatic ischemia reperfusion injury. Wild-type and jnk-2 -/- animals were subjected to hepatic ischemia reperfusion insults in two models: a total hepatic ischemia model involving timed Pringle maneuver, and a partial hepatic ischemia model involving selective occlusion of the portal pedicle supplying the left hepatic lobe. Optimal durations of injury were calibrated for each model. After 24 hr, animals were killed, and blood and tissues were collected for alanine aminotransferase, histologic injury scoring, and other analyses. Before total or partial hepatic ischemia reperfusion insults, some animals were subject to HO-1 inhibition with chromium mesoporphyrin IX or Kupffer cell depletion with liposomal clodronate. Bone marrow-derived monocytes were grown from hemopoietic progenitors taken from wild-type and jnk-2 -/- mice before stimulation with lipopolysaccharide and measurement of tumour necrosis factor-alpha production. Jnk-2 -/- animals were protected from hepatic ischemia reperfusion injury. HO-1 expression and activity was elevated in jnk-2 -/- animals (2.2-fold; P=0.006). Most HO-1 was expressed in Kupffer cells. Inhibition of HO-1 in jnk-2 -/- animals led to the loss of protection from ischemia. Depletion of Kupffer cells using liposomal clodronate led to loss of hepatic HO-1 expression and much more severe injury in wild-type and jnk-2 -/- animals. In vitro studies of cultured macrophages demonstrated reduced tumour necrosis factor-alpha secretion after lipopolysaccharide stimulus, an effect lost after HO-1 inhibition.
With recent 'working-time'-relate... more With recent 'working-time'-related changes to surgical training structure, the value of dedicated research during surgical training has been questioned. Online survey examining career and academic outcomes following a period of surgically related dedicated research at a Scottish University between 1972 and 2007. Of 58 individuals identified, contact details were available for 49 and 43 (88%) responded. Ninety-five percent (n = 41) of respondents continue to pursue a career in surgery and 41% (n = 17) are currently in academic positions. Ninety-one percent (n = 39) had published one or more first-author peer-reviewed articles directly related to their research, with 53% (n = 23) publishing three or more. Respondents with a clinical component to their research published significantly more papers than those with purely laboratory-based research (P = 0.04). Eighty-one percent (n = 35) thought that research was necessary for career progression, but only 42% (n = 18) felt research should be integral to training. In conclusion, the majority of surgical trainees completing a dedicated research period, published papers and continued to pursue a surgical career with a research interest. A period of dedicated research was thought necessary for career progression, but few thought dedicated research should be integral to surgical training.
Transplant international : official journal of the European Society for Organ Transplantation, Jan 20, 2015
We congratulate Weissenbacher and colleagues on their retrospective study examining the influence... more We congratulate Weissenbacher and colleagues on their retrospective study examining the influence of anastomosis time (AT) on outcomes after deceased donor kidney transplant, provocatively entitled "The Faster the Better" (1). The authors conclude that AT is independently associated with patient survival, but not overall graft survival, and suggest that AT is "one of the most important modifiable transplant factors [and] should be considered a major risk factor for long term outcome". This article is protected by copyright. All rights reserved.
Emergency abdominal surgery outcomes represent an internationally important marker of healthcare ... more Emergency abdominal surgery outcomes represent an internationally important marker of healthcare quality and capacity. In this study, a novel approach to investigating global surgical outcomes is proposed, involving collaborative methodology using 'snapshot' clinical data collection over a 2-week period. The primary aim is to identify internationally relevant, modifiable surgical practices (in terms of modifiable process, equipment and clinical management) associated with best care for emergency abdominal surgery. This is a multicentre, international, prospective cohort study. Any hospital in the world performing acute surgery can participate, and any patient undergoing emergency intraperitoneal surgery is eligible to enter the study. Centres will collect observational data on patients for a 14-day period during a 5-month window and required data points will be limited to ensure practicality for collaborators collecting data. The primary outcome measure is the 24 h periopera...
Enhanced recovery after surgery (ERAS) is a well-established pathway of perioperative care in sur... more Enhanced recovery after surgery (ERAS) is a well-established pathway of perioperative care in surgery in an increasing number of specialties. To implement protocols and maintain high levels of compliance, continued support from care providers and patients is vital. This survey aimed to assess the perceptions of care providers and patients of the relevance and importance of the ERAS targets and strategies. Pre- and post-operative surveys were completed by patients who underwent major hepatic, colorectal, or oesophagogastric surgery in three major centers in Scotland, Norway, and The Netherlands. Anonymous web-based and article surveys were also sent to surgeons, anesthetists, and nurses experienced in delivering enhanced recovery protocols. Each questionnaire asked the responder to rate a selection of enhanced recovery targets and strategies in terms of perceived importance. One hundred nine patients and 57 care providers completed the preoperative survey. Overall, both patients and ...
Social media use has become common for organisations in surgery, however the nature and reach of ... more Social media use has become common for organisations in surgery, however the nature and reach of these communications is unknown. This study aimed to characterise and compare the use of "Twitter" by five prominent organisations in surgery. Data were collected from Twitter and the scale, reach, nature and sentiment of messages analysed. Message influence was determined and content analysed by frequency and association using hierarchical clustering and network analysis. Poisson regression was used to compare institutional message and "re-tweet" counts. 7712 messages were analysed from a four-year period up to 13th April 2013. The American College of Surgeons (ACS) had tweeted most and posted the greatest number of messages per day (3.3/day). The number of followers reflects social reach and the Royal College of Surgeons of England (RCSEng) had the greatest number (11,600) followed by the ACS (7320). The number of "retweets" a message receives is a measure of influence with the RCSEng (2.0) demonstrating a significantly greater count than the Royal College of Surgeons of Ireland (RCSI; 0.8, p < 0.001) and the ACS (1.3, p < 0.001). Followers of the RCSEng and ACS appeared most influential. Terms relating to education feature prominently in messages posted by the RCSEng and RCSEd, but less so in those from the RCSI and ACS. Education and training terms were highly correlated with "events". Surgical colleges have significant international reach through social media. UK colleges frequently communicate about education/training opportunities while the ACS focuses on patient-related matters. Only one organisation was found to have an explicit social media policy, which would be considered best practice and can focus on-line activity.
Intermittent clamping of the porta hepatis (PHC) is commonly performed during liver surgery to re... more Intermittent clamping of the porta hepatis (PHC) is commonly performed during liver surgery to reduce blood loss and has been reported to precondition livers resulting in improved outcome after liver surgery (humans) and transplantation (animals). This study investigated the early expression of cytoprotective stress proteins during ischemia-reperfusion induced by PHC. Liver samples were taken before and after each event in a two-cycle ischemia-reperfusion protocol using 15 minutes of PHC followed by 5 minutes of reperfusion. Liver tissue was analyzed by real-time polymerase chain reaction for heme oxygenase (HO)-1 and heat shock protein (HSP)-70 mRNA expression. Extracted protein was analyzed by Western blot for HO-1, and HSP-70 and nuclear extracts were analyzed by DNA mobility shift assay for hypoxia inducible factor (HIF)-1alpha and heat shock factor (HSF)-1. Within minutes of PHC, significant increases in HO-1 mRNA expression were detected, and these were maintained throughout the protocol (P < 0.01). Protein expression of HO-1 (P < 0.03) and HO-1 activity (P < 0.05) were similarly increased between the start and end of ischemia- reperfusion (40 minutes). Binding of active HIF-1alpha to its consensus sequence was increased within 15 minutes of the start of the ischemia-reperfusion cycle. Although evidence of the transcriptionally active form of HSF-1 was detected at the same time point, this was not reflected in measurable changes in HSP-70 mRNA or protein. In conclusion, expression of the cytoprotective protein HO-1 is significantly up-regulated in the liver within minutes of PHC. It is likely that HO-1 contributes to the early protective effects of ischemic preconditioning.
Preconditioning treatments hold significant potential for improving outcomes in solid organ trans... more Preconditioning treatments hold significant potential for improving outcomes in solid organ transplantation. Protective phenotypes can be induced using certain drugs. Curcumin is a biologically active component of turmeric and has been reported to induce stress proteins in certain cell lines, leading to cell protection. This study investigates in detail the effect of curcumin on the stress-response in human hepatocytes, in particular its effect on heme oxygenase 1 (HO-1) and its cytoprotective effect. Pretreatment with curcumin protected hepatocytes in a model of oxidative injury and this protection was mediated through HO-1. In a model of cold preservation injury, curcumin pretreatment resulted in elevation of HO-1 throughout the cold storage and rewarming period, and was cytoprotective against oxidative injury. This is the first study to demonstrate that curcumin induces HO-1 in human hepatocytes, and that the protective effects of curcumin pretreatment may have clinical potential in hepatic transplantation.
Gender disparities in live kidney donation are well documented, but little is known about differe... more Gender disparities in live kidney donation are well documented, but little is known about differences that may exist in the moral reasoning of potential donors prior to donation. American psychologist Carol Gilligan hypothesized that men are more likely to consider moral dilemmas ...
The optimal analgesic technique following open abdominal surgery within an enhanced recovery prot... more The optimal analgesic technique following open abdominal surgery within an enhanced recovery protocol remains controversial. Thoracic epidural is often recommended; however, its role is increasingly being challenged and alternative techniques are being suggested as suitable replacements. To determine by meta-analysis whether epidurals are superior to alternative analgesic techniques following open abdominal surgery within an enhanced recovery setting in terms of postoperative morbidity and other markers of recovery. A literature search was performed of EMBASE, Medline, PubMed, and the Cochrane databases from 1966 through May 2013. All randomized clinical trials comparing epidurals with an alternative analgesic technique following open abdominal surgery within an enhanced recovery protocol were included. All studies were assessed by 2 independent reviewers. Study quality was assessed using the Cochrane bias assessment tool and the Jadad and Chalmers modified bias risk assessment tools. Dichotomous data were analyzed by random or fixed-effects odds ratios. Qualitative analysis was performed where appropriate. Seven trials with a total of 378 patients were identified. No significant difference in complication rate was detected between epidurals and alternative analgesic methods (odds ratio, 1.14; 95% CI, 0.49-2.64; P = .76). Subgroup analysis showed fewer complications in the patient-controlled analgesia group compared with epidural analgesia (odds ratio, 1.97; 95% CI, 1.10-3.53; P = .02). Following qualitative assessment, epidural analgesia was associated with faster return of gut function and reduced pain scores; however, no difference was observed in length of stay. Epidurals may be associated with superior pain control but this does not translate into improved recovery or reduced morbidity when compared with alternative analgesic techniques when used within an enhanced recovery protocol.
Donation after cardiac death (DCD) liver transplantation is increasingly common but concerns exis... more Donation after cardiac death (DCD) liver transplantation is increasingly common but concerns exist over the development of biliary complications and ischemic cholangiopathy (IC). This study aimed to compare outcomes between DCD and donation after brain death (DBD) liver grafts. Studies reporting on post-transplantation outcomes after Maastricht category III DCD liver transplantation were screened for inclusion. Odds ratios (OR) with 95% confidence intervals were produced using random-effects models for the incidence of biliary complications, IC, graft and recipient survival. Meta-regression was undertaken to identify between-study predictors of effect size for biliary complications and IC. PROSPERO Record: CRD42012002113. Twenty-five studies with 62 184 liver transplant recipients (DCD = 2478 and DBD = 59 706) were included. In comparison with DBD, there was a significant increase in biliary complications [OR = 2.4 (1.9, 3.1); P < 0.00001] and IC [OR = 10.5 (5.7, 19.5); P < 0.00001] following DCD liver transplantation. In comparison with DBD, at 1 year [OR = 0.7 (0.5, 0.8); P = 0.0002] and 3 years [OR = 0.6 (0.5, 0.8); P = 0.001], there was a significant decrease in graft survival following DCD liver transplantation. At 1 year, there was also a nonsignificant decrease [OR = 0.8 (0.6, 1.0); P = 0.08] and by 3 years a significant decrease [OR = 0.7 (0.5, 1.0); P = 0.04] found in recipient survival following DCD liver transplantation. Eleven factors were entered into meta-regression models, but none explained the variability in effect size between studies. DCD liver transplantation is associated with an increase in biliary complications, IC, graft loss and mortality. Significant unexplained differences in effect size exist between centers.
The incidence of acute kidney injury due to ischaemia-reperfusion injury (IRI) is rising but effe... more The incidence of acute kidney injury due to ischaemia-reperfusion injury (IRI) is rising but effective treatments and preventative approaches are currently lacking. IRI is also an inevitable consequence of kidney transplantation and significantly contributes to delayed graft function. Heat-shock proteins (Hsps) are highly conserved and ubiquitously expressed molecular chaperones that help maintain and restore normal cellular function in the kidney following IRI. Hsp70 is one of the most frequently studied Hsps because of potential cytoprotective properties and attractiveness as a therapeutic target. However, the protective properties of Hsp70 in renal IRI are not fully understood and putative modes of protection include correction of protein conformation, cytoskeletal stabilisation, anti-inflammatory effects, requirement in autophagy, anti-apoptotic properties, influence over macrophage phenotype and stimulation of regulatory T cells. Significant clinical interest has been generated about the possibility of applying pharmacological agents to induce Hsp70 and prevent renal IRI, but prior to this, an increased mechanistic understanding of the protective nature of Hsp70 is needed. In particular, further investigation of Hsp expression on inflammatory cell behaviour is required as this could lead to the development of new therapeutic strategies for enhancing recovery following renal IRI and broaden the range of these therapies to a wider group of patients.
Targeted deletion of c-jun amino terminal kinase-2 (jnk-2) upregulates the activator protein-1 tr... more Targeted deletion of c-jun amino terminal kinase-2 (jnk-2) upregulates the activator protein-1 transcription factor system. We hypothesized that this would lead to induction of hemeoxygenase-1 (HO-1) and confer protection from hepatic ischemia reperfusion injury. Wild-type and jnk-2 -/- animals were subjected to hepatic ischemia reperfusion insults in two models: a total hepatic ischemia model involving timed Pringle maneuver, and a partial hepatic ischemia model involving selective occlusion of the portal pedicle supplying the left hepatic lobe. Optimal durations of injury were calibrated for each model. After 24 hr, animals were killed, and blood and tissues were collected for alanine aminotransferase, histologic injury scoring, and other analyses. Before total or partial hepatic ischemia reperfusion insults, some animals were subject to HO-1 inhibition with chromium mesoporphyrin IX or Kupffer cell depletion with liposomal clodronate. Bone marrow-derived monocytes were grown from hemopoietic progenitors taken from wild-type and jnk-2 -/- mice before stimulation with lipopolysaccharide and measurement of tumour necrosis factor-alpha production. Jnk-2 -/- animals were protected from hepatic ischemia reperfusion injury. HO-1 expression and activity was elevated in jnk-2 -/- animals (2.2-fold; P=0.006). Most HO-1 was expressed in Kupffer cells. Inhibition of HO-1 in jnk-2 -/- animals led to the loss of protection from ischemia. Depletion of Kupffer cells using liposomal clodronate led to loss of hepatic HO-1 expression and much more severe injury in wild-type and jnk-2 -/- animals. In vitro studies of cultured macrophages demonstrated reduced tumour necrosis factor-alpha secretion after lipopolysaccharide stimulus, an effect lost after HO-1 inhibition.
With recent 'working-time'-relate... more With recent 'working-time'-related changes to surgical training structure, the value of dedicated research during surgical training has been questioned. Online survey examining career and academic outcomes following a period of surgically related dedicated research at a Scottish University between 1972 and 2007. Of 58 individuals identified, contact details were available for 49 and 43 (88%) responded. Ninety-five percent (n = 41) of respondents continue to pursue a career in surgery and 41% (n = 17) are currently in academic positions. Ninety-one percent (n = 39) had published one or more first-author peer-reviewed articles directly related to their research, with 53% (n = 23) publishing three or more. Respondents with a clinical component to their research published significantly more papers than those with purely laboratory-based research (P = 0.04). Eighty-one percent (n = 35) thought that research was necessary for career progression, but only 42% (n = 18) felt research should be integral to training. In conclusion, the majority of surgical trainees completing a dedicated research period, published papers and continued to pursue a surgical career with a research interest. A period of dedicated research was thought necessary for career progression, but few thought dedicated research should be integral to surgical training.
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