The aim of this paper is to develop a method based on Legendre expansion to compute numerical der... more The aim of this paper is to develop a method based on Legendre expansion to compute numerical derivatives of a function from its perturbed data. The Tikhonov regularization combined with a new penalty term is used to deal with the ill posed-ness of the problem. It has been shown that the solution process is uniform for various smoothness of functions. Moreover, the convergence rates can be obtained self-adaptively when we choose the regularization parameter by a discrepancy principle. Numerical tests show that the method gives good results.
Background: There have been substantial improvements in the management of acute pancreatitis sinc... more Background: There have been substantial improvements in the management of acute pancreatitis since the publication of the International Association of Pancreatology (IAP) treatment guidelines in 2002. A collaboration of the IAP and the American Pancreatic Association (APA) was undertaken to revise these guidelines using an evidence-based approach. Methods: Twelve multidisciplinary review groups performed systematic literature reviews to answer 38 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The review groups presented their recommendations during the 2012 joint IAP/APA meeting. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting. Results: The 38 recommendations covered 12 topics related to the clinical management of acute pancreatitis: A) diagnosis of acute pancreatitis and etiology, B) prognostication/predicting severity, C) imaging, D) fluid therapy, E) intensive care management, F) preventing infectious complications, G) nutritional support, H) biliary tract management, I) indications for intervention in necrotizing pancreatitis, J) timing of intervention in necrotizing pancreatitis, K) intervention strategies in necrotizing pancreatitis, and L) timing of cholecystectomy. Using the GRADE system, 21 of the 38 (55%) recommendations, were rated as 'strong' and plenary voting revealed 'strong agreement' for 34 (89%) recommendations. Conclusions: The 2012 IAP/APA guidelines provide recommendations concerning key aspects of medical and surgical management of acute pancreatitis based on the currently available evidence. These recommendations should serve as a reference standard for current management and guide future clinical research on acute pancreatitis.
Ben Lawrence1, Cherie Blenkiron2, Kate Parker1, Peter Tsai2, Sandra Fitzgerald2, Paula Shields2, ... more Ben Lawrence1, Cherie Blenkiron2, Kate Parker1, Peter Tsai2, Sandra Fitzgerald2, Paula Shields2, Tamsin Robb2, Mee Ling Yeong3, Nicole Kramer3, Sarah James2, Mik Black4, Vicky Fan2, Nooriyah Poonawala2, Patrick Yap3, Esther Coats1, Braden Woodhouse1, Reena Ramsaroop5, Masato Yozu6, Bridget Robinson7, Kimiora Henare8, Jonathan Koea5, Peter Johnston3, Richard Carroll9, Saxon Connor7, Helen Morrin7, Marianne Elston10, Christopher Jackson11, Papaarangi Reid12, John Windsor13, Andrew MacCormick6, Richard Babor6, Adam Bartlett13, Dragan Damianovich3, Nicholas Knowlton2, Sean Grimmond14, Michael Findlay15, Cristin Print2.
Background: Whipple operation is a procedure largely performed by hepatobiliary surgeons worldwid... more Background: Whipple operation is a procedure largely performed by hepatobiliary surgeons worldwide, however there are significant differences in perioperative management. The aim of this study is to evaluate the variations in practice patterns of IHPBA/AHPBA members across multiple institutions worldwide. Methods: From May to August 2015, a pilot crosssectional 25-item survey questionnaire was electronically distributed using Survey Monkey to IHPBA and AHPBA members regarding practice patterns and perioperative care of patients undergoing Whipple operation. Results: A total of 285 respondents were included. The majority of participants were from United States (34.7%) at academic institutions (56.1%) who performed 10e25 cases annually (48.8%). Most members do not routinely culture bile (59.5%) or postoperative drain fluid (75.3%), and do not extend perioperative antibiotic beyond 24 h postoperatively (48%). However, if indicated, 57% continue antibiotics for 5e7 days. Two self-suction drains are more commonly used (41%) and drain amylase is routinely measured in 83% of cases, usually on postoperative day 3 (46%). The majority of respondents do not use wound protectors (69.7%), use normal saline for wound irrigation (72.2%) and staples for skin closure (57.8%). Conclusions: Our survey evaluated the perioperative management of Whipple procedure at numerous global institutions. Management varies widely regarding antibiotic use and duration of therapy. However, similarities exist in routinely not culturing bile and consistently checking drain amylase. Further studies are warranted to elucidate the impact these variations pose to surgical outcomes on patients undergoing Whipple operation.
Objective: To isolate microRNAs (miRNAs) from mesenteric lymph (ML) and peripheral blood and iden... more Objective: To isolate microRNAs (miRNAs) from mesenteric lymph (ML) and peripheral blood and identify those that change with experimental acute pancreatitis (AP). To assess identified AP-associated miRNAs in patient plasma to evaluate them as clinical biomarkers of AP. Background: miRNAs, small non-protein-coding molecules that regulate gene expression, are present in many biological fluids. They are increasingly interesting as biomarkers of disease and as novel signaling molecules in pathogenesis. Methods: Affymetrix miRNA profiling was performed on ML collected from 3 groups of rats with either mild or moderate taurocholate-induced AP and sham controls. Quantitative reverse transcription-polymerase chain reaction was used to validate selected miRNAs in matched rat lymph and plasma and then measured in patients with mild or moderate AP and in healthy volunteers. Results: Eighty-five miRNAs were detectable in rat ML, and many were abundant in all animals irrespective of the presence of AP. Seven miRNAs, comprising miR-375,-217,-148a,-216a,-122,-214, and-138, were increased in ML from rats with AP (P < 0.01). Their abundance also altered with disease severity. miRNAs miR-217,-375,-122, and-148a were also increased in matched rat plasma samples by quantitative reverse transcription-polymerase chain reaction. In the clinical studies, plasma miR-216a was significantly increased in both mild and moderate AP. Conclusions: This study is the first to demonstrate both the presence of circulating miRNAs in lymph and the alteration of specific miRNAs in AP. Furthermore, these miRNAs alter in rat and human AP plasma and have potential to be explored as novel biomarkers of pancreatitis.
Major allele frequency in HSPA1A gene was 1 (A>G) for AP patients and 1 (A>G) for controls. For H... more Major allele frequency in HSPA1A gene was 1 (A>G) for AP patients and 1 (A>G) for controls. For HSPA1A, the gene major allele frequency was 0.672 (A>C) for patients and 0.7 (A>C) for controls, the major allele frequencies were 0.638 (A>G) and 0.672 (G>C) for patients and 0.85 (A>G) and 0.65 (G>C) for controls, respectively. The allele frequencies differed between AP patients with organ failure and those with mild disease. Following gene expression of HSPA1L and SNP relationship analysis, AP patients with heterozygous genotype had higher expression levels as compared to non-AP patients (p=0.014). Conclusions: Our data suggest that polymorphism of the HSP70 promoter region may be a risk factor for developing severe acute pancreatitis. Further study to determine the urine levels of HSP70 protein expression is needed to confirm the protective mechanism of HSP70.
2009 24th International Conference Image and Vision Computing New Zealand, 2009
Tracking the position and orientation of the human face with respect to a camera has valuable app... more Tracking the position and orientation of the human face with respect to a camera has valuable applications in human computer interaction (HCI). Examples are navigating through a virtual environment, controlling objects using head gestures, and enabling avatars in a virtual environment to reflect the user's behaviour. Tracking performance can be heavily influenced by environmental parameters. Developers and users of face tracking plugins without computer vision experience need guidelines how to optimise face tracking performance in real world setups and they need measures how environmental parameters influence the results. In this paper we develop a qualitative framework for determining ideal working conditions of face tracking algorithms. We apply our framework to a commercially available face tracking solution and present the results of this analysis.
to controls; IL-10 levels were significantly elevated by day 3; IL17A levels increased on day 2 a... more to controls; IL-10 levels were significantly elevated by day 3; IL17A levels increased on day 2 and significantly elevated at day 3 compared to controls declining to non-significant levels by day 4. Conclusion: Neither IFNg nor TNFa Th1 cytokines were elevated, however IL-17A and IL-10 (an anti-inflammatory cytokine implicated in suppressing Th17 cytokines secreted by macrophages and T cells) were elevated by day 3. Additionally IL-6, which helps drive development of Th17 cells, was significantly elevated at all time-points. These preliminary results imply that the underlying AP induced systemic inflammation is polarized to a Th17 rather than a Th1 response.
2008 23rd International Conference Image and Vision Computing New Zealand, 2008
In recent years, the increased use of simulation for the training of surgical skills has improved... more In recent years, the increased use of simulation for the training of surgical skills has improved the medical curriculum and the overall patient outcome. Advances in hardware and simulation techniques have resulted in many commercial applications for training technical skills. However, most of these simulators are extremely expensive and do not consider non-technical skills like teamwork and communication. This is a major drawback since recent research suggests that a a large percentage of mistakes in clinical settings are due to communication problems. In addition training teamwork can also improve the efficiency of a surgical team and as such reduce costs and workload. We present an inexpensive camera-based system for the acquisition of aspects of non-verbal communication of users participating in virtual environment-based teamwork simulations. This data can be used for the enhancement of virtual-environment-based simulations to increase the realism and effectiveness of team communication.
Controversy over whether intraoperative cholangiography (IOC) should be done routinely has intens... more Controversy over whether intraoperative cholangiography (IOC) should be done routinely has intensified since the advent of laparoscopic cholecystectomy (LC). As yet, no study has demonstrated a
To compare two priority access criteria scoring methods for elective cholecystectomy, with a scor... more To compare two priority access criteria scoring methods for elective cholecystectomy, with a score based on clinical judgement obtained using a linear analogue scale. Patients placed on the waiting list for elective laparoscopic cholecystectomy between June and October 1997 were prioritised using the three methods. Data were obtained for 22 patients. The distributions of scores were different but there was a significant correlation between them. However, limits of agreement analysis demonstrated little agreement between them with a difference of +/- 30 points (out of a 100) between scores obtained with each method. The proposed methods for establishing priority access to elective cholecystectomy are poor tools, require validation and bear little relation to expert clinical judgement.
Sepsis and multiple organ dysfunction syndrome (MODS) are major causes of morbidity and mortality... more Sepsis and multiple organ dysfunction syndrome (MODS) are major causes of morbidity and mortality in the intensive care unit. Recently mitochondrial dysfunction has been proposed as a key early cellular event in critical illness. A growing body of experimental evidence suggests that mitochondrial therapies are effective in sepsis and MODS. The aim of this article is to undertake a systematic review of the current experimental evidence for the use of therapies for mitochondrial dysfunction during sepsis and MODS and to classify these mitochondrial therapies. A search of the MEDLINE and PubMed databases (1950 to July 2009) and a manual review of reference lists were conducted to find experimental studies containing data on the efficacy of mitochondrial therapies in sepsis and sepsis-related MODS. Fifty-one studies were included in this review. Five categories of mitochondrial therapies were defined-substrate provision, cofactor provision, mitochondrial antioxidants, mitochondrial reactive oxygen species scavengers, and membrane stabilizers. Administration of mitochondrial therapies during sepsis was associated with improvements in mitochondrial electron transport system function, oxidative phosphorylation, and ATP production and a reduction in cellular markers of oxidative stress. Amelioration of proinflammatory cytokines, caspase activation, and prevention of the membrane permeability transition were reported. Restoration of mitochondrial bioenergetics was associated with improvements in hemodynamic parameters, organ function, and overall survival. A substantial body of evidence from experimental studies at both the cellular and the organ level suggests a beneficial role for the administration of mitochondrial therapies in sepsis and MODS. We expect that mitochondrial therapies will have an increasingly important role in the management of sepsis and MODS. Clinical trials are now required.
The thoracic duct (TD) transports ingested fat, drains lymph from the gastrointestinal vascular b... more The thoracic duct (TD) transports ingested fat, drains lymph from the gastrointestinal vascular bed, and delivers the lymph to central veins in the neck. Preliminary evidence suggests that diversion of TD lymph may mitigate the severity of end-organ dysfunction in critical illness. Variations in the anatomy of the TD may determine whether reliable and safe cannulation of the duct, a necessary step for diversion, is possible. A systematic review was undertaken using the Google Scholar, MEDLINE, PubMed, and Scopus databases until 31st March, 2013. Both English and non-English articles were searched for, and surgical, cadaveric, and radiologic studies were included. Fifty-seven articles from the past 102 years were retrieved. There are significant variations in the anatomy of the TD in terms of its formation at the cisterna chyli, its course through the thorax, and its termination in the venous system. The most common site of termination is at the internal jugular vein (46%), followed by the jugulosubclavian angle (32%), and the subclavian vein (18%). An improved understanding of the anatomy of the TD would help surgeons to avoid inadvertent injury and potentially afford new opportunities for diagnosis and intervention in patients with critical illness.
Background: Mitochondrial dysfunction occurs in the pancreas and in extra-pancreatic organs early... more Background: Mitochondrial dysfunction occurs in the pancreas and in extra-pancreatic organs early in experimental acute pancreatitis (AP). However, direct measurement of mitochondrial function (MtF) within these organs is not possible in clinical settings. Aims: To measure and describe changes in MtF in peripheral blood in experimental and clinical AP. Patients & methods: MtF was measured in peripheral blood mononuclear cells (PBMC) bymeasuringoxygenflux through the electron transport system(ETS) in anexperimental anda clinical study.MeasurementofMtFwas done in rats (n1⁄418) with caerulein induced mild AP (CAP) and in patients (n1⁄418) admittedwith predictedmild tomoderate AP. In both studiesMtFwas compared with appropriate controls. Mitochondrial superoxide production, cytochrome c, mitochondrial membrane potential (âˆy a a), and adenine triphosphate (ATP) were also measured in the clinical study. Results: MtF was successfully measured in the PBMC fraction of blood. The most significant alteration in MtF was increased endogenous respiration and leak respiration in both studies. The clinical study also revealed significant increases in mitochondrial superoxide and mitochondrial membrane potential and a decrease in cytochrome c but no change in total cell ATP content. Conclusion: This is the first study tomeasure changes in peripheral blood MtF inAP.MtF inPBMCwasaltered inboth theexperimental andclinical acute pancreatitis settings. Further studies should now investigate the time course of peripheral changes in MtF to explore whether it correlates with disease severity, end organ dysfunction and as an outcome predictor in AP.
The aim of this paper is to develop a method based on Legendre expansion to compute numerical der... more The aim of this paper is to develop a method based on Legendre expansion to compute numerical derivatives of a function from its perturbed data. The Tikhonov regularization combined with a new penalty term is used to deal with the ill posed-ness of the problem. It has been shown that the solution process is uniform for various smoothness of functions. Moreover, the convergence rates can be obtained self-adaptively when we choose the regularization parameter by a discrepancy principle. Numerical tests show that the method gives good results.
Background: There have been substantial improvements in the management of acute pancreatitis sinc... more Background: There have been substantial improvements in the management of acute pancreatitis since the publication of the International Association of Pancreatology (IAP) treatment guidelines in 2002. A collaboration of the IAP and the American Pancreatic Association (APA) was undertaken to revise these guidelines using an evidence-based approach. Methods: Twelve multidisciplinary review groups performed systematic literature reviews to answer 38 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The review groups presented their recommendations during the 2012 joint IAP/APA meeting. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting. Results: The 38 recommendations covered 12 topics related to the clinical management of acute pancreatitis: A) diagnosis of acute pancreatitis and etiology, B) prognostication/predicting severity, C) imaging, D) fluid therapy, E) intensive care management, F) preventing infectious complications, G) nutritional support, H) biliary tract management, I) indications for intervention in necrotizing pancreatitis, J) timing of intervention in necrotizing pancreatitis, K) intervention strategies in necrotizing pancreatitis, and L) timing of cholecystectomy. Using the GRADE system, 21 of the 38 (55%) recommendations, were rated as 'strong' and plenary voting revealed 'strong agreement' for 34 (89%) recommendations. Conclusions: The 2012 IAP/APA guidelines provide recommendations concerning key aspects of medical and surgical management of acute pancreatitis based on the currently available evidence. These recommendations should serve as a reference standard for current management and guide future clinical research on acute pancreatitis.
Ben Lawrence1, Cherie Blenkiron2, Kate Parker1, Peter Tsai2, Sandra Fitzgerald2, Paula Shields2, ... more Ben Lawrence1, Cherie Blenkiron2, Kate Parker1, Peter Tsai2, Sandra Fitzgerald2, Paula Shields2, Tamsin Robb2, Mee Ling Yeong3, Nicole Kramer3, Sarah James2, Mik Black4, Vicky Fan2, Nooriyah Poonawala2, Patrick Yap3, Esther Coats1, Braden Woodhouse1, Reena Ramsaroop5, Masato Yozu6, Bridget Robinson7, Kimiora Henare8, Jonathan Koea5, Peter Johnston3, Richard Carroll9, Saxon Connor7, Helen Morrin7, Marianne Elston10, Christopher Jackson11, Papaarangi Reid12, John Windsor13, Andrew MacCormick6, Richard Babor6, Adam Bartlett13, Dragan Damianovich3, Nicholas Knowlton2, Sean Grimmond14, Michael Findlay15, Cristin Print2.
Background: Whipple operation is a procedure largely performed by hepatobiliary surgeons worldwid... more Background: Whipple operation is a procedure largely performed by hepatobiliary surgeons worldwide, however there are significant differences in perioperative management. The aim of this study is to evaluate the variations in practice patterns of IHPBA/AHPBA members across multiple institutions worldwide. Methods: From May to August 2015, a pilot crosssectional 25-item survey questionnaire was electronically distributed using Survey Monkey to IHPBA and AHPBA members regarding practice patterns and perioperative care of patients undergoing Whipple operation. Results: A total of 285 respondents were included. The majority of participants were from United States (34.7%) at academic institutions (56.1%) who performed 10e25 cases annually (48.8%). Most members do not routinely culture bile (59.5%) or postoperative drain fluid (75.3%), and do not extend perioperative antibiotic beyond 24 h postoperatively (48%). However, if indicated, 57% continue antibiotics for 5e7 days. Two self-suction drains are more commonly used (41%) and drain amylase is routinely measured in 83% of cases, usually on postoperative day 3 (46%). The majority of respondents do not use wound protectors (69.7%), use normal saline for wound irrigation (72.2%) and staples for skin closure (57.8%). Conclusions: Our survey evaluated the perioperative management of Whipple procedure at numerous global institutions. Management varies widely regarding antibiotic use and duration of therapy. However, similarities exist in routinely not culturing bile and consistently checking drain amylase. Further studies are warranted to elucidate the impact these variations pose to surgical outcomes on patients undergoing Whipple operation.
Objective: To isolate microRNAs (miRNAs) from mesenteric lymph (ML) and peripheral blood and iden... more Objective: To isolate microRNAs (miRNAs) from mesenteric lymph (ML) and peripheral blood and identify those that change with experimental acute pancreatitis (AP). To assess identified AP-associated miRNAs in patient plasma to evaluate them as clinical biomarkers of AP. Background: miRNAs, small non-protein-coding molecules that regulate gene expression, are present in many biological fluids. They are increasingly interesting as biomarkers of disease and as novel signaling molecules in pathogenesis. Methods: Affymetrix miRNA profiling was performed on ML collected from 3 groups of rats with either mild or moderate taurocholate-induced AP and sham controls. Quantitative reverse transcription-polymerase chain reaction was used to validate selected miRNAs in matched rat lymph and plasma and then measured in patients with mild or moderate AP and in healthy volunteers. Results: Eighty-five miRNAs were detectable in rat ML, and many were abundant in all animals irrespective of the presence of AP. Seven miRNAs, comprising miR-375,-217,-148a,-216a,-122,-214, and-138, were increased in ML from rats with AP (P < 0.01). Their abundance also altered with disease severity. miRNAs miR-217,-375,-122, and-148a were also increased in matched rat plasma samples by quantitative reverse transcription-polymerase chain reaction. In the clinical studies, plasma miR-216a was significantly increased in both mild and moderate AP. Conclusions: This study is the first to demonstrate both the presence of circulating miRNAs in lymph and the alteration of specific miRNAs in AP. Furthermore, these miRNAs alter in rat and human AP plasma and have potential to be explored as novel biomarkers of pancreatitis.
Major allele frequency in HSPA1A gene was 1 (A>G) for AP patients and 1 (A>G) for controls. For H... more Major allele frequency in HSPA1A gene was 1 (A>G) for AP patients and 1 (A>G) for controls. For HSPA1A, the gene major allele frequency was 0.672 (A>C) for patients and 0.7 (A>C) for controls, the major allele frequencies were 0.638 (A>G) and 0.672 (G>C) for patients and 0.85 (A>G) and 0.65 (G>C) for controls, respectively. The allele frequencies differed between AP patients with organ failure and those with mild disease. Following gene expression of HSPA1L and SNP relationship analysis, AP patients with heterozygous genotype had higher expression levels as compared to non-AP patients (p=0.014). Conclusions: Our data suggest that polymorphism of the HSP70 promoter region may be a risk factor for developing severe acute pancreatitis. Further study to determine the urine levels of HSP70 protein expression is needed to confirm the protective mechanism of HSP70.
2009 24th International Conference Image and Vision Computing New Zealand, 2009
Tracking the position and orientation of the human face with respect to a camera has valuable app... more Tracking the position and orientation of the human face with respect to a camera has valuable applications in human computer interaction (HCI). Examples are navigating through a virtual environment, controlling objects using head gestures, and enabling avatars in a virtual environment to reflect the user's behaviour. Tracking performance can be heavily influenced by environmental parameters. Developers and users of face tracking plugins without computer vision experience need guidelines how to optimise face tracking performance in real world setups and they need measures how environmental parameters influence the results. In this paper we develop a qualitative framework for determining ideal working conditions of face tracking algorithms. We apply our framework to a commercially available face tracking solution and present the results of this analysis.
to controls; IL-10 levels were significantly elevated by day 3; IL17A levels increased on day 2 a... more to controls; IL-10 levels were significantly elevated by day 3; IL17A levels increased on day 2 and significantly elevated at day 3 compared to controls declining to non-significant levels by day 4. Conclusion: Neither IFNg nor TNFa Th1 cytokines were elevated, however IL-17A and IL-10 (an anti-inflammatory cytokine implicated in suppressing Th17 cytokines secreted by macrophages and T cells) were elevated by day 3. Additionally IL-6, which helps drive development of Th17 cells, was significantly elevated at all time-points. These preliminary results imply that the underlying AP induced systemic inflammation is polarized to a Th17 rather than a Th1 response.
2008 23rd International Conference Image and Vision Computing New Zealand, 2008
In recent years, the increased use of simulation for the training of surgical skills has improved... more In recent years, the increased use of simulation for the training of surgical skills has improved the medical curriculum and the overall patient outcome. Advances in hardware and simulation techniques have resulted in many commercial applications for training technical skills. However, most of these simulators are extremely expensive and do not consider non-technical skills like teamwork and communication. This is a major drawback since recent research suggests that a a large percentage of mistakes in clinical settings are due to communication problems. In addition training teamwork can also improve the efficiency of a surgical team and as such reduce costs and workload. We present an inexpensive camera-based system for the acquisition of aspects of non-verbal communication of users participating in virtual environment-based teamwork simulations. This data can be used for the enhancement of virtual-environment-based simulations to increase the realism and effectiveness of team communication.
Controversy over whether intraoperative cholangiography (IOC) should be done routinely has intens... more Controversy over whether intraoperative cholangiography (IOC) should be done routinely has intensified since the advent of laparoscopic cholecystectomy (LC). As yet, no study has demonstrated a
To compare two priority access criteria scoring methods for elective cholecystectomy, with a scor... more To compare two priority access criteria scoring methods for elective cholecystectomy, with a score based on clinical judgement obtained using a linear analogue scale. Patients placed on the waiting list for elective laparoscopic cholecystectomy between June and October 1997 were prioritised using the three methods. Data were obtained for 22 patients. The distributions of scores were different but there was a significant correlation between them. However, limits of agreement analysis demonstrated little agreement between them with a difference of +/- 30 points (out of a 100) between scores obtained with each method. The proposed methods for establishing priority access to elective cholecystectomy are poor tools, require validation and bear little relation to expert clinical judgement.
Sepsis and multiple organ dysfunction syndrome (MODS) are major causes of morbidity and mortality... more Sepsis and multiple organ dysfunction syndrome (MODS) are major causes of morbidity and mortality in the intensive care unit. Recently mitochondrial dysfunction has been proposed as a key early cellular event in critical illness. A growing body of experimental evidence suggests that mitochondrial therapies are effective in sepsis and MODS. The aim of this article is to undertake a systematic review of the current experimental evidence for the use of therapies for mitochondrial dysfunction during sepsis and MODS and to classify these mitochondrial therapies. A search of the MEDLINE and PubMed databases (1950 to July 2009) and a manual review of reference lists were conducted to find experimental studies containing data on the efficacy of mitochondrial therapies in sepsis and sepsis-related MODS. Fifty-one studies were included in this review. Five categories of mitochondrial therapies were defined-substrate provision, cofactor provision, mitochondrial antioxidants, mitochondrial reactive oxygen species scavengers, and membrane stabilizers. Administration of mitochondrial therapies during sepsis was associated with improvements in mitochondrial electron transport system function, oxidative phosphorylation, and ATP production and a reduction in cellular markers of oxidative stress. Amelioration of proinflammatory cytokines, caspase activation, and prevention of the membrane permeability transition were reported. Restoration of mitochondrial bioenergetics was associated with improvements in hemodynamic parameters, organ function, and overall survival. A substantial body of evidence from experimental studies at both the cellular and the organ level suggests a beneficial role for the administration of mitochondrial therapies in sepsis and MODS. We expect that mitochondrial therapies will have an increasingly important role in the management of sepsis and MODS. Clinical trials are now required.
The thoracic duct (TD) transports ingested fat, drains lymph from the gastrointestinal vascular b... more The thoracic duct (TD) transports ingested fat, drains lymph from the gastrointestinal vascular bed, and delivers the lymph to central veins in the neck. Preliminary evidence suggests that diversion of TD lymph may mitigate the severity of end-organ dysfunction in critical illness. Variations in the anatomy of the TD may determine whether reliable and safe cannulation of the duct, a necessary step for diversion, is possible. A systematic review was undertaken using the Google Scholar, MEDLINE, PubMed, and Scopus databases until 31st March, 2013. Both English and non-English articles were searched for, and surgical, cadaveric, and radiologic studies were included. Fifty-seven articles from the past 102 years were retrieved. There are significant variations in the anatomy of the TD in terms of its formation at the cisterna chyli, its course through the thorax, and its termination in the venous system. The most common site of termination is at the internal jugular vein (46%), followed by the jugulosubclavian angle (32%), and the subclavian vein (18%). An improved understanding of the anatomy of the TD would help surgeons to avoid inadvertent injury and potentially afford new opportunities for diagnosis and intervention in patients with critical illness.
Background: Mitochondrial dysfunction occurs in the pancreas and in extra-pancreatic organs early... more Background: Mitochondrial dysfunction occurs in the pancreas and in extra-pancreatic organs early in experimental acute pancreatitis (AP). However, direct measurement of mitochondrial function (MtF) within these organs is not possible in clinical settings. Aims: To measure and describe changes in MtF in peripheral blood in experimental and clinical AP. Patients & methods: MtF was measured in peripheral blood mononuclear cells (PBMC) bymeasuringoxygenflux through the electron transport system(ETS) in anexperimental anda clinical study.MeasurementofMtFwas done in rats (n1⁄418) with caerulein induced mild AP (CAP) and in patients (n1⁄418) admittedwith predictedmild tomoderate AP. In both studiesMtFwas compared with appropriate controls. Mitochondrial superoxide production, cytochrome c, mitochondrial membrane potential (âˆy a a), and adenine triphosphate (ATP) were also measured in the clinical study. Results: MtF was successfully measured in the PBMC fraction of blood. The most significant alteration in MtF was increased endogenous respiration and leak respiration in both studies. The clinical study also revealed significant increases in mitochondrial superoxide and mitochondrial membrane potential and a decrease in cytochrome c but no change in total cell ATP content. Conclusion: This is the first study tomeasure changes in peripheral blood MtF inAP.MtF inPBMCwasaltered inboth theexperimental andclinical acute pancreatitis settings. Further studies should now investigate the time course of peripheral changes in MtF to explore whether it correlates with disease severity, end organ dysfunction and as an outcome predictor in AP.
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Papers by John Windsor