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Richard J. Mellanby - One of the best experts on this subject based on the ideXlab platform.
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Hyperammonemia and Systemic Inflammatory Response Syndrome Predicts Presence of Hepatic Encephalopathy in Dogs with Congenital Portosystemic Shunts
2016Co-Authors: Michael Tivers, Rajiv Jalan, Ian H, Adamg Gow, Vicky J. Lipscomb, Richard J. MellanbyAbstract:Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common Congenital abnormalities in dogs is a Congenital Portosystemic Shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPS
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RESEARCH ARTICLE Attenuation of Congenital Portosystemic Shunt Reduces Inflammation in Dogs
2016Co-Authors: Michael Tivers, Victoria J Lipscomb, Rajiv Jalan, Ian H, Adamg Gow, Richard J. MellanbyAbstract:Liver disease is a major cause of morbidity and mortality. One of the most significant compli-cations in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incom-pletely understood, which has resulted in the development of a wide range of experimental models. Congenital Portosystemic Shunt is one of the most common Congenital disorders di-agnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiol-ogy of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a Congenital Portosystemic Shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have dem-onstrated an important role for ammonia and inflammation in the development of hepatic en-cephalopathy in dogs with a Congenital Portosystemic Shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil
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Surgical attenuation of spontaneous Congenital Portosystemic Shunts in dogs resolves hepatic encephalopathy but not hypermanganesemia
Metabolic Brain Disease, 2015Co-Authors: Adamg Gow, Carolyn A. Burton, Polly E. Frowde, Clive M. Elwood, Roger M. Powell, Simon W. Tappin, Rob D. Foale, Andrew Duncan, Richard J. MellanbyAbstract:Hypermanganesemia is commonly recognized in human patients with hepatic insufficiency and Portosystemic Shunting. Since manganese is neurotoxic, increases in brain manganese concentrations have been implicated in the development of hepatic encephalopathy although a direct causative role has yet to be demonstrated. Evaluate manganese concentrations in dogs with a naturally occurring Congenital Shunt before and after attenuation as well as longitudinally following the changes in hepatic encephalopathy grade. Our study demonstrated that attenuation of the Shunt resolved encephalopathy, significantly reduced postprandial bile acids, yet a hypermanganasemic state persisted. This study demonstrates that resolution of hepatic encephalopathy can occur without the correction of hypermanganesemia, indicating that increased manganese concentrations alone do not play a causative role in encephalopathy. Our study further demonstrates the value of the canine Congenital Portosystemic Shunt as a naturally occurring spontaneous model of human hepatic encephalopathy.
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Attenuation of Congenital Portosystemic Shunt reduces inflammation in dogs.
PloS one, 2015Co-Authors: Michael Tivers, Ian Handel, Adam Gow, Victoria J Lipscomb, Rajiv Jalan, Richard J. MellanbyAbstract:Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital Portosystemic Shunt is one of the most common Congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a Congenital Portosystemic Shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a Congenital Portosystemic Shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of Congenital Portosystemic Shunts in dogs. One hundred and forty dogs with a Congenital Portosystemic Shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical Congenital Portosystemic Shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of Congenital Portosystemic Shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder.
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Hepatic hepcidin gene expression in dogs with a Congenital Portosystemic Shunt.
Journal of veterinary internal medicine, 2014Co-Authors: P. E. Frowde, Adam Gow, Richard J. Mellanby, C. A. Burton, Roger Edwin Powell, Victoria Lipscomb, A K House, Michael TiversAbstract:Background Microcytic anemia is common in dogs with a Congenital Portosystemic Shunt (cPSS) and typically resolves after surgical attenuation of the anomalous vessel. However, the pathophysiology of the microcytic anemia remains poorly understood. Hepcidin has been a key role in controlling iron transport in both humans and animals and in mediating anemia of inflammatory disease in humans. The role of hepcidin in the development of microcytic anemia in dogs with a cPSS has not been examined. Hypothesis To determine whether hepatic hepcidin mRNA expression decreases, while red blood cell count (RBC) and mean corpuscular volume (MCV) increase in dogs after surgical attenuation of a cPSS. Animals Eighteen client-owned dogs with confirmed cPSS undergoing surgical attenuation. Method Prospective study. Red blood cell count (RBC) and mean corpuscular volume (MCV), together with hepatic gene expression of hepcidin, were measured in dogs before and after partial attenuation of a cPSS. Results There was a significant increase in both RBC (median pre 6.17 × 1012/L, median post 7.08 × 1012/L, P
Michael Tivers - One of the best experts on this subject based on the ideXlab platform.
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Incidence and risk factors for neurological signs after attenuation of a single Congenital Portosystemic Shunt in 50 cats.
Veterinary surgery : VS, 2020Co-Authors: Rhiannon Strickland, Michael Tivers, Robert C Fowkes, Victoria J LipscombAbstract:To determine the incidence, outcome, and risk factors for postattenuation neurological signs (PANS) in cats treated for single Congenital Portosystemic Shunts (CPSS). Retrospective cohort study. Cats (n = 50) with a single CPSS. Medical records of cats treated by surgical attenuation of a single CPSS between 2003 and 2017 were reviewed for signalment, surgical technique, preoperative management and postoperative clinical outcomes. Binary logistic regression was performed to investigate risk factors for occurrence of PANS and seizures. Congenital Portosystemic Shunts in 50 cats included 40 extrahepatic and 10 intrahepatic Shunts. Postattenuation neurological signs were recorded in 31 (62%) cats and graded as 1 in 10 cats, 2 in nine cats, and 3 in 12 cats. Postattenuation neurological signs included seizures in 11 cats. Five of 31 cats with PANS did not survive to discharge. No association was detected between PANS or seizures and the type of CPSS (intrahepatic or extrahepatic), degree of attenuation, age, or the use of perioperative levetiracetam or hepatic encephalopathy immediately preoperatively. Osmolality at a median 24 hours postoperatively was lower in cats with PANS (P < .049, Wald 3.867, odds ratio [Exp(B)] 0.855, CI 0.732-0.999). Postattenuation neurological signs are common complications in cats treated for CPSS. Preoperative levetiracetam did not prevent the occurrence of PANS or seizures. The only risk factor for PANS detected was lower postoperative Osmolality in cats with PANS at 24 hours. Postattenuation neurological signs including seizures occur frequently in cats undergoing surgical attenuation of a CPSS. Preoperative levetiracetam did not protect against the development of PANS. © 2020 The Authors. Veterinary Surgery published by Wiley Periodicals LLC. on behalf of American College of Veterinary Surgeons.
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Hyperammonemia and Systemic Inflammatory Response Syndrome Predicts Presence of Hepatic Encephalopathy in Dogs with Congenital Portosystemic Shunts
2016Co-Authors: Michael Tivers, Rajiv Jalan, Ian H, Adamg Gow, Vicky J. Lipscomb, Richard J. MellanbyAbstract:Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common Congenital abnormalities in dogs is a Congenital Portosystemic Shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPS
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RESEARCH ARTICLE Attenuation of Congenital Portosystemic Shunt Reduces Inflammation in Dogs
2016Co-Authors: Michael Tivers, Victoria J Lipscomb, Rajiv Jalan, Ian H, Adamg Gow, Richard J. MellanbyAbstract:Liver disease is a major cause of morbidity and mortality. One of the most significant compli-cations in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incom-pletely understood, which has resulted in the development of a wide range of experimental models. Congenital Portosystemic Shunt is one of the most common Congenital disorders di-agnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiol-ogy of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a Congenital Portosystemic Shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have dem-onstrated an important role for ammonia and inflammation in the development of hepatic en-cephalopathy in dogs with a Congenital Portosystemic Shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil
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Attenuation of Congenital Portosystemic Shunt reduces inflammation in dogs.
PloS one, 2015Co-Authors: Michael Tivers, Ian Handel, Adam Gow, Victoria J Lipscomb, Rajiv Jalan, Richard J. MellanbyAbstract:Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital Portosystemic Shunt is one of the most common Congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a Congenital Portosystemic Shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a Congenital Portosystemic Shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of Congenital Portosystemic Shunts in dogs. One hundred and forty dogs with a Congenital Portosystemic Shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical Congenital Portosystemic Shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of Congenital Portosystemic Shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder.
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Hepatic hepcidin gene expression in dogs with a Congenital Portosystemic Shunt.
Journal of veterinary internal medicine, 2014Co-Authors: P. E. Frowde, Adam Gow, Richard J. Mellanby, C. A. Burton, Roger Edwin Powell, Victoria Lipscomb, A K House, Michael TiversAbstract:Background Microcytic anemia is common in dogs with a Congenital Portosystemic Shunt (cPSS) and typically resolves after surgical attenuation of the anomalous vessel. However, the pathophysiology of the microcytic anemia remains poorly understood. Hepcidin has been a key role in controlling iron transport in both humans and animals and in mediating anemia of inflammatory disease in humans. The role of hepcidin in the development of microcytic anemia in dogs with a cPSS has not been examined. Hypothesis To determine whether hepatic hepcidin mRNA expression decreases, while red blood cell count (RBC) and mean corpuscular volume (MCV) increase in dogs after surgical attenuation of a cPSS. Animals Eighteen client-owned dogs with confirmed cPSS undergoing surgical attenuation. Method Prospective study. Red blood cell count (RBC) and mean corpuscular volume (MCV), together with hepatic gene expression of hepcidin, were measured in dogs before and after partial attenuation of a cPSS. Results There was a significant increase in both RBC (median pre 6.17 × 1012/L, median post 7.08 × 1012/L, P
Victoria J Lipscomb - One of the best experts on this subject based on the ideXlab platform.
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Incidence and risk factors for neurological signs after attenuation of a single Congenital Portosystemic Shunt in 50 cats.
Veterinary surgery : VS, 2020Co-Authors: Rhiannon Strickland, Michael Tivers, Robert C Fowkes, Victoria J LipscombAbstract:To determine the incidence, outcome, and risk factors for postattenuation neurological signs (PANS) in cats treated for single Congenital Portosystemic Shunts (CPSS). Retrospective cohort study. Cats (n = 50) with a single CPSS. Medical records of cats treated by surgical attenuation of a single CPSS between 2003 and 2017 were reviewed for signalment, surgical technique, preoperative management and postoperative clinical outcomes. Binary logistic regression was performed to investigate risk factors for occurrence of PANS and seizures. Congenital Portosystemic Shunts in 50 cats included 40 extrahepatic and 10 intrahepatic Shunts. Postattenuation neurological signs were recorded in 31 (62%) cats and graded as 1 in 10 cats, 2 in nine cats, and 3 in 12 cats. Postattenuation neurological signs included seizures in 11 cats. Five of 31 cats with PANS did not survive to discharge. No association was detected between PANS or seizures and the type of CPSS (intrahepatic or extrahepatic), degree of attenuation, age, or the use of perioperative levetiracetam or hepatic encephalopathy immediately preoperatively. Osmolality at a median 24 hours postoperatively was lower in cats with PANS (P < .049, Wald 3.867, odds ratio [Exp(B)] 0.855, CI 0.732-0.999). Postattenuation neurological signs are common complications in cats treated for CPSS. Preoperative levetiracetam did not prevent the occurrence of PANS or seizures. The only risk factor for PANS detected was lower postoperative Osmolality in cats with PANS at 24 hours. Postattenuation neurological signs including seizures occur frequently in cats undergoing surgical attenuation of a CPSS. Preoperative levetiracetam did not protect against the development of PANS. © 2020 The Authors. Veterinary Surgery published by Wiley Periodicals LLC. on behalf of American College of Veterinary Surgeons.
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long term serum bile acid concentrations in 51 dogs after complete extrahepatic Congenital Portosystemic Shunt ligation
Journal of Small Animal Practice, 2017Co-Authors: Poppy Bristow, Daniel J. Brockman, Michael Tivers, Rowena M A Packer, Victor Ortiz, Katie Newson, Victoria J LipscombAbstract:Objectives To report the long-term bile acid stimulation test results for dogs that have undergone complete suture ligation of a single Congenital extrahepatic Portosystemic Shunt. Materials and Methods Data were collected from the hospital records of all dogs that had undergone a complete suture ligation of a single Congenital extrahepatic Portosystemic Shunt. Owners were invited to return to the referral centre or their local veterinarian for repeat serum bile acid measurement. Dogs diagnosed with idiopathic epilepsy and undergoing bile acid stimulation tests were used as a comparison population. Results Fifty-one study dogs were included, with a mean follow-up time of 62 months. 48 dogs had no evidence of multiple acquired Shunts and a significant reduction in the pre- and post-prandial serum bile acid concentrations at long-term follow-up compared with pre-operative measurements. Pre- and post-prandial serum bile acids were statistically significantly greater for dogs that had undergone a full ligation (with no evidence of multiple acquired Shunts) at all time points compared to the control dogs (P<0·001 for all comparisons). Clinical Significance The results suggest that in dogs treated with complete suture ligation mild increases in serum bile acids are not clinically relevant if present in combination with no physical examination abnormalities, a normal body condition score and no relapse in clinical signs.
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RESEARCH ARTICLE Attenuation of Congenital Portosystemic Shunt Reduces Inflammation in Dogs
2016Co-Authors: Michael Tivers, Victoria J Lipscomb, Rajiv Jalan, Ian H, Adamg Gow, Richard J. MellanbyAbstract:Liver disease is a major cause of morbidity and mortality. One of the most significant compli-cations in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incom-pletely understood, which has resulted in the development of a wide range of experimental models. Congenital Portosystemic Shunt is one of the most common Congenital disorders di-agnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiol-ogy of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a Congenital Portosystemic Shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have dem-onstrated an important role for ammonia and inflammation in the development of hepatic en-cephalopathy in dogs with a Congenital Portosystemic Shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil
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Attenuation of Congenital Portosystemic Shunt reduces inflammation in dogs.
PloS one, 2015Co-Authors: Michael Tivers, Ian Handel, Adam Gow, Victoria J Lipscomb, Rajiv Jalan, Richard J. MellanbyAbstract:Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital Portosystemic Shunt is one of the most common Congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a Congenital Portosystemic Shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a Congenital Portosystemic Shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of Congenital Portosystemic Shunts in dogs. One hundred and forty dogs with a Congenital Portosystemic Shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical Congenital Portosystemic Shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of Congenital Portosystemic Shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder.
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Histopathological findings in the livers of cats with a Congenital Portosystemic Shunt before and after surgical attenuation
The Veterinary record, 2013Co-Authors: F. Swinbourne, Victoria J Lipscomb, Ken C. Smith, Michael TiversAbstract:Histopathological changes are reported in the livers of cats with Congenital Portosystemic Shunts (CPSS) before and after surgical attenuation. Medical records, portovenograms and liver biopsies from cats treated surgically for CPSS were reviewed. Biopsies were graded for histopathological features characteristic of CPSS. Of 40 cats with CPSS included in the study, all had portal vein hypoplasia and arteriolar hyperplasia at initial surgery, 20 (50 per cent) had hepatocyte swelling with microvesicular vacuolar change, 17 (42.5 per cent) had fibrosis, 12 (30 per cent) had hepatocyte swelling with macrovesicular vacuolar change, 8 (20 per cent) had biliary hyperplasia and 2 (5 per cent) had haemosiderin within Kupffer cells. Cats with macrovesicular vacuolar change were significantly older than cats without (P = 0.001), with median ages of 18.5 months and 8.5 months, respectively. Twenty-five cats had partial attenuation of the CPSS at initial surgery, and 16 of these had follow-up biopsy samples. There were no significant differences in the histopathological features of biopsies before and after partial attenuation. From first to second surgery, there was a significant improvement in intrahepatic vasculature on portovenography both before (P = 0.001) and after (P = 0.039) temporary complete attenuation. Following partial CPSS attenuation, there was no significant change in histopathological features despite an improvement in intrahepatic vasculature on portovenography.
Adam Gow - One of the best experts on this subject based on the ideXlab platform.
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Attenuation of Congenital Portosystemic Shunt reduces inflammation in dogs.
PloS one, 2015Co-Authors: Michael Tivers, Ian Handel, Adam Gow, Victoria J Lipscomb, Rajiv Jalan, Richard J. MellanbyAbstract:Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital Portosystemic Shunt is one of the most common Congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a Congenital Portosystemic Shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a Congenital Portosystemic Shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of Congenital Portosystemic Shunts in dogs. One hundred and forty dogs with a Congenital Portosystemic Shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical Congenital Portosystemic Shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of Congenital Portosystemic Shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder.
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Hepatic hepcidin gene expression in dogs with a Congenital Portosystemic Shunt.
Journal of veterinary internal medicine, 2014Co-Authors: P. E. Frowde, Adam Gow, Richard J. Mellanby, C. A. Burton, Roger Edwin Powell, Victoria Lipscomb, A K House, Michael TiversAbstract:Background Microcytic anemia is common in dogs with a Congenital Portosystemic Shunt (cPSS) and typically resolves after surgical attenuation of the anomalous vessel. However, the pathophysiology of the microcytic anemia remains poorly understood. Hepcidin has been a key role in controlling iron transport in both humans and animals and in mediating anemia of inflammatory disease in humans. The role of hepcidin in the development of microcytic anemia in dogs with a cPSS has not been examined. Hypothesis To determine whether hepatic hepcidin mRNA expression decreases, while red blood cell count (RBC) and mean corpuscular volume (MCV) increase in dogs after surgical attenuation of a cPSS. Animals Eighteen client-owned dogs with confirmed cPSS undergoing surgical attenuation. Method Prospective study. Red blood cell count (RBC) and mean corpuscular volume (MCV), together with hepatic gene expression of hepcidin, were measured in dogs before and after partial attenuation of a cPSS. Results There was a significant increase in both RBC (median pre 6.17 × 1012/L, median post 7.08 × 1012/L, P
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hepatic hepcidin gene expression in dogs with a Congenital Portosystemic Shunt
Journal of Veterinary Internal Medicine, 2014Co-Authors: P. E. Frowde, Adam Gow, Richard J. Mellanby, Victoria Lipscomb, A K House, C Burton, Roger Powell, Michael TiversAbstract:Background Microcytic anemia is common in dogs with a Congenital Portosystemic Shunt (cPSS) and typically resolves after surgical attenuation of the anomalous vessel. However, the pathophysiology of the microcytic anemia remains poorly understood. Hepcidin has been a key role in controlling iron transport in both humans and animals and in mediating anemia of inflammatory disease in humans. The role of hepcidin in the development of microcytic anemia in dogs with a cPSS has not been examined. Hypothesis To determine whether hepatic hepcidin mRNA expression decreases, while red blood cell count (RBC) and mean corpuscular volume (MCV) increase in dogs after surgical attenuation of a cPSS. Animals Eighteen client-owned dogs with confirmed cPSS undergoing surgical attenuation. Method Prospective study. Red blood cell count (RBC) and mean corpuscular volume (MCV), together with hepatic gene expression of hepcidin, were measured in dogs before and after partial attenuation of a cPSS. Results There was a significant increase in both RBC (median pre 6.17 × 1012/L, median post 7.08 × 1012/L, P < .001) and MCV (median pre 61.5fl, median post 65.5fl, P = .006) after partial surgical attenuation of the cPSS. Despite the increase in both measured red blood cell parameters, hepatic gene expression of hepcidin remained unchanged. Conclusions and Clinical Importance This study found no evidence that dysregulated production of hepcidin was associated with anemia in dogs with a cPSS.
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Plasma cytokine concentrations in dogs with a Congenital Portosystemic Shunt
Veterinary journal (London England : 1997), 2014Co-Authors: Scott Kilpatrick, Adam Gow, Rob Foale, Simon Tappin, Harvey Carruthers, Nicola Reed, Donald Yool, Samantha Woods, Ana Marques, Rajiv JalanAbstract:Congenital Portosystemic Shunts (cPSS) are a well-recognised vascular anomaly in dogs. Recent studies have shown an association between inflammation and hepatic encephalopathy (HE), which is a common clinical syndrome in dogs with a cPSS. Pro-inflammatory cytokines such as interleukin (IL)-6 and tumour necrosis factor (TNF)-α are frequently increased in the plasma of human patients with liver disease and have been implicated in the development of HE. In the current study, plasma concentrations of IL-2, IL-6, IL-8 and TNF-α were measured using a multiplex electrochemiluminescence immunoassay in 36 dogs with a cPSS and compared to 25 healthy dogs. There were no significant differences in plasma IL-2, IL-8 and TNF-α concentrations between the two groups; however, plasma concentrations of IL-6 were significantly higher in dogs with a cPSS compared to healthy dogs (P=0.02).
Haruo Shintaku - One of the best experts on this subject based on the ideXlab platform.
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Hepatic focal nodular hyperplasia with Congenital Portosystemic Shunt.
Pediatrics international : official journal of the Japan Pediatric Society, 2014Co-Authors: Yuki Cho, Taro Shimono, Haruo Shintaku, Hiroyasu Morikawa, Daisuke TokuharaAbstract:Hepatic focal nodular hyperplasia (FNH) is a rare benign tumor in children. Vascular anomalies have been identified as pathological features of FNH, but the etiology remains unclear. We describe a rare case including the time course of formation of hepatic FNH in response to Congenital Portosystemic Shunt (PSS). A 4-month-old girl was identified on newborn mass screening to have hypergalactosemia, but no inherited deficiencies in galactose-metabolizing enzymes were found. Ultrasonography and per-rectal portal scintigraphy showed intrahepatic PSS of the right lobe as a cause of the hypergalactosemia. At age 12 months, the patient had elevated hepatic enzymes and small hypoechoic hepatic lesions around the Shunt. On abdominal contrast-enhanced ultrasonography spoke-wheel sign and central stellate scar were seen, which are typical features of hepatic FNH without biopsy. Congenital intrahepatic PSS should be evaluated on abdominal contrast-enhanced ultrasonography and observed over time because of its potential to develop into hepatic FNH.
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Role of per-rectal portal scintigraphy in long-term follow-up of Congenital Portosystemic Shunt
Pediatric Research, 2014Co-Authors: Yuki Cho, Daisuke Tokuhara, Taro Shimono, Akira Yamamoto, Shigeaki Higashiyama, Kohei Kotani, Joji Kawabe, Yoshiyuki Okano, Susumu Shiomi, Haruo ShintakuAbstract:Background: Congenital Portosystemic Shunt (CPSS) has the potential to cause hepatic encephalopathy and thus needs long-term follow-up, but an effective follow-up method has not yet been established. We aimed to evaluate the importance of per-rectal portal scintigraphy (PRPS) for long-term follow-up of CPSS. Methods: We retrospectively examined Shunt severity time course in patients (median: 9.6 y, range: 5.2–16.6 y) with intrahepatic ( n = 3) or extrahepatic ( n = 3) CPSS by using blood tests, ultrasonography or computed tomography, and PRPS. Per-rectal portal Shunt index (cutoff: 10%) was calculated by PRPS. Results: PRPS demonstrated that the initial Shunt index was reduced in all intrahepatic cases (from 39.7 ± 9.8% (mean ± SD) to 14.6 ± 4.7%) and all extrahepatic cases (from 46.2 ± 10.9 to 27.5 ± 12.6%) during the follow-up period. However, ultrasonography and computed tomography disclosed different Shunt diameter time courses between intrahepatic and extrahepatic CPSSs. Initial Shunt diameter (5.8 ± 3.5 mm) reduced to 2.0 ± 0.3 mm in intrahepatic cases, but the initial diameter (6.3 ± 0.7 mm) increased to 10.6 ± 1.0 mm in extrahepatic cases. All patients had elevated serum total bile acid or ammonia levels at initial screening, but these blood parameters were insufficient to assess Shunt severity because the values fluctuate. Conclusion: PRPS can track changes in the Shunt severity of CPSS and is more reliable than ultrasonography and computed tomography in patients with extrahepatic CPSS.
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Role of per-rectal portal scintigraphy in long-term follow-up of Congenital Portosystemic Shunt.
Pediatric research, 2014Co-Authors: Yuki Cho, Daisuke Tokuhara, Taro Shimono, Akira Yamamoto, Shigeaki Higashiyama, Kohei Kotani, Joji Kawabe, Yoshiyuki Okano, Susumu Shiomi, Haruo ShintakuAbstract:Role of per-rectal portal scintigraphy in long-term follow-up of Congenital Portosystemic Shunt