Spontaneous splenorenal shunts in the absence of cirrhosis have rarely been reported as a cause hyperammonemia with encephalopathy. Several closure techniques of such lesions have been described. Here we report a case...Spontaneous splenorenal shunts in the absence of cirrhosis have rarely been reported as a cause hyperammonemia with encephalopathy. Several closure techniques of such lesions have been described. Here we report a case of a patient with no history of liver disease who developed significant confusion. After an extensive workup, he was found to have hyperammonemia and encephalopathy due to formation of a spontaneous splenorenal shunt. There was no evidence of cirrhosis on biopsy or imaging and no portal hypertension when directly measured. The shunt was 18 mm and too large for embolization so the segment of the splenic vein between the portal vein and the shunt was occluded using an Amplatzer plug. Thus, the superior mesenteric flow was directed entirely to the liver. After interventional radiology closure of the shunt using this technique there was complete resolution of symptoms.The case represents the first report of a successful closure of splenorenal shunt via percutaneous embolization of the splenic vein with an amplatzer plug using a common femoral vein approach.展开更多
AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats w...AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.展开更多
Ornithine transcarbamylase deficiency(OTCD) is an X-linked disorder,with an estimated prevalence of 1 per 80000 live births.Female patients with OTCD develop metabolic crises that are easily provoked by non-predictabl...Ornithine transcarbamylase deficiency(OTCD) is an X-linked disorder,with an estimated prevalence of 1 per 80000 live births.Female patients with OTCD develop metabolic crises that are easily provoked by non-predictable common disorders,such as genetic(private mutations and lyonization) and external factors;however,the outcomes of these conditions may differ.We resuscitated a female patient with OTCD from hyperammonemic crisis after she gave birth.Hyperammonemia after parturition in a female patient with OTCD can be fatal,and this type of hyperammonemia persists for an extended period of time.Here,we describe the cause and treatment of hyperammonemia in a female patient with OTCD after parturition.Once hyperammonemia crisis occurs after giving birth,it is difficult to improve the metabolic state.Therefore,it is important to perform an early intervention before hyperammonemia occurs in patients with OTCD or in carriers after parturition.展开更多
The clinical manifestations of hyperammonemia are usually easily identifiable to the clinician when associated with liver disease and lead to prompt diagnosis and treatment. However, hyperammonemia-induced encephalopa...The clinical manifestations of hyperammonemia are usually easily identifiable to the clinician when associated with liver disease and lead to prompt diagnosis and treatment. However, hyperammonemia-induced encephalopathy is rare in adults in the absence of overt liver disease, thus diagnosis is often delayed or missed leading to potentially life threatening complications. Without proper treatment, such patients can decompensate rapidly with poor outcomes including seizures, coma, and death. Early assessment of plasma ammonia levels in patients with normal hepatic function and characteristic symptoms of encephalopathy can lead to early intervention while investigating the underlying etiology. We describe a patient who presented with a 2-year progression of waxing and waning acute mental status changes after a Roux-en-Y gastric bypass surgery. He was found to have elevated ammonia level as well as orotic aciduria; results consistent with a urea cycle disorder. After consulting neurology as well as toxicology, he ultimately improved after dietary protein restriction, sodium benzoate and lactulose therapy. While rare, clinicians should have a high index of suspicion for late onset urea cycle disorders in symptomatic patients presenting with encephalopathy secondary to hyperammonemia.展开更多
Oxidative stress induced by a high ammonia concentration could modify protein expression in the brain. This study was undertaken in order to investigate the impact of hyperammonemia, caused by thioacetmide (TAA) in ra...Oxidative stress induced by a high ammonia concentration could modify protein expression in the brain. This study was undertaken in order to investigate the impact of hyperammonemia, caused by thioacetmide (TAA) in rats, on brain cortex protein expression using 2D-DIGE, and analyzing its role in the pathogenesis of HE. Hyperammonemia was induced with TAA. Ammonia and active oxidants were measured by L-glutamate dehydrogenase and dichlorodihydrofluorescein diacetate methods, respectively. Lipid peroxidation and protein oxidation biomarkers were also studied. Differential protein expression in the cortex of TAA- and control-rats was studied by 2D-DIGE. Image analysis was performed using the DeCyder? Software. Ammonia concentration in plasma and brain tissue was higher in TAA-rats compared to control-rats, 3.12 and 2.43 fold higher, respectively. Active oxidants production in TAA-rats was increased by 2.7 fold compared to control-rats. Measurements of MDA, HNE and carbonyl groups, biomarkers of lipid peroxidation and protein oxidation respectively, were found to be statistically significantly increased in TAA-rats compared to control-rats (3.16-, 2.44- and 1.95-fold, respectively), reflecting the presence of oxidative stress in the brain of TAA-rats. 2D-DIGE analysis of brain cortex protein allowed the detection of 2896 spots, however, image analysis showed no statistically significant differential protein expression between the proteins expressed in TAA- and control-rats. No statistical significant differential protein expression in the cortex of TAA-rats was observed, although oxidative stress biomarkers for lipid and proteins were higher in the brain of TAA-rats than in control-rats. These results support the idea that oxidative post-translational modifications are implicated in HE physiopathology.展开更多
BACKGROUND Ammonia is a normal constituent of body fluids and is found mainly through the formation of urea in the liver.Blood levels of ammonia must remain low as even slightly elevated concentrations(hyperammonemia)...BACKGROUND Ammonia is a normal constituent of body fluids and is found mainly through the formation of urea in the liver.Blood levels of ammonia must remain low as even slightly elevated concentrations(hyperammonemia)are toxic to the central nervous system.AIM To examine the relationship between the incidence of non-hepatic hyperammonemia(NHH)and the prognosis of patients who were admitted to the intensive care unit(ICU).METHODS This is a prospective,observational and single-center study.A total of 364 patients who were admitted to the ICU from November 2019 to February 2020 were initially enrolled.Changes in the levels of blood ammonia at the time of ICU admission and after ICU admission were continuously monitored.In addition,factors influencing the prognosis of NHH patients were analyzed.RESULTS A total of 204 patients who met the inclusion criteria were enrolled in this study,including 155 NHH patients and 44 severe-NHH patients.The incidence of NHH and severe-NHH was 75.98% and 21.57%,respectively.Patients with severe-NHH exhibited longer length of ICU stay and higher Acute Physiologic Assessment and Chronic Health Evaluation and Sequential Organ Failure Assessment scores compared to those with mild-NHH and non-NHH.Glasgow Coma Scale scores of patients with severe-NHH were than those of non-NHH patients.In addition,the mean and initial levels of ammonia in the blood might be helpful in predicting the prognosis of NHH.CONCLUSION High blood ammonia level is frequent among NHH patients admitted to the ICU,which is related to the clinical characteristics of patients.Furthermore,the level of blood ammonia may be helpful for prognosis prediction.展开更多
Chemotherapy with 5-fluorouracil (5 FU) has been widely used to treat advanced gastric cancer. Knowing the side effects is therefore important in order to better prevent them. Fluoropyrimidine-induced hyperammonemic e...Chemotherapy with 5-fluorouracil (5 FU) has been widely used to treat advanced gastric cancer. Knowing the side effects is therefore important in order to better prevent them. Fluoropyrimidine-induced hyperammonemic encephalopathy is a rare complication and characterized neurological status with elevated ammonia level without radiological abnormalities. We report the first case of 5 FU-induced hyperammonemic encephalopathy in women patients on induction chemotherapy for gastric cancer in Madagascar. His ammonia level (NH<sub>3</sub>) was 102 μmol/l. The patient recovered from his confusional state after two days of treatment with hyperhydration and vitamin therapy.展开更多
Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progre...Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progression and provide symptomatic improvement in patients with IEM.Each metabolic disorder is unique,with the missing enzyme or transporter protein causing substrate deficiency or toxic byproduct production.Knowledge about the distribution of deficient enzymes,the percentage of enzymes replaced by LT,and the extent of extrahepatic involvement helps anticipate and manage complications in the perioperative period.Most patients have multisystem involvement and can be on complex dietary regimens.Metabolic decompensation can be triggered due to the stress response to surgery,fasting and other unanticipated complications perioperatively.Thus,a multidisciplinary team’s input including those from metabolic specialists is essential to develop disease and patient-specific strategies for the perioperative management of these patients during LT.In this review,we outline the classification of IEM,indications for LT along with potential benefits,basic metabolic defects and their implications,details of extrahepatic involvement and perioperative management strategies for LT in children with some of the commonly presenting IEM,to assist anesthesiologists handling this cohort of patients.展开更多
Evidence suggests that the hyperammonemia （HA）-induced neuroinflammation and alterations in the serotonin （5-HT） system may contribute to cognitive decline and anxiety disorder during hepatic encephalopathy （HE）...Evidence suggests that the hyperammonemia （HA）-induced neuroinflammation and alterations in the serotonin （5-HT） system may contribute to cognitive decline and anxiety disorder during hepatic encephalopathy （HE）. Probiotics that maintain immune system homeostasis and regulate the 5-HT system may be potential treatment for HA-mediated neurological disorders in HE. In this study, we tested the efficacy of probiotic Lactobacillus helveticus strain NS8 in preventing cognitive decline and anxie- ty-like behavior in HA rats. Chronic HA was induced by intraperitoneal injection of ammonium acetate for four weeks in male Sprague-Dawley rats. HA rats were then given Lactobacillus helveticus strain NS8 （109 CFU mL 1） in drinking water as a dai- ly supplementation. The Morris water maze task assessed cognitive function, and the elevated plus maze test evaluated anxie- ty-like behavior. Neuroinflammation was assessed by measuring the inflammatory markers： inducible nitric oxide synthase, prostaglandin E2, and interleukin-1 13 in the brain. 5-HT system activity was evaluated by measuring 5-HT and its metabolite, 5-HIAA, and the 5-HT precursor, tryptophan. Probiotic treatment of HA rats significantly reduced the level of inflammatory markers, decreased 5-HT metabolism, restored cognitive function and improved anxiety-like behavior. These results indicate that probiotic L. helveticus strain NS8 is beneficial for the treatment of cognitive decline and anxiety-like behavior in HA rats.展开更多
Acute kidney injury(AKI)is common in patients with liver failure,and for a significant subset it is severe enough to require kidney replacement therapy(KRT).Patients with liver failure have distinct clinical character...Acute kidney injury(AKI)is common in patients with liver failure,and for a significant subset it is severe enough to require kidney replacement therapy(KRT).Patients with liver failure have distinct clinical characteristics(e.g.,cardiocirculatory dysfunction and a tendency to bleed)that mandate customization of their overall care including KRT.Herein,we provide an overview of AKI in liver failure,discuss the basic pathophysiology of hepatorenal syndrome,including the often-underemphasized role of the heart in its clinical manifestations,and the current therapies afforded to these patients.We also discuss the general aspects of KRT and how they apply to patients with liver failure(e.g.,preference for continuous renal replacement therapy and the need for regional,instead of systemic,anticoagulation).Moreover,we discuss hyperammonemia,an emerging non-renal indication of KRT in this patient population,and provide recommendations on how this therapy may be applied in this setting.展开更多
基金Supported by Department of Veterans Affairs,Veterans Health Administration,Office of Research and Development
文摘Spontaneous splenorenal shunts in the absence of cirrhosis have rarely been reported as a cause hyperammonemia with encephalopathy. Several closure techniques of such lesions have been described. Here we report a case of a patient with no history of liver disease who developed significant confusion. After an extensive workup, he was found to have hyperammonemia and encephalopathy due to formation of a spontaneous splenorenal shunt. There was no evidence of cirrhosis on biopsy or imaging and no portal hypertension when directly measured. The shunt was 18 mm and too large for embolization so the segment of the splenic vein between the portal vein and the shunt was occluded using an Amplatzer plug. Thus, the superior mesenteric flow was directed entirely to the liver. After interventional radiology closure of the shunt using this technique there was complete resolution of symptoms.The case represents the first report of a successful closure of splenorenal shunt via percutaneous embolization of the splenic vein with an amplatzer plug using a common femoral vein approach.
基金Supported by Grant #TB 56 from the University of Buenos Aires,Argentina
文摘AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.
基金Supported by A Grant-in-Aid for Guidelines and Lifetime Medical Support Systems for inborn errors of metabolism found by newborn screeninga Grant-in-Aid for the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and Development,AMED
文摘Ornithine transcarbamylase deficiency(OTCD) is an X-linked disorder,with an estimated prevalence of 1 per 80000 live births.Female patients with OTCD develop metabolic crises that are easily provoked by non-predictable common disorders,such as genetic(private mutations and lyonization) and external factors;however,the outcomes of these conditions may differ.We resuscitated a female patient with OTCD from hyperammonemic crisis after she gave birth.Hyperammonemia after parturition in a female patient with OTCD can be fatal,and this type of hyperammonemia persists for an extended period of time.Here,we describe the cause and treatment of hyperammonemia in a female patient with OTCD after parturition.Once hyperammonemia crisis occurs after giving birth,it is difficult to improve the metabolic state.Therefore,it is important to perform an early intervention before hyperammonemia occurs in patients with OTCD or in carriers after parturition.
文摘The clinical manifestations of hyperammonemia are usually easily identifiable to the clinician when associated with liver disease and lead to prompt diagnosis and treatment. However, hyperammonemia-induced encephalopathy is rare in adults in the absence of overt liver disease, thus diagnosis is often delayed or missed leading to potentially life threatening complications. Without proper treatment, such patients can decompensate rapidly with poor outcomes including seizures, coma, and death. Early assessment of plasma ammonia levels in patients with normal hepatic function and characteristic symptoms of encephalopathy can lead to early intervention while investigating the underlying etiology. We describe a patient who presented with a 2-year progression of waxing and waning acute mental status changes after a Roux-en-Y gastric bypass surgery. He was found to have elevated ammonia level as well as orotic aciduria; results consistent with a urea cycle disorder. After consulting neurology as well as toxicology, he ultimately improved after dietary protein restriction, sodium benzoate and lactulose therapy. While rare, clinicians should have a high index of suspicion for late onset urea cycle disorders in symptomatic patients presenting with encephalopathy secondary to hyperammonemia.
文摘Oxidative stress induced by a high ammonia concentration could modify protein expression in the brain. This study was undertaken in order to investigate the impact of hyperammonemia, caused by thioacetmide (TAA) in rats, on brain cortex protein expression using 2D-DIGE, and analyzing its role in the pathogenesis of HE. Hyperammonemia was induced with TAA. Ammonia and active oxidants were measured by L-glutamate dehydrogenase and dichlorodihydrofluorescein diacetate methods, respectively. Lipid peroxidation and protein oxidation biomarkers were also studied. Differential protein expression in the cortex of TAA- and control-rats was studied by 2D-DIGE. Image analysis was performed using the DeCyder? Software. Ammonia concentration in plasma and brain tissue was higher in TAA-rats compared to control-rats, 3.12 and 2.43 fold higher, respectively. Active oxidants production in TAA-rats was increased by 2.7 fold compared to control-rats. Measurements of MDA, HNE and carbonyl groups, biomarkers of lipid peroxidation and protein oxidation respectively, were found to be statistically significantly increased in TAA-rats compared to control-rats (3.16-, 2.44- and 1.95-fold, respectively), reflecting the presence of oxidative stress in the brain of TAA-rats. 2D-DIGE analysis of brain cortex protein allowed the detection of 2896 spots, however, image analysis showed no statistically significant differential protein expression between the proteins expressed in TAA- and control-rats. No statistical significant differential protein expression in the cortex of TAA-rats was observed, although oxidative stress biomarkers for lipid and proteins were higher in the brain of TAA-rats than in control-rats. These results support the idea that oxidative post-translational modifications are implicated in HE physiopathology.
基金Supported by Scientific research project of Heilongjiang Health and Family Planning Commission,No.2019045.
文摘BACKGROUND Ammonia is a normal constituent of body fluids and is found mainly through the formation of urea in the liver.Blood levels of ammonia must remain low as even slightly elevated concentrations(hyperammonemia)are toxic to the central nervous system.AIM To examine the relationship between the incidence of non-hepatic hyperammonemia(NHH)and the prognosis of patients who were admitted to the intensive care unit(ICU).METHODS This is a prospective,observational and single-center study.A total of 364 patients who were admitted to the ICU from November 2019 to February 2020 were initially enrolled.Changes in the levels of blood ammonia at the time of ICU admission and after ICU admission were continuously monitored.In addition,factors influencing the prognosis of NHH patients were analyzed.RESULTS A total of 204 patients who met the inclusion criteria were enrolled in this study,including 155 NHH patients and 44 severe-NHH patients.The incidence of NHH and severe-NHH was 75.98% and 21.57%,respectively.Patients with severe-NHH exhibited longer length of ICU stay and higher Acute Physiologic Assessment and Chronic Health Evaluation and Sequential Organ Failure Assessment scores compared to those with mild-NHH and non-NHH.Glasgow Coma Scale scores of patients with severe-NHH were than those of non-NHH patients.In addition,the mean and initial levels of ammonia in the blood might be helpful in predicting the prognosis of NHH.CONCLUSION High blood ammonia level is frequent among NHH patients admitted to the ICU,which is related to the clinical characteristics of patients.Furthermore,the level of blood ammonia may be helpful for prognosis prediction.
文摘Chemotherapy with 5-fluorouracil (5 FU) has been widely used to treat advanced gastric cancer. Knowing the side effects is therefore important in order to better prevent them. Fluoropyrimidine-induced hyperammonemic encephalopathy is a rare complication and characterized neurological status with elevated ammonia level without radiological abnormalities. We report the first case of 5 FU-induced hyperammonemic encephalopathy in women patients on induction chemotherapy for gastric cancer in Madagascar. His ammonia level (NH<sub>3</sub>) was 102 μmol/l. The patient recovered from his confusional state after two days of treatment with hyperhydration and vitamin therapy.
文摘Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progression and provide symptomatic improvement in patients with IEM.Each metabolic disorder is unique,with the missing enzyme or transporter protein causing substrate deficiency or toxic byproduct production.Knowledge about the distribution of deficient enzymes,the percentage of enzymes replaced by LT,and the extent of extrahepatic involvement helps anticipate and manage complications in the perioperative period.Most patients have multisystem involvement and can be on complex dietary regimens.Metabolic decompensation can be triggered due to the stress response to surgery,fasting and other unanticipated complications perioperatively.Thus,a multidisciplinary team’s input including those from metabolic specialists is essential to develop disease and patient-specific strategies for the perioperative management of these patients during LT.In this review,we outline the classification of IEM,indications for LT along with potential benefits,basic metabolic defects and their implications,details of extrahepatic involvement and perioperative management strategies for LT in children with some of the commonly presenting IEM,to assist anesthesiologists handling this cohort of patients.
基金supported by NS Bio JapanNS Health Biotechnology Beijing
文摘Evidence suggests that the hyperammonemia （HA）-induced neuroinflammation and alterations in the serotonin （5-HT） system may contribute to cognitive decline and anxiety disorder during hepatic encephalopathy （HE）. Probiotics that maintain immune system homeostasis and regulate the 5-HT system may be potential treatment for HA-mediated neurological disorders in HE. In this study, we tested the efficacy of probiotic Lactobacillus helveticus strain NS8 in preventing cognitive decline and anxie- ty-like behavior in HA rats. Chronic HA was induced by intraperitoneal injection of ammonium acetate for four weeks in male Sprague-Dawley rats. HA rats were then given Lactobacillus helveticus strain NS8 （109 CFU mL 1） in drinking water as a dai- ly supplementation. The Morris water maze task assessed cognitive function, and the elevated plus maze test evaluated anxie- ty-like behavior. Neuroinflammation was assessed by measuring the inflammatory markers： inducible nitric oxide synthase, prostaglandin E2, and interleukin-1 13 in the brain. 5-HT system activity was evaluated by measuring 5-HT and its metabolite, 5-HIAA, and the 5-HT precursor, tryptophan. Probiotic treatment of HA rats significantly reduced the level of inflammatory markers, decreased 5-HT metabolism, restored cognitive function and improved anxiety-like behavior. These results indicate that probiotic L. helveticus strain NS8 is beneficial for the treatment of cognitive decline and anxiety-like behavior in HA rats.
文摘Acute kidney injury(AKI)is common in patients with liver failure,and for a significant subset it is severe enough to require kidney replacement therapy(KRT).Patients with liver failure have distinct clinical characteristics(e.g.,cardiocirculatory dysfunction and a tendency to bleed)that mandate customization of their overall care including KRT.Herein,we provide an overview of AKI in liver failure,discuss the basic pathophysiology of hepatorenal syndrome,including the often-underemphasized role of the heart in its clinical manifestations,and the current therapies afforded to these patients.We also discuss the general aspects of KRT and how they apply to patients with liver failure(e.g.,preference for continuous renal replacement therapy and the need for regional,instead of systemic,anticoagulation).Moreover,we discuss hyperammonemia,an emerging non-renal indication of KRT in this patient population,and provide recommendations on how this therapy may be applied in this setting.
