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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propionic acidemia is an inherited disorder of organic acid metabolism characterized by a spectrum of clinical and biochemical findings. The usual presentation is life-threatening ketoacidosis and hyperammonemia. In this report we present a neonate with propionic acidemia presenting with prominent neurologic problems without ketoacidosis. The patient had a serum ammonia level of 3,500 microg/dl which was effectively lowered to normal values in 48 hours by peritoneal dialysis, with remarkable improvement in neurologic status. However, she developed Candida albicans peritonitis, and sepsis and died of cardiorespiratory failure. Infants who have an early onset propionic acidemia have a high mortality and morbidity rate. In conclusion, propionic acidemia should be in the differential diagnosis of patients with neurologic symptoms and hyperammonemia with or without acidosis.
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PMID:Neonatal onset propionic acidemia without acidosis: a case report. 1245 12

The liver, the largest organ in the body, is critical to a number of key metabolic functions. Its also plays an important role in removing the waste products of metabolism (particularly ammonia) and in detoxifying drugs and other substances such as endogenous hormones and steroid compounds. In addition, the liver plays a major role in the production of clotting factors, plasma proteins, bile salts, and bilirubin. Many neonates display signs of hepatic dysfunction such as hyperbilirubinemia, hepatomegaly, or elevated liver enzymes. These often occur secondary to systemic illness, such as sepsis or hypoxic injury, or following the use of drugs or parenteral nutrition to treat other problems. Although rare, primary liver disease does occur in neonates and must be recognized promptly, with treatment initiated in a timely manner to prevent unnecessary sequelae. This article, the third in a series on the liver, examines causes of liver dysfunction in neonates, beginning with an overview of jaundice and hepatomegaly and moving to a discussion of specific diseases.
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PMID:The neonatal liver: Part III: Pathophysiology of liver dysfunction. 1279 4

Acute liver failure is a rare and life-threatening clinical syndrome following severe hepatic injury. Depending on the rapidity of its development, two distinct complications contribute to a high mortality: in hyperacute liver failure, rapid development of massive hepatic necrosis and apoptosis gives rise to severe hyperammonemia, hepatic encephalopathy and life-threatening cerebral edema. The high risk of cerebral herniation requires early listing for emergency liver transplantation. Patients with hyperacute liver failure surviving the initial episode of cerebral edema have a substantial potential for hepatic recovery. If progressive hepatic failure develops more slowly, astrocytic osmoregulation prevents cerebral herniation in most instances. Unfortunately, these patients have a small potential of hepatic regeneration and transplantation should be performed before renal failure, sepsis or multiorgan failure emerge. Experimental treatment methods including detoxification by artificial or bioartificial liver support or by stimulating hepatic regeneration are currently evaluated. Recognition of ammonia toxicity has stimulated the search for early ammonia-lowering strategies and strongly renewed the interest in dialytic therapies. Anti-apoptotic interventions are among the most promising pharmacological options for the near future.
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PMID:Acute liver failure. 1500 14

Glutamine synthetase (GS) in the liver is restricted to a small perivenous hepatocyte population and plays an important role in the scavenging of ammonia that has escaped the periportal urea-synthesizing compartment. We examined the effect of a single intraperitoneal injection of lipopolysaccharide (LPS) in vivo on glutamine synthesis in rat liver. LPS injection induced expression of inducible nitric oxide synthase, which was maximal after 6 to 12 hours but returned toward control levels within 24 hours. Twenty-four hours after LPS injection, an approximately fivefold increase in tyrosine-nitrated proteins in liver was found, and GS protein expression was decreased by approximately 20%, whereas GS activity was lowered by 40% to 50%. GS was found to be tyrosine-nitrated in response to LPS, and immunodepletion of tyrosine-nitrated proteins decreased GS protein by approximately 50% but had no effect on GS activity. Together with the finding via mass spectrometry that peroxynitrite-induced inactivation of purified GS is associated with nitration of the active site tyrosine residue, our data suggest that tyrosine nitration critically contributes to inactivation of the enzyme. In line with GS inactivation, glutamine synthesis from ammonia (0.3 mmol/L) in perfused livers from 24-hour LPS-treated rats was decreased by approximately 50%, whereas urea synthesis was not significantly affected. In conclusion, LPS impairs hepatic ammonia detoxification by both downregulation of GS and its inactivation because of tyrosine nitration. The resulting defect of perivenous scavenger cell function with regard to ammonia elimination may contribute to sepsis-induced development of hyperammonemia in patients who have cirrhosis.
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PMID:Lipopolysaccharide-induced tyrosine nitration and inactivation of hepatic glutamine synthetase in the rat. 1584 46

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, which develops in patients with acute or chronic liver failure. It is widely accepted to be due to impairment of hepatic clearance of toxic products from the gut such as ammonia. Accumulation of ammonia induces a glutamate neurotoxicity leading to an increased tone of the gamma-aminobutyric acid A (GABA-A) receptor system in the brain which results in HE. Factors either increasing the ammonia levels (protein load, constipation, sepsis, or gastrointestinal bleeding) or potentiating the functional activity of the GABAergic system [natural benzodiazepine-like compounds (NBZDs) or exogenous benzodiazepines] may act as precipitating factors of HE. NBZDs are present in trace amounts in the blood of normal subjects and have been found to be increased in the blood of patients with liver cirrhosis, with or without HE. These compounds may derive either from the diet since they have been found in plants, vegetables and animals or from gut bacteria. The observation that intestinal bacterial flora is involved in the production of both primary agent of HE (ammonia) and precipitating factors (NBZDs) suggests that the use of nonabsorbable antibiotics such as rifaximin may be useful in preventing episodes of HE in patients with liver cirrhosis.
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PMID:Management of hepatic encephalopathy: role of rifaximin. 1585 52

The molecular adsorbents recirculating system (MARS) is a form of artificial extracorporeal liver support which has the potential to remove substantial quantities of albumin-bound toxins postulated to contribute to the pathogenesis of liver cell damage, hemodynamic instability and multi-organ failure in patients with acute liver failure and acute-on-chronic liver failure (AoCLF). We assessed the efficacy of MARS therapy in a cohort of patients with severe liver damage unresponsive to intensive medical therapy. MARS therapy was instituted late in the clinical course of six patients with severely impaired liver function refractory to intensive medical therapy, including four with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre-existing chronic liver disease. Outcome measures included markers of hemodynamic stability, renal function, serum bilirubin and bile acid levels, arterial ammonia levels, the arterial ketone body (acetoacetate/beta-hydroxybutyrate) ratio, hepatic encephalopathy grade and the plasma disappearance rate of indocyanine green. The rates of discharge from the intensive care unit and in-hospital mortality were determined. Our findings suggest that MARS treatment might be associated with some clinical efficacy even in patients with advanced multi-organ dysfunction occurring in the setting of severe liver damage and in whom treatment is instituted late in the clinical course. However, the overall survival rate (1/6; 17%) was poor. More data obtained from larger cohorts of patients enrolled in randomized controlled studies will be required in order to identify categories of liver failure patients who might benefit most from MARS treatment and to ascertain the most appropriate timing of intervention.
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PMID:An Australian experience with the molecular adsorbents recirculating system (Mars). 2245 3

Previous reports have attributed a stimulating action on hepatic gluconeogenesis to tumour necrosis factor alpha (TNFalpha) administered to rats at high doses (250 mug/kg). However, in adjuvant-induced arthritic rats, which present TNFalpha and other interleukins in the circulation, hepatic gluconeogenesis is diminished. The same occurs in some types of experimental cancer models as, for example, rats bearing the Walker-256 tumour. The present work represents an attempt of reproducing in rats gluconeogenesis inhibition by interleukins using low instead of high doses of both TNFalpha and interleukin 1beta (IL1beta). TNFalpha and IL1beta at doses of up to 10 mug/kg were given endovenously to rats and, after six hours, gluconeogenesis from alanine and several related parameters were evaluated in the isolated haemoglobin-free perfused rat liver. Livers from rats injected with TNFalpha and IL1beta, either alone or in combination, presented diminished gluconeogenesis. The degrees of inhibition caused by TNFalpha+IL1beta, TNFalpha and IL1beta were, respectively, 48.5, 38.8 and 30.4%. TNFalpha also diminished oxygen uptake. No action on urea and ammonia production was found. Possibly, both TNFalpha and IL1beta contribute to the decreased rates of hepatic gluconeogenesis that were found in rats with arthritis, sepsis and some kinds of cancer, but not to the decreased rates of ureagenesis.
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PMID:Low doses of tumour necrosis factor alpha and interleukin 1beta diminish hepatic gluconeogenesis from alanine in vivo. 1707 83

We report the first successful use of hepatocyte transplantation as a bridge to subsequent auxiliary partial orthotopic liver transplantation (APOLT) in a child antenatally diagnosed with severe ornithine transcarbamylase (OTC) deficiency. A total of 1.74 x 10(9) fresh and cryopreserved hepatocytes were administered intraportally into the liver over a period of 6 months. Immunosuppression was with tacrolimus and prednisolone. A sustained decrease in ammonia levels and a gradual increase in serum urea were observed except during episodes of sepsis in the first 6 months of life. The patient was able to tolerate a normal protein intake and presented a normal growth and neurological development. APOLT was successfully performed at 7 months of age. We conclude that hepatocyte transplantation can be used in conjunction with APOLT as an effective treatment for severe OTC-deficient patients, improving neurodevelopmental outcomes.
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PMID:Hepatocyte transplantation followed by auxiliary liver transplantation--a novel treatment for ornithine transcarbamylase deficiency. 1821 11

Inborn errors of metabolism (IEM) are an important cause of acute illness in newborns. Presentation may mimic common neonatal conditions such as sepsis. Prompt detection requires a high index of suspicion and the early measurement of biochemical markers such as blood ammonia. Diagnosis is important not only for treatment but also for genetic counselling. Guidelines for diagnosis and early management of IEM presenting in the neonatal period are described.
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PMID:Approach to inborn errors of metabolism presenting in the neonate. 1837 97

Technological advances in gear and fishing practices have driven the global expansion of the American lobster live seafood market. These changes have had a positive effect on the lobster industry by increasing capture efficiency. However, it is unknown what effect these improved methods will have on the post-capture fitness and survival of lobsters. This project utilized a repeated measures design to compare the physiological changes that occur in lobsters over time as the result of differences in depth, hauling rate, and storage methodology. The results indicate that lobsters destined for long distance transport or temporary storage in pounds undergo physiological disturbance as part of the capture process. These changes are significant over time for total hemocyte counts, crustacean hyperglycemic hormone, L-lactate, ammonia, and glucose. Repeated measures multivariate analysis of variance (MANOVA) for glucose indicates a significant interaction between depth and storage methodology over time for non-survivors. A Gram-negative bacterium, Photobacterium indicum, was identified in pure culture from hemolymph samples of 100% of weak lobsters. Histopathology revealed the presence of Gram-negative bacteria throughout the tissues with evidence of antemortem edema and necrosis suggestive of septicemia. On the basis of these findings, we recommend to the lobster industry that if a reduction in depth and hauling rate is not economically feasible, fishermen should take particular care in handling lobsters and provide them with a recovery period in recirculating seawater prior to land transport. The ecological role of P. indicum is not fully defined at this time. However, it may be an emerging opportunistic pathogen of stressed lobsters. Judicious preemptive antibiotic therapy may be necessary to reduce mortality in susceptible lobsters destined for high-density holding facilities.
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PMID:Factors affecting post-capture survivability of lobster Homarus americanus. 2066 72


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