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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino acid solution, Aminofusin hepar, was evaluated for treatment of hepatic encephalopathy and for parenteral nutrition of patients with liver cirrhosis in correlation to changes in amino acid levels. In contrast to amino acid solutions used for the parenteral nutrition of patients without liver disease, this solution contains an increased proportion of branch chained amino acids and of arginine and ornithine, and a reduced proportion of phenylalanine, methionine, glycine and threonine. The changes in the plasma amino acid levels after infusion of this solution were measured in 4 cirrhotics. The concentration of leucine, isoleucine, valine, ornithine and arginine increased markedly, whereas phenylalanine, methionine, tyrosine, glycine and threonine decreased. The ammonia level in venous blood increased slightly. 4 cirrhotics with encephalopathy were treated for 7 days. In 3 of them the neuropsychiatric symptoms were completely reversed, whereas in the remaining 1 no clinical improvement was achieved in spite of normalization of the plasma aminogramm. In this patient a constant rise of blood ammonia was noted. The indications for special amino acid solutions in liver diseases are discussed.
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PMID:[Parenteral feeding of patients with liver cirrhosis with hepatic encephalopathy]. 677 52

Hepatic-Aid is purported to ameliorate encephalopathy and promote positive nitrogen balance in protein-intolerant, cirrhotic patients by correcting their imbalanced amino acid profile. This study evaluated Hepatic-Acid by comparing a 50-g Casein diet with an identical diet with 20-g Casein/30-g Hepatic-Aid per day in a cross-over study. Four patients with biopsy-proven stable cirrhosis, encephalopathy, and under-nutrition were studied. Each study period included three days of equilibration and eight days of metabolic balance, with the following measured at baseline and on balance days 5 and 8: routine biochemistry, fasting ammonia, psychometric tests, EEG, and plasma amino acid profiles. There was no significant change in clinical status, routine biochemistry, fasting ammonia, psychometrics or EEG between the two study periods. Mean (+/-SD) nitrogen balance on the Casein diet at 1.5 +/- 1.5 g/day was not significantly different from that on the Hepatic-Aid diet at 1.5 +/- 1.2 g/day. Plasma amino acid profiles showed a significant fall (p less than 0.05) in fasting and intraprandial tyrosine (tyr) and phenylalanine (phe) on Hepatic-Aid, but only intraprandial leucine (leu), isoleucine (ile), and valine (val) were significantly increased (p less than 0.05) on Hepatic-Aid. The ratio leu + ile + val to tyr + phe was significantly increased (p less than 0.05) on Hepatic-Aid. It is concluded that Hepatic-Aid, as given in this study, maintains N balance similar to Casein, alters the amino acid profile towards normal, but does not ameliorate encephalopathy.
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PMID:Comparison of the effects of Hepatic-Aid and a Casein modular diet on encephalopathy, plasma amino acids, and nitrogen balance in cirrhotic patients. 683 Mar 37

1. Intravenous infusions of L-valine (600 mumol/min), L-isoleucine (150 mumol/min), L-leucine (300 mumol/min) and a mixture of the three branched-chain amino acids (70% L-leucine, 20% L-valine, 10% L-isoleucine; 270 mumol/min) were given to four groups of healthy volunteer subjects. Whole-blood concentrations of amino acids and glucose and serum insulin were measured before and during the infusions. 2. Valine and isoleucine infusions resulted in twelve- and six-fold increases in the respective amino acid. During valine infusion, tyrosine was the only amino acid for which a decrease in concentration was seen (25%, P less than 0.05). With isoleucine administration, no significant changes were found. In contrast, leucine infusion (during which the leucine concentration rose about sixfold) was accompanied by significant decreases in tyrosine (35%), phenylalanine (35%), methionine (50%), valine (40%) and isoleucine (55%). The arterial glucose concentration fell slightly (5%) and the insulin concentration increased 20% during leucine infusion. 3. Infusion of the mixture of the three branched-chain amino acids resulted in marked decreases in tyrosine (50%), phenylalanine (50%) and methionine (35%). The decreased amino acid levels remained low for 2 h after the end of the infusion. 4. The present findings demonstrate that intravenous infusion of leucine (not infusion of valine or isoleucine) results in marked reductions in the concentrations of the aromatic amino acids and methionine. Infusion of a mixture of the three branched-chain amino acids gives results similar to those obtained with leucine infusion alone. Thus a mixed branched-chain amino acid solution with leucine as its main constituent seems to be the best alternative in the treatment of patients with hepatic cirrhosis and encephalopathy.
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PMID:A comparison of the effects of intravenous infusion of individual branched-chain amino acids on blood amino acid levels in man. 701 2

Previous uncontrolled studies indicated a positive effect of keto analogs of amino acids on plasma ammonia in patients with cirrhosis of the liver and on portal-systemic encephalopathy. In the present double-blind study the influence of keto analogs of the branched chain amino acids valine, leucine and isoleucine on plasma ammonia and encephalopathy was investigated in 12 patients with cirrhosis of the liver and surgical portal systemic shunts. In addition to the usual therapy with lactulose and protein restriction (40 g protein/day) all patients received 15.24 g keto analogs and placebo orally over 4 weeks in a crossover regimen. In contrast to uncontrolled studies, plasma ammonia, which was elevated in all patients before the beginning of the study, was not significantly changed. In addition plasma amino acids, electroencephalogram, number connection test, clinical state and laboratory tests were not influenced by the therapy with keto analogs.
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PMID:Oral keto analogs of branched-chain amino acids in hyperammonemia in patients with cirrhosis of the liver. A double-blind crossover study. 712 54

Lower fractional concentrations of branched-chain amino acids were found in trauma-septic patients who did not survive than in those who survived (p values less than or equal to 0.046 to 0.001). A liver dysfunction scale was constructed on the basis of the levels of plasma bilirubin, albumin, SGOT, prothrombin time, and neurologic encephalopathy. Increased liver dysfunction was associated with reduced plasma fractional branched-chain amino acids for all branched-chain amino acids in both the surviving and nonsurviving patients except for valine in the nonsurviving group. This decrease was statistically significant (p less than or equal to 0.041 to 0.001) for leucine and isoleucine in the nonsurvivors and for valine in the survivors. The infusion of amino acids was associated with a decrease in the fractional concentrations in the nonsurvivors for leucine while the fractional concentrations of isoleucine in the nonsurvivors and isoleucine and valine in the survivors rose. The statistically significant changes (p less than 0.018 to 0.001) were for leucine in the nonsurvivors and isoleucine and valine in the survivors. When the liver dysfunction and amino acid infusion related changes are taken in;to account there were no significant differences in the fractional branched-chain concentrations between survivors and nonsurvivors. Liver dysfunction and low fractional branched-chain amino acids were linked in magnitude in a way that is consistent with the low branched-chain amino acids producing the liver dysfunction.
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PMID:Multiple systems organ failure: VII. Reduction in plasma branched-chain amino acids--correlations with liver failure and amino acid infusion. 729 66

Five infants from 3 families, one Egyptian, two Yemeni, are described with a progressive encephalopathy, four of whom have been studied in detail. All patients showed vascular lesions of the skin, characterized by waxing and waning petechiae and ecchymoses. Acrocyanosis was present in three patients. All patients showed retinal lesions characterized by tortuous veins. Protracted diarrhea was not a consistent finding, although they had metabolic crisis in association with diarrhea. They did not show failure to thrive. The neurologic symptoms were indicative of a progressive pyramidal tract disease. Three patients died following sudden emergence of severe basal ganglia, putaminal and head of caudate lesions. In one patient the CT changes in brain were suggestive of infarction. The patients who died manifested pulmonary congestion, or wet lung, and respiratory difficulties during the terminal stage of the disease. In all patients before and during the terminal event, mild-to-moderate hematuria, and in two RBC in CSF, was observed. In one patient there was mild hemoperitoneum at the terminal event. The urine organic acids indicated increased excretion of ethylmalonic, methylsuccinic, glutaric, and adipic acids. The patients invariably showed lactic acidosis, but no ketosis, during and in between the acidotic attacks of the disease. The acylcarnitine profile in blood of two patients showed a pronounced increase in C4 and C5 carnitine esters. In three patients, biopsies from petechiae indicated absence of an immune event, showing only fresh hemorrhage. An immunologic study in one patient was normal for the suppressor:cytotoxic lymphocyte ratio and concentration of interleukin-2 receptor during and in between hemorrhagic attacks. The cytochrome c oxidase activity in fibroblasts was normal. The rate of oxidation of glucose, leucine, isoleucine, valine, propionate and butyrate by fibroblasts was normal. The disease is not responsive to treatment with riboflavin, ascorbic acid, vitamin E, glycine, or carnitine. One patient remained stable on prolonged large doses of methylprednisolone. The biochemical defect leading to ethylmalonic aciduria in this disease remains unknown.
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PMID:Ethylmalonic aciduria: an organic acidemia with CNS involvement and vasculopathy. 772 76

Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative disorder characterized by the accumulation of aggregates of a cellular protein, PrP, in the brain. In both human and animals, genetic alterations to the gene encoding PrP (PRNP in human) modulate susceptibility to CJD. The recent epidemic of bovine spongi-form encephalopathy in the UK has raised the possibility of transmission from animal produce to humans. To provide a baseline against which to assess possible risk factors, we have determined the frequencies of predisposing mutations and allelic variants in PRNP and their relative contributions to disease. Systematic PRNP genotype analysis was performed on suspected CJD cases referred to the National Surveillance Unit in the UK over the period 1990-1993. Inspection of 120 candidate cases revealed 67 patients with definite and probable CJD, based on clinical and neuropathological criteria. No PRNP mutations were detected in any of the remaining 53 patients assessed as "non-CJD". A disease-associated mutation in the PRNP gene was identified in nine (13.4%) definite and probable cases of CJD, a reliable estimate of the incidence of PRNP-related inherited CJD based on a prospective epidemiological series. Within the group of sporadic CJD patients (lacking PRNP mutations), we confirmed that the genotype distribution with respect to the common methionine/valine (Met/Val) polymorphism at codon 129 within PRNP was significantly different from the normal Caucasian population. The incidence of Met homozygosity at this site was more than doubled and correlated with increased susceptibility to the development of sporadic CJD. Unlike other recent studies, Val homozygosity was also confirmed to be a significant risk factor in sporadic CJD, with the relative risks for the three genotypes Met/Met: Val/Val:Met/Val being 11:4:1.
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PMID:Genetic basis of Creutzfeldt-Jakob disease in the United Kingdom: a systematic analysis of predisposing mutations and allelic variation in the PRNP gene. 870 91

We describe a patient with the mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) phenotype in whom initial investigations in skeletal muscle failed to show any histochemical or biochemical defect. Subsequent analysis of the mitochondrial genome identified a new heteroplasmic mutation in the valine transfer RNA gene, the first described in this region.
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PMID:MELAS associated with a mutation in the valine transfer RNA gene of mitochondrial DNA. 879 38

Previous reports based on studies in brain tissue from humans and experimental animals suggest that aromatic amino acids (AAAs) and branched-chain amino acids (BCAA's) accumulate in brain in acute liver failure. In order to assess these changes in relation to the severity of neurological impairment and to the degree of hyperammonemia, AAAs and BCAAs were measured in vivo by cerebral microdialysis in frontal cortex of rats at various stages during the development of hepatic encephalopathy due to acute liver failure resulting from portacaval anastomosis followed by hepatic artery ligation. Extracellular brain concentrations of AAAs and of valine and leucine were elevated 2 to 4-fold following hepatic devascularization and these increases were significantly correlated to arterial ammonia concentration (r= 0.71-0.84, p<0.05). Extracellular concentrations of tyrosine paralleled the deterioration of neurological status in acute liver failure rats. In view of their role as precursors of monoamine neurotransmitters, ammonia-induced alterations of intracellular/extracellular brain concentration ratios for AAAs could account for altered neuronal excitability and contribute to the encephalopathy characteristic of acute liver failure.
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PMID:Selective increases of extracellular brain concentrations of aromatic and branched-chain amino acids in relation to deterioration of neurological status in acute (ischemic) liver failure. 947 99

Numerous studies suggest that modifications in concentrations of both excitatory and inhibitory amino acids are implicated in the pathophysiology of portal-systemic encephalopathy (PSE), a neuropsychiatric disorder associated with chronic liver disease in humans. In this study, amino acid levels were measured by High Performance Liquid Chromatography (HPLC) in Cerebrospinal Fluid (CSF) of 10 dogs (age range: 3 mo.- 3 yr 4 mo.) exhibiting a congenital portal-systemic shunt, either intra or extra-hepatic, and 8 age-matched control dogs who showed no signs of hepatic or neurologic disorders. Dogs with congenital shunts manifested signs of encephalopathy such as disorientation, head pressing, vocalization, depression, seizures and coma. CSF from dogs with congenital shunts contained significantly increased amounts of glutamate (2 to 3-fold increase, p<0.01), glutamine (6-fold increase, p<0.05) and aromatic amino acids (phenylalanine, tyrosine and tryptophan) compared to CSF of control dogs. Concentrations of GABA and branched chain amino acids (valine, leucine, isoleucine) were within normal limits. Modifications of brain glutamate (an excitatory amino acid) as well as tryptophan (the precursor of serotonin) could contribute to the neurological syndrome characteristic of congenital PSE in dogs.
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PMID:Selective alterations of cerebrospinal fluid amino acids in dogs with congenital portosystemic shunts. 947 3


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