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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper documents dose-dependent effects of ornithine aspartate (OA) on postprandial hyperammonemia and plasma amino acids. Ten patients with cirrhosis were randomized to undergo 1 out of 4 infusion series. Each series consisted of four 8-h infusions (09:00 h-17:00 h), with placebo (NaCl), 5 g, 20 g or 40 g of OA being administered on separate days in varying sequences. This 4-fold crossover design was double-blind. On infusion days, patients received 2 oral protein loads (0.25 g/kg at 09:00 h and 0.5 g/kg at 13:00 h). Venous blood samples were drawn every 2 h and the 24-h urine was collected. In addition to measuring plasma ammonia and amino acids, the urea production rate, serum glucose and serum insulin were analyzed. A significant postprandial rise in the ammonia concentration was noted during the infusions of placebo and 5 g of OA but did not occur with the dosages of 20 g (after the second protein load) and 40 g (after both protein loads). Furthermore, the latter dose, compared with placebo, significantly reduced plasma ammonia after the minor protein load. Urea production rate increased when 20 g or 40 g of OA was administered. Of the amino acids involved in the metabolic pathways of ornithine and/or aspartate, glutamate showed a rise in its plasma level following infusion of 40 g of OA, whereas glutamine did not. Concentrations of methionine, phenylalanine, tyrosine, threonine, serine and glycine declined progressively with increasing doses of OA (5-40 g). The highest dose of the drug caused hyperglycemia and hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. 815 Nov 4

To date, no attempt has been made to study alterations occurring in the amino acid profile in chronic models of thioacetamide-induced liver cirrhosis. In this work, changes in serum amino acids and proteins in rats with thioacetamide-induced liver cirrhosis are reported, together with changes in enzyme activities in the liver and serum. Seventeen female Wistar rats were used. Eight rats were given 300 mg thioacetamide/l in drinking water for 4 months and nine rats were given water ad libitum during the same time-period. Significant increases in glycine, alanine, serine, methionine, glutamate, ornithine, phenylalanine, tyrosine, histidine and proline were observed in rats with the resulting experimental liver cirrhosis. Threonine, taurine, glutamine, lysine and citrulline tended to increase while isoleucine, leucine, aspartate, arginine and tryptophan tended to decrease. Total and nonessential amino acids increased significantly in cirrhotic animals. Total essential and aromatic amino acids tended to increase in the thioacetamide-treated group, whereas branched chain amino acids tended to decrease in the same group. Regarding serum proteins, a decrease in albumin concentration in the thioacetamide-treated animals was the only change detected. The liver enzyme activities under observation (aspartate and alanine aminotransferases, glutamate dehydrogenase and threonine deaminase) were lower in the thioacetamide group. Decreases were significant for both transaminases and threonine deaminase. Results for serum activities showed that transaminases did not change in thioacetamide-treated rats in comparison with controls. In contrast, alkaline phosphatase rose dramatically in cirrhotic rats. We conclude that the serum amino acid pattern in this chronic model of liver cirrhosis resembles in part that of the corresponding human disease.
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PMID:Serum amino acid changes in rats with thioacetamide-induced liver cirrhosis. 857 92

The present study reports on the usefulness of laparoscopic microwave coagulonecrotic therapy as a new option in the treatment of hepatocellular carcinoma. Five patients with liver tumors associated with cirrhosis were treated from July 1993 to March 1994 with a microwave electrode (output 100 W, 3 to 4 cm long) devised for laparoscopic use. The tumors, all with diameters less than 3 cm and superficially located, were coagulated for a total radiation period of 20 to 30 min under laparoscopic, intraoperative ultrasonographic control. Postoperative complications were negligible, and laboratory values (glutamate-pyruvate transaminase, bilirubin, prothrombin time, platelet count) returned to preoperative levels within 7 days. Complete necrosis, including the surrounding liver tissue, was confirmed by a follow-up dynamic computed tomography scan during the follow-up period of 6 to 17 months (mean, 13 months). Laparoscopic microwave coagulonecrotic therapy can exert an effect on tumor equivalent to that obtained from a wedge resection but is noninvasive and may represent a new option for unresectable liver cancers.
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PMID:Laparoscopic microwave coagulonecrotic therapy for hepatocellular carcinoma. 861 89

The purpose of this study was to correlate the hyperintensity in the globus pallidus seen on T1-weighted magnetic resonance imaging (MRI) of the brain in chronic liver disease with changes in metabolite ratios measured from both proton and phosphorus-31 magnetic resonance spectroscopy (MRS) localised to the basal ganglia. T1-weighted spin echo (T1WSE) images were obtained in 21 patients with biopsy-proven cirrhosis (nine Child's grade A, eight Child's grade B and four Child's grade C). Four subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological testing, four showed evidence of subclinical hepatic encephalopathy and 13 had overt hepatic encephalopathy. Signal intensities of the globus pallidus and adjacent brain parenchyma were measured and contrast calculated, which correlated with the severity of the underlying liver disease, when graded according to the Pugh's score (p < 0.05). Proton MRS of the basal ganglia was performed in 12 patients and 14 healthy volunteers. Peak area ratios of choline (Cho), glutamine and glutamate (Glx) and N-acetylaspartate relative to creatine (Cr) were measured. Significant reductions in mean Cho/Cr and elevations in mean Glx/Cr ratios were observed in the patient population. Phosphorus-31 MRS of the basal ganglia was performed in the remaining nine patients and in 15 healthy volunteers. Peak area ratios of phosphomonoesters (PME), inorganic phosphate, phosphodiesters (PDE) and phosphocreatine relative to beta ATP (ATP) were then measured. Mean values of PME/ATP and PDE/ATP were significantly lower in the patient population. No correlation was found between the T1WSE MRI contrast measurements of the globus pallidus and the abnormalities in the metabolite ratios measured from either proton or phosphorus-31 MR spectra. Our results suggest that pallidal hyperintensity seen on T1WSE MR imaging of patients with chronic liver disease is not related to the functional abnormalities of the brain observed in hepatic encephalopathy.
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PMID:MR imaging and spectroscopy of the basal ganglia in chronic liver disease: correlation of T1-weighted contrast measurements with abnormalities in proton and phosphorus-31 MR spectra. 886 45

Hepatic encephalopathy is a common problem in cirrhosis. The pathogenesis of this complication of advanced liver disease still remains unclear. Magnetic resonance spectroscopy was used to assess prospectively cerebral metabolism in 51 patients with histologically proven cirrhosis (Child-Pugh classes A, B, and C, 18, 18, and 15, respectively) and 36 healthy volunteers. According to the results of psychometric tests, overt hepatic encephalopathy, subclinical encephalopathy, and no encephalopathy were found in 14, 21, and 16 patients, respectively. Myoinositol/creatine ratios in gray (.36 +/- .17) and white (.35 +/- .22) matter voxel were reduced significantly (P < .0001) in cirrhotic patients compared with healthy volunteers (gray matter, .51 +/- .11; white matter, .64 +/- .16). In addition, patients showed a significant reduction (P = .024) in white matter choline/creatine ratio (.77 +/- .27) compared with controls (.92 +/- .25), and glutamine/glutamate level was elevated in cirrhotic patients compared with controls (gray matter, P < .0001; white matter, P = .036). Changes in cerebral myoinositol and glutamine/glutamate levels correlated significantly with the severity of hepatic encephalopathy (P < .0001). However, these metabolic alterations were also detected in patients without hepatic encephalopathy (normal psychometric test results). N-acetyl aspartate/creatine ratios did not differ between patients and controls. Magnetic resonance imaging detected bright basal ganglia in 37 patients, which correlated significantly with portal-systemic shunting and elevation of glutamine/glutamate, but not with the degree of hepatic encephalopathy. In conclusion, magnetic resonance imaging and spectroscopy showed that alterations of cerebral metabolism are common in patients with cirrhosis, even without evidence of clinical or subclinical hepatic encephalopathy.
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PMID:Cerebral abnormalities in patients with cirrhosis detected by proton magnetic resonance spectroscopy and magnetic resonance imaging. 898 63

4.1 CURRENT STATUS. While an extensive clinical literature of MRS of muscle, brain, heart and liver has been achieved, the MRS technique is not considered essential for routine diagnosis because it is inherently insensitive and metabolic changes tend to be small. However, MRS techniques have proven to be of considerable value for prognosis in some circumstances, notably for predicting outcome following hypoxic-ischaemic injury in the newborn and also in predicting graft viability following organ transplantation. The chemical specificity of MRS has been illustrated, and exploiting the non-invasive nature of the technique, metabolic fingerprinting of pathophysiological processes throughout the natural history of a wide variety of diseases is now being accomplished. Particularly exciting are the applications of 13C MRS for measuring hepatic and muscle glycogen levels, for example in diabetics, and the use of hepatic 31P MRS for assessing liver function in cirrhosis. Other areas of excitement are the applications of 1H MRS in assessing neuronal function in epilepsy and stroke, and for measuring the evolution of lactate in stroke and hypoxic-ischaemic encephalopathy. Emphasis on technique development continues, and applications still tend to be technology-led. The availability of routine clinical MRI systems with spectroscopy capabilities has given MRS studies wider applicability. The recent improvements in spatial resolution have been impressive and the technique is slowly becoming more quantitative. 4.2. FUTURE PERSPECTIVES. Given the flexibility of clinical magnetic resonance techniques, particularly magnetic resonance imaging, it is likely that MRI will be the diagnostic tool of choice in a wider range of diseases, such as multiple sclerosis, stroke, neurodegenerative conditions, sports injuries and in staging malignancies. Since proton magnetic resonance spectroscopy packages have become a routine addition to many MRI systems, it is feasible to select the MRI sequences of most value in highlighting anatomical and pathological abnormalities and to incorporate specifically selected MRS sequences to emphasize biochemical differences. Improvements in technical methodologies are central to further developments. For example, use of internal coils, such as implantable or endoscopic coils, will enable small regions of tissue to be studied in considerable detail, which may otherwise be inaccessible to measurement. Chemical MRS studies have benefited from the use of higher magnetic fields, and the same may be expected for clinical MRS studies. Whole-body magnets up to 4 T have been used in a few centres, and certainly 3 T systems are becoming more widely available with the recent tremendous interest in functional imaging. Certainly, better control of artefacts can be expected; for example, improved definition of spectral changes due to voluntary or involuntary movements. Wider use of proton decoupling methods will improve the specificity of the spectra, by allowing definitive assignments of overlapping resonances, as well as the sensitivity. Comparing PET and MRS studies, it is becoming increasingly obvious that both will be required in parallel to explore parameters of brain metabolism and function. The ability to measure 13C MR signals in the brain has been demonstrated, which allows measurements of glutamate and glucose turnover. MRS measurements have the advantage of not requiring a radioactive isotope, as well as being insensitive to activity-related changes in regional cerebral blood flow. Also the study of cerebral glucose metabolism by MRS is very promising, allowing a resolution and sensitivity comparable to PET. A combination of MRS and PET studies will allow the pathogenesis of neuropsychiatric disorders to be better understood. (ABSTRACT TRUNCATED)
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PMID:Development and applications of in vivo clinical magnetic resonance spectroscopy. 902 41

A study was made of the dental findings in 100 patients with liver cirrhosis (LC) by examining the number of carious, missing and filled teeth. A significantly greater number of carious and missing teeth were observed in the patients with cirrhosis than in a control group of 50 healthy individuals. In the LC group, caries were found to affect more teeth in those patients with alcohol-induced LC than in those with liver disease of other causes. Finally, no relationship was observed between the number of carious, missing or filled teeth and certain determinations including serum glutamate pyruvate transaminase (SGPT), serum glutamate oxalacetate transaminase (SGOT), alkaline phosphate, platelet number, hepatitis B and C positivity markers, or antinuclear (ANA), antimitochondrial (AMA) or anti-smooth muscle autoantibodies (ASm).
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PMID:Dental findings in patients with liver cirrhosis. A study of 100 cases. 920 45

Since plasma is generally employed for amino acid analysis, we compared amino acid levels in plasma with those in serum for healthy individuals and examined the influence of separation and storage conditions on the stability of the samples. Then, we determined the amino acid levels of frozen serum samples obtained from sarin poisoned patients. A. Comparison of Amino Acid Levels in Plasma and Those in Serum Blood was collected from 5 healthy individuals. Then, heparinated plasma and serum were separated by centrifugation immediately after blood collection. Serum was also separated by centrifugation after standing whole blood at room temperature for 1 hour. Frozen plasma and serum were store at -40 degrees C for 5 months. All were subjected to analysis in an amino acid analyzer. It was found that the cystine (Cys) and 3-methyl-histidine (3-M-His) levels in serum and plasma were affected when stored in a frozen state, that the aspartate (Asp) level was changed according to the method of collecting serum, and that the taurine (Tau) and ornithine (Orn) levels were affected by standing blood. B. Analysis of Blood Taken from Sarin Poisoned Patients Twelve sarin poisoned patients were selected as subjects, and serum cholinesterase (Ch-E) and serum albumin (Alb) levels were determined. Amino acid analysis was conducted using an amino acid analyzer. Serum samples which had been obtained from the 6 patients and frozen and stored at -40 degrees C from 5 months were used for amino acid analysis. As a result, the serum Ch-E level decreased and the Alb level tended to rise. Since the Ch-E/Alb ratio was reduced in the sarin poisoned patients, it is considered useful for discrimination from liver cirrhosis in which both Ch-E and Alb levels decreased. Amino acid levels in the serum obtained from the sarin poisoned patients were compared with those of healthy individuals, both of which had been stored under the same conditions. There were significant differences in Asp, glutamate (Glu), phenylalanine (Phe), 3-M-His, glutamine (Gln), and Cys levels. The Glu, Phe, and Gln levels were not affected by storage of serum in a frozen state, while the Glu and Phe levels were elevated and the Gln level was reduced. Although Cys exhibited lower values in frozen serum samples, the Cys level was elevated with a rise in the serum Ch-E levels. Therefore, we deduced that Cys metabolism disorders also occur in sarin poisoning. As stated above, the Glu and Phe levels were elevated and the Gln and Cys levels were reduced, suggesting the presence of abnormal amino acid metabolism, in patients with sarin-poisoning.
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PMID:[Blood amino acid levels in sarin poisoning patients]. 928 31

CCl4-induced cirrhosis of rats was used for studying the influence of L-ornithine-L-aspartate (OA) on hyperammonemia. OA given to cirrhotic rats (2 g/kg daily) for 2 wk slightly increased net body weight and led to a significant increase in plasma urea levels and a decrease in plasma ammonia levels. Serum concentrations of glutamate, glutamine and arginine decreased significantly. In the livers of the OA-treated rats the activities of carbamoylphosphate synthetase I and arginase increased by 30 and 40%, respectively, approaching normal levels. No change in the activities of the other urea cycle enzymes as well as of glutamate dehydrogenase, glutaminase and glutamine synthetase was found. The negative correlation between glutamine synthetase activity and plasma ammonia levels reported previously for cirrhotic rats (Gebhardt and Reichen, Hepatology 20:684-691, 1994) was corroborated for cirrhotic animals not treated with OA, but was no longer apparent in OA-treated cirrhotic rats. Despite this improvement, plasma ammonia levels still varied considerably reflecting the variable accessibility and activities of glutamine synthetase in cirrhotics. Cultured hepatocytes from the two groups of rats showed a similar stimulation of urea production by addition of ammoniumacetate and/or OA to Hanks' buffered salt solution. In Williams medium E, however, the hepatocytes from the OA group produced significantly more urea than those from controls. These results suggest that treatment of cirrhotic rats with OA considerably improves urea production favoring the detoxification of ammonia that, however, is still limited by the severe alterations in liver architecture that are not influenced by OA in a 2-wk period.
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PMID:Treatment of cirrhotic rats with L-ornithine-L-aspartate enhances urea synthesis and lowers serum ammonia levels. 933 1

alpha 1-Antitrypsin is the archetypal member of the serine proteinase inhibitor or serpin superfamily. Members of the family show structural homology based on a dominant A beta-sheet and a mobile reactive centre loop. Our recent crystal structure of alpha 1-antitrypsin stabilized with a point mutation showed the loop to be in a canonical inhibitory conformation in the absence of significant insertion into the A beta-sheet. It could be argued that the stabilizing mutation may induce the reactive centre loop to adopt an artificial, and unrepresentative, conformation and the finding seems to be at variance with studies assessing rates of peptide insertion into the A beta-sheet and limited proteolysis of the reactive loop. Here we present a 2.9 A structure of recombinant wild-type alpha 1-antitrypsin with no stabilizing mutations. Again, the reactive loop is in a canonical conformation in the absence of significant insertion into the A beta-sheet. A stabilizing salt bridge between P5 glutamate and arginine residues 196, 223 and 281, already identified in the mutant, provides strong evidence that this conformation is not an artefact of crystallization but represents the conformation of the circulating inhibitor in vivo. Comparison with the structure of alpha 1-antitrypsin stabilized with the Phe51Leu mutation indicates that the increased thermal stability of the mutant results from enhanced packing of aromatic residues in the hydrophobic core of the molecule. The structure of wild-type alpha 1-antitrypsin reveals a hydrophobic pocket between s2A and helices D and E that is filled on reactive loop insertion and the formation of biologically relevant loop-sheet polymers. This pocket may provide a target for rational drug design to prevent the formation of polymers and the associated plasma deficiency, liver cirrhosis and emphysema.
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PMID:Wild-type alpha 1-antitrypsin is in the canonical inhibitory conformation. 946 20


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