Amino acid concentrations were determined in plasma, whole blood, cerebrospinal fluid and brain tissue of 45 patients with grade 3 or 4 coma due to fulminant hepatic failure. The concentration of 15 of the 19 amino acids determined were significantly increased in blood and the increases were greatest for the amino acids concerned with neurotransmitter metabolism. There was no correlation, however, between the plasma concentration of these amino acids and changes in the grade of hepatic coma. The plasma concentrations of the branched chain amino acids were normal except in those patients who subsequently recovered in whom levels were slightly decreased. Phenylalanine- tyrosine and methionine were among the 15 out of 18 amino acids which were significantly increased in cerebrospinal fluid and among the 15 out of 21 amino acids which were significantly increased in the brain. The increase in tryptophan was associated with a significant elevation in brain 5-hydroxyindoleacetic acid concentration suggesting an increase in 5-hydroxytryptamine turnover in hepatic coma. Brain to plasma ratios of most amino acids in hepatic coma patients were similar to control subjects suggesting that plasma concentration is the main factor controlling the cerebral concentration. However, for the branched chain amino acids, cerebrospinal fluid and brain concentrations were increased when plasma concentrations were normal suggesting an increase in brain uptake.
The interrelation of neurology and the gastrointestinal system includes defects of gut innervation, primary disorders of the nervous system (or muscle) which lead to gastrointestinal symptoms-for example, dysphagia-and, finally, certain gut disorders which include neurological features in their clinical range. The first of this trio will be discussed only briefly in this review, the second and third in more detail.
The histological appearances of the liver damage occurring after a paracetamol overdose are described in liver biopsies from 104 patients, of whom 38 developed fulminant hepatic failure. Confluent centrilobular necrosis of varying extent was followed by rapid disappearance of necrotic cells, leaving areas of reticulin collapse and a usually mild inflammatory reaction. The histological recovery in even the most severe cases was remarkable, and only one of the 17 survivors whose initial biopsy showed the pattern of interlobular bridging necrosis had appreciable residual fibrosis in a follow-up biopsy taken after 1 yr. A quantitative estimate was made of the amount of surviving liver parenchyma using a morphometric technique and the hepatocyte volume fraction (HVF) in biopsies performed within 10 days of the overdose correlated well with the clinical course and both the maximal prolongation of the prothrombin time and the peak plasma bilirubin concentration in the first 10 days. An HVF value (normal 85 +/- 5 per cent.) of less than 40 per cent. in a biopsy taken within 10 days of the overdose was found only in patients who died. However, HVF measurements on biopsies from three survivors taken later than 10 days after the overdose shows that survival is possible below this critical level.
SUMMARY Lymphocytes from 39 patients with HBsAg positive chronic liver disease were incubated with their own hepatocytes to investigate mechanisms of lymphocyte-mediated liver damage. Cytotoxicity was significantly increased in 46% overall, and in 73% of those with chronic active hepatitis. Unlike HBsAg negative chronic active hepatitis where only non-T cells were cytotoxic, HBsAg positive patients had both cytotoxic T and non-T cells. A purified liver membrane complex (LSP) and aggregated IgG both blocked non-T cytotoxicity without affecting T cell cytotoxicity; this suggests that the former is probably an antibody-dependent cell-mediated reaction against normal membrane components. This was confirmed in preliminary studies which demonstrated that preincubation of hepatocytes with the F(ab)' fragment of an anti-human IgG reduced non-T lymphocyte cytotoxicity. T-cell cytotoxicity was restricted to HBeAg-positive
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