A controlled study was carried out in two groups of 20 patients with cirrhosis of the liver and deep coma in order to compare the efficacy of intravenous branched-chain amino acid solutions in 20% glucose (group A) vs lactulose plus glucose in isocaloric amount (group B). There were 3 drop-outs from each group. Plasma amino acids and ammonia were assayed at fixed intervals throughout the 10-day observation period. Routine tests were assayed daily. Complete mental recovery was obtained in 70% of patients in group A and in 47% in group B. The difference was not significant, likely due to the lack of placebo group. With the exception of free tryptophan/all competing amino acids ratio, the modifications in plasma amino acid levels showed no correlation with the clinical course under either treatment. Ammonia, like free tryptophan, decreased significantly upon mental recovery, paralleling the clinical course throughout the study. In conclusion, branched-chain amino acids are at least as effective as lactulose in deep hepatic coma. It is suggested that branched-chain amino acids may reverse coma either by competing with brain entry of the aromatic amino acid or by metabolically decreasing free tryptophan and ammonia.

SUMMARY The efficacy of branched chain amino acids in two consecutive clinical studies in patients with severe hepatic encephalopathy was tested. In the preliminary uncontrolled study 19 patients with grade 3-4 hepatic encephalopathy were given an intravenous solution containing leucine 11 g/l, isoleucine 9 g/l, and valine 8.4 g/l in 20% dextrose. A complete recovery of mental state was obtained in all patients in a mean time of 20*5 hours. In a subsequent controlled study 40 patients with grade 3-4 hepatic encephalopathy were randomly assigned to receive intravenous branched chain amino acid in 20% dextrose (group A) or oral lactulose (group B). Twelve patients (70-6%) in group A and eight (47%) in group B regained consciousness in a mean time of 27-6 and 31*5 hours, respectively. The difference in the recovery rate between the two groups, although evident, was not significant. Intravenous branched chain amino acids are thus at least as effective as lactulose in reversing hepatic coma.These data argue strongly in favour of a therapeutic effect of branched chain amino acids in the treatment of hepatic encephalopathy in patients with chronic liver failure.

A case of chronic neutrophilic leukemia associated with multiple myeloma is described. The patient appears to be the longest surviving case reported in the literature. Since myeloma developed several years after leukemia, the possible precancerous role of myeloproliferative syndromes is proposed.

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Influenza activity was studied in the Rome population from 1956 to 1976 by analysis of mortality from respiratory causes and from all causes. During cold weather months, type A influenza virus was associated, as a rule, with epidemic excess deaths at two year intervals while type B virus was prevalent twice during isolation data were also compared with epidemic excess mortality during four consecutive years. The evidence obtained indicated that influenza virus isolation alone does not represent a reliable index of epidemic influenza activity in this population. The proportion of deaths attributed to respiratory causes consistently increased in every epidemic, the most pronounced increases occurring during large epidemics. The break-down by age of deaths from respiratory causes in the course of two epidemic periods showed that the percentage distribution of deaths was essentially the same as in non-epidemic periods. This evidence indicates that the same factors influencing the age-related distribution of mortality from respiratory causes during non-epidemic periods, probably affect the fatal outcome of influenza during epidemics.