SUMMARY Blood methanethiol and ammonia concentrations were measured in 16 healthy volunteers, 52 consecutive alcoholic cirrhotics without overt hepatic encephalopathy (HE), and 42 consecutive patients with alcoholic liver disease and overt HE. The mean concentration of blood methanethiol was significantly greater than normal in the cirrhotics without overt HE, and the means of both methanethiol and ammonia were significantly greater in the patients with than in those without overt HE. Only one patient with overt HE had both normal ammonia and methanethiol blood concentrations. Twenty of the patients with HE were followed serially. The directions of change in methanethiol and ammonia were consistent with the direction of change in mental status in 85 % and 60 % respectively. All of the patients who deteriorated and died had changes in blood methanethiol that correlated with the change in mental status. We conclude that blood methanethiol is a valuable adjunct to the ammonia determination in the evaluation of the patient with possible HE. It is especially helpful in following the course of a patient with hepatic encephalopathy, both as to prognosis and as an indicator of response to therapy. Mercaptans are extremely toxic sulphur-containing compounds that appear to be largely derived from colonic bacterial metabolism of methionine. Like ammonia, mercaptans are normally efficiently removed by the liver but escape detoxification with hepatic failure or shunting of intestinal blood around the liver. Animal studies have shown that small amounts of mercaptans can cause reversible coma and can act synergistically with ammonia and fatty acids to enhance the toxicity of these substances.' In 1955, Challenger and Walshe2 established the association of mercaptans with hepatic failure by isolating methanethiol (methyl mercaptan) from the urine of a woman in deep hepatic coma, and, in 1970, Chen and his colleagues3 reported a four-fold increase in breath methanethiol in patients with hepatic failure. Recently, a method for measuring mercaptans was developed that was sufficiently sensitive to detect methanethiol in the blood of patients for the first time.4 We have applied this method to patients with hepatic failure over the past two years and are now reporting the results of this initial experience.

SUMMARY Ammonia coma was produced in rats within 10 to 15 minutes of an intraperitoneal injection of 1.7 mmol NH4C1. This coma was prevented with 1-68 numol L-dopa given by gastric intubation 15 minutes before the ammonium salt injection. The effect of L-dopa was correlated with a decrease in blood and brain ammonia, an increase in brain dopamine, and an increase in renal excretion of ammonia and urea. Intraventricular infusion of dopamine sufficient to raise the brain dopamine to the same extent did not prevent the ammonia coma nor affect the blood and brain ammonia concentrations. Bilateral nephrectomy eliminated the beneficial effect of L-dopa on blood and brain ammonia and the ammonia coma was not prevented. Thus, the reduction in blood and brain ammonia, and the prevention of ammonia coma after L-dopa, can be accounted for by the peripheral effect of dopamine on renal function rather than its central action. These results provide a reasonable explanation for the beneficial effects observed in some encephalopathic patients receiving L-dopa.The arousal effect of L-dopa in hepatic coma has been observed repeatedly since the original observations (Parkes et al., 1970). The arousal response is observed in approximately one-half ofpatients treated and is temporary in all but a few (Fischer et al., 1976). The beneficial effect of L-dopa has generally been presumed to be a central effect of its derivative, dopamine, and has been cited as evidence supporting the false neurotransmitter hypothesis of the aetiology of hepatic coma (Fischer and Baldessarini, 1971). We studied the effect of L-dopa in experimental ammonia coma in rats, thinking that there might be an association between the arousal effect of L-dopa and the brain ammonia concentration. We found, indeed, that L-dopa in sufficient dosage prevented ammonia coma, and that the presence or absence of coma was related to the brain ammonia but not the brain dopamine concentration. We also observed that the reduction in brain and blood ammonia after L-dopa was associated with an increase in renal excretion of ammonia and urea, and that nephrectomy eliminated the effects of L-dopa on coma and on the blood and brain ammonia concentrations.

Many improvements and simplifications have been made in the analysis of phosphatides and water soluble phosphate esters of glycerol. Silicic acid impregnated paper techniques have greatly speeded up the process of identifying and quantitating phosphatides ( 1,2,3). Dawson and coworkers (4,s) have carried out extensive studies on paper of the hydrolysis products of phosphatides. With the introduction of TLC,* qualitative separation of lipids and phospholipids was speeded up remarkably. The precision of the separations offered the possibility of quantitating the compounds so separated on thin layer plates. Two groups have analyzed some phosphatides quantitatively by TLC (6,7). The separation of the hydrolysis products of phosphatides on TLC has also been reported recently (8,9) ; however the separations achieved were not suitable for quantitation.In this report we describe a procedure for quantitative analysis of phosphatides and of the water soluble choline and ethanolamine * The following abbreviations are used: TLC, thin layer chromatogram or

Incubation of human fecal homogenates with ethanol (0.078 g m per dl) resulted in accumulation of increased quantities of higher alcohols and other unidentified metabolites when compared with homogenates incubated without ethanol. Studies in rats demonstrated nearly perfect equilibration between blood and colonic luminal ethanol suggesting that the colonic flora in alcoholics is chronically exposed to ethanol concentrations in the range used in the homogenate experiments. The higher alcohols produced by the homogenates were rapidly absorbed from the colon. We hypothesize that, when exposed to ethanol, the colonic flora produced toxic compounds which are absorbed and influence the body's response to ingested ethanol. Individual differences in this bacterial metabolism may account for the wide individual differences in susceptibility to ethanolrelated organ injury.Alcoholics vary in their susceptibility to ethanolrelated organ injury. For example, organ injury occurs in only a minority of heavy alcoholics and the damaged organ (e.g., liver, pancreas, nervous system, or heart) varies from patient to patient. A number of yet unproven hypotheses concerning individual differences in the metabolism of ethanol or its metabolic product, acetaldehyde, have been proposed to explain the differences in susceptibility to ethanol.The purpose of this report is to suggest another, apparently novel hypothesis which might help to explain some of the variable susceptibility to the ravages of ethanol-namely, that the metabolism of the colonic flora influences the host's response to ethanol. MATERIALS AND METHODSThe influence of ethanol on the metabolism of colonic bacteria was studied by comparing the metabolic products produced by human feces when incubated in the presence or absence of ethanol. Freshly passed human feces were homogenized anaerobically in pH 7.4, 0.1 A4 PO, buffered saline (1 part feces3 parts buffer). Twentymilliliter aliquots of this homogenate were then anaerobically incubated at 37°C with or without the addition of pure ethanol (0.1% v/v or 0.078 gm per dl).Our initial gas chromatographic analyses of the volatiles produced during incubation showed a multiplicity of compounds in the ethanol-treated homogenate which were not present in the homogenate incubated without ethanol. To date, we have identified and quantitated the alcohols accumulating in homogenates of feces obtained from 20 healthy subjects. Two-milliliter aliquots of the homogenates were removed at 0, 3, 6, and 24 hr of incubation and analyzed by gas chromatography-mass spectroscopy as follows. Two grams of K&O3 (I) were added to 2 ml homogenate in a 30-ml sealed vial using isobutyl alcohol as an internal standard. The mixture was heated at 70°C for 30 min, and 5 ml of the gas space was then analyzed for alcohols by gas chromatographymass spectroscopy using a Hewlett-Packard, Model 5992-B. A 25-pm silica capillary column containing Carbowax (20 M ) was employed at an initial temperature of 10°C for 1 min and then programmed to increase at 10°C per min...

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