Glucose intolerance in liver cirrhosis.
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Biomedical subjects
Publications and source records attributed to F Rossi Fanelli.
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A sensitive radioenzymatic assay for the simultaneous determination of phenylethylamine, phenylethanolamine, tyramine and octopamine in plasma samples is reported. After extraction with ethanol, the amines are subjected to enzymatic N-methylation with labelled S-adenosylmethionine, preceded in the case of phenylethylamine and of tyramine, by an enzyme-catalyzed beta-hydroxylation step. The procedure is completed by extraction with toluene containing different amounts of isoamylalcohol, followed by controlled evaporation of the solvent. A generalized and highly significant increase in the concentration of all the four amines was found in plasma samples from patients suffering from hepatic encephalopathy.
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Octopamine and phenylethanolamine levels were measured by a radioenzymatic procedure in 30 cirrhotic patients with and without hepatic coma and in 15 normal controls. Octopamine data were obtained either by direct extraction with 40% isoamyl alcohol in toluene according to Molinoff et al. (Molinoff, P.B., Landsberg, L. and Axelrod, J. (1969) J. Pharm. Exp. Ther. 170, 253), or after pre-extraction of phenylethanolamine with 3% isoamyl alcohol in toluene. Phenylethanolamine was statistically correlated with the grade of hepatic encephalopathy. Octopamine levels also appeared to parallel the grade of coma, although the values obtained after pre-extraction were lower and less significant than those obtained with 40% isoamyl alcohol in toluene extraction. The higher values of directly extracted octopamine are due to contamination of other beta-hydroxylated phenylethylamines, among which is phenylethanolamine.
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It has been recently proposed that hepatic encephalopathy could be due to the accumulation of octopamine acting as a false neurotransmitter, and the increase of ammonia might reflect this accumulation. The simultaneous determination of octopamine and ammonia was performed in 88 cases with or without encephalopathy. The correlation between the two substances appeared to be good (P less than 0.01; r = 0.5), except in shunted patients. All the cases with low octopamine and high ammonia were patients who had been submitted to surgical portal-systemic anastomosis. This finding does not seem to be coincidental; in this type of patients, the mechanism of hepatic encephalopathy could involve other beta-hydroxyphenylethanolamines in addition to octopamine. The presence of the inhibition of the reaction of transmethylation constantly observed during octopamine plasma assay is in favour of this hypothesis.
The unesterified cholesterol content of plasma samples can be evaluated from the extent of inhibition of lucensomycin-induced hemolysis. The test measures, however, only the fraction of cholesterol which is available for interaction with lucensomycin, this availability being adversely affected by high phospholipid-cholesterol ratios.
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The tolerance to exogenous fats has been evaluated in patients with liver cirrhosis. A three-stage lipid clearance test with continuous infusion (3 hr) of a triglyceride emulsion, Intralipid, was performed on 10 patients with well compensated liver cirrhosis and 10 normolipidemic volunteers. During the infusion, blood samples were collected for the measurement of particulate triglycerides (TG) by nephelometry; samples were also collected for total TG, free fatty acids (FFA) and free tryptophan (TRP) determinations. Plasma endogenous triglycerides were calculated as the total minus exogenous, particulate, TG. The fractional removal rate (K2) and the maximal clearing capacity (K1) for exogenous TG were lower in patients than in controls, though a significant difference (p less than 0.05) was found only for K1. Endogenous TG and FFA showed a comparable rise in patients and controls during Intralipid infusion. A significant increase in free TRP was noted in cirrhotics upon maximal infusion rate. It is concluded that: in patients with well compensated liver cirrhosis the maximal clearing capacity (K1) for exogenous TG is impaired. Nonetheless, moderate amounts of fat may be removed at a normal rate from the bloodstream; a normal synthesis rate of exogenous TG may be maintained even in a severely damaged liver; considering the possible role of free TRP in the pathogenesis of hepatic encephalopathy (HE), the use of large amounts of lipids should be discouraged in patients with decompensated liver cirrhosis, or even avoided in those with impending or overt HE.
The coexistence of both kidney and colon primary malignancies is a rare condition. We report the case of a 75-year-old woman who presented with bilateral pulmonary nodules at chest X-ray and stratigraphy. Total-body CT scan showed multiple, apparently metastatic, bilateral pulmonary lesions, a diffusely dysomogeneous neoformation in the lower pole of the right kidney and a gross neoformation in the ascending colon. A right nephrectomy and a right hemicolectomy were performed and histology showed two primary neoplasms: clear cell renal carcinoma and undifferentiated adenocarcinoma of the colon.
Anorexia is an often underrated symptom in the clinical management of patients suffering from chronic diseases. Moreover, the anorexia accompanying chronic diseases (secondary anorexia) is often confused with anorexia nervosa, a typically neuropsychiatric disorder involving completely different pathogenic mechanisms and therapeutic strategies. Secondary anorexia is one of the main factors responsible for the development of malnutrition, which in turn negatively affects patient morbidity and mortality. Different mechanisms have been proposed to explain the pathogenesis of secondary anorexia. However, consistent experimental and clinical evidence seems to point to hypothalamic serotonergic system hyperactivity as a preeminent cause; this hyperactivity appears to be triggered by enhanced brain availability of tryptophan, the aminoacid precursor of serotonin. The hyperactive hypothalamic serotonergic system might also represent the final effector where different regulatory and modulating pathways, including cytokines, converge. The involvement of tryptophan and the hypothalamic serotonergic system is further supported by the effectiveness of a therapeutic strategy, based on the inhibition of tryptophan entry into the brain, in increasing the food intake of anorectic patients. Although these results represent an encouraging approach to the treatment of secondary anorexia, with possible beneficial effects on the nutritional status of patients, they need to be validated in larger trials.
High free tryptophan (F-TRP) plasma levels are found in cancer patients (CP). F-TRP plasma concentrations are affected by the levels of its carrier, albumin (ALB), and free fatty acids (FFA) competing with TRP for ALB binding sites. The lack of correlation between F-TRP, ALB and FFA in CP suggests a tumor-dependent effect on the rise in F-TRP. To verify this hypothesis, F-TRP, ALB and FFA levels were assayed in 12 lung and 16 breast CP susceptible to radical surgery, before and 15 days after surgical removal of the tumor. F-TRP levels significantly decreased after tumor ablation. Since no correlation was found between F-TRP, ALB and FFA variations, it is conceivable that the tumor itself may be responsible for the high F-TRP levels in CP.
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