A new priority policy for patients with hepatocellular carcinoma awaiting liver transplantation within the model for end-stage liver disease system.

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end-stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients, 29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS-CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC-MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial-final native MELD scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial-final: 15.1-15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC.     

A Case of Hypopigmented Mycosis Fungoides in a Young Caucasian Boy

Abstract: Hypopigmented mycosis fungoides is a variant of mycosis fungoides characterized by the presence of hypopigmented patches as the sole manifestation of the disease. It has been described aimost always in young black or dark-skinned patients. The only white patient described was a 64-year-oid woman who not oniy had hypopigmented lesions, but also nodular lesions with lymphadenopathy. We describe hypopigmented lesions arising in a white boy 12 years of age, born in northern Italy, without any foreign ancestors. The microscopic alterations, with epidermotropism, the immunoiogic markers, the negativity of T-cell receptor gene rearrangement, and the good response to PUVA therapy correspond to the main findings in black patients with this disease. Long-term follow-up of these patients is important to obtain better knowledge of the natural history of the disorder, Hypopigmented mycosis fungoides must now be included in the differential diagnosis of hypopigmented macular lesions not only in black or dark-skinned patients but also in white patients.     

Alcohol Intake and Withdrawal: Effects on Branched Chain Amino Acids and Alanine

The effects of chronic alcohol consumption on plasma branched chain amino acids and alanine concentrations were evaluated, and basal blood concentrations of these amino acids were determined after chronic ethanol intake and following a withdrawal period in 30 admitted alcoholics. After ethanol intake, alcoholics showed increased branched chain amino acid concentrations; the blood alanine concentrations were depressed after the withdrawal period. To evaluate the effect of ethanol on diurnal variations of these amino acids in the blood, a group of these patients underwent two isocaloric diets with and without wine. The diet with alcohol induced a sustained increase of branched chain amino acids persisting even after the postprandial phase with a decrease of alanine as compared to the diet without.     

Natural killer cell activity and serum immunoglobulins in epileptic patients

Serum immunoglobulins and the activity of natural killer (NK) cells of 50 epileptic patients (eight with idiopathic generalized epilepsy and 42 with cryptogenic partial epilepsy) and 28 controls have been studied. The values of IgA, IgG and IgM were the same-in patients and controls. The NK activity in controls was linearly related to the effector-to-target ratio, but this linear relationship was not observed in epileptic patients. The cytotoxic activity of NK cells at the lowest effector-to-target ratio was significantly greater in patients than in controls. This increase was observed in each therapy group. Our results seem to confirm a disturbance of the immune system in epileptic patients and suggest that this modification of cellular immunity is not a drug effect but is related to the illness itself.     

Urinary mercapturic acid diastereoisomers in rats subchronically exposed to styrene and ethanol

 Styrene is stereoselectively oxidized by cytochrome P450 to its reactive metabolite, styrene oxide. The (R)- and (S)-enantiomers of styrene oxide can be conjugated with glutathione (GSH) to both (R)- and (S)-diastereoisomers of the specific mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). Several investigations have indicated different toxic potential of the (R)- and (S)-configurations of styrene oxide and its GSH- and N-acetyl-conjugates. In this study the mercapturic acid diastereoisomers were measured in the urine of rats exposed to styrene in combination with ethanol, a good inducer of styrene metabolism. Male Sprague-Dawley rats were given an isocaloric liquid diet containing ethanol (5% w/v) for 3 weeks. Starting from the 2nd week, the animals were also exposed to styrene vapours (300 ppm, 6 h/day, 5 days/week) in a dynamic exposure chamber. Both the (R)- and (S)-diastereoisomers of the M1 and M2 as well as the conventional biomarkers, mandelic acid (MA) and phenylglyoxylic acid (PGA) were measured in urinary samples. Approximately 30 and 25% reduction of the levels of brain non-protein sulfhydryls (NPS) was observed in the animals given styrene and ethanol, respectively, while the combined ethanol and styrene treatment resulted in a 60% decrease. Ethanol consumption also resulted in higher urinary levels of the M1-R, M1-S and M2 metabolites associated with increased M1-R/S ratio and higher urinary MA excretion compared to animals treated with styrene. These results suggest that the urinary mercapturic acid diastereoisomers may be used as a noninvasive tool to examine stereoselective patterns of styrene metabolism in vivo, as well as their alterations caused by ethanol. These compound-specific mercapturic acids may also be valuable indicators of styrene-induced disorders of GSH homeostasis in nonaccessible organs. Received: 19 December 1995/Accepted: 10 May 1996