These results confirm that fludarabine is active when used as first-line treatment in patients with follicular lymphoma and has a low toxicity rate. It may be used as single treatment in elderly patients. Associations of fludarabine with other drugs active against follicular lymphoma need to be determined.

Ornithine alpha-ketoglutarate (OKG) has been successfully used as an enteral supplement in the treatment of catabolic states, including burn injury. However, specific questions remain unanswered concerning burn patients, including OKG metabolism and metabolite production, appropriate mode of administration, and dose. We thus performed a kinetic study and followed plasma ornithine and OKG metabolite concentrations on day 7 postburn in 42 (35 men, 7 women) consecutive burn patients aged 33 +/- 2 y with a mean (+/-SEM) total burn surface area (TBSA) of 31 +/- 1%. Patients were randomly assigned to receive OKG as a single bolus (10 g; n = 13) or in the form of a continuous gastric infusion (10, 20, or 30 g/d over 21 h; n = 13) or an isonitrogenous control (n = 16). Plasma pharmacokinetics of ornithine followed a one-compartment model with first-order input (r = 0.993, P < 0.005). OKG was extensively metabolized in these patients (absorption constant = 0.028 min-1, elimination half-life = 89 min), with the production of glutamine, arginine, and proline; proline was quantitatively the main metabolite [in OKG bolus, area under the curve (AUC)0-7h: proline, 41.4 +/- 5.6 mmol.min/L; glutamine, 20.4 +/- 5.7 mmol.min/L; and arginine, 7.3 +/- 1.9 mmol.min/L]. Proline production was dose-dependent and quantitatively similar between modes of OKG administration. Glutamine and arginine production were not dose-dependent and were higher in the bolus group than in the infusion group. Overall, the bolus mode of OKG administration appeared to be associated with higher metabolite production compared with continuous infusion in burn patients, especially for glutamine and arginine.

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We evaluated the rat cirrhosis model obtained by repeated intraperitoneal administration of CCl₄ (group C) with regard to biological and nutritional conditions in comparison to ad libitum (group AL) and pair-fed control rats. Cirrhotic rats were divided into two groups according to their clinical condition: group C1 (n = 4) represented those in good physical condition and group C2 those (n = 10) in poor physical condition. Autopsy indicated that rats in group C2 suffered from severe malnutrition as judged by body weight, carcass weight and the carcass/body weight ratio. However, all 14 treated rats presented the same micronodular cirrhosis and the same alterations in liver function, except for alkaline phosphatase activity (group C1: 110 ± 63 IU/1, group C2: 259 ± 110 IU/1; p < 0.05). In the cirrhosis groups, plasma levels of branched-chain amino acids (BCAA) and the BCAA/aromatic amino acid (AAA) ratio were significantly reduced, but values in groups Cl and C2 were not significantly different (BCAA/AAA: 1.9 ± 0.9 in group C1, 1.5 ± 0.8 in group C2, 2.8 ± 0.3 in group AL; C1 and C2, vs. AL: p < 0.05). These alterations were similar to those observed in human cirrhosis and were not solely the result of reduced food intake, as indicated by the lack of difference between pair-fed and ad libitum-fed control rats.