ckshs expression is linked to cell proliferation in normal and malignant human lymphoid cells.

Cyclin kinase sub-units (CKS) are known to interact with cyclin-dependent kinases (CDKs), but their functions are not completely understood and their expression in human tissues is not documented. For analyzing relationships of CKS with cell proliferation and/or with differentiation, we investigated the expression of ckshs1 and ckshs2 in normal and malignant human lymphoid cells. ckshs1 and ckshs2 expression appeared to be related to cell proliferation: (i) mRNAs increased with stimulation of normal peripheral-blood lymphocytes, and from the G1 to the SG2M phase in elutriated cells; (ii) P9 proteins were also induced by lymphocyte stimulation and were localized in nucleus where phosphorylated forms of CDK1 were also found; (iii) in vitro, the phosphorylated forms of CDK1 and CDK2 were preferentially linked to CKS. Among 45 patients presenting acute or chronic lymphoid malignancy, ckshs1 and ckshs2 mRNAs varied in a similar way and were significantly correlated to cell proliferation (p < 0.0001). When analysis was restricted solely to acute lymphoblastic leukemia (ALL) this correlation was still found and ckshs1 and ckshs2 were significantly more expressed in T-cell ALL than in B-cell-lineage ALL. These results confirm relationships between ckshs expression and cell proliferation, and pose the question of a link with cell differentiation.

[Clinical, pharmacokinetic and therapeutic study of amikacin with single daily dose and in combination in neutropenic children with fever]. / Etude clinique, pharmacocinétique et thérapeutique de l'amikacine en dose unique journalière et en association chez l'enfant neutropénique fébrile.

BACKGROUND: The efficacy of single daily dose of amikacin has been recently demonstrated in neutropenic children with fever. POPULATION AND METHODS: Eighteen children aged 1 to 15 years were included in the study. All patients were febrile and granulocytopenic and had indwelling intravenous catheter. Amikacin was administered as a 30-minute intravenous infusion once daily (20 mg/kg on day 1, then 15 mg/kg) for 3 to 30 days; the patients received amikacin in combination with piperacillin and vancomycin. Serum levels of amikacin were measured on days 1, 3, 6 and 10, and 30 min, 60 min and 180 min after the end of the infusion. RESULTS: All patients responded favourably to the antibiotic therapy. Sixty-two kinetics were performed: peak amikacin concentrations measured (30 min after 30-min infusion) on day 1 averaged 43.7 micrograms/mL (+/- 13.8). A significant increase in peak serum concentrations was observed during the treatment (day 3 vs day 10) without change in the trough serum concentrations. The volumes of distribution were considerably important in these granulocytopenic children and there was a large inter and intra-patient variability; the elimination half-life of the amikacin was short (1.45 h). There was no significant nephrotoxicity in any patient. CONCLUSION: The use of single daily dose amikacin in combination with a broad spectrum beta-lactam antibiotic and vancomycin was efficient and safe in febrile granulocytopenic children. The simulation of the amikacin behaviour in the deep compartment should be evaluated; in fact, it might reflect better accumulation of the drug than serum concentrations.

[Candida albicans arthritis during induction treatment of acute lymphoblastic leukemia]. / Arthrite à Candida albicans lors du traitement d'induction d'une leucémie aiguë lymphoblastique.

Candida arthritis is a rare event which is a result of direct intraarticular inoculation, or--in compromised host--of hematogenous spread. We report on the case of an 18-month-old boy who experienced such an infection during induction treatment for acute lymphoblastic leukemia with aplastic onset. He was healed by daily systemic amphotericin B administered over a period of 3 wks associated with intravenous flucytosine during the first 2 wks; the treatment was continued with oral administration of ketoconazole for 5 wks. Treatment control was performed by drug monitoring in plasma and synovial fluid, as well as by determination of Candida antigenemia and antibody levels. We consider that the required doses of amphotericin B should be based upon plasma concentrations greater than 0.5 or 1 mg/l to be maintained during 2-3 wks. Providing that there is no resistance, the association with flucytosine may be useful.