Idrapril is the prototype of a new class of angiotensin converting enzyme (ACE) inhibitors. Its pharmacokinetics and pharmacodynamics (plasma ACE activity) were investigated in rats, dogs (after intravenous and oral doses), and human volunteers (after oral doses). Following intravenous administration (1 mg/kg) to rats and dogs, elimination half-lives were 96 and 52 min, systemic clearance 19.6 and 9.5 ml/min kg, and volume of distribution 2.7 and 0.8 liters/kg, respectively. Pharmacokinetics appeared linear in dogs, within the dose range of 0.1-10 mg/kg. After oral administration of similar doses (approximately 2 mg/kg) in the three species studied, peak plasma concentrations were 182, 567, and 726 ng/ml; AUCs 25, 85, and 182 micrograms min/ml; and elimination half-lives 82, 54, and 174 min in rats, dogs, and healthy volunteers, respectively. Absolute oral bioavailability was calculated to be approximately 24% in rats and dogs. Idrapril did not bind to plasma proteins of the species studied. Plasma ACE was fully inhibited following oral administration of approximately 2 mg/kg in rats and humans, but in dogs maximal inhibition did not exceed 85%. Duration of action, measured as time for ACE to recover to 70% of initial activity, was approximately 5, 3, and 22 hr in rats, dogs, and humans, respectively. Idrapril plasma levels appeared correlated in a saturable way with inhibition of plasma ACE in all three species, yielding ex vivo IC50 values of approximately 7 ng/ml for both the rat and humans, and 91 ng/ml for dogs.

Administration, Oral↗

PubMedDate not supplied

Evaluation of minimal residual disease in high risk childhood acute lymphoblastic leukemia using an immunological approach during complete remission. AIEOP Cooperative Group for Immunology of Acute Leukemias.

BACKGROUND: Sensitive methods for detecting residual disease may complement conventional morphology while monitoring the response to treatment in leukemia patients. METHODS: We studied minimal residual disease (MRD) by selecting via a colony assay a peripheral blood (PB) cell population enriched in putative malignant cells and detecting occult leukemic cells by double immunologic analysis performed on colonyforming cells (CFC). Using this combined technique we assayed the PB of high risk children with acute lymphoblastic leukemia (ALL) in order to demonstrate possible differences in "the residual tumor cell burden" among leukemia patients and to correlate these with a 3-year clinical follow-up. RESULTS: In all 22 patients positive results were obtained for up to 18 months following induction chemotherapy at times of apparent hematologic remission. Common ALL (cALL) patients exhibited a mean of 9.6% cAlla+ cells (range: 2% to 30%), whereas cALL antigen (cALLA) and cALLA/Tdt or CD1a/Tdt combination were never found in the colonies derived from healthy individuals. Six out of 22 cALL patients expressed a mean of 16.5% cALLA+/Tdt+ CFC (range: 2% to 35%). Five T-ALL children presented a mean of 24% CD1a/Tdt+ cells (range: 8% to 44%). Extensive follow-up indicates a correlation between the percentage of CFC Tdt+/lymphoid marker+ cells (more than 10%) and subsequent clinical relapse. In one patient relapse occurred after 16 months with a dramatic increase in the number of leukemic cells. In contrast, the decline in malignant cells, observed in two cases, predicted a favourable course. Five patients tested before autologous bone marrow transplantation (ABMT) presented high number of positive cells and relapsed at various times. CONCLUSIONS: We conclude that this approach to the study of MRD could be valuable in monitoring the efficacy of chemotherapy, as well in evaluating the quality of purged marrow.

Adolescent↗

PubMedDate not supplied

Comparison of two application techniques of EMLA and pain assessment in pediatric oncology patients.

BACKGROUND AND OBJECTIVES: The study was designed to compare the analgesic efficacy of the local anesthetic EMLA when applied as a patch and as a cream in combination with a Tegaderm dressing to pediatric oncology patients undergoing repeated lumbar punctures. METHODS: The analgesic effect of the two products was assessed by a continuous or discrete visual analog scale in 24 children 3-16 years old, during two lumbar punctures. Distress was rated by use of the Observational Scale of Behavioral Distress. RESULTS: No significant differences were found between the pain and distress scores for the different preparations of EMLA. CONCLUSION: The EMLA patch and the EMLA cream are equally effective in alleviating pain associated with lumbar puncture. The EMLA patch simplifies and speeds up the application of EMLA. It also allows for control of the dose administered per application, thus preventing both over- and underdosing.

Administration, Cutaneous↗

PubMedDate not supplied

[Visceral leishmaniasis in children in the province of Florence].

Three cases of visceral leishmaniasis are presented: two children who got the disease in Florence and the imported case of a girl coming from Albania with her disease in act. The diagnosis was made showing Leishmania in bone marrow specimen. Therapy with melglumine antimonate was effective and well borne, leading the three children to a complete healing. In the province of Florence visceral leishmaniasis is very rare, but such protozoa and the sand flies are present as shown by the high number of dog with leishmaniasis.

Adolescent↗