The My Child Matters programme: effect of public-private partnerships on paediatric cancer care in low-income and middle-income countries.

In low-income and middle-income countries, an excess in treatment failure for children with cancer usually results from misdiagnosis, inadequate access to treatment, death from toxicity, treatment abandonment, and relapse. The My Child Matters programme of the Sanofi Espoir Foundation has funded 55 paediatric cancer projects in low-income and middle-income countries over 10 years. We assessed the impact of the projects in these regions by using baseline assessments that were done in 2006.

A pilot double-blind, randomized, and placebo-controlled study of orally administered IFN-alpha-n1 (Ins) in pediatric patients with measles.

To determine the safety and effectiveness of low-dose oral interferon-alpha (IFN-alpha) against measles, 30 confined pediatric patients were prospectively and randomly assigned to either a placebo or an oral IFN-alpha group and observed daily for 14 days in a double-blind manner. The IFN patients received a daily sublingual dose of 200 IU of human lymphoblastoid IFN-alpha. The IFN-treated group showed shorter average duration of malaise (3.

Biochemical and pharmacological factors causing induction and suppression of germination of Trichosporon beigelii.

Trichosporon beigelii is an emerging fungal pathogen, which is morphologically characterized by blastoconidia, arthroconidia and hyphae. The non-hyphal forms of T. beigelii germinate to form hyphae in plasma in vitro and in tissues in vivo, suggesting possible pathophysiological significance of this process.

Vascular catheter-associated fungemia in patients with cancer: analysis of 155 episodes.

We reviewed all 155 episodes of central venous catheter-associated fungemia among inpatients at the National Cancer Institute during a 10-year period. Candida species accounted for 98% of episodes. Fungemia was documented by culture of blood drawn through catheters in 50% of cases and by culture of both catheter-drawn and peripheral blood in 39%; mortality and the rate of dissemination were similar for these two groups.

Antifungal effects of the nonlinear pharmacokinetics of cilofungin, a 1,3-beta-glucan synthetase inhibitor, during continuous and intermittent intravenous infusions in treatment of experimental disseminated candidiasis.

Cilofungin (LY-121019) is a fungicidal cell wall-active 1,3-beta-glucan synthetase inhibitor with a short plasma half-life and saturable nonlinear plasma pharmacokinetics. To optimize the in vivo efficacy of this compound, we studied the effects of its linear and nonlinear pharmacokinetics during continuous versus intermittent intravenous infusion of cilofungin in the treatment of experimental disseminated candidiasis in persistently granulocytopenic rabbits. Six groups of rabbits were studied, untreated controls (n = 32) and five cilofungin dosage regimen groups consisting of the following: 25 mg/kg of body weight intravenously twice daily (VLoINT) (n = 9); 50 mg/kg twice daily (LoINT) (n = 9); 90 mg/kg twice daily (HiINT) (n = 11); 5 mg/kg/h for 18 h/day (LoCI) (n = 7); and 10 mg/kg/h for 18 h/day (HiCI) (n = 7).

Plasma pharmacokinetics and tissue penetration of a novel antifungal triazole, Bay R 3783, and its long-lasting active metabolite, Bay U 3625, in rabbits.

The plasma pharmacokinetics and tissue penetration of Bay R 3783 (BR), a new antifungal triazole, and one of its active metabolites, Bay U 3625 (BU), were studied in rabbits. Plasma levels of BR and BU were determined simultaneously in five rabbits for six days after a single oral dose of 20 or 40 mg/kg BR. For BR, the mean Cmax was 1.

Empiric therapy with amphotericin B in febrile granulocytopenic patients.

The early diagnosis of invasive fungal infection in granulocytopenic patients remains unreliable. Granulocytopenic patients who are persistently or recurrently febrile despite therapy with appropriate antibacterial agents are at high risk for the development of such infection. Two randomized clinical trials demonstrated that the empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients decreased the frequency, morbidity, and mortality of invasive fungal infection; these effects were especially marked in profoundly granulocytopenic patients who were not receiving antifungal prophylaxis.

Cilofungin (LY121019) shows nonlinear plasma pharmacokinetics and tissue penetration in rabbits.

We studied the plasma pharmacokinetics and tissue penetration of cilofungin (LY121019), a new echinocandin antifungal compound, by intermittent and continuous infusion in rabbits. Following a single intravenous dose of 50 mg/kg of body weight, the maximum concentration in plasma was 297 +/- 39 micrograms/ml, the area under the curve was 30.1 +/- 6.

SCH-39304 in prevention and treatment of disseminated candidiasis in persistently granulocytopenic rabbits.

To investigate the potential use of SCH-39304 for the prevention and treatment of disseminated candidiasis in granulocytopenic patients, we studied its in vivo antifungal activity as preventive, early, and late treatments in three models (acute, subacute, and chronic) of disseminated candidiasis in persistently granulocytopenic rabbits. SCH-39304 was an effective as amphotericin B alone and fluconazole alone for the prevention of disseminated candidiasis. SCH-39304 alone and fluconazole alone were as effective as amphotericin B plus flucytosine for early treatment of subacute disseminated candidiasis.

Trichosporon beigelii, an emerging pathogen resistant to amphotericin B.

Trichosporon beigelii caused fatal disseminated infections that were resistant to amphotericin B in two granulocytopenic patients. In vitro susceptibility studies demonstrated that both index strains of T. beigelii were inhibited but not killed by amphotericin B at achievable concentrations in serum.

Experimental basis for use of fluconazole for preventive or early treatment of disseminated candidiasis in granulocytopenic hosts.

To determine the potential for the use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, we investigated its activity and pharmacokinetics in models of acute, subacute, and chronic forms of disseminated candidiasis in persistently granulocytopenic rabbits. Fluconazole was administered for systemic prophylaxis, early treatment, and delayed treatment. Single-dose and steady-state plasma pharmacokinetics, tissue penetration, and dose-response studies of the investigational compound were studied in subacutely infected granulocytopenic rabbits.