Microbial coexistence through chemical-mediated interactions.

Many microbial functions happen within communities of interacting species. Explaining how species with disparate growth rates can coexist is important for applications such as manipulating host-associated microbiota or engineering industrial communities. Here, we ask how microbes interacting through their chemical environment can achieve coexistence in a continuous growth setup (similar to an industrial bioreactor or gut microbiota) where external resources are being supplied.

Exploring informed choice in the context of prenatal testing: findings from a qualitative study.

Purpose: This study explored whether and how a sample of women made informed choices about prenatal testing for foetal anomalies; its aim was to provide insights for future health policy and service provision.

Methods: We conducted semi-structured interviews with 38 mothers in Ottawa, Ontario, all of whom had been offered prenatal tests in at least one pregnancy. Using the Multi-dimensional Measure of Informed Choice as a general guide to analysis, we explored themes relevant to informed choice, including values and knowledge, and interactions with health professionals.

Identification of domains relevant to health-related quality of life in patients undergoing major surgery.

This study examined themes relevant to health-related quality of life as identified by patients undergoing major surgery and by health care providers. Semi-structured interviews were conducted with 52 patients undergoing major abdominal, cardiac, orthopedic, thoracic, or vascular surgical procedures and 33 health professionals from various disciplines. A total of 58 themes were identified by content analysis.

In children and adolescents, the pharmacodynamics of high-dose busulfan is dependent on the second alkylating agent used in the combined regimen (melphalan or thiotepa).

A strong relationship has been demonstrated between high systemic exposure to busulfan and the occurrence of hepatic veno-occlusive disease (HVOD) after a busulfan-cyclophosphamide regimen (BU CY). We report a prospective study aimed at exploring the pharmacodynamics of high-dose busulfan combined with either melphalan (BU MEL) or thiotepa (BU TTP) followed by autologous stem cell transplantation in children and adolescents with a malignant solid tumor. Busulfan was given orally at a total dose of 600 mg m(-2).

Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations.

High-dose busulphan-containing chemotherapy regimens have shown high response rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and medulloblastoma. However, the anti-tumour activity of busulfan as a single agent remains to be defined, and this was evaluated in athymic mice bearing advanced stage subcutaneous paediatric solid tumour xenografts. Because busulphan is highly insoluble in water, the use of several vehicles for enteral and parenteral administration was first investigated in terms of pharmacokinetics and toxicity.

Preclinical development of camptothecin derivatives and clinical trials in pediatric oncology.

Although the prognosis of childhood cancers has dramatically improved over the last three decades, new active drugs are needed. Camptothecins represent a very attractive new class of anticancer drugs to develop in paediatric oncology. The preclinical and clinical development of two of these DNA-topoisomerase I inhibitors, i.

Activity of fotemustine in medulloblastoma and malignant glioma xenografts in relation to O6-alkylguanine-DNA alkyltransferase and alkylpurine-DNA N-glycosylase activity.

Fotemustine is a chloroethylnitrosourea with antitumor activity in disseminated melanoma and adult primary brain tumors. Because new drugs are required for the treatment of medulloblastoma in children, we evaluated the preclinical antitumor activity of fotemustine in four s.c.

DNA-topoisomerase I, a new target for the treatment of neuroblastoma.

DNA-topoisomerase I is the nuclear target of new anticancer drugs, namely camptothecin and its derivatives. In order to establish the rational basis for their clinical development in paediatric oncology, the antitumour activity of irinotecan (CPT-11) and topotecan, two camptothecin water-soluble derivatives, was studied in nude mice bearing neuroblastoma xenografts. The panel was composed of 4 previously established subcutaneous xenograft lines (IGR-N835, IGR-N91, IGR-NB3, IGR-NB8) that exhibited the common biological markers of poor prognosis in children (MYCN amplification, 1p deletion, paradiploidy and/or MDR1 overexpression).

Potent therapeutic activity of irinotecan (CPT-11) and its schedule dependency in medulloblastoma xenografts in nude mice.

The anti-tumor activity of irinotecan (CPT-11), a DNA-topoisomerase 1 inhibitor, was evaluated in 5 advanced stage subcutaneous medulloblastoma xenografts in nude mice, using different schedules of administration. With a 5-day schedule, the highest i.v.

Therapeutic activity of CPT-11, a DNA-topoisomerase I inhibitor, against peripheral primitive neuroectodermal tumour and neuroblastoma xenografts.

The anti-tumour activity of CPT-11, a topoisomerase I inhibitor, was evaluated in four human neural-crest-derived paediatric tumour xenografts; one peripheral primitive neuroectodermal tumour (pPNET) (SK-N-MC) and three neuroblastomas. Two models, SK-N-MC and IGR-N835, were established in athymic mice from a previously established in vitro cell line. Two new neuroblastoma xenograft models, IGR-NB3 and IGR-NB8, were derived from previously untreated non-metastatic neuroblastomas.

Busulfan disposition and hepatic veno-occlusive disease in children undergoing bone marrow transplantation.

Hepatic veno-occlusive disease (HVOD) is a frequent life-threatening toxicity in patients undergoing bone marrow transplantation (BMT) after the administration of a high-dose busulfan-containing regimen. Recent studies have shown that the morbidity and mortality of HVOD may be reduced in adults by pharmacologically guided dose adjustment of busulfan. We analyzed the pharmacodynamic relationship between busulfan disposition and HVOD in 61 children (median age, 5.

Busulfan disposition below the age of three: alteration in children with lysosomal storage disease.

Busulfan disposition is age-dependent with a higher clearance and a larger volume of distribution in children than in adults. The optimal dosage of busulfan needed to achieve bone marrow (BM) displacement in young children with malignant or nonmalignant disease remains to be defined. Using a gas chromatography-mass spectrometry assay, we evaluated plasma pharmacokinetics of busulfan in 33 children (median age, 9 months; range, 2 months to 2.

Chronopharmacology of high-dose busulfan in children.

In bone marrow transplantation, high-dose busulfan is given p.o., usually every 6 h over 4 consecutive days.