Toxin-Triggered Liposomes for the Controlled Release of Antibiotics to Treat Infections Associated with Gram-Negative Bacteria.

Antibiotic resistance has become an urgent threat to health care in recent years. The use of drug delivery systems provides advantages over conventional administration of antibiotics and can slow the development of antibiotic resistance. In the current study, we developed a toxin-triggered liposomal antibiotic delivery system, in which the drug release is enabled by the leukotoxin (LtxA) produced by the Gram-negative pathogen, Aggregatibacter actinomycetemcomitans. LtxA has previously been shown to mediate membrane disruption by promoting a lipid phase change in nonlamellar lipids, such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-methyl (N-methyl-DOPE). In addition, LtxA has been observed to bind strongly and nearly irreversibly to membranes containing large amounts of cholesterol. Here, we designed a liposomal delivery system composed of N-methyl-DOPE and cholesterol to take advantage of these interactions. Specifically, we hypothesized that liposomes composed of N-methyl-DOPE and cholesterol, encapsulating antibiotics, would be sensitive to LtxA, enabling controlled antibiotic release. We observed that liposomes composed of N-methyl-DOPE were sensitive to the presence of low concentrations of LtxA, and cholesterol increased the extent and kinetics of content release. The liposomes were stable under various storage conditions for at least 7 days. Finally, we showed that antibiotic release occurs selectively in the presence of an LtxA-producing strain of A. actinomycetemcomitans but not in the presence of a non-LtxA-expressing strain. Together, these results demonstrate that the designed liposomal vehicle enables toxin-triggered delivery of antibiotics to LtxA-producing strains of A. actinomycetemcomitans.

Cytogenetic characterization of childhood acute lymphoblastic leukemia in Nicaragua.

BACKGROUND: Within the frame of a twinning programme with Nicaragua, The La Mascota project, we evaluated in our study the contribution of cytogenetic characterization of acute lymphoblastic leukemia (ALL) as prognostic factor compared to clinical, morphological, and immunohistochemical parameters. METHODS: All patients with ALL treated at the only cancer pediatric hospital in Nicaragua during 2006 were studied prospectively. Diagnostic immunophenotyping was performed locally and bone marrow or blood samples were sent to the cytogenetic laboratory of Zurich for fluorescence in situ hybridization (FISH) analysis and G-banding. RESULTS: Sixty-six patients with ALL were evaluated. Their mean age at diagnosis was 7.3 years, 31.8% were >or=10 years. Thirty-four patients (51.5%) presented with hyperleucocytosis >or=50 x 10(9)/L, 45 (68.2%) had hepatosplenomegaly. Immunophenotypically 63/66 patients (95%) had a B-precursor, 2 (3%) a T- and 1 (1.5%) a B-mature ALL. FISH analysis demonstrated a TEL/AML1 fusion in 9/66 (14%), BCR/ABL fusion in 1 (1.5%), MLL rearrangement in 2 (3.1%), iAMP21 in 2 (3.1%), MYC rearrangement in 1 (1.5%), and high-hyperdiploidy in 16 (24%). All patients but two with TEL/AML1 fusion and high-hyperdiploidy were clinically and hematologically in the standard risk group whereas those with poor cytogenetic factors had clinical high-risk features and were treated intensively. CONCLUSIONS: Compared to Europe, the ALL population in Nicaragua is older, has a higher proportion of poor prognostic clinical and hematological features and receives more intensive treatment, while patients with TEL/AML1 translocations and high-hyperdiploidy are clinically in the standard risk group. Cytogenetics did not contribute as an additional prognostic factor in this setting.

On the front line of primary health care: the profile of community health workers in rural Quechua communities in Peru.

OBJECTIVE: To describe the profile of community health workers--health promoters, traditional birth attendants and traditional healers--in rural Quechua communities from Ayacucho, Peru. METHODS: Basic quantitative and qualitative information was gathered as part of a community health project implemented between 1997 and 2002 in 40 Andean communities with information from questionnaires, personal interviews and group discussions. RESULTS: The majority of current community health workers are men with limited education who are primarily Quechua speakers undertaking their work on a voluntary basis. Health promoters are mostly young, male, high school graduates. There exists a high drop-out rate among these workers. In contrast, traditional healers and traditional birth attendants possess an almost diametrically opposite profile in terms of age, education and drop-out rates, though males still predominate. At the community level the health promoters are the most visible community health workers. CONCLUSION: It is very important to consider and to be aware of the profile of community health workers in order to provide appropriate alternatives when working with these groups as well as with the indigenous population, particularly in terms of culture, language and gender issues.

Resultado del seguimiento a un grupo de pacientes graves de dengue hemorrágico / Result of follow-up to a group of patients suffering severe heorrhagic dengue

Se estudiaron 150 niños que habían sufrido dengue hemorrágico y shock por dengue. Dos años después de su ingreso y gravedad no presentaban secuelas evidentes, solamente un caso tenía alteradas las pruebas de la función hepática, y se comprobó más tarde que la causa no fue el dengue. Al interrogatorio se encontró una tendencia a presentar dolor abdominal en comparación con el período anterior a la enfermedad. No hubo repercusión en otros aparatos o sistemas, tampoco se encontró afectación psicológica. Todos los familiares expresaron su reconocimiento por la atención durante la enfermedad y por la preocupación mostrada en el seguimiento de sus hijos. Fue importante la labor desempeñada por el personal de Enfermería con su ayuda a la pronta recuperación del paciente para incorporarlo a la sociedad

Resultado del seguimiento a un grupo de pacientes graves de dengue hemorrágico / Result of follow-up to a group of patients suffering severe hemorrhagic dengue

Se estudiaron 150 niños que habían sufrido dengue hemorrágico y shock por dengue. Dos años después de su ingreso y gravedad no presentaban secuelas evidentes, solamente un caso tenía alteradas las pruebas de la función hepática, y se comprobó más tarde que la causa no fue el dengue. Al interrogatorio se encontró una tendencia a presentar dolor abdominal en comparación con el período anterior a la enfermedad. No hubo repercusión en otros aparatos o sistemas, tampoco se encontró afectación psicológica. Todos los familiares expresaron su reconocimiento por la atención durante la enfermedad y por la preocupación mostrada en el seguimiento de sus hijos. Fue importante la labor desempeñada por el personal de Enfermería con su ayuda a la pronta recuperación del paciente para incorporarlo a la sociedad