Combination immunotherapy in a patient with hemodialysis therapy and metachronous bilateral clear cell renal cell carcinoma: Case report and literature review.

Combination immunotherapy is a treatment strategy in patients with renal cell carcinoma that has proved to be effective in phase III randomized clinical trials. These studies do not include patients with end stage kidney disease on hemodialysis. We discuss this case about a patient with metachronous bilateral clear cell renal cell carcinoma, managed with bilateral nephrectomy and ulterior requirement of hemodialysis, with lung and intestinal progression, managed with combination immunotherapy, with a partial response and absence of adverse effects related to treatment.

G6PD deficiency, primaquine treatment, and risk of haemolysis in malaria-infected patients.

BACKGROUND: The incidence of malaria in the Americas has decreased markedly in recent years. Honduras and the other countries of Mesoamerica and the island of Hispaniola have set the goal of eliminating native malaria by the year 2020. To achieve this goal, Honduras has recently approved national regulations to expand the possibilities of a shortened double dose primaquine (PQ) treatment for vivax malaria. Considering this new shortened anti-malarial treatment, the high frequency of G6PDd genotypes in Honduras, and the lack of routinely assessment of the G6PD deficiency status, this study aimed at investigating the potential association between the intake of PQ and haemolysis in malaria-infected G6PDd subjects. METHODS: This was a prospective cohort and open-label study. Participants with malaria were recruited. Plasmodium vivax infection was treated with 0.25 mg/kg of PQ daily for 14 days. Safety and signs of haemolysis were evaluated by clinical criteria and laboratory values before and during the 3rd and 7th day of PQ treatment. G6PD status was assessed by a rapid test (CareStart™) and two molecular approaches. RESULTS: Overall 55 participants were enrolled. The frequency of G6PD deficient genotypes was 7/55 (12.7%), where 5/7 (71.4%) were hemizygous A- males and 2/7 (28.6%) heterozygous A- females. Haemoglobin concentrations were compared between G6PD wild type (B) and G6PDd A- subjects, showing a significant difference between the means of both groups in the 3rd and 7th days. Furthermore, a statistically significant difference was evident in the change in haemoglobin concentration between the 3rd day and the 1st day for both genotypes, but there was no statistical difference for the change in haemoglobin concentration between the 7th day and the 1st day. Besides these changes in the haemoglobin concentrations, none of the patients showed signs or symptoms associated with severe haemolysis, and none needed to be admitted to a hospital for further medical attention. CONCLUSIONS: The findings support that the intake of PQ during 14 days of treatment against vivax malaria is safe in patients with a class III variant of G6PDd. In view of the new national regulations in the shortened treatment of vivax malaria for 7 days, it is advisable to be alert of potential cases of severe haemolysis that could occur among G6PD deficient hemizygous males with a class II mutation such as the Santamaria variant, previously reported in the country.

Calnexin, calreticulin and cytoskeleton-associated proteins modulate uptake and growth of Legionella pneumophila in Dictyostelium discoideum.

The haploid amoeba Dictyostelium discoideum is a versatile host system for studying cellular aspects of Legionella pathogenicity. Previous studies have shown that the internalization of L. pneumophila leads to an endoplasmic reticulum (ER)-derived organelle that supports intracellular replication of the bacteria. In this study a roadmap of host-cell factors involved in this process was developed. Phagocytosis assays with specific cellular inhibitors and the effects of well defined host-cell mutants revealed that cytoplasmic calcium levels, cytoskeleton-associated proteins and the calcium-binding proteins of the ER, calreticulin and calnexin, specifically influence the uptake and intracellular growth of L. pneumophila. Confocal microscopic time series with green fluorescent protein (GFP)-tagged calnexin and calreticulin demonstrated the accumulation of both proteins in the phagocytic cup of L. pneumophila-infected host cells. In contrast to the control experiment with Escherichia coli-containing phagosomes, both proteins decorated the replicative vacuole of L. pneumophila during the entire growth phase of the bacteria. The cumulative effects of cytosolic calcium levels, the spatial distribution of calnexin and calreticulin, and the defective invasion and replication of L. pneumophila in calnexin- and calreticulin-minus cells suggest that these factors are part of a regulatory system that leads to the specific vacuole of L. pneumophila.

Técnica pilates como alternativa para el tratamiento fisioterapéutico / Pilates technique as an alternative to the physiotherapy treatment

La revisión de técnicas alternativas, en las que se cuenta el pilates, es un punto de partida para evaluar su necesidad dentro del abordaje integral de la fisioterapia, que permitirá después la evaluación de dicha demanda a partir del manejo teórico de la misma.El presente estudio se realizó en dos etapas, la primera tuvo como fin evaluar mediante una encuesta el grado de conocimiento, aplicación y cobertura de utilización que tienen los docentes fisioterapeutas de todas las facultades a nivel de Bogotá, sobre la técnica Pilates, por lo cual se constituye como investigación de tipo descriptivo. Los resultados obtenidos en la encuesta mostraron que el 82% no tenían conocimiento acerca del tema.La segunda etapa fue de tipo tecnológico, y estuvo dirigida a la reproducción de un modulo de capacitación dirigido a cinco jueces fisioterapeutas, con el fin de dar validez y juzgar su pertinencia en el campo de la fisioterapia. Por medio de una encuesta que se realizó al final de la capacitación se demostró que el 100% de la población encontró interesante su aplicación en este campo, además quedó la inquietud de indagar y demostrar en qué tipo de población podría tener resultados benéficos o nocivos.

Various bacterial pathogens and symbionts infect the amoeba Dictyostelium discoideum.

The haploid soil amoeba Dictyostelium discoideum is a suitable model organism to study host-pathogen interactions with Legionella pneumophila. In this study we show that D. discoideum AX2 is also susceptible to infection with other important human pathogens and obligate intracellular symbionts. Infection assays demonstrated that Legionella-like amoebal pathogens (LLAP K62), Mycobacterium avium and the obligate intracellular endosymbionts of Acanthamoeba sp. strains TUME1, UWE25 and UWC6 were able to multiply within Dictyostelium. Salmonella typhimurium and Pseudomonas aeruginosa also invaded Dictyostelium, however were degraded shortly after uptake. Comitin-minus host cells were more permissive to infections with L. pneumophila and LLAP K62. Furthermore, this mutation significantly delayed the degradation of S. typhimurium. Accompanying electron and fluorescence microscopy of infected AX2 cells revealed that L. pneumophila and M. avium replicate within vacuoles, while LLAP K62, TUME1 and UWE25 were tightly enclosed by membranous structures within the cytoplasm. The beta-proteobacterium UWC6 was found to persist in the cytoplasm. The observed subcellular locations which correspond to the locations within the respective natural hosts suggest that D. discoideum is a representative model system for these pathogens and symbionts.