Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC).

BACKGROUND: BRCA1-associated breast cancers have been associated to a triple-negative phenotype. The prevalence of BRCA1 germline mutations in young onset TNBC based on informativeness of family history has not been reported. PATIENTS AND METHODS: From January 2008 to May 2009 were collected blood and tumor samples from patients with TNBC younger than 50 years and without a family history of breast and ovarian cancer in first- and second-degree relatives. Analysis of BRCA1 germline mutations was made. Age at diagnosis and informativeness of family history (presence of female in first- and second-degree relatives alive until age 45) was collected in all cases. Immunohistochemistry of basal-like features was performed centrally in all available tumors. RESULTS: Seven pathogenic mutations were detected in 92 patients (7.6 %), two of them in patients younger than 35 years (28.6 %) (Fisher's exact test, p = 0.631). Three non-classified variants were detected (3.2 %). Family history was informative in two patients with a pathogenic mutation (28.6 %) and not informative in five (71.4 %) (Fisher's exact test, p = 0.121). Of the seven patients with a pathogenic mutation, four had a basal-like phenotype. CONCLUSION: Patients with apparently sporadic TNBC younger than 50 years and a non-informative family history are candidates for germline genetic testing of BRCA1.

Application of magnetically induced hyperthermia in the model protozoan Crithidia fasciculata as a potential therapy against parasitic infections.

BACKGROUND: Magnetic hyperthermia is currently a clinical therapy approved in the European Union for treatment of tumor cells, and uses magnetic nanoparticles (MNPs) under time-varying magnetic fields (TVMFs). The same basic principle seems promising against trypanosomatids causing Chagas disease and sleeping sickness, given that the therapeutic drugs available have severe side effects and that there are drug-resistant strains. However, no applications of this strategy against protozoan-induced diseases have been reported so far. In the present study, Crithidia fasciculata, a widely used model for therapeutic strategies against pathogenic trypanosomatids, was targeted with Fe(3)O(4) MNPs in order to provoke cell death remotely using TVMFs. METHODS: Iron oxide MNPs with average diameters of approximately 30 nm were synthesized by precipitation of FeSO(4) in basic medium. The MNPs were added to C. fasciculata choanomastigotes in the exponential phase and incubated overnight, removing excess MNPs using a DEAE-cellulose resin column. The amount of MNPs uploaded per cell was determined by magnetic measurement. The cells bearing MNPs were submitted to TVMFs using a homemade AC field applicator (f = 249 kHz, H = 13 kA/m), and the temperature variation during the experiments was measured. Scanning electron microscopy was used to assess morphological changes after the TVMF experiments. Cell viability was analyzed using an MTT colorimetric assay and flow cytometry. RESULTS: MNPs were incorporated into the cells, with no noticeable cytotoxicity. When a TVMF was applied to cells bearing MNPs, massive cell death was induced via a nonapoptotic mechanism. No effects were observed by applying TVMF to control cells not loaded with MNPs. No macroscopic rise in temperature was observed in the extracellular medium during the experiments. CONCLUSION: As a proof of principle, these data indicate that intracellular hyperthermia is a suitable technology to induce death of protozoan parasites bearing MNPs. These findings expand the possibilities for new therapeutic strategies combating parasitic infection.

[Nephrotic syndrome associated with symmetrical multiple lipomatosis (Madelung's disease)]. / Síndrome nefrótico asociado a la lipomatosis múltiple simétrica. Enfermedad de Madelung.

We present a case of multiple symmetric lipomatosis Type I (Madelung's disease) with severe organic affection, hepatic cirrhosis, sever sensitive polyneuropathy and neuropathic ulceration at the left lower limb. A nephrotic syndrome developed in a larval form due to proliferative glomerulonephritis as the result of a metainfectious complications of the infection at the lower limb. We discuss the etiopathogenicity of the organic affection and we highlight the pathogenic links between the disease and its complications.

Activity of E-3846, a new fluoroquinolone, in vitro and in experimental cystitis and pyelonephritis in rats.

The in vitro antibacterial activity of E-3846, a new fluoroquinolone carboxylic acid derivative with a pyrrol ring substituent at position 7, was evaluated in comparison with norfloxacin and ciprofloxacin. E-3846 was more active than the reference quinolones against Staphylococcus species, including methicillin-resistant strains. E-3846 was similar to ciprofloxacin and more active than norfloxacin against Streptococcus (Enterococcus) faecalis. In general, E-3846 was more active than norfloxacin against members of the family Enterobacteriaceae, but less active than ciprofloxacin. For Pseudomonas aeruginosa, the MICs giving 90% inhibition for E-3846, norfloxacin, and ciprofloxacin were 2, 1, and 0.25 micrograms/ml, respectively. The activity of E-3846 increased at acid pH; in contrast, acid pH caused a pronounced decrease in the activity of norfloxacin and ciprofloxacin. In vivo, E-3846 demonstrated excellent therapeutic efficacy in treating experimental S. faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa cystitis and pyelonephritis in rats.

Muscular structural changes following fadenoperation.

The authors describe the macroscopic, histological, and ultrastructural findings observed in an experimental animal model of the fadenoperation . Grossly, muscular fibrosis and musculo-scleral adhesions were well established after the second postoperative month. Histologic findings demonstrated the development of a granulomatous, foreign body reaction around the musculo-scleral fixation suture, collagenization of the muscle tissue from the first postoperative month and degenerative phenomena in the muscle fibers. Electron transmission microscopic study showed atrophy and angulation with distortion of the myofibrillar matrix, along with alteration of the Z bands of muscle fibers, mitochondrial alteration, and dilatation of the sarcotubular system. All these experimental findings suggest the relative irreversible effects of the fadenoperation after the early postoperative period and for the first time, demonstrated that this surgical technique alters the muscle structure.