10 ns PEFs induce a histological response linked to cell death and cytotoxic T-lymphocytes in an immunocompetent mouse model of peritoneal metastasis.

PURPOSE: The application of nanosecond pulsed electric fields (nsPEFs) could be an effective therapeutic strategy for peritoneal metastasis (PM) from colorectal cancer (CRC). The aim of this study was to evaluate in vitro the sensitivity of CT-26 CRC cells to nsPEFs in combination with chemotherapeutic agents, and to observe the subsequent in vivo histologic response. METHODS: In vitro cellular assays were performed to assess the effects of exposure to 1, 10, 100, 500 and 1000 10 ns pulses in a cuvette or bi-electrode system at 10 and 200 Hz. nsPEF treatment was applied alone or in combination with oxaliplatin and mitomycin. Cell death was detected by flow cytometry, and permeabilization and intracellular calcium levels by fluorescent confocal microscopy after treatment. A mouse model of PM was used to investigate the effects of in vivo exposure to pulses delivered using a bi-electrode system; morphological changes in mitochondria were assessed by electron microscopy. Fibrosis was measured by multiphoton microscopy, while the histological response (HR; hematoxylin-eosin-safran stain), proliferation (KI67, DAPI), and expression of immunological factors (CD3, CD4, CD8) were evaluated by classic histology. RESULTS: 10 ns PEFs exerted a dose-dependent effect on CT-26 cells in vitro and in vivo, by inducing cell death and altering mitochondrial morphology after plasma membrane permeabilization. In vivo results indicated a specific CD8+ T cell immune response, together with a strong HR according to the Peritoneal Regression Grading Score (PRGS). CONCLUSIONS: The effects of nsPEFs on CT-26 were confirmed in a mouse model of CRC with PM.

Mother-to-child transmission of human T-lymphotropic virus type II.

OBJECTIVE: To determine the frequency of mother-to-child transmission of human T-lymphotropic virus type II (HTLV-II) and to explore its association with breast-feeding. DESIGN: Prospective study of children born to a cohort of HTLV-II-infected pregnant women and a cross-sectional study of older siblings of these children. METHODS: Maternal sera were screened with an HTLV-I enzyme immunoassay that detects antibody to both HTLV-I and HTLV-II. Confirmatory serologic testing and viral typing were performed by Western blot, radioimmunoprecipitation assay, enzyme immunoassay with HTLV type-specific proteins, and polymerase chain reaction (PCR) analysis of DNA from peripheral blood mononuclear cells. The presence of HTLV was evaluated in children by serial serologic and PCR testing. Molecular analysis of PCR products from infected mother-child pairs was performed by means of restriction fragment length polymorphism of HTLV-II long-terminal repeated sequences. RESULTS: Twenty-nine HTLV-II-infected women were identified, and these 29 women had 30 pregnancies during the study. Of 28 live infants born to infected women, 19 were examined and none was infected with HTLV-II. Sixteen older children less than 10 years of age who were born previously to the infected women were also examined; two were infected with HTLV-II. One infected child was breast fed for 2 months and the second was not breast fed. The viral patterns of restriction fragment length polymorphism in the two infected children were distinct, but the viral pattern in each child was identical to that of her mother's virus, suggesting mother-to-child transmission. Overall, among examined children, 1 of 7 breast-fed children (14%; 95% confidence interval: 0, 40) and 1 of 28 children who were not breast fed (3.6%; 95% confidence interval: 0, 10) were infected with HTLV-II. CONCLUSION: Mother-to-child transmission of HTLV-II occurs both with and without breast-feeding and at rates similar to those of HTLV-I. We believe that this is the first demonstration of mother-to-child transmission of HTLV-II in the absence of breast-feeding.

[A relatively good result: Western medicine among the Guajiro Indians]. / Un succès bien relatif: la médecine occidentale chez les Indiens Guajiro.

PIP: Disparities in underlying theoretical principles and methods of practice between Guajiro traditional medicine and Western medicine have seriously inhibited acceptance of Western medicine among the Guajiro of VEnezuela. Investigation of traditional Guajiro medicine discloses that 2 main disease categories are distinguished. In the less serious cases an assortment of home remedies are pragmatically applied, while in the more serious cases the ultimate cause of the illness must be determined by a shaman in consultation with auxiliary spirits before a treatment can be proposed. The treatment methods and social relationship between practitioner and patient are very different in Guajiro and Western medicine. The process of acculturation has affected the Guajiro in varying degrees; given present diversity it would be difficult to design a medical program suitable for all Guajiro. Sensitivity of Western practitioners working among the Guajiro to native medical theory would help insure that the recommended treatments were actually understood and carried out.^ieng