18 research outputs found

    Laparoscopic revision of a ventriculoperitoneal shunt

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    Ventriculoperitoneal (VP) shunts are the most common treatment modality for hydrocephalus. Distal catheter malfunction represents a surgical emergency and a significant cause of procedural morbidity. We report the case of a patient with acute abdominal pain following VP shunt insertion. On examination she had a tender, irreducible bulge at the abdominal laparotomy site. Exploratory laparoscopy of the abdomen yielded no abdominal wall abnormalities. At the same time, the distal catheter was noted to be absent. The abdominal bulge was incised along the laparotomy scar and clear cerebrospinal fluid was encountered. The incision was explored and the distal catheter was coiled and knotted within the preperitoneal space. The catheter was laparoscopically returned to the peritoneal cavity. This case exemplifies the utility of laparoscopy for VP shunt revision and we present a review of laparoscopic shunt revision

    Replication-Competent Herpes Simplex Virus Vector G207 and Cisplatin Combination Therapy for Head and Neck Squamous Cell Carcinoma

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    Replication-competent virus vectors are attractive therapeutic agents for cancer. G207, a second-generation, multimutated herpes simplex virus type 1 (HSV-1), is one such vector that is safe in primates and efficacious against human tumors in athymic mice. Squamous cell carcinoma is the most frequently encountered malignancy of the head and neck, and the chemotherapeutic agent cisplatin is a standard treatment for recurrent head and neck cancer. In this study we examine the therapeutic potential of G207, alone and in combination with cisplatin, against squamous cell carcinoma. Human squamous cell carcinoma cell lines are sensitive to G207 replication and cytotoxicity in vitro at a multiplicity of infection of 0.01, including cisplatin sensitive (UMSCC-22A), moderately sensitive (UMSCC-38), and weakly sensitive (SQ20B) cell lines. Cisplatin did not inhibit the cytopathic effect of G207. G207 inhibited the growth of established subcutaneous head and neck tumors in athymic mice. The therapeutic effects of cisplatin and G207 in vivo were independent. However, in cisplatin-sensitive tumors (UMSCC-38), combination therapy resulted in 100% cures in contrast to 42% with G207 or 14% with cisplatin alone. We conclude that G207 should be considered for the treatment of head and neck cancer and that combination with chemotherapeutic agents may improve efficacy

    World Health Organization Grades II and III meningiomas are rare in the cranial base and spine

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    OBJECTIVE: This study was undertaken to assess a possible relationship between the tumor location and the incidence of World Health Organization (WHO) Grades II and III meningiomas

    GBM Derived Gangliosides Induce T Cell Apoptosis through Activation of the Caspase Cascade Involving Both the Extrinsic and the Intrinsic Pathway

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    <div><p>Previously we demonstrated that human glioblastoma cell lines induce apoptosis in peripheral blood T cells through partial involvement of secreted gangliosides. Here we show that GBM-derived gangliosides induce apoptosis through involvement of the TNF receptor and activation of the caspase cascade. Culturing T lymphocytes with GBM cell line derived gangliosides (10-20μg/ml) demonstrated increased ROS production as early as 18 hrs as indicated by increased uptake of the dye H<sub>2</sub>DCFDA while western blotting demonstrated mitochondrial damage as evident by cleavage of Bid to t-Bid and by the release of cytochrome-c into the cytosol. Within 48-72 hrs apoptosis was evident by nuclear blebbing, trypan blue positivity and annexinV/7AAD staining. GBM-ganglioside induced activation of the effector caspase-3 along with both initiator caspases (-9 and -8) in T cells while both the caspase-8 and -9 inhibitors were equally effective in blocking apoptosis (60% protection) confirming the role of caspases in the apoptotic process. Ganglioside-induced T cell apoptosis did not involve production of TNF-α since anti-human TNFα antibody was unable to protect T cells from nuclear blebbing and subsequent cell death. However, confocal microscopy demonstrated co-localization of GM2 ganglioside with the TNF receptor and co-immunoprecipitation experiments showed recruitment of death domains FADD and TRADD with the TNF receptor post ganglioside treatment, suggesting direct interaction of gangliosides with the TNF receptor. Further confirmation of the interaction between GM2 and TNFR1 was obtained from confocal microscopy data with wild type and TNFR1 KO (TALEN mediated) Jurkat cells, which clearly demonstrated co-localization of GM2 and TNFR1 in the wild type cells but not in the TNFR1 KO clones. Thus, GBM-ganglioside can mediate T cell apoptosis by interacting with the TNF receptor followed by activation of both the extrinsic and the intrinsic pathway of caspases.</p></div

    Human apoptosis proteome profiler array demonstrates ganglioside induced activation of pro-apoptotic and downregulation of anti-apoptotic proteins.

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    <p>Differential expression of pro- and anti-apoptotic proteins were examined in T cells cultured with CCF52 ganglioside (15ÎĽg/ml) for 48hrs using a human proteome profiler array kit (R&D Biosystems) as represented in Fig 4A and 4B. Fig 4C shows the entire apoptosis proteome profile array of T cells in presence or absence of CCF52 ganglioside. Data is representative of a single experiment out of two experiments done.</p
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