Detrusor overactivity in patients with cauda equina syndrome.

STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVE: To delineate the neurogenic bladder type in patients with cauda equina syndrome (CES) and to suggest, in light of the clinical, radiological, and electrophysiological findings, a possible cause of bladder dysfunction. SUMMARY OF BACKGROUND DATA: Many patients with CES experience bladder dysfunction, although the type of neurogenic bladder is quite variable in the clinical setting. Bladder dysfunction in patients with CES is usually areflexic or acontractile detrusor. However, detrusor overactivity (DOA) also reported the cases that cannot be explained by pure root injuries in the cauda equina region. METHODS: Patients with CES with neurogenic bladder were studied, all of whom (n = 61; mean age ± SD, 48.0 ± 15.9 yr) underwent urodynamic analysis, magnetic resonance imaging (MRI), and electrophysiology. According to the urodynamic findings, the neurogenic bladder was classified into 2 types: DOA and detrusor underactivity or acontractility. The highest level of injury (HLI) or level of injury was determined and analyzed on the basis of the clinical-urodynamic and electrophysiological findings, respectively. RESULTS: Twenty patients with CES (32.8%) showed DOA; in most of them (85.0%, 17/20 patients), the HLI on electrophysiological assessment was L2 or above. Forty-one patients with CES showed detrusor underactivity or acontractility; and most of the patients with CES whose HLI was L3 or below showed detrusor underactivity or acontractility (91.2%, 31/34 patients). None of the HLI or level of injury from the clinical or magnetic resonance imaging findings correlated with neurogenic bladder type. We also found that urodynamic findings including maximal detrusor pressure and bladder capacity was partially correlated with the HLI on electrophysiological assessment (r² = 0.244, P < 0.001 and r² = 0.330; P < 0.001, respectively). CONCLUSION: DOA was seen most often in patients with CES whose HLI was L2 or above, and might be associated with combined conus medullaris lesion. Electrophysiology might be the most useful assessment tool for prediction of neurogenic bladder type in patients with CES.

Recovery from radiation-induced bone marrow damage by HSP25 through Tie2 signaling.

PURPOSE: Whole-body radiation therapy can cause severe injury to the hematopoietic system, and therefore it is necessary to identify a novel strategy for overcoming this injury. METHODS AND MATERIALS: Mice were irradiated with 4.5 Gy after heat shock protein 25 (HSP25) gene transfer using an adenoviral vector. Then, peripheral blood cell counts, histopathological analysis, and Western blotting on bone marrow (BM) cells were performed. The interaction of HSP25 with Tie2 was investigated with mouse OP9 and human BM-derived mesenchymal stem cells to determine the mechanism of HSP25 in the hematopoietic system. RESULTS: HSP25 transfer increased BM regeneration and reduced apoptosis following whole-body exposure to ionizing radiation (IR). The decrease in Tie2 protein expression that followed irradiation of the BM was blocked by HSP25 transfer, and Tie2-positive cells were more abundant among the BM cells of HSP25-transferred mice, even after IR exposure. Following systemic RNA interference of Tie2 before IR, HSP25-mediated radioprotective effects were partially blocked in both mice and cell line systems. Stability of Tie2 was increased by HSP25, a response mediated by the interaction of HSP25 with Tie2. IR-induced tyrosine phosphorylation of Tie2 was augmented by HSP25 overexpression; downstream events in the Tie2 signaling pathway, including phosphorylation of AKT and EKR1/2, were also activated. CONCLUSIONS: HSP25 protects against radiation-induced BM damage by interacting with and stabilizing Tie2. This may be a novel strategy for HSP25-mediated radioprotection in BM.

A case of cephalic tetanus with unilateral ptosis and facial palsy.

Cephalic tetanus is defined as a combination of trismus and paralysis of one or more cranial nerves. Cranial nerves III, IV, VI, VII, and XII may be affected, but the facial nerve is most frequently implicated. A 64-year-old female visited hospital for left ptosis followed by facial palsy after a left forehead abrasion in a car accident. At nine days post injury, left ptosis developed, left facial palsy developed twelve days post injury, and at fifteen days post injury, trismus and dysphagia developed. The following day, there was progression of symptoms to generalized tetanus, such as dyspnea and generalized rigidity. Videofluoroscopic swallow study showed penetration and aspiration. We report a case of cephalic tetanus with ptosis, facial palsy, and dysphagia, which progressed to generalized tetanus.

Collet-sicard syndrome in a patient with jefferson fracture.

Collet-Sicard syndrome is a rare condition characterized by the unilateral paralysis of the 9th through 12th cranial nerves. We describe a case of a 46-year-old man who presented with dysphagia after a falling down injury. Computed tomography demonstrated burst fracture of the atlas. Physical examination revealed decreased gag reflex on the left side, decreased laryngeal elevation, tongue deviation to the left side, and atrophy of the left trapezius muscle. Videofluoroscopic swallowing study (VFSS) revealed frequent aspirations of a massive amount of thick liquid and incomplete opening of the upper esophageal sphincter during the pharyngeal phase. We report a rare case of Collet-Sicard syndrome caused by Jefferson fracture.

Application of bioluminescence imaging to therapeutic intervention of herpes simplex virus type I - Thymidine kinase/ganciclovir in glioma.

Lentiviral vector containing the HSV1-tk and firefly luciferase (fLuc) gene was infected into C6 and C6-TL expressing HSV1-tk and fLuc gene was generated. C6-TL showed higher [(125)I]IVDU uptake than C6. The survival rate of C6-TL decreased more rapidly with increasing GCV dose and was well correlated with fLuc activity. The images of microPET clearly demonstrated higher uptake of [(18)F]FHBG into the C6-TL tumor. Inhibition of tumor growth was observed in C6-TL tumor-bearing mice treated with GCV through tumor size measurement and bioluminescence imaging. The therapeutic effect of HSV1-tk/GCV system can be monitored using bioluminescent imaging and tumor size measurement.

Synergistic growth inhibition by combination of adenovirus mediated p53 transfer and cisplatin in ovarian cancer cell lines.

OBJECTIVE: This study was to investigate the synergistic growth inhibitory effect by combination of adenovirus mediated p53 gene transfer and cisplatin in ovarian cancer cell lines with different p53 gene mutation patterns. METHODS: Three ovarian cancer cell lines, p53 deleted SKOV3, p53 mutated OVCAR-3, and PA-1 with wild-type p53 were transduced with human adenovirus vectors carrying p53 gene (Ad-p53) and treated with a sublethal concentration of cisplatin before and after Ad-p53. The cell number was counted daily for 5 days after Ad-p53 transduction. Western blotting was used to identify p53 and p21 protein expressions, and flow cytometric analysis was performed to investigate any change of DNA ploidy after Ad-p53 transfer. RESULTS: Ad-p53 transduced cells successfully expressed p53 and p21 proteins after 48 hours of Ad-p53 transduction. Synergistic growth inhibition by combination of Ad-p53 and cisplatin was detected only in SKOV3 and OVCAR-3 cells, but not in PA-1 cells. In p53 deleted SKOV3 cells, cisplatin treatment after Ad-p53 showed higher growth inhibition than the treatment before Ad-p53 transduction, and reverse relationship was observed in p53 mutated OVCAR-3 cells. In SKOV3 cells, the fraction of cells at G2/M phase increased after cisplatin treatment, however, it decreased dramatically with Ad-p53 transduction. CONCLUSION: The synergistic growth inhibition by combination of Ad-p53 and cisplatin may depend on the p53 status and the temporal sequence of cisplatin treatment, suggesting judicious selective application of this strategy in clinical trials.

Radioprotective effect of heat shock protein 25 on submandibular glands of rats.

Irradiation (IR) is a fundamental treatment modality for head and neck malignancies. However, a significant drawback of IR treatment is irreversible damage of salivary gland in the IR field. In the present study, we investigated whether heat shock protein (HSP) 25 could be used as a radioprotective molecule for radiation-induced salivary gland damage in rats. HSP25 as well as inducible HSP70 (HSP70i) that were delivered to the salivary gland via an adenoviral vector significantly ameliorated radiation-induced salivary fluid loss. Radiation-induced apoptosis, caspase-3 activation, and poly(ADP-ribose) polymerase cleavage in acinar cells, granular convoluted cells, and intercalated ductal cells were also inhibited by HSP25 or HSP70i transfer. The alteration of salivary contents, including amylase, protein, Ca+, Cl-, and Na+, was also attenuated by HSP25 transfer. Histological analysis revealed almost no radiation-induced damage in salivary gland when HSP25 was transferred. Aquaporin 5 expression in salivary gland was inhibited by radiation; and HSP25 transfer to salivary gland prevented this alteration. The protective effect of HSP70i on radiation-induced salivary gland damage was less or delayed than that of HSP25. These results indicate that HSP25 is a good candidate molecule to protect salivary gland from the toxicity of IR.

In vivo comparison of IVDU and IVFRU in HSV1-TK gene expressing tumor bearing rats.

(E)-5-(2-Iodovinyl)-2'-deoxyuridine (IVDU) and (E)-5-(2-iodovinyl)-2'-fluoro-2'-deoxyuridine (IVFRU) are potential substrates of Herpes Simplex Virus type 1 thymidine kinase (HSV-TK). In the present study, cellular uptake of radioiodinated substrates was found to be low in wild type MCA cells, but high in HSV-TK gene expressing cells. The carrier-free substrates, in particular, showed higher cellular uptake than carrier-added compounds. Biodistribution showed that the %ID/g of the MCA-TK/MCA tumor ratio of IVDU injected at 1, 4, and 24h were 1.1, 0.9 and 1.3, and those of IVFRU were 1.7, 1.7 and 1.8 respectively. Therefore, both IVDU and IVFRU could possibly be used as radiopharmaceuticals to evaluate reporter gene expression. However, IVFRU was more specific and stable than IVDU for selective non-invasive imaging of HSV-TK expression.

Gene therapy with GM-CSF, interleukin-4 and herpes simplex virus thymidine kinase shows strong antitumor effect on lung cancer.

BACKGROUND: Inadequate release of tumor antigens (TA) and a defective antigen presentation by dendritic cells (DC) are the major mechanisms for how tumor cells can escape the host immune surveillance. MATERIALS AND METHODS: Combined gene therapy of herpes simplex virus thymidine kinase (Tk), GM-CSF and IL-4 via adenoviral vector was tested to solve these problems. After establishing wild-type Lewis lung carcinoma (LLC), vaccinations with LLC transduced with Tk +/- GM-CSF +/- IL-4 were performed. RESULTS: The LLC-Tk and LLC-Tk-IL-4 vaccination groups failed to suppress the wild-type LLC growth. However, the LLC-Tk-GM-CSF group showed a delayed wild-type tumor growth and LLC-Tk-GM-CSF-IL-4 markedly suppressed tumor growth and increased the survival rate of mice. Immunohistochemistry of the spleen showed a dense infiltration of DCs in the mice treated with LLC-Tk-GM-CSF-IL-4. CONCLUSION: Combined gene therapy with Tk-GM-CSF-IL-4 was effective in inducing antitumor immunity by enhancing the DC functions.