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Sample records for single intratumoral injection

  1. Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer.

    Science.gov (United States)

    Tchou, Julia; Zhao, Yangbing; Levine, Bruce L; Zhang, Paul J; Davis, Megan M; Melenhorst, Jan Joseph; Kulikovskaya, Irina; Brennan, Andrea L; Liu, Xiaojun; Lacey, Simon F; Posey, Avery D; Williams, Austin D; So, Alycia; Conejo-Garcia, Jose R; Plesa, Gabriela; Young, Regina M; McGettigan, Shannon; Campbell, Jean; Pierce, Robert H; Matro, Jennifer M; DeMichele, Angela M; Clark, Amy S; Cooper, Laurence J; Schuchter, Lynn M; Vonderheide, Robert H; June, Carl H

    2017-12-01

    Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR T cells are ineffective for solid tumors to date. We found that the cell-surface molecule c-Met was expressed in ∼50% of breast tumors, prompting the construction of a CAR T cell specific for c-Met, which halted tumor growth in immune-incompetent mice with tumor xenografts. We then evaluated the safety and feasibility of treating metastatic breast cancer with intratumoral administration of mRNA-transfected c-Met-CAR T cells in a phase 0 clinical trial (NCT01837602). Introducing the CAR construct via mRNA ensured safety by limiting the nontumor cell effects (on-target/off-tumor) of targeting c-Met. Patients with metastatic breast cancer with accessible cutaneous or lymph node metastases received a single intratumoral injection of 3 × 10 7 or 3 × 10 8 cells. CAR T mRNA was detectable in peripheral blood and in the injected tumor tissues after intratumoral injection in 2 and 4 patients, respectively. mRNA c-Met-CAR T cell injections were well tolerated, as none of the patients had study drug-related adverse effects greater than grade 1. Tumors treated with intratumoral injected mRNA c-Met-CAR T cells were excised and analyzed by immunohistochemistry, revealing extensive tumor necrosis at the injection site, cellular debris, loss of c-Met immunoreactivity, all surrounded by macrophages at the leading edges and within necrotic zones. We conclude that intratumoral injections of mRNA c-Met-CAR T cells are well tolerated and evoke an inflammatory response within tumors. Cancer Immunol Res; 5(12); 1152-61. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Therapeutic Endoscopic Ultrasonography: Intratumoral Injection for Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Lawrence A. Shirley

    2013-01-01

    Full Text Available Pancreatic adenocarcinoma is an aggressive disease that has poor outcomes despite maximal traditional therapies. Thus, treatment of this cancer demands innovative strategies to be used in addition to standing therapies in order to provide new avenues of care. Here, we describe the technique of using endoscopic ultrasound in order to directly inject both novel and conventional therapies into pancreatic tumors. We detail the rationale behind this strategy and the many benefits it provides. We then describe our technique in detail, including our experience injecting the AdV-tk adenoviral vector to create an in situ vaccine effect.

  3. Investigation of acupuncture-point injection combined with intratumor injection of radionuclide phosphorus 32 in treatment of metastatic carcinoma

    International Nuclear Information System (INIS)

    Chou, H.C.

    1986-01-01

    Seventeen patients with carcinoma and three patients with benign lesions of the head were studied by acupuncture-point injection combined with intratumor injection of radionuclide P-32 for treatment of metastatic carcinoma. The metastatic cervical nodules shrank to half their original sizes within 2-3 weeks in five cases of nasopharyngeal carcinoma. The injected dose ranged from 0.222 to 0.421 mCi, approximately 10 times less than that given by the ordinary method. The acupuncture points are selected according to the Theory of Channels and Collaterals of Chinese traditional medicine. The mechanism of therapeutic action of radionuclide P-32 is possibly by the delivery of destructive ionizing radiation from beta emission properties of P-32. This method appears to offer a low-dose means of P-32 treatment of metastatic carcinoma

  4. Intratumor photosensitizer injection for photodynamic therapy: Pre-clinical experience with methylene blue, Pc 4, and Photofrin

    Science.gov (United States)

    Baran, Timothy M.; Foster, Thomas H.

    2016-03-01

    Intravenous administration of some photosensitizers, including the FDA-approved Photofrin, results in significant systemic photosensitivity and a 2-3-day drug-light interval. Direct intratumor injection of photosensitizer could potentially eliminate these negative aspects of photodynamic therapy (PDT), while requiring a lower photosensitizer dose to achieve comparable drug concentration in the target tissue. We performed PDT using intratumor injection of 3 photosensitizers, methylene blue (MB), Pc 4, and Photofrin, in mouse tumor models. After a 0-15 minute drug-light interval, illumination was delivered by appropriate diode lasers. For animals receiving MB or Pc 4, surface illumination was delivered using a microlens-terminated fiber. For animals receiving Photofrin, interstitial illumination was delivered by a 1 cm diffuser. In animals receiving MB or Pc 4, tumor dimensions were measured daily post-PDT, with a cure being defined as no palpable tumor 90 days post-treatment. For Photofrin, animals were sacrificed 24 hours post-PDT and tumors were excised, with samples HE stained to assess PDT-induced necrosis. 55% of tumors were cured with MB-PDT, and significant tumor growth delay (p=0.002) was observed for Pc 4. For Photofrin PDT, the mean necrosis radius was 3.4+/-0.8 mm, compared to 2.9+/-1.3 mm for systemic administration, which was not a significant difference (p=0.58). Intratumoral injection of the photosensitizers methylene blue, Pc 4, and Photofrin is feasible, and results in appreciable tumor response. Further investigation is necessary to optimize treatment protocols and assess the systemic photosensitivity induced by intratumor injection.

  5. Mammary lymphatic scintiscans by intratumoral injection in the assessment of breast cancer. 105 examinations in 100 patients

    International Nuclear Information System (INIS)

    Gabelle, P.; Comet, M.; Bodin, J.P.; Dupre, A; Carpentier, E.; Bolla, M.; Swiercz, P.

    1981-01-01

    One hundred and five scintiscans of the mammary lymphatic system were performed in 100 patients with breast cancer by intratumoral injection of 99m Tc-labelled colloidal rhenium. The progression of the radioactive colloidal agent was followed on a series of films taken 1, 2 and 4 hours after the injection, and the images obtained were compared with post-operative findings of lymph node involvement. Patients with more than 3 carcinomatous lymph nodes had less than 2 foci of activity, while those with less than 3 carcinomatous lymph nodes had more than 2 foci of activity, owing to more rapid progression of the compound. The difference was highly significant (p [fr

  6. Brachytherapy with Intratumoral Injections of Radiometal-Labeled Polymers That Thermoresponsively Self-Aggregate in Tumor Tissues.

    Science.gov (United States)

    Sano, Kohei; Kanada, Yuko; Kanazaki, Kengo; Ding, Ning; Ono, Masahiro; Saji, Hideo

    2017-09-01

    Brachytherapy is a type of radiotherapy wherein titanium capsules containing therapeutic radioisotopes are implanted within tumor tissues, enabling high-dose radioirradiation to tumor tissues around the seeds. Although marked therapeutic effects have been demonstrated, brachytherapy needs a complicated implantation technique under general anesthesia and the seeds could migrate to other organs. The aim of this study was to establish a novel brachytherapy using biocompatible, injectable thermoresponsive polymers (polyoxazoline [POZ]) labeled with 90 Y, which can self-aggregate above a specific transition temperature (Tt), resulting in long-term intratumoral retention of radioactivity and therapeutic effect. Therefore, we evaluated the tumor retention of radiolabeled POZ derivatives and their therapeutic effects. Methods: Using oxazoline derivatives with ethyl (Et), isopropyl (Isp), and propyl (Pr) side chains, we synthesized EtPOZ, IspPOZ, Isp-PrPOZ (heteropolymer), and PrPOZ and measured their characteristic Tts. The intratumoral retention of 111 In-labeled POZ was evaluated until 7 d after injection in nude mice bearing PC-3 human prostate cancer. The intratumoral localization of 111 In-labeled POZ derivatives was investigated by an autoradiographic study. Furthermore, a therapeutic study using 90 Y-labeled Isp-PrPOZ was performed, and tumor growth and survival rate were evaluated. Results: The Tts of EtPOZ, IspPOZ, Isp-PrPOZ, and PrPOZ (∼20 kDa) were greater than 70°C, 34°C, 25°C, and 19°C, respectively. In the intratumoral injection study, Isp-PrPOZ and PrPOZ (2,000 μM) with Tts lower than tumor temperature (33.5°C under anesthesia) showed a significantly higher retention of radioactivity at 1 d after injection (73.6% and 73.9%, respectively) than EtPOZ (5.6%) and IspPOZ (15.8%). Even at low injected dose (100 μM), Isp-PrPOZ exhibited high retention (68.3% at 1 d). The high level of radioactivity of Isp-PrPOZ was retained in the tumor 7 d after injection

  7. Pilot study of intratumoral injection of recombinant heat shock protein 70 in the treatment of malignant brain tumors in children

    Directory of Open Access Journals (Sweden)

    Shevtsov MA

    2014-06-01

    Full Text Available Maxim A Shevtsov,1,2 Alexander V Kim,2 Konstantin A Samochernych,2 Irina V Romanova,3 Boris A Margulis,1 Irina V Guzhova,1 Igor V Yakovenko,2 Alexander M Ischenko,4 William A Khachatryan2 1Institute of Cytology of the Russian Academy of Sciences, 2AL Polenov Russian Research Scientific Institute of Neurosurgery, 3IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 4Research Institute of Highly Pure Biopreparations, St Petersburg, Russian Federation Abstract: Intratumoral injections of recombinant heat shock protein (Hsp70 were explored for feasibility in patients with brain tumors. Patients aged 4.5–14 years with untreated newly diagnosed tumors (n=12 were enrolled. After tumor resection, five injections of recombinant Hsp70 (total 2.5 mg were administered into the resection cavity through a catheter. Before administration of Hsp70 and after the last injection, specific immune responses to the autologous tumor lysate were evaluated using the delayed-type hypersensitivity test. Further, peripheral blood was monitored to identify possible changes in lymphocyte subpopulations, cytokine levels, and the cytolytic activity of natural killer cells. The follow-up period in this trial was 12 months. Intratumoral injections of Hsp70 were well tolerated by patients. One patient had a complete clinical response documented by radiologic findings and one patient had a partial response. A positive delayed-type hypersensitivity test was observed in three patients. In peripheral blood, there was a shift from cytokines provided by Th2 cells toward cytokines of a Th1-cell-mediated response. These data corresponded to changes in lymphocyte subpopulations. Immunosuppressive T-regulatory cell levels were also reduced after injection of Hsp70, as well as production of interleukin-10. The cytolytic activity of natural killer cells was unchanged. The present study demonstrates the feasibility of intratumoral delivery

  8. Intratumoral Injection of an Adenovirus Expressing Interleukin 2 Induces Regression and Immunity in a Murine Breast Cancer Model

    Science.gov (United States)

    Addison, Christina L.; Braciak, Todd; Ralston, Robert; Muller, William J.; Gauldie, Jack; Graham, Frank L.

    1995-08-01

    Rodent tumor cells engineered to secrete cytokines such as interleukin 2 (IL-2) or IL-4 are rejected by syngeneic recipients due to an enhanced antitumor host immune response. An adenovirus vector (AdCAIL-2) containing the human IL-2 gene has been constructed and shown to direct secretion of high levels of human IL-2 in infected tumor cells. AdCAIL-2 induces regression of tumors in a transgenic mouse model of mammary adenocarcinoma following intratumoral injection. Elimination of existing tumors in this way results in immunity against a second challenge with tumor cells. These findings suggest that adenovirus vectors expressing cytokines may form the basis for highly effective immunotherapies of human cancers.

  9. In Situ Conversion of Melanoma Lesions into Autologous Vaccine by Intratumoral Injections of α-gal Glycolipids

    Directory of Open Access Journals (Sweden)

    Uri Galili

    2010-05-01

    Full Text Available Autologous melanoma associated antigens (MAA on murine melanoma cells can elicit a protective anti-tumor immune response following a variety of vaccine strategies. Most require effective uptake by antigen presenting cells (APC. APC transport and process internalized MAA for activation of anti-tumor T cells. One potential problem with clinical melanoma vaccines against autologous tumors may be that often tumor cells do not express surface markers that label them for uptake by APC. Effective uptake of melanoma cells by APC might be achieved by exploiting the natural anti-Gal antibody which constitutes ~1% of immunoglobulins in humans. This approach has been developed in a syngeneic mouse model using mice capable of producing anti-Gal. Anti-Gal binds specifically to α-gal epitopes (Galα1-3Galα1-4GlcNAc-R. Injection of glycolipids carrying α-gal epitopes (α-gal glycolipids into melanoma lesions results in glycolipid insertion into melanoma cell membranes, expression of α-gal epitopes on the tumor cells and binding of anti-Gal to these epitopes. Interaction between the Fc portions of bound anti-Gal and Fcγ receptors on APC induces effective uptake of tumor cells by APC. The resulting anti-MAA immune response can be potent enough to destroy distant micrometastases. A clinical trial is now open testing effects of intratumoral α-gal glycolipid injections in melanoma patients.

  10. In Situ Conversion of Melanoma Lesions into Autologous Vaccine by Intratumoral Injections of α-gal Glycolipids

    Energy Technology Data Exchange (ETDEWEB)

    Galili, Uri, E-mail: Uri.Galili@umassmed.edu [Department of Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655 (United States); Albertini, Mark R.; Sondel, Paul M. [University of Wisconsin Carbone Cancer Center, Madison, WI. 53792 (United States); Wigglesworth, Kim; Sullivan, Mary; Whalen, Giles F. [Department of Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655 (United States)

    2010-05-04

    Autologous melanoma associated antigens (MAA) on murine melanoma cells can elicit a protective anti-tumor immune response following a variety of vaccine strategies. Most require effective uptake by antigen presenting cells (APC). APC transport and process internalized MAA for activation of anti-tumor T cells. One potential problem with clinical melanoma vaccines against autologous tumors may be that often tumor cells do not express surface markers that label them for uptake by APC. Effective uptake of melanoma cells by APC might be achieved by exploiting the natural anti-Gal antibody which constitutes ~1% of immunoglobulins in humans. This approach has been developed in a syngeneic mouse model using mice capable of producing anti-Gal. Anti-Gal binds specifically to α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). Injection of glycolipids carrying α-gal epitopes (α-gal glycolipids) into melanoma lesions results in glycolipid insertion into melanoma cell membranes, expression of α-gal epitopes on the tumor cells and binding of anti-Gal to these epitopes. Interaction between the Fc portions of bound anti-Gal and Fcγ receptors on APC induces effective uptake of tumor cells by APC. The resulting anti-MAA immune response can be potent enough to destroy distant micrometastases. A clinical trial is now open testing effects of intratumoral α-gal glycolipid injections in melanoma patients.

  11. MRI-monitored intra-tumoral injection of iron-oxide labeled Clostridium novyi-NT anaerobes in pancreatic carcinoma mouse model.

    Directory of Open Access Journals (Sweden)

    Linfeng Zheng

    Full Text Available To validate the feasibility of labeling Clostridium novyi-NT (C.novyi-NT anaerobes with iron-oxide nanoparticles for magnetic resonance imaging (MRI and demonstrate the potential to use MRI to visualize intra-tumoral delivery of these iron-oxide labeled C.novyi-NT during percutaneous injection procedures.All studies were approved by IACUC. C.novyi-NT were labeled with hybrid iron-oxide Texas red nanoparticles. Growth of labeled and control samples were evaluated with optical density. Labeling was confirmed with confocal fluorescence and transmission electron microscopy (TEM. MRI were performed using a 7 Tesla scanner with T2*-weighted (T2*W sequence. Contrast-to-noise ratio (CNR measurements were performed for phantoms and signal-to-noise ratio (SNR measurements performed in C57BL/6 mice (n = 12 with Panc02 xenografts before and after percutaneous injection of iron-oxide labeled C.novyi-NT. MRI was repeated 3 and 7 days post-injection. Hematoxylin-eosin (HE, Prussian blue and Gram staining of tumor specimens were performed for confirmation of intra-tumoral delivery.Iron-oxide labeling had no influence upon C.novyi-NT growth. The signal intensity (SI within T2*W images was significantly decreased for iron-oxide labeled C.novyi-NT phantoms compared to unlabeled controls. Under confocal fluorescence microscopy, the iron-oxide labeled C.novyi-NT exhibited a uniform red fluorescence consistent with observed regions of DAPI staining and overall labeling efficiency was 100% (all DAPI stained C.novyi-NT exhibited red fluorescence. Within TEM images, a large number iron granules were observed within the iron-oxide labeled C.novyi-NT; these were not observed within unlabeled controls. Intra-procedural MRI measurements permitted in vivo visualization of the intra-tumoral distribution of iron-oxide labeled C.novyi-NT following percutaneous injection (depicted as punctate regions of SI reductions within T2*-weighted images; tumor SNR decreased

  12. Longitudinal immune monitoring of patients receiving intratumoral injection of a MART-1 T-cell receptor-transduced cell line (C-Cure 709)

    DEFF Research Database (Denmark)

    Køllgaard, Tania; Duval, Lone; Schmidt, Henrik

    2009-01-01

    BACKGROUND AIMS: Adoptive transfer of tumor-specific lymphocytes is a promising strategy in the treatment of cancer. We conducted intratumoral administration of an allogeneic irradiated continuous T-cell line (C-Cure 709) expressing an HLA-A2-restricted MART-1-specific T-cell receptor (TCR......) into HLA-A2(+) melanoma patients. The C-Cure 709 cell line is cytotoxic against MART-1(+) HLA-A2(+) melanoma cell lines and secretes several immune stimulatory cytokines upon stimulation. METHODS: Anti-tumor immune responses against the commonly expressed tumor antigen (Ag) MART-1 were longitudinally...... analyzed in peripheral blood by fluorescence-activated cell sorting (FACS) before and after intratumoral injection of C-Cure 709. RESULTS: No treatment-induced increase in Ag-specific T-cell frequencies was observed in peripheral blood, and the phenotype of MART-1-specific T cells was very stable during...

  13. CT-guided percutaneous intratumoral chemotherapy with a novel cisplatin/epinephrine injectable gel for the treatment of unresectable malignant liver tumors

    International Nuclear Information System (INIS)

    Engelmann, K.; Mack, M.G.; Straub, R.; Eichler, K.; Zangos, S.; Vogl, T.J.

    2000-01-01

    Purpose: To evaluate prospectively the volumetric changes of tumor and necrosis in unresectable malignant liver tumors and the clinical aspects after CT-guided direct intratumoral administration of a novel cisplatin/epinephrine injectable gel in a clinical phase II study. Patients and methods: 8 patients with 17 colorectal liver metastases with a mean volume of 42 ml were treated with a mean of 5.1 injections and 8 patients with 11 HCC nodules (mean volume of 22.1 ml) with a mean of 3.25 treatments with CT-guided local administration of a novel cisplatin/epinephrine gel. This method of administration provides a higher local and lower systemic drug concentration. Volumes of tumor and necrosis prior to and after treatment were measured by computer-generated volumetric analysis. Results: Contrast-enhanced studies verified pretherapeutic tumor necrosis with a value of 12.6% in the metastases and 0.6% in the HCC nodules. Intratumoral drug administration resulted in a necrotic volume of 110% in metastases and 128% in HCC versus the mean initial tumor volume, at least 4 treatments resulted in 122% necrosis in metastases and 130% in HCC. Local therapy control rate for the follow-up to 6 months was 38% and 83.3% for the group of metastases and HCC, respectively. Conclusions: Direct intratumoral injection of a novel cisplatin/epinephrine injectable gel results in an induction of a relevant necrosis in malignant liver tumors, with a substantially higher local therapy control rate for HCC compared to colorectal metastases. (orig.) [de

  14. Combination of External Beam Radiotherapy (EBRT) With Intratumoral Injection of Dendritic Cells as Neo-Adjuvant Treatment of High-Risk Soft Tissue Sarcoma Patients

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    Finkelstein, Steven E., E-mail: steven.finkelstein@moffitt.org [H. Lee Moffitt Cancer Center, Tampa, FL (United States); Iclozan, Cristina; Bui, Marilyn M.; Cotter, Matthew J.; Ramakrishnan, Rupal; Ahmed, Jamil; Noyes, David R.; Cheong, David; Gonzalez, Ricardo J.; Heysek, Randy V.; Berman, Claudia; Lenox, Brianna C.; Janssen, William; Zager, Jonathan S.; Sondak, Vernon K.; Letson, G. Douglas; Antonia, Scott J. [H. Lee Moffitt Cancer Center, Tampa, FL (United States); Gabrilovich, Dmitry I., E-mail: dmitry.gabrilovich@moffitt.org [H. Lee Moffitt Cancer Center, Tampa, FL (United States)

    2012-02-01

    Purpose: The goal of this study was to determine the effect of combination of intratumoral administration of dendritic cells (DC) and fractionated external beam radiation (EBRT) on tumor-specific immune responses in patients with soft-tissue sarcoma (STS). Methods and Material: Seventeen patients with large (>5 cm) high-grade STS were enrolled in the study. They were treated in the neoadjuvant setting with 5,040 cGy of EBRT, split into 28 fractions and delivered 5 days per week, combined with intratumoral injection of 10{sup 7} DCs followed by complete resection. DCs were injected on the second, third, and fourth Friday of the treatment cycle. Clinical evaluation and immunological assessments were performed. Results: The treatment was well tolerated. No patient had tumor-specific immune responses before combined EBRT/DC therapy; 9 patients (52.9%) developed tumor-specific immune responses, which lasted from 11 to 42 weeks. Twelve of 17 patients (70.6%) were progression free after 1 year. Treatment caused a dramatic accumulation of T cells in the tumor. The presence of CD4{sup +} T cells in the tumor positively correlated with tumor-specific immune responses that developed following combined therapy. Accumulation of myeloid-derived suppressor cells but not regulatory T cells negatively correlated with the development of tumor-specific immune responses. Experiments with {sup 111}In labeled DCs demonstrated that these antigen presenting cells need at least 48 h to start migrating from tumor site. Conclusions: Combination of intratumoral DC administration with EBRT was safe and resulted in induction of antitumor immune responses. This suggests that this therapy is promising and needs further testing in clinical trials design to assess clinical efficacy.

  15. Computed Tomography Demonstration of the Production and Distribution of Oxygen Gas Following Intratumoral Injection of a New Radiosensitizer (KORTUC) for Patients with Breast Cancer-Is Intratumoral Injection Not an Ideal Approach to Solve the Major Problem of Tumor Hypoxia in Radiotherapy?

    Science.gov (United States)

    Hayashi, Naoya; Ogawa, Yasuhiro; Kubota, Kei; Okino, Kazuhiro; Akima, Ryo; Morita-Tokuhiro, Shiho; Tsuzuki, Akira; Yaogawa, Shin; Nishioka, Akihito; Miyamura, Mitsuhiko

    2016-04-01

    We previously developed a new enzyme-targeting radiosensitization treatment named Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which contains hydrogen peroxide and sodium hyaluronate for injection into various types of tumors. For breast cancer treatment, the radiosensitization agent was injected into the tumor tissue twice a week under ultrasonographic guidance, immediately prior to each administration of radiation therapy. At approximately three hours after the second or third injection, computed tomography (CT) was performed to confirm the production and distribution of oxygen gas generated from the KORTUC radiosensitization agent by catalysis of peroxidases contained mainly in tumor tissue. The purpose of this study was to demonstrate that tumor hypoxia could be overcome by such a procedure and to evaluate the method of intratumoral injection in terms of confirming oxygen distribution in the target tumor tissue and around the tumor to be visualized on dedicated CT imaging. Three-dimensional reconstructed maximum intensity projection imaging of contrast-enhanced breast magnetic resonance imaging was used to compare the position of the tumor and that of the generated oxygen. Distributed oxygen gas was confirmed in the tumor tissue and around it in all 10 patients examined in the study. A region of oxygen gas was measured as an average value of -457.2 Hounsfield units (HU) as a region of interest. A slightly increased HU value compared to the density of air or oxygen was considered due to the presence of tumor tissue in the low-density area on 5-mm-thick reconstructed CT imaging. The results of this study showed that intratumoral oxygen was successfully produced by intratumoral KORTUC injection under ultrasonographic guidance, and that tumor hypoxia, which is considered a main cause of radioresistance in currently used Linac (linear accelerator) radiation therapy for malignant neoplasms, could be resolved by this method.

  16. Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: Effects of nonuniform intratumoral dose distribution

    International Nuclear Information System (INIS)

    Hrycushko, Brian A.; Li Shihong; Goins, Beth; Otto, Randal A.; Bao, Ande

    2011-01-01

    Purpose: Focused radiation therapy by direct intratumoral infusion of lipid nanoparticle (liposome)-carried beta-emitting radionuclides has shown promising results in animal model studies; however, little is known about the impact the intratumoral liposomal radionuclide distribution may have on tumor control. The primary objective of this work was to investigate the effects the intratumoral absorbed dose distributions from this cancer therapy modality have on tumor control and treatment planning by combining dosimetric and radiobiological modeling with in vivo imaging data. Methods: 99m Tc-encapsulated liposomes were intratumorally infused with a single injection location to human head and neck squamous cell carcinoma xenografts in nude rats. High resolution in vivo planar imaging was performed at various time points for quantifying intratumoral retention following infusion. The intratumoral liposomal radioactivity distribution was obtained from 1 mm resolution pinhole collimator SPECT imaging coregistered with CT imaging of excised tumors at 20 h postinfusion. Coregistered images were used for intratumoral dosimetric and radiobiological modeling at a voxel level following extrapolation to the therapeutic analogs, 186 Re/ 188 Re liposomes. Effective uniform dose (EUD) and tumor control probability (TCP) were used to assess therapy effectiveness and possible methods of improving upon tumor control with this radiation therapy modality. Results: Dosimetric analysis showed that average tumor absorbed doses of 8.6 Gy/MBq (318.2 Gy/mCi) and 5.7 Gy/MBq (209.1 Gy/mCi) could be delivered with this protocol of radiation delivery for 186 Re/ 188 Re liposomes, respectively, and 37-92 MBq (1-2.5 mCi)/g tumor administered activity; however, large intratumoral absorbed dose heterogeneity, as seen in dose-volume histograms, resulted in insignificant values of EUD and TCP for achieving tumor control. It is indicated that the use of liposomes encapsulating radionuclides with higher

  17. Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

    DEFF Research Database (Denmark)

    Gerlinger, Marco; Rowan, Andrew J.; Horswell, Stuart

    2012-01-01

    BACKGROUND: Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples.METHODSTo examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy ...

  18. Intratumoral injection of radioactive holmium-166 microspheres in recurrent head and neck squamous cell carcinoma : preliminary results of first use

    NARCIS (Netherlands)

    Bakker, Robbert C; van Es, Robert J J; Rosenberg, Antoine J W P; van Nimwegen, Sebastiaan A; Bastiaannet, Remco; de Jong, Hugo W A M; Nijsen, Johannes F W; Lam, Marnix G E H

    BACKGROUND: Limited treatment options exist for patients with locoregional recurrences of head and neck squamous cell carcinoma (HNSCC). In the palliative setting, a single session, minimally invasive, and relatively safe therapy is desirable. This case series illustrates the feasibility of a direct

  19. Tunneling spin injection into single layer graphene.

    Science.gov (United States)

    Han, Wei; Pi, K; McCreary, K M; Li, Yan; Wong, Jared J I; Swartz, A G; Kawakami, R K

    2010-10-15

    We achieve tunneling spin injection from Co into single layer graphene (SLG) using TiO₂ seeded MgO barriers. A nonlocal magnetoresistance (ΔR(NL)) of 130  Ω is observed at room temperature, which is the largest value observed in any material. Investigating ΔR(NL) vs SLG conductivity from the transparent to the tunneling contact regimes demonstrates the contrasting behaviors predicted by the drift-diffusion theory of spin transport. Furthermore, tunnel barriers reduce the contact-induced spin relaxation and are therefore important for future investigations of spin relaxation in graphene.

  20. Intratumoral Approaches for the Treatment of Melanoma.

    Science.gov (United States)

    Bommareddy, Praveen K; Silk, Ann W; Kaufman, Howard L

    There have been significant advances in the immunotherapy of melanoma over the last decade. The tumor microenvironment is now known to promote an immune-suppressive milieu that can block effective immune-mediated tumor rejection. Several novel strategies designed to overcome local immunosuppression hold promise for treatment of melanoma and other cancers. These approaches include oncolytic viruses, plasmid DNA delivery, Toll-like receptor agonists, inflammatory dyes, cytokines, checkpoint inhibitors, immunomodulatory agents, and host and pathogenic cell-based vectors. In addition, there are several novel methods for local drug delivery, including direct injection, image-guided, electroporation, and nanodelivery techniques under study. The approval of talimogene laherparepvec (Imlygic), an attenuated, recombinant oncolytic herpesvirus, for melanoma treatment is the first intratumoral agent to receive regulatory approval for the treatment of patients with melanoma. This review will focus on the rationale for intratumoral treatment in melanoma, describe the clinical and safety data for some of the agents in clinical development, and provide a perspective for future clinical investigation with intratumoral approaches. Melanoma has been a paradigm tumor for progress in targeted therapy and immunotherapy and will likely also be the tumor to establish the therapeutic role of intratumoral treatment for cancer.

  1. Discharge characteristics of a double injection-valve single-pump injection system

    Science.gov (United States)

    Lee, Dana W; Marsh, E T

    1937-01-01

    The discharge characteristics of two similar injection valves operated by a single-cylinder fuel-injection pump were determined with an apparatus that measured the quantity of fuel discharged from each valve during every 0.5 degrees of pump rotation. It was found that similar discharges took place from the two valves at all pump speeds when the valve-opening pressures, the nozzle-orifice diameters, and the injection-tube lengths were the same for both valves. Under these conditions, the effects of changing the pump speed, the pump throttle setting, or the nozzle orifice diameter were very similar to those occurring with a single-injection valve. By a proper selection of discharge-orifice areas and valve-opening pressures it was possible to obtain a great many combinations of discharge quantities, discharge rates, and injection timings for the two valves. A series of tests using injection tubes of unequal lengths for the two valves showed that under these conditions the injection timing and the fuel quantity discharged from each valve varies widely and erratically with changes in the pump speed.

  2. Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

    DEFF Research Database (Denmark)

    Gerlinger, Marco; Rowan, Andrew J.; Horswell, Stuart

    2012-01-01

    BACKGROUND: Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples.METHODSTo examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy...... and 4EBP phosphorylation in vivo and constitutive activation of mTOR kinase activity in vitro. Mutational intratumor heterogeneity was seen for multiple tumor-suppressor genes converging on loss of function; SETD2, PTEN, and KDM5C underwent multiple distinct and spatially separated inactivating...... mutations within a single tumor, suggesting convergent phenotypic evolution. Gene-expression signatures of good and poor prognosis were detected in different regions of the same tumor. Allelic composition and ploidy profiling analysis revealed extensive intratumor heterogeneity, with 26 of 30 tumor samples...

  3. Conversion of Tumors into Autologous Vaccines by Intratumoral Injection of α-Gal Glycolipids that Induce Anti-Gal/α-Gal Epitope Interaction

    Directory of Open Access Journals (Sweden)

    Uri Galili

    2011-01-01

    Full Text Available Anti-Gal is the most abundant antibody in humans, constituting 1% of immunoglobulins. Anti-Gal binds specifically α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R. Immunogenicity of autologous tumor associated antigens (TAA is greatly increased by manipulating tumor cells to express α-gal epitopes and bind anti-Gal. Glycolipids with αgal epitopes (α-gal glycolipids injected into tumors insert into the tumor cell membrane. Anti-Gal binding to the multiple α-gal epitopes de novo presented on the tumor cells results in targeting of these cells to APC via the interaction between the Fc portion of the bound anti-Gal and Fcγ; receptors on APC. The APC process and present immunogenic TAA peptides and thus, effectively activate tumor specific CD4+ helper T cells and CD8+ cytotoxic T cells which destroy tumor cells in micrometastases. The induced immune response is potent enough to overcome immunosuppression by Treg cells. A phase I clinical trial indicated that α-gal glycolipid treatment has no adverse effects. In addition to achieving destruction of micrometastases in cancer patients with advance disease, α-gal glycolipid treatment may be effective as neo-adjuvant immunotherapy. Injection of α-gal glycolipids into primary tumors few weeks prior to resection can induce a protective immune response capable of destroying micrometastases expressing autologous TAA, long after primary tumor resection.

  4. Performance characterization of pneumatic single pellet injection system

    International Nuclear Information System (INIS)

    Schuresko, D.D.; Milora, S.L.; Hogan, J.T.; Foster, C.A.; Combs, S.K.

    1982-01-01

    The Oak Ridge National Laboratory single-shot pellet injector, which has been used in plasma fueling experiments on ISX and PDX, has been upgraded and extensively instrumented in order to study the gas dynamics of pneumatic pellet injection. An improved pellet transport line was developed which utilizes a 0.3-cm-diam by 100-cm-long guide tube. Pellet gun performance was characterized by measurements of breech and muzzle dynamic pressures and by pellet velocity and mass determinations. Velocities up to 1.4 km/s were achieved for intact hydrogen pellets using hydrogen propellant at 5-MPa breech pressure. These data have been compared with new pellet acceleration calculations which include the effects of propellant friction, heat transfer, time-dependent boundary conditions, and finite gun geometry. These results provide a basis for the extrapolation of present-day pneumatic injection system performance to velocities in excess of 2 km/s

  5. A novel doxorubicin-loaded in situ forming gel based high concentration of phospholipid for intratumoral drug delivery.

    Science.gov (United States)

    Wu, Wenqi; Chen, Hui; Shan, Fengying; Zhou, Jing; Sun, Xun; Zhang, Ling; Gong, Tao

    2014-10-06

    The purpose of this study was to develop a safe and effective drug delivery system for local chemotherapy. A novel injectable in-situ-forming gel system was prepared using small molecule materials, including phospholipids, medium chain triglycerides (MCTs), and ethanol. Thus, this new sustained release system was named PME (first letter of phospholipids, MCT, and ethanol). PME has a well-defined molecule structure, a high degree of safety, and better biocompatible characteristics. It was in sol state with low viscosity in vitro and turned into a solid or semisolid gel in situ after injection. When loaded with doxorubicin (Dox), PME-D (doxorubicin-loaded PME) exhibited notably antitumor efficiency in S180 sarcoma tumors bearing mice after a single intratumoral injection. In vitro, PME-D had remarkable antiproliferative efficacies against MCF-7 breast cancer cells for over 5 days. Moreover, the initial burst effect can hardly be observed from PME system, which was different from many other in-situ-forming gels. The in vivo biodistribution study showed the high Dox concentration in tumors compared with other major organs after PME-D intratumoral administration. The strong signal in tumors was retained for more than 14 days after one single injection. The high concentration of Dox in tumor and long-term retention may explain the superior therapeutic efficacy and reduced side effects. The PME-D in-situ-forming gel system is a promising drug delivery system for local chemotherapy.

  6. Cost-Utility of a Single-Injection Combined Corticosteroid-Hyaluronic Acid Formulation vs a 2-Injection Regimen of Sequential Corticosteroid and Hyaluronic Acid Injections.

    Science.gov (United States)

    Belzile, Etienne L; Deakon, Robert T; Vannabouathong, Christopher; Bhandari, Mohit; Lamontagne, Martin; McCormack, Robert

    2017-01-01

    Research has shown early and sustained relief with a combination therapy of a corticosteroid (CS) and hyaluronic acid (HA) in knee osteoarthritis (OA) patients. This can be administered via a single injection containing both products or as separate injections. The former may be more expensive when considering only product cost, but the latter incurs the additional costs and time of a second procedure. The purpose of this study was to compare the cost-utility of the single injection with the 2-injection regimen. The results of this analysis revealed that the single-injection formulation of a CS and HA may be cost-effective, assuming a willingness-to-pay of $50 000 per quality-adjusted life year gained, for symptomatic relief of OA symptoms. This treatment may also be more desirable to patients who find injections to be inconvenient or unpleasant.

  7. Efficacy of a single ultrasound-guided injection for the treatment of hip osteoarthritis.

    LENUS (Irish Health Repository)

    Atchia, Ismaël

    2011-01-01

    Intra-articular injection is effective for osteoarthritis, but the best single injection strategy is not known, nor are there established predictors of response. The objectives of this study were to assess and predict response to a single ultrasound-guided injection in moderate to severe hip osteoarthritis.

  8. Increasing energy efficiency of a gasoline direct injection engine through optimal synchronization of single or double injection strategies

    International Nuclear Information System (INIS)

    Costa, Michela; Sorge, Ugo; Allocca, Luigi

    2012-01-01

    Highlights: ► Advantages of split injection in a GDI engine are studied through numerical simulation. ► At high load and speed, rich conditions, split injection does not improve engine performance. ► At moderate load and speed, lean conditions, double injection improves charge stratification. ► Optimal double injection increases work, reduces HC and increases NO. - Abstract: The greatest fuel efficiency advantages of gasoline direct injection (GDI) engines are achieved under the so-called mixed mode boosting, where mixture characteristics are properly adapted to the specific working condition. In particular, in the medium range of load and speed, overall lean mixtures are suitable of being used in the so-called direct injection stratified charge operation. Present paper reports the results of numerical optimization analyses aimed at increasing the energetic efficiency of a GDI engine equipped with a high pressure multi-hole injector under both single and double injection events. In moderate-load moderate-speed lean conditions, the single or double injection synchronization in the working cycle is effected through a procedure that couples a 3D numerical model of the in-cylinder processes with an optimization tool. The choice of both the start of the injection events and the time of spark advance is realized to maximize the engine work. The optimal double injection solution is shown to increase the engine energy efficiency with respect to the case injection is realized in one shot, thus confirming that split injections improve the quality of the charge stratification under lean operation. The effect on the major pollutants is also discussed.

  9. Magnetic nanoparticle biodistribution following intratumoral administration

    Energy Technology Data Exchange (ETDEWEB)

    Giustini, A J; Hoopes, P J [Dartmouth Medical School and the Thayer School of Engineering, 8000 Cummings Hall, Dartmouth College, Hanover, NH 03755 (United States); Ivkov, R, E-mail: andrew.j.giustini@dartmouth.edu [Triton BioSystems, Inc. , Chelmsford, MA 01824 (United States)

    2011-08-26

    Recently, heat generated by iron oxide nanoparticles (IONPs) stimulated by an alternating magnetic field (AMF) has shown promise in the treatment of cancer. To determine the mechanism of nanoparticle-induced cytotoxicity, the physical association of the cancer cells and the nanoparticles must be determined. We have used transmission electron microscopy (TEM) to define the time dependent cellular uptake of intratumorally administered dextran-coated, core-shell configuration IONP having a mean hydrodynamic diameter of 100-130 nm in a murine breast adenocarcinoma cell line (MTG-B) in vivo. Tumors averaging volumes of 115 mm{sup 3} were injected with iron oxide nanoparticles. The tumors were then excised and fixed for TEM at time 0.1-120 h post-IONP injection. Intracellular uptake of IONPs was 5.0, 48.8 and 91.1% uptake at one, 2 and 4 h post-injection of IONPs, respectively. This information is essential for the effective use of IONP hyperthermia in cancer treatment.

  10. Experimental investigations of a single cylinder genset engine with common rail fuel injection system

    Directory of Open Access Journals (Sweden)

    Gupta Paras

    2014-01-01

    Full Text Available Performance and emissions characteristics of compression ignition (CI engines are strongly dependent on quality of fuel injection. In an attempt to improve engine combustion, engine performance and reduce the exhaust emissions from a single cylinder constant speed genset engine, a common rail direct injection (CRDI fuel injection system was deployed and its injection timings were optimized. Results showed that 34°CA BTDC start of injection (SOI timings result in lowest brake specific fuel consumption (BSFC and smoke opacity. Advanced injection timings showed higher cylinder peak pressure, pressure rise rate, and heat release rate due to relatively longer ignition delay experienced.

  11. Radiosensitizing effect of intratumoral interleukin-12 gene electrotransfer in murine sarcoma

    Directory of Open Access Journals (Sweden)

    Sedlar Ales

    2013-01-01

    Full Text Available Abstract Background Interleukin-12 (IL-12 based radiosensitization is an effective way of tumor treatment. Local cytokine production, without systemic shedding, might provide clinical benefit in radiation treatment of sarcomas. Therefore, the aim was to stimulate intratumoral IL-12 production by gene electrotransfer of plasmid coding for mouse IL-12 (mIL-12 into the tumors, in order to explore its radiosensitizing effect after single or multiple intratumoral gene electrotransfer. Methods Solid SA-1 fibrosarcoma tumors, on the back of A/J mice, were treated intratumorally by mIL-12 gene electrotransfer and 24 h later irradiated with a single dose. Treatment effectiveness was measured by tumor growth delay and local tumor control assay (TCD50 assay. With respect to therapeutic index, skin reaction in the radiation field was scored. The tumor and serum concentrations of cytokines mIL-12 and mouse interferon γ (mIFNγ were measured. Besides single, also multiple intratumoral mIL-12 gene electrotransfer before and after tumor irradiation was evaluated. Results Single intratumoral mIL-12 gene electrotransfer resulted in increased intratumoral but not serum mIL-12 and mIFNγ concentrations, and had good antitumor (7.1% tumor cures and radiosensitizing effect (21.4% tumor cures. Combined treatment resulted in the radiation dose-modifying factor of 2.16. Multiple mIL-12 gene electrotransfer had an even more pronounced antitumor (50% tumor cures and radiosensitizing (86.7% tumor cures effect. Conclusions Single or multiple intratumoral mIL-12 gene electrotransfer resulted in increased intratumoral mIL-12 and mIFNγ cytokine level, and may provide an efficient treatment modality for soft tissue sarcoma as single or adjuvant therapy to tumor irradiation.

  12. Optimal sampling strategies to assess inulin clearance in children by the inulin single-injection method

    NARCIS (Netherlands)

    van Rossum, Lyonne K.; Mathot, Ron A. A.; Cransberg, Karlien; Vulto, Arnold G.

    2003-01-01

    Glomerular filtration rate in patients can be determined by estimating the plasma clearance of inulin with the single-injection method. In this method, a single bolus injection of inulin is administered and several blood samples are collected. For practical and convenient application of this method

  13. Injection molded nanofluidic chips: Fabrication method and functional tests using single-molecule DNA experiments

    DEFF Research Database (Denmark)

    Utko, Pawel; Persson, Karl Fredrik; Kristensen, Anders

    2011-01-01

    We demonstrate that fabrication of nanofluidic systems can be greatly simplified by injection molding of polymers. We functionally test our devices by single-molecule DNA experiments in nanochannels.......We demonstrate that fabrication of nanofluidic systems can be greatly simplified by injection molding of polymers. We functionally test our devices by single-molecule DNA experiments in nanochannels....

  14. Electroluminescence from single nanowires by tunnel injection: an experimental study

    OpenAIRE

    Zimmler, Mariano A.; Bao, Jiming; Shalish, Ilan; Yi, Wei; Yoon, Joonah; Narayanamurti, Venkatesh; Capasso, Federico

    2007-01-01

    We present a hybrid light-emitting diode structure composed of an n-type gallium nitride nanowire on a p-type silicon substrate in which current is injected along the length of the nanowire. The device emits ultraviolet light under both bias polarities. Tunnel-injection of holes from the p-type substrate (under forward bias) and from the metal (under reverse bias) through thin native oxide barriers consistently explains the observed electroluminescence behaviour. This work shows that the stan...

  15. Single-needle temporomandibular joint arthrocentesis with hyaluronic acid injections. Preliminary data after a five-injection protocol.

    Science.gov (United States)

    Manfredini, D; Guarda-Nardini, L; Ferronato, G

    2009-10-01

    The classical technique for temporomandibular joint (TMJ) arthrocentesis provides a double access to the joint space, which may lead to patient's postoperatory discomfort. For this reason, a less invasive, single-needle approach has been recently described, and the present investigation reports findings on a case series of patients with TMJ osteoarthritis treated with hyaluronic acid injections following a single needle arthrocentesis. METHODS. Fourteen consecutive patients with a diagnosis of TMJ osteoarthritis according to the Research Diagnostic Criteria for Temporo-mandibular Disorders were treated with a cycle of five weekly injections of hyaluronic acid after arthrocentesis. A number of subjective (pain at rest and mastication, masticatory efficiency, functional limitation, subjective efficacy of treatment, tolerability of treatment) and objective (maximum assisted and unassited mouth opening, protrusive and laterotrusive movements) outcome variables were assessed before and after the treatment period. At the end of the five-injection protocol, significant improvements were showed in almost all the subjective outcome variables. Tolerability of the treatment was good on a four-point ordinal scale since the time of the first injection. The present investigation suggested that the single needle technique for TMJ hyaluronic injection following arthrocentesis in osteoarthritic joints may have promising applications in the clinical setting, which have to be confirmed with future studies.

  16. Electroluminescence from single nanowires by tunnel injection: an experimental study

    Science.gov (United States)

    Zimmler, Mariano A.; Bao, Jiming; Shalish, Ilan; Yi, Wei; Yoon, Joonah; Narayanamurti, Venkatesh; Capasso, Federico

    2007-06-01

    We present a hybrid light-emitting diode structure composed of an n-type gallium nitride nanowire on a p-type silicon substrate in which current is injected along the length of the nanowire. The device emits ultraviolet light under both bias polarities. Tunnel injection of holes from the p-type substrate (under forward bias) and from the metal (under reverse bias) through thin native oxide barriers consistently explains the observed electroluminescence behaviour. This work shows that the standard p-n junction model is generally not applicable to this kind of device structure.

  17. Spread of dye after single thoracolumbar paravertebral injection in infants. A cadaveric study.

    Science.gov (United States)

    Albokrinov, Andrew A; Fesenko, Ulbolgan A

    2014-06-01

    Thoracolumbar paravertebral block (PVB) is one method of providing regional anaesthesia for abdominal wall surgery in children. It is common practice when performing a PVB for abdominal wall anaesthesia to inject a certain volume of local anaesthetic solution in the paravertebral space at several levels. This increases the duration of the procedure and makes it more invasive. To determine the character of dye spread in infants' paravertebral space, to check the feasibility of single injection PVB and to determine the optimal volume of injectate necessary to cover the paravertebral segments responsible for sensation of the lower abdomen. Experimental study. Single centre, University Hospital, April 2013 to August 2013. Twenty infant cadavers. Ultrasound-guided, single thoracolumbar paravertebral injections were performed on infant cadavers. The total number of paravertebral segments stained after dye injection and specific vertebral levels of cephalad and caudad spread of dye in the paravertebral space. Dye was present in the paravertebral spaces of all cadavers. Spread of dye within the paravertebral space was different depending on dye volume. Strong correlation was found between the volume of injectate and the number of paravertebral segments involved. The number of spinal nerve roots surrounded with dye corresponded with the number of paravertebral segments involved. T11, T12 and L1 nerve roots were stained in all cadavers. The optimal injectate volume to involve T10-L1 segments was defined as 0.2 to 0.3  ml  kg(-1). Single thoracolumbar paravertebral injection at T12-L1 level leads to caudad and cephalad spread of injectate in a dose-dependent manner. Single injection thoracolumbar paravertebral injections could be performed for lower abdomen anaesthesia in infants. We suggest that a single injection of 0.2 to 0.3  ml  kg(-1) of local anaesthetic in the thoracolumbar paravertebral space could provide adequate coverage of the dermatomes of the lower

  18. The potentiation of the effect of radiation treatment by intratumoral delivery of cisplatin

    International Nuclear Information System (INIS)

    Yapp, Donald T.T.; Lloyd, David K.; Zhu, Julian; Lehnert, Shirley M.

    1998-01-01

    Purpose: To compare potentiation of the effects of acute or fractionated radiation by cisplatin when the drug was delivered intratumorally by implanted biodegradable polymer, by intraperitoneal injection, or by intraperitoneal osmotic pump. Methods and Materials: Radiation was delivered to a mouse tumor (RIF-1) either in a single dose or in a fractionated regime in conjunction with cisplatin delivered either as a bolus injection, with an osmotic pump, or with a biodegradable polymer rod containing cisplatin. The osmotic pump was implanted in the intraperitoneal cavity of the mouse while the polymer implants were placed directly in the tumor. As the polymer degrades, the drug is released at the treatment site leading to high local concentrations. The osmotic pump, in contrast, leads to prolonged systemic exposure to the drug at low concentrations. Tumor growth delay (TGD) was used as an endpoint in these experiments. Results: The most effective treatment protocol, in terms of potentiating the effects of radiation was cisplatin delivered by polymer implanted 2 days before an acute dose of radiation (growth modification factor [DMF] = 2.2). Comparison of single and multifraction regimes where polymer implant was on the same day as the commencement of treatment showed greater potentiation of the effect of fractionated than of acute radiation treatment with the DMF for fractionated treatment remaining relatively constant (1.5-1.9) for 5, 8, and 12 fraction treatments. Cisplatin delivered via the osmotic pump did not deliver a high enough dose of cisplatin to produce therapeutic effect in this mouse tumor model and had little impact on response to treatment. Conclusions: Our results indicated that cisplatin delivered intratumorally by biodegradable polymer implant was effective in potentiating the effect of both acute and fractionated radiation. For the fractionated treatments the effect was maintained with increasing fraction numbers and treatment time

  19. Amplitude Noise Suppression and Orthogonal Multiplexing Using Injection-Locked Single-Mode VCSEL

    DEFF Research Database (Denmark)

    Lyubopytov, Vladimir; von Lerber, Tuomo; Lassas, Matti

    2017-01-01

    We experimentally demonstrate BER reduction and orthogonal modulation using an injection locked single-mode VCSEL. It allows us suppressing an amplitude noise of optical signal and/or double the capacity of an information channel....

  20. Multi-Element Lean Direct Injection Combustor Single Element Demonstration, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose to demonstrate the feasibility in a single element of a Multi-Element Lean Direct Injection, ME-LDI, Combustion concept. The concept will have the...

  1. All-in-polymer injection molded device for single cell capture using multilevel silicon master fabrication

    DEFF Research Database (Denmark)

    Tanzi, S.; Larsen, S.T.; Matteucci, M.

    2012-01-01

    This work demonstrates a novel all-in-polymer device for single cell capture applicable for biological recordings. The chip is injection molded and comprises a "cornered" (non planar) aperture. It has been demonstrated how cornered apertures are straightforward to mold in PDMS [1,2]. In this stud...... defects during demolding. Capturing of single PC12 cells has been demonstrated.......This work demonstrates a novel all-in-polymer device for single cell capture applicable for biological recordings. The chip is injection molded and comprises a "cornered" (non planar) aperture. It has been demonstrated how cornered apertures are straightforward to mold in PDMS [1,2]. In this study...

  2. 3D-CFD Simulation of Confined Cross-Flow Injection Process Using Single Piston Pump

    Directory of Open Access Journals (Sweden)

    M. Elashmawy

    2017-12-01

    Full Text Available Injection process into a confined cross flow is quite important for many applications including chemical engineering and water desalination technology. The aim of this study is to investigate the performance of the injection process into a confined cross-flow of a round pipe using a single piston injection pump. A computational fluid dynamics (CFD analysis has been carried out to investigate the effect of the locations of the maximum velocity and minimum pressure on the confined cross-flow process. The jet trajectory is analyzed and related to the injection pump shaft angle of rotation during the injection duty cycle by focusing on the maximum instant injection flow of the piston action. Results indicate a low effect of the jet trajectory within the range related to the injection pump operational conditions. Constant cross-flow was used and injection flow is altered to vary the jet to line flow ratio (QR. The maximum jet trajectory exhibits low penetration inside the cross-flow. The results showed three regions of the flow ratio effect zones with different behaviors. Results also showed that getting closer to the injection port causes a significant decrease on the locations of the maximum velocity and minimum pressure.

  3. A histological evaluation and in vivo assessment of intratumoral near infrared photothermal nanotherapy-induced tumor regression

    Directory of Open Access Journals (Sweden)

    Green HN

    2014-11-01

    Full Text Available Hadiyah N Green,1,2 Stephanie D Crockett,3 Dmitry V Martyshkin,1 Karan P Singh,2,4 William E Grizzle,2,5 Eben L Rosenthal,2,6 Sergey B Mirov11Department of Physics, Center for Optical Sensors and Spectroscopies, 2Comprehensive Cancer Center, 3Department of Pediatrics, Division of Neonatology, 4Department of Medicine, Division of Preventive Medicine, Biostatistics and Bioinformatics Shared Facility, 5Department of Pathology, 6Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, The University of Alabama at Birmingham, Birmingham, AL, USAPurpose: Nanoparticle (NP-enabled near infrared (NIR photothermal therapy has realized limited success in in vivo studies as a potential localized cancer therapy. This is primarily due to a lack of successful methods that can prevent NP uptake by the reticuloendothelial system, especially the liver and kidney, and deliver sufficient quantities of intravenously injected NPs to the tumor site. Histological evaluation of photothermal therapy-induced tumor regression is also neglected in the current literature. This report demonstrates and histologically evaluates the in vivo potential of NIR photothermal therapy by circumventing the challenges of intravenous NP delivery and tumor targeting found in other photothermal therapy studies.Methods: Subcutaneous Cal 27 squamous cell carcinoma xenografts received photothermal nanotherapy treatments, radial injections of polyethylene glycol (PEG-ylated gold nanorods and one NIR 785 nm laser irradiation for 10 minutes at 9.5 W/cm2. Tumor response was measured for 10–15 days, gross changes in tumor size were evaluated, and the remaining tumors or scar tissues were excised and histologically analyzed.Results: The single treatment of intratumoral nanorod injections followed by a 10 minute NIR laser treatment also known as photothermal nanotherapy, resulted in ~100% tumor regression in ~90% of treated tumors, which was statistically significant in a

  4. The efficacy of multiple versus single hyaluronic acid injections: a systematic review and meta-analysis.

    Science.gov (United States)

    Concoff, Andrew; Sancheti, Parag; Niazi, Faizan; Shaw, Peter; Rosen, Jeffrey

    2017-12-21

    Intra-articular hyaluronic acid (IA-HA) is a common therapy used to treat knee pain and suppress knee inflammation in knee osteoarthritis (OA), typically prescribed in regimens ranging from a single injection to 5 weekly injections given once weekly. We conducted a systematic review to determine the efficacy of IA-HA, with subgroup analyses to explore the differences in knee pain and adverse events (AEs) across different dosing regimens. We conducted a systematic search of the literature to identify studies evaluating IA-HA for the management of knee OA compared to IA-saline. Primary outcome measure was the mean knee pain score at 13 Weeks (3 months) or 26 weeks (6 months). Secondary outcome was the number of treatment-related AEs and treatment-related serious adverse events (SAEs). We evaluated differences in levels of pain and AEs/SAEs between dosing regimens compared to IA-Saline. Thirty articles were included. Overall, IA-HA injections were associated with less knee pain compared to IA-Saline injections for all dosing regimens. 2-4 injections of IA-HA vs. IA-Saline produced the largest effect size at both 3-months and 6-months (Standard mean difference [SMD] = -0.76; -0.98 to -0.53, 95% CI, P injection studies yielded a non-significant treatment effect at 3 and 6 months, while ≥5 5 injections demonstrated a significant improvement in pain only at 6 months. Five or more injections of IA-HA were associated with a higher risk of treatment-related AEs compared to IA-Saline (Risk ratio [RR] = 1.67; 1.09 to 2.56 95% CI, p = 0.02), which was a result not seen within the 1 and 2-4 injection subgroups. Overall, 2-4 and ≥5 injection regimens provided pain relief over IA-Saline, while single injection did not. Intra-articular injections of HA used in a 2-4 injection treatment regimen provided the greatest benefit when compared to IA-Saline with respect to pain improvement in patients with knee OA, and was generally deemed safe with few to no

  5. Intratumoral administration of IL2- and TNF-based fusion proteins cures cancer without establishing protective immunity.

    Science.gov (United States)

    Ziffels, Barbara; Pretto, Francesca; Neri, Dario

    2018-03-01

    The combination of tumor-targeting IL2- and TNF-based antibody-cytokine fusions has exhibited encouraging results in mouse and men. Here, we studied their combination to assess efficacy and mechanism of action in four different immunocompetent mouse models of cancer. Mice receiving a single intratumoral injection of F8-IL2, F8-TNF or the combination were investigated for tumor-infiltrating leukocytes and rechallenged when cured. In three models, a proportion of treated animals could be cured, most probably by infiltrating NK and CD8 + T cells. Most of the cured mice did not acquire protective immunity when rechallenged with the same tumor cell line. Immunocompetent mouse tumor models may not be adequate enough to predict the search for more efficacious therapy regimens.

  6. Intratumor Heterogeneity of ALK-Rearrangements and Homogeneity of EGFR-Mutations in Mixed Lung Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Federica Zito Marino

    Full Text Available Non Small Cell Lung Cancer is a highly heterogeneous tumor. Histologic intratumor heterogeneity could be 'major', characterized by a single tumor showing two different histologic types, and 'minor', due to at least 2 different growth patterns in the same tumor. Therefore, a morphological heterogeneity could reflect an intratumor molecular heterogeneity. To date, few data are reported in literature about molecular features of the mixed adenocarcinoma. The aim of our study was to assess EGFR-mutations and ALK-rearrangements in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas and adenosquamous carcinomas.590 Non Small Cell Lung Carcinomas tumor samples were revised in order to select mixed adenocarcinomas with available tumor components. Finally, only 105 mixed adenocarcinomas and 17 adenosquamous carcinomas were included in the study for further analyses. Two TMAs were built selecting the different intratumor histotypes. ALK-rearrangements were detected through FISH and IHC, and EGFR-mutations were detected through IHC and confirmed by RT-PCR.10/122 cases were ALK-rearranged and 7 from those 10 showing an intratumor heterogeneity of the rearrangements. 12/122 cases were EGFR-mutated, uniformly expressing the EGFR-mutated protein in all histologic components.Our data suggests that EGFR-mutations is generally homogeneously expressed. On the contrary, ALK-rearrangement showed an intratumor heterogeneity in both mixed adenocarcinomas and adenosquamous carcinomas. The intratumor heterogeneity of ALK-rearrangements could lead to a possible impact on the therapeutic responses and the disease outcomes.

  7. Single Cell Transfection through Precise Microinjection with Quantitatively Controlled Injection Volumes

    Science.gov (United States)

    Chow, Yu Ting; Chen, Shuxun; Wang, Ran; Liu, Chichi; Kong, Chi-Wing; Li, Ronald A.; Cheng, Shuk Han; Sun, Dong

    2016-04-01

    Cell transfection is a technique wherein foreign genetic molecules are delivered into cells. To elucidate distinct responses during cell genetic modification, methods to achieve transfection at the single-cell level are of great value. Herein, we developed an automated micropipette-based quantitative microinjection technology that can deliver precise amounts of materials into cells. The developed microinjection system achieved precise single-cell microinjection by pre-patterning cells in an array and controlling the amount of substance delivered based on injection pressure and time. The precision of the proposed injection technique was examined by comparing the fluorescence intensities of fluorescent dye droplets with a standard concentration and water droplets with a known injection amount of the dye in oil. Injection of synthetic modified mRNA (modRNA) encoding green fluorescence proteins or a cocktail of plasmids encoding green and red fluorescence proteins into human foreskin fibroblast cells demonstrated that the resulting green fluorescence intensity or green/red fluorescence intensity ratio were well correlated with the amount of genetic material injected into the cells. Single-cell transfection via the developed microinjection technique will be of particular use in cases where cell transfection is challenging and genetically modified of selected cells are desired.

  8. Ultrasound-guided single-penetration dual-injection block for leg and foot surgery

    DEFF Research Database (Denmark)

    Børglum, Jens; Johansen, Karina; Christensen, Karen Margrethe

    2014-01-01

    We describe a new approach to blocking the sciatic and saphenous nerves in the proximal thigh (level of the lesser trochanter or immediately below) using a single-penetration dual-injection (SPEDI) technique. The popliteal-sciatic approach necessitates repositioning of the leg exposing the poplit...

  9. Single intra-articular injection of high molecular weight hyaluronic acid for hip osteoarthritis.

    Science.gov (United States)

    Rivera, Fabrizio

    2016-03-01

    Intra-articular (IA) injection of hyaluronic acid (HA) into the hip joint appears to be safe and well tolerated but only a small number of randomized clinical trials in humans has been published. The objective of this prospective study was to evaluate the efficacy and safety of a single IA injection of high-molecular-weight (2800 kDa) HA (Coxarthrum) for hip osteoarthritis. All patients received a single IA administration of 2.5 % sodium hyaluronate (75 mg/3 mL) of high molecular weight. Fluoroscopy requires an iodized contrast medium (iopamidol, 1 ml) which highlights the capsule before administering HA. Patients were evaluated before IA injection (T0), after 3 months, after 6 months and after 1 year from injection. Results were evaluated by the Brief Pain Inventory (BPI II), Harris Hip Score and a visual analog scale of pain (pain VAS). All treated patients were considered for statistical analysis. Two hundred seven patients were included at T0. The mean age was 67 years (range 46-81). Regarding BPI severity score, changes in pain between T0 and the three following visits were statistically highly significant (p injection of Coxarthrum is effective from the third month and that the results are stable or continue to improve up to 1 year. IV.

  10. Spatio-temporally controlled transfection by quantitative injection into a single cell.

    Science.gov (United States)

    Kwon, Hyosung; Park, Hang-soo; Yu, Jewon; Hong, Sunghoi; Choi, Yeonho

    2015-10-01

    Transfection-based cellular control has been widely used in biology; however, conventional transfection methods cannot control spatio-temporal differences in gene expression or the quantity of delivered materials such as external DNA or RNA. Here, we present a non-viral and spatio-temporally controlled transfection technique of a quantitative injection into a single cell. DNA was quantitatively injected into a single cell at a desired location and time, and the optimal gene delivery and expression conditions were determined based on the amount of the delivered DNA and the transfection efficacy. Interestingly, an injection of 1500 DNAs produced an about average 30% gene expression efficiency, which was the optimal condition, and gene expression was sustained for more than 14 days. In a single cell, fluorescent intensity and polymerase chain reaction (PCR) results were compared for the quantity of gene expression. The high coincidence of both results suggests that the fluorescence intensity can reveal gene expression level which was investigated by PCR. In addition, 3 multiple DNA genes were successfully expressed in a single cell with different ratio. Overall, these results demonstrate that spatio-temporally controlled transfection by quantitative transfection is a useful technique for regulating gene expression in a single cell, which suggests that this technique may be used for stem cell research, including the creation of induced pluripotent stem (iPS) cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Impact of injection speed and volume on perceived pain during subcutaneous injections into the abdomen and thigh: a single-centre, randomized controlled trial.

    Science.gov (United States)

    Heise, T; Nosek, L; Dellweg, S; Zijlstra, E; Præstmark, K A; Kildegaard, J; Nielsen, G; Sparre, T

    2014-10-01

    The aim of this study was to assess pain associated with subcutaneous injection into the abdomen and thigh of different combinations of injection speeds and volumes. The study was a single-centre, one-visit, double-blinded, randomized controlled trial in 82 adults with type 1 or type 2 diabetes receiving daily injections of insulin or glucagon-like peptide-1 (GLP-1) agonists. Participants received 17 subcutaneous injections (12 in abdomen, 5 in thigh) of saline at different injection speeds (150, 300 and 450 µl/s), with different volumes (400, 800, 1200 and 1600 µl), and two needle insertions without any injection. Pain was evaluated on a 100-mm visual analogue scale (VAS) (0 mm no pain, 100 mm worst pain) and on a yes/no scale for pain acceptability. Injection speed had no impact on injection pain (p = 0.833). Injection of larger volumes caused significantly more pain [VAS least square mean differences 1600 vs. 400 µl, 7 · 2 mm (95% confidence interval - CI; 4.6-9.7; p technique to reduce their injection pain. Furthermore, these findings may have important implications for the development of new injection devices and drug formulations for clinical practice. © 2014 John Wiley & Sons Ltd.

  12. Ambiguity in measuring matrix diffusion with single-well injection/recovery tracer tests

    Science.gov (United States)

    Lessoff, S.C.; Konikow, Leonard F.

    1997-01-01

    Single-well injection/recovery tracer tests are considered for use in characterizing and quantifying matrix diffusion in dual-porosity aquifers. Numerical modeling indicates that neither regional drift in homogeneous aquifers, nor heterogeneity in aquifers having no regional drift, nor hydrodynamic dispersion significantly affects these tests. However, when drift is coupled simultaneously with heterogeneity, they can have significant confounding effects on tracer return. This synergistic effect of drift and heterogeneity may help explain irreversible flow and inconsistent results sometimes encountered in previous single-well injection/recovery tracer tests. Numerical results indicate that in a hypothetical single-well injection/recovery tracer test designed to demonstrate and measure dual-porosity characteristics in a fractured dolomite, the simultaneous effects of drift and heterogeneity sometimes yields responses similar to those anticipated in a homogeneous dual-porosity formation. In these cases, tracer recovery could provide a false indication of the occurrence of matrix diffusion. Shortening the shut-in period between injection and recovery periods may make the test less sensitive to drift. Using multiple tracers having different diffusion characteristics, multiple tests having different pumping schedules, and testing the formation at more than one location would decrease the ambiguity in the interpretation of test data.

  13. Single-frequency injection-seeded Q-switched Ho:YAG laser

    Science.gov (United States)

    Wang, Qing; Gao, Chunqing; Na, Quanxin; Zhang, Yixuan; Ye, Qing; Gao, Mingwei

    2017-04-01

    An injection-seeded Ho:YAG laser at 2090 nm with changeable pulse repetition frequency (PRF) is demonstrated. Containing a Ho:YAG nonplanar ring oscillator (NPRO) seed, a slave laser, and a single-pass amplifier, the laser delivered single-frequency pulses with energy ranging from 31.4 to 12.7 mJ. The corresponding pulse duration and PRF varied between 102-215 ns and 150-750 Hz, respectively. To the best of our knowledge, this is the highest PRF ever obtained from a single-frequency Ho:YAG laser.

  14. Injection of a single electron from static to moving quantum dots.

    Science.gov (United States)

    Bertrand, Benoit; Hermelin, Sylvain; Mortemousque, Pierre-André; Takada, Shintaro; Yamamoto, Michihisa; Tarucha, Seigo; Ludwig, Arne; Wieck, Andreas D; Bäuerle, Christopher; Meunier, Tristan

    2016-05-27

    We study the injection mechanism of a single electron from a static quantum dot into a moving quantum dot. The moving quantum dots are created with surface acoustic waves (SAWs) in a long depleted channel. We demonstrate that the injection process is characterized by an activation law with a threshold that depends on the SAW amplitude and on the dot-channel potential gradient. By sufficiently increasing the SAW modulation amplitude, we can reach a regime where the transfer has unity probability and is potentially adiabatic. This study points to the relevant regime to use moving dots in quantum information protocols.

  15. All-in-polymer injection molded device for single cell capture using multilevel silicon master fabrication

    DEFF Research Database (Denmark)

    Tanzi, S.; Larsen, S.T.; Matteucci, M.

    2012-01-01

    This work demonstrates a novel all-in-polymer device for single cell capture applicable for biological recordings. The chip is injection molded and comprises a "cornered" (non planar) aperture. It has been demonstrated how cornered apertures are straightforward to mold in PDMS [1,2]. In this study...... we demonstrate cornered apertures made in a thermoplastic polymer. One of the advantages of cornered apertures is the ease of microscopy under a standard inverted optical microscope, when using transparent materials. After the part is injection molded, the sealing of the chip is performed by thermal...

  16. Efficient spin-current injection in single-molecule magnet junctions

    Directory of Open Access Journals (Sweden)

    Haiqing Xie

    2018-01-01

    Full Text Available We study theoretically spin transport through a single-molecule magnet (SMM in the sequential and cotunneling regimes, where the SMM is weakly coupled to one ferromagnetic and one normal-metallic leads. By a master-equation approach, it is found that the spin polarization injected from the ferromagnetic lead is amplified and highly polarized spin-current can be generated, due to the exchange coupling between the transport electron and the anisotropic spin of the SMM. Moreover, the spin-current polarization can be tuned by the gate or bias voltage, and thus an efficient spin injection device based on the SMM is proposed in molecular spintronics.

  17. Assessment of nitrification potential in ground water using short term, single-well injection experiments.

    Science.gov (United States)

    Smith, R L; Baumgartner, L K; Miller, D N; Repert, D A; Böhlke, J K

    2006-01-01

    Nitrification was measured within a sand and gravel aquifer on Cape Cod, MA, using a series of single-well injection tests. The aquifer contained a wastewater-derived contaminant plume, the core of which was anoxic and contained ammonium. The study was conducted near the downgradient end of the ammonium zone, which was characterized by inversely trending vertical gradients of oxygen (270 to 0 microM) and ammonium (19 to 625 microM) and appeared to be a potentially active zone for nitrification. The tests were conducted by injecting a tracer solution (ambient ground water + added constituents) into selected locations within the gradients using multilevel samplers. After injection, the tracers moved by natural ground water flow and were sampled with time from the injection port. Rates of nitrification were determined from changes in nitrate and nitrite concentration relative to bromide. Initial tests were conducted with (15)N-enriched ammonium; subsequent tests examined the effect of adding ammonium, nitrite, or oxygen above background concentrations and of adding difluoromethane, a nitrification inhibitor. In situ net nitrate production exceeded net nitrite production by 3- to 6- fold and production rates of both decreased in the presence of difluoromethane. Nitrification rates were 0.02-0.28 mumol (L aquifer)(-1) h(-1) with in situ oxygen concentrations and up to 0.81 mumol (L aquifer)(-1) h(-1) with non-limiting substrate concentrations. Geochemical considerations indicate that the rates derived from single-well injection tests yielded overestimates of in situ rates, possibly because the injections promoted small-scale mixing within a transport-limited reaction zone. Nonetheless, these tests were useful for characterizing ground water nitrification in situ and for comparing potential rates of activity when the tracer cloud included non-limiting ammonium and oxygen concentrations.

  18. Assessment of nitrification potential in ground water using short term, single-well injection experiments

    Science.gov (United States)

    Smith, R.L.; Baumgartner, L.K.; Miller, D.N.; Repert, D.A.; Böhlke, J.K.

    2006-01-01

    Nitrification was measured within a sand and gravel aquifer on Cape Cod, MA, using a series of single-well injection tests. The aquifer contained a wastewater-derived contaminant plume, the core of which was anoxic and contained ammonium. The study was conducted near the downgradient end of the ammonium zone, which was characterized by inversely trending vertical gradients of oxygen (270 to 0 μM) and ammonium (19 to 625 μM) and appeared to be a potentially active zone for nitrification. The tests were conducted by injecting a tracer solution (ambient ground water + added constituents) into selected locations within the gradients using multilevel samplers. After injection, the tracers moved by natural ground water flow and were sampled with time from the injection port. Rates of nitrification were determined from changes in nitrate and nitrite concentration relative to bromide. Initial tests were conducted with 15N-enriched ammonium; subsequent tests examined the effect of adding ammonium, nitrite, or oxygen above background concentrations and of adding difluoromethane, a nitrification inhibitor. In situ net nitrate production exceeded net nitrite production by 3- to 6- fold and production rates of both decreased in the presence of difluoromethane. Nitrification rates were 0.02–0.28 μmol (L aquifer)−1 h−1 with in situ oxygen concentrations and up to 0.81 μmol (L aquifer)−1 h−1 with non-limiting substrate concentrations. Geochemical considerations indicate that the rates derived from single-well injection tests yielded overestimates of in situ rates, possibly because the injections promoted small-scale mixing within a transport-limited reaction zone. Nonetheless, these tests were useful for characterizing ground water nitrification in situ and for comparing potential rates of activity when the tracer cloud included non-limiting ammonium and oxygen concentrations.

  19. The acceptability of three vaccine injections given to infants during a single clinic visit in South Africa

    OpenAIRE

    Tabana, Hanani; Dudley, Lilian D.; Knight, Stephen; Cameron, Neil; Mahomed, Hassan; Goliath, Charlyn; Eggers, Rudolf; Wiysonge, Charles S.

    2016-01-01

    Abstract Background The Expanded Programme on Immunisation (EPI) has increased the number of antigens and injections administered at one visit. There are concerns that more injections at a single immunisation visit could decrease vaccination coverage. We assessed the acceptability and acceptance of three vaccine injections at a single immunisation visit by caregivers and vaccinators in South Africa. Methods A mixed methods exploratory study of caregivers and vaccinators at clinics in two prov...

  20. Manipulation and Immobilization of a Single Fluorescence Nanosensor for Selective Injection into Cells.

    Science.gov (United States)

    Hashim, Hairulazwan; Maruyama, Hisataka; Masuda, Taisuke; Arai, Fumihito

    2016-12-01

    Manipulation and injection of single nanosensors with high cell viability is an emerging field in cell analysis. We propose a new method using fluorescence nanosensors with a glass nanoprobe and optical control of the zeta potential. The nanosensor is fabricated by encapsulating a fluorescence polystyrene nanobead into a lipid layer with 1,3,3-trimethylindolino-6'-nitrobenzopyrylospiran (SP), which is a photochromic material. The nanobead contains iron oxide nanoparticles and a temperature-sensitive fluorescent dye, Rhodamine B. The zeta potential of the nanosensor switches between negative and positive by photo-isomerization of SP with ultraviolet irradiation. The positively-charged nanosensor easily adheres to a negatively-charged glass nanoprobe, is transported to a target cell, and then adheres to the negatively-charged cell membrane. The nanosensor is then injected into the cytoplasm by heating with a near-infrared (NIR) laser. As a demonstration, a single 750 nm nanosensor was picked-up using a glass nanoprobe with optical control of the zeta potential. Then, the nanosensor was transported and immobilized onto a target cell membrane. Finally, it was injected into the cytoplasm using a NIR laser. The success rates of pick-up and cell immobilization of the nanosensor were 75% and 64%, respectively. Cell injection and cell survival rates were 80% and 100%, respectively.

  1. Manipulation and Immobilization of a Single Fluorescence Nanosensor for Selective Injection into Cells

    Science.gov (United States)

    Hashim, Hairulazwan; Maruyama, Hisataka; Masuda, Taisuke; Arai, Fumihito

    2016-01-01

    Manipulation and injection of single nanosensors with high cell viability is an emerging field in cell analysis. We propose a new method using fluorescence nanosensors with a glass nanoprobe and optical control of the zeta potential. The nanosensor is fabricated by encapsulating a fluorescence polystyrene nanobead into a lipid layer with 1,3,3-trimethylindolino-6′-nitrobenzopyrylospiran (SP), which is a photochromic material. The nanobead contains iron oxide nanoparticles and a temperature-sensitive fluorescent dye, Rhodamine B. The zeta potential of the nanosensor switches between negative and positive by photo-isomerization of SP with ultraviolet irradiation. The positively-charged nanosensor easily adheres to a negatively-charged glass nanoprobe, is transported to a target cell, and then adheres to the negatively-charged cell membrane. The nanosensor is then injected into the cytoplasm by heating with a near-infrared (NIR) laser. As a demonstration, a single 750 nm nanosensor was picked-up using a glass nanoprobe with optical control of the zeta potential. Then, the nanosensor was transported and immobilized onto a target cell membrane. Finally, it was injected into the cytoplasm using a NIR laser. The success rates of pick-up and cell immobilization of the nanosensor were 75% and 64%, respectively. Cell injection and cell survival rates were 80% and 100%, respectively. PMID:27916931

  2. Manipulation and Immobilization of a Single Fluorescence Nanosensor for Selective Injection into Cells

    Directory of Open Access Journals (Sweden)

    Hairulazwan Hashim

    2016-12-01

    Full Text Available Manipulation and injection of single nanosensors with high cell viability is an emerging field in cell analysis. We propose a new method using fluorescence nanosensors with a glass nanoprobe and optical control of the zeta potential. The nanosensor is fabricated by encapsulating a fluorescence polystyrene nanobead into a lipid layer with 1,3,3-trimethylindolino-6′-nitrobenzopyrylospiran (SP, which is a photochromic material. The nanobead contains iron oxide nanoparticles and a temperature-sensitive fluorescent dye, Rhodamine B. The zeta potential of the nanosensor switches between negative and positive by photo-isomerization of SP with ultraviolet irradiation. The positively-charged nanosensor easily adheres to a negatively-charged glass nanoprobe, is transported to a target cell, and then adheres to the negatively-charged cell membrane. The nanosensor is then injected into the cytoplasm by heating with a near-infrared (NIR laser. As a demonstration, a single 750 nm nanosensor was picked-up using a glass nanoprobe with optical control of the zeta potential. Then, the nanosensor was transported and immobilized onto a target cell membrane. Finally, it was injected into the cytoplasm using a NIR laser. The success rates of pick-up and cell immobilization of the nanosensor were 75% and 64%, respectively. Cell injection and cell survival rates were 80% and 100%, respectively.

  3. Single injection thoracic paravertebral block (TPVB for breast surgery in morbidly obese patient

    Directory of Open Access Journals (Sweden)

    Anita Kulkarni

    2017-01-01

    Full Text Available Morbidly obese (MO patients with associated restrictive airway disease, obstructive sleep apnea, and coronary artery disease pose challenge to an anesthesiologist. Regional block combined with general anesthesia (GA is the anesthetic technique of choice as it will decrease the requirement of opioids, anesthetics, and postoperative respiratory depression. A MO patient for modified radical mastectomy was successfully managed with single-injection thoracic paravertebral block and conventional GA.

  4. Chemical castration by a single bilateral intra-testicular injection of ...

    African Journals Online (AJOL)

    ADEYEYE

    Sokoto Journal of Veterinary Sciences. (P-ISSN 1595-093X/ E-ISSN 2315-6201). Mohammed & James/Sokoto Journal of Veterinary Sciences (2013) 11(1): 62-65. http://dx.doi.org/10.4314/sokjvs.v11i1.10. Chemical castration by a single bilateral intra-testicular injection of chlorhexidine gluconate and cetrimide in bucks.

  5. Sonographic Guidance for Supraclavicular Brachial Plexus Blocks: Single vs. Double Injection Cluster Approach.

    Science.gov (United States)

    Choi, Jung Ju; Kwak, Hyun Jeong; Jung, Wol Seon; Chung, Seung Hyun; Lee, Mi Geum

    2017-09-01

    The cluster approach for supraclavicular brachial plexus block (SC-BPB) can be easily performed but may result in asymmetric local anesthetic (LA) spread. The authors hypothesized that the use of a cluster approach in each of the 2 planes would achieve better 3-dimensional LA distribution than the traditional single cluster approach. The purpose of the present study was to compare a double injection (DI) in 2 planes (one injection in each plane) with the traditional single injection (SI) cluster approach for ultrasound-guided SC-BPB. A randomized, controlled trial. Department of Anesthesiology and Pain Medicine, Gachon University Gil Medical Center. In the SI group (n = 18), 30 mL of LA was injected into the main neural cluster after penetrating the brachial plexus sheath laterally. In the DI group (n = 18), the needle penetrated the sheath in a downward direction at the first skin puncture, and 15 mL of LA was injected, and at the second skin puncture (behind the initial puncture site), the needle penetrated the sheath in an upward direction, and 15 mL was again injected. Ultrasound-guided SC-BPB was evaluated from immediately after the block every 5 minutes to 30 minutes by sensory and motor testing. The main outcome variables were procedural time; onset time (time for complete sensory and motor block of the median, radial, ulnar, and musculocutaneous nerves); and rate of blockage of all 4 nerves. Procedure times (medians [interquartile range]) were similar in the DI and SI groups (5.5 [4.75 - 8] vs. 5 [4 - 7] minutes, respectively; P = 0.137). Block onset time in the DI group was not significantly different from that in the SI group (10 [5 - 17.5] vs. 20 [6.25 - 30] minutes, P = 0.142). However, the rate of blockage of all 4 nerves was significantly higher in the DI group (94% vs. 67%, P = 0.035). Although the results of this study indicate LA distribution in the DI group was more evenly spread within brachial plexus sheaths than in the SI group, this was not

  6. A cost analysis of the establishment of a dedicated orthopaedic outpatient injection clinic at a single institution.

    Science.gov (United States)

    Curtin, M; O'Neill, S C; Keogh, P; Kenny, P

    2017-08-01

    Traditionally orthopaedic injections were performed in a theatre setting. A dedicated outpatient injection clinic was established at our institution to attempt to provide injections more cost effectively. Our aim was to perform a cost analysis of orthopaedic injections performed in theatre, compared to those performed in a dedicated OPD injection clinic. Patient data for all orthopaedic injections performed at a single institution from 2013 to 2014 was obtained using HIPE data. A detailed breakdown of costings for two scenarios; those performed in theatre and those in the dedicated OPD injection clinic was obtained from the hospital finance department. A unit cost per injection for theatre and OPD was derived from this financial information. A total of 487 injections were performed in 2013, with 491 performed in 2014. 134 (27.5%) injections were performed in the OPD in 2013 compared to 388 (79%) in 2014. The unit cost per injection was calculated as €52.13 for theatre and €23.85 for OPD, this represented a 115% decrease in cost per injection. The creation of a dedicated orthopaedic injection clinic resulted in considerable cost savings at our institution. We propose this may be a more cost-efficient model for delivery of injections in the orthopaedic setting.

  7. The acceptability of three vaccine injections given to infants during a single clinic visit in South Africa.

    Science.gov (United States)

    Tabana, Hanani; Dudley, Lilian D; Knight, Stephen; Cameron, Neil; Mahomed, Hassan; Goliath, Charlyn; Eggers, Rudolf; Wiysonge, Charles S

    2016-08-08

    The Expanded Programme on Immunisation (EPI) has increased the number of antigens and injections administered at one visit. There are concerns that more injections at a single immunisation visit could decrease vaccination coverage. We assessed the acceptability and acceptance of three vaccine injections at a single immunisation visit by caregivers and vaccinators in South Africa. A mixed methods exploratory study of caregivers and vaccinators at clinics in two provinces of South Africa was conducted. Quantitative and qualitative data were collected using questionnaires as well as observations of the administration of three-injection vaccination sessions. The sample comprised 229 caregivers and 98 vaccinators. Caregivers were satisfied with the vaccinators' care (97 %) and their infants receiving immunisation injections (93 %). However, many caregivers, (86 %) also felt that three or more injections were excessive at one visit. Caregivers had limited knowledge of actual vaccines provided, and reasons for three injections. Although vaccinators recognised the importance of informing caregivers about vaccination, they only did this sometimes. Overall, acceptance of three injections was high, with 97 % of caregivers expressing willingness to bring their infant for three injections again in future visits despite concerns about the pain and discomfort that the infant experienced. Many (55 %) vaccinators expressed concern about giving three injections in one immunisation visit. However, in 122 (95 %) observed three-injection vaccination sessions, the vaccinators administered all required vaccinations for that visit. The remaining seven vaccinations were not completed because of vaccine stock-outs. We found high acceptance by caregivers and vaccinators of three injections. Caregivers' poor understanding of reasons for three injections resulted from limited information sharing by vaccinators for caregivers. Acceptability of three injections may be improved through

  8. A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer.

    Science.gov (United States)

    Ganly, I; Kirn, D; Eckhardt, G; Rodriguez, G I; Soutar, D S; Otto, R; Robertson, A G; Park, O; Gulley, M L; Heise, C; Von Hoff, D D; Kaye, S B; Eckhardt, S G

    2000-03-01

    An E1B 55 kDa gene-deleted adenovirus, Onyx-015, which reportedly selectively replicates in and lyses p53-deficient cells, was administered by a single intratumoral injection to a total of 22 patients with recurrent head and neck cancer. The objectives of this Phase I study were to determine the safety, feasibility, and efficacy of this therapy and determine any correlation to p53 status. Six cohorts were investigated with a dose escalation from 10(7)-10(11) plaque-forming units. Toxicity was assessed using NCIC criteria. Tumor response was assessed by clinical and radiological measurement. Blood samples were taken to detect adenovirus DNA and neutralizing antibody to adenovirus. Tumor biopsies were taken to detect adenovirus by in situ hybridization. Treatment was well tolerated, with the main toxicity being grade 1/2 flu-like symptoms. Dose-limiting toxicity was not reached at the highest dose of 10(11) plaque-forming units. Twenty-one of the 22 patients treated showed an increase in neutralizing antibody to adenovirus. In situ hybridization showed viral replication in 4 of 22 patients treated, all of whom had mutant p53 tumors. Using conventional response criteria, no objective responses were observed. However, magnetic resonance imaging scans were suggestive of tumor necrosis at the site of viral injection in five patients, three of whom were classified using nonconventional criteria as partial responders, and two of whom were classified using nonconventional criteria as minor responders. Of these five cases, four had mutant p53 tumors. The response duration for the three partial responders was 4, 8, and 12 weeks. An additional eight patients had stable disease in the injected tumors lasting from 4-8 weeks. These preliminary results show that intratumoral administration of Onyx-015 is feasible, well tolerated, and associated with biological activity. Further investigation of Onyx-015, particularly with a more frequent injection protocol and in combination with

  9. Single injection of platelet-rich plasma as a novel treatment of carpal tunnel syndrome

    Directory of Open Access Journals (Sweden)

    Michael Alexander Malahias

    2015-01-01

    Full Text Available Both in vitro and in vivo experiments have confirmed that platelet-rich plasma has therapeutic effects on many neuropathies, but its effects on carpal tunnel syndrome remain poorly understood. We aimed to investigate whether single injection of platelet-rich plasma can improve the clinical symptoms of carpal tunnel syndrome. Fourteen patients presenting with median nerve injury who had suffered from mild carpal tunnel syndrome for over 3 months were included in this study. Under ultrasound guidance, 1-2 mL of platelet-rich plasma was injected into the region around the median nerve at the proximal edge of the carpal tunnel. At 1 month after single injection of platelet-rich plasma, Visual Analogue Scale results showed that pain almost disappeared in eight patients and it was obviously alleviated in three patients. Simultaneously, the disabilities of the arm, shoulder and hand questionnaire showed that upper limb function was obviously improved. In addition, no ultrasonographic manifestation of the carpal tunnel syndrome was found in five patients during ultrasonographic measurement of the width of the median nerve. During 3-month follow-up, the pain was not greatly alleviated in three patients. These findings show very encouraging mid-term outcomes regarding use of platelet-rich plasma for the treatment of carpal tunnel syndrome.

  10. Transcatheter aortic-valve implantation with one single minimal contrast media injection.

    Science.gov (United States)

    Arrigo, Mattia; Maisano, Francesco; Haueis, Sabine; Binder, Ronald K; Taramasso, Maurizio; Nietlispach, Fabian

    2015-06-01

    Performing transcatheter aortic valve implantation (TAVI) with the use of minimal contrast in patients at high-risk for acute kidney injury (AKI). Contrast-induced nephropathy (CIN) is a major cause of AKI following TAVI and is associated with increased morbidity and mortality. The amount of contrast media used increases the risk for CIN. Computed tomography was omitted during the screening process. For the procedure transfemoral access was default. The self-expanding CoreValve prosthesis was chosen in all patients to minimize the risk of annular rupture in case of oversizing. Valve sizing was based on echocardiography, aortography, calcification on fluoroscopy, as well as weight and height of the patient. A single contrast injection was performed to confirm correct position of the pigtail catheter at the level of the annulus. The pigtail then served as the marker for the device landing zone. Intraprocedural assessment of the implantation result relied on echocardiography and hemodynamics. Five patients with severe aortic stenosis and at high risk for developing CIN were included. Device success was achieved in all patients and no major complications occurred. The median dose of injected contrast media was 8 ml (4-9). All but one patient had improved renal function after the intervention compared to baseline. Our study shows feasibility of performing TAVI with a single minimal contrast media injection, using a self-expandable valve. This technique has the potential to reduce the incidence of CIN. © 2015 Wiley Periodicals, Inc.

  11. [Peribulbar anesthesia: efficacy of a single injection with a limited local anesthetic volume].

    Science.gov (United States)

    Clausel, H; Touffet, L; Havaux, M; Lamard, M; Savean, J; Cochener, B; Arvieux, C; Gueret, G

    2008-10-01

    Cataract surgery can be performed with peribulbar anesthesia. The classical technique consists of two injections of local anesthetics. The purpose of our study was to assess peribulbar anesthesia with a single injection and a limited volume of local anesthetics. After local ethics committee agreement and oral consent, patients scheduled for cataract surgery using peribulbar anesthesia were prospectively included. The lower temporal puncture was performed with a peribulbar needle with propofol sedation. The mixture of local anesthetics was administered with tactile control of orbital pressure. The puncture was followed by a 10-min compression of the ocular globe. Akinesia, analgesia, complications, and surgical conditions were noted. A total of 101 successive patients were included. We administered 1.2 mg/kg of propofol. The volume of local anesthetics administered was 5.0 +/- 0.9 ml. Ninety patients had akinesia at 10 min and 6.7% moderate chemosis. No puncture complication occurred. At the end of surgery, the pain noted by the patients was 0.4 +/- 2.1 out of 100 (range, 0-10). Surgical conditions were good for all patients. Peribulbar anesthesia performed with a single injection and a limited volume of local anesthetics allows cataract surgery in good conditions for the surgeon with very good analgesia for the patient.

  12. Opto-injection into single living cells by femtosecond near-infrared laser

    Science.gov (United States)

    Peng, Cheng

    This dissertation presents a novel technique to deliver membrane impermeable molecules into single living cells with the assistance of femtosecond (fs) near-infrared (NIR) laser pulses. This approach merges ultrafast laser technology with key biological, biomedical, and medical applications, such as gene transfection, gene therapy and drug delivery. This technique promises several major advantages, namely, very high transfection efficiency, high cell survival rate (≈100%) and fully preserved cell viabilities. It is also a promising method to deliver molecules into cells that are difficult or even completely resistant to established physical methods, such as microinjection by glass pipettes, electroporation, and biolistics. In this work, the system for fs NIR opto-injection was designed and built. Successful fs NIR opto-injection has been performed on several cell systems including single mammalian cells (bovine aortic endothelial cells), marine animal eggs (Spisula solidissima oocytes), and human cancer cells (fibrosarcoma HT1080) cultured in a tissue-like environment. The connections between laser parameters and cell responses were explored through further experiments and in-depth analyses, especially the relationship between dye uptake rate and incident laser intensity, and the relationship between pore size created on cell membranes and incident laser intensity. Dye uptake rate of the target cells was observed to depend on incident laser intensity. Pore size was found dependent on incident laser intensity. The conclusion was made that laser-induced breakdown and plasma-induced ablation in cell membrane are the physical principles that govern the process of fs NIR opto-injection.

  13. Symptomatic Spinal Epidural Lipomatosis After a Single Local Epidural Steroid Injection

    International Nuclear Information System (INIS)

    Tok, Chung Hong; Kaur, Shaleen; Gangi, Afshin

    2011-01-01

    Spinal epidural lipomatosis is a rare disorder that can manifest with progressive neurological deficits. It is characterized by abnormal accumulation of unencapsulated epidural fat commonly associated with the administration of exogenous steroids associated with a variety of systemic diseases, endocrinopathies, and Cushing syndrome (Fogel et al. Spine J 5:202–211, 2005). Occasionally, spinal epidural lipomatosis may occur in patients not exposed to steroids or in patients with endocrinopathies, primarily in obese individuals (Fogel et al. Spine J 5:202–211, 2005). However, spinal lumbar epidural lipomatosis resulting from local steroid injection has rarely been reported. We report the case of a 45-year-old diabetic man with claudication that was probably due to symptomatic lumbar spinal lipomatosis resulting from a single local epidural steroid injection.

  14. Reactive Power Injection Strategies for Single-Phase Photovoltaic Systems Considering Grid Requirements

    DEFF Research Database (Denmark)

    Yang, Yongheng; Wang, Huai; Blaabjerg, Frede

    2014-01-01

    .g. Germany and Italy. Those advanced features can be provided by next generation PV systems, and will be enhanced in the future to ensure an even efficient and reliable utilization of PV systems. In light of this, Reactive Power Injection (RPI) strategies for single-phase PV systems are explored...... like what the conventional power plants do today in the grid regulation participation. Requirements of ancillary services like Low-Voltage Ride-Through (LVRT) associated with reactive current injection and voltage support through reactive power control, have been in effectiveness in some countries, e...... in this paper. The RPI possibilities are: a) constant average active power control, b) constant active current control, c) constant peak current control and d) thermal optimized control strategy. All those strategies comply with the currently active grid codes, but are with different objectives. The proposed...

  15. Reactive Power Injection Strategies for Single-Phase Photovoltaic Systems Considering Grid Requirements

    DEFF Research Database (Denmark)

    Yang, Yongheng; Wang, Huai; Blaabjerg, Frede

    2014-01-01

    . Those advanced features can be provided by next-generation PV systems, and will be enhanced in the future to ensure an even efficient and reliable utilization of PV systems. In the light of this, Reactive Power Injection (RPI) strategies for single-phase PV systems are explored in this paper. The RPI...... like what the conventional power plants do today in the grid regulation participation. Requirements of ancillary services like Low-Voltage Ride-Through (LVRT) associated with reactive current injection and voltage support through reactive power control, have been in effectiveness in some countries...... possibilities are: a) constant average active power control, b) constant active current control, c) constant peak current control and d) thermal optimized control strategy. All those strategies comply with the currently active grid codes, but are with different objectives. The thermal optimized control strategy...

  16. Single injection 51Cr EDTA plasma clearance determination in children using capillary blood samples

    International Nuclear Information System (INIS)

    Broechner-Mortensen, J.; Christoffersen, J.

    1977-01-01

    The reliability of a determination of the total 51 Cr EDTA plasma clearance (e) (and with it the glomerular filtration rate), by a simplified single injection method (injected dose: 4.5 μCi per kg b.w.) using capillary blood samples (0.2 ml), was investigated in twenty children. Clearance values determined from capillary blood samples did not differ significantly from those measured simultaneously from venous blood samples, the mean ratio+-SD being 1.02+-0.06(n = 10). The reproducibility (total day-to-day variation) of E determined from capillary blood samples was 6.7% in children with decreased renal function (n = 3) and 6.9% in children with normal renal function (n = 7). The present data indicate that the use of capillary blood samples is an accurate and very precise approach for determination of E in children. (Auth.)

  17. Fat injection to correct contour deformities of the reconstructed breast: a single surgeon experience

    Directory of Open Access Journals (Sweden)

    Youssef Tahiri

    2015-06-01

    Full Text Available Aim: Autologous fat grafting has gained acceptance as a technique to improve aesthetic outcomes in breast reconstruction. The purpose of this study was to share our clinical experience using autologous fat injection to correct contour deformities during breast reconstruction. Methods: A single surgeon, prospectively maintained database of patients who underwent autologous fat injection during breast reconstruction from January 2008 to November 2013 at McGill University Health Center was reviewed. Patient characteristics, breast history, type of breast reconstruction, volume of fat injected, and complications were analyzed. Results: One hundred and twenty-four patients benefited from autologous fat injection from January 2008 to November 2013, for a total of 187 treated breasts. The patients were on average 49.3 years old (΁ 8.9 years. Fat was harvested from the medial thighs (20.5%, flanks (39.1%, medial thighs and flanks (2.9%, trochanters (13.3%, medial knees (2.7%, and abdomen (21.9%. An average of 49.25 mL of fat was injected into each reconstructed breast. A total of 187 breasts in 124 patients were lipo-infiltrated during the second stage of breast reconstruction. Thirteen breasts (in 12 separate patients were injected several years after having undergone lumpectomy and radiotherapy. Of the 187 treated breasts, 118 were reconstructed with expanders to implants, 45 with deep inferior epigastric perforator flaps, 9 with latissimus dorsi flaps with implants, 4 with transverse rectus abdominis myocutaneous flaps, and 13 had previously undergone lumpectomy and radiotherapy. Six complications were noted in the entire series, for a rate of 3.2%. All were in previously radiated breasts. Average follow-up time was 12 months (range: 2-36 months. Conclusion: Fat injection continues to grow in popularity as an adjunct to breast reconstruction. Our experience demonstrates a low complication rate as compared to most surgical interventions of the breast

  18. CT-guided intratumoral gene therapy in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Kauczor, H.U.; Heussel, C.P.; Thelen, M.; Schuler, M.; Huber, C.; Weymarn, A. von; Bongartz, G.; Rochlitz, C.

    1999-01-01

    The objective of this study was to prove the principle of CT-guided gene therapy by intratumoral injection of a tumor suppressor gene as an alternative treatment approach of incurable non-small-cell lung cancer. In a prospective clinical phase I trial six patients with non-small-cell lung cancer and a mutation of the tumor suppressor gene p53 were treated by CT-guided intratumoral gene therapy. Ten milliliters of a vector solution (replication-defective adenovirus with complete wild-type p53 cDNA) were injected under CT guidance. In four cases the vector solution was completely applied to the tumor center, whereas in two cases 2 ml aliquots were injected into different tumor areas. For the procedure the scan room had been approved as a biosafety cabinet. Gene transfer was assessed by reverse transcription and polymerase chain reaction in biopsy specimens obtained under CT guidance 24-48 h after therapy. Potential therapeutic efficacy was evaluated on day 28 after treatment using spiral CT. The CT-guided gene therapy was easily performed in all six patients without intervention-related complications. Besides flu-like symptoms, no significant adverse effects of gene therapy were noted. Three of the four patients with central injection exhibited gene transfer in the posttreatment biopsy. Gene transfer could not be proven in the two patients with multiple 2 ml injections. After 28 days, four of the six patients showed stable disease at the treated tumor site, whereas other tumor manifestations progressed. Computed tomography-guided injections are an adequate and easy-to-perform procedure for intratumoral gene therapy. (orig.)

  19. Ultrasound-Guided Single-Injection Infraclavicular Block Versus Ultrasound-Guided Double-Injection Axillary Block: A Noninferiority Randomized Controlled Trial.

    Science.gov (United States)

    Boivin, Ariane; Nadeau, Marie-Josée; Dion, Nicolas; Lévesque, Simon; Nicole, Pierre C; Turgeon, Alexis F

    2016-01-01

    Single-injection ultrasound-guided infraclavicular block is a simple, reliable, and effective technique. A simplified double-injection ultrasound-guided axillary block technique with a high success rate recently has been described. It has the advantage of being performed in a superficial and compressible location, with a potentially improved safety profile. However, its effectiveness in comparison with single-injection infraclavicular block has not been established. We hypothesized that the double-injection ultrasound-guided axillary block would show rates of complete sensory block at 30 minutes noninferior to the single-injection ultrasound-guided infraclavicular block. After approval by our research ethics committee and written informed consent, adults undergoing distal upper arm surgery were randomized to either group I, ultrasound-guided single-injection infraclavicular block, or group A, ultrasound-guided double-injection axillary block. In group I, 30 mL of 1.5% mepivacaine was injected posterior to the axillary artery. In group A, 25 mL of 1.5% mepivacaine was injected posteromedial to the axillary artery, after which 5 mL was injected around the musculocutaneous nerve. Primary outcome was the rate of complete sensory block at 30 minutes. Secondary outcomes were the onset of sensory and motor blocks, surgical success rates, performance times, and incidence of complications. All outcomes were assessed by a blinded investigator. The noninferiority of the double-injection ultrasound-guided axillary block was considered if the limits of the 90% confidence intervals (CIs) were within a 10% margin of the rate of complete sensory block of the infraclavicular block. At 30 minutes, the rate of complete sensory block was 79% in group A (90% CI, 71%-85%) compared with 91% in group I (90% CI, 85%-95%); the upper limit of CI of group A is thus included in the established noninferiority margin of 10%. The rate of complete sensory block was lower in group A (proportion

  20. Direct injection of functional single-domain antibodies from E. coli into human cells.

    Science.gov (United States)

    Blanco-Toribio, Ana; Muyldermans, Serge; Frankel, Gad; Fernández, Luis Ángel

    2010-12-08

    Intracellular proteins have a great potential as targets for therapeutic antibodies (Abs) but the plasma membrane prevents access to these antigens. Ab fragments and IgGs are selected and engineered in E. coli and this microorganism may be also an ideal vector for their intracellular delivery. In this work we demonstrate that single-domain Ab (sdAbs) can be engineered to be injected into human cells by E. coli bacteria carrying molecular syringes assembled by a type III protein secretion system (T3SS). The injected sdAbs accumulate in the cytoplasm of HeLa cells at levels ca. 10⁵-10⁶ molecules per cell and their functionality is shown by the isolation of sdAb-antigen complexes. Injection of sdAbs does not require bacterial invasion or the transfer of genetic material. These results are proof-of-principle for the capacity of E. coli bacteria to directly deliver intracellular sdAbs (intrabodies) into human cells for analytical and therapeutic purposes.

  1. Direct injection of functional single-domain antibodies from E. coli into human cells.

    Directory of Open Access Journals (Sweden)

    Ana Blanco-Toribio

    2010-12-01

    Full Text Available Intracellular proteins have a great potential as targets for therapeutic antibodies (Abs but the plasma membrane prevents access to these antigens. Ab fragments and IgGs are selected and engineered in E. coli and this microorganism may be also an ideal vector for their intracellular delivery. In this work we demonstrate that single-domain Ab (sdAbs can be engineered to be injected into human cells by E. coli bacteria carrying molecular syringes assembled by a type III protein secretion system (T3SS. The injected sdAbs accumulate in the cytoplasm of HeLa cells at levels ca. 10⁵-10⁶ molecules per cell and their functionality is shown by the isolation of sdAb-antigen complexes. Injection of sdAbs does not require bacterial invasion or the transfer of genetic material. These results are proof-of-principle for the capacity of E. coli bacteria to directly deliver intracellular sdAbs (intrabodies into human cells for analytical and therapeutic purposes.

  2. Performance of single cylinder, direct injection Diesel engine using water fuel emulsions

    International Nuclear Information System (INIS)

    Abu-Zaid, M.

    2004-01-01

    A single cylinder Diesel engine study of water-in-Diesel emulsions was conducted to investigate the effect of water emulsification on the engine performance and gases exhaust temperature. Emulsified Diesel fuels of 0, 5, 10, 15 and 20 water/Diesel ratios by volume, were used in a single cylinder, direct injection Diesel engine, operating at 1200-3300 rpm. The results indicate that the addition of water in the form of emulsion improves combustion efficiency. The engine torque, power and brake thermal efficiency increase as the water percentage in the emulsion increases. The average increase in the brake thermal efficiency for 20% water emulsion is approximately 3.5% over the use of Diesel for the engine speed range studied. The proper brake specific fuel consumption and gases exhaust temperature decrease as the percentage of water in the emulsion increases

  3. [Utility and advantages of single tracer subareolar injection in sentinel lymph node biopsy in breast cancer].

    Science.gov (United States)

    Armas, Fayna; Hernández, María Jesús; Vega, Víctor; Gutiérrez, Isabel; Jiménez, Concepción; Pavcovich, Marta; Báez, Beatriz; Pérez-Correa, Pedro; Núñez, Valentín

    2005-10-01

    Sentinel lymph node (SLN) biopsy is a reliable technique for determining axillary status in patients with early breast cancer. This technique is a minimally invasive procedure that can avoid the use of lymphadenectomy in patients without axillary involvement. We present a validation study of SLN biopsy with subareolar injection of 99mTc-nanocolloids. We studied 100 patients with early breast cancer (T1 and T2) over a 2-year period. All patients underwent deep subareolar-injection of 99mTc-nanocoloid for localization of the sentinel node. Images were obtained and when the sentinel node was seen, it was marked on the skin. All patients underwent tumor excision and radioguided SLN biopsy followed by complete lymphadenectomy. Histopathological analysis of sentinel nodes was performed by hematoxylin-eosin and immunohistochemistry with cytokeratins. The sentinel node was identified in all patients, and a mean of 1.95 sentinel nodes per patient were found. Lymphatic metastases in the sentinel node were found in 44 patients and in 15 of these tumoral spread was also found in the remaining axillary nodes. In the 56 remaining patients the sentinel node was free of metastasis, but in two of them a non-sentinel node was found to be positive (4.5% false negative rate). Sensitivity was 95.7% (44/46), specificity was 100% (54/54), the positive predictive value was 100% and the negative predictive value was 96.4% (54/56). SLN biopsy is an accurate alternative to complete axillary lymph node dissection in patients with early-stage breast cancer. This technique improves the staging of these patients and decreases the morbidity associated with lymphadenectomy. The advantages of subareolar injection are that a single injection site is required, the tumor does not have to be located by other techniques, it allows rapid visualization of the sentinel node and avoids the "shine through phenomenon" when the tumor is located near the axilla.

  4. Modeling Breast Cancer Intertumor and Intratumor Heterogeneity Using Xenografts.

    Science.gov (United States)

    Bruna, Alejandra; Rueda, Oscar M; Caldas, Carlos

    2016-01-01

    Breast cancer is a heterogeneous disease that can be stratified in at least 10 different subtypes. We present here a platform for derivation of preclinical models based on patient-derived tumor xenografts (PDTXs) that represent these subgroups. These models preserve the transcriptome, methylome, copy-number, and mutational landscape features of the tumor of origin through different passaging. Furthermore, the intratumoral composition of these models is formed by communities of clones very similar to the ones present in the originating tumor. Finally, we show that short-term cultures of cells from these models (PDTX-derived tumor cells, PDTCs) also preserve the molecular features of the tumor and can be used for high-throughput drug testing of single compounds or combinations, with high reproducibility and clinical predictive power. © 2016 Bruna et al; Published by Cold Spring Harbor Laboratory Press.

  5. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Görmeli, Gökay; Görmeli, Cemile Ayşe; Ataoglu, Baybars; Çolak, Cemil; Aslantürk, Okan; Ertem, Kadir

    2017-03-01

    To compare the effectiveness of intraarticular (IA) multiple and single platelet-rich plasma (PRP) injections as well as hyaluronic acid (HA) injections in different stages of osteoarthritis (OA) of the knee. A total of 162 patients with different stages of knee OA were randomly divided into four groups receiving 3 IA doses of PRP, one dose of PRP, one dose of HA or a saline injection (control). Then, each group was subdivided into two groups: early OA (Kellgren-Lawrence grade 0 with cartilage degeneration or grade I-III) and advanced OA (Kellgren-Lawrence grade IV). The patients were evaluated before the injection and at the 6-month follow-ups using the EuroQol visual analogue scale (EQ-VAS) and International Knee Documentation Committee (IKDC) subjective scores. Adverse events and patient satisfaction were recorded. There was a statistically significant improvement in the IKDC and EQ-VAS scores in all the treatment groups compared with the control group. The knee scores of patients treated with three PRP injections were significantly better than those patients of the other groups. There was no significant difference in the scores of patients injected with one dose of PRP or HA. In the early OA subgroups, significantly better clinical results were achieved in the patients treated with three PRP injections, but there was no significant difference in the clinical results of patients with advanced OA among the treatment groups. The clinical results of this study suggest IA PRP and HA treatment for all stages of knee OA. For patients with early OA, multiple (3) PRP injections are useful in achieving better clinical results. For patients with advanced OA, multiple injections do not significantly improve the results of patients in any group. I.

  6. Minimal-invasive magnetic heating of tumors does not alter intra-tumoral nanoparticle accumulation, allowing for repeated therapy sessions: an in vivo study in mice

    International Nuclear Information System (INIS)

    Kettering, Melanie; Kaiser, Werner Alois; Hilger, Ingrid; Richter, Heike; Wiekhorst, Frank; Trahms, Lutz; Bremer-Streck, Sibylle

    2011-01-01

    Localized magnetic heating treatments (hyperthermia, thermal ablation) using superparamagnetic iron oxide nanoparticles (MNPs) continue to be an active area of cancer research. For generating the appropriate heat to sufficiently target cell destruction, adequate MNP concentrations need to be accumulated into tumors. Furthermore, the knowledge of MNP bio-distribution after application and additionally after heating is significant, firstly because of the possibility of repeated heating treatments if MNPs remain at the target region and secondly to study potential adverse effects dealing with MNP dilution from the target region over time. In this context, little is known about the behavior of MNPs after intra-tumoral application and magnetic heating. Therefore, the present in vivo study on the bio-distribution of intra-tumorally injected MNPs in mice focused on MNP long term monitoring of pre and post therapy over seven days using multi-channel magnetorelaxometry (MRX). Subsequently, single-channel MRX was adopted to study the bio-distribution of MNPs in internal organs and tumors of sacrificed animals. We found no distinct change of total MNP amounts in vivo during long term monitoring. Most of the MNP amounts remained in the tumors; only a few MNPs were detected in liver and spleen and less than 1% of totally injected MNPs were excreted. Apparently, the application of magnetic heating and the induction of apoptosis did not affect MNP accumulation. Our results indicate that MNP mainly remained within the injection side after magnetic heating over a seven-days-observation and therefore not affecting healthy tissue. As a consequence, localized magnetic heating therapy of tumors might be applied periodically for a better therapeutic outcome.

  7. A closed-form analytical solution for thermal single-well injection-withdrawal tests

    Science.gov (United States)

    Jung, Yoojin; Pruess, Karsten

    2012-03-01

    Thermal single-well injection-withdrawal (SWIW) tests entail pumping cold water into a hot and usually fractured reservoir, and monitoring the temperature recovery during subsequent backflow. Such tests have been proposed as a potential means to characterize properties of enhanced geothermal systems (EGS), such as fracture spacing, connectivity, and porosity. In this paper we develop an analytical solution for thermal SWIW tests, using an idealized model of a single vertical fracture with linear flow geometry embedded in impermeable conductive wall rocks. The analytical solution shows that the time dependence of temperature recovery is dominated by the heat exchange between fracture and matrix rock, but strong thermal diffusivities of rocks as compared to typical solute diffusivities are not necessarily advantageous for characterizing fracture-matrix interactions. The effect of fracture aperture on temperature recovery during backflow is weak, particularly when the fracture aperture is smaller than 0.1 cm. The solution also shows that temperature recovery during backflow is independent of the applied injection and backflow rates. This surprising result implies that temperature recovery is independent of the height of the fracture, or the specific fracture-matrix interface areas per unit fracture length, suggesting that thermal SWIW tests will not be able to characterize fracture growth that may be achieved by stimulation treatments.

  8. Basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline.

    Science.gov (United States)

    Ashida, Terunao; Takato, Tetsuya; Matsuzaki, Gen; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

    2014-01-01

    We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion. Wall movement velocity of the left ventricular base was assessed by tissue Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later. Pathological lesions were identified by deposits of carbon particles. Animals were divided into two groups according to the infused dose of adrenaline. The small-dose group (group S, n = 15) received 1-10 μg and the large-dose group (group L, n = 23) received 15-60 μg of adrenaline. Adrenaline infusion induced premature ventricular contractions followed by monomorphic ventricular tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group S. Wall movement velocity of the left ventricular base decreased just after adrenaline infusion, remained low after 1 week, and recovered to near-baseline levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits of carbon particles were frequently observed on the left ventricular basal portion, almost always associated with the mitral valve and papillary muscles, but were never observed in the apical area. Lesions involving all areas of the left ventricular basal portion were observed in 22 of 23 animals in group L, but in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits with ventricular tachycardias induced by a single injection of adrenaline.

  9. A comparison of a single or triple injection technique for ultrasound-guided infraclavicular block: a prospective randomized controlled study.

    Science.gov (United States)

    Desgagnés, Marie-Christine; Lévesque, Simon; Dion, Nicolas; Nadeau, Marie-Josée; Coté, Dany; Brassard, Jean; Nicole, Pierre C; Turgeon, Alexis F

    2009-08-01

    Good success rates have been reported with ultrasound-guided infraclavicular block using one or multiple injections of local anesthetic. We hypothesized that a separate injection of local anesthetics on each cord enhances the onset of complete sensory block. We designed this prospective randomized study to compare the rate of complete sensory block using one or three injections of local anesthetic. Patients scheduled for hand, wrist, or elbow surgery were included in this study. All blocks were performed under ultrasound guidance. In Group S (single injection), 30 mL of mepivacaine 1.5% was injected posterior to the axillary artery. In Group T (triple injections), 10 mL of mepivacaine 1.5% was injected on the posterior, medial, and lateral aspects of the axillary artery. Sensory block was evaluated every 3 min up to 30 min. The primary end point was the rate of complete sensory block at 15 min. Forty-nine and 51 patients were randomized in Groups S and T, respectively. The rate of complete sensory block was comparable at 15 min (Group S: 84%, Group T: 78%, P = 0.61) and at each time interval up to 30 min. There was no statistically significant difference in the rate of complications between the two groups. The success rate and the onset of complete sensory block after ultrasound-guided infraclavicular block are not enhanced by a triple injection of local anesthetic compared with a single injection posterior to the axillary artery.

  10. Single injection of clenbuterol into newly hatched chicks decreases abdominal fat pad weight in growing broiler chickens.

    Science.gov (United States)

    Ijiri, Daichi; Ishitani, Kanae; El-Deep, Mahmoud Mohamed Hamza; Kawaguchi, Mana; Shimamoto, Saki; Ishimaru, Yoshitaka; Ohtsuka, Akira

    2016-10-01

    The aim of the current study was to examine the effects of clenbuterol injection into newly hatched chicks on both the abdominal fat pad tissue weight and the skeletal muscle weight during subsequent growth. Twenty-seven 1-day-old chicks were divided into two groups, receiving either a single intraperitoneal (i.p.) injection of clenbuterol (0.1 mg/kg body weight) or phosphate-buffered saline (PBS). Body weight gain, feed intake and feed conversion ratio were not affected by clenbuterol injection during the 5-week experimental period, while the abdominal fat pad tissue weight of the clenbuterol-injected chicks was lower than that of the control chicks at 5 weeks post-injection. Plasma non-esterified fatty acid concentrations were significantly increased in the clenbuterol-injected chicks, while plasma triacylglycerol concentrations did not differ. Additionally, the enzymatic activity of fatty acid synthase was lower in the liver of the clenbuterol-injected chicks. Conversely, the skeletal muscle weights were not affected by clenbuterol injection. These results suggest that a single clenbuterol injection into 1-day-old chicks decreases the abdominal fat pad tissue weight, but may not affect skeletal muscle weights during growth. © 2015 Japanese Society of Animal Science. © 2015 Japanese Society of Animal Science.

  11. Effects of Stator Shroud Injection on the Aerodynamic Performance of a Single-Stage Transonic Axial Compressor

    International Nuclear Information System (INIS)

    Dinh, Cong-Truong; Ma, Sang-Bum; Kim, Kwang Yong

    2017-01-01

    In this study, stator shroud injection in a single-stage transonic axial compressor is proposed. A parametric study of the effect of stator shroud injection on aerodynamic performances was conducted using the three-dimensional Reynolds-averaged Navier-Stokes equations. The curvature, length, width, and circumferential angle of the stator shroud injector and the air injection mass flow rate were selected as the test parameters. The results of the parametric study show that the aerodynamic performances of the single-stage transonic axial compressor were improved by stator shroud injection. The aerodynamic performances were the most sensitive to the injection mass flow rate. Further, the total pressure ratio and adiabatic efficiency were the maximum when the ratio of circumferential angle was 10%.

  12. Effects of Stator Shroud Injection on the Aerodynamic Performance of a Single-Stage Transonic Axial Compressor

    Energy Technology Data Exchange (ETDEWEB)

    Dinh, Cong-Truong; Ma, Sang-Bum; Kim, Kwang Yong [Inha Univ., Incheon (Korea, Republic of)

    2017-01-15

    In this study, stator shroud injection in a single-stage transonic axial compressor is proposed. A parametric study of the effect of stator shroud injection on aerodynamic performances was conducted using the three-dimensional Reynolds-averaged Navier-Stokes equations. The curvature, length, width, and circumferential angle of the stator shroud injector and the air injection mass flow rate were selected as the test parameters. The results of the parametric study show that the aerodynamic performances of the single-stage transonic axial compressor were improved by stator shroud injection. The aerodynamic performances were the most sensitive to the injection mass flow rate. Further, the total pressure ratio and adiabatic efficiency were the maximum when the ratio of circumferential angle was 10%.

  13. Understanding the effect of single-fracture heterogeneity from single-well injection-withdrawal (SWIW) tests

    Science.gov (United States)

    Larsson, Martin; Doughty, Christine; Tsang, Chin-Fu; Niemi, Auli

    2013-12-01

    The single-well injection-withdrawal (SWIW) tracer test is a method used to estimate the tracer retardation properties of a fracture or fracture zone. The effects of single-fracture aperture heterogeneity on SWIW-test tracer breakthrough curves are examined by numerical modelling. The effects of the matrix diffusion and sorption are accounted for by using a particle tracking method through the addition of a time delay added to the advective transport time. For a given diffusion and sorption property ( P m) value and for a heterogeneous fracture, the peak concentration is larger compared to a homogeneous fracture. The cumulative breakthrough curve for a heterogeneous fracture is similar to that for a homogeneous fracture and a less sorptive/diffusive tracer. It is demonstrated that the fracture area that meets the flowing water, the specific flow-wetted surface (sFWS) of the fracture, can be determined by matching the observed breakthrough curve for a heterogeneous fracture to that for a homogeneous fracture with an equivalent property parameter. SWIW tests are also simulated with a regional pressure gradient present. The results point to the possibility of distinguishing the effect of the regional pressure gradient from that of diffusion through the use of multiple tracers with different P m values.

  14. Heterogeneous intratumoral distribution of gadolinium nanoparticles within U87 human glioblastoma xenografts unveiled by micro-PIXE imaging.

    Science.gov (United States)

    Carmona, Asuncion; Roudeau, Stéphane; L'Homel, Baptiste; Pouzoulet, Frédéric; Bonnet-Boissinot, Sarah; Prezado, Yolanda; Ortega, Richard

    2017-04-15

    Metallic nanoparticles have great potential in cancer radiotherapy as theranostic drugs since, they serve simultaneously as contrast agents for medical imaging and as radio-therapy sensitizers. As with other anticancer drugs, intratumoral diffusion is one of the main limiting factors for therapeutic efficiency. To date, a few reports have investigated the intratumoral distribution of metallic nanoparticles. The aim of this study was to determine the quantitative distribution of gadolinium (Gd) nanoparticles after direct intratumoral injection within U87 human glioblastoma tumors grafted in mice, using micro-PIXE (Particle Induced X-ray Emission) imaging. AGuIX (Activation and Guiding of Irradiation by X-ray) 3 nm particles composed of a polysiloxane network surrounded by gadolinium chelates were used. PIXE results indicate that the direct injection of Gd nanoparticles in tumors results in their heterogeneous diffusion, probably related to variations in tumor density. All tumor regions contain Gd, but with markedly different concentrations, with a more than 250-fold difference. Also Gd can diffuse to the healthy adjacent tissue. This study highlights the usefulness of mapping the distribution of metallic nanoparticles at the intratumoral level, and proposes PIXE as an imaging modality to probe the quantitative distribution of metallic nanoparticles in tumors from experimental animal models with micrometer resolution. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. In Vivo Confocal Fluorescence Imaging of the Intratumor Distribution of the Photosensitizer Mono-l-Aspartylchlorin-e6

    Directory of Open Access Journals (Sweden)

    Soumya Mitra

    2008-05-01

    Full Text Available We present an in vivo fluorescence microscopic evaluation of intratumor distribution of the photosensitizer mono-l-aspartylchlorin-e6 (NPe6 in an intradermal mouse EMT6 tumor model. Although the identification of favorable photophysical and pharmacological properties has led to the development of new photosensitizers in photodynamic therapy, their intratumor distribution kinetics have remained relatively understudied. In this study, we used confocal fluorescence microscopy to follow the transport of NPe6 in vivo after systemic administration through the tail vein. Labeling of vasculature using fluorophore-conjugated anti-CD31 antibodies allows visualization of the uptake of NPe6 in tumor and normal vessels and its partitioning kinetics into the adjacent parenchyma for 3 hours after injection. During the initial 60 minutes after injection, the drug is predominantly confined to the vasculature. Subsequently, it significantly redistributes throughout the extravascular regions with no discernable difference in its extravasation rate between tumor and normal tissues. Further, we investigate the sensitizer’s altered intratumor distribution in response to photodynamic therapy irradiation and observe that treatment-induced changes in vessel permeability caused enhanced accumulation of NPe6 in the extravascular space. Our findings are of immediate clinical relevance and demonstrate the importance of an in vivo imaging approach to examine the dynamic process of intratumor drug distribution.

  16. Structure of Intratumor Heterogeneity: Is Cancer Hedging Its Bets?

    OpenAIRE

    Brutovsky, B.; Horvath, D.

    2013-01-01

    Development of resistance limits transferability of most anticancer therapies into curative treatment and understanding mechanisms beyond it remains a big challenge. Many high resolution experimental observations show enormous intratumor heterogeneity at molecular, genetic and cellular levels which is made responsible for emerging resistance to therapy. Therefore, researchers search techniques to influence development of intratumor heterogeneity, which requires understanding its role within t...

  17. Technique, pharmacokinetics, toxicity, and efficacy of intratumoral etanidazole and radiotherapy for treatment of spontaneous feline oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Evans, S.M.; LaCreta, F.; Helfand, S.; VanWinkle, T.; Curran, W.J. Jr.; Brown, D.Q.; Hanks, G.

    1991-01-01

    The histologic appearance, locoregional recurrence, and rate/site of metastases of spontaneous feline oral squamous cell carcinoma are similar to head and neck cancer in humans. A feasibility study of intratumoral Etanidazole, a hypoxic cell sensitizer, and radiation therapy were instituted in this model. Eleven cats with feline squamous cell carcinoma were treated with intratumoral Etanidazole and radiation therapy. Total Etanidazole doses were 1.5-24.0 gms/m2 (0.5-6.9 gms). The tumor partial response rate was 100% (11/11); the median volume regression was 70%. All cats have died as a result of tumor recurrence or tumor-related complications. Median survival was 116 days. Ten cats have been autopsied. Non-necrotic and necrotic tumor cells were identified at the treatment site in all cats. Pharmacokinetic studies were performed in six cats. Following intravenous infusion, the plasma elimination of the Etanidazole was biexponential. The systemic availability following intratumoral administration was 61.2 +/- 21.1%. Peak plasma Etanidazole levels were observed 14 minutes following intratumoral injection, after which elimination was biexponential. Thirty minutes following intratumoral Etanidazole administration, tumor Etanidazole levels were 62.8% of plasma levels. Feline squamous cell carcinoma appears to be a useful model of human head and neck cancer. Cats tolerate substantial doses of intratumoral and intravenous Etanidazole. Etanidazole and radiation therapy cause rapid regression, but not cure, of feline squamous cell carcinoma. There is a similarity between the intravenous kinetics of Etanidazole in humans and cats. Further studies in this model are planned

  18. Critical firing and misfiring boundary in a spark ignition methanol engine during cold start based on single cycle fuel injection

    International Nuclear Information System (INIS)

    Li, Zhaohui; Gong, Changming; Qu, Xiang; Liu, Fenghua; Sun, Jingzhen; Wang, Kang; Li, Yufeng

    2015-01-01

    The influence of the mass of methanol injected per cycle, ambient temperature, injection and ignition timing, preheating methods, and supplying additional liquefied petroleum gas (LPG) injection into the intake manifold on the critical firing and misfiring boundary of an electronically injection controlled spark ignition (SI) methanol engine during cold start were investigated experimentally based on a single cycle fuel injection with cycle-by-cycle control strategy. The critical firing and misfiring boundary was restricted by all parameters. For ambient temperatures below 16 °C, methanol engines must use auxiliary start-aids during cold start. Optimal control of the methanol injection and ignition timing can realize ideal next cycle firing combustion after injection. Resistance wire and glow plug preheating can provide critical firing down to ambient temperatures of 5 °C and 0 °C, respectively. Using an additional LPG injection into the intake manifold can provide critical firing down to an ambient temperature of −13 °C during cold start. As the ambient temperature decreases, the optimal angle difference between methanol injection timing and LPG injection timing for critical firing of a methanol engine increases rapidly during cold start. - Highlights: • A single cycle fuel injection and cycle-by-cycle control strategy are used to study. • In-cylinder pressure and instantaneous speed were used to determine firing boundary. • For the ambient temperatures below 16 °C, an auxiliary start-aids must be used. • A preheating and additional LPG were used to expand critical firing boundary. • Additional LPG can result in critical firing down to ambient temperature of −13 °C

  19. The acceptability of three vaccine injections given to infants during a single clinic visit in South Africa

    Directory of Open Access Journals (Sweden)

    Hanani Tabana

    2016-08-01

    Full Text Available Abstract Background The Expanded Programme on Immunisation (EPI has increased the number of antigens and injections administered at one visit. There are concerns that more injections at a single immunisation visit could decrease vaccination coverage. We assessed the acceptability and acceptance of three vaccine injections at a single immunisation visit by caregivers and vaccinators in South Africa. Methods A mixed methods exploratory study of caregivers and vaccinators at clinics in two provinces of South Africa was conducted. Quantitative and qualitative data were collected using questionnaires as well as observations of the administration of three-injection vaccination sessions. Results The sample comprised 229 caregivers and 98 vaccinators. Caregivers were satisfied with the vaccinators’ care (97 % and their infants receiving immunisation injections (93 %. However, many caregivers, (86 % also felt that three or more injections were excessive at one visit. Caregivers had limited knowledge of actual vaccines provided, and reasons for three injections. Although vaccinators recognised the importance of informing caregivers about vaccination, they only did this sometimes. Overall, acceptance of three injections was high, with 97 % of caregivers expressing willingness to bring their infant for three injections again in future visits despite concerns about the pain and discomfort that the infant experienced. Many (55 % vaccinators expressed concern about giving three injections in one immunisation visit. However, in 122 (95 % observed three-injection vaccination sessions, the vaccinators administered all required vaccinations for that visit. The remaining seven vaccinations were not completed because of vaccine stock-outs. Conclusions We found high acceptance by caregivers and vaccinators of three injections. Caregivers’ poor understanding of reasons for three injections resulted from limited information sharing by vaccinators for

  20. Highly efficient subcloning of rodent malaria parasites by injection of single merosomes or detached cells.

    Science.gov (United States)

    Stanway, Rebecca R; Graewe, Stefanie; Rennenberg, Annika; Helm, Susanne; Heussler, Volker T

    2009-01-01

    This protocol describes a method for obtaining rodent Plasmodium parasite clones with high efficiency, which takes advantage of the normal course of Plasmodium in vitro exoerythrocytic development. At the completion of development, detached cells/merosomes form, which contain hundreds to thousands of merozoites. As all parasites within a single detached cell/merosome derive from the same sporozoite, we predicted them to be genetically identical. To prove this, hepatoma cells were infected simultaneously with a mixture of Plasmodium berghei sporozoites expressing either GFP or mCherry. Subsequently, individual detached cells/merosomes from this mixed population were selected and injected into mice, resulting in clonal blood stage parasite infections. Importantly, as a large majority of mice become successfully infected using this protocol, significantly less mice are necessary than for the widely used technique of limiting dilution cloning. To produce a clonal P. berghei blood stage infection from a non-clonal infection using this procedure requires between 4 and 5 weeks.

  1. Single injection techniques in determining age-related changes in porcine renal function

    International Nuclear Information System (INIS)

    Robbins, M.E.C.

    1984-01-01

    Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined in 32 anaesthetised female Large White pigs, aged 4-24 months, from the plasma disappearance curves of [sup(99m)Tc]DTPA and [ 131 I]hippuran respectively. Clearance was also monitored by external counting over the heart. GFR and ERPF increased markedly with age in pigs up to 12 months old, reaching mean values of 242.06 +- 5.89 and 919.39 +- 79.01 mL/min. In pigs aged 12-24 months ERPF increased slightly but renal function remained essentially unchanged after 1 yr of age. These results for renal function were similar to previous estimates, using continuous infusion techniques inferring that GFR and ERPF could be accurately monitored using single injection procedures. (author)

  2. Baseline performance and emissions data for a single-cylinder, direct-injected diesel engine

    Science.gov (United States)

    Dezelick, R. A.; Mcfadden, J. J.; Ream, L. W.; Barrows, R. F.

    1983-01-01

    Comprehensive fuel consumption, mean effective cylinder pressure, and emission test results for a supercharged, single-cylinder, direct-injected, four-stroke-cycle, diesel test engine are documented. Inlet air-to-exhaust pressure ratios were varied from 1.25 to 3.35 in order to establish the potential effects of turbocharging techniques on engine performance. Inlet air temperatures and pressures were adjusted from 34 to 107 C and from 193 to 414 kPa to determine the effects on engine performance and emissions. Engine output ranged from 300 to 2100 kPa (brake mean effective pressure) in the speed range of 1000 to 3000 rpm. Gaseous and particulate emission rates were measured. Real-time values of engine friction and pumping loop losses were measured independently and compared with motored engine values.

  3. Influence of heat exchange of reservoir with rocks on hot gas injection via a single well

    Science.gov (United States)

    Nikolaev, Vladimir E.; Ivanov, Gavril I.

    2017-11-01

    In the computational experiment the influence of heat exchange through top and bottom of the gas-bearing reservoir on the dynamics of temperature and pressure fields during hot gas injection via a single well is investigated. The experiment was carried out within the framework of modified mathematical model of non-isothermal real gas filtration, obtained from the energy and mass conservation laws and the Darcy law. The physical and caloric equations of state together with the Newton-Riemann law of heat exchange of gas reservoir with surrounding rocks, are used as closing relations. It is shown that the influence of the heat exchange with environment on temperature field of the gas-bearing reservoir is localized in a narrow zone near its top and bottom, though the size of this zone is increased with time.

  4. Interpretation of injection-withdrawal tracer experiments conducted between two wells in a large single fracture.

    Science.gov (United States)

    Novakowski, K S; Bickerton, G; Lapcevic, P

    2004-09-01

    Tracer experiments conducted using a flow field established by injecting water into one borehole and withdrawing water from another are often used to establish connections and investigate dispersion in fractured rock. As a result of uncertainty in the uniqueness of existing models used for interpretation, this method has not been widely used to investigate more general transport processes including matrix diffusion or advective solute exchange between mobile and immobile zones of fluid. To explore the utility of the injection-withdrawal method as a general investigative tool and with the intent to resolve the transport processes in a discrete fracture, two tracer experiments were conducted using the injection-withdrawal configuration. The experiments were conducted in a fracture which has a large aperture (>500 microm) and horizontally pervades a dolostone formation. One experiment was conducted in the direction of the hydraulic gradient and the other in the direction opposite to the natural gradient. Two tracers having significantly different values of the free-water diffusion coefficient were used. To interpret the experiments, a hybrid numerical-analytical model was developed which accounts for the arcuate shape of the flow field, advection-dispersion in the fracture, diffusion into the matrix adjacent to the fracture, and the presence of natural flow in the fracture. The model was verified by comparison to a fully analytical solution and to a well-known finite-element model. Interpretation of the tracer experiments showed that when only one tracer, advection-dispersion, and matrix diffusion are considered, non-unique results were obtained. However, by using multiple tracers and by accounting for the presence of natural flow in the fracture, unique interpretations were obtained in which a single value of matrix porosity was estimated from the results of both experiments. The estimate of porosity agrees well with independent measurements of porosity obtained from

  5. Singles transmission scans performed post-injection for quantitative whole body FDG-PET

    Energy Technology Data Exchange (ETDEWEB)

    Smith, R.J.; Benard, F.; Karp, J.S. [Univ. of Pennsylvania, Philadelphia, PA (United States)] [and others

    1996-12-31

    Post-injection singles transmission scanning has been implemented in the septumless PENN PET 240H scanner (prototype of the GE QUEST). The method uses a 6 mCi point transmission source of {sup 137}Cs at the axial center and 37 cm of transaxial center of the camera field of view. Singles transmission scans of 1.8 minutes per bed axial position provide similar scan count densities to 15 minute coincidence transmission scans with 0.5 mCi {sup 68}Ge rod transmission source. Scatter and emission contamination suppression are achieved by applying a narrow 662 keV transmission photopeak energy window. The residual 511 keV emission contamination constitutes a background of uniform spatial distribution. Accurate and low noise attenuation correction is achieved by segmenting the singles transmission images into lung and soft tissue volumes. Established 511 keV gamma ray attenuation coefficients are then applied and these images are forward projected for attenuation correction. Expectation maximisation or OS-EM reconstruction of the transmission and emission images is used to improve image quality. Both the segmentation and OS-EM reconstruction maintain quantitative accuracy in the fully corrected emission images compared to measured coincidence transmission correction. Thus, a clinical protocol involving 40 minutes of emission scans followed by 20 minutes of singles transmission scans allow the 60 cm of the human torso to be fully scanned within 60 minutes. These quantitative whole body FDG PET images may then be used for tumor grading and assessment of tumor response to treatment.

  6. Magnetic resonance imaging of single co-labeled mesenchymal stromal cells after intracardial injection in mice

    Energy Technology Data Exchange (ETDEWEB)

    Salamon, J.; Adam, G.; Peldschus, K. [University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Dept. of Diagnostic and Interventional Radiology; Wicklein, D.; Schumacher, U. [University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Inst. of Anatomy II: Experimental Morphology; Didie, M. [Goettingen Univ. (Germany). Inst. of Pharmacology; Lange, C. [University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Dept. of Bone Marrow Transplantation

    2014-04-15

    Purpose: The aim of this study was to establish co-labeling of mesenchymal stromal cells (MSC) for the detection of single MSC in-vivo by MRI and histological validation. Materials and Methods: Mouse MSC were co-labeled with fluorescent iron oxide micro-particles and carboxyfluorescein succinimidyl ester (CFSE). The cellular iron content was determined by atomic absorption spectrometry. Cell proliferation and expression of characteristic surface markers were determined by flow cytometry. The chondrogenic differentiation capacity was assessed. Different amounts of cells (n1 = 5000, n2 = 15 000, n3 = 50 000) were injected into the left heart ventricle of 12 mice. The animals underwent sequential MRI on a clinical 3.0T scanner (Intera, Philips Medical Systems, Best, The Netherlands). For histological validation cryosections were examined by fluorescent microscopy. Results: Magnetic and fluorescent labeling of MSC was established (mean cellular iron content 23.6 ± 3 pg). Flow cytometry showed similar cell proliferation and receptor expression of labeled and unlabeled MSC. Chondrogenic differentiation of labeled MSC was verified. After cell injection MRI revealed multiple signal voids in the brain and fewer signal voids in the kidneys. In the brain, an average of 4.6 ± 1.2 (n1), 9.0 ± 3.6 (n2) and 25.0 ± 1.0 (n3) signal voids were detected per MRI slice. An average of 8.7 ± 3.1 (n1), 22.0 ± 6.1 (n2) and 89.8 ± 6.5 (n3) labeled cells per corresponding stack of adjacent cryosections could be detected in the brain. Statistical correlation of the numbers of MRI signal voids in the brain and single MSC found by histology revealed a correlation coefficient of r = 0.91. Conclusion: The study demonstrates efficient magnetic and fluorescent co-labeling of MSC and their detection on a single cell level in mice by in-vivo MRI and histology. The described techniques may broaden the methods for in-vivo tracking of MSC. (orig.)

  7. Positron emission tomography studies with 11C-ethanol in intratumoral therapy for cell carcinoma

    International Nuclear Information System (INIS)

    Dimitrakopoulou-Strauss, A.; Gutzler, F.; Strauss, L.G.; Irngartinger, G.; Oberdorfer, F.; Doll, J.; Stremmel, W.; Kaick, G. van

    1996-01-01

    Positron emission tomography (PET) is a noninvasive functional method for the study of solid tumor perfusion, metabolism and interaction with different therapeutic agents. The aim of the study was the investigation of the metabolism of hepatocellular carcinomas (HCC) and the kinetics during a treatment with intratumoral ethanol by PET. The ongoing study includes seven patients with child A cirrhosis and HCC (UICC stage III-IVA; tumor size 3-6 cm). Dynamic PET studies (60 min) with 18 F-fluordeoxyglucose (FDG) were performed prior to therapy to assess tumor viability. The evaluation of the FDG data demonstrated a liver-equivalent uptake in six of the tumors (well and moderately differentiated HCC), which were poorly delinated against the normal liver parenchyma. One moderately differentiated HCC showed an increased FDG metabolism, indicating no correlation between histology and metabolism. A dose of 37-80 MBq 11 C-ethanol was applied together with a nonlabelled therapeutic dose of the drug via a puncture needle positioned under sonography. Five out of seven tumors demonstrated a high 11 C uptake shortly after the end of the ethanol injection followed by constant 11 C-ethanol concentration during the whole study period of 45 min. The PET data demonstrated no significant elimination of the 11 C-ethanol from the tumor and no accumulation in the surrounding liver tissue. One case showed a decrease of the intratumoral 11 C -ethanol concentration due to a punkture of a tumor vein, and in another case the surrounding liver parenchyma demonstrated significant 11 C uptake in the early phase following paratumoral injection of the drug. In conclusion, PET is a useful tool for the study of the mechanism and the kinetics of percutaneous intratumoral ethanol injection of HCC. (orig.) [de

  8. Single well injection withdrawal tests (SWIW) in fractured rock. Some aspects on interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Neretnieks, Ivars [Dept. of Chemical Engineering and Technology, Royal Inst. of Technology, Stockholm (Sweden)

    2007-08-15

    Single-Well-Injection-Withdrawal, SWIW, tests are used to try to extract information on fracture apertures, sorption and diffusion properties and dispersion information in individual fractures. It is done by injecting a given amount of traced water into an isolated fracture. After a waiting period water is withdrawn from the fracture and the tracer concentration is measured. The concentration time curve is fitted to a model and the parameter values quantifying the different interaction mechanisms are determined. A number of different mechanisms influence the recovery of the tracer. One or more of the following mechanisms are considered. They include: dispersion due to velocity differences, sorption on fracture surface and on infill, diffusion in rock fragments in the fracture, diffusion between 'streamlines', diffusion into rock matrix and other stagnant water volumes, sorption kinetics and slow drift of the plume caused by the natural gradient. Many of the interaction mechanisms can influence the recovery curve in a similar way. For example, diffusion into rock matrix water and into stagnant water in the fracture adjacent to the flowing channels cannot be distinguished if only one tracer is used. Tracers with different properties can in principle be used but they will encounter different parts of the fracture, the sorbing tracer will move out less from the injection point than a nonsorbing tracer will. Diffusion and sorption in small particles in the flowpath can influence the recovery curve in a similar way as rock matrix diffusion does. Dispersion caused by diffusion between 'streamlines', Taylor dispersion, can give very different results in channels of different shapes. Such dispersion effects can be difficult to distinguish from matrix diffusion effects. Dispersion coefficients obtained in a SWIW test may have little relation to dispersion of a tracer moving from A to B. This is partly due to the different mechanisms and partly due to

  9. Single well injection withdrawal tests (SWIW) in fractured rock. Some aspects on interpretation

    International Nuclear Information System (INIS)

    Neretnieks, Ivars

    2007-08-01

    Single-Well-Injection-Withdrawal, SWIW, tests are used to try to extract information on fracture apertures, sorption and diffusion properties and dispersion information in individual fractures. It is done by injecting a given amount of traced water into an isolated fracture. After a waiting period water is withdrawn from the fracture and the tracer concentration is measured. The concentration time curve is fitted to a model and the parameter values quantifying the different interaction mechanisms are determined. A number of different mechanisms influence the recovery of the tracer. One or more of the following mechanisms are considered. They include: dispersion due to velocity differences, sorption on fracture surface and on infill, diffusion in rock fragments in the fracture, diffusion between 'streamlines', diffusion into rock matrix and other stagnant water volumes, sorption kinetics and slow drift of the plume caused by the natural gradient. Many of the interaction mechanisms can influence the recovery curve in a similar way. For example, diffusion into rock matrix water and into stagnant water in the fracture adjacent to the flowing channels cannot be distinguished if only one tracer is used. Tracers with different properties can in principle be used but they will encounter different parts of the fracture, the sorbing tracer will move out less from the injection point than a nonsorbing tracer will. Diffusion and sorption in small particles in the flowpath can influence the recovery curve in a similar way as rock matrix diffusion does. Dispersion caused by diffusion between 'streamlines', Taylor dispersion, can give very different results in channels of different shapes. Such dispersion effects can be difficult to distinguish from matrix diffusion effects. Dispersion coefficients obtained in a SWIW test may have little relation to dispersion of a tracer moving from A to B. This is partly due to the different mechanisms and partly due to different time scales

  10. Numerical simulations of single and multi-staged injection of H2 in a supersonic scramjet combustor

    Directory of Open Access Journals (Sweden)

    L. Abu-Farah

    2014-12-01

    Full Text Available Computational fluid dynamics (CFD simulations of a single staged injection of H2 through a central wedge shaped strut and a multi-staged injection through wall injectors are carried out by using Ansys CFX-12 code. Unstructured tetrahedral grids for narrow channel and quarter geometries of the combustor are generated by using ICEM CFD. Steady three-dimensional (3D Reynolds-averaged Navier-stokes (RANS simulations are carried out in the case of no H2 injection and compared with the simulations of single staged pilot and/or main H2 injections and multistage injection. Shear stress transport (SST based on k-ω turbulent model is adopted. Flow field visualization (complex shock waves interactions and static pressure distribution along the wall of the combustor are predicted and compared with the experimental schlieren images and measured wall static pressures for validation. A good agreement is found between the CFD predicted results and the measured data. The narrow and quarter geometries of the combustor give similar results with very small differences. Multi-staged injections of H2 enhance the turbulent H2/air mixing by forming vortices and additional shock waves (bow shocks.

  11. A prospective, randomized comparison between single- and multiple-injection techniques for ultrasound-guided subgluteal sciatic nerve block.

    Science.gov (United States)

    Yamamoto, Hiroto; Sakura, Shinichi; Wada, Minori; Shido, Akemi

    2014-12-01

    It is believed that local anesthetic injected to obtain circumferential spread around nerves produces a more rapid onset and successful blockade after some ultrasound-guided peripheral nerve blocks. However, evidence demonstrating this point is limited only to the popliteal sciatic nerve block, which is relatively easy to perform by via a high-frequency linear transducer. In the present study, we tested the hypothesis that multiple injections of local anesthetic to make circumferential spread would improve the rate of sensory and motor blocks compared with a single-injection technique for ultrasound-guided subgluteal sciatic nerve block, which is considered a relatively difficult block conducted with a low-frequency, curved-array transducer. Ninety patients undergoing knee surgery were divided randomly into 2 groups to receive the ultrasound-guided subgluteal approach to sciatic nerve block with 20 mL of 1.5% mepivacaine with epinephrine. For group M (the multiple-injection technique), the local anesthetic was injected to create circumferential spread around the sciatic nerve without limitation on the number of needle passes. For group S (the single-injection technique), the number of needle passes was limited to 1, and the local anesthetic was injected to create spread along the dorsal surface of the sciatic nerve, during which no adjustment of the needle tip was made. Sensory and motor blockade were assessed in double-blind fashion for 30 minutes after completion of the block. The primary outcome was sensory blockade of all sciatic components tested, including tibial, superficial peroneal, and sural nerves at 30 minutes after injection. Data from 86 patients (43 in each group) were analyzed. Block execution took more time for group M than group S. The proportion of patients with complete sensory blockade of all sciatic components at 30 minutes after injection was significantly larger for group M than group S (41.9% vs 16.3%, P = 0.018). Complete motor blockade of

  12. Single-dose methotrexate injection for treatment of ectopic pregnancy in women with relatively low levels of human chorionic gonadotropin.

    Science.gov (United States)

    Krissi, Haim; Peled, Yoav; Eitan, Ram; Bishara, Amani; Goldchmit, Chen; Ben-Haroush, Avi

    2013-05-01

    To evaluate potential risk factors at admission for failed single-dose methotrexate injection in women with ectopic pregnancy. File review of a tertiary medical center in Israel yielded 102 consecutive patients with ectopic pregnancy initially treated with single-dose methotrexate. Overall successful treatment was defined as normalization of human chorionic gonadotropin (hCG) levels after the first or second injection. The mean pretreatment hCG level for the whole cohort was 2350 ± 2955 mIU/mL (median, 1187 mIU/mL; 90th percentile, 5000 mIU/mL). Resolution of ectopic pregnancy was achieved after a single injection in 76/102 (74.5%) women and after a second dose in 16/21 (76.2%) women. The remaining 10 (9.8%) patients were treated surgically after the first (5/76) or the second (5/26) dose. The overall success rate for methotrexate treatment was 90.2%. On multivariate stepwise logistic analysis, fetal cardiac activity was an independent predictor of a failed first methotrexate injection, and presence of a yolk sac and mass size were independent predictors of overall methotrexate failure and need for secondary surgery. In patients with ectopic pregnancy and relatively low levels of serum hCG, the most important predictors of overall failure of methotrexate injection were the presence of a yolk sac and mass size. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  13. Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis.

    Science.gov (United States)

    van der Drift, Saskia G A; Houweling, Martin; Bouman, Marina; Koets, Ad P; Tielens, Aloysius G M; Nielen, Mirjam; Jorritsma, Ruurd

    2015-05-01

    This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene glycol twice daily for 3 days and were randomly assigned to a single intramuscular injection with sterile isotonic saline solution (n = 14) or dexamethasone-21-isonicotinate (n = 17). Metabolic blood variables were monitored for 6 days and adipose tissue variables for 3 days. β-Hydroxybutyrate (BHBA) concentrations in blood decreased in all cows during treatment, but were lower in glucocorticoid-treated cows. Cows treated with glucocorticoids had higher plasma glucose and insulin concentrations, whereas concentrations of non-esterified fatty acids, 3-methylhistidine and growth hormone were unaffected. mRNA expression of hormone-sensitive lipase, BHBA receptor and peroxisome proliferator-activated receptor type γ in adipose tissue was not affected. This shows that lipolytic effects do not appear to be important in ketotic cows when glucocorticoids are combined with PG. Plasma 3-methyl histidine concentrations were similar in both groups, suggesting that glucocorticoids did not increase muscle breakdown and that the greater rise in plasma glucose in glucocorticoid-treated cows may not be due to increased supply of glucogenic amino acids from muscle. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment

    Directory of Open Access Journals (Sweden)

    Agostinetto Rita

    2009-05-01

    Full Text Available Abstract Background Gonadotrophins are routinely administered in assisted reproductive technology (ART treatment protocols. Recombinant human follicle-stimulating hormone (r-hFSH; follitropin alfa and recombinant human luteinizing hormone (r-hLH; lutropin alfa can be administered individually or in a fixed combination. The ability to vary the FSH to LH dose ratio in a single injection without compromising the bioactivity of either gonadotrophin or generating losses of active principle is important for physicians and patients alike. Methods This study investigated whether follitropin alfa (GONAL-f (R, as lyophilized powder for reconstitution or solution from the GONAL-f (R (filled-by-mass [FbM] Prefilled Pen, could be used to reconstitute Pergoveris TM (follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder. In Ratio Groups 1 and 2, the r-hFSH:r-hLH ratio was 3:1; in Ratio Groups 3 and 4, the ratios of r-hFSH:r-hLH were 5:1 and 8:1, respectively. The protein content and bioactivity of each mixed solution were evaluated. The r-hFSH and r-hLH content was determined using reverse-phase high performance liquid chromatography. The biological activity of r-hFSH and r-hLH was assessed using the Steelman-Pohley and Van Hell in vivo bioassays in rats, respectively. Results Follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder could be successfully mixed with follitropin alfa 75 IU FbM solution that was either reconstituted from lyophilized powder or injected directly from the prefilled pen to create solutions with ratios of r-hFSH and r-hLH from 3:1 to 8:1. The measured content of r-hFSH and r-hLH corresponded favourably with the target protein content in Ratio Groups 1–4. The in vivo target and measured bioactivity of r-hFSH and r-hLH were also closely matched in all Ratio Groups. Conclusion Follitropin alfa lyophilized powder or solution can be accurately mixed with follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder to

  15. Reproducibility of Intratumor Distribution of 18F-Fluoromisonidazole in Head and Neck Cancer

    International Nuclear Information System (INIS)

    Nehmeh, Sadek A.; Lee, Nancy Y.; Schroeder, Heiko; Squire, Olivia; Zanzonico, Pat B.; Erdi, Yusuf E.; Greco, Carlo; Mageras, Gig; Pham, Hai S.; Larson, Steve M.; Ling, Clifton C.; Humm, John L.

    2008-01-01

    Purpose: Hypoxia is one of the main causes of the failure to achieve local control using radiotherapy. This is due to the increased radioresistance of hypoxic cells. 18 F-fluoromisonidazole ( 18 F-FMISO) positron emission tomography (PET) is a noninvasive imaging technique that can assist in the identification of intratumor regions of hypoxia. The aim of this study was to evaluate the reproducibility of 18 F-FMISO intratumor distribution using two pretreatment PET scans. Methods and Materials: We enrolled 20 head and neck cancer patients in this study. Of these, 6 were excluded from the analysis for technical reasons. All patients underwent an 18 F-fluorodeoxyglucose study, followed by two 18 F-FMISO studies 3 days apart. The hypoxic volumes were delineated according to a tumor/blood ratio ≥1.2. The 18 F-FMISO tracer distributions from the two 18 F-FMISO studies were co-registered on a voxel-by-voxel basis using the computed tomography images from the PET/computed tomography examinations. A correlation between the 18 F-FMISO intensities of the corresponding spatial voxels was derived. Results: A voxel-by-voxel analysis of the 18 F-FMISO distributions in the entire tumor volume showed a strong correlation in 71% of the patients. Restraining the correlation to putatively hypoxic zones reduced the number of patients exhibiting a strong correlation to 46%. Conclusion: Variability in spatial uptake can occur between repeat 18 F-FMISO PET scans in patients with head and neck cancer. Blood data for one patient was not available. Of 13 patients, 6 had well-correlated intratumor distributions of 18 F-FMISO-suggestive of chronic hypoxia. More work is required to identify the underlying causes of changes in intratumor distribution before single-time-point 18 F-FMISO PET images can be used as the basis of hypoxia-targeting intensity-modulated radiotherapy

  16. Knee Viscosupplementation: Cost-Effectiveness Analysis between Stabilized Hyaluronic Acid in a Single Injection versus Five Injections of Standard Hyaluronic Acid

    Directory of Open Access Journals (Sweden)

    Francisco J. Estades-Rubio

    2017-03-01

    Full Text Available Given the wide difference in price per vial between various presentations of hyaluronic acid, this study seeks to compare the effectiveness and treatment cost of stabilized hyaluronic acid (NASHA in a single injection with standard preparations of hyaluronic acid (HA in five injections in osteoarthritis (OA of the knee. Fifty-four patients with knee osteoarthritis (Kellgren–Lawrence Grade II and III and the Western Ontario and McMaster Universities Arthritis Index (WOMAC pain score greater than 7, with a homogeneous distribution of age, sex, BMI, and duration of disease, were included in this study. Patients were randomized into two groups: Group I was treated with NASHA (Durolane® and Group II with HA (Go-ON®. Patient’s evolution was followed up at the 1st, 2nd, 4th, 8th, 12th, and 26th week after treatment. A statistically significant improvement in WOMAC score was observed for patients treated with NASHA versus those who received HA at Week 26. In addition, the need for analgesia was significantly reduced at Week 26 in the NASHA-treated group. Finally, the economic analysis showed an increased cost of overall treatment with HA injections. Our data support the use of the NASHA class of products in the treatment of knee OA.

  17. Knee Viscosupplementation: Cost-Effectiveness Analysis between Stabilized Hyaluronic Acid in a Single Injection versus Five Injections of Standard Hyaluronic Acid.

    Science.gov (United States)

    Estades-Rubio, Francisco J; Reyes-Martín, Alvaro; Morales-Marcos, Victor; García-Piriz, Mercedes; García-Vera, Juan J; Perán, Macarena; Marchal, Juan A; Montañez-Heredia, Elvira

    2017-03-17

    Given the wide difference in price per vial between various presentations of hyaluronic acid, this study seeks to compare the effectiveness and treatment cost of stabilized hyaluronic acid (NASHA) in a single injection with standard preparations of hyaluronic acid (HA) in five injections in osteoarthritis (OA) of the knee. Fifty-four patients with knee osteoarthritis (Kellgren-Lawrence Grade II and III) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score greater than 7, with a homogeneous distribution of age, sex, BMI, and duration of disease, were included in this study. Patients were randomized into two groups: Group I was treated with NASHA (Durolane ® ) and Group II with HA (Go-ON ® ). Patient's evolution was followed up at the 1st, 2nd, 4th, 8th, 12th, and 26th week after treatment. A statistically significant improvement in WOMAC score was observed for patients treated with NASHA versus those who received HA at Week 26. In addition, the need for analgesia was significantly reduced at Week 26 in the NASHA-treated group. Finally, the economic analysis showed an increased cost of overall treatment with HA injections. Our data support the use of the NASHA class of products in the treatment of knee OA.

  18. The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections.

    Science.gov (United States)

    Goncars, Valdis; Jakobsons, Eriks; Blums, Kristaps; Briede, Ieva; Patetko, Liene; Erglis, Kristaps; Erglis, Martins; Kalnberzs, Konstantins; Muiznieks, Indrikis; Erglis, Andrejs

    2017-01-01

    The aim of this study was to compare treatment methods of the knee joint degenerative osteoarthritis, using autologous bone marrow-derived mononuclear cells and hyaluronic acid injections and observe prevalence of adverse effects in both groups. A prospective randomized controlled clinical trial was carried out. The analysis of pain and changes in osteoarthritis symptoms after a single intra-articular bone marrow-derived mononuclear cell injection into the knee joint in the Kellgren-Lawrence stage II-III osteoarthritis during the 12-month period were performed. The results were compared with the control group treated routinely by hyaluronic acid injections therapy. A therapy group of patients (n=28) received single bone marrow-derived mononuclear cell intra-articular injections. A control group of patients (n=28) was treated with a total of three sodium hyaluronate intra-articular injections each one performed a week apart. The clinical results were obtained using the Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) before and 3, 6, and 12 months after injection. A statistically significant improvement was observed in the mononuclear cell group over the starting point in all scores. At the endpoint at month 12, the KOOS score improved significantly (Phyaluronic acid versus the bone marrow-derived mononuclear cells group at time points 6 and 12 months demonstrated a statistically significant (Phyaluronic acid group. In both groups serious adverse effects were not observed. The intra-articular injection of bone marrow-derived mononuclear cells is a safe manipulation with no side effects during the 12-month period. This treatment provides statistically significant clinical improvement between the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic acid treatment, better pain relief in the long-term period of mononuclear cell group was observed. Copyright © 2017 The Lithuanian University of Health Sciences. Production

  19. Effect of injection pressure on performance, emission, and combustion characteristics of diesel-acetylene-fuelled single cylinder stationary CI engine.

    Science.gov (United States)

    Srivastava, Anmesh Kumar; Soni, Shyam Lal; Sharma, Dilip; Jain, Narayan Lal

    2018-03-01

    In this paper, the effect of injection pressure on the performance, emission, and combustion characteristics of a diesel-acetylene fuelled single cylinder, four-stroke, direct injection (DI) diesel engine with a rated power of 3.5 kW at a rated speed of 1500 rpm was studied. Experiments were performed in dual-fuel mode at four different injection pressures of 180, 190, 200, and 210 bar with a flow rate of 120 LPH of acetylene and results were compared with that of baseline diesel operation. Experimental results showed that highest brake thermal efficiency of 27.57% was achieved at injection pressure of 200 bar for diesel-acetylene dual-fuel mode which was much higher than 23.32% obtained for baseline diesel. Carbon monoxide, hydrocarbon, and smoke emissions were also measured and found to be lower, while the NO x emissions were higher at 200 bar in dual fuel mode as compared to those in other injection pressures in dual fuel mode and also for baseline diesel mode. Peak cylinder pressure, net heat release rate, and rate of pressure rise were also calculated and were higher at 200 bar injection pressure in dual fuel mode.

  20. Injection-locked single-mode VCSEL for orthogonal multiplexing and amplitude noise suppression

    DEFF Research Database (Denmark)

    Chipouline, Arkadi; Lyubopytov, Vladimir S.; Malekizandi, Mohammadreza

    2017-01-01

    an injection-locked 1550 nm VCSEL as a slave laser providing separation of amplitude and phase modulations, carrying independent information flows. To validate the possibility of phase modulation extraction by an injection-locked VCSEL, an experimental setup shown in Fig. 1 has been built....

  1. Engine with hydraulic fuel injection and ABS circuit using a single high pressure pump

    Science.gov (United States)

    Bartley, Bradley E.; Blass, James R.; Gibson, Dennis H.

    2001-01-01

    An engine system comprises a hydraulically actuated fuel injection system and an ABS circuit connected via a fluid flow passage that provides hydraulic fluid to both the fuel injection system and to the ABS circuit. The hydraulically actuated system includes a high pressure pump. The fluid control passage is in fluid communication with an outlet from the high pressure pump.

  2. Single mode operation of a tea CO2 laser by a CW CO2 laser radiation injection

    International Nuclear Information System (INIS)

    Silakhori, K.; Soltanmoradi, F.; Behjat, A.; Montazerghaem, M.; Sadr, R.

    2005-01-01

    In this research work, single mode operation based on injection of a CW laser beam into TEA CO 2 laser cavity has been demonstrated. The technique has vast applications in research programs for laser spectroscopy and optical pumping. The observed smooth pulse shapes indicated that the system is operating in a single mode of operation, where no additional PZT mounted elements or other cavity stabilizing devices have been used. In addition, it have been observed that the output energy has not been reduced when the laser was operating in a single mode of operation, compared with the case when the laser is operating in the multi-mode regime

  3. Experimental investigation of gasoline fumigation in a single cylinder direct injection (DI) diesel engine

    International Nuclear Information System (INIS)

    Sahin, Z.; Durgun, O.; Bayram, C.

    2008-01-01

    In the presented study, the effects of gasoline fumigation have been investigated experimentally in a single cylinder direct injection (DI) diesel engine. Gasoline has been introduced into the inlet air flow using an elementary carburetor and no other modification on the engine has been done. The effects of 2%, 4%, 6%, 8% and 10% (by vol.) gasoline fumigation have been investigated experimentally at the speeds of (900-1600) (rpm) and at the selected compression ratios of (18-23). From the experimental results it is determined that by application of gasoline fumigation effective power output increases at the levels of 4-9%, effective efficiency increases by approximately 1.5-4% and specific fuel consumption decreases by approximately 1.5-4%. It is also determined that 4-6% fumigation ratio range is the most favorable percentage interval of gasoline at the selected compression ratios for this engine. Because cost of gasoline is higher than diesel fuel in Turkey as well as in many of the other countries and the decrease ratio of specific fuel consumption is low, gasoline fumigation is not economic for this engine. In the presented study, heat balance tests have also been performed for 18 and 21 compression ratios. The heat balance has been investigated experimentally in respect of effective power, heat rejected to the cooling water, heat lost through exhaust, and other losses (unaccounted-for losses). Heat lost through exhaust decreases until 4-6% gasoline fumigation ratios and after these fumigation ratios it starts to increase because of increasing exhaust gas temperature. Heat rejected to the cooling water decreases at low fumigation ratios, but at high fumigation ratios it increases. Other losses generally exhibit an increasing tendency at low fumigation ratios

  4. Towards inverse modeling of intratumor heterogeneity

    Science.gov (United States)

    Brutovsky, Branislav; Horvath, Denis

    2015-08-01

    Development of resistance limits efficiency of present anticancer therapies and preventing it remains a big challenge in cancer research. It is accepted, at the intuitive level, that resistance emerges as a consequence of the heterogeneity of cancer cells at the molecular, genetic and cellular levels. Produced by many sources, tumor heterogeneity is extremely complex time dependent statistical characteristics which may be quantified by measures defined in many different ways, most of them coming from statistical mechanics. In this paper, we apply the Markovian framework to relate population heterogeneity to the statistics of the environment. As, from an evolutionary viewpoint, therapy corresponds to a purposeful modi- fication of the cells' fitness landscape, we assume that understanding general relationship between the spatiotemporal statistics of a tumor microenvironment and intratumor heterogeneity will allow to conceive the therapy as an inverse problem and to solve it by optimization techniques. To account for the inherent stochasticity of biological processes at cellular scale, the generalized distancebased concept was applied to express distances between probabilistically described cell states and environmental conditions, respectively.

  5. Shower emboli and digital necrosis after a single corticosteroid injection for trigger thumb: case report.

    Science.gov (United States)

    Park, Jonathan; Dumanian, Gregory A

    2009-02-01

    Local corticosteroid injection into the hand is the preferred initial step in the management of trigger finger owing to its safety and efficacy. We report the case of a patient with shower emboli and digital necrosis after a local corticosteroid injection for the treatment of trigger thumb. Given the patient's subsequent negative hypercoagulability workup, we suspect that the patient's symptoms resulted from the injection of steroids into the princeps pollicis artery, with subsequent retrograde flow into multiple other arteries of the hand. The patient was managed conservatively and ultimately her symptoms resolved. No new areas of digital necrosis have appeared in 8 years of follow-up.

  6. Rapid induction of dopamine sensitization in the nucleus accumbens shell induced by a single injection of cocaine.

    Science.gov (United States)

    Singer, Bryan F; Bryan, Myranda A; Popov, Pavlo; Robinson, Terry E; Aragona, Brandon J

    2017-05-01

    Repeated intermittent exposure to cocaine results in the neurochemical sensitization of dopamine (DA) transmission within the nucleus accumbens (NAc). Indeed, the excitability of DA neurons in the ventral tegmental area (VTA) is enhanced within hours of initial psychostimulant exposure. However, it is not known if this is accompanied by a comparably rapid change in the ability of cocaine to increase extracellular DA concentrations in the ventral striatum. To address this question we used fast-scan cyclic voltammetry (FSCV) in awake-behaving rats to measure DA responses in the NAc shell following an initial intravenous cocaine injection, and then again 2-h later. Both injections quickly elevated DA levels in the NAc shell, but the second cocaine infusion produced a greater effect than the first, indicating sensitization. This suggests that a single injection of cocaine induces sensitization-related plasticity very rapidly within the mesolimbic DA system. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Improved estimation of receptor density and binding rate constants using a single tracer injection and displacement

    International Nuclear Information System (INIS)

    Syrota, A.; Delforge, J.; Mazoyer, B.M.

    1988-01-01

    The possibility of improving receptor model parameter estimation using a displacement experiment in which an excess of an unlabeled ligand (J) is injected after a delay (t D ) following injection of trace amounts of the β + - labeled ligand (J*) is investigated. The effects of varying t D and J/J* on parameter uncertainties are studied in the case of 11 C-MQNB binding to myocardial acetycholine receptor using parameters identified in a dog experiment

  8. Single-shot measurements of low emittance beams from laser-plasma accelerators comparing two triggered injection methods

    Science.gov (United States)

    van Tilborg, Jeroen

    2017-10-01

    The success of laser plasma accelerator (LPA) based applications, such as a compact x-ray free electron laser (FEL), relies on the ability to produce electron beams with excellent 6D brightness, where brightness is defined as the ratio of charge to the product of the three normalized emittances. As such, parametric studies of the emittance of LPA generated electron beams are essential. Profiting from a stable and tunable LPA setup, combined with a carefully designed single-shot energy-dispersed emittance diagnostic, we present a direct comparison of charge dependent emittance measurements of electron beams generated by two different injection mechanisms: ionization injection and shock-induced density down-ramp injection. Both injection mechanisms have gained in popularity in recent years due to their demonstrated stable LPA performance. For the down-ramp injection configuration, normalized emittances a factor of two lower were recorded: less than 1 micron at spectral charge densities up to 2 pC/MeV. For both injection mechanisms, a contributing correlation of space charge to the emittance was identified. This measurement technique in general, and these results specifically, are critical to the evaluation of LPA injection methods and development of high-quality LPA beam lines worldwide. This work is supported by the U.S. DOE under Contract No. DE-AC02-05CH11231, by the U.S. DOE NNSA, DNN R&D (NA22), by the National Science Foundation under Grant No. PHY-1415596, and by the Gordon and Betty Moore Foundation under Grant ID GBMF4898.

  9. Numerical Simulations of Two-Phase Reacting Flow in a Single-Element Lean Direct Injection (LDI) Combustor Using NCC

    Science.gov (United States)

    Liu, Nan-Suey; Shih, Tsan-Hsing; Wey, C. Thomas

    2011-01-01

    A series of numerical simulations of Jet-A spray reacting flow in a single-element lean direct injection (LDI) combustor have been conducted by using the National Combustion Code (NCC). The simulations have been carried out using the time filtered Navier-Stokes (TFNS) approach ranging from the steady Reynolds-averaged Navier-Stokes (RANS), unsteady RANS (URANS), to the dynamic flow structure simulation (DFS). The sub-grid model employed for turbulent mixing and combustion includes the well-mixed model, the linear eddy mixing (LEM) model, and the filtered mass density function (FDF/PDF) model. The starting condition of the injected liquid spray is specified via empirical droplet size correlation, and a five-species single-step global reduced mechanism is employed for fuel chemistry. All the calculations use the same grid whose resolution is of the RANS type. Comparisons of results from various models are presented.

  10. Optimizing CT angiography in patients with Fontan physiology: single-center experience of dual-site power injection

    International Nuclear Information System (INIS)

    Sandler, K.L.; Markham, L.W.; Mah, M.L.; Byrum, E.P.; Williams, J.R.

    2014-01-01

    Aim: To identify adult patients with single-ventricle congenital heart disease and Fontan procedure palliation who have been misdiagnosed with or incompletely evaluated for pulmonary embolism. Additionally, this study was designed to demonstrate that simultaneous, dual-injection of contrast medium into an upper and lower extremity vein is superior to single-injection protocols for CT angiography (CTA) of the chest in this population. Materials and methods: Patients included in the study were retrospectively selected from the Adult Congenital Heart Disease (ACHD) database. Search criteria included history of Fontan palliation and available chest CT examination. Patients were evaluated for (1) type of congenital heart disease and prior operations;(2) indication for initial CT evaluation;(3) route of contrast medium administration for the initial CT examination and resulting diagnosis;(4) whether or not anticoagulation therapy was initiated; and (5) final diagnosis and treatment plan. Results: The query of the ACHD database resulted in 28 individuals or patients with Fontan palliation (superior and inferior venae cavae anastomosed to the pulmonary arteries). Of these, 19 patients with Fontan physiology underwent CTA of the pulmonary circulation, and 17 had suboptimal imaging studies. Unfortunately, seven of these 17 patients (41%) were started on anticoagulation therapy due to a diagnosis of pulmonary embolism that was later excluded. Conclusion: Patients with single-ventricle/Fontan physiology are at risk of thromboembolic disease. Therefore, studies evaluating their complex anatomy must be performed with the optimal imaging protocol to ensure diagnostic accuracy, which is best achieved with dual-injection of an upper and lower extremity central vein. - Highlights: • The adult congenital heart disease population is growing. • Many of these patients have single ventricle/Fontan physiology. • Patients with Fontan physiology are at increased risk for

  11. Imaging-documented repeated intratumoral hemorrhage in vestibular schwannoma: a case report

    NARCIS (Netherlands)

    Mandl, E. S.; Vandertop, W. P.; Meijer, O. W. M.; Peerdeman, S. M.

    2009-01-01

    Intratumoral hemorrhage in vestibular schwannomas is rare. Symptoms often have an acute onset and include headache, nausea, vomiting, vertigo, and depressed consciousness. Intratumoral hemorrhage is probably caused by vascular fragility associated with tumor characteristics and growth. With

  12. Injection molded polymer chip for electrochemical and electrophysiological recordings from single cells

    DEFF Research Database (Denmark)

    Tanzi, Simone; Larsen, Simon Tylsgaard; Taboryski, Rafael J.

    We present a novel method to fabricate an all in polymer injection molded chip for electrochemical cell recordings and lateral cell trapping. The complete device is molded in thermoplastic polymer and it results from assembling two halves. We tested spin-coated conductive polymer poly(3...

  13. Histopathological Alterations after Single Epidural Injection of Ropivacaine, Methylprednizolone Acetate, or Contrast Material in Swine

    International Nuclear Information System (INIS)

    Kitsou, Maria-Chrysanthi; Kostopanagiotou, Georgia; Kalimeris, Konstantinos; Vlachodimitropoulos, Demetrios; Soultanis, Konstantinos; Batistaki, Chrysanthi; Kelekis, Alexis

    2011-01-01

    Purpose: The consequences from the injection of different types of drugs in the epidural space remains unknown. Increasing evidence suggests that localized inflammation, fibrosis, and arachnoiditis can complicate sequential epidural blockades, or even epidural contrast injection. We investigate the in vivo effect of epidural injections in the epidural space in an animal model. Materials and Methods: A group of ten male adult pigs, five punctures to each at distinct vertebral interspaces under general anesthesia, were examined, testing different drugs, used regularly in the epidural space (iopamidol, methylprednisolone acetate, ropivacaine). Each site was marked with a percutaneous hook wire marker. Histological analysis of the epidural space, the meninges, and the underlying spinal cord of the punctured sites along with staining for caspase-3 followed 20 days later. Results: The epidural space did not manifest adhesions or any other pathology, and the outer surface of the dura was not impaired in any specimen. The group that had the contrast media injection showed a higher inflammation response compared to the other groups (P = 0.001). Positive staining for caspase-3 was limited to <5% of neurons with all substances used. Conclusion: No proof of arachnoiditis and/or fibrosis was noted in the epidural space with the use of the above-described drugs. A higher inflammation rate was noted with the use of contrast media.

  14. 229 nm UV LEDs on aluminum nitride single crystal substrates using p-type silicon for increased hole injection

    Science.gov (United States)

    Liu, Dong; Cho, Sang June; Park, Jeongpil; Seo, Jung-Hun; Dalmau, Rafael; Zhao, Deyin; Kim, Kwangeun; Gong, Jiarui; Kim, Munho; Lee, In-Kyu; Albrecht, John D.; Zhou, Weidong; Moody, Baxter; Ma, Zhenqiang

    2018-02-01

    AlGaN based 229 nm light emitting diodes (LEDs), employing p-type Si to significantly increase hole injection, were fabricated on single crystal bulk aluminum nitride (AlN) substrates. Nitride heterostructures were epitaxially deposited by organometallic vapor phase epitaxy and inherit the low dislocation density of the native substrate. Following epitaxy, a p-Si layer is bonded to the heterostructure. LEDs were characterized both electrically and optically. Owing to the low defect density films, large concentration of holes from p-Si, and efficient hole injection, no efficiency droop was observed up to a current density of 76 A/cm2 under continuous wave operation and without external thermal management. An optical output power of 160 μW was obtained with the corresponding external quantum efficiency of 0.03%. This study demonstrates that by adopting p-type Si nanomembrane contacts as a hole injector, practical levels of hole injection can be realized in UV light-emitting diodes with very high Al composition AlGaN quantum wells, enabling emission wavelengths and power levels that were previously inaccessible using traditional p-i-n structures with poor hole injection efficiency.

  15. Rapid dual-injection single-scan 13N-ammonia PET for quantification of rest and stress myocardial blood flows

    International Nuclear Information System (INIS)

    Rust, T C; DiBella, E V R; McGann, C J; Christian, P E; Hoffman, J M; Kadrmas, D J

    2006-01-01

    Quantification of myocardial blood flows at rest and stress using 13 N-ammonia PET is an established method; however, current techniques require a waiting period of about 1 h between scans. The objective of this study was to test a rapid dual-injection single-scan approach, where 13 N-ammonia injections are administered 10 min apart during rest and adenosine stress. Dynamic PET data were acquired in six human subjects using imaging protocols that provided separate single-injection scans as gold standards. Rest and stress data were combined to emulate rapid dual-injection data so that the underlying activity from each injection was known exactly. Regional blood flow estimates were computed from the dual-injection data using two methods: background subtraction and combined modelling. The rapid dual-injection approach provided blood flow estimates very similar to the conventional single-injection standards. Rest blood flow estimates were affected very little by the dual-injection approach, and stress estimates correlated strongly with separate single-injection values (r = 0.998, mean absolute difference = 0.06 ml min -1 g -1 ). An actual rapid dual-injection scan was successfully acquired in one subject and further demonstrates feasibility of the method. This study with a limited dataset demonstrates that blood flow quantification can be obtained in only 20 min by the rapid dual-injection approach with accuracy similar to that of conventional separate rest and stress scans. The rapid dual-injection approach merits further development and additional evaluation for potential clinical use

  16. Forecast of thermal-hydrological conditions and air injection test results of the single heater test at Yucca Mountain

    International Nuclear Information System (INIS)

    Birkholzer, J.T.; Tsang, Y.W.

    1996-12-01

    The heater in the Single Heater Test (SHT) in alcove 5 of the Exploratory Studies Facility (ESF) was turned on August 26, 1996. A large number of sensors are installed in the various instrumented boreholes to monitor the coupled thermal-hydrological-mechanical-chemical responses of the rock mass to the heat generated in the single heater. In this report the authors present the results of the modeling of both the heating and cooling phases of the Single Heater Test (SHT), with focus on the thermal-hydrological aspect of the coupled processes. Also in this report, the authors present simulations of air injection tests will be performed at different stages of the heating and cooling phase of the SHT

  17. An Optical Method for Measuring Injection Timing in Diesel Engines, Using a Single Port

    Science.gov (United States)

    2014-09-01

    5 and NATO F-76, the current fleet standards. However, the use of seawater compensated shipboard storage tanks, legacy engine technology , high flash...76 is 46 [4, 5]. SPK, produced using the Fischer-Tropsch process, was originally derived in Germany in the 1920s and 1930s in response to fuel...noise. Sugiyama et al. [18] tested a hydrotreated vegetable oil (HVO) in a direct injection, turbocharged, automotive diesel and found both decreased

  18. Chemical castration by a single bilateral intra-testicular injection of ...

    African Journals Online (AJOL)

    Six apparently healthy Borno white bucks weighing 15± 1.6 kg and aged 1.3± 0.3 years were used for this study. Two and half (2.5) ml Purit® (chlorhexidine gluconate 0.3% B.P W/V and cetrimide 3.0% B.P W/V CAPL Lagos) were injected bilaterally into the caudae of each epididymis following sedation with xylazine ...

  19. Methodological study on determining endogenous amino acid excretion of broiler chickens by single intravenous injection of 3H-leucine

    International Nuclear Information System (INIS)

    Yao Junhu; Wang Kangning; Yang Feng; Zhou Anguo; Cai Xuelin; Duanmu Dao

    1999-01-01

    Forty broiler chickens (1.5 kg of body weight, BW) were randomly divided into 20 groups. Every fifth group was force-fed a nitrogen-free diet (NFD) or a NFd + 3.20% enzyme hydrolysed casein (EHC) diet or diets with 5% and 20% crude protein (CP) in which soybean meal (sol.) was the sole nitrogen source. 30μCi 3 H-leucine/kg BW was intravenously injected into all birds just after the force-feeding. Venous blood samples were taken at 5 min, 4h, 24h, 36h and 48h after the injection, and the amount of excreta for the whole period of 48h was collected. The amino acids excreted after force-feeding NFD + 3.20% EHC of CP5% diet were theoretically endogenous. The ratios of specific radioactivity (SR) in excreta and the value of definite integral in free plasma from 0 to 48 h after injection of labelled leucine were not different (P > 0.05) when NFD, NFD + 3.20% EHC or CP5% diet was fed. From these results and theoretical analysis, it was suggested that for the birds with CP20% diet, the ratio of SR in endogenous leucine and value of definite integral in free plasma from 0 to 48 h after injection of labelled leucine would be the same as that of the birds with NFD diet, and thus endogenous losses of leucine and other amino acids, by the endogenous amino acid pattern measured with NFD diet, could be estimated for CP20% diet. The endogenous amino acid losses measured by this new technique was 120.50% of those measured by NFD method. It was suggested that single intravenous injection of 3 H-leucine first proposed would be more valuable for determining endogenous amino acid losses, especially when practical nitrogen-containing diet was fed

  20. Inhibition of Neuropathic Pain by a Single Intraperitoneal Injection of Diazepam in the Rat: Possible Role of Neurosteroids.

    Science.gov (United States)

    Chen, Shu-Ling; Zang, Ying; Zheng, Wen-Hui; Wei, Xu-Hong; Liu, Xian-Guo

    2016-02-29

    Diazepam binds with the same high affinity to the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor, which has been renamed translocator protein (TSPO). Both receptors could promote neurosteroid synthesis. In the present study, we investigated whether a single dose of diazepam could inhibit neuropathic pain induced by L5 spinal nerve ligation (L5 SNL), and whether CBR and TSPO mediated this effect. We found that a single intraperitoneal injection of diazepam 9 d after L5 SNL significantly depressed the established mechanical allodynia and thermal hyperalgesia, which persisted until the end of the experiments. Furthermore, the effects were mimicked by a single intraperitoneal injection of Ro5-4864, a specific TSPO agonist and pregnenolone, a neurosteroid precursor. In addition, we found that the inhibitory effect of diazepam was also completely blocked by pretreatment with a specific CBR antagonist, flumazenil. The effects of diazepam or Ro5-4864 on neuropathic pain were completely blocked by pretreatment with a neurosteroid synthesis inhibitor, aminoglutethimide (AMG). Finally, any one of the three drugs, diazepam, Ro5-4864 and pregnenolone, could reduce the activation of astrocytes and the production of interleukin-1beta (IL-1β) in the L5 spinal dorsal horn 14 d after L5 SNL. These results suggest that in addition to exerting effects on CBR, diazepam may inhibit neuropathic pain via TSPO, which promotes neurosteroid formation, subsequently reducing the activation of astrocytes and production of cytokines.

  1. Effectiveness of a single platelet-rich plasma injection to promote recovery in rugby players with ankle syndesmosis injury.

    Science.gov (United States)

    Samra, David J; Sman, Amy D; Rae, Katherine; Linklater, James; Refshauge, Kathryn M; Hiller, Claire E

    2015-01-01

    To determine whether a single ultrasound-guided platelet-rich plasma (PRP) injection into the anterior inferior tibiofibular ligament (AITFL) reduces the time for rugby athletes to return to function and match play following MRI confirmed ankle syndesmosis injury. Cohort controlled pilot study. 10 Rugby Union players were recruited during the 2014 season, and consented to receive a single autologous PRP injection into the AITFL within 14 days of MRI confirmed ankle syndesmosis injury. A historical control group included 11 comparable Rugby Union players between 2011 and 2013 who were treated conservatively with the same inclusion criteria and rehabilitation protocol as the intervention group. Participants followed a standardised rehabilitation protocol involving simple milestones for progression. Early functional tests were performed 2 weeks after the removal of the CAM (controlled ankle motion) boot. Time to return to play was recorded. Repeat functional testing occurred within 1 week of return to play. Groups were comparable in anthropometrics, playing position and MRI injury severity. Time to return to play was significantly less in the intervention group (p=0.048). Following return to play, athletes in the intervention group showed higher agility (p=0.002) and vertical jump (p=0.001). There was a lower level of fear avoidance associated with rugby in the intervention group (p=0.014). This pilot study shows that, following ankle syndesmosis injury, a single autologous PRP injection may accelerate safe and successful return to Rugby Union, with improved functional capacity and reduced fear avoidance. It demonstrates the feasibility of a randomised controlled trial to further assess this therapy. ANZCTRN12614000055606.

  2. Estimation of effective renal plasma flow in children by use of a single plasma sample after injection of orthoiodohippurate

    International Nuclear Information System (INIS)

    Tauxe, W.N.; Hagge, W.; Stickler, G.B.

    1975-01-01

    Estimates of effective renal plasma flow (ERPF) in adults have been greatly simplified by the use of recently developed regression equations based on a single plasma concentration of radioiodinated orthoiodohippurate (OIH) obtained 44 min after a single intravenous injection of the material. The paper reports similar equations for the prediction of ERPF in children. Studies were made in 30 children of both sexes, aged 4 to 16 years, with a wide variety of renal diseases. A single intravenous injection of labelled OIH was made and plasma was sampled at 10, 15, 20, 25, 30, 40, 50 and 60 min after injection. Plasma concentration curves were analysed by the conventional two-compartment analysis technique (Sapirstein, Matthews) and ERPF was computed from them. In addition to ERPF calculations, sizes of the two volumes of distribution (V 1 and V 2 ), intercompartmental flow rates and fractional rate constants were also calculated. Surface area (SA) was calculated from the DuBois height-weight regression formula. Reciprocals of the OIH plasma concentration in terms of per cent injected dose per litre were calculated at each sampling time; this reciprocal is designated x. These values at each sampling time were plotted against ERPF and regression equations and residual error (Sy.x) were calculated. The optimal sampling time was found to occur at 53 min and the corresponding linear regression equation was 19.33 + 3.87x with a Sy.x value of 36 ml. This compares with an optimal sampling time in adults of 44 min. The mean initial volume of distribution (V 1 ) was found to be 5.3 litres and the mean V 2 was found to be 6.8 litres. In contrast to findings in the previous study in adults these volumes were found to correlate well with SA. A mean intercompartmental flow rate of 276 ml/min was found. No correlation between this value and clinical diagnosis was found. The relationship of the concentration reciprocal and plasma flow was a linear one instead of the polynomial one

  3. A single injection technique for subtraction of blood background in 131I-hippuran renograms

    International Nuclear Information System (INIS)

    Rutland, M.D.

    1979-01-01

    A method of subtracting blood background during probe-renography is presented which does not require a prior injection of RIHSA and which produces results approximately 11% higher than the RIHSA method. The new method treats the renogram up to two-and-a-half minutes as a combination of a fraction of the blood curve and a fraction of the integral of the blood curve. Analysis of the data, using either a computer or a programmed calculator, enables these two fractions to be calculated, hence producing the 'background subtraction factor' and the 'uptake constant'. (author)

  4. Single well push-pull CO2 injection experiment for evaluating in-situ residual trapping at Heletz, Israel

    Science.gov (United States)

    Niemi, Auli; Bensabat, Jacob; Fagerlund, Fritjof; Ronen, Rona; Goren, Yoni; Perez, Lily; Tsarfis, Igal; Joodaki, Saba; Yang, Zhibing; Liang, Tian; Sauter, Martin; Hassan, Jawad; Gouze, Philippe; Rasmusson, Kristina

    2017-04-01

    The Heletz sands is a depleted oil reservoir at 1.6 km depth with saline water at its edges. In the saline part of the reservoir a CO2 injection experiment site has been developed for the purpose of scientifically motivated injection experiments, especially in the context of EU FP7 projects MUSTANG and TRUST. This presentation describes the single-well CO2 injection experiment carried out in September 2016, with the objective of determining field scale values of key CO2 trapping mechanisms, the residual and dissolution trapping. The sequence consisted in creating a residually trapped CO2 zone as well as reference hydraulic and heater tests prior and after the establishment of the zone, in order to determine the in-situ residual trapping. Monitoring included down-hole pressure and temperature measurement, distributed temperature sensing along the well via an optical fiber (DTS), U-tube sampling and tracers. We here present the experimental sequence, the monitoring and sampling system, the key results as well as the first interpretations.

  5. Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma

    International Nuclear Information System (INIS)

    Barreca, A; Martinengo, C; Annaratone, L; Righi, L; Chiappella, A; Ladetto, M; Demurtas, A; Chiusa, L; Stacchini, A; Crosetto, N; Oudenaarden, A van; Chiarle, R

    2014-01-01

    Most follicular lymphomas (FLs) are genetically defined by the t(14;18)(q32;q21) translocation that juxtaposes the BCL2 gene to the immunoglobulin heavy chain (IgH) 3' regulatory regions (IgH-3'RRs). Despite this recurrent translocation, FL cases are heterogeneous in terms of intratumoral clonal diversity for acquired mutations and variations in the tumor microenvironment. Here we describe an additional mechanism that contributes to inter- and intratumoral heterogeneity in FLs. By applying a novel single-molecule RNA fluorescence-based in situ hybridization (FISH) technique to detect mRNA molecules of BCL2 and IgH in single cells, we found marked heterogeneity in the number of BCL2 mRNA transcripts within individual lymphoma cells. Moreover, BCL2 mRNA molecules correlated with IgH mRNA molecules in individual cells both in t(14;18) lymphoma cell lines and in patient samples. Consistently, a strong correlation between BCL2 and IgH protein levels was found in a series of 205 primary FL cases by flow cytometry and immunohistochemistry. Inter- and intratumoral heterogeneity of BCL2 expression determined resistance to drugs commonly used in FL treatment and affected overall survival of FL patients. These data demonstrate that BCL2 and IgH expressions are heterogeneous and coregulated in t(14;18)-translocated cells, and determine the response to therapy in FL patients

  6. Direct current injection and thermocapillary flow for purification of aligned arrays of single-walled carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Xu; Islam, Ahmad E.; Seabron, Eric; Dunham, Simon N.; Du, Frank; Lin, Jonathan; Wilson, William L.; Rogers, John A., E-mail: jrogers@illinois.edu [Department of Materials Science and Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Wahab, Muhammad A.; Alam, Muhammad A. [School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States); Li, Yuhang [Institute of Solid Mechanics, Beihang University, Beijing 100191 (China); Tomic, Bojan [Department of Electrical Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Huang, Jiyuan [Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Burns, Branden [Department of Physics, Purdue University, West Lafayette, Indiana 47907 (United States); Song, Jizhou [Department of Engineering Mechanics and Soft Matter Research Center, Zhejiang University, Hangzhou 310027 (China); Huang, Yonggang [Department of Civil and Environmental Engineering, Department of Mechanical Engineering, Center for Engineering and Health, and Skin Disease Research Center, Northwestern University, Evanston, Illinois 60208 (United States)

    2015-04-07

    Aligned arrays of semiconducting single-walled carbon nanotubes (s-SWNTs) represent ideal configurations for use of this class of material in high performance electronics. Development of means for removing the metallic SWNTs (m-SWNTs) in as-grown arrays represents an essential challenge. Here, we introduce a simple scheme that achieves this type of purification using direct, selective current injection through interdigitated electrodes into the m-SWNTs, to allow their complete removal using processes of thermocapillarity and dry etching. Experiments and numerical simulations establish the fundamental aspects that lead to selectivity in this process, thereby setting design rules for optimization. Single-step purification of arrays that include thousands of SWNTs demonstrates the effectiveness and simplicity of the procedures. The result is a practical route to large-area aligned arrays of purely s-SWNTs with low-cost experimental setups.

  7. Direct current injection and thermocapillary flow for purification of aligned arrays of single-walled carbon nanotubes

    International Nuclear Information System (INIS)

    Xie, Xu; Islam, Ahmad E.; Seabron, Eric; Dunham, Simon N.; Du, Frank; Lin, Jonathan; Wilson, William L.; Rogers, John A.; Wahab, Muhammad A.; Alam, Muhammad A.; Li, Yuhang; Tomic, Bojan; Huang, Jiyuan; Burns, Branden; Song, Jizhou; Huang, Yonggang

    2015-01-01

    Aligned arrays of semiconducting single-walled carbon nanotubes (s-SWNTs) represent ideal configurations for use of this class of material in high performance electronics. Development of means for removing the metallic SWNTs (m-SWNTs) in as-grown arrays represents an essential challenge. Here, we introduce a simple scheme that achieves this type of purification using direct, selective current injection through interdigitated electrodes into the m-SWNTs, to allow their complete removal using processes of thermocapillarity and dry etching. Experiments and numerical simulations establish the fundamental aspects that lead to selectivity in this process, thereby setting design rules for optimization. Single-step purification of arrays that include thousands of SWNTs demonstrates the effectiveness and simplicity of the procedures. The result is a practical route to large-area aligned arrays of purely s-SWNTs with low-cost experimental setups

  8. Tunable single-longitudinal-mode operation of an injection-locked TEA CO2 laser. [ozone absorption spectroscopy

    Science.gov (United States)

    Megie, G.; Menzies, R. T.

    1979-01-01

    The tunable single-longitudinal-mode operation of a TEA CO2 laser by an injection technique using a CW waveguide laser as the master oscillator is reported. With the experimental arrangement described, in which the waveguide laser frequency is tuned to correspond to one of the oscillating longitudinal modes of the TEA laser, single-longitudinal-mode operation was achieved with no apparent reduction in the TEA output energy, on various CO2 lines with frequency offsets from the line center as large as 300 MHz. The capability of this technique for high-resolution spectroscopy or atmospheric lidar studies is demonstrated by the recording of the absorption spectrum of a strong ozone line.

  9. Geometry-induced injection dispersion in single-cell protein electrophoresis.

    Science.gov (United States)

    Pan, Qiong; Herr, Amy E

    2018-02-13

    Arrays of microwells are widely used to isolate individual cells, facilitate high throughput cytometry assays, and ensure compatibility of those assays with whole-cell imaging. Microwell geometries have recently been utilized for handling and preparation of single-cell lysate, prior to single-cell protein electrophoresis. It is in the context of single-cell electrophoresis that we investigate the interplay of microwell geometry (circular, rectangular, triangular) and transport (diffusion, electromigration) on the subsequent performance of single-cell polyacrylamide gel electrophoresis (PAGE) for protein targets. We define and measure injector-induced dispersion during PAGE, and develop a numerical model of band broadening sources, experimentally validate the numerical model, and then identify operating conditions (characterized through the Peclet number, Pe) that lead to microwell-geometry induced losses in separation performance. With analysis of mammalian cells as a case study, we sought to understand at what Pe is the PAGE separation performance adversely sensitized to the microwell geometry. In developing design rules, we find that for the microwell geometries that are the most suitable for isolation of mammalian cells and moderate mass protein targets, the Pe is usually small enough (Pe geometry on protein PAGE of single-cell lysate. In extreme cases where the largest mammalian cells are analyzed (Pe > ∼20), consideration of Pe suggests using a rectangular - and not the widely used circular - microwell geometry to maximize protein PAGE separation performance. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effect of intake swirl on the performance of single cylinder direct injection diesel engine

    Science.gov (United States)

    Sharma, Vinod Kumar; Mohan, Man; Mouli, Chandra

    2017-11-01

    In the present work, the effect of inlet manifold geometry and swirl intensity on the direct injection (DI) diesel engine performance was investigated experimentally. Modifications in inlet manifold geometry have been suggested to achieve optimized swirl for the better mixing of fuel with air. The intake swirl intensities of modified cylinder head were measured in swirl test rig at different valve lifts. Later, the overall performance of 435 CC DI diesel engine was measured using modified cylinder head. In addition, the performance of engine was compared for both modified and old cylinder head. For same operating conditions, the brake power and brake specific fuel consumption was improved by 6% and 7% respectively with modified cylinder head compared to old cylinder head. The maximum brake power of 9 HP was achieved for modified cylinder head. The results revealed that the intake swirl has great influence on engine performance.

  11. Symptomatic hepatic cyst in a child: treatment with single-shot injection of tetracycline hydrochloride

    International Nuclear Information System (INIS)

    Fabrizzi, Giancarlo; Lanza, Cecilia; Bolli, Valeria; Pieroni, Giovanni

    2009-01-01

    The prevalence of hepatic cysts is 0.1% to 0.5% based on autopsy studies, and 2.5% based on US examinations. Percutaneous therapies are a new alternative to surgery. They include simple percutaneous aspiration, catheter drainage alone, and catheter drainage with sclerotherapy. We present an 11-year-old boy admitted to hospital because of abdominal pain. A diagnosis of simple hepatic cyst was made, which was treated with aspiration and tetracycline hydrochloride solution (5%) injection into the cystic cavity. Complete regression was seen on US and MRI examination at 3 months, with total collapse and deflation of the cyst. The cyst regressed totally, leaving a hyperechoic linear scar on US examination at 1 year. On the basis of the clinical and imaging results obtained, percutaneous sclerotherapy of hepatic cysts can be recommended as the treatment of choice and as a valid alternative to laparoscopy in children. (orig.)

  12. Symptomatic hepatic cyst in a child: treatment with single-shot injection of tetracycline hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Fabrizzi, Giancarlo; Lanza, Cecilia; Bolli, Valeria; Pieroni, Giovanni [Azienda Ospedaliero-Universitaria Ospedali Riuniti, Servizio di Radiologia Generale e Pediatrica, Ancona (Italy)

    2009-10-15

    The prevalence of hepatic cysts is 0.1% to 0.5% based on autopsy studies, and 2.5% based on US examinations. Percutaneous therapies are a new alternative to surgery. They include simple percutaneous aspiration, catheter drainage alone, and catheter drainage with sclerotherapy. We present an 11-year-old boy admitted to hospital because of abdominal pain. A diagnosis of simple hepatic cyst was made, which was treated with aspiration and tetracycline hydrochloride solution (5%) injection into the cystic cavity. Complete regression was seen on US and MRI examination at 3 months, with total collapse and deflation of the cyst. The cyst regressed totally, leaving a hyperechoic linear scar on US examination at 1 year. On the basis of the clinical and imaging results obtained, percutaneous sclerotherapy of hepatic cysts can be recommended as the treatment of choice and as a valid alternative to laparoscopy in children. (orig.)

  13. Observing Exoplanets with High-dispersion Coronagraphy. II. Demonstration of an Active Single-mode Fiber Injection Unit

    Energy Technology Data Exchange (ETDEWEB)

    Mawet, D.; Ruane, G.; Xuan, W.; Echeverri, D.; Klimovich, N.; Randolph, M.; Fucik, J.; Wang, J.; Dekany, R.; Delorme, J.-R. [Department of Astronomy, California Institute of Technology, 1200 East California Boulevard, MC 249-17, Pasadena, CA 91125 (United States); Wallace, J. K.; Vasisht, G.; Mennesson, B.; Choquet, E.; Serabyn, E., E-mail: dmawet@astro.caltech.edu [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States)

    2017-04-01

    High-dispersion coronagraphy (HDC) optimally combines high-contrast imaging techniques such as adaptive optics/wavefront control plus coronagraphy to high spectral resolution spectroscopy. HDC is a critical pathway toward fully characterizing exoplanet atmospheres across a broad range of masses from giant gaseous planets down to Earth-like planets. In addition to determining the molecular composition of exoplanet atmospheres, HDC also enables Doppler mapping of atmosphere inhomogeneities (temperature, clouds, wind), as well as precise measurements of exoplanet rotational velocities. Here, we demonstrate an innovative concept for injecting the directly imaged planet light into a single-mode fiber, linking a high-contrast adaptively corrected coronagraph to a high-resolution spectrograph (diffraction-limited or not). Our laboratory demonstration includes three key milestones: close-to-theoretical injection efficiency, accurate pointing and tracking, and on-fiber coherent modulation and speckle nulling of spurious starlight signal coupling into the fiber. Using the extreme modal selectivity of single-mode fibers, we also demonstrated speckle suppression gains that outperform conventional image-based speckle nulling by at least two orders of magnitude.

  14. Single injection of the β2-adrenergic receptor agonist, clenbuterol, into newly hatched chicks alters abdominal fat pad mass in growing birds.

    Science.gov (United States)

    Ishimaru, Yoshitaka; Ijiri, Daichi; Shimamoto, Saki; Ishitani, Kanae; Nojima, Tsutomu; Ohtsuka, Akira

    2015-01-15

    Excessive energy is stored in white adipose tissue as triacylglycerols in birds as well as in mammals. Although β2-adrenergic receptor agonists reduce adipose tissue mass in birds, the underlying mechanism remains unclear. The aim of the current study was to examine the effects of a single intraperitoneal injection of the β2-adrenergic receptor agonist, clenbuterol, on the abdominal fat pad tissue development. Thirty-three chicks at 1-day-old were given a single intraperitoneal injection of clenbuterol (0.1mg/kg body weight) or phosphate-buffered saline. At 2 weeks post-dose, the weight of the abdominal fat tissue was decreased in the clenbuterol-injected chicks, and small adipocyte-like cells were observed in the abdominal fat pad tissue of the clenbuterol-injected chicks. Then, the expression of mRNAs encoding genes related to avian adipogenesis was examined in the abdominal fat pat tissue. The expression of mRNAs encoding Krüppel-like zinc finger transcription factor 5 (KLF-5), KLF-15, and zinc finger protein 423 in the abdominal fat pad tissue of the clenbuterol-injected chicks was significantly lower (Pclenbuterol-injected chicks, while clenbuterol injection did not affect FAS activity in liver. These results suggested that a single injection with clenbuterol into newly hatched chicks reduces their abdominal fat pad mass possibly via disrupting adipocyte development during later growth stages. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Direct observation of spin-injection in tyrosinate-functionalized single-wall carbon nanotubes

    NARCIS (Netherlands)

    Tsoufis, Theodoros; Ampoumogli, Asem; Gournis, Dimitrios; Georgakilas, Vasilios; Jankovic, Lubos; Christoforidis, Konstantinos C.; Deligiannakis, Yiannis; Mavrandonakis, Andreas; Froudakis, George E.; Maccallini, Enrico; Rudolf, Petra; Mateo-Alonso, Aurelio; Prato, Maurizio

    In this work, we report on the interaction of a tyrosinate radical with single wall carbon nanotubes (CNT). The tyrosinate radical was formed from tyrosine (ester) by Fenton's reagent and, reacted in situ with carbon nanotubes resulting in novel tyrosinated carbon nanotube derivatives. The covalent

  16. Controlled tunnel-coupled ferromagnetic electrodes for spin injection in organic single-crystal transistors

    NARCIS (Netherlands)

    Naber, W.J.M.; Craciun, M.F.; Lemmens, J.H.J.; Arkenbout, A.H.; Palstra, T.T.M.; Morpurgo, A.F.; van der Wiel, Wilfred Gerard

    2010-01-01

    We report on single-crystal rubrene field-effect transistors (FETs) with ferromagnetic Co electrodes, tunnel-coupled to the conduction channel via an Al2O3 tunnel barrier. Magnetic and electronic characterization shows that the Al2O3 film not only protects the Co from undesired oxidation, but also

  17. Controlled tunnel-coupled ferromagnetic electrodes for spin injection in organic single-crystal transistors

    NARCIS (Netherlands)

    Naber, W. J. M.; Craciun, M. F.; Lemmens, J. H. J.; Arkenbout, A. H.; Palstra, T. T. M.; Morpurgo, A. F.; van der Wiel, W. G.

    We report on single-crystal rubrene. eld-effect transistors (FETs) with ferromagnetic Co electrodes, tunnel-coupled to the conduction channel via an Al(2)O(3) tunnel barrier. Magnetic and electronic characterization shows that the Al(2)O(3) film not only protects the Co from undesired oxidation, but

  18. Administering Multiple Injectable Vaccines During a Single Visit-Summary of Findings From the Accelerated Introduction of Inactivated Polio Vaccine Globally.

    Science.gov (United States)

    Dolan, Samantha B; Patel, Manish; Hampton, Lee M; Burnett, Eleanor; Ehlman, Daniel C; Garon, Julie; Cloessner, Emily; Chmielewski, Elizabeth; Hyde, Terri B; Mantel, Carsten; Wallace, Aaron S

    2017-07-01

    In 2013, the World Health Organization's (WHO's) Strategic Advisory Group of Experts (SAGE) recommended that all 126 countries using only oral polio vaccine (OPV) introduce at least 1 dose of inactivated polio vaccine (IPV) into their routine immunization schedules by the end of 2015. In many countries, the addition of IPV would necessitate delivery of multiple injectable vaccines (hereafter, "multiple injections") during a single visit, with infants receiving IPV alongside pentavalent vaccine (which covers diphtheria, tetanus, and whole-cell pertussis; hepatitis B; and Haemophilus influenzae type b) and pneumococcal vaccine. Unanticipated concerns emerged from countries over acceptability of multiple injections, sites of administration, and safety. We contextualized the issues surrounding multiple injections by documenting concerns associated with administration of ≥3 injections, existing evidence in the published literature, and findings of a systematic review on administration practices and techniques. Concerns associated with multiple-injection visits were documented from meetings and personal communications with immunization program managers. Published literature on the acceptability of multiple injections by providers and caregivers was summarized, and a systematic review of the literature on administration practices was completed on the following topics: spacing between injection sites (ie, vaccine spacing), site of injection, route of injection, and procedural preparedness. WHO and United Nations Children's Fund data from 2013-2015 were used to assess multiple-injection visits included in national immunization schedules. Healthcare provider and caregiver attitudes and practices indicated concerns about infant pain, potential adverse effects, and uncertainty about vaccine effectiveness with multiple-injection visits. Published literature reinforced the record of safety and acceptance of the recommended schedule of IPV by the SAGE, but the evidence was

  19. Heat transfer characteristics around a single heated rod immersed in sodium pool with gas jet injection

    International Nuclear Information System (INIS)

    Hideto Niikura; Kazuo Soga; Ken-ichiro Sugiyama; Akira Yamaguchi

    2005-01-01

    In a steam generator using liquid sodium, water intensely reacts with sodium when it leaks out from a heat transfer tube. It is important to evaluate the influence of sodium-water reaction to surrounding tubes and the shell. Hence, it has been desired to develop the simulation code for the evaluation of sodium-water reaction. From this viewpoint, the Japan Nuclear Cycle is now developing the SERAPHIM code. We reported a preliminary study to establish an experimental method for a single heated rod immersed in sodium pool with steam jet impingement planned in the near future as well as to obtain a preliminary data to verify the adequacy of SERAPHIM code. We first measured local and mean heat transfer coefficients around a horizontal single heated rod immersed in a water pool and a sodium pool with a limited volume in the experimental apparatus. It was confirmed that the mean heat transfer coefficients fairly agreed with the existing data for natural convection in water and sodium. Secondary we measured local and mean heat transfer coefficients around a horizontal single heated rod with Ar gas jet impingement immersed in the limited water pool and in the limited sodium pool. It was clearly observed that the local heat transfer coefficients in the sodium pool keep almost the same values in every angle regardless of increase in Ar gas jet velocity varied from about 8.7m/s to about 78m/s. On the other hand, it was confirmed in the water pool that local heat transfer coefficients on the forward stagnation side exposed in the Ar gas jet impingement increase with increasing the jet velocity while the local heat transfer coefficients on the opposite surface keep almost same values regardless of increase in the velocity. (authors)

  20. Low-pressure, single-point grout injection for tank heel sludge mixing and in-situ immobilization

    International Nuclear Information System (INIS)

    Whyatt, G.A.; Hymas, C.R.

    1998-09-01

    This report describes tests conducted in an approximately 9-ft diameter test tank situated outside the 336 building in Hanford's 300 area. The tests were performed to measure the ability of jets of grout slurry to mobilize and mix simulated tank sludge. The technique is intended for in situ immobilization of tank waste heels. The current approach uses a single, rotated, larger-diameter nozzle driven at lower pressure. Due to the larger diameter, the potential for plugging is reduced and the effective radius around an injection point over which the jet is effective in mobilizing sludge from the tank bottom can be made larger. A total of three grout injection tests were conducted in a 9-ft diameter tank. In each case, a 2-in. layer of kaolin clay paste was placed on a dry tank floor to simulate a sludge heel. The clay was covered with 4 inches of water. The grout slurry, consisting of Portland cement, class F fly ash, and eater, was prepared and delivered by an offsite vendor. In the third test, the sludge in half of the tank was replaced by a layer of 20x50 mesh zeolite, and bentonite clay was added to the grout formulation. After injection, the grout was allowed to set and then the entire grout monolith was manually broken up and excavated using a jack hammer. Intact pieces of clay were visually apparent due to a sharp color contrast between the grout and clay. Remaining clay deposits were collected and weighed and suspended clay pieces within the monolith were photographed. The mobilization performance of the grout jets exceeded expectations

  1. Improved healing of transected rabbit Achilles tendon after a single injection of cartilage-derived morphogenetic protein-2.

    Science.gov (United States)

    Forslund, Carina; Aspenberg, Per

    2003-01-01

    Achilles tendon ruptures in humans might be treated more efficiently with the help of a growth factor. Cartilage-derived morphogenetic protein-2 has been shown to induce formation of tendon-like tissue. Cartilage-derived morphogenetic protein-2 has a positive effect on mechanical parameters for tendon healing in a rabbit model with Achilles tendon transection. Controlled laboratory study. The right Achilles tendon of 40 rabbits was transected without tendon suture. Cartilage-derived morphogenetic protein-2 (10 micro g) or vehicle control (acetate buffer) was injected locally 2 hours postoperatively. All tendons were tested biomechanically at 8 and 14 days, and treated tendons were histologically and radiographically evaluated at 56 days. At 14 days, both failure load and stiffness of treated tendons were increased by 35%. The treated tendons had significantly larger callus size at 8 and 14 days. Histologic and radiographic examination showed no signs of ossification in the treated tendons after 56 days. A single injection of cartilage-derived morphogenetic protein-2 led to a stronger and stiffer tendon callus than that in the controls without inducing bone formation. Similar results from a larger animal model would suggest a possible future use of cartilage-derived morphogenetic protein-2 in the treatment of human Achilles tendon ruptures.

  2. Performance and combustion analysis of Mahua biodiesel on a single cylinder compression ignition engine using electronic fuel injection system

    Directory of Open Access Journals (Sweden)

    Gunasekaran Anandkumar

    2016-01-01

    Full Text Available In this investigation, experiment is carried out on a 1500 rpm constant speed single cylinder Diesel engine. The test is carried out with Neat diesel, neat biodiesel, and blend B20. The engine considered was run with electronic fuel injection system supported by common rail direct injection to obtain high atomization and effective air utilization inside the combustion chamber. The performance of the engine in terms of break thermal efficiency and brake specific energy consumption was found and compared. The B20 blend shows 1.11% decrease in break thermal efficiency and 3.35% increase in brake specific energy consumption than diesel. The combustion characteristics found are in-cylinder pressure, rate of pressure rise, and heat release rate and compared for peak pressure load to understand the nature of combustion process. For each fuel test run, the maximum peak pressure is observed at part load condition. The rate of change of pressure and heat release rate of diesel is high compared to pure biodiesel and B20 blend. The diffusion combustion is observed to be predominant in case of B100 than B20 and Neat diesel.

  3. Curcumin protects dopaminergic neurons against inflammation-mediated damage and improves motor dysfunction induced by single intranigral lipopolysaccharide injection.

    Science.gov (United States)

    Sharma, Neha; Sharma, Sheetal; Nehru, Bimla

    2017-06-01

    Various studies have indicated a lower incidence and prevalence of neurological conditions in people consuming curcumin. The ability of curcumin to target multiple cascades, simultaneously, could be held responsible for its neuroprotective effects. The present study was designed to investigate the potential of curcumin in minimizing microglia-mediated damage in lipopolysaccharide (LPS) induced model of PD. Altered microglial functions and increased inflammatory profile of the CNS have severe behavioral consequences. In the current investigation, a single injection of LPS (5 ug/5 µl PBS) was injected into the substantia nigra (SN) of rats, and curcumin [40 mg/kg b.wt (i.p.)] was administered daily for a period of 21 days. LPS triggered an inflammatory response characterized by glial activation [Iba-1 and glial fibrillary acidic protein (GFAP)] and pro-inflammatory cytokine production (TNF-α and IL-1β) leading to extensive dopaminergic loss and behavioral abnormality in rats. The behavioral observations, biochemical markers, quantification of dopamine and its metabolites (DOPAC and HVA) using HPLC followed by IHC of tyrosine hydroxylase (TH) were evaluated after 21 days of LPS injection. Curcumin supplementation prevented dopaminergic degeneration in LPS-treated animals by normalizing the altered levels of biomarkers. Also, a significant improvement in TH levels as well as behavioral parameters (actophotometer, rotarod, beam walking and grid walking tests) were seen in LPS injected rats. Curcumin shielded the dopaminergic neurons against LPS-induced inflammatory response, which was associated with suppression of glial activation (microglia and astrocytes) and transcription factor NF-κB as depicted from RT-PCR and EMSA assay. Curcumin also suppressed microglial NADPH oxidase activation as observed from NADPH oxidase activity. The results suggested that one of the important mechanisms by which curcumin mediates its protective effects in the LPS-induced PD

  4. [Incidence rate of adverse reaction/event by Qingkailing injection: a Meta-analysis of single rate].

    Science.gov (United States)

    Ai, Chun-ling; Xie, Yan-ming; Li, Ming-quan; Wang, Lian-xin; Liao, Xing

    2015-12-01

    To systematically review the incidence rate of adverse drug reaction/event by Qingkailing injection. Such databases as the PubMed, EMbase, the Cochrane library, CNKI, VIP WanFang data and CBM were searched by computer from foundation to July 30, 2015. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and cross check data. Then, Meta-analysis was performed by using the R 3.2.0 software, subgroup sensitivity analysis was performed based on age, mode of medicine, observation time and research quality. Sixty-three studies involving 9,793 patients with Qingkailing injection were included, 367 cases of adverse reactions/events were reported in total. The incidence rate of adverse reaction in skin and mucosa group was 2% [95% CI (0.02; 0.03)]; the digestive system adverse reaction was 6% [95% CI(0.05; 0.07); the injection site adverse reaction was 4% [95% CI (0.02; 0.07)]. In the digestive system as the main types of adverse reactions/events, incidence of children and adults were 4.6% [0.021 1; 0.097 7] and 6.9% [0.053 5; 0.089 8], respectively. Adverse reactions to skin and mucous membrane damage as the main performance/event type, the observation time > 7 days and ≤ 7 days incidence of 3% [0.012 9; 0.068 3] and 1.9% [0.007 8; 0.046 1], respectively. Subgroup analysis showed that different types of adverse reactions, combination in the incidence of adverse reactions/events were higher than that of single drug, the difference was statistically significant (P reactions occur, and clinical rational drug use, such as combination, age and other fators, and the influence factors vary in different populations. Therefore, clinical doctors for children and the elderly use special care was required for a clear and open spirit injection, the implementation of individualized medication.

  5. Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats.

    Science.gov (United States)

    Ozeki, N; Muneta, T; Koga, H; Nakagawa, Y; Mizuno, M; Tsuji, K; Mabuchi, Y; Akazawa, C; Kobayashi, E; Matsumoto, K; Futamura, K; Saito, T; Sekiya, I

    2016-06-01

    We investigated the effects of single or repetitive intra-articular injections of synovial mesenchymal stem cells (MSCs) on a rat osteoarthritis (OA) model, and elucidated the behaviors and underlying mechanisms of the stem cells after the injection. One week after the transection of the anterior cruciate ligament (ACL) of wild type Lewis rats, one million synovial MSCs were injected into the knee joint every week. Cartilage degeneration was evaluated with safranin-o staining after the first injection. To analyze cell kinetics or MSC properties, luciferase, LacZ, and GFP expressing synovial MSCs were used. To confirm the role of MSCs, species-specific microarray and PCR analyses were performed using human synovial MSCs. Histological analysis for femoral and tibial cartilage showed that a single injection was ineffective but weekly injections had significant chondroprotective effects for 12 weeks. Histological and flow-cytometric analyses of LacZ and GFP expressing synovial MSCs revealed that injected MSCs migrated mainly into the synovium and most of them retained their undifferentiated MSC properties though the migrated cells rapidly decreased. In vivo imaging analysis revealed that MSCs maintained in knees while weekly injection. Species-specific microarray and PCR analyses showed that the human mRNAs on day 1 for 21 genes increased over 50-fold, and increased the expressions of PRG-4, BMP-2, and BMP-6 genes encoding chondroprotective proteins, and TSG-6 encoding an anti-inflammatory one. Not single but periodic injections of synovial MSCs maintained viable cells without losing their MSC properties in knees and inhibited osteoarthritis (OA) progression by secretion of trophic factors. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Will a single periarticular lidocaine-corticosteroid injection improve the clinical efficacy of intraarticular hyaluronic acid treatment of symptomatic knee osteoarthritis?

    Science.gov (United States)

    Ertürk, Cemil; Altay, Mehmet Akif; Altay, Nuray; Kalender, Ali Murat; Öztürk, İbrahim Avşin

    2016-11-01

    A local injection of corticosteroid-lidocaine into the periarticular soft tissue structures is used commonly for rapid pain relief. It is hypothesized that knee pain associated with knee osteoarthritis would be relieved quickly and effectively in patients receiving intraarticular hyaluronic acid combined with a periarticular lidocaine-corticosteroid injection. To test this hypothesis, the clinical effect of the combined treatment with hyaluronic acid injection alone in patients with symptomatic knee osteoarthritis as compared in this prospective single-blinded randomized trial. This study included 70 patients. Group 1 (n = 35) received intraarticular hyaluronic acid injections only, whereas group 2 (n = 35) received intraarticular hyaluronic acid injections combined with a single local injection of corticosteroid-lidocaine. Injections were administered to the most painful areas of the anterior or posterior medial condyle of the femur or tibia. The outcome was measured by independent assessors (blinded to treatment) using a linear VAS pain scale and WOMAC and HSS knee scores. Assessments were performed at baseline and at 1, 3, 6, 12, 26, and 52 weeks. During the first 3 weeks, group 2 patients showed significantly better all scores than did group 1 patients (p hyaluronic acid alone in patients with knee osteoarthritis and can be considered a useful adjunctive treatment modality. This combined method may provide early return to patient's daily activity. Therapeutic study, Level I.

  7. Use and safety of intratumoral application of European mistletoe (Viscum album L) preparations in Oncology.

    Science.gov (United States)

    Steele, Megan L; Axtner, Jan; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann

    2015-03-01

    Intratumoral (IT) injection of European mistletoe (Viscum album L) preparations might induce local tumor response through combined cytotoxic and immunomodulatory actions of the preparations. Although promising in vitro and in vivo data, along with clinical case studies suggest the need for validation of this hypothesis in prospective trials, the safety of IT mistletoe injections has yet to be thoroughly assessed. The present study summarizes the practice and safety of off-label IT mistletoe therapy within the Network Oncology, a conjoint clinical registry of German hospitals and outpatients specialized in anthroposophic and integrative medicine. Demographic, diagnosis and treatment data of cancer patients who received IT mistletoe applications between 2007 and 2013 were assessed. Suspected adverse drug reactions (ADRs) were analyzed in terms of type, frequency, severity, seriousness and potential risk factors. A total of 123 cancer patients received 862 IT mistletoe injections (preparations from Abnoba, Helixor and Iscucin). The most commonly applied preparations were Abnoba viscum Fraxini (71 patients) and Helixor Mali (54 patients). Of the total patients, 26 patients (21.1%) experienced 74 ADRs. All ADRs were in response to either Abnoba viscum Fraxini (25.4% of exposed patients) or Helixor Mali (18.5% of exposed patients). ADRs were mostly body temperature or immune related and of mild (83.8%) or moderate (14.9%) intensity. Only one possible ADR was described as severe (hypertension) and no serious ADRs occurred. The frequency of ADRs to IT mistletoe injections was 3 times and 5 times higher than has previously been found for subcutaneous and intravenous applications of mistletoe, respectively. IT injection of mistletoe preparations resulted in a relatively high frequency of ADRs. Nearly all ADRs were mild to moderate however, and no serious ADRs occurred. Furthermore, it is possible that immune-related ADRs such as pyrexia and local inflammatory reactions might

  8. Primary central nervous system lymphoma: is absence of intratumoral hemorrhage a characteristic finding on MRI?

    Science.gov (United States)

    Sakata, Akihiko; Okada, Tomohisa; Yamamoto, Akira; Kanagaki, Mitsunori; Fushimi, Yasutaka; Dodo, Toshiki; Arakawa, Yoshiki; Takahashi, Jun C; Miyamoto, Susumu; Togashi, Kaori

    2015-06-01

    Previous studies have shown that intratumoral hemorrhage is a common finding in glioblastoma multi-forme, but is rarely observed in primary central nervous system lymphoma. Our aim was to reevaluate whether intratumoral hemorrhage observed on T2-weighted imaging (T2WI) as gross intratumoral hemorrhage and on susceptibility-weighted imaging as intratumoral susceptibility signal can differentiate primary central nervous system lymphoma from glioblastoma multiforme. A retrospective cohort of brain tumors from August 2008 to March 2013 was searched, and 58 patients (19 with primary central nervous system lymphoma, 39 with glioblastoma multiforme) satisfied the inclusion criteria. Absence of gross intratumoral hemorrhage was examined on T2WI, and an intratumoral susceptibility signal was graded using a 3-point scale on susceptibility-weighted imaging. Results were compared between primary central nervous system lymphoma and glioblastoma multiforme, and values of P central nervous system lymphoma and 23 patients (59%) with glioblastoma multiforme. Absence of gross intratumoral hemorrhage could not differentiate between the two disorders (P = 0.20). However, intratumoral susceptibility signal grade 1 or 2 was diagnostic of primary central nervous system lymphoma with 78.9% sensitivity and 66.7% specificity (P central nervous system lymphoma from glioblastoma multiforme. However, specificity in this study was relatively low, and primary central nervous system lymphoma cannot be excluded based solely on the presence of an intratumoral susceptibility signal.

  9. The effects of a single intravenous injection of novel activin A/BMP-2 (AB204) on toxicity and the respiratory and central nervous systems.

    Science.gov (United States)

    Yoon, Byung-Hak; Lee, Jae Hyup; Na, Kyuheum; Ahn, Chihoon; Cho, Jongho; Ahn, Hyun Chan; Choi, Jungyoun; Oh, Hyosun; Kim, Byong Moon; Choe, Senyon

    2016-01-01

    The purpose of this study was to determine the effects of a single intravenous injection of a novel osteoinductive material, activin A/BMP-2 (AB204), to rodents on toxicity and their respiratory functions and central nervous system (CNS). A single intravenous injection of AB204 was given to Sprague-Dawley (SD) rats in doses of 0, 0.625, 2.5 and 10 mg/kg to observe the mortality rate, the general symptoms for 14 days. The experimental groups were also given 0.2, 0.4 and 0.8 mg/kg of AB204, respectively, and the respiration rate, the tidal volume and the minute volume were measured for 240 min. The experimental groups of imprinting control region (ICR) mice were given a single intravenous injection of 0.2, 0.4 and 0.8 mg/kg of AB204, respectively. Their body temperature was taken and general behaviors were observed to evaluate the effect of AB204 on the CNS for 240 min. The study on toxicity of a single intravenous injection found no death or abnormal symptoms, abnormal findings from autopsy, or abnormal body weight gain or loss in all the experimental groups. No abnormal variation associated with the test substance was observed in the respiration rate, the tidal volume, the minute volume, body temperature or the general behaviors. On the basis of these results, the approximate lethal dose of AB204 for a single intravenous injection exceeds 10 mg/kg for SD rats and a single intravenous injection of ≤0.8 mg/kg AB204 has no effect on their respiratory system for SD rat and no effect on their CNS for ICR mice.

  10. Efficient injection from large telescopes into single-mode fibres: Enabling the era of ultra-precision astronomy

    Science.gov (United States)

    Jovanovic, N.; Schwab, C.; Guyon, O.; Lozi, J.; Cvetojevic, N.; Martinache, F.; Leon-Saval, S.; Norris, B.; Gross, S.; Doughty, D.; Currie, T.; Takato, N.

    2017-08-01

    Photonic technologies offer numerous advantages for astronomical instruments such as spectrographs and interferometers owing to their small footprints and diverse range of functionalities. Operating at the diffraction-limit, it is notoriously difficult to efficiently couple such devices directly with large telescopes. We demonstrate that with careful control of both the non-ideal pupil geometry of a telescope and residual wavefront errors, efficient coupling with single-mode devices can indeed be realised. A fibre injection was built within the Subaru Coronagraphic Extreme Adaptive Optics (SCExAO) instrument. Light was coupled into a single-mode fibre operating in the near-IR (J - H bands) which was downstream of the extreme adaptive optics system and the pupil apodising optics. A coupling efficiency of 86% of the theoretical maximum limit was achieved at 1550 nm for a diffraction-limited beam in the laboratory, and was linearly correlated with Strehl ratio. The coupling efficiency was constant to within 40% for 84% of the time and >50% for 41% of the time. The laboratory results allow us to forecast that extreme adaptive optics levels of correction (Strehl ratio >90% in H-band) would allow coupling of >67% (of the order of coupling to multimode fibres currently) while standard levels of wavefront correction (Strehl ratio >20% in H-band) would allow coupling of >18%. For Strehl ratios <20%, few-port photonic lanterns become a superior choice but the signal-to-noise, and pixel availability must be considered. These results illustrate a clear path to efficient on-sky coupling into a single-mode fibre, which could be used to realise modal-noise-free radial velocity machines, very-long-baseline optical/near-IR interferometers and/or simply exploit photonic technologies in future instrument design.

  11. Reduction of waveform distortion in grid-injection current from single-phase utility interactive PV-inverter

    International Nuclear Information System (INIS)

    Hamid, Muhammad Imran; Jusoh, Awang

    2014-01-01

    Highlights: • A reduction scheme for harmonics from utility interactive PV-inverter is proposed. • Single-phase conditioner with 3-phase expandability structure is used. • The single-phase conditioner in 3-phase structure work independently. • The scheme works effectively within overall operation range of the PV-inverter. • Conditioner in the scheme also improves the PV-inverter and plant’s utility factor. - Abstract: As the natural behavior of energy source and design characteristic, the current generated by a grid-interactive PV-inverter may contain harmonics. This distortion component will be carried on from the PV-inverter during injection power into the grid. Excessive harmonics in a grid will lead to a variety of power quality problems. This paper presents a distortion reduction scheme, utilizing a fed forward single-phase, generation-side power conditioner with a structure that can be expanded for use in a three-phase system and can work independently under imbalanced condition. Conditioner is placed in parallel with the photovoltaic plant and it functions to compensate the plant’s output current distortion, so that the total current flow to the grid is sinusoidal. This method also includes the implementation of a simpler control system for the conditioner, which consists of a combination of distortion current extraction, synchronization and a current control system, and realized through a TMS320F28335: a 150 MHz floating point DSP controller. Testing of the conditioner prototype, which was conducted on a real operation of a PV plant, showed that the scheme worked effectively within the overall operation range of the PV plant. This paper also discusses the potential of utility factor improvement of the PV-inverter and plant due to implementation of conditioner in the scheme

  12. A prospective, randomized, single - blind study comparing intraplaque injection of thiocolchicine and verapamil in Peyronie's Disease: a pilot study

    Directory of Open Access Journals (Sweden)

    I. L. Toscano Jr.

    Full Text Available ABSTRACT Objectives: To compare the response to tiocolchicine and verapamil injection in the plaque of patients with Peyronie's disease. Materials and Methods: Prospective, single-blind, randomized study, selecting patients who have presented Peyronie's disease for less than 18 months. Thiocolchicine 4mg or verapamil 5mg were given in 7 injections (once a week. Patients who had received any treatment for Peyronie's disease in the past three months were excluded. The parameters used were the International Index of Erectile Function (IIEF-5 score, analysis of the curvature on pharmaco-induced erections and size of the plaque by ultrasonography. Results: Twenty-five patients were randomized, 13 received thiocolchicine and 12 were treated with verapamil. Both groups were statistically similar. The mean curvature was 46.7° and 36.2° before and after thiocolchicine, respectively (p=0.019 and 50.4° and 42.08° before and after verapamil, respectively (p=0.012. The curvature improved in 69% of patients treated with thiocolchicine and in 66% of those who received verapamil. Regarding sexual function, there was an increase in the IIEF-5 from 16.69 to 20.85 (p=0.23 in the thiocolchicine group. In the verapamil group the IIEF-5 score dropped from 17.50 to 16.25 (p=0.58. In the thiocolchicine group, the plaque was reduced in 61% of patients. In the verapamil group, 8% presented decreased plaque size. No adverse event was associated to thiocolchicine. Conclusion: The use of thiocolchicine in Peyronie's disease demonstrated improvement on penile curvature and reduction in plaque size. Thiocolchicine presented similar results to verapamil in curvature assessment. No significant side effects were observed with the use of tiocolchicine.

  13. Optimization of single injection liver arterial phase gadolinium enhanced MRI using bolus track real-time imaging.

    Science.gov (United States)

    Sharma, Puneet; Kalb, Bobby; Kitajima, Hiroumi D; Salman, Khalil N; Burrow, Bobbie; Ray, Gaye L; Martin, Diego R

    2011-01-01

    To measure contrast agent enhancement kinetics in the liver and to further evaluate and develop an optimized gadolinium enhanced MRI using a single injection real-time bolus-tracking method for reproducible imaging of the transient arterial-phase. A total of 18 subjects with hypervascular liver lesions were imaged with four dimensional (4D) perfusion scans to measure time-to-peak (TTP) delays of arterial (aorta-celiac axis), liver parenchyma, liver lesion, portal, and hepatic veins. Time delays were calculated from the TTP-aorta signal, and then related to the gradient echo (GRE) k-space acquisition design, to determine optimized timing for real-time bolus-track triggering methodology. As another measure of significance, 200 clinical patients were imaged with 3D-GRE using either a fixed time-interval or by individualized arterial bolus real-time triggering. Bolus TTP-aorta was calculated and arterial-phase acquisitions were compared for accuracy and reproducibility using specific vascular enhancement indicators. The mean bolus transit-time to peak-lesion contrast was 8.1 ± 2.7 seconds following arterial detection, compared to 32.1 ± 5.4 seconds from contrast injection, representing a 62.1% reduction in the time-variability among subjects (N = 18). The real-time bolus-triggered technique more consistently captured the targeted arterial phase (94%), compared to the fixed timing technique (73%), representing an expected improvement of timing accuracy in 28% of patients (P = 0.0001389). Our results show detailed timing window analysis required for optimized arterial real-time bolus-triggering acquisition of transient arterial phase features of liver lesions, with optimized arterial triggering expected to improve reproducibility in a significant number of patients. Copyright © 2010 Wiley-Liss, Inc.

  14. Comparison of a single- or double-injection technique for ultrasound-guided supraclavicular block: a prospective, randomized, blinded controlled study.

    Science.gov (United States)

    Roy, Mélanie; Nadeau, Marie-Josée; Côté, Dany; Levesque, Simon; Dion, Nicolas; Nicole, Pierre C; Turgeon, Alexis F

    2012-01-01

    Despite good success rates reported with ultrasound-guided supraclavicular block using 1 or multiple injections, no consensus exists on the best technique to use. We designed this study to test the hypothesis that a double-injection technique would hasten the onset of sensory block. Adult patients undergoing hand, wrist, or elbow surgery were enrolled in this prospective double-blind randomized study. Blocks were performed under ultrasound guidance. In group S (single injection), 30 mL of mepivacaine 1.5% was injected at the junction of the subclavian artery and the first rib. In group D (double injection), 15 mL of the same solution was injected at the site described above, then 15 mL was injected in the most superficial portion of the lateral aspect of the cluster formed by the brachial plexus trunks and divisions. The primary end point was the rate of complete sensory block at 15 mins. Secondary end points were the rates of sensory, motor, and surgical blocks and procedure time. Fifty-one patients were randomized to each group. The rate of complete sensory block was similar at 15 mins (group S: 49% [95% confidence interval, 36%-62%], group D: 53% [95% confidence interval, 40%-66%]; P = 0.80) and at each time interval. The rates of complete motor block and surgical block success were similar between groups. The procedure time was shorter in group S (179 ± 104 vs 275 ± 137 secs; P block.

  15. Parasellar dermoid tumor with intra-tumoral hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Mamata, H.; Yanagimachi, N.; Matsuyama, S. [Department of Radiology I, Tokai University School of Medicine, Kanagawa (Japan); Matsumae, M.; Takamiya, Y.; Tsugane, R. [Department of Neurosurgery, Tokai University School of Medicine, Kanagawa (Japan)

    1998-12-01

    We report a case of parasellar dermoid tumor with intra-tumoral hemorrhage. It is rare for a dermoid tumor that hemorrhage was detected as high attenuation on the initial CT. In the present case, the tumor content included a little fat component and mostly cholesterin-rich fluid which resulted in extremely low signal intensity on T2-weighted and high signal on T1-weighted MR images. In addition to this, hemosiderin accumulation in the tumor could be the reason for low signal intensity on T2-weighted images. (orig.) With 3 figs., 19 refs.

  16. Stepwise injection potentiometric determination of caffeine in saliva using single-drop microextraction combined with solvent exchange.

    Science.gov (United States)

    Timofeeva, I; Medinskaia, K; Nikolaeva, L; Kirsanov, D; Bulatov, A

    2016-04-01

    A flow potentiometric method for determination of caffeine in saliva is suggested. This task is important for non-invasive assessment of drug metabolizing system activity in hepatocytes. In the current study, stepwise injection analysis (SWIA) was successfully combined with single-drop liquid microextraction (SDLME) and solvent exchange procedure. The method is based on the caffeine SDLME with subsequent solvent evaporation and dissolution of analyte in sulfuric acid followed by potentiometric detection using poly(vinyl chloride) membrane electrode containing potassium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate as electroactive component. SDLME was employed for elimination of interfering matrix effects of saliva and caffeine metabolites such as theophylline, theobromine and paraxanthine. A linear range of 10(-5)-10(-2)M was established for caffeine with detection limit at 6 × 10(-6)M. The sample throughput was 6 samples h(-1). The proposed method was successfully applied to the determination of caffeine in saliva and the analytical results agreed well with the results obtained with reference HPLC method. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours

    NARCIS (Netherlands)

    Focke, Cornelia M.; Decker, Thomas; van Diest, Paul J.

    2016-01-01

    Aims: Regional differences in proliferative activity are commonly seen within breast cancers, but little is known on the extent of intratumoral heterogeneity of Ki67 expression. Our aim was to study the intratumoral heterogeneity of Ki67 expression in early breast cancers and its association with

  18. Erratum: PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis

    DEFF Research Database (Denmark)

    Cao, R.H.; Bjorndahl, M.A.; Religa, P.

    2006-01-01

    This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45.......This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45....

  19. Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer

    NARCIS (Netherlands)

    Mengelbier, Linda Holmquist; Karlsson, Jenny; Lindgren, David; Valind, Anders; Lilljebjörn, Henrik; Jansson, Caroline; Bexell, Daniel; Braekeveldt, Noémie; Ameur, Adam; Jonson, Tord; Kultima, Hanna Göransson; Isaksson, Anders; Asmundsson, Jurate; Versteeg, Rogier; Rissler, Marianne; Fioretos, Thoas; Sandstedt, Bengt; Börjesson, Anna; Backman, Torbjörn; Pal, Niklas; Øra, Ingrid; Mayrhofer, Markus; Gisselsson, David

    2015-01-01

    Genetic differences among neoplastic cells within the same tumour have been proposed to drive cancer progression and treatment failure. Whether data on intratumoral diversity can be used to predict clinical outcome remains unclear. We here address this issue by quantifying genetic intratumoral

  20. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate

    Science.gov (United States)

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-01-01

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate. PMID:24225910

  1. Different thallium-201 single-photon emission tomographic patterns in benign and aggressive meningiomas

    International Nuclear Information System (INIS)

    Tedeschi, E.; Soricelli, A.; Brunetti, A.; Romano, M.; Bucciero, A.; Iaconetta, G.; Alfieri, A.; Postiglione, A.; Salvatore, M.

    1996-01-01

    To evaluate the possibility of preoperatively obtaining an index of aggressiveness for intracranial meningiomas, we prospectively studied 22 patients with computed tomographic or magnetic resonance imaging evidence of meningeal tumour, using single-photon emission tomography (SPET) of the brain and thallium-201 ( 201 Tl). On a brain-dedicated SPET scanner, a rapid acquisition protocol with early, short scans was started simultaneously with the intravenous administration of 111 MBq 201 Tl, covering the initial intratumoral distribution of the tracer. Twenty minutes post injection, a delayed SPET scan was also obtained. On the reconstructed and attenuation-corrected images we calculated the 201 Tl concentration in tumour and normal contralateral brain tissue, and compared intratumoral tracer concentration in the initial and the final part of the rapid acquisition protocol. Benign and malignant meningiomas were classified as such based on histological examination. In malignant lesions, the ratio of the 201 Tl concentration at 2-4 min post injection to that at 14-16 min was found to be significantly higher than in non-aggressive neoplasms (mean±1 SD: 1.14±0.31 and 0.56±0.13, respectively, P 201 Tl concentration values at 2-4 and at 14-16 min. Our findings suggest that the comparative assessment of intratumoral 201 Tl concentration at 2-4 and at 14-16 min post injection could provide a fast, simple method to differentiate preoperatively intracranial meningiomas with different biological behaviour. (orig.). With 3 figs., 1 tab

  2. Experimental study of unsteady heat release in an unstable single element Lean Direct Injection (LDI) gas turbine combustor

    Science.gov (United States)

    Lakshmanan, Varun S.

    In an effort to curb emissions from gas turbine engines, many low emission engine concepts have been developed. Among the most promising of these is the LDI (Lean Direct Injection). These systems operate at relatively low equivalence ratios close to blowout and are prone to instabilities. Combustion instabilities can reduce the life of the combustor by causing large pressure fluctuations and enhanced heat release to the walls of the combustor and reduce the efficiency of the engines. The understanding of combustion instabilities is vital to the implementation of such systems. Combustion instabilities are studied in an self-excited single element gas turbine combustor that uses an LDI element for fuel injection at elevetaed chamber pressures. The LDI combustor uses a swirler to ensure mixing of the air and the fuel and expansion of the swirl through a pressure swirl venturi to create a swirl stabilized flame. This project aims to study the heat release modes that occur in the combustor through measurement of light emissions from the flame using photodiodes that are sensitive to wavelengths of light produced by the flame. These are used along with high frequency pressure transducers. The focus is on the flame behavior in the diverging section of the venturi where the swirl is expanded and the flame starts since optic access cannot be obtained in this section. The use of photodiodes also facilitates the study of hydrodynamic modes that occur in the combustor alongside the thermoacoustics. A section which could accommodate the photodiodes was designed and installed on the LDI test rig in the Gas Turbine Cell at Maurice J Zucrow Propulsion Labs at Purdue University. The combustor was tested with this section and dynamic data was obtained from the pressure transducers and the photodiodes for a range of inlet air temperatures and range of equivalence ratios for each inlet air temperature. The dominant instability modes in both sets of data were analyzed and are presented

  3. Intratumoral vaccination of adenoviruses expressing fusion protein RM4/tumor necrosis factor (TNF)-alpha induces significant tumor regression.

    Science.gov (United States)

    Wright, P; Zheng, C; Moyana, T; Xiang, J

    1998-01-01

    Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo gene delivery. VKCK is a murine myeloma cell line expressing the light chain of the fusion protein RM4/tumor necrosis factor (TNF)-alpha. The in vitro transfection of VKCK cells with the AdV AdV5LacZ, which contains the marker gene beta-galactosidase, can reach a maximal 75% at a multiplicity of infection of 1000. Intratumoral injections of AdV5LacZ (2 x 10(9) plaque-forming units) resulted in substantial gene transfer in nearly 50% of VKCK tumors. The AdV pLpA/M4-TNF-alpha, which contains a fused gene M4-TNF-alpha that codes for the heavy chain of fusion protein RM4/TNF-alpha, was constructed. After the in vitro transfection of pLpA/M4-TNF-alpha at a multiplicity of infection of 1000, transfected VKCK cells showed significant secretion of RM4/TNF-alpha (36 ng/mL/10(6) cells) containing the functional TNF-alpha moiety in tissue culture. The secretion peaks at day 3 and is diminished at day 6 following the viral infection. These transfected VKCK cells also became more immunogenic with enhanced expression of major histocompatibility complex class I antigen. Intratumoral injections of 2 x 10(9) plaque-forming units of pLpA/M4-TNF-alpha virus with a repeated booster resulted in significant VKCK tumor regression in immune-competent mice, but not in athymic nude mice with a mean tumor weight of 0.07 g that were compared with 1.58 g and 1.70 g for tumors injected with AdV5LacZ and phosphate-buffered saline, respectively (P management of solid human tumors.

  4. Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

    Directory of Open Access Journals (Sweden)

    Hohenforst-Schmidt W

    2013-07-01

    through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR negative stage IIIa–IV International Union Against Cancer 7 (UICC-7, and with Eastern Cooperative Oncology Group (ECOG 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of

  5. The mechanism of the transient depression of the erythropoietic rate induced in the rat by a single injection of uranyl nitrate

    International Nuclear Information System (INIS)

    Giglio, M.J.; Brandan, N.; Leal, T.L.; Bozzini, C.E.

    1989-01-01

    With the purpose of assessing the effect of uranyl nitrate (UN) on the rate of erythropoiesis, 1 mg/kg of the compound was injected iv to adult female Wistar rats. The dosing vehicle was injected into control animals. A single injection of UN induced a transient depression of the rate of red cell volume 59 Fe uptake, which reached its lowest value (68% depression) by the seventh postinjection day. By 14 days, 59 Fe incorporation had returned to normal. The amount of iron going to erythroid tissue per hour, reticulocyte count, and immunoreactive erythropoietin concentration in both plasma and kidney extracts were also significantly depressed in UN-treated rats in relation to these values in vehicle-injected rats by the seventh postinjection day. Dose-response curves for exogenous erythropoietin (Epo) performed in polycythemic intact and UN-treated rats 7 days after drug injection revealed a significant depression of the response in UN-injected animals. Moreover, bone marrow cells obtained from rats pretreated with UN formed a reduced number of erythroid colonies in vitro in response to Epo. Therefore, possible mechanisms for the observed transient depression in the rate of erythropoiesis associated with acute UN treatment include decreased Epo production and direct or indirect damage of erythroid progenitor cells

  6. The effects of bacterial endotoxin on lipide metabolism. I. The responses of the serum lipides of rabbits to single and repeated injections of Shear's polysaccharide.

    Science.gov (United States)

    LEQUIRE, V S; HUTCHERSON, J D; HAMILTON, R L; GRAY, M E

    1959-08-01

    Single intravenous injections of Shear's polysaccharide in varying dosages invariably produced an elevation in the levels of the total serum lipides 24 hours after injection of endotoxin. The total serum cholesterol and lipide phosphorus were also affected, although they did not change with smaller doses of endotoxin and were rarely elevated to the same degree as were the total serum lipides. The degree of elevation of the serum lipides was apparently related to the amount of endotoxin injected up to a certain point, beyond which there was no further increase. There were two types of response to endotoxin by the serum lipides, a moderate increase and an uncontrolled increase. Higher dosages of endotoxin and fasting apparently increased the incidence of the latter response. No direct correlation could be made between serum lipide responses and histologic evidence typical of the generalized Shwartzman reaction following this regimen of endotoxin injection. The Shwartzman reaction did occur with greater frequency and with lower dosages of endotoxin in fasted animals. Animals given repeated injections of endotoxin showed an initial increase in serum lipides followed by a progressive decrease to normal levels as tolerance to the febrile action of endotoxin appeared. The febrile tolerance as well as the unresponsiveness of the serum lipides to endotoxin was abolished by thorium dioxide (thorotrast) in these animals. In similar experiments a "breakthrough" of lipide unresponsiveness to endotoxin was obtained by increasing the amount of endotoxin injected. Some of the implications of these results for the metabolic alterations produced by bacterial endotoxins are discussed.

  7. Assessment of the efficacy and safety of single platelet-rich plasma injection on different types and grades of facial wrinkles.

    Science.gov (United States)

    Elnehrawy, Naema Y; Ibrahim, Zeinab A; Eltoukhy, Azza M; Nagy, Hala M

    2017-03-01

    Platelet-rich plasma (PRP) is considered as a growing modality for tissue regeneration and a developing research area for clinicians and researchers. PRP injection treatment provides supraphysiological concentrations of growth factors that may help in accelerated tissue remodeling and regeneration. To evaluate the efficacy and safety of single autologous PRP intradermal injection for treatment of facial wrinkles and for facial rejuvenation. A total of 20 subjects with different types of facial wrinkles were included in this study. All subjects received single PRP intradermal injection and were clinically assessed before and after treatment for a period of 8 weeks using Wrinkle Severity Rating Scale (WSRS), Skin Homogeneity and Texture (SHnT) Scale, Physician Assessment Scale, and Subject Satisfaction Scale. The mean value of WSRS reduced from 2.90 ± 0.91 before treatment to 2.10 ± 0.79 after 8 weeks of treatment. The most significant results were with younger subjects that have mild and moderate wrinkles of the nasolabial folds (NLFs). Fourteen of seventeen subjects with NLFs showed more than 25% improvement in their appearance. Side effects of PRP treatment were minimal to mild and with excellent tolerability. Single PRP intradermal injection is well tolerated and capable of rejuvenating the face and producing a significant correction of wrinkles especially the NLFs. © 2016 Wiley Periodicals, Inc.

  8. Treatment of autonomously functioning thyroid nodules at a single institution. Radioiodine therapy, surgery, and ethanol injection therapy

    International Nuclear Information System (INIS)

    Yano, Yukiko; Sugino, Kiminori; Akaishi, Junko

    2011-01-01

    The purpose of this study was to clarify the efficacy of radioiodine (RI) therapy in Japanese patients with autonomously functioning thyroid nodules (AFTNs). We performed a retrospective analysis to assess the management of AFTN patients. Thyroid lobectomy was performed to treat toxic adenoma (TA) patients, and total thyroidectomy to treat toxic multinodular goiter (TMNG) patients. RI therapy was administered in the form of a single dose (500 MBq) of isotope in the outpatient clinic. Percutaneous ethanol injection therapy (PEIT) was performed under ultrasound guidance. Of the total 205 patients, consisting of 159 TA and 46 TMNG patients, 99 underwent surgery, 50 received RI therapy, and 56 received PEIT. Remission of thyrotoxicosis was achieved in all of the patients who were treated surgically. Hypothyroidism was documented in six of the 72 patients who were treated surgically other than by total thyroidectomy. Remission of thyrotoxicosis was observed in 43 of the 50 patients who were treated by RI therapy. Nine TA patients developed hypothyroidism during the follow-up period after RI therapy. Several PEIT sessions were required to achieve a remission of thyrotoxicosis. Remission of thyrotoxicosis was achieved in 29 of the 56 patients treated by PEIT, and thyrotoxicosis recurred in 17 these 56 patients. Surgery is the treatment of choice for large nodules and nodules that are resistant to other treatments, because it allows prompt control of thyrotoxicosis. RI therapy is a safe and effective means of controlling thyrotoxicosis in AFTN patients. We conclude that RI therapy is the treatment of choice for definitive treatment of AFTN patients who do not have local compression symptoms. (author)

  9. Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus).

    Science.gov (United States)

    Grismer, B; Rowe, J D; Carlson, J; Wetzlich, S E; Tell, L A

    2014-04-01

    Eight adult female dairy goats received one subcutaneous administration of tulathromycin at a dosage of 2.5 mg/kg body weight. Blood and milk samples were assayed for tulathromycin and the common fragment of tulathromycin, respectively, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of tulathromycin was analyzed by a noncompartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of tulathromycin were as follows: C(max) (121.54 ± 19.01 ng/mL); T(max) (12 ± 12-24 h); area under the curve AUC(0→∞) (8324.54 ± 1706.56 ng·h/mL); terminal-phase rate constant λz (0.01 ± 0.002 h⁻¹); and terminal-phase rate constant half-life t1/2λz (67.20 h; harmonic). Mean milk pharmacokinetic parameters (±SD) following 45 days of sampling were as follows: Cmax (1594 ± 379.23 ng/mL); Tmax (12 ± 12-36 h); AUC(0→∞) (72,250.51 ± 18,909.57 ng·h/mL); λz (0.005 ± 0.001 h⁻¹); and t(1/2λz) (155.28 h; harmonic). All goats had injection-site reactions that diminished in size over time. The conclusions from this study were that tulathromycin residues are detectable in milk samples from adult goats for at least 45 days following subcutaneous administration, this therapeutic option should be reserved for cases where other treatment options have failed, and goat milk should be withheld from the human food chain for at least 45 days following tulathromycin administration. © 2013 John Wiley & Sons Ltd.

  10. 3D pulmonary perfusion MRI and MR angiography of pulmonary embolism in pigs after a single injection of a blood pool MR contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Fink, Christian; Ley, Sebastian; Puderbach, Michael; Plathow, Christian; Kauczor, Hans-Ulrich [Department of Radiology, Innovative Cancer Diagnostic and Therapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg (Germany); Bock, Michael [Department of Medical Physics in Radiology, Innovative Cancer Diagnostic and Therapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg (Germany)

    2004-07-01

    The purpose of this study was to assess the feasibility of contrast-enhanced 3D perfusion MRI and MR angiography (MRA) of pulmonary embolism (PE) in pigs using a single injection of the blood pool contrast Gadomer. PE was induced in five domestic pigs by injection of autologous blood thrombi. Contrast-enhanced first-pass 3D perfusion MRI (TE/TR/FA: 1.0 ms/2.2 ms/40 ; voxel size: 1.3 x 2.5 x 4.0 mm{sup 3}; TA: 1.8 s per data set) and high-resolution 3D MRA (TE/TR/FA: 1.4 ms/3.4 ms/40 ; voxel size: 0.8 x 1.0 x 1.6 mm{sup 3}) was performed during and after a single injection of 0.1 mmol/kg body weight of Gadomer. Image data were compared to pre-embolism Gd-DTPA-enhanced MRI and post-embolism thin-section multislice CT (n=2). SNR measurements were performed in the pulmonary arteries and lung. One animal died after induction of PE. In all other animals, perfusion MRI and MRA could be acquired after a single injection of Gadomer. At perfusion MRI, PE could be detected by typical wedge-shaped perfusion defects. While the visualization of central PE at MRA correlated well with the CT, peripheral PE were only visualized by CT. Gadomer achieved a higher peak SNR of the lungs compared to Gd-DTPA (21{+-}8 vs. 13{+-}3). Contrast-enhanced 3D perfusion MRI and MRA of PE can be combined using a single injection of the blood pool contrast agent Gadomer. (orig.)

  11. Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy

    DEFF Research Database (Denmark)

    Haahr, Martha Kirstine; Jensen, Charlotte Harken; Toyserkani, Navid Mohamadpour

    2016-01-01

    is registered with ClinicalTrials.gov, NCT02240823. FINDINGS: Intracavernous injection of ADRCs was well-tolerated and only minor events related to the liposuction and cell injections were reported at the one-month evaluation, but none at later time points. Overall during the study period, 8 of 17 men recovered...... to a mean difference of 0.57 (0.38-0.85; p = 0.0069), versus inclusion. In contrast, incontinent men did not regain erectile function (median IIEF1/3/6 months = 5 (95% CI 5-6); mean difference 1 (95% CI 0.85-1.18), p > 0.9999). INTERPRETATION: In this phase I trial a single intracavernosal injection...

  12. Single-dose Intramuscular-injection Toxicology Test of Water-soluble Carthami-flos and Cervi cornu parvum Pharmacopuncture in a Rat Model

    Directory of Open Access Journals (Sweden)

    Sunju Park

    2015-09-01

    Full Text Available Objectives: The aim of the study is to investigate both the single-dose intramuscular injection toxicity and the approximate lethal dose of water-soluble Carthami-flos and Cervi cornu parvum pharmacopuncture (WCFC in male and female Sprague-Dawley (SD rats. Methods: The study was conducted at Biotoxtech Co. according to the Good Laboratory Practice (GLP regulation and the toxicity test guidelines of the Ministry of Food and Drug Safety (MFDS after approval of the Institutional Animal Care and Use Committee. Dosages for the control, high dose, middle dose and low dose groups were 0.5 mL/animal of saline and 0.5, 0.25 and 0.125 mL/animal of WCFC, respectively. WCFC was injected into the muscle of the left femoral region by using a disposable syringe (1 mL, 26 gauge. The general symptoms and mortality were observed 30 minutes, 1, 2, 4, and 6 hours after the first injection and then daily for 14 days after the injection. The body weights of the SD rats were measured on the day of the injection (before injection and on the third, seventh, and fourteenth days after the injection. Serum biochemical and hematologic tests, necropsy examinations, and histopathologic examinations at the injection site were performed after the observation period. Results: No deaths, abnormal clinical symptoms, or significant weight changes were observed in either male or female SD rats in the control or the test (0.125, 0.25, and 0.5 mL/animal groups during the observation period. No significant differences in hematology and serum biochemistry and no macroscopic abnormalities at necropsy were found. No abnormal reactions at injection sites were noted on the topical tolerance tests. Conclusion: The results of this single-dose toxicity study show that WCFC is safe, its lethal doses in male and female SD rats being estimated to be higher than 0.5 mL/animal.

  13. Determination of the optional time for taking blood samples by single intravenous injection of 3H-leucine

    International Nuclear Information System (INIS)

    Meng Delian; Yao Junhu; Lu Jinyin; Wu Xiaobin; Liu Jun

    2003-01-01

    Twenty four young hens (1.5 kg of body weight, BW) were randomly divided into 4 groups. Every group was diet free (FAS) or force-fed a nitrogen-free diet (NFD) or the diet with 20% crude protein in which soybean meal or cotton seed meal was the sole nitrogen source (30 g DM/kg BW). 30 μCi 3 H-Leu/kg BW was intravenously injected into all birds just after force-fed or on fasting. Venous blood samples were taken at 5, 30 min, 4,24,36 and 48h after injection. The excreta during the whole period of 48h after injection was collected. Special radioactivities of nonprotein plasma at every time point and excreta were measured. The optional time of taking blood samples was 20-24 hours after injected 3 H-Leu

  14. Effect of steam injection on nox emissions and performance of a single cylinder diesel engine fuelled with soy methyl ester

    Directory of Open Access Journals (Sweden)

    Manickam Madhavan V.

    2017-01-01

    Full Text Available Biodiesel attracts most of the researchers and automotive industries in recent years as an alternative fuel for diesel engines, because of its better lubricity property, higher cetane number, and less greenhouse gas emissions. The use of bio diesel leads to reduction in hydro carbons, carbon monoxide, and particulate matter, but increase in NOx emissions. Increase in biodiesel blends in standard diesel leads to increase in NOx emission. In this study, an attempt is made to reduce the NOx emis-sions of a diesel engine fueled with pure soy methyl ester (B100 with low pressure steam injection. Experiments were carried out and studied for both standard diesel and pure biodiesel of soy methyl ester with steam injection ratio of 5, 10, and 15% on mass ratio basis of air in the inlet manifold. The present study has shown that around 30% reduction in NOx can be achieved for the steam injection rate of 10% and considerable reduction for all other steam injection rates when compared to standard diesel and B100. It is also observed that steam injection having signifi-cant impact on reduction of other emissions such as HC, CO, and CO2. The study also noted marginal improvement in the engine brake power, brake thermal effi-ciency and reduction in specific fuel consumption at part loads and minor increase during peak load operation for the low pressure steam injection on B100.

  15. The 15N-leucine single-injection method allows for determining endogenous losses and true digestibility of amino acids in cecectomized roosters.

    Directory of Open Access Journals (Sweden)

    Rujiu Hu

    Full Text Available This study was conducted to assess the influence of dietary protein content in poultry when using the 15N-leucine single-injection method to determine endogenous amino acid losses (EAALs in poultry. Forty-eight cecectomized roosters (2.39 ± 0.23 kg were randomly allocated to eight dietary treatments containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20 mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta samples were continuously collected during the course of the 48-h experiment. The ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05 across all treatments. The amino acid (AA profiles of total endogenous AAs, except isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not influenced (P > 0.05 by dietary protein contents. The predominant endogenous AAs in the excreta were glutamic acid, aspartic acid, threonine, serine and proline. The order of the relative proportions of these predominant AAs also remained relatively constant (P > 0.05. The endogenous losses of total AAs determined with the 15N-leucine single-injection method increased curvilinearly with the dietary protein contents. The true digestibility of most AAs and total AAs was independent of their respective dietary protein levels. Collectively, the 15N-leucine single-injection method is appropriate for determining EAALs and the true digestibility of AAs in poultry fed varying levels of protein-containing ingredients.

  16. A pilot study of the treatment of patients with recurrent malignant gliomas with intratumoral yttrium-90 radioimmunoconjugates

    International Nuclear Information System (INIS)

    Hopkins, K.; Chandler, C.; Bullimore, J.; Sandeman, D.; Coakham, H.; Kemshead, J.T.

    1995-01-01

    A pilot study of the treatment of patients with relapsed malignant gliomas with direct intratumoral injections of yttrium-90 ( 90 Y) radioimmunoconjugates has been completed. Patients were recruited following maximal tumour resection, and received 1-3 injections of 90 Y conjugated to a monoclonal antibody designated ERIC-1, which binds the neural cell-adhesion molecule. Data were collected to establish clinical toxicity, pharmacokinetics and radiation doses to the cavity wall and critical body organs. Twenty-three injections were completed in 15 patients, with a mean injected activity of 675 MBq (range 399-921). Early toxicity manifested as cerebral oedema and was readily controlled with dexamethasone. Delayed myelosuppression was observed but no intervention was required. Pharmacokinetic analysis confirmed prolonged retention of isotope in the cavity with correspondingly low activity in the bloodstream. These data were translated into estimates of absorbed radiation dose using the Medical Internal Radiation Dosimetry (MIRD) scheme. Mean doses, and dose rates, to the wall of the cavity, i.e. 'tumour,' were very high in comparison to normal tissue doses, with a further advantage if targeting was achieved

  17. Endoscopic treatment of vesicoureteral reflux in children with subureteral dextranomer/hyaluronic acid injection: a single-centre, 7-year experience

    Science.gov (United States)

    Biočíc, Mihovil; Todoríc, Jakov; Budimir, Dražen; Roíc, Andrea Cvitkovíc; Pogorelíc, Zenon; Juríc, Ivo; Šušnjar, Tomislav

    2012-01-01

    Background The goals of medical intervention in patients with vesicoureteral reflux are to allow normal renal growth, prevent infections and pyelonephritis, and prevent renal failure. We present our experience with endoscopic treatment of vesicoureteral reflux in children by subureteral dextranomer/hyaluronic acid copolymer injection. Methods Under cystoscopic guidance, dextranomer/hyaluronic acid copolymer underneath the intravesical portion of the ureter in a subureteral or submucosal location was injected in patients undergoing endoscopic correction of vesicoureteral reflux. Results A total of 282 patients (120 boys and 162 girls) underwent the procedure. There were 396 refluxed ureters altogether. The mean age of patients was 4.9 years. The mean overall follow-up period was 44 months. Among the 396 ureters treated, 76% were cured with a single injection. A second and third injection raised the cure rate to 93% and 94%, respectively. Twenty-two (6%) ureters failed all 3 injections, and were converted to open surgery. Conclusion Endoscopic treatment of vesicoureteral reflux can be recommended as a first-line therapy for most cases of vesicoureteral reflux, because of the short hospital stay, absence of complications and the high success rate. PMID:22854114

  18. Pharmacokinetics of meloxicam in red-eared slider turtles (Trachemys scripta elegans) after single intravenous and intramuscular injections.

    Science.gov (United States)

    Uney, Kamil; Altan, Feray; Aboubakr, Mohammed; Cetin, Gul; Dik, Burak

    2016-05-01

    OBJECTIVE To determine the pharmacokinetics of meloxicam after single IV and IM injections in red-eared slider turtles (Trachemys scripta elegans). ANIMALS 8 healthy red-eared slider turtles. PROCEDURES Turtles received 1 dose of meloxicam (0.2 mg/kg) IV or IM (4 turtles/route), a 30-day washout period was provided, and then turtles received the same dose by the opposite route. Blood samples were collected at predetermined times for measurement of plasma meloxicam concentration. Pharmacokinetic values for each administration route were determined with a 2-compartment open model approach. RESULTS For IV administration, mean ± SD values of major pharmacokinetic variables were 1.02 ± 0.41 hours for distribution half-life, 9.78 ± 2.23 hours for elimination half-life, 215 ± 32 mL/kg for volume of distribution at steady state, 11.27 ± 1.44 μg•h/mL for area under the plasma concentration versus time curve, and 18.00 ± 2.32 mL/h/kg for total body clearance. For IM administration, mean values were 0.35 ± 0.06 hours for absorption half-life, 0.72 ± 0.06 μg/mL for peak plasma concentration, 1.5 ± 0.0 hours for time to peak concentration, 3.73 ± 2.41 hours for distribution half-life, 13.53 ± 1.95 hours for elimination half-life, 11.33 ± 0.92 μg•h/mL for area under the plasma concentration versus time curve, and 101 ± 6% for bioavailability. No adverse reactions were detected. CONCLUSIONS AND CLINICAL RELEVANCE Long half-life, high bioavailability, and lack of immediate adverse reactions of meloxicam administered IM at 0.2 mg/kg suggested the possibility of safe and effective clinical use in turtles. Additional studies are needed to establish appropriate administration frequency and clinical efficacy.

  19. 10 mJ single-frequency, injection-seeded Q-switched Er:YAG laser pumped by a 1470 nm fiber-coupled LD

    Science.gov (United States)

    Gao, C. Q.; Shi, Y.; Ye, Q.; Wang, S.; Na, Q. X.; Wang, Q.; Gao, M. W.

    2018-02-01

    A 1645 nm injection-seeded Q-switched Er:YAG laser resonantly pumped by a 1470 nm fiber-coupled laser diode is demonstrated with a non-planar ring oscillator as a seed laser to realize the single-frequency operation. The maximum output pulse energy of the laser is 10.1 mJ, corresponding to a pulse width of 205 ns at a repetition rate of 200 Hz. The half-width of the pulse spectrum is 2.44 MHz measured by a heterodyne technique. The fluctuation of the center frequency of the pulsed laser is 1.43 MHz (RMS) in 1 h. To the best of our knowledge, this is highest energy obtained from a single-frequency, injection-seeded Er:YAG laser pumped by a laser diode.

  20. Quantitative Clinical Imaging Methods for Monitoring Intratumoral Evolution.

    Science.gov (United States)

    Kim, Joo Yeun; Gatenby, Robert A

    2017-01-01

    Solid tumors are multiscale, open, complex, dynamic systems: complex because they have many interacting components, dynamic because both the components and their interactions can change with time, and open because the tumor freely communicates with surrounding and even distant host tissue. Thus, it is not surprising that striking intratumoral variations are commonly observed in clinical imaging such as MRI and CT and that several recent studies found striking regional variations in the molecular properties of cancer cells from the same tumor. Interestingly, this spatial heterogeneity in molecular properties of tumor cells is typically ascribed to branching clonal evolution due to accumulating mutations while macroscopic variations observed in, for example, clinical MRI scans are usually viewed as functions of blood flow. The clinical significance of spatial heterogeneity has not been fully determined but there is a general consensus that the varying intratumoral landscape along with patient factors such as age, morbidity and lifestyle, contributes significantly to the often unpredictable response of individual patients within a disease cohort treated with the same standard-of-care therapy.Here we investigate the potential link between macroscopic tumor heterogeneity observed by clinical imaging and spatial variations in the observed molecular properties of cancer cells. We build on techniques developed in landscape ecology to link regional variations in the distribution of species with local environmental conditions that define their habitat. That is, we view each region of the tumor as a local ecosystem consisting of environmental conditions such as access to nutrients, oxygen, and means of waste clearance related to blood flow and the local population of tumor cells that both adapt to these conditions and, to some extent, change them through, for example, production of angiogenic factors. Furthermore, interactions among neighboring habitats can produce broader

  1. Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin.

    Science.gov (United States)

    Murphy, J E; Zhou, S; Giese, K; Williams, L T; Escobedo, J A; Dwarki, V J

    1997-12-09

    The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype that includes obesity and non-insulin-dependent diabetes mellitus. This phenotype closely resembles the morbid obesity seen in humans. In this study, we demonstrate that a single intramuscular injection of a recombinant adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in ob/ob mice leads to prevention of obesity and diabetes. The treated animals show normalization of metabolic abnormalities including hyperglycemia, insulin resistance, impaired glucose tolerance, and lethargy. The effects of a single injection have lasted through the 6-month course of the study. At all time points measured the circulating levels of leptin in the serum were similar to age-matched control C57 mice. These results demonstrate that maintenance of normal levels of leptin (2-5 ng/ml) in the circulation can prevent both the onset of obesity and associated non-insulin-dependent diabetes. Thus a single injection of a rAAV vector expressing a therapeutic gene can lead to complete and long-term correction of a genetic disorder. Our study demonstrates the long-term correction of a disease caused by a genetic defect and proves the feasibility of using rAAV-based vectors for the treatment of chronic disorders like obesity.

  2. Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin

    Science.gov (United States)

    Murphy, John E.; Zhou, Shangzhen; Giese, Klaus; Williams, Lewis T.; Escobedo, Jaime A.; Dwarki, Varavani J.

    1997-01-01

    The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype that includes obesity and non-insulin-dependent diabetes melitus. This phenotype closely resembles the morbid obesity seen in humans. In this study, we demonstrate that a single intramuscular injection of a recombinant adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in ob/ob mice leads to prevention of obesity and diabetes. The treated animals show normalization of metabolic abnormalities including hyperglycemia, insulin resistance, impaired glucose tolerance, and lethargy. The effects of a single injection have lasted through the 6-month course of the study. At all time points measured the circulating levels of leptin in the serum were similar to age-matched control C57 mice. These results demonstrate that maintenance of normal levels of leptin (2–5 ng/ml) in the circulation can prevent both the onset of obesity and associated non-insulin-dependent diabetes. Thus a single injection of a rAAV vector expressing a therapeutic gene can lead to complete and long-term correction of a genetic disorder. Our study demonstrates the long-term correction of a disease caused by a genetic defect and proves the feasibility of using rAAV-based vectors for the treatment of chronic disorders like obesity. PMID:9391128

  3. Reliability Analysis of Single-Phase PV Inverters with Reactive Power Injection at Night Considering Mission Profiles

    DEFF Research Database (Denmark)

    Anurag, Anup; Yang, Yongheng; Blaabjerg, Frede

    2015-01-01

    , especially at night when there is no solar irradiance. This serves as a motivation for utilizing the PV inverters at night for reactive power compensation. Thus, an analysis on the impact of reactive power injection by PV inverters outside feed-in operation on the thermal performance and the reliability has...... at night, the impact of PV sites on the economic value of the inverter is assessed. This analysis can be useful in choosing between conventional reactive power compensation devices or PV inverters for injecting reactive power to the grid....

  4. Watt-level widely tunable single-mode emission by injection-locking of a multimode Fabry-Perot quantum cascade laser

    Science.gov (United States)

    Chevalier, Paul; Piccardo, Marco; Anand, Sajant; Mejia, Enrique A.; Wang, Yongrui; Mansuripur, Tobias S.; Xie, Feng; Lascola, Kevin; Belyanin, Alexey; Capasso, Federico

    2018-02-01

    Free-running Fabry-Perot lasers normally operate in a single-mode regime until the pumping current is increased beyond the single-mode instability threshold, above which they evolve into a multimode state. As a result of this instability, the single-mode operation of these lasers is typically constrained to few percents of their output power range, this being an undesired limitation in spectroscopy applications. In order to expand the span of single-mode operation, we use an optical injection seed generated by an external-cavity single-mode laser source to force the Fabry-Perot quantum cascade laser into a single-mode state in the high current range, where it would otherwise operate in a multimode regime. Utilizing this approach, we achieve single-mode emission at room temperature with a tuning range of 36 cm-1 and stable continuous-wave output power exceeding 1 W at 4.5 μm. Far-field measurements show that a single transverse mode is emitted up to the highest optical power, indicating that the beam properties of the seeded Fabry-Perot laser remain unchanged as compared to free-running operation.

  5. Randomised trial of single and repeated fibrin glue compared with injection of polidocanol in treatment of bleeding peptic ulcer

    NARCIS (Netherlands)

    Rutgeerts, P.; Rauws, E.; Wara, P.; Swain, P.; Hoos, A.; Solleder, E.; Halttunen, J.; Dobrilla, G.; Richter, G.; Prassler, R.

    1997-01-01

    Although injection treatments for ulcer haemostasis seem to be effective, recurrent bleeding remains a serious problem. Large randomised clinical trials are required to show differences between treatment modalities for gastrointestinal bleeding. The aim of this study was to compare the safety and

  6. Single well field injection test of humate to enhance attenuation of uranium and other radionuclides in an acidic plume

    Energy Technology Data Exchange (ETDEWEB)

    Denham, M. [Savannah River Site (SRS), Aiken, SC (United States)

    2014-09-30

    This report documents the impact of the injected humate on targeted contaminants over a period of 4 months and suggests it is a viable attenuation-based remedy for uranium, potentially for I-129, but not for Sr-90. Future activities will focus on issues pertinent to scaling the technology to full deployment.

  7. Clinical Evaluation of Non-surgical Sterilization of Male Cats with Single Intra-testicular Injection of Calcium Chloride

    Directory of Open Access Journals (Sweden)

    Samanta Prabhat K

    2011-07-01

    Full Text Available Abstract Background Calcium chloride solution is an established injectable sterilant in dogs and other mammals. With cat populations a continuing problem, we sought to explore its first use in cats. Six cats per group were injected with 5%, 10% or 20% calcium chloride dihydrate in saline solution with lignocaine hydrochloride, a local anaesthetic. Results At the 60th day post-injection, cat testes were collected and showed complete testicular necrosis and replacement by fibrous tissue; very low sperm counts; and reduction of serum testosterone by at least 70% in 20% dose. Androgenic enzyme activities and their expressions were also reduced in all the treated groups along with intra-testicular testosterone concentration was also low. Increased testicular lipid peroxidation, with reduced antioxidants and mitochondrial membrane potential, were evident following calcium chloride treatments. However, there were no apparent changes in serum concentrations of cortisol, fasting blood sugar level, blood urea nitrogen, packed cell volume, or total serum protein following calcium chloride injection, suggesting that this method of sterilization is not associated with any general stress response. Conclusion Calcium chloride solution demonstrates potential for androgenesis-eliminating nonsurgical sterilization of male cats in addition to its proven efficacy in dogs and other mammals.

  8. Safety and effectiveness of a single and repeat intramuscular injection of a GnRH vaccine (GonaCon™) in adult female domestic cats.

    Science.gov (United States)

    Vansandt, L M; Kutzler, M A; Fischer, A E; Morris, K N; Swanson, W F

    2017-04-01

    Sterilization is a key strategy to reduce the number of domestic cats entering and killed in shelters each year. However, surgical sterilization is expensive and labour-intensive and cannot fully address the 70 million free-roaming cats estimated to exist in the United States. GonaCon™ is a gonadotropin-releasing hormone vaccine originally developed for use as a wildlife immunocontraceptive. An earlier formulation was tested in domestic cats and found to be safe and effective for long-term contraception. However, the current Environmental Protection Agency (EPA)-registered formulation consists of a different antigen-carrier protein and increased antigen concentration and has never been tested in cats. A pilot study was undertaken to evaluate the short-term safety of a single GonaCon immunization, assess the consequences of vaccinated cats receiving an accidental second GonaCon injection and determine the humoral immune response to immunization. During Phase 1, cats in Group A (n = 3) received a single intramuscular injection of GonaCon and Group B (n = 3) received a single intramuscular injection of saline. During Phase 2, Group A received a second GonaCon injection and Group B received their initial GonaCon injection. All cats developed GnRH antibodies within 30 days of vaccine administration. The endpoint titre (1:1,024,000) was similar among all cats, and levels remained high throughout the duration of the study. Four cats developed a sterile, painless, self-limiting mass at the site of injection. The mean number of days to mass development was 110.3 (range, 18-249 days). In conclusion, this preliminary study suggests that the EPA-registered GonaCon formulation is safe for continued testing in domestic cats, an accidental revaccination should not increase the risk of a vaccine reaction and the EPA-registered formulation effectively elicits a strong humoral immune response. © 2016 Blackwell Verlag GmbH.

  9. Dynamics of 1.55 μm Wavelength Single-Mode Vertical-Cavity Surface-Emitting Laser Output under External Optical Injection

    Directory of Open Access Journals (Sweden)

    Kyong Hon Kim

    2012-01-01

    Full Text Available We review the temporal dynamics of the laser output spectrum and polarization state of 1.55 μm wavelength single-mode (SM vertical-cavity surface-emitting lasers (VCSELs induced by external optical beam injection. Injection of an external continuous-wave laser beam to a gain-switched SM VCSEL near the resonance wavelength corresponding to its main polarization-mode output was critical for improvement of its laser pulse generation characteristics, such as pulse timing-jitter reduction, linewidth narrowing, pulse amplitude enhancement, and pulse width shortening. Pulse injection of pulse width shorter than the cavity photon lifetime into the SM VCSEL in the orthogonal polarization direction with respect to its main polarization mode caused temporal delay of the polarization recovery after polarization switching (PS, and its delay was found to be the minimum at an optimized bias current. Polarization-mode bistability was observed even in the laser output of an SM VCSEL of a standard circularly cylindrical shape and used for all-optical flip-flop operations with set and reset injection pulses of very low pulse energy of order of the 3.5~4.5 fJ.

  10. Elimination of Mange Mites Sarcoptes scabiei var. suis from Two Naturally Infested Danish Sow Herds Using a Single Injection Regime with Doramectin

    Science.gov (United States)

    Jensen, JCE; Nielsen, LH; Arnason, T; Cracknell, V

    2002-01-01

    Attempts to eliminate Sarcoptes scabiei var. suis were made in 2 naturally infested sow herds, by intramuscular (IM) injection of doramectin (Dectomax®, Pfizer, New York, USA). A single injection strategy was used. In one of the herds, the environment was treated with an acaricide following dry cleaning of floors, walls and equipment. In the second herd, no environmental treatment was performed. Results were measured by skin lesion scoring, ear scrapings to show Sarcoptes scabiei var. suis, and calculating rubbing index throughout the observation period of 20 months following treatment. Skin lesion scores decreased and stayed low following treatment for the entire observation period. Live Sarcoptes scabiei var. suis mites were isolated prior to treatment from both herds, but not following treatment. Rubbing index decreased following treatment, but was occasionally at or above 0.4. The results of these studies indicate that elimination of Sarcoptes scabiei var. suis from 2 naturally infested herds was successful, using doramectin in a single injection strategy. Precautions must be taken to ensure adequate dosing of every pig, and to avoid reinfestation due to poor biosecurity. PMID:12173505

  11. Elimination of Mange Mites Sarcoptes scabiei var. suis from Two Naturally Infested Danish Sow Herds Using a Single Injection Regime with Doramectin

    Directory of Open Access Journals (Sweden)

    Arnason T

    2002-06-01

    Full Text Available Attempts to eliminate Sarcoptes scabiei var. suis were made in 2 naturally infested sow herds, by intramuscular (IM injection of doramectin (Dectomax®, Pfizer, New York, USA. A single injection strategy was used. In one of the herds, the environment was treated with an acaricide following dry cleaning of floors, walls and equipment. In the second herd, no environmental treatment was performed. Results were measured by skin lesion scoring, ear scrapings to show Sarcoptes scabiei var. suis, and calculating rubbing index throughout the observation period of 20 months following treatment. Skin lesion scores decreased and stayed low following treatment for the entire observation period. Live Sarcoptes scabiei var. suis mites were isolated prior to treatment from both herds, but not following treatment. Rubbing index decreased following treatment, but was occasionally at or above 0.4. The results of these studies indicate that elimination of Sarcoptes scabiei var. suis from 2 naturally infested herds was successful, using doramectin in a single injection strategy. Precautions must be taken to ensure adequate dosing of every pig, and to avoid reinfestation due to poor biosecurity.

  12. Radiation Dosimetry from Intratumoral Injection of Radionuclides in Human Breast Cancer

    Science.gov (United States)

    2006-07-01

    necessary approach for the majority of women. More directed local treatment with radiotherapy appears to be safe and effective treatment...City Responsible for security, health and well being of approximately 100 people. Taking measures to avoid accidents by going on expedition routs

  13. Radiation Dosimetry of Intratumoral Injection of Radionuclides into Human Breast Cancer. Revision

    Science.gov (United States)

    2007-07-01

    radionuclides G. Who will perform experimental manipulations on the animals? 1. Kamran Ahrar; MD; Assistant Professor; YEARS EXPERIENCE WITH SPECIES: 3...directly involved with the animal Manipulations ) 1. Kenneth Wright; Diagnostic Radiology; CONTRIBUTION TO PROJECT: Provide facility, guidance and...Animal Care and Use Form -- 06-04-05871 -- Page 5 IV. Agents Used In Animal HAZARDOUS AGENTS: include carcinogenic chemicals, antineoplastic drugs

  14. Radiation Dosimetry of Intratumoral Injection of Radionuclides into Human Breast Cancer

    Science.gov (United States)

    2007-07-01

    radionuclides G. Who will perform experimental manipulations on the animals? 1. Kamran Ahrar; MD; Assistant Professor; YEARS EXPERIENCE WITH SPECIES: 3...directly involved with the animal Manipulations ) 1. Kenneth Wright; Diagnostic Radiology; CONTRIBUTION TO PROJECT: Provide facility, guidance and...Animal Care and Use Form -- 06-04-05871 -- Page 5 IV. Agents Used In Animal HAZARDOUS AGENTS: include carcinogenic chemicals, antineoplastic drugs

  15. Radiation Dosimetry of Intratumoral Injection of Radionuclides into Human Breast Cancer

    National Research Council Canada - National Science Library

    Wong, Franklin C

    2005-01-01

    .... While the refinement of the human protocol is ongoing, we continue on basic studies to investigate in vivo imaging methods and effects of other drugs under revised versions of our approved animal protocol...

  16. Rapid Quantitative Analysis of Multiple Explosive-Compound Classes on a Single Instrument via Flow-Injection Analysis Tandem Mass Spectrometry

    Science.gov (United States)

    2017-03-20

    on a Single In‐ strument via Flow‐Injection Analysis Tandem Mass  Spectrometry   Alla Ostrinskaya, Roderick R. Kunz, Michelle Clark, Rich P...alla.ostrinskaya@ll.mit.edu    ABSTRACT: A flow injection analysis (FIA) tandem mass spectrometry (MSMS) method was developed for rapid quantita- tive analysis of...and has redundant detection channels for reduced  error   rates necessary  for probative use,  (b)  is more  rapid  than existing methods to allow for

  17. Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors

    International Nuclear Information System (INIS)

    Valous, Nektarios A.; Lahrmann, Bernd; Halama, Niels; Grabe, Niels; Bergmann, Frank; Jäger, Dirk

    2016-01-01

    Purpose: The interactions of neoplastic cells with each other and the microenvironment are complex. To understand intratumoral heterogeneity, subtle differences should be quantified. Main factors contributing to heterogeneity include the gradient ischemic level within neoplasms, action of microenvironment, mechanisms of intercellular transfer of genetic information, and differential mechanisms of modifications of genetic material/proteins. This may reflect on the expression of biomarkers in the context of prognosis/stratification. Hence, a rigorous approach for assessing the spatial intratumoral heterogeneity of histological biomarker expression with accuracy and reproducibility is required, since patterns in immunohistochemical images can be challenging to identify and describe. Methods: A quantitative method that is useful for characterizing complex irregular structures is lacunarity; it is a multiscale technique that exhaustively samples the image, while the decay of its index as a function of window size follows characteristic patterns for different spatial arrangements. In histological images, lacunarity provides a useful measure for the spatial organization of a biomarker when a sampling scheme is employed and relevant features are computed. The proposed approach quantifies the segmented proliferative cells and not the textural content of the histological slide, thus providing a more realistic measure of heterogeneity within the sample space of the tumor region. The aim is to investigate in whole sections of primary pancreatic neuroendocrine neoplasms (pNENs), using whole-slide imaging and image analysis, the spatial intratumoral heterogeneity of Ki-67 immunostains. Unsupervised learning is employed to verify that the approach can partition the tissue sections according to distributional heterogeneity. Results: The architectural complexity of histological images has shown that single measurements are often insufficient. Inhomogeneity of distribution depends

  18. The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections

    Directory of Open Access Journals (Sweden)

    Valdis Goncars

    2017-01-01

    Conclusions: The intra-articular injection of bone marrow-derived mononuclear cells is a safe manipulation with no side effects during the 12-month period. This treatment provides statistically significant clinical improvement between the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic acid treatment, better pain relief in the long-term period of mononuclear cell group was observed.

  19. Bee venom acupuncture point injection for central post stroke pain: a preliminary single-blind randomized controlled trial.

    Science.gov (United States)

    Cho, Seung-Yeon; Park, Joo-Young; Jung, Woo-Sang; Moon, Sang-Kwan; Park, Jung-Mi; Ko, Chang-Nam; Park, Seong-Uk

    2013-06-01

    We investigated apipuncture, or acupuncture point injection with diluted bee venom, as a promising new treatment for central post stroke pain (CPSP). Bee venom, diluted to 0.005% in normal saline, was administered to the treatment group, and normal saline given to control group as twice-weekly injections for three weeks. The points were LI15, GB21, LI11, GB31, ST36 and GB39 of the affected side and the amount of injection was 0.05 ml at each point. Eight patients in each group were included in the analysis. After three weeks there were significant decreases in visual analogue pain scores compared with baseline in both groups and the treatment group improved more significantly than the control group (p = 0.009). Apipuncture significantly improved CPSP in this pilot trial. Further studies of its mechanisms and a larger and long-term follow-up trial will be needed to determine more definitely the efficacy of apipuncture and to elucidate duration of improvement. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. High-power actively Q-switched single-mode 1342 nm Nd:YVO4 ring laser, injection-locked by a cw single-frequency microchip laser.

    Science.gov (United States)

    Koch, Peter; Bartschke, Juergen; L'huillier, Johannes A

    2015-11-30

    In this paper we report on the realization of a single-mode Q-switched Nd:YVO4 ring laser at 1342 nm. Unidirectional and single-mode operation of the ring laser is achieved by injection-locking with a continuous wave Nd:YVO4 microchip laser, emitting a single-frequency power of up to 40 mW. The ring laser provides a single-mode power of 13.9 W at 10 kHz pulse repetition frequency with a pulse duration of 18.2 ns and an excellent beam quality (M2 laser, a power of 8.7 W at 671 nm with a pulse duration of 14.8 ns and a beam propagation factor of M2 < 1.1 is obtained. The 671 nm radiation features a long-term spectral width of 75 MHz.

  1. Evaluation of Plasma Creatine Phosphokinase (CPK Level Following a Single Injection of Methotrexate as a Predicator of Treatment Success in Ectopic Pregnancy.

    Directory of Open Access Journals (Sweden)

    Leila Safdarian

    2013-12-01

    Full Text Available To evaluate the plasma creatine phosphokinase (CPK level after a single injection of methotrexate (MTX as a predictor of treatment success in ectopic pregnancy (EP.In this prospective study, seventy nine women older than 18 years treated with methotrexate for ectopic pregnancy were evaluated for CPK and β-subunit of human chorionic gonadotropin (βhCG levels, while they received intramuscular MTX at a dose of 50 mg/m2. The day of injection was considered as day 1 (D1. CPK level on D1 was compared between the group 1(as treatment success group, treated by a single MTX injection, and the group 2, treated by two or three MTX injections or by surgery.The success rate of MTX treatment was 58 (73.3%. The mean of CPK was higher in treatment success group (group1 than failure group (group 2 (71.98 ± 15.711 vs. 64.43 ± 15.898, but the difference was not significant (p=0.06. The mean of βhCG was significantly lower in treatment success group (group 1 than failure group (group 2 (1187.52±631.45 vs. 1663.87±1096.845; p=0.01. Ultrasonographic findings of EP were seen in 63 patients, while the means of βHCG and CPK were higher in these patients than those with normal ultrasonography, but difference was not significant (p=0.37 and p=0.24, respectively.The sample was not large enough to indicate a significant difference in the CPK level, which can be considered as an indicator for differentiating between the successful and unsuccessful treatment groups. Moreover, the present study did not show any relation between initial β-hCG and CPK serum levels, so our findings indicate that they are not possibly considered as two independent biomarkers in ectopic pregnancy.

  2. Intratumoral Heterogeneous F 18 Fluorodeoxyglucose Uptake Corresponds with Glucose Transporter 1 and Ki-67 Expression in a Case of Krukenberg Tumor: Localization of Intratumoral Hypermetabolic Focus by Fused PET/MR

    Energy Technology Data Exchange (ETDEWEB)

    Im, Hyung Jun; Kim, Youg il; Kim, Woo Ho; Kim, Seung Hyup; Kang, Keon Wook [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2011-06-15

    The expression of glucose transporters (Glut 1, Glut 3), Hexokinase II, and Ki-67 has been proposed to explain intratumoral heterogeneous F-18 fluorodeoxyglucose (FDG) uptake. We report a case of Krukenberg tumor with intratumoral heterogeneous FDG uptake which corresponded well with the expression tomography (PET)/magnetic resonance (MR) imaging was helpful for localizing the metabolically active area in the tumor specimen. This report elucidates the relationship between the intratumoral heterogeneous FDG uptake and biologic heterogeneity, and shows the usefulness of PET/MR in research on intratumoral heterogeneity.

  3. Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

    International Nuclear Information System (INIS)

    Lee, Kwang-Hun; Liapi, Eleni A.; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A.; Ventura, Veronica Prieto; Geschwind, Jean-Francois H.

    2010-01-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  4. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    International Nuclear Information System (INIS)

    Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2011-01-01

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21 + follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response

  5. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Federica Marchesi

    2011-12-01

    Full Text Available Ectopic (or tertiary lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC. We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS. B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV. Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  6. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bergomas, Francesca [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Grizzi, Fabio [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Doni, Andrea; Pesce, Samantha [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Laghi, Luigi [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Allavena, Paola [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Mantovani, Alberto [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan, Milan 20089 (Italy); Marchesi, Federica, E-mail: federica.marchesi@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy)

    2011-12-28

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21{sup +} follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  7. Factors Controlling the Pharmacokinetics, Biodistribution and Intratumoral Penetration of Nanoparticles

    Science.gov (United States)

    Ernsting, Mark J.; Murakami, Mami; Roy, Aniruddha; Li, Shyh-Dar

    2014-01-01

    Nanoparticle drug delivery to the tumor is impacted by multiple factors: nanoparticles must evade clearance by renal filtration and the reticuloendothelial system, extravasate through the enlarged endothelial gaps in tumors, penetrate through dense stroma in the tumor microenvironment to reach the tumor cells, remain in the tumor tissue for a prolonged period of time, and finally release the active agent to induce pharmacological effect. The physicochemical properties of nanoparticles such as size, shape, surface charge, surface chemistry (PEGylation, ligand conjugation) and composition affect the pharmacokinetics, biodistribution, intratumoral penetration and tumor bioavailability. On the other hand, tumor biology (blood flow, perfusion, permeability, interstitial fluid pressure and stroma content) and patient characteristics (age, gender, tumor type, tumor location, body composition and prior treatments) also have impact on drug delivery by nanoparticles. It is now believed that both nanoparticles and the tumor microenvironment have to be optimized or adjusted for optimal delivery. This review provides a comprehensive summary of how these nanoparticle and biological factors impact nanoparticle delivery to tumors, with discussion on how the tumor microenvironment can be adjusted and how patients can be stratified by imaging methods to receive the maximal benefit of nanomedicine. Perspectives and future directions are also provided. PMID:24075927

  8. Identification and weighting factors influencing the establishment of a single minute exchange of dies in plastic injection industry using VIKOR and Shannon Entropy

    Directory of Open Access Journals (Sweden)

    Gholam Reza Hashemzadeh

    2014-05-01

    Full Text Available Single minute exchange of dies (SMED is one of the most important tools to achieve lean production system. The main idea of this system is to provide methods and to use creative and innovative solutions for continuous improvement. Due to the importance of this issue and its effect on reducing waste during the production process, this study presents a method to identify and to weight factors in the establishment of a single minute exchange of dies in 14 plastic injection factories. In this study, fourteen factories in injection industry were chosen and the factors influencing the implementation of single minute exchange of dies were identified. Following data collection, decision matrix was formed and the weight of each factor was determined by using Shannon Entropy. Then, in order to determine the readiness of factories, VIKOR method was used to rank companies. The results indicate priorities of the following factors in establishing SMED that include: Senior management support, technical capabilities, technical knowledge of staff and consultants, knowledge of mold design, manufacturing infrastructure, team work, combination of the project team work, benchmarking, training, clear understanding of project objectives, rewards and motivation, proper management expectation, project management, teamwork and organizational culture. Practical implications: Due to the factors, Top manager can make the best decision for implementing of SMED technique. This study develops factors influencing on SMED implementation based on Shannon and VIKOR methods for ranking parameters and plants.

  9. Single-injection method for evaluation of renal function with 14C-inulin and 3H-tetraethylammonium bromide in dogs and cats

    International Nuclear Information System (INIS)

    Fettman, M.J.; Allen, T.A.; Wilke, W.L.; Radin, M.J.; Eubank, M.C.

    1985-01-01

    A double-isotope single-injection method without urine collection for the estimation of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in dogs and cats was evaluated. The GFR was determined, using 14 C-inulin and ERPF was determined, using [ 3 H]tetraethylammonium bromide. Using a modified single exponential, 1-compartment mathematical model, the renal clearance of these solutes was estimated with a plasma radioactivity disappearance curve constructed from samples collected over a 150-minute time period. In 25 dogs, GFR, ERPF, and filtration fraction were 3.55 +/- 0.14 ml/kg/min, 10.51 +/- 0.72 ml/kg/min, and 0.34 +/- 0.02, respectively. In 25 cats, GFR, ERPF, and filtration fraction were 3.24 +/- 0.14 ml/kg/min, 8.14 +/- 0.53 ml/kg/min, and 0.39 +/- 0.02, respectively. This time-efficient and reliable method, using beta-emitting isotopes, yielded renal functional values well within the normal ranges reported by a variety of other isotopic and nonisotopic procedures. The advantages of the present procedure over previous double-isotope single-injection methods include the use of less costly, lower energy-using, and less penetrating beta emittors, as well as a shortened blood sampling schedule

  10. Pharmacokinetics of a single intramuscular injection of ceftiofur crystalline-free acid in red-tailed hawks (Buteo jamaicensis).

    Science.gov (United States)

    Sadar, Miranda J; Hawkins, Michelle G; Byrne, Barbara A; Cartoceti, Andrew N; Keel, Kevin; Drazenovich, Tracy L; Tell, Lisa A

    2015-12-01

    To determine the pharmacokinetics and adverse effects at the injection site of ceftiofur crystalline-free acid (CCFA) following IM administration of 1 dose to red-tailed hawks (Buteo jamaicensis). 7 adult nonreleasable healthy red-tailed hawks. In a randomized crossover study, CCFA (10 or 20 mg/kg) was administered IM to each hawk and blood samples were obtained. After a 2-month washout period, administration was repeated with the opposite dose. Muscle biopsy specimens were collected from the injection site 10 days after each sample collection period. Pharmacokinetic data were calculated. Minimum inhibitory concentrations of ceftiofur for various bacterial isolates were assessed. Mean peak plasma concentrations of ceftiofur-free acid equivalent were 6.8 and 15.1 μg/mL for the 10 and 20 mg/kg doses, respectively. Mean times to maximum plasma concentration were 6.4 and 6.7 hours, and mean terminal half-lives were 29 and 50 hours, respectively. Little to no muscle inflammation was identified. On the basis of a target MIC of 1 μg/mL and target plasma ceftiofur concentration of 4 μg/mL, dose administration frequencies for infections with gram-negative and gram-positive organisms were estimated as every 36 and 45 hours for the 10 mg/kg dose and every 96 and 120 hours for the 20 mg/kg dose, respectively. Study results suggested that CCFA could be administered IM to red-tailed hawks at 10 or 20 mg/kg to treat infections with ceftiofur-susceptible bacteria. Administration resulted in little to no inflammation at the injection site. Additional studies are needed to evaluate effects of repeated CCFA administration.

  11. Intratumor genetic heterogeneity of breast carcinomas as determined by fine needle aspiration and TaqMan low density array

    DEFF Research Database (Denmark)

    Lyng, Maria B.; Laenkholm, Anne-Vibeke; Pallisgaard, Niels

    2007-01-01

    surgery were split in halves and FNAs were obtained from each half. A tissue biopsy of the tumors was also snap-frozen for comparison. Non-amplified RNA was investigated by the novel qRT-PCR-based technique, Low Density Array (LDA) using 4 reference genes and 44 target genes. RESULTS: Comparison of gene...... expression at the single gene level in the two FNA samples from each tumor demonstrated various degrees of heterogeneity. However, compared as gene expression profiles, intratumor correlations for 9/12 patients were high and these pairs could in a theoretical blinding of all the FNAs be correctly matched...... by statistical analysis. High correlations between the gene profiles of tumor FNAs and tissue biopsies from the same patient were observed for all patients. A cluster analysis identified clustering of both the two FNAs and the tissue biopsy of the same 9 patients. CONCLUSION: The overall genetic heterogeneity...

  12. Effect of Pilot Injection Timings on the Combustion Temperature Distribution in a Single-Cylinder CI Engine Fueled with DME and ULSD

    Directory of Open Access Journals (Sweden)

    Jeon Joonho

    2016-01-01

    Full Text Available Many studies of DiMethyl Ether (DME as an alternative fuel in Compression-Ignition (CI engines have been performed. Although diverse DME engine research has been conducted, the investigation of combustion behavior and temperature distribution in the combustion engine has not progressed due to the fact that there is no sooting flame in DME combustion. In order to investigate the combustion characteristics in this study, the KIVA-3 V code was implemented to research various pilot injection strategies on a single-cylinder CI engines with DME and Ultra-Low-Sulfur Diesel (ULSD fuels. The combustion distribution results obtained from the numerical investigation were validated when compared with the measurement of flame temperature behaviors in the experimental approach. This study showed that long intervals between two injection timings enhanced pilot combustion by increasing the ambient pressure and temperature before the start of the main combustion. Different atomization properties between DME and ULSD fuels contributed to the formation of a fuel-air mixture at the nozzle tip and piston lip regions, separately, which strongly affected the temperature distribution of the two fuels. In addition, the pilot injection timing played a vital role in regard to ignition delay and peak combustion temperatures. Exhaust emissions, such as NOx and soot, are related to the local equivalence ratio and temperature in the combustion chamber, also illustrated by the contrary result on a Φ (equivalence ratio – T (temperature map.

  13. Tritium retention in the femoral bone marrow and spleens of mice receiving single intravenous injections of tritiated water and tritiated thymidine

    International Nuclear Information System (INIS)

    Joshima, Hisamasa; Matsushita, Satoru; Fukutsu, Kumiko; Kashima, Masatoshi

    1987-01-01

    To derive parameters necessary for evaluating the possible hazards of tritium, retention of tritium in total and TCA-insoluble fractions of the femoral marrow and spleen of mice were observed after single intravenous injections of tritiated water and tritiated thymidine. Retention curves of tritium in TCA-insoluble fractions of the femoral marrow and spleen were resolved fairly well into two exponential components. After injecting tritiated thymidine, most of the activity was detected in the TCA-insoluble fraction. Tritium in this fraction decreased with half-times of 2.2 days in the femoral marrow and 3.6 days in the spleen as the first component, and 23.9 days and 30.5 days, respectively, as the second component. After tritiated water injections, the tritium incorporated into the TCA-insoluble fraction was quite small. Most of the activity was considered to be in the TCA-soluble fraction. Tritium in this fraction was estimated to decrease with half-times of 2.6 days in the femoral marrow and 2.3 days in the spleen as the first component, and 8.0 days and 8.2 days, respectively, as the second component. It is concluded that the retention curves of tritium in the bone marrow are similar to those in the spleen for tritiated water, but not for tritiated thymidine. (author)

  14. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in swine hearts: a novel therapeutic approach for acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Hisaaki eIshiguro

    2011-06-01

    Full Text Available Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigate the cardioprotective effect of midkine (MK in swine subjected to ischemia/reperfusion (I/R. I/R was created in swine by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion (midkine injected group; MKT. Saline was injected in controls (CONT. Survival rate 24h after I/R was significantly higher in MKT than in CONT, whereas infarct size/area at risk was almost 5 times smaller. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher % fractional shortening and a lower E/e’ compared with CONT. LV catheterization in MKT showed a lower LVEDP, and a higher dP/dtmax compared with CONT. TUNEL-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we showed that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and mortality and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.

  15. A randomised non-inferiority controlled trial of a single versus a four intradermal sterile water injection technique for relief of continuous lower back pain during labour

    Directory of Open Access Journals (Sweden)

    Webster Joan

    2011-03-01

    Full Text Available Abstract Background Almost one third of women suffer continuous lower back pain during labour. Evidence from three systematic reviews demonstrates that sterile water injections (SWI provide statistically and clinically significant pain relief in women experiencing continuous lower back pain during labour. The most effective technique to administer SWI is yet to be determined. Therefore, the aim of this study is to determine if the single injection SWI technique is no less effective than the routinely used four injection SWI method in reducing continuous lower back pain during labour. Methods/design The trial protocol was developed in consultation with an interdisciplinary team of clinical researchers. We aim to recruit 319 women presenting at term, seeking analgesia for continuous severe lower back pain during labour. Participants will be recruited from two major maternity hospitals in Australia. Randomised participants are allocated to receive a four or single intradermal needle SWI technique. The primary outcome is the change in self-reported pain measured by visual analogue scale at baseline and thirty minutes post intervention. Secondary outcomes include VAS change scores at 10, 60, 90 and 120 min, analgesia use, mode of birth and maternal satisfaction. Statistical analysis Sample size was calculated to achieve 90% power at an alpha of 0.025 to detect a non-inferiority margin of ≤ 1 cm on the VAS, using a one-sided, two-sample t-test. Baseline demographic and clinical characteristics will be analysed for comparability between groups. Differences in primary (VAS pain score and secondary outcomes between groups will be analysed by intention to treat and per protocol analysis using Student's t-test and ANOVA. Conclusion This study will determine if a single intradermal SWI technique is no less effective than the routinely used four injection technique for lower back pain during labour. The findings will allow midwives to offer women

  16. Intratumoral hemorrhage in acoustic neurinoma after gamma knife therapy. A case report

    International Nuclear Information System (INIS)

    Misaki, Toshinari; Arai, Hiroshi; Sasaki, Teruo; Kobayashi, Masakazu; Okuguchi, Taku; Ogasawara, Kuniaki; Ogawa, Akira

    2005-01-01

    A patient who developed symptomatic intratumoral hemorrhage six years after gamma knife surgery for acoustic neurinoma is presented. The patient was a 72-year-old woman who was diagnosed with right acoustic neurinoma and underwent gamma knife surgery. Since symptomatic intratumoral hemorrhage was confirmed six years later, tumor resection was performed. Pathological analysis confirmed widespread hyaline thickening of the vascular endothelia. Symptomatic intratumoral hemorrhage is a relatively rare complication of schwannoma. The pathological features of spontaneous hemorrhage include such vascular anomalies as angioma, clusters of telangiectasia-like abnormal vessels, or numerous thin-walled, dilated vessels. In the present patient, hyaline thickening of vascular endothelia was noted. The association between this histological feature and spontaneous bleeding in neurinoma has not been previously reported in the literature. Delayed effects of radiation include hyaline thickening of the vascular endothelia and narrowing of the vascular lumen. These histological changes have been reported to occur in intratumoral hemorrhage in malignant brain tumors. In the present patient, as hyaline thickening of vascular endothelia due to the gamma knife surgery might have been implicated in symptomatic hemorrhage, the relationship between irradiation and symptomatic intratumoral hemorrhage was examined with reference to the relevant literature. (author)

  17. Comparison of circulating and intratumoral regulatory T cells in patients with renal cell carcinoma.

    Science.gov (United States)

    Asma, Gati; Amal, Gorrab; Raja, Marrakchi; Amine, Derouiche; Mohammed, Chebil; Amel, Ben Ammar Elgaaied

    2015-05-01

    The clear evidence that tumor-infiltrating lymphocytes (TIL) exists in the tumor microenvironment raises the question why renal cell carcinoma (RCC) progresses. Numerous studies support the implication of CD4(+)CD25(high) regulatory T (Treg) cells in RCC development. We aimed in this study to characterize the phenotype and function of circulating and intratumoral Treg cells of RCC patient in order to evaluate their implication in the inhibition of the local antitumor immune response. Our results demonstrate that the proportion of Treg in TIL was, in average, similar to that found in circulating CD4(+) T cells of patients or healthy donors. However, intratumoral Treg exhibit a marked different phenotype when compared with the autologous circulating Treg. A higher CD25 mean level, HLA-DR, Fas, and GITR, and a lower CD45RA expression were observed in intratumoral Treg, suggesting therefore that these cells are effector in the tumor microenvironment. Additionally, intratumoral Treg showed a higher inhibitory function on autologous CD4(+)CD25(-) T cells when compared with circulating Treg that may be explained by an overexpression of FoxP3 transcription factor. These findings suggest that intratumoral Treg could be major actors in the impairment of local antitumor immune response for RCC patients.

  18. Mathematical modeling analysis of intratumoral disposition of anticancer agents and drug delivery systems.

    Science.gov (United States)

    Popilski, Hen; Stepensky, David

    2015-05-01

    Solid tumors are characterized by complex morphology. Numerous factors relating to the composition of the cells and tumor stroma, vascularization and drainage of fluids affect the local microenvironment within a specific location inside the tumor. As a result, the intratumoral drug/drug delivery system (DDS) disposition following systemic or local administration is non-homogeneous and its complexity reflects the differences in the local microenvironment. Mathematical models can be used to analyze the intratumoral drug/DDS disposition and pharmacological effects and to assist in choice of optimal anticancer treatment strategies. The mathematical models that have been applied by different research groups to describe the intratumoral disposition of anticancer drugs/DDSs are summarized in this article. The properties of these models and of their suitability for prediction of the drug/DDS intratumoral disposition and pharmacological effects are reviewed. Currently available mathematical models appear to neglect some of the major factors that govern the drug/DDS intratumoral disposition, and apparently possess limited prediction capabilities. More sophisticated and detailed mathematical models and their extensive validation are needed for reliable prediction of different treatment scenarios and for optimization of drug treatment in the individual cancer patients.

  19. Quantitative analysis of fragrance in selectable one dimensional or two dimensional gas chromatography-mass spectrometry with simultaneous detection of multiple detectors in single injection.

    Science.gov (United States)

    Tan, Hui Peng; Wan, Tow Shi; Min, Christina Liew Shu; Osborne, Murray; Ng, Khim Hui

    2014-03-14

    A selectable one-dimensional ((1)D) or two-dimensional ((2)D) gas chromatography-mass spectrometry (GC-MS) system coupled with flame ionization detector (FID) and olfactory detection port (ODP) was employed in this study to analyze perfume oil and fragrance in shower gel. A split/splitless (SSL) injector and a programmable temperature vaporization (PTV) injector are connected via a 2-way splitter of capillary flow technology (CFT) in this selectable (1)D/(2)D GC-MS/FID/ODP system to facilitate liquid sample injections and thermal desorption (TD) for stir bar sorptive extraction (SBSE) technique, respectively. The dual-linked injectors set-up enable the use of two different injector ports (one at a time) in single sequence run without having to relocate the (1)D capillary column from one inlet to another. Target analytes were separated in (1)D GC-MS/FID/ODP and followed by further separation of co-elution mixture from (1)D in (2)D GC-MS/FID/ODP in single injection without any instrumental reconfiguration. A (1)D/(2)D quantitative analysis method was developed and validated for its repeatability - tR; calculated linear retention indices (LRI); response ratio in both MS and FID signal, limit of detection (LOD), limit of quantitation (LOQ), as well as linearity over a concentration range. The method was successfully applied in quantitative analysis of perfume solution at different concentration level (RSD≤0.01%, n=5) and shower gel spiked with perfume at different dosages (RSD≤0.04%, n=5) with good recovery (96-103% for SSL injection; 94-107% for stir bar sorptive extraction-thermal desorption (SBSE-TD). Copyright © 2014 Elsevier B.V. All rights reserved.

  20. A single-dose, open-label, parallel, randomized, dose-proportionality study of paliperidone after intramuscular injections of paliperidone palmitate in the deltoid or gluteal muscle in patients with schizophrenia.

    Science.gov (United States)

    Cleton, Adriaan; Rossenu, Stefaan; Crauwels, Herta; Berwaerts, Joris; Hough, David; Gopal, Srihari; Eerdekens, Marielle; Vandebosch, An; Remmerie, Bart; De Meulder, Marc; Rosso, Clara M

    2014-09-01

    Paliperidone palmitate (PP) is a long-acting injectable (LAI) antipsychotic, developed for monthly intramuscular (i.m.) administration into deltoid/gluteal muscle, approved for the treatment of schizophrenia in many countries. To assess the options for i.m. injection sites, dose-proportionality of PP was investigated after injection of a single dose (25-150 mg eq.) of PP in either gluteal (n = 106) or deltoid (n = 95) muscle of schizophrenic patients. Overall, mean (geometric) area under plasma concentration-time curve from time zero to infinity (AUC∞ ) of paliperidone increased proportionally with increasing PP doses, regardless of injection site. Mean maximum plasma concentration (Cmax ) was slightly less than dose-proportional for both injection sites at PP doses >50 mg eq. Mean Cmax was higher after injection in the deltoid compared with the gluteal muscle, except for the 100 mg eq. dose, while AUC∞ for both injection sites was comparable at all doses. Median time to reach Cmax (tmax ) ranged from 13-14 days after deltoid and 13-17 days after gluteal injection across all doses. Single PP injections in deltoid and gluteal muscles in the dose range of 25-150 mg eq. were generally tolerable both locally and systemically. © 2014, The American College of Clinical Pharmacology.

  1. Future considerations for pharmacologic adjuvants in single-injection peripheral nerve blocks for patients with diabetes mellitus.

    Science.gov (United States)

    Williams, Brian A; Murinson, Beth B; Grable, Benjamin R; Orebaugh, Steven L

    2009-01-01

    As the epidemics of obesity and diabetes expand, there are more patients with these disorders requiring elective surgery. For surgery on the extremities, peripheral nerve blocks have become a highly favorable anesthetic option when compared with general anesthesia. Peripheral blocks reduce respiratory and cardiac stresses, while potentially mitigating untreated peripheral pain that can foster physiologic conditions that increase risks for general health complications. However, local anesthetics are generally accepted to be a rare but possible cause of nerve damage, and there are no evidence-based recommendations for dosing local anesthetic nerve blocks in patients with diabetes. This is important because anesthesiologists do not want to potentially accelerate peripheral nerve dysfunction in diabetic patients at risk. This translational vignette (i) examines laboratory models of diabetes, (ii) summarizes the pharmacology of perineural adjuvants (epinephrine, clonidine, buprenorphine, midazolam, tramadol, and dexamethasone), and (iii) identifies areas that warrant further research to determine viability of monotherapy or combination therapy for peripheral nerve analgesia in diabetic patients. Conceivably, future translational research regarding peripheral nerve blocks in diabetic patients may logically include study of nontoxic injectable analgesic adjuvants, in combination, to provide desired analgesia, while possibly avoiding peripheral nerve toxicity that diabetic animal models have exhibited when exposed to traditional local anesthetics.

  2. Double injection/single detection asymmetric flow injection manifold for spectrophotometric determination of ascorbic acid and uric acid: Selection the optimal conditions by MCDM approach based on different criteria weighting methods

    Science.gov (United States)

    Boroumand, Samira; Chamjangali, Mansour Arab; Bagherian, Ghadamali

    2017-03-01

    A simple and sensitive double injection/single detector flow injection analysis (FIA) method is proposed for the simultaneous kinetic determination of ascorbic acid (AA) and uric acid (UA). This method is based upon the difference between the rates of the AA and UA reactions with Fe3 + in the presence of 1, 10-phenanthroline (phen). The absorbance of Fe2 +/1, 10-phenanthroline (Fe-phen) complex obtained as the product was measured spectrophotometrically at 510 nm. To reach a good accuracy in the differential kinetic determination via the mathematical manipulations of the transient signals, different criteria were considered in the selection of the optimum conditions. The multi criteria decision making (MCDM) approach was applied for the selection of the optimum conditions. The importance weights of the evaluation criteria were determined using the analytic hierarchy process, entropy method, and compromised weighting (CW). The experimental conditions (alternatives) were ranked by the technique for order preference by similarity to an ideal solution. Under the selected optimum conditions, the obtained analytical signals were linear in the ranges of 0.50-5.00 and 0.50-4.00 mg L- 1 for AA and UA, respectively. The 3σ detection limits were 0.07 mg L- 1 for AA and 0.12 mg L- 1 for UA. The relative standard deviations for four replicate determinations of AA and UA were 2.03% and 3.30% respectively. The method was also applied for the analysis of analytes in the blood serum, Vitamine C tablets, and tap water with satisfactory results.

  3. Intra-Articular, Single-Shot Hylan G-F 20 Hyaluronic Acid Injection Compared with Corticosteroid in Knee Osteoarthritis: A Double-Blind, Randomized Controlled Trial.

    Science.gov (United States)

    Tammachote, Nattapol; Kanitnate, Supakit; Yakumpor, Thanasak; Panichkul, Phonthakorn

    2016-06-01

    The treatment of knee osteoarthritis with hyaluronic acid or corticosteroid injection has been widely used. The purpose of this study was to compare the efficacy of hyaluronic acid (hylan G-F 20) with triamcinolone acetonide as a single intra-articular injection for knee osteoarthritis. This study was a prospective, randomized, double-blind clinical trial. Participants with symptomatic knee osteoarthritis were recruited. They were randomized to receive a single-shot, intra-articular injection of either 6 mL of hylan G-F 20 or 6 mL of a solution comprising 1 mL of 40-mg triamcinolone acetonide and 5 mL of 1% lidocaine with epinephrine. The primary outcomes were knee pain severity, knee function, and range of motion at 6 months. Ninety-nine patients were assessed before injection and underwent a 6-month follow-up. Patients and evaluators were blinded. Multilevel regression models were used to estimate differences between the groups. At the 6-month follow-up, compared with patients who took hylan G-F 20, patients who took triamcinolone acetonide had similar improvement in knee pain, knee function, and range of motion. The difference in mean outcome scores between groups was, with regard to knee pain, a visual analog scale (VAS) score of 3 points (95% confidence interval [95% CI], -6 to 11 points); with regard to knee function, a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of 0 points (95% CI, -8 to 6 points); and, with regard to range of motion, flexion of -1° (95% CI, -5° to 2°) and extension of 0° (95% CI, -0.5° to 0.5°). However, patients who took triamcinolone acetonide had better pain improvement from 24 hours until 1 week after injection; the mean difference between groups with regard to the VAS score was 12 points (95% CI, 5 to 20 points; p = 0.002) at 24 hours and 9 points (95% CI, 1 to 15 points; p = 0.018) at 1 week. At 2 weeks after injection, patients who took triamcinolone acetonide also had better knee

  4. Spray and atomization of diesel fuel and its alternatives from a single-hole injector using a common rail fuel injection system

    KAUST Repository

    Chen, PinChia

    2013-01-01

    Fuel spray and atomization characteristics play an important role in the performance of internal combustion engines. As the reserves of petroleum fuel are expected to be depleted within a few decades, finding alternative fuels that are economically viable and sustainable to replace the petroleum fuel has attracted much research attention. In this work, the spray and atomization characteristics were investigated for commercial No. 2 diesel fuel, biodiesel (FAME) derived from waste cooking oil (B100), 20% biodiesel blended diesel fuel (B20), renewable diesel fuel produced in house, and civil aircraft jet fuel (Jet-A). Droplet diameters and particle size distributions were measured by a laser diffraction particle analyzing system and the spray tip penetrations and cone angles were acquired using a high speed imaging technique. All experiments were conducted by employing a common-rail high-pressure fuel injection system with a single-hole nozzle under room temperature and pressure. The experimental results showed that biodiesel and jet fuel had different features compared with diesel. Longer spray tip penetration and larger droplet diameters were observed for B100. The smaller droplet size of the Jet-A were believed to be caused by its relatively lower viscosity and surface tension. B20 showed similar characteristics to diesel but with slightly larger droplet sizes and shorter tip penetration. Renewable diesel fuel showed closer droplet size and spray penetration to Jet-A with both smaller than diesel. As a result, optimizing the trade-off between spray volume and droplet size for different fuels remains a great challenge. However, high-pressure injection helps to optimize the trade-off of spray volume and droplet sizes. Furthermore, it was observed that the smallest droplets were within a region near the injector nozzle tip and grew larger along the axial and radial direction. The variation of droplet diameters became smaller with increasing injection pressure.

  5. Cell turnover in the odontogenic organ of the rat incisor as visualized by graphic reconstructions following a single injection of 3H-thymidine.

    Science.gov (United States)

    Smith, C E

    1980-07-01

    Turnover of cells within the odontogenic organ was studied in three dimensions by preparing serial sections of incisors from young male rats killed at various times following a single intraperitoneal injection of 1 muCi/g body weight of 3H-thymidine. Radioautographs showed that at 1 hour after injection labeled cells were present in all cell layers throughout the entire depth of the odontogenic organ. They were encountered frequently within the inner dental epithelium and stratum intermedium but appeared less abundant within the stellate reticulum and outer dental epithelium. With time, the frequency of labeled cells in each layer declined progressively, and more rapidly at the anterior and labial side of the odontogenic organ than toward its posterior and lingual side. Hence labeled cells were observed over the longest time interval in regions where cell layers were in closest proximity to the opening of the apical foramen, that is, near the apical and cervical loops. By 32 days after injection, numerous labeled cells could still be identified within the outer dental epithelium and stellate reticulum near the apical loop (bulbous part of the odontogenic organ) and the outer dental epithelium near the cervical loops ("U"-shaped part of the odontogenic organ). These findings support the hypothesis that cells originate within the bulbous part of the odontogenic organ and migrate anteriorly through the "U"-shaped and root sheath parts of the odontogenic organ during renewal of the incisor. It appears that individual stem cell compartments may be maintained for surface (outer/inner dental epithelium) and intermediate layers (stellate reticulum/stratum intermedium) in the odontogenic epithelium.

  6. Detection of active alveolar bone destruction in human periodontal disease by analysis of radiopharmaceutical uptake after a single injection of 99m-Tc-methylene diphosphonate

    International Nuclear Information System (INIS)

    Jeffcoat, M.K.; Williams, R.C.; Holman, B.L.; English, R.; Goldhaber, P.

    1986-01-01

    Previous studies have shown that, following a single injection of 99m-Tc-MDP, measurement of bone-seeking radiopharmaceutical uptake can detect ''active'' alveolar bone loss due to periodontal disease in beagle dogs, as determined by radiographs taken at the time of, and several months after, the nuclear medicine procedure. The efficacy of this diagnostic test, however, had not been assessed in human periodontal disease. The ability of a single boneseeking radiopharmaceutical uptake examination to detect ''active'' alveolar bone loss due to periodontal disease in human patients was assessed by comparing a single uptake measurement to the rate of bone loss determined from serial radiographs taken over a 6-month period. Uptake was expressed as a ratio of the cpm from the alveolar bone divided by the cpm from the non-tooth supporting bone of the nuchal crest. High uptake ratios were associated with ''active'' loss and low uptake ratios were associated with little if any change in alveolar bone height (p<0.001). The nuclear medicine examination was an accurate detector of periodontal disease activity in nearly 80% of the individual teeth studied. These data indicate that high bone-seeking radiopharmaceutical uptake ratios may be pathognomonic of active bone loss in human periodontal disease. (author)

  7. CT-guided single high-dose percutaneous acetic acid injection for small hepatocellular carcinoma: A long-term follow-up study

    International Nuclear Information System (INIS)

    Ma Heng; Liu Jing; Liu Fengli

    2012-01-01

    Objective: To evaluate the long-term outcome of CT-guided single high-dose percutaneous acetic acid injection (PAI) for the treatment of small hepatocellular carcinoma (SHCC). Materials and methods: Sixty-eight consecutive patients (37 men and 31 women; age 52 ± 16 years) with SHCC have undergone CT-guided single high-dose PAI therapy since December 2000. Complications of high-dose PAI were recorded. Tumour survival and recurrence rates were assessed. Results: All PAI therapies were successful and no severe complications developed. The average follow-up period was 46 ± 18 months. The overall survival rates at 1, 2, 3, 4 and 5 years were 93%, 82%, 68%, 59% and 51%, respectively. The cumulative local recurrence rates for the main tumour at 1, 2, 3, 4 and 5 years were 18%, 22%, 25%, 28% and 28%, respectively. The cumulative new tumour recurrence rates at 1, 2, 3, 4 and 5 years were 24%, 40%, 43%, 60% and 62%, respectively. Conclusion: CT-guided single high-dose PAI is safe and effective for the treatment of SHCC after long-term follow-up.

  8. The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model.

    Science.gov (United States)

    Jeon, Min Jeong; Ahn, Cheol-Hee; Kim, Hyeonjin; Chung, In Jae; Jung, Seulhee; Kim, Young-Hwa; Youn, Hyewon; Chung, Jin Wook; Kim, Young Il

    2014-07-18

    Local hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model. HCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7-8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured. The rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively. The intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model.

  9. Development of on-line single-drop micro-extraction sequential injection system for electrothermal atomic absorption spectrometric determination of trace metals

    International Nuclear Information System (INIS)

    Anthemidis, Aristidis N.; Adam, Ibrahim S.I.

    2009-01-01

    A novel automatic sequential injection (SI) single-drop micro-extraction (SDME) system is proposed as versatile approach for on-line metal preconcentration and/or separation. Coupled to electrothermal atomic absorption spectrometry (ETAAS) the potentials of this SI scheme are demonstrated for trace cadmium determination in water samples. A non-charged complex of cadmium with ammonium diethyldithiophosphate (DDPA) was produced and extracted on-line into a 60 μL micro-drop of di-isobutyl ketone (DIBK). The extraction procedure was performed into a newly designed flow-through extraction cell coupled on a sequential injection manifold. As the complex Cd(II)-DDPA flowed continuously around the micro-droplet, the analyte was extracting into the solvent micro-drop. All the critical parameters were optimized and offered good performance characteristics and high preconcentration ratios. For 600 s micro-extraction time, the enhancement factor was 10 and the sampling frequency was 6 h -1 . The detection limit was 0.01 μg L -1 and the precision (RSD at 0.1 μg L -1 of cadmium) was 3.9%. The proposed method was evaluated by analyzing certified reference material

  10. Cyano-substituted oligo(p-phenylene vinylene) single-crystal with balanced hole and electron injection and transport for ambipolar field-effect transistors.

    Science.gov (United States)

    Deng, Jian; Tang, Jia; Xu, Yuanxiang; Liu, Liqun; Wang, Yan; Xie, Zengqi; Ma, Yuguang

    2015-02-07

    High and balanced hole and electron mobilities were achieved in OFETs based on the high photoluminescence of a 1,4-bis(2-cyano-2-phenylethenyl)benzene single-crystal with symmetric electrodes. For electron and hole, the operation voltage in the OFETs based on symmetric gold electrodes was 30 and -20 V, respectively. The accumulation threshold voltage is low enough for the OFETs to operate in an ambipolar model with the source/drain voltage (Vds) around 50 V despite the high injection barrier. The highest electron and hole mobility was 0.745 cm(2) V(-1) s(-1) and 0.239 cm(2) V(-1) s(-1), and the current density reached 90.7 and 27.4 A cm(-2), respectively with an assumed 10 nm accumulation layer. The high mobility comes from the strong π-π interactions. In addition, the highly ordered hydrogen bonding matrix may create an efficient route to pump the charge to the inner layer which can improve the injection ability.

  11. Immersed single-drop microextraction interfaced with sequential injection analysis for determination of Cr(VI) in natural waters by electrothermal-atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Pena, Francisco; Lavilla, Isela; Bendicho, Carlos

    2008-01-01

    Single-drop microextraction (SDME) and sequential injection analysis have been hyphenated for ultratrace metal determination by Electrothermal-Atomic Absorption Spectrometry (ETAAS). The novel method was targeted on extraction of the Cr(VI)-APDC chelate and encompasses the potential of SDME as a miniaturized and virtually solvent-free preconcentration technique, the ability of sequential injection analysis to handle samples and the versatility of furnace autosamplers for introducing microliter samples in ETAAS. The variables influencing the microextraction of Cr(VI) onto an organic solvent drop, i.e., type of organic solvent, microextraction time, stirring rate of the sample solution, drop volume, immersion depth of the drop, salting-out effect, temperature of the sample, concentration of the complexing agent and pH of the sample solution were fully investigated. For a 5 and 20 min microextraction time, the preconcentration factors were 20 and 70, respectively. The detection limit was 0.02 μg/L of Cr(VI) and the repeatability expressed as relative standard deviation was 7%. The SDME-SIA-ETAAS technique was validated against BCR CRM 544 (lyophilized solution) and applied to ultrasensitive determination of Cr(VI) in natural waters

  12. Effects of local microwave diathermy on shoulder pain and function in patients with rotator cuff tendinopathy in comparison to subacromial corticosteroid injections: a single-blind randomized trial.

    Science.gov (United States)

    Rabini, Alessia; Piazzini, Diana B; Bertolini, Carlo; Deriu, Laura; Saccomanno, Maristella F; Santagada, Domenico A; Sgadari, Antonio; Bernabei, Roberto; Fabbriciani, Carlo; Marzetti, Emanuele; Milano, Giuseppe

    2012-04-01

    Single-blind randomized clinical trial, with a follow-up of 24 weeks. To determine the effects of hyperthermia via localized microwave diathermy on pain and disability in comparison to subacromial corticosteroid injections in patients with rotator cuff tendinopathy. Hyperthermia improves symptoms and function in several painful musculoskeletal disorders. However, the effects of microwave diathermy in rotator cuff tendinopathy have not yet been established. Ninety-two patients with rotator cuff tendinopathy and pain lasting for at least 3 months were recruited from the outpatient clinic of the Department of Orthopaedics and Traumatology, University Hospital, Rome, Italy. Participants were randomly allocated to either local microwave diathermy or subacromial corticosteroids. The primary outcome measure was the short form of the Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH). Secondary outcome measures were the Constant-Murley shoulder outcome score and a visual analog scale for pain assessment. At the end of treatment and at follow-up, both treatment groups experienced improvements in all outcome measures relative to baseline values. Changes over time in QuickDASH, Constant-Murley, and visual analog scale scores were not different between treatment arms. In patients with rotator cuff tendinopathy, the effects of localized microwave diathermy on disability, shoulder function, and pain are equivalent to those elicited by subacromial corticosteroid injections.

  13. Whole genome sequence analysis suggests intratumoral heterogeneity in dissemination of breast cancer to lymph nodes.

    Directory of Open Access Journals (Sweden)

    Kevin Blighe

    Full Text Available Intratumoral heterogeneity may help drive resistance to targeted therapies in cancer. In breast cancer, the presence of nodal metastases is a key indicator of poorer overall survival. The aim of this study was to identify somatic genetic alterations in early dissemination of breast cancer by whole genome next generation sequencing (NGS of a primary breast tumor, a matched locally-involved axillary lymph node and healthy normal DNA from blood.Whole genome NGS was performed on 12 µg (range 11.1-13.3 µg of DNA isolated from fresh-frozen primary breast tumor, axillary lymph node and peripheral blood following the DNA nanoball sequencing protocol. Single nucleotide variants, insertions, deletions, and substitutions were identified through a bioinformatic pipeline and compared to CIN25, a key set of genes associated with tumor metastasis.Whole genome sequencing revealed overlapping variants between the tumor and node, but also variants that were unique to each. Novel mutations unique to the node included those found in two CIN25 targets, TGIF2 and CCNB2, which are related to transcription cyclin activity and chromosomal stability, respectively, and a unique frameshift in PDS5B, which is required for accurate sister chromatid segregation during cell division. We also identified dominant clonal variants that progressed from tumor to node, including SNVs in TP53 and ARAP3, which mediates rearrangements to the cytoskeleton and cell shape, and an insertion in TOP2A, the expression of which is significantly associated with tumor proliferation and can segregate breast cancers by outcome.This case study provides preliminary evidence that primary tumor and early nodal metastasis have largely overlapping somatic genetic alterations. There were very few mutations unique to the involved node. However, significant conclusions regarding early dissemination needs analysis of a larger number of patient samples.

  14. Concentration-dependent optical properties of TGA stabilized CdTe Quantum dots synthesized via the single injection hydrothermal method in the ambient environment

    Science.gov (United States)

    Jai Kumar, B.; Mahesh, H. M.

    2017-04-01

    Thioglycolic acid (TGA) stabilized aqueous CdTe Quantum dots (QDs) were synthesized using a facile, cost efficient Single Injection Hydrothermal (SIH) method. The complete preparation of precursors and growth of QDs was carried out in the ambient environment without inter gas protection. The Cadmium and Tellurium precursors were prepared from cadmium nitrate and elemental tellurium powder with sodium borohydride as reducing agent respectively. A systematic investigation was carried out in order to study the effect of 0.04M and 0.08M TGA concentration on ease synthesis, stability and size-tunable optical absorbance, bandgap, photoluminescence (PL) and Quantum yield (QY) of CdTe QDs. The Structure of QDs was verified by XRD and optical properties by absorbance and PL spectra. Experimental results revealed that the 0.08M TGA QDs possess good chemical and optical stability with high luminescence and decent QY, ready to use in optoelectronics, photovoltaic and biological application.

  15. Assessment of infection control practices for interventional techniques: a best evidence synthesis of safe injection practices and use of single-dose medication vials.

    Science.gov (United States)

    Manchikanti, Laxmaiah; Falco, Frank J E; Benyamin, Ramsin M; Caraway, David L; Helm Ii, Standiford; Wargo, Bradley W; Hansen, Hans; Parr, Allan T; Singh, Vijay; Hirsch, Joshua A

    2012-01-01

    It is universally accepted that transmission of bloodborne pathogens during health care procedures continues to occur because of the use of unsafe and improper injection, infusion, and medication administration practices by health care professionals in various clinical settings. This resulted in development of multiple guidelines based on case reports; however, these case reports are confounded by multiple factors without causal relationship to a single factor. Even then, single-dose vials used for multiple patients have been singled out and became the focus of infection control policies resulting in inordinate expenses for practices without improving patient safety. The cost of implementation of single dose vial policy in interventional pain management for drugs alone may cost $750 million, whereas with single use radional gloves may exceed $1 billion per year. Best evidence synthesis. To critically appraise and synthesize the literature on infection control practices for interventional techniques, including safe injection and medication vial utilization. The available literature on infection control practices was reviewed. Due to the nature of the studies involved, with the majority being case reports, and a few prospective evaluations, quality assessment and clinical relevance criteria were not applied. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 through June 2012, literature from the Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration (FDA), and manual searches of the bibliographies of known primary and review articles. The primary outcome measure was correlating infection to a breach of standards in infection control practices. The secondary objective was to assess the contribution of single-dose vials independently for infection. A total of 60 reports met inclusion criteria, with 16 reports related to pain management and other procedures, of which 9 reports were

  16. An Experimental Investigation of Self-Excited Combustion Dynamics in a Single Element Lean Direct Injection (LDI) Combustor

    Science.gov (United States)

    Gejji, Rohan M.

    The management of combustion dynamics in gas turbine combustors has become more challenging as strict NOx/CO emission standards have led to engine operation in a narrow, lean regime. While premixed or partially premixed combustor configurations such as the Lean Premixed Pre-vaporized (LPP), Rich Quench Lean burn (RQL), and Lean Direct Injection (LDI) have shown a potential for reduced NOx emissions, they promote a coupling between acoustics, hydrodynamics and combustion that can lead to combustion instabilities. These couplings can be quite complex, and their detailed understanding is a pre-requisite to any engine development program and for the development of predictive capability for combustion instabilities through high-fidelity models. The overarching goal of this project is to assess the capability of high-fidelity simulation to predict combustion dynamics in low-emissions gas turbine combustors. A prototypical lean-direct-inject combustor was designed in a modular configuration so that a suitable geometry could be found by test. The combustor comprised a variable length air plenum and combustion chamber, air swirler, and fuel nozzle located inside a subsonic venturi. The venturi cross section and the fuel nozzle were consistent with previous studies. Test pressure was 1 MPa and variables included geometry and acoustic resonance, inlet temperatures, equivalence ratio, and type of liquid fuel. High-frequency pressure measurements in a well-instrumented metal chamber yielded frequencies and mode shapes as a function of inlet air temperature, equivalence ratio, fuel nozzle placement, and combustor acoustic resonances. The parametric survey was a significant effort, with over 105 tests on eight geometric configurations. A good dataset was obtained that could be used for both operating-point-dependent quantitative comparisons, and testing the ability of the simulation to predict more global trends. Results showed a very strong dependence of instability amplitude on

  17. A single intraperitoneal injection of bovine fetuin-A attenuates bone resorption in a murine calvarial model of particle-induced osteolysis.

    Science.gov (United States)

    Jablonski, Heidrun; Polan, Christina; Wedemeyer, Christian; Hilken, Gero; Schlepper, Rüdiger; Bachmann, Hagen Sjard; Grabellus, Florian; Dudda, Marcel; Jäger, Marcus; Kauther, Max Daniel

    2017-12-01

    Particle-induced osteolysis, which by definition is an aseptic inflammatory reaction to implant-derived wear debris eventually leading to local bone destruction, remains the major reason for long-term failure of orthopedic endoprostheses. Fetuin-A, a 66kDa glycoprotein with diverse functions, is found to be enriched in bone. Besides being an important inhibitor of ectopic calcification, it has been described to influence the production of mediators of inflammation. Furthermore, a regulatory role in bone metabolism has been assigned. In the present study, the influence of a single dose of bovine fetuin-A, intraperitoneally injected in mice subjected to particle-induced osteolysis of the calvaria, was analyzed. Twenty-eight male C57BL/6 mice, twelve weeks of age, were randomly divided into four groups. Groups 2 and 4 were subjected to ultra-high molecular weight polyethylene (UHMWPE) particles placed on their calvariae while groups 1 and 3 were sham-operated. Furthermore, groups 3 and 4 received a single intraperitoneal injection of 20mg bovine fetuin-A while groups 1 and 2 were treated with physiologic saline. After 14days calvarial bone was qualitatively and quantitatively assessed using microcomputed tomography (μCT) and histomorphometrical approaches. Application of fetuin-A led to a reduction of particle-induced osteolysis in terms of visible osteolytic lesions and eroded bone surface. The reduction of bone thickness and bone volume, as elicited by UHMWPE, was alleviated by fetuin-A. In conclusion, fetuin-A was found to exert an anti-resorptive effect on particle-induced osteolysis in-vivo. Thus, fetuin-A could play a potentially osteoprotective role in the treatment of bone metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. REDUCTION OF INTRATUMORAL PH BY THE MITOCHONDRIAL INHIBITOR M-IODOBENZYLGUANIDINE AND MODERATE HYPERGLYCEMIA

    NARCIS (Netherlands)

    KUIN, A; SMETS, L; VOLK, T; PAANS, A; ADAMS, G; ATEMA, A; JAHDE, E; MAAS, A; RAJEWSKY, MF; VISSER, G; WOOD, P

    1994-01-01

    The interstitial pH of RIF-1 tumors was selectively lowered by i.p. administration of the mitochondrial inhibitor meta-iodobenzylguanidine (MIBG; 40-100 mg/kg), supported by sustained moderate hyperglycemia (plasma glucose concentration, 14 mM) in rats or by a single i.p. bolus injection of glucose

  19. Testosterone Injection

    Science.gov (United States)

    ... typical male characteristics. Testosterone injection works by supplying synthetic testosterone to replace the testosterone that is normally ... as a pellet to be injected under the skin.Testosterone injection may control your symptoms but will ...

  20. Pathological Bases and Clinical Impact of Intratumor Heterogeneity in Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    López, José I; Angulo, Javier C

    2018-01-27

    Intratumor heterogeneity is an inherent event in tumor development that is receiving much attention in the last years since it is responsible for most failures of current targeted therapies. The purpose of this review is to offer clinicians an updated insight of the multiple manifestations of a complex event that impacts significantly patient's life. Clear cell renal cell carcinoma is the most common renal tumor and a paradigmatic example of a heterogeneous neoplasm. Next-generation sequencing has demonstrated that intratumor heterogeneity encompasses genetic, epigenetic, and microenvironmental variability. Currently accepted protocols of tumor sampling seem insufficient in unveiling intratumor heterogeneity with reliability and need to be updated. This variability challenges the precise morphological diagnosis, its molecular characterization, and the selection of optimal personalized therapies in clear cell renal cell carcinoma, a neoplasm traditionally considered chemo- and radio-resistant. We review the state of the art of the different approaches to intratumor heterogeneity in clear cell renal cell carcinomas, from the simple morphology to the most sophisticated massive sequencing tools.

  1. Uveal Melanoma with Histopathologic Intratumoral Heterogeneity Associated with Gene Expression Profile Discordance.

    Science.gov (United States)

    Miller, Audra K; Benage, Matthew J; Wilson, David J; Skalet, Alison H

    2017-07-01

    To report a case of intratumoral gene expression profile discordance in a malignant uveal melanoma, associated with intratumoral heterogeneity based upon histopathologic features. The clinical history, fundus findings, imaging and histopathologic features, and DecisionDx-UM gene expression profile results (Castle Biosciences, Inc., Phoenix, AZ, USA) of the tumor were reviewed. A trans-retinal fine-needle aspiration biopsy was performed for a thin, pigmented choroidal tumor in a 33-year-old man. Cells obtained from this biopsy were tested using the DecisionDx-UM gene expression profile test and the tumor was classified as class 1A. Cytology confirmed melanoma. The patient subsequently elected to undergo enucleation. On microscopic examination of the globe, the tumor was composed primarily of spindle B cells, but had a focal area composed of epithelioid cells. This portion of the tumor was subsequently tested and demonstrated a class 1B gene expression profile. Intratumoral discordance in gene expression profile results has been described in uveal melanomas. Here we demonstrate that this discordance may be associated in some cases with intratumoral heterogeneity based upon histopathologic features.

  2. Two-Step Delivery: Exploiting the Partition Coefficient Concept to Increase Intratumoral Paclitaxel Concentrations In vivo Using Responsive Nanoparticles

    Science.gov (United States)

    Colby, Aaron H.; Liu, Rong; Schulz, Morgan D.; Padera, Robert F.; Colson, Yolonda L.; Grinstaff, Mark W.

    2016-01-01

    Drug dose, high local target tissue concentration, and prolonged duration of exposure are essential criteria in achieving optimal drug performance. However, systemically delivered drugs often fail to effectively address these factors with only fractions of the injected dose reaching the target tissue. This is especially evident in the treatment of peritoneal cancers, including mesothelioma, ovarian, and pancreatic cancer, which regularly employ regimens of intravenous and/or intraperitoneal chemotherapy (e.g., gemcitabine, cisplatin, pemetrexed, and paclitaxel) with limited results. Here, we show that a “two-step” nanoparticle (NP) delivery system may address this limitation. This two-step approach involves the separate administration of NP and drug where, first, the NP localizes to tumor. Second, subsequent administration of drug then rapidly concentrates into the NP already stationed within the target tissue. This two-step method results in a greater than 5-fold increase in intratumoral drug concentrations compared to conventional “drug-alone” administration. These results suggest that this unique two-step delivery may provide a novel method for increasing drug concentrations in target tissues.

  3. Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.

    Science.gov (United States)

    Karthik, Govindasamy-Muralidharan; Rantalainen, Mattias; Stålhammar, Gustav; Lövrot, John; Ullah, Ikram; Alkodsi, Amjad; Ma, Ran; Wedlund, Lena; Lindberg, Johan; Frisell, Jan; Bergh, Jonas; Hartman, Johan

    2017-11-29

    Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics. In this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications. Molecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications. Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.

  4. Intratumoral interleukin-21 increases antitumor immunity, tumor-infiltrating CD8+ T-cell density and activity, and enlarges draining lymph nodes

    DEFF Research Database (Denmark)

    Søndergaard, Henrik; Galsgaard, Elisabeth D; Bartholomaeussen, Monica

    2010-01-01

    Interleukin (IL)-21 is a novel cytokine in clinical development for the treatment of cancer. In this study, we have compared the efficacy of subcutaneous and intratumoral (IT) administration of IL-21 protein in two syngeneic mouse tumor models, RenCa renal cell carcinoma and B16 melanoma......, and investigated the mechanisms by which IL-21 enhances CD8 T-cell-mediated antitumor immunity. We found that in comparison to subcutaneous administration, IT administration of IL-21 more potently inhibited tumor growth and increased survival. This correlated with increased densities of tumor-infiltrating CD8...... and CD4CD25 T cells, but not CD4CD25FoxP3 T cells. Furthermore, IT administration of IL-21 increased degranulation, and expression of interferon-gamma and granzyme B in tumor-infiltrating CD8 T cells. Tumors injected with IL-21 grew slower than contralateral tumors, suggesting that the increased efficacy...

  5. Intratumoral Interleukin-21 Increases Antitumor Immunity, Tumor-infiltrating CD8(+) T-cell Density and Activity, and Enlarges Draining Lymph Nodes

    DEFF Research Database (Denmark)

    Sondergaard, H.; Galsgaard, E.D.; Bartholomaeussen, M.

    2010-01-01

    Interleukin (IL)-21 is a novel cytokine in clinical development for the treatment of cancer. In this study, we have compared the efficacy of subcutaneous and intratumoral (IT) administration of IL-21 protein in two syngeneic mouse tumor models, RenCa renal cell carcinoma and B16 melanoma......, and investigated the mechanisms by which IL-21 enhances CD8(+) T-cell-mediated antitumor immunity. We found that in comparison to subcutaneous administration, IT administration of IL-21 more potently inhibited tumor growth and increased survival. This correlated with increased densities of tumor-infiltrating CD8......(+) and CD4(+) CD25(-) T cells, but not CD4(+) CD25(+) FoxP3(+) T cells. Furthermore, IT administration of IL-21 increased degranulation, and expression of interferon-gamma and granzyme B in tumor-infiltrating CD8(+) T cells. Tumors injected with IL-21 grew slower than contralateral tumors, suggesting...

  6. Comparison of clinical applications of single-dose intravenous injection of mivacurium and cisatracurium in adults’ vocalcordpolyps resection under self-retaining laryngoscope

    Directory of Open Access Journals (Sweden)

    Han Fanglei

    2017-01-01

    Full Text Available Objective: Through comparing the clinical observation of mivacurium and cisatracurium in vocal polyp extraction, to study the advantage of mivacurium in vocal polyp extraction. Methods: Forty American Society of Anesthesiologists(ASA physical status I~II patients for vocal polyp extraction, aged 18~60 years old, were randomly divided into two groups as Mivacurium injection group(Group M and Cis-atracurium injection group(Group C, each group includes 20 subjects. None of the patients are allergic, has serious diseases of cardiovascular system, liver or kidney.None of them has asthma, airway high response, difficult airway or neuromuscular diseases.Those patients who use beta-blockers or calcium channel blockers for a long time were excluded .All the subjects had the same premedication, fasting and fluid fobidden time. All the subjects who get into the operating room get the routine monitoring of electrocardiogram(EEG, blood pressure(BP, heart rate(HR, pulse oxygen saturation(SpO2 and the TOF WATCH SX. Each group gives the same medicine other than the muscle relaxant during induction of general anesthesia to do the vocal polyp extraction by the same experienced operator. Two groups were recorded in each index of anesthesia induction and tracheal intubation conditions, operation conditions, anesthesia, muscle relaxation monitoring. Results: There are no statistically significant in Cormack-Lehane grading system,Cooper’s grading system and operation satifaction(p>0.05. 2. Group A have shorter intubation time than Group B(p0.05. Conclusion: 1. A single intubating dose of mivacurium can provide similar intubation and surgeon satisfaction for the vocal polyp extraction. 2. Compared with cis-atracurium, mivacurium can shorten the intubation time and the recovery time of anesthesia. The adverse reactions of mivacurium is mild, and it has less Residual muscle relaxation. Therefore mivacurium is more suitable for the vocal polyp extraction than cis-atracurium.

  7. A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-α and IL-18

    Directory of Open Access Journals (Sweden)

    Bossù Paola

    2012-05-01

    Full Text Available Abstract Background Systemic inflammation might cause neuronal damage and sustain neurodegenerative diseases and behavior impairment, with the participation of pro-inflammatory cytokines, like tumor necrosis factor (TNF-α and interleukin (IL-18. However, the potential contribution of these cytokines to behavioral impairment in the long-term period has not been fully investigated. Methods Wistar rats were treated with a single intraperitoneal injection of LPS (5 mg/kg or vehicle. After 7 days and 10 months, the animal behavior was evaluated by testing specific cognitive functions, as mnesic, discriminative, and attentional functions, as well as anxiety levels. Contextually, TNF-α and IL-18 protein levels were measured by ELISA in defined brain regions (that is, frontal cortex, hippocampus, striatum, cerebellum, and hypothalamus. Results Behavioral testing demonstrated a specific and persistent cognitive impairment characterized by marked deficits in reacting to environment modifications, possibly linked to reduced motivational or attentional deficits. Concomitantly, LPS induced a TNF-α increase in the hippocampus and frontal cortex (from 7 days onward and cerebellum (only at 10 months. Interestingly, LPS treatment enhanced IL-18 expression in these same areas only at 10 months after injection. Conclusions Overall, these results indicate that the chronic neuroinflammatory network elicited by systemic inflammation involves a persistent participation of TNF-α accompanied by a differently regulated contribution of IL-18. This leads to speculation that, though with still unclear mechanisms, both cytokines might take part in long-lasting modifications of brain functions, including behavioral alteration.

  8. Single Event Analysis and Fault Injection Techniques Targeting Complex Designs Implemented in Xilinx-Virtex Family Field Programmable Gate Array (FPGA) Devices

    Science.gov (United States)

    Berg, Melanie D.; LaBel, Kenneth; Kim, Hak

    2014-01-01

    An informative session regarding SRAM FPGA basics. Presenting a framework for fault injection techniques applied to Xilinx Field Programmable Gate Arrays (FPGAs). Introduce an overlooked time component that illustrates fault injection is impractical for most real designs as a stand-alone characterization tool. Demonstrate procedures that benefit from fault injection error analysis.

  9. Pharmacokinetic properties and safety profile of histamine dihydrochloride injection in Chinese healthy volunteers: a phase I, single-center, open-label, randomized study.

    Science.gov (United States)

    Li, Jiapeng; Huang, Xiaojun; Wang, Qian; Jing, Shan; Jiang, Hao; Wei, Zhongna; Zang, Yannan; Liu, Yang; Zhao, Libo; Fang, Yi; Feng, Wanyu

    2015-10-01

    Histamine dihydrochloride (HDC) injection has been approved in Europe for the treatment of adults with acute myeloid leukemia, used in combination therapy with the T-cell-derived cytokine interleukin-2. Despite years of clinical applications of HDC in Europe, no data are available on its tolerability and pharmacokinetic properties in Chinese patients. The objective of this study was to determine the safety profile and pharmacokinetic properties of HDC in Chinese healthy volunteers (HVs). In this Phase I, single-center, open-label, randomized study, 20 Chinese HVs were randomized to receive a single dose of 0.5 or 1.0 mg HDC via a 10-minute subcutaneous injection. Whole-blood and urine samples were collected at designated time points after dosing. Plasma and urine concentrations of histamine and metabolite N-methyl histamine were measured using a validated HPLC-MS/MS method. Pharmacokinetic parameters were estimated through noncompartmental procedures based on concentration-time data. Adverse events and evaluation of clinical laboratory tests were used to assess the safety profile. The pharmacokinetic profile for a single-dose of 1.0 mg HDC in Chinese HVs was compared with that in Western HVs. No severe adverse events occurred in this study, and the severity of all adverse events was grade I according to the Common Terminology Criteria for Adverse Events, version 4.0. For the pharmacokinetic parameters of histamine at the 0.5-mg and 1.0-mg dose levels, t½ was 0.50 and 1.02 hours; Tmax was 0.15 and 0.14 hours; mean Cmax was 26.59 and 71.01 nmol/L; AUC0-t was 8.35 and 20.43 nmol/h/L; AUC0-∞ was 9.61 and 22.69 nmol/h/L; accumulated amount excreted in urine within 24 hours was 125.93 and 145.52 nmol; and maximum urine excretion rates were 21.85 and 38.94 nmol/h, respectively. For N-methyl histamine at the 0.5-mg and 1.0-mg dose levels, t½ was 0.58 and 0.66 hours; Tmax was 0.28 and 0.26 hours; mean Cmax was 17.01 and 23.54 nmol/L; AUC0-t was 7.72 and 17.08 nmol

  10. Intra-tumoral Heterogeneity of KRAS and BRAF Mutation Status in Patients with Advanced Colorectal Cancer (aCRC and Cost-Effectiveness of Multiple Sample Testing

    Directory of Open Access Journals (Sweden)

    Susan D. Richman

    2011-01-01

    Full Text Available KRAS mutation status is established as a predictive biomarker of benefit from anti-EGFr therapies. Mutations are normally assessed using DNA extracted from one formalin-fixed, paraffin-embedded (FFPE tumor block. We assessed heterogeneity of KRAS and BRAF mutation status intra-tumorally (multiple blocks from the same primary tumor. We also investigated the utility and efficiency of genotyping a ‘DNA cocktail’ prepared from multiple blocks. We studied 68 consenting patients in two randomized clinical trials. DNA was extracted, from ≥2 primary tumor FFPE blocks per patient. DNA was genotyped by pyrosequencing for KRAS codons 12, 13 and 61 and BRAF codon 600. In patients with heterogeneous mutation status, DNA cocktails were prepared and genotyped. Among 69 primary tumors in 68 patients, 7 (10.1% showed intratumoral heterogeneity; 5 (7.2% at KRAS codons 12, 13 and 2 (2.9% at BRAF codon 600. In patients displaying heterogeneity, the relevant KRAS or BRAF mutation was also identified in ‘DNA cocktail’ samples when including DNA from mutant and wild-type blocks. Heterogeneity is uncommon but not insignificant. Testing DNA from a single block will wrongly assign wild-type status to 10% patients. Testing more than one block, or preferably preparation of a ‘DNA cocktail’ from two or more tumor blocks, improves mutation detection at minimal extra cost.

  11. Quantitative evaluation of oxygen metabolism in the intratumoral hypoxia: 18F-fluoromisonidazole and 15O-labelled gases inhalation PET.

    Science.gov (United States)

    Watabe, Tadashi; Kanai, Yasukazu; Ikeda, Hayato; Horitsugi, Genki; Matsunaga, Keiko; Kato, Hiroki; Isohashi, Kayako; Abe, Kohji; Shimosegawa, Eku; Hatazawa, Jun

    2017-12-01

    Intratumoral hypoxia is one of the resistant factors in radiotherapy and chemotherapy for cancer. Although it is detected by 18 F-fluoromisonidazole (FMISO) PET, the relationship between intratumoral hypoxia and oxygen metabolism has not been studied. The purpose of this study was to evaluate the intratumoral perfusion and oxygen metabolism in hypoxic regions using the rat xenograft model. Ten male Fischer rats with C6 glioma (body weight = 220 ± 15 g) were investigated with 18 F-FMISO PET and steady-state inhalation method of 15 O-labelled gases PET. The tumoral blood flow (TBF), tumoral metabolic rate of oxygen (TMRO 2 ), oxygen extraction fraction (OEF), and tumoral blood volume (TBV) were measured under artificial ventilation with 15 O-CO 2 , 15 O-O 2 , and 15 O-CO gases. Multiple volumes of interest (1-mm diameter sphere) were placed on the co-registered 18 F-FMISO (3 h post injection) and functional 15 O-labelled gases PET images. The TBF, TMRO 2 , OEF, and TBV values were compared among the three groups classified by the 18 F-FMISO uptake as follows: group Low (L), less than 1.0; group Medium (M), between 1.0 and 2.0; and group High (H), more than 2.0 in the 18 F-FMISO standardized uptake value (SUV). There were moderate negative correlations between 18 F-FMISO SUV and TBF (r = -0.56 and p < 0.01), and weak negative correlations between 18 F-FMISO SUV and TMRO 2 (r = -0.38 and p < 0.01) and 18 F-FMISO SUV and TBV (r = -0.38 and p < 0.01). Quantitative values were as follows: TBF, (L) 55 ± 30, (M) 32 ± 17, and (H) 30 ± 15 mL/100 mL/min; OEF, (L) 33 ± 14, (M) 36 ± 17, and (H) 41 ± 16%; TMRO 2 , (L) 2.8 ± 1.3, (M) 1.9 ± 1.0, and (H) 2.1 ± 1.1 mL/100 mL/min; and TBV, (L) 5.7 ± 2.1, (M) 4.3 ± 1.9, and (H) 3.9 ± 1.2 mL/100 mL, respectively. Intratumoral hypoxic regions (M and H) showed significantly lower TBF, TMRO 2 , and TBV values than non-hypoxic regions (L). OEF

  12. Intratumoral Delivery of Doxorubicin on Folate-Conjugated Graphene Oxide by In-Situ Forming Thermo-Sensitive Hydrogel for Breast Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yi Teng Fong

    2017-11-01

    Full Text Available By taking advantage of the pH-sensitive drug release property of graphene oxide (GO after intracellular uptake, we prepared folic acid (FA-conjugated GO (GOFA for targeted delivery of the chemotherapeutic drug doxorubicin (DOX. GOFA-DOX was further encapsulated in an injectable in-situ forming thermo-sensitive hyaluronic acid-chitosan-g-poly(N-isopropylacrylamide (HACPN hydrogel for intratumoral delivery of DOX. As the degradation time of HACPN could be extended up to 3 weeks, intratumoral delivery of GOFA-DOX/HACPN could provide controlled and targeted delivery of DOX through slow degradation HACPN and subsequent cellular uptake of released GOFA-DOX by tumor cells through interactions of GOFA with folate receptors on the tumor cell’s surface. GOFA nano-carrier and HACPN hydrogel were first characterized for the physico-chemical properties. The drug loading experiments indicated the best preparation condition of GOFA-DOX was by reacting 0.1 mg GOFA with 2 mg DOX. GOFA-DOX showed pH-responsive drug release with ~5 times more DOX released at pH 5.5 than at pH 7.4 while only limited DOX was released from GOFA-DOX/HACPN at pH 7.4. Intracellular uptake of GOFA by endocytosis and release of DOX from GOFA-DOX in vitro could be confirmed from transmission electron microscopic and confocal laser scanning microscopic analysis with MCF-7 breast cancer cells. The targeting effect of FA was revealed when intracellular uptake of GOFA was blocked by excess FA. This resulted in enhanced in vitro cytotoxicity as revealed from the lower half maximal inhibitory concentration (IC50 value of GOFA-DOX (7.3 μg/mL compared with that of DOX (32.5 μg/mL and GO-DOX (10 μg/mL. The flow cytometry analysis indicated higher apoptosis rates for cells treated with GOFA-DOX (30% compared with DOX (8% and GO-DOX (11%. Animal studies were carried out with subcutaneously implanted MCF-7 cells in BALB/c nude mice and subject to intratumoral administration of drugs. The relative

  13. Intratumoral Administration of Holmium-166 Acetylacetonate Microspheres : Antitumor Efficacy and Feasibility of Multimodality Imaging in Renal Cancer

    NARCIS (Netherlands)

    Bult, Wouter; Kroeze, Stephanie G. C.; Elschot, Mattijs; Seevinck, Peter R.; Beekman, Freek J.; de Jong, Hugo W. A. M.; Uges, Donald R. A.; Kosterink, Jos G. W.; Luijten, Peter R.; Hennink, Wim E.; Schip, Alfred D. van Het; Bosch, J. L. H. Ruud; Nijsen, J. Frank W.; Jans, Judith J. M.

    2013-01-01

    Purpose: The increasing incidence of small renal tumors in an aging population with comorbidities has stimulated the development of minimally invasive treatments. This study aimed to assess the efficacy and demonstrate feasibility of multimodality imaging of intratumoral administration of

  14. Intratumoral administration of Holmium-166 Acetylacetonate Microspheres : Antitumor efficacy and feasibility of multimodality imaging in renal cancer

    NARCIS (Netherlands)

    Bult, W.; Kroeze, S.G.C.; Elschot, M.; Seevinck, P.R.; Beekman, F.J.; De Jong, H.W.A.M.; Uges, D.R.A.; Kosterink, J.G.W.; Luijten, P.R.; Hennink, W.E.

    2013-01-01

    The increasing incidence of small renal tumors in an aging population with comorbidities has stimulated the development of minimally invasive treatments. This study aimed to assess the efficacy and demonstrate feasibility of multimodality imaging of intratumoral administration of holmium-166

  15. A single exposure to cocaine during development elicits regionally-selective changes in basal basic Fibroblast Growth Factor (FGF-2) gene expression and alters the trophic response to a second injection.

    Science.gov (United States)

    Giannotti, Giuseppe; Caffino, Lucia; Malpighi, Chiara; Melfi, Simona; Racagni, Giorgio; Fumagalli, Fabio

    2015-02-01

    During adolescence, the brain is maturing and more sensitive to drugs of abuse that can influence its developmental trajectory. Recently, attention has been focused on basic fibroblast growth factor (FGF-2) given that its administration early in life enhances the acquisition of cocaine self-administration and sensitization at adulthood (Turner et al. (Pharmacol Biochem Behav 92:100-4, 2009), Clinton et al. (Pharmacol Biochem Behav103:6-17, 2012)). Additionally, we found that abstinence from adolescent cocaine exposure long lastingly dysregulates FGF-2 transcription (Giannotti et al. (Psychopharmacology (Berl) 225:553-60, 2013 ). The objectives of the study are to evaluate if (1) a single injection of cocaine (20 mg/kg) at postnatal day 35 alters FGF-2 messenger RNA (mRNA) levels and (2) the first injection influences the trophic response to a second injection (10 mg/kg) provided 24 h or 7 days later. We found regional differences in the FGF-2 expression pattern as either the first or the second injection of cocaine by themselves upregulated FGF-2 mRNA in the medial prefrontal cortex and nucleus accumbens while downregulating it in the hippocampus. The first injection influences the trophic response of the second. Of note, 24 h after the first injection, accumbal and hippocampal FGF-2 changes produced by cocaine in saline-pretreated rats were prevented in cocaine-pretreated rats. Conversely, in the medial prefrontal cortex and hippocampus 7 days after the first injection, the cocaine-induced FGF-2 changes were modified by the subsequent exposure to the psychostimulant. These findings show that a single cocaine injection is sufficient to produce enduring changes in the adolescent brain and indicate that early cocaine priming alters the mechanisms regulating the trophic response in a brain region-specific fashion.

  16. A model of reaction field in gas-injected arc-in-water method to synthesize single-walled carbon nanohorns: Influence of water temperature

    International Nuclear Information System (INIS)

    Poonjarernsilp, Chantamanee; Sano, Noriaki; Tamon, Hajime; Charinpanitkul, Tawatchai

    2009-01-01

    The method to synthesize single-walled carbon nanohorns (SWCNHs) using gas-injected arc in water (GI-AIW) has been experimentally studied. GI-AIW is known as one of the cost-effective methods to obtain SWCNHs. It was revealed that the yield of SWCNHs significantly decreases with the increase in water temperature although the purity of SWCNHs is not dependent on the temperature change. Then the model of relevant reactions in the GI-AIW system was proposed by accounting the emission of carbon vapor, formation of SWCNHs, and diffusion of water vapor in three zones inside the cathode hole (arc plasma zone, quenching zone, and downstream zone). The side reaction between H 2 O and C produces H 2 gas and consumes a certain amount of carbon vapor, resulting in the hindered SWCNH formation. Moreover the observation of the optical spectra emitting from the arc plasma zone strongly supported that the H 2 generating reaction does not occur at arc plasma zone since N 2 flow can purge H 2 O out. The model proposed in this study can precisely explain the correlation between H 2 gas production and water temperature.

  17. Combined magnetic resonance imaging of deep venous thrombosis and pulmonary arteries after a single injection of a blood pool contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Hansch, Andreas; Neumann, Steffi; Baltzer, Pascal; Waginger, Matthias; Kaiser, Werner A.; Mentzel, Hans-Joachim [Friedrich-Schiller-University Jena, Institute of Diagnostic and Interventional Radiology, Jena (Germany); Betge, Stefan; Poehlmann, Gunther [Friedrich-Schiller-University Jena, Department of Internal Medicine I, Jena (Germany); Pfeil, Alexander; Wolf, Gunter [Friedrich-Schiller-University Jena, Department of Internal Medicine III, Jena (Germany); Boettcher, Joachim [SRH Klinikum Gera, Institute of Diagnostic and Interventional Radiology, Gera (Germany)

    2011-02-15

    Agreement rate between magnetic resonance imaging (MRI) and Doppler ultrasound (DUS) for the detection of deep vein thrombosis (DVT) in the lower extremities was attempted by using the intravascular MRI contrast agent gadofosveset trisodium. The potential of this method to detect pulmonary embolism (PE) was also evaluated. Forty-three consecutive inpatients with ultrasound-confirmed DVT but no clinical signs of PE were prospectively enrolled in this feasibility study. MRI was performed after a single injection of gadofosveset trisodium. The pulmonary arteries were imaged using a 3D Fast Low Angle Shot (FLASH) gradient recalled echo sequence. Additionally, pulmonary arteries, abdominal veins, pelvic and leg veins were imaged using a fat-suppressed 3D gradient echo Volume Interpolated Breath-hold Examination (VIBE FS). Gadofosveset trisodium-enhanced MRI detected more thrombi in the pelvic region, upper leg and lower leg than the initial DUS. In addition, PE was detected in 16 of the 43 DVT patients (37%). This study shows the feasibility of a combined protocol for the MRI diagnosis of DVT and PE using gadofosveset trisodium. This procedure is not only more sensitive in detecting DVT compared to standard DUS, but is also able to detect PE in asymptomatic patients. (orig.)

  18. Attenuation values of the intracranial arterial and venous vessels by bolus injection of various contrast agents. A study with a single-detector helical CT scanner

    International Nuclear Information System (INIS)

    Nagahata, Morio; Abe, Yoshinao; Ono, Shuichi; Yamaguchi, Hikaru; Miura, Hiroyuki; Ohata, Takashi; Tsushima, Fumiyasu; Morimoto, Kohei; Seino, Hiroko

    2007-01-01

    We evaluated the arteriovenous contrast on the source images of intracranial three-dimensional computed tomography (CT) angiography (3D-CTA) using a high-concentration (370 mgI/ml) contrast agent in comparison with intermediate-concentration (300 mgI/ml) contrast. With a fixed intravenous injection rate and scanning delay, 3D-CTA was performed using a single-detector helical CT scanner in 30 consecutive patients. We used 100 ml of iohexol 300 for 10 patients, 100 ml of iopamidol 300 for 10 patients, and 80 ml of iopamidol 370 for 10 patients. Attenuation values of the bilateral internal carotid arteries, bilateral middle cerebral arteries, basilar artery trunk, bilateral cavernous sinuses, bilateral basal veins, and Galenic vein were measured quantitatively on the axial CT angiographic source images. High-concentration contrast significantly increased the attenuation values of the intracranial arterial system without increasing the attenuation of the venous system. High-concentration contrast is helpful for obtaining valuable arteriovenous contrast on source images with intracranial 3D-CTA. (author)

  19. Pharmacokinetic/pharmacodynamic evaluation of marbofloxacin as a single injection for Pasteurellaceae respiratory infections in cattle using population pharmacokinetics and Monte Carlo simulations.

    Science.gov (United States)

    Paulin, A; Schneider, M; Dron, F; Woehrle, F

    2018-02-01

    Population pharmacokinetic of marbofloxacin was investigated with 52 plasma concentration-time profiles obtained after intramuscular administration of Forcyl® in cattle. Animal's status, pre-ruminant, ruminant, or dairy cow, was retained as a relevant covariate for clearance. Monte Carlo simulations were performed using a stratification by status, and 1000 virtual disposition curves were generated in each bovine subpopulation for the recommended dosage regimen of 10 mg/kg as a single injection. The probability of target attainment (PTA) of pharmacokinetic/pharmacodynamic (PK/PD) ratios associated with clinical efficacy and prevention of resistance was determined in each simulated subpopulation. The cumulative fraction of response (CFR) of animals achieving a PK/PD ratio predictive of positive clinical outcome was then calculated for the simulated dosage regimen, taking into account the minimum inhibitory concentration (MIC) distribution of Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni. When considering a ratio of AUC 0-24 hr /MIC (area under the curve/minimum inhibitory concentration) greater than 125 hr, CFRs ranging from 85% to 100% against the three Pasteurellaceae in each bovine subpopulation were achieved. The PTA of the PK/PD threshold reflecting the prevention of resistances was greater than 90% up to MPC (mutant prevention concentration) values of 1 μg/ml in pre-ruminants and ruminants and 0.5 μg/ml in dairy cows. © 2017 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  20. Psoriasis responds to intralesional injections of alefacept and may predict systemic response to intramuscular alefacept: interim results of a single-arm, open-label study.

    Science.gov (United States)

    Gattu, Shilpa; Busse, Kristine; Bhutani, Tina; Chiang, Charles; Nguyen, Thao; Becker, Emily; Koo, John Y M

    2012-04-01

    Alefacept is a remittive treatment for generalized psoriasis but is rarely used due to its erratic efficacy. To determine if psoriasis plaques will respond to intralesional alefacept and if this predicts a systemic response to intramuscular (IM) alefacept. We describe a 25-week, single-center, open-label study. Patients received weekly intralesional alefacept of increasing concentrations into target plaques for 3 weeks followed by IM injections for 12 weeks and concluded with an observation period of 9 weeks. The psoriasis area and severity index (PASI) was used to assess the efficacy of IM alefacept. Interim results are reported for the first seven patients enrolled. Two patients responded intralesionally to the most dilute 1:100 concentration of alefacept to sterile water and achieved a 59% and 100% improvement in PASI. Five patients did not respond intralesionally to the most dilute form of alefacept and none achieved PASI 75. Two of these five patients did not respond to any concentration and achieved a 26% and 38% improvement in PASI. Limitations to this study include a small sample size and being non-placebo-controlled. Alefacept is effective intralesionally and may predict a systemic response - challenging the concept that biologics must work systemically.

  1. The efficiency enhancement of single-layer solution-processed blue phosphorescent organic light emitting diodes by hole injection layer modification

    International Nuclear Information System (INIS)

    Yeoh, K H; Talik, N A; Whitcher, T J; Ng, C Y B; Woon, K L

    2014-01-01

    Poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) PEDOT : PSS is extensively used as a hole injection layer (HIL) in solution-processed organic light emitting diodes (OLEDs). The high work function of a HIL is crucial in improving OLED efficiency. The work function of PEDOT : PSS is usually around 5.1–5.3 eV. By adding perfluorinated ionomer (PFI), the work function of PEDOT : PSS has been reported to reach as high as 5.95 eV. We investigated the effects of PFI-modified PEDOT : PSS in a single-layer solution-processed blue phosphorescent OLED (PHOLED). We observed that high concentrations of a PFI in PEDOT : PSS has detrimental effects on the device efficiency due to the low conductivity of the PFI. Using this approach, blue PHOLEDs with efficiencies of 9.4 lm W −1 (18.2 cd A −1 ) and 7.9 lm W −1 (20.4 cd A −1 ) at 100 cd m −2 and 1000 cd m −2 , respectively, were demonstrated. (paper)

  2. Patient-rated suitability of a novel electronic device for self-injection of subcutaneous interferon beta-1a in relapsing multiple sclerosis: an international, single-arm, multicentre, Phase IIIb study.

    Science.gov (United States)

    Devonshire, Virginia; Arbizu, Txomin; Borre, Bjorn; Lang, Michael; Lugaresi, Alessandra; Singer, Barry; Verdun di Cantogno, Elisabetta; Cornelisse, Peter

    2010-04-30

    Multiple sclerosis (MS) currently requires long-term treatment with disease-modifying drugs, administered parenterally up to once daily. The need for regular self-injection can be a barrier to treatment for many patients. Autoinjectors can help patients overcome problems or concerns with self-injection and could, therefore, improve treatment adherence. This study was performed to assess the suitability of a new electronic device for the subcutaneous (sc) administration of interferon (IFN) beta-1a, 44 mcg three times weekly, for relapsing MS. In this Phase IIIb, multicentre, single-arm study, patients with relapsing MS who had been consistently self-injecting sc IFN beta-1a using an autoinjector for at least 6 weeks were taught to use the new device and self-administered treatment for 12 weeks thereafter. Patient-rated suitability of the device was assessed at the end of Week 12 using the Patient User Trial Questionnaire. Patient satisfaction with, and evaluation of, the injection process was assessed using the MS Treatment Concern Questionnaire. Trainers evaluated the device using the Trainer User Trial Questionnaire. At Week 12, 71.6% (73/102) of patients considered the device 'very suitable' or 'suitable' for self-injection; 92.2% (94/102) reported some degree of suitability and only 7.8% (8/102) found the device 'not at all suitable'. At Weeks 4, 8 and 12, most patients reported that injection preparation and clean-up, performing injections and ease of device use in the previous 4 weeks compared favourably with, or was equivalent to, their previous experience of self-injection. Injection-related pain, injection reactions and 'flu-like' symptoms remained stable over the 12 weeks. Each device feature was rated 'very useful' or 'useful' by at least 80% of patients. All trainers and 95.2% (99/104) of patients found device functions 'very easy' or 'easy' to use. Overall convenience was considered the most important benefit of the device. Most patients considered the

  3. Cefoxitin Injection

    Science.gov (United States)

    ... injection is used to treat infections caused by bacteria including pneumonia and other lower respiratory tract (lung) infections; and urinary tract, abdominal (stomach area), female reproductive organs, blood, ... by killing bacteria.Antibiotics such as cefoxitin injection will not work ...

  4. Golimumab Injection

    Science.gov (United States)

    ... damaged, and do not use an auto-injection device if the security seal is broken. Look through the viewing window on the prefilled syringe or auto-injection device. The liquid inside should be clear and colorless ...

  5. Doxycycline Injection

    Science.gov (United States)

    ... may have been exposed to anthrax in the air. Doxycycline injection is in a class of medications ... decrease the effectiveness of hormonal contraceptives (birth control pills, patches, rings, or injections). Talk to your doctor ...

  6. Abaloparatide Injection

    Science.gov (United States)

    ... injection may cause osteosarcoma (bone cancer) in laboratory rats. It is not known whether abaloparatide injection increases ... too have too much calcium in the blood, hyperparathyroidism (condition in which the body produces too much ...

  7. Paliperidone Injection

    Science.gov (United States)

    Paliperidone extended-release injections (Invega Sustenna, Invega Trinza) are used to treat schizophrenia (a mental illness that ... interest in life, and strong or inappropriate emotions). Paliperidone extended-release injection (Invega Sustenna) is also used ...

  8. Doripenem Injection

    Science.gov (United States)

    ... injection is in a class of medications called carbapenem antibiotics. It works by killing bacteria.Antibiotics such ... if you are allergic to doripenem injection; other carbapenem antibiotics such as imipenem/cilastatin (Primaxin) or meropenem ( ...

  9. Ceftriaxone Injection

    Science.gov (United States)

    Ceftriaxone injection is used to treat certain infections caused by bacteria such as gonorrhea (a sexually transmitted ... skin, urinary tract, blood, bones, joints, and abdomen. Ceftriaxone injection is also sometimes given before certain types ...

  10. Nalbuphine Injection

    Science.gov (United States)

    ... injection is in a class of medications called opioid agonist-antagonists. It works by changing the way ... suddenly stop using nalbuphine injection, you may experience withdrawal symptoms including restlessness; teary eyes; runny nose; yawning; ...

  11. Naltrexone Injection

    Science.gov (United States)

    ... Videos & Tools Español You Are Here: Home → Drugs, Herbs and Supplements → Naltrexone Injection URL of this page: ... become depressed and sometimes try to harm or kill themselves. Receiving naltrexone injection does not decrease the ...

  12. Comprehensive low-dose imaging of carotid and coronary arteries with a single-injection dual-source CT angiography protocol

    International Nuclear Information System (INIS)

    Tognolini, A.; Arellano, C.S.; Marfori, W.; Heidari, G.; Sayre, J.W.; Krishnam, M.S.; Ruehm, S.G.

    2014-01-01

    Aim: To assess the feasibility of a fast single-bolus combined carotid and coronary computed tomography angiography (CTA) protocol in asymptomatic patients. Materials and methods: Thirty-three consecutive patients (18 women and 15 men) with a median age of 61 ± 14 years old (range 37–87 years) with known or suspected atherosclerotic disease were enrolled in this prospective study. A single breath-hold, single biphasic injection protocol (50 ml at 3 ml/s, 50 ml at 5 ml/s, 50 ml saline flush at 5 ml/s) was used for combined CTA imaging of the supra-aortic (SAA) and coronary arteries (CA) on a 64-slice dual-source CT (DSCT) machine. Helical CTA acquisition of the SAA was followed by prospective electrocardiography (ECG)-triggered coronary CTA. Subjective (four-point scale) image quality and objective signal-to-noise (SNR) and contrast-to-noise (CNR) measurements were performed. Vascular disease was graded on a four-point scale (grade 1: absent; grade 2: mild, grade 3: moderate; grade 4: severe). The radiation dose was recorded for each patient. Results: The average enhancement and subjective quality score of SAA and CA segments were 396 HU/358 HU and 1.2 ± 0.3/1.72 ± 0.4, respectively. The SNR was 27.1 ± 1.7 in the SAA and 21.6 ± 1.6 in the CA (p < 0.0001). The CNR was 18.1 ± 1.2 and 15.9 ± 1.8, respectively (p = 0.4). Four percent of SAA and 14% of CA segments (mostly due to peri-venous streak artefacts and small calibre, respectively) produced non-diagnostic images. SAA findings were as follows: 26/33 (79%) patients showed no disease and 6/33 (18%) had grade 2 and 1/33 (3%) had grade 3 disease. CA findings were as follows: 25/33 (76%) showed no disease and 6/33 (18%) patients had grade 2 and 2/33 (6%) had grade 3 disease. Five patients had disease in both districts. The average radiation dose for the combined CTA angiogram was 4.3 ± 0.6 mSv. Conclusion: A fast, low-dose combined DSCT angiography protocol appears technically feasible for imaging carotid and

  13. Comprehensive low-dose imaging of carotid and coronary arteries with a single-injection dual-source CT angiography protocol.

    Science.gov (United States)

    Tognolini, A; Arellano, C S; Marfori, W; Heidari, G; Sayre, J W; Krishnam, M S; Ruehm, S G

    2014-03-01

    To assess the feasibility of a fast single-bolus combined carotid and coronary computed tomography angiography (CTA) protocol in asymptomatic patients. Thirty-three consecutive patients (18 women and 15 men) with a median age of 61 ± 14 years old (range 37-87 years) with known or suspected atherosclerotic disease were enrolled in this prospective study. A single breath-hold, single biphasic injection protocol (50 ml at 3 ml/s, 50 ml at 5 ml/s, 50 ml saline flush at 5 ml/s) was used for combined CTA imaging of the supra-aortic (SAA) and coronary arteries (CA) on a 64-slice dual-source CT (DSCT) machine. Helical CTA acquisition of the SAA was followed by prospective electrocardiography (ECG)-triggered coronary CTA. Subjective (four-point scale) image quality and objective signal-to-noise (SNR) and contrast-to-noise (CNR) measurements were performed. Vascular disease was graded on a four-point scale (grade 1: absent; grade 2: mild, grade 3: moderate; grade 4: severe). The radiation dose was recorded for each patient. The average enhancement and subjective quality score of SAA and CA segments were 396 HU/358 HU and 1.2 ± 0.3/1.72 ± 0.4, respectively. The SNR was 27.1 ± 1.7 in the SAA and 21.6 ± 1.6 in the CA (p grade 2 and 1/33 (3%) had grade 3 disease. CA findings were as follows: 25/33 (76%) showed no disease and 6/33 (18%) patients had grade 2 and 2/33 (6%) had grade 3 disease. Five patients had disease in both districts. The average radiation dose for the combined CTA angiogram was 4.3 ± 0.6 mSv. A fast, low-dose combined DSCT angiography protocol appears technically feasible for imaging carotid and coronary atherosclerotic disease. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  14. Myocardial blood flow rate and capillary permeability for 99mTc-DTPA in patients with angiographically normal coronary arteries. Evaluation of the single-injection, residue detection method with intracoronary indicator bolus injection and the use of a mobile gamma camera

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Kelbaek, H; Efsen, F

    1994-01-01

    The aims of the present study were to quantitate myocardial perfusion and capillary permeability in the human heart by means of the single-injection, residue detection method using a mobile gamma camera. With this method, the intravascular mean transit time and the capillary extraction fraction (...

  15. Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

    Science.gov (United States)

    Carvalho, Filomena M; Zaganelli, Fabricia L; Almeida, Bernardo G L; Goes, Joao Carlos Sampaio; Baracat, Edmund C; Carvalho, Jesus P

    2010-01-01

    OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2‐40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6%) cases, with 29/31 (93.5%) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node‐positive cases was lower than that of node‐negative (18.9% vs. 22.6%, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8%) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host‐tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas. PMID:21340215

  16. Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

    Directory of Open Access Journals (Sweden)

    Filomena M Carvalho

    2010-01-01

    Full Text Available OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6% cases, with 29/31 (93.5% of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9% vs. 22.6%, respectively. Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8% cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively, although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.

  17. Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours.

    Science.gov (United States)

    Focke, Cornelia M; Decker, Thomas; van Diest, Paul J

    2016-11-01

    Regional differences in proliferative activity are commonly seen within breast cancers, but little is known on the extent of intratumoral heterogeneity of Ki67 expression. Our aim was to study the intratumoral heterogeneity of Ki67 expression in early breast cancers and its association with clinicopathological features, such as oestrogen receptor (ER) status, grade and histological subtype. The Ki67-labelling index (Ki67-LI) was assessed in hot, cold and intermediate spots of 233 invasive breast cancers by counting a total of 1020 cells, according to a protocol of the International Ki67 in Breast Cancer Working Group. Differences between the spots per tumour were analysed further for clinicopathological subgroups defined by ER status, grade and histological subtype. All clinicopathological subgroups showed significant differences in Ki67-LI between hot, intermediate and cold spots (P cancers (72.6 versus 49.2%, P cancers. Nested analysis of variance indicated that in both ER-positive and ER-negative cancers, variance in Ki67-LI within tumours contributed more to the total variance (56% for ER-positive, 60% for ER-negative cancers) than the variance between tumours. Intratumoral heterogeneity in Ki67-LI is a ubiquitous phenomenon across various pathological subgroups of breast cancer that may impact assessment of Ki67 levels for clinical decision-making, and sheds new light on recommended cut-offs. © 2016 John Wiley & Sons Ltd.

  18. Intratumoral Photodynamic Therapy With Newly Synthesized Pheophorbide a in Murine Oral Cancer.

    Science.gov (United States)

    Ahn, Mee-Young; Yoon, Hyo-Eun; Moon, Seong-Yong; Kim, Yong-Chul; Yoon, Jung-Hoon

    2017-01-26

    Photodynamic therapy (PDT) is a therapeutic alternative for malignant tumors that uses a photosensitizer. Our group recently synthesized photosensitizer pheophorbide a (Pa) from chlorophyll-a. The present study investigated the therapeutic effect of PDT using intratumoral administration of the synthetic photosensitizer Pa in an in vivo murine oral squamous cell carcinoma (OSCC) animal model. Pa accumulation was measured using the fluorescence spectrum and imaging in living C3H mice. Intratumoral treatment of Pa-PDT (IT Pa-PDT) significantly inhibited the growth of transplanted OSCC cells. Histopathological examination of tumor tissues showed that PCNA expression was significantly decreased, while TUNEL-stained cells were markedly increased in the IT Pa-PDT group compared to controls. IT Pa-PDT-induced apoptosis was confirmed by immunoblot. Reduction of Bcl-2 and cleavage of caspase 3 and PARP were observed in IT Pa-PDT. These data demonstrate that IT Pa-PDT inhibited tumor cell proliferation and induced apoptosis, which is correlated with the anticancer activity of IT Pa-PDT. These potent antitumor activities of IT Pa-PDT were observed in both the immunohistochemistry and Western blot experiments. Our findings suggest the intratumoral therapeutic potential of Pa-PDT on OSCC. Additionally, demonstrated detection of Pa using a fluorescence spectroscopy system or molecular imaging system provides a means for simultaneous diagnosis and treatment of OSCC.

  19. Improved Intratumoral Oxygenation Through Vascular Normalization Increases Glioma Sensitivity to Ionizing Radiation

    International Nuclear Information System (INIS)

    McGee, Mackenzie C.; Hamner, J. Blair; Williams, Regan F.; Rosati, Shannon F.; Sims, Thomas L.; Ng, Catherine Y.; Gaber, M. Waleed; Calabrese, Christopher; Wu Jianrong; Nathwani, Amit C.; Duntsch, Christopher; Merchant, Thomas E.; Davidoff, Andrew M.

    2010-01-01

    Purpose: Ionizing radiation, an important component of glioma therapy, is critically dependent on tumor oxygenation. However, gliomas are notable for areas of necrosis and hypoxia, which foster radioresistance. We hypothesized that pharmacologic manipulation of the typically dysfunctional tumor vasculature would improve intratumoral oxygenation and, thus, the antiglioma efficacy of ionizing radiation. Methods and Materials: Orthotopic U87 xenografts were treated with either continuous interferon-β (IFN-β) or bevacizumab, alone, or combined with cranial irradiation (RT). Tumor growth was assessed by quantitative bioluminescence imaging; the tumor vasculature using immunohistochemical staining, and tumor oxygenation using hypoxyprobe staining. Results: Both IFN-β and bevaziumab profoundly affected the tumor vasculature, albeit with different cellular phenotypes. IFN-β caused a doubling in the percentage of area of perivascular cell staining, and bevacizumab caused a rapid decrease in the percentage of area of endothelial cell staining. However, both agents increased intratumoral oxygenation, although with bevacizumab, the effect was transient, being lost by 5 days. Administration of IFN-β or bevacizumab before RT was significantly more effective than any of the three modalities as monotherapy or when RT was administered concomitantly with IFN-β or bevacizumab or 5 days after bevacizumab. Conclusion: Bevacizumab and continuous delivery of IFN-β each induced significant changes in glioma vascular physiology, improving intratumoral oxygenation and enhancing the antitumor activity of ionizing radiation. Additional investigation into the use and timing of these and other agents that modify the vascular phenotype, combined with RT, is warranted to optimize cytotoxic activity.

  20. PD-1 Blockade Expands Intratumoral Memory T Cells

    DEFF Research Database (Denmark)

    Ribas, Antoni; Shin, Daniel Sanghoon; Zaretsky, Jesse

    2016-01-01

    Tumor responses to programmed cell death protein 1 (PD-1) blockade therapy are mediated by T cells, which we characterized in 102 tumor biopsies obtained from 53 patients treated with pembrolizumab, an antibody to PD-1. Biopsies were dissociated, and single-cell infiltrates were analyzed by multi...

  1. A Three-arm Randomized Clinical Trial Comparing Continuous Femoral Plus Single-injection Sciatic Peripheral Nerve Blocks versus Periarticular Injection with Ropivacaine or Liposomal Bupivacaine for Patients Undergoing Total Knee Arthroplasty.

    Science.gov (United States)

    Amundson, Adam W; Johnson, Rebecca L; Abdel, Matthew P; Mantilla, Carlos B; Panchamia, Jason K; Taunton, Michael J; Kralovec, Michael E; Hebl, James R; Schroeder, Darrell R; Pagnano, Mark W; Kopp, Sandra L

    2017-06-01

    Multimodal analgesia is standard practice for total knee arthroplasty; however, the role of regional techniques in improved perioperative outcomes remains unknown. The authors hypothesized that peripheral nerve blockade would result in lower pain scores and opioid consumption than two competing periarticular injection solutions. This three-arm, nonblinded trial randomized 165 adults undergoing unilateral primary total knee arthroplasty to receive (1) femoral catheter plus sciatic nerve blocks, (2) ropivacaine-based periarticular injection, or (3) liposomal bupivacaine-based periarticular injection. Primary outcome was maximal pain during postoperative day 1 (0 to 10, numerical pain rating scale) in intention-to-treat analysis. Additional outcomes included pain scores and opioid consumption for postoperative days 0 to 2 and 3 months. One hundred fifty-seven study patients received peripheral nerve block (n = 50), ropivacaine (n = 55), or liposomal bupivacaine (n = 52) and reported median maximal pain scores on postoperative day 1 of 3, 4, and 4.5 and on postoperative day 0 of 1, 4, and 5, respectively (average pain scores for postoperative day 0: 0.6, 1.7, and 2.4 and postoperative day 1: 2.5, 3.5, and 3.7). Postoperative day 1 median maximal pain scores were significantly lower for peripheral nerve blockade compared to liposomal bupivacaine-based periarticular injection (P = 0.016; Hodges-Lehmann median difference [95% CI] = -1 [-2 to 0]). After postanesthesia care unit discharge, postoperative day 0 median maximal and average pain scores were significantly lower for peripheral nerve block compared to both periarticular injections (ropivacaine: maximal -2 [-3 to -1]; P bupivacaine: maximal -3 [-4 to -2]; P bupivacaine over ropivacaine in periarticular injections for total knee arthroplasty.

  2. Intratumoral lipids in 1H MRS in vivo in brain tumors: experience of the Siemens cooperative clinical trial.

    Science.gov (United States)

    Negendank, W; Sauter, R

    1996-01-01

    Fifteen institutions cooperated to examine the ability of 1H MRS to characterize metabolism in vivo in 102 primary brain tumors. Spectra were acquired from single 8 cc voxels in the tumor using a spin-echo method with an echo time of 135 ms. The most intense lipid signal was that of fatty acyl methylene protons at 1.3 ppm. Intratumoral lipid signals were not detected in oligodendrogliomas, ependymomas, or meningiomas and were evident in only 1 of 6 primitive neuroectodermal tumors. Among 75 astrocytic tumors, lipid signals occurred in 16% of low grade astrocytomas (AS), 36% of anaplastic astrocytomas (AA), and 44% of glioblastomas (GB). The amount of lipids, expressed as a ratio of the intensity of the methylene signal to that of choline, increased progressively with histopathological grade (p = 0.05). Greater amounts of mobile lipids in vivo in GB, which usually contain necrosis, is in accord with the recently discovered correlation between the fraction of microscopic necrosis and the intensity of the mobile lipid signal observed ex vivo using 1H MRS. The observation of lipid signals in AA, which do not contain necrosis, suggests that mobile fatty acids may appear at a stage of metabolic insult that precedes microscopic signs of cell death, and raises the possibility of an independent correlation between 1H MRS-detectable lipids and prognosis in patients with astrocytic tumors.

  3. Monochromatic subdiffusive spatial frequency domain imaging provides in-situ sensitivity to intratumoral morphological heterogeneity in a murine model.

    Science.gov (United States)

    McClatchy, David M; Hoopes, P Jack; Pogue, Brian W; Kanick, Stephen Chad

    2017-02-01

    For the first time, spatially resolved quantitative metrics of light scattering recovered with sub-diffusive spatial frequency domain imaging (sd-SFDI) are shown to be sensitive to changes in intratumoral morphology and viability by direct comparison to histopathological analysis. Two freshly excised subcutaneous murine tumor cross-sections were measured with sd-SFDI, and recovered optical scatter parameter maps were co-registered to whole mount histology. Unique clustering of the optical scatter parameters μs' vs. γ (i.e. diffuse scattering vs. relative backscattering) evaluated at a single wavelength showed complete separation between regions of viable tumor, aggresive tumor with stromal growth, varying levels of necrotic tumor, and also peritumor muscle. The results suggest that with further technical development, sd-SFDI may represent a non-destructive screening tool for analysis of excised tissue or a non-invasive approach to investigate suspicious lesions without the need for exogenous labels or spectrally resolved imaging. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Synthesis of chemically-modified single-walled carbon nanotubes by counter-current ammonia gas injection into the induction thermal plasma process

    Science.gov (United States)

    Shahverdi, Ali

    Pristine single-walled carbon nanotubes (SWCNTs) are poorly dispersible and insoluble in many solvents and need to be chemically modified prior to their use in many applications. This work is focused on the investigation of the synthesis of chemically modified SWCNTs material through an in situ approach. The main objectives of the presented research are: 1) to explore the in situ chemical process during the synthesis of SWCNT and 2) to closely examine the effect of a reactive environment on SWCNTs. Effects of the catalyst type and content on the SWCNTs final product, synthesized by induction thermal plasma (ITP), were studied to replace toxic cobalt (Co) in the feedstock. In this regard, three different catalyst mixtures (i.e. Ni-Y2O3, Ni-Co-Y2O3, and Ni-Mo-Y2O3) were used. Experimental results showed that the catalyst type affects the quality of the SWCNT final product. Similar quality SWCNTs can be produced when the same amount of Co was replaced by Ni. Moreover, the results observed in this experimental work were further explained by thermodynamic calculation results. Thermogravimetry (TG) was used throughout the work to characterize the SWCNTs product. TG was firstly standardized by studying the effects of three main instrumental parameters (temperature ramp, TR, initial mass of the sample, IM, and gas flow rate, FR) on the Tonset and full-width half maximum (FWHM) obtained from TG and derivative TG graphs of carbon black, respectively. Therefore, a two-level factorial statistical design was performed. The statistical analysis showed that the effect of TR, IM, and to a lower extent, FR, is significant on FWHM and insignificant on Tonset. A methodology was then developed based upon the SWCNTs synthesis using the ITP system, through an in situ chemistry approach. Ammonia (NH3) was selected and counter-currently injected into the ITP reactor at three different flow rates and by four different nozzle designs. Numerical simulation indicated a better mixing of NH3 in

  5. Dose-dependent effect of a single GnRHa injection on the spawning of meagre (Argyrosomus regius broodstock reared in captivity

    Directory of Open Access Journals (Sweden)

    Hipolito Fernandez-Palacios

    2014-10-01

    Full Text Available The present study aimed to determine the spawning efficacy, egg quality and quantity of captive breed meagre induced with a single gonadotrophin‐releasing hormone agonist (GnRHa injection of 0, 1, 5, 10, 15, 20, 25, 30, 40 or 50 µg kg-1 to determine a recommended optimum dose to induce spawning. The doses 10, 15 and 20 μg kg-1 gave eggs with the highest quality (measured as: percentage of viability, floating, fertilisation and hatch and quantity (measured as: total number of eggs, number of viable eggs, number of floating eggs, number of hatched larvae and number of larvae that reabsorbed the yolk sac. All egg quantity parameters were described by Gaussian regression analysis with R2=0.89 or R2=0.88. The Gaussian regression analysis identified that the optimal dose used was 15 μg kg-1. The regression analysis highlighted that this comprehensive study examined doses that ranged from low doses insufficient to stimulate a high spawning response (significantly lower egg quantities, p<0.05 compared to 15 μg kg-1 through to high doses that stimulated the spawning of significantly lower egg quantities and eggs with significantly lower quality (egg viability. In addition, the latency period (time from hormone application to spawning decreased with increasing doses to give a regression (R2=0.93 which suggests that higher doses accelerated oocyte development that in turn reduced egg quality and quantity. The identification of an optimal dose for the spawning of meagre, which has high aquaculture potential, represents an important advance for the Mediterranean aquaculture industry.

  6. Image-guided percutaneous lipiodol-pingyangmycin suspension injection therapy for sacral chordoma

    International Nuclear Information System (INIS)

    Huang, Dexiao; Chen, Yong; Zeng, Qingie; Li, Yanhao; Wu, Renhua

    2013-01-01

    A 74-year-old man presented with a progressively worsening pain in sacrum and was diagnosed to have a sacral chordoma by biopsy in May, 2004. Percutaneous intratumoral injection with lipiodol-pingyangmycin suspension (LPS) was carried out under image guidance and repeated when the pain in sacrum recurred and the tumor increased. During a 6-year follow-up period, three sessions of this treatment were executed. CT imaging and Karnofsky Performance Score were used to evaluate the size of tumor and quality of life, respectively. The patient was free of pain after each procedure and had a high quality of life with a Karnofsky Performance Score above 80 points. The tumor lesion in sacral area was effectively controlled. No complications were observed. Percutaneous intratumoral injection with LPS under image guidance may be an effective and safe alternative for the patients with sacral chordoma.

  7. Growth factor-based therapies provide additional benefit beyond physical therapy in resistant elbow tendinopathy: a prospective, single-blind, randomised trial of autologous blood injections versus platelet-rich plasma injections.

    Science.gov (United States)

    Creaney, Leon; Wallace, Andrew; Curtis, Mark; Connell, David

    2011-09-01

    Growth factor technologies are increasingly used to enhance healing in musculoskeletal injuries, particularly in sports medicine. Two such products; platelet-rich plasma (PRP) and autologous blood, have a growing body of supporting evidence. No previous trial has directly compared the efficacy of these two methods. Growth factor administration improves tissue regeneration in patients who have failed to respond to conservative therapy. A prospective, double-blind, randomised trial. Elbow tendinopathy patients who had failed conservative physical therapy were divided into two patient groups: PRP injection (N=80) and autologous blood injection (ABI) (N=70). Each patient received two injections at 0 and 1 month. Patient-related tennis elbow evaluation (PRTEE) was recorded by a blinded investigator at 0, 1, 3 and 6 months. The main outcome measure was PRTEE, a validated composite outcome for pain, activities of daily living and physical function, utilising a 0-100 scale. At 6 months the authors observed a 66% success rate in the PRP group versus 72% in the ABI group, p=NS. There was a higher rate of conversion to surgery in the ABI group (20%) versus the PRP group (10%). In patients who are resistant to first-line physical therapy such as eccentric loading, ABI or PRP injections are useful second-line therapies to improve clinical outcomes. In this study, up to seven out of 10 additional patients in this difficult to treat cohort benefit from a surgery-sparing intervention.

  8. Intratumoral delivery of CpG-conjugated anti-MUC1 antibody enhances NK cell anti-tumor activity.

    Science.gov (United States)

    Schettini, Jorge; Kidiyoor, Amritha; Besmer, Dahlia M; Tinder, Teresa L; Roy, Lopamudra Das; Lustgarten, Joseph; Gendler, Sandra J; Mukherjee, Pinku

    2012-11-01

    Monoclonal antibodies (mAbs) against tumor-associated antigens are useful anticancer agents. Antibody-dependent cellular cytotoxicity (ADCC) is one of the major mechanisms responsible for initiating natural killer cell (NK)-mediated killing of tumors. However, the regulation of ADCC via NK cells is poorly understood. We have investigated the cytolytic activity of NK cells against pancreatic cancer cells that were coated with an antibody directed against the human tumor antigen, Mucin-1 designated HMFG-2, either alone or conjugated to CpG oligodeoxynucleotide (CpG ODN). Conjugated antibodies were tested for their ability to elicit ADCC in vitro and in vivo against pancreatic cancer cells. NK cells cultured in the presence of immobilized CpG ODN, HMFG-2 Ab, or CpG ODN-conjugated HMFG-2 Ab were able to up-regulate perforin similarly. Interestingly, a significant higher ADCC was observed when CpG ODN-conjugated HMFG-2-coated tumor cells were co-cultured with NK cells compared to unconjugated HMFG-2 Ab or CpG ODN alone. Moreover, MyD88-deficient NK cells can perform ADCC in vitro. Furthermore, intratumoral injections of CpG ODN-conjugated HMFG-2 induced a significant reduction in tumor burden in vivo in an established model of pancreatic tumor in nude mice compared to CpG ODN or the HMFG-2 alone. Depletion of macrophages or NK cells before treatment confirmed that both cells were required for the anti-tumor response in vivo. Results also suggest that CpG ODN and HMFG-2 Ab could be sensed by NK cells on the mAb-coated tumor cells triggering enhanced ADCC in vitro and in vivo.

  9. Thermal Performance and Reliability Analysis of Single-Phase PV Inverters with Reactive Power Injection Outside Feed-In Operating Hours

    DEFF Research Database (Denmark)

    Anurag, Anup; Yang, Yongheng; Blaabjerg, Frede

    2015-01-01

    there is no solar irradiance. However, reactive power injection causes additional power losses in the switching components leading to a temperature rise in the devices. Thus, this paper analyses the impact of reactive power injection by PV inverters outside feed-in operation on the thermal performance...... of their power switching components. A thermal analysis based on the mission profile (i.e., solar irradiance and ambient temperature) has been incorporated, so as to determine the additional temperature rise in the components induced by the operation outside feed-in hours. An analytical lifetime model has been...... used. The damage produced on the transistors has been quantified using Palmgren Miner rule. A reliability analysis has been carried out on a PV inverter with and without the injection of reactive power into the utility grid at nights. Economic impacts of injecting reactive power from PV inverters...

  10. Effects of single injection of local anesthetic agents on intervertebral disc degeneration: ex vivo and long-term in vivo experimental study.

    Directory of Open Access Journals (Sweden)

    Koji Iwasaki

    Full Text Available Analgesic discography (discoblock can be used to diagnose or treat discogenic low back pain by injecting a small amount of local anesthetics. However, recent in vitro studies have revealed cytotoxic effects of local anesthetics on intervertebral disc (IVD cells. Here we aimed to investigate the deteriorative effects of lidocaine and bupivacaine on rabbit IVDs using an organotypic culture model and an in vivo long-term follow-up model.For the organotypic culture model, rabbit IVDs were harvested and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine or 0.5% bupivacaine. Nucleus pulposus (NP cell death was measured using confocal microscopy. Histological and TUNEL assays were performed. For in vivo study, each local anesthetic was injected into rabbit lumbar IVDs under a fluoroscope. Six or 12 months after the injection, each IVD was prepared for magnetic resonance imaging (MRI and histological analysis.In the organotypic culture model, both anesthetic agents induced time-dependent NP cell death; when compared with injected saline solution, significant effects were detected within 7 days. Compared with the saline group, TUNEL-positive NP cells were significantly increased in the bupivacaine group. In the in vivo study, MRI analysis did not show any significant difference. Histological analysis revealed that IVD degeneration occurred to a significantly level in the saline- and local anesthetics-injected groups compared with the untreated control or puncture-only groups. However, there was no significant difference between the saline and anesthetic agents groups.In the in vivo model using healthy IVDs, there was no strong evidence to suggest that discoblock with local anesthetics has the potential of inducing IVD degeneration other than the initial mechanical damage of the pressurized injection. Further studies should be performed to investigate the deteriorative effects of the local injection of analgesic agents

  11. A Single-blind, Split-face, Randomized, Pilot Study Comparing the Effects of Intradermal and Intramuscular Injection of Two Commercially Available Botulinum Toxin A Formulas to Reduce Signs of Facial Aging

    Science.gov (United States)

    Sapra, Priya; Sapra, Sheetal; Khanna, Julie; Mraud, Kelli; Bonadonna, Jennifer

    2017-01-01

    Objective: To examine the effectiveness of intradermal botulinum toxin type A injection in improving skin texture and midface lift while reducing pore size and sebum production, as well as investigate the differences in effectiveness between onabotulinumtoxinA and abobotulinumtoxinA using intradermal and intramuscular injection methods. Design: A 16-week, single-blind, split-face, randomized study. Each patient served as their own control, receiving onabotulinumtoxinA and abobotulinumtoxinA randomized to either the left or right side of the face. Patients received intradermal botulinum toxin type A injections at Week 0 and intramuscular botulinum toxin type A injections at Week 2. Participants: Ten women aged 35 to 65 years who exhibited static rhytids in the glabellar and periorbital area. Measurements: The primary endpoint was efficacy of split-face treatment of intradermal and intramuscular onabotulinumtoxinA and abobotulinumtoxinA as assessed by a blinded evaluator using baseline and post-treatment photographs. The secondary endpoints included safety as assessed by adverse events and patient satisfaction measured by questionnaires completed at baseline and post-treatment. Results: Intradermal injection of botulinum toxin type A led to a statistically significant improvement in skin texture (p=0.004) while also resulting in mild midface lift (p=0.024), but did not provide a significant reduction of pore size and sebum production. There was no statistically significant difference between onabotulinumtoxinA and abobotulinumtoxinA when injected intradermally or intramuscularly. Conclusion: Intradermal injection of botulinum toxin type A appears to be a safe and effective therapy that provides an improvement in facial skin texture and midface lift. Registry: clinicaltrials.gov (ID#: NCT02907268). PMID:28367260

  12. Clinical and instrumental evaluation of a cross-linked hyaluronic acid filler dermal injection: effects on nasolabial folds skin biophysical parameters and augmentation from a single-dose, monocentric, open-label trial.

    Science.gov (United States)

    Cameli, Norma; Mariano, Maria; Serio, Mirko; Berardesca, Enzo

    2016-10-01

    When a hyaluronic acid dermal device to fill soft tissues is chosen, efficacy, safety and durability are key concerns. This is an open-label prospective study to instrumentally evaluate the effects of HA filler dermal injection on nasolabial folds skin biophysical parameters and augmentation. A single Italian site treated female subjects aged 40-55, for nasolabial folds, with a single standardized injection. The outcome was evaluated with objective quantitative measurements after 90 (T1) and 180 days (T2) from the injection comparing to baseline (T0) by means of Corneometer (skin hydration measurement), Cutometer (skin elasticity measurement), and Visioface devices for digital and UV computerized image analysis. Secondary endpoints were safety assessment, subject investigator satisfaction with the intervention. Assessment of aesthetic results included photographic documentation. The computerized image analysis confirmed the clinical assessment showing statistically significant reduction in nasolabial folds both at T1 and T2. Visioface® indexes showed a marked and statistical significant response. An excellent profile of satisfaction of the product at T2 from investigators and patients was recorded. Skin hydration and elasticity did not show significant changes. In our study, a standardized HA filler dermal injection on nasolabial folds did not influence skin biophysical parameters such as skin hydration and elasticity. Nasolabial folds showed a persistent and significative response at T2 confirmed by instrumental evaluation. The tolerability and safety profile of the product was excellent.

  13. Periodontal ligament injection versus routine local infiltration for nonsurgical single posterior maxillary permanent tooth extraction: comparative double-blinded randomized clinical study

    Directory of Open Access Journals (Sweden)

    Al-Shayyab MH

    2017-10-01

    Full Text Available Mohammad H Al-Shayyab Department of Oral and Maxillofacial Surgery, Oral Medicine and Periodontology, School of Dentistry, University of Jordan, Amman, Jordan Aim: The aim of this study was to evaluate the efficacy of, and patients’ subjective responses to, periodontal ligament (PDL anesthetic injection compared to traditional local-anesthetic infiltration injection for the nonsurgical extraction of one posterior maxillary permanent tooth. Materials and methods: All patients scheduled for nonsurgical symmetrical maxillary posterior permanent tooth extraction in the Department of Oral and Maxillofacial Surgery at the University of Jordan Hospital, Amman, Jordan over a 7-month period were invited to participate in this prospective randomized double-blinded split-mouth study. Every patient received the recommended volume of 2% lidocaine with 1:100,000 epinephrine for PDL injection on the experimental side and for local infiltration on the control side. A visual analog scale (VAS and verbal rating scale (VRS were used to describe pain felt during injection and extraction, respectively. Statistical significance was based on probability values <0.05 and measured using Χ2 and Student t-tests and nonparametric Mann–Whitney and Kruskal–Wallis tests. Results: Of the 73 patients eligible for this study, 55 met the inclusion criteria: 32 males and 23 females, with a mean age of 34.87±14.93 years. Differences in VAS scores and VRS data between the two techniques were statistically significant (P<0.001 and in favor of the infiltration injection. Conclusion: The PDL injection may not be the alternative anesthetic technique of choice to routine local infiltration for the nonsurgical extraction of one posterior maxillary permanent tooth. Keywords: PDL injection, infiltration, anesthesia, extraction

  14. Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience

    Directory of Open Access Journals (Sweden)

    Julian Berrocal

    2017-01-01

    Full Text Available Background. Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods. Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results. At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1–15. There were 512 cases (21.9% in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2% with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion. Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient.

  15. Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas.

    Science.gov (United States)

    Takagi, Mayu; Miki, Yasuhiro; Miyashita, Minoru; Hata, Shuko; Yoda, Tomomi; Hirakawa, Hisashi; Sagara, Yasuaki; Rai, Yoshiaki; Ohi, Yasuyo; Tamaki, Kentaro; Ishida, Takanori; Suzuki, Takashi; Ouchi, Noriaki; Sasano, Hironobu

    2016-02-01

    The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.

  16. Growth responses following a single intra-muscular hGH plasmid administration compared to daily injections of hGH in dwarf mice.

    Science.gov (United States)

    Higuti, Eliza; Cecchi, Claudia R; Oliveira, Nelio A J; Vieira, Daniel P; Jensen, Thomas G; Jorge, Alexander A L; Bartolini, Paolo; Peroni, Cibele N

    2012-12-01

    In previous work, sustained levels of circulating human growth hormone (hGH) and a highly significant weight increase were observed after electrotransfer of naked plasmid DNA (hGH-DNA) into the muscle of immunodeficient dwarf mice (lit/scid). In the present study, the efficacy of this in vivo gene therapy strategy is compared to daily injections (5 μg/twice a day) of recombinant hGH (r-hGH) protein, as assessed on the basis of several growth parameters. The slopes of the two growth curves were found to be similar (P > 0.05): 0.095 g/mouse/d for protein and 0.094 g/mouse/d for DNA injection. In contrast, the weight increases averaged 35.5% (P hGH-DNA administration thus appears to be comparable to repeated hormone injections for promoting growth and may represent a feasible alternative for the treatment of growth hormone deficiency.

  17. Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing phase IV study

    Directory of Open Access Journals (Sweden)

    Bashaireh K

    2015-04-01

    Full Text Available Khaldoon Bashaireh,1 Ziad Naser,2 Khaled Al Hawadya,2 Sorour Sorour,2 Rami Nabeel Al-Khateeb3 1Department of Orthopedics Surgery, King Abdullah University Hospital, Jordan University of Science and Technology, Irbid, Jordan; 2Private Clinic, 3Elaf Medical Supplies Company, Amman, Jordan Purpose: The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period.Materials and methods: The study was a post-marketing phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1–4 in the tibio–femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection.Main outcome measure(s: An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated.Main results: The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3

  18. Phase I, first-in-human study of BMS747158, a novel 18F-labeled tracer for myocardial perfusion PET: dosimetry, biodistribution, safety, and imaging characteristics after a single injection at rest.

    Science.gov (United States)

    Maddahi, Jamshid; Czernin, Johannes; Lazewatsky, Joel; Huang, Sung-Cheng; Dahlbom, Magnus; Schelbert, Heinrich; Sparks, Richard; Ehlgen, Alexander; Crane, Paul; Zhu, Qi; Devine, Marybeth; Phelps, Michael

    2011-09-01

    (18)F-labeled BMS747158 is a novel myocardial perfusion imaging tracer that targets mitochondrial complex 1. The objectives of this phase I study were to evaluate radiation dosimetry, biodistribution, human safety, tolerability, and early elimination of (18)F activity in urine after injection of a single dose of the tracer at rest in healthy subjects. Thirteen healthy subjects were injected with 170-244 MBq (4.6-6.6 mCi) of BMS747158 intravenously. Dynamic PET was obtained over the heart for 10 min, followed by sequential whole-body imaging for 5 h. Blood samples and urinary excretion were collected for up to 8 h. Heart rate, electrocardiogram, and blood pressure were monitored before and during imaging. The residence times were determined from multiexponential regression of organ region-of-interest data normalized by injected dose. Absorbed dose estimates for all target organs were determined using MIRD schema with OLINDA/EXM software. The organ receiving the largest mean absorbed dose was the kidneys at 0.066 mSv/MBq (0.24 rem/mCi), followed by the heart wall at 0.048 mSv/MBq (0.18 rem/mCi). The mean effective dose was 0.019 mSv/MBq (0.072 rem/mCi). The heart exhibited high and sustained retention of BMS747158 from the earliest images through approximately 5 h after injection. There were no drug-related adverse events, and the tracer was well tolerated in all subjects. Mean urinary excretion was 4.83 percentage injected dose (range, 0.64-12.41 percentage injected dose). These preliminary data suggest that (18)F-labeled BMS747158 appears to be well tolerated and has a unique potential for myocardial perfusion PET.

  19. Hemorragia maciça intratumoral em esclerose tuberosa estudo autóptico de um caso

    Directory of Open Access Journals (Sweden)

    Lígia M. Barbosa-Coutinho

    1991-12-01

    Full Text Available O caso de um menino com esclerose tuberosa, apresentando o quadro clínico típico e que morreu com hemorragia intratumoral maciça, é estudado. A autópsia parcial de crânio revelou hemorragia cerebral maciça à esquerda, no interior da qual se identificou um tumor que, à microscopia, mostrou se tratar de astrocitoma subependimário de células gigantes. Este é o segundo caso, na literatura, no qual um paciente com esclerose tuberosa morre de hemorragia maciça intratumoral, com inundação ventricular.

  20. Cefazolin Injection

    Science.gov (United States)

    ... is used to treat certain infections caused by bacteria including skin, bone, joint, genital, blood, heart valve, respiratory tract (including pneumonia), biliary tract, and urinary tract infections. Cefazolin injection ...

  1. Atezolizumab Injection

    Science.gov (United States)

    ... is in a class of medications called monoclonal antibodies. It works by blocking the action of a ... infection breath that smells fruity slowed, fast or irregular heartbeat Atezolizumab injection may cause other side effects. ...

  2. Cidofovir Injection

    Science.gov (United States)

    Cidofovir injection is used along with another medication (probenecid) to treat cytomegaloviral retinitis (CMV retinitis) in people ... body's response to the medication.You must take probenecid tablets by mouth with each dose of cidofovir. ...

  3. Acyclovir Injection

    Science.gov (United States)

    ... It is also used to treat first-time genital herpes outbreaks (a herpes virus infection that causes sores ... in the body. Acyclovir injection will not cure genital herpes and may not stop the spread of genital ...

  4. Alirocumab Injection

    Science.gov (United States)

    ... further decrease the amount of low-density lipoprotein (LDL) cholesterol ('bad cholesterol') in the blood. Alirocumab injection is ... antibodies. It works by blocking the production of LDL cholesterol in the body to decrease the amount of ...

  5. Pegloticase Injection

    Science.gov (United States)

    ... doctor if you have glucose-6-phosphate dehydrogenase (G6PD) deficiency (an inherited blood disease). Your doctor may test you for G6PD deficiency before you start to receive pegloticase injection. If ...

  6. Risperidone Injection

    Science.gov (United States)

    ... of interest in life, and strong or inappropriate emotions). Risperidone extended-release injection is used alone or ... during your treatment: extreme thirst, frequent urination, extreme hunger, blurred vision, or weakness. It is very important ...

  7. Olanzapine Injection

    Science.gov (United States)

    ... of interest in life, and strong or inappropriate emotions). Olanzapine injection is used to treat episodes of ... during your treatment: extreme thirst, frequent urination, extreme hunger, blurred vision, or weakness. It is very important ...

  8. Tacrolimus Injection

    Science.gov (United States)

    ... in people who have received kidney, liver, or heart transplants. Tacrolimus injection should only be used by people ... or nurse will watch you closely during the first 30 minutes of your treatment and then will ...

  9. Omalizumab Injection

    Science.gov (United States)

    ... injection is used to decrease the number of asthma attacks (sudden episodes of wheezing, shortness of breath, and ... about how to treat symptoms of a sudden asthma attack. If your asthma symptoms get worse or if ...

  10. Daclizumab Injection

    Science.gov (United States)

    ... neck, armpits, or groin; diarrhea; bloody stools; stomach pain; or any new, unexplained symptom affecting any part of your body.Because of the risks with this medication, daclizumab injection is available only through a special ...

  11. Temozolomide Injection

    Science.gov (United States)

    ... balance or coordination fainting dizziness hair loss insomnia memory problems pain, itching, swelling, or redness in the place where the medication was injected changes in vision Some side effects can be serious. If you ...

  12. Moxifloxacin Injection

    Science.gov (United States)

    ... tendon area, or inability to move or to bear weight on an affected area.Using moxifloxacin injection ... muscle weakness) and cause severe difficulty breathing or death. Tell your doctor if you have myasthenia gravis. ...

  13. Delafloxacin Injection

    Science.gov (United States)

    ... a tendon area, or inability to move or bear weight on an affected area.Using delafloxacin injection ... muscle weakness) and cause severe difficulty breathing or death. Tell your doctor if you have myasthenia gravis. ...

  14. Levofloxacin Injection

    Science.gov (United States)

    ... tendon area, or inability to move or to bear weight on an affected area.Using levofloxacin injection ... muscle weakness) and cause severe difficulty breathing or death. Tell your doctor if you have myasthenia gravis. ...

  15. Ciprofloxacin Injection

    Science.gov (United States)

    ... a tendon area, or inability to move or bear weight on an affected area.Using ciprofloxacin injection ... muscle weakness) and cause severe difficulty breathing or death. Tell your doctor if you have myasthenia gravis. ...

  16. Butorphanol Injection

    Science.gov (United States)

    ... Butorphanol is in a class of medications called opioid agonist-antagonists. It works by changing the way ... suddenly stop using butorphanol injection, you may experience withdrawal symptoms such as nervousness, agitation, shakiness, diarrhea, chills, ...

  17. Haloperidol Injection

    Science.gov (United States)

    ... of interest in life, and strong or inappropriate emotions). Haloperidol injection is also used to control motor ... and the laboratory. Your doctor may order certain lab tests to check your body's response to haloperidol ...

  18. Ketorolac Injection

    Science.gov (United States)

    ... of ketorolac by intravenous (into a vein) or intramuscular (into a muscle) injection in a hospital or ... You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ ...

  19. Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study.

    Science.gov (United States)

    Bashaireh, Khaldoon; Naser, Ziad; Hawadya, Khaled Al; Sorour, Sorour; Al-Khateeb, Rami Nabeel

    2015-01-01

    The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period. The study was a post-marketing Phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1-4) in the tibio-femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection. An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated. The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3.36, the stiffness score was 0.42, and the physical performance score was 11.5. All side effects were local and transient, and included pain, swelling, and redness of the knee. Most side effects were treated. Hyaluronan should be encouraged as an alternative or adjunct treatment to oral analgesics to reduce their required doses, and delay potential future surgical intervention.

  20. Collagenase injections for the treatment of single cords in cases of Dupuytren’s contracture – a prospective intervention study of long-term experience with Xiapex

    Directory of Open Access Journals (Sweden)

    Fischer, Lisa Maria

    2017-04-01

    Full Text Available Introduction: The gold standard in the treatment of Dupuytren’s contracture is surgical therapy. Alternatives are percutaneous needle fasciotomy and radiation in exceptional cases. Injection treatments with Xiapex (Pfizer are a new therapy option. This collagenase, extracted from clostridium histolyticum, is used to break down the affected tissue cords. The objective of this study is to examine the effect and long-term success of treatment with Xiapex.Methods: In this study, Xiapex treatment was conducted on a sample group of 19 patients with Dupuytren’s contracture. The injection was placed either on the cord at the level of the metacarpophalangeal (MCP joint (n=17 or of the proximal interphalangeal (PIP joint (n=7. Break-up of the cord occurred 24 hours after the injection. The neutral zero method was used to assess the extent of movement. The Michigan Hand Outcomes Questionnaire (MHQ was selected for evaluation of the general hand function in 16 patients. The WHO-5 and the EQ-5D VAS Score were used as a measure of the patients’ satisfaction and their state of health. All values were collected both pre-injection as well as 1 year post-injection.Results: Out of 19 patients in our sample group, 16 patients (≈84% benefitted in terms of improvement in mobility. Overall, the range of movement increased by Ø 26° in the affected finger. A separate assessment demonstrated that:The range of movement increased by 77% in the MCP joint. The extent of movement pre-injection was Ø (0-28-78 and post-injection it was Ø (0-9-81 with an improvement of Ø 22°. In the PIP joint, only slight improvement was observed (Ø pre (0-27-93; post (0-24-95.The MHQ increased from Ø 76% (R: 32–97% to 81% (R: 39–100%.The painfulness decreased from Ø 19% (R: 0–55% to Ø11% (R: 0–55%, corresponding to Ø 43%. Satisfaction increased in 72% of patients by Ø 21%.According to WHO-5, patient satisfaction pre-injection was Ø 20 (R: 11–25, and 1 year after

  1. Efficacy and Safety of Single Botulinum Toxin Type A (Botox®) Injection for Relief of Upper Trapezius Myofascial Trigger Point: A Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Kwanchuay, Photsawee; Petchnumsin, Thavatchai; Yiemsiri, Pichet; Pasuk, Nakkamol; Srikanok, Wannarat; Hathaiareerug, Chanasak

    2015-12-01

    Botulinum toxin injection has been applied for pain relief in various chronic pain syndromes. Recently, systematic review studies reported inconclusive effects of Botulinum toxin in myofascial pain management. The present study aimed to demonstrate the efficacy and safety of Botulinum toxin type A (BTxA) (Botox®) injection for pain reduction in myofascial trigger point (MTrP) of the upper trapezius muscle. Thirty-three patients with 48 MTrP on the upper trapezius muscles over three months with moderate to severe pain intensity diagnosed at physical medicine and rehabilitation outpatient department were recruited between December 2011 and March 2012. Eligible patients were blinded and randomly injected with single 0.2 ml (20 IU) of BTxA for 24 MTrP and 0.2 ml of 0.9% NaCl solution for 24 MTrP at the most tender trigger point on the upper trapezius muscle. All patients were advised for stretching exercise and ergonomic adaptation throughout the study. At 3- and 6-week after injections, visual analogue scale (VAS), the pressure pain threshold (PPT), and reported adverse effects were measured. Both BTxA and control groups demonstrated statistically significant differences in VAS reduction and increased PPT after 3 weeks and 6 weeks compared with before treatment. There were no statistically significant differences in VAS reduction from baseline between the two groups at 3- and 6-week after treatment. A statistically significant difference in improvement of PPT from baseline and 6-week after BTxA injection compared with 0.9% NaCl group was shown (1.0 ± 0.9 and 0.5 ± 0.7, p = 0.036). There was mild degree side-effects that spontaneous resolved within one week in both groups without significant difference in percentage. No severe adverse effects were reported during the study. The efficacy in VAS reduction of a single 20 IU of Botulinum toxin type A (Botox®) injection was not different from 0.9% NaCl for myofascial trigger point at the upper trapezius muscle. However

  2. [Non invasive intracranial hyperthermia with Electric Capacitive Transference -ECT- Intratumoral and cerebral thermometry results].

    Science.gov (United States)

    Ley-Valle, A

    2003-02-01

    The aim of this work is to present the results of thermic increase obtained at the brain and intratumoral levels through a non invasive technique -Electric Capacitive Transference- (ECT), developed in 1985 by Indiba. A review of the literature does not provide any reference of cerebral and intratumoral thermometry in real time with a non invasive technique of intracranial hyperthermia. In the 8 studied patients, the increases of temperature in the brain, ranged between 0.7 and 1.5 degrees C in relation to the depth of the thermometric probe and the incidence angle of the external electrode. Between tumoral and perilesional brain tissues, thermic increase was 0.3 to 0.7 degrees C greater at tumoral level. The observation that in no case the surrounding brain tissue registered a temperature over 39.2 degrees C supports the harmlessness of the technique regarding the potential damage to healthy brain tissue and seems to confirm previous data obtained in anatomopathological studies in animal experimentation performed in 1990, which showed an absence of lesions in tissues and organs. The greater and somewhat more prolonged thermic increase observed at tumoral level has been called the "greenhouse effect".

  3. Modulation of the Intratumoral Immune Landscape by Oncolytic Herpes Simplex Virus Virotherapy

    Directory of Open Access Journals (Sweden)

    Jie Yin

    2017-06-01

    Full Text Available Vaccines and immunotherapeutic approaches to cancers with the advent of immune checkpoint inhibitors and chimeric antigen receptor-modified T cells have recently demonstrated preclinical success and entered clinical trials. Despite advances in these approaches and combinatorial therapeutic regimens, depending on the nature of the cancer and the immune and metabolic landscape within the tumor microenvironment, current immunotherapeutic modalities remain inadequate. Recent clinical trials have demonstrated clear evidence of significant, and sometimes dramatic, antitumor activity, and long-term survival effects of a variety of oncolytic viruses (OVs, particularly oncolytic herpes simplex virus (oHSV. Acting as a multifaceted gene therapy vector and potential adjuvant-like regimens, oHSV can carry genes encoding immunostimulatory molecules in its genome. The oncolytic effect of oHSV and the inflammatory response that the virus stimulates provide a one-two punch at attacking tumors. However, mechanisms underlying oHSV-induced restoration of intratumoral immunosuppression demand extensive research in order to further improve its therapeutic efficacy. In this review, we discuss the current OV-based therapy, with a focus on the unique aspects of oHSV-initiated antiviral and antitumor immune responses, arising from virus-mediated immunological cell death to intratumoral innate and adaptive immunity.

  4. High intratumoral accumulation of stealth liposomal doxorubicin in sarcomas--rationale for combination with radiotherapy

    International Nuclear Information System (INIS)

    Koukourakis, M.I.; Koukouraki, S.; Giatromanolaki, A.; Kakolyris, S.; Georgoulias, V.; Velidaki, A.; Archimandritis, S.; Karkavitsas, N.N.

    2000-01-01

    Sarcomas are radioresistant tumors, the only curative therapy being radical surgical resection. Stealth liposomal doxorubicin (Caelyx) is a novel drug formulation that allows prolonged circulation and high intratumoral concentration. This study investigates the concurrent use of radiotherapy with Caelyx in a cohort of 7 patients with locally advanced or recurrent sarcoma. Radiotherapy was given as a standard fractionation regimen to a total dose of 70 Gy. Caelyx was given as a 30-min infusion at a dose of 25 mg/m 2 every 2 weeks. Scintigraphic imaging with Caelyx- 99m Tc-DTPA showed an increased (2.8 +/- 0.9 times higher) intratumoral drug accumulation compared to the surrounding healthy tissue. The regimen was well tolerated without any severe hematological or systemic toxicity. 'In field' radiation toxicity was not increased. Complete response was observed in 4/7 cases. It is concluded that combined chemo-radiotherapy with stealth liposomal doxorubicin for locally advanced sarcomas is feasible and promising, the benefit expected from the unique ability of the stealth liposomes to accumulate selectively in the tumoral tissue

  5. A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds.

    Science.gov (United States)

    Bruna, Alejandra; Rueda, Oscar M; Greenwood, Wendy; Batra, Ankita Sati; Callari, Maurizio; Batra, Rajbir Nath; Pogrebniak, Katherine; Sandoval, Jose; Cassidy, John W; Tufegdzic-Vidakovic, Ana; Sammut, Stephen-John; Jones, Linda; Provenzano, Elena; Baird, Richard; Eirew, Peter; Hadfield, James; Eldridge, Matthew; McLaren-Douglas, Anne; Barthorpe, Andrew; Lightfoot, Howard; O'Connor, Mark J; Gray, Joe; Cortes, Javier; Baselga, Jose; Marangoni, Elisabetta; Welm, Alana L; Aparicio, Samuel; Serra, Violeta; Garnett, Mathew J; Caldas, Carlos

    2016-09-22

    The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection of breast cancer patient-derived tumor xenografts (PDTXs), in which the morphological and molecular characteristics of the originating tumor are preserved through passaging in the mouse. An integrated platform combining in vivo maintenance of these PDTXs along with short-term cultures of PDTX-derived tumor cells (PDTCs) was optimized. Remarkably, the intra-tumor genomic clonal architecture present in the originating breast cancers was mostly preserved upon serial passaging in xenografts and in short-term cultured PDTCs. We assessed drug responses in PDTCs on a high-throughput platform and validated several ex vivo responses in vivo. The biobank represents a powerful resource for pre-clinical breast cancer pharmacogenomic studies (http://caldaslab.cruk.cam.ac.uk/bcape), including identification of biomarkers of response or resistance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. A population genetics perspective on the determinants of intra-tumor heterogeneity.

    Science.gov (United States)

    Hu, Zheng; Sun, Ruping; Curtis, Christina

    2017-04-01

    Cancer results from the acquisition of somatic alterations in a microevolutionary process that typically occurs over many years, much of which is occult. Understanding the evolutionary dynamics that are operative at different stages of progression in individual tumors might inform the earlier detection, diagnosis, and treatment of cancer. Although these processes cannot be directly observed, the resultant spatiotemporal patterns of genetic variation amongst tumor cells encode their evolutionary histories. Such intra-tumor heterogeneity is pervasive not only at the genomic level, but also at the transcriptomic, phenotypic, and cellular levels. Given the implications for precision medicine, the accurate quantification of heterogeneity within and between tumors has become a major focus of current research. In this review, we provide a population genetics perspective on the determinants of intra-tumor heterogeneity and approaches to quantify genetic diversity. We summarize evidence for different modes of evolution based on recent cancer genome sequencing studies and discuss emerging evolutionary strategies to therapeutically exploit tumor heterogeneity. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Presence of intratumoral platelets is associated with tumor vessel structure and metastasis

    International Nuclear Information System (INIS)

    Li, Rong; Zhang, Xu; Zhang, Zhuo; Zhang, Xiao; Ran, Bing; Wu, Jianbo; Ren, Meiping; Chen, Ni; Luo, Mao; Deng, Xin; Xia, Jiyi; Yu, Guang; Liu, Jinbo; He, Bing

    2014-01-01

    Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells. Abundant platelets were detected in the tumor microenvironment outside of the blood vessel, thus, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. However, it is unclear that platelet depletion affects tumor vessel structure and dynamics. Using thrombocytopenia induction in two different tumor-bearing mouse models, tumor tissues were performed by Westernblotting and immunohistochemical staining. Vascular permeability was evaluated by determination of intratumoral Evans blue and Miles vascular permeability assay. Furthermore, microdialysis was used to examining the intratumoral extracellular angiogenic growth factors (VEGF, TGF-β) by ELISA. Platelet depletion showed no change in tumor growth and reduced lung metastasis. Platelet depletion led to reduced tumor hypoxia and Met receptor activation and was associated with a decreased release of MMP-2, 9, PAI-1, VEGF, and TGF-β. Tumor vessels in platelet-depleted mice showed impaired vessel density and maturation. Our findings demonstrate that platelets within the primary tumor microenvironment play a critical role in the induction of vascular permeability and initiation of tumor metastasis

  8. Ovarian fibromas: MR imaging findings with emphasis on intratumoral cyst formation

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Hiroki, E-mail: hkato@gifu-u.ac.jp [Department of Radiology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Kanematsu, Masayuki, E-mail: masa_gif@yahoo.co.jp [Department of Radiology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); High-level Imaging Diagnosis Center, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1194 (Japan); Ono, Hiromi, E-mail: hiromi11_br@yahoo.co.jp [Department of Radiology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Yano, Ryuichiro, E-mail: yanoryu@gifu-u.ac.jp [Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu (Japan); Furui, Tatsuro, E-mail: furui@gifu-u.ac.jp [Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu (Japan); Morishige, Ken-ichirou, E-mail: mken@gifu-u.ac.jp [Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu (Japan); Hatano, Yuichiro, E-mail: yuha@gifu-u.ac.jp [Department of Pathology, Gifu University School of Medicine, Gifu (Japan)

    2013-09-15

    Purpose: The purpose of this study was to assess MR imaging findings of ovarian fibromas with emphasis on intratumoral cyst formation. Materials and methods: MR images with a 1.5-T unit obtained in 17 consecutive patients (age range, 18–87 years; mean age, 58 years) with 17 histologically proven ovarian fibromas were retrospectively reviewed for the size, configuration, signal intensity of solid components, and presence of cystic degeneration and edema within tumor. Size, number, and location of intratumoral cysts were also assessed. Results: The maximum diameter of tumors ranged from 3.3 to 19.1 cm (mean, 10.9 cm). Seven (41%) tumors were multinodular. On T2-weighted images, solid components of tumors were heterogeneously mixed hypo- and hyperintensity in 16 (94%) tumors. Nine (53%) tumors demonstrated cysts and 16 (94%) demonstrated edema within tumor. The maximum diameter of the largest cysts ranged from 1.0 to 13.2 cm (mean, 6.4 cm), and the number of cysts per tumor ranged from 1 to 60 (mean, 15.6). Of the nine tumors with cystic formation, the predominant location of the cysts was peripheral in five (56%), exophytic in two (22%), central (11%) in one, and diffuse in one (11%). Conclusion: Peripheral or exophytic cyst formation may be characteristic MR imaging features with ovarian fibromas.

  9. A single injection of the anabolic bone agent, parathyroid hormone-collagen binding domain (PTH-CBD), results in sustained increases in bone mineral density for up to 12 months in normal female mice.

    Science.gov (United States)

    Ponnapakkam, Tulasi; Katikaneni, Ranjitha; Suda, Hirofumi; Miyata, Shigeru; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert C

    2012-09-01

    Parathyroid hormone (PTH) is the most effective osteoporosis treatment, but it is only effective if administered by daily injections. We fused PTH(1-33) to a collagen binding domain (PTH-CBD) to extend its activity, and have shown an anabolic bone effect with monthly dosing. We tested the duration of action of this compound with different routes of administration. Normal young C57BL/6J mice received a single intraperitoneal injection of PTH-CBD (320 μg/kg). PTH-CBD treated mice showed a 22.2 % increase in bone mineral density (BMD) at 6 months and 12.8 % increase at 12 months. When administered by subcutaneous injection, PTH-CBD again caused increases in BMD, 15.2 % at 6 months and 14.3 % at 12 months. Radiolabeled PTH-CBD was concentrated in bone and skin after either route of administration. We further investigated skin effects of PTH-CBD, and histological analysis revealed an apparent increase in anagen VI hair follicles. A single dose of PTH-CBD caused sustained increases in BMD by >10 % for 1 year in normal mice, regardless of the route of administration, thus showing promise as a potential osteoporosis therapy.

  10. 5.7  W cw single-frequency laser at 671  nm by single-pass second harmonic generation of a 17.2  W injection-locked 1342  nm Nd : YVO4 ring laser using periodically poled MgO : LiNbO3.

    Science.gov (United States)

    Koch, Peter; Ruebel, Felix; Bartschke, Juergen; L'huillier, Johannes A

    2015-11-20

    We demonstrate a continuous wave single-frequency laser at 671.1 nm based on a high-power 888 nm pumped Nd:YVO4 ring laser at 1342.2 nm. Unidirectional operation of the fundamental ring laser is achieved with the injection-locking technique. A Nd:YVO4 microchip laser serves as the injecting seed source, providing a tunable single-frequency power of up to 40 mW. The ring laser emits a single-frequency power of 17.2 W with a Gaussian beam profile and a beam propagation factor of M2beam profile and a beam propagation factor of M2lasers. This work opens possibilities in cold atoms experiments with lithium, allowing the use of larger ensembles in magneto-optical traps or higher diffraction orders in atomic beam interferometers.

  11. Arterio-venous concentration difference of [51Cr]EDTA after a single injection in man. Significance of renal function and local blood flow

    DEFF Research Database (Denmark)

    Rehling, M; Hyldstrup, L; Henriksen, Jens Henrik Sahl

    1989-01-01

    , whereas the difference was very sensitive to even small changes in forearm blood flow within the physiological range. For measurement of renal plasma clearance it is recommended to use one long period: from the time of injection until 300 min p.i. or longer. If the clearance period is too short, the use......, different results may be obtained from venous and arterial samples. The simplified techniques using venous blood samples--which usually include some empirical corrections--should be sufficiently reliable in daily clinical practice provided the forearm blood flow is reasonably high, e.g. exposure to cold...... introduced in the measurement of renal plasma clearance and total plasma clearance by using venous blood samples instead of arterial. In 13 patients with GFR ranging from 29 to 150 ml min-1, Ca was higher than Cv immediately after the injection. After mean 38 min (range 12-82 min) the two curves crossed...

  12. Experimental investigations of a four-stroke single cylinder direct injection diesel engine operated on dual fuel mode with producer gas as inducted fuel and Honge oil and its methyl ester (HOME) as injected fuels

    Energy Technology Data Exchange (ETDEWEB)

    Banapurmath, N.R.; Tewari, P.G. [Department of Mechanical Engineering, B.V.B. College of Engineering and Technology, Hubli 580031, Karnataka (India); Hosmath, R.S. [Department of Mechanical Engineering, K.L.E Society' s College of Engineering and Technology, Belgaum, Karnataka (India)

    2008-09-15

    In order to meet the energy requirements, there has been growing interest in alternative fuels like biodiesels, methyl alcohol, ethyl alcohol, biogas, hydrogen and producer gas to provide a suitable diesel oil substitute for internal combustion engines. Vegetable oils present a very promising alternative to diesel oil since they are renewable and have similar properties. Vegetable oils offer almost the same power output with slightly lower thermal efficiency when used in diesel engine [Srivastava A, Prasad R. Triglycerides-based diesel fuels. Renew Sustain Energy Rev 2000;4:111-33.; Vellguth G. Performance of vegetable oils and their monoesters as fuels for diesel engines. SAE 831358, 1983.; Demirbas A. Biodiesel production from vegetable oils via catalytic and non-catalytic supercritical methanol transesterification methods. Int J Prog Energy Combust Sci 2005;31:466-87.; Jajoo BN, Keoti RS. Evaluation of vegetable oils as supplementary fuels for diesel engines. In: Proceedings of the XV national conference on IC engines and combustion, Anna University Chennai, 1997.; Altin R, Cetinkaya S, Yucesu HS. The potential of using vegetable oil fuels as fuel for diesel engines. Int J Energy Convers Manage 2000;42:529-38, 248.; Gajendra Babu MK, Chandan Kumar Das LM. Experimental investigations on a Karanja oil methyl ester fuelled DI diesel engine. SAE 2006-01-0238, 2006.; Agarwal D, Kumar Agarwal A. Performance and emission characteristics of a Jatropha oil (preheated and blends) in a direct injection compression ignition engine. Int J Appl Therm Eng 2007;27:2314-23. ]. Research in this direction with edible oils have yielded encouraging results, but their use as fuel for diesel engine has limited applications due to higher domestic requirement [Scholl Kyle W, Sorenson Spencer C. Combustion Analysis of soyabean oil methyl ester in a direct injection diesel engine. SAE 930934, 1993.; Nwafor OMI. Effect of advanced injection timing on the performance of rapeseed oil in

  13. Effect of Pilot Injection Timings on the Combustion Temperature Distribution in a Single-Cylinder CI Engine Fueled with DME and ULSD

    OpenAIRE

    Jeon Joonho; Park Yong Hee; Kwon Sang Il; Park Sungwook

    2016-01-01

    Many studies of DiMethyl Ether (DME) as an alternative fuel in Compression-Ignition (CI) engines have been performed. Although diverse DME engine research has been conducted, the investigation of combustion behavior and temperature distribution in the combustion engine has not progressed due to the fact that there is no sooting flame in DME combustion. In order to investigate the combustion characteristics in this study, the KIVA-3 V code was implemented to research various pilot injection st...

  14. Axonal transport in rats rendered paraplegic following a single subarachnoid injection of either batrachotoxin or 6-aminonicotinamide into the spinal cord.

    Science.gov (United States)

    Boegman, R J; Albuquerque, E X

    1980-05-01

    Batrachotoxin (BTX) or 6-aminonicotinamide (6-AN) when injected into the subarachnoidal space of the lumbar spinal cord block fast axonal transport of 3H-protein in motor nerves. Axonal transport recovers partially within one day after administering BTX while the effect of 6-AN lasts for more than 21 days. These observations are discussed in relation to the onset and recovery of membrane depolarization observed in the extensor muscle.

  15. Single center experience with endoscopic subureteral dextranomer/hyaluronic acid injection as first line treatment in 1,551 children with intermediate and high grade vesicoureteral reflux.

    Science.gov (United States)

    Puri, Prem; Kutasy, Balazs; Colhoun, Eric; Hunziker, Manuela

    2012-10-01

    In recent years the endoscopic injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis and the surgical management of vesicoureteral reflux. We determined the safety and effectiveness of the endoscopic injection of dextranomer/hyaluronic acid as first line treatment for high grade vesicoureteral reflux. Between 2001 and 2010, 1,551 children (496 male, 1,055 female, median age 1.6 years) underwent endoscopic correction of intermediate and high grade vesicoureteral reflux using dextranomer/hyaluronic acid soon after the diagnosis of vesicoureteral reflux on initial voiding cystourethrogram. Vesicoureteral reflux was unilateral in 761 children and bilateral in 790. Renal scarring was detected in 369 (26.7%) of the 1,384 patients who underwent dimercapto-succinic acid imaging. Reflux grade in the 2,341 ureters was II in 98 (4.2%), III in 1,340 (57.3%), IV in 818 (34.9%) and V in 85 (3.6%). Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure, and renal ultrasound was performed annually thereafter. Patients were followed for 3 months to 10 years (median 5.6 years). Vesicoureteral reflux resolved after the first, second and third endoscopic injection of dextranomer/hyaluronic acid in 2,039 (87.1%), 264 (11.3%) and 38 (1.6%) ureters, respectively. Febrile urinary tract infections developed during followup in 69 (4.6%) patients. None of the patients in the series needed reimplantation of ureters or experienced any significant complications. Our results confirm the safety and efficacy of the endoscopic injection of dextranomer/hyaluronic acid in the eradication of high grade vesicoureteral reflux. We recommend this 15-minute outpatient procedure as the first line of treatment for high grade vesicoureteral reflux. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  16. Single intradiscal injection of the interleukin-6 receptor antibody tocilizumab provides short-term relief of discogenic low back pain; prospective comparative cohort study.

    Science.gov (United States)

    Sainoh, Takeshi; Orita, Sumihisa; Miyagi, Masayuki; Inoue, Gen; Yamauchi, Kazuyo; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Inage, Kazuhide; Sato, Jun; Nakata, Yukio; Aoki, Yasuchika; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-01-01

    Inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, are gaining attention as important etiologic factors associated with discogenic low back pain. We conducted a prospective cohort study to evaluate the efficacy and safety of intradiscal injection of the interleukin-6 receptor antibody tocilizumab in patients with discogenic low back pain. Thirty-two consecutive patients were intradiscally injected with 2 mL of 0.5% bupivacaine (control group). Another 31 consecutive patients were intradiscally injected with 40 mg tocilizumab and 1-2 mL of 0.5% bupivacaine (tocilizumab group) at the same time. Prior to treatment, the vertebral origin of low back pain was confirmed in all patients based on pain provocation during discography and pain relief with 1 mL of 1% xylocaine. Numeric rating scale and Oswestry disability index scores were used to evaluate pain level before and after treatment between the 2 groups. The association between pain relief with tocilizumab and intervertebral disc degeneration grade was also determined. At the end of the study (8 weeks after treatment), 30 patients in each group were evaluable. In the tocilizumab group, numeric rating scale and Oswestry disability index scores improved significantly at 2 and 4 weeks after treatment, respectively. Intervertebral disc degeneration was not associated with improvement of numeric rating scale score in the tocilizumab group. Local infection (i.e., discitis) was observed in 1 patient in the tocilizumab group. The results demonstrate the clinical relevance of interleukin-6 in discogenic low back pain. Intradiscal tocilizumab injection was shown to exert a short-term analgesic effect in patients with discogenic low back pain. Further research is required to determine the long-term effects of intradiscal tocilizumab therapy in patients with discogenic low back pain. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  17. Oxytocin via Uniject (a prefilled single-use injection) versus oral misoprostol for prevention of postpartum haemorrhage at the community level: a cluster-randomised controlled trial

    OpenAIRE

    Ayisha Diop, MPH; Bocar Daff, MD; Maimouna Sow, MA; Jennifer Blum, MPH; Mamadou Diagne, PhD; Nancy L Sloan, DrPH; Beverly Winikoff, MD

    2016-01-01

    Background: Access to injectable uterotonics for management of postpartum haemorrhage remains limited in Senegal outside health facilities, and misoprostol and oxytocin delivered via Uniject have been deemed viable alternatives in community settings. We aimed to compare the efficacy of these drugs when delivered by auxiliary midwives at maternity huts. Methods: We did an unmasked cluster-randomised controlled trial at maternity huts in three districts in Senegal. Maternity huts with auxili...

  18. Pharmacokinetics and Bioavailability of the GnRH Analogs in the Form of Solution and Zn2+-Suspension After Single Subcutaneous Injection in Female Rats.

    Science.gov (United States)

    Suszka-Świtek, Aleksandra; Ryszka, Florian; Dolińska, Barbara; Dec, Renata; Danch, Alojzy; Filipczyk, Łukasz; Wiaderkiewicz, Ryszard

    2017-04-01

    Although many synthetic gonadoliberin analogs have been developed, only a few of them, including buserelin, were introduced into clinical practice. Dalarelin, which differs from buserelin by just one aminoacid in the position 6 (D-Ala), is not widely used so far. Gonadotropin-releasing hormone (GnRH) analogs are used to treat many different illnesses and are available in different forms like solution for injection, nasal spray, microspheres, etc. Unfortunately, none of the above drug formulations can release the hormones for 24 h. We assumed that classical suspension could solve this problem. Two sets of experiments were performed. In the first one, buserelin and dalarelin were injected into mature female rats in two forms: suspension, in which the analogs are bounded by Zn 2+ ions and solution. The pharmacokinetic parameters and bioavailability of the analogs were calculated, based on their concentration in the plasma measured by high-performance liquid chromatography method (HPLC). In the second experiment, the hormones in two different forms were injected into superovulated immature female rats and then the concentration of Luteinizing hormone (LH), Follicle-stimulating hormone (FSH) and 17β-estradiol in the serum was measured by radioimmunological method. The Extent of Biological Availability (EBA), calculated on the base of AUC 0-∞ , showed that in the form of solution buserelin and dalarelin display, respectively, only 13 and 8 % of biological availability of their suspension counterparts. Comparing both analogs, the EBA of dalarelin was half (53 %) that of buserelin delivered in the form of solution and 83 % when they were delivered in the form of suspension. The injection of buserelin or dalarelin, in the form of solution or suspension, into superovulated female rats increased LH, FSH and estradiol concentration in the serum. However, after injection of the analogs in the form of suspension, the high concentration of LH and FSH in the serum persisted

  19. Transcriptional profiling of dividing tumor cells detects intratumor heterogeneity linked to cell proliferation in a brain tumor model

    Czech Academy of Sciences Publication Activity Database

    Endaya, B.; Lam, P.Y.P.; Meedeniya, A.C.B.; Neužil, Jiří

    2016-01-01

    Roč. 10, č. 1 (2016), s. 126-137 ISSN 1574-7891 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Intratumor heterogeneity * Click chemistry * Proliferation * Gene profiling Subject RIV: FD - Oncology ; Hematology Impact factor: 5.314, year: 2016

  20. Rapid Quantitative Analysis of Multiple Explosive-Compound Classes on a Single Instrument via Flow-Injection Analysis Tandem Mass Spectrometry

    Science.gov (United States)

    2017-06-09

    tailoring the ionization method , declustering potentials, and collision energies for each specific analyte. In doing so, a single instrument can be...of both conventional explosives, homemade explosives, and their related compounds, and many of these methods require special instrumentation . A...10%, respectively, compare favorably to existing methods . Use of a single instrument for detection of multiple explosive classes also reduces the

  1. Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance

    Directory of Open Access Journals (Sweden)

    Berteau C

    2015-11-01

    Full Text Available Cecile Berteau,1 Orchidée Filipe-Santos,1 Tao Wang,2 Humberto E Rojas,2 Corinne Granger,1 Florence Schwarzenbach1 1Becton-Dickinson Medical Pharmaceutical Systems, Le Pont de Claix, France; 2Eli Lilly and Company, Indianapolis, IN, USA Aim: The primary objective of this study was to evaluate the impact of fluid injection viscosity in combination with different injection volumes and flow rates on subcutaneous (SC injection pain tolerance. Methods: The study was a single-center, comparative, randomized, crossover, Phase I study in 24 healthy adults. Each participant received six injections in the abdomen area of either a 2 or 3 mL placebo solution, with three different fluid viscosities (1, 8–10, and 15–20 cP combined with two different injection flow rates (0.02 and 0.3 mL/s. All injections were performed with 50 mL syringes and 27G, 6 mm needles. Perceived injection pain was assessed using a 100 mm visual analog scale (VAS (0 mm/no pain, 100 mm/extreme pain. The location and depth of the injected fluid was assessed through 2D ultrasound echography images. Results: Viscosity levels had significant impact on perceived injection pain (P=0.0003. Specifically, less pain was associated with high viscosity (VAS =12.6 mm than medium (VAS =16.6 mm or low (VAS =22.1 mm viscosities, with a significant difference between high and low viscosities (P=0.0002. Target injection volume of 2 or 3 mL was demonstrated to have no significant impact on perceived injection pain (P=0.89. Slow (0.02 mL/s or fast (0.30 mL/s injection rates also showed no significant impact on perceived pain during SC injection (P=0.79. In 92% of injections, the injected fluid was located exclusively in SC tissue whereas the remaining injected fluids were found located in SC and/or intradermal layers. Conclusion: The results of this study suggest that solutions of up to 3 mL and up to 15–20 cP injected into the abdomen within 10 seconds are well tolerated without pain. High

  2. Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Rubin, Daniel L. [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Department of Medicine (Biomedical Informatics Research), Stanford University School of Medicine, Stanford, California (United States); Napel, Sandy [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Li, Ruijiang, E-mail: rli2@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States)

    2016-08-01

    Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust

  3. Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

    International Nuclear Information System (INIS)

    Bonde, Anne-Katrine; Tischler, Verena; Kumar, Sushil; Soltermann, Alex; Schwendener, Reto A

    2012-01-01

    Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT) at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM) reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC). Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. Data presented here identify a novel role for macrophages in EMT

  4. Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

    Directory of Open Access Journals (Sweden)

    Bonde Anne-Katrine

    2012-01-01

    Full Text Available Abstract Background Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. Methods We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC. Results Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. Conclusions Data

  5. Combined treatment with ipilimumab and intratumoral interleukin-2 in pretreated patients with stage IV melanoma-safety and efficacy in a phase II study.

    Science.gov (United States)

    Weide, Benjamin; Martens, Alexander; Wistuba-Hamprecht, Kilian; Zelba, Henning; Maier, Ludwig; Lipp, Hans-Peter; Klumpp, Bernhard D; Soffel, Daniel; Eigentler, Thomas K; Garbe, Claus

    2017-04-01

    Treatment of advanced melanoma patients with ipilimumab results in improved survival. However, only about 20% of treated patients experience long-term benefit. Combining treatment of ipilimumab with other drugs may improve immune activation and potentially enhance clinical efficacy. The aims of the phase II clinical trial reported here were to investigate tolerability and efficacy of a combined immunotherapeutic strategy comprising standard systemic ipilimumab at 3 mg/kg four times at 3-week intervals and intratumorally injected IL-2 at 9 MIU daily twice weekly for four weeks in pretreated melanoma patients with distant metastasis. The primary endpoint was the disease control rate according to immune-related response criteria at week 12; tolerability according to Common Terminology Criteria for Adverse Events criteria was secondary endpoint. No objective responses were observed in the 15 enrolled patients. Three patients had stable disease 12 weeks after starting treatment, yielding a disease control rate of 20%. Tolerability of this combination treatment was acceptable. Observed adverse events were those expected from the respective monotherapies. Autoimmune colitis was observed in two patients. Grade III/IV adverse events were observed in 40% of patients, and no treatment-related deaths occurred. Thus, this combined immunotherapy is associated with adverse events similar to those associated with the respective monotherapies. However, this study does not provide any evidence of improved efficacy of the combination over ipilimumab alone.

  6. Synthesis of Poly[APMA]-DOTA-64Cu Conjugates for Interventional Radionuclide Therapy of Prostate Cancer: Assessment of Intratumoral Retention by Micro–Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    Jianchao Yuan

    2007-01-01

    Full Text Available To develop new radiopharmaceuticals for interventional radionuclide therapy of locally recurrent prostate cancer, poly[N-(3-aminopropylmethacrylamide] [poly(APMA] polymers were synthesized by free radical precipitation polymerization in acetonedimethylsulfoxide using N,N‘-azobis(isobutyronitrile as the initiator. The polymers were characterized with nuclear magnetic resonance, size exclusion chromatography, and dynamic light scattering (Mn 5 2.40 × 104, Mw/Mn = 1.87. Subsequently, poly[APMA] was coupled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA using 1-(3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride as an activator, followed by conjugation with 64Cu radionuclide. Prolonged retention of poly[APMA]-DOTA-64Cu conjugates within the tumor tissues was demonstrated by micro–positron emission tomography at 24 hours following intra-tumoral injection of the conjugates to human prostate xenografts in mice. The data suggest that the poly[APMA]-DOTA-64Cu conjugates might be useful for interventional radionuclide therapy of locally recurrent prostate cancer in humans.

  7. Comparative efficacy of intra-articular hyaluronic acid and corticoid injections in osteoarthritis of the first carpometacarpal joint: results of a 6-month single-masked randomized study.

    Science.gov (United States)

    Monfort, Jordi; Rotés-Sala, Delfin; Segalés, Nuria; Montañes, Francisco-Jose; Orellana, Cristobal; Llorente-Onaindia, Jone; Mojal, Sergi; Padró, Isabel; Benito, Pere

    2015-03-01

    The study aim was to compare the efficacy and safety of ultrasound-guided intra-articular injections of hyaluronic acid and betamethasone in the management of patients with osteoarthritis of the thumb. Eighty-eight evaluable patients diagnosed with osteoarthritis of the thumb (Kellgren-Lawrence grade II-III) received ultrasound-guided intra-articular treatment with hyaluronic acid (48) or betamethasone (40). In total, 3 local injections were scheduled at 7-day intervals. Assessments were performed at baseline and at 7, 14, 30, 90, and 180 days. In both study groups, the pain Visual Analogue Scale and Functional Index for Hand Osteoarthritis scores decreased significantly during follow-up compared to baseline. There were no significant differences between the groups. However, at 90 days, the functional score showed a trend towards greater clinical improvement in the hyaluronic acid group (P 0.071). A subanalysis of patients with Functional Index score≥5 and Visual Analogue Scale score≥3 at baseline showed a significantly higher median functionality score in the hyaluronic acid group (P 0.005 at 90 days and P 0.020 at 180 days). Further limiting analysis to a baseline pain score≥5 showed significantly greater improvement in functionality score (P 0.004 at 180 days), which was already apparent after the second intra-articular injection at 14 days (P 0.028). In this patient subset, the mean pain score also improved significantly at 180 days (P 0.02). Both hyaluronic acid and betamethasone were effective and well-tolerated for the management of rhizarthrosis. Hyaluronic acid was more effective over time and more efficiently improved functionality and pain in patients with more severe symptoms. Copyright © 2014 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  8. Bringing SASI back: Single session selective arterial secretin injection and transarterial embolization of intrahepatic pancreatic neuroendocrine metastasis in a MEN-1 patient

    Directory of Open Access Journals (Sweden)

    Jawad S. Hussain, MD, MS

    2018-04-01

    Full Text Available SASI (selective arterial secretin injection is a form of ASVS (arterial stimulation and venous sampling used to localize pancreatic gastrinomas. This report aims to review the protocol for SASI and demonstrate its utility in localizing functional and nonfunctional gastrinomas. Even if a patient has a pancreatic mass and a laboratory profile fitting a specific endocrine syndrome, these may or may not be associated as has been previously demonstrated with adrenal vein sampling. We present a case where a patient underwent simultaneous SASI and bland embolization of a hepatic metastasis to facilitate partial pancreatectomy for Zollinger-Ellison syndrome. Keywords: SASI, ASVS, Gastrinoma, Sampling

  9. Ceftazidime Injection

    Science.gov (United States)

    ... is used to treat certain infections caused by bacteria including pneumonia and other lower respiratory tract (lung) infections; meningitis (infection of the membranes that surround the brain and spinal cord) and ... killing bacteria.Antibiotics such as ceftazidime injection will not work ...

  10. Teduglutide Injection

    Science.gov (United States)

    ... who need additional nutrition or fluids from intravenous (IV) therapy. Teduglutide injection is in a class of medications ... of the ingredients.tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking ...

  11. Dexrazoxane Injection

    Science.gov (United States)

    ... are used to treat or prevent certain side effects that may be caused by chemotherapy medications. Dexrazoxane injection (Zinecard) is used to prevent or decrease heart damage caused by doxorubicin in women who are taking the medication to treat breast cancer that has spread to other parts of the ...

  12. Dulaglutide Injection

    Science.gov (United States)

    ... thyroid carcinoma (MTC; a type of thyroid cancer). Laboratory animals who were given dulaglutide developed tumors, but it ... your doctor will probably tell you not to use dulaglutide injection. If you ... doctor and the laboratory. Your doctor may order certain tests to check ...

  13. Albiglutide Injection

    Science.gov (United States)

    ... thyroid carcinoma (MTC; a type of thyroid cancer). Laboratory animals who were given medications similar to albiglutide developed ... your doctor will probably tell you not to use albiglutide injection. If you ... doctor and the laboratory. Your doctor may order certain tests to check ...

  14. Semaglutide Injection

    Science.gov (United States)

    ... thyroid carcinoma (MTC; a type of thyroid cancer). Laboratory animals who were given semaglutide developed tumors, but it ... your doctor will probably tell you not to use semaglutide injection. If you ... doctor and the laboratory. Your doctor may order certain tests to check ...

  15. Liraglutide Injection

    Science.gov (United States)

    ... thyroid carcinoma (MTC; a type of thyroid cancer). Laboratory animals who were given liraglutide developed tumors, but it ... your doctor will probably tell you not to use liraglutide injection. If you ... doctor and the laboratory. Your doctor may order certain tests to check ...

  16. Exenatide Injection

    Science.gov (United States)

    ... thyroid carcinoma (MTC; a type of thyroid cancer). Laboratory animals who were given exenatide developed tumors, but it ... your doctor will probably tell you not to use exenatide injection. If you ... doctor and the laboratory. Your doctor may order certain tests to check ...

  17. Etoposide Injection

    Science.gov (United States)

    ... used in combination with other medications to treat cancer of the testicles that has not improved or that has worsened after treatment with other medications or radiation therapy. Etoposide injection ... type of lung cancer (small cell lung cancer; SCLC). Etoposide is in ...

  18. Cefepime Injection

    Science.gov (United States)

    ... infection because they have a low number of white blood cells. Cefepime injection is in a class ... In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has ...

  19. Triptorelin Injection

    Science.gov (United States)

    ... puberty too soon, resulting in faster than normal bone growth and development of sexual characteristics) in children 2 years and older. Triptorelin injection is in a class of medications called gonadotropin-releasing hormone (GnRH) agonists. It works by decreasing the amount ...

  20. Out-of-plane integration of a multimode optical fiber for single particle/cell detection at multiple points on a microfluidic device with applications to particle/cell counting, velocimetry, size discrimination and the analysis of single cell lysate injections.

    Science.gov (United States)

    Sadeghi, Jalal; Patabadige, Damith E W; Culbertson, Anne H; Latifi, Hamid; Culbertson, Christopher T

    2016-12-20

    In this paper a single particle/cell-tracking microfluidic device that integrates an out-of-plane multimode optical fiber (OP-MMF) is reported. This OP-MMF is used to generate three excitation light-lines and three detection spots using only one excitation source and one detector. It takes advantage of an optical tunneling mode to create two excitation lines in a microfluidic channel emanating from a single fiber end. This method was used to accurately count particles/cells and perform velocity measurements and size discrimination. The velocity and size distributions of 5, 7, and 10 μm fluorescently labeled polystyrene beads were determined using the OP-MMF. Additionally, this method was used to analyze cell lysates with the third excitation line in the separation channel. The OP-MMF setup accurately detected an intact cell twice ∼2 mm prior to lysis, determined its velocity, and detected the injected cell lysate 3 mm downstream of the injection point in the separation channel. Using this setup, the velocity of cells entering the lysis intersection and the absolute migration times of fluorescently labeled analytes injected into the separation channel were determined in an automated fashion. This method enabled us to determine a lysing/injection efficiency coefficient (K) using signals from the injected lysate signal and from the intact cell before lysing. K provided a reliable measurement of the amount of cell lysate that was injected into the separation channel. The approach reported here could be used in the future to track particles, cells or droplets in a variety of existing microfluidic devices without the need for multiplexed masks, layers, bulky optical elements or complex optical designs.

  1. Optimum time of blood sampling for determination of glomerular filtration rate by single-injection [51Cr]EDTA plasma clearance

    International Nuclear Information System (INIS)

    Broechner-Mortensen, J.; Roedbro, P.

    1976-01-01

    We have investigated the influence on reproducibility of total [ 51 Cr]EDTA plasma clearance (E) of various times and numbers of blood samples in patients with normal (13 patients) and low (14 patients) renal function. The study aims at fixing a clinically useful procedure suitable for all levels of renal function. Six different types of E were evaluated with time periods for blood sampling between 3 and 5 h after tracer injection, and the variation from counting radioactivity, s 1 , was determined as part of the total variation, s 2 . Optimum mean time, t(E), for blood sampling was calculated as a function of E, as the mean time giving the least change in E for a given change in the 'final slope' of the plasma curve. For patients with normal E, s 1 did not contribute significantly to s 2 , and t(E) was about 2h. For patients with low renal function s 1 contributed significantly to s 2 , and t(E) increased steeply with decreasing E. The relative error in s 1 from fixed Etypes was calculated for all levels of renal function. The results indicate that blood sampling individualized according to predicted E values is not necessary. A sufficient precision of E can be achieved for all function levels from three blood samples drawn at 180, 240, and 300 min after injection. (Auth.)

  2. Experimental study of the injection conditions influence over n-dodecane and diesel sprays with two ECN single-hole nozzles. Part I: Inert atmosphere

    International Nuclear Information System (INIS)

    Gimeno, Jaime; Bracho, Gabriela; Martí-Aldaraví, Pedro; Peraza, Jesús E.

    2016-01-01

    In this research, two Engine Combustion Network (ECN) mono-orifice nozzles, referred to as Spray C and Spray D respectively, were analyzed by performing visualization tests through Schlieren and Diffused Backlight Illumination (DBI) techniques under a wide range of ambient conditions in a non-reactive atmosphere. Spray C presents a straight nozzle designed with a sharp fillet in opposition to Spray D that has similar hydraulic properties, but with a convergent nozzle construction and a smoother corner. The experiments were carried out injecting two distinct fuels at different injection pressure ranges, from 50 MPa to 150 MPa with n-dodecane and to 200 MPa for diesel. The images were processed with Matlab home-built routines to calculate parameters as spray penetration, spreading angle, quasi-steady liquid length, as well as the spray penetration derivative respect to the square root of time, presented in this document as R-parameter. The results showed a clear influence of nozzle geometry in all measured parameters, due mainly to the nature of Spray C to cavitation, which increase the spreading angle and consequently a reduction in vapor penetration. On the other hand, fuel properties also affected spray penetration due to its dependency on viscous forces expressed in terms of the Reynolds number and its volatility in case of liquid length. This last parameter was calculated employing two processing methodologies, finding a good general agreement between them.

  3. The role of intratumoral and systemic IL-6 in breast cancer

    DEFF Research Database (Denmark)

    Dethlefsen, Christine; Højfeldt, Grith Westergaard; Hojman, Pernille

    2013-01-01

    Chronic low-grade inflammation plays an important role in the pathogenesis of several cancer forms including breast cancer. The pleiotropic cytokine IL-6 is a key player in systemic inflammation, regulating both the inflammatory response and tissue metabolism during acute stimulations. Here, we...... review the associations between IL-6 and breast cancer ranging from in vitro cell culture studies to clinical studies, covering the role of IL-6 in controlling breast cancer cell growth, regulation of cancer stem cell renewal, as well as breast cancer cell migration. Moreover, associations between......, while high circulating IL-6 levels are correlated with a poor prognosis in breast cancer patients. This discrepancy reflects distinct roles of IL-6, with elevated systemic levels being a biomarker for tumor burden, physical inactivity, and impaired metabolism, while local intratumoral IL-6 signaling...

  4. Tumor treatment by sustained intratumoral release of cisplatin: effects of drug alone and combined with radiation

    International Nuclear Information System (INIS)

    Yapp, Donald T.T.; Lloyd, David K.; Zhu, Julian; Lehnert, Shirley M.

    1997-01-01

    Purpose: The effect of intratumoral delivery of cisplatin to a mouse tumor model (RIF-1) by means of a biodegradable polymer implant with and without radiation was studied. Methods and Materials: The polymer bis(p-carboxyphenoxy)propane-sebacic acid (CPP:SA; 80:20) and its degradation products have been characterized. Polymer rods (8 x 0.5 mm) containing 17% cisplatin by weight were prepared by extrusion, and the in vitro degradation rate measured. The implants were placed into mouse tumors and their effect (with and without radiation) on tumor growth delay studied. The levels of Pt in the mouse kidney, tumor, and blood plasma at selected intervals after implant were also determined. These results were compared with those obtained when cisplatin was delivered systematically. Results: When cisplatin was delivered by the polymer implants, higher levels were present in the tumor for longer time periods (cf. systemic delivery of the drug). For both nonirradiated and irradiated tumors, those treated with the polymer implants had significantly longer tumor growth delays compared to nonimplanted controls and to systematically treated tumors. Conclusions: The results show that intratumoral delivery of cisplatin is more efficient than systemic delivery. Using the biodegradable polymer implant, higher doses of cisplatin can be tolerated by the animal as the drug is localized within the tumor, and the high levels of the drug in the tumor can be maintained for an extended period of time. When radiation is given in conjunction with cisplatin, the tumor response is supraadditive for all modes of cisplatin administration but is potentiated to a greater extent when cisplatin is delivered through the polymer implant. The greatest effect is seen for treatment with cisplatin delivered by polymer implant combined with fractionated radiation

  5. Pointwise mutual information quantifies intratumor heterogeneity in tissue sections labeled with multiple fluorescent biomarkers

    Directory of Open Access Journals (Sweden)

    Daniel M Spagnolo

    2016-01-01

    Full Text Available Background: Measures of spatial intratumor heterogeneity are potentially important diagnostic biomarkers for cancer progression, proliferation, and response to therapy. Spatial relationships among cells including cancer and stromal cells in the tumor microenvironment (TME are key contributors to heterogeneity. Methods: We demonstrate how to quantify spatial heterogeneity from immunofluorescence pathology samples, using a set of 3 basic breast cancer biomarkers as a test case. We learn a set of dominant biomarker intensity patterns and map the spatial distribution of the biomarker patterns with a network. We then describe the pairwise association statistics for each pattern within the network using pointwise mutual information (PMI and visually represent heterogeneity with a two-dimensional map. Results: We found a salient set of 8 biomarker patterns to describe cellular phenotypes from a tissue microarray cohort containing 4 different breast cancer subtypes. After computing PMI for each pair of biomarker patterns in each patient and tumor replicate, we visualize the interactions that contribute to the resulting association statistics. Then, we demonstrate the potential for using PMI as a diagnostic biomarker, by comparing PMI maps and heterogeneity scores from patients across the 4 different cancer subtypes. Estrogen receptor positive invasive lobular carcinoma patient, AL13-6, exhibited the highest heterogeneity score among those tested, while estrogen receptor negative invasive ductal carcinoma patient, AL13-14, exhibited the lowest heterogeneity score. Conclusions: This paper presents an approach for describing intratumor heterogeneity, in a quantitative fashion (via PMI, which departs from the purely qualitative approaches currently used in the clinic. PMI is generalizable to highly multiplexed/hyperplexed immunofluorescence images, as well as spatial data from complementary in situ methods including FISSEQ and CyTOF, sampling many different

  6. Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hai-Jeon [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Kim, Yemi [Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of); Kim, Bom Sahn [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of)

    2015-12-15

    This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent {sup 18}F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV{sub max} and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC{sub min}) and ADC difference (ADC{sub diff}) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV{sub max} (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC{sub min} (p = 0.016) and higher ADC{sub diff} (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of {sup 18}F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

  7. Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

    International Nuclear Information System (INIS)

    Yoon, Hai-Jeon; Kim, Yemi; Kim, Bom Sahn

    2015-01-01

    This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent 18 F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV max and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC min ) and ADC difference (ADC diff ) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV max (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC min (p = 0.016) and higher ADC diff (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of 18 F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

  8. Lymph Node Metastases in Papillary and Medullary Thyroid Carcinoma Are Independent of Intratumoral Lymphatic Vessel Density

    Science.gov (United States)

    Pereira, Filipe; Pereira, Sofia S.; Mesquita, Marta; Morais, Tiago; Costa, Madalena M.; Quelhas, Pedro; Lopes, Carlos; Monteiro, Mariana P.; Leite, Valeriano

    2017-01-01

    Background Blood and lymph vessel invasion are well-recognized markers of tumor aggressiveness, as these are the routes that lead to metastases. Thyroid tumors, depending on the histological variant, tend to have distinctive biological behaviors and use different vascular routes to metastasize, yet the mechanisms underlying the metastatic process are still poorly understood. Objectives The aim of this study was to assess how the lymph vessel density (LVD) in different histological types of thyroid tumors, and in their surrounding tissue, correlate with the presence of lymph node metastases (LNM) and tumor pathological features. Methods Lymph vessels of papillary thyroid carcinomas (PTC), of the classical (CVPTC, n = 50) and follicular variants (FVPTC, n = 18), and medullary thyroid carcinomas (MTC, n = 34) were immunohistochemically stained against antigen D2-40. The stained area was quantified using a computerized morphometric analysis tool and correlated with the tumor pathological characteristics. Results LVD within all analyzed thyroid tumor subtypes was significantly lower than in the surrounding thyroid tissues (p < 0.001). Despite intratumoral LVD being significantly higher in CVPTC than in FVPTC, and peritumoral LVD being significantly higher in MTC than in PTC (p < 0.05), no correlations were found between LVD (either intratumoral or peritumoral) and the presence of lymph node metastasis. Conclusions As no LVD differences were found amongst thyroid tumors with or without LNM, dissemination is more likely to depend on the tumor ability to invade the abundant lymph vessel network of the surrounding thyroid tissue than on the ability of the tumor to promote de novo lymphangiogenesis. PMID:28589086

  9. The efficacy of preventive parasternal single injection of bupivacaine on intubation time, blood gas parameters, narcotic requirement, and pain relief after open heart surgery: A randomized clinical trial study

    Directory of Open Access Journals (Sweden)

    Mahmoud Saeidi

    2011-01-01

    Full Text Available Background: Postsurgical pain usually results in some complications in the patients. This study has tried to investigate the effects of parasternal single injection of bupivacaine on postoperative pulmonary and pain consequences in patients after open heart surgery. Methods: : In a prospective double blind clinical study, 100 consenting patients undergoing elective open heart surgery were randomized into two groups. In case group, bupivacaine was injected at both sides of sternum, immediately before sternal closure. In the control group, no intervention was performed. Then, the patients were investigated regarding intubation period, length of ICU stay, arterial blood gas (ABG parameters, morphine requirement, and their severity of postoperative pain using a visual analogue scale (VAS device. Results: No differences were found between the two groups regarding to age, sex, pump time, operation time, and body mass index and preoperative cardiac ejection fraction. Mean intubation length in case group was much shorter than that in control group. Mean PaO 2 in case group was lower in different checking times in postoperative period. The patients in the case group needed less morphine compared to those in the control group during the 24-hour observation period in the ICU. Finally, mean VAS scores of pain in case group were significantly lower than those in control group at 6, 12, and 24 hours postoperatively. Conclusions: Patients′ pain relief by parasternal single injection of bupivacaine in early postoperative period can facilitate earlier ventilator weaning and tracheal extubation after open heart surgery as well as achieving lower pain scores and narcotic requirements.

  10. Predictive factors of adverse events after intravesical suburothelial onabotulinumtoxina injections for overactive bladder syndrome-A real-life practice of 290 cases in a single center.

    Science.gov (United States)

    Jiang, Yuan-Hong; Ong, Hueih-Ling; Kuo, Hann-Chorng

    2017-01-01

    Patients often experience adverse events (AEs) after intravesical onabotulinumtoxinA (BoNT-A) treatment for overactive bladder refractory to antimuscarinic agents. We investigated the prevalence and predictive factors of AEs in such patients. A total of 290 patients underwent intravesical BoNT-A (100 U) suburothelial injection. The age, gender, overactive bladder subtypes, medical co-morbidities, and neurological diseases of the patients were recorded. The maximum flow rate (Q max ), voided volume, post-void residual (PVR) volume, and voiding efficiency (VE) at baseline were analyzed to identify adverse events within 3 months after treatment. Acute urinary retention (AUR) developed in 24 patients (8.3%), and urinary tract infection (UTI) occurred in 44 (15.2%) within 3 months of treatment. Large PVR volume (>200 ml) occurred in 81 (27.9%), 68 (24.3%), and 49 (18.4%) patients 1, 3, and 6 months after treatment, respectively. AUR developed significantly more often in men, patients >61 years old, those with a baseline Q max ≤15 ml/sec, PVR ≥100 ml, and VE 61 years, low Q max , low voiding efficiency, and large PVR at baseline were also risk factors for adverse events. AUR, UTI, and large PVR volume are common AEs after BoNT-A treatment. Patients with overactive bladders that are at risk of developing AEs after BoNT-A injection should be informed of the possible AEs. Neurourol. Urodynam. 36:142-147, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  11. Significant changes in endogenous retinal gene expression assessed 1 year after a single intraocular injection of AAV-CNTF or AAV-BDNF

    Directory of Open Access Journals (Sweden)

    Chrisna J LeVaillant

    2016-01-01

    Full Text Available Use of viral vectors to deliver therapeutic genes to the central nervous system holds promise for the treatment of neurodegenerative diseases and neurotrauma. Adeno-associated viral (AAV vectors encoding brain-derived neurotrophic factor (BDNF or ciliary derived neurotrophic factor (CNTF promote the viability and regeneration of injured adult rat retinal ganglion cells. However, these growth-inducing transgenes are driven by a constitutively active promoter, thus we examined whether long-term AAV-mediated secretion of BDNF or CNTF affected endogenous retinal gene expression. One year after the intravitreal injection of AAV-green fluorescent protein (GFP, bi-cistronic AAV-BDNF-GFP or AAV-CNTF-GFP, mRNA was extracted and analyzed using custom 96 well polymerase chain reaction arrays. Of 93 test genes, 56% showed significantly altered expression in AAV-BDNF-GFP and/or AAV-CNTF-GFP retinas compared with AAV-GFP controls. Of these genes, 73% showed differential expression in AAV-BDNF versus AAV-CNTF injected eyes. To focus on retinal ganglion cell changes, quantitative polymerase chain reaction was undertaken on mRNA (16 genes obtained from fixed retinal sections in which the ganglion cell layer was enriched. The sign and extent of fold changes in ganglion cell layer gene expression differed markedly from whole retinal samples. Sustained and global alteration in endogenous mRNA expression after gene therapy should be factored into any interpretation of experimental/clinical outcomes, particularly when introducing factors into the central nervous system that require secretion to evoke functionality.

  12. Treatment of pediatric vesicoureteral reflux using endoscopic injection of hyaluronic acid/dextranomer gel: intermediate-term experience by a single surgeon.

    Science.gov (United States)

    Hsieh, Michael H; Madden-Fuentes, Ramiro J; Lindsay, Nicholas E; Roth, David R

    2010-07-01

    Endoscopic injection of non-animal-stabilized hyaluronic acid/dextranomer gel is an increasingly recognized treatment option for vesicoureteral reflux. The procedure is minor compared with open surgery and, when successful, avoids the need for long-term antibiotic prophylaxis. We present data from 3 years of using non-animal-stabilized hyaluronic acid/dextranomer gel to treat children with vesicoureteral reflux. Pediatric patients aged 16 years with uncomplicated primary vesicoureteral reflux were recruited for endoscopic treatment with non-animal-stabilized hyaluronic acid/dextranomer gel. A follow-up voiding cystourethrogram was scheduled at 2 weeks after treatment, and vesicoureteral reflux resolution was defined as grade 0. Repeat non-animal-stabilized hyaluronic acid/dextranomer gel treatment was offered to patients with persistent vesicoureteral reflux. Of 178 patients treated, 12 were lost to follow-up or yet to undergo post-treatment voiding cystourethrogram. The 166 remaining patients (efficacy population) had a mean age of 4.21 years (range: 0-16), and the median reflux grade was 3 (range: 1-5). Vesicoureteral reflux was resolved in 81.9% of patients and 86.4% of ureters after initial endoscopic treatment with non-animal-stabilized hyaluronic acid/dextranomer gel. The overall reflux resolution rate for patients increased to 89.6% after a second treatment in 19 patients, and 90.2% after a third treatment in 1 patient. No adverse events were reported. Five patients underwent open ureteral reimplantation after failed endoscopic injections. Endoscopic treatment with non-animal-stabilized hyaluronic acid/dextranomer gel is effective in a high proportion of children with vesicoureteral reflux and, in our opinion, should be considered as a first-line treatment option. Copyright 2010 Elsevier Inc. All rights reserved.

  13. Single-frequency operation of a broad-area laser diode by injection locking of a complex spatial mode via a double phase conjugate mirror

    NARCIS (Netherlands)

    van Voorst, P.D.; Offerhaus, Herman L.; Boller, Klaus J.

    2006-01-01

    We demonstrate what is believed to be the first phase-coherent locking of a high-power broad-area diode to a single-frequency master laser. We use photorefractive double phase conjugation to lock the diode in a selfoptimized complex spatial mode while the photorefractive crystal diffracts that

  14. Ecological effects of a single intraperitoneal injection of [{sup 14}C]-2,3,4,7,8-pentachlorodibenzofuran on feral populations of lake trout and white suckers

    Energy Technology Data Exchange (ETDEWEB)

    Delorme, P.D. [Univ. of Manitoba, Winnipeg (Canada); Lockhart, W.L.; Muir, D.C.G.; Mills, K.H.; Brown, S.B. [Dept. of Fisheries and Oceans, Winnipeg, Manitoba (Canada). Freshwater Inst.

    1994-12-31

    In 1989 a total of 24 lake trout and 35 white suckers from a small lake located in the Experimental Lakes Area (ELA) in northwestern Ontario were each targeted with an I.P. injection of [{sup 14}C]-s,3,4,7,8-pentachlorodibenzofuran in corn oil, to a dose of 1 ng{center_dot}g{sup {minus}1}. Fish were tagged, returned to the lake and recaptured during spawning runs in 1990, 1991 and 1992. Sub-samples of treated and control fish were sacrificed each year for residue and biochemical analyses. Treated females were spawned in 1990 and 1991. Analysis of tag-recapture data showed lower survival of treated lake trout over four years. Growth was significantly lower in white suckers in all years but unaffected in lake trout. Fertilization rate of eggs was lower in eggs from treated female white suckers, but not in lake trout. However, only 1 of 4 treated female lake trout recaptured had undergone oogenesis in the last two years of recaptures. Measurements of EROD showed sustained induction in both lake trout and white suckers. Hepatic levels of retinoids were significantly decreased in lake trout but not in white suckers. Calculated half-lives of P{sub 5}CDF were 9.6 years for lake trout and 4.3 years for white suckers. It appears that long term ecological performance was impaired in both species.

  15. Effect of palm methyl ester-diesel blends performance and emission of a single-cylinder direct-injection diesel engine

    Science.gov (United States)

    Said, Mazlan; Aziz, Azhar Abdul; Said, Mohd Farid Muhamad

    2012-06-01

    The purpose of this study is to investigate engine performance and exhaust emission when using several blends of neat palm oil methyl ester (POME) with conventional diesel (D2) in a small direct injection diesel engine, and to compare the outcomes to that of the D2 fuel. Engine performances, exhaust emissions, and some other important parameters were observed as a function of engine load and speed. In addition, the effect of modifying compression ratio was also carried out in this study. From the engine experimental work, neat and blended fuels behaved comparably to diesel (D2) in terms of fuel consumption, thermal efficiency and rate of heat released. Smoke density showed better results than that emitted by D2, operating under similar conditions due to the presence of inherited oxygen and lower sulphur content in the biofuel and its blends. The emissions of CO, CO2, and HC were also lower using blended mixtures and in its neat form. However, NOx concentrations were found to be slight higher for POME and its blends and this was largely due to higher viscosity of POME and possibly the presence of nitrogen in the palm methyl ester. General observation indicates that biofuel blends can be use without many difficulties in this type of engine but for optimized operation minor modifications to the engine and its auxiliaries are required.

  16. Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial

    Science.gov (United States)

    Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Ahangar, Azadeh Gharooee; Abadi, Porya Hassan; Mojgani, Parviz; Ahangar, Omid Gharooi

    2017-01-01

    Background and objectives: Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. Methods: In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. Results: A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P = .001), respectively (between subjects P = .631). There was no significant difference between PRGF and HA groups in patients’ satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. Conclusions: In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis. PMID:29051707

  17. Correlation of intra-tumor 18F-FDG uptake heterogeneity indices with perfusion CT derived parameters in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Florent Tixier

    Full Text Available Thirty patients with proven colorectal cancer prospectively underwent integrated 18F-FDG PET/DCE-CT to assess the metabolic-flow phenotype. Both CT blood flow parametric maps and PET images were analyzed. Correlations between PET heterogeneity and perfusion CT were assessed by Spearman's rank correlation analysis.Blood flow visualization provided by DCE-CT images was significantly correlated with 18F-FDG PET metabolically active tumor volume as well as with uptake heterogeneity for patients with stage III/IV tumors (|ρ|:0.66 to 0.78; p-value<0.02.The positive correlation found with tumor blood flow indicates that intra-tumor heterogeneity of 18F-FDG PET accumulation reflects to some extent tracer distribution and consequently indicates that 18F-FDG PET intra-tumor heterogeneity may be associated with physiological processes such as tumor vascularization.

  18. Port Site Local Anesthetic Infiltration Vs Single-dose Intrathecal Opioid Injection to Control Perioperative Pain in Children Undergoing Minimal Invasive Surgery: A Comparative Analysis.

    Science.gov (United States)

    Srinivasan, Arun K; Shrivastava, Dhiren; Kurzweil, Rebecca E; Weiss, Dana A; Long, Christopher J; Shukla, Aseem R

    2016-11-01

    To compare the efficacy of the intrathecal opiate vs wound site local anesthetic infiltration for perioperative pain control during and after surgery in patients undergoing minimally invasive pediatric urologic procedures. Using an Institutional Review Board-approved registry database, we identified patients who underwent minimally invasive urologic procedures at our institution between 2009 and 2013. We collected all relevant preoperative variables and postoperative outcomes. Patients in intrathecal injection of opioids (ITO) group were matched with patients who received local anesthetic infiltration (LAI) based on age, diagnosis, and procedure. Perioperative analgesic requirements were converted to morphine equivalents standardized to body weight. Statistical analysis was performed using SPSS, and parametric comparisons were completed to determine difference in morphine equivalents between the 2 groups. One hundred thirty children (78 girls and 52 boys) were included in our study. Sixty-six patients underwent ITO and 66 received LAI. Sixty-six patients underwent ureteral reimplantation, 60 underwent pyeloplasty, and 4 underwent nephrectomy. Ages ranged from 0.5 to 19.9 years. There was no significant difference in cumulative morphine equivalents or weight administered between the ITO and LAI groups for the total period of hospitalization (0.76 units vs 0.79 units, P > .05). Multivariate regression analysis predicted that older age corresponds to higher analgesic requirements. ITO does not impact total analgesic requirements during the hospital stay compared to LAI following minimally invasive surgery. Considering the potential complications of ITO, LAI may be the preferred modality for pain management for minimally invasive surgery in children. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Presurgical localization of abnormal parathyroid glands using a single injection of technetium-99m methoxyisobutylisonitrile: comparison of different techniques including factor analysis of dynamic structures

    Energy Technology Data Exchange (ETDEWEB)

    Blocklet, D. [Hopital Universitaire Erasme, Univ. Libre de Bruxelles (Belgium); Martin, P. [Hopital Universitaire Brugmann, Univ. Libre de Bruxelles (Belgium); Schoutens, A. [Hopital Universitaire Erasme, Univ. Libre de Bruxelles (Belgium); Verhas, M. [Hopital Universitaire Brugmann, Univ. Libre de Bruxelles (Belgium); Hooghe, L. [Hopital Universitaire Brugmann, Univ. Libre de Bruxelles (Belgium); Kinnaert, P. [Hopital Universitaire Erasme, Univ. Libre de Bruxelles (Belgium)

    1997-01-01

    The aims of this study were to determine which of the analytical techniques described for this method time-activity curves analysis of dynamic structures corresponds best with surgical findings, and to ascertain the potential overall contribution of presurgical scintigraphy. 55P patients were studied, 34 of whom presented with primary hyperparathyroidism (HPT) and 21 with secondary HPT. After a 925 MBq injection of technetium-99m MIBI, a 40-min dynamic acquisition was performed and static images were acquired at 5, 20, 40 and 120 min using a gamma camera equipped with a pinhole collimator. Sensitivity was 84.4%, 74% and 65% in adenoma and 76%, 66.6% and 45% in hyperplasia for 15`-120`, FADS and TACs, respectively. Surgical accuracy was 72%, 56% and 59% in adenoma and 53%, 30% and 22% in hyperplasia for 15`-120`, FADS and TACs, respectively. The visual comparison method scored best in all cases. FADS was found to be sensitive in cases of adenoma but was handicapped by more false-positive localizations. TACs were particular inefficient in hyperplasia. With respect to the detection of adenomas, we found a relationship between the gland weight and scintigraphic positivity. This dependence was not found in hyperplasia. The poorer results obtained with all techniques for surgical accuracy can be explained by the need for a complete scintigraphic description of all pathological glands found by the surgeon in a patient. This study demonstrates that the 15`-120` visual comparison method is more efficient However, it was less efficient than neck exploration by an experienced surgeon. (orig./ vhe) (orig.). With 4 figs., 4 tabs.

  20. Impact of intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction on left ventricular perfusion and function: a 6-month follow-up gated {sup 99m}Tc-MIBI single-photon emission computed tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Lipiec, Piotr [Medical University of Lodz, 2nd Department of Cardiology, Lodz (Poland); Medical University of Lodz, 2nd Department of Cardiology, Bieganski Hospital, Lodz (Poland); Krzeminska-Pakula, Maria; Plewka, Michal; Kasprzak, Jaroslaw D. [Medical University of Lodz, 2nd Department of Cardiology, Lodz (Poland); Kusmierek, Jacek; Plachcinska, Anna; Szuminski, Remigiusz [Medical University of Lodz, Department of Nuclear Medicine, Lodz (Poland); Robak, Tadeusz; Korycka, Anna [Medical University of Lodz, Department of Hematology, Lodz (Poland)

    2009-04-15

    We investigated the impact of intracoronary injection of autologous mononuclear bone marrow cells (BMC) in patients with acute ST elevation myocardial infarction (STEMI) on left ventricular volumes, global and regional systolic function and myocardial perfusion. The study included 39 patients with first anterior STEMI treated successfully with primary percutaneous coronary intervention. They were randomly assigned to the treatment group or the control group in a 2:1 ratio. The patients underwent baseline gated single-photon emission computed tomography (G-SPECT) 3-10 days after STEMI with quantitative and qualitative analysis of left ventricular perfusion and systolic function. On the following day, patients from the BMC treatment group were subjected to bone marrow aspiration, mononuclear BMC isolation and intracoronary injection. No placebo procedure was performed in the control group. G-SPECT was repeated 6 months after STEMI. Baseline and follow-up G-SPECT studies were available for 36 patients. At 6 months in the BMC group we observed a significantly enhanced improvement in the mean extent of the perfusion defect, the left ventricular perfusion score index, the infarct area perfusion score and the infarct area wall motion score index compared to the control group (p=0.01-0.04). However, the changes in left ventricular volume, ejection fraction and the left ventricular wall motion score index as well as the relative changes in the infarct area wall motion score index did not differ significantly between the groups. Intracoronary injection of autologous mononuclear BMC in patients with STEMI improves myocardial perfusion at 6 months. The benefit in infarct area systolic function is less pronounced and there is no apparent improvement of global left ventricular systolic function. (orig.)

  1. VCSEL Transmission at 10 Gb/s for 20 km Single Mode Fiber WDM-PON without Dispersion Compensation or Injection Locking

    DEFF Research Database (Denmark)

    Gibbon, Timothy Braidwood; Prince, Kamau; Pham, Tien Thang

    2011-01-01

    how off-center wavelength filtering of the VCSEL spectrum at an array waveguide grating can be used to mitigate the effect of chirp and the dispersion penalty. Transmission at 10Gb/s VCSEL over 23.6 km of single mode fiber is experimentally demonstrated, with a dispersion penalty of only 2.9 d......B. Simulated results are also presented which show that off-center wavelength filtering can extend the 10 Gb/s network reach from 11.7 km to 25.8 km for a 4 dB dispersion penalty. This allows for cheap and simple dispersion mitigation in next generation VCSEL based optical access networks....

  2. A simple and effective approach for treatment of situs tumor and metastasis:to promote intratumor pus formation

    Directory of Open Access Journals (Sweden)

    Hong Li

    2015-12-01

    Full Text Available Purpose: The recent emergence of the tumor microenvironment as the critical determinant in cancer outcome opens a new routes to fight cancer, however, the clinical results of targeting microenvironment for treating human cancer have not met expectations. Our purpose is to investigate how to target microenvironment for treatment of situs tumor and metastasis.Methods : We suppose that tumor is a robber from times of anarchy and disorder and can be eradicated in flourishing age. We also suppose that carcinogenesis is largely attributed to physically weak that cann’t get rid of ulcer by pus formation. In vivo,the subcutaneous implant model and pulmonary metastasis model of lewis lung cancer were established. Tumor bearing mice were taken water decoction of Astragalus mongholicus(huangqi and Spina Gleditsiae (zaojiaoci by intragastric administration b.i.d for ten weeks, and the influences of Astragalus mongholicus and Spina Gleditsiae  on tumor progression were evaluated by body temperature,blood oxygen saturation,red cell ATPase,blood  rheology,intratumor hypoxia,capillary permeability, matrix metalloproteinase (MMPs and intratumor pus formation.  Results:We found that both of Astragalus mongholicus and Spina Gleditsiae could keep body temperature,blood oxygen saturation,red cell ATPase and blood rheology,and improve intratumor hypoxia,capillary permeability and MMPs in tumor bearing mice,which led to slower tumor growth and less metastasis. Astragalus mongholicus could remove body poison and stimulate immune responses, and Spina Gleditsiae  could  promote pus formation and proteolytic enzymes. The combination of  Astragalus mongholicus and Spina Gleditsiae favored the restoration of tumor immune responses and proteolytic activity at the tumor site, which not only result to an increase in aseptic pus formation, but also to a decrease in necrotic tissue accumulation, and finally caused a complete intratumor pus

  3. Prognostic value of preoperative intratumoral FDG uptake heterogeneity in patients with epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Maria; Kim, Hee Seung; Chung, Hyun Hoon; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Lee, Hyunjong; Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Cancer Research Institute, Seoul (Korea, Republic of)

    2017-01-15

    To investigate the prognostic value of intratumoral FDG uptake heterogeneity (IFH) derived from PET/CT in patients with epithelial ovarian cancer (EOC). We retrospectively reviewed patients with pathologically proven epithelial ovarian cancer who underwent preoperative {sup 18}F-FDG PET/CT scans. PET/CT parameters such as maximum and average standardized uptake values (SUV{sub max} and SUV{sub avg}), sum of all metabolic tumour volume (MTV), cumulative total lesion glycolysis (TLG) and IFH were assessed. Regression analyses were used to identify clinicopathological and imaging variables associated with disease-free survival (DFS). Clinicopathological data were reviewed for 61 eligible patients. The median duration of DFS was 13 months (range, 6-26 months), and 18 (29.5 %) patients experienced recurrence. High IFH values were associated with tumour recurrence (P = 0.005, hazard ratio 4.504, 95 % CI 1.572-12.902). The Kaplan-Meier survival graphs showed that DFS significantly differed in groups categorized based on IFH (P = 0.002, log-rank test). Moreover, there were significant differences in DFS (P = 0.009) and IFH (P = 0.040) between patients with and without recurrence. Preoperative IFH measured by {sup 18}F-FDG PET/CT was significantly associated with EOC recurrence. FDG-based heterogeneity could be a useful and potential predicator of EOC recurrence before treatment. (orig.)

  4. Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications

    Directory of Open Access Journals (Sweden)

    George D. Cresswell

    2016-07-01

    Full Text Available The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT; current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution.

  5. [Antitumor effect of intratumoral administration of a Coriolus preparation, PSK: inhibition of tumor invasion in vitro].

    Science.gov (United States)

    Ebina, T; Murata, K

    1994-09-01

    The antitumor effects of biological response modifiers (BRM) in an experimental mouse model, the "double grafted tumor system," were analysed. Intratumoral administration of PSK (polysaccharide Kureha), a Coriolus preparation into primary tumor induced a cure of not only the primary solid tumor but also the metastatic, distant tumor. The effect of PSK on in vitro invasion by murine RL male-1 leukemia cells was studied using Biocoat Matrigel Invasion Chamber (Becton Dickinson Labware). We determined the ability of tumor cells to penetrate matrigel-coated filters in the presence or absence of PSK. PSK (100 micrograms/ml) reduced to half the number of invasive tumor cells for 3 hr incubation. PSK inhibited tumor cell invasion of matrigel-coated filters in a dose-dependent manner. Matrigel includes laminin, collagen, fibronectin and heparan sulfate proteoglycan. It is possible, therefore, that PSK may inhibit enzymes which digest the components of basement membranes, extra cellular matrices (ECM). This phenomenon suggests that PSK also inhibits metastatic activity of tumor cells in vivo.

  6. MRI mediated, non-invasive tracking of intratumoral distribution of nanocarriers in rat glioma

    International Nuclear Information System (INIS)

    Karathanasis, Efstathios; Park, Jaekeun; Agarwal, Abhiruchi; Patel, Vijal; Zhao Fuqiang; Hu Xiaoping; Bellamkonda, Ravi V; Annapragada, Ananth V

    2008-01-01

    Nanocarrier mediated therapy of gliomas has shown promise. The success of systemic nanocarrier-based chemotherapy is critically dependent on the so-called leaky vasculature to permit drug extravasation across the blood-brain barrier. Yet, the extent of vascular permeability in individual tumors varies widely, resulting in a correspondingly wide range of responses to the therapy. However, there exist no tools currently for rationally determining whether tumor blood vessels are amenable to nanocarrier mediated therapy in an individualized, patient specific manner today. To address this need for brain tumor therapy, we have developed a multifunctional 100 nm scale liposomal agent encapsulating a gadolinium-based contrast agent for contrast-enhanced magnetic resonance imaging with prolonged blood circulation. Using a 9.4 T MRI system, we were able to track the intratumoral distribution of the gadolinium-loaded nanocarrier in a rat glioma model for a period of three days due to improved magnetic properties of the contrast agent being packaged in a nanocarrier. Such a nanocarrier provides a tool for non-invasively assessing the suitability of tumors for nanocarrier mediated therapy and then optimizing the treatment protocol for each individual tumor. Additionally, the ability to image the tumor in high resolution can potentially constitute a surgical planning tool for tumor resection

  7. Quantitative computed tomographic descriptors associate tumor shape complexity and intratumor heterogeneity with prognosis in lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Olya Grove

    Full Text Available Two CT features were developed to quantitatively describe lung adenocarcinomas by scoring tumor shape complexity (feature 1: convexity and intratumor density variation (feature 2: entropy ratio in routinely obtained diagnostic CT scans. The developed quantitative features were analyzed in two independent cohorts (cohort 1: n = 61; cohort 2: n = 47 of patients diagnosed with primary lung adenocarcinoma, retrospectively curated to include imaging and clinical data. Preoperative chest CTs were segmented semi-automatically. Segmented tumor regions were further subdivided into core and boundary sub-regions, to quantify intensity variations across the tumor. Reproducibility of the features was evaluated in an independent test-retest dataset of 32 patients. The proposed metrics showed high degree of reproducibility in a repeated experiment (concordance, CCC≥0.897; dynamic range, DR≥0.92. Association with overall survival was evaluated by Cox proportional hazard regression, Kaplan-Meier survival curves, and the log-rank test. Both features were associated with overall survival (convexity: p = 0.008; entropy ratio: p = 0.04 in Cohort 1 but not in Cohort 2 (convexity: p = 0.7; entropy ratio: p = 0.8. In both cohorts, these features were found to be descriptive and demonstrated the link between imaging characteristics and patient survival in lung adenocarcinoma.

  8. Comparison of detection pattern of HCC by ferumoxide-enhanced MRI and intratumoral blood flow pattern

    International Nuclear Information System (INIS)

    Itou, Naoki; Kotake, Fumio; Saitou, Kazuhiro; Abe, Kimihiko

    2000-01-01

    We compared the detection rate and pattern of ferumoxide-enhanced magnetic resonance imaging (Fe-MRI) with the intratumoral blood flow pattern determined by CT angiography (CTA) and CT portography (CTAP) in 124 nodes (34 cases) diagnosed as hepatocellular carcinoma (HCC) or borderline HCC, based on the clinical course. Sequences to obtain a T1-weighted images (T1W), proton density-weighted images (PDW), T2-weighted images (T2W), T2*-weighted images (T2*W) were used in Fe-MRI. In nodes shown to be hypervascular on CTA, the detection rate by Fe-MRI was 69.7%. In nodes shown to be avascular by CTAP, the detection rate by Fe-MRI was 67.3%. These rates were higher than with other flow patterns. In nodes showing high signal intensity (HSI) on any sequences, arterial blood flow was increased and portal blood flow decreased in comparison with nodes without high signal intensity. All nodes showing HSI, both on Fe-MRI T2W and T2*W, were hypervascular on CTA, and portal blood flow was absent on CTAP. Nodes showing HSI on both T2*W and T2W were considered to have greater arterial blood flow and decreased portal blood flow compared with nodes appearing as HSI on T2*W, but only as iso- or low signal intensity on T2W (Mann-Whitney U-test; p<0.05). (author)

  9. Oxytocin via Uniject (a prefilled single-use injection) versus oral misoprostol for prevention of postpartum haemorrhage at the community level: a cluster-randomised controlled trial.

    Science.gov (United States)

    Diop, Ayisha; Daff, Bocar; Sow, Maimouna; Blum, Jennifer; Diagne, Mamadou; Sloan, Nancy L; Winikoff, Beverly

    2016-01-01

    Access to injectable uterotonics for management of postpartum haemorrhage remains limited in Senegal outside health facilities, and misoprostol and oxytocin delivered via Uniject have been deemed viable alternatives in community settings. We aimed to compare the efficacy of these drugs when delivered by auxiliary midwives at maternity huts. We did an unmasked cluster-randomised controlled trial at maternity huts in three districts in Senegal. Maternity huts with auxiliary midwives located 3-21 km from the closest referral centre were randomly assigned (1:1; via a computer-generated random allocation overseen by Gynuity Health Projects) to either 600 μg oral misoprostol or 10 IU oxytocin in Uniject (intramuscular), stratified by reported previous year clinic volume (deliveries) and geographical location (inland or coastal). Maternity huts that had been included in a previous study of misoprostol for prevention of postpartum haemorrhage were excluded to prevent contamination. Pregnant women in their third trimester were screened for eligibility either during community outreach or at home-based prenatal visits. Only women delivered by the auxiliary midwives in the maternity huts were eligible for the study. Women with known allergies to prostaglandins or pregnancy complications were excluded. The primary outcome was mean change in haemoglobin concentration measured during the third trimester and after delivery. This study was registered with ClinicalTrials.gov, number NCT01713153. 28 maternity hut clusters were randomly assigned-14 to the misoprostol group and 14 to the oxytocin group. Between June 6, 2012, and Sept 21, 2013, 1820 women were recruited. 647 women in the misoprostol group and 402 in the oxytocin group received study drug and had recorded pre-delivery and post-delivery haemoglobin concentrations, and overall 1412 women delivered in the study maternity huts. The mean change in haemoglobin concentrations was 3·5 g/L (SD 16·1) in the misoprostol group

  10. Safety, pharmacokinetics, and pharmacodynamics of TV-1380, a novel mutated butyrylcholinesterase treatment for cocaine addiction, after single and multiple intramuscular injections in healthy subjects.

    Science.gov (United States)

    Cohen-Barak, Orit; Wildeman, Jacqueline; van de Wetering, Jeroen; Hettinga, Judith; Schuilenga-Hut, Petra; Gross, Aviva; Clark, Shane; Bassan, Merav; Gilgun-Sherki, Yossi; Mendzelevski, Boaz; Spiegelstein, Ofer

    2015-05-01

    Human plasma butyrylcholinesterase (BChE) contributes to cocaine metabolism and has been considered for use in treating cocaine addiction and cocaine overdose. TV-1380 is a recombinant protein composed of the mature form of human serum albumin fused at its amino terminus to the carboxy-terminus of a truncated and mutated BChE. In preclinical studies, TV-1380 has been shown to rapidly eliminate cocaine in the plasma thus forestalling entry of cocaine into the brain and heart. Two randomized, blinded phase I studies were conducted to evaluate the safety, pharmacokinetics, and pharmacodynamics of TV-1380, following single and multiple administration in healthy subjects. TV-1380 was found to be safe and well tolerated with a long half-life (43-77 hours) and showed a dose-proportional increase in systemic exposure. Consistent with preclinical results, the ex vivo cocaine hydrolysis, TV-1380 activity clearly increased upon treatment in a dose-dependent manner. In addition, there was a direct relationship between ex vivo cocaine hydrolysis (kel ) and TV-1380 serum concentrations. There was no evidence that TV-1380 affected heart rate, the uncorrected QT interval, or the heart-rate-corrected QTcF interval. TV-1380, therefore, offers a safe once-weekly therapy to increase cocaine hydrolysis. © 2015 The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  11. Study on a Single-Dose Toxicity Test of D-Amino Acid Oxidase (DAAO Extracts Injected into the Tail Vein of Rats

    Directory of Open Access Journals (Sweden)

    Kang Jungue

    2013-06-01

    Full Text Available Objective: This study was performed to analyze the single-dose toxicity of D-amino acid oxidase (DAAO extracts. Methods: All experiments were conducted at the Korea Testing & Research Institute (KTR, an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP. Sprague-Dawley rats were chosen for the pilot study. Doses of DAAO extracts, 0.1 to 0.3 cc, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: In all 4 groups, no deaths occurred, and the LD50 of DAAO extracts administered by IV was over 0.3 ml/kg. No significant changes in the weight between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ, the results showed no significant differences in any organs or tissues. Conclusion: The above findings suggest that treatment with D-amino acid oxidase extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.

  12. Alteration of sensitivity of intratumor quiescent and total cells to γ-rays following thermal neutron irradiation with or without 10B-compound

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Sakurai, Yoshinori; Kobayashi, Tooru; Takagaki, Masao; Kinashi, Yuko; Akaboshi, Mitsuhiko

    2000-01-01

    Purpose: Changes in the sensitivity of intratumor quiescent (Q) and total cells to γ-rays following thermal neutron irradiation with or without 10 B-compound were examined. Methods and Materials: 5-Bromo-2'-deoxyuridine (BrdU) was injected to SCC VII tumor-bearing mice intraperitoneally 10 times to label all the proliferating (P) tumor cells. As priming irradiation, thermal neutrons alone or thermal neutrons with 10 B-labeled sodium borocaptate (BSH) or dl-p-boronophenylalanine (BPA) were administered. The tumor-bearing mice then received a series of γ-ray radiation doses, 0 through 24 h after the priming irradiation. During this period, no BrdU was administered. Immediately after the second irradiation, the tumors were excised, minced, and trypsinized. Following incubation of tumor cells with cytokinesis blocker, the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells at the time of priming irradiation) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU before the priming irradiation. To determine the BrdU-labeled cell ratios in the tumors at the time of the second irradiation, each group also included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the priming irradiation. Results: In total cells, during the interval between the two irradiations, the tumor sensitivity to γ-rays relative to that immediately after priming irradiation decreased with the priming irradiation ranking in the following order: thermal neutrons only > thermal neutrons with BSH > thermal neutrons with BPA. In contrast, in Q cells, during that time the sensitivity increased in the following order: thermal neutrons only 10 B-compound, especially BPA, in thermal neutron irradiation causes the recruitment from the Q to P population

  13. Semi-quantification of endolymphatic size on MR imaging after intravenous injection of single-dose gadodiamide: comparison between two types of processing strategies.

    Science.gov (United States)

    Naganawa, Shinji; Suzuki, Kojiro; Nakamichi, Rei; Bokura, Kiminori; Yoshida, Tadao; Sone, Michihiko; Homann, Georg; Nakashima, Tsutomu; Ikeda, Mitsuru

    2013-12-25

    Many inner ear disorders, including Ménière's disease, are believed to be based on endolymphatic hydrops. We evaluated a newly proposed method for semi-quantification of endolymphatic size in patients with suspected endolymphatic hydrops that uses 2 kinds of processed magnetic resonance (MR) images. Twenty-four consecutive patients underwent heavily T2-weighted (hT2W) MR cisternography (MRC), hT2W 3-dimensional (3D) fluid-attenuated inversion recovery (FLAIR) with inversion time of 2250 ms (positive perilymph image, PPI), and hT2W-3D-IR with inversion time of 2050 ms (positive endolymph image, PEI) 4 hours after intravenous administration of single-dose gadolinium-based contrast material (IV-SD-GBCM). Two images were generated using 2 new methods to process PPI, PEI, and MRC. Three radiologists contoured the cochlea and vestibule on MRC, copied regions of interest (ROIs) onto the 2 kinds of generated images, and semi-quantitatively measured the size of the endolymph for the cochlea and vestibule by setting a threshold pixel value. Each observer noted a strong linear correlation between endolymphatic size of both the cochlea and vestibule of the 2 kinds of generated images. The Pearson correlation coefficients (r) were 0.783, 0.734, and 0.800 in the cochlea and 0.924, 0.930, and 0.933 in the vestibule (P<0.001, for all). In both the cochlea and vestibule, repeated-measures analysis of variance showed no statistically significant difference between observers. Use of the 2 kinds of generated images generated from MR images obtained 4 hours after IV-SD-GBCM might enable semi-quantification of endolymphatic size with little observer dependency.

  14. Effect of injection timing and injection pressure on the performance ...

    African Journals Online (AJOL)

    This paper discusses the feasibility study on the utilization of biodiesel ester of Honge oil (EHO) in common rail direct injection (CRDI) engine. Biodiesel of EHO has been obtained by transesterification process and characterization has been done. Existing single cylinder diesel engine fitted with conventional mechanical ...

  15. Effect of injection timing and injection pressure on the performance ...

    African Journals Online (AJOL)

    DR OKE

    This paper discusses the feasibility study on the utilization of biodiesel ester of Honge oil (EHO) in common rail direct injection. (CRDI) engine. Biodiesel of EHO has been obtained by transesterification process and characterization has been done. Existing single cylinder diesel engine fitted with conventional mechanical ...

  16. Effect of a single injection of gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) on testicular blood flow measured by color doppler ultrasonography in male Shiba goats.

    Science.gov (United States)

    Samir, Haney; Sasaki, Kazuaki; Ahmed, Eman; Karen, Aly; Nagaoka, Kentaro; El Sayed, Mohamed; Taya, Kazuyoshi; Watanabe, Gen

    2015-05-01

    Although color Doppler ultrasonography has been used to evaluate testicular blood flow in many species, very little has been done in goat. Eight male Shiba goats were exposed to a single intramuscular injection of either gonadotropin-releasing hormone (GnRH group; 1 µg/kg BW) or human chorionic gonadotropin (hCG group; 25 IU/kg BW). Plasma testosterone (T), estradiol (E2) and inhibin (INH) were measured just before (0 hr) and at different intervals post injection by radioimmunoassay. Testis volume (TV) and Doppler indices, such as resistive index (RI) and pulsatility index (PI) of the supratesticular artery, were measured by B-mode and color Doppler ultrasonography, respectively. The results indicated an increase in testicular blood flow in both groups, as RI and PI decreased significantly (P<0.05), but this increase was significant higher and earlier in hCG group (1 hr) than in the GnRH group (2 hr). A high correlation was found for RI and PI with both T (RI, r= -0.862; PI, r= -0.707) and INH in the GnRH group (RI, r=0.661; PI, r=0.701). However, a significant (P<0.05) correlation was found between E2 and both RI (r= -0.610) and PI (r= -0.763) in hCG group. In addition, TV significantly increased and was highly correlated with RI in both groups (GnRH, r= -0.718; hCG, r= -0.779). In conclusion, hCG and GnRH may improve testicular blood flow and TV in Shiba goats.

  17. Standardized Follow-up of Patients with Symptomatic Knee Osteoarthritis Treated with a Single Intra-articular Injection of a Combination of Cross-Linked Hyaluronic Acid and Mannitol

    Directory of Open Access Journals (Sweden)

    Thierry Conrozier

    2016-01-01

    Full Text Available Objectives The objective of this study is to obtain pilot data from daily practice conditions of a viscosupplement made of a cross-linked high-molecular-weight hyaluronic acid (HA combined with mannitol in patients with knee osteoarthritis (KOA. Methods The data of 40 consecutive patients, 29 women and 11 men, who were prospectively followed up for 6 months, using a standardized procedure, were retrospectively analyzed. All patients have received a single intra-articular injection of H Anox-M-XL (4.4 mL, viscosupplement made of a cross-linked HA (16 mg/mL + mannitol (35 mg/mL, in the target knee. The primary outcome was safety. The secondary end points included 3- and 6-month change in the WOMAC pain (0–50 and WOMAC total (0–240 and patient's global assessment (PGA. Patient's self-assessment of treatment efficacy (0–3 and analgesic consumption were obtained at months 3 and 6. An intent-to-treat analysis was performed. Results Mean (SD age was 60.7 (13.9 years, and mean BMI was 28.6 (5.0. Kellgren–Lawrence radiological grade was I/II and III/IV in 13 and 27 of the subjects, respectively. The average WOMAC pain and WOMAC total scores at baseline were 21.5 (9.8 and 89.9 (42.8, respectively. Thirty-nine patients completed the follow-up. HAnox-M-XL was well tolerated; two patients experienced knee pain after injection, which resolved within three days. No treatment-related severe adverse event was reported. Mean (SD variations in WOMAC pain and WOMAC total scores were –8.2 (8.9 and –38.4 (35.6, respectively, at month 6 ( P = 0.001. PGA decreased from 5.5 (2.0 to 3.0 (2.2 ( P = 0.006. Efficacy was rated as good or very good in 76.9% of the cases. Most of the regular analgesics users decreased their consumption. Conclusion Treatment with one injection of 4.4 mL HAnox-M-XL is effective to alleviate KOA symptoms over six months, without safety concern. Controlled trials are needed to confirm these pilot data.

  18. MHC Intratumoral Heterogeneity May Predict Cancer Progression and Response to Immunotherapy.

    Science.gov (United States)

    Romero, Irene; Garrido, Cristina; Algarra, Ignacio; Chamorro, Virginia; Collado, Antonia; Garrido, Federico; Garcia-Lora, Angel M

    2018-01-01

    An individual tumor can present intratumoral phenotypic heterogeneity, containing tumor cells with different phenotypes that do not present irreversible genetic alterations. We have developed a mouse cancer model, named GR9, derived from a methylcholanthrene-induced fibrosarcoma that was adapted to tissue culture and cloned into different tumor cell lines. The clones showed diverse MHC-I phenotypes, ranging from highly positive to weakly positive MHC-I expression. These MHC-I alterations are due to reversible molecular mechanisms, because surface MHC-I could be recovered by IFN-γ treatment. Cell clones with high MHC-I expression demonstrated low local oncogenicity and high spontaneous metastatic capacity, whereas MHC-I-low clones showed high local oncogenicity and no spontaneous metastatic capacity. Although MHC-I-low clones did not metastasize, they produced MHC-I-positive dormant micrometastases controlled by the host immune system, i.e., in a state of immunodormancy. The metastatic capacity of each clone was directly correlated with the host T-cell subpopulations; thus, a strong decrease in cytotoxic and helper T lymphocytes was observed in mice with numerous metastases derived from MHC-I positive tumor clones but a strong increase was observed in those with dormant micrometastases. Immunotherapy was administered to the hosts after excision of the primary tumor, producing a recovery in their immune status and leading to the complete eradication of overt spontaneous metastases or their decrease. According to these findings, the combination of MHC-I surface expression in primary tumor and metastases with host T-cell subsets may be a decisive indicator of the clinical outcome and response to immunotherapy in metastatic disease, allowing the identification of responders to this approach.

  19. Multiple statistical analysis techniques corroborate intratumor heterogeneity in imaging mass spectrometry datasets of myxofibrosarcoma.

    Directory of Open Access Journals (Sweden)

    Emrys A Jones

    Full Text Available MALDI mass spectrometry can generate profiles that contain hundreds of biomolecular ions directly from tissue. Spatially-correlated analysis, MALDI imaging MS, can simultaneously reveal how each of these biomolecular ions varies in clinical tissue samples. The use of statistical data analysis tools to identify regions containing correlated mass spectrometry profiles is referred to as imaging MS-based molecular histology because of its ability to annotate tissues solely on the basis of the imaging MS data. Several reports have indicated that imaging MS-based molecular histology may be able to complement established histological and histochemical techniques by distinguishing between pathologies with overlapping/identical morphologies and revealing biomolecular intratumor heterogeneity. A data analysis pipeline that identifies regions of imaging MS datasets with correlated mass spectrometry profiles could lead to the development of novel methods for improved diagnosis (differentiating subgroups within distinct histological groups and annotating the spatio-chemical makeup of tumors. Here it is demonstrated that highlighting the regions within imaging MS datasets whose mass spectrometry profiles were found to be correlated by five independent multivariate methods provides a consistently accurate summary of the spatio-chemical heterogeneity. The corroboration provided by using multiple multivariate methods, efficiently applied in an automated routine, provides assurance that the identified regions are indeed characterized by distinct mass spectrometry profiles, a crucial requirement for its development as a complementary histological tool. When simultaneously applied to imaging MS datasets from multiple patient samples of intermediate-grade myxofibrosarcoma, a heterogeneous soft tissue sarcoma, nodules with mass spectrometry profiles found to be distinct by five different multivariate methods were detected within morphologically identical regions of

  20. Safe injection procedures, injection practices, and needlestick ...

    African Journals Online (AJOL)

    Safe injection procedures, injection practices, and needlestick injuries among health care workers in operating rooms. Nermine Mohamed Tawfik Foda, Noha Selim Mohamed Elshaer, Yasmine Hussein Mohamed Sultan ...

  1. Salivary gland tumors of the parotid gland: CT and MR imaging findings with emphasis on intratumoral cystic components

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Hiroki; Watanabe, Haruo [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Kanematsu, Masayuki [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Gifu University Hospital, High-Level Imaging Diagnosis Center, Gifu (Japan); Mizuta, Keisuke; Aoki, Mitsuhiro [Gifu University School of Medicine, Department of Otolaryngology, Gifu (Japan)

    2014-09-15

    The purpose of this study was to assess computed tomography (CT) and magnetic resonance (MR) imaging findings of salivary gland tumors of the parotid gland with emphasis on intratumoral cystic components. Seventy-two histopathologically confirmed salivary gland tumors of the parotid gland (44 benign and 28 malignant), which underwent both CT and MR imaging including contrast-enhanced study, were included in this study. We retrospectively reviewed images for the presence, number, occupying rate, margin characteristics, distribution, and predominant MR signal intensity of intratumoral cystic components. The prevalence of cystic components was greater in malignant than benign tumors (79 vs. 50 %, p < 0.05). The number and occupying rate were similar between benign and malignant tumors. The irregular margins were more frequent in malignant than benign tumors (73 vs. 27 %, p < 0.01). The frequency of eccentric location was greater in benign than malignant tumors (91 vs. 55 %, p < 0.01), whereas the frequency of centric location was greater in malignant than benign tumors (32 vs. 0 %, p < 0.01). On T1-weighted images, the frequency of hyperintensity was greater in benign than malignant tumors (50 vs. 9 %, p < 0.01), whereas that of isointensity was greater in malignant than benign tumors (50 vs. 0 %, p < 0.01). Multiple logistic regression analysis showed that the absence of irregular margins of cystic components only was significantly correlated with the presence of benign salivary gland tumors (p < 0.01). Imaging features of intratumoral cystic components may help to differentiate benign from malignant tumors of the parotid salivary gland. (orig.)

  2. Intratumoral administration of holmium-166 acetylacetonate microspheres: antitumor efficacy and feasibility of multimodality imaging in renal cancer.

    Directory of Open Access Journals (Sweden)

    Wouter Bult

    Full Text Available PURPOSE: The increasing incidence of small renal tumors in an aging population with comorbidities has stimulated the development of minimally invasive treatments. This study aimed to assess the efficacy and demonstrate feasibility of multimodality imaging of intratumoral administration of holmium-166 microspheres ((166HoAcAcMS. This new technique locally ablates renal tumors through high-energy beta particles, while the gamma rays allow for nuclear imaging and the paramagnetism of holmium allows for MRI. METHODS: (166HoAcAcMS were administered intratumorally in orthotopic renal tumors (Balb/C mice. Post administration CT, SPECT and MRI was performed. At several time points (2 h, 1, 2, 3, 7 and 14 days after MS administration, tumors were measured and histologically analyzed. Holmium accumulation in organs was measured using inductively coupled plasma mass spectrometry. RESULTS: (166HoAcAcMS were successfully administered to tumor bearing mice. A striking near-complete tumor-control was observed in (166HoAcAcMS treated mice (0.10±0.01 cm(3 vs. 4.15±0.3 cm(3 for control tumors. Focal necrosis and inflammation was present from 24 h following treatment. Renal parenchyma outside the radiated region showed no histological alterations. Post administration CT, MRI and SPECT imaging revealed clear deposits of (166HoAcAcMS in the kidney. CONCLUSIONS: Intratumorally administered (166HoAcAcMS has great potential as a new local treatment of renal tumors for surgically unfit patients. In addition to strong cancer control, it provides powerful multimodality imaging opportunities.

  3. Safe injection procedures, injection practices, and needlestick ...

    African Journals Online (AJOL)

    Nermine Mohamed Tawfik Foda

    2017-01-10

    Jan 10, 2017 ... tionnaire was administered to HCWs (n = 318) at the Alexandria Main University Hospital. Results: Safe injection procedures regarding final waste disposal were sufficiently adopted, while mea- sures regarding disposable injection equipment, waste containers, hand hygiene, as well as injection practices ...

  4. Sodium Iodide Symporter (NIS)-Mediated Radionuclide (131I, 188Re) Therapy of Liver Cancer After Transcriptionally Targeted Intratumoral in Vivo NIS Gene Delivery

    Science.gov (United States)

    Klutz, Kathrin; Willhauck, Michael J.; Wunderlich, Nathalie; Zach, Christian; Anton, Martina; Senekowitsch-Schmidtke, Reingard; Göke, Burkhard

    2011-01-01

    Abstract We reported the therapeutic efficacy of 131I in hepatocellular carcinoma (HCC) cells stably expressing the sodium iodide symporter (NIS) under the control of the tumor-specific α-fetoprotein (AFP) promoter. In the current study we investigated the efficacy of adenovirus-mediated in vivo NIS gene transfer followed by 131I and 188Re administration for the treatment of HCC xenografts. We used a replication-deficient adenovirus carrying the human NIS gene linked to the mouse AFP promoter (Ad5-AFP-NIS) for in vitro and in vivo NIS gene transfer. Functional NIS expression was confirmed by in vivo γ-camera imaging, followed by analysis of NIS protein and mRNA expression. Human HCC (HepG2) cells infected with Ad5-AFP-NIS concentrated 50% of the applied activity of 125I, which was sufficiently high for a therapeutic effect in an in vitro clonogenic assay. Four days after intratumoral injection of Ad5-AFP-NIS (3×109 plaque-forming units) HepG2 xenografts accumulated 14.5% injected dose (ID)/g 123I with an effective half-life of 13 hr (tumor-absorbed dose, 318 mGy/MBq 131I). In comparison, 9.2% ID/g 188Re was accumulated in tumors with an effective half-life of 12.8 hr (tumor-absorbed dose, 545 mGy/MBq). After adenovirus-mediated NIS gene transfer in HepG2 xenografts administration of a therapeutic dose of 131I or 188Re (55.5 MBq) resulted in a significant delay in tumor growth and improved survival without a significant difference between 188Re and 131I. In conclusion, a therapeutic effect of 131I and 188Re was demonstrated in HepG2 xenografts after tumor-specific adenovirus-mediated in vivo NIS gene transfer. PMID:21488714

  5. Metaplastic thymoma with myasthenia gravis presumably caused by an accumulation of intratumoral immature T cells: a case report.

    Science.gov (United States)

    Tajima, Shogo; Yanagiya, Masahiro; Sato, Masaaki; Nakajima, Jun; Fukayama, Masashi

    2015-01-01

    Among human neoplasms, thymomas are well known for their association with paraneoplastic autoimmune diseases such as myasthenia gravis. However, regarding rare metaplastic thymoma, only one case of an association with myasthenia gravis has been reported. Here, we present the second case of a 44-year-old woman with metaplastic thymoma associated with myasthenia gravis. In metaplastic thymoma, intratumoral terminal deoxynucleotidyl transferase-positive T-cells (immature T-cells) are generally scarce, while they were abundant in the present case. We believe that these immature T-cells could be related to the occurrence of myasthenia gravis.

  6. Penicillin G Procaine Injection

    Science.gov (United States)

    Penicillin G procaine injection is used to treat certain infections caused by bacteria. Penicillin G procaine injection should not be used to treat ... in the treatment of certain serious infections. Penicillin G procaine injection is in a class of medications ...

  7. Initial and delayed stress phase imaging in a single-injection double-acquisition SPECT. The potential value of early {sup 99m}Tc-MIBI redistribution in assessment of myocardial perfusion reversibility in patients with coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Beiki, D. [Research Inst. for Nuclear Medicine, Tehran Univ. of Medical Sciences, Tehran (Iran); Dept. of Nuclear Pharmacy, Tehran Univ. of Medical Sciences, Tehran (Iran); Fallahi, B.; Fard-Esfahani, A.; Eftekhari, M. [Research Inst. for Nuclear Medicine, Tehran Univ. of Medical Sciences, Tehran (Iran); Mohseni, Z.; Khalaj, A. [Dept. of Nuclear Pharmacy, Tehran Univ. of Medical Sciences, Tehran (Iran)

    2010-07-01

    Some studies reported that {sup 99m}Tc-MIBI may redistribute in ischaemic myocardium and this phenomenon may have potential role for better assessment of viability by delayed {sup 99m}Tc-MIBI imaging. Some studies also suggested that infusion of low dose dobutamine during delayed imaging may enhance the value of {sup 99m}Tc-MIBI imaging for evaluation of viability. The aim of this study is to determine whether the observed changes of perfusion defects on delayed images are caused by early radiotracer redistribution or as a result of reversal partial volume effect secondary to inotropic stimulation. Patients, methods: 89 patients with angiographically proven coronary artery disease (CAD) were enrolled in this randomized clinical trial study. In all cases, gated-SPECT images were obtained 60 minutes after stress with dipyridamole injection. Subsequently the patients were randomly allocated in two groups and the second imaging was performed at 120{sup th} minute during low dose dobutamine (dobutamine group; 45 cases) or placebo infusion (placebo group; 44 cases). Difference between summed stress score of the first (SSS{sub 1}) and second (SSS{sub 2}) stress images ({delta}SSS) was considered as a marker of reversibility in single-injection double-acquisition (SIDA) protocol. Also summed difference score (SDS) was recorded as a marker of reversibility in standard stress/rest, double-injection double-acquisition (DIDA) protocol. {delta}SSS of the two studied groups were compared. Also the correlation and agreement between {delta}SSS and SDS were analyzed. Results: A significant difference was found between SSS{sub 1} (median 15, range 0-48) and SSS{sub 2} (median 11, range 0-42) in total patients (p < 0.0001). A significant correlation was noted between {delta}SSS and SDS in dobutamine group (r = 0.58, p = 0.002) as well as in placebo group (r = 0.57, p < 0.0001). Considering DIDA protocol as a standard reference method, the influence of dobutamine infusion was not

  8. Does giving segmental muscle vibration alter the response to botulinum toxin injections in the treatment of spasticity in people with multiple sclerosis? A single-blind randomized controlled trial.

    Science.gov (United States)

    Paoloni, Marco; Giovannelli, Morena; Mangone, Massimiliano; Leonardi, Laura; Tavernese, Emanuela; Di Pangrazio, Elisabetta; Bernetti, Andrea; Santilli, Valter; Pozzilli, Carlo

    2013-09-01

    To determine if segmental muscle vibration and botulinum toxin-A injection, either alone or in combination, reduces spasticity in a sample of patients with multiple sclerosis. Single-blind, randomized controlled trial. Physical medicine and rehabilitation outpatients service. Forty-two patients affected by the secondary progressive form of multiple sclerosis randomized to group A (30 minutes of 120 Hz segmental muscle vibration over the rectus femoris and gastrocnemius medial and lateral, three per week, over a period of four weeks), group B (botulinum toxin in the rectus femoris, gastrocnemius medial and lateral and soleus, and segmental muscle vibration) and group C (botulinum toxin). Modified Ashworth Scale at knee and ankle, and Fatigue Severity Scale. All the measurements were performed at baseline (T0), 10 weeks (T1) and 22 weeks (T2) postallocation. Modified Ashworth Scale at knee and ankle significantly decreased over time (p spasticity at T2 when compared with T1 (p spasticity and improves fatigue in the medium-term follow-up in patients with multiple sclerosis.

  9. Time-resolved C-arm cone beam CT angiography (TR-CBCTA) imaging from a single short-scan C-arm cone beam CT acquisition with intra-arterial contrast injection

    Science.gov (United States)

    Li, Yinsheng; Garrett, John W.; Li, Ke; Wu, Yijing; Johnson, Kevin; Schafer, Sebastian; Strother, Charles; Chen, Guang-Hong

    2018-04-01

    Time-resolved C-arm cone-beam CT (CBCT) angiography (TR-CBCTA) images can be generated from a series of CBCT acquisitions that satisfy data sufficiency condition in analytical image reconstruction theory. In this work, a new technique was developed to generate TR-CBCTA images from a single short-scan CBCT data acquisition with contrast media injection. The reconstruction technique enabling this application is a previously developed image reconstruction technique, synchronized multi-artifact reduction with tomographic reconstruction (SMART-RECON). In this new application, the acquired short-scan CBCT projection data were sorted into a union of several sub-sectors of view angles and each sub-sector of view angles corresponds to an individual image volume to be reconstructed. The SMART-RECON method was then used to jointly reconstruct all of these individual image volumes under two constraints: (1) each individual image volume is maximally consistent with the measured cone-beam projection data within the corresponding view angle sector and (2) the nuclear norm of the image matrix is minimized. The difference between these reconstructed individual image volumes is used to generated the desired subtracted angiograms. To validate the technique, numerical simulation data generated from a fractal tree angiogram phantom were used to quantitatively study the accuracy of the proposed method and retrospective in vivo human subject studies were used to demonstrate the feasibility of generating TR-CBCTA in clinical practice.

  10. [A phase II pharmacological study of leuprolide acetate 6-month depot, TAP-144-SR (6M), in treatment-Nazve patients with prostatic cancer who received a single subcutaneous or intramuscular injection].

    Science.gov (United States)

    Komura, Emiko; Fujimoto, Tsukasa; Takabayashi, Nobuyoshi; Okamoto, Hiroyuki; Akaza, Hideyuki

    2014-05-01

    The aim of this phase II study was to evaluate the pharmacokinetics, pharmacodynamics, efficacy, and safety of a 6- month depot formulation of a luteinizing hormone-releasing hormone (LH-RH) agonist, TAP-144-SR (6M), in Japanese treatment-naÏve patients with prostatic cancer. Each subject received a single subcutaneous or intramuscular injection of TAP- 144-SR (6M) and was monitored for 24 weeks. The primary endpoint was the change in serum testosterone levels. The serum testosterone level in six subjects who received 22.5 mg of TAP-144 (SR) subcutaneously decreased below the castrate level after 4 weeks and remained suppressed during the 24 weeks of follow-up. With regard to safety, TAP-144-SR (6M)was not associated with any additional concerns compared to those reported for the approved 1-month and 3-month depot formulations of TAP-144-SR. In addition, 30 mg of TAP-144-SR (6M) was administered subcutaneously to six subjects, and, on the basis of the results, the optimal clinical dosage of TAP-144-SR (6M) in Japan was considered to be 22.5 mg. Outcomes with 22.5mg TAP-144-SR (6M) administered intramuscularly were similar to those with TAP-144-SR (6M) administered subcutaneously.

  11. Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments? Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers.

    Science.gov (United States)

    Vaegter, Katarina Kebbon; Lakic, Tatevik Ghukasyan; Olovsson, Matts; Berglund, Lars; Brodin, Thomas; Holte, Jan

    2017-03-01

    To construct a prediction model for live birth after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and single-embryo transfer (SET) after 2 days of embryo culture. Prospective observational cohort study. University-affiliated private infertility center. SET in 8,451 IVF/ICSI treatments in 5,699 unselected consecutive couples during 1999-2014. A total of 100 basal patient characteristics and treatment data were analyzed for associations with live birth after IVF/ICSI (adjusted for repeated treatments) and subsequently combined for prediction model construction. Live birth rate (LBR) and performance of live birth prediction model. Embryo score, treatment history, ovarian sensitivity index (OSI; number of oocytes/total dose of FSH administered), female age, infertility cause, endometrial thickness, and female height were all independent predictors of live birth. A prediction model (training data set; n = 5,722) based on these variables showed moderate discrimination, but predicted LBR with high accuracy in subgroups of patients, with LBR estimates ranging from 40%. Outcomes were similar in an internal validation data set (n = 2,460). Based on 100 variables prospectively recorded during a 15-year period, a model for live birth prediction after strict SET was constructed and showed excellent calibration in internal validation. For the first time, female height qualified as a predictor of live birth after IVF/ICSI. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Intratumoral convergence of the TCR repertoires of effector and Foxp3+ CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Michal Kuczma

    2010-10-01

    Full Text Available The presence of Foxp3(+ regulatory CD4(+ T cells in tumor lesions is considered one of the major causes of ineffective immune response in cancer. It is not clear whether intratumoral T(reg cells represent T(reg cells pre-existing in healthy mice, or arise from tumor-specific effector CD4(+ T cells and thus representing adaptive T(reg cells. The generation of T(reg population in tumors could be further complicated by recent evidence showing that both in humans and mice the peripheral population of T(reg cells is heterogenous and consists of subsets which may differentially respond to tumor-derived antigens. We have studied T(reg cells in cancer in experimental mice that express naturally selected, polyclonal repertoire of CD4(+ T cells and which preserve the heterogeneity of the T(reg population. The majority of T(reg cells present in healthy mice maintained a stable suppressor phenotype, expressed high level of Foxp3 and an exclusive set of TCRs not used by naive CD4(+ T cells. A small T(reg subset, utilized TCRs shared with effector T cells and expressed a lower level of Foxp3. We show that response to tumor-derived antigens induced efficient clonal recruitment and expansion of antigen-specific effector and T(reg cells. However, the population of T(reg cells in tumors was dominated by cells expressing TCRs shared with effector CD4(+ T cells. In contrast, T(reg cells expressing an exclusive set of TCRs, that dominate in healthy mice, accounted for only a small fraction of all T(reg cells in tumor lesions. Our results suggest that the T(reg repertoire in tumors is generated by conversion of effector CD4(+ T cells or expansion of a minor subset of T(reg cells. In conclusion, successful cancer immunotherapy may depend on the ability to block upregulation of Foxp3 in effector CD4(+ T cells and/or selectively inhibiting the expansion of a minor T(reg subset.

  13. Myocardial blood flow rate and capillary permeability for 99mTc-DTPA in patients with angiographically normal coronary arteries. Evaluation of the single-injection, residue detection method with intracoronary indicator bolus injection and the use of a mobile gamma camera

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Kelbaek, H; Efsen, F

    1994-01-01

    The aims of the present study were to quantitate myocardial perfusion and capillary permeability in the human heart by means of the single-injection, residue detection method using a mobile gamma camera. With this method, the intravascular mean transit time and the capillary extraction fraction (E...... capillary permeability area product (PS) were determined. Spontaneous 15 min variations (mean of two values) for the LAD and the CX territory, respectively, gave a mean fpl(LAD) of 74.2 (measurement 1) and 77.8 ml.(100 g.min)-1 (measurement 2) (SD of the difference 7.5 ml.(100 g.min)-1) and fpl(CX) of 82.......7 and 92.1 ml. (100 g.min)-1, respectively (SD of the difference 16.1 ml.(100 g.min)-1), and E(LAD) was 51.0 and 55.7%, respectively (SD of the difference 8.4%), and E(CX) was 52.9 and 50.4%, respectively (SD of the difference 5.9%). During atrial pacing, the rate-pressure product increased by 97...

  14. Secondary Central Nerve System Lymphoma With Intratumoral Hemorrhage Suggested as Intravascular Lymphoma by Autopsy: A Case Report.

    Science.gov (United States)

    Suzuki, Yutaro; Tanaka, Hiroaki; Suyama, Kennichiro; Mochida, Hidetoshi; Suzuki, Yoshio

    2017-11-01

    Intravascular large B-cell lymphoma (IVL) is a rare type of extranodal diffuse large B-cell lymphoma (DLBCL), which often infiltrates the central nervous system (CNS) during the clinical course. Cerebral hemorrhage in patients with CNS lymphoma at presentation is rare. Herein, we describe a case of secondary CNS lymphoma with intratumoral hemorrhage, which was suggested as IVL from autopsy findings. A 76-year-old Japanese man with a history of treatment for B-cell non-Hodgkin's lymphoma was transferred to our hospital in an ambulance for generalized convulsions. Brain CT scan revealed a high-density tumor with edema and intratumoral hemorrhage in the left temporal lobes. He died in a rapid course, and autopsy revealed a focal hemorrhage with diffuse infiltration of lymphoma cells in the left temporal lobe and findings suggestive of IVL. Furthermore, the autopsy revealed a discrepancy in the CD20 immunostaining of lymphoma cells between the brain and other organs. Clinicians should not eliminate CNS lymphoma from the differential diagnosis of intracranial tumor with hemorrhage. Although many patients with IVL have rapidly progressive courses, it is very important to diagnose IVL at the initial onset, even in serious situations, to consider CNS prophylaxis.

  15. Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome.

    Science.gov (United States)

    Kuroda, Naoto; Furuya, Mitsuko; Nagashima, Yoji; Gotohda, Hiroko; Moritani, Suzuko; Kawakami, Fumi; Imamura, Yoshiaki; Bando, Yoshimi; Takahashi, Masayuki; Kanayama, Hiro-omi; Ota, Satoshi; Michal, Michal; Hes, Ondrej; Nakatani, Yukio

    2014-06-01

    In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Multisite tumor sampling enhances the detection of intratumor heterogeneity at all different temporal stages of tumor evolution.

    Science.gov (United States)

    Erramuzpe, Asier; Cortés, Jesús M; López, José I

    2018-02-01

    Intratumor heterogeneity (ITH) is an inherent process of tumor development that has received much attention in previous years, as it has become a major obstacle for the success of targeted therapies. ITH is also temporally unpredictable across tumor evolution, which makes its precise characterization even more problematic since detection success depends on the precise temporal snapshot at which ITH is analyzed. New and more efficient strategies for tumor sampling are needed to overcome these difficulties which currently rely entirely on the pathologist's interpretation. Recently, we showed that a new strategy, the multisite tumor sampling, works better than the routine sampling protocol for the ITH detection when the tumor time evolution was not taken into consideration. Here, we extend this work and compare the ITH detections of multisite tumor sampling and routine sampling protocols across tumor time evolution, and in particular, we provide in silico analyses of both strategies at early and late temporal stages for four different models of tumor evolution (linear, branched, neutral, and punctuated). Our results indicate that multisite tumor sampling outperforms routine protocols in detecting ITH at all different temporal stages of tumor evolution. We conclude that multisite tumor sampling is more advantageous than routine protocols in detecting intratumor heterogeneity.

  17. TCR Repertoire Intratumor Heterogeneity in Localized Lung Adenocarcinomas: An Association with Predicted Neoantigen Heterogeneity and Postsurgical Recurrence.

    Science.gov (United States)

    Reuben, Alexandre; Gittelman, Rachel; Gao, Jianjun; Zhang, Jiexin; Yusko, Erik C; Wu, Chang-Jiun; Emerson, Ryan; Zhang, Jianhua; Tipton, Christopher; Li, Jun; Quek, Kelly; Gopalakrishnan, Vancheswaran; Chen, Runzhe; Vence, Luis M; Cascone, Tina; Vignali, Marissa; Fujimoto, Junya; Rodriguez-Canales, Jaime; Parra, Edwin R; Little, Latasha D; Gumbs, Curtis; Forget, Marie-Andrée; Federico, Lorenzo; Haymaker, Cara; Behrens, Carmen; Benzeno, Sharon; Bernatchez, Chantale; Sepesi, Boris; Gibbons, Don L; Wargo, Jennifer A; William, William N; Swisher, Stephen; Heymach, John V; Robins, Harlan; Lee, J Jack; Sharma, Padmanee; Allison, James P; Futreal, P Andrew; Wistuba, Ignacio I; Zhang, Jianjun

    2017-10-01

    Genomic intratumor heterogeneity (ITH) may be associated with postsurgical relapse of localized lung adenocarcinomas. Recently, mutations, through generation of neoantigens, were shown to alter tumor immunogenicity through T-cell responses. Here, we performed sequencing of the T-cell receptor (TCR) in 45 tumor regions from 11 localized lung adenocarcinomas and observed substantial intratumor differences in T-cell density and clonality with the majority of T-cell clones restricted to individual tumor regions. TCR ITH positively correlated with predicted neoantigen ITH, suggesting that spatial differences in the T-cell repertoire may be driven by distinct neoantigens in different tumor regions. Finally, a higher degree of TCR ITH was associated with an increased risk of postsurgical relapse and shorter disease-free survival, suggesting a potential clinical significance of T-cell repertoire heterogeneity. Significance: The present study provides insights into the ITH of the T-cell repertoire in localized lung adenocarcinomas and its potential biological and clinical impact. The results suggest that T-cell repertoire ITH may be tightly associated to genomic ITH and disease relapse. Cancer Discov; 7(10); 1088-97. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1047 . ©2017 American Association for Cancer Research.

  18. Deltoid injections of risperidone long-acting injectable in patients with schizophrenia.

    Science.gov (United States)

    Quiroz, Jorge A; Rusch, Sarah; Thyssen, An; Palumbo, Joseph M; Kushner, Stuart

    2011-06-01

    Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. Risperidone long-acting injectable was administered in an open-label, single-dose, two-way crossover study, with patients randomized to receive either 25mg gluteal/37.5mg deltoid crossover in two treatment periods or 50mg gluteal/50mg deltoid injections crossover; each treatment period was separated by an 85-day observation period (Study 1) and an open-label, multiple-dose study (4 sequential 37.5mg or 50mg deltoid injections every 2 weeks) (Study 2). The pharmacokinetic results from both the studies have already been published. In Study 1 (n=170), the majority of patients had no local injection-site findings, based on investigator and patient-rated evaluations. In Study 2 (n=53), seven of the 51 patients who received at least two deltoid injections discontinued (primary endpoint). However, none of the discontinuations were due to injection-site related reasons. The 90-percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5.7 percent. No moderate or severe injection-site reactions were reported. Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability. The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid (37.5mg and 50mg) and gluteal (25mg and 50mg) sites.

  19. SNS Injection and Extraction Devices

    CERN Document Server

    Raparia, Deepak

    2005-01-01

    The Spallation Neutron Source (SNS) is a second generation pulsed neutron source (1.5 MW) and is presently in the sixth year of a seven-year construction cycle at Oak Ridge National Laboratory. The operation of the facility will begin in 2006. The most stringent requirement for the SNS accelerator complex is to allow hands-on maintenance. Operational experiences show that the most losses occur in the injection and extraction. SNS accumulator ring injection and extraction has been design with grate care to reduce uncontrolled losses. Injection systems consist of fast programmable kicker magnets and DC dump magnets to paint the beam in transverse phase space. Extraction systems consist of fast kicker magnets and a Lamberton magnet to extract beam in single turn. Paper will discuss design, construction and testing of these devices.

  20. Differentiating intratumoral melanocytes from Langerhans cells in nonmelanocytic pigmented skin tumors in vivo by label-free third-harmonic generation microscopy

    Science.gov (United States)

    Weng, Wei-Hung; Liao, Yi-Hua; Tsai, Ming-Rung; Wei, Ming-Liang; Huang, Hsin-Yi; Sun, Chi-Kuang

    2016-07-01

    Morphology and distribution of melanocytes are critical imaging information for the diagnosis of melanocytic lesions. However, how to image intratumoral melanocytes noninvasively in pigmented skin tumors is seldom investigated. Third-harmonic generation (THG) is shown to be enhanced by melanin, whereas high accuracy has been demonstrated using THG microscopy for in vivo differential diagnosis of nonmelanocytic pigmented skin tumors. It is thus desirable to investigate if label-free THG microscopy was capable to in vivo identify intratumoral melanocytes. In this study, histopathological correlations of label-free THG images with the immunohistochemical images stained with human melanoma black (HMB)-45 and cluster of differentiation 1a (CD1a) were made. The correlation results indicated that the intratumoral THG-bright dendritic-cell-like signals were endogenously derived from melanocytes rather than Langerhans cells (LCs). The consistency between THG-bright dendritic-cell-like signals and HMB-45 melanocyte staining showed a kappa coefficient of 0.807, 84.6% sensitivity, and 95% specificity. In contrast, a kappa coefficient of -0.37, 21.7% sensitivity, and 30% specificity were noted between the THG-bright dendritic-cell-like signals and CD1a staining for LCs. Our study indicates the capability of noninvasive label-free THG microscopy to differentiate intratumoral melanocytes from LCs, which is not feasible in previous in vivo label-free clinical-imaging modalities.

  1. Intra-tumor heterogeneity of microRNA-92a, microRNA-375 and microRNA-424 in colorectal cancer

    DEFF Research Database (Denmark)

    Jepsen, Rikke Karlin; Novotny, Guy Wayne; Klarskov, Louise Laurberg

    2016-01-01

    Various microRNAs (miRNAs) have been investigated in order to improve diagnostics and risk assessment in colorectal cancer (CRC). To clarify the potential of miRNA profiling in CRC, knowledge of intra-tumor heterogeneity in expression levels is crucial. The study aim was to estimate the intra-tum...

  2. Intratumoral Heterogeneity of Breast Cancer Xenograft Models: Texture Analysis of Diffusion-Weighted MR Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Bo La; Cho, Nariya; Li, Mulun; Song, In Chan; Moon, Woo Kyung [Dept. of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jang, Min Hye; Park, So Yeon; Kim, Bo Young [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Kang, Ho Chul [Dept. of Computer Science and Engineering, Seoul National University, Seoul (Korea, Republic of)

    2014-10-15

    .464), kurtosis (r = -0.581, r = -0.389), contrast (r = -0.473, r = -0.549) and COR (r = 0.588, r = 0.580) correlated with MVDmean and MVDdiff (p < 0.05 for all). The texture analysis of ADC maps may help to determine the intratumoral spatial heterogeneity of necrosis patterns, amount of cellular proliferation and the vascularity in MCF-7 and MDA-MB-231 xenograft breast cancer models.

  3. Increased intratumoral FOXP3-positive regulatory immune cells during interleukin-2 treatment in metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, Hanne Krogh; Donskov, Frede; Nordsmark, Marianne

    2009-01-01

    PURPOSE: The administration of interleukin-2 (IL-2) may increase the frequency of peripherally circulating FOXP3-positive regulatory immune cells, thus potentially compromising this treatment option for patients with metastatic renal cell carcinoma. The impact of IL-2-based therapy...... on the accumulation of FOXP3-positive immune cells in the tumor microenvironment in metastatic renal cell carcinoma is unknown. EXPERIMENTAL DESIGN: Baseline (n = 58) and on-treatment (n = 42) tumor core biopsies were prospectively obtained from patients with clear cell metastatic renal cell carcinoma before...... and during IL-2-based immunotherapy. Immunohistochemical expression of FOXP3 was estimated by stereological counting technique and correlated with other immune cell subsets and overall survival. RESULTS: A significant increase in absolute intratumoral FOXP3-positive immune cells was observed comparing...

  4. Cluster beam injection

    International Nuclear Information System (INIS)

    Bottiglioni, F.; Coutant, J.; Fois, M.

    1977-11-01

    Areas of possible applications of cluster injection are discussed. The deposition inside the plasma of molecules, issued from the dissociation of the injected clusters, has been computed. Some empirical scaling laws for the penetration are given

  5. Cluster beam injection

    International Nuclear Information System (INIS)

    Bottiglioni, F.; Coutant, J.; Fois, M.

    1978-01-01

    Areas of possible applications of cluster injection are discussed. The deposition inside the plasma of molecules, issued from the dissociation of the injected clusters, has been computed. Some empirical scaling laws for the penetration are given

  6. Sodium Ferric Gluconate Injection

    Science.gov (United States)

    Sodium ferric gluconate injection is used to treat iron-deficiency anemia (a lower than normal number of ... are also receiving the medication epoetin (Epogen, Procrit). Sodium ferric gluconate injection is in a class of ...

  7. Aminocaproic Acid Injection

    Science.gov (United States)

    Aminocaproic acid injection is used to control bleeding that occurs when blood clots are broken down too quickly. This ... the baby is ready to be born). Aminocaproic acid injection is also used to control bleeding in ...

  8. Deoxycholic Acid Injection

    Science.gov (United States)

    Deoxycholic acid injection is used to improve the appearance and profile of moderate to severe submental fat ('double chin'; fatty tissue located under the chin). Deoxycholic acid injection is in a class of medications called ...

  9. Corticotropin, Repository Injection

    Science.gov (United States)

    ... injection is used to treat the following conditions:infantile spasms (seizures that usually begin during the first year ... tell how corticotropin repository injection works to treat infantile spasms.

  10. Effect of intra-tumoral magnetic nanoparticle hyperthermia and viral nanoparticle immunogenicity on primary and metastatic cancer

    Science.gov (United States)

    Hoopes, P. Jack; Mazur, Courtney M.; Osterberg, Bjorn; Song, Ailin; Gladstone, David J.; Steinmetz, Nicole F.; Veliz, Frank A.; Bursey, Alicea A.; Wagner, Robert J.; Fiering, Steven N.

    2017-02-01

    Although there is long association of medical hyperthermia and immune stimulation, the relative lack of a quantifiable and reproducible effect has limited the utility and advancement of this relationship in preclinical/clinical cancer and non-cancer settings. Recent cancer-based immune findings (immune checkpoint modulators etc.) including improved mechanistic understanding and biological tools now make it possible to modify and exploit the immune system to benefit conventional cancer treatments such as radiation and hyperthermia. Based on the prior experience of our research group including; cancer-based heat therapy, magnetic nanoparticle (mNP) hyperthermia, radiation biology, cancer immunology and Cowpea Mosaic Virus that has been engineered to over express antigenic proteins without RNA or DNA (eCPMV/VLP). This research was designed to determine if and how the intra-tumoral delivery of mNP hyperthermia and VLP can work together to improve local and systemic tumor treatment efficacy. Using the C3H mouse/MTG-B mammary adenocarcinoma cell model and the C57-B6 mouse/B-16-F10 melanoma cancer cell model, our data suggests the appropriate combination of intra-tumoral mNP heat (e.g. 43°C /30-60 minutes) and VLP (100 μg/200 mm3 tumor) not only result in significant primary tumor regression but the creation a systemic immune reaction that has the potential to retard secondary tumor growth (abscopal effect) and resist tumor rechallenge. Molecular data from these experiments suggest treatment based cell damage and immune signals such as Heat Shock Protein (HSP) 70/90, calreticulin, MTA1 and CD47 are potential targets that can be exploited to enhance the local and systemic (abscopal effect) immune potential of hyperthermia cancer treatment

  11. Genetic diversity in normal cell populations is the earliest stage of oncogenesis leading to intra-tumor heterogeneity

    Directory of Open Access Journals (Sweden)

    Cory L Howk

    2013-04-01

    Full Text Available Random mutations and epigenetic alterations provide a rich substrate for microevolutionary phenomena to occur in proliferating epithelial tissues. Genetic diversity resulting from random mutations in normal cells is critically important for understanding the genetic basis of oncogenesis. However, evaluation of the cell-specific role of individual (epi-genetic alterations in living tissues is extremely difficult from a direct experimental perspective. We have developed a theoretical model for uterine epithelial cell proliferation. Computational simulations have shown that a base-line mutation rate of two mutations per cell division is sufficient to explain sporadic endometrial cancer as a rare evolutionary consequence with an incidence similar to that reported in SEER data. Simulation of the entire oncogenic process has allowed us to analyze the features of the tumor initiating cells and their clonal expansion. Analysis of the malignant features of individual cancer cells, such as de-differentiation status, proliferation potential, and immortalization status, permits a mathematical characterization of malignancy and a comparison of intra-tumor heterogeneity between individual tumors. We found, under the conditions specified, that cancer stem cells account for approximately 7% of the total cancer cell population. Taken together, our mathematical modeling describes the genetic diversity and evolution in a normal cell population at the early stages of oncogenesis and characterizes intra-tumor heterogeneity. This model has explored the role of accumulation of a large number of genetic alterations in oncogenesis as an alternative to traditional biological approaches emphasizing the driving role of a small number of genetic mutations, and this accumulation, along with environmental factors, has a significant impact on the growth advantage of and selection pressure on individual cancer cells and the resulting tumor composition and progression.

  12. Geothermal injection monitoring project

    Energy Technology Data Exchange (ETDEWEB)

    Younker, L.

    1981-04-01

    Background information is provided on the geothermal brine injection problem and each of the project tasks is outlined in detail. These tasks are: evaluation of methods of monitoring the movement of injected fluid, preparation for an eventual field experiment, and a review of groundwater regulations and injection programs. (MHR)

  13. Injection moulding antireflective nanostructures

    DEFF Research Database (Denmark)

    Christiansen, Alexander Bruun; Clausen, Jeppe Sandvik; Mortensen, N. Asger

    2014-01-01

    in an injection moulding process, to fabricate the antireflective surfaces. The cycle-time was 35 s. The injection moulded structures had a height of 125 nm, and the visible spectrum reflectance of injection moulded black polypropylene surfaces was reduced from 4.5±0.5% to 2.5±0.5%. The gradient of the refractive...

  14. Injection moulding antireflective nanostructures

    DEFF Research Database (Denmark)

    Christiansen, Alexander Bruun; Clausen, Jeppe Sandvik; Mortensen, N. Asger

    in an injection moulding process, to fabricate the antireflective surfaces. The cycle-time was 35 s. The injection moulded structures had a height of 125 nm, and the visible spectrum reflectance of injection moulded black polypropylene surfaces was reduced from 4.5±0.5% to 2.5±0.5%. The gradient of the refractive...

  15. Impact of physical properties of biodiesel on the injection process in a common-rail direct injection system

    International Nuclear Information System (INIS)

    Boudy, Frederic; Seers, Patrice

    2009-01-01

    This paper presents the influence of biodiesel fuel properties on the injection mass flow rate of a diesel common-rail injection system. Simulations are first performed with ISO 4113 diesel fuel on a four-cylinder common-rail system to evaluate a single and triple injection strategies. For each injection strategy, the impact of modifying a single fuel property at a time is evaluated so as to quantify its influence on the injection process. The results show that fuel density is the main property that affects the injection process, such as total mass injected and pressure wave in the common-rail system. The fuel's viscosity and bulk modulus also influence, but to a lessen degree, the mass flow rate of the injector notably during multiple injection strategies as individual properties change the fuel's dampening property and friction coefficient.

  16. Injection moulding for macro and micro products

    DEFF Research Database (Denmark)

    Islam, Mohammad Aminul

    The purpose of the literature survey is to investigate the injection moulding technology in the macro and micro areas from the basic to the state-of-the-art recent technology. Injection moulding is a versatile production process for the manufacturing of plastic parts and the process is extensively...... used for macro products but with the ages it is going deep into the micro areas having machine and process improvements. Extensive research work on injection moulding is going on all over the world. New ideas are flowing into the machines, materials and processes. The technology has made significant...... advancement in the area of micro injection moulding, multi-component and two component injection mounding. In near future it is likely to be the way of manufacturing moulded interconnects devices (MID) for a low cost integration of electrical and mechanical functionalities on a single device. This paper...

  17. Effects of Multiple Injection of Bone Marrow Mononuclear Cells on Spinal Cord Injury of Rats.

    Science.gov (United States)

    Kanekiyo, Kenji; Nakano, Norihiko; Homma, Tamami; Yamada, Yoshihiro; Tamachi, Masahiro; Suzuki, Yoshihisa; Fukushima, Masanori; Saito, Fukuki; Ide, Chizuka

    2017-11-01

    The effects of multiple injection of bone marrow mononuclear cells (BMNCs) on spinal cord injury (SCI) were compared with those of single injection in rats. BMNCs separated by density-gradient centrifugation from a bone marrow perfusate were injected three times (once weekly) through the cerebrospinal fluid (CSF) via the fourth ventricle, and the locomotor improvement and tissue recovery, including axonal regeneration, were compared with those of single injection. While the single-injection group showed a steep elevation of the Basso-Beattie-Bresnahan (BBB) score 1 week after transplantation, the multiple-injection group maintained a similar steep elevation for 2 weeks after transplantation, and the BBB scores of the multiple-injection group remained thereafter at a level approximately 2-3 points higher than those of the single-injection group until the end of the experiment. There were significant differences between the single- and multiple-injection groups at 3, 4, and 8 weeks after transplantation. The difference in BBB scores at 8 weeks after transplantation suggested that there was a marked difference in the quality of locomotor behaviors between the single-and multiple-injection groups at this stage. An extensive outgrowth of regenerating axons through the astrocyte-devoid areas and a marked reduction of cavity formation were found in both the single- and multiple-injection groups. There were, however, no significant differences in the density of regenerating axons or volumes of cavities between the single- and multiple-injection groups. These results showed that although tissue recoveries were similar between single and multiple injection, the multiple injection of BMNCs was more beneficial for locomotor improvement than single injection for the treatment of SCI. Considering the technically simple and low-cost procedures for the preparation and injection of BMNCs, multiple injection of BMNCs by lumbar puncture has an advantage over single injection on

  18. Spin Injection in Indium Arsenide

    Directory of Open Access Journals (Sweden)

    Mark eJohnson

    2015-08-01

    Full Text Available In a two dimensional electron system (2DES, coherent spin precession of a ballistic spin polarized current, controlled by the Rashba spin orbit interaction, is a remarkable phenomenon that’s been observed only recently. Datta and Das predicted this precession would manifest as an oscillation in the source-drain conductance of the channel in a spin-injected field effect transistor (Spin FET. The indium arsenide single quantum well materials system has proven to be ideal for experimental confirmation. The 2DES carriers have high mobility, low sheet resistance, and high spin orbit interaction. Techniques for electrical injection and detection of spin polarized carriers were developed over the last two decades. Adapting the proposed Spin FET to the Johnson-Silsbee nonlocal geometry was a key to the first experimental demonstration of gate voltage controlled coherent spin precession. More recently, a new technique measured the oscillation as a function of channel length. This article gives an overview of the experimental phenomenology of the spin injection technique. We then review details of the application of the technique to InAs single quantum well (SQW devices. The effective magnetic field associated with Rashba spin-orbit coupling is described, and a heuristic model of coherent spin precession is presented. The two successful empirical demonstrations of the Datta Das conductance oscillation are then described and discussed.

  19. Epidural injections for back pain

    Science.gov (United States)

    ESI; Spinal injection for back pain; Back pain injection; Steroid injection - epidural; Steroid injection - back ... pillow under your stomach. If this position causes pain, you either sit up or lie on your ...

  20. Injection moulding antireflective nanostructures

    DEFF Research Database (Denmark)

    Christiansen, Alexander Bruun; Clausen, Jeppe Sandvik; Mortensen, N. Asger

    We present a method for injection moulding antireflective nanostructures on large areas, for high volume production. Nanostructured black silicon masters were fabricated by mask-less reactive ion etching, and electroplated with nickel. The nickel shim was antistiction coated and used in an inject......We present a method for injection moulding antireflective nanostructures on large areas, for high volume production. Nanostructured black silicon masters were fabricated by mask-less reactive ion etching, and electroplated with nickel. The nickel shim was antistiction coated and used...... in an injection moulding process, to fabricate the antireflective surfaces. The cycle-time was 35 s. The injection moulded structures had a height of 125 nm, and the visible spectrum reflectance of injection moulded black polypropylene surfaces was reduced from 4.5±0.5% to 2.5±0.5%. The gradient of the refractive...

  1. SQL injection detection system

    OpenAIRE

    Vargonas, Vytautas

    2017-01-01

    SQL injection detection system Programmers do not always ensure security of developed systems. That is why it is important to look for solutions outside being reliant on developers. In this work SQL injection detection system is proposed. The system analyzes HTTP request parameters and detects intrusions. It is based on unsupervised machine learning. Trained by regular request data system detects outlier user parameters. Since training is not reliant on previous knowledge of SQL injections, t...

  2. Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells.

    Science.gov (United States)

    Jovanovic, Ivan P; Pejnovic, Nada N; Radosavljevic, Gordana D; Pantic, Jelena M; Milovanovic, Marija Z; Arsenijevic, Nebojsa N; Lukic, Miodrag L

    2014-04-01

    The role of IL-33/ST2 pathway in antitumor immunity is unclear. Using 4T1 breast cancer model we demonstrate time-dependent increase of endogenous IL-33 at both the mRNA and protein levels in primary tumors and metastatic lungs during cancer progression. Administration of IL-33 accelerated tumor growth and development of lung and liver metastases, which was associated with increased intratumoral accumulation of CD11b(+) Gr-1(+) TGF-β1(+) myeloid-derived suppressor cells (MDSCs) that expressed IL-13α1R, IL-13-producing Lin(-) Sca-1(+) ST2(+) innate lymphoid cells (ILCs) and CD4(+) Foxp3(+) ST2(+) IL-10(+) Tregs compared to untreated mice. Higher incidence of monocytic vs. granulocytic MDSCs and plasmocytoid vs. conventional dendritic cells (DCs) was present in mammary tumors of IL-33-treated mice. Intratumoral NKp46(+) NKG2D(+) and NKp46(+) FasL(+) cells were markedly reduced after IL-33 treatment, while phosphate-buffered saline-treated ST2-deficient mice had increased frequencies of these tumoricidal natural killer (NK) cells compared to untreated wild-type mice. IL-33 promoted intratumoral cell proliferation and neovascularization, which was attenuated in the absence of ST2. Tumor-bearing mice given IL-33 had increased percentages of splenic MDSCs, Lin(-) Sca-1(+) ILCs, IL-10-expressing CD11c(+) DCs and alternatively activated M2 macrophages and higher circulating levels of IL-10 and IL-13. A significantly reduced NK cell, but not CD8(+) T-cell cytotoxicity in IL-33-treated mice was observed and the mammary tumor progression was not affected when CD8(+) T cells were in vivo depleted. We show a previously unrecognized role for IL-33 in promoting breast cancer progression through increased intratumoral accumulation of immunosuppressive cells and by diminishing innate antitumor immunity. Therefore, IL-33 may be considered as an important mediator in the regulation of breast cancer progression. © 2013 UICC.

  3. Joint and Soft Tissue Injections

    Science.gov (United States)

    ... Injections Joint and Soft Tissue Injections Share Print What is a joint and soft tissue injection? Joint and soft tissue injections are shots ... many injections do I need and how often? What restrictions do I have after an ... tissue injection, treatment April 1, 2004 Copyright © American Academy ...

  4. Piezoelectric Injection Systems

    Science.gov (United States)

    Mock, R.; Lubitz, K.

    The origin of direct injection can be doubtlessly attributed to Rudolf Diesel who used air assisted injection for fuel atomisation in his first self-ignition engine. Although it became apparent already at that time that direct injection leads to reduced specific fuel consumption compared to other methods of fuel injection, it was not used in passenger cars for the moment because of its disadvantageous noise generation as the requirements with regard to comfort were seen as more important than a reduced specific consumption.

  5. Intratumoral Infection with Murine Cytomegalovirus Synergizes with PD-L1 Blockade to Clear Melanoma Lesions and Induce Long-term Immunity

    Science.gov (United States)

    Erkes, Dan A; Xu, Guangwu; Daskalakis, Constantine; Zurbach, Katherine A; Wilski, Nicole A; Moghbeli, Toktam; Hill, Ann B; Snyder, Christopher M

    2016-01-01

    Cytomegalovirus is an attractive cancer vaccine platform because it induces strong, functional CD8+ T-cell responses that accumulate over time and migrate into most tissues. To explore this, we used murine cytomegalovirus expressing a modified gp100 melanoma antigen. Therapeutic vaccination by the intraperitoneal and intradermal routes induced tumor infiltrating gp100-specific CD8+ T-cells, but provided minimal benefit for subcutaneous lesions. In contrast, intratumoral infection of established tumor nodules greatly inhibited tumor growth and improved overall survival in a CD8+ T-cell-dependent manner, even in mice previously infected with murine cytomegalovirus. Although murine cytomegalovirus could infect and kill B16F0s in vitro, infection was restricted to tumor-associated macrophages in vivo. Surprisingly, the presence of a tumor antigen in the virus only slightly increased the efficacy of intratumoral infection and tumor-specific CD8+ T-cells in the tumor remained dysfunctional. Importantly, combining intratumoral murine cytomegalovirus infection with anti-PD-L1 therapy was synergistic, resulting in tumor clearance from over half of the mice and subsequent protection against tumor challenge. Thus, while a murine cytomegalovirus-based vaccine was poorly effective against established subcutaneous tumors, direct infection of tumor nodules unexpectedly delayed tumor growth and synergized with immune checkpoint blockade to promote tumor clearance and long-term protection. PMID:27434584

  6. A case of meningeal myxoid solitary fibrous tumor/hemangiopericytoma with unique NAB2-STAT6 fusion gene and symptomatic intratumoral hemorrhage

    Directory of Open Access Journals (Sweden)

    Takako Kihara, MD

    2017-11-01

    Full Text Available We experienced a case of meningeal solitary fibrous tumor (SFT/hemangiopericytoma (HPC with symptomatic intratumoral hemorrhage in a 67-year-old Japanese woman. Her chief complaints were sudden onset of motor aphasia and right hemiparesis. Brain computed tomography showed the hemorrhagic mass adjacent to the superior sagittal sinus. The mass was resected and pathological examination of the specimen revealed a tumor that is rich in vessels and accompanied with intratumoral hemorrhage. Short spindle tumor cells were proliferating with myxoid stroma. Tumor cells appeared to be arranged around the vessels and sometimes attached to the vessel wall directly. Although hyalinization of the vessel wall was observed, neither patternless pattern nor staghorn vessels were seen. Immunohistochemistry revealed that the tumor cells were positive for both CD34 and nuclear STAT6. Moreover, gene analyses revealed unique NAB2-STAT6 fusion. Immunohistochemical findings and fusion-gene analyses enabled us to make the definite diagnosis of meningeal myxoid SFT/HPC. The present case showed the three unique features such as clinically symptomatic intratumoral hemorrhage at the onset, rare variant of myxoid SFT/HPC, and unique NAB2-STAT6 fusion.

  7. Intratumoral Infection with Murine Cytomegalovirus Synergizes with PD-L1 Blockade to Clear Melanoma Lesions and Induce Long-term Immunity.

    Science.gov (United States)

    Erkes, Dan A; Xu, Guangwu; Daskalakis, Constantine; Zurbach, Katherine A; Wilski, Nicole A; Moghbeli, Toktam; Hill, Ann B; Snyder, Christopher M

    2016-08-01

    Cytomegalovirus is an attractive cancer vaccine platform because it induces strong, functional CD8(+) T-cell responses that accumulate over time and migrate into most tissues. To explore this, we used murine cytomegalovirus expressing a modified gp100 melanoma antigen. Therapeutic vaccination by the intraperitoneal and intradermal routes induced tumor infiltrating gp100-specific CD8(+) T-cells, but provided minimal benefit for subcutaneous lesions. In contrast, intratumoral infection of established tumor nodules greatly inhibited tumor growth and improved overall survival in a CD8(+) T-cell-dependent manner, even in mice previously infected with murine cytomegalovirus. Although murine cytomegalovirus could infect and kill B16F0s in vitro, infection was restricted to tumor-associated macrophages in vivo. Surprisingly, the presence of a tumor antigen in the virus only slightly increased the efficacy of intratumoral infection and tumor-specific CD8(+) T-cells in the tumor remained dysfunctional. Importantly, combining intratumoral murine cytomegalovirus infection with anti-PD-L1 therapy was synergistic, resulting in tumor clearance from over half of the mice and subsequent protection against tumor challenge. Thus, while a murine cytomegalovirus-based vaccine was poorly effective against established subcutaneous tumors, direct infection of tumor nodules unexpectedly delayed tumor growth and synergized with immune checkpoint blockade to promote tumor clearance and long-term protection.

  8. Cryo-Assisted Resection En Bloc, and Cryoablation In Situ, of Primary Breast Cancer Coupled With Intraoperative Ultrasound-Guided Tracer Injection: A Preliminary Clinical Study.

    Science.gov (United States)

    Korpan, Nikolai N; Xu, Kecheng; Schwarzinger, Philipp; Watanabe, Masashi; Breitenecker, Gerhard; Patrick, Le Pivert

    2018-01-01

    The aim of the study was to perform cryosurgery on a primary breast tumor, coupled with simultaneous peritumoral and intratumoral tracer injection of a blue dye, to evaluate lymphatic mapping. We explored the ability of our strategy to prevent tumor cells, but not that of injected tracers, to migrate to the lymphovascular drainage during conventional resection of frozen breast malignancies. Seventeen patients aged 51 (14) years (mean [standard deviation]), presenting primary breast cancer with stage I to IV, were randomly selected and treated in The Rudolfinerhaus Private Clinic in Vienna, Austria, and included in this preliminary clinical study. Under intraoperative ultrasound, 14 patients underwent curative cryo-assisted tumor resection en bloc, coupled with peritumoral tracer injection, which consisted of complete tumor freezing and concomitant peritumor injection with a blue dye, before resection and sentinel lymph node dissection (group A). Group B consists of 3 patients previously refused any standard therapy and had palliative tumor cryoablation in situ combined with intratumoral tracer injection. The intraoperative ultrasound facilitated needle positioning and dye injection timing. In group A, the frozen site extruded the dye that was distributed through the unfrozen tumor, the breast tissue, and the resection cavity for 12 patients. One to 4 lymph nodes were stained for 10 of 14 patients. The resection margin was evaluable. Our intraoperative ultrasound-guided performance revealed the injection and migration of a blue dye during the frozen resection en bloc and cryoablation in situ of primary breast tumors. Sentinel lymph node mapping, pathological determination of the tumor, and resection margins were achievable. The study paves the way for intraoperative cryo-assisted therapeutic strategies for breast cancer.

  9. MO-FG-BRA-01: Development of An Image-Guided Dosimetric Planning System for Injectable Brachytherapy Using ELP Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Lafata, K [Duke University, Durham, North Carolina (United States); Duke University Medical Center, Durham, NC (United States); Schaal, J; Liu, W [Duke University, Durham, North Carolina (United States); Cai, J [Duke University Medical Center, Durham, NC (United States)

    2015-06-15

    Purpose: To develop, validate, and evaluate a methodology for determining dosimetry for intratumoral injections of elastin-like-polypeptide (ELP) brachytherapy nanoparticles. These organic-polymer-based nanoparticles are injectable, biodegradable, and genetically tunable. We present a genetically encoded polymer-solution, composed of novel radiolabeled-ELP nanoparticles that are custom-designed to self-assemble into a local source upon intratumoral injection. Our preliminary results of a small animal study demonstrate 100% tumor response, effective radionuclide retention-rates, strong in vivo stability, and no polymer-induced toxicities. While our approach is therefore highly promising for improved brachytherapy, the current workflow lacks a dosimetry framework. Methods: We are developing a robust software framework that provides image-guided dosimetric-planning capabilities for ELP brachytherapy. The user graphically places ELP injection sites within a µCT-planning-image, and independently defines each injection volume, concentration, and radioisotope to be used. The resulting internal dosimetry is then pre-determined by first modeling post-injection ELP advection-diffusion, and then calculating the resulting dose distribution based on a point- dose-kernel-convolution algorithm. We have experimentally measured ELP steady-state concentrations via µSPECT acquisition, and validated our dose calculation algorithm against Monte Carlo simulations of several radioactivity distributions. Finally, we have investigated potential advantages and limitations of various ELP injection parameters. Results: The µSPECT results demonstrated inhomogeneous steady-state distributions of ELP in tissue, and Monte Carlo radioactivity distributions were designed accordingly. Our algorithm yielded a root-mean-square-error of less than 2% for each distribution tested (average root-mean-square-error was 0.73%). Dose-Volume-Histogram analysis of five different plans showed how strategic

  10. Electron injection in microtron

    International Nuclear Information System (INIS)

    Axinescu, S.

    1977-01-01

    A review of the methods of injecting electrons in the microtron is presented. A special attention is paid to efficient injection systems developed by Wernholm and Kapitza. A comparison of advantages and disadvantages of both systems is made in relation to the purpose of the microtron. (author)

  11. Glenohumeral Joint Injections

    Science.gov (United States)

    Gross, Christopher; Dhawan, Aman; Harwood, Daniel; Gochanour, Eric; Romeo, Anthony

    2013-01-01

    Context: Intra-articular injections into the glenohumeral joint are commonly performed by musculoskeletal providers, including orthopaedic surgeons, family medicine physicians, rheumatologists, and physician assistants. Despite their frequent use, there is little guidance for injectable treatments to the glenohumeral joint for conditions such as osteoarthritis, adhesive capsulitis, and rheumatoid arthritis. Evidence Acquisition: We performed a comprehensive review of the available literature on glenohumeral injections to help clarify the current evidence-based practice and identify deficits in our understanding. We searched MEDLINE (1948 to December 2011 [week 1]) and EMBASE (1980 to 2011 [week 49]) using various permutations of intra-articular injections AND (corticosteroid OR hyaluronic acid) and (adhesive capsulitis OR arthritis). Results: We identified 1 and 7 studies that investigated intra-articular corticosteroid injections for the treatment of osteoarthritis and adhesive capsulitis, respectively. Two and 3 studies investigated the use of hyaluronic acid in osteoarthritis and adhesive capsulitis, respectively. One study compared corticosteroids and hyaluronic acid injections in the treatment of osteoarthritis, and another discussed adhesive capsulitis. Conclusion: Based on existing studies and their level of evidence, there is only expert opinion to guide corticosteroid injection for osteoarthritis as well as hyaluronic acid injection for osteoarthritis and adhesive capsulitis. PMID:24427384

  12. Tolerability of hypertonic injectables.

    Science.gov (United States)

    Wang, Wei

    2015-07-25

    Injectable drug products are ideally developed as isotonic solutions. Often, hypertonic injectables may have to be marketed for a variety of reasons such as product solubilization and stabilization. A key concern during product formulation development is the local and systemic tolerability of hypertonic products upon injection. This report reviews and discusses the tolerability in terms of local discomfort, irritation, sensation of heat and pain, along with other observed side effects of hypertonicity in both in-vitro systems and in-vivo animal and human models. These side effects clearly depend on the degree of hypertonicity. The sensation of pain among different injection routes seems to follow this order: intramuscular>subcutaneous>intravenous or intravascular. It is recommended that the upper osmolality limit should be generally controlled under 600 mOsm/kg for drug products intended for intramuscular or subcutaneous injection. For drug products intended for intravenous or intravascular injection, the recommended upper limit should be generally controlled under 1,000 mOsm/kg for small-volume injections (≤ 100 mL) and 500 mOsm/kg for large-volume injections (>100mL). Several options are available for minimization of hypertonicity-induced pain upon product administration. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. [A Case of Intrahepatic Cholangiocarcinoma with Invasion to the Transverse Colon and Gallbladder, Forming an Intra-Tumor Abscess].

    Science.gov (United States)

    Okada, Nami; Kametaka, Hisashi; Koyama, Takashi; Seike, Kazuhiro; Makino, Hironobu; Fukada, Tadaomi; Sato, Yutaka; Miyazaki, Masaru

    2015-11-01

    An 81-year-old man was referred to our institution for evaluation of high fever and a liver tumor that had been detected by ultrasonography. Computed tomography revealed a low-density mass with peripheral ring-like enhancement in S5 of the liver. The liver mass was in contact with the gallbladder, and the boundary between the mass and the gallbladder was unclear. On the suspicion of liver abscess, percutaneous transhepatic drainage was performed. The cavity of the abscess communicated with the gallbladder. Because the cavity had no tendency to reduce in size, we performed surgical resection under a preoperative diagnosis of liver abscess or primary liver carcinoma invading to the gallbladder. Intraoperative findings revealed a liver tumor invading the transverse colon and gallbladder. Subsegmentectomy of S4a and S5 of the liver combined with gallbladder and transverse colon resection was performed. Histopathological findings indicated the growth of a mass forming type intrahepatic cholangiocarcinoma with invasion to the transverse colon and gallbladder, and the pathological stage of the tumor was pT3N0M0, fStage Ⅲ. Thus far, the patient is alive without recurrence 9 months after surgery. Here, we report an extremely rare case of intrahepatic cholangiocarcinoma that invaded other organs and was associated with an intra-tumor abscess.

  14. From Chemotherapy to Combined Targeted Therapeutics: In Vitro and in Vivo Models to Decipher Intra-tumor Heterogeneity

    Directory of Open Access Journals (Sweden)

    Guido Gambara

    2018-02-01

    Full Text Available Recent advances in next-generation sequencing and other omics technologies capable to map cell fate provide increasing evidence on the crucial role of intra-tumor heterogeneity (ITH for cancer progression. The different facets of ITH, from genomic to microenvironmental heterogeneity and the hierarchical cellular architecture originating from the cancer stem cell compartment, contribute to the range of tumor phenotypes. Decoding these complex data resulting from the analysis of tumor tissue complexity poses a challenge for developing novel therapeutic strategies that can counteract tumor evolution and cellular plasticity. To achieve this aim, the development of in vitro and in vivo cancer models that resemble the complexity of ITH is crucial in understanding the interplay of cells and their (microenvironment and, consequently, in testing the efficacy of new targeted treatments and novel strategies of tailoring combinations of treatments to the individual composition of the tumor. This challenging approach may be an important cornerstone in overcoming the development of pharmaco-resistances during multiple lines of treatment. In this paper, we report the latest advances in patient-derived 3D (PD3D cell cultures and patient-derived tumor xenografts (PDX as in vitro and in vivo models that can retain the genetic and phenotypic heterogeneity of the tumor tissue.

  15. Effect of the Ethanol Injection Moment During Compression Stroke on the Combustion of Ethanol - Diesel Dual Direct Injection Engine

    Science.gov (United States)

    Liang, Yu; Zhou, Liying; Huang, Haomin; Xu, Mingfei; Guo, Mei; Chen, Xin

    2018-01-01

    A set of GDI system is installed on a F188 single-cylinder, air-cooled and direct injection diesel engine, which is used for ethanol injection, with the injection time controlled by the crank angle signal collected by AVL angle encoder. The injection of ethanol amounts to half of the thermal equivalent of an original diesel fuel. A 3D combustion model is established for the ethanol - diesel dual direct injection engine. Diesel was injected from the original fuel injection system, with a fuel supply advance angle of 20°CA. The ethanol was injected into the cylinder during compression process. Diesel injection began after the completion of ethanol injection. Ethanol injection starting point of 240°CA, 260°CA, 280°CA, 300°CA and 319.4°CA were simulated and analyzed. Due to the different timing of ethanol injection, the ignition of the ethanol mixture when diesel fires, results in non-uniform ignition distribution and flame propagation rate, since the distribution and concentration gradients of the ethanol mixture in the cylinder are different, thus affecting the combustion process. The results show that, when ethanol is injected at 319.4°CA, the combustion heat release rate and the pressure rise rate during the initial stage are the highest. Also, the maximum combustion pressure, with a relatively advance phase, is the highest. In case of later initial ethanol injection, the average temperature in the cylinder during the initial combustion period will have a faster rise. In case of initial injection at 319.4°CA, the average temperature in the cylinder is the highest, followed by 240°CA ethanol injection. In the post-combustion stage, the earlier ethanol injection will result in higher average temperature in the cylinder and more complete fuel combustion. The injection of ethanol at 319.4°CA produces earlier and highest NOX emissions.

  16. Bolus injections of measured amounts of radioactivity

    International Nuclear Information System (INIS)

    Wesolowski, C.A.; Hogendoorn, P.; Vandierendonck, R.; Driedger, A.A.

    1988-01-01

    Many time-based radionuclide techniques, such as glomerular filtration rate measurement (GFR), require prompt intravenous delivery of and accurately measured tracer bolus with minimal residual tracer retention at the injection site. The quality assurance aspects of two antecubital vein, quantitative injection techniques were investigated. A flush bolus technique using a tuberculin syringe piggybacked onto a 10-ml saline flush was compared to a single blood pressure cuff injection technique. Scintillation camera data for each technique were compared for bolus duration in the abdominal aorta and for residual activity at the injection site at 5 min. Bolus times were measured as the FWHM of the gamma variate fit to the abdominal aortic regional time-activity curves. Relatively little focal activity was seen in the antecubital injection site following the flush bolus: marked residual activity was seen following the blood pressure cuff injections. The injection site/arm background ratios averaged 1.3 for the flush bolus and 30.1 for the cuff technique. Although both methods allowed accurate in vitro determination of administered radioactivity, only the tuberculin syringe flush bolus technique was acceptable for time-based quantitation because of its superior in vivo characteristics

  17. AA injection kicker in its tank

    CERN Multimedia

    CERN PhotoLab

    1980-01-01

    For single-turn injection of the antiprotons, a septum at the end of the injection line made the beam parallel to the injection orbit, and a quarter of a betatron-wavelength downstream a fast kicker corrected the angle. Kicker type: lumped delay line. PFN voltage 56 kV. Bending angle 7.5 mrad; kick-strength 0.9 Tm; fall-time 95%-5% in 150 ns. The injection orbit is to the left, the stack orbit to the far right. A fast shutter near the central orbit had to be closed before the kicker fired, so as to protect the stack core from being shaken by the kicker's fringe field. The shutter is shown in closed position.

  18. Intratumoral heterogeneity as a therapy resistance mechanism: role of melanoma subpopulations.

    Science.gov (United States)

    Somasundaram, Rajasekharan; Villanueva, Jessie; Herlyn, Meenhard

    2012-01-01

    Malignant melanoma is an aggressive form of skin cancer whose incidence continues to increase worldwide. Increased exposure to sun, ultraviolet radiation, and the use of tanning beds can increase the risk of melanoma. Early detection of melanomas is the key to successful treatment mainly through surgical excision of the primary tumor lesion. But in advanced stage melanomas, once the disease has spread beyond the primary site to distant organs, the tumors are difficult to treat and quickly develop resistance to most available forms of therapy. The advent of molecular and cellular techniques has led to a better characterization of tumor cells revealing the presence of heterogeneous melanoma subpopulations. The discovery of gene mutations and alterations of cell-signaling pathways in melanomas has led to the development of new targeted drugs that show dramatic response rates in patients. Single-agent therapies generally target one subpopulation of tumor cells while leaving others unharmed. The surviving subpopulations will have the ability to repopulate the original tumors that can continue to progress. Thus, a rational approach to target multiple subpopulations of tumor cells with a combination of drugs instead of single-agent therapy will be necessary for long-lasting inhibition of melanoma lesions. In this context, the recent development of immune checkpoint reagents provides an additional armor that can be used in combination with targeted drugs to expand the presence of melanoma reactive T cells in circulation to prevent tumor recurrence. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. THE RHIC INJECTION SYSTEM.

    Energy Technology Data Exchange (ETDEWEB)

    FISCHER,W.; GLENN,J.W.; MACKAY,W.W.; PTITSIN,V.; ROBINSON,T.G.; TSOUPAS,N.

    1999-03-29

    The RHIC injection system has to transport beam from the AGS-to-RHIC transfer line onto the closed orbits of the RHIC Blue and Yellow rings. This task can be divided into three problems. First, the beam has to be injected into either ring. Second, once injected the beam needs to be transported around the ring for one turn. Third, the orbit must be closed and coherent beam oscillations around the closed orbit should be minimized. We describe our solutions for these problems and report on system tests conducted during the RHIC Sextant test performed in 1997. The system will be fully commissioned in 1999.

  20. UV-visible digital imaging of split injection in a Gasoline Direct Injection engine

    Directory of Open Access Journals (Sweden)

    Merola Simona Silvia

    2015-01-01

    Full Text Available Ever tighter limits on pollutant emissions and the need to improve energy conversion efficiency have made the application of gasoline direct injection (GDI feasible for a much wider scale of spark ignition engines. Changing the way fuel is delivered to the engine has thus provided increased flexibility but also challenges, such as higher particulate emissions. Therefore, alternative injection control strategies need to be investigated in order to obtain optimum performance and reduced environmental impact. In this study, experiments were carried out on a single-cylinder GDI optical engine fuelled with commercial gasoline in lean-burn conditions. The single-cylinder was equipped with the head of a commercial turbocharged engine with similar geometrical specifications (bore, stroke, compression ratio and wall guided fuel injection. Optical accessibility was ensured through a conventional elongated hollow Bowditch piston and an optical crown, accommodating a fused-silica window. Experimental tests were performed at fixed engine speed and injection pressure, whereas the injection timing and the number of injections were adjusted to investigate their influence on combustion and emissions. UV-visible digital imaging was applied in order to follow the combustion process, from ignition to the late combustion phase. All the optical data were correlated with thermodynamic analysis and measurements of exhaust emissions. Split injection strategies (i.e. two injections per cycle with respect to single injection increased combustion efficiency and stability thanks to an improvement of fuel air mixing. As a consequence, significant reduction in soot formation and exhaust emission with acceptable penalty in terms of HC and NOx were measured.

  1. Characterization of genetic intratumor heterogeneity in colorectal cancer and matching patient-derived spheroid cultures

    DEFF Research Database (Denmark)

    Árnadóttir, Sigrid S; Jeppesen, Maria; Lamy, Philippe

    2018-01-01

    Patient-derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs...... and spheroids contained private mutations. Therefore, multiple cultures from spatially distinct sites of the tumor increase the insight into the genetic profile of the entire tumor. Molecular subtypes were called from RNA sequencing data. When based on transcripts from both cancer and noncancerous cells......, the subtypes were largely independent of sampling site. In contrast, subtyping based on cancer cell transcripts alone was dependent on sample site and genetic ITH. In conclusion, all examined CRC tumors showed genetic ITH. Spheroid cultures partly reflected this ITH, and having multiple cultures from distinct...

  2. Parathyroid Hormone Injection

    Science.gov (United States)

    ... the blood in people with certain types of hypoparathyroidism (condition in which the body does not produce ... are taking this medication.Parathyroid hormone injection controls hypoparathyroidism but does not cure it. Continue to use ...

  3. Collagenase Clostridium Histolyticum Injection

    Science.gov (United States)

    ... disease (a thickening of tissue [plaque] inside the penis that causes the penis to curve). Collagenase Clostridium histolyticum injection is in ... the plaque of thickened tissue and allows the penis to be straightened.

  4. Premixed direct injection disk

    Science.gov (United States)

    York, William David; Ziminsky, Willy Steve; Johnson, Thomas Edward; Lacy, Benjamin; Zuo, Baifang; Uhm, Jong Ho

    2013-04-23

    A fuel/air mixing disk for use in a fuel/air mixing combustor assembly is provided. The disk includes a first face, a second face, and at least one fuel plenum disposed therebetween. A plurality of fuel/air mixing tubes extend through the pre-mixing disk, each mixing tube including an outer tube wall extending axially along a tube axis and in fluid communication with the at least one fuel plenum. At least a portion of the plurality of fuel/air mixing tubes further includes at least one fuel injection hole have a fuel injection hole diameter extending through said outer tube wall, the fuel injection hole having an injection angle relative to the tube axis. The invention provides good fuel air mixing with low combustion generated NOx and low flow pressure loss translating to a high gas turbine efficiency, that is durable, and resistant to flame holding and flash back.

  5. Endoscopic injection therapy

    Directory of Open Access Journals (Sweden)

    Sang Woon Kim

    2017-06-01

    Full Text Available Since the U.S. Food and Drug Administration approved dextranomer/hyaluronic acid copolymer (Deflux for the treatment of vesicoureteral reflux, endoscopic injection therapy using Deflux has become a popular alternative to open surgery and continuous antibiotic prophylaxis. Endoscopic correction with Deflux is minimally invasive, well tolerated, and provides cure rates approaching those of open surgery (i.e., approximately 80% in several studies. However, in recent years a less stringent approach to evaluating urinary tract infections (UTIs and concerns about long-term efficacy and complications associated with endoscopic injection have limited the use of this therapy. In addition, there is little evidence supporting the efficacy of endoscopic injection therapy in preventing UTIs and vesicoureteral reflux-related renal scarring. In this report, we reviewed the current literature regarding endoscopic injection therapy and provided an updated overview of this topic.

  6. Endoscopic injection therapy

    Science.gov (United States)

    Kim, Sang Woon; Lee, Yong Seung

    2017-01-01

    Since the U.S. Food and Drug Administration approved dextranomer/hyaluronic acid copolymer (Deflux) for the treatment of vesicoureteral reflux, endoscopic injection therapy using Deflux has become a popular alternative to open surgery and continuous antibiotic prophylaxis. Endoscopic correction with Deflux is minimally invasive, well tolerated, and provides cure rates approaching those of open surgery (i.e., approximately 80% in several studies). However, in recent years a less stringent approach to evaluating urinary tract infections (UTIs) and concerns about long-term efficacy and complications associated with endoscopic injection have limited the use of this therapy. In addition, there is little evidence supporting the efficacy of endoscopic injection therapy in preventing UTIs and vesicoureteral reflux-related renal scarring. In this report, we reviewed the current literature regarding endoscopic injection therapy and provided an updated overview of this topic. PMID:28612059

  7. Piperacillin and Tazobactam Injection

    Science.gov (United States)

    ... cause infection. Tazobactam is in a class called beta-lactamase inhibitor. It works by preventing bacteria from destroying piperacillin.Antibiotics such as piperacillin and tazobactam injection will ... your risk of getting an infection later that resists antibiotic treatment.

  8. Injection and Dump Systems

    CERN Document Server

    Bracco, C; Barnes, M J; Carlier, E; Drosdal, L N; Goddard, B; Kain, V; Meddahi, M; Mertens, V; Uythoven, J

    2012-01-01

    Performance and failures of the LHC injection and ex- traction systems are presented. In particular, a comparison with the 2010 run, lessons learnt during operation with high intensity beams and foreseen upgrades are described. UFOs, vacuum and impedance problems related to the injection and extraction equipment are analysed together with possible improvements and solutions. New implemented features, diagnostics, critical issues of XPOC and IQC applications are addressed.

  9. Dimethyl Ether Injection Studies

    DEFF Research Database (Denmark)

    Sorenson, Spencer C.; Glensvig, Michael; Abata, Duane L.

    1998-01-01

    A series of preliminary investigations has been performed in order to investigate the behavior of DME in a diesel injection environment. These studies have in-cluded visual observations of the spray penetration and angles for high pressure injection into Nitrogen using conventional jerk pump inje...... well with the experimentally observed combustion rates during the mixing controlled portions of the combustion in a naturally aspirated direct injection diesel engine.......A series of preliminary investigations has been performed in order to investigate the behavior of DME in a diesel injection environment. These studies have in-cluded visual observations of the spray penetration and angles for high pressure injection into Nitrogen using conventional jerk pump...... injection equipment. It was shown that the penetration of the DME spray can be predicted with the methods developed for diesel fuel by Hiroyasu and co-workers. Some anomalies in spray shape, such as rapid lateral spreading at the base of the spray and spray bifurcation have been observed.The compressibility...

  10. Intratumor heterogeneous distribution of 10B-compounds suggested by the radiobiological findings from in vivo mouse studies

    International Nuclear Information System (INIS)

    Masunaga, S.; Ono, K.; Sakurai, Y.; Takagaki, M.; Kobayashi, T.; Kinashi, Y.; Akaboshi, M.; Akuta, K.

    2000-01-01

    After continuous labeling with or without 5-bromo-2'-deoxyuridine (BrdU), SCC VII tumor-bearing mice received one of the following treatments in vivo; 1) Tumor excision right after thermal neutron irradiation following sodium borocaptate- 10 B (BSH) or p-boronophenylalanine- 10 B (BPA) administration. 2) Tumor excision 5 min through 72 h after thermal neutron or γ-ray irradiation. 3) Determination of hypoxic fraction (HF) of implanted tumors by γ-ray test irradiation 5 min through 72 h after thermal neutron or γ-ray irradiation. 4) Determination of the tumor sensitivity to γ-rays 0-24 h after thermal neutron or γ-ray irradiation. The following results were obtained; 1) BSH and BPA sensitized quiescent (Q) and total (proliferating (P) + Q) tumor cells, respectively, and the use of 10 B-compound, especially BPA, widened the sensitivity difference between Q and total cells. 2) The use of 10 B-compound, especially BPA, increased the repair capacity from potentially lethal damage (PLDR) and induced PLDR pattern like post-γ-ray irradiation. 3) Reoxygenation after thermal neutron irradiation following 10 B-compound, especially BPA, administration occurred slowly, compared with after neutron irradiation only and looked like after γ-ray irradiation. 4) The use of 10 B-compound, especially BPA, promoted sublethal damage repair (SLDR) in total cells and the recruitment from Q to P state, compared with after thermal neutron irradiation alone. All these findings suggested the difficulty in distribution of 10 B-compound, especially BPA, in Q cells and the heterogeneity in intratumor distribution of 10 B-compound. (author)

  11. Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

    Science.gov (United States)

    Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

    2016-08-15

    A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

  12. Intratumoral Immunization by p19Arf and Interferon-β Gene Transfer in a Heterotopic Mouse Model of Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    João Paulo Portela Catani

    2016-12-01

    Full Text Available Therapeutic strategies that act by eliciting and enhancing antitumor immunity have been clinically validated as an effective treatment modality but may benefit from the induction of both cell death and immune activation as primary stimuli. Using our AdRGD-PG adenovector platform, we show here for the first time that in situ gene transfer of p19Arf and interferon-β (IFNβ in the LLC1 mouse model of lung carcinoma acts as an immunotherapy. Although p19Arf is sufficient to induce cell death, only its pairing with IFNβ significantly induced markers of immunogenic cell death. In situ gene therapy with IFNβ, either alone or in combination with p19Arf, could retard tumor progressio