Sample records for abdominal hyperthermia combined

  1. Magnetic nanoparticle-conjugated polymeric micelles for combined hyperthermia and chemotherapy

    NASA Astrophysics Data System (ADS)

    Kim, Hyun-Chul; Kim, Eunjoo; Jeong, Sang Won; Ha, Tae-Lin; Park, Sang-Im; Lee, Se Guen; Lee, Sung Jun; Lee, Seung Woo

    2015-10-01

    Magnetic nanoparticle-conjugated polymeric micelles (MNP-PMs) consisting of poly(ethylene glycol)-poly(lactide) (PEG-PLA) and iron oxide nanoparticles were prepared and used as nanocarriers for combined hyperthermia and chemotherapy. Doxorubicin (DOX) was encapsulated in MNP-PMs, and an alternating magnetic field (AMF) resulted in an increase to temperature within a suitable range for inducing hyperthermia and a higher rate of drug release than observed without AMF. In vitro cytotoxicity and hyperthermia experiments were carried out using human lung adenocarcinoma A549 cells. When MNP-PMs encapsulated with an anticancer drug were used to treat A549 cells in combination with hyperthermia under AMF, 78% of the cells were killed by the double effects of heat and the drug, and the combination was more effective than either chemotherapy or hyperthermia treatment alone. Therefore, MNP-PMs encapsulated with an anticancer drug show potential for combined chemotherapy and hyperthermia.Magnetic nanoparticle-conjugated polymeric micelles (MNP-PMs) consisting of poly(ethylene glycol)-poly(lactide) (PEG-PLA) and iron oxide nanoparticles were prepared and used as nanocarriers for combined hyperthermia and chemotherapy. Doxorubicin (DOX) was encapsulated in MNP-PMs, and an alternating magnetic field (AMF) resulted in an increase to temperature within a suitable range for inducing hyperthermia and a higher rate of drug release than observed without AMF. In vitro cytotoxicity and hyperthermia experiments were carried out using human lung adenocarcinoma A549 cells. When MNP-PMs encapsulated with an anticancer drug were used to treat A549 cells in combination with hyperthermia under AMF, 78% of the cells were killed by the double effects of heat and the drug, and the combination was more effective than either chemotherapy or hyperthermia treatment alone. Therefore, MNP-PMs encapsulated with an anticancer drug show potential for combined chemotherapy and hyperthermia. Electronic

  2. The role of temperature increase rate in combinational hyperthermia chemotherapy treatment

    NASA Astrophysics Data System (ADS)

    Tang, Yuan; McGoron, Anthony J.

    2010-02-01

    Hyperthermia in combination with chemotherapy has been widely used in cancer treatment. Our previous study has shown that rapid rate hyperthermia in combination with chemotherapy can synergistically kill cancer cells whereas a sub-additive effect was found when a slow rate hyperthermia was applied. In this study, we explored the basis of this difference. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. P-glycoprotein (P-gp) expression, Caspase 3 activity, and heat shock protein 70 (HSP 70) expression following the two different modes of heating were measured. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. Slow rate hyperthermia was provided by a cell culture incubator. Two sets of thermal doses were delivered by either slow rate or rapid rate hyperthermia. HSP70 expression was highly elevated under low dose slow rate incubator hyperthermia while maintained at the baseline level under the other three treatments. Caspase3 level slightly increased after low dose slow rate incubator hyperthermia while necrotic cell death was found in the other three types of heat treatment. In conclusion, when given at the same thermal dose, slow rate hyperthermia is more likely to induce thermotolerance. Meanwhile, hyperthermia showed a dose dependent capability in reversing P-gp mediated MDR; when MDR is reversed, the combinational treatment induced extensive necrotic cell death. During this process, the rate of heating also played a very important role; necrosis was more dramatic in rapid rate hyperthermia than in slow rate hyperthermia even though they were given at the same dose.

  3. Intra-Peritoneal Hyperthermia Combining α-Galactosylceramide in the Treatment of Ovarian Cancer

    PubMed Central

    Hsu, Yun-Ting; Huang, Jung-Tang; Wu, T. -C; Hung, Chien-Fu; Yang, Yuh-Cheng; Chang, Chih-Long

    2013-01-01

    The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8+/IFN-γ+ tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer. PMID:23935988

  4. High pressure enhances the effect of hyperthermia in intraperitoneal chemotherapy with oxaliplatin: an experimental study.

    PubMed

    Facy, Olivier; Al Samman, Sophie; Magnin, Guy; Ghiringhelli, Francois; Ladoire, Sylvain; Chauffert, Bruno; Rat, Patrick; Ortega-Deballon, Pablo

    2012-12-01

    Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) achieve good results in selected patients with peritoneal carcinomatosis. High intra-abdominal pressure could enhance the penetration of chemotherapy drugs. The aim of this study was to compare the effects of high pressure and hyperthermia when used separately and when combined in terms of blood and tissue absorption of oxaliplatin in a swine model of intraperitoneal chemotherapy. Four groups of 5 pigs each underwent laparotomy and open intraperitoneal chemotherapy with oxaliplatin at a constant concentration (150 mg/L) for 30 minutes in normothermia and atmospheric pressure (group 1), or hyperthermia (42°C) and atmospheric pressure (group 2), or normothermia and high pressure (25 cm H2O) (group 3), or hyperthermia and high pressure (group 4). High pressure was achieved thorough a water column over the abdomen. Systemic absorption and abdominal tissue mapping of the penetration of oxaliplatin in each group were studied. Blood concentrations of oxaliplatin were similar in the different groups. Hyperthermia achieved higher concentrations in visceral surfaces (P = 0.0014), but not in parietal surfaces. High pressure enhanced diffusion of the drug in both the visceral and parietal peritoneum (P = 0.0058 and P = 0.0044, respectively). The combination of hyperthermia and high pressure significantly increased the penetration of oxaliplatin and achieved the highest tissue concentrations (10.39 mg/kg vs 5.48 mg/kg; P = 0.00001 in the visceral peritoneum, and 66.16 mg/kg vs 35.62 mg/kg; P = 0.0003 in the parietal peritoneum). Open high-pressure HIPEC with oxaliplatin is feasible in the pig. Hyperthermia enhances diffusion in the visceral peritoneum, whereas high pressure is effective in the visceral and parietal peritoneum. The combination of the two achieves the highest tissue concentrations of oxaliplatin.

  5. Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment

    NASA Astrophysics Data System (ADS)

    Quinto, Christopher A.; Mohindra, Priya; Tong, Sheng; Bao, Gang

    2015-07-01

    Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy.Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could

  6. 'Smart' gold nanoshells for combined cancer chemotherapy and hyperthermia.

    PubMed

    Liang, Zhongshi; Li, Xingui; Xie, Yegui; Liu, Shunying

    2014-04-01

    Nanomaterials that circulate in the body have great potential in the diagnosis and treatment of diseases. Here we report that 'smart' gold nanoshells can carry a drug payload, and that their intrinsic near-infrared (NIR) plasmon resonance enables the combination of chemotherapeutic and hyperthermia therapies. The 'smart' gold nanoshells (named DOX/A54@GNs) consist of (a) gold nanoshells (GNs) with NIR plasmon resonance, which not only act as nanoblocks but also produce local heat to allow hyperthermia; (b) an anticancer drug, doxorubicin (DOX), which was conjugated onto the nanoblocks by pH-dependent biodegradable copolymer thiol poly(ethylene glycol) derivatives via carbamate linkage; and (c) the targeting peptide A54 (AGKGTPSLETTP) to facilitate its orientation to liver cancer cells and enhance cellular uptake. The conjugated DOX was released from the DOX/A54@GNs much more rapidly in an acidic environment (pH 5.3) than in a neutral environment (pH 7.4), which is a desirable characteristic for intracellular tumor drug release. DOX-modified GNs showed pH-dependent release behavior, and the in vitro cell uptake experiment using ICP-AES and microscopy showed greater internalization of A54-modified GNs in the human liver cancer cell line BEL-7402 than of those without A54. Flow cytometry and fluoroscopy analysis were conducted to reveal the enhanced cell apoptosis caused by the A54-modified GNs under combined chemotherapeutic and hyperthermia therapies. These results imply that DOX/A54@GNs could be used as a multifunctional nanomaterial system with pH-triggered drug-releasing properties for tumor-targeted chemotherapy and hyperthermia.

  7. [Chemotherapy in combination with laser coagulation or interstitial hyperthermia--effective combined therapy for disseminated skin melanoma].

    PubMed

    Akimov, M A; Gel'fond, M L; Gershanovich, M L; Barchuk, A S

    2003-01-01

    Thirty-eight patients with disseminated skin melanoma received chemotherapy in conjunction with laser coagulation or interstitial hyperthermia of intra- or subcutaneous metastases. Use of combination therapy was followed by a rise to 37% in total response and 16%--complete regression, respectively. Most effectiveness was attained when the dacarbazine + cisplatin + BCNU + tamoxifen regime was employed. In this group of 16 patients (46%), total response was 56% and, what is most significant, 31% in complete regression. In all cases of apparent response, polychemotherapy was administered both before and after laser coagulation or interstitial hyperthermia.

  8. Combined magnetic nanoparticle-based microRNA and hyperthermia therapy to enhance apoptosis in brain cancer cells.

    PubMed

    Yin, Perry T; Shah, Birju P; Lee, Ki-Bum

    2014-10-29

    A novel therapy is demonstrated utilizing magnetic nanoparticles for the dual purpose of delivering microRNA and inducing magnetic hyperthermia. In particular, the combination of lethal-7a microRNA (let-7a), which targets a number of the survival pathways that typically limit the effectiveness of hyperthermia, with magnetic hyperthermia greatly enhances apoptosis in brain cancer cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment.

    PubMed

    Quinto, Christopher A; Mohindra, Priya; Tong, Sheng; Bao, Gang

    2015-08-07

    Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy.

  10. Can magneto-plasmonic nanohybrids efficiently combine photothermia with magnetic hyperthermia?

    NASA Astrophysics Data System (ADS)

    Espinosa, Ana; Bugnet, Mathieu; Radtke, Guillaume; Neveu, Sophie; Botton, Gianluigi A.; Wilhelm, Claire; Abou-Hassan, Ali

    2015-11-01

    Multifunctional hybrid-design nanomaterials appear to be a promising route to meet the current therapeutics needs required for efficient cancer treatment. Herein, two efficient heat nano-generators were combined into a multifunctional single nanohybrid (a multi-core iron oxide nanoparticle optimized for magnetic hyperthermia, and a gold branched shell with tunable plasmonic properties in the NIR region, for photothermal therapy) which impressively enhanced heat generation, in suspension or in vivo in tumours, opening up exciting new therapeutic perspectives.Multifunctional hybrid-design nanomaterials appear to be a promising route to meet the current therapeutics needs required for efficient cancer treatment. Herein, two efficient heat nano-generators were combined into a multifunctional single nanohybrid (a multi-core iron oxide nanoparticle optimized for magnetic hyperthermia, and a gold branched shell with tunable plasmonic properties in the NIR region, for photothermal therapy) which impressively enhanced heat generation, in suspension or in vivo in tumours, opening up exciting new therapeutic perspectives. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06168g

  11. Modeling the heat transfer problem for the novel combined cryosurgery and hyperthermia system.

    PubMed

    Zhao, Gang; Bai, Xue-Fei; Luo, Da-Wei; Gao, Da-Yong

    2006-01-01

    A multidimensional, finite element analysis (FEA) for the freezing, holding, rewarming and heating processes of biological tissues during the cryosurgery process of the new Combined Cryosurgery/Hyperthermia System is presented to theoretically test its validity. The tissues are treated as nonideal materials freezing over a temperature range, and the thermophysical properties of which are temperature dependent. The enthalpy method is applied to solve the highly nonlinear problem. It was found that when the same boundary condition and the same target tissue presented, the novel Cryosurgery/Hyperthermia System could supply the target tissue an approximative cooling rate, a much lower minimal temperature, a much greater warming rate, and a much greater thermal gradients compared with that of the simplified Endocare system. The numerical simulation indicates that the novel combined cryosurgery and hyperthermia system can provide an excellent curative effect in the corresponding cryotherapy. And the most attractive feature of this FEA framework is that it can be easily mastered by the surgeon without in-depth theory of heat transfer to analyze the cryosurgery process beforehand due to the friendly GUI (graphical user interface) of Ansys software.

  12. Cisplatin combined with hyperthermia kills HepG2 cells in intraoperative blood salvage but preserves the function of erythrocytes.

    PubMed

    Yang, Jin-ting; Tang, Li-hui; Liu, Yun-qing; Wang, Yin; Wang, Lie-ju; Zhang, Feng-jiang; Yan, Min

    2015-05-01

    The safe use of intraoperative blood salvage (IBS) in cancer surgery remains controversial. Here, we investigated the killing effect of cisplatin combined with hyperthermia on human hepatocarcinoma (HepG2) cells and erythrocytes from IBS in vitro. HepG2 cells were mixed with concentrated erythrocytes and pretreated with cisplatin (50, 100, and 200 μg/ml) alone at 37 °C for 60 min and cisplatin (25, 50, 100, and 200 μg/ml) combined with hyperthermia at 42 °C for 60 min. After pretreatment, the cell viability, colony formation and DNA metabolism in HepG2 and the Na(+)-K(+)-ATPase activity, 2,3-diphosphoglycerate (2,3-DPG) concentration, free hemoglobin (Hb) level, osmotic fragility, membrane phosphatidylserine externalization, and blood gas variables in erythrocytes were determined. Pretreatment with cisplatin (50, 100, and 200 μg/ml) combined with hyperthermia (42 °C) for 60 min significantly decreased HepG2 cell viability, and completely inhibited colony formation and DNA metabolism when the HepG2 cell concentration was 5×10(4) ml(-1) in the erythrocyte (P<0.01). Erythrocytic Na(+)-K(+)-ATPase activity, 2,3-DPG level, phosphatidylserine externalization, and extra-erythrocytic free Hb were significantly altered by hyperthermia plus high concentrations of cisplatin (100 and 200 μg/ml) (P<0.05), but not by hyperthermia plus 50 μg/ml cisplatin (P>0.05). In conclusion, pretreatment with cisplatin (50 μg/ml) combined with hyperthermia (42 °C) for 60 min effectively eliminated HepG2 cells from IBS but did not significantly affect erythrocytes in vitro.

  13. Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kok, H. Petra, E-mail: H.P.Kok@amc.uva.nl; Crezee, Johannes; Franken, Nicolaas A.P.

    2014-03-01

    Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Methods and Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy{sup −1}) and β (Gy{sup −2}) of the linear–quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normalmore » tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear–quadratic model. Results: The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. Conclusion: A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from

  14. Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy

    NASA Astrophysics Data System (ADS)

    Kim, Kyoung Sub; Kim, Jiyoung; Lee, Joo Young; Matsuda, Shofu; Hideshima, Sho; Mori, Yasurou; Osaka, Tetsuya; Na, Kun

    2016-06-01

    Despite magnetic nanoparticles having shown great potential in cancer treatment, tremendous challenges related to diagnostic sensitivity and treatment efficacy for clinical application remain. Herein, we designed optimized multifunctional magnetite nanoparticles (AHP@MNPs), composed of Fe3O4 nanoparticles and photosensitizer conjugated hyaluronic acid (AHP), to achieve enhanced tumor diagnosis and therapy. Fe3O4 nanoparticles (MNPs) were synthesized by a facile hydrolysis method. MNPs have higher biocompatibility, controllable particle sizes, and desirable magnetic properties. The fabricated AHP@MNPs have enhanced water solubility (average size: 108.13 +/- 1.08 nm), heat generation properties, and singlet oxygen generation properties upon magnetic and laser irradiation. The AHP@MNPs can target tumors via CD44 receptor-mediated endocytosis, which have enhanced tumor therapeutic effects through photodynamic/hyperthermia-combined treatment without any drugs. We successfully detected tumors implanted in mice via magnetic resonance imaging and optical imaging. Furthermore, we demonstrated the photodynamic/hyperthermia-combined therapeutic efficacy of AHP@MNPs with synergistically enhanced efficacy against cancer.Despite magnetic nanoparticles having shown great potential in cancer treatment, tremendous challenges related to diagnostic sensitivity and treatment efficacy for clinical application remain. Herein, we designed optimized multifunctional magnetite nanoparticles (AHP@MNPs), composed of Fe3O4 nanoparticles and photosensitizer conjugated hyaluronic acid (AHP), to achieve enhanced tumor diagnosis and therapy. Fe3O4 nanoparticles (MNPs) were synthesized by a facile hydrolysis method. MNPs have higher biocompatibility, controllable particle sizes, and desirable magnetic properties. The fabricated AHP@MNPs have enhanced water solubility (average size: 108.13 +/- 1.08 nm), heat generation properties, and singlet oxygen generation properties upon magnetic and laser

  15. Can magneto-plasmonic nanohybrids efficiently combine photothermia with magnetic hyperthermia?

    PubMed

    Espinosa, Ana; Bugnet, Mathieu; Radtke, Guillaume; Neveu, Sophie; Botton, Gianluigi A; Wilhelm, Claire; Abou-Hassan, Ali

    2015-12-07

    Multifunctional hybrid-design nanomaterials appear to be a promising route to meet the current therapeutics needs required for efficient cancer treatment. Herein, two efficient heat nano-generators were combined into a multifunctional single nanohybrid (a multi-core iron oxide nanoparticle optimized for magnetic hyperthermia, and a gold branched shell with tunable plasmonic properties in the NIR region, for photothermal therapy) which impressively enhanced heat generation, in suspension or in vivo in tumours, opening up exciting new therapeutic perspectives.

  16. Deep hyperthermia with the HYPERcollar system combined with irradiation for advanced head and neck carcinoma - a feasibility study.

    PubMed

    Verduijn, G M; de Wee, E M; Rijnen, Z; Togni, P; Hardillo, J A U; Ten Hove, I; Franckena, M; van Rhoon, G C; Paulides, M M

    2018-05-11

    Radiotherapy (RT) treatment of locally-advanced and recurrent head and neck carcinoma (HNC) results in disappointing outcomes. Combination of RT with cisplatin or cetuximab improves survival but the increased toxicity and patient's comorbidity warrant the need for a less-toxic radiosensitizer. Stimulated by several randomized studies demonstrating the radio-sensitizing effect of hyperthermia, we developed the HYPERcollar. Here, we report early experience and toxicity in patients with advanced HNC. 119 hyperthermia treatments given to 27 patients were analyzed. Hyperthermia was applied once a week by the HYPERcollar aimed at achieving 39-43 °C in the target area, up to patients' tolerance. Pre-treatment planning was used to optimize treatment settings. When possible, invasive thermometry catheters were placed. Mean power applied during the 119 hyperthermia treatments ranged from 120 to 1007 W (median 543 W). 15 (13%) hyperthermia treatments were not fully completed due to: pain allocated to hyperthermia (6/15), dyspnea from sticky saliva associated with irradiation (2/15) and unknown reasons (7/15). No severe complications or enhanced thermal or mucosal toxicities were observed. Excluding post-operative treatment, response rates after 3 months were 46% (complete) and 7% (partial). Hyperthermia with the HYPERcollar proved to be safe and feasible with good compliance and promising outcome.

  17. Efficient treatment of breast cancer xenografts with multifunctionalized iron oxide nanoparticles combining magnetic hyperthermia and anti-cancer drug delivery.

    PubMed

    Kossatz, Susanne; Grandke, Julia; Couleaud, Pierre; Latorre, Alfonso; Aires, Antonio; Crosbie-Staunton, Kieran; Ludwig, Robert; Dähring, Heidi; Ettelt, Volker; Lazaro-Carrillo, Ana; Calero, Macarena; Sader, Maha; Courty, José; Volkov, Yuri; Prina-Mello, Adriele; Villanueva, Angeles; Somoza, Álvaro; Cortajarena, Aitziber L; Miranda, Rodolfo; Hilger, Ingrid

    2015-05-13

    Tumor cells can effectively be killed by heat, e.g. by using magnetic hyperthermia. The main challenge in the field, however, is the generation of therapeutic temperatures selectively in the whole tumor region. We aimed to improve magnetic hyperthermia of breast cancer by using innovative nanoparticles which display a high heating potential and are functionalized with a cell internalization and a chemotherapeutic agent to increase cell death. The superparamagnetic iron oxide nanoparticles (MF66) were electrostatically functionalized with either Nucant multivalent pseudopeptide (N6L; MF66-N6L), doxorubicin (DOX; MF66-DOX) or both (MF66-N6LDOX). Their cytotoxic potential was assessed in a breast adenocarcinoma cell line MDA-MB-231. Therapeutic efficacy was analyzed on subcutaneous MDA-MB-231 tumor bearing female athymic nude mice. All nanoparticle variants showed an excellent heating potential around 500 W/g Fe in the alternating magnetic field (AMF, conditions: H=15.4 kA/m, f=435 kHz). We could show a gradual inter- and intracellular release of the ligands, and nanoparticle uptake in cells was increased by the N6L functionalization. MF66-DOX and MF66-N6LDOX in combination with hyperthermia were more cytotoxic to breast cancer cells than the respective free ligands. We observed a substantial tumor growth inhibition (to 40% of the initial tumor volume, complete tumor regression in many cases) after intratumoral injection of the nanoparticles in vivo. The proliferative activity of the remaining tumor tissue was distinctly reduced. The therapeutic effects of breast cancer magnetic hyperthermia could be strongly enhanced by the combination of MF66 functionalized with N6L and DOX and magnetic hyperthermia. Our approach combines two ways of tumor cell killing (magnetic hyperthermia and chemotherapy) and represents a straightforward strategy for translation into the clinical practice when injecting nanoparticles intratumorally.

  18. Evaluation of The Combined Effects of Hyperthermia, Cobalt-60 Gamma Rays and IUdR on Cultured Glioblastoma Spheroid Cells and Dosimetry Using TLD-100

    PubMed Central

    Neshasteh-Riz, Ali; Rahdani, Rozhin; Mostaar, Ahmad

    2014-01-01

    Objective In radiation treatment, the irradiation which is effective enough to control the tumors far exceeds normal-tissues tolerance. Thus to avoid such unfavourable outcomes, some methods sensitizing the tumor cells to radiation are used. Iododeoxyuridine (IUdR) is a halogenated thymidine analogue that known to be effective as a radiosensitizer in human cancer therapy. Improving the potential efficacy of radiation therapy after combining to hyperthermia depends on the magnitude of the differential sensitization of the hyperthermic effects or on the differential cytotoxicity of the radiation effects on the tumor cells. In this study, we evaluated the combined effects of IUdR, hyperthermia and gamma rays of 60Co on human glioblastoma spheroids culture. Materials and Methods In this experimental study,the cultured spheroids with 100µm diameter were treated by 1 µM IUdR, 43°C hyperthermia for an hour and 2 Gy gamma rays, respectively. The DNA damages induced in cells were compared using alkaline comet assay method, and dosimetry was then performed by TLD-100. Comet scores were calculated as mean ± standard error of mean (SEM) using one-way ANOVA. Results Comparison of DNA damages induced by IUdR and hyperthermia + gamma treatment showed 2.67- and 1.92-fold enhancement, respectively, as compared to the damages induced by radiation alone or radiation combined IUdR. Dosimetry results showed the accurate dose delivered to cells. Conclusion Analysis of the comet tail moments of spheroids showed that the radiation treatments combined with hyperthermia and IUdR caused significant radiosensitization when compared to related results of irradiation alone or of irradiation with IUdR. These results suggest a potential clinical advantage of combining radiation with hyperthermia and indicate effectiveness of hyperthermia treatment in inducing cytotoxicity of tumor cells. PMID:24611138

  19. Combined hyperthermia and radiotherapy for the treatment of cancer.

    PubMed

    Kaur, Punit; Hurwitz, Mark D; Krishnan, Sunil; Asea, Alexzander

    2011-09-30

    Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an in-tegral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, car-diac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threat-ening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic

  20. Combined Hyperthermia and Radiotherapy for the Treatment of Cancer

    PubMed Central

    Kaur, Punit; Hurwitz, Mark D.; Krishnan, Sunil; Asea, Alexzander

    2011-01-01

    Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an integral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, cardiac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threatening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic

  1. Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

    PubMed

    Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing; Ware, Matthew J; Law, Justin J; Newton, Jared M; Nguyen, Lam; Curley, Steven A; Corr, Stuart J

    2018-04-02

    Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  2. A Study for Cryosurgery-Hyperthermia Treatment System

    NASA Astrophysics Data System (ADS)

    Takahashi, Daishi; Takahashi, Tomoya; Sone, Kazuya; Fukumoto, Ichiro

    Cryosurgical system utilizing liquid nitrogen and argon gas as cryogens has been used for the treatment of malignant tumors. Those devices fail to cool the tissues to the low temperatures that completely destroy the bulky tumors. It is of course difficult for the low power cooling devices using Peltier effect, to destroy the large tumors. Therefore adjunctive treatment such as hyperthermia treatment is needed to intensify the tissue destruction. Actually, hyperthermia has been clinically used to destroy tumors, but it is unclear that the hyperthermia enhances the tissue injury in cryosurgery because there have been few studies of the combination use of hyperthermia and cryosurgery. The purposes of this study are to produce the cryosurgery-hyperthermia treatment system utilizing Peltier device and Stirling cooler and to evaluate the effects of hyperthermia treatment immediately after thawing in cryosurgery onto the living normal liver tissue of mouse. In the no-load running test of our system, the minimum temperature of the cryoprobe reached -74.0 degrees C in 30 minutes. The findings of the stained tissues suggested that the combination treatment of both was effective to destroy the tissue and the higher temperature applied immediately after freezing and thawing in cryosurgery might reinforce the tissue destruction.

  3. Boosted Hyperthermia Therapy by Combined AC Magnetic and Photothermal Exposures in Ag/Fe3O4 Nanoflowers.

    PubMed

    Das, R; Rinaldi-Montes, N; Alonso, J; Amghouz, Z; Garaio, E; García, J A; Gorria, P; Blanco, J A; Phan, M H; Srikanth, H

    2016-09-28

    Over the past two decades, magnetic hyperthermia and photothermal therapy are becoming very promising supplementary techniques to well-established cancer treatments such as radiotherapy and chemotherapy. These techniques have dramatically improved their ability to perform controlled treatments, relying on the procedure of delivering nanoscale objects into targeted tumor tissues, which can release therapeutic killing doses of heat either upon AC magnetic field exposure or laser irradiation. Although an intense research effort has been made in recent years to study, separately, magnetic hyperthermia using iron oxide nanoparticles and photothermal therapy based on gold or silver plasmonic nanostructures, the full potential of combining both techniques has not yet been systematically explored. Here we present a proof-of-principle experiment showing that designing multifunctional silver/magnetite (Ag/Fe3O4) nanoflowers acting as dual hyperthermia agents is an efficient route for enhancing their heating ability or specific absorption rate (SAR). Interestingly, the SAR of the nanoflowers is increased by at least 1 order of magnitude under the application of both an external magnetic field of 200 Oe and simultaneous laser irradiation. Furthermore, our results show that the synergistic exploitation of the magnetic and photothermal properties of the nanoflowers reduces the magnetic field and laser intensities that would be required in the case that both external stimuli were applied separately. This constitutes a key step toward optimizing the hyperthermia therapy through a combined multifunctional magnetic and photothermal treatment and improving our understanding of the therapeutic process to specific applications that will entail coordinated efforts in physics, engineering, biology, and medicine.

  4. Core–Shell Nanoparticle-Based Peptide Therapeutics and Combined Hyperthermia for Enhanced Cancer Cell Apoptosis

    PubMed Central

    2015-01-01

    Mitochondria-targeting peptides have garnered immense interest as potential chemotherapeutics in recent years. However, there is a clear need to develop strategies to overcome the critical limitations of peptides, such as poor solubility and the lack of target specificity, which impede their clinical applications. To this end, we report magnetic core–shell nanoparticle (MCNP)-mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail-anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells. Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic efficacy of ATAP, while the presence of targeting ligands afforded selective delivery to cancer cells. Induction of MCNP-mediated hyperthermia further potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP delivery and subsequent hyperthermia resulted in an enhanced effect on mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis. PMID:25133971

  5. Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

    NASA Astrophysics Data System (ADS)

    de Paula, Leonardo B.; Primo, Fernando L.; Pinto, Marcelo R.; Morais, Paulo C.; Tedesco, Antonio C.

    2015-04-01

    The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×1013 or 1.50×1013 particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×1013 or 1.50×1013 magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments.

  6. Multifunctional magnetic Fe3O4 nanoparticles combined with chemotherapy and hyperthermia to overcome multidrug resistance

    PubMed Central

    Ren, Yanyan; Zhang, Haijun; Chen, Baoan; Cheng, Jian; Cai, Xiaohui; Liu, Ran; Xia, Guohua; Wu, Weiwei; Wang, Shuai; Ding, Jiahua; Gao, Chong; Wang, Jun; Bao, Wen; Wang, Lei; Tian, Liang; Song, Huihui; Wang, Xuemei

    2012-01-01

    Background Multidrug resistance in cancer is a major obstacle for clinical therapeutics, and is the reason for 90% of treatment failures. This study investigated the efficiency of novel multifunctional Fe3O4 magnetic nanoparticles (Fe3O4-MNP) combined with chemotherapy and hyperthermia for overcoming multidrug resistance in an in vivo model of leukemia. Methods Nude mice with tumor xenografts were randomly divided into a control group, and the treatment groups were allocated to receive daunorubicin, 5-bromotetrandrine (5-BrTet) and daunorubicin, Fe3O4-MNP, and Fe3O4-MNP coloaded with daunorubicin and 5-bromotetrandrine (Fe3O4-MNP-DNR-5-BrTet), with hyperthermia in an alternating magnetic field. We investigated tumor volume and pathology, as well as P-glycoprotein, Bcl-2, Bax, and caspase-3 protein expression to elucidate the effect of multimodal treatment on overcoming multidrug resistance. Results Fe3O4-MNP played a role in increasing tumor temperature during hyperthermia. Tumors became significantly smaller, and apoptosis of cells was observed in both the Fe3O4-MNP and Fe3O4-MNP-DNR-5-BrTet groups, especially in the Fe3O4-MNP-DNR-5-BrTet group, while tumor volumes in the other groups had increased after treatment for 12 days. Furthermore, Fe3O4-MNP-DNR-5-BrTet with hyperthermia noticeably decreased P-glycoprotein and Bcl-2 expression, and markedly increased Bax and caspase-3 expression. Conclusion Fe3O4-MNP-DNR-5-BrTet with hyperthermia may be a potential approach for reversal of multidrug resistance in the treatment of leukemia. PMID:22619560

  7. Multifunctional magnetic Fe3O4 nanoparticles combined with chemotherapy and hyperthermia to overcome multidrug resistance.

    PubMed

    Ren, Yanyan; Zhang, Haijun; Chen, Baoan; Cheng, Jian; Cai, Xiaohui; Liu, Ran; Xia, Guohua; Wu, Weiwei; Wang, Shuai; Ding, Jiahua; Gao, Chong; Wang, Jun; Bao, Wen; Wang, Lei; Tian, Liang; Song, Huihui; Wang, Xuemei

    2012-01-01

    Multidrug resistance in cancer is a major obstacle for clinical therapeutics, and is the reason for 90% of treatment failures. This study investigated the efficiency of novel multifunctional Fe(3)O(4) magnetic nanoparticles (Fe(3)O(4)-MNP) combined with chemotherapy and hyperthermia for overcoming multidrug resistance in an in vivo model of leukemia. Nude mice with tumor xenografts were randomly divided into a control group, and the treatment groups were allocated to receive daunorubicin, 5-bromotetrandrine (5-BrTet) and daunorubicin, Fe(3)O(4)-MNP, and Fe(3)O(4)-MNP coloaded with daunorubicin and 5-bromotetrandrine (Fe(3)O(4)-MNP-DNR-5-BrTet), with hyperthermia in an alternating magnetic field. We investigated tumor volume and pathology, as well as P-glycoprotein, Bcl-2, Bax, and caspase-3 protein expression to elucidate the effect of multimodal treatment on overcoming multidrug resistance. Fe(3)O(4)-MNP played a role in increasing tumor temperature during hyperthermia. Tumors became significantly smaller, and apoptosis of cells was observed in both the Fe(3)O(4)-MNP and Fe(3)O(4)-MNP-DNR-5-BrTet groups, especially in the Fe(3)O(4)-MNP-DNR-5-BrTet group, while tumor volumes in the other groups had increased after treatment for 12 days. Furthermore, Fe(3)O(4)-MNP-DNR-5-BrTet with hyperthermia noticeably decreased P-glycoprotein and Bcl-2 expression, and markedly increased Bax and caspase-3 expression. Fe(3)O(4)-MNP-DNR-5-BrTet with hyperthermia may be a potential approach for reversal of multidrug resistance in the treatment of leukemia.

  8. Malignant hyperthermia

    MedlinePlus

    ... about MH: Malignant Hyperthermia Association of the United States -- www.mhaus.org National Organization for Rare Disorders -- rarediseases.org/rare-diseases/malignant-hyperthermia NIH Genetics Home Reference -- ghr.nlm.nih.gov/condition/malignant-hyperthermia

  9. Current Status and Perspectives of Hyperthermia in Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Hiraoka, Masahiro; Nagata, Yasushi; Mitsumori, Michihide; Sakamoto, Masashi; Masunaga, Shin-ichiro

    2004-08-01

    Clinical trials of hyperthermia in combination with radiation therapy or chemotherapy undertaken over the past decades in Japan have been reviewed. Originally developed heating devices were mostly used for these trials, which include RF (radiofrequency) capacitive heating devices, a microwave heating device with a lens applicator, an RF intracavitary heating device, an RF current interstitial heating device, and ferromagnetic implant heating device. Non-randomized trials for various cancers, demonstrated higher response rate in thermoradiotherapy than in radiotherapy alone. Randomized trials undertaken for esophageal cancers also demonstrated improved local response with the combined use of hyperthermia. Furthermore, the complications associated with treatment were not generally serious. These clinical results indicate the benefit of combined treatment of hyperthermia and radiotherapy for various malignancies. On the other hand, the presently available heating devices are not satisfactory from the clinical viewpoints. With the advancement of heating and thermometry technologies, hyperthermia will be more widely and safely used in the treatment of cancers.

  10. Hyperthermia in the treatment of cancer: A review of the radiobiological basis

    NASA Technical Reports Server (NTRS)

    Baker, D. G.

    1978-01-01

    Temperatures in the range 41.5 C to 43.5 C tend to be more damaging to malignant than nonmalignant cells. Where local hyperthermia (41.5 C to 43.5 C) is combined with ionizing radiation, a significant therapeutic ratio may be realized. Total body hyperthermia, alone or combined with other therapeutic modalities, can provide palliation for some systemic malignancies but may not be as effective as local hyperthermia for treating local disease. The influence of hyperthermia on immune mechanisms and the risk of metastatic spread of potential tumor growth stimulation need further investigation. Among other questions needing elucidation before hyperthermia can be considered a standard treatment modality are the time-dose (for heating) relationships to produce an optimal therapeutic ratio and whether the late sequela of combined heat and ionizing radiation may result in an unacceptable risk of patient morbidity.

  11. Synergistic chemotherapy by combined moderate hyperthermia and photochemical internalization.

    PubMed

    Christie, Catherine; Molina, Stephanie; Gonzales, Jonathan; Berg, Kristian; Nair, Rohit Kumar; Huynh, Khoi; Madsen, Steen J; Hirschberg, Henry

    2016-04-01

    Combination therapies of photochemical internalization (PCI) and moderate hyperthermia (MHT) were investigated in an in vitro system consisting of human and rat glioma spheroids. PCI using the amphiphilic photosensitizer, AlPcS2a and two anti cancer agents BLM or 5-FU were used. Spheroids were irradiated with λ = 670 nm laser light in an incubator at temperatures ranging from 37 to 44°C. For each temperature investigated, spheroids were divided into 4 groups: control, drug-only, photodynamic therapy (PDT), and PCI. PDT and PCI spheroids were exposed to radiant exposures ranging from 0.3 to 2.5 J cm(-2) using an irradiance of 5 mW cm(-2). Toxicity was evaluated from spheroid growth kinetics. The combination of PCI and MHT resulted in significant increases in BLM efficacy at 44°C for both cell line derived spheroids compared to controls at 37°C over the range of radiant exposures examined. 5-FU PCI was ineffective for the human cell line at both 37 and 44°C.

  12. Synergistic chemotherapy by combined moderate hyperthermia and photochemical internalization

    PubMed Central

    Christie, Catherine; Molina, Stephanie; Gonzales, Jonathan; Berg, Kristian; Nair, Rohit Kumar; Huynh, Khoi; Madsen, Steen J.; Hirschberg, Henry

    2016-01-01

    Combination therapies of photochemical internalization (PCI) and moderate hyperthermia (MHT) were investigated in an in vitro system consisting of human and rat glioma spheroids. PCI using the amphiphilic photosensitizer, AlPcS2a and two anti cancer agents BLM or 5-FU were used. Spheroids were irradiated with λ = 670 nm laser light in an incubator at temperatures ranging from 37 to 44°C. For each temperature investigated, spheroids were divided into 4 groups: control, drug-only, photodynamic therapy (PDT), and PCI. PDT and PCI spheroids were exposed to radiant exposures ranging from 0.3 to 2.5 J cm−2 using an irradiance of 5 mW cm−2. Toxicity was evaluated from spheroid growth kinetics. The combination of PCI and MHT resulted in significant increases in BLM efficacy at 44°C for both cell line derived spheroids compared to controls at 37°C over the range of radiant exposures examined. 5-FU PCI was ineffective for the human cell line at both 37 and 44°C. PMID:27446650

  13. Biotin-Containing Reduced Graphene Oxide-Based Nanosystem as a Multieffect Anticancer Agent: Combining Hyperthermia with Targeted Chemotherapy.

    PubMed

    Mauro, Nicolò; Scialabba, Cinzia; Cavallaro, Gennara; Licciardi, Mariano; Giammona, Gaetano

    2015-09-14

    Among the relevant properties of graphene derivatives, their ability of acting as an energy-converting device so as to produce heat (i.e., thermoablation and hyperthermia) was more recently taken into account for the treatment of solid tumors. In this pioneering study, for the first time, the in vitro RGO-induced hyperthermia was assessed and combined with the stimuli-sensitive anticancer effect of a biotinylated inulin-doxorubicin conjugate (CJ-PEGBT), hence, getting to a nanosystem endowed with synergic anticancer effects and high specificity. CJ-PEGBT was synthesized by linking pentynoic acid and citraconic acid to inulin. The citraconylamide pendants, used as pH reversible spacer, were exploited to further conjugate doxorubicin, whereas the alkyne moiety was orthogonally functionalized with an azido PEG-biotin derivative by copper(II) catalyzed 1,3-dipolar cycloaddition. DSC measures, AFM, and UV spectrophotometry were employed to systematically investigate adsorption of CJ-PEGBT onto RGO and its physicochemical stability in aqueous media, demonstrating that a stable π-staked nanosystem can be obtained. In vitro tests using cancer breast cells (MCF-7) showed the ability of the RGO/CJ-PEGBT of efficiently killing cancer cells both via a selective laser beam thermoablation and hyperthermia-triggered chemotherapy. If compared with the nonbiotinylated nanosystem, including virgin RGO and the free conjugate, RGO/CJ-PEGBT is endowed with a smart combination of properties which warrant potential as an anticancer nanomedicine.

  14. Temporary Abdominal Closure Combined With an Irrigating System Utilizing Hypochlorous Acid Solution to Decrease Abdominal Mucopurulence

    PubMed Central

    Matthews, Marc R.; Quan, Asia N.; Weir, Alexandra S.; Foster, Kevin N.; Caruso, Daniel M.

    2018-01-01

    Introduction: Leaving the abdominal cavity open is a well-described and frequently utilized technique in the treatment of severe intra-abdominal sepsis. Irrigation through a negative pressure wound therapy device is a technique employed to assist in the closure of wounds as well as the reduction of bacterial contamination. Furthermore, hypochlorous acid has been found to be safe and effective in microorganismal elimination from extremity wounds. There is no literature regarding the infusion of hypochlorous solution into the abdominal cavity for intra-abdominal sepsis or mucopurulent abscesses or biofilm. Objectives: A 47-year-old man with granulomatosis polyangiitis was started on weekly rituximab. After 4 infusions, skin sloughing, ultimately diagnosed as toxic epidermal necrolysis, developed. During the hospital course, he developed sepsis and bowel perforation necessitating an exploratory laparotomy. The abdomen was left open with a temporary abdominal closure using the Abthera open abdomen negative wound therapy device; however, the abdomen remained infected with visually diffuse, thickening mucopurulence despite multiple washouts. Therefore, a VAC Vera-Flo irrigation device was combined with the Abthera open abdomen negative wound therapy device and cyclical irrigation of hypochlorous acid. After 72 hours, the purulence visually was improved and no adverse events were recorded with the placement of intra-abdominal hypochlorous acid. Conclusions: The combination of two medical devices for the intra-abdominal instillation of irrigation is considered “off-label use” from the manufacturer's recommendations. In addition, the repeated instillation of hypochlorous acid solution has not been described but was noted to have visually decreased the contaminated effluent within the intra-abdominal fluid. PMID:29527250

  15. Marshall J. Edwards: discoverer of maternal hyperthermia as a human teratogen.

    PubMed

    Graham, John M

    2005-11-01

    In a series of animal studies performed over a career spanning 40 years at the University of Sydney, Professor Marshall J. Edwards investigated the hypothesis that maternal hyperthermia during gestation can be teratogenic to the developing fetus. He is one of few investigators to have discovered a known human teratogen primarily through animal studies. In 1970 he earned his Ph.D. from the University of Sydney, writing a doctoral thesis entitled "A Study of Some Factors Affecting Fertility of Animals with Particular Reference to the Effects of Hyperthermia on Gestation and Prenatal Development of the Guinea-Pig." He went on to prove that hyperthermia-induced malformations in animals involve many organs and structures, particularly the central nervous system. Other defects include craniofacial anomalies, heart defects and hypodactyly, cataracts and coloboma, kyphoscoliosis, renal anomalies, dental agenesis, and abdominal wall defects. In a series of carefully planned and executed experiments, he demonstrated that the type of defect is related to the timing of the hyperthermic insult, and analyzed the underlying mechanisms. Cell death, membrane disruption, vascular disruption, and placental infarction were all implicated in causing embryonic damage. This special article reviews the scientific discoveries and personal philosophy of Marshall J. Edwards, the discoverer of maternal hyperthermia as a human teratogen.

  16. Magnetic fluid hyperthermia enhances cytotoxicity of bortezomib in sensitive and resistant cancer cell lines.

    PubMed

    Alvarez-Berríos, Merlis P; Castillo, Amalchi; Rinaldi, Carlos; Torres-Lugo, Madeline

    2014-01-01

    The proteasome inhibitor bortezomib (BZ) has shown promising results in some types of cancer, but in others it has had minimal activity. Recent studies have reported enhanced efficacy of BZ when combined with hyperthermia. However, the use of magnetic nanoparticles to induce hyperthermia in combination with BZ has not been reported. This novel hyperthermia modality has shown better potentiation of chemotherapeutics over other types of hyperthermia. We hypothesized that inducing hyperthermia via magnetic nanoparticles (MFH) would enhance the cytotoxicity of BZ in BZ-sensitive and BZ-resistant cancer cells more effectively than hyperthermia using a hot water bath (HWH). Studies were conducted using BZ in combination with MFH in two BZ-sensitive cell lines (MDA-MB-468, Caco-2), and one BZ-resistant cell line (A2780) at two different conditions, ie, 43°C for 30 minutes and 45°C for 30 minutes. These experiments were compared with combined application of HWH and BZ. The results indicate enhanced potentiation between hyperthermic treatment and BZ. MFH combined with BZ induced cytotoxicity in sensitive and resistant cell lines to a greater extent than HWH under the same treatment conditions. The observation that MFH sensitizes BZ-resistant cell lines makes this approach a potentially effective anticancer therapy platform.

  17. Intra-abdominal infection combined with intra-abdominal hypertension aggravates the intestinal mucosal barrier dysfunction.

    PubMed

    Li, Yuan; Ren, Jianan; Wu, Xiuwen; Li, Jieshou

    2018-02-28

    Some patients with intra-abdominal infection (IAI) may develop intra-abdominal hypertension (IAH) during treatment. The present study investigated the impact of IAI combined with IAH on the intestinal mucosal barrier in a rabbit model. Forty-eight New Zealand white rabbits were randomly divided into four groups: (i) IAI and IAH; (ii) IAI alone; (iii) IAH alone; and (iv) Control group. IAI model: cecal ligation and puncture for 48 h; IAH model: raised intra-abdominal pressure (IAP) of 20 mmHg for 4 h. Pathological changes in intestinal mucosa were confirmed by light and scanning electron microscopy. FITC-conjugated dextran (FITC-dextran) by gavage was used to measure intestinal mucosal permeability in plasma. Endotoxin, d-Lactate, and diamine oxidase (DAO) in plasma were measured to determine intestinal mucosal damage. Malonaldehyde (MDA), superoxide dismutase (SOD), and GSH in ileum tissues were measured to evaluate intestinal mucosal oxidation and reducing state. Histopathologic scores were significantly higher in the IAI and IAH group, followed by IAI alone, IAH alone, and the control group. FITC-dextran, d-Lactate, DAO, and endotoxin in plasma and MDA in ileum tissues had similar trends. GSH and SOD were significantly lowest the in IAI and IAH group. Occludin levels were lowest in the ileums of the IAI and IAH group. All differences were statistically significant ( P -values <0.001). IAI combined with IAH aggravates damage of the intestinal mucosal barrier in a rabbit model. The combined effects were significantly more severe compared with a single factor. IAI combined with IAH should be prevented and treated effectively. © 2018 The Author(s).

  18. An overview of interstitial brachytherapy and hyperthermia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brandt, B.B.; Harney, J.

    Interstitial thermoradiotherapy, an experimental cancer treatment that combines interstitial radiation implants (brachytherapy) and interstitial hyperthermia, is in the early stages of investigation. In accordance with the procedure used in a current national trial protocol, a 60-minute hyperthermia treatment is administered after catheters are placed into the tumor area while the patient is under general anesthesia. This is immediately followed by loading of radioactive Iridium-192 seeds into the catheters for a defined period of time. Once the prescribed radiation dose is delivered, the radioactive sources are removed and a second, 60-minute hyperthermia treatment is administered. Clinical trials with hyperthermia in combinationmore » with radiation have increased in recent years. Nurses caring for these patients need to become more knowledgeable about this investigational therapy. This paper provides an overview of the biologic rationale for this therapy, as well as a description of the delivery method and clinical application. Specific related nursing interventions are defined in a nursing protocol.23 references.« less

  19. Cyclooxygenase inhibitors are potent sensitizers of prostate tumours to hyperthermia and radiation.

    PubMed

    Asea, A; Mallick, R; Lechpammer, S; Ara, G; Teicher, B A; Fiorentino, S; Stevenson, M A; Calderwood, S K

    2001-01-01

    It has previously been demonstrated that hyperthermia can activate prostaglandin synthesis and that prostaglandins are protective against hyperthermia. This study examined the use of inhibitors of prostaglandin synthesis on the response of prostate tumours to hyperthermia. The non-steroidal anti-inflammatory drugs (NSAID) ibuprofen and sulindac, known cyclooxygenase inhibitors that inhibit prostaglandin production, were effective hyperthermia sensitizers and augmented growth delay of DU-145 and PC-3 prostate tumours to combined radiation and hyperthermia treatment protocols. Pre-treatment of mice with ibuprofen and sulindac at hyperthermia sensitizing doses resulted in significant (p < 0.01) inhibition of hyperthemia-induced serum prostaglandin E2. These findings indicate that NSAID may have both sensitizing effects on prostate tumour growth and may function by inhibiting prostaglandin synthesis.

  20. Magnetic Nanomaterials for Hyperthermia-based Therapy and Controlled Drug Delivery

    PubMed Central

    Kumar, Challa S. S. R.; Mohammad, Faruq

    2011-01-01

    Previous attempts to review the literature on magnetic nanomaterials for hyperthermia-based therapy focused primarily on magnetic fluid hyperthermia (MFH) using mono metallic/metal oxide nanoparticles. The term “Hyperthermia” in the literature was also confined only to include use of heat for therapeutic applications. Recently, there have been a number of publications demonstrating magnetic nanoparticle-based hyperthermia to generate local heat resulting in the release of drugs either bound to the magnetic nanoparticle or encapsulated within polymeric matrices. In this review article, we present a case for broadening the meaning of the term “hyperthermia” by including thermotherapy as well as magnetically modulated controlled drug delivery. We provide a classification for controlled drug delivery using hyperthermia: Hyperthermia-based controlled Drug delivery through Bond Breaking (DBB) and Hyperthermia-based controlled Drug delivery through Enhanced Permeability (DEP). The review also covers, for the first time, core-shell type magnetic nanomaterials, especially nanoshells prepared using layer-by-layer self-assembly, for the application of hyperthermia-based therapy and controlled drug delivery. The highlight of the review article is to portray potential opportunities in the combination of hyperthermia-based therapy and controlled drug release paradigms for successful application in personalized medicine. PMID:21447363

  1. Application and possible mechanisms of combining LLLT (low level laser therapy), infrared hyperthermia and ionizing radiation in the treatment of cancer

    NASA Astrophysics Data System (ADS)

    Abraham, Edward H.; Woo, Van H.; Harlin-Jones, Cheryl; Heselich, Anja; Frohns, Florian

    2014-02-01

    Benefit of concomitant infrared hyperthermia and low level laser therapy and ionizing radiation is evaluated in this study. The purpose/objectives: presentation with locally advanced bulky superficial tumors is clinically challenging. To enhance the efficacy of chemotherapy and IMRT (intensity-modulated radiation therapy) and/or electron beam therapy we have developed an inexpensive and clinically effective infrared hyperthermia approach that combines black-body infrared radiation with halogen spectrum radiation and discrete wave length infrared clinical lasers LLLT. The goal is to produce a composite spectrum extending from the far infrared to near infrared and portions of the visible spectrum with discrete penetrating wavelengths generated by the clinical infrared lasers with frequencies of 810 nm and/or 830 nm. The composite spectrum from these sources is applied before and after radiation therapy. We monitor the surface and in some cases deeper temperatures with thermal probes, but use an array of surface probes as the limiting safe thermal constraint in patient treatment while at the same time maximizing infrared entry to deeper tissue layers. Fever-grade infrared hyperthermia is produced in the first centimeters while non-thermal infrared effects act at deeper tissue layers. The combination of these effects with ionizing radiation leads to improved tumor control in many cancers.

  2. Radiation enhanced efficiency of combined electromagnetic hyperthermia and chemotherapy of lung carcinoma using cisplatin functionalized magnetic nanoparticles.

    PubMed

    Babincová, M; Kontrisova, K; Durdík, S; Bergemann, C; Sourivong, P

    2014-02-01

    The effect of trimodality treatment consisting of hyperthermia, cisplatin and radiation was investigated in two non-small lung carcinoma cell lines with different sensitivities to cisplatin. Hyperthermia treatment was performed using heat released via Neél and Brown relaxation of magnetic nanoparticles in an alternating magnetic field. Radiation with dose 1.5 Gy was performed after 15 min electromagnetic hyperthermia and cisplatin treatment. Electromagnetic hyperthermia enhanced cisplatin-induced radiosensitization in both the cisplatin-sensitive H460 (viability 11.2 +/- 1.8 %) and cisplatin-resistant A549 (viability 14.5 +/- 2.3 %) lung carcinoma cell line. Proposed nanotechnology based trimodality cancer treatment may have therefore important clinical applications.

  3. Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia. Results of a phase II trial.

    PubMed

    Dinges, S; Harder, C; Wurm, R; Buchali, A; Blohmer, J; Gellermann, J; Wust, P; Randow, H; Budach, V

    1998-10-01

    The disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia. From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherapy and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4 x 5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions. The acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One patient did not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7 degrees C (range 40.3 to 43.2 degrees C), 41.1 degrees C (range 39.2 to 42.5 degrees C) and 39.9 degrees C (range 37.7 to 41.9 degrees C), respectively. Cumulative

  4. Nanoparticle-induced intraperitoneal hyperthermia and targeted photoablation in treating ovarian cancer

    PubMed Central

    Wu, Chao-Chih; Yang, Yuh-Cheng; Hsu, Yun-Ting; Wu, T.-C.; Hung, Chien-Fu; Huang, Jung-Tang; Chang, Chih-Long

    2015-01-01

    Hyperthermic intraperitoneal chemotherapy is effective in treating various intra-abdominal malignancies. However, this therapeutic modality can only be performed during surgical operations and cannot be used repeatedly. We propose repeatedly noninvasive hyperthermia mediated by pegylated silica-core gold nanoshells (pSGNs) in vivo with external near-infrared (NIR) laser irradiation. This study demonstrated that repeated photothermal treatment can effectively eliminate intraperitoneal tumors in mouse ovarian cancer models without damage of normal tissues. By conjugating pSGNs with anti-human CD47 monoclonal antibody, a significant photoablative effect can be achieved using lower amount of pSGNs and shorter NIR laser irradiation. Conjugated pSGNs specifically targeted and bound to cancer cells inside the peritoneal cavity. Our results indicate the possibility of a noninvasive method of repeated hyperthermia and photoablative therapies using nanoparticles. This has substantial clinical potential in treating ovarian and other intraperitoneal cancers. PMID:26318039

  5. Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy.

    PubMed

    Spirou, Spiridon V; Costa Lima, Sofia A; Bouziotis, Penelope; Vranješ-Djurić, Sanja; Efthimiadou, Eleni Κ; Laurenzana, Anna; Barbosa, Ana Isabel; Garcia-Alonso, Ignacio; Jones, Carlton; Jankovic, Drina; Gobbo, Oliviero L

    2018-05-06

    Magnetic nanoparticle (MNP)-mediated hyperthermia (MH) coupled with radiation therapy (RT) is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy ("Radiomag"). The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a) in vitro evaluation of MNPs; (b) in vitro evaluation of MNP-cell interactions; (c) in vivo evaluation of the MNPs; (d) MH combined with RT; and (e) pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this work.

  6. CT-guided thermocouple placement for hyperthermia treatment.

    PubMed

    Banerian, K G; Roberts, J L; Borrego, J C; Martinez, A

    1990-05-01

    There is a well-documented synergistic cytotoxic effect when heat is combined with ionizing radiation. An integral component of hyperthermia treatments is the placement of thermocouple probes used for thermal dosimetry. With the surge in interest in the clinical use of hyperthermia, our department is performing an increasing number of thermocouple placements under computed tomographic (CT) guidance. We describe our technique for CT-guided thermocouple placement with two different systems: a trocar introduction system and a peel-away needle introduction system. We discuss the rationale for thermocouple placement, our early experience with this technique, and some potential complications.

  7. Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia

    PubMed Central

    LIU, JIAYI; LI, NING; LI, LI; LI, DANYE; LIU, KAI; ZHAO, LINGYUN; TANG, JINTIAN; LI, LIYA

    2013-01-01

    Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment. PMID:24260045

  8. Feasibility of on-line temperature-based hyperthermia treatment planning to improve tumour temperatures during locoregional hyperthermia.

    PubMed

    Kok, H P; Korshuize-van Straten, L; Bakker, A; de Kroon-Oldenhof, R; Westerveld, G H; Versteijne, E; Stalpers, L J A; Crezee, J

    2017-11-16

    The effectiveness of hyperthermia is strongly dependent on the achieved tumour temperatures. Phased-array systems allow flexible power steering to realise good tumour heating while avoiding excessive heating in normal tissue, but the limited quantitative accuracy of pre-treatment planning complicates realising optimal tumour heating. On-line hyperthermia treatment planning could help to improve the heating quality. This paper demonstrates the feasibility of using on-line temperature-based treatment planning to improve the heating quality during hyperthermia in three patients. Hyperthermia treatment planning was performed using the Plan2Heat software package combined with a dedicated graphical user interface for on-line application. Electric fields were pre-calculated to allow instant update and visualisation of the predicted temperature distribution for user-selected phase-amplitude settings during treatment. On-line treatment planning using manual variation of system settings for the AMC-8 hyperthermia system was applied in one patient with a deep-seated pelvic melanoma metastasis and two cervical cancer patients. For a clinically relevant improvement the increase in average target temperature should be at least 0.2 °C. With the assistance of on-line treatment planning a substantial improvement in tumour temperatures was realised for all three patients. In the melanoma patient, the average measured target temperature increased from 38.30 °C to 39.15 °C (i.e. +0.85 °C). In the cervical cancer patients, the average measured target temperature increased from 41.30 °C to 42.05 °C (i.e. +0.75 °C) and from 41.70 °C to 42.80 °C (i.e. +1.1 °C), respectively. On-line temperature-based treatment planning is clinically feasible to improve tumour temperatures. A next, worthwhile step is automatic optimisation for a larger number of patients.

  9. Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy †

    PubMed Central

    Costa Lima, Sofia A.; Bouziotis, Penelope; Vranješ-Djurić, Sanja; Efthimiadou, Eleni Κ.; Laurenzana, Anna; Barbosa, Ana Isabel; Jones, Carlton; Jankovic, Drina; Gobbo, Oliviero L.

    2018-01-01

    Magnetic nanoparticle (MNP)-mediated hyperthermia (MH) coupled with radiation therapy (RT) is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (“Radiomag”). The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a) in vitro evaluation of MNPs; (b) in vitro evaluation of MNP-cell interactions; (c) in vivo evaluation of the MNPs; (d) MH combined with RT; and (e) pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this work. PMID:29734795

  10. Gold Nanoparticle Hyperthermia Reduces Radiotherapy Dose

    PubMed Central

    Lin, Lynn; Slatkin, Daniel N.; Dilmanian, F. Avraham; Vadas, Timothy M.; Smilowitz, Henry M.

    2014-01-01

    Gold nanoparticles can absorb near infrared light, resulting in heating and ablation of tumors. Gold nanoparticles have also been used for enhancing the dose of X-rays in tumors during radiotherapy. The combination of hyperthermia and radiotherapy is synergistic, importantly allowing a reduction in X-ray dose with improved therapeutic results. Here we intratumorally infused small 15 nm gold nanoparticles engineered to be transformed from infrared-transparent to infrared-absorptive by the tumor, which were then heated by infrared followed by X-ray treatment. Synergy was studied using a very radioresistant subcutaneous squamous cell carcinoma (SCCVII) in mice. It was found that the dose required to control 50% of the tumors, normally 55 Gy, could be reduced to <15 Gy (a factor of >3.7). Gold nanoparticles therefore provide a method to combine hyperthermia and radiotherapy to drastically reduce the X-ray radiation needed, thus sparing normal tissue, reducing the side effects, and making radiotherapy more effective. PMID:24990355

  11. Orthotopic Esophageal Cancers: Intraesophageal Hyperthermia-enhanced Direct Chemotherapy in Rats

    PubMed Central

    Shi, Yaoping; Zhang, Feng; Bai, Zhibin; Wang, Jianfeng; Qiu, Longhua; Li, Yonggang; Meng, Yanfeng; Valji, Karim

    2017-01-01

    Purpose To determine the feasibility of using intraesophageal radiofrequency (RF) hyperthermia to enhance local chemotherapy in a rat model with orthotopic esophageal squamous cancers. Materials and Methods The animal protocol was approved by the institutional animal care and use committee and the institutional review board. Human esophageal squamous cancer cells were transduced with luciferase lentiviral particles. Cancer cells, mice with subcutaneous cancer esophageal xenografts, and nude rats with orthotopic esophageal cancers in four study groups of six animals per group were treated with (a) combination therapy of magnetic resonance imaging heating guidewire–mediated RF hyperthermia (42°C) plus local chemotherapy (cisplatin and 5-fluorouracil), (b) chemotherapy alone, (c) RF hyperthermia alone, and (d) phosphate-buffered saline. Bioluminescent optical imaging and transcutaneous ultrasonographic imaging were used to observe bioluminescence signal and changes in tumor size among the groups over 2 weeks, which were correlated with subsequent histologic results. The nonparametric Mann-Whitney U test was used for comparisons of variables. Results Compared with chemotherapy alone, RF hyperthermia alone, and phosphate-buffered saline, combination therapy with RF hyperthermia and chemotherapy induced the lowest cell proliferation (relative absorbance of formazan: 23.4% ± 7, 44.6% ± 7.5, 95.8% ± 2, 100%, respectively; P < .0001), rendered the smallest relative tumor volume (0.65 mm3 ± 0.15, P < .0001) and relative bioluminescence optical imaging photon signal (0.57 × 107 photons per second per square millimeter ± 0.15, P < .001) of mice with esophageal cancer xenografts, as well as the smallest relative tumor volume (0.68 mm3 ± 0.13, P < .05) and relative photon signal (0.56 × 107 photons per second per square millimeter ± 0.11. P < .001) of rat orthotopic esophageal cancers. Conclusion Intraesophageal RF hyperthermia can enhance the effect of chemotherapy

  12. Molecular mechanisms of hyperthermia-induced apoptosis enhanced by withaferin A.

    PubMed

    Cui, Zheng-Guo; Piao, Jin-Lan; Rehman, Mati U R; Ogawa, Ryohei; Li, Peng; Zhao, Qing-Li; Kondo, Takashi; Inadera, Hidekuni

    2014-01-15

    Hyperthermia is a good therapeutic tool for non-invasive cancer therapy; however, its cytotoxic effects are not sufficient. In the present study, withaferin A (WA), a steroidal lactone derived from the plant Withania somnifera Dunal, has been investigated for its possible enhancing effects on hyperthermia-induced apoptosis. In HeLa cells, treatment with 0.5 or 1.0μM WA at 44°C for 30min induced significant apoptosis accompanied by decreased intracellular GSH/GSSG ratio and caspase-3 activation, while heat or WA alone did not induce such changes. The upregulation in apoptosis was significantly inhibited by glutathione monoethyl ester, a cell permeable glutathione precursor. Mitochondrial transmembrane potentials were dramatically decreased by the combined treatment, with increases in pro-apoptotic Bcl-2-family proteins tBid and Noxa, and downregulation of antiapoptotic Bcl-2 and Mcl-1. Combined treatment with hyperthermia and WA induced significant increases in JNK phosphorylation (p-JNK), and decreases in the phosphorylation of ERK (p-ERK) compared with either treatment alone. These results suggest that WA enhances hyperthermia-induced apoptosis via a mitochondria-caspase-dependent pathway; its underlying mechanism involves elevated intracellular oxidative stress, mitochondria dysfunction, and JNK activation. © 2013 Elsevier B.V. All rights reserved.

  13. Simultaneous hyperthermia-chemotherapy with controlled drug delivery using single-drug nanoparticles.

    PubMed

    Sato, Itaru; Umemura, Masanari; Mitsudo, Kenji; Fukumura, Hidenobu; Kim, Jeong-Hwan; Hoshino, Yujiro; Nakashima, Hideyuki; Kioi, Mitomu; Nakakaji, Rina; Sato, Motohiko; Fujita, Takayuki; Yokoyama, Utako; Okumura, Satoshi; Oshiro, Hisashi; Eguchi, Haruki; Tohnai, Iwai; Ishikawa, Yoshihiro

    2016-04-22

    We previously investigated the utility of μ-oxo N,N'- bis(salicylidene)ethylenediamine iron (Fe(Salen)) nanoparticles as a new anti-cancer agent for magnet-guided delivery with anti-cancer activity. Fe(Salen) nanoparticles should rapidly heat up in an alternating magnetic field (AMF), and we hypothesized that these single-drug nanoparticles would be effective for combined hyperthermia-chemotherapy. Conventional hyperthermic particles are usually made of iron oxide, and thus cannot exhibit anti-cancer activity in the absence of an AMF. We found that Fe(Salen) nanoparticles induced apoptosis in cultured cancer cells, and that AMF exposure enhanced the apoptotic effect. Therefore, we evaluated the combined three-fold strategy, i.e., chemotherapy with Fe(Salen) nanoparticles, magnetically guided delivery of the nanoparticles to the tumor, and AMF-induced heating of the nanoparticles to induce local hyperthermia, in a rabbit model of tongue cancer. Intravenous administration of Fe(Salen) nanoparticles per se inhibited tumor growth before the other two modalities were applied. This inhibition was enhanced when a magnet was used to accumulate Fe(Salen) nanoparticles at the tongue. When an AMF was further applied (magnet-guided chemotherapy plus hyperthermia), the tumor masses were dramatically reduced. These results indicate that our strategy of combined hyperthermia-chemotherapy using Fe(Salen) nanoparticles specifically delivered with magnetic guidance represents a powerful new approach for cancer treatment.

  14. Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study.

    PubMed

    Ranieri, Girolamo; Ferrari, Cristina; Di Palo, Alessandra; Marech, Ilaria; Porcelli, Mariangela; Falagario, Gianmarco; Ritrovato, Fabiana; Ramunni, Luigi; Fanelli, Margherita; Rubini, Giuseppe; Gadaleta, Cosmo Damiano

    2017-07-06

    As an angiogenesis inhibitor, bevacizumab has been investigated in combination with different chemotherapeutic agents, achieving an established role for metastatic cancer treatment. However, potential synergic anti-angiogenic effects of hyperthermia have not tested to date in literature. The aim of our study was to analyze efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia (HT) in metastatic cancer patients. Twenty-three patients with metastatic colorectal ( n = 16), ovarian ( n = 5), and breast ( n = 2) cancer were treated with HT in addition to a standard bevacizumab-based chemotherapy regimen. Treatment response assessment was performed, according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST), at 80 days (timepoint-1) and at 160 days (timepoint-2) after therapy. Disease Response Rate (DRR), considered as the proportion of patients who had the best response rating (complete response (CR), partial response (PR), or stable disease (SD)), was assessed at timepoint-1 and timepoint-2. Chi-squared for linear trend test was performed to evaluated the association between response groups (R/NR) and the number of previous treatment (none, 1, 2, 3), number of chemotherapy cycles (<6, 6, 12, >12), number of hyperthermia sessions (<12, 12, 24, >24), and lines of chemotherapy (I, II). Survival curves were estimated by Kaplan-Meier method. DRR was 85.7% and 72.2% at timepoint-1 and timepoint-2, respectively. HT was well tolerated without additional adverse effects on chemotherapy-related toxicity. Chi-squared for linear trend test demonstrated that the percentage of responders grew in relation to the number of chemotherapy cycles ( p = 0.015) and to number of HT sessions ( p < 0.001) performed. Both overall survival (OS) and time to progression (TTP) were influenced by the number of chemotherapy cycles ( p < 0.001) and HT sessions ( p < 0.001) performed. Our preliminary data, that

  15. Effects of hyperthermia and hyperglycemia on the metastases formation and on survival of rat bearing W256 carcinosarcoma.

    PubMed

    Shah, S A; Jain, R K; Finney, P L

    1982-01-01

    Hyperthermia (temperatures less than 42 degrees C) is widely used in the treatment of cancer. Current thrust in this field is directed towards using agents which can potentiate the effects of hyperthermia. Combined local hyperthermia (43 degrees C/2 hours) and hyperglycemia (6g glucose/kg body weight; mean blood glucose levels of 500 mg%) was investigated for treating a metastasizing form of a rat W256 carcinosarcoma. Glucose loading of the tumor-bearing rats rendered the foot tumors physically more easy to heat (due to inhibition of tumor blood flow), but combined hyperthermia and hyperglycemia lead to a decrease in survival rate (13% compared to 41% with heat alone), most animals died with widespread metastases in lymph nodes, lungs and kidneys. The data does not support the postulate that hyperglycemia leads to sensitization of tumor destruction by hyperthermia. We suggest that Corynebacterium parvum, a non-specific immunostimulant, should be thoroughly investigated as a potentiator of hyperthermia.

  16. Comparison of microwave and magnetic nanoparticle hyperthermia radiosensitization in murine breast tumors

    NASA Astrophysics Data System (ADS)

    Giustini, Andrew J.; Petryk, Alicia A.; Hoopes, Paul J.

    2011-03-01

    Hyperthermia has been shown to be an effective radiosensitizer. Its utility as a clinical modality has been limited by a minimally selective tumor sensitivity and the inability to be delivered in a tumor-specific manner. Recent in vivo studies (rodent and human) have shown that cancer cell-specific cytotoxicity can be effectively and safely delivered via iron oxide magnetic nanoparticles (mNP) and an appropriately matched noninvasive alternating magnetic field (AMF). To explore the tumor radiosensitization potential of mNP hyperthermia we used a syngeneic mouse breast cancer model, dextran-coated 110 nm hydrodynamic diameter mNP and a 169 kHz / 450 Oe (35.8 kA/m) AMF. Intradermally implanted (flank) tumors (150 +/- 40 mm3) were treated by injection of 0.04 ml mNP (7.5 mg Fe) / cm3 into the tumor and an AMF (35.8 kA/m and 169 kHz) exposure necessary to achieve a CEM (cumulative equivalent minute) thermal dose of 60 (CEM 60). Tumors were treated with mNP hyperthermia (CEM 60), radiation alone (15 Gy, single dose) and in combination. Compared to the radiation and heat alone treatments, the combined treatment resulted in a greater than two-fold increase in tumor regrowth tripling time (tumor treatment efficacy). None of the treatments resulted in significant normal tissue toxicity or morbidity. Studies were also conducted to compare the radiosensitization effect of mNP hyperthermia with that of microwave-induced hyperthermia. The effects of incubation of nanoparticles within tumors (to allow nanoparticles to be endocytosed) before application of AMF and radiation were determined. This preliminary information suggests cancer cell specific hyperthermia (i.e. antibody-directed or anatomically-directed mNP) is capable of providing significantly greater radiosensitization / therapeutic ratio enhancement than other forms of hyperthermia delivery.

  17. Micro-Nanomaterials for Tumor Microwave Hyperthermia: Design, Preparation, and Application.

    PubMed

    Chen, Xue; Tan, Longfei; Liu, Tianlong; Meng, Xianwei

    2017-01-01

    Cancer hyperthermia is attracting much attention in basic science and clinics. Among the hyperthermia techniques, microwave (MW) heating is most commonly used for cancer treatment. It offers highly competitive advantages: faster heat generation from microwave radiation, less susceptibility to heat up local tissues, maneuverability, and depth of penetration in tissues and capability of killing tumor cells. Although the encouraging clinical results are being collected, MW hyperthermia has its own challenges, such as inaccurate targeting and low selectivity, which lead to damage to the surrounding vital organs and tissues. To address these issues, this review aims to introduce micronanomaterials as promising agents for receiving the electromagnetic wave, which should be beneficial for improving the efficacy of MW hyperthermia. We have searched many peer-reviewed papers in medical and chemical material databases about micro-nanomaterials for tumor microwave hyperthermia. Distinguishing features and important progresses are introduced in this review. One hundred and forty papers were chosen and included in this review. Four parts were described, including hyperthermia techniques and the application of micro-nanomaterials, microwave thermal therapy and treatment principle, microwave absorbing micro-nanomaterials, the preparation and application of micro-nanomaterials in microwave thermal therapy. We review the most recent literatures on micro-nanomaterials-based MW heating strategies for cancer treatment, with the aim to give the reader an overview of the state-of-the-art of MW hyperthermia therapy. The future of MW responsive materials will also be discussed, including combination of imaging probes and targeting moieties. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Thermosensitive gemcitabine-magnetoliposomes for combined hyperthermia and chemotherapy

    NASA Astrophysics Data System (ADS)

    Ferreira, Roberta V.; da Mata Martins, Thaís Maria; Goes, Alfredo Miranda; Fabris, José D.; Cavalcante, Luis Carlos D.; Eugenio Fernandez Outon, Luis; Domingues, Rosana Z.

    2016-02-01

    The combination of magnetic hyperthermia therapy with the controlled release of chemotherapeutic agents in tumors may be an efficient therapeutic with few side effects because the bioavailability, tolerance and amount of the drug can be optimized. Here, we prepared magnetoliposomes consisting of magnetite nanoparticle cores and the anticancer drug gemcitabine encapsulated by a phospholipid bilayer. The potential of these magnetoliposomes for controlled drug release and cancer treatment via hyperthermic behavior was investigated. The magnetic nanoparticle encapsulation efficiency was dependent on the initial amount of magnetite nanoparticles present at the encapsulation stage; the best formulation was 66%. We chose this formulation to characterize the physicochemical properties of the magnetoliposomes and to encapsulate gemcitabine. The mean particle size and distribution were determined by dynamic light scattering (DLS), and the zeta potential was measured. The magnetoliposome formulations all had acceptable characteristics for systemic administration, with a mean size of approximately 150 nm and a polydispersity index <0.2. The magnetoliposomes were stable in aqueous suspension for at least one week, as determined by DLS. Temperature increases due to the dissipation energy of magnetoliposome suspensions subjected to an applied alternating magnetic field (AMF) were measured at different magnetic field intensities, and the values were appropriated for cancer treatments. The drug release profile at 37 °C showed that 17% of the gemcitabine was released after 72 h. Drug release from magnetoliposomes exposed to an AMF for 5 min reached 70%.

  19. Enhanced Microwave Hyperthermia of Cancer Cells with Fullerene.

    PubMed

    Sun, Mingrui; Kiourti, Asimina; Wang, Hai; Zhao, Shuting; Zhao, Gang; Lu, Xiongbin; Volakis, John L; He, Xiaoming

    2016-07-05

    Hyperthermia generated with various energy sources including microwave has been widely studied for cancer treatment. However, the potential damage due to nontargeted heating of normal tissue is a major hurdle to its widespread application. Fullerene is a potential agent for improving cancer therapy with microwave hyperthermia but is limited by its poor solubility in water for biomedical applications. Here we report a combination therapy for enhanced cancer cell destruction by combining microwave heating with C60-PCNPs consisting of fullerene (C60) encapsulated in Pluronic F127-chitosan nanoparticles (PCNPs) with high water solubility. A cell culture dish integrated with an antenna was fabricated to generate microwave (2.7 GHz) for heating PC-3 human prostate cancer cells either with or without the C60-PCNPs. The cell viability data show that the C60-PCNPs alone have minimal cytotoxicity. The combination of microwave heating and C60-PCNPs is significantly more effective than the microwave heating alone in killing the cancer cells (7.5 versus 42.2% cell survival). Moreover, the combination of microwave heating and C60-PCNPs is significantly more destructive to the cancer cells than the combination of simple water-bath heating (with a similar thermal history to microwave heating) and C60-PCNPs (7.5 versus 32.5% survival) because the C60 in the many nanoparticles taken up by the cells can absorb the microwave energy and convert it into heat to enhance heating inside the cells under microwave irradiation. These data suggest the great potential of targeted heating via fullerene for enhanced cancer treatment by microwave hyperthermia.

  20. Numerical modeling for an electric-field hyperthermia applicator

    NASA Technical Reports Server (NTRS)

    Wu, Te-Kao; Chou, C. K.; Chan, K. W.; Mcdougall, J.

    1993-01-01

    Hyperthermia, in conjunction with radiation and chemotherapy for treatment of cancers, is an area of current concern. Experiments have shown that hyperthermia can increase the potency of many chemotherapy drugs and the effectiveness of radiation for treating cancer. A combination of whole body or regional hyperthermia with chemotherapy or radiation should improve treatment results. Conventional methods for inducing whole body hyperthermia, such as exposing a patient in a radiant cabinet or under a hot water blanket, conduct heat very slowly from the skin to the body core. Thus a more efficient system, such as the three-plate electric-field hyperthermia applicator (EHA), is developed. This three-plate EHA has one top plate over and two lower plates beneath the patient. It is driven at 27.12 MHz with 500 Watts through a matching circuit. Using this applicator, a 50 kg pig was successfully heated to 42 C within 45 minutes. However, phantom and animal studies have indicated non-uniform heating near the side of the body. In addition, changes in the size and distance between the electrode plates can affect the heating (or electromagnetic field) pattern. Therefore, numerical models using the method of moments (MOM) or the finite difference time domain (FDTD) technique are developed to optimize the heating pattern of this EHA before it is used for human trials. The accuracy of the numerical modeling has been achieved by the good agreement between the MOM and FDTD results for the three-plate EHA without a biological body. The versatile FDTD technique is then applied to optimize the EHA design with a human body. Both the numerical and measured data in phantom blocks will be presented. The results of this study will be used to design an optimized system for whole body or regional hyperthermia.

  1. Gold Rods Irradiated with Ultrasound for Combination of Hyperthermia and Cancer Chemotherapy.

    PubMed

    Barros, Andre; Austerlitz, Carlos; Gkigkitzis, Ioannis; Campos, Diana; Andrade, Jeyce; Peixoto, Christina; Aguiar, Jaciana; Nascimento, Silene; Silva, Teresinha G; Haranas, Ioannis

    2017-01-01

    The aim of this study was to analyze feasibility (in vitro and in vivo) the use of hyperthermia produced by gold rods irradiated with ultrasound and their combination with chemotherapy with doxorubicin. initially was determined the cell viability and Hsp70 levels after treatment by gold rods irradiated with ultrasound (GR+U) in cell culture. The pretreatment with GR+U combined with doxorubicin (DOX) was evaluated from IC 50 , caspase-3 expression and mechanisms of cell death by electron microscopy. For evaluate the in vivo effects was used solid Ehrlich carcinoma (SEC) Tumor. The animals received three treatments with the combination of GR+U+DOX over 16 days. The cell viability was completely inhibited after 40 min of treatment with GR+U and significant increases the expression of HSP70 was only observed after 10 min of treatment. GR+U+DOX presented significant reduction of IC 50 representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. GR+U+DOX presented significant reduction of IC 50 representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. The caspase-3 level and ultraestructural analysis showed that treatment with GR+U+DOX enhances induction of apoptosis. Pretreatment with GR+U combined with doxorubicin (1 mg) showed 87% inhibition against SEC. and no showed cardiotoxic effect. The combined treatment of GR+U and DOX exhibit synergistic characteristics observed by increasing the efficiency of doxorubicin.

  2. Characterization of the effect of hyperthermia on nanoparticle extravasation from tumor vasculature.

    PubMed

    Kong, G; Braun, R D; Dewhirst, M W

    2001-04-01

    The efficacy of novel cancer therapeutics can be hampered by inefficient delivery of agents to the tumor at effective concentrations. Liposomes have been used as a method to overcome some delivery issues and, in combination with hyperthermia, have been shown to increase drug delivery to tumors. This study investigates the effects of a range of temperatures (34-42 degrees C) and hyperthermia treatment scheduling (time between hyperthermia and drug administration as well as between consecutive hyperthermia treatments) on the extravasation of nanoparticles (100-nm liposomes) from tumor microvasculature in a human tumor (SKOV-3 ovarian carcinoma) xenograft grown in athymic nude mouse window chambers. Under normothermic conditions (34 degrees C) and at 39 degrees C, nanoparticles were unable to extravasate into the tumor interstitium. From 40 to 42 degrees C, nanoparticle extravasation increased with temperature, reaching maximal extravasation at 42 degrees C. Temperatures higher than 42 degrees C led to hemorrhage and stasis in tumor vessels. Enhanced nanoparticle extravasation was observed several hours after heating, decaying back to baseline at 6 h postheating. Reheating (42 degrees C for 1 h) 8 h after an initial heating (42 degrees C for 1 h) did not result in any increased nanoparticle extravasation, indicating development of vascular thermotolerance. The results of this study have implications for the application and scheduling of hyperthermia combined with other therapeutics (e.g., liposomes, antibodies, and viral vectors) for the treatment of cancer.

  3. Low-density lipoprotein transport through an arterial wall under hyperthermia and hypertension conditions--An analytical solution.

    PubMed

    Iasiello, Marcello; Vafai, Kambiz; Andreozzi, Assunta; Bianco, Nicola

    2016-01-25

    An analytical solution for Low-Density Lipoprotein transport through an arterial wall under hyperthermia conditions is established in this work. A four-layer model is used to characterize the arterial wall. Transport governing equations are obtained as a combination between Staverman-Kedem-Katchalsky membrane equations and volume-averaged porous media equations. Temperature and solute transport fields are coupled by means of Ludwig-Soret effect. Results are in excellent agreement with numerical and analytical literature data under isothermal conditions, and with numerical literature data for the hyperthermia case. Effects of hypertension combined with hyperthermia, are also analyzed in this work. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Combined Parameter and State Estimation Problem in a Complex Domain: RF Hyperthermia Treatment Using Nanoparticles

    NASA Astrophysics Data System (ADS)

    Bermeo Varon, L. A.; Orlande, H. R. B.; Eliçabe, G. E.

    2016-09-01

    The particle filter methods have been widely used to solve inverse problems with sequential Bayesian inference in dynamic models, simultaneously estimating sequential state variables and fixed model parameters. This methods are an approximation of sequences of probability distributions of interest, that using a large set of random samples, with presence uncertainties in the model, measurements and parameters. In this paper the main focus is the solution combined parameters and state estimation in the radiofrequency hyperthermia with nanoparticles in a complex domain. This domain contains different tissues like muscle, pancreas, lungs, small intestine and a tumor which is loaded iron oxide nanoparticles. The results indicated that excellent agreements between estimated and exact value are obtained.

  5. Temperature mapping and thermal dose calculation in combined radiation therapy and 13.56 MHz radiofrequency hyperthermia for tumor treatment

    NASA Astrophysics Data System (ADS)

    Kim, Jung Kyung; Prasad, Bibin; Kim, Suzy

    2017-02-01

    To evaluate the synergistic effect of radiotherapy and radiofrequency hyperthermia therapy in the treatment of lung and liver cancers, we studied the mechanism of heat absorption and transfer in the tumor using electro-thermal simulation and high-resolution temperature mapping techniques. A realistic tumor-induced mouse anatomy, which was reconstructed and segmented from computed tomography images, was used to determine the thermal distribution in tumors during radiofrequency (RF) heating at 13.56 MHz. An RF electrode was used as a heat source, and computations were performed with the aid of the multiphysics simulation platform Sim4Life. Experiments were carried out on a tumor-mimicking agar phantom and a mouse tumor model to obtain a spatiotemporal temperature map and thermal dose distribution. A high temperature increase was achieved in the tumor from both the computation and measurement, which elucidated that there was selective high-energy absorption in tumor tissue compared to the normal surrounding tissues. The study allows for effective treatment planning for combined radiation and hyperthermia therapy based on the high-resolution temperature mapping and high-precision thermal dose calculation.

  6. Intra-operative post-induction hyperthermia, possibly malignant hyperthermia: Anesthetic implications, challenges and management

    PubMed Central

    Gulabani, Michell; Gurha, Pavan; Ahmad, Sabih; Dass, Prashant

    2014-01-01

    Malignant Hyperthermia is a pharmacogenetic disorder. Classical manifestations comprise of tachycardia, increase in expired carbon dioxide levels, muscle rigidity, hyperthermia (>38.8°C) and unexpected acidosis. Here we report a case of 16-year-old female patient, ASA-I with chronic rhino-sinusitis and slight strabismus of the left eye posted for functional endoscopic sinus surgery, developing a rise in ETCO2 and temperature immediately following anesthesia induction. She was aggressively managed to an uneventful recovery. We present a case of intra-operative post-induction hyperthermia possibly MH, its anesthetic implications, challenges encountered and its management. PMID:25425784

  7. Developing Antitumor Magnetic Hyperthermia: Principles, Materials and Devices.

    PubMed

    Tishin, Alexander M; Shtil, Alexander A; Pyatakov, Alexander P; Zverev, Vladimir I

    2016-01-01

    Methods of local or loco-regional anticancer treatment are of the utmost importance because the therapeutic 'power' is applied directly to the disease site. Consequently, general toxicity is minimized. Hyperthermia, that is, a sustained increase of intratumoral temperature up to 45oC, has been investigated as a perspective treatment modality alone and/or in combination with ionizing radiation or chemotherapy. Still, the surrounding tissues can be damaged by the external heat. Development of new materials and devices gave rise to methods of inducing hyperthermia by a high frequency magnetic or electromagnetic field applied to the tumor with exogenous nanosized particles captured within it. The idea of this approach is the release of local heat in the vicinity of the magnetic nanoparticle in a time-varying magnetic field due to transfer of external magnetic field energy into the heat. Therefore, tumor cells are heated whereas the peritumoral non-malignant tissues are spared. This review analyzes recent advances in understanding physical principles that underlie magnetic hyperthermia as well as novel approaches to obtain nanoparticles with optimized physico-chemical, toxicological and tumoricidal properties. Special focus is made on the construction of devices for therapeutic purposes. The review covers recent patents and general literature sources regarding magnetic hyperthermia, the developing approach to treat otherwise intractable malignancies. </p><p>.

  8. Preliminary results of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced or metastatic transitional cell carcinoma of the urothelium.

    PubMed

    Yamada, Yoshiaki; Itoh, Youko; Aoki, Shigeyuki; Nakamura, Kogenta; Taki, Tomohiro; Naruse, Katsuya; Tobiume, Motoi; Zennami, Kenji; Katsuda, Remi; Kato, Yoshiharu; Watanabe, Masahito; Nishikawa, Genya; Minami, Miwako; Nakahira, Mariko; Ukai, Sayaka; Sawada, Masaki; Kitamura, Akiko; Honda, Nobuaki

    2009-11-01

    We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of the urothelium. For mild hyperthermia, the patients' oral temperature was elevated to about 38 degrees C by heating for 20 min and retaining the heat for 20 min with a far-infrared heater. The antitumor effect was evaluated according to the RECIST, while adverse drug reactions were assessed based on the NCI-CTC. The antitumor effect was rated as partial remission (PR) in 10 of the 12 patients and stable disease in 2 patients, with an efficacy rate of 83% (10/12). All 10 patients who had achieved PR received three courses of treatment. Of the 12 patients, 5 died during the observation period, with survival for 9-23 months (mean: 15.6 months). Adverse drug reactions included myelosuppression in all patients (Grade 3 in 4 patients, Grade 4 in 8), and gastrointestinal toxicity, such as nausea or vomiting, which was mild (Grade 0 in 2 patients, Grade 1 in 8, Grade 2 in 1, Grade 3 in 1). The results of the present study suggest that M-VAC chemotherapy combined with mild hyperthermia, which potentiates the anticancer effect and reduces adverse drug reactions such as gastrointestinal symptoms, is a useful and safe method for the treatment of advanced transitional cell carcinoma of the urothelium.

  9. Hyperthermia using nanoparticles--Promises and pitfalls.

    PubMed

    Kaur, Punit; Aliru, Maureen L; Chadha, Awalpreet S; Asea, Alexzander; Krishnan, Sunil

    2016-01-01

    An ever-increasing body of literature affirms the physical and biological basis for sensitisation of tumours to conventional therapies such as chemotherapy and radiation therapy by mild temperature hyperthermia. This knowledge has fuelled the efforts to attain, maintain, measure and monitor temperature via technological advances. A relatively new entrant in the field of hyperthermia is nanotechnology which capitalises on locally injected or systemically administered nanoparticles that are activated by extrinsic energy sources to generate heat. This review describes the kinds of nanoparticles available for hyperthermia generation, their activation sources, their characteristics, and the unique opportunities and challenges with nanoparticle-mediated hyperthermia.

  10. Preparation of carboplatin-Fe@C-loaded chitosan nanoparticles and study on hyperthermia combined with pharmacotherapy for liver cancer.

    PubMed

    Li, Fu-rong; Yan, Wen-hui; Guo, Yue-hua; Qi, Hui; Zhou, Han-xin

    2009-08-01

    Magnetic fluid hyperthermia is a kind of technology for treating tumors based on nanotechnology. It is suitable to various types of tumors. The purpose of this study was to prepare carboplatin-Fe@C-loaded chitosan nanoparticles with Fe@C as a magnetic core and to investigate efficacy of hyperthermia combined with chemotherapy for transplanted liver cancer in rats. Fe@C nanopowder was treated with dilute hydrochloric acid to prepare Fe@C nanocage. Carboplatin-Fe@C-loaded chitosan nanoparticles were prepared by reverse microemulsion method with the nanocages as the magnetic cores, chitosan as the matrix. The shape, size, drug-loading rate, and in vitro cumulative release of the nanoparticles were observed and heat product under high frequency alternating electromagnetic field in vitro was explored. Eighty rats with transplanted liver cancer were randomly divided into 4 groups (group A: control group, group B: free carboplatin group, group C: nanoparticles with static magnetic field group, and group D: nanoparticles with static field and alternating magnetic field). Drug was injected into the hepatic artery. The therapeutic effect of hyperthermia combined with chemotherapy for tumor, toxicity and rat survival time were observed. Carboplatin-Fe@C-loaded chitosan nanoparticles were spherical in shape with an average size of (207 +/- 21) nm and high saturation magnetization. The drug-loading rate of the nanoparticles was 11.0 +/- 1.1%. The cumulative release percentage of carboplatin-Fe@C-loaded chitosan nanoparticles in vitro at different point time phase of 24 h, 48 h, 72 h, 96 h and 120 h were 51%, 68%, 80%, 87% and 91%, respectively. With an increase in carboplatin-Fe@C-loaded chitosan nanoparticle concentration and magnetic field strength, the heating rate and constant temperature of carboplatin-Fe@C-loaded chitosan nanoparticles dispersed in physiological saline were increased in an alternating magnetic field. In vivo experiments showed that after particle

  11. Microwave and radiofrequency techniques for clinical hyperthermia.

    PubMed Central

    Cheung, A. Y.

    1982-01-01

    Biological and practical constraints on the use of clinical hyperthermia for the management of cancer are discussed. Commonly used electromagnetic techniques for producing clinical hyperthermia are reviewed and compared. Innovative engineering designs leading to the realization of an integrated, safe and reliable clinical hyperthermia system are also presented. PMID:6950753

  12. Prostacyclin-induced hyperthermia - Implication of a protein mediator

    NASA Technical Reports Server (NTRS)

    Kandasamy, S. B.; Williams, B. A.

    1982-01-01

    The mechanism of the prostacyclin-linked hyperthermia is studied in rabbits. Results show that intracerebroventricular administration of prostacyclin (PGI2) induces dose-related hyperthermia at room temperature (21 C), as well as at low (4 C) and high (30 C) ambient temperatures. It is found that this PGI2-induced hyperthermia is not mediated by its stable metabolite 6-keto prostaglandin F-1(alpha). Only one of the three anion transport systems, the liver transport system, appears to be important to the central inactivation of pyrogen, prostaglandin E2, and PGI2. Phenoxybenzamine and pimozide have no thermolytic effect on PGI2-induced hyperthermia, while PGI2 still induces hyperthermia after norepinephrine (NE) and dopamine levels are depleted by 6-hydroxydopamine. Indomethacin and SC-19220 (a PG antagonist) do not antagonize PGI2 induced hyperthermia, while theophylline does not accentuate the PGI2-induced hyperthermia. However, the hyperthermic response to PGI2 is attenuated by central administration of the protein synthesis inhibitor, anisomycin. It is concluded that PGI2-induced hyperthermia is not induced by NE, dopamine, or cyclic AMP, but rather that a protein mediator is implicated in the induction of fever by PG12.

  13. Single dose x irradiation and concomitant hyperthermia on a murine fibroscarcoma. [Sensitizing effects of hyperthermia on tumors in mice subjected to local radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hahn, E.W.; Alfieri, A.A.; Kim, J.H.

    1978-12-01

    The objectives of this study were to quantitate the effects of local tumor hyperthermia (LTH) and concomitant x irradiation (RAD) on a moderately radioresistant murine fibrosarcoma in situ. Comparisons were made to the combined treatment response on the Ridgway osteogenic sarcoma, a radiosensitive tumor previously used in this laboratory and to establish the Meth-A fibrosarcoma as a model system for combined modality studies. 1.0 cm/sup 3/ tumors were exposed to single doses of RAD ranging from 0.5 to 3.8 krad alone or 0.5 to 2.3 krad in combination with LTH (water bath at 43.1 +- .05 C for 20 minutes)more » applied immediately postirradiation. LTH significantly enhanced the action of radiation as measured by tumor volume analysis, mean survival time and cures. The ratio of radiation doses vs. RAD + LTH required to produce an equivalent response ranged from 1.4 to 2.5 depending upon the endpoints evaluated. These findings are consistent with single dose studies on the radiosensitive Ridgway osteogenic sarcoma and suggest that the tumoricidal effectiveness of combination radiation and hyperthermia cannot be predicted on the basis of the radiation alone responsiveness of tumor.« less

  14. Cancer hyperthermia using magnetic nanoparticles.

    PubMed

    Kobayashi, Takeshi

    2011-11-01

    Magnetic-nanoparticle-mediated intracellular hyperthermia has the potential to achieve localized tumor heating without any side effects. The technique consists of targeting magnetic nanoparticles to tumor tissue followed by application of an external alternating magnetic field that induces heat through Néel relaxation loss of the magnetic nanoparticles. The temperature in tumor tissue is increased to above 43°C, which causes necrosis of cancer cells, but does not damage surrounding normal tissue. Among magnetic nanoparticles available, magnetite has been extensively studied. Recent years have seen remarkable advances in magnetite-nanoparticle-mediated hyperthermia; both functional magnetite nanoparticles and alternating-magnetic-field generators have been developed. In addition to the expected tumor cell death, hyperthermia treatment has also induced unexpected biological responses, such as tumor-specific immune responses as a result of heat-shock protein expression. These results suggest that hyperthermia is able to kill not only local tumors exposed to heat treatment, but also tumors at distant sites, including metastatic cancer cells. Currently, several research centers have begun clinical trials with promising results, suggesting that the time may have come for clinical applications. This review describes recent advances in magnetite nanoparticle-mediated hyperthermia. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Hyperthermia Using Nanoparticles – Promises and Pitfalls

    PubMed Central

    Kaur, Punit; Aliru, Maureen L.; Chadha, Awalpreet S.; Asea, Alexzander; Krishnan, Sunil

    2016-01-01

    An ever-increasing body of literature affirms the physical and biological basis for sensitization of tumors to conventional therapies such as chemotherapy and radiation therapy by mild temperature hyperthermia. This knowledge has fueled the efforts to attain, maintain, measure and monitor temperature via technological advances. A relatively new entrant in the field of hyperthermia is nanotechnology which capitalizes on locally injected or systemically administered nanoparticles that are activated by extrinsic energy sources to generate heat. This review describes the kinds of nanoparticles available for hyperthermia generation, their activation sources, their characteristics, and the unique opportunities and challenges with nanoparticle-mediated hyperthermia. PMID:26757879

  16. Cell biological effects of hyperthermia alone or combined with radiation or drugs: a short introduction to newcomers in the field.

    PubMed

    Kampinga, Harm H

    2006-05-01

    Hyperthermia results in protein unfolding that, if not properly chaperoned by Heat Shock Proteins (HSP), can lead to irreversible and toxic protein aggregates. Elevating HSP prior to heating makes cells thermotolerant. Hyperthermia also can enhance the sensitivity of cells to radiation and drugs. This sensitization to drugs or radiation is not directly related to altered HSP expression. However, altering HSP expression before heat and radiation or drug treatment will affect the extent of thermal sensitization because the HSP will attenuate the heat-induced protein damage that is responsible for radiation- or drug-sensitization. For thermal radiosensitization, nuclear protein damage is considered to be responsible for hyperthermic effects on DNA repair, in particular base excision repair. Hyperthermic drug sensitization can be seen for a number of anti-cancer drugs, especially of alkylating agents. Synergy between heat and drugs may arise from multiple events such as heat damage to ABC transporters (drug accumulation), intra-cellular drug detoxification pathways and repair of drug-induced DNA adducts. This may be why cells with acquired drug resistance (often multi-factorial) can be made responsive to drugs again by combining the drug treatment with heat.

  17. Hyperthermia-enhanced TRAIL- and mapatumumab-induced apoptotic death is mediated through mitochondria in human colon cancer cells

    PubMed Central

    Song, Xinxin; Kim, Han-Cheon; Kim, Seog-Young; Basse, Per; Park, Bae-Hang; Lee, Byeong-Chel; Lee, Yong J.

    2012-01-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world; death usually results from uncontrolled metastatic disease. Previously, we developed a novel strategy of TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) in combination with hyperthermia to treat hepatic colorectal metastases. However, previous studies suggest a potential hepatocyte cytotoxicity with TRAIL. Unlike TRAIL, anti-human TRAIL receptor antibody induces apoptosis without hepatocyte toxicity. In this study, we evaluated the anti-tumor efficacy of humanized anti-death receptor 4 (DR4) antibody mapatumumab (Mapa) by comparing it with TRAIL in combination with hyperthermia. TRAIL, which binds to both DR4 and death receptor 5 (DR5), was approximately 10-fold more effective than Mapa in inducing apoptosis. However, hyperthermia enhances apoptosis induced by either agent. We observed that the synergistic effect was mediated through elevation of reactive oxygen species, c-Jun N-terminal kinase activation, Bax oligomerization and translocalization to the mitochondria, loss of mitochondrial membrane potential, release of cytochrome c to cytosol, activation of caspases and increase in poly(ADP-ribose) polymerase cleavage. We believe that the successful outcome of this study will support the application of Mapa in combination with hyperthermia to colorectal hepatic metastases. PMID:22174016

  18. Hyperthermia-enhanced TRAIL- and mapatumumab-induced apoptotic death is mediated through mitochondria in human colon cancer cells.

    PubMed

    Song, Xinxin; Kim, Han-Cheon; Kim, Seog-Young; Basse, Per; Park, Bae-Hang; Lee, Byeong-Chel; Lee, Yong J

    2012-05-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world; death usually results from uncontrolled metastatic disease. Previously, we developed a novel strategy of TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) in combination with hyperthermia to treat hepatic colorectal metastases. However, previous studies suggest a potential hepatocyte cytotoxicity with TRAIL. Unlike TRAIL, anti-human TRAIL receptor antibody induces apoptosis without hepatocyte toxicity. In this study, we evaluated the anti-tumor efficacy of humanized anti-death receptor 4 (DR4) antibody mapatumumab (Mapa) by comparing it with TRAIL in combination with hyperthermia. TRAIL, which binds to both DR4 and death receptor 5 (DR5), was approximately tenfold more effective than Mapa in inducing apoptosis. However, hyperthermia enhances apoptosis induced by either agent. We observed that the synergistic effect was mediated through elevation of reactive oxygen species, c-Jun N-terminal kinase activation, Bax oligomerization, and translocalization to the mitochondria, loss of mitochondrial membrane potential, release of cytochrome c to cytosol, activation of caspases, and increase in poly(ADP-ribose) polymerase cleavage. We believe that the successful outcome of this study will support the application of Mapa in combination with hyperthermia to colorectal hepatic metastases. Copyright © 2011 Wiley Periodicals, Inc.

  19. Biphasic magnetic nanoparticles-nanovesicle hybrids for chemotherapy and self-controlled hyperthermia.

    PubMed

    Gogoi, Manashjit; Sarma, Haladhar D; Bahadur, Dhirendra; Banerjee, Rinti

    2014-05-01

    The aim was to develop magnetic nanovesicles for chemotherapy and self-controlled hyperthermia that prevent overheating of tissues. Magnetic nanovesicles containing paclitaxel and a dextran-coated biphasic suspension of La0.75Sr0.25MnO3 and Fe3O4 nanoparticles (magnetic nanoparticles) were developed. Encapsulation efficiencies of magnetic nanoparticles and paclitaxel were 67 ± 5 and 83 ± 3%, respectively. Sequential release performed at 37°C for 1 h followed by 44°C for another 1 h (as expected for intratumoral injection), showed a cumulative release of 6.6% (109.6 µg), which was above the IC50 of the drug. In an alternating current magnetic field, the temperature remained controlled at 44°C and a synergistic cytotoxicity of paclitaxel and hyperthermia was observed in MCF-7 cells. Magnetic nanovesicles containing biphasic suspensions La0.75Sr0.25MnO3 and Fe3O4 nanoparticles encapsulating paclitaxel have potential for combined self-controlled hyperthermia and chemotherapy.

  20. Effects of the flavonoid drug quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo.

    PubMed

    Asea, A; Ara, G; Teicher, B A; Stevenson, M A; Calderwood, S K

    2001-01-01

    Tumour hyperthermia, although potentially a powerful therapeutic agent and radiation sensitizer, is hindered by a number of considerations including inhomogeneous heating of deep seated tumours due to energy deposition and perfusion issues. One solution is to design hyperthermia sensitizers to amplify the effects of hyperthermia, particularly at cold spots within the tumour undergoing treatment. This study examined the use of Quercetin, a flavonoid drug shown previously to antagonize the expression of HSP72 and induce apoptosis as a sensitizer of prostate cancer growth in vivo. Quercetin dose-dependently suppressed PC-3 tumour growth in vitro and in vivo. When combined in a treatment protocol with hyperthermia, quercetin drastically inhibited tumour growth and potently amplified the effects of hyperthermia on two prostate tumour types, PC-3 and DU-145 in vivo. These experiments, thus, suggest the use of Quercetin as a hyperthermia sensitizer in the treatment of prostate carcinoma.

  1. Hyperthermia enhances mapatumumab-induced apoptotic death through ubiquitin-mediated degradation of cellular FLIP(long) in human colon cancer cells

    PubMed Central

    Song, X; Kim, S-Y; Zhou, Z; Lagasse, E; Kwon, Y T; Lee, Y J

    2013-01-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world; the main cause of death of colorectal cancer is hepatic metastases, which can be treated with hyperthermia using isolated hepatic perfusion (IHP). In this study, we report that mild hyperthermia potently reduced cellular FLIP(long), (c-FLIPL), a major regulator of the death receptor (DR) pathway of apoptosis, thereby enhancing humanized anti-DR4 antibody mapatumumab (Mapa)-mediated mitochondria-independent apoptosis. We observed that overexpression of c-FLIPL in CX-1 cells abrogated the synergistic effect of Mapa and hyperthermia, whereas silencing of c-FLIP in CX-1 cells enhanced Mapa-induced apoptosis. Hyperthermia altered c-FLIPL protein stability without concomitant reductions in FLIP mRNA. Ubiquitination of c-FLIPL was increased by hyperthermia, and proteasome inhibitor MG132 prevented heat-induced downregulation of c-FLIPL. These results suggest the involvement of the ubiquitin-proteasome system in this process. We also found lysine residue 195 (K195) to be essential for c-FLIPL ubiquitination and proteolysis, as mutant c-FLIPL lysine 195 arginine (arginine replacing lysine) was left virtually un-ubiquitinated and was refractory to hyperthermia-triggered degradation, and thus partially blocked the synergistic effect of Mapa and hyperthermia. Our observations reveal that hyperthermia transiently reduced c-FLIPL by proteolysis linked to K195 ubiquitination, which contributed to the synergistic effect between Mapa and hyperthermia. This study supports the application of hyperthermia combined with other regimens to treat colorectal hepatic metastases. PMID:23559011

  2. Combined Abdominal and Spine Injuries after High Energy Flexion-Distraction Trauma.

    PubMed

    Woltmann, Alexander; Beisse, Rudolph; Eckardt, Henrik; Potulski, Michael; Bühren, Volker

    2007-10-01

    Combined abdominal (AT) and spine (ST) trauma in the multiply traumatized patient (MT) requires optimal clinical management. At the Traumacenter Murnau, Germany all multiply injured patients (injury severity score ≥ 16) are registered in a large prospective database (DGU-Tramaregister). From 1 January 2002 until 31 December 2004, 731 multiply injured patients (ISS ≥ 16) were admitted to the Trauma Center Murnau. In this population, ST was diagnosed in 287 patients (39%), AT was diagnosed in 100 patients (14%), and in 35 patients (5%) a combined ST and AT was observed. The most frequent injury mechanism in patients with a combined ST and AT was high-energy flexion-distraction trauma caused by motor vehicle accident with seat belt fastened passengers, bicycle accident, and fall from great height. In the cohort group of 35 patients, 29 required either abdominal or spinal operation. In 23 patients the AT and in 18 patients the ST necessitated operation. In 14 patients both the AT and ST called for surgery. The AT was predominately treated with splenectomies, resections and suturing of the intestine. The ST resulted in 14 posterior and four postponed anterior stabilizations of the thoracolumbar and four anterior fusions of the cervical spine. Mean age of these patients was 37 years in comparison to 47 years in the control group (MT without combined AT and ST). ISS of patients with combined AT and ST was 38 points compared to 26 points in the control group, and mortality was 7% in the combined group compared to 14% in the control group. The present study documents that damage control principles applied to patients sustaining the complex combination of AT and ST can result in low mortality rates despite the severity of this injury.

  3. Safely combining abdominoplasty with aggressive abdominal liposuction based on perforator vessels: technique and a review of 300 consecutive cases.

    PubMed

    Smith, Lane F; Smith, Lane F

    2015-05-01

    There continues to be controversy about performing abdominoplasty concurrently with abdominal liposuction. The concern is that liposuction on the already vascularly compromised abdominal flap will lead to increased complications and flap necrosis. The central abdomen is supplied by the epigastric system. If perforator vessels from this system are spared, the blood supply to the abdomen can be spared and liposuction should be able to be safely performed on the elevated abdominal flap. The purpose of this study was to evaluate the safety of abdominoplasty with concurrent abdominal liposuction when a perforator vessel is spared. A standard abdominoplasty was performed, sparing one or two perforator vessels from the deep superior epigastric artery system. A retrospective chart review of 300 consecutive patients who underwent abdominoplasty surgery combined with concurrent abdominal liposuction was performed. Complications, total volume of abdominal liposuction, and results were reviewed. The overall complication rate was 17.3 percent (52 patients). Sixteen percent (48 patients) suffered minor complications and 1.3 percent (four patients) suffered major complications. Abdominoplasty can be combined safely with concurrent abdominal liposuction when a perforator vessel is spared. The combination of concurrent liposuction with abdominoplasty showed no increase in complication rates when a perforator vessel was spared. The perforator vessels are located consistently in a 2-cm radius located 4 cm from the midline and 6 cm from the subcostal margin. The potential advantages of abdominoplasty with concurrent liposuction include a better postoperative cosmetic result. Therapeutic, IV.

  4. Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia.

    PubMed

    Garami, Andras; Shimansky, Yury P; Pakai, Eszter; Oliveira, Daniela L; Gavva, Narender R; Romanovsky, Andrej A

    2010-01-27

    Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia.

  5. Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia

    PubMed Central

    Garami, Andras; Shimansky, Yury P.; Pakai, Eszter; Oliveira, Daniela L.; Gavva, Narender R.; Romanovsky, Andrej A.

    2010-01-01

    Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We have found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia. PMID:20107070

  6. Role of CTGF in sensitivity to hyperthermia in ovarian and uterine cancers

    DOE PAGES

    Hatakeyama, Hiroto; Wu, Sherry Y.; Lyons, Yasmin A.; ...

    2016-11-01

    Even though hyperthermia is a promising treatment for cancer, the relationship between specific temperatures and clinical benefits and predictors of sensitivity of cancer to hyperthermia is poorly understood. Ovarian and uterine tumors have diverse hyperthermia sensitivities. Integrative analyses of the specific gene signatures and the differences in response to hyperthermia between hyperthermia-sensitive and -resistant cancer cells identified CTGF as a key regulator of sensitivity. CTGF silencing sensitized resistant cells to hyperthermia. CTGF small interfering RNA (siRNA) treatment also sensitized resistant cancers to localized hyperthermia induced by copper sulfide nanoparticles and near-infrared laser in orthotopic ovarian cancer models. Lastly, CTGF silencingmore » aggravated energy stress induced by hyperthermia and enhanced apoptosis of hyperthermia-resistant cancers.« less

  7. Nanotechnology in hyperthermia cancer therapy: From fundamental principles to advanced applications.

    PubMed

    Beik, Jaber; Abed, Ziaeddin; Ghoreishi, Fatemeh S; Hosseini-Nami, Samira; Mehrzadi, Saeed; Shakeri-Zadeh, Ali; Kamrava, S Kamran

    2016-08-10

    In this work, we present an in-depth review of recent breakthroughs in nanotechnology for hyperthermia cancer therapy. Conventional hyperthermia methods do not thermally discriminate between the target and the surrounding normal tissues, and this non-selective tissue heating can lead to serious side effects. Nanotechnology is expected to have great potential to revolutionize current hyperthermia methods. To find an appropriate place in cancer treatment, all nanotechnology-based hyperthermia methods and their risks/benefits must be thoroughly understood. In this review paper, we extensively examine and compare four modern nanotechnology-based hyperthermia methods. For each method, the possible physical mechanisms of heat generation and enhancement due to the presence of nanoparticles are explained, and recent in vitro and in vivo studies are reviewed and discussed. Nano-Photo-Thermal Therapy (NPTT) and Nano-Magnetic Hyperthermia (NMH) are reviewed as the two first exciting approaches for targeted hyperthermia. The third novel hyperthermia method, Nano-Radio-Frequency Ablation (NaRFA) is discussed together with the thermal effects of novel nanoparticles in the presence of radiofrequency waves. Finally, Nano-Ultrasound Hyperthermia (NUH) is described as the fourth modern method for cancer hyperthermia. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Hyperthermia enhances mapatumumab-induced apoptotic death through ubiquitin-mediated degradation of cellular FLIP(long) in human colon cancer cells.

    PubMed

    Song, X; Kim, S-Y; Zhou, Z; Lagasse, E; Kwon, Y T; Lee, Y J

    2013-04-04

    Colorectal cancer is the third leading cause of cancer-related mortality in the world; the main cause of death of colorectal cancer is hepatic metastases, which can be treated with hyperthermia using isolated hepatic perfusion (IHP). In this study, we report that mild hyperthermia potently reduced cellular FLIP(long), (c-FLIP(L)), a major regulator of the death receptor (DR) pathway of apoptosis, thereby enhancing humanized anti-DR4 antibody mapatumumab (Mapa)-mediated mitochondria-independent apoptosis. We observed that overexpression of c-FLIP(L) in CX-1 cells abrogated the synergistic effect of Mapa and hyperthermia, whereas silencing of c-FLIP in CX-1 cells enhanced Mapa-induced apoptosis. Hyperthermia altered c-FLIP(L) protein stability without concomitant reductions in FLIP mRNA. Ubiquitination of c-FLIP(L) was increased by hyperthermia, and proteasome inhibitor MG132 prevented heat-induced downregulation of c-FLIP(L). These results suggest the involvement of the ubiquitin-proteasome system in this process. We also found lysine residue 195 (K195) to be essential for c-FLIP(L) ubiquitination and proteolysis, as mutant c-FLIP(L) lysine 195 arginine (arginine replacing lysine) was left virtually un-ubiquitinated and was refractory to hyperthermia-triggered degradation, and thus partially blocked the synergistic effect of Mapa and hyperthermia. Our observations reveal that hyperthermia transiently reduced c-FLIP(L) by proteolysis linked to K195 ubiquitination, which contributed to the synergistic effect between Mapa and hyperthermia. This study supports the application of hyperthermia combined with other regimens to treat colorectal hepatic metastases.

  9. Ag-doped manganite nanoparticles: new materials for temperature-controlled medical hyperthermia.

    PubMed

    Melnikov, O V; Gorbenko, O Yu; Markelova, M N; Kaul, A R; Atsarkin, V A; Demidov, V V; Soto, C; Roy, E J; Odintsov, B M

    2009-12-15

    The purpose of this study was to introduce newly synthesized nanomaterials as an alternative to superparamagnetic ironoxide based particles (SPIO) and thus to launch a new platform for highly controllable hyperthermia cancer therapy and imaging. The new material that forms the basis for this article is lanthanum manganite particles with silver ions inserted into the perovskite lattice: La(1-x)Ag(x)MnO(3+delta). Adjusting the silver doping level, it is possible to control the Curie temperature (T(c)) in the hyperthermia range of interest (41-44 degrees C). A new class of nanoparticles based on silver-doped manganites La(1-x)Ag(x)MnO(3+delta) is suggested. New nanoparticles are stable, and their properties were not affected by the typical ambient conditions in the living tissue. It is possible to monitor the particle uptake and retention by MRI. When these particles are placed into an alternating magnetic field, their temperature increases to the definite value near T(c) and then remains constant if the magnetic field is maintained. During the hyperthermia procedure, the temperature can be restricted, thereby preventing the necrosis of normal tissue. A new class of nanoparticles based on silver-doped manganites La(1-x)Ag(x)MnO(3+delta) was suggested. Ag-doped perovskite manganites particles clearly demonstrated the effect of adjustable Curie temperature necessary for highly controllable cellular hyperthermia. The magnetic relaxation properties of the particles are comparable with that of SPIO, and so we were able to monitor the particle movement and retention by MRI. Thus, the new material combines the MRI contrast enhancement capability with targeted hyperthermia treatment.

  10. Safely Combining Abdominoplasty with Aggressive Abdominal Liposuction Based on Perforator Vessels: Technique and a Review of 300 Consecutive Cases

    PubMed Central

    Smith, Lane F.

    2015-01-01

    Background: There continues to be controversy about performing abdominoplasty concurrently with abdominal liposuction. The concern is that liposuction on the already vascularly compromised abdominal flap will lead to increased complications and flap necrosis. The central abdomen is supplied by the epigastric system. If perforator vessels from this system are spared, the blood supply to the abdomen can be spared and liposuction should be able to be safely performed on the elevated abdominal flap. The purpose of this study was to evaluate the safety of abdominoplasty with concurrent abdominal liposuction when a perforator vessel is spared. Methods: A standard abdominoplasty was performed, sparing one or two perforator vessels from the deep superior epigastric artery system. A retrospective chart review of 300 consecutive patients who underwent abdominoplasty surgery combined with concurrent abdominal liposuction was performed. Complications, total volume of abdominal liposuction, and results were reviewed. Results: The overall complication rate was 17.3 percent (52 patients). Sixteen percent (48 patients) suffered minor complications and 1.3 percent (four patients) suffered major complications. Conclusions: Abdominoplasty can be combined safely with concurrent abdominal liposuction when a perforator vessel is spared. The combination of concurrent liposuction with abdominoplasty showed no increase in complication rates when a perforator vessel was spared. The perforator vessels are located consistently in a 2-cm radius located 4 cm from the midline and 6 cm from the subcostal margin. The potential advantages of abdominoplasty with concurrent liposuction include a better postoperative cosmetic result. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID:25919250

  11. Magnetically responsive smart nanoparticles for cancer treatment with a combination of magnetic hyperthermia and remote-control drug release.

    PubMed

    Hayashi, Koichiro; Nakamura, Michihiro; Miki, Hirokazu; Ozaki, Shuji; Abe, Masahiro; Matsumoto, Toshio; Sakamoto, Wataru; Yogo, Toshinobu; Ishimura, Kazunori

    2014-01-01

    We report the synthesis of smart nanoparticles (NPs) that generate heat in response to an alternating current magnetic field (ACMF) and that sequentially release an anticancer drug (doxorubicin, DOX). We further study the in vivo therapeutic efficacy of the combination of magnetic hyperthermia (MHT) and chemotherapy using the smart NPs for the treatment of multiple myeloma. The smart NPs are composed of a polymer with a glass-transition temperature (T g) of 44°C, which contains clustered Fe3O4 NPs and DOX. The clustered Fe3O4 NPs produce heat when the ACMF is applied and rise above 44°C, which softens the polymer phase and leads to the release of DOX. The combination of MHT and chemotherapy using the smart NPs destroys cancer cells in the entire tumor and achieves a complete cure in one treatment without the recurrence of malignancy. Furthermore, the smart NPs have no significant toxicity.

  12. Characteristics of hyperthermia-induced hyperventilation in humans

    PubMed Central

    Tsuji, Bun; Hayashi, Keiji; Kondo, Narihiko; Nishiyasu, Takeshi

    2016-01-01

    ABSTRACT In humans, hyperthermia leads to activation of a set of thermoregulatory responses that includes cutaneous vasodilation and sweating. Hyperthermia also increases ventilation in humans, as is observed in panting dogs, but the physiological significance and characteristics of the hyperventilatory response in humans remain unclear. The relative contribution of respiratory heat loss to total heat loss in a hot environment in humans is small, and this hyperventilation causes a concomitant reduction in arterial CO2 pressure (hypocapnia), which can cause cerebral hypoperfusion. Consequently, hyperventilation in humans may not contribute to the maintenance of physiological homeostasis (i.e., thermoregulation). To gain some insight into the physiological significance of hyperthermia-induced hyperventilation in humans, in this review, we discuss 1) the mechanisms underlying hyperthermia-induced hyperventilation, 2) the factors modulating this response, and 3) the physiological consequences of the response. PMID:27227102

  13. Thermometric analysis of intra-cavitary hyperthermia for esophageal cancer.

    PubMed

    Qi, C; Li, D J

    1999-01-01

    Thermometric analysis was carried out in 51 patients with esophageal cancer treated with intra-cavitary hyperthermia combined with radio chemotherapy, to test whether temperature index (T20, T50) and T90) could be used as an indicator for tumour control. Hyperthermia was administered by intra-cavitary microwave applicator. The T20, T50 and T90 were deducted from the temperature sensors T0 and T3 situated at the center of the tumour surface and 3cm from it. Eighteen patients with local control > or =36 months were named long term control patients (LC), 24 patients with local recurrence within 24 months (LR) (there were no events occurring between 24 and 36 months) and nine patients died of metastasis without local recurrence (DM). The overall survival rates were 80.4 +/- 5.6% at 1 year, 38.3 +/- 6.9% at 3 years and 31 +/- 6.7% at 5 years, respectively. Chi-square test showed no influence of the number of hyperthermia sessions on the local control (p > 0.25). The 5-year local control rate was 18.8% for the patients with T90 < 43 degrees C and 45% for those with T90 > or = 43 degrees C (p < 0.01). The average T90 was 43.76 +/- 0.74 degrees C for the LC patients and 43.17 +/- 0.57 degrees C for those LR (p = 0.024). The mean T90 was higher than 43 degrees C in 94.4% of LC, whereas in 58.8% of LR. The study suggested that T90 was a good parameter for thermal dose in the intracavitary hyperthermia for the treatment of esophageal cancer.

  14. TU-B-210-02: MRg HIFU - Advanced Approaches for Ablation and Hyperthermia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moonen, C.

    2015-06-15

    MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advancedmore » techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, “MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue”, will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, “MRI guided High Intensity Focused Ultrasound – Advanced Approaches for Ablation and Hyperthermia”, will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. Learning Objectives: Learn background on devices and techniques for MR guided HIFU for cancer therapy Understand issues and current status of clinical MRg HIFU Understand strategies for compensating for organ movement during MRgHIFU Understand strategies for strategies for delivering hyperthermia with MRgHIFU CM - research collaboration with Philips.« less

  15. Anticancer effects of β-elemene with hyperthermia in lung cancer cells

    PubMed Central

    Wu, Zhibing; Wang, Ting; Zhang, Yanmei; Zheng, Zhishuang; Yu, Shuhuan; Jing, Saisai; Chen, Sumei; Jiang, Hao; Ma, Shenglin

    2017-01-01

    β-elemene is a novel, plant-derived anticancer drug, which has been used to target multiple solid tumor types. Hyperthermia is an adjuvant therapeutic modality to treat cancer. However, the underlying mechanisms associated with the efficacy of these two treatments are largely unknown. The aim of the present study was to evaluate the effects of β-elemene combined with hyperthermia in lung cancer cell lines. An MTT assay was used to determine cell viability. The cell cycle and apoptosis were analyzed using flow cytometry. The morphology of cells during apoptosis was determined using a transmission electron microscope. The expression levels of P21, survivin, caspase-9, B-cell lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax) mRNA were detected using quantitative polymerase chain reaction. β-elemene with hyperthermia treatment significantly inhibited the viability and increased the apoptosis rate of A549 cells compared with β-elemene treatment alone (P<0.01), and significantly decreased the proportion of cells in S phase compared with the control (P<0.01). Morphological observation using transmission electron microscopy indicated cross-sectional features of apoptosis: Chromatin condensation, reduced integrity of the plasma membrane, increased cellular granularity, nuclear collapse and the formation of apoptotic bodies. β-elemene with hyperthermia treatment significantly promoted P21 and Bax mRNA expression (P<0.01) and significantly decreased caspase-9, Bcl-2 and survivin mRNA expression (P<0.01) in A549 cells. In conclusion, β-elemene with hyperthermia has a significant inhibitory effect on A549 cells. This occurs through reducing S phase and inducing apoptosis, via an increase in P21 and Bax expression and a decrease in caspase-9, Bcl-2 and survivin expression. PMID:28588670

  16. Evaluation of the Cytotoxic Effects of Hyperthermia and 5-Fluorouracil Loaded Magnetic Nanoparticles on Human Colon Cancer Cell Line HT-29.

    PubMed

    Eynali, Samira; Khoei, Samideh; Khoei, Sepideh; Esmaelbeygi, Elaheh

    2016-10-04

    The purpose of this study was to evaluate the combined effects of heat and poly lactic-co-glycolic acid (PLGA) nanoparticles, as 5-fluorouracil carriers with/without iron oxide core, on the viability and proliferation capacity of human colon cancer cell line HT-29 in the spheroid model. HT-29 spheroid cells were treated with different concentrations of 5-FU or 5-FU loaded into both nanoparticles for 74 h. Hyperthermia was then performed at 43°C for 60 min. Finally, the effects of the mentioned treatments on cell viability and proliferation capacity were evaluated using the trypan blue dye exclusion test and colony formation assay, respectively. Our results showed that hyperthermia, in combination with 5-FU or PLGA nanoparticles as 5-FU carriers, significantly enhanced the cytotoxic effects as compared to the control group. Considering that nanoparticles could increase the intracellular concentration of drugs in cancer cells, the extent of cytotoxic effects following treatment with 5-FU loaded into both nanoparticles was significantly higher than that with free 5-FU. In addition, the presence of iron oxide cores in nanoparticles during hyperthermia enhanced the cytotoxic effects of hyperthermia compared with nanoparticles without iron oxide core. Based on this study, hyperthermia in combination with 5-FU-loaded PLGA nanoparticles with iron oxide core drastically reduced the proliferation capacity of HT-29 cells; therefore, it may be considered a new direction in the treatment of colon cancer.

  17. Acute whole-body cooling for exercise-induced hyperthermia: a systematic review.

    PubMed

    McDermott, Brendon P; Casa, Douglas J; Ganio, Matthew S; Lopez, Rebecca M; Yeargin, Susan W; Armstrong, Lawrence E; Maresh, Carl M

    2009-01-01

    To assess existing original research addressing the efficiency of whole-body cooling modalities in the treatment of exertional hyperthermia. During April 2007, we searched MEDLINE, EMBASE, Scopus, SportDiscus, CINAHL, and Cochrane Reviews databases as well as ProQuest for theses and dissertations to identify research studies evaluating whole-body cooling treatments without limits. Key words were cooling, cryotherapy, water immersion, cold-water immersion, ice-water immersion, icing, fanning, bath, baths, cooling modality, heat illness, heat illnesses, exertional heatstroke, exertional heat stroke, heat exhaustion, hyperthermia, hyperthermic, hyperpyrexia, exercise, exertion, running, football, military, runners, marathoner, physical activity, marathoning, soccer, and tennis. Two independent reviewers graded each study on the Physiotherapy Evidence Database (PEDro) scale. Seven of 89 research articles met all inclusion criteria and a minimum score of 4 out of 10 on the PEDro scale. After an extensive and critical review of the available research on whole-body cooling for the treatment of exertional hyperthermia, we concluded that ice-water immersion provides the most efficient cooling. Further research comparing whole-body cooling modalities is needed to identify other acceptable means. When ice-water immersion is not possible, continual dousing with water combined with fanning the patient is an alternative method until more advanced cooling means can be used. Until future investigators identify other acceptable whole-body cooling modalities for exercise-induced hyperthermia, ice-water immersion and cold-water immersion are the methods proven to have the fastest cooling rates.

  18. CDRH RF phantom for hyperthermia systems evaluations.

    PubMed

    Allen, S; Kantor, G; Bassen, H; Ruggera, P

    1988-01-01

    The National Cancer Institute (NCI) sponsored clinical evaluations of investigational 'regional' hyperthermia systems at four clinical institutions. To support this project, the Center for Devices and Radiological Health (CDRH) developed a series of test instruments to evaluate the magnitude and repeatability of the induced heating by radiofrequency (RF) systems. Data from three institutions using the same model hyperthermia system have been analyzed. After heating, the average temperature from measurements taken at several points in the test phantom at each institution agree within +/- 0.002 degrees C. These differences are about equal to the measurement uncertainty. Thus, this technique can be used for preclinical evaluation and quality control of the total system operation. After one of the institutions relocated its hyperthermia system, a subsequent set of data showed inconsistencies compared to their earlier data. Investigation traced this to cable loss and power meter interference. From the analysis of the data from the three institutions, the utility of the CDRH RF phantom for hyperthermia systems evaluation is demonstrated.

  19. Effector CD8+ T cell IFN-γ production and cytotoxicity are enhanced by mild hyperthermia

    PubMed Central

    Mace, Thomas A.; Zhong, Lingwen; Kokolus, Kathleen M.; Repasky, Elizabeth A.

    2012-01-01

    Purpose Clinical trials combining hyperthermia with radiation and/or chemotherapy for cancer treatment have resulted in improved overall survival and control of local recurrences. The contribution of thermally enhanced anti-immune function in these effects is of considerable interest, but not understood; studies on the fundamental effects of elevated temperature on immune effector cells are needed. The goal of this study is to investigate the potential of mild hyperthermia to impact tumor antigen-specific (Ag) effector CD8+ T cell functions. Method Pmel-1 Ag-specific CD8+ T cells were exposed to mild hyperthermia and tested for changes in IFN-γ production and cytotoxicity. Additionally, overall plasma membrane organization and the phosphorylation of signaling proteins were also investigated following heat treatment. Results Exposing effector Pmel-1 specific CD8+ T cells to mild hyperthermia (39.5°C) resulted in significantly enhanced Ag-specific IFN-γ production and tumor target cell killing compared to that seen using lower temperatures (33 and 37°C). Further, inhibition of protein synthesis during hyperthermia did not reduce subsequent Ag-induced IFN-γ production by CD8+ T cells. Correlated with these effects, we observed a distinct clustering of GM1+ lipid microdomains at the plasma membrane and enhanced phosphorylation of LAT and PKCθ which may be related to an observed enhancement of Ag-specific effector CD8+ T cell IFN-γ gene transcription following mild hyperthermia. However, mitogen–mediated production of IFN-γ, which bypasses T cell receptor activation with antigen, was not enhanced. Conclusions Antigen-dependent effector T cell activity is enhanced following mild hyperthermia. These effects could potentially occur in patients being treated with thermal therapies. These data also provide support for the use of thermal therapy as an adjuvant for immunotherapies to improve CD8+ effector cell function. PMID:22235780

  20. Peptide and non-peptide opioid-induced hyperthermia in rabbits

    NASA Technical Reports Server (NTRS)

    Kandasamy, S. B.; Williams, B. A.

    1983-01-01

    The intracerebroventricular administration of prototype nonpeptide opioid receptor (mu, kappa, and sigma) agonists, morphine, ketocyclazocine, and N-allyl-normetazocine was found to induce hyperthermia in rabbits. The similar administration of peptide opioids like beta-endorphin (BE), methionine-enkephalin (ME), and its synthetic analogue D-ala2-methionine-enkephalinamide (DAME) was also found to cause hyperthermia. Results indicate that only the liver-like transport system is important to the ventricular inactivation of BE and DAME. Prostaglandins and norepinephrine were determined not to be involved in peptide and nonpeptide opioid-induced hyperthermia. In addition, cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to peptide and nonpeptide opioids. Naloxone-sensitive receptors were found to be involved in the induction of hyperthermia by morphine, BE, ME, and DAME since naloxone attenuated them. However, the hyperthermic response to ketocyclazocine and N-allyl-normetazocine was not antagonized by naloxone.

  1. Intratumoral iron oxide nanoparticle hyperthermia and radiation cancer treatment

    NASA Astrophysics Data System (ADS)

    Hoopes, P. J.; Strawbridge, R. R.; Gibson, U. J.; Zeng, Q.; Pierce, Z. E.; Savellano, M.; Tate, J. A.; Ogden, J. A.; Baker, I.; Ivkov, R.; Foreman, A. R.

    2007-02-01

    The potential synergism and benefit of combined hyperthermia and radiation for cancer treatment is well established, but has yet to be optimized clinically. Specifically, the delivery of heat via external arrays /applicators or interstitial antennas has not demonstrated the spatial precision or specificity necessary to achieve appropriate a highly positive therapeutic ratio. Recently, antibody directed and possibly even non-antibody directed iron oxide nanoparticle hyperthermia has shown significant promise as a tumor treatment modality. Our studies are designed to determine the effects (safety and efficacy) of iron oxide nanoparticle hyperthermia and external beam radiation in a murine breast cancer model. Methods: MTG-B murine breast cancer cells (1 x 106) were implanted subcutaneous in 7 week-old female C3H/HeJ mice and grown to a treatment size of 150 mm3 +/- 50 mm3. Tumors were then injected locally with iron oxide nanoparticles and heated via an alternating magnetic field (AMF) generator operated at approximately 160 kHz and 400 - 550 Oe. Tumor growth was monitored daily using standard 3-D caliper measurement technique and formula. specific Mouse tumors were heated using a cooled, 36 mm diameter square copper tube induction coil which provided optimal heating in a 1 cm wide region in the center of the coil. Double dextran coated 80 nm iron oxide nanoparticles (Triton Biosystems) were used in all studies. Intra-tumor, peri-tumor and rectal (core body) temperatures were continually measured throughout the treatment period. Results: Preliminary in vivo nanoparticle-AMF hyperthermia (167 KHz and 400 or 550 Oe) studies demonstrated dose responsive cytotoxicity which enhanced the effects of external beam radiation. AMF associated eddy currents resulted in nonspecific temperature increases in exposed tissues which did not contain nanoparticles, however these effects were minor and not injurious to the mice. These studies also suggest that iron oxide nanoparticle

  2. Photoacoustic-Based-Close-Loop Temperature Control for Nanoparticle Hyperthermia.

    PubMed

    Xiaohua, Feng; Fei, Gao; Yuanjin, Zheng

    2015-07-01

    Hyperthermia therapy requires tight temperature control to achieve selective killing of cancerous tissue with minimal damage on surrounding healthy tissues. To this end, accurate temperature monitoring and subsequent heating control are critical. However, an economic, portable, and real-time temperature control solution is currently lacking. To bridge this gap, we present a novel portable close-loop system for hyperthermia temperature control, in which photoacoustic technique is proposed for noninvasive real-time temperature measurement. Exploiting the high sensitivity of photoacoustics, the temperature is monitored with an accuracy of around 0.18 °C and then fed back to a controller implemented on field programmable gate array (FPGA) for temperature control. Dubbed as portable hyperthermia feedback controller (pHFC), it stabilizes the temperature at preset values by regulating the hyperthermia power with a proportional-integral-derivative (PID) algorithm; and to facilitate digital implementation, the pHFC further converts the PID output into switching values (0 and 1) with the pulse width modulation (PWM) algorithm. Proof-of-concept hyperthermia experiments demonstrate that the pHFC system is able to bring the temperature from baseline to predetermined value with an accuracy of 0.3° and a negligible temperature overshoot. The pHFC can potentially be translated to clinical applications with customized hyperthermia system design. This paper can facilitate future efforts in seamless integration of close-loop temperature control solution and various clinical hyperthermia systems.

  3. The Role of Bcl-xL in Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia on Human Colon Cancer

    PubMed Central

    Song, Xinxin; Kim, Seog-Young; Lee, Yong J.

    2012-01-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world. The main cause of death of colorectal cancer is hepatic metastases which can be treated using isolated hepatic perfusion (IHP), allowing treatment of colorectal metastasis with various methods. In this study we present a novel potent multimodality strategy comprising humanized death receptor 4 (DR4) antibody mapatumumab (Mapa) in combination with oxaliplatin and hyperthermia to treat human colon cancer cells. Oxaliplatin and hyperthermia sensitized colon cancer cells to Mapa in the mitochondrial dependent apoptotic pathway and increased reactive oxygen species production, leading to Bcl-xL phosphorylation at Serine 62 in a c-Jun N-terminal kinase (JNK)-dependent manner. Overexpression of Bcl-xL reduced the efficacy of the multimodality treatment, while phosphorylation of Bcl-xL decreased its anti-apoptotic activity. The multimodality treatment dissociated Bcl-xL from Bax, allowing Bax oligomerization to induce cytochrome c release from mitochondria. In addition, the multimodality treatment significantly inhibited colorectal cancer xenografts’ tumor growth. The successful outcome of this study will support the application of multimodality strategy to colorectal hepatic metastases. PMID:23051936

  4. Hyperthermia increases interleukin-6 in mouse skeletal muscle

    PubMed Central

    Welc, Steven S.; Phillips, Neil A.; Oca-Cossio, Jose; Wallet, Shannon M.; Chen, Daniel L.

    2012-01-01

    Skeletal muscles produce and contribute to circulating levels of IL-6 during exercise. However, when core temperature is reduced, the response is attenuated. Therefore, we hypothesized that hyperthermia may be an important and independent stimulus for muscle IL-6. In cultured C2C12 myotubes, hyperthermia (42°C) increased IL-6 gene expression 14-fold after 1 h and 35-fold after 5 h of 37°C recovery; whereas exposure to 41°C resulted in a 2.6-fold elevation at 1 h. IL-6 protein was secreted and significantly elevated in the cell supernatant. Similar but reduced responses to heat were seen in C2C12 myoblasts. Isolated soleus muscles from mice, exposed ex vivo to 41°C for 1 h, yielded similar IL-6 gene responses (>3-fold) but without a significant effect on protein release. When whole animals were exposed to passive hyperthermia, such that core temperature increased to 42.4°C, IL-6 mRNA in soleus increased 5.4-fold compared with time matched controls. Interestingly, TNF-α gene expression was routinely suppressed at all levels of hyperthermia (40.5–42°C) in the isolated models, but TNF-α was elevated (4.2-fold) in the soleus taken from intact mice exposed, in vivo, to hyperthermia. Muscle HSP72 mRNA increased as a function of the level of hyperthermia, and IL-6 mRNA responses increased proportionally with HSP72. In cultured C2C12 myotubes, when heat shock factor was pharmacologically blocked with KNK437, both HSP72 and IL-6 mRNA elevations, induced by heat, were suppressed. These findings implicate skeletal muscle as a “heat stress sensor” at physiologically relevant hyperthermia, responding with a programmed cytokine expression pattern characterized by elevated IL-6. PMID:22673618

  5. Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Franckena, Martine; Stalpers, Lukas J.A.; Koper, Peter C.M.

    2008-03-15

    Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a medianmore » total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.« less

  6. [Efficacy of alverina citrate and simethicone combination in abdominal pain and discomfort of irritable bowel syndrome].

    PubMed

    Wittmann, T; Paradovsky, L; Ducrotte, P; Bueno, L; Andro-Delestrain, M C T

    2011-01-01

    The alverina citrate and simethicone combination (ACS-Meteospazmil) is used for irritable bowel syndrome (IBS) for almost 20 years, but the supporting scientific evidence for efficacy is limited. to evaluate the effectiveness of ACS in patients with abdominal pain and discomfort at IBS. In a double-blind, randomized, placebo-controlled study enrolled 412 patients with IBS conform to Rome criteria III. Selection criterion in the study was to evaluate the intensity of abdominal pain or discomfort during the 2-week run-in period without medication, which according to analog scale (VAS) was to be 60-100 mm. With the help of an interactive voice communication system (IVCS), patients were randomized to treatment with either alverin citrate 60 mg with Simethicone 300 mg three times daily or corresponding placebo for 4 weeks. For analyze of the results of the study were selected 409 patients. After 4 weeks, patients treated with ACS, was observed lower scores in the VAS assessment of abdominal pain or discomfort compared to placebo (mean--40 and 50 mm, p = 0.047) and a higher level of response to treatment (46.8% and 34.3%, respectively). Recorded side effects were similar in both groups. The combination of ACS was significantly more effective in patients with IBS compared to placebo in reducing abdominal pain or discomfort.

  7. Magnetic hyperthermia with hard-magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Kashevsky, Bronislav E.; Kashevsky, Sergey B.; Korenkov, Victor S.; Istomin, Yuri P.; Terpinskaya, Tatyana I.; Ulashchik, Vladimir S.

    2015-04-01

    Recent clinical trials of magnetic hyperthermia have proved, and even hardened, the Ankinson-Brezovich restriction as upon magnetic field conditions applicable to any site of human body. Subject to this restriction, which is harshly violated in numerous laboratory and small animal studies, magnetic hyperthermia can relay on rather moderate heat source, so that optimization of the whole hyperthermia system remains, after all, the basic problem predetermining its clinical perspectives. We present short account of our complex (theoretical, laboratory and small animal) studies to demonstrate that such perspectives should be related with the hyperthermia system based on hard-magnetic (Stoner-Wohlfarth type) nanoparticles and strong low-frequency fields rather than with superparamagnetic (Brownian or Neél) nanoparticles and weak high-frequency fields. This conclusion is backed by an analytical evaluation of the maximum absorption rates possible under the field restriction in the ideal hard-magnetic (Stoner-Wohlarth) and the ideal superparamagnetic (single relaxation time) systems, by theoretical and experimental studies of the dynamic magnetic hysteresis in suspensions of movable hard-magnetic particles, by producing nanoparticles with adjusted coercivity and suspensions of such particles capable of effective energy absorption and intratumoral penetration, and finally, by successful treatment of a mice model tumor under field conditions acceptable for whole human body.

  8. Effective elimination of cancer stem cells by magnetic hyperthermia.

    PubMed

    Sadhukha, Tanmoy; Niu, Lin; Wiedmann, Timothy Scott; Panyam, Jayanth

    2013-04-01

    Cancer stem cells (CSCs) are a subpopulation of cancer cells that have stem cell-like properties and are thought to be responsible for tumor drug resistance and relapse. Therapies that can effectively eliminate CSCs will, therefore, likely inhibit tumor recurrence. The objective of our study was to determine the susceptibility of CSCs to magnetic hyperthermia, a treatment that utilizes superparamagnetic iron oxide nanoparticles placed in an alternating magnetic field to generate localized heat and achieve selective tumor cell kill. SPIO NPs having a magnetite core of 12 nm were used to induce magnetic hyperthermia in A549 and MDA-MB-231 tumor cells. Multiple assays for CSCs, including side population phenotype, aldehyde dehydrogenase expression, mammosphere formation, and in vivo xenotransplantation, indicated that magnetic hyperthermia reduced or, in some cases, eliminated the CSC subpopulation in treated cells. Interestingly, conventional hyperthermia, induced by subjecting cells to elevated temperature (46 °C) in a water bath, was not effective in eliminating CSCs. Our studies show that magnetic hyperthermia has pleiotropic effects, inducing acute necrosis in some cells while stimulating reactive oxygen species generation and slower cell kill in others. These results suggest the potential for lower rates of tumor recurrence after magnetic hyperthermia compared to conventional cancer therapies.

  9. Investigation properties of superparamagnetic nanoparticles and magnetic field-dependent hyperthermia therapy

    NASA Astrophysics Data System (ADS)

    Hedayatnasab, Z.; Abnisa, F.; Daud, W. M. A. Wan

    2018-03-01

    The application of superparamagnetic nanoparticles as heating agents in hyperthermia therapy has made a therapeutic breakthrough in cancer treatment. The high efficiency of this magnetic hyperthermia therapy has derived from a great capability of superparamagnetic nanoparticles to generate focused heat in inaccessible tumors being effectively inactivated. The main challenges of this therapy are the improvement of the induction heating power of superparamagnetic nanoparticles and the control of the hyperthermia temperature in a secure range of 42 °C to 47 °C, at targeted area. The variation of these hyperthermia properties is principally dependent on the magnetic nanoparticles as well as the magnetic field leading to enhance the efficiency of magnetic hyperthermia therapy at targeted area and also avoid undue heating to healthy cells. The present study evaluates the magnetic hyperthermia therapy through the determination of superparamagnetic nanoparticles properties and magnetic field’ parameters.

  10. A theranostic nrGO@MSN-ION nanocarrier developed to enhance the combination effect of sonodynamic therapy and ultrasound hyperthermia for treating tumor

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Wei; Liu, Tse-Ying; Chang, Po-Hsueh; Hsu, Po-Hung; Liu, Hao-Li; Lin, Hong-Cheu; Chen, San-Yuan

    2016-06-01

    Sonodynamic therapy (SDT), which induces activation of sonosensitizers in cancer cells through ultrasound irradiation, has emerged as an alternative and promising noninvasive therapeutic approach to kill both superficial and deep parts of tumors. In this study, mesoporous silica (MSN) grown on reduced graphene oxide nanosheet (nrGO) capped with Rose Bengal (RB)-PEG-conjugated iron-oxide nanoparticles (IONs), nrGO@MSN-ION-PEG-RB, was strategically designed to have targeted functionality and therapeutic efficacy under magnetic guiding and focused ultrasound (FUS) irradiation, respectively. The singlet oxygen produced by ultrasound-activated RB and the ultrasound-induced heating effect was enhanced by rGO and IONs, which improved the cytotoxic effect in cancer cells. In an animal experiment, we demonstrated that the combination of sonodynamic/hyperthermia therapy with magnetic guidance using this nanocomposite therapeutic agent can produce remarkable efficacious therapy in tumor growth inhibition. Furthermore, the combination effect induced by FUS irradiation produces significant damage to both superficial and deep parts of the targeted tumor.Sonodynamic therapy (SDT), which induces activation of sonosensitizers in cancer cells through ultrasound irradiation, has emerged as an alternative and promising noninvasive therapeutic approach to kill both superficial and deep parts of tumors. In this study, mesoporous silica (MSN) grown on reduced graphene oxide nanosheet (nrGO) capped with Rose Bengal (RB)-PEG-conjugated iron-oxide nanoparticles (IONs), nrGO@MSN-ION-PEG-RB, was strategically designed to have targeted functionality and therapeutic efficacy under magnetic guiding and focused ultrasound (FUS) irradiation, respectively. The singlet oxygen produced by ultrasound-activated RB and the ultrasound-induced heating effect was enhanced by rGO and IONs, which improved the cytotoxic effect in cancer cells. In an animal experiment, we demonstrated that the combination of

  11. Cardiopulmonary and arterial baroreceptor unloading during passive hyperthermia does not contribute to hyperthermia-induced hyperventilation

    PubMed Central

    Lucas, Rebekah A. I.; Pearson, James; Schlader, Zachary J.; Crandall, Craig G.

    2016-01-01

    This study tested the hypothesis that baroreceptor unloading during passive hyperthermia contributes to increases in ventilation and decreases in end-tidal partial pressure of carbon dioxide (PET,CO2) during that exposure. Two protocols were performed, in which healthy subjects underwent passive hyperthermia (increasing intestinal temperature by ~1.8°C) to cause a sustained increase in ventilation and reduction in PET,CO2. Upon attaining hyperthermic hyperventilation, in protocol 1 (n = 10; three females) a bolus (19 ± 2 ml kg−1) of warm (~38°C) isotonic saline was rapidly (5–10 min) infused intravenously to restore reductions in central venous pressure, whereas in protocol 2 (n = 11; five females) phenylephrine was infused intravenously (60–120 μg min−1) to return mean arterial pressure to normothermic levels. In protocol 1, hyperthermia increased ventilation (by 2.2 ± 1.7 l min−1, P < 0.01), while reducing PET,CO2 (by 4 ± 3 mmHg, P = 0.04) and central venous pressure (by 5 ± 1 mmHg, P <0.01). Saline infusion increased central venous pressure by 5 ± 1 mmHg (P < 0.01), restoring it to normothermic values, but did not change ventilation or PET,CO2 (P > 0.05). In protocol 2, hyperthermia increased ventilation (by 5.0 ± 2.7l min−1, P <0.01) and reduced PET ,CO2 (by 5 ± 2 mmHg, P < 0.01) and mean arterial pressure (by 9 ± 7 mmHg, P <0.01). Phenylephrine infusion increased mean arterial pressure by 12 ± 3 mmHg (P < 0.01), restoring it to normothermic values, but did not change ventilation or PET,CO2 (P > 0.05). The absence of a reduction in ventilation upon reloading the cardiopulmonary and arterial baroreceptors to pre-hyperthermic levels indicates that baroreceptor unloading with hyperthermia is unlikely to contribute to hyperthermic hyperventilation in humans. PMID:26299270

  12. The exposure of cancer cells to hyperthermia, iron oxide nanoparticles, and mitomycin C influences membrane multidrug resistance protein expression levels.

    PubMed

    Franke, Karolin; Kettering, Melanie; Lange, Kathleen; Kaiser, Werner A; Hilger, Ingrid

    2013-01-01

    The presence of multidrug resistance-associated protein (MRP) in cancer cells is known to be responsible for many therapeutic failures in current oncological treatments. Here, we show that the combination of different effectors like hyperthermia, iron oxide nanoparticles, and chemotherapeutics influences expression of MRP 1 and 3 in an adenocarcinoma cell line. BT-474 cells were treated with magnetic nanoparticles (MNP; 1.5 to 150 μg Fe/cm(2)) or mitomycin C (up to 1.5 μg/cm(2), 24 hours) in the presence or absence of hyperthermia (43°C, 15 to 120 minutes). Moreover, cells were also sequentially exposed to these effectors (MNP, hyperthermia, and mitomycin C). After cell harvesting, mRNA was extracted and analyzed via reverse transcription polymerase chain reaction. Additionally, membrane protein was isolated and analyzed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. When cells were exposed to the effectors alone or to combinations thereof, no effects on MRP 1 and 3 mRNA expression were observed. In contrast, membrane protein expression was influenced in a selective manner. The effects on MRP 3 expression were less pronounced compared with MRP 1. Treatment with mitomycin C decreased MRP expression at high concentrations and hyperthermia intensified these effects. In contrast, the presence of MNP only increased MRP 1 and 3 expression, and hyperthermia reversed these effects. When combining hyperthermia, magnetic nanoparticles, and mitomycin C, no further suppression of MRP expression was observed in comparison with the respective dual treatment modalities. The different MRP 1 and 3 expression levels are not associated with de novo mRNA expression, but rather with an altered translocation of MRP 1 and 3 to the cell membrane as a result of reactive oxygen species production, and with shifting of intracellular MRP storage pools, changes in membrane fluidity, etc, at the protein level. Our results could be used to develop

  13. The exposure of cancer cells to hyperthermia, iron oxide nanoparticles, and mitomycin C influences membrane multidrug resistance protein expression levels

    PubMed Central

    Franke, Karolin; Kettering, Melanie; Lange, Kathleen; Kaiser, Werner A; Hilger, Ingrid

    2013-01-01

    Purpose The presence of multidrug resistance-associated protein (MRP) in cancer cells is known to be responsible for many therapeutic failures in current oncological treatments. Here, we show that the combination of different effectors like hyperthermia, iron oxide nanoparticles, and chemotherapeutics influences expression of MRP 1 and 3 in an adenocarcinoma cell line. Methods BT-474 cells were treated with magnetic nanoparticles (MNP; 1.5 to 150 μg Fe/cm2) or mitomycin C (up to 1.5 μg/cm2, 24 hours) in the presence or absence of hyperthermia (43°C, 15 to 120 minutes). Moreover, cells were also sequentially exposed to these effectors (MNP, hyperthermia, and mitomycin C). After cell harvesting, mRNA was extracted and analyzed via reverse transcription polymerase chain reaction. Additionally, membrane protein was isolated and analyzed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Results When cells were exposed to the effectors alone or to combinations thereof, no effects on MRP 1 and 3 mRNA expression were observed. In contrast, membrane protein expression was influenced in a selective manner. The effects on MRP 3 expression were less pronounced compared with MRP 1. Treatment with mitomycin C decreased MRP expression at high concentrations and hyperthermia intensified these effects. In contrast, the presence of MNP only increased MRP 1 and 3 expression, and hyperthermia reversed these effects. When combining hyperthermia, magnetic nanoparticles, and mitomycin C, no further suppression of MRP expression was observed in comparison with the respective dual treatment modalities. Discussion The different MRP 1 and 3 expression levels are not associated with de novo mRNA expression, but rather with an altered translocation of MRP 1 and 3 to the cell membrane as a result of reactive oxygen species production, and with shifting of intracellular MRP storage pools, changes in membrane fluidity, etc, at the protein level. Our

  14. Cardiopulmonary and arterial baroreceptor unloading during passive hyperthermia does not contribute to hyperthermia-induced hyperventilation.

    PubMed

    Lucas, Rebekah A I; Pearson, James; Schlader, Zachary J; Crandall, Craig G

    2015-11-01

    What is the central question of this study? Does baroreceptor unloading during passive hyperthermia contribute to increases in ventilation and decreases in end-tidal carbon dioxide during that exposure? What is the main finding and its importance? Hyperthermic hyperventilation is not mitigated by expanding central blood volume and reloading the cardiopulmonary baroreceptors via rapid saline infusion or by reloading the arterial baroreceptors via phenylephrine administration. The absence of a reduction in ventilation upon reloading the baroreceptors to pre-hyperthermic levels indicates that cardiopulmonary and arterial baroreceptor unloading with hyperthermia is unlikely to contribute to hyperthermic hyperventilation in humans. This study tested the hypothesis that baroreceptor unloading during passive hyperthermia contributes to increases in ventilation and decreases in end-tidal partial pressure of carbon dioxide (P ET ,CO2) during that exposure. Two protocols were performed, in which healthy subjects underwent passive hyperthermia (increasing intestinal temperature by ∼1.8°C) to cause a sustained increase in ventilation and reduction in P ET ,CO2. Upon attaining hyperthermic hyperventilation, in protocol 1 (n = 10; three females) a bolus (19 ± 2 ml kg(-1) ) of warm (∼38°C) isotonic saline was rapidly (5-10 min) infused intravenously to restore reductions in central venous pressure, whereas in protocol 2 (n = 11; five females) phenylephrine was infused intravenously (60-120 μg min(-1) ) to return mean arterial pressure to normothermic levels. In protocol 1, hyperthermia increased ventilation (by 2.2 ± 1.7 l min(-1) , P < 0.01), while reducing P ET ,CO2 (by 4 ± 3 mmHg, P = 0.04) and central venous pressure (by 5 ± 1 mmHg, P <0.01). Saline infusion increased central venous pressure by 5 ± 1 mmHg (P < 0.01), restoring it to normothermic values, but did not change ventilation or P ET ,CO2 (P > 0.05). In protocol 2

  15. Computational evaluation of amplitude modulation for enhanced magnetic nanoparticle hyperthermia.

    PubMed

    Soetaert, Frederik; Dupré, Luc; Ivkov, Robert; Crevecoeur, Guillaume

    2015-10-01

    Magnetic nanoparticles (MNPs) can interact with alternating magnetic fields (AMFs) to deposit localized energy for hyperthermia treatment of cancer. Hyperthermia is useful in the context of multimodality treatments with radiation or chemotherapy to enhance disease control without increased toxicity. The unique attributes of heat deposition and transfer with MNPs have generated considerable attention and have been the focus of extensive investigations to elucidate mechanisms and optimize performance. Three-dimensional (3D) simulations are often conducted with the finite element method (FEM) using the Pennes' bioheat equation. In the current study, the Pennes' equation was modified to include a thermal damage-dependent perfusion profile to improve model predictions with respect to known physiological responses to tissue heating. A normal distribution of MNPs in a model liver tumor was combined with empirical nanoparticle heating data to calculate tumor temperature distributions and resulting survival fraction of cancer cells. In addition, calculated spatiotemporal temperature changes were compared among magnetic field amplitude modulations of a base 150-kHz sinusoidal waveform, specifically, no modulation, sinusoidal, rectangular, and triangular modulation. Complex relationships were observed between nanoparticle heating and cancer tissue damage when amplitude modulation and damage-related perfusion profiles were varied. These results are tantalizing and motivate further exploration of amplitude modulation as a means to enhance efficiency of and overcome technical challenges associated with magnetic nanoparticle hyperthermia (MNH).

  16. [Regional electro-hyperthermia--technical principles, clinical results and health insurance aspects].

    PubMed

    Heyll, Uwe

    2012-06-01

    The method of electro-hyperthermia is based on the production of alternating currents from capacitive coupled electrodes. Because of the associated heating of body tissues, the electro-hyperthermia is promoted as an alternative to the more sophisticated methods of scientific hyperthermia, which find use in oncologic diseases. The analysis of technical data, however, reveals that the electro-hyperthermia is not qualified for a focused, effective and therapeutically useful heating of circumscribed target areas. Data from clinical studies demonstrating efficacy for defined indications are not available. The application of electro-hyperthermia is excluded form the German system of public health insurance. As proof of medical necessity cannot be provided, there is also no claim for reimbursement from private health insurance. According to legal regulations in Germany, an invoice as hyperthermia treatment is usually not possible. Rather, an item from the electrotherapy section of the official provision of medical fees (GOA) has to be chosen.

  17. [Use of an iliac branched endoprostheis in endovascular treatment for an abdominal aortic aneurysm combined with aneurysms of both common iliac arteries].

    PubMed

    Imaev, T E; Kuchin, I V; Lepilin, P M; Kolegaev, A S; Medvedeva, I S; Komlev, A E; Akchurin, R S

    An abdominal aortic aneurysm appears to be combined with aneurysmatic lesions of the common iliac arteries in 30-40% of cases. Like abdominal aortic aneurysms, aneurysms of the common iliac arteries rarely manifest themselves clinically. The lethality rate in case of rupture is comparable to that for rupture of an abdominal aortic aneurysm. During endoprosthetic repair of abdominal aortic aneurysms combined with aneurysms of the common iliac arteries, in order to prevent endoleaks and to improve the distal zone of fixation of endografts surgeons often resort to embolization of internal iliac arteries, which may lead to ischaemic postoperative complications. One of the methods of preserving pelvic blood flow is the use of an iliac branched endograft. A series of studies evaluating long-term outcomes demonstrated that this method proved to be both safe and effective, and with the suitable anatomy is a method of choice in high surgical risk patients. The present article deals with a clinical case report concerning bilateral endoprosthetic repair of the common iliac arteries, combined with endoprosthetic repair of an abdominal aortic aneurysm, with the description of technical peculiarities of implanting an iliac branched graft.

  18. Circulatory failure during severe hyperthermia in dog.

    PubMed

    Miki, K; Morimoto, T; Nose, H; Itoh, T; Yamada, S

    1983-01-01

    The effect of acute hyperthermia on circulatory function was studied in 6 mongrel dogs. At a core temperature of about 40 degrees C, central venous pressure and stroke volume were maintained at almost normal level. Cardiac output significantly increased (26 ml/(kg . min)) while systemic vascular resistance significantly decreased (1.2 mmHg . sec/ml). In addition, significant decrease in vascular compliance by 40% was observed. When body temperature was raised further (severe hyperthermia), an abrupt fall of arterial pressure was observed at the rectal temperature of about 41-42 degrees C. Concomitant decreases in central venous pressure (3 mmHg), stroke volume (2.1 ml/beat) and cardiac output (29 ml/(kg . min)) were observed while heart rate increased (48 beats/min). These results suggest that the decrease in cardiac output during severe hyperthermia is due to the fall of central venous pressure, and the fall was attributed to the increase in unstressed vascular volume of systemic circulation due to the heat-induced cutaneous vasodilation. The observed decrease in systemic vascular compliance is considered to have a significant role in the maintenance of central venous pressure under hyperthermia.

  19. Nanosized As2O3/Fe2O3 complexes combined with magnetic fluid hyperthermia selectively target liver cancer cells.

    PubMed

    Wang, Zi-Yu; Song, Jian; Zhang, Dong-Sheng

    2009-06-28

    To study the methods of preparing the magnetic nano-microspheres of Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complexes and their therapeutic effects with magnetic fluid hyperthermia (MFH). Nanospheres were prepared by chemical co-precipitation and their shape and diameter were observed. Hemolysis, micronucleus, cell viability, and LD(50) along with other in vivo tests were performed to evaluate the Fe(2)O(3) microsphere biocompatibility. The inhibition ratio of tumors after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated. Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) particles were round with an average diameter of 20 nm and 100 nm as observed under transmission electron microscope. Upon exposure to an alternating magnetic field (AMF), the temperature of the suspension of magnetic particles increased to 41-51 degrees C, depending on different particle concentrations, and remained stable thereafter. Nanosized Fe(2)O(3) microspheres are a new kind of biomaterial without cytotoxic effects. The LD(50) of both Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) in mice was higher than 5 g/kg. One to four weeks after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complex injections into healthy pig livers, no significant differences were found in serum AST, ALT, BUN and Cr levels among the pigs of all groups (P > 0.05), and no obvious pathological alterations were observed. After exposure to alternating magnetic fields, the inhibition ratio of the tumors was significantly different from controls in the Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) groups (68.74% and 82.79%, respectively; P < 0.01). Tumors of mice in treatment groups showed obvious necrosis, while normal tissues adjoining the tumor and internal organs did not. Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complexes exerted radiofrequency-induced hyperthermia and drug toxicity on tumors without any liver or kidney damage. Therefore, nanospheres are ideal carriers for tumor-targeted therapy.

  20. Long duration mild temperature hyperthermia and brachytherapy.

    PubMed

    Armour, E P; Raaphorst, G P

    2004-03-01

    Combining long duration mild temperature hyperthermia (LDMH) and low dose-rate (LDR) brachytherapy to enhance therapeutic killing of cancer cells was proposed many years ago. The cellular and tumour research that supports this hypothesis is presented in this review. Research describing LDMH interaction with pulsed brachytherapy and high dose-rate brachytherapy using clinically relevant parameters are compared with LDMH/LDR brachytherapy. The mechanism by which LDMH sensitizes LDR has been established as the inhibition of sublethal damage repair. The molecular mechanisms have been shown to involve DNA repair enzymes, but the exact nature of these processes is still under investigation. The relative differences between LDMH interactions with human and rodent cells are presented to help in the understanding of possible roles of LDMH in clinical application. The role of LDMH in modifying tumour blood flow and its possible role in LDR sensitization of tumours is also presented. The positive aspects of LDMH-brachytherapy for clinical application are sixfold; (1) the thermal goals (temperature, time and volume) are achievable with currently available technology, (2) the hyperthermia by itself has no detectable toxic effects, (3) thermotolerance appears to play a minor if any role in radiation sensitization, (4) TER of around 2 can be expected, (5) hypoxic fraction may be decreased due to blood flow modification and (6) simultaneous chemotherapy may also be sensitized. Combined LDMH and brachytherapy is a cancer therapy that has established biological rationale and sufficient technical and clinical advancements to be appropriately applied. This modality is ripe for clinical testing.

  1. A facile microwave synthetic route for ferrite nanoparticles with direct impact in magnetic particle hyperthermia.

    PubMed

    Makridis, A; Chatzitheodorou, I; Topouridou, K; Yavropoulou, M P; Angelakeris, M; Dendrinou-Samara, C

    2016-06-01

    The application of ferrite magnetic nanoparticles (MNPs) in medicine finds its rapidly developing emphasis on heating mediators for magnetic hyperthermia, the ever-promising "fourth leg" of cancer treatment. Usage of MNPs depends largely on the preparation processes to select optimal conditions and effective routes to finely tailor MNPs. Microwave heating, instead of conventional heating offers nanocrystals at significantly enhanced rate and yield. In this work, a facile mass-production microwave hydrothermal synthetic approach was used to synthesize stable ferromagnetic manganese and cobalt ferrite nanoparticles with sizes smaller than 14 nm from metal acetylacetonates in the presence of octadecylamine. Prolonging the reaction time from 15 to 60 min, led to ferrites with improved crystallinity while the sizes are slight increased. The high crystallinity magnetic nanoparticles showed exceptional magnetic heating parameters. In vitro application was performed using the human osteosarcoma cell line Saos-2 incubated with manganese ferrite nanoparticles. Hyperthermia applied in a two cycle process, while AC magnetic field remained on until the upper limit of 45 °C was achieved. The comparative results of the AC hyperthermia efficiency of ferrite nanoparticles in combination with the in vitro study coincide with the magnetic features and their tunability may be further exploited for AC magnetic hyperthermia driven applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Prospective treatment planning to improve locoregional hyperthermia for oesophageal cancer.

    PubMed

    Kok, H P; van Haaren, P M A; van de Kamer, J B; Zum Vörde Sive Vörding, P J; Wiersma, J; Hulshof, M C C M; Geijsen, E D; van Lanschot, J J B; Crezee, J

    2006-08-01

    In the Academic Medical Center (AMC) Amsterdam, locoregional hyperthermia for oesophageal tumours is applied using the 70 MHz AMC-4 phased array system. Due to the occurrence of treatment-limiting hot spots in normal tissue and systemic stress at high power, the thermal dose achieved in the tumour can be sub-optimal. The large number of degrees of freedom of the heating device, i.e. the amplitudes and phases of the antennae, makes it difficult to avoid treatment-limiting hot spots by intuitive amplitude/phase steering. Prospective hyperthermia treatment planning combined with high resolution temperature-based optimization was applied to improve hyperthermia treatment of patients with oesophageal cancer. All hyperthermia treatments were performed with 'standard' clinical settings. Temperatures were measured systemically, at the location of the tumour and near the spinal cord, which is an organ at risk. For 16 patients numerically optimized settings were obtained from treatment planning with temperature-based optimization. Steady state tumour temperatures were maximized, subject to constraints to normal tissue temperatures. At the start of 48 hyperthermia treatments in these 16 patients temperature rise (DeltaT) measurements were performed by applying a short power pulse with the numerically optimized amplitude/phase settings, with the clinical settings and with mixed settings, i.e. numerically optimized amplitudes combined with clinical phases. The heating efficiency of the three settings was determined by the measured DeltaT values and the DeltaT-ratio between the DeltaT in the tumour (DeltaToes) and near the spinal cord (DeltaTcord). For a single patient the steady state temperature distribution was computed retrospectively for all three settings, since the temperature distributions may be quite different. To illustrate that the choice of the optimization strategy is decisive for the obtained settings, a numerical optimization on DeltaT-ratio was performed for

  3. EFFECTS OF HYPERTHERMIA AND HYPERTHERMIA PLUS MICROWAVES ON RAT BRAIN ENERGY METABOLISM

    EPA Science Inventory

    The effects of hyperthermia, alone and in conjunction with microwave exposure, on brain energetics were studied in anesthetized male Sprague-Dawley rats. The effects of temperature on adenosine triphosphate concentration (ATP) and creatine phosphate concentration (CP) was determi...

  4. Randomized trial of amino acid mixture combined with physical activity promotion for abdominal fat reduction in overweight adults.

    PubMed

    Ueda, Keisuke; Sasai, Hiroyuki; Tsujimoto, Takehiko; Sanbongi, Chiaki; Ikegami, Shuji; Kobayashi, Hiroyuki; Shioya, Nobuhiko; Suzuki, Satoru; Nakata, Yoshio

    2018-01-01

    The purpose of this study was to test the efficacy of arginine, alanine, and phenylalanine mixture (A-mix) ingestion at 1,500 mg/day in combination with the promotion of physical activity for abdominal fat reduction in overweight adults. A placebo-controlled, double-blind, parallel-group, randomized trial for 12 weeks combined with a 4-week follow-up period was conducted at a single center in Minato-ku, Tokyo, Japan, between December 2016 and May 2017. Data were analyzed between June and August 2017. The study participants were 200 overweight adults within the age range of 20-64 years. The participants were randomly assigned to the A-mix group (n=100) or a placebo group (n=100) and were administered 500 mL of test beverage containing 1,500 or 0 mg of A-mix, respectively, for 12 weeks. All participants maintained a physically active lifestyle between week 0 and week 12 through monthly sessions of physical activity. The primary outcomes were the 12-week changes in the abdominal total, subcutaneous, and visceral fat areas, as assessed by computed tomography. Of the 200 enrolled participants, 199 (99%) accomplished the 12-week intervention and 4-week follow-up period. The per-protocol-based analysis for 194 participants demonstrated that the abdominal total fat area decreased significantly in the A-mix group compared with that in the placebo group (difference, 10.0 cm 2 ; 95% confidence interval [CI]: 0.4-19.6 cm 2 ; P =0.041). Comparable outcomes were obtained for the abdominal subcutaneous fat area (difference, 7.4 cm 2 ; 95% CI: 0.1-14.7 cm 2 ; P =0.047). No study-related unfavorable events occurred. A-mix supplementation in combination with physical activity promotion facilitated abdominal fat reduction in overweight adults.

  5. Mean-field and linear regime approach to magnetic hyperthermia of core-shell nanoparticles: can tiny nanostructures fight cancer?

    NASA Astrophysics Data System (ADS)

    Carrião, Marcus S.; Bakuzis, Andris F.

    2016-04-01

    The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia model for core-shell nanoparticles is developed. The theoretical calculation, different from previous models, highlights the importance of heterogeneity by identifying the role of surface and core spins on nanoparticle heat generation. We found that the most efficient nanoparticles should be obtained by selecting materials to reduce the surface to core damping factor ratio, increasing the interface exchange parameter and tuning the surface to core anisotropy ratio for each material combination. From our results we propose a novel heat-based hyperthermia strategy with the focus on improving the heating efficiency of small sized nanoparticles instead of larger ones. This approach might have important implications for cancer treatment and could help improving clinical efficacy.The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia model for core-shell nanoparticles is developed. The theoretical calculation, different from previous models, highlights the importance of heterogeneity by identifying the role of surface and core spins on nanoparticle heat generation. We found that the most efficient nanoparticles should be obtained by selecting materials to reduce the surface to core damping factor ratio, increasing the interface exchange parameter and tuning the surface to core anisotropy ratio for each material combination. From our results we propose a novel heat-based hyperthermia strategy with the focus on improving the heating efficiency of small sized nanoparticles instead of larger ones. This approach might have important implications for cancer

  6. Similarities and differences in ablative and non-ablative iron oxide nanoparticle hyperthermia cancer treatment

    NASA Astrophysics Data System (ADS)

    Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Mazur, Courtney M.; Petryk, James D.; Hoopes, P. Jack

    2015-03-01

    The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. It has been demonstrated by many research groups that ablative temperatures and cytotoxicity can be produced with locally NP-based hyperthermia. Such ablative NP techniques have demonstrated the potential for success. Much attention has also been given to the fact that NP may be administered systemically, resulting in a broader cancer therapy approach, a lower level of tumor NP content and a different type of NP cancer therapy (most likely in the adjuvant setting). To use NP based hyperthermia successfully as a cancer treatment, the technique and its goal must be understood and utilized in the appropriate clinical context. The parameters include, but are not limited to, NP access to the tumor (large vs. small quantity), cancer cell-specific targeting, drug carrying capacity, potential as an ionizing radiation sensitizer, and the material properties (magnetic characteristics, size and charge). In addition to their potential for cytotoxicity, the material properties of the NP must also be optimized for imaging, detection and direction. In this paper we will discuss the differences between, and potential applications for, ablative and non-ablative magnetic nanoparticle hyperthermia.

  7. Weather, geography, and vehicle-related hyperthermia in children.

    PubMed

    Grundstein, Andrew; Null, Jan; Meentemeyer, Vernon

    2011-01-01

    Vehicle-related hyperthermia is an unfortunate tragedy that leads to the accidental deaths of children each year. This research utilizes the most extensive dataset of child vehicle-related hyperthermia deaths in the United States, including 414 deaths between 1998 and 2008. Deaths follow a seasonal pattern, with a peak in July and no deaths in December or January. Also, deaths occurred over a wide range of temperature and radiation levels and across virtually all regions, although most of them took place across the southern United States. In particular, the Phoenix, Houston, Dallas, and Las Vegas metropolitan areas had the greatest number of deaths. We utilize our vehicle hyperthermia index (vhi) to compare expected deaths versus actual deaths in a metropolitan area, based on the number of children in the area who are under the age of five and on the frequency of hot days in the area. The vhi indicates that the Memphis, West Palm Beach-Boca Raton, and Las Vegas metropolitan areas are the most dangerous places for vehicle-related hyperthermia. We conclude by discussing several recommendations with public health policy implications.

  8. Changes in ryanodine-induced contractures by stimulus frequency in malignant hyperthermia susceptible and malignant hyperthermia nonsusceptible dog skeletal muscle.

    PubMed

    Sudo, R T; Nelson, T E

    1997-09-01

    Elective diagnosis of malignant hyperthermia depends on halothane and caffeine contracture testing of biopsied skeletal muscle. Ryanodine-induced contractures may provide greater sensitivity and specificity for malignant hyperthermia (MH) diagnosis. This study investigated the effects of ryanodine concentration and stimulus frequency to distinguish between MH susceptible (MHS) and MH non-susceptible (MHN) dogs. Increasing ryanodine concentrations (1, 2.5 and 5 microM) increased peak isometric contracture tension, but similar responses in MHS and MHN muscle precluded use for diagnosis. Time to tension onset and to peak tension decreased with increasing ryanodine concentration, and these times were shorter in MH skeletal muscle. Increasing stimulus frequency (0.1, 0.5 and 1 Hz) decreased the time to tension onset and to peak tension, but the effect was greater in MHN muscle which decreased the difference between MHN and MHS muscle responses. When ryanodine contracture tension onset time was selected to detect MHS muscle, combinations of either 0.1 Hz and 1 microM ryanodine or 0.5 Hz and 1 microM ryanodine reduced the probabilty of a false diagnosis to less than 1%. Similar studies performed on human muscle might identify optimal stimulus frequency and ryanodine concentration for detecting MH in patients.

  9. In Hyperthermia Increased ERK and WNT Signaling Suppress Colorectal Cancer Cell Growth

    PubMed Central

    Bordonaro, Michael; Shirasawa, Senji; Lazarova, Darina L.

    2016-01-01

    Although neoplastic cells exhibit relatively higher sensitivity to hyperthermia than normal cells, hyperthermia has had variable success as an anti-cancer therapy. This variable outcome might be due to the fact that cancer cells themselves have differential degrees of sensitivity to high temperature. We hypothesized that the varying sensitivity of colorectal cancer (CRC) cells to hyperthermia depends upon the differential induction of survival pathways. Screening of such pathways revealed that Extracellular Signal-Regulated Kinase (ERK) signaling is augmented by hyperthermia, and the extent of this modulation correlates with the mutation status of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS). Through clonal growth assays, apoptotic analyses and transcription reporter assays of CRC cells that differ only in KRAS mutation status we established that mutant KRAS cells are more sensitive to hyperthermia, as they exhibit sustained ERK signaling hyperactivation and increased Wingless/Integrated (WNT)/beta-catenin signaling. We propose that whereas increased levels of WNT and ERK signaling and a positive feedback between the two pathways is a major obstacle in anti-cancer therapy today, under hyperthermia the hyperinduction of the pathways and their positive crosstalk contribute to CRC cell death. Ascertaining the causative association between types of mutations and hyperthermia sensitivity may allow for a mutation profile-guided application of hyperthermia as an anti-cancer therapy. Since KRAS and WNT signaling mutations are prevalent in CRC, our results suggest that hyperthermia-based therapy might benefit a significant number, but not all, CRC patients. PMID:27187477

  10. Radiotherapy and Hyperthermia for Treatment of Primary Locally Advanced Cervix Cancer: Results in 378 Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Franckena, Martine; Lutgens, Ludy C.; Koper, Peter C.

    2009-01-01

    Purpose: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series. Methods and Materials: From 1996 to 2005, a total of 378 patients with LACC (International Federation of Gynecology and Obstetrics Stage IB2-IVA) were treated with RHT. External beam radiotherapy (RT) was applied to 46-50.4 Gy and combined with brachytherapy. The hyperthermia (HT) was prescribed once weekly. Primary end points were complete response (CR) and local control. Secondary end points were overall survival, disease-specific survival,more » and late toxicity. Patient, tumor, and treatment characteristics predictive for the end points were identified in univariate and multivariate analyses. Results: Overall, a CR was achieved in 77% of patients. At 5 years, local control, disease-specific survival, and incidence of late toxicity Common Terminology Criteria for Adverse Events Grade 3 or higher were 53%, 47%, and 12%, respectively. In multivariate analysis, number of HT treatments emerged as a predictor of outcome in addition to commonly identified prognostic factors. Conclusions: The CR, local control, and survival rates are similar to previously observed results of RHT in the randomized Dutch Deep Hyperthermia Trial. Reported treatment results for currently applied combined treatment modalities (i.e., RT with chemotherapy and/or HT) do not permit definite conclusions about which combination is superior. The present results confirm previously shown beneficial effects from adding HT to RT and justify the application of RHT as first-line treatment in patients with LACC as an alternative to chemoradiation.« less

  11. Nanoparticle-mediated hyperthermia in cancer therapy

    PubMed Central

    Chatterjee, Dev Kumar; Diagaradjane, Parmeswaran; Krishnan, Sunil

    2011-01-01

    A small rise in tumor temperature (hyperthermia) makes cancer cells more susceptible to radiation and chemotherapy. The means of achieving this is not trivial, and traditional methods have certain drawbacks. Loading tumors with systematically asministered energy-transducing nanoparticles can circumvent several of the obstacles to achieve tumor hyperthermia. However, nanoparticles also face unique challenges prior to clinical implementation. This article summarizes the state-of-the-art current technology and discusses the advantages and challenges of the three major nanoparticle formulations in focus: gold nanoshells and nanorods, superparamagnetic iron oxide particles and carbon nanotubes. PMID:22506095

  12. Multifunctional magnetic nanostructured hardystonite scaffold for hyperthermia, drug delivery and tissue engineering applications.

    PubMed

    Farzin, Ali; Fathi, Mohammadhossein; Emadi, Rahmatollah

    2017-01-01

    Hyperthermia and local drug delivery have been proposed as potential therapeutic approaches for killing cancer cells. The development of bioactive materials such as Hardystonite (HT) with magnetic and drug delivery properties can potentially meet this target. This new class of magnetic bioceramic can replace the widely used magnetic iron oxide nanoparticles, whose long-term biocompatibility is not clear. Magnetic HT can be potentially employed to develop new ceramic scaffolds for bone surgery and anticancer therapies. With this in mind, a synthesis procedure was developed to prepare multifunctional bioactive scaffold for tissue engineering, hyperthermia and drug delivery applications. To this end, iron (Fe 3+ )-containing HT scaffolds were prepared. The effect of Fe on biological, magnetic and drug delivery properties of HT scaffolds were investigated. The results showed that obtained Fe-HT is bioactive and magnetic with no magnetite or maghemite as secondary phases. The Fe-HT scaffolds obtained also possessed high specific surface areas and demonstrated sustained drug delivery. These results potentially open new aspects for biomaterials aimed at regeneration of large-bone defects caused by malignant bone tumors through a combination of hyperthermia, local drug delivery and osteoconductivity. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. The Effects of Combined Exercise on Health-Related Fitness, Endotoxin, and Immune Function of Postmenopausal Women with Abdominal Obesity.

    PubMed

    Park, Sung-Mo; Kwak, Yi-Sub; Ji, Jin-Goo

    2015-01-01

    This study was conducted to examine the effects of combined exercise on health-related fitness, endotoxin concentrations, and immune functions of postmenopausal women with abdominal obesity. 20 voluntary participants were recruited and they were randomly allocated to the combined exercise group (n = 10) or the control group (n = 10). Visceral obesity was defined as a visceral-to-subcutaneous fat ratio ≥ 0.4 based on computed tomography (CT) results. Body composition, exercise stress testing, fitness measurement, CT scan, and blood variables were analyzed to elucidate the effects of combined exercise. The SPSS Statistics 18.0 program was used to calculate means and standard deviations for all variables. Significant differences between the exercise group and control group were determined with 2-way ANOVA and paired t-tests. The exercise group's abdominal obesity was mitigated due to visceral fat reduction; grip strength, push-ups, and oxygen uptake per weight improved; and HDL-C and IgA level also increased, while TNF-α, CD14, and endotoxin levels decreased. Lowered TNF-α after exercise might have an important role in the obesity reduction. Therefore, we can conclude that combined exercise is effective in mitigating abdominal obesity, preventing metabolic diseases, and enhancing immune function.

  14. Clinical application of entire gastrointestinal barium meal combined with multi-temporal abdominal films in patients with intestinal neuronal dysplasia type B.

    PubMed

    Li, Xiao-Yun; Li, Xiao-Gang; Du, Ming-Guo; Chen, Zhi-Dan; Tao, Zheng-Gui; Liao, Xiao-Feng

    2013-01-01

    To report and evaluate the application of entire gastrointestinal barium meal combined with multi-temporal abdominal films in the diagnosis of patients with intestinal neuronal dysplasia type B (IND type B). Thirty-six patients with symptoms of long-standing constipation were enrolled in this study. The study took place at the Department of General Surgery, Xiangyang Central Hospital, Hubei Province, China from July 2007 to October 2012. All of them had already been subjected to the tests of barium enema and anorectal manometry and were suspected to be IND type B, but were not confirmed by mucous membrane acetylcholinesterase determination. All underwent the entire gastrointestinal barium meal combined with multi-temporal abdominal films. The data was collected and then analyzed retrospectively. After entire gastrointestinal barium meal combined with multi-temporal abdominal films, 30 out of 36 cases in this group were diagnosed with intestinal neuronal diseases, and then were treated with appropriate surgical treatment. The postoperative pathological diagnosis was IND type B. The other 6 patients in this group still could not be diagnosed explicitly after the test; thus, we treated them with conservative treatment. Entire gastrointestinal barium meal combined with multi-temporal abdominal films has the advantage of being able to test the gastrointestinal transfer capabilities and to find physiological and pathological changes simultaneously. It could provide important proof for the diagnosis of patients with intestinal neuronal dysplasia type B.

  15. Magnetic mesoporous silica nanoparticles for potential delivery of chemotherapeutic drugs and hyperthermia.

    PubMed

    Tao, Cuilian; Zhu, Yufang

    2014-11-07

    Magnetic mesoporous silica (MMS) nanoparticles with controllable magnetization have been synthesized by encapsulating Fe3O4 nanoparticles in a mesoporous silica matrix. The structure, magnetic heating capacity and drug delivery ability of MMS nanoparticles were evaluated. The results showed that MMS nanoparticles had an average particle size of 150 nm and showed low cytotoxicity and efficient cell uptake ability. MMS nanoparticles exhibited a sustained drug release in the medium of pH 5.0, but a very slow release in the medium of pH 7.4. On the other hand, MMS nanoparticles could controllably generate heat to reach the hyperthermia temperature within a short time upon exposure to an alternating magnetic field due to the superparamagnetic behavior and controllable magnetization. Therefore, MMS nanoparticles could provide a promising multifunctional platform for the combination of chemotherapy and hyperthermia for cancer therapy.

  16. Simulation techniques in hyperthermia treatment planning

    PubMed Central

    Paulides, MM; Stauffer, PR; Neufeld, E; Maccarini, P; Kyriakou, A; Canters, RAM; Diederich, C; Bakker, JF; Van Rhoon, GC

    2013-01-01

    Clinical trials have shown that hyperthermia (HT), i.e. an increase of tissue temperature to 39-44°C, significantly enhance radiotherapy and chemotherapy effectiveness (1). Driven by the developments in computational techniques and computing power, personalized hyperthermia treatment planning (HTP) has matured and has become a powerful tool for optimizing treatment quality. Electromagnetic, ultrasound, and thermal simulations using realistic clinical setups are now being performed to achieve patient-specific treatment optimization. In addition, extensive studies aimed to properly implement novel HT tools and techniques, and to assess the quality of HT, are becoming more common. In this paper, we review the simulation tools and techniques developed for clinical hyperthermia, and evaluate their current status on the path from “model” to “clinic”. In addition, we illustrate the major techniques employed for validation and optimization. HTP has become an essential tool for improvement, control, and assessment of HT treatment quality. As such, it plays a pivotal role in the quest to establish HT as an efficacious addition to multi-modality treatment of cancer. PMID:23672453

  17. Magnetic fluid hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Jordan, Andreas; Scholz, Regina; Wust, Peter; Fähling, Horst; Felix, Roland

    1999-07-01

    The story of hyperthermia with small particles in AC magnetic fields started in the late 1950s, but most of the studies were unfortunately conducted with inadequate animal systems, inexact thermometry and poor AC magnetic field parameters, so that any clinical implication was far behind the horizon. More than three decades later, it was found, that colloidal dispersions of superparamagnetic (subdomain) iron oxide nanoparticles exhibit an extraordinary specific absorption rate (SAR [ W/ g]), which is much higher at clinically tolerable H 0 f combinations in comparison to hysteresis heating of larger multidomain particles. This was the renaissance of a cancer treatment method, which has gained more and more attention in the last few years. Due to the increasing number of randomized clinical trials preferentially in Europe with conventional E-field hyperthermia systems, the general medical and physical experience in hyperthermia application is also rapidly growing. Taking this increasing clinical experience carefully into account together with the huge amount of new biological data on heat response of cells and tissues, the approach of magnetic fluid hyperthermia (MFH) is nowadays more promising than ever before. The present contribution reviews the current state of the art and some of the future perspectives supported by advanced methods of the so-called nanotechnology.

  18. Ultrastructure of rabbit embryos exposed to hyperthermia and anti-Hsp 70.

    PubMed

    Olexikova, L; Makarevich, A V; Pivko, J; Chrenek, P

    2013-08-01

    The aim of the study was to determine the effect of short-term hyperthermia and Hsp70 blockage on ultrastructural changes in cell organelles and nucleoli of rabbit preimplantation embryos. The embryos were cultured either at 37.5°C (control, C) or 41.5°C (hyperthermia, HT) during 6 h. The antibody against Hsp70 was added into the culture medium (4 μg/ml) of morula stage embryos from C and HT groups. After termination of the culture, the embryos were processed for transmission electron microscopy. The embryos exposed to hyperthermia showed increased volume of lipid droplets, considerable occurrence of cellular debris in the perivitelline space and slight changes in the occurrence of microvilli on the surface of trophoblastic cells. In the embryos exposed to anti-Hsp 70 at 37.5°C, there were considerable changes in mitochondria morphology, decreased volume of dense bodies in the cytoplasm and considerable changes in the occurrence of microvilli on the surface of trophoblastic cells. In the group of embryos exposed simultaneously to hyperthermia and anti-Hsp 70, mitochondria were also expanded and swollen; the volume of flocculent vesicles and lipid droplets was increased and the volume of dense bodies in the cytoplasm was diminished. General organization of the cytoplasm in groups with anti-Hsp70 was characterized by cell organelle segregation. Averaged size of the nucleolar area was significantly increased in the embryos exposed to hyperthermia, whereas in the group exposed to the anti-Hsp70 without hyperthermia it was significantly diminished. Hyperthermia also caused disintegration of compact status of the nucleoli. In presence of anti-Hsp 70, the structural changes, described within the nucleoli during hyperthermia, were not observed. In conclusion, these results document ultrastructural changes in cell organelles of rabbit preimplantation embryo caused by hyperthermia, and also changes in the nucleolar structures, at which presence of Hsp-70 inhibit these

  19. Magnetic nanoparticles for enhancing the effectiveness of ultrasonic hyperthermia

    NASA Astrophysics Data System (ADS)

    Józefczak, A.; Kaczmarek, K.; Hornowski, T.; Kubovčíková, M.; Rozynek, Z.; Timko, M.; Skumiel, A.

    2016-06-01

    Ultrasonic hyperthermia is a method of cancer treatment in which tumors are exposed to an elevated cytotoxic temperature using ultrasound (US). In conventional ultrasonic hyperthermia, the ultrasound-induced heating in the tumor is achieved through the absorption of wave energy. However, to obtain appropriate temperature in reasonable time, high US intensities, which can have a negative impact on healthy tissues, are required. The effectiveness of US for medical purposes can be significantly improved by using the so-called sonosensitizers, which can enhance the thermal effect of US on the tissue by increasing US absorption. One possible candidate for such sonosensitizers is magnetic nanoparticles with mean sizes of 10-300 nm, which can be efficiently heated because of additional attenuation and scattering of US. Additionally, magnetic nanoparticles are able to produce heat in the alternating magnetic field (magnetic hyperthermia). The synergetic application of ultrasonic and magnetic hyperthermia can lead to a promising treatment modality.

  20. Chronic Abdominal Wall Pain.

    PubMed

    Koop, Herbert; Koprdova, Simona; Schürmann, Christine

    2016-01-29

    Chronic abdominal wall pain is a poorly recognized clinical problem despite being an important element in the differential diagnosis of abdominal pain. This review is based on pertinent articles that were retrieved by a selective search in PubMed and EMBASE employing the terms "abdominal wall pain" and "cutaneous nerve entrapment syndrome," as well as on the authors' clinical experience. In 2% to 3% of patients with chronic abdominal pain, the pain arises from the abdominal wall; in patients with previously diagnosed chronic abdominal pain who have no demonstrable pathological abnormality, this likelihood can rise as high as 30% . There have only been a small number of clinical trials of treatment for this condition. The diagnosis is made on clinical grounds, with the aid of Carnett's test. The characteristic clinical feature is strictly localized pain in the anterior abdominal wall, which is often mischaracterized as a "functional" complaint. In one study, injection of local anesthesia combined with steroids into the painful area was found to relieve pain for 4 weeks in 95% of patients. The injection of lidocaine alone brought about improvement in 83-91% of patients. Long-term pain relief ensued after a single lidocaine injection in 20-30% of patients, after repeated injections in 40-50% , and after combined lidocaine and steroid injections in up to 80% . Pain that persists despite these treatments can be treated with surgery (neurectomy). Chronic abdominal wall pain is easily diagnosed on physical examination and can often be rapidly treated. Any physician treating patients with abdominal pain should be aware of this condition. Further comparative treatment trials will be needed before a validated treatment algorithm can be established.

  1. Fundamentals and advances in magnetic hyperthermia

    NASA Astrophysics Data System (ADS)

    Périgo, E. A.; Hemery, G.; Sandre, O.; Ortega, D.; Garaio, E.; Plazaola, F.; Teran, F. J.

    2015-12-01

    Nowadays, magnetic hyperthermia constitutes a complementary approach to cancer treatment. The use of magnetic particles as heating mediators, proposed in the 1950s, provides a novel strategy for improving tumor treatment and, consequently, patient's quality of life. This review reports a broad overview about several aspects of magnetic hyperthermia addressing new perspectives and the progress on relevant features such as the ad hoc preparation of magnetic nanoparticles, physical modeling of magnetic heating, methods to determine the heat dissipation power of magnetic colloids including the development of experimental apparatus and the influence of biological matrices on the heating efficiency.

  2. The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

    NASA Astrophysics Data System (ADS)

    Hoopes, P. Jack; Wagner, Robert J.; Song, Ailin; Osterberg, Bjorn; Gladstone, David J.; Bursey, Alicea A.; Fiering, Steven N.; Giustini, Andrew J.

    2017-02-01

    It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

  3. Erythrocyte Osmotic Fragility Testing and the Prediction of Canine Malignant Hyperthermia Susceptibility

    PubMed Central

    Cribb, Peter H.; Olfert, Ernest A.; Reynolds, F. Barry

    1986-01-01

    A Doberman-German Shepherd cross-bred male dog, previously diagnosed as malignant hyperthermia susceptible, was mated to an unrelated nonsusceptible German Shepherd cross-bred female. The resultant litter was subjected to hematological, biochemical and erythrocyte osmotic fragility testing in an endeavor to predict the susceptibility of individuals to malignant hyperthermia. Laboratory evaluations were repeated at one year of age and the litter subjected to the halothane challenge test. No significant difference in erythrocyte osmotic fragility was found between malignant hyperthermia susceptible and nonsusceptible siblings at six weeks or at one year of age. Erythrocyte osmotic fragility, in both malignant hyperthermia susceptible and nonsusceptible animals, increased between six weeks and one year of age. Dantrolene sodium was an effective treatment for malignant hyperthermia in the dog when administered early in an episode and in adequate dosage. The initial sign of a malignant hyperthermia episode was a very rapid increase in end tidal partial pressure of carbon dioxide. This finding reinforces the value of capnographic monitoring in anesthesia. PMID:17422730

  4. FDTD analysis of a noninvasive hyperthermia system for brain tumors

    PubMed Central

    2012-01-01

    Background Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. Methods The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. Results The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. Conclusions The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors. PMID:22891953

  5. FDTD analysis of a noninvasive hyperthermia system for brain tumors.

    PubMed

    Yacoob, Sulafa M; Hassan, Noha S

    2012-08-14

    Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40-45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

  6. Effects of hyperthermia on ventilation and metabolism during hypoxia in conscious mice.

    PubMed

    Iwase, Michiko; Izumizaki, Masahiko; Kanamaru, Mitsuko; Homma, Ikuo

    2004-02-01

    Hyperthermia and hypoxia influence ventilation and metabolism; however, their synergistic effects remain unanswered. We hypothesized that an enhancement of ventilation induced by hyperthermia is competitive with hypoxic hypometabolism. We then examined the relationship of body temperature, hypoxia, and respiration in conscious mice, measuring minute ventilation (VE), aerobic metabolism, and arterial blood gases. All parameters were measured at two different body temperatures (BTs), approximately 37 degrees C (normothermia) and 39 degrees C (hyperthermia), under both normoxia (room air inhalation) and hypoxia (7% O2 inhalation). Under normoxia, VE and O2 consumption (VO2) were lower at hyperthermia than at normothermia, and the VE-VO2 ratio remained constant. PaCO2 values were normal at both BTs under normoxia. Hypoxic gas inhalation increased VE, which reached a peak in 2 min, then decreased at both BTs. VE remained at a higher level during hyperthermia than during normothermia throughout the 10 min experiment. VO2 decreased during hypoxia at both BTs. Hypoxia increased the VE-VO2 ratio because of relatively high VE with respect to the decreased VO2, which means hyperventilation. At hypoxia under hyperthermia, serious hyperventilation occurred with a further increase in VE. The augmented ventilation may be due to the thermal stimulus and a lowered thermoregulatory set point for hypoxia. Thus hyperthermia reduces ventilation and metabolism to maintain normocapnia; as a result, thermogenesis is reduced under normoxia. Hyperthermia augments hyperventilation induced by hypoxia, leading to severe hypoxic hypocapnia. Thermal stimuli may impair the adjustment of ventilation and metabolism when O2 is limited.

  7. Hyperthermia apparatus

    DOEpatents

    Larsen, Lawrence E.

    2000-01-01

    A hyperthermia apparatus, suitable for transurethral application, has an energy radiating element comprising a leaky-wave antenna. The leaky wave antenna radiation pattern is characterized by a surface wave which propagates along an aperture formed by openings (small in comparison to a wavelength) in the outer conductor of a transmission line. Appropriate design of the leaky wave antenna produces a uniform, broadside pattern of temperature elevation that uniformly heats all or part of the periurethral tissues.

  8. Effects of acute hyperthermia on the carotid baroreflex control of heart rate in humans

    NASA Astrophysics Data System (ADS)

    Yamazaki, F.; Sagawa, S.; Torii, R.; Endo, Y.; Shiraki, K.

    The purpose of this study was to examine the effect of hyperthermia on the carotid baroreceptor-cardiac reflexes in humans. Nine healthy males underwent acute hyperthermia (esophageal temperature 38.0° C) produced by hot water-perfused suits. Beat-to-beat heart rate (HR) responses were determined during positive and negative R-wave-triggered neck pressure steps from +40 to -65 mm Hg during normothermia and hyperthermia. The carotid baroreceptor-cardiac reflex sensitivity was evaluated from the maximum slope of the HR response to changes in carotid distending pressure. Buffering capacity of the HR response to carotid distending pressure was evaluated in % from a reference point calculated as (HR at 0 mm Hg neck pressure-minimum HR)/HR range ×100. An upward shift of the curve was evident in hyperthermia because HR increased from 57.7+/-2.4 beats/min in normothermia to 88.7+/-4.1 beats/min in hyperthermia (P<0.05) without changes in mean arterial pressure. The maximum slope of the curve in hyperthermia was similar to that in normothermia. The reference point was increased (P<0.05) during hyperthermia. These results suggest that the sensitivity of the carotid baroreflex of HR remains unchanged in hyperthermia. However, the capacity for tachycardia response to rapid onset of hypotension is reduced and the capacity for bradycardia response to sudden hypertension is increased during acute hyperthermia.

  9. Mean-field and linear regime approach to magnetic hyperthermia of core-shell nanoparticles: can tiny nanostructures fight cancer?

    PubMed

    Carrião, Marcus S; Bakuzis, Andris F

    2016-04-21

    The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia model for core-shell nanoparticles is developed. The theoretical calculation, different from previous models, highlights the importance of heterogeneity by identifying the role of surface and core spins on nanoparticle heat generation. We found that the most efficient nanoparticles should be obtained by selecting materials to reduce the surface to core damping factor ratio, increasing the interface exchange parameter and tuning the surface to core anisotropy ratio for each material combination. From our results we propose a novel heat-based hyperthermia strategy with the focus on improving the heating efficiency of small sized nanoparticles instead of larger ones. This approach might have important implications for cancer treatment and could help improving clinical efficacy.

  10. Recent advances in nanosized Mn-Zn ferrite magnetic fluid hyperthermia for cancer treatment.

    PubMed

    Lin, Mei; Huang, Junxing; Sha, Min

    2014-01-01

    This paper reviews the recent research and development of nanosized manganese zinc (Mn-Zn) ferrite magnetic fluid hyperthermia (MFH) for cancer treatment. Mn-Zn ferrite MFH, which has a targeted positioning function that only the temperature of tumor tissue with magnetic nanoparticles can rise, while normal tissue without magnetic nanoparticles is not subject to thermal damage, is a promising therapy for cancer. We introduce briefly the composition and properties of magnetic fluid, the concept of MFH, and features of Mn-Zn ferrite magnetic nanoparticles for MFH such as thermal bystander effect, universality, high specific absorption rate, the targeting effect of small size, uniformity of hyperthermia temperature, and automatic temperature control and constant temperature effect. Next, preparation methods of Mn-Zn ferrite magnetic fluid are discussed, and biocompatibility and biosecurity of Mn-Zn ferrite magnetic fluid are analyzed. Then the applications of nanosized Mn-Zn ferrite MFH in cancer are highlighted, including nanosized Mn-Zn ferrite MFH alone, nanosized Mn-Zn ferrite MFH combined with As2O3 chemotherapy, and nanosized Mn-Zn ferrite MFH combined with radiotherapy. Finally, the combination application of nanosized Mn-Zn ferrite MFH and gene-therapy is conceived, and the challenges and perspectives for the future of nanosized Mn-Zn ferrite MFH for oncotherapy are discussed.

  11. Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

    PubMed

    Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

    2004-01-01

    Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external

  12. Hyperthermia phased arrays pre-treatment evaluation.

    PubMed

    Bardati, Fernando; Tognolatti, Piero

    2016-12-01

    In the hyperthermia treatment of deep-seated tumours by a phased array of radiofrequency (RF) antennas, heatability will be investigated in terms of power-to-tumour and other figures-of-merit of hyperthermia treatments to be optimised. The assumption is that each source is individually constrained to not exceed a maximal nominal power. The nominal power may differ from a source to another as a physical limit or an operative modality. Under such constraint, new procedures for the maximisation of (i) power-to-tumour, (ii) heating efficiency and, in general, (iii) power ratios as tumour-heating selectivity are proposed. (iv) The problem whether a tumour is equally heatable after turning off some antennas is addressed as array thinning. An array of eight dipoles arranged on two lines around a head/neck is introduced to perform a numerical analysis. The achievable power-to-tumour according to the new optimizations and other performance indices adopted from the literature is tested against values of power that can be found to be sufficient for heating tumours to clinical temperatures. New solutions to data rendering in hyperthermia heating are proposed.

  13. [Malignant hyperthermia - problem in dental surgery. An introductory report].

    PubMed

    Kamińska, Ewa; Janas, Anna; Osica, Piotr

    2014-01-01

    Malignant hyperthermia is a genetic defect of uncontrolled hypermetabolic skeletal muscle response to anesthetic triggering drugs. Some congenital myopathies are regarded as risk increasing factors. The use of volatile anaesthetics or suxamethonium (succinylcholine) in patients who are predisposed to malignant hyperthermia leads to an increase in Ca2+ release from sarcoplasmic reticulum, which in turn causes a set of biochemical and clinical symptoms, which can be a cause of death, if dantrolene is not administered adequately. The aim of the study was to draw attention to the problem of malignant hyperthermia, which is hardly ever described in Polish literature, and requires the necessity of intensifying the cooperation between the dentist and specialists from other medical fields. The origin of the article was a case of congenital myopathy with recognized malignant hyperthermia in an 18-year-old patient, in whom surgical extraction of teeth was indicated. The course of diagnostics and treatment showed once more that contemporary medicine is in need of holistic approach, and in consequence, promising and effective cooperation of many specialists.

  14. Genetics Home Reference: malignant hyperthermia

    MedlinePlus

    ... Genetic and Rare Diseases Information Center (2 links) King Denborough syndrome Malignant hyperthermia Educational Resources (4 links) ... 19 [updated 2013 Jan 31]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean ...

  15. Inhalable Magnetic Nanoparticles for Targeted Hyperthermia in Lung Cancer Therapy

    PubMed Central

    Sadhukha, Tanmoy; Wiedmann, Timothy Scott; Panyam, Jayanth

    2015-01-01

    Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia. PMID:23591395

  16. Graphene Quantum Dots-Capped Magnetic Mesoporous Silica Nanoparticles as a Multifunctional Platform for Controlled Drug Delivery, Magnetic Hyperthermia, and Photothermal Therapy.

    PubMed

    Yao, Xianxian; Niu, Xingxing; Ma, Kexin; Huang, Ping; Grothe, Julia; Kaskel, Stefan; Zhu, Yufang

    2017-01-01

    A multifunctional platform is reported for synergistic therapy with controlled drug release, magnetic hyperthermia, and photothermal therapy, which is composed of graphene quantum dots (GQDs) as caps and local photothermal generators and magnetic mesoporous silica nanoparticles (MMSN) as drug carriers and magnetic thermoseeds. The structure, drug release behavior, magnetic hyperthermia capacity, photothermal effect, and synergistic therapeutic efficiency of the MMSN/GQDs nanoparticles are investigated. The results show that monodisperse MMSN/GQDs nanoparticles with the particle size of 100 nm can load doxorubicin (DOX) and trigger DOX release by low pH environment. Furthermore, the MMSN/GQDs nanoparticles can efficiently generate heat to the hyperthermia temperature under an alternating magnetic field or by near infrared irradiation. More importantly, breast cancer 4T1 cells as a model cellular system, the results indicate that compared with chemotherapy, magnetic hyperthermia or photothermal therapy alone, the combined chemo-magnetic hyperthermia therapy or chemo-photothermal therapy with the DOX-loaded MMSN/GQDs nanosystem exhibits a significant synergistic effect, resulting in a higher efficacy to kill cancer cells. Therefore, the MMSN/GQDs multifunctional platform has great potential in cancer therapy for enhancing the therapeutic efficiency. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Porcine malignant hyperthermia susceptibility: hypersensitive calcium-release mechanism of skeletal muscle sarcoplasmic reticulum.

    PubMed Central

    O'Brien, P J

    1986-01-01

    This study tested the hypothesis that calcium-release from sarcoplasmic reticulum isolated from malignant hyperthermia swine had abnormal concentration-dependency on release modulators. Halothane stimulated half-maximal calcium-release at similar concentrations for malignant hyperthermia and control sarcoplasmic reticulum (0.10 +/- 0.04 mM). However, concentrations causing half-maximal calcium-release were lower for malignant hyperthermia sarcoplasmic reticulum (P less than 0.001) by an order of magnitude for Ca2+ (28.1 +/- 8.3 versus 1.23 +/- 0.45 nM), adenosine triphosphate (0.33 +/- 0.09 versus 0.023 +/- 0.014 mM) and caffeine (7.79 +/- 1.56 versus 0.80 +/- 0.44 mM). Half-maximal inhibition by Mg2+ occurred at threefold higher concentrations for malignant hyperthermia sarcoplasmic reticulum (0.23 +/- 0.02 versus 0.78 +/- 0.17 mM). The Ca2+-sensitivity curves for calcium-release by sarcoplasmic reticulum isolated from heterozygotes for the malignant hyperthermia-defect were indistinguishable from the averages of the curves for controls and malignant hyperthermia-homozygotes. Results of this study suggest that malignant hyperthermia is initiated due to a hypersensitive calcium-release mechanism which is inherited in an autosomal, codominant pattern and may be diagnosed using calcium-release sensitivity-tests on isolated sarcoplasmic reticulum. Images Fig. 1. PMID:3742367

  18. Social factors modulate restraint stress induced hyperthermia in mice.

    PubMed

    Watanabe, Shigeru

    2015-10-22

    Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. On the temperature control in self-controlling hyperthermia therapy

    NASA Astrophysics Data System (ADS)

    Ebrahimi, Mahyar

    2016-10-01

    In self-controlling hyperthermia therapy, once the desired temperature is reached, the heat generation ceases and overheating is prevented. In order to design a system that generates sufficient heat without thermal ablation of surrounding healthy tissue, a good understanding of temperature distribution and its change with time is imperative. This study is conducted to extend our understanding about the heat generation and transfer, temperature distribution and temperature rise pattern in the tumor and surrounding tissue during self-controlling magnetic hyperthermia. A model consisting of two concentric spheres that represents the tumor and its surrounding tissue is considered and temperature change pattern and temperature distribution in tumor and surrounding tissue are studied. After describing the model and its governing equations and constants precisely, a typical numerical solution of the model is presented. Then it is showed that how different parameters like Curie temperature of nanoparticles, magnetic field amplitude and nanoparticles concentration can affect the temperature change pattern during self-controlling magnetic hyperthermia. The model system herein discussed can be useful to gain insight on the self-controlling magnetic hyperthermia while applied to cancer treatment in real scenario and can be useful for treatment strategy determination.

  20. Enhanced antitumor effect of curcumin liposomes with local hyperthermia in the LL/2 model.

    PubMed

    Tang, Jian-Cai; Shi, Hua-Shan; Wan, Li-Qiang; Wang, Yong-Sheng; Wei, Yu-Quan

    2013-01-01

    Curcumin previously was proven to inhibit angiogenesis and display potent antitumor activity in vivo and in vitro. In the present study, we investigated whether a combination curcumin with hyperthermia would have a synergistic antitumor effect in the LL/2 model. The results indicated that combination therapy significantly inhibited cell proliferation of MS-1 and LL/2 in vitro. LL/2 experiment model also demonstrated that the combination therapy inhibited tumor growth and prolonged the life span in vivo. Furthermore, combination therapy reduced angiogenesis and increased tumor apoptosis. Our findings suggest that the combination therapy exerted synergistic antitumor effects, providing a new perspective fpr clinical tumor therapy.

  1. Anisotropic Magnetic Nanostructures For Enhanced Hyperthermia

    NASA Astrophysics Data System (ADS)

    Torres, D.; Das, R.; Alonso, J.; Phan, M. H.; Srikanth, H.

    Magnetic nanoparticles assisted hyperthermia is one of the most promising techniques for cancer treatment. By the use of magnetic nanoparticles in an external AC magnetic field, one can target a specific tumor location and deliver toxic doses of heat to the tumor area without damaging the surrounding healthy tissue. Magnetite is typically used in biomedical applications due to its biocompatibility, but the heating efficiency of the commonly used magnetite nanoparticles is not enough to obtain the best results in cancer treatment. Therefore, novel magnetic nanostructures are required in order to improve the heating efficiency. Recently, it has been proposed by different groups that it is possible to increase the heating efficiency of the nanoparticles by tuning their effective anisotropy. Considering this, we have synthesized high aspect ratio magnetic nanorods with increased effective anisotropy. A thorough structural and magnetic characterization has revealed high crystallinity and optimal magnetic properties of these nanorods. The hyperthermia response shows that by increasing the aspect ratio from 5 to 11, their heating efficiency is increased by 150%. In addition, we have observed that a good alignment of the nanorods with the magnetic field ensures the best heating results. Hence, these nanorods appear to be promising candidates for cancer treatment with magnetic hyperthermia.

  2. Canine blood volume and cardiovascular function during hyperthermia.

    PubMed

    Miki, K; Morimoto, T; Nose, H; Itoh, T; Yamada, S

    1983-08-01

    The effect of acute hyperthermia on hemodynamic functions and blood volume regulation was examined on eight splenectomized dogs. Elevation of core body temperature by 2 degrees C over 90 min caused significant increase in cardiac output (11.2 +/- 12.5 ml X min-1 X kg-1 or about 10%) and significant decrease in total peripheral resistance (TPR; -1.3 +/- 1.0 mmHg X s X ml-1 or about 20%), whereas blood volume (BV), plasma oncotic pressure, and intravascular protein mass remained unchanged. Thus the raised core temperature caused peripheral vasodilation with decreased TPR and compensatory increase in cardiac output. Because BV remained unchanged during warming, mobilization of extravascular fluid did not occur; only the redistribution of blood to the vasodilated cutaneous circulation took place. To assess the effects of heat stress on transvascular fluid equilibrium, Ringer solution (10.7 ml X kg-1 X 10 min-1) was infused under normothermic and hyperthermic conditions. The volume of fluid retained within the intravascular space under equilibrium state was 33.5% in hyperthermia and 9.4% in normothermia. In hyperthermia, the transvascular fluid shift and urinary output were decreased both during and after infusion. The role of preferential fluid retention within the intravascular space observed during hyperthermia was discussed in relation to the mechanism to maintain cardiovascular function and BV under heat stress.

  3. Improved intratumoral nanoparticle extravasation and penetration by mild hyperthermia.

    PubMed

    Li, Li; ten Hagen, Timo L M; Bolkestein, Michiel; Gasselhuber, Astrid; Yatvin, Jeremy; van Rhoon, Gerard C; Eggermont, Alexander M M; Haemmerich, Dieter; Koning, Gerben A

    2013-04-28

    Accumulation of nanoparticles in solid tumors depends on their extravasation. However, vascular permeability is very heterogeneous within a tumor and among different tumor types, hampering efficient delivery. Local hyperthermia at a tumor can improve nanoparticle delivery by increasing tumor vasculature permeability, perfusion and interstitial fluid flow. The aim of this study is to investigate hyperthermia conditions required to improve tumor vasculature permeability, subsequent liposome extravasation and interstitial penetration in 4 tumor models. Tumors are implanted in dorsal skin flap window chambers and observed for liposome (~85 nm) accumulation by intravital confocal microscopy. Local hyperthermia at 41°C for 30 min initiates liposome extravasation through permeable tumor vasculature in all 4 tumor models. A further increase in nanoparticle extravasation occurs while continuing heating to 1h, which is a clinically relevant duration. After hyperthermia, the tumor vasculature remains permeable for 8h. We visualize gaps in the endothelial lining of up to 10 μm induced by HT. Liposomes extravasate through these gaps and penetrate into the interstitial space to at least 27.5 μm in radius from the vessel walls. Whole body optical imaging confirms HT induced extravasation while liposome extravasation was absent at normothermia. In conclusion, a thermal dose of 41°C for 1h is effective to induce long-lasting permeable tumor vasculature for liposome extravasation and interstitial penetration. These findings hold promise for improved intratumoral drug delivery upon application of local mild hyperthermia prior to administration of nanoparticle-based drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Inhalable magnetic nanoparticles for targeted hyperthermia in lung cancer therapy.

    PubMed

    Sadhukha, Tanmoy; Wiedmann, Timothy S; Panyam, Jayanth

    2013-07-01

    Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Hyperthermia and radiotherapy in the management of head and neck cancers: A systematic review and meta-analysis.

    PubMed

    Datta, Niloy R; Rogers, Susanne; Ordóñez, Silvia Gómez; Puric, Emsad; Bodis, Stephan

    2016-01-01

    A systematic review and meta-analysis was conducted to evaluate the outcome of controlled clinical trials in head and neck cancers (HNCs) using hyperthermia and radiotherapy versus radiotherapy alone. A total of 498 abstracts were screened from four databases and hand searched as per the PRISMA guidelines. Only two-arm studies treating HNCs with either radiotherapy alone, or hyperthermia and radiotherapy without concurrent chemotherapy or surgery were considered. The evaluated end point was complete response (CR). Following a detailed screening of the titles, abstracts and full text papers, six articles fulfilling the above eligibility criteria were considered. In total 451 clinical cases from six studies were included in the meta-analysis. Five of six trials were randomised. The overall CR with radiotherapy alone was 39.6% (92/232) and varied between 31.3% and 46.9% across the six trials. With thermoradiotherapy, the overall CR reported was 62.5% (137/219), (range 33.9-83.3%). The odds ratio was 2.92 (95% CI: 1.58-5.42, p = 0.001); the risk ratio was 1.61 (95% CI: 1.32-1.97, p < 0.0001) and the risk difference was 0.25 (95% CI: 0.12-0.39, p < 0.0001), all in favour of combined treatment with hyperthermia and radiotherapy over radiotherapy alone. Acute and late grade III/IV toxicities were reported to be similar in both the groups. Hyperthermia along with radiotherapy enhances the likelihood of CR in HNCs by around 25% compared to radiotherapy alone with no significant additional acute and late morbidities. This level I evidence should justify the integration of hyperthermia into the multimodality therapy of HNCs.

  6. Effect of intra-tumoral magnetic nanoparticle hyperthermia and viral nanoparticle immunogenicity on primary and metastatic cancer

    NASA Astrophysics Data System (ADS)

    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

  7. Optimized Hyperthermia Treatment of Prostate Cancer Using a Novel Intracavitary Ultrasound Array

    DTIC Science & Technology

    2006-01-01

    Overgaard J, Gonzalez GD, Hulshof MC, Arcangeli G, Dahl O, Mella O, et al. 1995. Randomised trial of hyperthermia as adjuvant to radiotherapy for...Gonzalez, G. D., Hulshof , M. C., Arcangeli, G., Dahl, O., Mella, O., and Bentzen, S. M., "Hyperthermia as an adjuvant to radiation therapy of recurrent or...25 pp. 79-85, 1993. 9. Overgaard, J., Gonzalez, G. D., Hulshof , M. C., Arcangeli, G., Dahl, O., Mella, O., and Bentzen, S. M.: Hyperthermia as an

  8. Magnetomotive Optical Coherence Elastography for Magnetic Hyperthermia Dosimetry Based on Dynamic Tissue Biomechanics

    PubMed Central

    Huang, Pin-Chieh; Pande, Paritosh; Ahmad, Adeel; Marjanovic, Marina; Spillman, Darold R.; Odintsov, Boris; Boppart, Stephen A.

    2016-01-01

    Magnetic nanoparticles (MNPs) have been used in many diagnostic and therapeutic biomedical applications over the past few decades to enhance imaging contrast, steer drugs to targets, and treat tumors via hyperthermia. Optical coherence tomography (OCT) is an optical biomedical imaging modality that relies on the detection of backscattered light to generate high-resolution cross-sectional images of biological tissue. MNPs have been utilized as imaging contrast and perturbative mechanical agents in OCT in techniques called magnetomotive OCT (MM-OCT) and magnetomotive elastography (MM-OCE), respectively. MNPs have also been independently used for magnetic hyperthermia treatments, enabling therapeutic functions such as killing tumor cells. It is well known that the localized tissue heating during hyperthermia treatments result in a change in the biomechanical properties of the tissue. Therefore, we propose a novel dosimetric technique for hyperthermia treatment based on the viscoelasticity change detected by MM-OCE, further enabling the theranostic function of MNPs. In this paper, we first review the basic principles and applications of MM-OCT, MM-OCE, and magnetic hyperthermia, and present new preliminary results supporting the concept of MM-OCE-based hyperthermia dosimetry. PMID:28163565

  9. Simultaneous hyperthermia and doxorubicin delivery from polymer-coated magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Iglesias, G. R.; Delgado, A. V.; González-Caballero, F.; Ramos-Tejada, M. M.

    2017-06-01

    In this work, the hyperthermia response, (i.e., heating induced by an externally applied alternating magnetic field) and the simultaneous release of an anti-cancer drug (doxorubicin) by polymer-coated magnetite nanoparticles have been investigated. After describing the setup for hyperthermia measurements in suspensions of magnetic nanoparticles, the hyperthermia (represented by the rate of suspension heating and, ultimately, by the specific absorption rate or SAR) of magnetite nanoparticles (both bare and polymer-coated as drug nanocarriers) is discussed. The effect of the applied ac magnetic field on doxorubicin release is also studied, and it is concluded that the field does not interfere with the release process, demonstrating the double functionality of the investigated particles.

  10. Iron oxide nanoparticles with controlled morphology for advanced hyperthermia

    NASA Astrophysics Data System (ADS)

    Nemati Porshokouh, Zohreh; Khurshid, Hafsa; Alonso Messa, Javier; Phan, Manh-Huong; Srikanth, Hariharan

    2015-03-01

    Magnetic nanoparticles (NPs) are interesting for a wide range of applications. In biomedicine, they have been exploited for use in drug delivery, magnetic resonance imaging, and magnetic hyperthermia. While magnetic hyperthermia, using NPs to convert electromagnetic energy into heat to destroy the cancer cells, represents a novel cancer treatment technique, a poor heating conversion efficiency of the existing NPs restricts its practical use. Different strategies have been proposed to overcome this limitation, mainly by tuning the size, saturation magnetization and effective anisotropy of the NPs. Here we report a magnetic hyperthermia study on Fe3O4 NPs, where the effective anisotropy was tuned by varying particle morphology from the spherical to octopod shape. The Fe3O4 NPs were synthesized using a thermal decomposition method. Transmission electron microscopy (TEM) and high-resolution TEM images show high crystalline monodisperse nanoparticles. X-ray diffraction patterns confirm the presence of Fe3O4 phase. Hyperthermia experiments indicate that the octopods possess a higher SAR as compared to their spherical counterpart. Our findings provide an effective approach to improve the SAR of NPs by manipulating the shape anisotropy of the nanoparticles. Research was supported by USAMRMC through Grant Numbers W81XWH-07-1-0708 and W81XWH1020101/3349.

  11. Ultrasonic phased array controller for hyperthermia applications.

    PubMed

    Benkeser, P J; Pao, T L; Yoon, Y J

    1991-01-01

    Multiple and mechanically scanned ultrasound transducer systems have demonstrated the efficacy of using ultrasound to produce deep localized hyperthermia. The use of ultrasonic phased arrays has been proposed as an alternative to these systems. A phased array offers a more flexible approach to heating tumours in that the size, shape, and position of its focal region can be altered during the course of treatment in order to achieve the desired temperature distribution. This added flexibility comes at the cost of increased complexity of the hardware necessary to drive the transducer because each element requires its own amplifer with both phase and amplitude control. In order for phased arrays with large numbers of elements to be feasible for hyperthermia applications, the complexity of this circuitry must be minimized. This paper describes a circuit design which simplifies the electronics required to control a phased array transducer system for hyperthermia applications. The design is capable of controlling virtually any type of phased array transducer operating at frequencies less than 2 MHz. The system performance was verified through beam profile measurements using a 48-element tapered phased array transducer.

  12. A review on hyperthermia via nanoparticle-mediated therapy.

    PubMed

    Sohail, Ayesha; Ahmad, Zaki; Bég, O Anwar; Arshad, Sarmad; Sherin, Lubna

    2017-05-01

    Hyperthermia treatment, generated by magnetic nanoparticles (MNPs) is promising since it is tumour-focused, minimally invasive and uniform. The most unique feature of magnetic nanoparticles is its reaction and modulation by a magnetic force basically responsible for enabling its potential as heating mediators for cancer therapy. In magnetic nanoparticle hyperthermia, a tumour is preferentially loaded with systemically administered nanoparticles with high-absorption cross-section for transduction of an extrinsic energy source to heat. To maximize the energy deposited in the tumour while limiting the exposure to healthy tissues, the heating is achieved by exposing the region of tissue containing magnetic nanoparticles to an alternating magnetic field. The magnetic nanoparticles dissipate heat from relaxation losses thereby heating localized tissue above normal physiological ranges. Besides thermal efficiency, the biocompatibility of magnetite nanoparticles assisted its deployment as efficient drug carrier for targeted therapeutic regimes. In the present article, we provide a state-of-the-art review focused on progress in nanoparticle induced hyperthermia treatments that have several potential advantages over both global and local hyperthermia treatments achieved without nanoparticles. Green bio-nanotechnology has attracted substantial attention and has demonstrable abilities to improve cancer therapy. Furthermore, we have listed the challenges associated with this treatment along with future prospective that could attract the interest of biomedical engineers, biomaterials scientists, medical researchers and pharmacological research groups. Copyright © 2017 Société Française du Cancer. All rights reserved.

  13. Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles.

    PubMed

    Wang, Lufang; Dong, Jian; Ouyang, Weiwei; Wang, Xiaowen; Tang, Jintian

    2012-03-01

    We investigated the effect and feasibility of hyperthermia treatment on subcutaneous pancreatic cancer in female Kunming mice, using a murine pancreatic cancer cell line (MPC-83) established by us and found in this study to originate from epithelial pancreatic acinus. Magnetic fluid (MF) with ferromagnetic particles of about 20 nm in size was used as a heating mediator. MF was injected into the subcutaneous nodules with subaxillary regions of mice 10 days after tumor transplantation; homogeneous distribution of magnetic nanoparticles in nodules was easily detected by X-ray 24 h later. Mice were allocated to four groups as follows: no treatment (control); MF injection alone; alternating magnetic field (AMF) irradiation alone; and MF injection and hyperthermia generated by applying AMF (300 kHz, 110 Gs). The two hyperthermia-treated subgroup tumors reached central temperatures of 47 and 51˚C, respectively, for 30 min; while rectal temperature in both subgroups remained below 36˚C. Tumor growth was inhibited and survival significantly prolonged in the hyperthermia group compared with other groups (P<0.05). Tumor cells near the MF in the hyperthermia group apoptosed or necrosed immediately after hyperthermia. By day 14, there were no subcutaneous nodules; and residual magnetic nanoparticles were ingested by phagocytes. Nuclear proliferating cell nuclear antigen (PCNA) decreased in hyperthermia group tumor cells compared to the other groups; cytoplasmic heat shock protein 70 (HSP 70) was conspicuously higher immediately after hyperthermia (P<0.05). This technique had therapeutic potential and provided a new idea in the treatment of pancreatic cancer.

  14. Phencyclidine-induced malignant hyperthermia causing submassive liver necrosis.

    PubMed

    Armen, R; Kanel, G; Reynolds, T

    1984-07-01

    This report describes three male patients arrested for aggressive and combative behavior, characteristic of phencyclidine intoxication, in whom severe hyperthermia, respiratory failure, and coma developed. Two days after the malignant hyperthermic event, serum transaminase levels rose acutely to extremely high levels with concomitant elevations in bilirubin levels and a fall in prothrombin activity. Liver biopsy specimens in two patients showed marked perivenular necrosis and collapse. No specific treatment was directed at the phencyclidine intoxication. Two of the three patients survived. Submassive liver necrosis caused by malignant hyperthermia is an unusual complication of phencyclidine abuse.

  15. Biocompatibility and therapeutic evaluation of magnetic liposomes designed for self-controlled cancer hyperthermia and chemotherapy.

    PubMed

    Gogoi, Manashjit; Jaiswal, Manish K; Sarma, Haladhar Dev; Bahadur, Dhirendra; Banerjee, Rinti

    2017-06-19

    Magnetic liposome-mediated combined chemotherapy and hyperthermia is gaining importance as an effective therapeutic modality for cancer. However, control and maintenance of optimum hyperthermia are major challenges in clinical settings due to the overheating of tissues. To overcome this problem, we developed a novel magnetic liposomes formulation co-entrapping a dextran coated biphasic suspension of La 0.75 Sr 0.25 MnO 3 (LSMO) and iron oxide (Fe 3 O 4 ) nanoparticles for self-controlled hyperthermia and chemotherapy. However, the general apprehension about biocompatibility and safety of the newly developed formulation needs to be addressed. In this work, in vitro and in vivo biocompatibility and therapeutic evaluation studies of the novel magnetic liposomes are reported. Biocompatibility study of the magnetic liposomes formulation was carried out to evaluate the signs of preliminary systemic toxicity, if any, following intravenous administration of the magnetic liposomes in Swiss mice. Therapeutic efficacy of the magnetic liposomes formulation was evaluated in the fibrosarcoma tumour bearing mouse model. Fibrosarcoma tumour-bearing mice were subjected to hyperthermia following intratumoral injection of single or double doses of the magnetic liposomes with or without chemotherapeutic drug paclitaxel. Hyperthermia (three spurts, each at 3 days interval) with drug loaded magnetic liposomes following single dose administration reduced the growth of tumours by 2.5 fold (mean tumour volume 2356 ± 550 mm 3 ) whereas the double dose treatment reduced the tumour growth by 3.6 fold (mean tumour volume 1045 ± 440 mm 3 ) compared to their corresponding control (mean tumour volume 3782 ± 515 mm 3 ). At the end of the tumour efficacy studies, the presence of MNPs was studied in the remnant tumour tissues and vital organs of the mice. No significant leaching or drainage of the magnetic liposomes during the study was observed from the tumour site to the other vital organs of

  16. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    PubMed

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

  17. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction

    PubMed Central

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results. PMID:26105141

  18. Preparation of magnetic mesoporous silica nanoparticles as a multifunctional platform for potential drug delivery and hyperthermia

    NASA Astrophysics Data System (ADS)

    Yu, Xia; Zhu, Yufang

    2016-01-01

    We report the preparation of magnetic mesoporous silica (MMS) nanoparticles with the potential multifunctionality of drug delivery and magnetic hyperthermia. Carbon-encapsulated magnetic colloidal nanoparticles (MCN@C) were used to coat mesoporous silica shells for the formation of the core-shell structured MMS nanoparticles (MCN@C/mSiO2), and the rattle-type structured MMS nanoparticles (MCN/mSiO2) were obtained after the removal of the carbon layers from MCN@C/mSiO2 nanoparticles. The morphology, structure, magnetic hyperthermia ability, drug release behavior, in vitro cytotoxicity and cellular uptake of MMS nanoparticles were investigated. The results revealed that the MCN@C/mSiO2 and MCN/mSiO2 nanoparticles had spherical morphology and average particle sizes of 390 and 320 nm, respectively. The MCN@C/mSiO2 nanoparticles exhibited higher magnetic hyperthermia ability compared to the MCN/mSiO2 nanoparticles, but the MCN/mSiO2 nanoparticles had higher drug loading capacity. Both MCN@C/mSiO2 and MCN/mSiO2 nanoparticles had similar drug release behavior with pH-controlled release and temperature-accelerated release. Furthermore, the MCN@C/mSiO2 and MCN/mSiO2 nanoparticles showed low cytotoxicity and could be internalized into HeLa cells. Therefore, the MCN@C/mSiO2 and MCN/mSiO2 nanoparticles would be promising for the combination of drug delivery and magnetic hyperthermia treatment in cancer therapy.

  19. Preparation of magnetic mesoporous silica nanoparticles as a multifunctional platform for potential drug delivery and hyperthermia.

    PubMed

    Yu, Xia; Zhu, Yufang

    2016-01-01

    We report the preparation of magnetic mesoporous silica (MMS) nanoparticles with the potential multifunctionality of drug delivery and magnetic hyperthermia. Carbon-encapsulated magnetic colloidal nanoparticles (MCN@C) were used to coat mesoporous silica shells for the formation of the core-shell structured MMS nanoparticles (MCN@C/mSiO 2 ), and the rattle-type structured MMS nanoparticles (MCN/mSiO 2 ) were obtained after the removal of the carbon layers from MCN@C/mSiO 2 nanoparticles. The morphology, structure, magnetic hyperthermia ability, drug release behavior, in vitro cytotoxicity and cellular uptake of MMS nanoparticles were investigated. The results revealed that the MCN@C/mSiO 2 and MCN/mSiO 2 nanoparticles had spherical morphology and average particle sizes of 390 and 320 nm, respectively. The MCN@C/mSiO 2 nanoparticles exhibited higher magnetic hyperthermia ability compared to the MCN/mSiO 2 nanoparticles, but the MCN/mSiO 2 nanoparticles had higher drug loading capacity. Both MCN@C/mSiO 2 and MCN/mSiO 2 nanoparticles had similar drug release behavior with pH-controlled release and temperature-accelerated release. Furthermore, the MCN@C/mSiO 2 and MCN/mSiO 2 nanoparticles showed low cytotoxicity and could be internalized into HeLa cells. Therefore, the MCN@C/mSiO 2 and MCN/mSiO 2 nanoparticles would be promising for the combination of drug delivery and magnetic hyperthermia treatment in cancer therapy.

  20. Thermosensitive Nanostructured Media for imaging and Hyperthermia Cancer Treatment

    NASA Astrophysics Data System (ADS)

    Martirosyan, Karen

    2011-03-01

    Hyperthermia has been used for many years to treat a wide variety of tumors in patients. The most commonly applied method of hyperthermia is capacitive heating by using microwave. Magnetic fluids based on iron oxide (Fe3O4), stabilized by biocompatible surfactants are typically used as heating agent. However, significant limitations of using commercial available magnetic particles are non-selectivity and overheating of surrounding normal tissues. To improve the efficacy of hyperthermia treatment we intend to develop Curie temperature (Tc)-tuned nanostructured media having T2 relaxation response on MRI for selective and self-controlled hyperthermia cancer treatment. As an active part of this media we fabricated superparamagnetic, biocompatible and dextran coated ferrite nanoparticles Mg1+xTixFe2(1-x)O4 at 0.3 x < 0.5 with low Curie temperature. To tune Tc we produced a large number of ferrites powders with x = 0.05 by aqueous combustion synthesis. This process typically involves a reaction in a solution containing metal nitrates and different fuels, which are classified based on the type of reactive groups (e.g., amino, hydroxyl, carboxyl) connected to a hydrocarbon chain, such as glycine, hydrazine, or urea. Our experiments revealed that ferrite with formula Mg1.35Ti0.35Fe1.3O4 appears with Curie temperature within 46-50rC. NSF, grant # 0933140.

  1. Feasibility of A-mode ultrasound attenuation as a monitoring method of local hyperthermia treatment.

    PubMed

    Manaf, Noraida Abd; Aziz, Maizatul Nadwa Che; Ridzuan, Dzulfadhli Saffuan; Mohamad Salim, Maheza Irna; Wahab, Asnida Abd; Lai, Khin Wee; Hum, Yan Chai

    2016-06-01

    Recently, there is an increasing interest in the use of local hyperthermia treatment for a variety of clinical applications. The desired therapeutic outcome in local hyperthermia treatment is achieved by raising the local temperature to surpass the tissue coagulation threshold, resulting in tissue necrosis. In oncology, local hyperthermia is used as an effective way to destroy cancerous tissues and is said to have the potential to replace conventional treatment regime like surgery, chemotherapy or radiotherapy. However, the inability to closely monitor temperature elevations from hyperthermia treatment in real time with high accuracy continues to limit its clinical applicability. Local hyperthermia treatment requires real-time monitoring system to observe the progression of the destroyed tissue during and after the treatment. Ultrasound is one of the modalities that have great potential for local hyperthermia monitoring, as it is non-ionizing, convenient and has relatively simple signal processing requirement compared to magnetic resonance imaging and computed tomography. In a two-dimensional ultrasound imaging system, changes in tissue microstructure during local hyperthermia treatment are observed in terms of pixel value analysis extracted from the ultrasound image itself. Although 2D ultrasound has shown to be the most widely used system for monitoring hyperthermia in ultrasound imaging family, 1D ultrasound on the other hand could offer a real-time monitoring and the method enables quantitative measurement to be conducted faster and with simpler measurement instrument. Therefore, this paper proposes a new local hyperthermia monitoring method that is based on one-dimensional ultrasound. Specifically, the study investigates the effect of ultrasound attenuation in normal and pathological breast tissue when the temperature in tissue is varied between 37 and 65 °C during local hyperthermia treatment. Besides that, the total protein content measurement was also

  2. Clinical applications of magnetic nanoparticles for hyperthermia.

    PubMed

    Thiesen, Burghard; Jordan, Andreas

    2008-09-01

    Magnetic fluids are increasingly used for clinical applications such as drug delivery, magnetic resonance imaging and magnetic fluid hyperthermia. The latter technique that has been developed as a cancer treatment for several decades comprises the injection of magnetic nanoparticles into tumors and their subsequent heating in an alternating magnetic field. Depending on the applied temperature and the duration of heating this treatment either results in direct tumor cell killing or makes the cells more susceptible to concomitant radio- or chemotherapy. Numerous groups are working in this field worldwide, but only one approach has been tested in clinical trials so far. Here, we summarize the clinical data gained in these studies on magnetic fluid induced hyperthermia.

  3. nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but not hyperthermia in mice.

    PubMed

    Itzhak, Y; Martin, J L; Ail, S F

    2000-09-11

    Methamphetamine (METH)-induced dopaminergic neurotoxicity is associated with hyperthermia. We investigated the effect of several neuronal nitric oxide synthase (nNOS) inhibitors on METH-induced hyperthermia and striatal dopaminergic neurotoxicity. Administration of METH (5 mg/kg; q. 3 h x 3) to Swiss Webster mice produced marked hyperthermia and 50-60% depletion of striatal dopaminergic markers 72 h after METH administration. Pretreatment with the nNOS inhibitors S-methylthiocitrulline (SMTC; 10 mg/kg) or 3-bromo-7-nitroindazole (3-Br-7-NI; 20 mg/kg) before each METH injection did not affect the persistent hyperthermia produced by METH, but afforded protection against the depletion of dopaminergic markers. A low dose (25 mg/kg) of the nNOS inhibitor 7-nitroindazole (7-NI) did not affect METH-induced hyperthermia, but a high dose (50 mg/kg) produced significant hypothermia. These findings indicate that low dose of selective nNOS inhibitors protect against METH-induced neurotoxicity with no effect on body temperature and support the hypothesis that nitric oxide (NO) and peroxynitrite have a major role in METH-induced dopaminergic neurotoxicity.

  4. Monitoring nanoparticle-mediated cellular hyperthermia with a high-sensitivity biosensor

    PubMed Central

    Mukherjee, Amarnath; Castanares, Mark; Hedayati, Mohammad; Wabler, Michele; Trock, Bruce; Kulkarni, Prakash; Rodriguez, Ronald; Getzenberg, Robert H; DeWeese, Theodore L; Ivkov, Robert; Lupold, Shawn E

    2014-01-01

    Aim To develop and apply a heat-responsive and secreted reporter assay for comparing cellular response to nanoparticle (NP)- and macroscopic-mediated sublethal hyperthermia. Materials & methods Reporter cells were heated by water bath (macroscopic heating) or iron oxide NPs activated by alternating magnetic fields (nanoscopic heating). Cellular responses to these thermal stresses were measured in the conditioned media by secreted luciferase assay. Results & conclusion Reporter activity was responsive to macroscopic and nanoparticle heating and activity correlated with measured macroscopic thermal dose. Significant cellular responses were observed with NP heating under doses that were insufficient to measurably change the temperature of the system. Under these conditions, the reporter response correlated with proximity to cells loaded with heated nanoparticles. These results suggest that NP and macroscopic hyperthermia may be distinctive under conditions of mild hyperthermia. PMID:24547783

  5. Pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia.

    PubMed

    Beam, Teresa A; Loudermilk, Emily F; Kisor, David F

    2017-02-01

    A review of the pharmacogenetics (PGt) and pathophysiology of calcium voltage-gated channel subunit alpha1 S (CACNA1S) mutations in malignant hyperthermia susceptibility type 5 (MHS5; MIM #60188) is presented. Malignant hyperthermia (MH) is a life-threatening hypermetabolic state of skeletal muscle usually induced by volatile, halogenated anesthetics and/or the depolarizing neuromuscular blocker succinylcholine. In addition to ryanodine receptor 1 (RYR1) mutations, several CACNA1S mutations are known to be risk factors for increased susceptibility to MH (MHS). However, the presence of these pathogenic CACNA1S gene variations cannot be used to positively predict MH since the condition is genetically heterogeneous with variable expression and incomplete penetrance. At present, one or at most six CACNA1S mutations display significant linkage or association either to clinically diagnosed MH or to MHS as determined by contracture testing. Additional pathogenic variants in CACNA1S, either alone or in combination with genes affecting Ca 2+ homeostasis, are likely to be discovered in association to MH as whole exome sequencing becomes more commonplace. Copyright © 2017 the American Physiological Society.

  6. Inflammation, edema and poor outcome are associated with hyperthermia in hypertensive intracerebral hemorrhages.

    PubMed

    Iglesias-Rey, Ramón; Rodríguez-Yáñez, Manuel; Arias, Susana; Santamaría, María; Rodríguez-Castro, Emilio; López-Dequidt, Iria; Hervella, Pablo; Sobrino, Tomás; Campos, Francisco; Castillo, José

    2018-05-11

    The deleterious effect of hyperthermia on intracerebral hemorrhage (ICH) has been studied, however the results are not completely conclusive and new studies are needed to elucidate clinical factors that condition the poor outcome. The aim of this study was to identify the clinical factors (including ICH etiology) that influence the poor outcome associated with hyperthermia on ICH. We additionally tried to identify potential mechanisms involved in hyperthermia during ICH. From a prospective registry, we conducted a retrospective study enrolling non-traumatic ICH patients. We used logistic regression models to analyze the influence of hyperthermia in relation to different inflammatory and endothelial dysfunction markers, hematoma growth and edema volume in hypertensive and non-hypertensive ICH patients. We included 887 ICH patients: 433 hypertensive, 50 amyloid, 117 by anticoagulants and 287 by other causes. Patients with hypertensive ICH showed the higher body temperature (37.5±0.8°C) as well as the maximum increase in temperature (0.9±0.1°C) within the first 24 hours. ICH patients with hypertensive etiologic origin, who presented hyperthermia, showed a 5.3 fold-higher risk to have poor outcome at 3 months. We found a positive relationship (r=0.717, P<0.0001) between edema volume and hyperthermia during the first 24 hours but only in ICH patients with hypertensive etiologic origin, and this relationship seems to be mediated by inflammatory markers. Our data suggest that hyperthermia, together with inflammation and edema is associated with poor outcome only in ICH from hypertensive etiology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Intra-Abdominal Hypertension and Abdominal Compartment Syndrome after Abdominal Wall Reconstruction: Quaternary Syndromes?

    PubMed

    Kirkpatrick, A W; Nickerson, D; Roberts, D J; Rosen, M J; McBeth, P B; Petro, C C; Berrevoet, Frederik; Sugrue, M; Xiao, Jimmy; Ball, C G

    2017-06-01

    Reconstruction with reconstitution of the container function of the abdominal compartment is increasingly being performed in patients with massive ventral hernia previously deemed inoperable. This situation places patients at great risk of severe intra-abdominal hypertension and abdominal compartment syndrome if organ failure ensues. Intra-abdominal hypertension and especially abdominal compartment syndrome may be devastating systemic complications with systematic and progressive organ failure and death. We thus reviewed the pathophysiology and reported clinical experiences with abnormalities of intra-abdominal pressure in the context of abdominal wall reconstruction. Bibliographic databases (1950-2015), websites, textbooks, and the bibliographies of previously recovered articles for reports or data relating to intra-abdominal pressure, intra-abdominal hypertension, and the abdominal compartment syndrome in relation to ventral, incisional, or abdominal hernia repair or abdominal wall reconstruction. Surgeons should thus consider and carefully measure intra-abdominal pressure and its resultant effects on respiratory parameters and function during abdominal wall reconstruction. The intra-abdominal pressure post-operatively will be a result of the new intra-peritoneal volume and the abdominal wall compliance. Strategies surgeons may utilize to ameliorate intra-abdominal pressure rise after abdominal wall reconstruction including temporizing paralysis of the musculature either temporarily or semi-permanently, pre-operative progressive pneumoperitoneum, permanently removing visceral contents, or surgically releasing the musculature to increase the abdominal container volume. In patients without complicating shock and inflammation, and in whom the abdominal wall anatomy has been so functionally adapted to maximize compliance, intra-abdominal hypertension may be transient and tolerable. Intra-abdominal hypertension/abdominal compartment syndrome in the specific setting of

  8. THREE-DIMENSIONAL MODEL FOR HYPERTHERMIA CALCULATIONS

    EPA Science Inventory

    Realistic three-dimensional models that predict temperature distributions with a high degree of spatial resolution in bodies exposed to electromagnetic (EM) fields are required in the application of hyperthermia for cancer treatment. To ascertain the thermophysiologic response of...

  9. Implantable chemothermal brachytherapy seeds: A synergistic approach to brachytherapy using polymeric dual drug delivery and hyperthermia for malignant solid tumor ablation.

    PubMed

    Aguilar, Ludwig Erik; Thomas, Reju George; Moon, Myeong Ju; Jeong, Yong Yeon; Park, Chan Hee; Kim, Cheol Sang

    2018-08-01

    Chemothermal brachytherapy seeds have been developed using a combination of polymeric dual drug chemotherapy and alternating magnetic field induced hyperthermia. The synergistic effect of chemotherapy and hyperthermia brachytherapy has been investigated in a way that has never been performed before, with an in-depth analysis of the cancer cell inhibition property of the new system. A comprehensive in vivo study on athymic mice model with SCC7 tumor has been conducted to determine optimal arrays and specifications of the chemothermal seeds. Dual drug chemotherapy has been achieved via surface deposition of polydopamine that carries bortezomib, and also via loading an acidic pH soluble hydrogel that contains 5-Fluorouracil inside the chemothermal seed; this increases the drug loading capacity of the chemothermal seed, and creates dual drug synergism. An external alternating magnetic field has been utilized to induce hyperthermia conditions, using the inherent ferromagnetic property of the nitinol alloy used as the seed casing. The materials used in this study were fully characterized using FESEM, H 1 NMR, FT-IR, and XPS to validate their properties. This new approach to experimental cancer treatment is a pilot study that exhibits the potential of thermal brachytherapy and chemotherapy as a combined treatment modality. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. [Posttraumatic retroperitoneal hematoma in injured persons with severe closed multiple and combined abdominal trauma].

    PubMed

    Rylov, A I; Kravets, N S

    2001-01-01

    The experience of treatment of 69 injured persons with posttraumatic retroperitoneal hematoma suffering severe multiple combined abdominal trauma was analyzed. Application of the classification proposed permits to formulate diagnosis and to choose the tactic of treatment correctly. The intraoperative tactics algorithm was elaborated. It promotes the correct analysis of intraoperative findings and reduction of the diagnostic mistakes frequency as well. In the presence of vast defect, making impossible to suture over the parietal peritoneum, extraperitonization using cerebral dura mater was done. Operative intervention was concluded by drainage with subsequent laserotherapy.

  11. The Dartmouth Center for Cancer Nanotechnology Excellence: magnetic hyperthermia.

    PubMed

    Baker, Ian; Fiering, Steve N; Griswold, Karl E; Hoopes, P Jack; Kekalo, Katerina; Ndong, Christian; Paulsen, Keith; Petryk, Alicea A; Pogue, Brian; Shubitidze, Fridon; Weaver, John

    2015-01-01

    The Dartmouth Center for Cancer Nanotechnology Excellence - one of nine funded by the National Cancer Institute as part of the Alliance for Nanotechnology in Cancer - focuses on the use of magnetic nanoparticles for cancer diagnostics and hyperthermia therapy. It brings together a diverse team of engineers and biomedical researchers with expertise in nanomaterials, molecular targeting, advanced biomedical imaging and translational in vivo studies. The goal of successfully treating cancer is being approached by developing nanoparticles, conjugating them with Fabs, hyperthermia treatment, immunotherapy and sensing treatment response.

  12. Regional hyperthermia in conjunction with definitive radiotherapy against recurrent or locally advanced prostate cancer T3 pN0 M0.

    PubMed

    Tilly, Wolfgang; Gellermann, Johanna; Graf, Reinhold; Hildebrandt, Bert; Weissbach, Lothar; Budach, Volker; Felix, Roland; Wust, Peter

    2005-01-01

    Since long-term results of the standard treatment of locally advanced or recurrent prostatic carcinoma are unsatisfactory, the role for additional regional hyperthermia was evaluated in a phase I/II study. From 08/1996 to 03/2000, 22 patients were treated by a standard irradiation regimen (68.4 Gy) in combination with regional hyperthermia (weekly, five to six times), and five of 22 patients received short-term (neoadjuvant) hormonal treatment. Of these, 15 patients had primary prostatic carcinoma T3 pN0 M0 and seven a histologically confirmed local recurrence after radical prostatectomy. Feasibility of hyperthermia, and acute/late toxicity as well as long-term follow-up (prostate- specific antigen [PSA] control, overall survival) were analyzed. Clinical endpoints were correlated with thermal parameters. Mean maximum temperatures along the urethra of 41.4 degrees C (41.0 degrees C for the recurrences), and mean T(90) values of 40.7 degrees C could be achieved. Severe acute toxicity of grade 3 occurred at the rectum in three, at the urethra in four, at the intestine in one, and a burn induced by hyperthermia in one of 22 patients. Late toxicity was only observed rectally in one patient (grade 3) and at the urethra in two patients (grade 2). There was no correlation between thermal parameters and any toxicity. The survival curves showed a PSA control for primary prostatic carcinoma > 50% after 6 years, but no long-term PSA control for the recurrences. Overall survival after 6 years was 95% for primary carcinoma, and 60% for the recurrences. There was a clear correlation between higher temperatures or thermal doses with long-term PSA control. Regional hyperthermia might be a low-toxicity approach to increase PSA control of common treatment schedules. Further evaluation, in particular employing improved hyperthermia technology, is worthwhile.

  13. Predicting thermal history a-priori for magnetic nanoparticle hyperthermia of internal carcinoma

    NASA Astrophysics Data System (ADS)

    Dhar, Purbarun; Sirisha Maganti, Lakshmi

    2017-08-01

    This article proposes a simplistic and realistic method where a direct analytical expression can be derived for the temperature field within a tumour during magnetic nanoparticle hyperthermia. The approximated analytical expression for thermal history within the tumour is derived based on the lumped capacitance approach and considers all therapy protocols and parameters. The present method is simplistic and provides an easy framework for estimating hyperthermia protocol parameters promptly. The model has been validated with respect to several experimental reports on animal models such as mice/rabbit/hamster and human clinical trials. It has been observed that the model is able to accurately estimate the thermal history within the carcinoma during the hyperthermia therapy. The present approach may find implications in a-priori estimation of the thermal history in internal tumours for optimizing magnetic hyperthermia treatment protocols with respect to the ablation time, tumour size, magnetic drug concentration, field strength, field frequency, nanoparticle material and size, tumour location, and so on.

  14. The effects of combined liquid and membrane barriers in prevention of post-operative intra-abdominal adhesions after experimental jejunal anastomosis in dogs.

    PubMed

    el-Ghoul, W

    2005-01-01

    The study was carried out on 40 apparently clinical healthy dogs classified into 5 groups of 8 dogs each. Adhesion was experimentally induced by transsection and reanastomosis of jejunum. In the control group the site of anastomosis and abdominal cavity was lavaged with 250 ml saline solution. In group two lavage was done with 250 ml of a liquid barrier composed of a combination of high molecular weight solution (1% sodium carboxymethylcellulose) as a carrier, non-steroidal anti-inflammatory drug (Piroxecam), broad spectrum antibiotic (Cephalosporin), anticoagulant (Heparin) and antioxidant (0.5% methylene blue). In group three the anastomosis site was covered with a sodium hyalouronate/carboxymethylcellulose bioresorbable membrane (Seprafilm). In group four a natural biocompatible collagen sheet (VET BIO SIS T) was applied on the anastomosis site. In group five the abdominal cavity was lavaged with 250 ml liquid barrier and the anastomosis site was covered by either Seprafilm membrane or VET BIO SIS T sheet. At the fourteen day after operation, adhesion was assessed by ultrasonography after instillation of 1000 ml of physiological saline solution into the abdominal cavity. The dogs were sacrificed and an autopsy examination was carried out with the attention to the number, density and site of the adhesion formation. The results revealed that all the control dogs and some dogs in the treatment groups had positive ultrasonographic findings. Transabdominal sonogram clearly showed echogenic bands floating in the abdominal cavity and echogenic masses in more serious subjects. Necropsy examination showed that all the control dogs had intra-abdominal adhesions (8 of 8 dogs) and treatment with liquid barrier (4 of 8 dogs), seprafilm membrane barrier (3 of 8 dogs), VET BIO SIS T sheet barrier (4 of 8 dogs) and combination of fluid and membrane barrier groups (4 of 8 dogs) significantly (p < 0.05) reduced the incidence of adhesion formation. The adhesion severity in the

  15. Induction of cytogenetic damage in human lymphocytes in vitro and of antineoplastic effects in Ehrlich ascites tumor cells in vivo treated by methotrexate, hyperthermia and/or caffeine.

    PubMed

    Maskaleris, T; Lialiaris, T; Triantaphyllidis, C

    1998-12-03

    The synergistic effect of methotrexate (at concentrations between 3. 1 and 100 nM) and its combinations with caffeine (618 microM) and/or hyperthermia (42 degreesC for 2 h) on the frequency of sister chromatid exchanges (SCEs), the proliferating rate index and the mitotic index in cultured human lymphocytes, was examined. Also, the in vivo antineoplastic effects of methotrexate (at a concentration of 0.45 microg/g body weight) and its combination with caffeine (120 microg/g body weight), both on the survival time and the increase of the weight of tumor of BALB/c mice inoculated with Ehrlich ascites tumor cells was examined in the present study. The results indicated that: (a) the triple combination of methotrexate, caffeine and hyperthermia synergistically increased the levels of SCEs and exerted cytostatic and cytotoxic action and (b) the combination of methotrexate and caffeine significantly increased the survival span of the mice inoculated with Ehrlich ascites tumor cells and reduced the increase of the weight of their tumors at rates higher than in the case of methotrexate by itself. It is suggested that the above triple combination (methotrexate plus caffeine plus hyperthermia) could achieve increased effectiveness of methotrexate, better therapy results, and could be successfully applied in the treatment of various types of cancer. Copyright 1998 Elsevier Science B.V.

  16. Abdominal wall reconstruction using a combination of free tensor fasciae lata and anterolateral thigh myocutaneous flap: a prospective study in 16 patients.

    PubMed

    Lv, Yang; Cao, Dongsheng; Guo, Fangfang; Qian, Yunliang; Wang, Chen; Wang, Danru

    2015-08-01

    Reconstruction of the abdominal wall continues to be a challenging problem for plastic surgeons. Transposition of well-vascularized flap tissue is the most effective way to repair composite abdominal wall defects. We retrospectively reviewed the treatment of such patients and assessed the reconstructive technique using combination of an inlay of bioprosthetic materials and a united thigh flap. A retrospective review of patients' records in the department was carried out. In total, 16 patients who underwent immediate abdominal wall reconstruction between 2000 and 2013 were identified. Patients' health status, defect sizes, and surgical technique were obtained from medical charts. The immediate reconstruction surgery of the abdominal wall was successful in all patients. One patient with dermatofibrosarcoma protuberans experienced recurrences at the former site. One patient died because of liver metastases at 21 months after surgery. No incisional hernia or infection in this series of patients was observed. Full-thickness, giant defects of the complicated abdominal wall can be repaired successfully with relatively minor complications using this reconstructive technique. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. A Newborn With Abdominal Pain.

    PubMed

    Alwan, Riham; Drake, Meredith; Gurria Juarez, Juan; Emery, Kathleen H; Shaaban, Aimen F; Szabo, Sara; Sobolewski, Brad

    2017-11-01

    A previously healthy 3-week-old boy presented with 5 hours of marked fussiness, abdominal distention, and poor feeding. He was afebrile and well perfused. His examination was remarkable for localized abdominal tenderness and distention. He was referred to the emergency department in which an abdominal radiograph revealed gaseous distention of the bowel with a paucity of gas in the pelvis. Complete blood cell count and urinalysis were unremarkable. His ongoing fussiness and abnormal physical examination prompted consultation with surgery and radiology. Our combined efforts ultimately established an unexpected diagnosis. Copyright © 2017 by the American Academy of Pediatrics.

  18. Barium titanate core--gold shell nanoparticles for hyperthermia treatments.

    PubMed

    FarrokhTakin, Elmira; Ciofani, Gianni; Puleo, Gian Luigi; de Vito, Giuseppe; Filippeschi, Carlo; Mazzolai, Barbara; Piazza, Vincenzo; Mattoli, Virgilio

    2013-01-01

    The development of new tools and devices to aid in treating cancer is a hot topic in biomedical research. The practice of using heat (hyperthermia) to treat cancerous lesions has a long history dating back to ancient Greece. With deeper knowledge of the factors that cause cancer and the transmissive window of cells and tissues in the near-infrared region of the electromagnetic spectrum, hyperthermia applications have been able to incorporate the use of lasers. Photothermal therapy has been introduced as a selective and noninvasive treatment for cancer, in which exogenous photothermal agents are exploited to achieve the selective destruction of cancer cells. In this manuscript, we propose applications of barium titanate core-gold shell nanoparticles for hyperthermia treatment against cancer cells. We explored the effect of increasing concentrations of these nanoshells (0-100 μg/mL) on human neuroblastoma SH-SY5Y cells, testing the internalization and intrinsic toxicity and validating the hyperthermic functionality of the particles through near infrared (NIR) laser-induced thermoablation experiments. No significant changes were observed in cell viability up to nanoparticle concentrations of 50 μg/mL. Experiments upon stimulation with an NIR laser revealed the ability of the nanoshells to destroy human neuroblastoma cells. On the basis of these findings, barium titanate core-gold shell nanoparticles resulted in being suitable for hyperthermia treatment, and our results represent a promising first step for subsequent investigations on their applicability in clinical practice.

  19. Real-Time Analysis of Magnetic Hyperthermia Experiments on Living Cells under a Confocal Microscope.

    PubMed

    Connord, Vincent; Clerc, Pascal; Hallali, Nicolas; El Hajj Diab, Darine; Fourmy, Daniel; Gigoux, Véronique; Carrey, Julian

    2015-05-01

    Combining high-frequency alternating magnetic fields (AMF) and magnetic nanoparticles (MNPs) is an efficient way to induce biological responses through several approaches: magnetic hyperthermia, drug release, controls of gene expression and neurons, or activation of chemical reactions. So far, these experiments cannot be analyzed in real-time during the AMF application. A miniaturized electromagnet fitting under a confocal microscope is built, which produces an AMF of frequency and amplitude similar to the ones used in magnetic hyperthermia. AMF application induces massive damages to tumoral cells having incorporated nanoparticles into their lysosomes without affecting the others. Using this setup, real-time analyses of molecular events occurring during AMF application are performed. Lysosome membrane permeabilization and reactive oxygen species production are detected after only 30 min of AMF application, demonstrating they occur at an early stage in the cascade of events leading eventually to cell death. Additionally, lysosomes self-assembling into needle-shaped organization under the influence of AMF is observed in real-time. This experimental approach will permit to get a deeper insight into the physical, molecular, and biological process occurring in several innovative techniques used in nanomedecine based on the combined use of MNPs and high-frequency magnetic fields. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study

    PubMed Central

    GADALETA-CALDAROLA, GENNARO; INFUSINO, STEFANIA; GALISE, IDA; RANIERI, GIROLAMO; VINCIARELLI, GIANLUCA; FAZIO, VITO; DIVELLA, ROSA; DANIELE, ANTONELLA; FILIPPELLI, GIANFRANCO; GADALETA, COSMO DAMIANO

    2014-01-01

    The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55–73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2–6.2) and 10.4 (95% CI, 10–11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC. PMID:25202410

  1. In-vivo optical molecular imaging for laser hyperthermia

    NASA Astrophysics Data System (ADS)

    Zeng, Shaoqun; Zhang, Zhihong; Zhou, Wei; Luo, Qingming

    2002-04-01

    Green fluorescent protein (GFP) transfected Hela cell was planted in naked mice, to construct an in vivo model for monitoring the therapeutic effect of laser hyperthermia in real time. A cooled CCD fluorescence imaging system was used to record the tumor fluorescence image during the hyperthermia process. Primary experimental results were presented in this paper. To make sure the fluorescent probe GFP does not have strong effect on the biologic function of the host tumor cell (Hela cell), several conventional biological processes were observed in real time. First, neurons, which are much more tender than tumor cells, were transfected with GFP (cameleons). No morphological inhomogenities were observed, and normal functional responses of the neurons were observed when stimulated with histamine. In the second step, the mitosis process of cultured Hela cell was monitored. The features observed during mitosis confirmed that the transfection does not ruin the mitosis process of the tumor cell. At last, naked mice with tumor cell was constructed, which emit fluorescence in the tumor region when excited with faint laser. This presentation provides an in vivo biological model for quick monitoring of the therapeutic results of tumor hyperthermia.

  2. The Dartmouth Center for Cancer Nanotechnology Excellence: magnetic hyperthermia

    PubMed Central

    Baker, Ian; Fiering, Steve N; Griswold, Karl E; Hoopes, P Jack; Kekalo, Katerina; Ndong, Christian; Paulsen, Keith; Petryk, Alicea A; Pogue, Brian; Shubitidze, Fridon; Weaver, John

    2015-01-01

    The Dartmouth Center for Cancer Nanotechnology Excellence – one of nine funded by the National Cancer Institute as part of the Alliance for Nanotechnology in Cancer – focuses on the use of magnetic nanoparticles for cancer diagnostics and hyperthermia therapy. It brings together a diverse team of engineers and biomedical researchers with expertise in nanomaterials, molecular targeting, advanced biomedical imaging and translational in vivo studies. The goal of successfully treating cancer is being approached by developing nanoparticles, conjugating them with Fabs, hyperthermia treatment, immunotherapy and sensing treatment response. PMID:26080693

  3. Radiotherapy and hyperthermia in the treatment of fibrosarcomas in the dog.

    PubMed

    Brewer, W G; Turrel, J M

    1982-07-15

    Ten dogs with oral or external nasal fibrosarcoma were treated sequentially with orthovoltage radiation and radiofrequency (RF)-induced hyperthermia. Total radiation doses ranged from 3,200 to 4,800 rad given in 8 to 12 fractions of 400 rad. Immediately after 2 to 4 radiation treatments, hyperthermia was given. Six oral fibrosarcomas were heated to 50 C for 30 sec, using a hand-held RF generator. Four nasomaxillary fibrosarcomas were heated to 43 C for 30 minutes, using a 500-kHz RF generator. Hyperthermia of 50 C resulted in tumor necrosis and infection in 3 dogs and fatal septicemia in 1 dog. Nine of 10 tumors responded to therapy. One year after therapy, 5 dogs were free of disease. Tumor regrowth occurred in 5 dogs. Mean time to tumor regrowth and mean survival time of all dogs were 343 and 398 days, respectively. The results suggested that sequential radiation-hyperthermia is an effective therapeutic regimen for canine fibrosarcoma. It was concluded that this modality not only may be beneficial in the treatment of canine tumors but may be useful for designing new therapeutic approaches to similar tumors in man.

  4. Combining abdominal and cosmetic breast surgery does not increase short-term complication rates: a comparison of each individual procedure and pretreatment risk stratification tool.

    PubMed

    Khavanin, Nima; Jordan, Sumanas W; Vieira, Brittany L; Hume, Keith M; Mlodinow, Alexei S; Simmons, Christopher J; Murphy, Robert X; Gutowski, Karol A; Kim, John Y S

    2015-11-01

    Combined abdominal and breast surgery presents a convenient and relatively cost-effective approach for accomplishing both procedures. This study is the largest to date assessing the safety of combined procedures, and it aims to develop a simple pretreatment risk stratification method for patients who desire a combined procedure. All women undergoing abdominoplasty, panniculectomy, augmentation mammaplasty, and/or mastopexy in the TOPS database were identified. Demographics and outcomes for combined procedures were compared to individual procedures using χ(2) and Student's t-tests. Multiple logistic regression provided adjusted odds ratios for the effect of a combined procedure on 30-day complications. Among combined procedures, a logistic regression model determined point values for pretreatment risk factors including diabetes (1 point), age over 53 (1), obesity (2), and 3+ ASA status (3), creating a 7-point pretreatment risk stratification tool. A total of 58,756 cases met inclusion criteria. Complication rates among combined procedures (9.40%) were greater than those of aesthetic breast surgery (2.66%; P < .001) but did not significantly differ from abdominal procedures (9.75%; P = .530). Nearly 77% of combined cases were classified as low-risk (0 points total) with a 9.78% complication rates. Medium-risk patients (1 to 3 points) had a 16.63% complication rate, and high-risk (4 to 7 points) 38.46%. Combining abdominal and breast procedures is safe in the majority of patients and does not increase 30-day complications rates. The risk stratification tool can continue to ensure favorable outcomes for patients who may desire a combined surgery. 4 Risk. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  5. New Experiences of Treatment in Multiple Tumors with HIFU Ablation and Whole Body Hyperthermia

    NASA Astrophysics Data System (ADS)

    Takeuchi, Akira; Gondo, Hideki; Iijima, Norio; Xia, Yuantian; Takeuchi, Takashi

    2007-05-01

    We have performed some 5000 whole body hyperthermia (WBH) treatments using far-infrared equipment (RHD 7500: Enthermics medical systems, USA) in 1000 cancer patients since 1991 at Luke Hospital & Clinic (Nakano, Japan). Hyperthermia is a natural treatment whereby patients are heated within the fever temperature range of 41-42 C. However, this therapy alone is poorly suited to advanced cancer patients, where regional tumor control is needed. The potential of HIFU therapy for theses cases deserves further investigation. We have treated 20 times in 12 advanced cancer patients, since importing a new HIFU device (Sonic CZ901: Mianyang some electronic Ltd: China) last December and are able to report some interesting results of combination treatment with HIFU and WBH. Our first experience was a 20-year old female pharyngeal cancer patient with lung and multiple liver metastases. Her lung tumor reduced following WBH (given weekly, 4 times in total) and her liver tumor clearly reduced following HIFU treatment. Our second experience of combinative treatment was in a 65-year old male suffering from a neck tumor with bone metastasis. He received WBH after HIFU treatment into 7th lib bone metastasis. After 10 days, his neck tumor grew with evidence of internal necrosis, and finally ruptured. CT images showed necrotic changes in the focus of the neck tumor and also lib bone metastasis. We believe that this new thermal combinative therapy shows great promise.

  6. The combination of dynapenia and abdominal obesity as a risk factor for worse trajectories of IADL disability among older adults.

    PubMed

    Alexandre, Tiago da Silva; Scholes, Shaun; Ferreira Santos, Jair Licio; Duarte, Yeda Aparecida de Oliveira; de Oliveira, Cesar

    2017-10-02

    The concept of dynapenic obesity has been gaining great attention recently. However, there is little epidemiological evidence demonstrating that dynapenic abdominal obese individuals have worse trajectories of disability than those with dynapenia and abdominal obesity alone. Our aim was to investigate whether dynapenia combined with abdominal obesity can result in worse trajectories of instrumental activities of daily living (IADL) among English and Brazilian older adults over eight and ten years of follow-up, respectively. We used longitudinal data from 3374 participants from the English Longitudinal Study of Ageing (ELSA) and 1040 participants from the Brazilian Health, Well-being and Aging Study (SABE) who were free from disability as assessed by IADL at baseline. IADL disability was defined herein as a difficulty to perform the following: preparing meals, managing money, using transportation, shopping, using the telephone, house cleaning, washing clothes, and taking medications according to the Lawton IADL modified scale. The study population in each country was categorized into non-dynapenic/non-abdominal obese (reference group), abdominal obese, dynapenic and dynapenic abdominal obese according to their handgrip strength (<26 kg for men and <16 kg for women) and waist circumference (>102 cm for men and >88 cm for women). We used generalized linear mixed models with IADL as the outcome. The estimated change over time in IADL disability was significantly higher for participants with dynapenic abdominal obesity compared to those with neither condition in both cohorts (ELSA: +0.023, 95% CI = 0.012-0.034, p < 0.001; SABE: +0.065, 95% CI = 0.038-0.091, p < 0.001). Abdominal obesity was also associated with changes over time in IADL disability (ELSA: +0.009, 95% CI = 0.002-0.015, p < 0.05; SABE: +0.021, 95% CI = 0.002-0.041, p < 0.05), which was not observed for dynapenia. Abdominal obesity is an important risk factor for IADL decline but

  7. Shape-controlled fabrication of magnetite silver hybrid nanoparticles with high performance magnetic hyperthermia.

    PubMed

    Ding, Qi; Liu, Dongfang; Guo, Dawei; Yang, Fang; Pang, Xingyun; Che, Renchao; Zhou, Naizhen; Xie, Jun; Sun, Jianfei; Huang, Zhihai; Gu, Ning

    2017-04-01

    Superparamagnetic Fe 3 O 4 nanoparticles (NPs)-based hyperthermia is a promising non-invasive approach for cancer therapy. However, the heat transfer efficiency of Fe 3 O 4 NPs is relative low, which hinders their practical clinical applications. Therefore, it is promising to improve the magnetic hyperthermia efficiency by exploring the higher performance magnetic NPs-based hybrid nanostructures. In the current study, it presents a straightforward in situ reduction method for the shape-controlled preparation of magnetite (Fe 3 O 4 ) silver (Ag) hybrid NPs designed as magnetic hyperthermia heat mediators. The magnetite silver hybrid NPs with core-shell (Fe 3 O 4 @Ag) or heteromer (Fe 3 O 4 -Ag) structures exhibited a higher biocompatibility with SMMC-7721 cells and L02 cells than the individual Ag NPs. Importantly, in the magnetic hyperthermia, with the exposure to alternating current magnetic field, the Fe 3 O 4 @Ag and Fe 3 O 4 -Ag hybrid NPs indicated much better tumor suppression effect against SMMC-7721 cells than the individual Fe 3 O 4 NPs in vitro and in vivo. These results demonstrate that the hybridisation of Fe 3 O 4 and Ag NPs could greatly enhance the magnetic hyperthermia efficiency of Fe 3 O 4 NPs. Therefore, the Fe 3 O 4 @Ag and Fe 3 O 4 -Ag hybrid NPs can be used to be as high performance magnetic hyperthermia mediators based on a simple and effective preparation approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Further Studies of Porcine Malignant Hyperthermia

    PubMed Central

    Hall, L. W.; Trim, Cynthia M.; Woolf, N.

    1972-01-01

    A non-lethal procedure for identifying pigs apt to develop malignant hyperthermia is described. Susceptible animals were exposed to a variety of anaesthetic and other agents and it was shown that thiopentone sodium and CT 1341 (Glaxo) afforded a measure of protection against the development of the syndrome. Pretreatment with procaine did not prevent the onset of the condition and the administration of procaine when muscle rigidity was present failed to prevent a fatal outcome. The syndrome was induced in susceptible animals by halothane, chloroform, and a combination of halothane with suxamethonium. The effects of cyclopropane in susceptible pigs could not be predicted, and other tests showed that suxamethonium alone would not induce muscle contracture. Pretreatment with lignocaine failed to prevent induction of the syndrome by halothane. We believe that the porcine syndrome may result from more than one defect and that in one particular type the most effective treatment is immediate cooling coupled with the administration of sodium bicarbonate. PMID:5017306

  9. Combined abdominal and perineal approach for delayed restoration of bowel continuity after low anterior resection in females.

    PubMed

    Abou-Zeid, Ahmed A; Makki, Mahmoud T

    2007-04-01

    Restoration of bowel continuity after Hartmann's operation is the surgeon's goal and the patient's hope. This operation is technically demanding with reportedly high morbidity and mortality. A short distal rectal stump often makes the operation more difficult. In this article, we describe a combined abdominal and perineal approach, which can possibly make delayed restoration of bowel continuity after low anterior rectal resection an easier procedure.

  10. Thermal dosimetry for bladder hyperthermia treatment. An overview.

    PubMed

    Schooneveldt, Gerben; Bakker, Akke; Balidemaj, Edmond; Chopra, Rajiv; Crezee, Johannes; Geijsen, Elisabeth D; Hartmann, Josefin; Hulshof, Maarten C C M; Kok, H Petra; Paulides, Margarethus M; Sousa-Escandon, Alejandro; Stauffer, Paul R; Maccarini, Paolo F

    2016-06-01

    The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

  11. The influence of hyperthermia on intracranial pressure, cerebral oximetry and cerebral metabolism in traumatic brain injury

    PubMed Central

    Nyholm, Lena; Howells, Tim; Lewén, Anders; Hillered, Lars; Enblad, Per

    2017-01-01

    Background Hyperthermia is a common secondary insult in traumatic brain injury (TBI). The aim was to evaluate the relationship between hyperthermia and intracranial pressure (ICP), and if intracranial compliance and cerebral blood flow (CBF) pressure autoregulation affected that relationship. The relationships between hyperthermia and cerebral oximetry (BtipO2) and cerebral metabolism were also studied. Methods A computerized multimodality monitoring system was used for data collection at the neurointensive care unit. Demographic and monitoring data (temperature, ICP, blood pressure, microdialysis, BtipO2) were analyzed from 87 consecutive TBI patients. ICP amplitude was used as measure of compliance, and CBF pressure autoregulation status was calculated using collected blood pressure and ICP values. Mixed models and comparison between groups were used. Results The influence of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and BtipO2) was small, but individual differences were seen. Linear mixed models showed that hyperthermia raises ICP slightly more when temperature increases in the groups with low compliance and impaired CBF pressure autoregulation. There was also a tendency (not statistically significant) for increased BtipO2, and for increased pyruvate and lactate, with higher temperature, while the lactate/pyruvate ratio and glucose were stable. Conclusions The major finding was that the effects of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and BtipO2) were not extensive in general, but there were exceptional cases. Hyperthermia treatment has many side effects, so it is desirable to identify cases in which hyperthermia is dangerous. Information from multimodality monitoring may be used to guide treatment in individual patients. PMID:28463046

  12. Clinical trial: the efficacy of alverine citrate/simeticone combination on abdominal pain/discomfort in irritable bowel syndrome--a randomized, double-blind, placebo-controlled study.

    PubMed

    Wittmann, T; Paradowski, L; Ducrotté, P; Bueno, L; Andro Delestrain, M-C

    2010-03-01

    Alverine citrate and simeticone combination has been used for almost 20 years in irritable bowel syndrome (IBS), but supportive scientific evidence of efficacy was limited. To evaluate the efficacy of alverine citrate and simeticone combination in patients with IBS-related abdominal pain/discomfort. A total of 412 IBS patients meeting ROME III criteria were included in this double-blind randomized placebo-controlled study if their abdominal pain/discomfort intensity was at least 60 mm on a 0-100 mm visual analogue scale (VAS) during a 2-week run-in treatment-free period. Patients were randomly assigned through the use of Interactive Voice Response System to receive either alverine citrate 60 mg with simeticone 300 mg three times daily or matching placebo for 4 weeks. The full analysis set included 409 patients (71.4% female: mean age: 46.2 +/- 13.9 years). At week 4, alverine citrate and simeticone group had lower VAS scores of abdominal pain/discomfort (median: 40 mm vs. 50 mm, P = 0.047) and higher responder rate (46.8% vs. 34.3%, OR = 1.3; P = 0.01) as compared with placebo group. Patient receiving alverine citrate and simeticone reported greater global symptom improvement compared with those receiving placebo (P = 0.0001). Reported adverse events were similar in both groups. Alverine citrate/simeticone combination was significantly more effective than placebo in relieving abdominal pain/discomfort in patients with IBS.

  13. Outcomes after environmental hyperthermia.

    PubMed

    LoVecchio, Frank; Pizon, Anthony F; Berrett, Christopher; Balls, Adam

    2007-05-01

    This study was conducted to describe the characteristics and outcomes of patients who presented to the emergency department (ED) with presumed environmental hyperthermia. A retrospective chart review was performed in 2 institutions with patients who were seen in the ED and had a discharge diagnosis of hyperthermia, heat stroke, heat exhaustion, or heat cramps. Exclusion criteria were an alternative diagnosis potentially explaining the hyperthermia (pneumonia, etc). Research assistants, who were blinded to the purpose of the study, performed a systematic chart review after a structured training session. If necessary, a third reviewer acted as a tiebreaker. Data regarding patient demographics, comorbidities, vital signs, laboratory results, and short-term outcome were collected. Data were analyzed with Excel and STATA software. We enrolled 52 patients with a mean age of 42.6 years (range, 0.4-81 years) from August 1, 2003 to August 31, 2005. The mean high daily temperature was 103.6 degrees F (range, 88-118 degrees F). At presentation, the mean body temperature was 105.1 degrees F (range, 100.2-111.2 degrees F) and the Glasgow Coma Scale score was less than 14 in 36 (69.2%) patients. Laboratory results demonstrated that 21 (40.4%) patients had a creatinine level of more than 1.5 mg/dL, 35 (67.3%) patients had a creatine kinase (CK) of more than 200 U/L, 30 patients (57.7%) had a prothrombin time of more than 13 seconds, 29 (55.8%) patients had an aspartate aminotransferase (AST) of more than 45 U/L, and only 3 patients (5.7%) had a glucose of less than 60 mg/dL. Ethanol or illicit drugs were involved in 18 (34.6%) cases. The mean hospital stay was 4.7 days (range, 1-30 days), and there were 15 deaths (28.8%). A kappa score for interreviewer reliability was 0.69. Major limitations were the retrospective nature and lack of homogeneity in patient evaluation and test ordering. Hyperthermic patients with higher initial temperatures, hypotension, or low Glasgow Coma Scale

  14. Clinical implementation of electrical impedance tomography with hyperthermia.

    PubMed

    Moskowitz, M J; Ryan, T P; Paulsen, K D; Mitchell, S E

    1995-01-01

    We describe the use of electrical impedance tomography (EIT) for non-invasive thermal imaging in conjunction with a clinical treatment of a superficial scalp lesion utilizing a spiral microstrip antenna. This is our first reported use of EIT with a clinical hyperthermia treatment and perhaps the first world-wide. The thermal measurements recorded during treatment compare favourably with the images reconstructed from impedance data gathered during heating. A linear relation, measured in phantom material, between the change in temperature with the change in reconstructed impedance was assumed. The average discrepancy between the measured temperature changes with the temperatures reconstructed from the impedance changes was 1.4 degrees C, with the maximum being 8.9 degrees C. These preliminary data suggest that impedance changes can be measured during hyperthermia delivery and temperature estimates based on these observed changes are possible in the clinical setting. These findings also point to the complex, yet critical nature of the impedance versus temperature relationship for tissue in vivo. The reconstructed thermal images may provide complementary information about the overall thermal damage imposed during heating. Based on this initial clinical experience we feel that EIT has great potential as a viable clinical aid in imaging the temperature changes imposed during hyperthermia.

  15. Thermometry system development for thermoradiotherapy of deep-seated tumours

    NASA Astrophysics Data System (ADS)

    Fadeev, A. M.; Ivanov, S. M.; Perelstein, E. A.; Polozov, S. M.

    2017-12-01

    Therapeutic hyperthermia (including RF hyperthermia) in combination with radiotherapy (called thermoradiotherapy) is one of widely used contemporary cancer treatment methods. The independent electron linac and RF system or their combinations are necessary for effective therapy. Whole-body hyperthermia is used for treatment of metastatic cancer that was spread throughout the body, regional one is used for treatment of part of the body (for instance leg or abdominal cavity). Local hyperthermia with characteristic size of heating volume of 20-100 mm permits to heat tumour without overheating of healthy tissues. The thermometry of deep suited tissues during the hyperthermia process is an important and complex task. Invasive methods as thermistors, optical sensors or thermo-couples can not be widely used because all of them are able to transport tumor cells to the healthy region of the patient body. Distant methods of the temperature measurement such, as radiothermometry and acoustic thermometry can not be used for tissues seated deeper than 5-7 cm. One of possible ways to solve the problem of temperature measurement of the deep suited tissues is discussed in this article: it was proposed to use the same electrodes for RF hyperthermia and thermometry. As known electrodynamics characteristics of tissues are sufficiently depends on temperature. It was proposed to use this effect for active radiothermometry in local hyperthermia. Two opposite RF dipoles can be used as generator and receiver of pick-up signal.

  16. Localised hyperthermia in rodent models using an MRI-compatible high-intensity focused ultrasound system

    PubMed Central

    Bing, Chenchen; Nofiele, Joris; Staruch, Robert; Ladouceur-Wodzak, Michelle; Chatzinoff, Yonatan; Ranjan, Ashish; Chopra, Rajiv

    2015-01-01

    Purpose Localised hyperthermia in rodent studies is challenging due to the small target size. This study describes the development and characterisation of an MRI-compatible high-intensity focused ultrasound (HIFU) system to perform localised mild hyperthermia treatments in rodent models. Material and methods The hyperthermia platform consisted of an MRI-compatible small animal HIFU system, focused transducers with sector-vortex lenses, a custom-made receive coil, and means to maintain systemic temperatures of rodents. The system was integrated into a 3T MR imager. Control software was developed to acquire images, process temperature maps, and adjust output power using a proportional-integral-derivative feedback control algorithm. Hyperthermia exposures were performed in tissue-mimicking phantoms and in a rodent model (n = 9). During heating, an ROI was assigned in the heated region for temperature control and the target temperature was 42 °C; 30 min mild hyperthermia treatment followed by a 10-min cooling procedure was performed on each animal. Results 3D-printed sector-vortex lenses were successful at creating annular focal regions which enables customisation of the heating volume. Localised mild hyperthermia performed in rats produced a mean ROI temperature of 42.1 ± 0.3 °C. The T10 and T90 percentiles were 43.2 ± 0.4 °C and 41.0 ± 0.3 °C, respectively. For a 30-min treatment, the mean time duration between 41–45 °C was 31.1 min within the ROI. Conclusions The MRI-compatible HIFU system was successfully adapted to perform localised mild hyperthermia treatment in rodent models. A target temperature of 42 °C was well-maintained in a rat thigh model for 30 min. PMID:26540488

  17. Killing of Staphylococcus aureus via Magnetic Hyperthermia Mediated by Magnetotactic Bacteria

    PubMed Central

    Chen, Changyou; Chen, Linjie; Yi, Yong; Chen, Chuanfang

    2016-01-01

    Staphylococcus aureus is a common hospital and household pathogen. Given the emergence of antibiotic-resistant derivatives of this pathogen resulting from the use of antibiotics as general treatment, development of alternative therapeutic strategies is urgently needed. Here, we assess the feasibility of killing S. aureus cells in vitro and in vivo through magnetic hyperthermia mediated by magnetotactic bacteria that possess magnetic nanocrystals and demonstrate magnetically steered swimming. The S. aureus suspension was added to magnetotactic MO-1 bacteria either directly or after coating with anti-MO-1 polyclonal antibodies. The suspensions were then subjected to an alternating magnetic field (AMF) for 1 h. S. aureus viability was subsequently assessed through conventional plate counting and flow cytometry. We found that approximately 30% of the S. aureus cells mixed with uncoated MO-1 cells were killed after AMF treatment. Moreover, attachment between the magnetotactic bacteria and S. aureus increased the killing efficiency of hyperthermia to more than 50%. Using mouse models, we demonstrated that magnetic hyperthermia mediated by antibody-coated magnetotactic MO-1 bacteria significantly improved wound healing. These results collectively demonstrated the effective eradication of S. aureus both in vitro and in vivo, indicating the potential of magnetotactic bacterium-mediated magnetic hyperthermia as a treatment for S. aureus-induced skin or wound infections. PMID:26873320

  18. Depletion of serotonin synthesis with p-CPA pretreatment alters EEG in urethane anesthetized rats under whole body hyperthermia.

    PubMed

    Sinha, Rakesh Kumar; Aggarwal, Yogender

    2007-01-01

    Serotonin is believed as an important factor in brain function. The role of serotonin in cerebral psycho-patho-physiology has already been well established. However, the function of serotonin antagonist in anesthetized subjects under hyperthermia has not been studied properly. Experiments were performed in three groups of urethane-anesthetized rats, such as: (i) control group, (ii) whole body hyperthermia group and (iii) p-CPA (para-Chlorophenylalanine) pretreated hyperthermia group. Hyperthermia was produced by subjecting the rats to high ambient temperature of 38 +/- 1 degrees C (relative humidity 45-50%). Each group was divided for EEG (electroencephalogram) study and for determination of edematous swelling in the brain. Urethane anesthetized rats under hyperthermia show highly significant reduction in their survival time. The body temperature recorded during the hyperthermia was observed with significant and linear rise with marked increase in brain water content, which was analyzed just after the death of the subjects. The results of the electroencephalographic study in urethane-anesthetized rats recorded before death indicate that brain function varies in systematic manner during hyperthermia as sequential changes in EEG patterns were observed. However, a serotonin antagonist, p-CPA pretreatment increases the survival time with significant reduction in edematous swelling in brain but it does not affect the relationship between the core body temperature and the brain cortical potentials as observed in urethane anesthetized subjects exposed to whole body hyperthermia. The core body temperature in p-CPA pretreated rats show non-linear relationship with respect to the exposure time as it was observed in drug untreated subjects. The findings of the present study indicate that although pretreatment of p-CPA in rats has a marked correlation between the extravasations of the blood-brain barrier under hyperthermia but shows minimum effect on the EEG in a model of

  19. A case of malignant hyperthermia captured by an anesthesia information management system.

    PubMed

    Maile, Michael D; Patel, Rajesh A; Blum, James M; Tremper, Kevin K

    2011-04-01

    Many cases of malignant hyperthermia triggered by volatile anesthetic agents have been described. However, to our knowledge, there has not been a report describing the precise changes in physiologic data of a human suffering from this process. Here we describe a case of malignant hyperthermia in which monitoring information was frequently and accurately captured by an anesthesia information management system.

  20. Superparamagnetic nanoparticle clusters for cancer theranostics combining magnetic resonance imaging and hyperthermia treatment.

    PubMed

    Hayashi, Koichiro; Nakamura, Michihiro; Sakamoto, Wataru; Yogo, Toshinobu; Miki, Hirokazu; Ozaki, Shuji; Abe, Masahiro; Matsumoto, Toshio; Ishimura, Kazunori

    2013-01-01

    Superparamagnetic nanoparticles (SPIONs) could enable cancer theranostics if magnetic resonance imaging (MRI) and magnetic hyperthermia treatment (MHT) were combined. However, the particle size of SPIONs is smaller than the pores of fenestrated capillaries in normal tissues because superparamagnetism is expressed only at a particle size <10 nm. Therefore, SPIONs leak from the capillaries of normal tissues, resulting in low accumulation in tumors. Furthermore, MHT studies have been conducted in an impractical way: direct injection of magnetic materials into tumor and application of hazardous alternating current (AC) magnetic fields. To accomplish effective enhancement of MRI contrast agents in tumors and inhibition of tumor growth by MHT with intravenous injection and a safe AC magnetic field, we clustered SPIONs not only to prevent their leakage from fenestrated capillaries in normal tissues, but also for increasing their relaxivity and the specific absorption rate. We modified the clusters with folic acid (FA) and polyethylene glycol (PEG) to promote their accumulation in tumors. SPION clustering and cluster modification with FA and PEG were achieved simultaneously via the thiol-ene click reaction. Twenty-four hours after intravenous injection of FA- and PEG-modified SPION nanoclusters (FA-PEG-SPION NCs), they accumulated locally in cancer (not necrotic) tissues within the tumor and enhanced the MRI contrast. Furthermore, 24 h after intravenous injection of the NCs, the mice were placed in an AC magnetic field with H = 8 kA/m and f = 230 kHz (Hf = 1.8×10(9) A/m∙s) for 20 min. The tumors of the mice underwent local heating by application of an AC magnetic field. The temperature of the tumor was higher than the surrounding tissues by ≈6°C at 20 min after treatment. Thirty-five days after treatment, the tumor volume of treated mice was one-tenth that of the control mice. Furthermore, the treated mice were alive after 12 weeks; control mice died up to 8 weeks

  1. Barium titanate core – gold shell nanoparticles for hyperthermia treatments

    PubMed Central

    FarrokhTakin, Elmira; Ciofani, Gianni; Puleo, Gian Luigi; de Vito, Giuseppe; Filippeschi, Carlo; Mazzolai, Barbara; Piazza, Vincenzo; Mattoli, Virgilio

    2013-01-01

    The development of new tools and devices to aid in treating cancer is a hot topic in biomedical research. The practice of using heat (hyperthermia) to treat cancerous lesions has a long history dating back to ancient Greece. With deeper knowledge of the factors that cause cancer and the transmissive window of cells and tissues in the near-infrared region of the electromagnetic spectrum, hyperthermia applications have been able to incorporate the use of lasers. Photothermal therapy has been introduced as a selective and noninvasive treatment for cancer, in which exogenous photothermal agents are exploited to achieve the selective destruction of cancer cells. In this manuscript, we propose applications of barium titanate core–gold shell nanoparticles for hyperthermia treatment against cancer cells. We explored the effect of increasing concentrations of these nanoshells (0–100 μg/mL) on human neuroblastoma SH-SY5Y cells, testing the internalization and intrinsic toxicity and validating the hyperthermic functionality of the particles through near infrared (NIR) laser-induced thermoablation experiments. No significant changes were observed in cell viability up to nanoparticle concentrations of 50 μg/mL. Experiments upon stimulation with an NIR laser revealed the ability of the nanoshells to destroy human neuroblastoma cells. On the basis of these findings, barium titanate core–gold shell nanoparticles resulted in being suitable for hyperthermia treatment, and our results represent a promising first step for subsequent investigations on their applicability in clinical practice. PMID:23847415

  2. Hydroxyapatite Coated Iron Oxide Nanoparticles: A Promising Nanomaterial for Magnetic Hyperthermia Cancer Treatment.

    PubMed

    Mondal, Sudip; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Nguyen, Van Tu; Kim, Hye Hyun; Nam, Seung Yun; Lee, Kang Dae; Oh, Junghwan

    2017-12-04

    Targeting cancer cells without injuring normal cells is the prime objective in treatment of cancer. In this present study, solvothermal and wet chemical precipitation techniques were employed to synthesize iron oxide (IO), hydroxyapatite (HAp), and hydroxyapatite coated iron oxide (IO-HAp) nanoparticles for magnetic hyperthermia mediated cancer therapy. The synthesized well dispersed spherical IO-HAp nanoparticles, magnetite, and apatite phases were confirmed by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and Field emission transmission electron microscopy (FETEM) with Energy Dispersive X-ray spectroscopy (EDS). The non-toxic behavior of synthesized IO-HAp nanoparticles was confirmed by cytotoxicity assay (Trypan blue and MTT assay). The synthesized nanoparticles revealed a remarkable magnetic saturation of 83.2 emu/g for IO and 40.6 emu/g for IO-HAp nanoparticles in presence of 15,000 Oe (1.5 T) magnetic field at room temperature (300 K). The magnetic hyperthermia study that was performed with IO-HAp nanoparticles showed an excellent hyperthermia effect (SAR value 85 W/g) over MG-63 osteosarcoma cells. The in vitro hyperthermia temperature (~45 °C) was reached within 3 min, which shows a very high efficiency and kills nearly all of the experimental MG-63 osteosarcoma cells within 30 min exposure. These results could potentially open new perceptions for biomaterials that are aimed for anti-cancer therapies based on magnetic hyperthermia.

  3. Hydroxyapatite Coated Iron Oxide Nanoparticles: A Promising Nanomaterial for Magnetic Hyperthermia Cancer Treatment

    PubMed Central

    Mondal, Sudip; Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Santha Moorthy, Madhappan; Nguyen, Van Tu; Kim, Hye Hyun; Nam, Seung Yun; Lee, Kang Dae; Oh, Junghwan

    2017-01-01

    Targeting cancer cells without injuring normal cells is the prime objective in treatment of cancer. In this present study, solvothermal and wet chemical precipitation techniques were employed to synthesize iron oxide (IO), hydroxyapatite (HAp), and hydroxyapatite coated iron oxide (IO-HAp) nanoparticles for magnetic hyperthermia mediated cancer therapy. The synthesized well dispersed spherical IO-HAp nanoparticles, magnetite, and apatite phases were confirmed by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and Field emission transmission electron microscopy (FETEM) with Energy Dispersive X-ray spectroscopy (EDS). The non-toxic behavior of synthesized IO-HAp nanoparticles was confirmed by cytotoxicity assay (Trypan blue and MTT assay). The synthesized nanoparticles revealed a remarkable magnetic saturation of 83.2 emu/g for IO and 40.6 emu/g for IO-HAp nanoparticles in presence of 15,000 Oe (1.5 T) magnetic field at room temperature (300 K). The magnetic hyperthermia study that was performed with IO-HAp nanoparticles showed an excellent hyperthermia effect (SAR value 85 W/g) over MG-63 osteosarcoma cells. The in vitro hyperthermia temperature (~45 °C) was reached within 3 min, which shows a very high efficiency and kills nearly all of the experimental MG-63 osteosarcoma cells within 30 min exposure. These results could potentially open new perceptions for biomaterials that are aimed for anti-cancer therapies based on magnetic hyperthermia. PMID:29207552

  4. Influence of patient mispositioning on SAR distribution and simulated temperature in regional deep hyperthermia

    NASA Astrophysics Data System (ADS)

    Aklan, Bassim; Gierse, Pia; Hartmann, Josefin; Ott, Oliver J.; Fietkau, Rainer; Bert, Christoph

    2017-06-01

    Patient positioning plays an important role in regional deep hyperthermia to obtain a successful hyperthermia treatment. In this study, the influence of possible patient mispositioning was systematically assessed on specific absorption rate (SAR) and temperature distribution. With a finite difference time domain approach, the SAR and temperature distributions were predicted for six patients at 312 positions. Patient displacements and rotations as well as the combination of both were considered inside the Sigma-Eye applicator. Position sensitivity is assessed for hyperthermia treatment planning -guided steering, which relies on model-based optimization of the SAR and temperature distribution. The evaluation of the patient mispositioning was done with and without optimization. The evaluation without optimization was made by creating a treatment plan for the patient reference position in the center of the applicator and applied for all other positions, while the evaluation with optimization was based on creating an individual plan for each position. The parameter T90 was used for the temperature evaluation, which was defined as the temperature that covers 90% of the gross tumor volume (GTV). Furthermore, the hotspot tumor quotient (HTQ) was used as a goal function to assess the quality of the SAR and temperature distribution. The T90 was shown considerably dependent on the position within the applicator. Without optimization, the T90 was clearly decreased below 40 °C by patient shifts and the combination of shifts and rotations. However, the application of optimization for each positon led to an increase of T90 in the GTV. Position inaccuracies of less than 1 cm in the X-and Y-directions and 2 cm in the Z-direction, resulted in an increase of HTQ of less than 5%, which does not significantly affect the SAR and temperature distribution. Current positioning precision is sufficient in the X (right-left)-direction, but position accuracy is required in the Y-and Z-directions.

  5. Catheter-based ultrasound hyperthermia with HDR brachytherapy for treatment of locally advanced cancer of the prostate and cervix

    NASA Astrophysics Data System (ADS)

    Diederich, Chris J.; Wootton, Jeff; Prakash, Punit; Salgaonkar, Vasant; Juang, Titania; Scott, Serena; Chen, Xin; Cunha, Adam; Pouliot, Jean; Hsu, I. C.

    2011-03-01

    A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length × 180 deg and 3-4 cm × 360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers × dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target

  6. Specific loss power in superparamagnetic hyperthermia: nanofluid versus composite

    NASA Astrophysics Data System (ADS)

    Osaci, M.; Cacciola, M.

    2017-01-01

    Currently, the magnetic hyperthermia induced by nanoparticles is of great interest in biomedical applications. In the literature, we can find a lot of models for magnetic hyperthermia, but many of them do not give importance to a significant detail, such as the geometry of nanoparticle positions in the system. Usually, a nanofluid is treated by considering random positions of the nanoparticles, geometry that is actually characteristic to the composite nanoparticles. To assess the error which is frequently made, in this paper we propose a comparative analysis between the specific loss power (SLP) in case of a nanofluid and the SLP in case of a composite with magnetic nanoparticles. We are going to use a superparamagnetic hyperthermia model based on the improved model for calculating the Néel relaxation time in a magnetic field oblique to the nanoparticle magnetic anisotropy axes, and on the improved theoretical model LRT (linear response theory) for SLP. To generate the nanoparticle geometry in the system, we are going to apply a Monte Carlo method to a nanofluid, by minimising the interaction potentials in liquid medium and, for a composite environment, a method for generating random positions of the nanoparticles in a given volume.

  7. Transcriptome Analysis of Neonatal Larvae after Hyperthermia-Induced Seizures in the Contractile Silkworm, Bombyx mori

    PubMed Central

    Nie, Hongyi; Liu, Chun; Zhang, Yinxia; Zhou, Mengting; Huang, Xiaofeng; Peng, Li; Xia, Qingyou

    2014-01-01

    The ability to respond quickly and efficiently to transient extreme environmental conditions is an important property of all biota. However, the physiological basis of thermotolerance in different species is still unclear. Here, we found that the cot mutant showed a seizure phenotype including contraction of the body, rolling, vomiting gut juice and a momentary cessation of movement, and the heartbeat rhythm of the dorsal vessel significantly increases after hyperthermia. To comprehensively understand this process at the molecular level, the transcriptomic profile of cot mutant, which is a behavior mutant that exhibits a seizure phenotype, was investigated after hyperthermia (42°C) that was induced for 5 min. By digital gene expression profiling, we determined the gene expression profile of three strains (cot/cot ok/ok, +/+ ok/ok and +/+ +/+) under hyperthermia (42°C) and normal (25°C) conditions. A Venn diagram showed that the most common differentially expressed genes (DEGs, FDR<0.01 and log2 Ratio≥1) were up-regulated and annotated with the heat shock proteins (HSPs) in 3 strains after treatment with hyperthermia, suggesting that HSPs rapidly increased in response to high temperature; 110 unique DEGs, could be identified in the cot mutant after inducing hyperthermia when compared to the control strains. Of these 110 unique DEGs, 98.18% (108 genes) were up-regulated and 1.82% (two genes) were down-regulated in the cot mutant. KEGG pathways analysis of these unique DEGs suggested that the top three KEGG pathways were “Biotin metabolism,” “Fatty acid biosynthesis” and “Purine metabolism,” implying that diverse metabolic processes are active in cot mutant induced-hyperthermia. Unique DEGs of interest were mainly involved in the ubiquitin system, nicotinic acetylcholine receptor genes, cardiac excitation–contraction coupling or the Notch signaling pathway. Insights into hyperthermia-induced alterations in gene expression and related pathways could

  8. A rat model of spontaneous myopathy and malignant hyperthermia.

    PubMed Central

    Gonzalez, L. E.; Meléndez-Vásquez, C. V.; Gregson, N. A.; File, S. E.

    1998-01-01

    Malignant hyperthermia is a main cause of death during general anesthesia, particularly in children. However, research has been hampered by the lack of a convenient animal model, the only one available being a special strain of pig. In this study, we describe spontaneous myopathy and a fatal syndrome of generalized muscle rigidity triggered by halothane in an outbred strain of rat. Histological examination of skeletal muscle reveals severe abnormalities indicating chronic underlying myopathy. The association of histological abnormalities with an acute, fatal syndrome clinically resembling malignant hyperthermia provides a strong basis for a new and extremely useful animal model to study this fatal disorder. Images Figure 1 Figure 2 PMID:9546371

  9. Reduced-order modeling for hyperthermia control.

    PubMed

    Potocki, J K; Tharp, H S

    1992-12-01

    This paper analyzes the feasibility of using reduced-order modeling techniques in the design of multiple-input, multiple-output (MIMO) hyperthermia temperature controllers. State space thermal models are created based upon a finite difference expansion of the bioheat transfer equation model of a scanned focused ultrasound system (SFUS). These thermal state space models are reduced using the balanced realization technique, and an order reduction criterion is tabulated. Results show that a drastic reduction in model dimension can be achieved using the balanced realization. The reduced-order model is then used to design a reduced-order optimal servomechanism controller for a two-scan input, two thermocouple output tissue model. In addition, a full-order optimal servomechanism controller is designed for comparison and validation purposes. These two controllers are applied to a variety of perturbed tissue thermal models to test the robust nature of the reduced-order controller. A comparison of the two controllers validates the use of open-loop balanced reduced-order models in the design of MIMO hyperthermia controllers.

  10. The effects of hyperthermia on the immunomodulatory properties of human umbilical cord vein mesenchymal stem cells (MSCs).

    PubMed

    Hesami, Shilan; Mohammadi, Mehdi; Rezaee, Mohamad Ali; Jalili, Ali; Rahmani, Mohammad Reza

    2017-11-01

    Hyperthermia can modulate inflammation and the immune response. Based on the recruitment of mesenchymal stem cells (MSCs) to inflamed tissues and the immunomodulatory properties of these cells, the aim of this study was to examine the effects of hyperthermia on the immunomodulatory properties of MSCs in a mixed lymphocyte reaction (MLR). Passages 4-6 of human umbilical cord vein mesenchymal stem cells were co-cultured in a two-way MLR. Cells in the hyperthermia groups were incubated at 41 °C for 45 min. A colorimetric assay was employed to examine the effects of MSCs on cell proliferation. The levels of IL-4 and TNF-α proteins in the cell culture supernatant were measured, and non-adherent cells were used for RNA extraction, which was then used for cDNA synthesis. RT-PCR was utilised to assess levels of IL-10, IL-17A, IL-4, TNF-α, TGF-β1, FOX P 3 , IFN-γ, CXCL12 and β-actin mRNA expression. UCV-MSCs co-cultured in an MLR reduced lymphocyte proliferation at 37 °C, whereas hyperthermia attenuated this effect. Hyperthermia increased expression of IL-10, TGF-β1 and FOXP3 mRNAs in co-culture; however, no effects on IL-17A and IFN-γ were observed, and it reduced CXCL12 expression. In co-culture, IL-4 mRNA and protein increased at 37 °C, an effect that was reduced by hyperthermia. No considerable change in TNF-α mRNA expression was found in hyperthermia-treated cells. Hyperthermia increases cell proliferation of the peripheral blood mononuclear cells and modifies the cytokine profile in the presence of UCV-MSCs.

  11. Noninvasive Thermometry Assisted by a Dual Function Ultrasound Transducer for Mild Hyperthermia

    PubMed Central

    Lai, Chun-Yen; Kruse, Dustin E.; Caskey, Charles F.; Stephens, Douglas N.; Sutcliffe, Patrick L.; Ferrara, Katherine W.

    2010-01-01

    Mild hyperthermia is increasingly important for the activation of temperature-sensitive drug delivery vehicles. Noninvasive ultrasound thermometry based on a 2-D speckle tracking algorithm was examined in this study. Here, a commercial ultrasound scanner, a customized co-linear array transducer, and a controlling PC system were used to generate mild hyperthermia. Because the co-linear array transducer is capable of both therapy and imaging at widely separated frequencies, RF image frames were acquired during therapeutic insonation and then exported for off-line analysis. For in vivo studies in a mouse model, before temperature estimation, motion correction was applied between a reference RF frame and subsequent RF frames. Both in vitro and in vivo experiments were examined; in the in vitro and in vivo studies, the average temperature error had a standard deviation of 0.7°C and 0.8°C, respectively. The application of motion correction improved the accuracy of temperature estimation, where the error range was −1.9 to 4.5°C without correction compared with −1.1 to 1.0°C following correction. This study demonstrates the feasibility of combining therapy and monitoring using a commercial system. In the future, real-time temperature estimation will be incorporated into this system. PMID:21156363

  12. Functionalized graphene oxide-based thermosensitive hydrogel for magnetic hyperthermia therapy on tumors

    NASA Astrophysics Data System (ADS)

    Zhu, Xiali; Zhang, Huijuan; Huang, Heqing; Zhang, Yingjie; Hou, Lin; Zhang, Zhenzhong

    2015-09-01

    A novel locally injectable, biodegradable, and thermo-sensitive hydrogel made from chitosan and β-glycerophosphate salt was prepared. It incorporated polyethylenimine (PEI)-modified super-paramagnetic graphene oxide (GO/IONP/PEI) as a form of minimally invasive treatment of cancer lesions by magnetically induced local hyperthermia. Doxorubicin (DOX) was mixed into the hydrogel which was pre-loaded on GO/IONP/PEI to create a drug delivery system DOX-GO/IONP/PEI-gel. In addition to the evaluation of in vitro and in vivo antitumor activities, the physicochemical properties, magnetic properties and DOX release profile of the DOX-GO/IONP/PEI-gel were determined. The aqueous solution of the hydrogel showed a sol-gel transition behavior depending on temperature changes. Magnetization loops indicated the super-paramagnetic properties of GO/IONP/PEI. Compared with free DOX, DOX-GO/IONP/PEI could efficiently pass through cell membranes, leading to more apoptosis and demonstrating higher antitumor efficacy on MCF-7 cells in vitro. Furthermore, DOX-GO/IONP/PEI-gel intratumorally injected (i.t.) showed high antitumor efficacy on tumor-bearing mice in vivo, with no obvious toxicity. The antitumor efficacy was higher when combined with an alternating magnetic field (AMF), showing that DOX-GO/IONP/PEI-gel under AMF has great potential for cancer magnetic hyperthermia therapy.

  13. Hypo-fractionated radiation, magnetic nanoparticle hyperthermia and a viral immunotherapy treatment of spontaneous canine cancer

    NASA Astrophysics Data System (ADS)

    Hoopes, P. Jack; Moodie, Karen L.; Petryk, Alicia A.; Petryk, James D.; Sechrist, Shawntel; Gladstone, David J.; Steinmetz, Nicole F.; Veliz, Frank A.; Bursey, Alicea A.; Wagner, Robert J.; Rajan, Ashish; Dugat, Danielle; Crary-Burney, Margaret; Fiering, Steven N.

    2017-02-01

    It has recently been shown that cancer treatments such as radiation and hyperthermia, which have conventionally been viewed to have modest immune based anti-cancer effects, may, if used appropriately stimulate a significant and potentially effective local and systemic anti-cancer immune effect (abscopal effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic virus-like nanoparticle (VLP, 2 x 200 μg) are capable of delivering a highly effective cancer treatment that includes an immunogenic component. Two tumors received all three therapeutic modalities, one tumor received radiation and hyperthermia, two tumors received radiation and VLP, and three tumors received only mNP hyperthermia. The treatment regimen is conducted over a 14-day period. All patients tolerated the treatments without complication and have had local and distant tumor responses that significantly exceed responses observed following conventional therapy (surgery and/or radiation). The results suggest that both hypofractionated radiation and hyperthermia have effective immune responses that are enhanced by the intratumoral VLP treatment. Molecular data from these tumors suggest Heat Shock Protein (HSP) 70/90, calreticulin and CD47 are targets that can be exploited to enhance the local and systemic (abscopal effect) immune potential of radiation and hyperthermia cancer treatment.

  14. A printed Yagi-Uda antenna for application in magnetic resonance thermometry guided microwave hyperthermia applicators

    NASA Astrophysics Data System (ADS)

    Paulides, M. M.; Mestrom, R. M. C.; Salim, G.; Adela, B. B.; Numan, W. C. M.; Drizdal, T.; Yeo, D. T. B.; Smolders, A. B.

    2017-03-01

    Biological studies and clinical trials show that addition of hyperthermia stimulates conventional cancer treatment modalities and significantly improves treatment outcome. This supra-additive stimulation can be optimized by adaptive hyperthermia to counteract strong and dynamic thermoregulation. The only clinically proven method for the 3D non-invasive temperature monitoring required is by magnetic resonance (MR) temperature imaging, but the currently available set of MR compatible hyperthermia applicators lack the degree of heat control required. In this work, we present the design and validation of a high-frequency (433 MHz ISM band) printed circuit board antenna with a very low MR-footprint. This design is ideally suited for use in a range of hyperthermia applicator configurations. Experiments emulating the clinical situation show excellent matching properties of the antenna over a 7.2% bandwidth (S 11  <  -15 dB). Its strongly directional radiation properties minimize inter-element coupling for typical array configurations (S 21  <  -23 dB). MR imaging distortion by the antenna was found negligible and MR temperature imaging in a homogeneous muscle phantom was highly correlated with gold-standard probe measurements (root mean square error: RMSE  =  0.51 °C and R 2  =  0.99). This work paves the way for tailored MR imaging guided hyperthermia devices ranging from single antenna or incoherent antenna-arrays, to real-time adaptive hyperthermia with phased-arrays.

  15. Alternating magnetic field-induced hyperthermia increases iron oxide nanoparticle cell association/uptake and flux in blood-brain barrier models.

    PubMed

    Dan, Mo; Bae, Younsoo; Pittman, Thomas A; Yokel, Robert A

    2015-05-01

    Superparamagnetic iron oxide nanoparticles (IONPs) are being investigated for brain cancer therapy because alternating magnetic field (AMF) activates them to produce hyperthermia. For central nervous system applications, brain entry of diagnostic and therapeutic agents is usually essential. We hypothesized that AMF-induced hyperthermia significantly increases IONP blood-brain barrier (BBB) association/uptake and flux. Cross-linked nanoassemblies loaded with IONPs (CNA-IONPs) and conventional citrate-coated IONPs (citrate-IONPs) were synthesized and characterized in house. CNA-IONP and citrate-IONP BBB cell association/uptake and flux were studied using two BBB Transwell(®) models (bEnd.3 and MDCKII cells) after conventional and AMF-induced hyperthermia exposure. AMF-induced hyperthermia for 0.5 h did not alter CNA-IONP size but accelerated citrate-IONP agglomeration. AMF-induced hyperthermia for 0.5 h enhanced CNA-IONP and citrate-IONP BBB cell association/uptake. It also enhanced the flux of CNA-IONPs across the two in vitro BBB models compared to conventional hyperthermia and normothermia, in the absence of cell death. Citrate-IONP flux was not observed under these conditions. AMF-induced hyperthermia also significantly enhanced paracellular pathway flux. The mechanism appears to involve more than the increased temperature surrounding the CNA-IONPs. Hyperthermia induced by AMF activation of CNA-IONPs has potential to increase the BBB permeability of therapeutics for the diagnosis and therapy of various brain diseases.

  16. Thermal dosimetry analysis combined with patient-specific thermal modeling of clinical interstitial ultrasound hyperthermia integrated within HDR brachytherapy for treatment of locally advanced prostate cancer

    NASA Astrophysics Data System (ADS)

    Salgaonkar, Vasant A.; Wootton, Jeff; Prakash, Punit; Scott, Serena; Hsu, I. C.; Diederich, Chris J.

    2017-03-01

    This study presents thermal dosimetry analysis from clinical treatments where ultrasound hyperthermia (HT) was administered following high-dose rate (HDR) brachytherapy treatment for locally advanced prostate cancer as part of a clinical pilot study. HT was administered using ultrasound applicators from within multiple 13-g brachytherapy catheters implanted along the posterior periphery of the prostate. The heating applicators were linear arrays of sectored tubular transducers (˜7 MHz), with independently powered array elements enabling energy deposition with 3D spatial control. Typical heat treatments employed time-averaged peak acoustic intensities of 1 - 3 W/cm2 and lasted for 60 - 70 minutes. Throughout the treatments, temperatures at multiple points were monitored using multi-junction thermocouples, placed within available brachytherapy catheters throughout mid-gland prostate and identified as the hyperthermia target volume (HTV). Clinical constraints allowed placement of 8 - 12 thermocouple sensors in the HTV and patient-specific 3D thermal modeling based on finite element methods (FEM) was used to supplement limited thermometry. Patient anatomy, heating device positions, orientations, and thermometry junction locations were obtained from patient CT scans and HDR and hyperthermia planning software. The numerical models utilized the applied power levels recorded during the treatments. Tissue properties such as perfusion and acoustic absorption were varied within physiological ranges such that squared-errors between measured and simulated temperatures were minimized. This data-fitting was utilized for 6 HT treatments to estimate volumetric temperature distributions achieved in the HTV and surrounding anatomy devoid of thermocouples. For these treatments, the measured and simulated T50 values in the hyperthermia target volume (HTV) were between 40.1 - 43.9 °C and 40.3 - 44.9 °C, respectively. Maximum temperatures between 46.8 - 49.8 °C were measured during

  17. Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis

    PubMed Central

    Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

    2006-01-01

    Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2–0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the Ih current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes. PMID:16819552

  18. Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

    PubMed

    Schuchmann, Sebastian; Schmitz, Dietmar; Rivera, Claudio; Vanhatalo, Sampsa; Salmen, Benedikt; Mackie, Ken; Sipilä, Sampsa T; Voipio, Juha; Kaila, Kai

    2006-07-01

    Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

  19. Implant strategies for endocervical and interstitial ultrasound hyperthermia adjunct to HDR brachytherapy for the treatment of cervical cancer

    NASA Astrophysics Data System (ADS)

    Wootton, Jeffery H.; Prakash, Punit; Hsu, I.-Chow Joe; Diederich, Chris J.

    2011-07-01

    Catheter-based ultrasound devices provide a method to deliver 3D conformable heating integrated with HDR brachytherapy delivery. Theoretical characterization of heating patterns was performed to identify implant strategies for these devices which can best be used to apply hyperthermia to cervical cancer. A constrained optimization-based hyperthermia treatment planning platform was used for the analysis. The proportion of tissue >=41 °C in a hyperthermia treatment volume was maximized with constraints Tmax <= 47 °C, Trectum <= 41.5 °C, and Tbladder <= 42.5 °C. Hyperthermia treatment was modeled for generalized implant configurations and complex configurations from a database of patients (n = 14) treated with HDR brachytherapy. Various combinations of endocervical (360° or 2 × 180° output; 6 mm OD) and interstitial (180°, 270°, or 360° output; 2.4 mm OD) applicators within catheter locations from brachytherapy implants were modeled, with perfusion constant (1 or 3 kg m-3 s-1) or varying with location or temperature. Device positioning, sectoring, active length and aiming were empirically optimized to maximize thermal coverage. Conformable heating of appreciable volumes (>200 cm3) is possible using multiple sectored interstitial and endocervical ultrasound devices. The endocervical device can heat >41 °C to 4.6 cm diameter compared to 3.6 cm for the interstitial. Sectored applicators afford tight control of heating that is robust to perfusion changes in most regularly spaced configurations. T90 in example patient cases was 40.5-42.7 °C (1.9-39.6 EM43 °C) at 1 kg m-3 s-1 with 10/14 patients >=41 °C. Guidelines are presented for positioning of implant catheters during the initial surgery, selection of ultrasound applicator configurations, and tailored power schemes for achieving T90 >= 41 °C in clinically practical implant configurations. Catheter-based ultrasound devices, when adhering to the guidelines, show potential to generate conformal therapeutic

  20. Effect of Daikenchuto (TJ-100) on abdominal bloating in hepatectomized patients.

    PubMed

    Hanazaki, Kazuhiro; Ichikawa, Kengo; Munekage, Masaya; Kitagawa, Hiroyuki; Dabanaka, Ken; Namikawa, Tsutomu

    2013-04-27

    To evaluate the clinical usefulness of Daikenchuto (DKT) in hepatecomized patients. Twenty patients were enrolled with informed consent. Two patients were excluded because of cancelled operations. The remaining 18 patients were randomly chosen for treatment with DKT alone or combination therapy of DKT and lactulose (n = 9, each group). Data were prospectively collected. Primary end points were Visual Analogue Scale (VAS) score for abdominal bloating, total Gastrointestinal Symptoms Rating Scale (GSRS) score for abdominal symptoms, and GSRS score for abdominal bloating. The VAS score for abdominal bloating and total GSRS score for abdominal symptoms recovered to levels that were not significantly different to preoperative levels by 10 d postoperation. Combination therapy of DKT and lactulose was associated with a significantly poorer outcome in terms of VAS and GSRS scores for abdominal bloating, total GSRS score, and total daily calorie intake, when compared with DKT alone therapy. DKT is a potentially effective drug for postoperative management of hepatectomized patients, not only to ameliorate abdominal bloating, but also to promote nutritional support by increasing postoperative dietary intake.

  1. Effect of Daikenchuto (TJ-100) on abdominal bloating in hepatectomized patients

    PubMed Central

    Hanazaki, Kazuhiro; Ichikawa, Kengo; Munekage, Masaya; Kitagawa, Hiroyuki; Dabanaka, Ken; Namikawa, Tsutomu

    2013-01-01

    AIM: To evaluate the clinical usefulness of Daikenchuto (DKT) in hepatecomized patients. METHODS: Twenty patients were enrolled with informed consent. Two patients were excluded because of cancelled operations. The remaining 18 patients were randomly chosen for treatment with DKT alone or combination therapy of DKT and lactulose (n = 9, each group). Data were prospectively collected. Primary end points were Visual Analogue Scale (VAS) score for abdominal bloating, total Gastrointestinal Symptoms Rating Scale (GSRS) score for abdominal symptoms, and GSRS score for abdominal bloating. RESULTS: The VAS score for abdominal bloating and total GSRS score for abdominal symptoms recovered to levels that were not significantly different to preoperative levels by 10 d postoperation. Combination therapy of DKT and lactulose was associated with a significantly poorer outcome in terms of VAS and GSRS scores for abdominal bloating, total GSRS score, and total daily calorie intake, when compared with DKT alone therapy. CONCLUSION: DKT is a potentially effective drug for postoperative management of hepatectomized patients, not only to ameliorate abdominal bloating, but also to promote nutritional support by increasing postoperative dietary intake. PMID:23671738

  2. Application of hyperthermia for cancer treatment: recent patents review.

    PubMed

    Soares, Paula I P; Ferreira, Isabel M M; Igreja, Rui A G B N; Novo, Carlos M M; Borges, Joao P M R

    2012-01-01

    Cancer is one of the main causes of death in the world and its incidence increases every day. Current treatments are insufficient and present many breaches. Hyperthermia is an old concept and since early it was established as a cancer treatment option, mainly in superficial cancers. More recently the concept of intracellular hyperthermia emerged wherein magnetic particles are concentrated at the tumor site and remotely heated using an applied magnetic field to achieve hyperthermic temperatures (42-45°C). Many patents have been registered in this area since the year 2000. This review presents the most relevant information, organizing them according to the hyperthermic method used: 1) external Radio-Frequency devices; 2) hyperthermic perfusion; 3) frequency enhancers; 4) apply heating to the target site using a catheter; 5) injection of magnetic and ferroelectric particles; 6) injection of magnetic nanoparticles that may carry a pharmacological active drug. The use of magnetic nanoparticles is a very promising treatment approach since it may be used for diagnostic and treatment. An ideal magnetic nanoparticle would be able to detect and diagnose the tumor, carry a pharmacological active drug to be delivered in the tumor site, apply hyperthermia through an external magnetic field and allow treatment monitoring by magnetic resonance imaging.

  3. Abdominal Adhesions

    MedlinePlus

    ... Clearinghouse What are abdominal adhesions? Abdominal adhesions are bands of fibrous tissue that can form between abdominal ... Esophagus Stomach Large intestine Adhesion Abdominal adhesions are bands of fibrous tissue that can form between abdominal ...

  4. Abdominal Pain

    MedlinePlus

    ... and Recurrent or Functional Abdominal Pain (RAP or FAP) What is abdominal pain? Abdominal pain , or stomachache, ... recurrent abdominal pain (RAP) or functional abdominal pain (FAP)? If your health care provider has ruled out ...

  5. Treadmill running restores MDMA-mediated hyperthermia prevented by inhibition of the dorsomedial hypothalamus

    PubMed Central

    Zaretsky, Dmitry V; Zaretskaia, Maria V; Durant, Pamela J; Rusyniak, Daniel E

    2015-01-01

    The contribution of exercise to hyperthermia mediated by MDMA is not known. We recently showed that inhibiting the dorsomedial hypothalamus (DMH) attenuated spontaneous locomotion and hyperthermia and prevented deaths in rats given MDMA in a warm environment. The goal of this study was to confirm that restoring locomotion through a treadmill would reverse these effects thereby confirming that locomotion mediated by the DMH contributes to MDMA-mediated hyperthermia. Rats were randomized to receive bilateral microinjections, into the region of the DMH, of muscimol (80 pmol/100nl) or artificial CSF followed by a systemic dose of either MDMA (7.5 mg/kg, i.v.) or saline. Immediately after the systemic injection, rats were placed on a motorized treadmill maintained at 32°C. Rats were exercised at a fixed speed (10 m/min) until their core temperature reached 41°C. Our results showed that a fixed exercise load abolished the decreases in temperature and mortality, seen previously with inhibition of the DMH in freely moving rats. Therefore, locomotion mediated by neurons in the DMH is critical to the development of hyperthermia from MDMA. PMID:25725382

  6. Treadmill running restores MDMA-mediated hyperthermia prevented by inhibition of the dorsomedial hypothalamus.

    PubMed

    Zaretsky, Dmitry V; Zaretskaia, Maria V; Durant, Pamela J; Rusyniak, Daniel E

    2015-05-22

    The contribution of exercise to hyperthermia mediated by MDMA is not known. We recently showed that inhibiting the dorsomedial hypothalamus (DMH) attenuated spontaneous locomotion and hyperthermia and prevented deaths in rats given MDMA in a warm environment. The goal of this study was to confirm that restoring locomotion through a treadmill would reverse these effects thereby confirming that locomotion mediated by the DMH contributes to MDMA-mediated hyperthermia. Rats were randomized to receive bilateral microinjections, into the region of the DMH, of muscimol (80pmol/100nl) or artificial CSF followed by a systemic dose of either MDMA (7.5mg/kg, i.v.) or saline. Immediately after the systemic injection, rats were placed on a motorized treadmill maintained at 32°C. Rats were exercised at a fixed speed (10m/min) until their core temperature reached 41°C. Our results showed that a fixed exercise load abolished the decreases in temperature and mortality, seen previously with inhibition of the DMH in freely moving rats. Therefore, locomotion mediated by neurons in the DMH is critical to the development of hyperthermia from MDMA. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. A numerical study on dual-phase-lag model of bio-heat transfer during hyperthermia treatment.

    PubMed

    Kumar, P; Kumar, Dinesh; Rai, K N

    2015-01-01

    The success of hyperthermia in the treatment of cancer depends on the precise prediction and control of temperature. It was absolutely a necessity for hyperthermia treatment planning to understand the temperature distribution within living biological tissues. In this paper, dual-phase-lag model of bio-heat transfer has been studied using Gaussian distribution source term under most generalized boundary condition during hyperthermia treatment. An approximate analytical solution of the present problem has been done by Finite element wavelet Galerkin method which uses Legendre wavelet as a basis function. Multi-resolution analysis of Legendre wavelet in the present case localizes small scale variations of solution and fast switching of functional bases. The whole analysis is presented in dimensionless form. The dual-phase-lag model of bio-heat transfer has compared with Pennes and Thermal wave model of bio-heat transfer and it has been found that large differences in the temperature at the hyperthermia position and time to achieve the hyperthermia temperature exist, when we increase the value of τT. Particular cases when surface subjected to boundary condition of 1st, 2nd and 3rd kind are discussed in detail. The use of dual-phase-lag model of bio-heat transfer and finite element wavelet Galerkin method as a solution method helps in precise prediction of temperature. Gaussian distribution source term helps in control of temperature during hyperthermia treatment. So, it makes this study more useful for clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.

    PubMed

    Kleiter, Miriam M; Yu, Daohai; Mohammadian, Lenore A; Niehaus, Nelsen; Spasojevic, Ivan; Sanders, Linda; Viglianti, Benjamin L; Yarmolenko, Pavel S; Hauck, Marlene; Petry, Neil A; Wong, Terence Z; Dewhirst, Mark W; Thrall, Donald E

    2006-11-15

    A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m (99mTc)-labeled liposomes could be used to quantify the effect of local hyperthermia on intratumoral Doxil extravasation. Experiments were carried out in a rat fibrosarcoma model with transplanted thigh tumors. Liposomes of approximately same size and composition as Doxil were radiolabeled using [technetium-99m (99mTc)]exametazime. Eight treatment groups received either Doxil, a tracer dose or a large dose of 99mTc-labeled liposomes, or a combination of tracer and Doxil, with or without hyperthermia. This design was chosen to assure that coadministration of both liposomal formulations did not influence their intratumoral distribution. Hyperthermia was done for 45 minutes. Scintigraphic images were obtained at 5 and 18 hours. At 18 hours, tumors were removed and gamma counts as well as doxorubicin concentrations were measured. Intratumoral extravasation of the 99mTc-labeled tracer could be imaged scintigraphically under normothermic and hyperthermic conditions. The thermal enhancement ratio was slightly higher for radiolabeled liposomes than for doxorubicin concentration. However, there was a significant positive correlation of intratumoral doxorubicin concentration and intratumoral uptake of the radiolabeled tracer (expressed as percentage of the injected dose per gram of tissue). Coadministration of radiolabeled liposomes did not negatively influence the amount of drug delivered with Doxil. The use of a radiolabeled tracer has potential value to monitor drug delivery and estimate the effect of an intervention aimed to increase liposomal accumulation, such as local hyperthermia.

  9. Factors associated with high risk of marginal hyperthermia in elderly patients living in an institution.

    PubMed Central

    Vassallo, M.; Gera, K. N.; Allen, S.

    1995-01-01

    The elderly, the very young, and the sick are known to be adversely affected by high environmental temperatures. In a retrospective open case-note review of 872 patients in a large institution during a hot summer we identified characteristics in the elderly that increase the risk of marginal hyperthermia. Women were more likely to be affected than men (25.6% vs 16.9%). We found an age-related increase in marginal hyperthermia, 15.7% of those below 60 years developed a hyperthermia compared to 18.9% in those between 70-79 years (non-significant), 28.3% in those between 80-89 years (p = 0.01) and 50% in those above 90 years (p < 0.01). There was also a direct relationship between the incidence of hyperthermia and the ambient temperature (29% in the warmer wards, compared to 17.2% in cooler ones; p < 0.01) and with the level of dependence (42.3% of the bedridden group, p < 0.01, and 20.4% of the semi-dependent, p < 0.01, compared to 11.1% of the mobile group). These factors were more significant as predictors of risk than the diagnosis. Identifying high risk patients early and taking appropriate measures to avoid hyperthermia and dehydration is important to try to decrease mortality during heatwaves. PMID:7784280

  10. Thermal analysis in the rat glioma model during directly multipoint injection hyperthermia incorporating magnetic nanoparticles.

    PubMed

    Liu, Lianke; Ni, Fang; Zhang, Jianchao; Wang, Chunyu; Lu, Xiang; Guo, Zhirui; Yao, Shaowei; Shu, Yongqian; Xu, Ruizhi

    2011-12-01

    Hyperthermia incorporating magnetic nanoparticles (MNPs) is a hopeful therapy to cancers and steps into clinical tests at present. However, the clinical plan of MNPs deposition in tumors, especially applied for directly multipoint injection hyperthermia (DMIH), and the information of temperature rise in tumors by DMIH is lack of studied. In this paper, we mainly discussed thermal distributions induced by MNPs in the rat brain tumors during DMIH. Due to limited experimental measurement for detecting thermal dose of tumors, and in order to acquire optimized results of temperature distributions clinically needed, we designed the thermal model in which three types of MNPs injection for hyperthermia treatments were simulated. The simulated results showed that MNPs injection plan played an important role in determining thermal distribution, as well as the overall dose of MNPs injected. We found that as injected points enhanced, the difference of temperature in the whole tumor volume decreased. Moreover, from temperature detecting data by Fiber Optic Temperature Sensors (FOTSs) in glioma bearing rats during MNPs hyperthermia, we found the temperature errors by FOTSs reduced as the number of points injected enhanced. Finally, the results showed that the simulations are preferable and the optimized plans of the numbers and spatial positions of MNPs points injected are essential during direct injection hyperthermia.

  11. Magnetic hyperthermia enhances cell toxicity with respect to exogenous heating.

    PubMed

    Sanz, Beatriz; Calatayud, M Pilar; Torres, Teobaldo E; Fanarraga, Mónica L; Ibarra, M Ricardo; Goya, Gerardo F

    2017-01-01

    Magnetic hyperthermia is a new type of cancer treatment designed for overcoming resistance to chemotherapy during the treatment of solid, inaccessible human tumors. The main challenge of this technology is increasing the local tumoral temperature with minimal side effects on the surrounding healthy tissue. This work consists of an in vitro study that compared the effect of hyperthermia in response to the application of exogenous heating (EHT) sources with the corresponding effect produced by magnetic hyperthermia (MHT) at the same target temperatures. Human neuroblastoma SH-SY5Y cells were loaded with magnetic nanoparticles (MNPs) and packed into dense pellets to generate an environment that is crudely similar to that expected in solid micro-tumors, and the above-mentioned protocols were applied to these cells. These experiments showed that for the same target temperatures, MHT induces a decrease in cell viability that is larger than the corresponding EHT, up to a maximum difference of approximately 45% at T = 46 °C. An analysis of the data in terms of temperature efficiency demonstrated that MHT requires an average temperature that is 6 °C lower than that required with EHT to produce a similar cytotoxic effect. An analysis of electron microscopy images of the cells after the EHT and MHT treatments indicated that the enhanced effectiveness observed with MHT is associated with local cell destruction triggered by the magnetic nano-heaters. The present study is an essential step toward the development of innovative adjuvant anti-cancer therapies based on local hyperthermia treatments using magnetic particles as nano-heaters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Hyperthermia promotes and prevents respiratory epithelial apoptosis through distinct mechanisms.

    PubMed

    Nagarsekar, Ashish; Tulapurkar, Mohan E; Singh, Ishwar S; Atamas, Sergei P; Shah, Nirav G; Hasday, Jeffrey D

    2012-12-01

    Hyperthermia has been shown to confer cytoprotection and to augment apoptosis in different experimental models. We analyzed the mechanisms of both effects in the same mouse lung epithelial (MLE) cell line (MLE15). Exposing MLE15 cells to heat shock (HS; 42°C, 2 h) or febrile-range hyperthermia (39.5°C) concurrent with activation of the death receptors, TNF receptor 1 or Fas, greatly accelerated apoptosis, which was detectable within 30 minutes and was associated with accelerated activation of caspase-2, -8, and -10, and the proapoptotic protein, Bcl2-interacting domain (Bid). Caspase-3 activation and cell death were partially blocked by inhibitors targeting all three initiator caspases. Cells expressing the IκB superrepessor were more susceptible than wild-type cells to TNF-α-induced apoptosis at 37°C, but HS and febrile-range hyperthermia still increased apoptosis in these cells. Delaying HS for 3 hours after TNF-α treatment abrogated its proapoptotic effect in wild-type cells, but not in IκB superrepressor-expression cells, suggesting that TNF-α stimulates delayed resistance to the proapoptotic effects of HS through an NF-κB-dependent mechanism. Pre-exposure to 2-hour HS beginning 6 to16 hours before TNF-α treatment or Fas activation reduced apoptosis in MLE15 cells. The antiapoptotic effects of HS pretreatment were reduced in TNF-α-treated embryonic fibroblasts from heat shock factor-1 (HSF1)-deficient mice, but the proapoptotic effects of concurrent HS were preserved. Thus, depending on the temperature and timing relative to death receptor activation, hyperthermia can exert pro- and antiapoptotic effects through distinct mechanisms.

  13. Reactive oxygen species scavenger N-acetyl cysteine reduces methamphetamine-induced hyperthermia without affecting motor activity in mice

    PubMed Central

    Sanchez-Alavez, Manuel; Bortell, Nikki; Galmozzi, Andrea; Conti, Bruno; Marcondes, Maria Cecilia G.

    2014-01-01

    Hyperthermia is a potentially lethal side effect of Methamphetamine (Meth) abuse, which involves the participation of peripheral thermogenic sites such as the Brown Adipose Tissue (BAT). In a previous study we found that the anti-oxidant N-acetyl cysteine (NAC) can prevent the high increase in temperature in a mouse model of Meth-hyperthermia. Here, we have further explored the ability of NAC to modulate Meth-induced hyperthermia in correlation with changes in BAT. We found that NAC treatment in controls causes hypothermia, and, when administered prior or upon the onset of Meth-induced hyperthermia, can ameliorate the temperature increase and preserve mitochondrial numbers and integrity, without affecting locomotor activity. This was different from Dantrolene, which decreased motor activity without affecting temperature. The effects of NAC were seen in spite of its inability to recover the decrease of mitochondrial superoxide induced in BAT by Meth. In addition, NAC did not prevent the Meth-induced decrease of BAT glutathione. Treatment with S-adenosyl-L-methionine, which improves glutathione activity, had an effect in ameliorating Meth-induced hyperthermia, but also modulated motor activity. This suggests a role for the remaining glutathione for controlling temperature. However, the mechanism by which NAC operates is independent of glutathione levels in BAT and specific to temperature. Our results show that, in spite of the absence of a clear mechanism of action, NAC is a pharmacological tool to examine the dissociation between Meth-induced hyperthermia and motor activity, and a drug of potential utility in treating the hyperthermia associated with Meth-abuse. PMID:26346736

  14. Temperature distribution in the human body under various conditions of induced hyperthermia

    NASA Technical Reports Server (NTRS)

    Korobko, O. V.; Perelman, T. L.; Fradkin, S. Z.

    1977-01-01

    A mathematical model based on heat balance equations was developed for studying temperature distribution in the human body under deep hyperthermia which is often induced in the treatment of malignant tumors. The model yields results which are in satisfactory agreement with experimental data. The distribution of temperature under various conditions of induced hyperthermia, i.e. as a function of water temperature and supply rate, is examined on the basis of temperature distribution curves in various body zones.

  15. Late response to whole-lung irradiation alone and with whole-body hyperthermia in dogs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gillette, S.M.; Gillette, E.L.; Dawson, C.A.

    1997-02-01

    The late effects of whole-lung irradiation with and without whole-body hyperthermia were studied in beagle dogs. The reference doses ranged from 18 to 49.5 Gy given in 1.5-Gy fractions over 6 weeks. Whole-body hyperthermia was given in three 2-h treatments to a deep rectal temperature of 42.0{degrees}C. Radiation was given simultaneously with hyperthermia on those days. Physiological and histopathological responses were evaluated. Physiological changes included decreases in cardiac output, systemic blood pressure, dynamic compliance and serotonin uptake. Early changes included an increase in extravascular water and total protein in the lavage. These changes were considered mild, were compensated for andmore » occurred only in dogs receiving doses of 40.5 Gy or greater given in 1.5-Gy fractions over 6 weeks. Histopathological change were typical of irradiated lung and included pleural fibrosis, interstitial fibrosis, fibrotic foci, and peribronchial and perivascular fibrosis. There was no enhancement of late injury to lung by hyperthermia seen in this study. 17 refs., 3 figs., 2 tabs.« less

  16. A case report of suspected malignant hyperthermia where patient survived the episode.

    PubMed

    Iqbal, Asif; Badoo, Shoaib; Naqeeb, Ruqsana

    2017-01-01

    Malignant hyperthermia is rare inherited disorder in our part of the world; there are only few cases reported in literature in India who were suspected of having this condition. The overall incidence of malignant hyperthermia during general anesthesia is estimated to range from 1: 5000 to 1: 50,000-100,000 and mortality rate is estimated to be <5% in the presence of standard care. In India, there is no center where in vitro halothane caffeine contraction test is performed to confirm diagnosis in suspected cases. Second, dantrolene drug of choice for this condition is not freely available in market in India and is stored only in some hospitals in few major cities. Among the cases reported of suspected of malignant hyperthermia in India almost 50% have survived the condition despite nonavailability of dantrolene emphasizing role of early detection and aggressive management in these cases.

  17. A case report of suspected malignant hyperthermia where patient survived the episode

    PubMed Central

    Iqbal, Asif; Badoo, Shoaib; Naqeeb, Ruqsana

    2017-01-01

    Malignant hyperthermia is rare inherited disorder in our part of the world; there are only few cases reported in literature in India who were suspected of having this condition. The overall incidence of malignant hyperthermia during general anesthesia is estimated to range from 1: 5000 to 1: 50,000–100,000 and mortality rate is estimated to be <5% in the presence of standard care. In India, there is no center where in vitro halothane caffeine contraction test is performed to confirm diagnosis in suspected cases. Second, dantrolene drug of choice for this condition is not freely available in market in India and is stored only in some hospitals in few major cities. Among the cases reported of suspected of malignant hyperthermia in India almost 50% have survived the condition despite nonavailability of dantrolene emphasizing role of early detection and aggressive management in these cases. PMID:28442967

  18. Thermal Skin Damage During Reirradiation and Hyperthermia Is Time-Temperature Dependent

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bakker, Akke, E-mail: akke.bakker@amc.uva.nl; Kolff, M. Willemijn; Holman, Rebecca

    Purpose: To investigate the relationship of thermal skin damage (TSD) to time–temperature isoeffect levels for patients with breast cancer recurrence treated with reirradiation plus hyperthermia (reRT + HT), and to investigate whether the treatment history of previous treatments (scar tissue) is a risk factor for TSD. Methods and Materials: In this observational study, temperature characteristics of hyperthermia sessions were analyzed in 262 patients with recurrent breast cancer treated in the AMC between 2010 and 2014 with reirradiation and weekly hyperthermia for 1 hour. Skin temperature was measured using a median of 42 (range, 29-82) measurement points per hyperthermia session. Results: Sixty-eight patients (26%) developed 79more » sites of TSD, after the first (n=26), second (n=17), third (n=27), and fourth (n=9) hyperthermia session. Seventy percent of TSD occurred on or near scar tissue. Scar tissue reached higher temperatures than other skin tissue (0.4°C, P<.001). A total of 102 measurement points corresponded to actual TSD sites in 35 of 79 sessions in which TSD developed. Thermal skin damage sites had much higher maximum temperatures than non-TSD sites (2.8°C, P<.001). Generalized linear mixed models showed that the probability of TSD is related to temperature and thermal dose values (P<.001) and that scar tissue is more at risk (odds ratio 0.4, P<.001). Limiting the maximum temperature of a measurement point to 43.7°C would mean that the probability of observing TSD was at most 5%. Conclusion: Thermal skin damage during reRT + HT for recurrent breast cancer was related to higher local temperatures and time–temperature isoeffect levels. Scar tissue reached higher temperatures than other skin tissue, and TSD occurred at lower temperatures and thermal dose values in scar tissue compared with other skin tissue. Indeed, TSD developed often on and around scar tissue from previous surgical procedures.« less

  19. Thermoseeds for interstitial magnetic hyperthermia: from bioceramics to nanoparticles

    NASA Astrophysics Data System (ADS)

    Baeza, A.; Arcos, D.; Vallet-Regí, M.

    2013-12-01

    The development of magnetic materials for interstitial hyperthermia treatment of cancer is an ever evolving research field which provides new alternatives to antitumoral therapies. The development of biocompatible magnetic materials has resulted in new biomaterials with multifunctional properties, which are able to adapt to the complex scenario of tumoral processes. Once implanted or injected in the body, magnetic materials can behave as thermoseeds under the effect of AC magnetic fields. Magnetic bioceramics aimed to treat bone tumors and magnetic nanoparticles are among the most studied thermoseeds, and supply different solutions for the different scenarios in cancerous processes. This paper reviews some of the biomaterials used for bone cancer treatment and skeletal reinforcing, as well as the more complex topic of magnetic nanoparticles for intracellular targeting and hyperthermia.

  20. Thermoseeds for interstitial magnetic hyperthermia: from bioceramics to nanoparticles.

    PubMed

    Baeza, A; Arcos, D; Vallet-Regí, M

    2013-12-04

    The development of magnetic materials for interstitial hyperthermia treatment of cancer is an ever evolving research field which provides new alternatives to antitumoral therapies. The development of biocompatible magnetic materials has resulted in new biomaterials with multifunctional properties, which are able to adapt to the complex scenario of tumoral processes. Once implanted or injected in the body, magnetic materials can behave as thermoseeds under the effect of AC magnetic fields. Magnetic bioceramics aimed to treat bone tumors and magnetic nanoparticles are among the most studied thermoseeds, and supply different solutions for the different scenarios in cancerous processes. This paper reviews some of the biomaterials used for bone cancer treatment and skeletal reinforcing, as well as the more complex topic of magnetic nanoparticles for intracellular targeting and hyperthermia.

  1. Localized Hyperthermia for Enhanced Targeted Delivery of Polymer Therapeutics

    NASA Astrophysics Data System (ADS)

    Frazier, Nicholas

    It is estimated that in 2016, more than 848,000 new cases of cancer will be diagnosed in men with more than a quarter being prostate cancer and more than 26,000 deaths attributed to this disease. Prostate cancer poses a limited risk when detected at an early stage and treatment of stages II-III has a 5-year survival rate of almost 100%. However, these early-stage cancers can eventually progress and develop into stage IV, dramatically dropping the 5-year survival rate to 28%. Thus, development of a new therapy is needed to fully eliminate these tumors. Combination of heat and chemotherapy improves therapeutic efficacy while allowing for reduced dosing of drugs and limiting side effects. Localized hyperthermia has been used to enhance the delivery of polymer therapeutics to prostate tumors through increased blood flow, vascular permeability, and incorporation of heat shock targeting. This strategy has been shown to increase the delivery and retention of polymer-drug conjugates leading to enhanced efficacy. Although much work has been done using this strategy, the effects of different thermal dosing on polymer accumulation are unknown. The first aim of this research is to examine how altering heating parameters influences polymer tumor accumulation. The hypothesis for this aim is that there is an optimal thermal treatment that leads to the maximal amount of polymer accumulation in the tumors. Additionally, the previously used heating method of plasmonic photothermal therapy (PPTT) can result in long-term accumulation of gold nanoparticles in healthy organs, potentially limiting clinical applicability. The second aim of this proposal will be focused on investigating the alternative method of high intensity focused ultrasound (HIFU) for selective heating of tumors and enhancing macromolecular delivery. HIFU has shown the capability for precise, noninvasive heating of specific regions within the prostate through magnetic resonance imaging (MRI) guidance. The hypothesis

  2. Application of Albumin-embedded Magnetic Nanoheaters for Release of Etoposide in Integrated Chemotherapy and Hyperthermia of U87-MG Glioma Cells.

    PubMed

    Babincová, Melánia; Vrbovská, Hana; Sourivong, Paul; Babinec, Peter; Durdík, Štefan

    2018-05-01

    Malignant gliomas remain refractory to several therapeutic approaches and the requirement for novel treatment modalities is critical to combat this disease. Etoposide is a topoisomerase-II inhibitor, which promotes DNA damage and apoptosis of cancer cells. In this study, we prepared albumin with embedded magnetic nanoparticles and etoposide for in vitro evaluation of combined hyperthermia and chemotherapy. Magnetic nanoparticles were prepared by a modified co-precipitation method in the presence of human serum albumin and etoposide. A cellular proliferation assay was used to determine the effects of these nanostructures on the viability of U87 glioma cells in an alternating magnetic field. The in vitro experiments showed that cell viability decreased to 59.4% after heat treatment alone and to 53.8% on that with free etoposide, while combined treatment resulted in 7.8% cell viability. Integrating hyperthermia and chemotherapy using albumin co-embedded magnetic nanoheaters and etoposide may represent a promising therapeutic option for glioblastoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Response of transformed and normal mouse cell lines to anti-melanin compounds, hyperthermia, and radiation.

    PubMed

    Raaphorst, G P; Azzam, E I

    1992-02-01

    Five cell lines (one parental, two transformed melanin producing, and two transformed non-melanin producing) were evaluated for the responses to 2- and 4-hydroxyanisole (2HA, 4HA) alone or combined with hyperthermia or radiation. All cells exhibited a non-specific toxic response to the two compounds and the effect was exposure time and concentration dependent and was greater for 4HA compared to 2HA. In addition, the two melanin-producing cell lines were more sensitive, demonstrating specific toxicity to such cell lines. The treatment with either 2HA or 4HA combined with heat and radiation resulted mostly in additive or antagonistic effects, except for one combination of 2HA plus radiation in the melanin-producing R25 cells. Thus, while these compounds may be useful in therapy for pigmented melanomas, combined treatment with radiation is not recommended.

  4. Effects of hyperthermia on enzymes and electrolytes in blood and cerebrospinal fluid in dogs

    NASA Astrophysics Data System (ADS)

    Deswal, K.; Chohan, I. S.

    1981-09-01

    The effects of exposure to various degrees of heat stress on serum glutamate—oxaloacetate transaminase (SGOT), serum glutamate-pyruvate transaminase (SGPT), alkaline phosphatase (ALK-P-ase), calcium and chlorides have been studied on 75 dogs. Rectal temperature (Tre) was recorded before and after exposure to heat stress. These dogs were divided into 5 groups, according to the Tre level attained after exposure to heat stress. Rectal temperature was raised from normal to 39.45±0.47‡C in the first group, to 40.93±0.17‡C in the second group, to 41.87±0.22‡C in the third group, to 42.90 ± 0.21‡C in the fourth group and to 43.93±0.19‡C in the fifth group. The concentration of enzymes SGOT, SGPT and ALK-P-ase in blood and cerebrospinal fluid (CSF) increased significantly with hyperthermia. Calcium and chlorides concentrations in blood and in CSF tended to increase in hyperthermia. The integrity of the blood brain barrier for these enzymes and calcium is maintained under mild hyperthermia but it breaks down partially under influence of more severe hyperthermia. Core temperature above 41‡C results in damage to tissues and consequential rise of plasma enzymes. This degree of hyperthermia also seems to mark the beginning of injury to blood brain barrier. Critical core temperature tolerated by 50% of animals was 44‡C.

  5. Thermal tolerance reduces hyperthermia-induced disruption of working memory: a role for endogenous opiates?

    PubMed

    Mickley, G A; Cobb, B L

    1998-03-01

    Previous reports indicate that microwave-induced hyperthermia can impair learning and memory. Here, we report that preexposure to a single 20-min period of hyperthermia can produce thermal tolerance and, thereby, attenuate future physiological and behavioral reactions to heating. Because endogenous opioids have been implicated in thermoregulation and reactions to microwave exposure, we also determined how opioid receptor antagonism might modulate these effects. In an initial experiment, rats were exposed daily, over 5 successive days, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. In animals exposed to microwaves, thermal tolerance was evidenced by declining rectal temperatures over time. Temperature reductions following microwave exposure were prominent after a single previous exposure. Therefore, in a second study, a single hyperthermic episode was used to induce thermal tolerance. On Day 1, rats were either exposed, over a 20-min period, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. Just prior to radiation/sham-radiation treatment, rats received either saline or naltrexone (0.1 or 10 mg/kg, intraperitoneally (i.p.)). The following day (Day 2), rats were either microwave or sham exposed and tested on a task which measures the relative time subjects explore a familiar versus a novel stimulus object. Normothermic rats spend significantly more time in contact with new environmental components and less time with familiar objects. Brain (dura) and rectal temperatures were recorded on both days of the study. Microwave exposure produced a reliable hyperthermia which was significantly lower (on Day 2) in rats receiving repeated treatments (tolerant group). On the behavioral test, rats exposed only once to microwave-induced hyperthermia (nontolerant group) exhibited significantly different patterns of object discrimination than did tolerant or sham-exposed animals. Sham

  6. Abdominal tap

    MedlinePlus

    Peritoneal tap; Paracentesis; Ascites - abdominal tap; Cirrhosis - abdominal tap; Malignant ascites - abdominal tap ... abdominal cavity ( most often cancer of the ovaries ) Cirrhosis of the liver Damaged bowel Heart disease Infection ...

  7. [Possible malignant hyperthermia as reaction to an overdose of myotonolytic, antidepressive and sedative drugs (author's transl)].

    PubMed

    Hackl, J M; Engl, J; Hofstädter, F; Bonelli, S; Rumpl, E; Dworzak, E; Puschendorf, B

    1981-08-07

    A 51-year-old male patient with no history of musculo-skeletal or myopathic abnormalities, but suffering from manic-depressive psychosis, attempted suicide with an overdose of dolpersin hydrochloride (Mydocalm), dipenzepine hydrochloride (Noveril), meprobamate (Mepronox) and nitrazepam (Mogadon). He developed high fever, muscle rigidity, tachycardia, arrhythmias, hypotension and mottled cyanosis, symptoms well-known in persons with malignant hyperthermia, an autosomally inherited disease of skeletal muscle. There is also discussed the manifestation and the symptoms of an acute rhabdomyolysis. The diagnosis was confirmed by chemical pathological laboratory findings, including respiratory and metabolic acidosis, myoglobinaemia accompanied by myoglobin diuresis, and elevated creatine phosphokinase (CPK values up to 2790 U/l). Electron microscopic examination of muscle tissue revealed signs of myolysis and mitochondrial reactions with pleoconic hyperplasia. No inhalation anaesthetics or skeletal muscle relaxants, such as succinyl choline, were used in this case. Therefore, malignant hyperthermia might have been induced by a combination of drugs which were not known to induce this abnormal muscular reaction. However, the muscle relaxant effect of dolpersin hydrochloride may have acted as a possible inducer of the attack.

  8. Staged abdominal re-operation for abdominal trauma.

    PubMed

    Taviloglu, Korhan

    2003-07-01

    To review the current developments in staged abdominal re-operation for abdominal trauma. To overview the steps of damage control laparotomy. The ever increasing importance of the resuscitation phase with current intensive care unit (ICU) support techniques should be emphasized. General surgeons should be familiar to staged abdominal re-operation for abdominal trauma and collaborate with ICU teams, interventional radiologists and several other specialties to overcome this entity.

  9. Microstrip-antenna design for hyperthermia treatment of superficial tumors.

    PubMed

    Montecchia, F

    1992-06-01

    Microstrip antennas have many different advantages over other RF/MW radiative applicators employed for superficial hyperthermia treatment. This is mainly due to their compact and body-conformable structure as well as to printed circuit board techniques, both of which allow a wide design flexibility for superficial tumor heating. Among the wide variety of radiator configurations, three microstrip antennas of increasing complexity with electromagnetic and heating characteristics potentially suitable as applicators for superficial hyperthermia have been designed, developed, and tested in different radiative conditions: a microstrip disk, a microstrip annular-slot, and a microstrip spiral. Electromagnetic design criteria are presented together with the determinations of the applicator return loss versus frequency and thermograms of the near-field heating pattern in muscle-like phantom. The results are in good agreement with theory and indicate that: i) the operating frequency is either single or multiple according to the applicator-mode, "resonant" or "traveling-wave," and can be chosen in the useful frequency range for hyperthermia (200-1000 MHz) according to the tumor cross-section and depth; ii) the heating pattern flexibility increases going from the simple geometry disk to the annular-slot and spiral applicators; iii) a distilled-water bolus is required; iv) the annular-slot applicator exhibits the highest efficiency, while the spiral applicator provides the best performance.

  10. Does this adult patient have a blunt intra-abdominal injury?

    PubMed

    Nishijima, Daniel K; Simel, David L; Wisner, David H; Holmes, James F

    2012-04-11

    physical examination findings (adjusted summary LR, 30; 95% CI, 20-46); conversely, a normal ultrasound result decreases the chance of injury detection (adjusted summary LR, 0.26; 95% CI, 0.19-0.34). Test results increasing the likelihood of intra-abdominal injury include a base deficit less than -6 mEq/L (LR, 18; 95% CI, 11-30), elevated liver transaminases (LR range, 2.5-5.2), hematuria (LR range, 3.7-4.1), anemia (LR range, 2.2-3.3), and abnormal chest radiograph (LR range, 2.5-3.8). Symptoms and signs may be most useful in combination, particularly in identification of patients who do not need further diagnostic workup. Bedside ultrasonography has the highest accuracy of all individual findings, but a normal result does not rule out an intra-abdominal injury. Combinations of clinical findings may be most useful to determine which patients do not require further evaluation, but the ideal combination of variables for identifying patients without intra-abdominal injury requires further study.

  11. Effect of abdominal resistance exercise on abdominal subcutaneous fat of obese women: a randomized controlled trial using ultrasound imaging assessments.

    PubMed

    Kordi, Ramin; Dehghani, Saeed; Noormohammadpour, Pardis; Rostami, Mohsen; Mansournia, Mohammad Ali

    2015-01-01

    The aim of this study was to compare the effect of diet and an abdominal resistance training program to diet alone on abdominal subcutaneous fat thickness and waist circumference of overweight and obese women. This randomized clinical trial included 40 overweight and obese women randomly divided into 2 groups: diet only and diet combined with 12 weeks of abdominal resistance training. Waist and hip circumferences and abdominal skin folds of the subjects were measured at the beginning and 12 weeks after the interventions. In addition, abdominal subcutaneous fat thickness of the subjects was measured using ultrasonography. Percentage body fat and lean body mass of all the subjects were also measured using a bioelectric impedance device. After 12 weeks of intervention, the weight of participants in both groups decreased; but the difference between the 2 groups was not significant (P = .45). Similarly, other variables including abdominal subcutaneous fat, waist circumference, hip circumference, body mass index, body fat percentage, and skin fold thickness were reduced in both groups; but there were no significant differences between the groups. This study found that abdominal resistance training besides diet did not reduce abdominal subcutaneous fat thickness compared to diet alone in overweight or obese women. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

  12. Methamphetamine-induced toxicity: an updated review on issues related to hyperthermia

    PubMed Central

    Matsumoto, Rae R.; Seminerio, Michael J.; Turner, Ryan C.; Robson, Matthew J.; Nguyen, Linda; Miller, Diane B.; O’Callaghan, James P.

    2015-01-01

    Reports of methamphetamine-related emergency room visits suggest that elevated body temperature is a universal presenting symptom, with lethal overdoses generally associated with extreme hyperthermia. This review summarizes the available information on methamphetamine toxicity as it pertains to elevations in body temperature. First, a brief overview of thermoregulatory mechanisms is presented. Next, central and peripheral targets that have been considered for potential involvement in methamphetamine hyperthermia are discussed. Finally, future areas of investigation are proposed, as further studies are needed to provide greater insight into the mechanisms that mediate the alterations in body temperature elicited by methamphetamine. PMID:24836729

  13. Tailored magnetic nanoparticles for optimizing magnetic fluid hyperthermia.

    PubMed

    Khandhar, Amit P; Ferguson, R Matthew; Simon, Julian A; Krishnan, Kannan M

    2012-03-01

    Magnetic Fluid Hyperthermia (MFH) is a promising approach towards adjuvant cancer therapy that is based on the localized heating of tumors using the relaxation losses of iron oxide magnetic nanoparticles (MNPs) in alternating magnetic fields (AMF). In this study, we demonstrate optimization of MFH by tailoring MNP size to an applied AMF frequency. Unlike conventional aqueous synthesis routes, we use organic synthesis routes that offer precise control over MNP size (diameter ∼10 to 25 nm), size distribution, and phase purity. Furthermore, the particles are successfully transferred to the aqueous phase using a biocompatible amphiphilic polymer, and demonstrate long-term shelf life. A rigorous characterization protocol ensures that the water-stable MNPs meet all the critical requirements: (1) uniform shape and monodispersity, (2) phase purity, (3) stable magnetic properties approaching that of the bulk, (4) colloidal stability, (5) substantial shelf life, and (6) pose no significant in vitro toxicity. Using a dedicated hyperthermia system, we then identified that 16 nm monodisperse MNPs (σ-0.175) respond optimally to our chosen AMF conditions (f = 373 kHz, H₀ = 14 kA/m); however, with a broader size distribution (σ-0.284) the Specific Loss Power (SLP) decreases by 30%. Finally, we show that these tailored MNPs demonstrate maximum hyperthermia efficiency by reducing viability of Jurkat cells in vitro, suggesting our optimization translates truthfully to cell populations. In summary, we present a way to intrinsically optimize MFH by tailoring the MNPs to any applied AMF, a required precursor to optimize dose and time of treatment. Copyright © 2011 Wiley Periodicals, Inc.

  14. Tailored Magnetic Nanoparticles for Optimizing Magnetic Fluid Hyperthermia

    PubMed Central

    Khandhar, Amit; Ferguson, R. Matthew; Simon, Julian A.; Krishnan, Kannan M.

    2011-01-01

    Magnetic Fluid Hyperthermia (MFH) is a promising approach towards adjuvant cancer therapy that is based on the localized heating of tumors using the relaxation losses of iron oxide magnetic nanoparticles (MNPs) in alternating magnetic fields (AMF). In this study, we demonstrate optimization of MFH by tailoring MNP size to an applied AMF frequency. Unlike conventional aqueous synthesis routes, we use organic synthesis routes that offer precise control over MNP size (diameter ~ 10–25 nm), size distribution and phase purity. Furthermore, the particles are successfully transferred to the aqueous phase using a biocompatible amphiphilic polymer, and demonstrate long-term shelf life. A rigorous characterization protocol ensures that the water-stable MNPs meet all the critical requirements: (1) uniform shape and monodispersity, (2) phase purity, (3) stable magnetic properties approaching that of the bulk, (4) colloidal stability, (5) substantial shelf life and (6) pose no significant in vitro toxicity. Using a dedicated hyperthermia system, we then identified that 16 nm monodisperse MNPs (σ ~ 0.175) respond optimally to our chosen AMF conditions (f = 373 kHz, Ho = 14 kA/m); however, with a broader size distribution (σ ~ 0.284) the Specific Loss Power (SLP) decreases by 30%. Finally, we show that these tailored MNPs demonstrate maximum hyperthermia efficiency by reducing viability of Jurkat cells in vitro, suggesting our optimization translates truthfully to cell populations. In summary, we present a way to intrinsically optimize MFH by tailoring the MNPs to any applied AMF, a required precursor to optimize dose and time of treatment. PMID:22213652

  15. Analytical modeling of hyperthermia using magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Bensenane, Mohamed Nassim; Senoudi, Assia Rachida; Benmouna, Reda; Ould-Kaddour, Fouzia

    2018-06-01

    Hyperthermia using magnetic nanoparticles (MNPs) is one of many techniques to treat cancer causing minimal damage to healthy tissues. In the present work we give an analytical resolution of the bio-heat equation (based on Pennes model) providing the temperature rise as a function of the characteristics of the magnetic nanoparticles, the applied magnetic field and the biological properties of the tissue. The temperature inside the tumor was found to be very sensitive to the frequency f of alternating magnetic field, magnetic field amplitude H0 and volume fraction φ. This study optimizes the intensity of magnetic field to reach ideal hyperthermia conditions. When f varies between 50 and 150 KHz, temperature increases from 39 °C until 53 °C; when H0 is ranged from 5 - 15 kA/m, it increases from 39.5 °C until 49 °C, and when volume fraction φ of MNPs is ranged from 2 × 10-4 to 3 × 10-4 it increases from 44 °C until 48 °C.

  16. A thermo-fluid analysis in magnetic hyperthermia

    NASA Astrophysics Data System (ADS)

    Iordana, Astefanoaei; Ioan, Dumitru; Alexandra, Stancu; Horia, Chiriac

    2014-04-01

    In the last years, hyperthermia induced by the heating of magnetic nanoparticles (MNPs) in an alternating magnetic field received considerable attention in cancer therapy. The thermal effects could be automatically controlled by using MNPs with selective magnetic absorption properties. In this paper, we analyze the temperature field determined by the heating of MNPs, injected in a malignant tissue, subjected to an alternating magnetic field. The main parameters which have a strong influence on temperature field are analyzed. The temperature evolution within healthy and tumor tissues are analyzed by finite element method (FEM) simulations in a thermo-fluid model. The cooling effect produced by blood flow in blood vessels from the tumor is considered. A thermal analysis is conducted under different distributions of MNP injection sites. The interdependence between the optimum dose of the nanoparticles and various types of tumors is investigated in order to understand their thermal effect on hyperthermia therapy. The control of the temperature field in the tumor and healthy tissues is an important step in the healing treatment.

  17. Methamphetamine-induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents.

    PubMed

    Albers, D S; Sonsalla, P K

    1995-12-01

    Neurotoxic doses of methamphetamine (METH) can cause hyperthermia in experimental animals. Damage sustained to dopaminergic nerve terminals by this stimulant can be reduced by environmental cooling or by pharmacological manipulation which attenuates the hyperthermia. Many pharmacological agents with very diverse actions protect against METH-induced neuropathology. Several of these compounds, as well as drugs which do not protect, were investigated to determine if there was a relationship between protection and METH-induced hyperthermia. Mice received METH with or without concurrent administration of other drugs and core (i.e., colonic) temperature was monitored during treatment. The animals were sacrificed > or = 5 days later and neostriatal tyrosine hydroxylase activity and dopamine were measured. Core temperature was significantly elevated (> or = 2 degrees C) in mice treated with doses of METH which produced > or = 90% losses in striatal dopamine but not in mice less severally affected (only 50% loss of dopamine). Concurrent treatment of mice with METH and pharmacological agents which protected partially or completely from METH-induced toxicity also prevented the hyperthermic response (i.e., dopamine receptor antagonists, fenfluramine, dizocilpine, alpha-methyl-p-tyrosine, phenytoin, aminooxyacetic acid and propranol). These findings are consistent with the hypothesis that the hyperthermia produced by METH contributes to its neuropathology. However, studies with reserpine, a compound which dramatically lowers core temperature, demonstrated that hyperthermia per se is not a requirement for METH-induced neurotoxicity. Although core temperature was elevated in reserpinized mice treated with METH as compared with reserpinized control mice, their temperatures remained significantly lower than in nonreserpinized control mice. However, the hypothermic state produced in the reserpinized mice did not provide protection from METH-induced toxicity. These data demonstrate

  18. Spatial variation in hyperthermia emergency department visits among those with employer-based insurance in the United States - a case-crossover analysis.

    PubMed

    Saha, Shubhayu; Brock, John W; Vaidyanathan, Ambarish; Easterling, David R; Luber, George

    2015-03-04

    Predictions of intense heat waves across the United States will lead to localized health impacts, most of which are preventable. There is a need to better understand the spatial variation in the morbidity impacts associated with extreme heat across the country to prevent such adverse health outcomes. Hyperthermia-related emergency department (ED) visits were obtained from the Truven Health MarketScan(®) Research dataset for 2000-2010. Three measures of daily ambient heat were constructed using meteorological observations from the National Climatic Data Center (maximum temperature, heat index) and the Spatial Synoptic Classification. Using a time-stratified case crossover approach, odds ratio of hyperthermia-related ED visit were estimated for the three different heat measures. Random effects meta-analysis was used to combine the odds ratios for 94 Metropolitan Statistical Areas (MSA) to examine the spatial variation by eight latitude categories and nine U.S. climate regions. Examination of lags for all three temperature measures showed that the odds ratio of ED visit was statistically significant and highest on the day of the ED visit. For heat waves lasting two or more days, additional statistically significant association was observed when heat index and synoptic classification was used as the temperature measure. These results were insensitive to the inclusion of air pollution measures. On average, the maximum temperature on the day of an ED visit was 93.4°F in 'South' and 81.9°F in the 'Northwest' climatic regions of United States. The meta-analysis showed higher odds ratios of hyperthermia ED visit in the central and the northern parts of the country compared to the south and southwest. The results showed spatial variation in average temperature on days of ED visit and odds ratio for hyperthermia ED visits associated with extreme heat across United States. This suggests that heat response plans need to be customized for different regions and the potential

  19. Design of a compact antenna with flared groundplane for a wearable breast hyperthermia system.

    PubMed

    Curto, Sergio; Prakash, Punit

    2015-01-01

    Currently available microwave hyperthermia systems for breast cancer treatment do not conform to the intact breast and provide limited control of heating patterns, thereby hindering an effective treatment. A compact patch antenna with a flared groundplane that may be integrated within a wearable hyperthermia system for the treatment of the intact breast disease is proposed. A 3D simulation-based approach was employed to optimise the antenna design with the objective of maximising the hyperthermia treatment volume (41 °C iso-therm) while maintaining good impedance matching. The optimised antenna design was fabricated and experimentally evaluated with ex vivo tissue measurements. The optimised compact antenna yielded a -10 dB bandwidth of 90 MHz centred at 915 MHz, and was capable of creating hyperthermia treatment volumes up to 14.4 cm(3) (31 mm × 28 mm × 32 mm) with an input power of 15 W. Experimentally measured reflection coefficient and transient temperature profiles were in good agreement with simulated profiles. Variations of + 50% in blood perfusion yielded variations in the treatment volume up to 11.5%. When compared to an antenna with a similar patch element employing a conventional rectangular groundplane, the antenna with flared groundplane afforded 22.3% reduction in required power levels to reach the same temperature, and yielded 2.4 times larger treatment volumes. The proposed patch antenna with a flared groundplane may be integrated within a wearable applicator for hyperthermia treatment of intact breast targets and has the potential to improve efficiency, increase patient comfort, and ultimately clinical outcomes.

  20. Hyperthermia increases accumulation of technetium-99m-labeled liposomes in feline sarcomas.

    PubMed

    Matteucci, M L; Anyarambhatla, G; Rosner, G; Azuma, C; Fisher, P E; Dewhirst, M W; Needham, D; Thrall, D E

    2000-09-01

    The effect of hyperthermia on the accumulation of technetium-99m-labeled liposomes was studied in feline sarcomas. Each cat received two separate injections of liposomes. The first was used to quantify the amount of technetium-99m-labeled liposomes within the tumor under normothermic conditions. The second injection was made at the beginning of a 60-min hyperthermia procedure. Planar scintigraphy was used to measure the activity of technetium-99m-labeled liposomes within the tumor at predetermined times up to 18 h after injection. Regions of interest were drawn for the tumor, lungs, liver, kidney, and aorta. Counts in the regions of interest were decay corrected. Counts/pixel in the tumor under normothermic and hyperthermic conditions were normalized to aorta counts/pixel. A total of 16 cats were eligible for the study. In two of the 16 cats, incomplete count data precluded analysis. In the remaining 14 cats, hyperthermia resulted in a significant increase in liposome accumulation in the tumor (P = 0.001). Tumor volume ranged from 1.2 to 236.2 cm3, and thermal dose ranged from 2.0 to 243.3 CEM43CT90 (equivalent time that the 10th percentile temperature was equal to 43 degrees C). There was not a relationship between either tumor volume or hyperthermia dose on the magnitude of increased liposome accumulation, suggesting that this method has application across a range of tumor volumes and degrees of heatibility.

  1. Functional Abdominal Pain: "Get" the Function, Loose the Pain.

    PubMed

    Draeger-Muenke, Reinhild

    2015-07-01

    Functional abdominal pain is a mind-body, psychosocial, and self-reinforcing experience with significant consequences for the sufferer and the surrounding support network. The occurrence of unpredictable symptoms and their severity add an element of dread and feeling out-of-control to daily life and often reduce overall functioning in a downward spiral. Two clinical presentations of functional abdominal pain are offered in this article (composites to protect confidentiality) dealing with abdominal pain syndrome and abdominal migraines. The treatment demonstrates the use of hypnotic principles for self-regulation, exploration, and meaning-making. Hypnosis treatment is conducted in combination with mindfulness-based interventions and Traditional Chinese Medicine's (TCM) teachings regarding abdominal health and illness. The clinical examples illustrate medical findings that suggest children with early life stress and an early onset of gastrointestinal somatization may not simply outgrow their functional abdominal pain but may suffer into adulthood.

  2. Doxorubicin loaded dual pH- and thermo-responsive magnetic nanocarrier for combined magnetic hyperthermia and targeted controlled drug delivery applications

    NASA Astrophysics Data System (ADS)

    Hervault, Aziliz; Dunn, Alexander E.; Lim, May; Boyer, Cyrille; Mott, Derrick; Maenosono, Shinya; Thanh, Nguyen T. K.

    2016-06-01

    Magnetic nanocarriers have attracted increasing attention for multimodal cancer therapy due to the possibility to deliver heat and drugs locally. The present study reports the development of magnetic nanocomposites (MNCs) made of an iron oxide core and a pH- and thermo-responsive polymer shell, that can be used as both hyperthermic agent and drug carrier. The conjugation of anticancer drug doxorubicin (DOX) to the pH- and thermo-responsive MNCs via acid-cleavable imine linker provides advanced features for the targeted delivery of DOX molecules via the combination of magnetic targeting, and dual pH- and thermo-responsive behaviour which offers spatial and temporal control over the release of DOX. The iron oxide cores exhibit a superparamagnetic behaviour with a saturation magnetization around 70 emu g-1. The MNCs contained 8.1 wt% of polymer and exhibit good heating properties in an alternating magnetic field. The drug release experiments confirmed that only a small amount of DOX was released at room temperature and physiological pH, while the highest drug release of 85.2% was obtained after 48 h at acidic tumour pH under hyperthermia conditions (50 °C). The drug release kinetic followed Korsmeyer-Peppas model and displayed Fickian diffusion mechanism. From the results obtained it can be concluded that this smart magnetic nanocarrier is promising for applications in multi-modal cancer therapy, to target and efficiently deliver heat and drug specifically to the tumour.Magnetic nanocarriers have attracted increasing attention for multimodal cancer therapy due to the possibility to deliver heat and drugs locally. The present study reports the development of magnetic nanocomposites (MNCs) made of an iron oxide core and a pH- and thermo-responsive polymer shell, that can be used as both hyperthermic agent and drug carrier. The conjugation of anticancer drug doxorubicin (DOX) to the pH- and thermo-responsive MNCs via acid-cleavable imine linker provides advanced

  3. MR thermometry characterization of a hyperthermia ultrasound array designed using the k-space computational method

    PubMed Central

    Al-Bataineh, Osama M; Collins, Christopher M; Park, Eun-Joo; Lee, Hotaik; Smith, Nadine Barrie

    2006-01-01

    Background Ultrasound induced hyperthermia is a useful adjuvant to radiation therapy in the treatment of prostate cancer. A uniform thermal dose (43°C for 30 minutes) is required within the targeted cancerous volume for effective therapy. This requires specific ultrasound phased array design and appropriate thermometry method. Inhomogeneous, acoustical, three-dimensional (3D) prostate models and economical computational methods provide necessary tools to predict the appropriate shape of hyperthermia phased arrays for better focusing. This research utilizes the k-space computational method and a 3D human prostate model to design an intracavitary ultrasound probe for hyperthermia treatment of prostate cancer. Evaluation of the probe includes ex vivo and in vivo controlled hyperthermia experiments using the noninvasive magnetic resonance imaging (MRI) thermometry. Methods A 3D acoustical prostate model was created using photographic data from the Visible Human Project®. The k-space computational method was used on this coarse grid and inhomogeneous tissue model to simulate the steady state pressure wavefield of the designed phased array using the linear acoustic wave equation. To ensure the uniformity and spread of the pressure in the length of the array, and the focusing capability in the width of the array, the equally-sized elements of the 4 × 20 elements phased array were 1 × 14 mm. A probe was constructed according to the design in simulation using lead zerconate titanate (PZT-8) ceramic and a Delrin® plastic housing. Noninvasive MRI thermometry and a switching feedback controller were used to accomplish ex vivo and in vivo hyperthermia evaluations of the probe. Results Both exposimetry and k-space simulation results demonstrated acceptable agreement within 9%. With a desired temperature plateau of 43.0°C, ex vivo and in vivo controlled hyperthermia experiments showed that the MRI temperature at the steady state was 42.9 ± 0.38°C and 43.1 ± 0.80

  4. MR thermometry characterization of a hyperthermia ultrasound array designed using the k-space computational method.

    PubMed

    Al-Bataineh, Osama M; Collins, Christopher M; Park, Eun-Joo; Lee, Hotaik; Smith, Nadine Barrie

    2006-10-25

    Ultrasound induced hyperthermia is a useful adjuvant to radiation therapy in the treatment of prostate cancer. A uniform thermal dose (43 degrees C for 30 minutes) is required within the targeted cancerous volume for effective therapy. This requires specific ultrasound phased array design and appropriate thermometry method. Inhomogeneous, acoustical, three-dimensional (3D) prostate models and economical computational methods provide necessary tools to predict the appropriate shape of hyperthermia phased arrays for better focusing. This research utilizes the k-space computational method and a 3D human prostate model to design an intracavitary ultrasound probe for hyperthermia treatment of prostate cancer. Evaluation of the probe includes ex vivo and in vivo controlled hyperthermia experiments using the noninvasive magnetic resonance imaging (MRI) thermometry. A 3D acoustical prostate model was created using photographic data from the Visible Human Project. The k-space computational method was used on this coarse grid and inhomogeneous tissue model to simulate the steady state pressure wavefield of the designed phased array using the linear acoustic wave equation. To ensure the uniformity and spread of the pressure in the length of the array, and the focusing capability in the width of the array, the equally-sized elements of the 4 x 20 elements phased array were 1 x 14 mm. A probe was constructed according to the design in simulation using lead zerconate titanate (PZT-8) ceramic and a Delrin plastic housing. Noninvasive MRI thermometry and a switching feedback controller were used to accomplish ex vivo and in vivo hyperthermia evaluations of the probe. Both exposimetry and k-space simulation results demonstrated acceptable agreement within 9%. With a desired temperature plateau of 43.0 degrees C, ex vivo and in vivo controlled hyperthermia experiments showed that the MRI temperature at the steady state was 42.9 +/- 0.38 degrees C and 43.1 +/- 0.80 degrees C

  5. Hysteresis losses and specific absorption rate measurements in magnetic nanoparticles for hyperthermia applications.

    PubMed

    Coïsson, Marco; Barrera, Gabriele; Celegato, Federica; Martino, Luca; Kane, Shashank N; Raghuvanshi, Saroj; Vinai, Franco; Tiberto, Paola

    2017-06-01

    Magnetic hysteresis loops areas and hyperthermia on magnetic nanoparticles have been studied with the aim of providing reliable and reproducible methods of measuring the specific absorption rate (SAR). The SAR of Fe 3 O 4 nanoparticles with two different mean sizes, and Ni 1-x Zn x Fe 2 O 4 ferrites with 0 ≤ x ≤ 0.8 has been measured with three approaches: static hysteresis loops areas, dynamic hysteresis loops areas and hyperthermia of a water solution. For dynamic loops and thermometric measurements, specific experimental setups have been developed, that operate at comparable frequencies (≈ 69kHz and ≈ 100kHz respectively) and rf magnetic field peak values (up to 100mT). The hyperthermia setup has been fully modelled to provide a direct measurement of the SAR of the magnetic nanoparticles by taking into account the heat exchange with the surrounding environment in non-adiabatic conditions and the parasitic heating of the water due to ionic currents. Dynamic hysteresis loops are shown to provide an accurate determination of the SAR except for superparamagnetic samples, where the boundary with a blocked regime could be crossed in dynamic conditions. Static hysteresis loops consistently underestimate the specific absorption rate but can be used to select the most promising samples. A means of reliably measure SAR of magnetic nanoparticles by different approaches for hyperthermia applications is presented and its validity discussed by comparing different methods. This work fits within the general subject of metrological traceability in medicine with a specific focus on magnetic hyperthermia. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Identification and functional characterization of a novel ryanodine receptor mutation causing malignant hyperthermia in North American and South American families.

    PubMed

    Sambuughin, N; Nelson, T E; Jankovic, J; Xin, C; Meissner, G; Mullakandov, M; Ji, J; Rosenberg, H; Sivakumar, K; Goldfarb, L G

    2001-09-01

    Malignant hyperthermia is a pharmacogenetic disorder associated with mutations in Ca(2+) regulatory proteins. It manifests as a hypermetabolic crisis triggered by commonly used anesthetics. Malignant hyperthermia susceptibility is a dominantly inherited predisposition to malignant hyperthermia that can be diagnosed by using caffeine/halothane contracture tests. In a multigenerational North American family with a severe form of malignant hyperthermia that has caused four deaths, a novel RYR1 A2350T missense mutation was identified in all individuals testing positive for malignant hyperthermia susceptibility. The same A2350T mutation was identified in an Argentinean family with two known fatal MH reactions. Functional analysis in HEK-293 cells revealed an altered Ca(2+) dependence and increased caffeine sensitivity of the expressed mutant protein thus confirming the pathogenic potential of the RYR1 A2350T mutation.

  7. Endocavity Ultrasound Hyperthermia for Locally Advanced Cervical Cancer: Patient-specific Modeling, Experimental Verification, and Combination with HDR Brachytherapy

    NASA Astrophysics Data System (ADS)

    Wootton, Jeffery; Chen, Xin; Prakash, Punit; Juang, Titania; Diederich, Chris

    2010-03-01

    The feasibility of targeted hyperthermia delivery by an intrauterine ultrasound applicator to patient-specific treatment volumes in conjunction with HDR brachytherapy was investigated using theory and experiment. 30 HDR brachytherapy treatment plans were inspected to define hyperthermia treatment volumes (HTVs) based on tumor and radiation target volumes. Several typical cases were imported into a patient-specific treatment planning platform that optimized acoustic output power from an endocavity multisectored tubular array to conform temperature and thermal dose to HTVs. Perfusion was within a clinical range of 0.5-3 kg m-3 s-1. Applicators were constructed with 1-3 elements at 6.5-8 MHz with 90°-360° sectoring and 25-35 mm heating length housed in a water-cooled PET catheter. Acoustic output was compared to heating in ex vivo tissue assessed with implanted thermometry. Radiation attenuation through the device was measured in an ionization chamber. The HTV extends 2-4 cm in diameter and 2-4 cm in length. The bladder and rectum can be within 10-12 mm. HTV targets can be covered with temperature clouds >41° and thermal dose t43>5 min with 45° C maximum temperature and rectal temperature <41.5° C. Sectored applicators preferentially direct energy laterally into the parametrium to limit heating of rectum and bladder. Interstitial brachytherapy catheters within the HTV could be used for thermal feedback during HT treatment. Temperature distributions in phantom show preferential heating within sectors and align well with acoustic output. Heating control along the device length and in angle is evident. A 4-6% reduction in radiation transmission through the transducers was observed, which could likely be compensated for in planning. Patient-specific modeling and experimental heating demonstrated 3-D conformal heating capabilities of endocavity ultrasound applicators.

  8. Effects of combined physical activity and dietary intervention on obesity and metabolic parameters in adults with abdominal obesity.

    PubMed

    Soon, Heng Kiang; Saad, Hazizi Abu; Taib, Mohd Nasir Mohd; Rahman, Hejar Abd; Mun, Chan Yoke

    2013-03-01

    A twelve-week controlled intervention trial was carried out to evaluate the effects of combined physical activity and dietary intervention on obesity and metabolic risk factors among employees of Universiti Putra Malaysia. Participants consisted of adults aged 25-55 years with no reported chronic diseases but with abdominal obesity. They were assigned to either a combined physical activity and dietary intervention group or a control group. The final sample consisted of 56 participants, with an equal number of 28 for each study group. No significant group effect was observed for any variable except for hip circumference (HC) and fasting plasma glucose (FPG). There was a significant increase in HC (p=0.007) and reduction in FPG (p=0.02) in the intervention group compared to the control group. In the intervention group, HC (p=0.002), triglycerides (TG) (p=0.0001), total cholesterol (TC) (p=0.0001), LDL cholesterol (LDLC) (p=0.0001) and FPG (p=0.005) were significantly reduced, while waist circumference (WC) (p=0.025) and the waist-to-hip ratio (WHR) (p=0.027) were significantly reduced in the control group. No significant change in steps/day or calorie intake'was observed in either group. Taken together, these data indicate that the combined physical activity and dietary intervention was not effective at improving diet or physical activity level. However, the intervention was effective in improving FPG among participants with abdominal obesity. The significant increase in HC in the interventions group warrants further study. These findings will be useful to further improve group-based intervention for the prevention and management of obesity.

  9. Safety and efficacy of combined epidural/general anesthesia during major abdominal surgery in patients with increased intracranial pressure: a cohort study.

    PubMed

    Zabolotskikh, Igor; Trembach, Nikita

    2015-05-15

    The increased intracranial pressure can significantly complicate the perioperative period in major abdominal surgery, increasing the risk of complications, the length of recovery from the surgery, worsening the outcome. Epidural anesthesia has become a routine component of abdominal surgery, but its use in patients with increased intracranial pressure remains controversial. The goal of the study was to evaluate the safety and efficacy of epidural anesthesia, according to monitoring of intracranial pressure in patients with increased intracranial pressure. The study includes 65 surgical patients who were routinely undergone the major abdominal surgery under combined epidural/general anesthesia. Depending on the initial ICP all patients were divided into 2 groups: 1 (N group) - patients with the normal intracranial pressure (≤12 mm Hg, n = 35) and 2 (E group) - patients with the elevated intracranial pressure (ICP > 12 mm Hg, n = 30). During the surgery we evaluated ICP, blood pressure, cerebral perfusion pressure (CPP). The parameters of recovery from anesthesia and the effectiveness of postoperative analgesia were also assessed. In N group ICP remained stable. In E group ICP decreased during anesthesia, the overall decline was 40% at the end of the operation (from 15 to 9 mm Hg (P <0.05)). The correction of MAP with vasopressors to maintain normal CPP was required mainly in patients with increased ICP (70% vs. 45%, p <0.05). CPP declined by 19% in N group. In E group the CPP reduction was 23%, and then it remained stable at 60 mm Hg. No significant differences in time of the recovery of consciousness, effectiveness of postoperative analgesia and complications between patients with initially normal levels of ICP and patients with ICH were noted. The combination of general and epidural anesthesia is safe and effective in patients with increased intracranial pressure undergoing elective abdominal surgery under the condition of maintaining the arterial

  10. The in vivo performance of biomagnetic hydroxyapatite nanoparticles in cancer hyperthermia therapy.

    PubMed

    Hou, Chun-Han; Hou, Sheng-Mou; Hsueh, Yu-Sheng; Lin, Jinn; Wu, Hsi-Chin; Lin, Feng-Huei

    2009-08-01

    Hyperthermia therapy for cancer has drawn more and more attention these days. In this study, we conducted an in vivo cancer hyperthermia study of the new magnetic hydroxyapatite nanoparticles by a mouse model. The magnetic hydroxyapatite nanoparticles were first made by co-precipitation method with the addition of Fe(2+). Then, magnetic-HAP powder (mHAP) or pure HAP powder (HAP) was mixed with phosphate buffer solution (PBS), respectively. The mixture was injected around the tumor. In order to achieve hyperthermia, the mice were placed into an inductive heater with high frequency and alternating magnetic field. Only the mice which were injected with mHAP and had been treated inside the magnetic field showed dramatic reduction of tumor volume, in the 15-day observation period. No local recurrence was noted. The blood test of mice proved that mHAP powders possessed good biocompatibility and little toxicity when injected subcutaneously. Therefore, our new magnetic hydroxyapatite nanoparticles have demonstrated therapeutic effect in a mouse model with little toxicity. Further study should be done before its application inside the human body.

  11. Bacterially synthesized ferrite nanoparticles for magnetic hyperthermia applications.

    PubMed

    Céspedes, Eva; Byrne, James M; Farrow, Neil; Moise, Sandhya; Coker, Victoria S; Bencsik, Martin; Lloyd, Jonathan R; Telling, Neil D

    2014-11-07

    Magnetic hyperthermia uses AC stimulation of magnetic nanoparticles to generate heat for cancer cell destruction. Whilst nanoparticles produced inside magnetotactic bacteria have shown amongst the highest reported heating to date, these particles are magnetically blocked so that strong heating occurs only for mobile particles, unless magnetic field parameters are far outside clinical limits. Here, nanoparticles extracellularly produced by the bacteria Geobacter sulfurreducens are investigated that contain Co or Zn dopants to tune the magnetic anisotropy, saturation magnetization and nanoparticle sizes, enabling heating within clinical field constraints. The heating mechanisms specific to either Co or Zn doping are determined from frequency dependent specific absorption rate (SAR) measurements and innovative AC susceptometry simulations that use a realistic model concerning clusters of polydisperse nanoparticles in suspension. Whilst both particle types undergo magnetization relaxation and show heating effects in water under low AC frequency and field, only Zn doped particles maintain relaxation combined with hysteresis losses even when immobilized. This magnetic heating process could prove important in the biological environment where nanoparticle mobility may not be possible. Obtained SARs are discussed regarding clinical conditions which, together with their enhanced MRI contrast, indicate that biogenic Zn doped particles are promising for combined diagnostics and cancer therapy.

  12. Artefacts in intracavitary temperature measurements during regional hyperthermia.

    PubMed

    Kok, H P; Van den Berg, C A T; Van Haaren, P M A; Crezee, J

    2007-09-07

    For adequate hyperthermia treatments, reliable temperature information during treatment is essential. During regional hyperthermia, temperature information is preferably obtained non-invasively from intracavitary or intraluminal measurements to avoid implant risks for the patient. However, for intracavitary or intraluminal thermometry optimal tissue contact is less natural as for invasive thermometry. In this study, the reliability of intraluminal/intracavitary measurements was examined in phantom experiments and in a numerical model for various extents of thermal contact between thermometry and the surroundings. Both thermocouple probes and fibre optic probes were investigated. Temperature rises after a 30 s power pulse of the 70 MHz AMC-4 hyperthermia system were measured in a tissue-equivalent phantom using a multisensor thermocouple probe placed centrally in a hollow tube. The tube was filled with (1) air, (2) distilled water or (3) saline solution that mimics the properties of tissue, simulating situations with (1) bad thermal contact and no power dissipation in the tube, (2) good thermal contact but no power dissipation or (3) good thermal contact and tissue representative power dissipation. For numerical simulations, a cylindrical symmetric model of a thermocouple probe or a fibre optic probe in a cavity was developed. The cavity was modelled as air, distilled water or saline solution. A generalised E-Field distribution was assumed, resulting in a power deposition. With this power deposition, the temperature rise after a 30 s power pulse was calculated. When thermal contact was bad (1), both phantom measurements and simulations with a thermocouple probe showed very high temperature rises (>0.5 degrees C), which are artefacts due to self-heating of the thermocouple probe, since no power is dissipated in air. Simulations with a fibre optic probe showed almost no temperature rise when the cavity was filled with air. When thermal contact was good, but no power

  13. Automatic tissue segmentation of head and neck MR images for hyperthermia treatment planning

    NASA Astrophysics Data System (ADS)

    Fortunati, Valerio; Verhaart, René F.; Niessen, Wiro J.; Veenland, Jifke F.; Paulides, Margarethus M.; van Walsum, Theo

    2015-08-01

    A hyperthermia treatment requires accurate, patient-specific treatment planning. This planning is based on 3D anatomical models which are generally derived from computed tomography. Because of its superior soft tissue contrast, magnetic resonance imaging (MRI) information can be introduced to improve the quality of these 3D patient models and therefore the treatment planning itself. Thus, we present here an automatic atlas-based segmentation algorithm for MR images of the head and neck. Our method combines multiatlas local weighting fusion with intensity modelling. The accuracy of the method was evaluated using a leave-one-out cross validation experiment over a set of 11 patients for which manual delineation were available. The accuracy of the proposed method was high both in terms of the Dice similarity coefficient (DSC) and the 95th percentile Hausdorff surface distance (HSD) with median DSC higher than 0.8 for all tissues except sclera. For all tissues, except the spine tissues, the accuracy was approaching the interobserver agreement/variability both in terms of DSC and HSD. The positive effect of adding the intensity modelling to the multiatlas fusion decreased when a more accurate atlas fusion method was used. Using the proposed approach we improved the performance of the approach previously presented for H&N hyperthermia treatment planning, making the method suitable for clinical application.

  14. A Parallel 2D Numerical Simulation of Tumor Cells Necrosis by Local Hyperthermia

    NASA Astrophysics Data System (ADS)

    Reis, R. F.; Loureiro, F. S.; Lobosco, M.

    2014-03-01

    Hyperthermia has been widely used in cancer treatment to destroy tumors. The main idea of the hyperthermia is to heat a specific region like a tumor so that above a threshold temperature the tumor cells are destroyed. This can be accomplished by many heat supply techniques and the use of magnetic nanoparticles that generate heat when an alternating magnetic field is applied has emerged as a promise technique. In the present paper, the Pennes bioheat transfer equation is adopted to model the thermal tumor ablation in the context of magnetic nanoparticles. Numerical simulations are carried out considering different injection sites for the nanoparticles in an attempt to achieve better hyperthermia conditions. Explicit finite difference method is employed to solve the equations. However, a large amount of computation is required for this purpose. Therefore, this work also presents an initial attempt to improve performance using OpenMP, a parallel programming API. Experimental results were quite encouraging: speedups around 35 were obtained on a 64-core machine.

  15. Immunohistochemistry of catecholamines in the hypothalamic-pituitary-adrenal system with special regard to fatal hypothermia and hyperthermia.

    PubMed

    Ishikawa, Takaki; Yoshida, Chiemi; Michiue, Tomomi; Perdekamp, Markus Grosse; Pollak, Stefan; Maeda, Hitoshi

    2010-05-01

    Catecholamines are involved in various stress responses. Previous studies have suggested applicability of the postmortem blood levels to investigations of physical stress responses or toxic/hyperthermic neuronal dysfunction during death process. The present study investigated cellular immunopositivity for adrenaline (Adr), noradrenaline (Nad) and dopamine (DA) in the hypothalamus, adenohypophysis and adrenal medulla with special regard to fatal hypothermia (cold exposure) and hyperthermia (heat stroke) to examine forensic pathological significance. Medicolegal autopsy cases (n=290, within 3 days postmortem) were examined. The proportions of catecholamine (Adr, Nad and DA)-positive cells (% positivity) in each tissue were quantitatively estimated using immunostaining. Hyperthermia cases (n=12) showed a lower neuronal DA-immunopositivity in the hypothalamus than hypothermia cases (n=20), while Nad- and DA-immunopositivities in the adrenal medulla were higher for hyperthermia than for hypothermia. Rates of Nad-immunopositivity in the adrenal medulla were very low for hypothermia. No such difference between hypothermia and hyperthermia was seen in the adenohypophysis. In hypothermia cases, cellular Nad-immunopositivity in the adrenal medulla correlated with the Nad level in cerebrospinal fluid (r=0.591, p<0.01). These observations suggest a characteristic immunohistochemical pattern of systemic stress response to fatal hypothermia and hyperthermia, involving the hypothalamus and adrenal medulla. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Thermosensitive Ni-based magnetic particles for self-controlled hyperthermia applications

    NASA Astrophysics Data System (ADS)

    Pandey, Sudip; Quetz, Abdiel; Aryal, Anil; Dubenko, Igor; Mazumdar, Dipanjan; Stadler, Shane; Ali, Naushad

    2017-04-01

    A number of ferromagnetic alloys in the bulk-form "thermoseeds" have been investigated for localized self-controlled hyperthermia treatment of cancer by substituting V, Mo, Cu, and Ga for Ni. The samples were prepared by arc-melting technique and annealed at 1223 K (950 °C) for 12 h in sealed quartz tubes. The structural, magnetic, and magnetocaloric properties of the samples were studied, using room temperature X-ray diffraction and a Superconducting Quantum Interference Device (SQUID) magnetometer. The magnetocaloric parameters (magnetic entropy changes, refrigeration capacity (RC), and hysteretic effects) have been calculated. It has been shown that recrystallization, i.e., annealing time and temperature, is crucial for controlling the heating characteristics of the seeds. A linear decrease in Curie temperature (TC) from 380 K (107 °C) to 200 K (-73 °C) was observed with increasing substitution of Ni by V, Mo, Cu, and Ga, while the magnetization value remained nearly constant for all substitutions. The optimal composition of these Ni-based alloys has been determined in order to allow self-controlling hyperthermia, implying a Curie temperature near the therapeutic level, 315-318 K (41-45 °C). The results showed that an extraordinary self-regulating heating effect has been achieved in Ni-based magnetic materials, which may create new vistas for hyperthermia cancer treatment.

  17. [Abdominal trauma].

    PubMed

    Sido, B; Grenacher, L; Friess, H; Büchler, M W

    2005-09-01

    Blunt abdominal trauma is much more frequent than penetrating abdominal trauma in Europe. As a consequence of improved quality of computed tomography, even complex liver injuries are increasingly being treated conservatively. However, missed hollow viscus injuries still remain a problem, as they considerably increase mortality in multiply injured patients. Laparoscopy decreases the rate of unnecessary laparotomies in perforating abdominal trauma and helps to diagnose injuries of solid organs and the diaphragm. However, the sensitivity in detecting hollow viscus injuries is low and the role of laparoscopy in blunt abdominal injury has not been defined. If intra-abdominal bleeding is difficult to control in hemodynamically unstable patients, damage control surgery with packing of the liver, total splenectomy, and provisional closure of hollow viscus injuries is of importance. Definitive surgical treatment follows hemodynamic stabilization and restoration of hemostasis. Injuries of the duodenum and pancreas after blunt abdominal trauma are often associated with other intra-abdominal injuries and the treatment depends on their location and severity.

  18. Targeted Magnetic Hyperthermia for Lung Cancer

    DTIC Science & Technology

    2013-09-01

    REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE 2. REPORT TYPE...3. DATES COVERED 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK...been reported to date . Using various in vitro and in vivo assays, we evaluated the ability of SPIO NP-mediated magnetic hyperthermia to effectively

  19. Hyperthermia treatment of spontaneously occurring oral cavity tumors using a computer-controlled Nd:YAG laser system

    NASA Astrophysics Data System (ADS)

    Panjehpour, Masoud; Overholt, Bergein F.; Frazier, Donita L.; Klebanow, Edward R.

    1991-05-01

    Conventional hyperthermia treatment of superficial tumors in the oral cavity is difficult due to inability in accessing the lesion. A new hyperthermia technique employing near infrared Nd:YAG irradiation delivered through an optical fiber is introduced for heating oral and nasal tumors in animals. This system consisted of an Nd:YAG laser, a He-Ne laser, a computer controlled optical shutter, an interstitial thermometer, computer and a printer. The tumors were heated via surface illumination of the lesion. A thermocouple implanted in the base of the tumor provided temperature feedback for laser energy regulation. Three spontaneously occurring canine (two squamous cell carcinoma on the gum, one pigmented melanoma on the hard palate) and one feline tumor (squamous cell carcinoma on the nose) have been treated with the Nd:YAG laser-induced hyperthermia delivered following radiation therapy. The tumor temperature was maintained between 43.2-43.5 degree(s)C for one hour. Nd:YAG hyperthermia allowed efficient delivery of heat to veterinary oral and nasal lesions otherwise impossible to treat with conventional heating techniques.

  20. Experimental ex-vivo validation of PMMA-based bone cements loaded with magnetic nanoparticles enabling hyperthermia of metastatic bone tumors

    NASA Astrophysics Data System (ADS)

    Harabech, Mariem; Kiselovs, Normunds Rungevics; Maenhoudt, Wim; Crevecoeur, Guillaume; Van Roost, Dirk; Dupré, Luc

    2017-05-01

    Percutaneous vertebroplasty comprises the injection of Polymethylmethacrylate (PMMA) bone cement into vertebrae and can be used for the treatment of compression fractures of vertebrae. Metastatic bone tumors can cause such compression fractures but are not treated when injecting PMMA-based bone cement. Hyperthermia of tumors can on the other hand be attained by placing magnetic nanoparticles (MNPs) in an alternating magnetic field (AMF). Loading the PMMA-based bone cement with MNPs could both serve vertebra stabilization and metastatic bone tumor hyperthermia when subjecting this PMMA-MNP to an AMF. A dedicated pancake coil is designed with a self-inductance of 10 μH in series with a capacitance of 0.1 μF that acts as resonant inductor-capacitor circuit to generate the AMF. The thermal rise is appraised in beef vertebra placed at 10 cm from the AMF generating circuit using optical temperatures sensors, i.e. in the center of the PMMA-MNP bone cement, which is located in the vicinity of metastatic bone tumors in clinical applications; and in the spine, which needs to be safeguarded to high temperature exposures. Results show a temperature rise of about 7 °C in PMMA-MNP whereas the temperature rise in the spine remains limited to 1 °C. Moreover, multicycles heating of PMMA-MNP is experimentally verified, validating the technical feasibility of having PMMA-MNP as basic component for percutaneous vertebroplasty combined with hyperthermia treatment of metastatic bone tumors.

  1. Controllable in vivo hyperthermia effect induced by pulsed high intensity focused ultrasound with low duty cycles

    PubMed Central

    Tu, Juan; Ha Hwang, Joo; Chen, Tao; Fan, Tingbo; Guo, Xiasheng; Crum, Lawrence A.; Zhang, Dong

    2012-01-01

    High intensity focused ultrasound (HIFU)-induced hyperthermia is a promising tool for cancer therapy. Three-dimensional nonlinear acoustic-bioheat transfer-blood flow-coupling model simulations and in vivo thermocouple measurements were performed to study hyperthermia effects in rabbit auricular vein exposed to pulsed HIFU (pHIFU) at varied duty cycles (DCs). pHIFU-induced temperature elevations are shown to increase with increasing DC. A critical DC of 6.9% is estimated for temperature at distal vessel wall exceeding 44 °C, although different tissue depths and inclusions could affect the DC threshold. The results demonstrate clinic potentials of achieving controllable hyperthermia by adjusting pHIFU DCs, while minimizing perivascular thermal injury. PMID:23112347

  2. Chronic abdominal wall pain misdiagnosed as functional abdominal pain.

    PubMed

    van Assen, Tijmen; de Jager-Kievit, Jenneke W A J; Scheltinga, Marc R; Roumen, Rudi M H

    2013-01-01

    The abdominal wall is often neglected as a cause of chronic abdominal pain. The aim of this study was to identify chronic abdominal wall pain syndromes, such as anterior cutaneous nerve entrapment syndrome (ACNES), in a patient population diagnosed with functional abdominal pain, including irritable bowel syndrome, using a validated 18-item questionnaire as an identification tool. In this cross-sectional analysis, 4 Dutch primary care practices employing physicians who were unaware of the existence of ACNES were selected. A total of 535 patients ≥18 years old who were registered with a functional abdominal pain diagnosis were approached when they were symptomatic to complete the questionnaire (maximum 18 points). Responders who scored at least the 10-point cutoff value (sensitivity, 0.94; specificity, 0.92) underwent a diagnostic evaluation to establish their final diagnosis. The main outcome was the presence and prevalence of ACNES in a group of symptomatic patients diagnosed with functional abdominal pain. Of 535 patients, 304 (57%) responded; 167 subjects (31%) recently reporting symptoms completed the questionnaire. Of 23 patients who scored above the 10-point cutoff value, 18 were available for a diagnostic evaluation. In half of these subjects (n = 9) functional abdominal pain (including IBS) was confirmed. However, the other 9 patients were suffering from abdominal wall pain syndrome, 6 of whom were diagnosed with ACNES (3.6% prevalence rate of symptomatic subjects; 95% confidence interval, 1.7-7.6), whereas the remaining 3 harbored a painful lipoma, an abdominal herniation, and a painful scar. A clinically relevant portion of patients previously diagnosed with functional abdominal pain syndrome in a primary care environment suffers from an abdominal wall pain syndrome such as ACNES.

  3. Prolonged environment-induced hyperthermia alters autophagy in oxidative skeletal muscle in Sus scrofa.

    PubMed

    Ganesan, Shanthi; Brownstein, Alexandra J; Pearce, Sarah C; Hudson, Matthew B; Gabler, Nicolas K; Baumgard, Lance H; Rhoads, Robert P; Selsby, Joshua T

    2018-05-01

    Prolonged heat stress represents a continuing threat to human health and agricultural production. Despite the broad, negative impact of prolonged hyperthermia little is known about underlying pathological mechanisms leading to negative health outcomes, which has limited the development of etiological interventions and left clinicians and producers with only cooling and rehydration strategies. The purpose of this investigation was to determine the extent to which prolonged environment-induced hyperthermia altered autophagy in oxidative skeletal muscle in a large animal model, serving the dual purpose of accurately modeling human physiology as well as agricultural production. We hypothesized that prolonged hyperthermia would induce autophagy in skeletal muscle, independent of the accompanying caloric restriction. To test this hypothesis pigs were treated as follows: thermoneutral (20 °C), heat stress (35 °C), or were held under thermoneutral conditions but pair-fed to the heat stress group for seven days. Upon euthanasia the red portion of the semitendinosus was collected. We found that prolonged hyperthermic exposure increased oxidative stress without a corresponding change in antioxidant enzyme activities. Hyperthermia prevented initiation of autophagy despite increased markers of nucleation, elongation and autophagosome formation. However, p62 relative protein abundance, which is inversely correlated with autophagic degradation, was strongly increased suggesting suppressed degradation of autophagosomes. Markers of mitophagy and mitochondrial abundance were largely similar between groups. These data indicate that faulty autophagy plays a key role in hyperthermic muscle dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Hyperthermia in low aspect-ratio magnetic nanotubes for biomedical applications

    NASA Astrophysics Data System (ADS)

    Gutierrez-Guzman, D. F.; Lizardi, L. I.; Otálora, J. A.; Landeros, P.

    2017-03-01

    A simple model for the magnetization reversal process of low aspect-ratio ferromagnetic nanotubes (MNTs) is presented. Because of advantages over other geometries, these structures are interesting for biomedical applications, such as magnetic hyperthermia cancer therapy, where the heat released during magnetic reversal is used to destroy tumors. For example, the tubular geometry provides two independent functional surfaces that may be selectively manipulated and also gives a storage cavity. Owing to their large surface to weight ratio and low mass density, MNTs are not decanted by gravity. We calculated magnetic phase diagrams, energy barriers, nucleation fields, and the amount of dissipated heat and specific absorption rate for magnetite nanotubes. The geometrical parameters were varied, and simple formulae were used to optimize the tube response under alternating excitation, as required for magnetic hyperthermia applications.

  5. Repressive effects of a capacitive-resistive electric transfer (CRet) hyperthermic apparatus combined with provitamin C on intracellular lipid-droplets formation in adipocytes.

    PubMed

    Kato, Shinya; Saitoh, Yasukazu; Miwa, Nobuhiko

    2013-01-01

    The aim of this study was to evaluate inhibitory effects of L-ascorbic acid-2-O-phosphate-Na(2) (APS), a pro-vitamin C, combined with hyperthermia on adipogenic differentiation of mouse stromal cells, OP9. OP9 preadipocytes were differentiated with serum replacement, administered with APS, and simultaneously treated with hyperthermia using a capacitive-resistive electric transfer (CRet) apparatus, which was conducted repeatedly twice a day. After 2 days, intracellular lipid droplets were stained with Oil Red O, then observed by microscopy and assessed spectrophotometrically. After stimulation by serum replacement for 2 days, lipid droplets were accumulated surrounding nucleus of OP9 cells. When APS of 0.15-0.6 mM was administered without hyperthermia, the amount of lipid droplets was markedly suppressed to 50.5%∼-11.3% versus the undifferentiated control, and diminished huge aggregates of lipid droplets. In OP9 cells treated by hyperthermia at 42°C for 0.5 min, 1 min or 3 min in the absence of APS, adipogenesis was suppressed abruptly in a time-dependent manner to 95.4%, 18.7% or -5.5%, respectively. Whereas, the percentage of adipogenesis was 96.8% in OP9 cells treated by mild hyperthermia alone at 41°C for 1 min. The simultaneous application of APS and hyperthermia at 41°C for 1 min markedly suppressed the accumulation of lipid droplets to 25.7%∼-66.2%. By scanning electron microscopy (SEM) observation, the surface of OP9 cells treated with APS and hyperthermia appeared to have the morphological property of undifferentiated OP9 cells. Combined treatment of APS and mild hyperthermia suppresses adipogenesis in OP9 cells, particularly in lipid droplets accumulation during spontaneous differentiation of OP9 preadipocytes.

  6. Comparison of magnetic nanoparticle and microwave hyperthermia cancer treatment methodology and treatment effect in a rodent breast cancer model.

    PubMed

    Petryk, Alicia A; Giustini, Andrew J; Gottesman, Rachel E; Trembly, B Stuart; Hoopes, P Jack

    2013-12-01

    The purpose of this study was to compare the efficacy of iron oxide/magnetic nanoparticle hyperthermia (mNPH) and 915 MHz microwave hyperthermia at the same thermal dose in a mouse mammary adenocarcinoma model. A thermal dose equivalent to 60 min at 43 °C (CEM60) was delivered to a syngeneic mouse mammary adenocarcinoma flank tumour (MTGB) via mNPH or locally delivered 915 MHz microwaves. mNPH was generated with ferromagnetic, hydroxyethyl starch-coated magnetic nanoparticles. Following mNP delivery, the mouse/tumour was exposed to an alternating magnetic field (AMF). The microwave hyperthermia treatment was delivered by a 915 MHz microwave surface applicator. Time required for the tumour to reach three times the treatment volume was used as the primary study endpoint. Acute pathological effects of the treatments were determined using conventional histopathological techniques. Locally delivered mNPH resulted in a modest improvement in treatment efficacy as compared to microwave hyperthermia (p = 0.09) when prescribed to the same thermal dose. Tumours treated with mNPH also demonstrated reduced peritumoral normal tissue damage. Our results demonstrate similar tumour treatment efficacy when tumour heating is delivered by locally delivered mNPs and 915 MHz microwaves at the same measured thermal dose. However, mNPH treatments did not result in the same type or level of peritumoral damage seen with the microwave hyperthermia treatments. These data suggest that mNP hyperthermia is capable of improving the therapeutic ratio for locally delivered tumour hyperthermia. These results further indicate that this improvement is due to improved heat localisation in the tumour.

  7. Spatial and Temporal Control of Hyperthermia Using Real Time Ultrasonic Thermal Strain Imaging with Motion Compensation, Phantom Study

    PubMed Central

    Foiret, Josquin; Ferrara, Katherine W.

    2015-01-01

    Mild hyperthermia has been successfully employed to induce reversible physiological changes that can directly treat cancer and enhance local drug delivery. In this approach, temperature monitoring is essential to avoid undesirable biological effects that result from thermal damage. For thermal therapies, Magnetic Resonance Imaging (MRI) has been employed to control real-time Focused Ultrasound (FUS) therapies. However, combined ultrasound imaging and therapy systems offer the benefits of simple, low-cost devices that can be broadly applied. To facilitate such technology, ultrasound thermometry has potential to reliably monitor temperature. Control of mild hyperthermia was previously achieved using a proportional-integral-derivative (PID) controller based on thermocouple measurements. Despite accurate temporal control of heating, this method is limited by the single position at which the temperature is measured. Ultrasound thermometry techniques based on exploiting the thermal dependence of acoustic parameters (such as longitudinal velocity) can be extended to create thermal maps and allow an accurate monitoring of temperature with good spatial resolution. However, in vivo applications of this technique have not been fully developed due to the high sensitivity to tissue motion. Here, we propose a motion compensation method based on the acquisition of multiple reference frames prior to treatment. The technique was tested in the presence of 2-D and 3-D physiological-scale motion and was found to provide effective real-time temperature monitoring. PID control of mild hyperthermia in presence of motion was then tested with ultrasound thermometry as feedback and temperature was maintained within 0.3°C of the requested value. PMID:26244783

  8. Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors.

    PubMed

    Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

    2015-02-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are serotonin (5-HT) analogs often abused together, which alters thermoregulation that may indicate the severity of serotonin toxicity. Our recent studies have revealed that co-administration of monoamine oxidase inhibitor harmaline leads to greater and prolonged exposure to 5-HT agonist 5-MeO-DMT that might be influenced by cytochrome P450 2D6 (CYP2D6) status. This study was to define the effects of harmaline and 5-MeO-DMT on thermoregulation in wild-type and CYP2D6-humanized (Tg-CYP2D6) mice, as well as the involvement of 5-HT receptors. Animal core body temperatures were monitored noninvasively in the home cages after implantation of telemetry transmitters and administration of drugs. Harmaline (5 and 15 mg/kg, i.p.) alone was shown to induce hypothermia that was significantly affected by CYP2D6 status. In contrast, higher doses of 5-MeO-DMT (10 and 20 mg/kg) alone caused hyperthermia. Co-administration of harmaline (2, 5 or 15 mg/kg) remarkably potentiated the hyperthermia elicited by 5-MeO-DMT (2 or 10 mg/kg), which might be influenced by CYP2D6 status at certain dose combination. Interestingly, harmaline-induced hypothermia was only attenuated by 5-HT1A receptor antagonist WAY-100635, whereas 5-MeO-DMT- and harmaline-5-MeO-DMT-induced hyperthermia could be suppressed by either WAY-100635 or 5-HT2A receptor antagonists (MDL-100907 and ketanserin). Moreover, stress-induced hyperthermia under home cage conditions was not affected by WAY-100635 but surprisingly attenuated by MDL-100907 and ketanserin. Our results indicate that co-administration of monoamine oxidase inhibitor largely potentiates 5-MeO-DMT-induced hyperthermia that involves the activation of both 5-HT1A and 5-HT2A receptors. These findings shall provide insights into development of anxiolytic drugs and new strategies to relieve the lethal hyperthermia in serotonin toxicity.

  9. Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors

    PubMed Central

    Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

    2014-01-01

    5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are serotonin (5-HT) analogs often abused together, which alters thermoregulation that may indicate the severity of serotonin toxicity. Our recent studies have revealed that co-administration of monoamine oxidase inhibitor harmaline leads to greater and prolonged exposure to 5-HT agonist 5-MeO-DMT that might be influenced by cytochrome P450 2D6 (CYP2D6) status. This study was to define the effects of harmaline and 5-MeO-DMT on thermoregulation in wild-type and CYP2D6-humanized (Tg-CYP2D6) mice, as well as the involvement of 5-HT receptors. Animal core body temperatures were monitored noninvasively in the home cages after implantation of telemetry transmitters and administration of drugs. Harmaline (5 and 15 mg/kg, i.p.) alone was shown to induce hypothermia that was significantly affected by CYP2D6 status. In contrast, higher doses of 5-MeO-DMT (10 and 20 mg/kg) alone caused hyperthermia. Co-administration of harmaline (2, 5 or 15 mg/kg) remarkably potentiated the hyperthermia elicited by 5-MeO-DMT (2 or 10 mg/kg), which might be influenced by CYP2D6 status at certain dose combination. Interestingly, harmaline-induced hypothermia was only attenuated by 5-HT1A receptor antagonist WAY-100635, whereas 5-MeO-DMT- and harmaline-5-MeO-DMT-induced hyperthermia could be suppressed by either WAY-100635 or 5-HT2A receptor antagonists (MDL-100907 and ketanserin). Moreover, stress-induced hyperthermia under home cage conditions was not affected by WAY-100635 but surprisingly attenuated by MDL-100907 and ketanserin. Our results indicate that co-administration of monoamine oxidase inhibitor largely potentiates 5-MeO-DMT-induced hyperthermia that involves the activation of both 5-HT1A and 5-HT2A receptors. These findings shall provide insights into development of anxiolytic drugs and new strategies to relieve the lethal hyperthermia in serotonin toxicity. PMID:25446678

  10. Induced apoptosis by mild hyperthermia occurs via telomerase inhibition on the three human myeloid leukemia cell lines: TF-1, K562, and HL-60.

    PubMed

    Deezagi, Abdolkhaleg; Manteghi, Sanaz; Khosravani, Pardis; Vaseli-Hagh, Neda; Soheili, Zahra-Soheila

    2009-09-01

    The purpose of this research was to understand the effect of hyperthermia on the telomerase activity in human leukemic cell lines (HL-60, K562, and TF-1). The cells were treated by hyperthermia at the range of 41-44 degrees C for 120 min and incubated for 96 h. Then telomerase activity, cell proliferation, and apoptosis were assessed. The results indicated that hyperthermia significantly induced apoptosis on the cells. The cells exhibited pre-apoptotic pattern at 41 and 42 degrees C at 60-120 min and apoptotic pattern at 43 and 44 degrees C over 30 min after hyperthermia. Telomerase activity (that was assayed immediately after hyperthermia) was stable at 41-42 degrees C for 60 min but decreased to 35-40% at 120 min. However, at severe hyperthermia (43-44 degrees C) telomerase activity was decreased in a time- and dose-dependent manner. Following hyperthermia (41-44 degrees C up to 120 min), the cells were incubated for 96 h. In these conditions, the telomerase activity was decreased by about 60-80% in comparison with that untreated control cells.

  11. Heating efficiency in magnetic nanoparticle hyperthermia

    NASA Astrophysics Data System (ADS)

    Deatsch, Alison E.; Evans, Benjamin A.

    2014-03-01

    Magnetic nanoparticles for hyperthermic treatment of cancers have gained significant attention in recent years. In magnetic hyperthermia, three independent mechanisms result in thermal energy upon stimulation: Néel relaxation, Brownian relaxation, and hysteresis loss. The relative contribution of each is strongly dependent on size, shape, crystalline anisotropy, and degree of aggregation or agglomeration of the nanoparticles. We review the effects of each of these physical mechanisms in light of recent experimental studies and suggest routes for progress in the field.

  12. Design of optimal hyperthermia protocols for prostate cancer by controlling HSP expression through computer modeling (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Rylander, Marissa N.; Feng, Yusheng; Diller, Kenneth; Bass, J.

    2005-04-01

    Heat shock proteins (HSP) are critical components of a complex defense mechanism essential for preserving cell survival under adverse environmental conditions. It is inevitable that hyperthermia will enhance tumor tissue viability, due to HSP expression in regions where temperatures are insufficient to coagulate proteins, and would likely increase the probability of cancer recurrence. Although hyperthermia therapy is commonly used in conjunction with radiotherapy, chemotherapy, and gene therapy to increase therapeutic effectiveness, the efficacy of these therapies can be substantially hindered due to HSP expression when hyperthermia is applied prior to these procedures. Therefore, in planning hyperthermia protocols, prediction of the HSP response of the tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of overall tissue response. In this paper, we present a highly accurate, adaptive, finite element tumor model capable of predicting the HSP expression distribution and tissue damage region based on measured cellular data when hyperthermia protocols are specified. Cubic spline representations of HSP27 and HSP70, and Arrhenius damage models were integrated into the finite element model to enable prediction of the HSP expression and damage distribution in the tissue following laser heating. Application of the model can enable optimized treatment planning by controlling of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution.

  13. Echinococcus multilocularis Detection in Live Eurasian Beavers (Castor fiber) Using a Combination of Laparoscopy and Abdominal Ultrasound under Field Conditions

    PubMed Central

    Gottstein, Bruno; Cracknell, John; Schwab, Gerhard; Rosell, Frank

    2015-01-01

    Echinococcus multilocularis is an important pathogenic zoonotic parasite of health concern, though absent in the United Kingdom. Eurasian beavers (Castor fiber) may act as a rare intermediate host, and so unscreened wild caught individuals may pose a potential risk of introducing this parasite to disease-free countries through translocation programs. There is currently no single definitive ante-mortem diagnostic test in intermediate hosts. An effective non-lethal diagnostic, feasible under field condition would be helpful to minimise parasite establishment risk, where indiscriminate culling is to be avoided. This study screened live beavers (captive, n = 18 or wild-trapped in Scotland, n = 12) and beaver cadavers (wild Scotland, n = 4 or Bavaria, n = 11), for the presence of E. multilocularis. Ultrasonography in combination with minimally invasive surgical examination of the abdomen by laparoscopy was viable under field conditions for real-time evaluation in beavers. Laparoscopy alone does not allow the operator to visualize the parenchyma of organs such as the liver, or inside the lumen of the gastrointestinal tract, hence the advantage of its combination with abdominal ultrasonography. All live beavers and Scottish cadavers were largely unremarkable in their haematology and serum biochemistry with no values suspicious for liver pathology or potentially indicative of E. multilocularis infection. This correlated well with ultrasound, laparoscopy, and immunoblotting, which were unremarkable in these individuals. Two wild Bavarian individuals were suspected E. multilocularis positive at post-mortem, through the presence of hepatic cysts. Sensitivity and specificity of a combination of laparoscopy and abdominal ultrasonography in the detection of parasitic liver cyst lesions was 100% in the subset of cadavers (95%Confidence Intervals 34.24–100%, and 86.7–100% respectively). For abdominal ultrasonography alone sensitivity was only 50% (95%CI 9.5–90.6%), with

  14. Canine Malignant Hyperthermia: Diagnosis of Susceptibility in a Breeding Colony

    PubMed Central

    O'Brien, P. J.; Cribb, P. H.; White, R. J.; Olfert, E. D.; Steiss, J. E.

    1983-01-01

    Fifteen related dogs were studied for susceptibility to malignant hyperthermia using halothane challenge and caffeine contracture tests. These dogs had hypertrophied muscles, were of a nervous temperament and had rectal temperatures at the upper limit of the normal range. Clinical pathology findings were mild elevations of serum aspartate transaminase and mean corpuscular hemoglobin. In vitro caffeine contracture tests were performed on muscle biopsies from five of these dogs. The concentration of caffeine required to increase resting tension by 1 g in biopsy specimens of these dogs was significantly lower than that required for control dogs: 7.6 ± 1.38 (x̄ ± SEM) versus 15.5 ± 2.52 mM (P < 0.025), and in the presence of 1% halothane, 3.6 ± 1.44 versus 10.6 ± 2.19 mM (P < 0.05). Internal nuclei, fiber caliber variation and fiber hypertrophy were found in histological studies of muscle biopsies. Two other dogs possibly died of a canine stress syndrome analagous to the porcine stress syndrome which occurs in malignant hyperthermia susceptible swine. Eight others of this family were anesthetized with halothane or methoxyflurane. Methoxyflurane did not trigger the syndrome. The first exposure to halothane caused death from malignant hyperthermia in two dogs and a third died on the second exposure to halothane. Postmortem findings were nonspecific. The other three dogs exposed to halothane recovered uneventfully. Inheritance of the defect conforms to a multifactorial pattern, with gradations of susceptibility. PMID:17422267

  15. Estimating abdominal adipose tissue with DXA and anthropometry.

    PubMed

    Hill, Alison M; LaForgia, Joe; Coates, Alison M; Buckley, Jonathan D; Howe, Peter R C

    2007-02-01

    To identify an anatomically defined region of interest (ROI) from DXA assessment of body composition that when combined with anthropometry can be used to accurately predict intra-abdominal adipose tissue (IAAT) in overweight/obese individuals. Forty-one postmenopausal women (age, 49 to 66 years; BMI, 26 to 37 kg/m(2)) underwent anthropometric and body composition assessments. ROI were defined as quadrilateral boxes extending 5 or 10 cm above the iliac crest and laterally to the edges of the abdominal soft tissue. A single-slice computed tomography (CT) scan was measured at the L3 to L4 intervertebral space, and abdominal skinfolds were taken. Forward step-wise regression revealed the best predictor model of IAAT area measured by CT (r(2) = 0.68, standard error of estimate = 17%) to be: IAAT area (centimeters squared) = 51.844 + DXA 10-cm ROI (grams) (0.031) + abdominal skinfold (millimeters) (1.342). Interobserver reliability for fat mass (r = 0.994; coefficient of variation, 2.60%) and lean mass (r = 0.986, coefficient of variation, 2.67%) in the DXA 10-cm ROI was excellent. This study has identified a DXA ROI that can be reliably measured using prominent anatomical landmarks, in this case, the iliac crest. Using this ROI, combined with an abdominal skinfold measurement, we have derived an equation to predict IAAT in overweight/obese postmenopausal women. This approach offers a simpler, safer, and more cost-effective method than CT for assessing the efficacy of lifestyle interventions aimed at reducing IAAT. However, this warrants further investigation and validation with an independent cohort.

  16. High-performance iron oxide nanoparticles for magnetic particle imaging - guided hyperthermia (hMPI)

    NASA Astrophysics Data System (ADS)

    Bauer, Lisa M.; Situ, Shu F.; Griswold, Mark A.; Samia, Anna Cristina S.

    2016-06-01

    Magnetic particle imaging (MPI) is an emerging imaging modality that allows the direct and quantitative mapping of iron oxide nanoparticles. In MPI, the development of tailored iron oxide nanoparticle tracers is paramount to achieving high sensitivity and good spatial resolution. To date, most MPI tracers being developed for potential clinical applications are based on spherical undoped magnetite nanoparticles. For the first time, we report on the systematic investigation of the effects of changes in chemical composition and shape anisotropy on the MPI performance of iron oxide nanoparticle tracers. We observed a 2-fold enhancement in MPI signal through selective doping of magnetite nanoparticles with zinc. Moreover, we demonstrated focused magnetic hyperthermia heating by adapting the field gradient used in MPI. By saturating the iron oxide nanoparticles outside of a field free region (FFR) with an external static field, we can selectively heat a target region in our test sample. By comparing zinc-doped magnetite cubic nanoparticles with undoped spherical nanoparticles, we could show a 5-fold improvement in the specific absorption rate (SAR) in magnetic hyperthermia while providing good MPI signal, thereby demonstrating the potential for high-performance focused hyperthermia therapy through an MPI-guided approach (hMPI).Magnetic particle imaging (MPI) is an emerging imaging modality that allows the direct and quantitative mapping of iron oxide nanoparticles. In MPI, the development of tailored iron oxide nanoparticle tracers is paramount to achieving high sensitivity and good spatial resolution. To date, most MPI tracers being developed for potential clinical applications are based on spherical undoped magnetite nanoparticles. For the first time, we report on the systematic investigation of the effects of changes in chemical composition and shape anisotropy on the MPI performance of iron oxide nanoparticle tracers. We observed a 2-fold enhancement in MPI signal

  17. Irradiation-hyperthermia in canine hemangiopericytomas: large-animal model for therapeutic response.

    PubMed

    Richardson, R C; Anderson, V L; Voorhees, W D; Blevins, W E; Inskeep, T K; Janas, W; Shupe, R E; Babbs, C F

    1984-11-01

    Results of irradiation-hyperthermia treatment in 11 dogs with naturally occurring hemangiopericytoma were reported. Similarities of canine and human hemangiopericytomas were described. Orthovoltage X-irradiation followed by microwave-induced hyperthermia resulted in a 91% objective response rate. A statistical procedure was given to evaluate quantitatively the clinical behavior of locally invasive, nonmetastatic tumors in dogs that were undergoing therapy for control of local disease. The procedure used a small sample size and demonstrated distribution of the data on a scaled response as well as transformation of the data through classical parametric and nonparametric statistical methods. These statistical methods set confidence limits on the population mean and placed tolerance limits on a population percentage. Application of the statistical methods to human and animal clinical trials was apparent.

  18. Heating characteristics of the TRIPAS hyperthermia system for deep seated malignancy.

    PubMed

    Surowiec, A; Bicher, H I

    1995-01-01

    A deep heating hyperthermia device TRIPAS (a triapplicator system) consisting of three independent, dielectrically loaded horn applicators operating in phase at 300 MHz was investigated. The heating characteristics produced by this hyperthermia system were analyzed by means of thermochromic liquid-crystal cards and a modified CDRH (Center for Devices and Regulatory Health) elliptical phantom. Both homogenous and inhomogeneous phantoms were used, simulating high and low permittivity tissues (muscle and lung). These equivalent tissues were made of polyacrylamide gel. The semiquantitative heating pattern analysis showed a central heating of 1/3 of maximum heating at a depth of 10 cm in both homogenous (muscle) and heterogenous (muscle/fat) phantoms. Also more uniform temperature/SAR distributions were generated in muscle equivalent material than those in lung.

  19. The role of size polydispersity in magnetic fluid hyperthermia: average vs. local infra/over-heating effects.

    PubMed

    Munoz-Menendez, Cristina; Conde-Leboran, Ivan; Baldomir, Daniel; Chubykalo-Fesenko, Oksana; Serantes, David

    2015-11-07

    An efficient and safe hyperthermia cancer treatment requires the accurate control of the heating performance of magnetic nanoparticles, which is directly related to their size. However, in any particle system the existence of some size polydispersity is experimentally unavoidable, which results in a different local heating output and consequently a different hyperthermia performance depending on the size of each particle. With the aim to shed some light on this significant issue, we have used a Monte Carlo technique to study the role of size polydispersity in heat dissipation at both the local (single particle) and global (macroscopic average) levels. We have systematically varied size polydispersity, temperature and interparticle dipolar interaction conditions, and evaluated local heating as a function of these parameters. Our results provide a simple guide on how to choose, for a given polydispersity degree, the more adequate average particle size so that the local variation in the released heat is kept within some limits that correspond to safety boundaries for the average-system hyperthermia performance. All together we believe that our results may help in the design of more effective magnetic hyperthermia applications.

  20. The use of abdominal muscle training, breathing exercises and abdominal massage to treat paediatric chronic functional constipation.

    PubMed

    Silva, C A G; Motta, M E F A

    2013-05-01

    The effect of muscular training, abdominal massage and diaphragmatic breathing was compared with medical treatment in a prospective randomized trial of patients with chronic functional constipation. Patients aged 4-18 years old with functional constipation according to the Rome III criteria were randomized to physiotherapy or medical treatment. In the physiotherapy group, exercises (isometric training of the abdominal muscles, diaphragmatic breathing exercises and abdominal massage) were employed during 12 40-min sessions twice a week by a trained physiotherapist, with laxatives. Patients in the medication group were only given laxatives. Primary outcome measures were frequency of defaecation and faecal incontinence. The analysis was performed by intention-to-treat. After 6 weeks of treatment, the frequency of bowel movements was higher in the physiotherapy group [5.1 (2.1) days/week] than in the medication group [3.9 (2.0) days/week] (P = 0.01). The frequency of faecal incontinence was no different between the groups [3.6 (1.9) days/week vs 3.0 (2.1) days/week] (P = 0.31). The combined use of isometric training of abdominal muscles, breathing exercises and abdominal massage increased defaecation frequency after 6 weeks but faecal incontinence remained unchanged. Physiotherapy may be a useful treatment for constipation. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

  1. Review article: the functional abdominal pain syndrome.

    PubMed

    Sperber, A D; Drossman, D A

    2011-03-01

    Functional abdominal pain syndrome (FAPS) is a debilitating disorder with constant or nearly constant abdominal pain, present for at least 6 months and loss of daily functioning. To review the epidemiology, pathophysiology and treatment of FAPS. A literature review using the keywords: functional abdominal pain, chronic abdominal pain, irritable bowel syndrome and functional gastrointestinal disorders. No epidemiological studies have focused specifically on FAPS. Estimates of prevalence range from 0.5% to 1.7% and tend to show a female predominance. FAPS pathophysiology appears unique in that the pain is caused primarily by amplified central perception of normal visceral input, rather than by enhanced peripheral stimulation from abdominal viscera. The diagnosis of FAPS is symptom-based in accordance with the Rome III diagnostic criteria. These criteria are geared to identify patients with severe symptoms as they require constant or nearly constant abdominal pain with loss of daily function and are differentiated from IBS based on their non-association with changes in bowel habit, eating or other gut-related events. As cure is not feasible, the aims of treatment are reduced suffering and improved quality of life. Treatment is based on a biopsychosocial approach with a therapeutic patient-physician partnership at its base. Therapeutic options include central nonpharmacological and pharmacological modalities and peripheral modalities. These can be combined to produce an augmentation effect. Although few studies have assessed functional abdominal pain syndrome or its treatment specifically, the treatment strategies outlined in this paper appear to be effective. © 2011 Blackwell Publishing Ltd.

  2. Hyperthermia: an effective strategy to induce apoptosis in cancer cells.

    PubMed

    Ahmed, Kanwal; Tabuchi, Yoshiaki; Kondo, Takashi

    2015-11-01

    Heat has been used as a medicinal and healing modality throughout human history. The combination of hyperthermia (HT) with radiation and anticancer agents has been used clinically and has shown positive results to a certain extent. However, the clinical results of HT treatment alone have been only partially satisfactory. Cell death following HT treatment is a function of both temperature and treatment duration. HT induces cancer cell death through apoptosis; the degree of apoptosis and the apoptotic pathway vary in different cancer cell types. HT-induced reactive oxygen species production are responsible for apoptosis in various cell types. However, the underlying mechanism of signal transduction and the genes related to this process still need to be elucidated. In this review, we summarize the molecular mechanism of apoptosis induced by HT, enhancement of heat-induced apoptosis, and the genetic network involved in HT-induced apoptosis.

  3. Management of intra-abdominal hypertension and abdominal compartment syndrome: a review

    PubMed Central

    2014-01-01

    Patients in the intensive care unit (ICU) are at risk of developing of intra abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). Aim: This review seeks to define IAH and ACS, identify the aetiology and presentation of IAH and ACS, identify IAP measurement techniques, identify current management and discuss the implications of IAH and ACS for nursing practice. A search of the electronic databases was supervised by a health librarian. The electronic data bases Cumulative Index of Nursing and Allied Health Literature (CINAHL); Medline, EMBASE, and the World Wide Web was undertaken from 1996- January 2011 using MeSH and key words which included but not limited to: abdominal compartment syndrome, intra -abdominal hypertension, intra-abdominal pressure in adult populations met the search criteria and were reviewed by three authors using a critical appraisal tool. Data derived from the retrieved material are discussed under the following themes: (1) etiology of intra-abdominal hypertension; (2) strategies for measuring intra-abdominal pressure (3) the manifestation of abdominal compartment syndrome; and (4) the importance of nursing assessment, observation and interventions. Intra-abdominal pressure (IAP) and abdominal compartment syndrome (ACS) have the potential to alter organ perfusion and compromise organ function. PMID:24499574

  4. Microprocessor-controlled Nd:YAG laser for hyperthermia induction in the RIF-1 tumor.

    PubMed

    Waldow, S M; Russell, G E; Wallner, P E

    1992-01-01

    Near-infrared radiation from a Nd:YAG laser at 1,064 nm was used interstitially or superficially to induce hyperthermia in RIF-1 tumors in C3H male mice. A single 600-microns quartz fiber with a 0.5-cm cylindrical diffusor or a weakly diverging microlens at its distal end was used to deliver laser energy to tumors in the hind leg (mean volume = 100 mm3). Two thermocouples were inserted into each tumor. One thermocouple controlled a microprocessor-driven hyperthermia program (maximum output of 3.5 Watts) to maintain the desired temperature. Tumors were exposed to various temperature-time combinations (42-45 degrees C/30 min). Our initial results indicated that excellent temperature control to within 0.2 degrees C of the desired temperature at the feedback thermocouple was achievable during both superficial and interstitial heat treatments. Temperatures at the second thermocouple, however, were found to be lower by as much as 2.3 degrees C (using the cylindrical diffusor) or higher by up to 4.6 degrees C (using the microlens) when compared to the feedback thermocouple temperature. Several correlations were seen between total dose, tumor growth delay, percent skin necrosis, and temperature at the second thermocouple after several superficial and interstitial treatments. Statistically significant improvements in tumor growth delay (at 42 and 45 degrees C) and increased percent skin necrosis at all temperatures were observed after superficial versus interstitial treatment.

  5. A Pilot Study of Catheter-Based Ultrasound Hyperthermia with HDR Brachytherapy for Treatment of Locally Advanced Cancer of the Prostate and Cervix

    NASA Astrophysics Data System (ADS)

    Diederich, Chris J.; Wootton, Jeff; Prakash, Punit; Salgaonkar, Vasant; Juang, Titania; Scott, Serena; Chen, Xin; Cunha, Adam; Pouliot, Jean; Hsu, I. C.

    2011-09-01

    Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within temporary HDR brachytherapy implants during radiation therapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length×180 deg and 3-4 cm×360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers x dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and four prostate implants. 100% of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions.

  6. The development of magnetic degradable DP-Bioglass for hyperthermia cancer therapy.

    PubMed

    Wang, Tzu-Wei; Wu, Hsi-Chin; Wang, Wei-Ren; Lin, Feng-Huei; Lou, Pei-Jen; Shieh, Ming-Jium; Young, Tai-Horng

    2007-12-01

    In this study, a novel magnetic degradable material was developed by adding Fe ions into DP-Bioglass (Na(2)O-CaO-P(2)O(5)-SiO(2)) as thermoseed for hyperthermia cancer therapy under an alternating magnetic field. We have investigated the properties of developed magnetic DP-Bioglass including morphology, chemical composition, and magnetism. The degradability was conducted by measuring the released concentrations of Na, Ca, Si, P, and Fe ions. The biocompatibility was analyzed by biological assays, and the functional hyperthermia effect to cancer cells was evaluated by in vitro cell culture test. In the results, the morphology of synthesized magnetic DP-Bioglass was revealed in sphere and rod shape with particle size around 50-100 nm. From the hysteresis loop analysis, it showed that the group of Fe/Bioglass = 0.2 possessed the maximum magnetization property. When cultured with fibroblasts, the magnetic DP-Bioglass had no significant influence on cell viability and mediated low cytotoxicity. The thermal-induced property demonstrated that after exposure to an alternating magnetic field, the cell number of human Caucasian lung carcinoma cells (A549) was significantly decreased when temperature was increasing to 45 degrees C. In brief, successfully incorporated with Fe ions by sol-gel method, this magnetic degradable DP-Bioglass possessed the potential and properties of hyperthermia effect to lung carcinoma cells. Copyright 2007 Wiley Periodicals, Inc.

  7. Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells.

    PubMed

    Cellai, Filippo; Munnia, Armelle; Viti, Jessica; Doumett, Saer; Ravagli, Costanza; Ceni, Elisabetta; Mello, Tommaso; Polvani, Simone; Giese, Roger W; Baldi, Giovanni; Galli, Andrea; Peluso, Marco E M

    2017-04-29

    Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3 H )-one deoxyguanosine (M₁dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe₃O₄-nanoparticles (NPs) versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF) of 186 kHz using 32 P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe₃O₄-NPs. Significant dose-response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.

  8. Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique.

    PubMed

    Johannsen, M; Gneveckow, U; Eckelt, L; Feussner, A; Waldöfner, N; Scholz, R; Deger, S; Wust, P; Loening, S A; Jordan, A

    2005-11-01

    The aim of this pilot study was to evaluate whether the technique of magnetic fluid hyperthermia can be used for minimally invasive treatment of prostate cancer. This paper presents the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated while rectum and urethra were spared. Nanoparticle suspensions were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans, using an alternating current magnetic field with a frequency of 100 kHz and variable field strength (0-18 kA m(-1)). Invasive thermometry of the prostate was carried out in the first and last of six weekly hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive estimation of temperature values in the prostate, based on intra-tumoural distribution of magnetic nanoparticles, can be performed and correlated with invasively measured intra-prostatic temperatures. Using a specially designed cooling device, treatment was well tolerated without anaesthesia. In the first patient treated, maximum and minimum intra-prostatic temperatures measured at a field strength of 4.0-5.0 kA m(-1) were 48.5 degrees C and 40.0 degrees C during the 1st treatment and 42.5 degrees C and 39.4 degrees C

  9. Effective heating of magnetic nanoparticle aggregates for in vivo nano-theranostic hyperthermia.

    PubMed

    Wang, Chencai; Hsu, Chao-Hsiung; Li, Zhao; Hwang, Lian-Pin; Lin, Ying-Chih; Chou, Pi-Tai; Lin, Yung-Ya

    2017-01-01

    Magnetic resonance (MR) nano-theranostic hyperthermia uses magnetic nanoparticles to target and accumulate at the lesions and generate heat to kill lesion cells directly through hyperthermia or indirectly through thermal activation and control releasing of drugs. Preclinical and translational applications of MR nano-theranostic hyperthermia are currently limited by a few major theoretical difficulties and experimental challenges in in vivo conditions. For example, conventional models for estimating the heat generated and the optimal magnetic nanoparticle sizes for hyperthermia do not accurately reproduce reported in vivo experimental results. In this work, a revised cluster-based model was proposed to predict the specific loss power (SLP) by explicitly considering magnetic nanoparticle aggregation in in vivo conditions. By comparing with the reported experimental results of magnetite Fe 3 O 4 and cobalt ferrite CoFe 2 O 4 magnetic nanoparticles, it is shown that the revised cluster-based model provides a more accurate prediction of the experimental values than the conventional models that assume magnetic nanoparticles act as single units. It also provides a clear physical picture: the aggregation of magnetic nanoparticles increases the cluster magnetic anisotropy while reducing both the cluster domain magnetization and the average magnetic moment, which, in turn, shift the predicted SLP toward a smaller magnetic nanoparticle diameter with lower peak values. As a result, the heating efficiency and the SLP values are decreased. The improvement in the prediction accuracy in in vivo conditions is particularly pronounced when the magnetic nanoparticle diameter is in the range of ~10-20 nm. This happens to be an important size range for MR cancer nano-theranostics, as it exhibits the highest efficacy against both primary and metastatic tumors in vivo. Our studies show that a relatively 20%-25% smaller magnetic nanoparticle diameter should be chosen to reach the maximal

  10. Is Limb Salvage With Microwave-induced Hyperthermia Better Than Amputation for Osteosarcoma of the Distal Tibia?

    PubMed

    Han, Kang; Dang, Peiye; Bian, Na; Chen, Xiang; Yang, Tongtao; Fan, QingYu; Zhou, Yong; Zhao, Tingbao; Wang, Pingshan

    2017-06-01

    Amputation has been the standard surgical treatment for distal tibia osteosarcoma owing to its unique anatomic features. Preliminary research suggested that microwave-induced hyperthermia may have a role in treating osteosarcoma in some locations of the body (such as the pelvis), but to our knowledge, no comparative study has evaluated its efficacy in a difficult-to-treat location like the distal tibia. Does microwave-induced hyperthermia result in (1) improved survival, (2) decreased local recurrence, (3) improved Musculoskeletal Tumor Society (MSTS) scores, or (4) fewer complications than amputation in patients with a distal tibial osteosarcoma? Between 2000 and 2015, we treated 79 patients for a distal tibia osteosarcoma without metastases. Of those, 52 were treated with microwave-induced hyperthermia, and 27 with amputation. Patients were considered eligible for microwave-induced hyperthermia if they had an at least 20-mm available distance from the tumor edge to the articular surface, good clinical and imaging response to neoadjuvant chemotherapy, and no pathologic fracture. Patients not meeting these indications were treated with amputation. In addition, if neither the posterior tibial artery nor the dorsalis pedis artery was salvageable, the patients were treated with amputation and were not included in any group in this study. A total of 13 other patients were treated with conventional limb-salvage resections and reconstructions (at the request of the patient, based on patient preference) and were not included in this study. All 79 patients in this retrospective study were available for followup at a minimum of 12 months (mean followup in the hyperthermia group, 79 months, range 12-158 months; mean followup in the amputation group, 95 months, range, 15-142 months). With the numbers available, the groups were no different in terms of sex, age, tumor grade, tumor stage, or tumor size. All statistical tests were two-sided, and a probability less than 0.05 was

  11. Impact of Ambient Temperature on Hyperthermia Induced by (±)3,4-Methylenedioxymethamphetamine in Rhesus Macaques

    PubMed Central

    Von Huben, Stefani N.; Lay, Christopher C.; Crean, Rebecca D.; Davis, Sophia A.; Katner, Simon N.; Taffe, Michael A.

    2007-01-01

    The ambient temperature (TA) under which rodents are exposed to (±)3,4-methylenedioxymethamphetamine (MDMA) affects the direction and magnitude of the body temperature response, and the degree of hypo/hyperthermia generated in subjects can modify the severity of lasting brain changes in “neurotoxicity” models. The thermoregulatory effects of MDMA have not been well described in nonhuman primates and it is unknown if TA has the potential to affect acute hyperthermia and therefore other lasting consequences of MDMA. The objective of this study was to determine if the temperature alteration produced by MDMA in nonhuman primates depends on TA as it does in rats and mice. Body temperature and spontaneous home cage activity were monitored continuously in six male rhesus monkeys via radiotelemetry. The subjects were challenged intramuscularly with 0.56-2.4 mg/kg (±)MDMA under each of three TA conditions (18°C, 24°C, 30°C) in a randomized order. Temperature was significantly elevated following injection with all doses of MDMA under each ambient temperature. The magnitude of mean temperature change was ~1°C in most conditions suggesting a closely controlled thermoregulatory response in monkeys across a range of doses and ambient temperatures. Activity levels were generally suppressed by MDMA, however a 50% increase over vehicle was observed after 0.56 MDMA under the 30°C condition. It is concluded that MDMA produces very a similar degree of hyperthermia in rhesus monkeys across a range of TA conditions which result in hypothermia or exaggerated hyperthermia in rodents. Monkey temperature responses to MDMA appear to be more similar to humans than to rodents and therefore the monkey may offer an improved model of effects related to MDMA-induced hyperthermia. PMID:16641942

  12. Mechanisms of Hypothermia, Delayed Hyperthermia and Fever Following CNS Injury

    EPA Science Inventory

    Central nervous system (CNS) damage is often associated with robust body temperature changes, such as hypothermia and delayed hyperthermia. Hypothermia is one of the most common body temperature changes to CNS insults in rodents and is often associated with improved outcome. Alth...

  13. Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model

    PubMed Central

    Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.

    2017-01-01

    Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30–40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors. PMID:28287120

  14. Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model.

    PubMed

    Ware, Matthew J; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A; Corr, Stuart J

    2017-03-13

    Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30-40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

  15. Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model

    NASA Astrophysics Data System (ADS)

    Ware, Matthew J.; Krzykawska-Serda, Martyna; Chak-Shing Ho, Jason; Newton, Jared; Suki, Sarah; Law, Justin; Nguyen, Lam; Keshishian, Vazrik; Serda, Maciej; Taylor, Kimberly; Curley, Steven A.; Corr, Stuart J.

    2017-03-01

    Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30-40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

  16. Abdominal Wall Desmoid during Pregnancy: Diagnostic Challenges

    PubMed Central

    Awwad, Johnny; Hammoud, Nadine; Farra, Chantal; Fares, Farah; Abi Saad, George; Ghazeeri, Ghina

    2013-01-01

    Background. Desmoids are benign tumors, with local invasive features and no metastatic potential, which have rarely been described to be pregnancy associated. Case. We described the rapid growth of an anterior abdominal wall mass in a 40-year-old pregnant woman. Due to its close proximity to the enlarged uterus, it was misdiagnosed to be a uterine leiomyoma by ultrasound examination. Final tissue diagnosis and radical resection were done at the time of abdominal delivery. Conclusion. Due to the diagnostic limitations of imaging techniques, desmoids should always be considered when the following manifestations are observed in combination: progressive growth of a solitary abdominal wall mass during pregnancy and well-delineated smooth tumor margins demonstrated by imaging techniques. This case emphasizes the importance of entertaining uncommon medical conditions in the differential diagnosis of seemingly common clinical manifestations. PMID:23346436

  17. [Diagnosis and treatment of patients with closed injury of abdominal cavity organs in combination with craniocerebral trauma].

    PubMed

    Kravets, A V; Kravets, V P

    2003-07-01

    Results of diagnosis and treatment of 114 injured persons with closed abdominal trauma, combined with craniocerebral trauma were suggested. In 34 (29.8%) observations the injury of two or more organs of peritoneal cavity was diagnosed, the parenchymatous organs trauma--in 35 (30.7%) and the hole organs trauma--in 45 (39.5%). Cerebral concussion was established in 61 (53.5%) of injured persons, cerebral contusion--in 26 (22.8%), cerebral compression on the contusion background--in 16 (14%) and subdural hematoma--in 11 (9.7%). In all the injured persons the operative intervention was performed. In 32 (28%) the blood of their own was transfused. To reduce the endogenous intoxication severity there were performed the forced diuresis, hemosorption--in 10 (8.7%), the blood ultraviolet irradiation--in 41 (35.9%), intravenous laserotherapy--in 40 (35%). After the operation 14 (12.3%) of patients died. High mortality in combined cranioabdominal trauma is caused by the injury severity, the traumatic shock and mutual burden syndrome presence.

  18. Localised heating of tumours utilising injectable magnetic nanoparticles for hyperthermia cancer therapy.

    PubMed

    Tseng, H-Y; Lee, G-B; Lee, C-Y; Shih, Y-H; Lin, X-Z

    2009-06-01

    This study reports an investigation of hyperthermia cancer therapy utilising an alternating magnetic field to induce a localised temperature increase on tumours by using injectable magnetic nanoparticles. In-vitro and in-vivo experiments represent the feasibility of hyperthermia cancer therapy. A feedback temperature control system was first developed to keep the nanoparticles at a constant temperature to prevent overheating in the tumours such that a safer and more precise cancer therapy becomes feasible. By using the feedback temperature control system, magnetic nanoparticles can be heated up to the specific constant temperatures, 37, 40, 42, 45, 46 and 47 degrees C, respectively, with a variation less than 0.2 degrees C. With this approach, the in-vitro survival rate of tumour cells at different temperatures can be systematically explored. It was experimentally found that the survival rate of cancer cells can be greatly reduced while CT-26 cancer cells were heated above 45 degrees C. Besides, localised temperatures increase as high as 59.5 degrees C can be successfully generated in rat livers by using the proposed method. Finally, complete regression of tumour was achieved. The developed method used injectable magnetic nanoparticles and may provide a promising approach for hyperthermia cancer therapy.

  19. Shape Effect of Magnetic Nanoparticles on Hyperthermia Applications

    NASA Astrophysics Data System (ADS)

    Mohapatra, Jeotikanta; Zeng, F.; Elkins, K.; Poudyal, N.; Gandha, K.; Liu, J. Ping

    Magnetic Fe3O4 nanoparticles (NPs) are extensively studied for their applications in advanced technologies. Incorporation of different transition metal ions and control of their sizes from nanometre to submicron scale are the keys for the magnetic property manipulation. We have investigated an alternative approach to optimize the magnetic properties by tailoring the shape of the NPs based on the observation that anisotropy of the NPs plays a crucial role in defining the magnetic characteristics. To synthesize monodisperse Fe3O4 NPs we have modified the conventional thermal decomposition to a `solvent-less' synthesis approach where long chain amine/acid acts as reducing and surface functionalizing agent. Various shapes like spheres, rods, octahedrons and cubes are obtained through simple alteration in reaction conditions. Octahedral and cube shaped Fe3O4 NPs exhibit bulk magnetization (92 emu/g) value due to the reduced surface spin disorder. These anisotropic NPs serve better in hyperthermia applications compared to the conventional spherical NPs. The cube and octahedron NPs show significantly higher SAR value, making them a potential candidate for hyperthermia treatment. This work has been supported by the U.S. DoD/ARO under Grant W911NF-11-0507.

  20. The induction of hyperthermia in rabbit liver by means of duplex stainless steel thermoseeds.

    PubMed

    Park, Byeong Ho; Koo, Bong Sig; Kim, Young Kon; Kim, Moon Kon

    2002-01-01

    To determine the heating characteristics of needle-shaped duplex stainless steel thermoseeds, and to evaluate their effectiveness in the induction of hyperthermia in rabbit liver. Thermoseeds of the two different shapes, L-shaped for single doses of hyperthermia and I-shaped for in-vitro study and repeated hyperthermic induction, were prepared. For the in-vitro study, an I-shaped thermoseed 0.23 mm in diameter and 25 mm long was placed inside a plastic tube filled with water. Heat was applied for 30 minutes within an induction magnetic field, and during this time changes in temperature were recorded using three thermocouples. For the in-vivo study, fifteen New Zealand white rabbits were divided into five equal groups. An I-shaped or L-shaped thermoseed was inserted in each rabbit's liver, and then placed within the center of the magnetic induction coil during a 30-minute period of hyperthermia. The rabbits in the first group were sacrificed immediately after hyperthermia was induced once, while those in the other groups were sacrificed at 1, 3, and 7 days, respectively, also after one induction. The remaining three rabbits were sacrificed 4 days after three consecutive daily treatment sessions. The resected segments of liver were subsequently evaluated histopathologically for the extent of coagulation necrosis caused by heating of the thermoseed. The in-vitro study demonstrated that the temperature in the thermoseed, which was 25.9 degrees C before heating and 54.8 degrees C after heating, rose rapidly at first but progressively less rapidly as time elapsed. Light microscopic examination of the rabbits' livers revealed coagulation necrosis and infiltration by inflammatory cells around the insertion site of the thermoseed. The maximum diameter of coagulation necrosis was 2.81+/-1.68 mm, and this occurred in the rabbits that were sacrificed 7 days after heat induction. Needle-shaped duplex stainless steel thermoseeds show temperature-dependent-type heating

  1. Abdominal epilepsy as an unusual cause of abdominal pain: a case report.

    PubMed

    Yunus, Yilmaz; Sefer, Ustebay; Dondu, Ulker Ustebay; Ismail, Ozanli; Yusuf, Ehi

    2016-09-01

    Abdominal pain, in etiology sometimes difficult to be defined, is a frequent complaint in childhood. Abdominal epilepsy is a rare cause of abdominal pain. In this article, we report on 5 year old girl patient with abdominal epilepsy. Some investigations (stool investigation, routine blood tests, ultrasonography (USG), electrocardiogram (ECHO) and electrocardiograpy (ECG), holter for 24hr.) were done to understand the origin of these complaints; but no abnormalities were found. Finally an EEG was done during an episode of abdominal pain and it was shown that there were generalized spikes especially precipitated by hyperventilation. The patient did well on valproic acid therapy and EEG was normal 1 month after beginning of the treatment. The cause of chronic recurrent paroxymal abdominal pain is difficult for the clinicians to diagnose in childhood. A lot of disease may lead to paroxysmal gastrointestinal symptoms like familial mediterranean fever and porfiria. Abdominal epilepsy is one of the rare but easily treatable cause of abdominal pain. In conclusion, abdominal epilepsy should be suspected in children with recurrent abdominal pain.

  2. Ultra-small superparamagnetic iron oxide mediated magnetic hyperthermia in treatment of neck lymph node metastasis in rabbit pyriform sinus VX2 carcinoma.

    PubMed

    Wang, Peng; Xie, Xiaofeng; Wang, Jian; Shi, Yuan; Shen, Na; Huang, Xinsheng

    2015-09-01

    Lymph node metastasis of rabbit VX2 pyriform sinus carcinoma can be enhanced by MR scanning after injecting ultra-small superparamagnetic iron oxide (USPIO) into the submucosa beside the tumor. The metastasis lymph node which fit in with the diagnostic criteria will be placed into the alternating magnetic field after MR scanning. Then, magnetic particles can be heated to the effective therapeutic temperature. And it evaluates the possibility of diagnosis together with therapy in cervical metastasis of pyriform sinus carcinoma. Twenty rabbits bearing VX2 tumor in pyriform sinuses were randomly divided into hyperthermia group and control group after USPIO MR scanning; each group contained 10 rabbits. The hyperthermia for the experimental group was conducted by the alternating magnetic field. After hyperthermia, the detection of apoptosis for the two groups was tested by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL), transmission electron microscopy (TEM), and the expression of Bcl-2 and Bax evaluated by immunohistochemical analysis. The apoptosis rate detected by TUNEL in hyperthermia group was 100 %, while the control group was only 20 % (p < 0.05). TEM observation showed that cell chromatin condensation and clumping, condensed cytoplasm, endoplasmic reticulum membrane fusion with loose change, and the formation of a bubble could be seen in the hyperthermia group. However, the control group showed a more complete cytoplasm and nucleus. Bcl-2 protein expression in the hyperthermia group was lower than the control group, and Bax protein expression in hyperthermia group was higher (p < 0.05). USPIO indirect lymphography could localize the metastatic lymph nodes for hyperthermia. And it could make the metastatic cervical lymph nodes apoptosis when placed into the alternating magnetic field.

  3. Experimental and theoretical investigation of intratumoral nanoparticle distribution to enhance magnetic nanoparticle hyperthermia

    NASA Astrophysics Data System (ADS)

    Attaluri, Anilchandra

    Magnetic nanoparticles have gained prominence in recent years for use in clinical applications such as imaging, drug delivery, and hyperthermia. Magnetic nanoparticle hyperthermia is a minimally invasive and effective approach for confined heating in tumors with little collateral damage. One of the major problems in the field of magnetic nanoparticle hyperthermia is irregular heat distribution in tumors which caused repeatable heat distribution quite impossible. This causes under dosage in tumor area and overheating in normal tissue. In this study, we develop a unified approach to understand magnetic nanoparticle distribution and temperature elevations in gel and tumors. A microCT imaging system is first used to visualize and quantify nanoparticle distribution in both tumors and tissue equivalent phantom gels. The microCT based nanoparticle concentration is related to specific absorption rate (SAR) of the nanoparticles and is confirmed by heat distribution experiments in tissue equivalent phantom gels. An optimal infusion protocol is identified to generate controllable and repeatable nanoparticle distribution in tumors. In vivo animal experiments are performed to measure intratumoral temperature elevations in PC3 xenograft tumors implanted in mice during magnetic nanoparticle hyperthermia. The effect of nanofluid injection parameters on the resulted temperature distribution is studied. It shows that the tumor temperatures can be elevated above 50°C using very small amounts of ferrofluid with a relatively low magnetic field. Slower ferrofluid infusion rates result in smaller nanoparticle distribution volumes in the tumors, however, it gives the much required controllability and repeatability when compared to the higher infusion rates. More nanoparticles occupy a smaller volume in the vicinity of the injection site with slower infusion rates, causing higher temperature elevations in the tumors. Based on the microCT imaging analyses of nanoparticles in tumors, a mass

  4. Immunomodulation of Hyperthermia for Recurrent Prostate Cancer

    DTIC Science & Technology

    2006-03-01

    cells treated with Hyperthermia (HT). HT was administered either as incubation in a 43.7oC water bath or by High frequency focused ultrasound ( HIFU ...immunity and improve local and distant tumor regression. B. BODY B.1. HT induced by water bath (43.7C,1hr) in vivo was compared to HIFU in vivo... HIFU induces coagulative tissue necrosis in the focal zone by rapidly elevating tissue temperature in a short exposure (seconds) while keeping the

  5. A Reconstruction Method for the Estimation of Temperatures of Multiple Sources Applied for Nanoparticle-Mediated Hyperthermia.

    PubMed

    Steinberg, Idan; Tamir, Gil; Gannot, Israel

    2018-03-16

    Solid malignant tumors are one of the leading causes of death worldwide. Many times complete removal is not possible and alternative methods such as focused hyperthermia are used. Precise control of the hyperthermia process is imperative for the successful application of such treatment. To that end, this research presents a fast method that enables the estimation of deep tissue heat distribution by capturing and processing the transient temperature at the boundary based on a bio-heat transfer model. The theoretical model is rigorously developed and thoroughly validated by a series of experiments. A 10-fold improvement is demonstrated in resolution and visibility on tissue mimicking phantoms. The inverse problem is demonstrated as well with a successful application of the model for imaging deep-tissue embedded heat sources. Thereby, allowing the physician then ability to dynamically evaluate the hyperthermia treatment efficiency in real time.

  6. Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus

    PubMed Central

    Seminerio, Michael J.; Robson, Matthew J.; McCurdy, Christopher R.; Matsumoto, Rae R.

    2013-01-01

    Methamphetamine is currently one of the most widely abused drugs worldwide, with hyperthermia being a leading cause of death in methamphetamine overdose situations. Methamphetamine-induced hyperthermia involves a variety of cellular mechanisms, including increases in hypothalamic interleukin-1 beta (IL-1β) expression. Methamphetamine also interacts with sigma receptors and previous studies have shown that sigma receptor antagonists mitigate many of the behavioral and physiological effects of methamphetamine, including hyperthermia. The purpose of the current study was to determine if the attenuation of methamphetamine-induced hyperthermia by the sigma receptor antagonists, AZ66 and SN79, is associated with a concomitant attenuation of IL-1β mRNA expression, particularly in the hypothalamus. Methamphetamine produced doseand time-dependent increases in core body temperature and IL-1β mRNA expression in the hypothalamus, striatum, and cortex in male, Swiss Webster mice. Pretreatment with the sigma receptor antagonists, AZ66 and SN79, significantly attenuated methamphetamine-induced hyperthermia, but further potentiated IL-1β mRNA in the mouse hypothalamus when compared to animals treated with methamphetamine alone. These findings suggest sigma receptor antagonists attenuate methamphetamine-induced hyperthermia through a different mechanism from that involved in the modulation of hypothalamic IL-1β mRNA expression. PMID:22820108

  7. Design of a Subtarsal Ultrasonic Transducer for Mild Hyperthermia Treatment of Dry Eye Disease.

    PubMed

    Hynes, Michael B; Bujak, Matthew C; Chérin, Emmanuel; Sade, Shachar; Foster, F Stuart

    2016-01-01

    Dry eye disease is a disorder of the ocular surface that causes pain and low vision in a significant portion of the adult population. A common cause is obstructive Meibomian gland dysfunction, whereby the Meibomian glands secrete abnormal meibum with a melting point elevated by 3°C-4°C; hence, hyperthermia is the typical treatment. A design is proposed for an ultrasound hyperthermia device made of a transducer contained inside a contact lens with an internal air gap. The transducer heats the posterior of the tarsus, and the air gap provides an air backing to the transducer, preventing direct heating of the cornea. A prototype device was built, and hyperthermia experiments were performed on a porcine subject in vivo. A therapeutic temperature rise of 5°C-7°C was achievable in 10-15 min. The temperature of the cornea did not rise more than 2°C during any of the experiments. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  8. Arrangement at the nanoscale: Effect on magnetic particle hyperthermia

    NASA Astrophysics Data System (ADS)

    Myrovali, E.; Maniotis, N.; Makridis, A.; Terzopoulou, A.; Ntomprougkidis, V.; Simeonidis, K.; Sakellari, D.; Kalogirou, O.; Samaras, T.; Salikhov, R.; Spasova, M.; Farle, M.; Wiedwald, U.; Angelakeris, M.

    2016-11-01

    In this work, we present the arrangement of Fe3O4 magnetic nanoparticles into 3D linear chains and its effect on magnetic particle hyperthermia efficiency. The alignment has been performed under a 40 mT magnetic field in an agarose gel matrix. Two different sizes of magnetite nanoparticles, 10 and 40 nm, have been examined, exhibiting room temperature superparamagnetic and ferromagnetic behavior, in terms of DC magnetic field, respectively. The chain formation is experimentally visualized by scanning electron microscopy images. A molecular Dynamics anisotropic diffusion model that outlines the role of intrinsic particle properties and inter-particle distances on dipolar interactions has been used to simulate the chain formation process. The anisotropic character of the aligned samples is also reflected to ferromagnetic resonance and static magnetometry measurements. Compared to the non-aligned samples, magnetically aligned ones present enhanced heating efficiency increasing specific loss power value by a factor of two. Dipolar interactions are responsible for the chain formation of controllable density and thickness inducing shape anisotropy, which in turn enhances magnetic particle hyperthermia efficiency.

  9. Studies On Endoscopic Local Hyperthermia Using Nd-YAG Laser

    NASA Astrophysics Data System (ADS)

    Tsunekawa, H.; Kanemaki, N.; Furusawa, A.; Hotta, M.; Kuroiwa, A.; Nishida, M.; Mori, N.; Watanabe, Y.; Morise, K.; Iizuka, A.

    1987-03-01

    Attempting a new method of laser irradiation for depressed gastric carcinoma, using a newly developed interstitial probe and laser attenuator, we applied local hyperthermia with prolonged low watt contact irradiation. Experimental studies were performed with this probe, using BDF1 mice injected hypodermically with Lewis lung carcinoma. A laser power of 2.0 w at the tip of fiber produced the most desirable temperature curve, about 43 - 60°C at the irradiation site. Clinical applications were carried out on 15 patients with early gastric carcinoma (mainly depressed), 10 preoperative pilot cases and 5 inoperable cases. In follow-up operations and biopsies gastric carcinoma was found to have completely dis-appeared in 2 of the preoperative and 4 of the inoperable cases. In the remaining 8 preoperative cases residual traces of carcinoma were found at the margin of the laser ulcer, but not at the bottom of it. We propose that endoscopic local hyperthermia using interstitial probe and low power irradiation (2.0 W) is the safest and most suitable method of dealing with depressed carcinoma.

  10. Combining hard and soft magnetism into a single core-shell nanoparticle to achieve both hyperthermia and image contrast

    PubMed Central

    Yang, Qiuhong; Gong, Maogang; Cai, Shuang; Zhang, Ti; Douglas, Justin T; Chikan, Viktor; Davies, Neal M; Lee, Phil; Choi, In-Young; Ren, Shenqiang; Forrest, M Laird

    2015-01-01

    Background A biocompatible core/shell structured magnetic nanoparticles (MNPs) was developed to mediate simultaneous cancer therapy and imaging. Methods & results A 22-nm MNP was first synthesized via magnetically coupling hard (FePt) and soft (Fe3O4) materials to produce high relative energy transfer. Colloidal stability of the FePt@Fe3O4 MNPs was achieved through surface modification with silane-polyethylene glycol (PEG). Intravenous administration of PEG-MNPs into tumor-bearing mice resulted in a sustained particle accumulation in the tumor region, and the tumor burden of treated mice was a third that of the mice in control groups 2 weeks after a local hyperthermia treatment. In vivo magnetic resonance imaging exhibited enhanced T2 contrast in the tumor region. Conclusion This work has demonstrated the feasibility of cancer theranostics with PEG-MNPs. PMID:26606855

  11. Thermo-responsive magnetic liposomes for hyperthermia-triggered local drug delivery.

    PubMed

    Dai, Min; Wu, Cong; Fang, Hong-Ming; Li, Li; Yan, Jia-Bao; Zeng, Dan-Lin; Zou, Tao

    2017-06-01

    We prepared and characterised thermo-responsive magnetic liposomes, which were designed to combine features of magnetic targeting and thermo-responsive control release for hyperthermia-triggered local drug delivery. The particle size and zeta-potential of the thermo-responsive magnetic ammonium bicarbonate (MagABC) liposomes were about 210 nm and -14 mV, respectively. The MagABC liposomes showed encapsulation efficiencies of about 15% and 82% for magnetic nanoparticles (mean crystallite size 12 nm) and doxorubicin (DOX), respectively. The morphology of the MagABC liposomes was visualised using transmission electron microscope (TEM). The MagABC liposomes showed desired thermo-responsive release. The MagABC liposomes, when physically targeted to tumour cells in culture by a permanent magnetic field yielded a substantial increase in intracellular accumulation of DOX as compared to non-magnetic ammonium bicarbonate (ABC) liposomes. This resulted in a parallel increase in cytotoxicity for DOX loaded MagABC liposomes over DOX loaded ABC liposomes in tumour cells.

  12. Intra-Abdominal Hypertension and Abdominal Compartment Syndrome in Association with Ruptured Abdominal Aortic Aneurysm in the Endovascular Era: Vigilance Remains Critical

    PubMed Central

    Bozeman, Matthew C.; Ross, Charles B.

    2012-01-01

    Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are common complications of ruptured abdominal aortoiliac aneurysms (rAAAs) and other abdominal vascular catastrophes even in the age of endovascular therapy. Morbidity and mortality due to systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) are significant. Recognition and management of IAH are key critical care measures which may decrease morbidity and improve survival in these vascular patients. Two strategies have been utilized: expectant management with prompt decompressive laparotomy upon diagnosis of threshold levels of IAH versus prophylactic, delayed abdominal closure based upon clinical parameters at the time of initial repair. Competent management of the abdominal wound with preservation of abdominal domain is also an important component of the care of these patients. In this review, we describe published experience with IAH and ACS complicating abdominal vascular catastrophes, experience with ACS complicating endovascular repair of rAAAs, and techniques for management of the abdominal wound. Vigilance and appropriate management of IAH and ACS remains critically important in decreasing morbidity and optimizing survival following catastrophic intra-abdominal vascular events. PMID:22454763

  13. Intra-abdominal hypertension and abdominal compartment syndrome in association with ruptured abdominal aortic aneurysm in the endovascular era: vigilance remains critical.

    PubMed

    Bozeman, Matthew C; Ross, Charles B

    2012-01-01

    Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are common complications of ruptured abdominal aortoiliac aneurysms (rAAAs) and other abdominal vascular catastrophes even in the age of endovascular therapy. Morbidity and mortality due to systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) are significant. Recognition and management of IAH are key critical care measures which may decrease morbidity and improve survival in these vascular patients. Two strategies have been utilized: expectant management with prompt decompressive laparotomy upon diagnosis of threshold levels of IAH versus prophylactic, delayed abdominal closure based upon clinical parameters at the time of initial repair. Competent management of the abdominal wound with preservation of abdominal domain is also an important component of the care of these patients. In this review, we describe published experience with IAH and ACS complicating abdominal vascular catastrophes, experience with ACS complicating endovascular repair of rAAAs, and techniques for management of the abdominal wound. Vigilance and appropriate management of IAH and ACS remains critically important in decreasing morbidity and optimizing survival following catastrophic intra-abdominal vascular events.

  14. Abdominal Assessment.

    PubMed

    Fritz, Deborah; Weilitz, Pamela Becker

    2016-03-01

    Abdominal pain is one of the most common complaints by patients, and assessment of abdominal pain and associated symptoms can be challenging for home healthcare providers. Reasons for abdominal pain are related to inflammation, organ distention, and ischemia. The history and physical examination are important to narrow the source of acute or chronic problems, identify immediate interventions, and when necessary, facilitate emergency department care.

  15. Mild Hyperthermia Downregulates Receptor-dependent Neutrophil Function

    PubMed Central

    Fröhlich, Dieter; Wittmann, Sigrid; Rothe, Gregor; Sessler, Daniel I.; Vogel, Peter; Taeger, Kai

    2005-01-01

    Mild hypothermia impairs resistance to infection and, reportedly, impairs phagocytosis and oxidative killing of un-opsonized bacteria. We evaluated various functions at 33 to 41°C in neutrophils taken from volunteers. Adhesion on endothelial cells was determined using light microscopy. Adhesion molecules expression and receptors, phagocytosis, and release of reactive oxidants were assessed using flow cytometric assays. Adhesion protein CD11b expression on resting neutrophils was temperature independent. However, upregulation of CD11b with TNF-α was increased by hypothermia and decreased with hyperthermia. Neutrophil adhesion to either resting or activated endothelial cells was not temperature dependent. Bacterial uptake was inversely related to temperature, more so with E. coli than S. aureus. Temperature dependence of phagocytosis occurred only with opsonized bacteria. Hypothermia slightly increased N-Formyl-L-methionyl-L-leucyl-phenylalanine (FMLP) receptors on neutrophils: hyperthermia decreased expression, especially with TNF-α. FMLP-induced H2O2 production was inversely related to temperature, especially in the presence of TNF-α. Conversely, phorbol-13-myristate-12-acetate, an activator of protein kinase C, induced an extreme and homogenous release of reactive oxidants that increased with temperature. In contrast to non-receptor dependent phagocytosis and oxidative killing, several crucial receptor-dependent neutrophil activities show temperature-dependent regulation, with hypothermia increasing function. The temperature dependence of neutrophil function is thus more complicated than previously appreciated. PMID:15281545

  16. Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells

    PubMed Central

    Cellai, Filippo; Munnia, Armelle; Viti, Jessica; Doumett, Saer; Ravagli, Costanza; Ceni, Elisabetta; Mello, Tommaso; Polvani, Simone; Giese, Roger W.; Baldi, Giovanni; Galli, Andrea; Peluso, Marco E. M.

    2017-01-01

    Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe3O4-nanoparticles (NPs) versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF) of 186 kHz using 32P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe3O4-NPs. Significant dose–response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death. PMID:28468256

  17. Effects of Enzymatically Synthesized Glycogen and Exercise on Abdominal Fat Accumulation in High-Fat Diet-Fed Mice.

    PubMed

    Tamura, Shohei; Honda, Kazuhisa; Morinaga, Ryoji; Saneyasu, Takaoki; Kamisoyama, Hiroshi

    2017-01-01

    The combination of diet and exercise is the first choice for the treatment of obesity and metabolic syndrome. We previously reported that enzymatically synthesized glycogen (ESG) suppresses abdominal fat accumulation in obese rats. However, the effect of the combination of ESG and exercise on abdominal fat accumulation has not yet been investigated. Our goal in this study was therefore to evaluate the effects of dietary ESG and its combination with exercise on abdominal fat accumulation in high-fat diet (HFD)-fed mice. Male ICR mice were assigned to four groups: HFD, HFD containing 20% ESG, HFD with exercise, HFD containing 20% ESG with exercise. Treadmill exercise was performed for 3 wk (25 m/min, 30 min/d, 3 d/wk) after 5-d adaption to running at that speed. Both ESG and exercise significantly reduced the weights of abdominal adipose tissues. In addition, the combination of ESG and exercise significantly suppressed abdominal fat accumulation, suggesting that ESG and exercise showed an additive effect. Exercise significantly increased the mRNA levels of lipid metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor delta; factor-delta (PPARδ), carnitin palmitoyltransferase b, adipose triglyceride lipase (ATGL), and uncoupling protein-3 in the gastrocnemius muscle. On the other hand, dietary ESG significantly decreased the mRNA levels of PPARδ and ATGL in the gastrocnemius muscle. These results suggest that the combined treatment of ESG and exercise effectively suppresses abdominal fat accumulation in HFD-fed mice by different mechanisms.

  18. Abdominal Aortic Aneurysm

    MedlinePlus

    ... Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management End-of-Life ... familydoctor.org editorial staff Categories: Family Health, Men, Seniors, WomenTags: abdominal aorta, abdominal aortic aneurysm, abdominal pain, ...

  19. Magnetic hyperthermia performance of magnetite nanoparticle assemblies under different driving fields

    NASA Astrophysics Data System (ADS)

    Wu, Kai; Wang, Jian-Ping

    2017-05-01

    The heating performance of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) is dependent on several factors. Optimizing these factors improves the heating efficiency for cancer therapy and meanwhile lowers the MNP treatment dosage. AMF is one of the most easily controllable variables to enhance the efficiency of heat generation. This paper investigated the optimal magnetic field strength and frequency for an assembly of magnetite nanoparticles. For hyperthermia treatment in clinical applications, monodispersed NPs are forming nanoclusters in target regions where a strong magnetically interactive environment is anticipated, which leads to a completely different situation than MNPs in ferrofluids. Herein, the energy barrier model is revisited and Néel relaxation time is tailored for high MNP packing densities. AMF strength and frequency are customized for different magnetite NPs to achieve the highest power generation and the best hyperthermia performance.

  20. Glucocorticoid effects on sheep peripheral blood mononuclear cell proliferation and cytokine production under in vitro hyperthermia.

    PubMed

    Caroprese, M; Ciliberti, M G; De Palo, P; Santillo, A; Sevi, A; Albenzio, M

    2018-06-27

    The present experiment aimed at understanding the effects of cortisol levels on sheep peripheral blood mononuclear cell (PBMC) proliferation and cytokine production during hyperthermia. To mimic stress related to the exposition of high ambient temperatures, PBMC were cultured at 43°C for 12 h, and subsequently at 39°C for additional 12 h. Cells in normothermia were cultured at 39°C for 24 h. Phytohemagglutinin-stimulated PBMC were cultured with different cortisol levels: 0 ng/mL; 100 ng/mL, representing the physiological cortisol concentration simulating stress condition (Cort100); and 1,000 ng/mL, representing the hyperactivated hypothalamic-pituitary-adrenal axis (Cort1000). Phytohemagglutinin-stimulated PBMC with 0 ng/mL of cortisol concentration represented the positive control, whereas nonstimulated PBMC without cortisol represented the negative control (NC). The free cell supernatants were collected for the determination of IL-6, IL-1β, and IL-10 by ELISA. Bromodeoxyuridine assay was performed on cells to determine cell proliferation. Exposition to hyperthermia negatively affected cell proliferation, IL-6, IL-1β, and IL-10 concentrations in cell supernatants. The interaction of hyperthermia and cortisol level affected both cell proliferation and IL-10 production. Both PBMC proliferation and IL-10 production in positive control, Cort100, and Cort100 decreased at 43°C as compared with 39°C NC. On average, the Cort100 treatment displayed higher concentrations of IL-6 than NC. The present experiment demonstrated that the action of cortisol concentration simulating stress condition on cell proliferation and cytokine production was a permissive/stimulatory action during normothermia, whereas it was a suppressive action during hyperthermia. These data confirmed that cortisol concentration simulating stress condition could have a role in the immune system of sheep via mediating cellular homeostasis in the condition of hyperthermia. The negative effects of

  1. Hypothermia in a combined intoxication with doxepin and moclobemide in an adolescent.

    PubMed

    Armbrust, Sven; Nikischin, Werner; Rochholz, Gertrud; Franzelius, Cornelia; Bielstein, Andreas; Kramer, Hans-Heiner

    2010-02-25

    Intoxication with antidepressants, frequently encountered in pediatric emergency medicine, can often lead to life threatening situations. While hyperthermia, hypertonicity and rigidity are symptoms indicative of a serotonin syndrome triggered by an intoxication with serotonin reuptake inhibitors or monoamine oxidase inhibitors, cardiotoxicity, coma and ECG changes are typical of an intoxication with tricyclic antidepressants. Hypothermia (instead of the expected hyperthermia) is described for the first time as a persistent symptom during the course of a combined moclobemide-doxepin intoxication in an attempted suicide of a 16-year-old adolescent. The administration of serotonin reuptake inhibitors alone or in combination with other medication which increases the level of 5-hydroxytryptamine, i.e. serotonin, in the synaptic cleft mainly leads to hyperthermia. According to a recent study, however, the application of a selective 5-HT(1a) agonist to transgenic mice with a prominent overexpression of the 5-HT(1a) receptor lead to immobility and hypothermia. These findings might help to explain the hypothermia observed in the case of the intoxicated 16-year-old. Intoxication with antidepressants should not be excluded a priori in a hypothermic patient who displays other clinical signs of the said intoxication. 2009. Published by Elsevier Ireland Ltd.

  2. LSMO Nanoparticles Coated by Hyaluronic Acid for Magnetic Hyperthermia

    NASA Astrophysics Data System (ADS)

    Chen, Yuanwei; Wang, Ying; Liu, Xi; Lu, Mai; Cao, Jiangwei; Wang, Tao

    2016-12-01

    Magnetic hyperthermia with the treating temperature range of 41-46 °C is an alternative therapy for cancer treatment. In this article, lanthanum strontium manganates (La1- x Sr x MnO3, 0.25 ≤ × ≤ 0.35) magnetic nanoparticles coated by hyaluronic acid (HA) which possesses the ability of targeting tumor cells were prepared by a simple hydrothermal method combined with a high-energy ball milling technique. The crystal structure, morphology, magnetic properties of the HA-coated magnetic nanoparticles (MNPs), and their heating ability under alternating magnetic field were investigated. It was found the HA-coated La0.7Sr0.3MnO3, with particle diameter of 100 nm, Curie temperature of 45 °C at a concentration 6 mg/ml, gave the optimal induction heating results. The heating temperature saturates at 45.7 °C, and the ESAR is 5.7 × 10-3 W/g · kHz · (kA/m2) which is much higher than other reported results.

  3. Development of a spherically focused phased array transducer for ultrasonic image-guided hyperthermia

    PubMed Central

    Liu, Jingfei; Foiret, Josquin; Stephens, Douglas N.; Le Baron, Olivier; Ferrara, Katherine W.

    2016-01-01

    A 1.5 MHz prolate spheroidal therapeutic array with 128 circular elements was designed to accommodate standard imaging arrays for ultrasonic image-guided hyperthermia. The implementation of this dual-array system integrates real-time therapeutic and imaging functions with a single ultrasound system (Vantage 256, Verasonics). To facilitate applications involving small animal imaging and therapy the array was designed to have a beam depth of field smaller than 3.5 mm and to electronically steer over distances greater than 1 cm in both the axial and lateral directions. In order to achieve the required f number of 0.69, 1-3 piezocomposite modules were mated within the transducer housing. The performance of the prototype array was experimentally evaluated with excellent agreement with numerical simulation. A focal volume (2.70 mm (axial) × 0.65 mm (transverse) × 0.35 mm (transverse)) defined by the −6 dB focal intensity was obtained to address the dimensions needed for small animal therapy. An electronic beam steering range defined by the −3 dB focal peak intensity (17 mm (axial) × 14 mm (transverse) × 12 mm (transverse)) and −8 dB lateral grating lobes (24 mm (axial) × 18 mm (transverse) × 16 mm (transverse)) was achieved. The combined testing of imaging and therapeutic functions confirmed well-controlled local heating generation and imaging in a tissue mimicking phantom. This dual-array implementation offers a practical means to achieve hyperthermia and ablation in small animal models and can be incorporated within protocols for ultrasound-mediated drug delivery. PMID:27353347

  4. Functionalized magnetic iron oxide/alginate core-shell nanoparticles for targeting hyperthermia

    PubMed Central

    Liao, Shih-Hsiang; Liu, Chia-Hung; Bastakoti, Bishnu Prasad; Suzuki, Norihiro; Chang, Yung; Yamauchi, Yusuke; Lin, Feng-Huei; Wu, Kevin C-W

    2015-01-01

    Hyperthermia is one of the promising treatments for cancer therapy. However, the development of a magnetic fluid agent that can selectively target a tumor and efficiently elevate temperature while exhibiting excellent biocompatibility still remains challenging. Here a new core-shell nanostructure consisting of inorganic iron oxide (Fe3O4) nanoparticles as the core, organic alginate as the shell, and cell-targeting ligands (ie, D-galactosamine) decorated on the outer surface (denoted as Fe3O4@Alg-GA nanoparticles) was prepared using a combination of a pre-gel method and coprecipitation in aqueous solution. After treatment with an AC magnetic field, the results indicate that Fe3O4@Alg-GA nanoparticles had excellent hyperthermic efficacy in a human hepatocellular carcinoma cell line (HepG2) owing to enhanced cellular uptake, and show great potential as therapeutic agents for future in vivo drug delivery systems. PMID:26005343

  5. Functionalized magnetic iron oxide/alginate core-shell nanoparticles for targeting hyperthermia.

    PubMed

    Liao, Shih-Hsiang; Liu, Chia-Hung; Bastakoti, Bishnu Prasad; Suzuki, Norihiro; Chang, Yung; Yamauchi, Yusuke; Lin, Feng-Huei; Wu, Kevin C-W

    2015-01-01

    Hyperthermia is one of the promising treatments for cancer therapy. However, the development of a magnetic fluid agent that can selectively target a tumor and efficiently elevate temperature while exhibiting excellent biocompatibility still remains challenging. Here a new core-shell nanostructure consisting of inorganic iron oxide (Fe3O4) nanoparticles as the core, organic alginate as the shell, and cell-targeting ligands (ie, D-galactosamine) decorated on the outer surface (denoted as Fe3O4@Alg-GA nanoparticles) was prepared using a combination of a pre-gel method and coprecipitation in aqueous solution. After treatment with an AC magnetic field, the results indicate that Fe3O4@Alg-GA nanoparticles had excellent hyperthermic efficacy in a human hepatocellular carcinoma cell line (HepG2) owing to enhanced cellular uptake, and show great potential as therapeutic agents for future in vivo drug delivery systems.

  6. Targeted thermal therapy with genetically engineered magnetite magnetosomes@RGD: Photothermia is far more efficient than magnetic hyperthermia.

    PubMed

    Plan Sangnier, Anouchka; Preveral, Sandra; Curcio, Alberto; K A Silva, Amanda; Lefèvre, Chistopher T; Pignol, David; Lalatonne, Yoann; Wilhelm, Claire

    2018-06-10

    Providing appropriate means for heat generation by low intratumoral nanoparticle concentrations is a major challenge for cancer nanotherapy. Here we propose RGD-tagged magnetosomes (magnetosomes@RGD) as a biogenic, genetically engineered, inorganic platform for multivalent thermal cancer treatment. Magnetosomes@RGD are biomagnetite nanoparticles synthesized by genetically modified magnetotactic bacteria thanks to a translational fusion of the RGD peptide with the magnetosomal protein MamC. Magnetosomes@RGD thus combine the high crystallinity of their magnetite core with efficient surface functionalization. The specific affinity of RGD was first quantified by single-cell magnetophoresis with a variety of cell types, including immune, muscle, endothelial, stem and cancer cells. The highest affinity and cellular uptake was observed with PC3 prostatic and HeLa uterine cancer cells. The efficiency of photothermia and magnetic hyperthermia was then compared on PC3 cells. Unexpectedly, photothermia was far more efficient than magnetic hyperthermia, which was almost totally inhibited by the cellular environment. RGD targeting was then assessed in vivo at tumor site, in mice bearing PC3 tumors. As a result, we demonstrate that targeted magnetic nanoparticles could generate heat on a therapeutic level after systemic administration, but only under laser excitation, and successfully inhibit tumor progression. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Temporary abdominal closure with zipper-mesh device for management of intra-abdominal sepsis.

    PubMed

    Utiyama, Edivaldo Massazo; Pflug, Adriano Ribeiro Meyer; Damous, Sérgio Henrique Bastos; Rodrigues, Adilson Costa; Montero, Edna Frasson de Souza; Birolini, Claudio Augusto Vianna

    2015-01-01

    to present our experience with scheduled reoperations in 15 patients with intra-abdominal sepsis. we have applied a more effective technique consisting of temporary abdominal closure with a nylon mesh sheet containing a zipper. We performed reoperations in the operating room under general anesthesia at an average interval of 84 hours. The revision consisted of debridement of necrotic material and vigorous lavage of the involved peritoneal area. The mean age of patients was 38.7 years (range, 15 to 72 years); 11 patients were male, and four were female. forty percent of infections were due to necrotizing pancreatitis. Sixty percent were due to perforation of the intestinal viscus secondary to inflammation, vascular occlusion or trauma. We performed a total of 48 reoperations, an average of 3.2 surgeries per patient. The mesh-zipper device was left in place for an average of 13 days. An intestinal ostomy was present adjacent to the zipper in four patients and did not present a problem for patient management. Mortality was 26.6%. No fistulas resulted from this technique. When intra-abdominal disease was under control, the mesh-zipper device was removed, and the fascia was closed in all patients. In three patients, the wound was closed primarily, and in 12 it was allowed to close by secondary intent. Two patients developed hernia; one was incisional and one was in the drain incision. the planned reoperation for manual lavage and debridement of the abdomen through a nylon mesh-zipper combination was rapid, simple, and well-tolerated. It permitted effective management of severe septic peritonitis, easy wound care and primary closure of the abdominal wall.

  8. Ablation effects of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells.

    PubMed

    Chen, Kaiyun; Zhu, Shuguang; Xiang, Guoan; Duan, Xiaopeng; He, Jiwen; Chen, Guihua

    2016-05-01

    To have in-depth analysis of clinical ablation effect of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells, this paper collected liver cancer patients' treatment information from 10 hospitals during January 2010 and December 2011, from which 1050 cases of patients were randomly selected as study object of observation group who underwent noninvasive radiofrequency field-induced hyperthermia treatment; in addition, 500 cases of liver cancer patients were randomly selected as study object of control group who underwent clinical surgical treatment. After treatment was completed, three years of return visit were done, survival rates of the two groups of patients after 1 year, 2 years, and 3 years were compared, and clinical effects of radiofrequency ablation of liver cancer were evaluated. Zoom results show that the two groups are similar in terms of survival rate, and the difference is without statistical significance. 125 patients in observation group had varying degrees of adverse reactions, while 253 patients in control group had adverse reactions. There was difference between groups P < 0.05, with significant statistical significance. It can be concluded that radiofrequency ablation of liver cancer is more secure. Therefore, the results of this study fully demonstrate that liver cancer treatment with noninvasive radiofrequency field-induced hyperthermia is with safety effect and satisfactory survival rate, thus with relatively high clinical value in clinical practice.

  9. Abdominal Aortic Emergencies.

    PubMed

    Lech, Christie; Swaminathan, Anand

    2017-11-01

    This article discusses abdominal aortic emergencies. There is a common thread of risk factors and causes of these diseases, including age, male gender, hypertension, dyslipidemia, and connective tissue disorders. The most common presenting symptom of these disorders is pain, usually in the chest, flank, abdomen, or back. Computed tomography scan is the gold standard for diagnosis of pathologic conditions of the aorta in the hemodynamically stable patient. Treatment consists of a combination of blood pressure and heart rate control and, in many cases, emergent surgical intervention. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Optimization of the sources in local hyperthermia using a combined finite element-genetic algorithm method.

    PubMed

    Siauve, N; Nicolas, L; Vollaire, C; Marchal, C

    2004-12-01

    This article describes an optimization process specially designed for local and regional hyperthermia in order to achieve the desired specific absorption rate in the patient. It is based on a genetic algorithm coupled to a finite element formulation. The optimization method is applied to real human organs meshes assembled from computerized tomography scans. A 3D finite element formulation is used to calculate the electromagnetic field in the patient, achieved by radiofrequency or microwave sources. Space discretization is performed using incomplete first order edge elements. The sparse complex symmetric matrix equation is solved using a conjugate gradient solver with potential projection pre-conditionning. The formulation is validated by comparison of calculated specific absorption rate distributions in a phantom to temperature measurements. A genetic algorithm is used to optimize the specific absorption rate distribution to predict the phases and amplitudes of the sources leading to the best focalization. The objective function is defined as the specific absorption rate ratio in the tumour and healthy tissues. Several constraints, regarding the specific absorption rate in tumour and the total power in the patient, may be prescribed. Results obtained with two types of applicators (waveguides and annular phased array) are presented and show the faculties of the developed optimization process.

  11. Intra-abdominal hypertension and abdominal compartment syndrome in pediatrics. A review.

    PubMed

    Thabet, Farah Chedly; Ejike, Janeth Chiaka

    2017-10-01

    To consolidate pediatric intensivists' understanding of the pathophysiology, definition, incidence, monitoring, and management of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS); and to highlight the characteristics related to the pediatric population. This is a narrative review article that utilized a systematic search of the medical literature published in the English language between January 1990 and august 2016. Studies were identified by conducting a comprehensive search of Pub Med databases. Search terms included "intra-abdominal hypertension and child", "intra-abdominal hypertension and pediatrics", "abdominal compartment syndrome and child", and "abdominal compartment syndrome and pediatrics". Intra-abdominal hypertension and ACS are associated with a number of pathophysiological disturbances and increased morbidity and mortality. These conditions have been well described in critically ill adults. In children, the IAH and the ACS have a reported incidence of 13% and 0.6 to 10% respectively; they carry similar prognostic impact but are still under-diagnosed and under-recognized by pediatric health care providers. Intra-abdominal hypertension and ACS are conditions that are regularly encountered in critically ill children. They are associated with an increased morbidity and mortality. Early recognition, prevention and timely management of this critical condition are necessary to improve its outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Effect of short-term scrotal hyperthermia on spermatological parameters, testicular blood flow and gonadal tissue in dogs.

    PubMed

    Henning, H; Masal, C; Herr, A; Wolf, K; Urhausen, C; Beineke, A; Beyerbach, M; Kramer, S; Günzel-Apel, A-R

    2014-02-01

    The objective was to assess the effect of a short-term scrotal hyperthermia in dogs on quantitative and qualitative ejaculate parameters, testicular blood flow and testicular and epididymal histology. After a control period, the scrotum of seven normospermic adult beagle dogs was insulated with a self-made suspensory for 48 h. Nine weeks later, two animals were castrated, while in five animals, scrotal hyperthermia was repeated. Dogs were castrated either 10 or 40 days thereafter. In each phase of scrotal insulation, average scrotal surface temperature increased by 3.0°C. Semen was collected twice weekly throughout the experiment. Total sperm count did not change after the first hyperthermia, but it slightly decreased after the second (p < 0.05). Profiles of sperm morphology and velocity parameters (CASA) rather indicated subtle physiological variations in sperm quality than effects of a local heat stress. Chromatin stability of ejaculated spermatozoa as indicated by SCSA remained constant throughout the experiment. Perfusion characteristics of the gonads, that is, systolic peak velocity, pulsatility and resistance index at the marginal location of the testicular artery, did not change due to hyperthermia (p > 0.05). Histological examination of excised testes and epididymides for apoptotic (TUNEL and activated caspase-3) and proliferating cells (Ki-67 antigen) indicated only marginal effects of scrotal insulation on tissue morphology. In conclusion, a mild short-term scrotal hyperthermia in dogs does not cause substantial changes in sperm quantity and quality. In contrast to other species, canine testes and epididymides may have a higher competence to compensate such thermal stress. © 2013 Blackwell Verlag GmbH.

  13. Plain abdominal radiography in acute abdominal pain; past, present, and future

    PubMed Central

    Gans, Sarah L; Stoker, Jaap; Boermeester, Marja A

    2012-01-01

    Several studies have demonstrated that a diagnosis based solely on a patient’s medical history, physical examination, and laboratory tests is not reliable enough, despite the fact that these aspects are essential parts of the workup of a patient presenting with acute abdominal pain. Traditionally, imaging workup starts with abdominal radiography. However, numerous studies have demonstrated low sensitivity and accuracy for plain abdominal radiography in the evaluation of acute abdominal pain as well as various specific diseases such as perforated viscus, bowel obstruction, ingested foreign body, and ureteral stones. Computed tomography, and in particular computed tomography after negative ultrasonography, provides a better workup than plain abdominal radiography alone. The benefits of computed tomography lie in decision-making for management, planning of a surgical strategy, and possibly even avoidance of negative laparotomies. Based on abundant available evidence, major advances in diagnostic imaging, and changes in the management of certain diseases, we can conclude that there is no place for plain abdominal radiography in the workup of adult patients with acute abdominal pain presenting in the emergency department in current practice. PMID:22807640

  14. Effective heating of magnetic nanoparticle aggregates for in vivo nano-theranostic hyperthermia

    PubMed Central

    Wang, Chencai; Hsu, Chao-Hsiung; Li, Zhao; Hwang, Lian-Pin; Lin, Ying-Chih; Chou, Pi-Tai; Lin, Yung-Ya

    2017-01-01

    Magnetic resonance (MR) nano-theranostic hyperthermia uses magnetic nanoparticles to target and accumulate at the lesions and generate heat to kill lesion cells directly through hyperthermia or indirectly through thermal activation and control releasing of drugs. Preclinical and translational applications of MR nano-theranostic hyperthermia are currently limited by a few major theoretical difficulties and experimental challenges in in vivo conditions. For example, conventional models for estimating the heat generated and the optimal magnetic nanoparticle sizes for hyperthermia do not accurately reproduce reported in vivo experimental results. In this work, a revised cluster-based model was proposed to predict the specific loss power (SLP) by explicitly considering magnetic nanoparticle aggregation in in vivo conditions. By comparing with the reported experimental results of magnetite Fe3O4 and cobalt ferrite CoFe2O4 magnetic nanoparticles, it is shown that the revised cluster-based model provides a more accurate prediction of the experimental values than the conventional models that assume magnetic nanoparticles act as single units. It also provides a clear physical picture: the aggregation of magnetic nanoparticles increases the cluster magnetic anisotropy while reducing both the cluster domain magnetization and the average magnetic moment, which, in turn, shift the predicted SLP toward a smaller magnetic nanoparticle diameter with lower peak values. As a result, the heating efficiency and the SLP values are decreased. The improvement in the prediction accuracy in in vivo conditions is particularly pronounced when the magnetic nanoparticle diameter is in the range of ~10–20 nm. This happens to be an important size range for MR cancer nano-theranostics, as it exhibits the highest efficacy against both primary and metastatic tumors in vivo. Our studies show that a relatively 20%–25% smaller magnetic nanoparticle diameter should be chosen to reach the maximal

  15. Increased auditory startle reflex in children with functional abdominal pain.

    PubMed

    Bakker, Mirte J; Boer, Frits; Benninga, Marc A; Koelman, Johannes H T M; Tijssen, Marina A J

    2010-02-01

    To test the hypothesis that children with abdominal pain-related functional gastrointestinal disorders have a general hypersensitivity for sensory stimuli. Auditory startle reflexes were assessed in 20 children classified according to Rome III classifications of abdominal pain-related functional gastrointestinal disorders (13 irritable bowel syndrome [IBS], 7 functional abdominal pain syndrome; mean age, 12.4 years; 15 girls) and 23 control subjects (14 girls; mean age, 12.3 years) using a case-control design. The activity of 6 left-sided muscles and the sympathetic skin response were obtained by an electromyogram. We presented sudden loud noises to the subjects through headphones. Both the combined response of 6 muscles and the blink response proved to be significantly increased in patients with abdominal pain compared with control subjects. A significant increase of the sympathetic skin response was not found. Comorbid anxiety disorders (8 patients with abdominal pain) or Rome III subclassification did not significantly affect these results. This study demonstrates an objective hyperresponsivity to nongastrointestinal stimuli. Children with abdominal pain-related functional gastrointestinal disorders may have a generalized hypersensitivity of the central nervous system. Copyright 2010 Mosby, Inc. All rights reserved.

  16. Iatrogenic hyperthermia during cardiac magnetic resonance imaging.

    PubMed

    Kussman, Barry D; Mulkern, Robert V; Holzman, Robert S

    2004-10-01

    We report the occurrence of accidental hyperthermia in a young child undergoing anesthesia for cardiac magnetic resonance imaging. Although the tendency during anesthesia is to develop hypothermia, the absorbed radiofrequency energy from magnetic resonance scanning is added to metabolic energy and must be balanced by appropriate heat loss to maintain normothermia. In addition to stressing the clinical importance of temperature monitoring, this report suggests that the recommended specific absorption rates to prevent excessive patient heating may need to be revised for infants and young children.

  17. Abdominal Trauma Revisited.

    PubMed

    Feliciano, David V

    2017-11-01

    Although abdominal trauma has been described since antiquity, formal laparotomies for trauma were not performed until the 1800s. Even with the introduction of general anesthesia in the United States during the years 1842 to 1846, laparotomies for abdominal trauma were not performed during the Civil War. The first laparotomy for an abdominal gunshot wound in the United States was finally performed in New York City in 1884. An aggressive operative approach to all forms of abdominal trauma till the establishment of formal trauma centers (where data were analyzed) resulted in extraordinarily high rates of nontherapeutic laparotomies from the 1880s to the 1960s. More selective operative approaches to patients with abdominal stab wounds (1960s), blunt trauma (1970s), and gunshot wounds (1990s) were then developed. Current adjuncts to the diagnosis of abdominal trauma when serial physical examinations are unreliable include the following: 1) diagnostic peritoneal tap/lavage, 2) surgeon-performed ultrasound examination; 3) contrast-enhanced CT of the abdomen and pelvis; and 4) diagnostic laparoscopy. Operative techniques for injuries to the liver, spleen, duodenum, and pancreas have been refined considerably since World War II. These need to be emphasized repeatedly in an era when fewer patients undergo laparotomy for abdominal trauma. Finally, abdominal trauma damage control is a valuable operative approach in patients with physiologic exhaustion and multiple injuries.

  18. Arrhenius analysis of the relationship between hyperthermia and Hsp70 promoter activation: a comparison between ex vivo and in vivo data.

    PubMed

    Deckers, Roel; Debeissat, Christelle; Fortin, Pierre-Yves; Moonen, Chrit T W; Couillaud, Franck

    2012-01-01

    Tight regulation of gene expression in the region where therapy is necessary and for the duration required to achieve a therapeutic effect and to minimise systemic toxicity is very important for clinical applications of gene therapy. Hyperthermia in combination with a temperature sensitive heat shock protein (Hsp70) promoter presents a unique approach allowing non-invasive spatio-temporal control of transgene expression. In this study we investigated the in vivo and ex vivo relationship between temperature and duration of thermal stress with respect to the resulting gene expression using an Arrhenius analysis. A transgenic mouse expressing the luciferase reporter gene under the transcriptional control of a thermosensitive promoter was used to assure identical genotype for in vivo (mouse leg) and ex vivo (bone marrow mononuclear and embryonic fibroblast cells) studies. The mouse leg and cells were heated at different temperatures and different exposure times. Bioluminescence imaging and in vitro enzymatic assay were used to measure the resulting transgene expression. We showed that temperature-induced Hsp70 promoter activation was modulated by both temperature as well as duration of hyperthermia. The relationship between temperature and duration of hyperthermia and the resulting reporter gene expression can be modelled by an Arrhenius analysis for both in vivo as well as ex vivo. However, the increase in reporter gene expression after elevating the temperature of the thermal stress with 1°C is not comparable for in vivo and ex vivo situations. This information may be valuable for optimising clinical gene therapy protocols.

  19. Utility and translatability of mathematical modeling, cell culture and small and large animal models in magnetic nanoparticle hyperthermia cancer treatment research

    NASA Astrophysics Data System (ADS)

    Hoopes, P. J.; Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Pearce, John A.; Ryan, Thomas P.

    2015-03-01

    For more than 50 years, hyperthermia-based cancer researchers have utilized mathematical models, cell culture studies and animal models to better understand, develop and validate potential new treatments. It has been, and remains, unclear how and to what degree these research techniques depend on, complement and, ultimately, translate accurately to a successful clinical treatment. In the past, when mathematical models have not proven accurate in a clinical treatment situation, the initiating quantitative scientists (engineers, mathematicians and physicists) have tended to believe the biomedical parameters provided to them were inaccurately determined or reported. In a similar manner, experienced biomedical scientists often tend to question the value of mathematical models and cell culture results since those data typically lack the level of biologic and medical variability and complexity that are essential to accurately study and predict complex diseases and subsequent treatments. Such quantitative and biomedical interdependence, variability, diversity and promise have never been greater than they are within magnetic nanoparticle hyperthermia cancer treatment. The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and, recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. The goal of this paper is to use proven concepts and current research to address the potential pathobiology, modeling and quantification of the effects of treatment as pertaining to the similarities and differences in energy delivered by known external delivery techniques and iron oxide nanoparticles.

  20. Magnetic-mediated hyperthermia for cancer treatment: Research progress and clinical trials

    NASA Astrophysics Data System (ADS)

    Zhao, Ling-Yun; Liu, Jia-Yi; Ouyang, Wei-Wei; Li, Dan-Ye; Li, Li; Li, Li-Ya; Tang, Jin-Tian

    2013-10-01

    Research progress and frontiers of magnetic-mediated hyperthermia (MMH) are presented, along with clinical trials in Germany, the US, Japan, and China. Special attention is focused on MMH mediated by magnetic nanoparticles, and multifunctional magnetic devices for cancer multimodality treatment are also introduced.

  1. Online Adaptive Hyperthermia Treatment Planning During Locoregional Heating to Suppress Treatment-Limiting Hot Spots.

    PubMed

    Kok, H Petra; Korshuize-van Straten, Linda; Bakker, Akke; de Kroon-Oldenhof, Rianne; Geijsen, Elisabeth D; Stalpers, Lukas J A; Crezee, Johannes

    2017-11-15

    Adequate tumor temperatures during hyperthermia are essential for good clinical response, but excessive heating of normal tissue should be avoided. This makes locoregional heating using phased array systems technically challenging. Online application of hyperthermia treatment planning could help to improve the heating quality. The aim of this study was to evaluate the clinical benefit of online treatment planning during treatment of pelvic tumors heated with the AMC-8 locoregional hyperthermia system. For online adaptive hyperthermia treatment planning, a graphical user interface was developed. Electric fields were calculated in a preprocessing step using our in-house-developed finite-difference-based treatment planning system. This allows instant calculation of the temperature distribution for user-selected phase-amplitude settings during treatment and projection onto the patient's computed tomographic scan for online visualization. Online treatment planning was used for 14 treatment sessions in 8 patients to reduce the patients' reports of hot spots while maintaining the same level of tumor heating. The predicted decrease in hot spot temperature should be at least 0.5°C, and the tumor temperature should decrease less than 0.2°C. These predictions were compared with clinical data: patient feedback about the hot spot and temperature measurements in the tumor region. In total, 17 hot spot reports occurred during the 14 sessions, and the alternative settings predicted the hot spot temperature to decrease by at least 0.5°C, which was confirmed by the disappearance of all 17 hot spot reports. At the same time, the average tumor temperature was predicted to change on average -0.01°C (range, -0.19°C to 0.34°C). The measured tumor temperature change was on average only -0.02°C (range, -0.26°C to 0.31°C). In only 2 cases the temperature decrease was slightly larger than 0.2°C, but at most it was 0.26°C. Online application of hyperthermia treatment planning is

  2. The Induction of Hyperthermia in Rabbit Liver by means of Duplex Stainless Steel Thermoseeds

    PubMed Central

    Koo, Bong Sig; Kim, Young Kon; Kim, Moon Kon

    2002-01-01

    Objective To determine the heating characteristics of needle-shaped duplex stainless steel thermoseeds, and to evaluate their effectiveness in the induction of hyperthermia in rabbit liver. Materials and Methods Thermoseeds of the two different shapes, L-shaped for single doses of hyperthermia and I-shaped for in-vitro study and repeated hyperthermic induction, were prepared. For the in-vitro study, an I-shaped thermoseed 0.23 mm in diameter and 25 mm long was placed inside a plastic tube filled with water. Heat was applied for 30 minutes within an induction magnetic field, and during this time changes in temperature were recorded using three thermocouples. For the in-vivo study, fifteen New Zealand white rabbits were divided into five equal groups. An I-shaped or L-shaped thermoseed was inserted in each rabbit's liver, and then placed within the center of the magnetic induction coil during a 30-minute period of hyperthermia. The rabbits in the first group were sacrificed immediately after hyperthermia was induced once, while those in the other groups were sacrificed at 1, 3, and 7 days, respectively, also after one induction. The remaining three rabbits were sacrificed 4 days after three consecutive daily treatment sessions. The resected segments of liver were subsequently evaluated histopathologically for the extent of coagulation necrosis caused by heating of the thermoseed. Results The in-vitro study demonstrated that the temperature in the thermoseed, which was 25.9℃ before heating and 54.8℃ after heating, rose rapidly at first but progressively less rapidly as time elapsed. Light microscopic examination of the rabbits' livers revealed coagulation necrosis and infiltration by inflammatory cells around the insertion site of the thermoseed. The maximum diameter of coagulation necrosis was 2.81 ± 1.68 mm, and this occurred in the rabbits that were sacrificed 7 days after heat induction. Conclusion Needle-shaped duplex stainless steel thermoseeds show

  3. Magnetic hyperthermia in water based ferrofluids: Effects of initial susceptibility and size polydispersity on heating efficiency

    NASA Astrophysics Data System (ADS)

    Lahiri, B. B.; Ranoo, Surojit; Muthukumaran, T.; Philip, John

    2018-04-01

    The effects of initial susceptibility and size polydispersity on magnetic hyperthermia efficiency in two water based ferrofluids containing phosphate and TMAOH coated superparamagnetic Fe3O4 nanoparticles were studied. Experiments were performed at a fixed frequency of 126 kHz on four different concentrations of both samples and under different external field amplitudes. It was observed that for field amplitudes beyond 45.0 kAm-1, the maximum temperature rise was in the vicinity of 42°C (hyperthermia limit) which indicated the suitability of the water based ferrofluids for hyperthermia applications. The maximum temperature rise and specific absorption rate were found to vary linearly with square of the applied field amplitudes, in accordance with theoretical predictions. It was further observed that for a fixed sample concentration, specific absorption rate was higher for the phosphate coated samples which was attributed to the higher initial static susceptibility and lower size polydispersity of phosphate coated Fe3O4.

  4. Magnetic, structural and magnetocaloric properties of Ni-Si and Ni-Al thermoseeds for self-controlled hyperthermia.

    PubMed

    Pandey, Sudip; Quetz, Abdiel; Aryal, Anil; Dubenko, Igor; Mazumdar, Dipanjan; Stadler, Shane; Ali, Naushad

    2017-11-01

    Self-controlled hyperthermia is a non-invasive technique used to kill or destroy cancer cells while preserving normal surrounding tissues. We have explored bulk magnetic Ni-Si and Ni-Al alloys as a potential thermoseeds. The structural, magnetic and magnetocaloric properties of the samples were investigated, including saturation magnetisation, Curie temperature (T C ), and magnetic and thermal hysteresis, using room temperature X-ray diffraction and magnetometry. The annealing time, temperature and the effects of homogenising the thermoseeds were studied to determine the functional hyperthermia applications. The bulk Ni-Si and Ni-Al binary alloys have Curie temperatures in the desired range, 316 K-319 K (43 °C-46 °C), which is suitable for magnetic hyperthermia applications. We have found that T C strictly follows a linear trend with doping concentration over a wide range of temperature. The magnetic ordering temperature and the magnetic properties can be controlled through substitution in these binary alloys.

  5. alpha-Phenyl-N-tert-butyl nitrone attenuates methamphetamine-induced depletion of striatal dopamine without altering hyperthermia.

    PubMed

    Cappon, G D; Broening, H W; Pu, C; Morford, L; Vorhees, C V

    1996-10-01

    Methamphetamine (MA) administration to adult rats (4 x 10 mg/kg s.c.) induces neurotoxicity predominately characterized by a persistent reduction of neostriatal dopamine (DA) content. Hyperthermia following MA administration potentiates the resulting DA depletion. DA-derived free radicals are postulated to be a mechanism through which MA-induced neurotoxicity is produced. The spin trapping agent PBN reacts with free radicals to form nitroxyl adducts, thereby preventing damaging free radical reactions with cellular substrates. MA with saline pretreatment (Sal-MA) reduced neostriatal DA by 55% (P < 0.01 vs. Sal-Sal). MA with PBN pretreatment (PBN-MA) at 36 or 60 mg/kg reduced neostriatal DA by 36 and 22%, respectively (P < 0.05 and P < 0.01 vs Sal-MA) indicating partial protection. PBN pretreatment did not alter MA-induced hyperthermia. Thus, PBN does not attenuate MA-induced neurotoxicity by reducing MA-induced hyperthermia. These results support a role for free radicals in the generation of MA-induced dopaminergic neurotoxicity.

  6. Management of complex abdominal wall defects associated with penetrating abdominal trauma.

    PubMed

    Arul, G Suren; Sonka, B J; Lundy, J B; Rickard, R F; Jeffery, S L A

    2015-03-01

    The paradigm of Damage Control Surgery (DCS) has radically improved the management of abdominal trauma, but less well described are the options for managing the abdominal wall itself in an austere environment. This article describes a series of patients with complex abdominal wall problems managed at the UK-led Role 3 Medical Treatment Facility (MTF) in Camp Bastion, Afghanistan. Contemporaneous review of a series of patients with complex abdominal wall injuries who presented to the Role 3 MTF between July and November 2012. Five patients with penetrating abdominal trauma associated with significant damage to the abdominal wall were included. All patients were managed using DCS principles, leaving the abdominal wall open at the end of the first procedure. Subsequent management of the abdominal wall was determined by a multidisciplinary team of general and plastic surgeons, intensivists and specialist nurses. The principles of management identified included minimising tissue loss on initial laparotomy by joining adjacent wounds and marginal debridement of dead tissue; contraction of the abdominal wall was minimised by using topical negative pressure dressing and dermal-holding sutures. Definitive closure was timed to allow oedema to settle and sepsis to be controlled. Closure techniques include delayed primary closure with traction sutures, components separation, and mesh closure with skin grafting. A daily multidisciplinary team discussion was invaluable for optimal decision making regarding the most appropriate means of abdominal closure. Dermal-holding sutures were particularly useful in preventing myostatic contraction of the abdominal wall. A simple flow chart was developed to aid decision making in these patients. This flow chart may prove especially useful in a resource-limited environment in which returning months or years later for closure of a large ventral hernia may not be possible. Published by the BMJ Publishing Group Limited. For permission to use

  7. Synergistic Effect of Combined Hollow Viscus Injuries on Intra-Abdominal Abscess Formation.

    PubMed

    Paulus, Elena M; Croce, Martin A; Shahan, Charles P; Zarzaur, Ben L; Sharpe, John P; Dileepan, Amirtha; Boyd, Brandon S; Fabian, Timothy C

    2015-07-01

    The strong association between penetrating colon injuries and intra-abdominal abscess (IAA) formation is well established and attributed to high colon bacterial counts. Since trauma patients are rarely fasting at injury, stomach and small bowel colony counts are also elevated. We hypothesized that there is a synergistic effect of increased IAA formation with concomitant stomach and/or colon injuries when compared to small bowel injuries alone. Consecutive patients at a level one trauma center with penetrating small bowel (SB), stomach (S), and/or colon (C) injuries from 1996 to 2012 were reviewed. Logistic regression determined associations with IAA, adjusting for age, gender, Injury Severity Score (ISS), admission Glasgow Coma Score, transfusions, and concurrent pancreas or liver injury. A total of 1518 patients (91% male, ISS = 15.9 ± 8.4) were identified: 496 (33%) SB, 231 (15%) S, 288 (19%) C, 40 (3%) S + SB, 69 (5%) S + C, 338 (22%) C + SB, and 56 (4%) S + C + SB. 148 (10%) patients developed IAA: 4 per cent SB, 9 per cent S, 10 per cent C, 5 per cent S + SB, 22 per cent S + C, 13 per cent C + SB, and 25 per cent S + C + SB. Multiple logistic regression demonstrated that ISS, 24 hour blood transfusions, and concomitant pancreatic or liver injuries were associated with IAA. Compared with reference SB, S or S + SB injuries were no more likely to develop IAA. However, S + C, SB + C, and S + C + SB injuries were significantly more likely to have IAA. In conclusion, combined stomach + colon, small bowel + colon, and stomach, colon, + small bowel injuries have a synergistic effect leading to increased IAA formation after penetrating injuries. Heightened clinical suspicion for IAA formation is necessary in these combined hollow viscus injury patients.

  8. The value of plain abdominal radiographs in management of abdominal emergencies in Luth.

    PubMed

    Ashindoitiang, J A; Atoyebi, A O; Arogundade, R A

    2008-01-01

    The plain abdominal x-ray is still the first imaging modality in diagnosis of acute abdomen. The aim of this study was to find the value of plain abdominal x-ray in the management of abdominal emergencies seen in Lagos university teaching hospital. The accurate diagnosis of the cause of acute abdominal pain is one of the most challenging undertakings in emergency medicine. This is due to overlapping of clinical presentation and non-specific findings of physical and even laboratory data of the multifarious causes. Plain abdominal radiography is one investigation that can be obtained readily and within a short period of time to help the physician arrive at a correct diagnosis The relevance of plain abdominal radiography was therefore evaluated in the management of abdominal emergencies seen in Lagos over a 12 month period (April 2002 to March 2003). A prospective study of 100 consecutively presenting patients with acute abdominal conditions treated by the general surgical unit of Lagos University Teaching Hospital was undertaken. All patients had supine and erect abdominal x-ray before any therapeutic intervention was undertaken. The diagnostic features of the plain films were compared with final diagnosis to determine the usefulness of the plain x-ray There were 54 males and 46 females (M:F 1.2:1). Twenty-four percent of the patients had intestinal obstruction, 20% perforated typhoid enteritis; gunshot injuries and generalized peritonitis each occurred in 13%, blunt abdominal trauma in 12%, while 8% and 10% had acute appendicitis and perforated peptic ulcer disease respectively. Of 100 patients studied, 54% had plain abdominal radiographs that showed positive diagnostic features. Plain abdominal radiograph showed high sensitivity in patients with intestinal obstruction 100% and perforated peptic ulcer 90% but was less sensitive in patients with perforated typhoid, acute appendicitis, and blunt abdominal trauma and generalized peritonitis. In conclusion, this study

  9. Evaluation of the levels of metalloproteinsase-2 in patients with abdominal aneurysm and abdominal hernias.

    PubMed

    Antoszewska, Magdalena

    2013-05-01

    Abdominal aortic aneurysms and abdominal hernias become an important health problems of our times. Abdominal aortic aneurysm and its rupture is one of the most dangerous fact in vascular surgery. There are some theories pointing to a multifactoral genesis of these kinds of diseases, all of them assume the attenuation of abdominal fascia and abdominal aortic wall. The density and continuity of these structures depend on collagen and elastic fibers structure. Reducing the strength of the fibers may be due to changes in the extracellular matrix (ECM) by the proteolytic enzymes-matrix metalloproteinases (MMPs) that degrade extracellular matrix proteins. These enzymes play an important role in the development of many disease: malignant tumors (colon, breast, lung, pancreas), cardiovascular disease (myocardial infarction, ischemia-reperfusion injury), connective tissue diseases (Ehler-Danlos Syndrome, Marfan's Syndrome), complications of diabetes (retinopathy, nephropathy). One of the most important is matrix metalloproteinase-2 (MMP-2). The aim of the study was an estimation of the MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia, and in patients with only abdominal aortic aneurysm. The study involved 88 patients aged 42 to 89 years, including 75 men and 13 women. Patients were divided into two groups: patients with abdominal aortic aneurysm and primary abdominal hernia (45 persons, representing 51.1% of all group) and patients with only abdominal aortic aneurysm (43 persons, representing 48,9% of all group). It was a statistically significant increase in MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia compared to patients with only abdominal aortic aneurysm. It was a statistically significant increase in the prevalence of POCHP in patients with only abdominal aortic aneurysm compared to patients with abdominal aortic aneurysm and primary abdominal hernia. Statistically significant

  10. [Malignant hyperthermia in a black child. A case report].

    PubMed

    Hugo, J M; Ungerer, M J; Erasmus, F R; du Toit, P W; Muller, F O; van Velden, D J

    1978-05-20

    A case of malignant hyperthermia in a Black boy is presented. He developed this condition during repair of a cleft palate, with halothane as the triggering agent. The importance of the high incidence of malignant hyperthermia in patients with certain musculoskeletal abnormalities is stressed. Despite a cool and well air-conditioned theatre, the patient's temperature was 41 degree C when the condition was suspected. At that stage general muscle rigidity was present. The patient was successfully treated with procainamide, sodium bicarbonate and hydrocortisone; surface cooling (with ice packs) was instituted and the stomach was washed out with ice-cold Ringer's solution. Over a period of 14 days serum creatine phosphokinase values decreased from 630 IU (on the day of the incident) to 12 IU. A muscle biopsy showed variation in muscle fibre size. Electron microscopical studies showed myofibrillar disruption and folding of the basement membrane. A modified version of Denborough's technique was used for the in vitro exposure of muscle strips to halothane and suxamethonium. Isometric contraction was measured and recorded. A severe contraction followed the exposure of muscle strips to halothane, which confirmed the diagnosis.

  11. Enhancing cancer therapeutics using size-optimized magnetic fluid hyperthermia

    NASA Astrophysics Data System (ADS)

    Khandhar, Amit P.; Ferguson, R. Matthew; Simon, Julian A.; Krishnan, Kannan M.

    2012-04-01

    Magnetic fluid hyperthermia (MFH) employs heat dissipation from magnetic nanoparticles to elicit a therapeutic outcome in tumor sites, which results in either cell death (>42 °C) or damage (<42 °C) depending on the localized rise in temperature. We investigated the therapeutic effect of MFH in immortalized T lymphocyte (Jurkat) cells using monodisperse magnetite (Fe3O4) nanoparticles (MNPs) synthesized in organic solvents and subsequently transferred to aqueous phase using a biocompatible amphiphilic polymer. Monodisperse MNPs, ˜16 nm diameter, show maximum heating efficiency, or specific loss power (watts/g Fe3O4) in a 373 kHz alternating magnetic field. Our in vitro results, for 15 min of heating, show that only 40% of cells survive for a relatively low dose (490 μg Fe/ml) of these size-optimized MNPs, compared to 80% and 90% survival fraction for 12 and 13 nm MNPs at 600 μg Fe/ml. The significant decrease in cell viability due to MNP-induced hyperthermia from only size-optimized nanoparticles demonstrates the central idea of tailoring size for a specific frequency in order to intrinsically improve the therapeutic potency of MFH by optimizing both dose and time of application.

  12. Advanced abdominal pregnancy: an increasingly challenging clinical concern for obstetricians

    PubMed Central

    Huang, Ke; Song, Lei; Wang, Longxia; Gao, Zhiying; Meng, Yuanguang; Lu, Yanping

    2014-01-01

    Advanced abdominal pregnancy is rare. The low incidence, high misdiagnosis rate, and lack of specific clinical signs and symptoms explain the fact that there are no standard diagnostic and treatment options available for advanced abdominal pregnancy. We managed a case of abdominal pregnancy in a woman who was pregnant for the first time. This case was further complicated by a concurrent singleton intrauterine pregnancy; the twin pregnancy was not detected until 20 weeks of pregnancy. The case was confirmed at 26 weeks gestational age using MRI to be an abdominal combined with intrauterine pregnancy. The pregnancy was terminated by cesarean section at 33 + 5 weeks gestation. We collected the relevant data of the case while reviewing the advanced abdominal pregnancy-related English literature in the Pubmed, Proquest, and OVID databases. We compared and analyzed the pregnancy history, gestational age when the diagnosis was confirmed, the placental colonization position, the course of treatment and surgical processes, related concurrency rate, post-operative drug treatment programs, and follow-up results with the expectation to provide guidance for other physicians who might encounter similar cases. PMID:25337188

  13. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    NASA Astrophysics Data System (ADS)

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  14. [A commonly seen cause of abdominal pain: abdominal cutaneous nerve entrapment syndrome].

    PubMed

    Solmaz, Ilker; Talay, Mustafa; Tekindur, Şükrü; Kurt, Ercan

    2012-01-01

    Although abdominal cutaneous nerve entrapment syndrome (ACNES) is accepted as a rare condition, it is a syndrome that should be diagnosed more commonly when the clinical signs cannot explain the cause of abdominal pain. Abdominal pain is commonly considered by physicians to be based on intra-abdominal causes. Consequently, redundant tests and consultations are requested for these patients, and unnecessary surgical procedures may be applied. Patients with this type of pain are consulted to many clinics, and because their definitive diagnoses cannot be achieved, they are assessed as psychiatric patients. Actually, a common cause of abdominal wall pain is nerve entrapment on the lateral edge of the rectus abdominis muscle. In this paper, we would like to share information about the diagnosis and treatment of a patient who, prior to presenting to us, had applied to different clinics for chronic abdominal pain and had undergone many tests and consultations; abdominal surgery was eventually decided.

  15. Modeling the thermo-acoustic effects of thermal-dependent speed of sound and acoustic absorption of biological tissues during focused ultrasound hyperthermia.

    PubMed

    López-Haro, S A; Gutiérrez, M I; Vera, A; Leija, L

    2015-10-01

    To evaluate the effects of thermal dependence of speed of sound (SOS) and acoustic absorption of biological tissues during noninvasive focused ultrasound (US) hyperthermia therapy. A finite element (FE) model was used to simulate hyperthermia therapy in the liver by noninvasive focused US. The model consisted of an ultrasonic focused transducer radiating a four-layer biological medium composed of skin, fat, muscle, and liver. The acoustic field and temperature distribution along the layers were obtained after 15 s of hyperthermia therapy using the bio-heat equation. The model solution was found with and without the thermal dependence of SOS and acoustic absorption of biological tissues. The inclusion of the thermal dependence of the SOS generated an increment of 0.4 mm in the longitudinal focus axis of the acoustic field. Moreover, results indicate an increment of the hyperthermia area (zone with temperature above 43 °C), and a maximum temperature difference of almost 3.5 °C when the thermal dependence of absorption was taken into account. The increment of the achieved temperatures at the treatment zone indicated that the effects produced by the thermal dependence of SOS and absorption must be accounted for when planning hyperthermia treatment in order to avoid overheating undesired regions.

  16. Physical mechanism and modeling of heat generation and transfer in magnetic fluid hyperthermia through Néelian and Brownian relaxation: a review.

    PubMed

    Suriyanto; Ng, E Y K; Kumar, S D

    2017-03-23

    Current clinically accepted technologies for cancer treatment still have limitations which lead to the exploration of new therapeutic methods. Since the past few decades, the hyperthermia treatment has attracted the attention of investigators owing to its strong biological rationales in applying hyperthermia as a cancer treatment modality. Advancement of nanotechnology offers a potential new heating method for hyperthermia by using nanoparticles which is termed as magnetic fluid hyperthermia (MFH). In MFH, superparamagnetic nanoparticles dissipate heat through Néelian and Brownian relaxation in the presence of an alternating magnetic field. The heating power of these particles is dependent on particle properties and treatment settings. A number of pre-clinical and clinical trials were performed to test the feasibility of this novel treatment modality. There are still issues yet to be solved for the successful transition of this technology from bench to bedside. These issues include the planning, execution, monitoring and optimization of treatment. The modeling and simulation play crucial roles in solving some of these issues. Thus, this review paper provides a basic understanding of the fundamental and rationales of hyperthermia and recent development in the modeling and simulation applied to depict the heat generation and transfer phenomena in the MFH.

  17. The Effects of Ionizing Radiation and Hyperthermia on Mouse Spinal Cord.

    NASA Astrophysics Data System (ADS)

    Lo, Yeh-Chi

    Assays were developed to quantify spinal cord damage in the mouse following radiation (X), hyperthermia (H) and their combination. The spinal cord (T_9-L _5) of C3Hf/Sed//Kam mice was irradiated with single (12-75 Gy) or fractionated doses (2 Gy to 23 Gy per fraction). Four arbitrary scales of neurological change were used. Findings for X were: (1) Radiation induces progressive damage, from mild to severe. (2) The latency to damage depended on the dose and the level of damage. Following doses around the ED50 (20-27 Gy), the onset of paralysis occurred between 6 and 8 months. (3) For the NSD equation, the exponent for N was 0.36-0.33 for mild to severe paralysis (score 1-3). Comparison of ED_{rm 50s} for 2 fractions separated by various intervals showed no time effect until 30-60 days. (4) If the data for higher doses per fraction were excluded (>10 Gy), the alpha/beta ratios were 3.5-5.6 for score 1-3. (5) Histological evidence of demyelination was evident at the time of paralysis. Using a water bath, the spinal cord was heated at 42.0 to 43.0^circC for 10-100 min. The results were: (1) Hyperthermia produces an acute reversible damage in the surviving mice. (2) No detectable late effects were seen up to 1.5 years. (3) A value of 0.48 for R in the thermal dose equation was found. (4) Heat lesions included neuronal and vascular damage, but this was seen only at high thermal dose. Mild thermal doses (42.5^circ C for 20-50 min.) were combined with single radiation doses ranging from 12 to 35 Gy in various sequences and time intervals. Findings were: (1) An acute and reversible potentiated damage (score 1) was found when H was given 5 min. before or 5 min., 7, 30, 60 and 150 days after X, but not in 7 days before or 1 day or 90 days after X. (2) An enhanced late effect was found when H was given 5 min. or 150 days after X. (3) Late effects were reduced when heat was given 5 min. or 1 day before or 1 day after X. (4) It seems that target cells (or targets within cells

  18. Reconstruction with latissimus dorsi, external abdominal oblique and cranial sartorius muscle flaps for a large defect of abdominal wall in a dog after surgical removal of infiltrative lipoma

    PubMed Central

    FENG, Yu-Ching; CHEN, Kuan-Sheng; CHANG, Shih-Chieh

    2016-01-01

    This animal was presented with a large-sized infiltrative lipoma in the abdominal wall that had been noted for 4 years. This lipoma was confirmed by histological examination from a previous biopsy, and the infiltrative features were identified by a computerized tomography scan. The surgical removal created a large-sized abdominal defect that was closed by a combination of latissimus dorsi and external abdominal oblique muscle flaps in a pedicle pattern. A small dehiscence at the most distal end of the muscle flap resulted in a small-sized abdominal hernia and was repaired with cranial sartorius muscle flap 14 days after surgery. The dog was in good general health with no signs of tumor recurrence after 18 months of follow-up. PMID:27476526

  19. Magnetic nanoparticle-induced hyperthermia with appropriate payloads: Paul Ehrlich's "magic (nano)bullet" for cancer theranostics?

    PubMed

    Datta, N R; Krishnan, S; Speiser, D E; Neufeld, E; Kuster, N; Bodis, S; Hofmann, H

    2016-11-01

    Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology. The rapid developments in multifunctional nanoparticles provide ample opportunities to integrate both diagnostic and therapeutic modalities into a single effective cancer "theranostic" vector. Nanoparticles could extravasate passively into the tumour tissues in preference to the adjacent normal tissues by capitalizing on the enhanced permeability and retention effect. Tumour targeting might be further augmented by conjugating tumour-specific peptides and antibodies onto the surface of these nanoparticles or by activation through electromagnetic radiations, laser or ultrasound. Magnetic nanoparticles can induce hyperthermia in the presence of an alternating magnetic field, thereby multifunctionally with tumour-specific payloads empowering tumour specific radiotheranostics (for both imaging and radiotherapy), chemotherapy drug delivery, immunotherapy and gene silencing therapy. Such a (nano)bullet could realise the "magic bullet" conceived by Paul Ehrlich more than a century ago. This article discusses the various aspects of this "magic (nano)bullet" and the challenges that need to be addressed to usher in this new paradigm in modern cancer diagnostics and therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Mitigation of eddy current heating during magnetic nanoparticle hyperthermia therapy.

    PubMed

    Stigliano, Robert V; Shubitidze, Fridon; Petryk, James D; Shoshiashvili, Levan; Petryk, Alicia A; Hoopes, P Jack

    2016-11-01

    Magnetic nanoparticle hyperthermia therapy is a promising technology for cancer treatment, involving delivering magnetic nanoparticles (MNPs) into tumours then activating them using an alternating magnetic field (AMF). The system produces not only a magnetic field, but also an electric field which penetrates normal tissue and induces eddy currents, resulting in unwanted heating of normal tissues. Magnitude of the eddy current depends, in part, on the AMF source and the size of the tissue exposed to the field. The majority of in vivo MNP hyperthermia therapy studies have been performed in small animals, which, due to the spatial distribution of the AMF relative to the size of the animals, do not reveal the potential toxicity of eddy current heating in larger tissues. This has posed a non-trivial challenge for researchers attempting to scale up to clinically relevant volumes of tissue. There is a relative dearth of studies focused on decreasing the maximum temperature resulting from eddy current heating to increase therapeutic ratio. This paper presents two simple, clinically applicable techniques for decreasing maximum temperature induced by eddy currents. Computational and experimental results are presented to understand the underlying physics of eddy currents induced in conducting, biological tissues and leverage these insights to mitigate eddy current heating during MNP hyperthermia therapy. Phantom studies show that the displacement and motion techniques reduce maximum temperature due to eddy currents by 74% and 19% in simulation, and by 77% and 33% experimentally. Further study is required to optimise these methods for particular scenarios; however, these results suggest larger volumes of tissue could be treated, and/or higher field strengths and frequencies could be used to attain increased MNP heating when these eddy current mitigation techniques are employed.

  1. The changing face of malignant hyperthermia: less fulminant, more insidious..

    PubMed

    Heytens, L; Forget, P; Scholtès, J L; Veyckemans, F

    2015-07-01

    Modern anaesthetic techniques have resulted in the clinical presentation of malignant hyperthermia to be more often indolent and/or insidious than truly fulminant, as previously known in the anaesthetic community. We present four recently referred cases to illustrate this point: one late-onset case, two patients with slowly progressive hypercapnia as the sole sign and a fourth patient with postoperative myalgias and elevated creatine kinase. We also discuss the reasons for the shift in typical clinical presentation. The more insidious character of malignant hyperthermia is most likely due to the lower triggering potency of modern volatile anaesthetics, the mitigating effects of several intravenous drugs (neuromuscular blocking agents, alpha 2 adrenergic receptor agonists, beta adrenergic blockade) or techniques (neuraxial anaesthesia) and the routine use of end-tidal CO2 monitoring leading to the early withdrawal of triggering drugs. Awareness among anaesthetists of this change in presentation is important since the clinical diagnosis is often more doubtful and, if corroborative evidence is not sought, the diagnosis may be delayed or missed altogether.

  2. Fibromyalgia with severe forms of progression in a multidisciplinary therapy setting with emphasis on hyperthermia therapy--a prospective controlled study.

    PubMed

    Romeyke, Tobias; Scheuer, Hans Christoph; Stummer, Harald

    2015-01-01

    Fibromyalgia syndrome (FMS) is a multi-factorial disease involving physiological as well as psychological factors. The aim of the study was to investigate a multidisciplinary inpatient treatment with emphasis on hyperthermia therapy by patients with widespread pain. The study involved 104 patients suffering from severely progressive FMS. A convenience sample and a prospective cohort design were used. The patients were treated in an acute hospital focusing on rheumatologic pain therapy and multidisciplinary complementary medicine. One patient group was treated with inclusion of hyperthermia therapy and the other group without. The therapy density (number of performed therapies per patient) was determined for every patient. Functional capacity measured by the Hannover functional status questionnaire (Funktionsfragebogen Hannover) and symptoms (von Zerssen complaint list) were analyzed for both groups on admission and on discharge. On admission, no significant difference could be established between control group (CG; multimodal without hyperthermia) and hyperthermia group (HG; multimodal with hyperthermia) (functional capacity, P=0.936). Functional capacity improved for the CG and the HG. On discharge, there was a significant difference between the two groups (functional capacity, P=0.039). There were no significant differences in fibromyalgia symptoms between CG (mean 41.8) and HG (mean 41.8) on their admission to hospital (P=0.988). On discharge, there was a significant difference (P=0.024) between the two groups (HG, mean 30.6; CG, mean 36.6). The inpatient therapy of patients with severely progressive fibromyalgia is characterized by a high frequency of therapy input. FMS, especially with severe progression and a high degree of chronification, demands a multidisciplinary approach. In addition to the use of complementary medical procedures, integration of hyperthermia in the treatment process is a useful option.

  3. MWCNT-MnFe2O4 nanocomposite for efficient hyperthermia applications

    NASA Astrophysics Data System (ADS)

    Seal, Papori; Hazarika, Monalisa; Paul, Nibedita; Borah, J. P.

    2018-04-01

    In this work we present synthesis of multi-walled carbon nanotube (MWCNT)-Manganese ferrite (MnFe2O4) nanocomposite and its probable application in hyperthermia. MnFe2O4 nanoparticles were synthesized by co-precipitation method. X ray diffractogram (XRD) confirms the formation of cubic phase of MnFe2O4 with preferred crystallographic orientation along (311) plane. High resolution electron microscope (HRTEM) image of the composites confirms the presence of MnFe2O4 spherical nanoparticles on the surface of CNT which are bound strongly to the surface. MWCNT-MnFe2O4 nanocomposite were prepared after acid functionalization of MWCNT. Vibrational features of the synthesized samples were confirmed through Fourier transformed infra-red spectroscopy (FTIR). FTIR spectra of acid functionalized MWCNT shows a peak positioned at ˜1620cm-1 which corresponds to C=O functional group of carboxylic acid. Prepared MnFe2O4 nanoparticles and MWCNT-MnFe2O4 nanocomposites were subjected to hyperthermia studies.

  4. Antitumor effects of nano-bubble hydrogen-dissolved water are enhanced by coexistent platinum colloid and the combined hyperthermia with apoptosis-like cell death.

    PubMed

    Asada, Ryoko; Kageyama, Katsuhiro; Tanaka, Hiroshi; Matsui, Hisakazu; Kimura, Masatsugu; Saitoh, Yasukazu; Miwa, Nobuhiko

    2010-12-01

    In order to erase reactive oxygen species (ROS) related with the proliferation of tumor cells by reducing activity of hydrogen, we developed functional water containing nano-bubbles (diameters: <900 nm for 71%/population) hydrogen of 1.1-1.5 ppm (the theoretical maximum: 1.6 ppm) with a reducing ability (an oxidation-reduction potential -650 mV, normal water: +100-200 mV) using a microporous-filter hydrogen-jetting device. We showed that hydrogen water erased ROS indispensable for tumor cell growth by ESR/spin trap, the redox indicator CDCFH-DA assay, and was cytotoxic to Ehrlich ascites tumor cells as assessed by WST-8 assay, crystal violet dye stain and scanning electron microscopy, after 24-h or 48-h incubation sequent to warming at 37°C or 42°C. Hydrogen water supplemented with platinum colloid (0.3 ppm Pt in 4% polyvinylpyrrolidone) had more antitumor activity than hydrogen water alone, mineral water alone (15.6%), hydrogen water plus mineral water, or platinum colloid alone as observed by decreased cell numbers, cell shrinkage and pycnosis (nuclear condensation)/karyorrhexis (nuclear fragmentation) indicative of apoptosis, together with cell deformation and disappearance of microvilli on the membrane surface. These antitumor effects were promoted by combination with hyperthermia at 42°C. Thus, the nano-bubble hydrogen water with platinum colloid is potent as an anti-tumor agent.

  5. Focused abdominal sonography for trauma (FAST) in blunt paediatric abdominal trauma.

    PubMed

    Faruque, Ahmad Vaqas; Qazi, Saqib Hamid; Khan, Muhammad Arif Mateen; Akhtar, Wassem; Majeed, Amina

    2013-03-01

    To evaluate the role of focussed abdominal sonography for trauma in blunt paediatric abdominal trauma patients, and to see if the role of computed tomography scan could be limited to only those cases in which sonography was positive. The retrospective study covered 10 years, from January 1,2000 to December 31,2009, and was conducted at the Department of Radiology and Department of Emergency Medicine, Aga Khan University Hospital, Karachi. It comprised cases of 174 children from birth to 14 years who had presented with blunt abdominal trauma and had focussed abdominal sonography for trauma done at the hospital. The findings were correlated with computed tomography scan of the abdomen and clinical follow-up. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of focussed abdominal sonography for trauma were calculated for blunt abdominal trauma. SPSS 17 was used for statistical analysis. Of the total 174 cases, 31 (17.81%) were later confirmed by abdominal scan. Of these 31 children, sonography had been positive in 29 (93.54%) children. In 21 (67.74%) of the 31 children, sonograpy had been true positive; 8 (25%) (8/31) were false positive; and 2 (6%) (2/31) were false negative. There were 6 (19.3%) children in which sonography was positive and converted to laparotomy. There was no significant difference on account of gender (p>0.356). Focussed abdominal sonography for trauma in the study had sensitivity of 91%, specificity of 95%, positive predictive value of 73%, and negative predictive value of 73% with accuracy of 94%. All patients who had negative sonography were discharged later, and had no complication on clinical follow-up. Focussed abdominal sonography for trauma is a fairly reliable mode to assess blunt abdominal trauma in children. It is a useful tool to pick high-grade solid and hollow viscous injury. The results suggest that the role of computed tomography scan can be limited to those cases in which focussed

  6. Targeting to carcinoma cells with chitosan- and starch-coated magnetic nanoparticles for magnetic hyperthermia.

    PubMed

    Kim, Dong-Hyun; Kim, Kyoung-Nam; Kim, Kwang-Mahn; Lee, Yong-Keun

    2009-01-01

    The delivery of hyperthermic thermoseeds to a specific target site with minimal side effects is an important challenge in targeted hyperthermia, which employs magnetic method and functional polymers. An external magnetic field is used to control the site-specific targeting of the magnetic nanoparticles. Polymer-coated magnetic nanoparticles can confer a higher affinity to the biological cell membranes. In this study, uncoated, chitosan-coated, and starch-coated magnetic nanoparticles were synthesized for use as a hyperthermic thermoseed. Each sample was examined with respect to their applications to hyperthermia using XRD, VSM, and FTIR. In addition, the temperature changes under an alternating magnetic field were observed. As in vitro tests, the magnetic responsiveness of chitosan- and starch-coated magnetite was determined by a simple blood vessel model under various intensities of magnetic field. L929 normal cells and KB carcinoma cells were used to examine the cytotoxicity and affinity of each sample using the MTT method. The chitosan-coated magnetic nanoparticles generated a higher DeltaT of 23 degrees C under an AC magnetic field than the starch-coated magnetite, and the capturing rate of the particles was 96% under an external magnetic field of 0.4 T. The highest viability of L929 cells was 93.7%. Comparing the rate of KB cells capture with the rate of L929 cells capture, the rate of KB cells capture relatively increased with 10.8% in chitosan-coated magnetic nanoparticles. Hence, chitosan-coated magnetic nanoparticles are biocompatible and have a selective affinity to KB cells. The targeting of magnetic nanoparticles in hyperthermia was improved using a controlled magnetic field and a chitosan-coating. Therefore, chitosan-coated magnetic nanoparticles are expected to be promising materials for use in magnetic targeted hyperthermia. 2008 Wiley Periodicals, Inc.

  7. Adjuvant properties of thermal component of hyperthermia enhanced transdermal immunization: effect on dendritic cells.

    PubMed

    Joshi, Neha; Duhan, Vikas; Lingwal, Neelam; Bhaskar, Sangeeta; Upadhyay, Pramod

    2012-01-01

    Hyperthermia enhanced transdermal (HET) immunization is a novel needle free immunization strategy employing application of antigen along with mild local hyperthermia (42°C) to intact skin resulting in detectable antigen specific Ig in serum. In the present study, we investigated the adjuvant effect of thermal component of HET immunization in terms of maturation of dendritic cells and its implication on the quality of the immune outcome in terms of antibody production upon HET immunization with tetanus toxoid (TT). We have shown that in vitro hyperthermia exposure at 42°C for 30 minutes up regulates the surface expression of maturation markers on bone marrow derived DCs. This observation correlated in vivo with an increased and accelerated expression of maturation markers on DCs in the draining lymph node upon HET immunization in mice. This effect was found to be independent of the antigen delivered and depends only on the thermal component of HET immunization. In vitro hyperthermia also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell response. HET immunization also induced a systemic T cell response to TT, as suggested by proliferation of splenocytes from immunized animal upon in vitro stimulation by TT. Exposure to heat during primary immunization led to generation of mainly IgG class of antibodies upon boosting, similar to the use of conventional alum adjuvant, thus highlighting the adjuvant potential of heat during HET immunization. Lastly, we have shown that mice immunized by tetanus toxoid using HET route exhibited protection against challenge with a lethal dose of tetanus toxin. Thus, in addition to being a painless, needle free delivery system it also has an immune modulatory potential.

  8. Spontaneous temperature-sensitive Pluronic(®) based niosomes: Triggered drug release using mild hyperthermia.

    PubMed

    Tavano, Lorena; Oliviero Rossi, Cesare; Picci, Nevio; Muzzalupo, Rita

    2016-09-25

    Inclusion of lipids or polymers with a transition temperature closer to physiological body temperature (40-42°C) is a strategy used in tumor therapy for more than 30 years, because it allows induction of drug release from delivery systems by mild hyperthermia. Unfortunately, most of these thermo-sensitive carriers are removed from circulation before completion of their function. Thus, novel multi-functional niosomes possessing spontaneous stealth and thermo-sensitive properties were developed from L64 Pluronic(®) and L64ox as its derivative, in presence or absence of cholesterol. The use of L64 both as amphiphilic constituent and thermo-sensitive molecule, gave the possibility to bypass the use of additional excipients and increased the system biocompatibility. Niosomes diameter ranged from 400 to 750nm and were long term stable. Calcein and 5-FU possess great affinity to niosomal matrices rich in PEO groups. Negative Z-potential values were attributed to the negative charges onto the niosomes surface and generally change according to the temperature. The in vitro drugs release studies were performed at 25°C, 37°C and 42°C, that are representative of certain conditions (storage, physiological condition and mild hyperthermia, respectively). Results showed that L64-based niosomes possess spontaneous thermo-sensitive properties: drugs releases were found to be more pronounced at 42°C. These early results are a promising first step for the development of multi-functional devices that combine several advantages such as stealth properties and temperature controllability at the desired location and time, for a more specific and efficient pharmacological therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. An implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release.

    PubMed

    Sasikala, Arathyram Ramachandra Kurup; Unnithan, Afeesh Rajan; Yun, Yeo-Heung; Park, Chan Hee; Kim, Cheol Sang

    2016-02-01

    The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a p

  10. The effect of hyperthermia on the radiation response of crypt cells in mouse jejunum

    NASA Technical Reports Server (NTRS)

    Wilson, J. D.

    1978-01-01

    The effect of hyperthermia and/or gamma-radiation on the survival of intestinal crypt cells was studied in BDF sub 1 mice using a microcolony assay. Hyperthermia treatments, which in themselves caused no detectable cell lethality, inhibited the capacity of crypt cells to repair sublethal radiation damage. In addition, heat applied either before or after single radiation exposures potentiated lethal damage to crypt cells; the degree of enhancement was dependent on the time interval between treatments. At the levels of heating employed, DNA synthesis in the intestinal epithelium was significantly reduced immediately following exposure, but returned rapidly to normal levels. No further disturbances in cellular kinetics were observed for up to 10 days after heating.

  11. Clearance of genital warts in pregnant women by mild local hyperthermia: a pilot report.

    PubMed

    Huo, Wei; Di, Zheng-Hong; Xiao, Bi-Huan; Qi, Rui-Qun; Weiland, Matthew; Gao, Xing-Hua

    2014-01-01

    Genital warts acquired during pregnancy tend to grow fast, and management is challenging. We treated two cases of primipara with extensive genital warts by local hyperthermia at 44°C for 30 minutes a day for 3 consecutive days plus 2 additional days 1 week later, then once a week till there showed signs of clinical regression. The warty lesions in the patients resolved in 5 and 7 weeks, respectively. There was no sign of recurrence during a 6-month follow-up. This suggests that local hyperthermia seems to be a promising method for treating genital warts in pregnant women. © 2013 China Medical University. ; Dermatologic Therapy © 2013 Wiley Periodicals, Inc.

  12. Child with Abdominal Pain.

    PubMed

    Iyer, Rajalakshmi; Nallasamy, Karthi

    2018-01-01

    Abdominal pain is one of the common symptoms reported by children in urgent care clinics. While most children tend to have self-limiting conditions, the treating pediatrician should watch out for underlying serious causes like intestinal obstruction and perforation peritonitis, which require immediate referral to an emergency department (ED). Abdominal pain may be secondary to surgical or non-surgical causes, and will differ as per the age of the child. The common etiologies for abdominal pain presenting to an urgent care clinic are acute gastro-enteritis, constipation and functional abdominal pain; however, a variety of extra-abdominal conditions may also present as abdominal pain. Meticulous history taking and physical examination are the best tools for diagnosis, while investigations have a limited role in treating benign etiologies.

  13. Combined Therapy against Recurrent Hemangiopericytoma: A Case Report

    PubMed Central

    Li, Xiao-dong; Jiang, Jing-ting; Wu, Chang-ping

    2012-01-01

    Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China A patient with a seven-year history of recurrent metastatic hemangiopericytoma (HPC) was admitted. During his treatment, he received surgical resection, radiotherapy, radiofrequency hyperthermia and chemotherapy using combined doxorubicin, dacarbazin, vincristine, ginsenoside Rg3, and recombinant human endostatin. This synergistic method provides an encouraging model for treating HPC. PMID:23691471

  14. Modelling mass and heat transfer in nano-based cancer hyperthermia.

    PubMed

    Nabil, M; Decuzzi, P; Zunino, P

    2015-10-01

    We derive a sophisticated mathematical model for coupled heat and mass transport in the tumour microenvironment and we apply it to study nanoparticle delivery and hyperthermic treatment of cancer. The model has the unique ability of combining the following features: (i) realistic vasculature; (ii) coupled capillary and interstitial flow; (iii) coupled capillary and interstitial mass transfer applied to nanoparticles; and (iv) coupled capillary and interstitial heat transfer, which are the fundamental mechanisms governing nano-based hyperthermic treatment. This is an improvement with respect to previous modelling approaches, where the effect of blood perfusion on heat transfer is modelled in a spatially averaged form. We analyse the time evolution and the spatial distribution of particles and temperature in a tumour mass treated with superparamagnetic nanoparticles excited by an alternating magnetic field. By means of numerical experiments, we synthesize scaling laws that illustrate how nano-based hyperthermia depends on tumour size and vascularity. In particular, we identify two distinct mechanisms that regulate the distribution of particle and temperature, which are characterized by perfusion and diffusion, respectively.

  15. Vasomotor response of the human face: laser-Doppler measurements during mild hypo- and hyperthermia.

    PubMed

    Rasch, W; Cabanac, M

    1993-04-01

    The skin of the face is reputed not to vasoconstrict in response to cold stress because the face skin temperature remains steady during hypothermia. The purpose of the present work was to measure the vasomotor response of the human face to whole-body hypothermia, and to compare it with hyperthermia. Six male subjects were immersed in cold and in warm water to obtain the two conditions. Skin blood flow, evaporation, and skin temperature (Tsk) were recorded in three loci of the face, the forehead, the infra orbital area, and the cheek. Tympanic (Tty) and oesophageal (Toes) temperatures were also recorded during the different thermal states. Normothermic measurements served as control. Blood flow was recorded with a laser-Doppler flowmeter, evaporation measured with an evaporimeter. Face Tsk remained stable between normo-, hypo-, and hyperthermia. Facial blood flow, however, did not follow the same pattern. The facial blood flow remained at minimal vasoconstricted level when the subjects' condition was changed from normo- to hypothermia. When the condition changed from hypo- to hyperthermia a 3 to 9-fold increase in the blood flow was recorded. From these results it was concluded that a vasoconstriction seems to be the general vasomotor state in the face during normothermia.

  16. How gastrin-releasing peptide receptor (GRPR) and αvβ3 integrin expression reflect reorganization features of tumors after hyperthermia treatments.

    PubMed

    Hallasch, Sandra; Frick, Sindy; Jung, Maximilian; Hilger, Ingrid

    2017-07-31

    The outcome of tumor treatment via hyperthermia in the clinic has been reported to be heterogeneous. Here, we assessed how the presence of gastrin-releasing peptide receptor (GRPR) and α v β 3 integrin together with the morphology of the vascularization reflects the growth behavior of tumors after hyperthermia treatment. MDA-MB-231 tumor bearing mice were treated either with high (46 °C) or low dose (42 °C) water hyperthermia for 60 min. Changes of GRPR and α v β 3 integrin expression were assessed via multiplexed optical imaging. Vascularization was reconstructed and quantified by µCT imaging after contrast agent injection. We found that high dose hyperthermia is capable of increasing the expression of GRPR, α v β 3 integrin, CD31, and Ki67 in tumors. Also the morphology of tumor vasculature changed (increased relative blood volume and small-diameter vessel density, decreased expression of α-SMA). Low dose hyperthermia induced comparatively moderate effects on the investigated protein expression pattern and vascular remodeling. We conclude that under defined circumstances, specific temperature doses affect the reorganization of tumor regrowth, which is triggered by residual "dormant" cells even though tumor volumes are transiently decreasing. Further on, GRPR, α v β 3 integrin expression are versatile tools to surveil potential tumor regrow during therapy, beyond the conventional determination of tumor volumes.

  17. Transient Mild Hyperthermia Induces E-selectin Mediated Localization of Mesoporous Silicon Vectors in Solid Tumors

    PubMed Central

    Kirui, Dickson K.; Mai, Juahua; Palange, Anna-Lisa; Qin, Guoting; van de Ven, Anne L.; Liu, Xuewu; Shen, Haifa; Ferrari, Mauro

    2014-01-01

    Background Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT) to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs). We also determined the optimal time window at which maximal accumulation occur. Results In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm2) amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm) adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion. Conclusions Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy. PMID:24558362

  18. Abdominal wall fat pad biopsy

    MedlinePlus

    Amyloidosis - abdominal wall fat pad biopsy; Abdominal wall biopsy; Biopsy - abdominal wall fat pad ... most common method of taking an abdominal wall fat pad biopsy . The health care provider cleans the ...

  19. High skeletal muscle adenylate cyclase in malignant hyperthermia.

    PubMed Central

    Willner, J H; Cerri, C G; Wood, D S

    1981-01-01

    Malignant hyperthermia occurs in humans with several congenital myopathies, usually in response to general anesthesia. Commonly, individuals who develop this syndrome lack symptoms of muscle disease, and their muscle lacks specific pathological changes. A biochemical marker for this myopathy has not previously been available; we found activity of adenylate cyclase and content of cyclic AMP to be abnormally high in skeletal muscle. Secondary modification of protein phosphorylation could explain observed abnormalities of phosphorylase activation and sarcoplasmic reticulum function. PMID:6271806

  20. Precise determination of the heat delivery during in vivo magnetic nanoparticle hyperthermia with infrared thermography.

    PubMed

    Rodrigues, Harley F; Capistrano, Gustavo; Mello, Francyelli M; Zufelato, Nicholas; Silveira-Lacerda, Elisângela; Bakuzis, Andris F

    2017-05-21

    Non-invasive and real-time monitoring of the heat delivery during magnetic nanoparticle hyperthermia (MNH) is of fundamental importance to predict clinical outcomes for cancer treatment. Infrared thermography (IRT) can determine the surface temperature due to three-dimensional heat delivery inside a subcutaneous tumor, an argument that is supported by numerical simulations. However, for precise temperature determination, it is of crucial relevance to use a correct experimental configuration. This work reports an MNH study using a sarcoma 180 murine tumor containing 3.9 mg of intratumorally injected manganese-ferrite nanoparticles. MNH was performed at low field amplitude and non-uniform field configuration. Five 30 min in vivo magnetic hyperthermia experiments were performed, monitoring the surface temperature with a fiber optical sensor and thermal camera at distinct angles with respect to the animal's surface. The results indicate that temperature errors as large as [Formula: see text]C can occur if the experiment is not properly designed. A new IRT error model is found to explain the data. More importantly, we show how to precisely monitor temperature with IRT during hyperthermia, which could positively impact heat dosimetry and clinical planning.

  1. Precise determination of the heat delivery during in vivo magnetic nanoparticle hyperthermia with infrared thermography

    NASA Astrophysics Data System (ADS)

    Rodrigues, Harley F.; Capistrano, Gustavo; Mello, Francyelli M.; Zufelato, Nicholas; Silveira-Lacerda, Elisângela; Bakuzis, Andris F.

    2017-05-01

    Non-invasive and real-time monitoring of the heat delivery during magnetic nanoparticle hyperthermia (MNH) is of fundamental importance to predict clinical outcomes for cancer treatment. Infrared thermography (IRT) can determine the surface temperature due to three-dimensional heat delivery inside a subcutaneous tumor, an argument that is supported by numerical simulations. However, for precise temperature determination, it is of crucial relevance to use a correct experimental configuration. This work reports an MNH study using a sarcoma 180 murine tumor containing 3.9 mg of intratumorally injected manganese-ferrite nanoparticles. MNH was performed at low field amplitude and non-uniform field configuration. Five 30 min in vivo magnetic hyperthermia experiments were performed, monitoring the surface temperature with a fiber optical sensor and thermal camera at distinct angles with respect to the animal’s surface. The results indicate that temperature errors as large as 7~\\circ C can occur if the experiment is not properly designed. A new IRT error model is found to explain the data. More importantly, we show how to precisely monitor temperature with IRT during hyperthermia, which could positively impact heat dosimetry and clinical planning.

  2. Biodegradable magnesium nanoparticle-enhanced laser hyperthermia therapy

    PubMed Central

    Wang, Qian; Xie, Liping; He, Zhizhu; Di, Derui; Liu, Jing

    2012-01-01

    Background Recently, nanoparticles have been demonstrated to have tremendous merit in terms of improving the treatment specificity and thermal ablation effect on tumors. However, the potential toxicity and long-term side effects caused by the introduced nanoparticles and by expelling them out of the body following surgery remain a significant challenge. Here, we propose for the first time to directly adopt magnesium nanoparticles as the heating enhancer in laser thermal ablation to avoid these problems by making full use of the perfect biodegradable properties of this specific material. Methods To better understand the new nano “green” hyperthermia modality, we evaluated the effects of magnesium nanoparticles on the temperature transients inside the human body subject to laser interstitial heating. Further, we experimentally investigated the heating enhancement effects of magnesium nanoparticles on a group of biological samples: oil, egg white, egg yolk, in vitro pig tissues, and the in vivo hind leg of rabbit when subjected to laser irradiation. Results Both the theoretical simulations and experimental measurements demonstrated that the target tissues injected with magnesium nanoparticles reached much higher temperatures than tissues without magnesium nanoparticles. This revealed the enhancing behavior of the new nanohyperthermia method. Conclusion Given the unique features of magnesium nanoparticles – their complete biological safety and ability to enhance heating – which most other advanced metal nanoparticles do not possess, the use of magnesium nanoparticles in hyperthermia therapy offers an important “green” nanomedicine modality for treating tumors. This method has the potential to be used in clinics in the near future. PMID:22956872

  3. High permittivity patch radiator for single and multi-element hyperthermia applicators.

    PubMed

    Andreuccetti, D; Bini, M; Ignesti, A; Olmi, R; Priori, S; Vanni, R

    1993-07-01

    This paper describes a compact, low-profile patch radiator which is the base element for efficient, small-size applicators suitable for superficial hyperthermia. The design criteria and the technological processes involved are presented. The electromagnetic characteristics of the patch element are outlined, and possible application of the radiator are discussed.

  4. Radio frequency induced hyperthermia mediated by dextran stabilized LSMO nanoparticles: in vitro evaluation of heat shock protein response

    NASA Astrophysics Data System (ADS)

    Bhayani, K. R.; Rajwade, J. M.; Paknikar, K. M.

    2013-01-01

    Dextran stabilized La0.7Sr0.3MnO3 (Dex-LSMO) is an alternative cancer hyperthermia agent holding considerable promise. Here, we have carried out a comparative study on radio frequency (˜264 kHz) induced Dex-LSMO mediated heating and extraneous heating (mimicking generalized hyperthermia) in terms of changes in the morphology, proliferation pattern and induction of heat shock proteins in a human melanoma cell line (A375). Our results clearly show that the cellular effects seen with extraneous heating (60 min at 43 °C) could be reproduced by just six minutes of radio frequency induced Dex-LSMO mediated heating. More importantly, the observed enhanced levels of HSP 70 and 90 (molecular markers of heat shock that trigger favorable immunological reactions) seen with Dex-LSMO mediated heating were comparable to extraneous heating. These results suggest the possible utility of Dex-LSMO as a cancer hyperthermia agent.

  5. Fibromyalgia with severe forms of progression in a multidisciplinary therapy setting with emphasis on hyperthermia therapy – a prospective controlled study

    PubMed Central

    Romeyke, Tobias; Scheuer, Hans Christoph; Stummer, Harald

    2015-01-01

    Introduction Fibromyalgia syndrome (FMS) is a multi-factorial disease involving physiological as well as psychological factors. The aim of the study was to investigate a multidisciplinary inpatient treatment with emphasis on hyperthermia therapy by patients with widespread pain. Materials and methods The study involved 104 patients suffering from severely progressive FMS. A convenience sample and a prospective cohort design were used. The patients were treated in an acute hospital focusing on rheumatologic pain therapy and multidisciplinary complementary medicine. One patient group was treated with inclusion of hyperthermia therapy and the other group without. The therapy density (number of performed therapies per patient) was determined for every patient. Functional capacity measured by the Hannover functional status questionnaire (Funktionsfragebogen Hannover) and symptoms (von Zerssen complaint list) were analyzed for both groups on admission and on discharge. Results On admission, no significant difference could be established between control group (CG; multimodal without hyperthermia) and hyperthermia group (HG; multimodal with hyperthermia) (functional capacity, P=0.936). Functional capacity improved for the CG and the HG. On discharge, there was a significant difference between the two groups (functional capacity, P=0.039). There were no significant differences in fibromyalgia symptoms between CG (mean 41.8) and HG (mean 41.8) on their admission to hospital (P=0.988). On discharge, there was a significant difference (P=0.024) between the two groups (HG, mean 30.6; CG, mean 36.6). The inpatient therapy of patients with severely progressive fibromyalgia is characterized by a high frequency of therapy input. Conclusion FMS, especially with severe progression and a high degree of chronification, demands a multidisciplinary approach. In addition to the use of complementary medical procedures, integration of hyperthermia in the treatment process is a useful option

  6. Hyperthermia modifies muscle metaboreceptor and baroreceptor modulation of heat loss in humans.

    PubMed

    Binder, Konrad; Lynn, Aaron G; Gagnon, Daniel; Kondo, Narihiko; Kenny, Glen P

    2012-02-15

    The relative influence of muscle metabo- and baroreflex activity on heat loss responses during post-isometric handgrip (IHG) exercise ischemia remains unknown, particularly under heat stress. Therefore, we examined the separate and integrated influences of metabo- and baroreceptor-mediated reflex activity on sweat rate and cutaneous vascular conductance (CVC) under increasing levels of hyperthermia. Twelve men performed 1 min of IHG exercise at 60% of maximal voluntary contraction followed by 2 min of ischemia with simultaneous application of lower body positive pressure (LBPP, +40 mmHg), lower body negative pressure (LBNP, -20 mmHg), or no pressure (control) under no heat stress. On separate days, trials were repeated under heat stress conditions of 0.6°C (moderate heat stress) and 1.4°C (high heat stress) increase in esophageal temperature. For all conditions, mean arterial pressure was greater with LBPP and lower with LBNP than control during ischemia (all P ≤ 0.05). No differences in sweat rate were observed between pressure conditions, regardless of the level of hyperthermia (P > 0.05). Under moderate heat stress, no differences in CVC were observed between pressure conditions. However, under high heat stress, LBNP significantly reduced CVC by 21 ± 4% (P ≤ 0.05) and LBPP significantly elevated CVC by 14 ± 5% (P ≤ 0.05) relative to control. These results show that sweating during post-IHG exercise ischemia is activated by metaboreflex stimulation, and not by baroreflexes. In contrast, our results suggest that baroreflexes can influence the metaboreflex modulation of CVC, but only at greater levels of hyperthermia.

  7. Abdominal Obesity and Risk of Hip Fracture: A Systematic Review and Meta-Analysis of Prospective Studies.

    PubMed

    Sadeghi, Omid; Saneei, Parvaneh; Nasiri, Morteza; Larijani, Bagher; Esmaillzadeh, Ahmad

    2017-09-01

    Data on the association between general obesity and hip fracture were summarized in a 2013 meta-analysis; however, to our knowledge, no study has examined the association between abdominal obesity and the risk of hip fracture. The present systematic review and meta-analysis of prospective studies was undertaken to summarize the association between abdominal obesity and the risk of hip fracture. We searched online databases for relevant publications up to February 2017, using relevant keywords. In total, 14 studies were included in the systematic review and 9 studies, with a total sample size of 295,674 individuals (129,964 men and 165,703 women), were included in the meta-analysis. Participants were apparently healthy and aged ≥40 y. We found that abdominal obesity (defined by various waist-hip ratios) was positively associated with the risk of hip fracture (combined RR: 1.24, 95% CI: 1.05, 1.46, P = 0.01). Combining 8 effect sizes from 6 studies, we noted a marginally significant positive association between abdominal obesity (defined by various waist circumferences) and the risk of hip fracture (combined RR: 1.36; 95% CI: 0.97, 1.89, P = 0.07). This association became significant in a fixed-effects model (combined effect size: 1.40, 95% CI: 1.25, 1.58, P < 0.001). Based on 5 effect sizes, we found that a 0.1-U increase in the waist-hip ratio was associated with a 16% increase in the risk of hip fracture (combined RR: 1.16, 95% CI: 1.04, 1.29, P = 0.007), whereas a 10-cm increase in waist circumference was not significantly associated with a higher risk of hip fracture (combined RR: 1.13, 95% CI: 0.94, 1.36, P = 0.19). This association became significant, however, when we applied a fixed-effects model (combined effect size: 1.21, 95% CI: 1.15, 1.27, P < 0.001). We found that abdominal obesity was associated with a higher risk of hip fracture in 295,674 individuals. Further studies are needed to test whether there are associations between abdominal obesity and

  8. A novel fenestration technique for abdominal aortic dissection membranes using a combination of a needle re-entry catheter and the "cheese-wire" technique.

    PubMed

    Kos, Sebastian; Gürke, Lorenz; Jacob, Augustinus L

    2011-12-01

    This study was designed to demonstrate the applicability of a combined needle-based re-entry catheter and "cheese-wire" technique for fenestration of abdominal aortic dissection membranes. Four male patients (mean age: 65 years) with acute complicated aortic type B dissections were treated at our institution by fenestrating the abdominal aortic dissection membrane using a hybrid technique. This technique combined an initial membrane puncture with a needle-based re-entry catheter using a transfemoral approach. A guidewire was passed through the re-entry catheter and across the membrane. Using a contralateral transfemoral access, this guidewire was then snared, creating a through-and-through wire access. The membrane was then fenestrated using the cheese-wire maneuver. We successfully performed: (a) membrane puncture; (b) guidewire passage; (c) guidewire snaring; and (d) cheese-wire maneuver in all four cases. After this maneuver, decompression of the false lumen and acceptable arterial inflow into the true lumen was observed in all cases. The dependent visceral arteries were reperfused. In one case, portions of the fenestrated membrane occluded the common iliac artery, which was immediately and successfully stented. In another case, long-standing intestinal hypoperfusion before the fenestration resulted in reperfusion-related shock and intraoperative death of the patient. The described hybrid approach for fenestration of dissection membranes is technically feasible and may be established as a therapeutic method in cases with a complicated type B dissection.

  9. [Rational therapy of patients with essential hypertension and abdominal obesity with concomitant subclinical hypothyroidism].

    PubMed

    Pligovka, V M

    2014-11-01

    It was determined the characteristics of lipid status of patients with essential hypertension, abdominal obesity with concomitant subclinical hypothyroidism--mostly increased levels of total and LDL cholesterol. In assessing the effectiveness of statin therapy in combination with levothyroxine replacement therapy compared with statin monotherapy, combination therapy showed the best result in terms of achievement of target levels of both total cholesterol and LDL. The obtained results allow us to recommend the use of combination therapy for patients with hypertension, abdominal obesity with concomitant subclinical hypothyroidism in order to achieve the target values of LDL and thus to reduce the cardiovascular risk of these patients.

  10. EFFECTS OF HYPERTHERMIA AND BORIC ACID ON SKELETAL DEVELOPMENT IN RAT EMBRYOS

    EPA Science Inventory

    BACKGROUND: The individual effects of boric acid (BA) and hyperthermia on the development of the axial skeleton have previously been reported. Both cause an increased incidence of axial skeletal defects including a decrease in the total number of ribs and vertebrae. Because of th...

  11. Optimizing Cold Water Immersion for Exercise-Induced Hyperthermia: A Meta-analysis.

    PubMed

    Zhang, Yang; Davis, Jon-Kyle; Casa, Douglas J; Bishop, Phillip A

    2015-11-01

    Cold water immersion (CWI) provides rapid cooling in events of exertional heat stroke. Optimal procedures for CWI in the field are not well established. This meta-analysis aimed to provide structured analysis of the effectiveness of CWI on the cooling rate in healthy adults subjected to exercise-induced hyperthermia. An electronic search (December 2014) was conducted using the PubMed and Web of Science. The mean difference of the cooling rate between CWI and passive recovery was calculated. Pooled analyses were based on a random-effects model. Sources of heterogeneity were identified through a mixed-effects model Q statistic. Inferential statistics aggregated the CWI cooling rate for extrapolation. Nineteen studies qualified for inclusion. Results demonstrate CWI elicited a significant effect: mean difference, 0.03°C·min(-1); 95% confidence interval, 0.03-0.04°C·min(-1). A conservative, observed estimate of the CWI cooling rate was 0.08°C·min(-1) across various conditions. CWI cooled individuals twice as fast as passive recovery. Subgroup analyses revealed that cooling was more effective (Q test P < 0.10) when preimmersion core temperature ≥38.6°C, immersion water temperature ≤10°C, ambient temperature ≥20°C, immersion duration ≤10 min, and using torso plus limbs immersion. There is insufficient evidence of effect using forearms/hands CWI for rapid cooling: mean difference, 0.01°C·min(-1); 95% confidence interval, -0.01°C·min(-1) to 0.04°C·min(-1). A combined data summary, pertaining to 607 subjects from 29 relevant studies, was presented for referencing the weighted cooling rate and recovery time, aiming for practitioners to better plan emergency procedures. An optimal procedure for yielding high cooling rates is proposed. Using prompt vigorous CWI should be encouraged for treating exercise-induced hyperthermia whenever possible, using cold water temperature (approximately 10°C) and maximizing body surface contact (whole-body immersion).

  12. Don't Forget the Abdominal Wall: Imaging Spectrum of Abdominal Wall Injuries after Nonpenetrating Trauma.

    PubMed

    Matalon, Shanna A; Askari, Reza; Gates, Jonathan D; Patel, Ketan; Sodickson, Aaron D; Khurana, Bharti

    2017-01-01

    Abdominal wall injuries occur in nearly one of 10 patients coming to the emergency department after nonpenetrating trauma. Injuries range from minor, such as abdominal wall contusion, to severe, such as abdominal wall rupture with evisceration of abdominal contents. Examples of specific injuries that can be detected at cross-sectional imaging include abdominal muscle strain, tear, or hematoma, including rectus sheath hematoma (RSH); traumatic abdominal wall hernia (TAWH); and Morel-Lavallée lesion (MLL) (closed degloving injury). These injuries are often overlooked clinically because of (a) a lack of findings at physical examination or (b) distraction by more-severe associated injuries. However, these injuries are important to detect because they are highly associated with potentially grave visceral and vascular injuries, such as aortic injury, and because their detection can lead to the diagnosis of these more clinically important grave traumatic injuries. Failure to make a timely diagnosis can result in delayed complications, such as bowel hernia with potential for obstruction or strangulation, or misdiagnosis of an abdominal wall neoplasm. Groin injuries, such as athletic pubalgia, and inferior costochondral injuries should also be considered in patients with abdominal pain after nonpenetrating trauma, because these conditions may manifest with referred abdominal pain and are often included within the field of view at cross-sectional abdominal imaging. Radiologists must recognize and report acute abdominal wall injuries and their associated intra-abdominal pathologic conditions to allow appropriate and timely treatment. © RSNA, 2017.

  13. Correlation between intra-abdominal pressure and pulmonary volumes after superior and inferior abdominal surgery.

    PubMed

    Cleva, Roberto de; Assumpção, Marianna Siqueira de; Sasaya, Flavia; Chaves, Natalia Zuniaga; Santo, Marco Aurelio; Fló, Claudia; Lunardi, Adriana C; Jacob Filho, Wilson

    2014-07-01

    Patients undergoing abdominal surgery are at risk for pulmonary complications. The principal cause of postoperative pulmonary complications is a significant reduction in pulmonary volumes (FEV1 and FVC) to approximately 65-70% of the predicted value. Another frequent occurrence after abdominal surgery is increased intra-abdominal pressure. The aim of this study was to correlate changes in pulmonary volumes with the values of intra-abdominal pressure after abdominal surgery, according to the surgical incision in the abdomen (superior or inferior). We prospectively evaluated 60 patients who underwent elective open abdominal surgery with a surgical time greater than 240 minutes. Patients were evaluated before surgery and on the 3rd postoperative day. Spirometry was assessed by maximal respiratory maneuvers and flow-volume curves. Intra-abdominal pressure was measured in the postoperative period using the bladder technique. The mean age of the patients was 56 ± 13 years, and 41.6% 25 were female; 50 patients (83.3%) had malignant disease. The patients were divided into two groups according to the surgical incision (superior or inferior). The lung volumes in the preoperative period showed no abnormalities. After surgery, there was a significant reduction in both FEV1 (1.6 ± 0.6 L) and FVC (2.0 ± 0.7 L) with maintenance of FEV1/FVC of 0.8 ± 0.2 in both groups. The maximum intra-abdominal pressure values were similar (p=0.59) for the two groups. There was no association between pulmonary volumes and intra-abdominal pressure measured in any of the groups analyzed. Our results show that superior and inferior abdominal surgery determines hypoventilation, unrelated to increased intra-abdominal pressure. Patients at high risk of pulmonary complications should receive respiratory care even if undergoing inferior abdominal surgery.

  14. Fever-range hyperthermia improves the anti-apoptotic effect induced by low pH on human neutrophils promoting a proangiogenic profile.

    PubMed

    Díaz, Fernando Erra; Dantas, Ezequiel; Cabrera, Maia; Benítez, Constanza A; Delpino, María V; Duette, Gabriel; Rubione, Julia; Sanjuan, Norberto; Trevani, Analía S; Geffner, Jorge

    2016-10-27

    Neutrophils have the shortest lifespan among leukocytes and usually die via apoptosis, limiting their deleterious potential. However, this tightly regulated cell death program can be modulated by pathogen-associated molecular patterns (PAMPs), danger-associated molecular pattern (DAMPs), and inflammatory cytokines. We have previously reported that low pH, a hallmark of inflammatory processes and solid tumors, moderately delays neutrophil apoptosis. Here we show that fever-range hyperthermia accelerates the rate of neutrophil apoptosis at neutral pH but markedly increases neutrophil survival induced by low pH. Interestingly, an opposite effect was observed in lymphocytes; hyperthermia plus low pH prevents lymphocyte activation and promotes the death of lymphocytes and lymphoid cell lines. Analysis of the mechanisms through which hyperthermia plus low pH increased neutrophil survival revealed that hyperthermia further decreases cytosolic pH induced by extracellular acidosis. The fact that two Na + /H + exchanger inhibitors, 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and amiloride, reproduced the effects induced by hyperthermia suggested that it prolongs neutrophil survival by inhibiting the Na + /H + antiporter. The neutrophil anti-apoptotic effect induced by PAMPs, DAMPs, and inflammatory cytokines usually leads to the preservation of the major neutrophil effector functions such as phagocytosis and reactive oxygen species (ROS) production. In contrast, our data revealed that the anti-apoptotic effect induced by low pH and hyperthermia induced a functional profile characterized by a low phagocytic activity, an impairment in ROS production and a high ability to suppress T-cell activation and to produce the angiogenic factors VEGF, IL-8, and the matrix metallopeptidase 9 (MMP-9). These results suggest that acting together fever and local acidosis might drive the differentiation of neutrophils into a profile able to promote both cancer progression and tissue repair during

  15. A study on thermal damage during hyperthermia treatment based on DPL model for multilayer tissues using finite element Legendre wavelet Galerkin approach.

    PubMed

    Kumar, Dinesh; Rai, K N

    2016-12-01

    Hyperthermia is a process that uses heat from the spatial heat source to kill cancerous cells without damaging the surrounding healthy tissues. Efficacy of hyperthermia technique is related to achieve temperature at the infected cells during the treatment process. A mathematical model on heat transfer in multilayer tissues in finite domain is proposed to predict the control temperature profile at hyperthermia position. The treatment technique uses dual-phase-lag model of heat transfer in multilayer tissues with modified Gaussian distribution heat source subjected to the most generalized boundary condition and interface at the adjacent layers. The complete dual-phase-lag model of bioheat transfer is solved using finite element Legendre wavelet Galerkin approach. The present solution has been verified with exact solution in a specific case and provides a good accuracy. The effect of the variability of different parameters such as lagging times, external heat source, metabolic heat source and the most generalized boundary condition on temperature profile in multilayer tissues is analyzed and also discussed the effective approach of hyperthermia treatment. Furthermore, we studied the modified thermal damage model with regeneration of healthy tissues as well. For viewpoint of thermal damage, the least thermal damage has been observed in boundary condition of second kind. The article concludes with a discussion of better opportunities for future clinical application of hyperthermia treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Hyperthermia in bone generated with MR imaging-controlled focused ultrasound: control strategies and drug delivery.

    PubMed

    Staruch, Robert; Chopra, Rajiv; Hynynen, Kullervo

    2012-04-01

    To evaluate the feasibility of achieving image-guided drug delivery in bone by using magnetic resonance (MR) imaging-controlled focused ultrasound hyperthermia and temperature-sensitive liposomes. Experiments were approved by the institutional animal care committee. Hyperthermia (43°C, 20 minutes) was generated in 10-mm-diameter regions at a muscle-bone interface in nine rabbit thighs by using focused ultrasound under closed-loop temperature control with MR thermometry. Thermosensitive liposomal doxorubicin was administered systemically during heating. Heating uniformity and drug delivery were evaluated for control strategies with the temperature control image centered 10 mm (four rabbits) or 0 mm (five rabbits) from the bone. Simulations estimated temperature elevations in bone. Drug delivery was quantified by using the fluorescence of doxorubicin extracted from bone marrow and muscle and was compared between treated and untreated thighs by using the one-sided Wilcoxon signed rank test. With ultrasound focus and MR temperature control plane 0 mm and 10 mm from the bone interface, average target region temperatures were 43.1°C and 43.3°C, respectively; numerically estimated bone temperatures were 46.8°C and 78.1°C. The 10-mm offset resulted in thermal ablation; numerically estimated muscle temperature was 66.1°C at the bone interface. Significant increases in doxorubicin concentration occurred in heated versus unheated marrow (8.2-fold, P = .002) and muscle (16.8-fold, P = .002). Enhancement occurred for 0- and 10-mm offsets, which suggests localized drug delivery in bone is possible with both hyperthermia and thermal ablation. MR imaging-controlled focused ultrasound can achieve localized hyperthermia in bone for image-guided drug delivery in bone with temperature-sensitive drug carriers. © RSNA, 2012.

  17. The genetics of malignant hyperthermia.

    PubMed Central

    Ball, S P; Johnson, K J

    1993-01-01

    Malignant hyperthermia susceptibility remains the commonest cause of death owing to general anaesthesia. This is despite the availability of presymptomatic testing, admittedly by a highly invasive method, and a recognised treatment for implementation immediately a patient shows signs of developing a crisis. Recently the finding of linkage to markers from chromosome 19q13.1-13.2 and the identification of mutations in a candidate gene held out hope of genetic diagnosis being available. However, it is likely that only about 50% of families have a mutation of the skeletal muscle calcium release channel gene. With this degree of genetic heterogeneity, presymptomatic testing based on DNA markers can only be offered at present to a limited number of families where linkage to markers from 19q13.1-13.2 has been clearly shown. Images PMID:8383206

  18. Magnetic hyperthermia properties of iron oxide nanoparticles: The effect of concentration

    NASA Astrophysics Data System (ADS)

    Ebrahimisadr, Saeid; Aslibeiki, Bagher; Asadi, Reza

    2018-06-01

    We investigated the effect of concentration on magnetic hyperthermia properties of Fe3O4 nanoparticles (NPs). The NPs were synthesized by co-precipitation method at 80 °C. Scanning electron microscope image showed that the mean diameter of NPs is about 18 nm. The XRD pattern indicated that the sample is pure Fe3O4 with spinel structure and the FT-IR spectroscopy confirmed formation of metal-oxygen bonds in the octahedral and tetrahedral spinel sub-lattice which further confirmed crystalline structure of the sample. The hyperthermia property of Fe3O4 NPs was investigated via an induction heater generating alternating magnetic field with frequency of 92 kHz. The temperature rise (ΔT) of suspension in the AC magnetic field was studied on different concentrations of NPs and the specific absorption rate (SAR) was obtained from Box-Lucas equation and linear fitting of ΔT-time curve. The results showed that the ΔT sharply increases with increasing the NPs concentration while the SAR remains almost constant.

  19. Hyperthermia mediated by dextran-coated La0.7Sr0.3MnO3 nanoparticles: in vivo studies

    PubMed Central

    Haghniaz, Reihaneh; Umrani, Rinku D; Paknikar, Kishore M

    2016-01-01

    Purpose The aim of this study was to evaluate radiofrequency-induced dextran-coated lanthanum strontium manganese oxide nanoparticles-mediated hyperthermia to be used for tumor regression in mice. Materials and methods Nanoparticles were injected intra-tumorally in melanoma-bearing C57BL/6J mice and were subjected to radiofrequency treatment. Results Hyperthermia treatment significantly inhibited tumor growth (~84%), increased survival (~50%), and reduced tumor proliferation in mice. Histopathological examination demonstrated immense cell death in treated tumors. DNA fragmentation, increased terminal deoxynucleotidyl transferase-dUTP nick end labeling signal, and elevated levels of caspase-3 and caspase-6 suggested apoptotic cell death. Enhanced catalase activity suggested reactive oxygen species-mediated cell death. Enhanced expression of heat shock proteins 70 and 90 in treated tumors suggested the possible development of “antitumor immunity”. Conclusion The dextran-coated lanthanum strontium manganese oxide-mediated hyperthermia can be used for the treatment of cancer. PMID:27175076

  20. Development of a spherically focused phased array transducer for ultrasonic image-guided hyperthermia

    NASA Astrophysics Data System (ADS)

    Liu, Jingfei; Foiret, Josquin; Stephens, Douglas N.; Le Baron, Olivier; Ferrara, Katherine W.

    2016-07-01

    A 1.5 MHz prolate spheroidal therapeutic array with 128 circular elements was designed to accommodate standard imaging arrays for ultrasonic image-guided hyperthermia. The implementation of this dual-array system integrates real-time therapeutic and imaging functions with a single ultrasound system (Vantage 256, Verasonics). To facilitate applications involving small animal imaging and therapy the array was designed to have a beam depth of field smaller than 3.5 mm and to electronically steer over distances greater than 1 cm in both the axial and lateral directions. In order to achieve the required f number of 0.69, 1-3 piezocomposite modules were mated within the transducer housing. The performance of the prototype array was experimentally evaluated with excellent agreement with numerical simulation. A focal volume (2.70 mm (axial)  ×  0.65 mm (transverse)  ×  0.35 mm (transverse)) defined by the  -6 dB focal intensity was obtained to address the dimensions needed for small animal therapy. An electronic beam steering range defined by the  -3 dB focal peak intensity (17 mm (axial)  ×  14 mm (transverse)  ×  12 mm (transverse)) and  -8 dB lateral grating lobes (24 mm (axial)  ×  18 mm (transverse)  ×  16 mm (transverse)) was achieved. The combined testing of imaging and therapeutic functions confirmed well-controlled local heating generation and imaging in a tissue mimicking phantom. This dual-array implementation offers a practical means to achieve hyperthermia and ablation in small animal models and can be incorporated within protocols for ultrasound-mediated drug delivery.

  1. Development of a spherically focused phased array transducer for ultrasonic image-guided hyperthermia.

    PubMed

    Liu, Jingfei; Foiret, Josquin; Stephens, Douglas N; Le Baron, Olivier; Ferrara, Katherine W

    2016-07-21

    A 1.5 MHz prolate spheroidal therapeutic array with 128 circular elements was designed to accommodate standard imaging arrays for ultrasonic image-guided hyperthermia. The implementation of this dual-array system integrates real-time therapeutic and imaging functions with a single ultrasound system (Vantage 256, Verasonics). To facilitate applications involving small animal imaging and therapy the array was designed to have a beam depth of field smaller than 3.5 mm and to electronically steer over distances greater than 1 cm in both the axial and lateral directions. In order to achieve the required f number of 0.69, 1-3 piezocomposite modules were mated within the transducer housing. The performance of the prototype array was experimentally evaluated with excellent agreement with numerical simulation. A focal volume (2.70 mm (axial)  ×  0.65 mm (transverse)  ×  0.35 mm (transverse)) defined by the  -6 dB focal intensity was obtained to address the dimensions needed for small animal therapy. An electronic beam steering range defined by the  -3 dB focal peak intensity (17 mm (axial)  ×  14 mm (transverse)  ×  12 mm (transverse)) and  -8 dB lateral grating lobes (24 mm (axial)  ×  18 mm (transverse)  ×  16 mm (transverse)) was achieved. The combined testing of imaging and therapeutic functions confirmed well-controlled local heating generation and imaging in a tissue mimicking phantom. This dual-array implementation offers a practical means to achieve hyperthermia and ablation in small animal models and can be incorporated within protocols for ultrasound-mediated drug delivery.

  2. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    DTIC Science & Technology

    2013-10-01

    ABSTRACT Based upon the results obtained from these studies, we can draw the following conclusions: 1) Airway hyperresponsiveness developed in Ova ...hyperthermia in Ova -sensitized rats. The manuscript reporting the results obtained frim this study has been accepted for publication by the Journal of...to increasing airway temperature. Our results showed: 1) In Brown-Norway rats actively sensitized by ovalbumin ( Ova ), isocapnic hyperventilation with

  3. Indwelling catheter and conservative measures in the treatment of abdominal compartment syndrome in fulminant acute pancreatitis

    PubMed Central

    Sun, Zhao-Xi; Huang, Hai-Rong; Zhou, Hong

    2006-01-01

    AIM: To study the effect of combined indwelling catheter, hemofiltration, respiration support and traditional Chinese medicine (e.g. Dahuang) in treating abdominal compartment syndrome of fulminant acute pancreatitis. METHODS: Patients with fulminant acute pancreatitis were divided randomly into 2 groups of combined indwelling catheter celiac drainage and intra-abdominal pressure monitoring and routine conservative measures group (group 1) and control group (group 2). Routine non-operative conservative treatments including hemofiltration, respiration support, gastrointestinal TCM ablution were also applied in control group patients. Effectiveness of the two groups was observed, and APACHE II scores were applied for analysis. RESULTS: On the second and fifth days after treatment, APACHE II scores of group 1 and 2 patients were significantly different. Comparison of effectiveness (abdominalgia and burbulence relief time, hospitalization time) between groups 1 and 2 showed significant difference, as well as incidence rates of cysts formation. Mortality rates of groups 1 and 2 were 10.0% and 20.7%, respectively. For patients in group 1, celiac drainage quantity and intra-abdominal pressure, and hospitalization time were positively correlated (r = 0.552, 0.748, 0.923, P < 0.01) with APACHE II scores. CONCLUSION: Combined indwelling catheter celiac drainage and intra-abdominal pressure monitoring, short veno-venous hemofiltration (SVVH), gastrointestinal TCM ablution, respiration support have preventive and treatment effects on abdominal compartment syndrome of fulminant acute pancreatitis. PMID:16937509

  4. Overlap between functional abdominal pain disorders and organic diseases in children.

    PubMed

    Langshaw, A H; Rosen, J M; Pensabene, L; Borrelli, O; Salvatore, S; Thapar, N; Concolino, D; Saps, M

    2018-04-02

    Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  5. Halothane and halothane/succinylcholine induced malignant hyperthermia (porcine stress syndrome) in a population of Ontario boars.

    PubMed

    Seeler, D C; McDonell, W N; Basrur, P K

    1983-07-01

    This paper recounts a study of the prevalence of malignant hyperthermia in a population of boars entering the Record of Performance Test Station at New Hamburg, Ontario over a period of ten months. The literature is briefly reviewed and an account of the present status of malignant hyperthermia (porcine stress syndrome) in Ontario boars using the halothane or halothane/succinylcholine screening tests is presented. It was determined in this population of boars that there was a 1.5% prevalence rate of malignant hyperthermia susceptible boars. This was based on a five minute halothane challenge carried out on 786 boars from 107 herds. The halothane reactors came from a total of eight herds or 7.5% of the total number of herds. A majority of 58.3% of the animals reacted after the three minute mark of the halothane challenge. In contrast, an 18.0% prevalence rate was determined using halothane/succinylcholine challenge on 123 boars. This further identified an additional eight herds with the problem, bringing the total to 16 or 15% of the total number of herds. It is suggested that the prevalence of malignant hyperthermia in Ontario breeding herds is much higher than was originally thought and that the halothane challenge is an inadequate screening test for this trait if the intention is to remove the genetic trait from the breeding herd. At the same time halothane challenge testing will identify those animals which have a strong susceptibility to the trait and if used on key breeding stock will help to maintain some control on the condition until a more definitive test is readily available.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Catheter enterostomy and patch repair of the abdominal wall for gastroschisis with intestinal atresia: report of a case.

    PubMed

    Ohno, Koichi; Nakamura, Tetsuro; Azuma, Takashi; Yoshida, Tatsuyuki; Yamada, Hiroto; Hayashi, Hiroaki; Masahata, Kazunori

    2009-01-01

    A male infant, weighing 2177 g, was born with the entire intestine protruding through a defect on the right side of the navel. Intestinal atresia, approximately 70 cm from the Treitz ligament, was also confirmed. Primary anastomosis and abdominal wall repair were impossible because of the intestinal dilation and thick peel, as well as the small abdominal cavity. Thus, we initially performed catheter enterostomy with a 14-F balloon catheter and patch repair of the abdominal wall, to enable the baby to be fed. Secondary anastomosis and abdominal wall repair was safely performed when the baby was 106 days old. The combination of catheter enterostomy and patch repair of the abdominal wall does not require dissection of the intestine and it can be safely performed in low-birth-weight babies. It also enables feeding and weight gain, and the overlying skin prevents contamination of the artificial sheet. We recommend this combination for neonates with both gastroschisis and intestinal atresia.

  7. Bimetallic redox nanoprobe enhances the therapeutic efficacy of hyperthermia in drug-resistant cancer cells

    NASA Astrophysics Data System (ADS)

    Vishwakarma, Sandeep Kumar; Lakkireddy, Chandrakala; Marjan, Tuba; Fatima, Anjum; Bardia, Avinash; Paspala, Syed Ameer Basha; Habeeb, Md. Aejaz; Khan, Aleem Ahmed

    2018-05-01

    Cancer nanotheranostics has emerged as one of the most promising fields of medicine wherein nano-sized molecules/agents are used for combined diagnosis and treatment of cancer. Despite promises of novel cancer therapeutic approaches, several crucial challenges have remained to be overcome for successful clinical translation of such agents. Hence, the present study has been aimed to investigate the therapeutic efficacy of bimetallic gadolinium super-paramagnetic iron oxide nanoformulation of ascorbic acid in synergism with hyperthermia on ascorbic acid-resistant breast cancer cells. This particular strategy provides real-time MRI-based non-invasive imaging of drug loading in resistant cancer cells along with highly enhanced therapeutic efficacy. This unique redox nanoprobe is capable of reversing drug-resistance mechanism in cancer cells and offers better therapeutic possibilities in targeted and effective destruction of drug-resistant cancer cells.

  8. Abdominal obesity, ethnicity and gastro‐oesophageal reflux symptoms

    PubMed Central

    Corley, Douglas A; Kubo, Ai; Zhao, Wei

    2007-01-01

    Objective To evaluate the associations between abdominal obesity and gastro‐oesophageal reflux disease (GORD), and their interactions with ethnicity and gender. Design A cross‐sectional study. Participants completed detailed symptom questionnaires and underwent a standardised examination, including anthropometric measurements. Setting A large integrated healthcare system. Patients 80 110 members of the Kaiser Permanente multiphasic health check‐up cohort. Main outcome measures Gastro‐oesophageal reflux‐type symptoms. Results Recent reflux‐type symptoms were present in 11% of the population. The multivariate OR for symptoms with an abdominal diameter (adjusted for body mass index (BMI)) of ⩾26 vs <16.3 cm was 1.85 (95% CI 1.55 to 2.21) for the white population, 0.95 (95% CI 0.61 to 1.48) for the black population and 0.64 (95% CI 0.18 to 2.30) for Asians. The mean abdominal diameter was greater in men (22.0 cm, 95% CI 21.9 to 22.0) than in women (20.1 cm, 95% CI 20.0 to 20.1, p<0.01), but the risk of symptoms for any given diameter did not differ markedly by gender. The association between increasing BMI and symptoms was also much stronger among the white population than among the black population. The association between BMI and reflux‐type symptoms was partially mediated through abdominal diameter. Conclusions There was a consistent association between abdominal diameter (independent of BMI) and reflux‐type symptoms in the white population, but no consistent associations in the black population or Asians. The BMI association was also strongest among the white population. These findings, combined with the increased prevalence of abdominal obesity in male subjects, suggest that an increased obesity may disproportionately increase GORD‐type symptoms in the white population and in male subjects. PMID:17047097

  9. Reconstruction of infected abdominal wall defects using latissimus dorsi free flap.

    PubMed

    Kim, Sang Wha; Han, Sang Chul; Hwang, Kyu Tae; Ahn, Byung Kyu; Kim, Jeong Tae; Kim, Youn Hwan

    2013-12-01

    Infected abdominal defects are a challenge to surgeons. In this study, we describe 10 cases in which the latissimus dorsi myocutaneous flap was used for successful reconstruction of abdominal wall defects severely infected with methicillin-resistant Staphylococcus aureus (MRSA). Retrospective review of 10 patients with abdominal wall defects that were reconstructed using the latissimus dorsi myocutaneous flap between 2002 and 2010. All patients had abdominal defects with hernias, combined with MRSA infections. The sizes of the flaps ranged from 120 to 364 cm(2) . The deep inferior epigastric artery was the recipient vessel in nine patients and the internal mammary vessels were used for one patient. There were no complications relating to the flaps, although there were other minor complications including wound dehiscence, haematoma and fluid correction. After reconstruction, there were no signs of infection during follow-up periods, and the patients were satisfied with the final results. Reconstruction using the latissimus dorsi myocutaneous flap, including muscle fascia structures, is a potential treatment option for severely infected large abdominal wall defects. © 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.

  10. [Anesthesia unrelated triggering of a fatal malignant hyperthermia crisis].

    PubMed

    Olthoff, D; Vonderlind, C

    1997-12-01

    For incidents of malignant hyperthermia (MH) outside the hospital, a high number of unrecorded cases must be reckoned with because of an insufficient knowledge of emergency services and poor identification and documentation that make it impossible to classify acute situations under the diagnosis of malignant hyperthermia crisis. As a result, there are no statistical data in this field, and only case reports with a broad spectrum of suspected trigger mechanisms have been published. The case described in this report is a proved example of a non-anesthesia-related triggering of MH in a 21-year-old man who had had an anesthetic-induced MH manifestation in childhood, which was confirmed with an in vitro contracture test. After visiting a restaurant, he became unconscious and convulsive after consuming a high level of alcohol (2.9/1000). The first cardiocirculatory arrest occurred directly before hospitalization. After admission, the patient showed a full-blown MH episode whose subsequent fatality was unavoidable in spite of adapted and optimal therapy. Suspected trigger mechanisms seem to be multifactoral (excessive alcohol consumption, over-heating, mental stress) as a forensic investigation did not point to any particular signs of typical trigger substances. The case demonstrates again that an MH attack might be triggered under certain non-anaesthesia-related situations. For patients with an MH disposition, additional information on their behavior outside the hospital is required.

  11. Appendicitis following blunt abdominal trauma.

    PubMed

    Cobb, Travis

    2017-09-01

    Appendicitis is a frequently encountered surgical problem in the Emergency Department (ED). Appendicitis typically results from obstruction of the appendiceal lumen, although trauma has been reported as an infrequent cause of acute appendicitis. Intestinal injury and hollow viscus injury following blunt abdominal trauma are well reported in the literature but traumatic appendicitis is much less common. The pathophysiology is uncertain but likely results from several mechanisms, either in isolation or combination. These include direct compression/crush injury, shearing injury, or from indirect obstruction of the appendiceal lumen by an ileocecal hematoma or traumatic impaction of stool into the appendix. Presentation typically mirrors that of non-traumatic appendicitis with nausea, anorexia, fever, and right lower quadrant abdominal tenderness and/or peritonitis. Evaluation for traumatic appendicitis requires a careful history and physical exam. Imaging with ultrasound or computed tomography is recommended if the history and physical do not reveal an acute surgical indication. Treatment includes intravenous antibiotics and surgical consultation for appendectomy. This case highlights a patient who developed acute appendicitis following blunt trauma to the abdomen sustained during a motor vehicle accident. Appendicitis must be considered as part of the differential diagnosis in any patient who presents to the ED with abdominal pain, including those whose pain begins after sustaining blunt trauma to the abdomen. Because appendicitis following trauma is uncommon, timely diagnosis requires a high index of suspicion. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    DTIC Science & Technology

    2012-10-01

    conclusions: 1) Airway hyperresponsiveness developed in Ova-sensitized mice was less pronounced in TRPV1 -null mice, indicating an important role of TRPV1 ...expression of the transient receptor potential vanilloid type 1 ( TRPV1 ) channel is up-regulated in the airway mucosa of patients with mild asthma... TRPV1 channel in triggering the bronchoconstriction caused by airway hyperthermia, and to determine whether this acute bronchoconstrictive effect was

  13. Beyond Traditional Hyperthermia: In Vivo Cancer Treatment with Magnetic-Responsive Mesoporous Silica Nanocarriers.

    PubMed

    Guisasola, Eduardo; Asín, Laura; Beola, Lilianne; de la Fuente, Jesús M; Baeza, Alejandro; Vallet-Regí, María

    2018-04-18

    In this study, we present an innovation in the tumor treatment in vivo mediated by magnetic mesoporous silica nanoparticles. This device was built with iron oxide magnetic nanoparticles embedded in a mesoporous silica matrix and coated with an engineered thermoresponsive polymer. The magnetic nanoparticles act as internal heating sources under an alternating magnetic field (AMF) that increase the temperature of the surroundings, provoking the polymer transition and consequently the release of a drug trapped inside the silica pores. By a synergic effect between the intracellular hyperthermia and chemotherapy triggered by AMF application, significant tumor growth inhibition was achieved in 48 h after treatment. Furthermore, the small magnetic loading used in the experiments indicates that the treatment is carried out without a global temperature rise of the tissue, which avoids the problem of the necessity to employ large amounts of magnetic cores, as is common in current magnetic hyperthermia.

  14. Laserthermia: a new computer-controlled contact Nd: YAG system for interstitial local hyperthermia.

    PubMed

    Daikuzono, N; Suzuki, S; Tajiri, H; Tsunekawa, H; Ohyama, M; Joffe, S N

    1988-01-01

    Contact Nd:YAG laser surgery is assuming a greater importance in endoscopic and open surgery, allowing coagulation, cutting, and vaporization with greater precision and safety. A new contact probe allows a wider angle of irradiation and diffusion of low-power laser energy (less than 5 watts), using the interstitial technique for producing local hyperthermia. Temperature sensors that monitor continuously can be placed directly into the surrounding tissue or tumor. Using a computer program interfaced with the laser and sensors, a controlled and stable temperature (e.g., 42 degrees C) can be produced in a known volume of tissue over a prolonged period of time (e.g., 20-40 min). This new laserthermia system, using a single low-power Nd:YAG laser for interstitial local hyperthermia, may offer many new advantages in the experimental treatment and clinical management of carcinoma. A multiple system is now being developed.

  15. Intra-operative hyperthermia in a young Angus bull with a fatal outcome.

    PubMed

    Skelding, Alicia; Valverde, Alexander

    2017-06-01

    A healthy, 9-month-old black Angus bull was presented for elective penile-preputial translocation and caudal epididymectomy. After premedication and induction, general anesthesia was maintained with inhalant anesthetic. Over an hour into the anesthetic period the bull developed severe hyperthermia and hypercapnia that resulted in fatality despite treatment efforts.

  16. Retrospective comparison of abdominal ultrasonography and radiography in the investigation of feline abdominal disease

    PubMed Central

    Won, Wylen Wade; Sharma, Ajay; Wu, Wenbo

    2015-01-01

    Abdominal radiography and ultrasonography are commonly used as part of the initial diagnostic plan for cats with nonspecific signs of abdominal disease. This retrospective study compared the clinical usefulness of abdominal radiography and ultrasonography in 105 feline patients with signs of abdominal disease. The final diagnosis was determined more commonly with ultrasonography (59%) compared to radiography (25.7%). Ultrasonography was also able to provide additional clinically relevant information in 76% of cases, and changed or refined the diagnosis in 47% of cases. Based on these findings, ultrasonography may be sufficient as an initial diagnostic test for the investigation of feline abdominal disease. PMID:26483582

  17. Ultrasound-guided transversus abdominal plane block with multimodal analgesia for pain management after total abdominal hysterectomy.

    PubMed

    Gasanova, Irina; Grant, Erica; Way, Megan; Rosero, Eric B; Joshi, Girish P

    2013-07-01

    Transversus abdominis plane (TAP) block has been shown to provide pain relief after abdominal procedures. However, TAP block combined with multimodal analgesia technique have not been assessed in a randomized controlled trial. This randomized, controlled, observer-blinded study was designed to evaluate the analgesic efficacy of bilateral ultrasound-guided TAP blocks with or without acetaminophen and non-steroidal anti-inflammatory drug (NSAID) combination. Patients undergoing total abdominal hysterectomy were randomized to one of three groups. Group 1 (n = 25) received a TAP block and ketorolac 30 mg, IV at the end of surgery and then ketorolac plus paracetamol 650 mg, orally, every 6 h for 24 h. Group 2 (n = 24) received only TAP block at the end of surgery. Group 3 (n = 25) received ketorolac 30 mg, IV at the end of surgery and then ketorolac plus paracetamol 650 mg, orally, every 6 h for 24 h. All patients received IV-PCA morphine for 24-h, postoperatively. All patients received a standardized general anaesthetic technique and dexamethasone 4 mg and ondansetron 4 mg, IV for antiemetic prophylaxis. There were no statistically significant differences in pain at rest between the groups. However, the pain on coughing (dynamic pain) in Group 1 was significantly less variable, compared with the other two groups (P = 0.012). Opioid consumption and occurrences of nausea, vomiting, and rescue antiemetic were similar in three the groups. The combination of TAP block and acetaminophen and NSAID provided less variability in dynamic pain compared with either treatment alone.

  18. The Tribolium homeotic gene Abdominal is homologous to abdominal-A of the Drosophila bithorax complex

    NASA Technical Reports Server (NTRS)

    Stuart, J. J.; Brown, S. J.; Beeman, R. W.; Denell, R. E.; Spooner, B. S. (Principal Investigator)

    1993-01-01

    The Abdominal gene is a member of the single homeotic complex of the beetle, Tribolium castaneum. An integrated developmental genetic and molecular analysis shows that Abdominal is homologous to the abdominal-A gene of the bithorax complex of Drosophila. abdominal-A mutant embryos display strong homeotic transformations of the anterior abdomen (parasegments 7-9) to PS6, whereas developmental commitments in the posterior abdomen depend primarily on Abdominal-B. In beetle embryos lacking Abdominal function, parasegments throughout the abdomen are transformed to PS6. This observation demonstrates the general functional significance of parasegmental expression among insects and shows that the control of determinative decisions in the posterior abdomen by homeotic selector genes has undergone considerable evolutionary modification.

  19. The Tribolium homeotic gene Abdominal is homologous to abdominal-A of the Drosophila bithorax complex.

    PubMed

    Stuart, J J; Brown, S J; Beeman, R W; Denell, R E

    1993-01-01

    The Abdominal gene is a member of the single homeotic complex of the beetle, Tribolium castaneum. An integrated developmental genetic and molecular analysis shows that Abdominal is homologous to the abdominal-A gene of the bithorax complex of Drosophila. abdominal-A mutant embryos display strong homeotic transformations of the anterior abdomen (parasegments 7-9) to PS6, whereas developmental commitments in the posterior abdomen depend primarily on Abdominal-B. In beetle embryos lacking Abdominal function, parasegments throughout the abdomen are transformed to PS6. This observation demonstrates the general functional significance of parasegmental expression among insects and shows that the control of determinative decisions in the posterior abdomen by homeotic selector genes has undergone considerable evolutionary modification.

  20. Hyperthermia with implanted electrodes.

    PubMed

    Brezovich, I A; Young, J H

    1981-01-01

    A general solution is given for the steady state form of the heat conduction equation applied to a simple tumor model which is imagined as being heated by means of electrical currents flowing between metallic electrodes. The model assumes a homogeneous tumor with no bloodflow. The solution for the special case of constant temperature and potential at the surface of the heated volume is examined in detail. The solution shows that there exists, independent of the particular tumor and electrode geometry, a close relationship between the steady state temperature distribution and the electrical potential. Among the more important implications of this relationship are that equipotential surfaces within the heated volume are also isothermal surfaces and that no areas of excessive heat at or near any sharp edges or corners of the electrodes should develop, despite the high electric field intensity. Based on the theory, a procedure is outlined which might greatly facilitate the determination of temperature distributions in phantoms. Finally, the usefulness and the limitations of the theoretical models in clinical hyperthermia are discussed.

  1. Analysis of clinical data to determine the minimum number of sensors required for adequate skin temperature monitoring of superficial hyperthermia treatments.

    PubMed

    Bakker, Akke; Holman, Rebecca; Rodrigues, Dario B; Dobšíček Trefná, Hana; Stauffer, Paul R; van Tienhoven, Geertjan; Rasch, Coen R N; Crezee, Hans

    2018-04-27

    Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients. Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23 × 2 Gy) and hyperthermia using single 434 MHz applicators (effective field size 351-396 cm 2 ). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset simulating continuous thermal mapping of the skin. Temperature differences (ΔT) between subsets and complete sets of sensors were evaluated in terms of overall minimum (T min ) and maximum (T max ) temperature, as well as T90 and T10. Eighty patients were included yielding a total of 400 hyperthermia sessions. Median ΔT was <0.01 °C for T90, its 95% confidence interval (95%CI) decreased to ≤0.5 °C when >50 sensors were used. Subsets of <10 sensors result in underestimation of T max up to -2.1 °C (ΔT 95%CI), which decreased to -0.5 °C when >50 sensors were used. Thermal profiles (8-21 probes) yielded a median ΔT < 0.01 °C for T90 and T max , with a 95%CI of -0.2 °C and 0.4 °C, respectively. The detection rate of T max  ≥43 °C is ≥85% while using >50 stationary sensors or thermal profiles. Adequate coverage of the skin temperature distribution during superficial hyperthermia treatment requires the use of >50 stationary sensors per 400 cm 2 applicator. Thermal mapping is a valid alternative.

  2. Segmenting the thoracic, abdominal and pelvic musculature on CT scans combining atlas-based model and active contour model

    NASA Astrophysics Data System (ADS)

    Zhang, Weidong; Liu, Jiamin; Yao, Jianhua; Summers, Ronald M.

    2013-03-01

    Segmentation of the musculature is very important for accurate organ segmentation, analysis of body composition, and localization of tumors in the muscle. In research fields of computer assisted surgery and computer-aided diagnosis (CAD), muscle segmentation in CT images is a necessary pre-processing step. This task is particularly challenging due to the large variability in muscle structure and the overlap in intensity between muscle and internal organs. This problem has not been solved completely, especially for all of thoracic, abdominal and pelvic regions. We propose an automated system to segment the musculature on CT scans. The method combines an atlas-based model, an active contour model and prior segmentation of fat and bones. First, body contour, fat and bones are segmented using existing methods. Second, atlas-based models are pre-defined using anatomic knowledge at multiple key positions in the body to handle the large variability in muscle shape. Third, the atlas model is refined using active contour models (ACM) that are constrained using the pre-segmented bone and fat. Before refining using ACM, the initialized atlas model of next slice is updated using previous atlas. The muscle is segmented using threshold and smoothed in 3D volume space. Thoracic, abdominal and pelvic CT scans were used to evaluate our method, and five key position slices for each case were selected and manually labeled as the reference. Compared with the reference ground truth, the overlap ratio of true positives is 91.1%+/-3.5%, and that of false positives is 5.5%+/-4.2%.

  3. [Differential diagnosis of abdominal pain].

    PubMed

    Frei, Pascal

    2015-09-02

    Despite the frequency of functional abdominal pain, potentially dangerous causes of abdominal pain need to be excluded. Medical history and clinical examination must focus on red flags and signs for imflammatory or malignant diseases. See the patient twice in the case of severe and acute abdominal pain if lab parameters or radiological examinations are normal. Avoid repeated and useless X-ray exposure whenever possible. In the case of subacute or chronic abdominal pain, lab tests such as fecal calprotectin, helicobacter stool antigen and serological tests for celiac disease are very useful. Elderly patients may show atypical or missing clinical signs. Take care of red herrings and be skeptical whether your initial diagnosis is really correct. Abdominal pain can frequently be an abdominal wall pain.

  4. Integrating Hyperthermia into Modern Radiation Oncology: What Evidence Is Necessary?

    PubMed Central

    Peeken, Jan C.; Vaupel, Peter; Combs, Stephanie E.

    2017-01-01

    Hyperthermia (HT) is one of the hot topics that have been discussed over decades. However, it never made its way into primetime. The basic biological rationale of heat to enhance the effect of radiation, chemotherapeutic agents, and immunotherapy is evident. Preclinical work has confirmed this effect. HT may trigger changes in perfusion and oxygenation as well as inhibition of DNA repair mechanisms. Moreover, there is evidence for immune stimulation and the induction of systemic immune responses. Despite the increasing number of solid clinical studies, only few centers have included this adjuvant treatment into their repertoire. Over the years, abundant prospective and randomized clinical data have emerged demonstrating a clear benefit of combined HT and radiotherapy for multiple entities such as superficial breast cancer recurrences, cervix carcinoma, or cancers of the head and neck. Regarding less investigated indications, the existing data are promising and more clinical trials are currently recruiting patients. How do we proceed from here? Preclinical evidence is present. Multiple indications benefit from additional HT in the clinical setting. This article summarizes the present evidence and develops ideas for future research. PMID:28713771

  5. [Results of combined reconstructions of the renal arteries, abdominal aorta and its other branches in patients with atherosclerosis].

    PubMed

    Semenov, D V; Ignashov, A M; Turobova, E P; Martynenko, G I; Vakhitov, K M

    2012-01-01

    A comparative analysis was made of clinical indices and long-term survival in 20 patients (13 men and 7 women of mean age 62 +/- 2 years), having multifocal atherosclerosis of the renal arteries (RA), abdominal aorta and arteries of lower extremities (LE) (11 aneurysms, 7 occlusive lesions of the aorta and 3 of its unpaired branches) who underwent combined reconstructions, with patients having similar lesions, but not operated (12) or operated only on RA or on the arteries of LE (45). The groups of patients had no great differences except more pronounced renal dysfunction (RD) in the first of them. In spite of high postoperative lethality (20%) mainly due to acute renal failure (3), long-term survival proved to be significantly higher (14 from 16), than in not operated (3 from 12) (p = 0.00001) and had better tendency than in those operated on the same basin (35 from 45). In addition, the patients after combined operations had substantially decreased systolic and diastolic arterial pressure (159 +/- 13 vs. 132 +/- 9, p = 0.00001; 91 +/- 5 vs. 83 +/- 7, p = 0.010) and also stabilized renal function.

  6. Three-Dimensional Microwave Hyperthermia for Breast Cancer Treatment in a Realistic Environment Using Particle Swarm Optimization.

    PubMed

    Nguyen, Phong Thanh; Abbosh, Amin; Crozier, Stuart

    2017-06-01

    In this paper, a technique for noninvasive microwave hyperthermia treatment for breast cancer is presented. In the proposed technique, microwave hyperthermia of patient-specific breast models is implemented using a three-dimensional (3-D) antenna array based on differential beam-steering subarrays to locally raise the temperature of the tumor to therapeutic values while keeping healthy tissue at normal body temperature. This approach is realized by optimizing the excitations (phases and amplitudes) of the antenna elements using the global optimization method particle swarm optimization. The antennae excitation phases are optimized to maximize the power at the tumor, whereas the amplitudes are optimized to accomplish the required temperature at the tumor. During the optimization, the technique ensures that no hotspots exist in healthy tissue. To implement the technique, a combination of linked electromagnetic and thermal analyses using MATLAB and the full-wave electromagnetic simulator is conducted. The technique is tested at 4.2 GHz, which is a compromise between the required power penetration and focusing, in a realistic simulation environment, which is built using a 3-D antenna array of 4 × 6 unidirectional antenna elements. The presented results on very dense 3-D breast models, which have the realistic dielectric and thermal properties, validate the capability of the proposed technique in focusing power at the exact location and volume of tumor even in the challenging cases where tumors are embedded in glands. Moreover, the models indicate the capability of the technique in dealing with tumors at different on- and off-axis locations within the breast with high efficiency in using the microwave power.

  7. [Experience of the three-stage strategy for intestinal fistula complicated with complex abdominal infection].

    PubMed

    Zhao, Qingchuan; Li, Xuzhao; Li, Xiaohua; Wang, Juan

    2017-03-25

    Intestinal fistula, as a serious complication after abdominal surgery, not only leads to a series of pathophysiological changes such as fluid loss, malnutrition and organ dysfunction, but also causes the severe abdominal infection, which often threatens the life of patients. How to make the diagnosis and give the treatment of intestinal fistula is the key to save the lives of high-risk patients. In our hospital, during the past course of diagnosis and treatment for intestinal fistula complicated with severe abdominal infection, based on the combination of literatures at home and abroad with our clinical experiences for many years, an effective three-stage prevention and treatment strategy was formed gradually, which included early diagnosis, effective treatment of infection source, open drainage of abdominal infection and early enteral nutrition support. This strategy subverts the traditional concept of surgery alone, and becomes an effective means to save patients with severe abdominal infection.

  8. High doses of L-naloxone but neither D-naloxone nor beta-funaltrexamine prevent hyperthermia-induced seizures in rat pups.

    PubMed

    Laorden, M L; Miralles, F S; Puig, M M

    1988-03-01

    The effects of the non-specific opiate antagonist L-naloxone and the inactive isomer D-naloxone, as well as the specific mu receptor antagonist beta-funaltrexamine, have been examined on hyperthermia-induced seizures in unrestrained 15 days old rats. Saline-injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 42 +/- 0.1 degrees C at 50 min exposure. At this time all the pups had seizures and died. Similar results were obtained when the animals were pretreated with different doses of D-naloxone and beta-funaltrexamine. Rats pretreated with L-naloxone also showed an increase in rectal temperature; but the temperature was lower than in saline-injected animals. Only high doses of L-naloxone prevented seizures and deaths. These data indicate that endogenous opioid peptides may play a role in seizures induced by hyperthermia and that receptors other than mu receptors could be involved in hyperthermia-induced seizures.

  9. A microangiographic study of the effect of hyperthermia on the rabbit bladder

    NASA Technical Reports Server (NTRS)

    Hietala, S. O.; Howells, R.; Hazra, I. A.

    1978-01-01

    A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.

  10. Chronic abdominal wall pain and ultrasound-guided abdominal cutaneous nerve infiltration: a case series.

    PubMed

    Kanakarajan, Saravanakumar; High, Kristina; Nagaraja, Ravi

    2011-03-01

    Chronic abdominal wall pain occurs in about 10-30% of patients presenting with chronic abdominal pain. Entrapment of abdominal cutaneous nerves at the lateral border of the rectus abdominis muscle has been attributed as a cause of abdominal wall pain. We report our experience of treating such patients using ultrasound-guided abdominal cutaneous nerve infiltration. We conducted a retrospective audit of abdominal cutaneous nerve infiltration performed in the period between September 2008 to August 2009 in our center. All patients had received local anesthetic and steroid injection under ultrasound guidance. The response to the infiltration was evaluated in the post-procedure telephone review as well as in the follow-up clinic. Brief pain inventory (BPI) and numerical rating scale pain scores were collated from two points: the initial outpatient clinic and the follow up clinic up to 5 months following the injection. Nine patients had abdominal cutaneous nerve injections under ultrasound guidance in the period under review. Six patients reported 50% pain relief or more (responders) while three patients did not. Pain and BPI scores showed a decreasing trend in responders. The median duration of follow-up was 12 weeks. Ultrasound can reliably be used for infiltration of the abdominal cutaneous nerves. This will improve the safety as well as diagnostic utility of the procedure. Wiley Periodicals, Inc.

  11. Intramuscular injection of malignant hyperthermia trigger agents induces hypermetabolism in susceptible and nonsusceptible individuals.

    PubMed

    Metterlein, Thomas; Schuster, Frank; Kranke, Peter; Roewer, Norbert; Anetseder, Martin

    2010-01-01

    A new minimally invasive metabolic test for the diagnosis of susceptibility for malignant hyperthermia measuring intramuscular p(CO(2)) and lactate following local application of caffeine and halothane in humans was recently proposed. The present study tested the hypothesis that a more simplified test protocol allows a differentiation between malignant hyperthermia susceptible (MHS) and malignant hyperthermia nonsusceptible (MHN) and control individuals. With approval of the local ethics committee and informed consent, microdialysis and p(CO(2)) probes with attached microtubing were placed into the lateral vastus muscle of six MHS, seven MHN and seven control individuals. Following equilibration, boluses of 500 microl caffeine 80 mmol l(-1) and halothane 10 vol% dissolved in soybean oil were injected locally. p(CO(2)) and lactate were measured spectrophotometrically. The maximal rate of p(CO(2)) increase was significantly higher in MHS than in MHN and control individuals following application of halothane and caffeine, respectively. Intramuscular caffeine injection leads to a significantly higher increase of local lactate levels in MHS than in MHN and control individuals, whereas halothane increased local lactate levels in all investigated groups. Haemodynamic and systemic metabolic parameters did not differ between the investigated groups. Local caffeine and halothane injection increased intramuscular metabolism in MHS individuals significantly more than in the two other groups. In contrast to previous investigations, direct injection of the concentrations of halothane described here increased lactate and p(CO(2)) even in MHN skeletal muscle.

  12. Using eye tracking technology to compare the effectiveness of malignant hyperthermia cognitive aid design.

    PubMed

    King, Roderick; Hanhan, Jaber; Harrison, T Kyle; Kou, Alex; Howard, Steven K; Borg, Lindsay K; Shum, Cynthia; Udani, Ankeet D; Mariano, Edward R

    2018-05-15

    Malignant hyperthermia is a rare but potentially fatal complication of anesthesia, and several different cognitive aids designed to facilitate a timely and accurate response to this crisis currently exist. Eye tracking technology can measure voluntary and involuntary eye movements, gaze fixation within an area of interest, and speed of visual response and has been used to a limited extent in anesthesiology. With eye tracking technology, we compared the accessibility of five malignant hyperthermia cognitive aids by collecting gaze data from twelve volunteer participants. Recordings were reviewed and annotated to measure the time required for participants to locate objects on the cognitive aid to provide an answer; cumulative time to answer was the primary outcome. For the primary outcome, there were differences detected between cumulative time to answer survival curves (P < 0.001). Participants demonstrated the shortest cumulative time to answer when viewing the Society for Pediatric Anesthesia (SPA) cognitive aid compared to four other publicly available cognitive aids for malignant hyperthermia, and this outcome was not influenced by the anesthesiologists' years of experience. This is the first study to utilize eye tracking technology in a comparative evaluation of cognitive aid design, and our experience suggests that there may be additional applications of eye tracking technology in healthcare and medical education. Potentially advantageous design features of the SPA cognitive aid include a single page, linear layout, and simple typescript with minimal use of single color blocking.

  13. A comparison of reduced-order modelling techniques for application in hyperthermia control and estimation.

    PubMed

    Bailey, E A; Dutton, A W; Mattingly, M; Devasia, S; Roemer, R B

    1998-01-01

    Reduced-order modelling techniques can make important contributions in the control and state estimation of large systems. In hyperthermia, reduced-order modelling can provide a useful tool by which a large thermal model can be reduced to the most significant subset of its full-order modes, making real-time control and estimation possible. Two such reduction methods, one based on modal decomposition and the other on balanced realization, are compared in the context of simulated hyperthermia heat transfer problems. The results show that the modal decomposition reduction method has three significant advantages over that of balanced realization. First, modal decomposition reduced models result in less error, when compared to the full-order model, than balanced realization reduced models of similar order in problems with low or moderate advective heat transfer. Second, because the balanced realization based methods require a priori knowledge of the sensor and actuator placements, the reduced-order model is not robust to changes in sensor or actuator locations, a limitation not present in modal decomposition. Third, the modal decomposition transformation is less demanding computationally. On the other hand, in thermal problems dominated by advective heat transfer, numerical instabilities make modal decomposition based reduction problematic. Modal decomposition methods are therefore recommended for reduction of models in which advection is not dominant and research continues into methods to render balanced realization based reduction more suitable for real-time clinical hyperthermia control and estimation.

  14. Calcific tendinopathy of the rotator cuff. Conservative management with 434 Mhz local microwave diathermy (hyperthermia): a case study.

    PubMed

    Di Cesare, Annalisa; Giombini, Arrigo; Dragoni, Stefano; Agnello, Luciano; Ripani, Maurizio; Saraceni, Vincenzo Maria; Maffulli, Nicola

    2008-01-01

    To report the effects of local microwave diathermy (hyperthermia) at 434 Mhz on calcific tendinopathy of the shoulder in two middle aged patients. Two middle-aged women with calcific tendinopathy of the shoulder were treated with local microwave diathermy (hyperthermia) at 434 Mhz three times a week for four weeks. Plain radiographs and ultrasonography demonstrated calcific deposits in the area of infraspinatus or supraspinatus. Shoulder Pain and Disability Index (SPADI) and passive Range of Motion (ROM) were used to assess the response to treatment. At the end of the treatment period, the improvement as measured by the SPADI score was respectively 30% for the first patient and 40% for the second patient with an improvement of the shoulder passive ROM for both patients. The calcific deposits seen on the initial radiographs and ultrasonography were no longer visible. At 1 year follow-up, both patients continued to be symptom free. Hyperthermia is a safe option in the management of calcific tendinopathy of the shoulder. Prospective randomized controlled studies with long term assessment are needed to further document its therapeutic efficacy.

  15. Effect of tumor properties on energy absorption, temperature mapping, and thermal dose in 13.56-MHz radiofrequency hyperthermia.

    PubMed

    Prasad, Bibin; Kim, Subin; Cho, Woong; Kim, Suzy; Kim, Jung Kyung

    2018-05-01

    Computational techniques can enhance personalized hyperthermia-treatment planning by calculating tissue energy absorption and temperature distribution. This study determined the effect of tumor properties on energy absorption, temperature mapping, and thermal dose distribution in mild radiofrequency hyperthermia using a mouse xenograft model. We used a capacitive-heating radiofrequency hyperthermia system with an operating frequency of 13.56 MHz for in vivo mouse experiments and performed simulations on a computed tomography mouse model. Additionally, we measured the dielectric properties of the tumors and considered temperature dependence for thermal properties, metabolic heat generation, and perfusion. Our results showed that dielectric property variations were more dominant than thermal properties and other parameters, and that the measured dielectric properties provided improved temperature-mapping results relative to the property values taken from previous study. Furthermore, consideration of temperature dependency in the bio heat-transfer model allowed elucidation of precise thermal-dose calculations. These results suggested that this method might contribute to effective thermoradiotherapy planning in clinics. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Significance of computed tomography finding of intra-abdominal free fluid without solid organ injury after blunt abdominal trauma: time for laparotomy on demand.

    PubMed

    Mahmood, Ismail; Tawfek, Zainab; Abdelrahman, Yassir; Siddiuqqi, Tariq; Abdelrahman, Husham; El-Menyar, Ayman; Al-Hassani, Ammar; Tuma, Mazin; Peralta, Ruben; Zarour, Ahmad; Yakhlef, Sawsan; Hamzawi, Hazim; Al-Thani, Hassan; Latifi, Rifat

    2014-06-01

    Optimal management of patients with intra-abdominal free fluid found on computed tomography (CT) scan without solid organ injury remains controversial. The purpose of this study was to determine the significance of CT scan findings of free fluid in the management of blunt abdominal trauma patients who otherwise have no indications for laparotomy. During the 3-year study period, all patients presenting with blunt abdominal trauma who underwent abdominal CT examination were retrospectively reviewed. All hemodynamically stable patients who presented with abdominal free fluid without solid organ injury on CT scan were analyzed for radiological interpretation, clinical management, operative findings, and outcome. A total of 122 patients were included in the study, 91 % of whom were males. The mean age of the patients was 33 ± 12 years. A total of 34 patients underwent exploratory laparotomy, 31 of whom had therapeutic interventions. Small bowel injuries were found in 12 patients, large bowel injuries in ten, and mesenteric injuries in seven patients. One patient had combined small and large bowel injury, and one had traumatic gangrenous appendix. In the remaining three patients, laparotomy was non-therapeutic. A total of 36 patients had associated pelvic fractures and 33 had multiple lumbar transverse process fractures. Detection of intra-peritoneal fluid by CT scan is inaccurate for prediction of bowel injury or need for surgery. However, the correlation between CT scan findings and clinical course is important for optimal diagnosis of bowel and mesenteric injuries.

  17. Local modulated electro-hyperthermia in combination with traditional Chinese medicine vs. intraperitoneal chemoinfusion for the treatment of peritoneal carcinomatosis with malignant ascites: A phase II randomized trial

    PubMed Central

    Pang, Clifford L.K.; Zhang, Xinting; Wang, Zhen; Ou, Junwen; Lu, Yimin; Chen, Pengfei; Zhao, Changlin; Wang, Xiaopu; Zhang, Hongyu; Roussakow, Sergey V.

    2017-01-01

    The purpose of this study was to develop a safe and non-toxic alternative to the conventional conservative treatment of peritoneal carcinomatosis with malignant ascites (PCMA) by investigating the efficacy and safety of local modulated electro-hyperthermia (mEHT) combined with the traditional Chinese medicine (TCM) ‘Shi Pi’ herbal decoction, compared with standard intraperitoneal chemoinfusion (IPCI). A randomized, controlled, single-center, open-label clinical trial (phase II) with two parallel groups (allocation ratio, 1:1) was conducted to investigate the efficacy and safety of mEHT+TCM (study group, SG) vs. standard IPCI (control group, CG) in patients with PCMA by intention-to-treat analysis. A total of 260 patients with PCMA were randomly allocated into the two groups (130/130); mEHT was applied for 60 min per session every second day for 4 weeks, for a total of 14 sessions. The TCM decoction was administered orally, at 400 ml daily. In CG, occlusive IPCI with cisplatin (30–60 mg) and fluorouracil (500–600 mg/m2) was applied twice, biweekly. The objective response rate (ORR), quality of life (QoL) and adverse event rate (AER) in the two groups were evaluated 1 month after treatment, analyzed and compared. The present study is registered on ClinicalTrials.gov (NCT02638051). No case was lost or excluded (0/260). The ORR in SG was 77.69% (101/130) vs. 63.85% (73/130) in CG (P<0.05). The QoL in SG was 49.23% vs. 32.3% in CG (P<0.05). The AER in SG was 2.3% (3/130) vs. 12.3% (16/130) in CG (P<0.05). All the adverse events were grade I. In conclusion, the combination of mEHT with TCM achieves better control of PCMA compared with standard IPCI, with less toxicity. Both components of the combination are non-toxic treatments easily tolerated by patients. Thus, this combined treatment may be preferred due to the better benefit-harm balance. PMID:28529748

  18. Intracranial dual-mode IVUS and hyperthermia using circular arrays: preliminary experiments.

    PubMed

    Patel, Vivek; Light, Edward; Herickhoff, Carl; Grant, Gerald; Britz, Gavin; Wilson, Christy; Palmeri, Mark; Smith, Stephen

    2013-01-01

    In this study, we investigated the feasibility of using 3.5-Fr (3 Fr = 1 mm) circular phased-array intravascular ultrasound (IVUS) catheters for minimally invasive, image-guided hyperthermia treatment of tumors in the brain. Feasibility was demonstrated in two ways: (1) by inserting a 3.5-Fr IVUS catheter through skull burr holes, for 20 MHz brain imaging in the pig model, and (2) by testing a modified circular array for therapy potential with 18.5-MHz and 9-MHz continuous wave (CW) excitation. The imaging transducer's performance was superior to our previous 9-MHz mechanical IVUS prototype. The therapy catheter transducer was driven by CW electrical power at 18.5 MHz, achieving temperature changes reaching +8°C at a depth of 2 mm in a human glioblastoma grown on the flank of a mouse with minimal transducer resistive heating of +2°C. Further hyperthermia trials showed that 9-MHz CW excitation produced temperature changes of +4.5°C at a depth of 12 mm-a sufficient temperature rise for our long-term goal of targeted, controlled drug release via thermosensitive liposomes for therapeutic treatment of 1-cm-diameter glioblastomas.

  19. Intracranial Dual-Mode IVUS and Hyperthermia Using Circular Arrays: Preliminary Experiments

    PubMed Central

    Patel, Vivek; Light, Edward; Herickhoff, Carl; Grant, Gerald; Britz, Gavin; Wilson, Christy; Palmeri, Mark; Smith, Stephen

    2013-01-01

    In this study, we investigated the feasibility of using 3.5-Fr (3 Fr = 1 mm) circular phased-array intravascular ultrasound (IVUS) catheters for minimally invasive, image-guided hyperthermia treatment of tumors in the brain. Feasibility was demonstrated in two ways: (1) by inserting a 3.5-Fr IVUS catheter through skull burr holes, for 20 MHz brain imaging in the pig model, and (2) by testing a modified circular array for therapy potential with 18.5-MHz and 9-MHz continuous wave (CW) excitation. The imaging transducer’s performance was superior to our previous 9-MHz mechanical IVUS prototype. The therapy catheter transducer was driven by CW electrical power at 18.5 MHz, achieving temperature changes reaching +8°C at a depth of 2 mm in a human glioblastoma grown on the flank of a mouse with minimal transducer resistive heating of +2°C. Further hyperthermia trials showed that 9-MHz CW excitation produced temperature changes of +4.5°C at a depth of 12 mm—a sufficient temperature rise for our long-term goal of targeted, controlled drug release via thermosensitive liposomes for therapeutic treatment of 1-cm-diameter glioblastomas. PMID:23287504

  20. The histaminergic system is involved in psychological stress-induced hyperthermia in rats.

    PubMed

    Lkhagvasuren, Battuvshin; Oka, Takakazu

    2017-04-01

    The histaminergic system modulates numerous physiological functions such as wakefulness, circadian rhythm, feeding, and thermoregulation. However, it is not yet known if this system is also involved in psychological stress-induced hyperthermia (PSH) and, if so, which histamine (H) receptor subtype mediates the effect. Therefore, we investigated the effects of pretreatments with intraperitoneal injections of mepyramine (an H1 receptor inverse agonist), cimetidine (an H2 receptor antagonist), and ciproxifan (an H3 receptor inverse agonist) on cage-exchange stress-induced hyperthermia (a model of PSH) by monitoring core body temperature ( T c ) during both light (10:00 am-12:00 pm) and dark (10:00 pm-12:00 am) phases in conscious, freely moving rats. We also investigated the effects of these drugs on stress-induced changes in locomotor activity ( L a ) to rule out the possibility that effects on T c are achieved secondary to altered L a Cage-exchange stress increased T c within 20 min followed by a gradual decrease back to baseline T c during both phases. In the light phase, mepyramine and cimetidine markedly attenuated PSH, whereas ciproxifan did not affect it. In contrast, in the dark phase, mepyramine dropped T c by 1 °C without affecting cage-exchange stress-induced hyperthermia, whereas cimetidine and ciproxifan did not affect both postinjection T c and PSH Cage-exchange stress induced an increase in L a , especially in the light phase, but none of these drugs altered cage-exchange stress-induced L a in either circadian rhythm phase. These results suggest that the histaminergic system is involved in the physiological mechanisms underlying PSH, particularly through H1 and H2 receptors, without influencing locomotor activity. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  1. Thermo-sensitively and magnetically ordered mesoporous carbon nanospheres for targeted controlled drug release and hyperthermia application.

    PubMed

    Chen, Lin; Zhang, Huan; Zheng, Jing; Yu, Shiping; Du, Jinglei; Yang, Yongzhen; Liu, Xuguang

    2018-03-01

    A multifunctional nanoplatform based on thermo-sensitively and magnetically ordered mesoporous carbon nanospheres (TMOMCNs) is developed for effective targeted controlled release of doxorubicin hydrochloride (DOX) and hyperthermia in this work. The morphology, specific surface area, porosity, thermo-stability, thermo-sensitivity, as well as magnetism properties of TMOMCNs were verified by high resolution transmission electron microscopy, field emission scanning electron microscopy, thermo-gravimetric analysis, X-ray diffraction, Brunauer-Emmeltt-Teller surface area analysis, dynamic light scattering and vibrating sample magnetometry measurement. The results indicate that TMOMCNs have an average diameter of ~146nm with a lower critical solution temperature at around 39.5°C. They are superparamagnetic with a magnetization of 10.15emu/g at 20kOe. They generate heat when inductive magnetic field is applied to them and have a normalized specific absorption rate of 30.23W/g at 230kHz and 290Oe, showing good potential for hyperthermia. The DOX loading and release results illustrate that the loading capacity is 135.10mg/g and release performance could be regulated by changing pH and temperature. The good targeting, DOX loading and release and hyperthermia properties of TMOMCNs offer new probabilities for high effectiveness and low toxicity of cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Electromagnetic redesign of the HYPERcollar applicator: toward improved deep local head-and-neck hyperthermia.

    PubMed

    Togni, P; Rijnen, Z; Numan, W C M; Verhaart, R F; Bakker, J F; van Rhoon, G C; Paulides, M M

    2013-09-07

    Accumulating evidence shows that hyperthermia improves head-and-neck cancer treatment. Over the last decade, we introduced a radiofrequency applicator, named HYPERcollar, which enables local heating also of deep locations in this region. Based on clinical experience, we redesigned the HYPERcollar for improved comfort, reproducibility and operator handling. In the current study, we analyze the redesign from an electromagnetic point of view. We show that a higher number of antennas and their repositioning allow for a substantially improved treatment quality. Combined with the much better reproducibility of the water bolus, this will substantially minimize the risk of underexposure. All improvements combined enable a reduction of hot-spot prominence (hot-spot to target SAR quotient) by 32% at an average of 981 W, which drastically reduces the probability for system power to become a treatment limiting source. Moreover, the power deposited in the target selectively can be increased by more than twofold. Hence, we expect that the HYPERcollar redesign currently under construction allows us to double the clinically applied power to the target while reducing the hot-spots, resulting in higher temperatures and, consequently, better clinical outcome.

  3. Abdominal elephantiasis: a case report.

    PubMed

    Hanna, Dominique; Cloutier, Richard; Lapointe, Roch; Desgagné, Antoine

    2004-01-01

    Elephantiasis is a well-known condition in dermatology usually affecting the legs and external genitalia. It is characterized by chronic inflammation and obstruction of the lymphatic channels and by hypertrophy of the skin and subcutaneous tissues. The etiology is either idiopathic or caused by a variety of conditions such as chronic filarial disease, leprosy, leishmaniasis, and chronic recurrent cellulites. Elephantiasis of the abdominal wall is very rare. A complete review of the English and French literature showed only two cases reported in 1966 and 1973, respectively. We report a third case of abdominal elephantiasis and we briefly review this entity. We present the case of a 51-year-old woman who had progressively developed an enormous pediculated abdominal mass hanging down her knees. The skin was thickened, hyperpigmented, and fissured. She had a history of multiple abdominal cellulites. She underwent an abdominal lipectomy. Histopathology of the specimen confirmed the diagnosis of abdominal elephantiasis. Abdominal elephantiasis is a rare disease that represents end-stage failure of lymph drainage. Lipectomy should be considered in the management of this condition.

  4. Combined treatment with bexarotene and rosuvastatin reduces angiotensin-II-induced abdominal aortic aneurysm in apoE-/- mice and angiogenesis

    PubMed Central

    Escudero, P; Navarro, A; Ferrando, C; Furio, E; Gonzalez-Navarro, H; Juez, M; Sanz, M J; Piqueras, L

    2015-01-01

    Background and Purpose Abdominal aortic aneurysm (AAA) is a degenerative vascular disease associated with angiogenesis. Bexarotene is a retinoid X receptor (RXR) ligand with anti-angiogenic activity. Statins also exert anti-angiogenic activity and activate PPARs. Because RXR ligands form permissive heterodimers with PPARs and a single anti-angiogenic drug may not be sufficient to combat the wide array of angiogenic factors produced during AAA, we evaluated the effect of combined low doses of bexarotene and rosuvastatin in a mouse model of AAA. Experimental Approach The effect of the combined treatment was investigated in a murine model of angiotensin II-induced AAA in apoE−/− mice. This combination therapy was also evaluated in in vivo (Matrigel plug assay) and in vitro (endothelial cell differentiation assay) models of angiogenesis as well as the underlying mechanisms involved. Key Results Co-treatment with bexarotene plus rosuvastatin reduced aneurysm formation, inflammation and neovascularization compared with each single treatment. In HUVEC, the combination of suboptimal concentrations of bexarotene and rosuvastatin inhibited angiotensin II-induced morphogenesis, proliferation and migration. These effects were accompanied by diminished production of pro-angiogenic chemokines (CXCL1, CCL2 or CCL5) and VEGF, and seemed to be mediated by RXRα/PPARα and RXRα/PPARγ activation. This combined therapy reduced the activation of members of the downstream PI3K pathway (Akt/mTOR and p70S6K1) in vivo and in vitro. Conclusions and Implications The combination of RXR agonists with statins at low doses synergistically interferes with the signalling pathways that modulate inflammation and angiogenesis and may constitute a new and safer therapeutic treatment for the control of AAA. PMID:25630951

  5. Fundamental solutions to the bioheat equation and their application to magnetic fluid hyperthermia.

    PubMed

    Giordano, Mauricio A; Gutierrez, Gustavo; Rinaldi, Carlos

    2010-01-01

    Methods of predicting temperature profiles during local hyperthermia treatment are very important to avoid damage to healthy tissue. With this aim, fundamental solutions of Pennes' bioheat equation are derived in rectangular, cylindrical, and spherical coordinates. The medium is idealised as isotropic with effective thermal properties. Temperature distributions due to space- and time-dependent heat sources are obtained by the solution method presented. Applications of the fundamental solutions are addressed with emphasis on a particular problem of Magnetic Fluid Hyperthermia (MFH) consisting of a thin shell of magnetic nanoparticles in the outer surface of a spherical solid tumour. It is observed from the solution of this particular problem that the temperature profiles are strongly dependent on the distribution of the magnetic nanoparticles within the tissue. An almost uniform temperature profile is obtained inside the tumour with little penetration of therapeutic temperatures to the outer region of healthy tissue. The fundamental solutions obtained can be used to develop boundary element methods to predict temperature profiles with more complicated geometries.

  6. Effect of magnetic dipolar interactions on nanoparticle heating efficiency: Implications for cancer hyperthermia

    PubMed Central

    Branquinho, Luis C.; Carrião, Marcus S.; Costa, Anderson S.; Zufelato, Nicholas; Sousa, Marcelo H.; Miotto, Ronei; Ivkov, Robert; Bakuzis, Andris F.

    2013-01-01

    Nanostructured magnetic systems have many applications, including potential use in cancer therapy deriving from their ability to heat in alternating magnetic fields. In this work we explore the influence of particle chain formation on the normalized heating properties, or specific loss power (SLP) of both low- (spherical) and high- (parallelepiped) anisotropy ferrite-based magnetic fluids. Analysis of ferromagnetic resonance (FMR) data shows that high particle concentrations correlate with increasing chain length producing decreasing SLP. Monte Carlo simulations corroborate the FMR results. We propose a theoretical model describing dipole interactions valid for the linear response regime to explain the observed trends. This model predicts optimum particle sizes for hyperthermia to about 30% smaller than those previously predicted, depending on the nanoparticle parameters and chain size. Also, optimum chain lengths depended on nanoparticle surface-to-surface distance. Our results might have important implications to cancer treatment and could motivate new strategies to optimize magnetic hyperthermia. PMID:24096272

  7. In vitro comparison of intra-abdominal hypertension development after different temporary abdominal closure techniques.

    PubMed

    Benninger, Emanuel; Labler, Ludwig; Seifert, Burkhardt; Trentz, Otmar; Menger, Michael D; Meier, Christoph

    2008-01-01

    To compare volume reserve capacity (VRC) and development of intra-abdominal hypertension after different in vitro temporary abdominal closure (TAC) techniques. A model of the abdomen was designed. The abdominal wall was simulated with polychloroprene, a synthetic rubber compound. A lentil-shaped defect of 150 cm(2) was cut into the anterior aspect of the abdominal wall. TAC of this defect was performed by a zipper system (ZS), a bag silo closure (BSC), or a vacuum assisted closure (VAC) with subatmospheric pressures ranging from 0- to 200 mmHg. The model with intact abdominal wall served as reference. The model was filled with water to baseline level. The intra-abdominal pressure was increased in 2 mmHg steps from baseline level (6 mmHg) to 40 mmHg by adding volume to the system according to a standardized protocol. VRC with corresponding intra-abdominal pressure were analyzed and compared for the different TAC techniques. VRC was the highest after BSC at all pressure levels studied (P < 0.05). VAC and ZS resulted in significantly lower VRC compared with BSC and reference (P < 0.05). The magnitude of negative pressure on the VAC did not significantly influence the VRC. In the present in vitro model, BSC demonstrated the highest VRC of all evaluated TAC techniques. Different levels of subatmospheric pressures applied to the VAC did not affect VRC. The results for ZS and VAC indicate that these TAC techniques may increase the risk for recurrent intra-abdominal hypertension and should therefore not be used in high-risk patients during the initial phase after abdominal decompression.

  8. Strontium hexaferrite (SrFe12O19) based composites for hyperthermia applications

    NASA Astrophysics Data System (ADS)

    Rashid, Amin Ur; Southern, Paul; Darr, Jawwad A.; Awan, Saifullah; Manzoor, Sadia

    2013-10-01

    Mixed phase composites of SrFe12O19/MgFe2O4/ZrO2 were prepared via the citrate gel technique as potential candidate materials for magnetic hyperthermia. Structural and magnetic properties of the samples were studied using powder X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and a vibrating sample magnetometer. XRD and FE-SEM data confirm that magnesium ferrite and zirconium oxide phases increased with increasing Mg and Zr content in the precursors. Magnetization loops for the composites were measured at room temperature and showed significant variation of saturation magnetization, coercivity and remanence depending on the amount of the highly anisotropic Sr-hexaferrite phase. The sample with the highest Mg and Zr content had the lowest coercivity (80 Oe) and saturation magnetization (41 emu/g). The composite samples each were exposed to a 214 kHz alternating magnetic field of amplitude 22 Oe and a significant heating effect was observed in selected samples, which suggests potential for use in magnetic hyperthermia.

  9. Iron Oxide Nanospheres and Nanocubes for Magnetic Hyperthermia Therapy: A Comparative Study

    NASA Astrophysics Data System (ADS)

    Nemati, Z.; Das, R.; Alonso, J.; Clements, E.; Phan, M. H.; Srikanth, H.

    2017-06-01

    Improving the heating capacity of magnetic nanoparticles (MNPs) for hyperthermia therapy is an important but challenging task. Through a comparative study of the inductive heating properties of spherical and cubic Fe3O4 MNPs with two distinct average volumes (˜7000 nm3 and 80,000 nm3), we demonstrate that, for small size (˜7000 nm3), the cubic MNPs heat better compared with the spherical MNPs. However, the opposite trend is observed for larger size (˜80,000 nm3). The improvement in heating efficiency in cubic small-sized MNPs (˜7000 nm3) can be attributed to enhanced anisotropy and the formation of chain-like aggregates, whereas the decrease of the heating efficiency in cubic large-sized MNPs (˜80,000 nm3) has been attributed to stronger aggregation of particles. Physical motion is shown to contribute more to the heating efficiency in case of spherical than cubic MNPs, when dispersed in water. These findings are of crucial importance in understanding the role of shape anisotropy and optimizing the heating response of magnetic nano-structures for advanced hyperthermia.

  10. Synthesis and application of magnetite dextran-spermine nanoparticles in breast cancer hyperthermia.

    PubMed

    Avazzadeh, Reza; Vasheghani-Farahani, Ebrahim; Soleimani, Masoud; Amanpour, Saeid; Sadeghi, Mohsen

    2017-09-01

    Cancer treatment has been very challenging in recent decades. One of the most promising cancer treatment methods is hyperthermia, which increases the tumor temperature (41-45 °C). Magnetic nanoparticles have been widely used for selective targeting of cancer cells. In the present study, magnetic dextran-spermine nanoparticles, conjugated with Anti-HER2 antibody to target breast cancer cells were developed. The magnetic dextran-spermine nanoparticles (DMNPs) were prepared by ionic gelation, followed by conjugation of antibody to them using EDC-NHS method. Then the Prussian blue method was used to estimate the targeting ability and cellular uptake. Cytotoxicity assay by MTT showed that antibody-conjugated MNPs (ADMNPs) have no toxic effect on SKBR3 and human fibroblast cells. Finally, the hyperthermia was applied to show that synthesized ADMNPs, could increase the cancer cells temperature up to 45 °C and kill most of them without affecting normal cells. These observations proved that Anti-HER2 conjugated magnetic dextran-spermine nanoparticles can target and destroy cancer cells and are potentially suitable for cancer treatment.

  11. Abdominal hernias: Radiological features

    PubMed Central

    Lassandro, Francesco; Iasiello, Francesca; Pizza, Nunzia Luisa; Valente, Tullio; Stefano, Maria Luisa Mangoni di Santo; Grassi, Roberto; Muto, Roberto

    2011-01-01

    Abdominal wall hernias are common diseases of the abdomen with a global incidence approximately 4%-5%. They are distinguished in external, diaphragmatic and internal hernias on the basis of their localisation. Groin hernias are the most common with a prevalence of 75%, followed by femoral (15%) and umbilical (8%). There is a higher prevalence in males (M:F, 8:1). Diagnosis is usually made on physical examination. However, clinical diagnosis may be difficult, especially in patients with obesity, pain or abdominal wall scarring. In these cases, abdominal imaging may be the first clue to the correct diagnosis and to confirm suspected complications. Different imaging modalities are used: conventional radiographs or barium studies, ultrasonography and Computed Tomography. Imaging modalities can aid in the differential diagnosis of palpable abdominal wall masses and can help to define hernial contents such as fatty tissue, bowel, other organs or fluid. This work focuses on the main radiological findings of abdominal herniations. PMID:21860678

  12. A magnetic induction heating system with multi-cascaded coils and adjustable magnetic circuit for hyperthermia.

    PubMed

    Huang, Chi-Fang; Chao, Hsuan-Yi; Chang, Hsun-Hao; Lin, Xi-Zhang

    2016-01-01

    Based on the characteristics of cancer cells that cannot survive in an environment with temperature over 42 °C, a magnetic induction heating system for cancer treatment is developed in this work. First, the methods and analyses for designing the multi-cascaded coils magnetic induction hyperthermia system are proposed, such as internal impedance measurement of power generator, impedance matching of coils, and analysis of the system. Besides, characteristics of the system are simulated by a full-wave package for engineering optimization. Furthermore, by considering the safety factor of patients, a two-sectional needle is designed for hyperthermia. Finally, this system is employed to test the liver of swine in ex-vivo experiments, and through Hematoxylin and Eosin (H&E) stain and NADPH oxidase activity assay, the feasibility of this system is verified.

  13. Model-based feasibility assessment and evaluation of prostate hyperthermia with a commercial MR-guided endorectal HIFU ablation array

    PubMed Central

    Salgaonkar, Vasant A.; Prakash, Punit; Rieke, Viola; Ozhinsky, Eugene; Plata, Juan; Kurhanewicz, John; Hsu, I-C. (Joe); Diederich, Chris J.

    2014-01-01

    Purpose: Feasibility of targeted and volumetric hyperthermia (40–45 °C) delivery to the prostate with a commercial MR-guided endorectal ultrasound phased array system, designed specifically for thermal ablation and approved for ablation trials (ExAblate 2100, Insightec Ltd.), was assessed through computer simulations and tissue-equivalent phantom experiments with the intention of fast clinical translation for targeted hyperthermia in conjunction with radiotherapy and chemotherapy. Methods: The simulations included a 3D finite element method based biothermal model, and acoustic field calculations for the ExAblate ERUS phased array (2.3 MHz, 2.3 × 4.0 cm2, ∼1000 channels) using the rectangular radiator method. Array beamforming strategies were investigated to deliver protracted, continuous-wave hyperthermia to focal prostate cancer targets identified from representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Preliminary experiments included beamformed sonications in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W). Results: Acoustic intensities considered during simulation were limited to ensure mild hyperthermia (Tmax < 45 °C) and fail-safe operation of the ExAblate array (spatial and time averaged acoustic intensity ISATA < 3.4 W/cm2). Tissue volumes with therapeutic temperature levels (T > 41 °C) were estimated. Numerical simulations indicated that T > 41 °C was calculated in 13–23 cm3 volumes for sonications with planar or diverging beam patterns at 0.9–1.2 W/cm2, in 4.5–5.8 cm3 volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm2, and in ∼6.0 cm3 for curvilinear (cylindrical) beam patterns at 0.75 W/cm2. Focused heating patterns may be practical for treating focal disease in a single posterior quadrant of the prostate and diffused heating patterns may be

  14. Hyperthermia combined with ethanol administration induces c-fos expression in the central amygdaloid nucleus of the mouse brain. A possible mechanism of heatstroke under the influence of ethanol intake.

    PubMed

    Kibayashi, Kazuhiko; Nakao, Ken-ichiro; Shojo, Hideki

    2009-09-01

    Heatstroke is defined as a core body temperature that rises above 40.6 degrees C and is accompanied by mental status abnormalities such as delirium, convulsions, or coma resulting from exposure to environmental heat. There is fairly wide agreement that ethanol intake is a predisposing factor in heatstroke. This study was performed to identify the brain changes induced by heatstroke, using a mouse hyperthermia model with and without preceding ethanol administration. Exposure to heat of 42 degrees C until the core temperature reached to 43 degrees C followed by exposure to 37 degrees C for 15 min decreased the levels of partial pressures of O(2) in blood. Preceding ethanol administration and heat exposure induced hypotension, severe metabolic acidosis and respiratory failure, and, accordingly, produced heatstroke. Immunohistochemistry of the brains showed that preceding ethanol administration increased the number of c-fos-immunoreactive neurons, as a marker of neuronal activation, in the central amygdaloid nucleus, which is involved in thermoregulation. These results indicate that combined effects of ethanol and heat exposure induce heatstroke that is associated with activation of the central amygdaloid nucleus, implicating the pathophysiology and mechanisms of heatstroke under the influence of ethanol intake.

  15. Abdominal binders may reduce pain and improve physical function after major abdominal surgery - a systematic review.

    PubMed

    Rothman, Josephine Philip; Gunnarsson, Ulf; Bisgaard, Thue

    2014-11-01

    Evidence for the effect of post-operative abdominal binders on post-operative pain, seroma formation, physical function, pulmonary function and increased intra-abdominal pressure among patients after surgery remains largely un-investigated. A systematic review was conducted. The PubMed, EMBASE and Cochrane databases were searched for studies on the use of abdominal binders after abdominal surgery or abdominoplasty. All types of clinical studies were included. Two independent assessors evaluated the scientific quality of the studies. The primary outcomes were pain, seroma formation and physical function. A total of 50 publications were identified; 42 publications were excluded leaving eight publications counting a total of 578 patients for analysis. Generally, the scientific quality of the studies was poor. Use of abdominal binder revealed a non-significant tendency to reduce seroma formation after laparoscopic ventral herniotomy and a non-significant reduction in pain. Physical function was improved, whereas evidence supports a beneficial effect on psychological distress after open abdominal surgery. Evidence also supports that intra-abdominal pressure increases with the use of abdominal binders. Reduction of pulmonary function during use of abdominal binders has not been revealed. Abdominal binders reduce post-operative psychological distress, but their effect on post-operative pain after laparotomy and seroma formation after ventral hernia repair remains unclear. Due to the sparse evidence and poor quality of the literature, solid conclusions may be difficult to make, and procedure-specific, high-quality randomised clinical trials are warranted.

  16. Abdominal 4D flow MR imaging in a breath hold: combination of spiral sampling and dynamic compressed sensing for highly accelerated acquisition.

    PubMed

    Dyvorne, Hadrien; Knight-Greenfield, Ashley; Jajamovich, Guido; Besa, Cecilia; Cui, Yong; Stalder, Aurélien; Markl, Michael; Taouli, Bachir

    2015-04-01

    L/sec). The combination of highly efficient spiral sampling with dynamic compressed sensing results in major acceleration for 4D flow MR imaging, which allows comprehensive assessment of abdominal vessel hemodynamics in a single breath hold.

  17. Circadian aspects of hyperthermia in mice induced by Aconitum napellus.

    PubMed

    de la Peña, Salvador Sánchez; Sothern, Robert B; López, Fernando Santillán; Lujambio, Irene Mendoza; Waizel-Bucay, José; Sánchez, Carolina Olarte; Monroy, Claudia Pérez; Betancourt, Eduardo Tena

    2011-07-01

    Aconitum napellus (Acn) is used topically to relieve pain, itching and inflammation, and internally to reduce febrile states, among others. Any circadian time-related consequences of Acn administration are unknown. The objective of this study was to explore the effects of two doses of Acn on body temperature (BT) of mice treated at six different times over 24 hours. BALB/c female mice were housed in six chambers (six mice each) with air temperature 24 ± 3°C, humidity 60 ± 4%, and a 12-hours light (L)/12-hours dark cycle, but with L-onset staggered by 4 hours between chambers so that study at one external test time resulted in six test times (02, 06, 10, 14, 18 and 22 hours [h] after light onset). Rectal temperature (RT; in °C) was measured at baseline (B) and 1 hour after oral treatment with placebo (P) or two doses of Acn (6C and 30C, two studies each) in six studies over an 8 day span. The difference in RT for each mouse from the respective B + P timepoint mean RT was computed following each Acn treatment, and data from each of the six studies (original RT and difference from B + P) were analyzed for time-effect by analysis of variance (ANOVA) and for circadian rhythm by 24-hour cosine fitting. A CIRCADIAN RHYTHM IN RT WAS FOUND AT B AND AFTER P (MEAN: 35.58°C vs. 35.69°C; peak: 15:31 h vs. 15:40 h) and after each Acn dose (30C or 6C). Acn induced hyperthermia and the overall change in BT was rhythmically significant for each dose (mean = +1.95°C vs. +1.70°C), with greatest hyperthermia observed during the L-span for each dose (peak = 08:56 h vs. 05:17 h). Acn administered around the clock induced hyperthermia overall and in a time-dependent manner, with greatest effects during the resting (L) span. Thus, time of day may significantly impact the outcome of Acn and other homeopathic treatments and should be considered in determining optimal dosing and treatment time(s) in order to increase the desired outcome and decrease undesired effects.

  18. Experience with a small animal hyperthermia ultrasound system (SAHUS): report on 83 tumours

    NASA Astrophysics Data System (ADS)

    Novák, P.; Moros, E. G.; Parry, J. J.; Rogers, B. E.; Myerson, R. J.; Zeug, A.; Locke, J. E.; Rossin, R.; Straube, W. L.; Singh, A. K.

    2005-11-01

    An external local ultrasound (US) system was developed to induce controlled hyperthermia of subcutaneously implanted tumours in small animals (e.g., mice and rats). It was designed to be compatible with a small animal positron emission tomography scanner (microPET) to facilitate studies of hyperthermia-induced tumour re-oxygenation using a PET radiopharmaceutical, but it is applicable for any small animal study requiring controlled heating. The system consists of an acrylic applicator bed with up to four independent 5 MHz planar disc US transducers of 1 cm in diameter, a four-channel radiofrequency (RF) generator, a multiple thermocouple thermometry unit, and a personal computer with custom monitoring and controlling software. Although the system presented here was developed to target tumours of up to 1 cm in diameter, the applicator design allows for different piezoelectric transducers to be exchanged and operated within the 3.5-6.5 MHz band to target different tumour sizes. Temperature feedback control software was developed on the basis of a proportional-integral-derivative (PID) approach when the measured temperatures were within a selectable temperature band about the target temperature. Outside this band, an on/off control action was applied. Perfused tissue-mimicking phantom experiments were performed to determine optimum controller gain constants, which were later employed successfully in animal experiments. The performance of the SAHUS (small animal hyperthermia ultrasound system) was tested using several tumour types grown in thighs of female nude (nu/nu) mice. To date, the system has successfully treated 83 tumours to target temperatures in the range of 41-43 °C for periods of 65 min on average.

  19. Thermal sensation during mild hyperthermia is modulated by acute postural change in humans

    NASA Astrophysics Data System (ADS)

    Takeda, Ryosuke; Imai, Daiki; Suzuki, Akina; Ota, Akemi; Naghavi, Nooshin; Yamashina, Yoshihiro; Hirasawa, Yoshikazu; Yokoyama, Hisayo; Miyagawa, Toshiaki; Okazaki, Kazunobu

    2016-12-01

    Thermal sensation represents the primary stimulus for behavioral and autonomic thermoregulation. We assessed whether the sensation of skin and core temperatures for the driving force of behavioral thermoregulation was modified by postural change from the supine (Sup) to sitting (Sit) during mild hyperthermia. Seventeen healthy young men underwent measurements of noticeable increase and decrease (±0.1 °C/s) of skin temperature (thresholds of warm and cold sensation on the skin, 6.25 cm2 of area) at the forearm and chest and of the whole-body warm sensation in the Sup and Sit during normothermia (NT; esophageal temperature (Tes), ˜36.6 °C) and mild hyperthermia (HT; Tes, ˜37.2 °C; lower legs immersion in 42 °C of water). The threshold for cold sensation on the skin at chest was lower during HT than NT in the Sit ( P < 0.05) but not in Sup, and at the forearm was lower during HT than NT in the Sup and further in Sit (both, P < 0.05), with interactive effects of temperature (NT vs. HT) × posture (Sup vs. Sit) (chest, P = 0.08; forearm, P < 0.05). The threshold for warm sensation on the skin at both sites remained unchanged with changes in body posture or temperature. The whole-body warm sensation was higher during HT than NT in both postures and higher in the Sit than Sup during both NT and HT (all, P < 0.05). Thus, thermal sensation during mild hyperthermia is modulated by postural change from supine to sitting to sense lesser cold on the skin and more whole-body warmth.

  20. A newly developed Fe-doped calcium sulfide nanoparticles with magnetic property for cancer hyperthermia

    NASA Astrophysics Data System (ADS)

    Wu, Steven Yueh-Hsiu; Tseng, Ching-Li; Lin, Feng-Huei

    2010-05-01

    In this study, a magnetic iron-doped calcium sulfide (Fe-CaS) nanoparticle was newly developed and studied for the purpose of hyperthermia due to its promising magnetic property, adequate biodegradation rate, and relatively good biocompatibility. Fe-CaS nanoparticles were synthesized by a wet chemical co-precipitation process with heat treatment in a N2 atmosphere, and were subsequently cooled in N2 and exposed to air at a low temperature. The crystal structure of the Fe-CaS nanoparticles was similar to that of the CaS, which was identified by an X-ray diffractometer (XRD). The particle size was less than 40 nm based on a Debye-Scherrer equation and transmission electron microscope (TEM) examination. Magnetic properties obtained from the SQUID magnetometer demonstrated that the synthesized CaS was a diamagnetic property. Once the Fe ions were doped, the synthesized Fe-CaS converted into paramagnetism which showed no hysteresis loop. Having been heated above 600 °C in N2, the Fe-CaS showed a promising magnetic property to produce enough energy to increase the temperature for hyperthermia. 10 mg/ml of the Fe-CaS was able to generate heat to elevate the media temperature over 42.5 °C within 6 min. The area of the hysteresis loop increased with the increasing of the treated temperature, especially at 800 °C for 1 h. This is because more Fe ions replaced Ca ions in the lattice at the higher heat treatment temperature. The heat production was also increasing with the increasing of heat treatment temperature, which resulted in an adequate specific absorption ratio (SAR) value, which was found to be 45.47 W/g at 37 °C under an alternative magnetic field of f = 750 KHz , H = 10 Oe. The in vitro biocompatibility test of the synthesized Fe-CaS nanoparticles examined by the LDH assay showed no cytotoxicity to 3T3 fibroblast. The result of in vitro cell hyperthermia shows that under magnetic field the Fe-CaS nanoparticles were able to generate heat and kill the CT-26 cancer