WorldWideScience

Sample records for compartmental intrathecal radioimmunotherapy

  1. Pretargeted radioimmunotherapy

    International Nuclear Information System (INIS)

    Meredith, Ruby F.; Buchsbaum, Donald J.

    2006-01-01

    This brief review covers the concept of pretargeted radioimmunotherapy and summarize the results obtained in preclinical animal models and initial phase I clinical trials. Reagents studied have been a bifunctional antibody prepared by crosslinking Fab' fragments from two antibodies with different specificity, one binding the target antigen expressed on tumors and the other binding a radiolabeled peptide. The alternative system is a conjugate of streptavidin linked to the pretargeting agent and radiolabeled biotin. After reaching optimal tumor targeting of the pretargeting agent, a synthetic mono-biotin poly N-acetyl-galactosamine compound was used to clear unbound targeting agent from the circulation before the injection of radiolabeled biotin. Promising therapeutic responses were obtained in various tumor xenograft models in athymic nude mice. A phase I study of an anti-CD20/streptavidin pretargeting agent and 15 mCi/m 2 9 Y-biotin produced objective responses with minimal toxicity among lymphoma patients, with an average tumor-to-whole-body radiation dose ratio of 49. Pretargeting radioimmunotherapy approaches have shown higher tumor-to-whole-body ratios than that usually obtained with one-step radioimmunotherapy

  2. Compartmentalization today

    Science.gov (United States)

    Kevin T. Smith

    2006-01-01

    For more than 30 years, the compartmentdization concept has helped tree care practitioners and land managers interpret patterns of decay in living trees. Understanding these patterns can help guide the selection of treatments that meet the needs of people and communities while respecting the underlying tree biology. At its simplest, compartmentalization resists the...

  3. Radio-immunotherapy; La radio-immunotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Bodet-Milin, C.; Oudoux, A.; Kraeber-Bodere, F. [Hopital Hotel-Dieu, Service de Medecine Nucleaire, 44 - Nantes (France); Kraeber-Bodere, F. [Inserm U892, CRCNA, 44 - Nantes (France); Kraeber-Bodere, F. [Centre Rene-Gauducheau, Service de Medecine Nucleaire, 44 - Saint-Herblain (France)

    2009-02-15

    Radioimmunotherapy (R.I.T.) is a new modality of targeted therapy in which irradiation from radionuclides is delivered to tumor targets using monoclonal antibodies (MAb) directed to tumor-associated antigen. R.I.T. has been developed for more than 20 years. Today, R.I.T. can be used in clinical practice using non-ablative activity of murine anti-CD20 {sup 90}Y-ibritumomab tiuxetan (Zevalin) for treatment of patients with relapsed or refractory follicular lymphomas (F.L.), with overall response rate of 70 to 80% and 20 to 30% of complete response. Different approaches are explored to improve efficacy of R.I.T. in N.H.L.: myelo-ablative R.I.T. or HD treatment, R.I.T. as consolidation after chemotherapy to target M.R.D., R.I.T. in first-line treatment, fractionated R.I.T., R.I.T. using other Ag targets. For solid tumors, interesting results have been obtained using anti-CEA R.I.T. delivered as consolidation treatment or using pre-targeting system. (authors)

  4. Radioimmunotherapy (II): clinical application

    International Nuclear Information System (INIS)

    Cheon, Gi Jeong; Kang, Hye Jin; Lim, Sang Moo

    2006-01-01

    Molecular targeting may be defined as the specific concentration of a diagnostic or therapeutic tracer by its interaction with a molecular species that is distinctly present or absent in a disease state. Monoclonal antibody (mAb) is one of the successful agents for targeted therapy in cancer. To enhance the therapeutic effect. the concept of targeting radionuclides to tumors using radiolabeled mAbs against tumor-associated antigens, radioimmunotherapy, was proposed. The efficacy of radioimmunotherapy, however, has to be further optimized. Several strategies to improve targeting of tumors with radiolabeled mAbs have been developed, such as the use of mAb fragments, the use of high-affinity mAbs, the use of labeling techniques that are stable in vivo, active removal of the radiolabeled mAb from the circulation, and pretargeting strategies. Until now, however, there are many kinds of obstacles to be solved in the use of mAb for the targeted therapy. Major technical challenges to molecular targeting are related to the rapid and specific delivery of tracers to the target, the elimination of unwanted background activity, and the development of more specific targets to create a cytocidal effect. Further development of this field will be determined by success in solving these challenges

  5. Intrathecal Ropivacaine in Cesarean Delivery

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Conclusion: Ropivacaine administration produced rapid induction of ... KEYWORDS: Ropivacaine, spinal anesthesia, intrathecal, cesarean section. Intrathecal .... expressed as mean standard deviation (SD). One-way.

  6. Compartmental distribution of radiotracers

    International Nuclear Information System (INIS)

    Robertson, J.S.; Colombetti, L.G.

    1983-01-01

    This book examines the use of radioisotopes in medical diagnosis. Topics considered include compartmental analysis, data processing in nuclear medicine, historical aspects, basic principles, mathematical methods, the application of computers in obtaining numerical solutions to compartmental models, the SAAM and CONSAM programs, some statistical principles in compartmental analysis, and applications

  7. Candidate immune biomarkers for radioimmunotherapy.

    Science.gov (United States)

    Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric

    2017-08-01

    Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy. Copyright © 2017. Published by Elsevier B.V.

  8. Compartmental distribution of radiotracers

    International Nuclear Information System (INIS)

    Roberton, J.S.

    1983-01-01

    Emphasizes applications of compartmental analysis in physiology, pharmacology, and other areas of biology and medicine. Details of computer methods and applications of statistical principles as they apply to compartmental analysis are presented. Of special interest is a step-by-step discussion of Berman's SAAM program in modeling at several different levels of difficulty. Extensive references and sources of additional information in mathematical methods and in applications to specific problems are provided. Contents: Historical Development. Basic Principles, Mathematical Methods. Application of Computers for Obtaining Numerical Solutions to Compartmental Models. Use of Computers in Compartmental Analysis: SAAM and CONSAAM Programs. Some Statistical Principals in Compartmental Analysis. Applications. Index

  9. Radioimmunotherapy (I): development of radioimmunoconjugates

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Tea Hyun; Lim, Sang Moo [Korea Institute of Radiological and Medicine, Seoul (Korea, Republic of)

    2006-04-15

    Monoclonal antibodies are designed to bind specifically to certain antigen, give therapeutic effect to the target and to be produced in large scale with homogeneity. The monoclonal conjugated with radionuclide can deliver therapeutic irradiation to the target, and showed successful results in certain malignancies, which is known as radioimmunotherapy. The target-to-background ratio depends on the antigen expression in the target and normal tissues, which is related to the therapeutic efficacy and toxicity in radioimmunotherapy. For the solid tumor beta-ray energy should be high, but lower beta energy is better for the hematological malignancies. I-131 is widely used in thyroid cancer with low cost and high availability. Labeling monoclonal antibody with I-131 is relatively simple and reproducible. Some preclinical data for the I-131 labeled monoclonal antibodies including acute toxicity and efficacy are available from already published literatures. In KIRAMS, physician sponsored clinical trial protocols using Rituximab, KFDA approved anti-CD20 chimeric monoclonal antibody and I-131 were approved by KFDA and currently are ongoing.

  10. Improved radioimmunotherapy of hematologic malignancies

    International Nuclear Information System (INIS)

    Press, O.W.

    1992-01-01

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ( 131 Iodine, 111 Indium, 90 Yttrium, 99m Technetium, 186 Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer

  11. Improved radioimmunotherapy of hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  12. Radioimmunotherapy [INIS-UY-GEO--700

    International Nuclear Information System (INIS)

    Cacchione, R.

    2015-01-01

    This presentation is about the radiotherapy, chemo-immunotherapy and radioimmunotherapy treatment. Its adequate response in Non-Hodgkin Lymphoma as well as the tolerance and reversibly hematologic toxicity

  13. Choice of radionuclides for radioimmunotherapy

    International Nuclear Information System (INIS)

    DeNardo, S.J.; Jungerman, J.A.; DeNardo, G.L.; Lagunas-Solar, M.C.; Cole, W.C.; Meares, C.F.

    1985-01-01

    Innumerable questions need to be answered and obstacles overcome before radioimmunotherapy can be generally successful in cancer patients. Major developments have greatly enhanced the likelihood of success. The important development of appropriate radionuclides and radiochemistry for this therapy must be intimately linked with the biological and biochemical realities. All aspects must be considered, such as the specific nature of the antigenic target, the pharmacokinetics of the antibody fragment carrier, the capability of in vivo quantitation of tumor uptake and turnover time, as well as total body kinetics. With this knowledge, then, practical radiochemistry methods can be integrated with the suitable radionuclide choices, and production methods can be developed which will deliver effective and dependable products for patient therapy

  14. Intrathecal tramadol versus intrathecal fentanyl for visceral pain ...

    African Journals Online (AJOL)

    Intrathecal tramadol versus intrathecal fentanyl for visceral pain control during bupivacaine subarachnoid block for open appendicectomy. ... Visual analog scale scores and frequency of subjective symptoms among patients in the three groups formed the primary outcome measure of this study. Results: Effective ...

  15. Intrathecal tramadol versus intrathecal fentanyl for visceral pain ...

    African Journals Online (AJOL)

    2013-10-29

    Oct 29, 2013 ... Nigerian Journal of Clinical Practice • May-Jun 2014 • Vol 17 • Issue 3. Original ... intrathecal fentanyl and a normal saline placebo‑controlled protocol for ..... pain experienced by pregnant women during Caesarean section.

  16. Delayed postoperative gastric emptying following intrathecal morphine and intrathecal bupivacaine.

    LENUS (Irish Health Repository)

    Lydon, A M

    2012-02-03

    PURPOSE: A decrease in the rate of gastric emptying can delay resumption of enteral feeding, alter bioavailability of orally administered drugs, and result in larger residual gastric volumes, increasing the risk of nausea and vomiting. We compared the effects of 1) intrathecal bupivacaine (17.5 mg) and 2) the combination of intrathecal morphine (0.6 mg) and intrathecal bupivacaine (17.5 mg) on the rate of gastric emptying in patients undergoing elective hip arthroplasty. METHODS: Twenty four fasting ASA 1-3 patients were randomly assigned, in a double blind manner, to receive intrathecal hyperbaric bupivacaine (17.5 mg), either alone (group 1), or followed by intrathecal morphine (0.6 mg) (group 2). Gastric emptying was measured (using an acetaminophen absorption technique), twice in each patient; preoperatively, and approximately one hour postoperatively. Gastric emptying parameters are: AUC (area under the plasma acetaminophen concentration time curve), maximum plasma acetaminophen concentration (Cmax), and time to Cmax (tCmax), analyzed using paired Student\\'s t tests. RESULTS: Gastric emptying rates were reduced in both group 1 (AUC = 14.98 (3.8) and 11.05 (4.6) pre- and postoperatively, respectively) and group 2 (AUC = 13.93 (3.59) and 6.4 (3.42) pre- and postoperatively, respectively); the magnitude of the reduction was greater in group 2 [AUC (P = 0.04), Cmax (P = 0.05), tCmax (P = 0.13)]. CONCLUSION: The combination of intrathecal morphine (0.6 mg) and intrathecal bupivacaine (17.5 mg) delays gastric emptying postoperatively.

  17. Radioimmunotherapy of non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Batista Cuellar, Juan F.

    2016-01-01

    Non-Hodgkin lymphoma have a worse prognosis compared with other varieties of lymphoma and conventional therapy has specific onco higher incidence of unsatisfactory answers becoming more frequent recurrences of the disease. Radioimmunotherapy has proven to be an effective adjuvant therapy often in cases where conventional therapy this not proving effective. In this paper an exhibition of the current international state of the therapeutic and experiences and possibilities that exist in our environment to develop their use is done. (author)

  18. Intrathecal Baclofen Pump for Spasticity

    Science.gov (United States)

    2005-01-01

    Executive Summary Objective To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of intrathecal baclofen for spasticity. The Technology Spasticity is a motor disorder characterized by tight or stiff muscles that may interfere with voluntary muscle movements and is a problem for many patients with multiple sclerosis (MS), spinal cord injury (SCI), cerebral palsy (CP), and acquired brain injury (ABI).(1). Increased tone and spasm reduces mobility and independence, and interferes with activities of daily living, continence and sleep patterns. Spasticity may also be associated with significant pain or discomfort (e.g., due to poor fit in braces, footwear, or wheelchairs), skin breakdown, contractures, sleep disorders and difficulty in transfer. Goals of treatment are to decrease spasticity in order to improve range of motion, facilitate movement, reduce energy expenditure and reduce risk of contractures. Existing treatments include physical therapy, oral medications, injections of phenol or botulinum toxin, or surgical intervention. Baclofen is the oral drug most frequently prescribed for spasticity in cases of SCI and MS.(1) Baclofen is a muscle relaxant and antispasticity drug. In the brain, baclofen delivered orally has some supraspinal activity that may contribute to clinical side effects. The main adverse effects of oral baclofen include sedation, excessive weakness, dizziness, mental confusion, and somnolence.(2) The incidence of adverse effects is reported to range from 10% to 75%.(2) Ochs et al. estimated that approximately 25-30% of SCI and MS patients fail to respond to oral baclofen.(3;4) Adverse effects appear to be dose-related and may be minimized by initiating treatment at a low dose and gradually titrating upwards.(2) Adverse effects usually appear at doses >60 mg/day.(2) The rate of treatment discontinuation due to intolerable adverse effects has generally been reported to range from 4% to 27%.(2) When baclofen is

  19. Inadvertent intrathecal injection of atracurium.

    Science.gov (United States)

    Zirak, Nahid; Soltani, Ghasem; Ghomian, Naiere; Hasanpour, Mohamad Reza; Mashayekhi, Zahra

    2011-04-01

    This report relates how tracurium was given by mistake, intrathecally, during spinal anesthesia, to a 38-year-old woman, who was a candidate for abdominal hysterectomy. When no analgesia was observed, the mistake in giving the injection was understood. She was evaluated postoperatively by train of four ratio, measuring her breathing rate, eye opening, and protruding of tongue at one, two, twenty-four, and forty-eight hours, and then at one and two weeks, with the final evaluation the following month. The patient had normal timings during the operation and postoperation periods, and no abnormal findings were observed through the first month. This finding was contrary to several studies, which described adverse reactions due to accidental intrathecal injection of neuromuscular blocking drugs.

  20. Inadvertent intrathecal injection of atracurium

    Directory of Open Access Journals (Sweden)

    Nahid Zirak

    2011-01-01

    Full Text Available This report relates how tracurium was given by mistake, intrathecally, during spinal anesthesia, to a 38-year-old woman, who was a candidate for abdominal hysterectomy. When no analgesia was observed, the mistake in giving the injection was understood. She was evaluated postoperatively by train of four ratio, measuring her breathing rate, eye opening, and protruding of tongue at one, two, twenty-four, and forty-eight hours, and then at one and two weeks, with the final evaluation the following month. The patient had normal timings during the operation and postoperation periods, and no abnormal findings were observed through the first month. This finding was contrary to several studies, which described adverse reactions due to accidental intrathecal injection of neuromuscular blocking drugs.

  1. Improved radioimmunotherapy of hematologic malignancies. [Final report

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  2. Compartmental study of biological systems

    International Nuclear Information System (INIS)

    Moretti, J.L.

    1975-01-01

    The compartmental analysis of biological system is dealt with on several chapters devoted successively to: terminology; a mathematical and symbolic account of a system at equilibrium; different compartment systems; analysis of the experimental results. For this it is pointed out that the application of compartmental systems to biological phenomena is not always without danger. Sometimes the compartmental system established in a reference subject fails to conform in the patient. The compartments can divide into two or join together, completely changing the aspect of the system so that parameters calculated with the old model become entirely false. The conclusion is that the setting up of a compartmental system to represent a biological phenomenon is a tricky undertaking and the results must be constantly criticized and questioned [fr

  3. Radioimmunotherapy: Development of an effective approach

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    Goals of this program are to answer the fundamental scientific questions for the development of an effective approach for delivering radiation therapy to cancer on antibody-based radiopharmaceuticals. The following list consists of highlights of developments from our program: documented therapeutic response of lymphoma in patients receiving radioimmunotherapy; development and application of quantitative radionuclide imaging techniques for therapy planning and dosimetry calculations; multicompartmental modeling and analysis of the in vivo MoAb kinetics in patients; a MoAb macrocycle chelate for Cu-67: development, production, in vitro and in vivo testing; NMR analysis of immunoradiotherapeutic effects on the metabolism of lymphoma; analysis of the variable molecular characteristics of the MoAb radiopharmaceutical, and their significance; in vivo studies in mice and patients of the metabolism of radioiodinated MoAb as well as In-111 CITC MoAb; and biodistribution of Cu-67 TETA MoAb in nude mice with human lymphoma.

  4. Radioimmunotherapy: Development of an effective approach

    International Nuclear Information System (INIS)

    1987-01-01

    Goals of this program are to answer the fundamental scientific questions for the development of an effective approach for delivering radiation therapy to cancer on antibody-based radiopharmaceuticals. The following list consists of highlights of developments from our program: documented therapeutic response of lymphoma in patients receiving radioimmunotherapy; development and application of quantitative radionuclide imaging techniques for therapy planning and dosimetry calculations; multicompartmental modeling and analysis of the in vivo MoAb kinetics in patients; a MoAb macrocycle chelate for Cu-67: development, production, in vitro and in vivo testing; NMR analysis of immunoradiotherapeutic effects on the metabolism of lymphoma; analysis of the variable molecular characteristics of the MoAb radiopharmaceutical, and their significance; in vivo studies in mice and patients of the metabolism of radioiodinated MoAb as well as In-111 CITC MoAb; and biodistribution of Cu-67 TETA MoAb in nude mice with human lymphoma

  5. Immunoscintigraphy and radioimmunotherapy of transplanted pancreatic carcinoma

    International Nuclear Information System (INIS)

    Klapdor, R.; Greten, H.; Saccavini, J.C.; Dietel, M.

    1985-01-01

    The immunoscintigraphic results in 12 human pancreatic carcinomas established on nude mice (Nu-Nu-Balb-C) are reported. 131 I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125 were used. The result show that pancreatic carcinomas are detectable with the antibodies applied here. The quality of the scintigraphic detection depends, among other factors, on the antibody affinity to the tumor, the localization and the size of the tumor. Preliminary results of the studies on radioimmunotherapy of pancreatic cancer with 131 I-anti-CA 19-9 indicate that effective absorbed doses in the tumor may be achieved via intravenous application only in cases with a rather high expression of the tumor antigen. But direct instillation into the tumor enables therapeutic radiation doses to the tumor even with moderate affinity and a low whole-body burden. (orig./MG) [de

  6. Radio-immunotherapy of solid tumors

    International Nuclear Information System (INIS)

    Chatal, J.F.; Faivre Chauvet, A.; Bardies, M.; Kraeber-Bodere, F.; Barbet, J.

    2001-01-01

    A convincing efficacy of radio-immunotherapy of solid tumors has not been documented yet in clinical studies. Consequently, a methodological optimization is needed within the scope in increasing absorbed doses delivered to tumor targets by amplifying cumulative tumor activity and in the same time in reducing absorbed doses delivered normal organs. Multi-step pre-targeting techniques allow to approach these goals. The most developed technique is based on the high affinity for biotin. In a first step an anti-tumor antibody coupled to avidin or biodin is injected. In a second step, 24 hours later, the circulating residual immuno-conjugate is bound to a molecular complex and eliminated through the reticulo endothelial system of the liver ('chase'phase). A third step, a few hours later, consists in injecting biotin coupled to DOTA chelating agent and labeled with yttrium 90. This small molecule rapidly diffuses to tumor targets and binds to pre-localized immuno-conjugate. Another technique, designed and developed in France, is based on antigen-antibody affinity. In a first step an anti-tumor / anti-hapten bi-specific antibody is injected and, in a second step, a few days later, the small hapten molecule is radiolabeled with I-131 and injected. It diffuses rapidly to the tumor targets and binds to the anti-hapten arm of the pre-localized bi-specific antibody. An alternative way to increase radio-immunotherapy efficacy consists in combining this low-dose rate irradiation to radiosensitizing molecules within the scope of an additive or supra additive effect which has previously documented. (author)

  7. Benefits of using intrathecal buprenorphine.

    Science.gov (United States)

    Rabiee, Seyed Mozaffar; Alijanpour, Ebrahim; Jabbari, Ali; Rostami, Sara

    2014-01-01

    General anesthesia draws attention to the most commonly used modalities for post cesarean delivery pain relief in systemic administration of opioids, while the administration of small dose of intrathecal opioid during spinal anesthesia can be a possible alternative. The aim of this study was to evaluate the effects of buprenorphine on cesarean section prescribed intrathecally. This double blind randomized clinical trial study was conducted in patients for cesarean section under spinal anesthesia. The patients were randomly divided into case and control groups. Case group (208 patients) received 65-70 mg of 5% lidocaine plus 0.2 ml of buprenorphine while the same amount of 5% lidocaine diluted with 0.2 ml of normal saline was given to 234 cases in the control group. Hemodynamic changes and neonatal APGAR scores (Appearance, Pulse, Grimace, Activity, Respiration) were recorded. Pain score was recorded according to the visual analog scale. This study was registered in the Iranian Registry of clinical Trials; IRCT2013022112552N1. The mean age of case and control groups was 24.4±5.38 and 26.84±5.42 years, respectively. Systolic blood pressure was not significantly different until the 45th minute but diastolic blood pressure showed a significant difference at the 15th and the 60th minutes (P<0.001). Heart rate changes were significantly different between cases and controls at the initial 5th, 15th and after 60th minutes (P<0.001). Pain-free period was significantly different between two groups (1.25 h versus 18.73 h) (P<0.001). The results show that prescription of intratechal buprenorphine prolongs the duration of analgesia without any significant considerable side effects.

  8. Trial Watch: Radioimmunotherapy for oncological indications.

    Science.gov (United States)

    Bloy, Norma; Pol, Jonathan; Manic, Gwenola; Vitale, Ilio; Eggermont, Alexander; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-10-01

    During the past two decades, it has become increasingly clear that the antineoplastic effects of radiation therapy do not simply reflect the ability of X-, β- and γ-rays to damage transformed cells and directly cause their permanent proliferative arrest or demise, but also involve cancer cell-extrinsic mechanisms. Indeed, among other activities, radiotherapy has been shown to favor the establishment of tumor-specific immune responses that operate systemically, underpinning the so-called 'out-of-field' or 'abscopal' effect. Thus, ionizing rays appear to elicit immunogenic cell death, a functionally peculiar variant of apoptosis associated with the emission of a particularly immunostimulatory combination of damage-associated molecular patterns. In line with this notion, radiation therapy fosters, and thus exacerbates, the antineoplastic effects of various treatment modalities, including surgery, chemotherapy and various immunotherapeutic agents. Here, we summarize recent advances in the use of ionizing rays as a means to induce or potentiate therapeutically relevant anticancer immune responses. In addition, we present clinical trials initiated during the past 12 months to test the actual benefit of radioimmunotherapy in cancer patients.

  9. Intraperitoneal alpha-radioimmunotherapy in mice using different specific activities

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Haglund, Elin

    2009-01-01

    The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At.......The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At....

  10. Improved radioimmunotherapy of hematologic malignancies. Final technical report

    International Nuclear Information System (INIS)

    Press, O.W.

    1996-01-01

    Experiments were performed to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells. An attempt was made to examine in vivo the effects of lysosomotropic amines and thioamides on the retention of radiolabeled monoclonal antibodies by tumor cells. Experiments also examined the impact of newer radioiodination techniques on the metabolic degradation of radioiodinated antibodies, and on the radioimmunoscintigraphy and radioimmunotherapy of neoplasms. The endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with I-131, In-111, and Y-90 were compared. The utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer was investigated

  11. Radioimmunotherapy of solid cancers. A review

    International Nuclear Information System (INIS)

    Kairemo, K.J.A.

    1996-01-01

    Depending on radionuclide characteristics, radioimmunotherapy (RIT) relies on radioactivity to destroy cells distant from immunotargeted cells. Therefore, even heterogeneous tumors (for antigen recognition) can be treated, because not all cells have to be targeted. Substantial complete response rates have been reported in patients with non-Hodgkin's lymphoma. Much more modest results have been reported for patients iwth bulky solid tumors, e.g. adenocarcinomas. The radiation doses delivered by targeting antibodies are generally too low to achieve major therapeutic responses. Dose escalation is limited by myelotoxicity, and higher doses need to be delivered to neoplasmas less radiosensitive than lymphomas. Various trials for both systematic and regional RIT have been reported on. Intraperitoneal adminostration has been applied for colorectal and ovarian carcinomas. Our own results indicate that, e.g., intraperitoneal pseudomyxoma can be treated with RIT. Myelotoxicity can be reduced by anti-antibody-enhancement, 2- and 3-step strategies, bispecific monoclonal antibodies (MABs), and extracorporeal immunoadsorption. The radionuclide has to be selected properly for each purpose; it can be a β-emitter, e.g. I-131, Y-90, Re-188, Re-186, Lu-177 or Sm-153, an α-emitter At-211 or Bi-212 or an Auger-emitter, e.g. I-125, I-123. One major problem with RIT, besides slow penetration rate into tumor tissue and low tumor-to-normal tissue ratio, is the HAMA response, which can be partly avoided by the use of humanized MAbs and immunosuppression. However, RIT will be, because of all the recent developments, an important form of cancer management. (orig.)

  12. Radioimmunotherapy: Development of an effective approach

    International Nuclear Information System (INIS)

    DeNardo, S.J.

    1991-01-01

    We plan to extend our success in treating B cell malignancies with 131 I labeled Lym-1 by a major effort in therapy with 67 Cu Lym-1. Yttrium-90 labeled by a macrocycle, DOTA will be studied in patients as a continuation of the 111 In-BAD (DOTA) Lym-1 studies. Excellent images and pharmacokinetics of the 111 In-BAD(DOTA)-Lym-1 studies. Lymphomas and related diseases represent a special case for radioimmunotherapy because of their documented radiosensitivity and immunodeficiency, and thus offer a unique opportunity to conduct therapeutic feasibility studies in a responsive human model. Using marine and chimeric L6 and other MoAb to breast cancer, we have applied the strategies that were developed in taking Lym-1 antibody from the bench to the patient. We have examined a number of monoclonal antibodies for treatment of breast cancer and chose chimeric L6 for prototype studies because of certain characteristics. The chemistry of attachment of conjugates to antibodies and their impact on immunological targeting biological activities (cytotoxicity), metabolic fate, and therapeutic index will continue to be a major strength and function of this program. This grant has supported the conception, synthesis, and development of the first macrocylic, bifunctional chelating agent TETA (6-p-nitrobenzyl-1,4,8,11-tetraazatetradecane-N,N',N double-prime, N'double-prime-tetraacetic acid and its derivatives, including Lym-1-2IT-BAT), for use in Cu-67-based radioimmunodiagnosis and therapy. This work has led to the further development of several new macrocylic bifunctional chelating agents for copper, indium, yttrium and other metals. In addition, successful Cu-67 labelings of Lym-1-2IT-BAT for human radiopharmaceutical have shown patient pharmacokinetics of 67 Cu-BAT(TETA)-Lym-1 with promising therapeutic dosimetry

  13. Chemotherapy synergizes with radioimmunotherapy targeting La autoantigen in tumors.

    Directory of Open Access Journals (Sweden)

    Fares Al-Ejeh

    Full Text Available To date, inefficient delivery of therapeutic doses of radionuclides to solid tumors limits the clinical utility of radioimmunotherapy. We aim to test the therapeutic utility of Yttrium-90 ((90Y-radio-conjugates of a monoclonal antibody, which we showed previously to bind specifically to the abundant intracellular La ribonucleoprotein revealed in dead tumor cells after DNA-damaging treatment.Immunoconjugates of the DAB4 clone of the La-specific monoclonal antibody, APOMAB, were prepared using the metal chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA, and then radiolabeled with (90Y. Mice bearing established subcutaneous tumors were treated with (90Y-DOTA-DAB4 alone or after chemotherapy. Non-radiosensitizing cyclophosphamide/etoposide chemotherapy was used for the syngeneic EL4 lymphoma model. Radiosensitizing cisplatin/gemcitabine chemotherapy was used for the syngeneic Lewis Lung carcinoma (LL2 model, and for the xenograft models of LNCaP prostatic carcinoma and Panc-1 pancreatic carcinoma. We demonstrate the safety, specificity, and efficacy of (90Y-DOTA-DAB4-radioimmunotherapy alone or combined with chemotherapy. EL4 lymphoma-bearing mice either were cured at higher doses of radioimmunotherapy alone or lower doses of radioimmunotherapy in synergy with chemotherapy. Radioimmunotherapy alone was less effective in chemo- and radio-resistant carcinoma models. However, radioimmunotherapy synergized with radiosensitizing chemotherapy to retard significantly tumor regrowth and so prolong the survival of mice bearing LL2, LNCaP, or Panc-1 subcutaneous tumor implants.We report proof-of-concept data supporting a unique form of radioimmunotherapy, which delivers bystander killing to viable cancer cells after targeting the universal cancer antigen, La, created by DNA-damaging treatment in neighboring dead cancer cells. Subsequently we propose that DAB4-targeted ionizing radiation induces additional cycles of tumor cell death

  14. A comparison between post-operative analgesia after intrathecal nalbuphine with bupivacaine and intrathecal fentanyl with bupivacaine after cesarean section

    Directory of Open Access Journals (Sweden)

    Hala Mostafa Gomaa

    2014-10-01

    Conclusion: Either intrathecal nalbuphine 0.8 mg or intrathecal fentanyl 25 μg combined with 10 mg bupivacaine provides good intra-operative and early post-operative analgesia in cesarean section.

  15. A comparison of intrathecal dexmedetomidine verses intrathecal fentanyl with epidural bupivacaine for combined spinal epidural labor analgesia

    Directory of Open Access Journals (Sweden)

    P K Dilesh

    2014-01-01

    Conclusion: 10 μg dexmedetomidine intrathecally provides a longer duration of analgesia with lesser incidence of pruritus compared to 20 μg fentanyl intrathecally for CSE labor analgesia with comparable neonatal side-effects.

  16. Aneurysm, arachnoiditis and intrathecal Au (gold)

    International Nuclear Information System (INIS)

    Pence, D.M.; Kim, T.H.; Levitt, S.H.

    1990-01-01

    This report is a 20-year follow-up of 14 patients treated with external beam craniospinal irradiation and intrathecal gold (10-45 mCi) for medulloblastoma. Six of the patients died within 2 years of treatment from persistent disease. No patients are alive without complications. Six of eight surviving patients developed arachnoiditis and cauda equina syndrome within 5 to 10 years of treatment. Seven of eight survivors developed aneurysms and/or cerebrovascular accidents 9 to 20 years after treatment. Four of the cerebrovascular events were fatal. Intrathecal gold pools in the basal cisterns and cauda equina delivering an extremely inhomogeneous dose throughout the neuroaxis. Its use is discouraged

  17. Compartmental modeling and tracer kinetics

    CERN Document Server

    Anderson, David H

    1983-01-01

    This monograph is concerned with mathematical aspects of compartmental an­ alysis. In particular, linear models are closely analyzed since they are fully justifiable as an investigative tool in tracer experiments. The objective of the monograph is to bring the reader up to date on some of the current mathematical prob­ lems of interest in compartmental analysis. This is accomplished by reviewing mathematical developments in the literature, especially over the last 10-15 years, and by presenting some new thoughts and directions for future mathematical research. These notes started as a series of lectures that I gave while visiting with the Division of Applied ~1athematics, Brown University, 1979, and have developed in­ to this collection of articles aimed at the reader with a beginning graduate level background in mathematics. The text can be used as a self-paced reading course. With this in mind, exercises have been appropriately placed throughout the notes. As an aid in reading the material, the e~d of a ...

  18. Intrathecal ropivacaine in cesarean delivery | Ateser | Nigerian ...

    African Journals Online (AJOL)

    Objective: The aim of the present study was to evaluate the optimum dose of ropivacaine by comparing three different dosing regimens of isobaric ropivacaine 1% (naropin 10 mg/ml, Astra Zeneca) administered intrathecally and to demonstrate the effects of anesthesia in pregnant women scheduled for cesarean section.

  19. Interest of a treatment combined by radioimmunotherapy and Avastin 1 in a murine model of thyroid medullary carcinoma; Interet d'un traitement combine par radioimmunotherapie et Avastin1 dans un modele murin de carcinome medullaire de la thyroide

    Energy Technology Data Exchange (ETDEWEB)

    Salaun, P.Y.; Bodet-Milin, C.; Paris, F.; Frampas, E.; Sai Maurel, C.; Faivre Chauvet, A.; Barbet, J.; Kraeber Bodere, F. [Unite Inserm U892, Brest, (France)

    2009-05-15

    The objective of this study was to evaluate the efficiency and the toxicity of the association radioimmunotherapy and bevacizumab on a murine model grafted by the human line T.T. of thyroid medullar cancer. After results it appears that in pretreatment, bevacizumab (Avastin) improves the efficiency of radioimmunotherapy without increasing the toxicity face the radioimmunotherapy alone. (N.C.)

  20. Radio-immunotherapy of non Hodgkin lymphomas: Experience from Lille

    International Nuclear Information System (INIS)

    Huglo, D.; Morschhauser, F.; Steinling, M.; Huglo, D.; Prangere, T.; Robu, D.; Malek, E.; Petyt, G.; Steinling, M.; Huglo, D.; Morschhauser, F.; Robu, D.

    2009-01-01

    From an experience of radio-immunotherapy of non Hodgkin lymphomas from March 2002 to December 2008 (near 7 years), corresponding to 160 treatments, an analysis of indications has been done: clinical research trials, authorized indications from A.M.M. or medically justified. Some elements which could be problematic are pointed: coordination between the regional Haematology departments and our Nuclear Medicine department, radio labelling and radioprotection. (authors)

  1. Interest of a treatment combined by radioimmunotherapy and Avastin 1 in a murine model of thyroid medullary carcinoma

    International Nuclear Information System (INIS)

    Salaun, P.Y.; Bodet-Milin, C.; Paris, F.; Frampas, E.; Sai Maurel, C.; Faivre Chauvet, A.; Barbet, J.; Kraeber Bodere, F.

    2009-01-01

    The objective of this study was to evaluate the efficiency and the toxicity of the association radioimmunotherapy and bevacizumab on a murine model grafted by the human line T.T. of thyroid medullar cancer. After results it appears that in pretreatment, bevacizumab (Avastin) improves the efficiency of radioimmunotherapy without increasing the toxicity face the radioimmunotherapy alone. (N.C.)

  2. Protocell design through modular compartmentalization.

    Science.gov (United States)

    Miller, David; Booth, Paula J; Seddon, John M; Templer, Richard H; Law, Robert V; Woscholski, Rudiger; Ces, Oscar; Barter, Laura M C

    2013-10-06

    De novo synthetic biological design has the potential to significantly impact upon applications such as energy generation and nanofabrication. Current designs for constructing organisms from component parts are typically limited in scope, as they utilize a cut-and-paste ideology to create simple stepwise engineered protein-signalling pathways. We propose the addition of a new design element that segregates components into lipid-bound 'proto-organelles', which are interfaced with response elements and housed within a synthetic protocell. This design is inspired by living cells, which utilize multiple types of signalling molecules to facilitate communication between isolated compartments. This paper presents our design and validation of the components required for a simple multi-compartment protocell machine, for coupling a light transducer to a gene expression system. This represents a general design concept for the compartmentalization of different types of artificial cellular machinery and the utilization of non-protein signal molecules for signal transduction.

  3. Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.

    Science.gov (United States)

    de Almeida, Sergio M; Rotta, Indianara; Ribeiro, Clea E; Oliveira, Michelli F; Chaillon, Antoine; de Pereira, Ana Paula; Cunha, Ana Paula; Zonta, Marise; Bents, Joao França; Raboni, Sonia M; Smith, Davey; Letendre, Scott; Ellis, Ronald J

    2017-06-01

    Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

  4. Intrathecal analgesia and palliative care: A case study

    Directory of Open Access Journals (Sweden)

    Naveen S Salins

    2010-01-01

    Full Text Available Intrathecal analgesia is an interventional form of pain relief with definite advantages and multiple complications. Administration of intrathecal analgesia needs a good resource setting and expertise. Early complications of intrathecal analgesia can be very distressing and managing these complications will need a high degree of knowledge, technical expertise and level of experience. Pain control alone cannot be the marker of quality in palliative care. A holistic approach may need to be employed that is more person and family oriented.

  5. Dosimetry in intrathecal radiogold therapy. 2

    International Nuclear Information System (INIS)

    Doege, H.; Hennig, K.

    1978-01-01

    Measurements of 198 Au colloid adsorbed at the surface of the subarachnoid cavities are described. 24 hours after intrathecal administration less than 1% of radiogold is freely moving in the liquor, i.e., more than 99% are adsorbed on the walls of the cavities. Therefore, in calculating the absorbed dose the surface of all anatomic structures forming the boundary of the subarachnoid cavities has to be taken into account. (author)

  6. Histologic examination of the rat central nervous system after intrathecal administration of human beta-endorphin

    DEFF Research Database (Denmark)

    Hée, P.; Klinken, Leif; Ballegaard, Martin

    1992-01-01

    Neuropathology, analgesics - intrathecal, central nervous system, histology, human beta-endorphin, toxicity......Neuropathology, analgesics - intrathecal, central nervous system, histology, human beta-endorphin, toxicity...

  7. Radioimmunotherapy: Opportunities, obstacles and challenges, with special reference to developing countries

    International Nuclear Information System (INIS)

    Divgi, C.

    2001-01-01

    The targeting characteristics of, combined with the ease of radionuclide conjugation to, monoclonal antibodies makes them ideally suited for the selective delivery of potentially cytotoxic radioactivity to tumour. While early murine monoclonal antibodies were immunogenic, precluding repeat administration, genetic engineering has made possible the development of less immunogenic molecules, including fragments that can be grown in bacterial systems at relatively low cost. It is therefore currently feasible to produce relatively non-immunogenic tumour targeting antibody molecules at a reasonable cost, permitting their application in developing countries. As with chemotherapy, the utility of radioimmunotherapy has been most evident in lymphoma and leukemia. Progress in solid tumours has been exciting but slow. As with thyroid cancer therapy, the most utilized radionuclide in radioimmunotherapy has been iodine-131. The use of radioimmunotherapy as first- or second-line therapy in lymphoma and leukemia is being studied, and it appears likely that radioimmunotherapy could be a suitable, lower-cost alternative to chemotherapy in the treatment of these disorders, especially in developing countries. The cost-benefit of radioimmunotherapy compared to chemotherapy is especially stark when the cost of treating complications of chemotherapy is taken into account. Radioimmunotherapy as cost-effective therapy in developing countries is therefore feasible and has tremendous potential. This review will highlight milestones and pitfalls; suggest guidelines for future development; and outline potential clinical utility for radioimmunotherapy in developing countries. (author)

  8. Radiolabeled bivalent haptens for tumor immunodetection and radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Gruaz-Guyon, A.; Janevik-Ivanovska, E.; Raguin, O. [Hopital Saint-Antoine, Faculte' de Medecine, Paris (France); De Labriolle-Vaylet, C. [Hopital Saint-Antoine, Faculte' de Medecine, Paris (France); Hopital Saint-Antoine, Service de Medecine Nucleaire, Paris (France); Barbet, J. [Universite' de la Mediterranee, Faculte' de Medecine, Marseille (France)

    2001-06-01

    The pre targeting technique referred to as the Affinity Enhancement System (AES) uses bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells in vivo. Experimental and clinical data demonstrate that DTPA bivalent haptens can deliver large radiation doses to tumor cells with high tumor to normal tissue contrast ratios and long activity residence time in tumors. Preliminary clinical results of radioimmunotherapy of medullary thyroid carcinomas and lung cancers look promising. Very encouraging results in biodistribution and radioimmunotherapy experiments in animals have been obtained with new haptens bearing two histamine-hemisuccinate suitable for {sup 131}I, {sup 99m}Tc and {sup 188}Re labeling. Targeting isotopes to double antigen positive tumor cells provides a binding enhancement that increases specificity for tumor cells as compared to single antigen targeting on normal cells. This approach may be beneficial for targeting isotopes to B type acute lymphoblastic leukemia and Burkitt lymphoma, as well as others tumors co-expressing two markers of low specificity, and might increase tumor irradiation with minimal irradiation of normal cells.

  9. Radiolabeled bivalent haptens for tumor immunodetection and radioimmunotherapy

    International Nuclear Information System (INIS)

    Gruaz-Guyon, A.; Janevik-Ivanovska, E.; Raguin, O.; De Labriolle-Vaylet, C.; Barbet, J.

    2001-01-01

    The pre targeting technique referred to as the Affinity Enhancement System (AES) uses bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells in vivo. Experimental and clinical data demonstrate that DTPA bivalent haptens can deliver large radiation doses to tumor cells with high tumor to normal tissue contrast ratios and long activity residence time in tumors. Preliminary clinical results of radioimmunotherapy of medullary thyroid carcinomas and lung cancers look promising. Very encouraging results in biodistribution and radioimmunotherapy experiments in animals have been obtained with new haptens bearing two histamine-hemisuccinate suitable for 131 I, 99m Tc and 188 Re labeling. Targeting isotopes to double antigen positive tumor cells provides a binding enhancement that increases specificity for tumor cells as compared to single antigen targeting on normal cells. This approach may be beneficial for targeting isotopes to B type acute lymphoblastic leukemia and Burkitt lymphoma, as well as others tumors co-expressing two markers of low specificity, and might increase tumor irradiation with minimal irradiation of normal cells

  10. A Network Thermodynamic Approach to Compartmental Analysis

    Science.gov (United States)

    Mikulecky, D. C.; Huf, E. G.; Thomas, S. R.

    1979-01-01

    We introduce a general network thermodynamic method for compartmental analysis which uses a compartmental model of sodium flows through frog skin as an illustrative example (Huf and Howell, 1974a). We use network thermodynamics (Mikulecky et al., 1977b) to formulate the problem, and a circuit simulation program (ASTEC 2, SPICE2, or PCAP) for computation. In this way, the compartment concentrations and net fluxes between compartments are readily obtained for a set of experimental conditions involving a square-wave pulse of labeled sodium at the outer surface of the skin. Qualitative features of the influx at the outer surface correlate very well with those observed for the short circuit current under another similar set of conditions by Morel and LeBlanc (1975). In related work, the compartmental model is used as a basis for simulation of the short circuit current and sodium flows simultaneously using a two-port network (Mikulecky et al., 1977a, and Mikulecky et al., A network thermodynamic model for short circuit current transients in frog skin. Manuscript in preparation; Gary-Bobo et al., 1978). The network approach lends itself to computation of classic compartmental problems in a simple manner using circuit simulation programs (Chua and Lin, 1975), and it further extends the compartmental models to more complicated situations involving coupled flows and non-linearities such as concentration dependencies, chemical reaction kinetics, etc. PMID:262387

  11. Compartmentalized storage tank for electrochemical cell system

    Science.gov (United States)

    Piecuch, Benjamin Michael (Inventor); Dalton, Luke Thomas (Inventor)

    2010-01-01

    A compartmentalized storage tank is disclosed. The compartmentalized storage tank includes a housing, a first fluid storage section disposed within the housing, a second fluid storage section disposed within the housing, the first and second fluid storage sections being separated by a movable divider, and a constant force spring. The constant force spring is disposed between the housing and the movable divider to exert a constant force on the movable divider to cause a pressure P1 in the first fluid storage section to be greater than a pressure P2 in the second fluid storage section, thereby defining a pressure differential.

  12. Radioimmunotherapy: Development of an effective approach. Progress report, 1987

    Energy Technology Data Exchange (ETDEWEB)

    1987-12-31

    Goals of this program are to answer the fundamental scientific questions for the development of an effective approach for delivering radiation therapy to cancer on antibody-based radiopharmaceuticals. The following list consists of highlights of developments from our program: documented therapeutic response of lymphoma in patients receiving radioimmunotherapy; development and application of quantitative radionuclide imaging techniques for therapy planning and dosimetry calculations; multicompartmental modeling and analysis of the in vivo MoAb kinetics in patients; a MoAb macrocycle chelate for Cu-67: development, production, in vitro and in vivo testing; NMR analysis of immunoradiotherapeutic effects on the metabolism of lymphoma; analysis of the variable molecular characteristics of the MoAb radiopharmaceutical, and their significance; in vivo studies in mice and patients of the metabolism of radioiodinated MoAb as well as In-111 CITC MoAb; and biodistribution of Cu-67 TETA MoAb in nude mice with human lymphoma.

  13. Criteria for the selection of nuclides for radioimmunotherapy

    International Nuclear Information System (INIS)

    Adelstein, S.J.; Kassis, A.I.

    1986-01-01

    This report describes many factors that need to be considered if radioimmunotherapy is to become a commonplace reality. For beta-emitting radionuclides, two physical features of importance are half-life and energy, with the latter determining the range. These features must be matched to the pharmacokinetics of the carrier and the distribution of the radionuclide, both macroscopically and microscopically. Alpha-particle emitters could be considered for cells that are readily accessible to the labeled antibody and for populations that uniformly and constantly display the targeted antigen or idiotype, e.g., trafficking cells such as T or B lymphocytes. For cells that concentrate the radioactive label, the use of low-energy electrons should be examined. If the radionuclide is translocated to the nucleus, the Auger effect can be particularly lethal because of the high LET-like biological response. 15 refs., 3 figs., 2 tabs

  14. Criteria for the selection of radionuclides for tumor radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.; Mausner, L.F.; Mease, R.C.

    1991-01-01

    The potential of utilizing monoclonal antibodies as carriers of radionuclides for the selective destruction of tumors (radioimmunotherapy, RIT) has stimulated much research activity. From dosimetric and other considerations, the choice of radiolabel is an important factor that needs to be optimized for maximum effectiveness of RIT. This paper reviews and assesses a number of present and future radionuclides that are particularly suitable for RIT based on the various physical, chemical, and biological considerations. Intermediate to high-energy beta emitters' (with and without gamma photons in their emission) are emphasized since they possess a number of advantages over alpha and Auger emitters. Factors relating to the production and availability of candidate radiometals as well as their stable chemical attachment to monoclonal antibodies are discussed. 34 refs., 4 tabs.

  15. Radioimmunotherapy for malignant diseases. Current contributions and future options

    International Nuclear Information System (INIS)

    Mahe, M.A.; Chatal, J.F.

    1995-01-01

    Radioimmunotherapy is based on the use of radioactive agents (iodine 131, yttrium 90), murine-derived monoclonal antibodies and specific tumour-related membrane antigens. This new treatment modality was applied in 800 patients with different types of malignant tumours which had not responded to traditional therapy. Among the haematologic tumours, the most promising results were obtained in B phenotype non-Hodgkin lymphoma. More modest results were obtained for solid tumours although good results were observed after intraperitoneal administration in patients with cancer of the ovary. The main side effects are acute reversible anaphylactic shock, haematologic toxicity and development of anti-murine human antibodies. Several methods are currently under study to increase irradiation dose delivered at the tumoural site since less than 1% of the injected radioactive dose is absorbed by tumoural cells. Several clinical studies are to be conducted in France, particularly for malignant non-Hodgkin lymphoma and cancer of the ovary. (authors). 31 refs

  16. Monoclonal Antibodies Radiolabeling with Rhenium-188 for Radioimmunotherapy

    Science.gov (United States)

    Martini, Petra; Pasquali, Micol

    2017-01-01

    Rhenium-188, obtained from an alumina-based tungsten-188/rhenium-188 generator, is actually considered a useful candidate for labeling biomolecules such as antibodies, antibody fragments, peptides, and DNAs for radiotherapy. There is a widespread interest in the availability of labeling procedures that allow obtaining 188Re-labeled radiopharmaceuticals for various therapeutic applications, in particular for the rhenium attachment to tumor-specific monoclonal antibodies (Mo)Abs for immunotherapy. Different approaches have been developed in order to obtain 188Re-radioimmunoconjugates in high radiochemical purity starting from the generator eluted [188Re]ReO4−. The aim of this paper is to provide a short overview on 188Re-labeled (Mo)Abs, focusing in particular on the radiolabeling methods, quality control of radioimmunoconjugates, and their in vitro stability for radioimmunotherapy (RIT), with particular reference to the most important contributions published in literature in this topic. PMID:28951872

  17. 177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

    Science.gov (United States)

    Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Alonso, Omar; Chammas, Roger; Riva, Eloisa; Gambini, Juan Pablo; Cabral, Pablo

    2017-01-01

    Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Practical aspects of the use of intrathecal chemotherapy

    OpenAIRE

    Olmos-Jiménez, Raquel; Espuny-Miró, Alberto; Cárceles-Rodríguez, Carlos; Díaz-Carrasco, María Sacramento

    2017-01-01

    Abstract Introduction: Intrathecal chemotherapy is frequently used in clinical practice for treatment and prevention of neoplastic meningitis. Despite its widespread use, there is little information about practical aspects such as the volume of drug to be administered or its preparation and administration. Objective: To conduct a literature review about practical aspects of the use of intrathecal chemotherapy. Materials: Search in PubMed/ Medline using the terms “chemotherapy AND intrat...

  19. Comparison of radioimmunotherapy and external beam radiotherapy in colon cancer xenografts

    International Nuclear Information System (INIS)

    Buras, R.R.; Wong, J.F.C.; Kuhn, J.A.; Beatty, B.G.; Williams, L.E.; Beatty, J.D.; Wanek, P.M.

    1993-01-01

    Radioimmunotherapy and external beam radiotherapy were compared in a nude mouse human colon cancer model. Radioimmunotherapy was delivered by intraperitoneal injection of 90 Y-labeled anticarcinoembryonic antigen monoclonal antibody (anti-CEA MAB). Single fraction external beam radiotherapy was delivered using a 60 Co teletherapy unit. Control groups received saline, unlabeled anit-CEA monoclonal antibody and labeled nonspecific monoclonal antibody. Tumor growth suppression was expressed as delay to reach 2g compared to saline controls. Unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody had no effect. External beam radiotherapy of 300, 600, 1000 and 2000 cGy produced growth delays of 3, 12, 17, and 22 days, respectively. Radioimmunotherapy with 120 μCi, 175 μCi, and 225 μCi resulted in growth delays of 20, 34, and 36 days. Estimated absorbed tumor dose was 1750 cGy in the 120 μCi group. Similar comparisons were done with the more radioresistant WiDr human colon carcinoma cell line. External beam radiotherapy doses of 400, 800, 1200, and 1600 cGy resulted in growth delays of 6, 21, 36 and 48 days, respectively. Radioimmunotherapy of 120 μCi and 175 μCi resulted in growth delays of 9 and 19 days, respectively. The 120 μCi dose delivered an estimated absorbed tumor dose of 1080 cGy to WiDr tumors. In summary, for the radiosensitive LS174T line, radioimmunotherapy produced biologic effects that were comparable to a similar dose of single fraction external beam radiotherapy. For the more radioresistant WiDr tumor, radioimmunotherapy produced a biologic effect which was less than a similar dose of single fraction external beam radiotherapy. These studies suggest that a tumor's response to radioimmunotherapy relative to that of external beam radiotherapy is, in part, dependent on tumor radiosensitivity and repair capacity. 23 refs., 5 figs. 4 tabs

  20. Repeated Intraperitoneal alpha-Radioimmunotherapy of Ovarian Cancer in Mice

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Jensen, Holger

    2010-01-01

    The aim of this study was to investigate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice using different fractionated treatment regimens. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. Methods....... Nude mice were intraperitoneally inoculated with ~1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later 6 groups of animals were given 400 kBq (211)At-MX35 F(ab')(2) as a single or as a repeated treatment of up to 6 times (n = 18 in each group). The fractionated treatments were given every...... seventh day. Control animals were treated with unlabeled MX35 F(ab')(2) (n = 12). Eight weeks posttreatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Results. The tumor-free fractions (TFFs) of the animals, defined as the fraction of animals...

  1. Dosimetric considerations in radioimmunotherapy of patients with hepatoma

    International Nuclear Information System (INIS)

    Leichner, P.K.; Klein, J.L.; Order, S.E.

    1986-01-01

    Dosimetric studies of I-131 labeled antiferritin have provided the foundation for preparative and administrative aspects of radiolabeled antibody treatment of patients with hepatoma. Tumor response to I-131 labeled antiferritin IgG was encouraging and radioimmunotherapy with Y-90 labeled antiferritin IgG was recently initiated. For these patients, In-111 labeled antiferritin IgG was used as the imaging agent, with administered activities ranging from 0.8 - 7 mCi. Serial gamma camera imaging from 30 minutes to 6 days post injection demonstrated that 5-30% of the administered activity localized in hepatomas (8/12 patients). The mean value of the effective half-life in the tumor and liver was 2.8 d. Disappearance curves for the blood circulation, spleen, and other normal tissues were biphasic such that 50% of the activity disappeared within 24 hours post injection. The eight patients who demonstrated sufficient tumor localization where subsequently treated with Y-90 labeled antiferritin IgG. Administered activities were dependent on tumor volume and uptake of radiolabeled IgG and ranged from 8 - 20 mCi. The remaining patients were treated under other existing protocols. 10 references

  2. Radioimmunotherapy. Dose calculation and radionuclides used in treatment

    International Nuclear Information System (INIS)

    Savolainen, S.

    1995-10-01

    In radioimmunotherapy (RIT) monoclonal antibodies to cancer-associated antigens can be utilized for the transport of therapeutic radioisotopes to cancer cells. Intravenous administration of radiolabelled antibody is a potentially curative form of therapy in hematological amignancies as circulating antibodies have easy access to tumour sites. Intravenous RIT is less effective in the treatment of solid tumours because of the low fractional uptake of the injected dose, particularly in the central parts of tumours. In solid tumours more promising results have been achieved by local RIT applications. The choice of radiation - α, β or γ - will depend of the characteristics of the tumour. The importance of radiation delivered by Auger electrons has been largely underestimated in the past, but recent research has resulted in a remarkable reassessment of this issue significantly influencing the selection of radioisotopes for RIT. Research is now being focused on the therapeutic aspects of different isotopes and microdosimetric problems. There are now good prospects of RIT becoming an important form of cancer treatment before year 2000. (orig.) (78 refs., 3 figs., 1 tab.)

  3. Secondary antibodies as tools to improve tumor to non tumor ratio at radioimmunolocalisation and radioimmunotherapy

    International Nuclear Information System (INIS)

    Ullen, A.; Riklund Aalstroem, K.; Hietala, S.O.; Nilsson, B.; Aerlestig, L.; Stigbrand, T.

    1996-01-01

    One way of selectively improving the efficiency of radioimmunolocalization and radioimmunotherapy is to eliminate redundant, circulating, non-targeting radiolabeled antibodies after saturation of the target sites. Secondary antibodies of different types have been proposed as clearing agents for such purposes. The conceptually different approaches of the 'secondary antibody' strategy including its advantages and limitations are discussed. This mini-review also presents a model describing the kinetics of the components (the antigen, the primary and secondary antibodies) and approaches required to improve the efficacy of both radioimmunolocalization and radioimmunotherapy. (orig.)

  4. Calculation of dose point kernels for five radionuclides used in radio-immunotherapy

    International Nuclear Information System (INIS)

    Okigaki, S.; Ito, A.; Uchida, I.; Tomaru, T.

    1994-01-01

    With the recent interest in radioimmunotherapy, attention has been given to calculation of dose distribution from beta rays and monoenergetic electrons in tissue. Dose distribution around a point source of a beta ray emitting radioisotope is referred to as a beta dose point kernel. Beta dose point kernels for five radionuclides such as 131 I, 186 Re, 32 P, 188 Re, and 90 Y appropriate for radioimmunotherapy are calculated by Monte Carlo method using the EGS4 code system. Present results were compared with the published data of experiments and other calculations. Accuracy and precisions of beta dose point kernels are discussed. (author)

  5. Advanced compositional gradient and compartmentalization analysis

    Energy Technology Data Exchange (ETDEWEB)

    Canas, Jesus A.; Petti, Daniela; Mullins, Oliver [Schlumberger Servicos de Petroleo Ltda., Rio de Janeiro, RJ (Brazil)

    2008-07-01

    Acquisition of hydrocarbons samples from the reservoir prior to oil or gas production is essential in order to design production strategies and production facilities. In addition, reservoir compartmentalization and hydrocarbon compositional grading magnify the necessity to map fluid properties vertically and laterally in the reservoir prior to production. Formation testers supply a wealth of information to observe and predict the state of fluids in hydrocarbon reservoirs, through detailed pressure and fluid analysis measurements. With the correct understanding of the state of fluids in the reservoirs, reserve calculations and adequate development plans can be prepared. Additionally, flow barriers may then be revealed. This paper describes a new Downhole Fluid Analysis technology (DFA) for improved reservoir management. DFA is a unique process that combines new fluid identification sensors, which allow real time monitoring of a wide range of parameters as GOR, fluid density, viscosity, fluorescence and composition (CH{sub 4}, C2- C5, C6 +, CO{sub 2}), free gas and liquid phases detection, saturation pressure, as well WBM and OBM filtrate differentiation and pH. This process is not limited to light fluid evaluation and we extended to heavy oil (HO) reservoirs analysis successfully. The combination of DFA Fluid Profiling with pressure measurements has shown to be very effective for compartmentalization characterization. The ability of thin barriers to hold off large depletion pressures has been established, as the gradual variation of hydrocarbon quality in biodegraded oils. In addition, heavy oils can show large compositional variation due to variations in source rock charging but without fluid mixing. Our findings indicates that steep gradients are common in gas condensates or volatile oils, and that biodegradation is more common in HO than in other hydrocarbons, which generate fluid gradients and heavy ends tars near the OWC, limiting the aquifer activity and

  6. Intrathecal chemotherapy for refractory disseminated medulloblastoma.

    Science.gov (United States)

    Yoshimura, Junichi; Nishiyama, Kenichi; Mori, Hiroshi; Takahashi, Hideaki; Fujii, Yukihiko

    2008-05-01

    To analyze the effect of intrathecal (IT) chemotherapy for disseminated medulloblastoma. Twenty-one patients received IT chemotherapy using the chemotherapeutic agents of methotrexate (MTX) and nitrosoureas (ACNU, MCNU) including nine patients for residual leptomeningeal lesions after initial surgery and radiation, and 12 for a recurrence with leptomeningeal dissemination. Of these 21 patients, 12 received a lumbar and/or ventricular bolus injection of the chemotherapeutic agents, one received the ventriculolumbar perfusion of the agents, and eight received both the perfusion and bolus injection. The doses ranged from 6-7 mg/m(2) of ACNU for perfusion and 3-3.5 mg/m(2) of ACNU, MCNU, or MTX for the bolus injection, and the cycles were administered from 3 to 12 times for perfusion and from 5 to 54 times for the bolus injection. The effects of chemotherapy were assessed by both radiological and cytological examinations, and the clinical symptoms were also assessed. Radiological and/or cytological responses were observed in 10 of 21 patients (47.6%), including seven cases demonstrating a complete remission. The 5-year overall survival rate and 5-year survival rate after dissemination were 61.5 and 46.4%, respectively. Five patients who received a lumbar bolus injection of nitrosoureas experienced paraplegia and double incontinence. One patient who received a ventricular injection of nitrosoureas experienced truncal ataxia. IT chemotherapy was found to be effective in some cases with refractory disseminated medulloblastoma and it seems to be an appropriate treatment choice for leptomeningeal recurrence. However, the frequent bolus injections of nitrosoureas should be avoided to prevent the side effects.

  7. Radioimmunotherapy of B-cell non-Hodgkin’s lymphoma

    Directory of Open Access Journals (Sweden)

    Caroline eBodet-Milin

    2013-07-01

    Full Text Available This manuscript reviews current advances in the use of radioimmunotherapy (RIT for the treatment of B-cell non-Hodgkin’s lymphoma (NHL. RIT has been in use for more than 20 years and has progressed significantly with the discovery of new molecular targets, the development of new stable chelates, the humanization of monoclonal antibodies (MAbs, and the use of pretargeting techniques. Today, two products targeting the CD20 antigen are approved: 131I-tositumomab, (Bexxar® and 90Y-ibritumomab tiuxetan, (Zevalin®. 131I-tositumomab is available in the United States, and 90Y-ibritumumab tiuxetan in Europe, the United States, Asia, and Africa. RIT can be integrated in clinical practice using non-ablative activities for treatment of patients with relapsed or refractory follicular lymphoma (FL or as consolidation after induction chemotherapy in front-line treatment in FL patients. Despite the lack of phase III studies to clearly define the efficacy of RIT in the management of B lymphoma in the era of rituximab-based therapy, RIT efficacy in NHL has been demonstrated. In relapsing refractory FL and transformed NHL, RIT as a monotherapy induces around 30% complete response with a possibility of durable remissions. RIT consolidation after induction therapy significantly improves the quality of the response. Dose-limiting toxicity of RIT is hematological, depending on bone marrow involvement and prior treatment. Non-hematological toxicity is generally low. Different studies have been published assessing innovative protocols of RIT or new indications, in particular treatment in patients with aggressive lymphomas. High-dose treatment, RIT as consolidation after different therapeutic induction modalities, RIT in first-line treatment or fractionated RIT showed promising results. New MAbs, in particular humanized MAbs, or combinations of naked and radiolabeled MAbs, also appear promising. Personalized dosimetry protocols should be developed to determine

  8. Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

    International Nuclear Information System (INIS)

    Jandl, Thomas; Revskaya, Ekaterina; Jiang, Zewei; Harris, Matthew; Dorokhova, Olena; Tsukrov, Dina; Casadevall, Arturo; Dadachova, Ekaterina

    2013-01-01

    Introduction: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium( 188 Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. Methods: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi 188 Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188 Re-labeled non-specific IgM. Results: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. Conclusions: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers

  9. Combination radioimmunotherapy approaches and quantification of immuno-PET

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2016-06-15

    Monoclonal antibodies (mAbs), which play a prominent role in cancer therapy, can interact with specific antigens on cancer cells, thereby enhancing the patient' immune response via various mechanisms, or mAbs can act against cell growth factors and, thereby, arrest the proliferation of tumor cells. Radionuclide-labeled mAbs, which are used in radioimmunotherapy (RIT), are effective for cancer treatment because tumor associated-mAbs linked to cytotoxic radionuclides can selectively bind to tumor antigens and release targeted cytotoxic radiation. Immunological positron emission tomography (immuno-PET), which is the combination of PET with mAb, is an attractive option for improving tumor detection and mAb quantification. However, RIT remains a challenge because of the limited delivery of mAb into tumors. The transport and uptake of mAb into tumors is slow and heterogeneous. The tumor microenvironment contributed to the limited delivery of the mAb. During the delivery process of mAb to tumor, mechanical drug resistance such as collagen distribution or physiological drug resistance such as high intestinal pressure or absence of lymphatic vessel would be the limited factor of mAb delivery to the tumor at a potentially lethal mAb concentration. When α-emitter-labeled mAbs were used, deeper penetration of α-emitter-labeled mAb inside tumors was more important because of the short range of the α emitter. Therefore, combination therapy strategies aimed at improving mAb tumor penetration and accumulation would be beneficial for maximizing their therapeutic efficacy against solid tumors.

  10. A pretargeting system for tumor PET imaging and radioimmunotherapy

    Directory of Open Access Journals (Sweden)

    Françoise eKraeber-Bodéré

    2015-03-01

    Full Text Available Labeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed.

  11. Compartmentation of redox metabolism in malaria parasites.

    Directory of Open Access Journals (Sweden)

    Sebastian Kehr

    Full Text Available Malaria, caused by the apicomplexan parasite Plasmodium, still represents a major threat to human health and welfare and leads to about one million human deaths annually. Plasmodium is a rapidly multiplying unicellular organism undergoing a complex developmental cycle in man and mosquito - a life style that requires rapid adaptation to various environments. In order to deal with high fluxes of reactive oxygen species and maintain redox regulatory processes and pathogenicity, Plasmodium depends upon an adequate redox balance. By systematically studying the subcellular localization of the major antioxidant and redox regulatory proteins, we obtained the first complete map of redox compartmentation in Plasmodium falciparum. We demonstrate the targeting of two plasmodial peroxiredoxins and a putative glyoxalase system to the apicoplast, a non-photosynthetic plastid. We furthermore obtained a complete picture of the compartmentation of thioredoxin- and glutaredoxin-like proteins. Notably, for the two major antioxidant redox-enzymes--glutathione reductase and thioredoxin reductase--Plasmodium makes use of alternative-translation-initiation (ATI to achieve differential targeting. Dual localization of proteins effected by ATI is likely to occur also in other Apicomplexa and might open new avenues for therapeutic intervention.

  12. Biodistribution of Idursulfase Formulated for Intrathecal Use (Idursulfase-IT in Cynomolgus Monkeys after Intrathecal Lumbar Administration.

    Directory of Open Access Journals (Sweden)

    Jou-Ku Chung

    Full Text Available Enzyme replacement therapy with intravenous idursulfase (recombinant iduronate-2-sulfatase is approved for the treatment of Hunter syndrome. Intravenous administration does not, however, treat the neurological manifestations, due to its low central nervous system bioavailability. Using intrathecal-lumbar administration, iduronate-2-sulfatase is delivered directly to the central nervous system. This study investigates the central nervous system biodistribution of intrathecal-lumbar administered iduronate-2-sulfatase in cynomolgus monkeys. Twelve monkeys were administered iduronate-2-sulfatase in one 30 mg intrathecal-lumbar injection. Brain, spinal cord, liver, and kidneys were collected for iduronate-2-sulfatase concentration (measured by an enzyme linked immunosorbent assay and enzyme activity measurement (via a method utilizing 4-methylumbelliferyl-α-iduronate-2-sulfate at 1, 2, 5, 12, 24, and 48 hours following administration. The tissue enzyme linked immunosorbent assay confirmed iduronate-2-sulfatase uptake to the brain, spinal cord, kidneys, and liver in a time-dependent manner. In spinal cord and brain, iduronate-2-sulfatase appeared as early as 1 hour following administration, and peak concentrations were observed at ~2 and ~5 hours. Iduronate-2-sulfatase appeared in liver and kidneys 1 hour post intrathecal-lumbar dose with peak concentrations between 5 and 24 hours. Liver iduronate-2-sulfatase concentration was approximately 10-fold higher than kidney. The iduronate-2-sulfatase localization and enzyme activity in the central nervous system, following intrathecal administration, demonstrates that intrathecal-lumbar treatment with iduronate-2-sulfatase may be considered for further investigation as a treatment for Hunter syndrome patients with neurocognitive impairment.

  13. Intentional intrathecal opioid detoxification in 3 patients: characterization of the intrathecal opioid withdrawal syndrome.

    Science.gov (United States)

    Jackson, Tracy P; Lonergan, Daniel F; Todd, R David; Martin, Peter R

    2013-04-01

    Intrathecal (IT) drug delivery systems for patients with chronic non-malignant pain are intended to improve pain and quality of life and reduce side effects of systemic use. A subset of patients may have escalating pain, functional decline, and/or intolerable side effects even as IT opioid doses are increased. Discontinuation of IT medications may represent a viable treatment option but strategies to accomplish this are needed. Three patients with intrathecal drug delivery systems (IDDS), inadequate pain control, and declining functionality underwent abrupt IT opioid cessation. This was accomplished through a standardized protocol with symptom-triggered administration of clonidine and buprenorphine, monitored using the clinical opiate withdrawal scale. Symptoms of IT withdrawal were similar in all patients and included diuresis, agitation, hyperalgesia, mild diarrhea, yawning, and taste and smell aversion. Hypertension and tachycardia were effectively controlled by clonidine administration. Classic symptoms of withdrawal, such as piloerection, chills, severe diarrhea, nausea, vomiting, diaphoresis, myoclonus, and mydriasis, were not noted. At 2 to 3 months follow-up, patients reported decreased, but ongoing pain, with improvements in functional capacity and quality of life. This preliminary work demonstrates the safety of abrupt IT opioid cessation utilizing standardized inpatient withdrawal protocols. To our knowledge, these are among the first reported cases of intentional, controlled IT opioid cessation without initiation of an opioid bridge: self-reported pain scores, functional capacity, and quality of life improved. The IT opioid withdrawal syndrome is characterized based upon our observations and a review of the literature. © 2012 The Authors. Pain Practice © 2012 World Institute of Pain.

  14. Cure of human ovarian carcinoma solid xenografts by fractionated [211At] alpha-radioimmunotherapy

    DEFF Research Database (Denmark)

    Bäck, Tom A; Chouin, Nicolas; Lindegren, Sture

    2017-01-01

    The goal of this study was to investigate if targeted alpha therapy (TAT) could be used to successfully treat also macro tumors, in addition to its established role for treating micrometastatic and minimal disease. We used an intravenous (i.v.) fractionated regimen of alpha-radioimmunotherapy (α-...

  15. Dosimetry and quantitative radionuclide imaging in radioimmunotherapy: Final report, July 15, 1992-July 14, 1996

    International Nuclear Information System (INIS)

    Leichner, P.K.

    1996-09-01

    Brief summaries of the principal accomplishments of this project on the development of quantitative SPECT for high energy photons (87Y, 19F) and stability testing of 87Y-labeled antibodies in the nude mouse model, development of an unified approach to photon and beta particle dosimetry, quantitative SPECT for nonuniform attenuation, and development of patient-specific dosimetry in radioimmunotherapy

  16. Labour analgesia with intrathecal fentanyl decreases maternal stress.

    Science.gov (United States)

    Cascio, M; Pygon, B; Bernett, C; Ramanathan, S

    1997-06-01

    Lumbar epidural analgesia (LEA) decreases maternal stress as measured by maternal circulating plasma catecholamine concentrations. Intrathecal fentanyl (ITF) provides effective labour analgesia but its effect on maternal epinephrine (Epi) and norepinephrine (NE) concentrations is not known. This study assesses whether ITF reduces maternal stress in the same manner as conventional LEA. Twenty-four healthy women in active labour received either 25 micrograms ITF (n = 12) or epidural lidocaine 1.5% (n = 12) for analgesia. Venous blood samples were collected before anaesthesia and at five minute intervals for 30 min following anaesthesia for the measurement of plasma Epi and NE by high performance liquid chromatography. Maternal blood pressure (BP), heart rate (HR), visual analog scores (VAS) to pain and pruritus were recorded at the same time. Both ITF and LEA decreased pain VAS scores, maternal BP, and plasma Epi concentrations with only minimal effects on plasma NE concentrations. Intrathecal fentanyl (ITF) and LEA reduced plasma epi to a similar extent, with ITF reducing the levels slightly faster than LEA. Intrathecal fentanyl(ITF) and LEA reduced plasma Epi concentrations by 52% and 51%, respectively (P value < 0.01). We conclude that ITF is as effective as LEA in producing pain relief in the labouring patient. Intrathecal Fentanyl (ITF) is also capable of reducing maternal plasma epinephrine concentration, thus avoiding the possibly deleterious side effects of excess amounts of this catecholamine during labour.

  17. The effect of intrathecal midazolam on the characteristics of ...

    African Journals Online (AJOL)

    Objectives: The present study was undertaken to determine the onset of sensory block, the time to achieve the maximum level of sensory block and the analgesic efficacy of intrathecal midazolam when given in combination with bupivacaine, and also to observe any undesirable side-effects produced by the ...

  18. Efficacy of intrathecal midazolam versus fentanyl for endoscopic

    African Journals Online (AJOL)

    intrathecal midazolam versus fentanyl as an adjunct to bupivacaine for endoscopic urology surgery. Methods: Sixty adult ASA grade I–II patients undergoing transurethral resection of prostate or bladder tumor under spinal block. Postoperative analgesia was provided with intravenous diclofenac. The onset and duration of ...

  19. Italian multicentre study on intrathecal fluorescein for craniosinusal fistulae.

    Science.gov (United States)

    Felisati, G; Bianchi, A; Lozza, P; Portaleone, S

    2008-08-01

    Cerebrospinal fluid leak (CSF), clinical sign of a dural lesion of the skull base, is a relatively rare event that can present with a variety of symptoms. Every craniosinus fistula should be considered a serious, potentially life-threatening situation (even those cases with hidden CSF leak). Reports of experience concerning diagnosis and treatment of craniosinus fistulae have appeared in the Literature. In the last few years, the endoscopic nasal approach is proving effective as it makes diagnosis much easier and is the least invasive surgical approach, with the greatest percentage of success. Various classifications are being proposed to improve clinical evaluation of CSF leaks and to simplify the diagnostic and therapeutic approach. The most common parameters of classification are: aetiology (traumatic, iatrogenic, non-traumatic, etc.) site, type of flow (high or low pressure) and, as far as concerns treatment, the type of graft used, all of which have contributed to various diagnostic and therapeutic algorithms being proposed. Therefore, the subject seems to be widely schematized and the therapeutic attitude widely agreed. However, one of the diagnostic and therapeutic approaches is now being questioned. For some, it is the heart of the clinical approach, while for others, it is a useful tool yet too dangerous to be used on account of potential side effects: namely, the fluorescein test. This procedure, consisting of intrathecal injection of a colorant (fluorescein), is well known by the Food and Drug Administration (FDA) which neither explicitly prohibits it, nor allows it, intrathecal administration is, therefore, an off label use. As far as the Authors know, authorization of this procedure has not been forthcoming anywhere in the world although the procedure itself is widely employed. As far as concerns the use of intrathecal fluorescein, many scientific papers have been written, clearly supporting its clinical usefulness. One limit to the use of fluorescein

  20. Passive Noise Filtering by Cellular Compartmentalization.

    Science.gov (United States)

    Stoeger, Thomas; Battich, Nico; Pelkmans, Lucas

    2016-03-10

    Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Intrathecal catheter-syringe adaptor for short-term intrathecal analgesia with an externalized pump: a case report.

    Science.gov (United States)

    Wilkes, Denise; Cook, Michael; Solanki, Daneshvari

    2010-01-01

    In most patients, cancer pain is effectively treated with conservative medical management consisting of oral and/or transdermal analgesics. Cancer patients tend to fail conservative medical management near the end of their life expectancy, thus requiring alternative routes of analgesia such as intravenous, epidural, or intrathecal. The intrathecal route provides the most effective analgesia due to the close proximity of the opioid receptors in the spinal cord. Though there are many techniques that exist for intrathecal drug delivery, complications can limit effectiveness such as infection, bleeding, cerebrospinal fluid (CSF) leaks, post-dural puncture headaches (PDPH), pump and/or catheter malfunctions, or limitations of technical expertise. Therefore, an important goal in palliative cancer pain therapy is to use equipment that is going to have the fewest number of complications and will be the most familiar to the health care providers. We describe the combination of the Medtronic Indura 1P catheter, which has the least catheter-related complications and can be used with any external drug infusion pump. These are regular infusion pumps that the health care workers are familiar with so they can provide excellent and efficient service to the patient. In an operating room, the intrathecal catheter was placed using sterile technique under fluoroscopic guidance. The epidural space was identified with loss of resistance technique. Then the introducer needle (supplied in the Indura 1P catheter kit) was advanced until free-flowing CSF was obtained. The spinal catheter was advanced into the intrathecal space through the introducer needle to lumbar 2-3 level. The catheter was tunneled subcutaneously 10 cm lateral to the catheter exit site. A syringe filling device was inserted into the catheter opening and was secured with silk suture. A luer lock syringe was attached to the syringe filling device and CSF was aspirated. The syringe filling device was capped and later

  2. Field Testing of Compartmentalization Methods for Multifamily Construction

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, K. [Building Science Corporation, Westford, MA (United States); Lstiburek, J. W. [Building Science Corporation, Westford, MA (United States)

    2015-03-01

    The 2012 International Energy Conservation Code (IECC) has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure (3 ACH50) for single-family and multifamily construction (in climate zones 3–8). The Leadership in Energy & Environmental Design certification program and ASHRAE Standard 189 have comparable compartmentalization requirements. ASHRAE Standard 62.2 will soon be responsible for all multifamily ventilation requirements (low rise and high rise); it has an exceptionally stringent compartmentalization requirement. These code and program requirements are driving the need for easier and more effective methods of compartmentalization in multifamily buildings.

  3. Intrathecal baclofen pump for spasticity: an evidence-based analysis.

    Science.gov (United States)

    2005-01-01

    To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of intrathecal baclofen for spasticity. Spasticity is a motor disorder characterized by tight or stiff muscles that may interfere with voluntary muscle movements and is a problem for many patients with multiple sclerosis (MS), spinal cord injury (SCI), cerebral palsy (CP), and acquired brain injury (ABI).(1). Increased tone and spasm reduces mobility and independence, and interferes with activities of daily living, continence and sleep patterns. Spasticity may also be associated with significant pain or discomfort (e.g., due to poor fit in braces, footwear, or wheelchairs), skin breakdown, contractures, sleep disorders and difficulty in transfer. Goals of treatment are to decrease spasticity in order to improve range of motion, facilitate movement, reduce energy expenditure and reduce risk of contractures. Existing treatments include physical therapy, oral medications, injections of phenol or botulinum toxin, or surgical intervention. Baclofen is the oral drug most frequently prescribed for spasticity in cases of SCI and MS.(1) Baclofen is a muscle relaxant and antispasticity drug. In the brain, baclofen delivered orally has some supraspinal activity that may contribute to clinical side effects. The main adverse effects of oral baclofen include sedation, excessive weakness, dizziness, mental confusion, and somnolence.(2) The incidence of adverse effects is reported to range from 10% to 75%.(2) Ochs et al. estimated that approximately 25-30% of SCI and MS patients fail to respond to oral baclofen.(3;4) Adverse effects appear to be dose-related and may be minimized by initiating treatment at a low dose and gradually titrating upwards.(2) Adverse effects usually appear at doses >60 mg/day.(2) The rate of treatment discontinuation due to intolerable adverse effects has generally been reported to range from 4% to 27%.(2) When baclofen is administered orally, only a small portion of the

  4. Combined spinal epidural analgesia for labor using sufentanil epidurally versus intrathecally: a retrospective study on the influence on fetal heart trace

    NARCIS (Netherlands)

    Everaert, Nele; Coppens, Marc; Vlerick, Peter; Braems, Geert; Wouters, Patrick; de Hert, Stefan

    2015-01-01

    Objective: We retrospectively compared a protocol using sufentanil and ropivacaine intrathecally with a protocol in which only ropivacaine was administered intrathecally and sufentanil was used epidurally to evaluate whether banning sufentanil from the intrathecal space results in a decreased

  5. Compartmentalization of Aquaporins in the Human Intestine

    Directory of Open Access Journals (Sweden)

    Rajendram V. Rajnarayanan

    2008-06-01

    Full Text Available Improper localization of water channel proteins called aquaporins (AQP induce mucosal injury which is implicated in Crohn’s disease and ulcerative colitis. The amino acid sequences of AQP3 and AQP10 are 79% similar and belong to the mammalian aquaglyceroporin subfamily. AQP10 is localized on the apical compartment of the intestinal epithelium called the glycocalyx while AQP3 is selectively targeted to the basolateral membrane. Despite the high sequence similarity and evolutionary relatedness, the molecular mechanism involved in the polarity, selective targeting and function of AQP3 and AQP10 in the intestine is largely unknown. Our hypothesis is that the differential polarity and selective targeting of AQP3 and AQP10 in the intestinal epithelial cells is influenced by amino acid signal motifs. We performed sequence and structural alignments to determine differences in signals for localization and posttranslational glycosylation. The basolateral sorting motif “YRLL” is present in AQP3 but absent in AQP10; while Nglycosylation signals are present in AQP10 but absent in AQP3. Furthermore, the C-terminal region of AQP3 is longer compared to AQP10. The sequence and structural differences between AQP3 and AQP10 provide insights into the differential compartmentalization and function of these two aquaporins commonly expressed in human intestines.

  6. Compartmentalization and Transport in Synthetic Vesicles

    Directory of Open Access Journals (Sweden)

    Christine eSchmitt

    2016-02-01

    Full Text Available Nano-scale vesicles have become a popular tool in life sciences. Besides liposomes that are generated from phospholipids of natural origin, polymersomes fabricated of synthetic block copolymers enjoy increasing popularity, as they represent more versatile membrane building blocks that can be selected based on their specific physicochemical properties, like permeability, stability or chemical reactivity.In this review, we focus on the application of simple and nested artificial vesicles in synthetic biology. First, we provide an introduction into the utilization of multi-compartmented vesosomes as compartmentalized nano-scale bioreactors. In the bottom-up development of protocells from vesicular nano-reactors, the specific exchange of pathway intermediates across compartment boundaries represents a bottleneck for future studies. To date, most compartmented bioreactors rely on unspecific exchange of substrates and products. This is either based on changes in permeability of the coblock polymer shell by physicochemical triggers or by the incorporation of unspecific porin proteins into the vesicle membrane. Since the incorporation of membrane transport proteins into simple and nested artificial vesicles offers the potential for specific exchange of substances between subcompartments, it opens new vistas in the design of protocells. Therefore we devote the main part of the review to summarize the technical advances in the use of phospholipids and block copolymers for the reconstitution of membrane proteins.

  7. Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Michio [Minamata City Hospital and Medical Center, Minamata City, Kumamoto 867 (Japan); Kortylewicz, Zbigniew P.; Enke, Charles A.; Mack, Elizabeth; Baranowska-Kortylewicz, Janina, E-mail: jbaranow@unmc.edu [Department of Radiation Oncology, J. Bruce Henriksen Cancer Research Laboratories, University of Nebraska Medical Center, Omaha, NE 68198 (United States)

    2011-05-25

    Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of human and murine PDGFr-β/PDGF-B pathways in SW1990 pancreatic cancer xenografts revealed that the human branch is practically dormant in untreated tumors but the insult on the stromal component produces massive responses of human cancer cells. Inhibition of the stromal PDGFr-β with imatinib activates human PDGFr-β/PDGF-B signaling loop, silent in untreated xenografts, via an apparent paracrine rescue pathway. Responses are treatment-and time-dependent. Soon after treatment, levels of human PDGFr-β, compared to untreated tumors, are 3.4×, 12.4×, and 5.7× higher in imatinib-, radioimmunotherapy + imatinib-, and radioimmunotherapy-treated tumors, respectively. A continuous 14-day irradiation of imatinib-treated xenografts reduces levels of PDGFr-β and phosphorylated PDGFr-β by 5.3× and 4×, compared to earlier times. Human PDGF-B is upregulated suggesting that the survival signaling via the autocrine pathway is also triggered after stromal injury. These findings indicate that therapies targeting pancreatic cancer stromal components may have unintended mitogenic effects and that these effects can be reversed when imatinib is used in conjunction with radioimmunotherapy.

  8. Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer

    International Nuclear Information System (INIS)

    Abe, Michio; Kortylewicz, Zbigniew P.; Enke, Charles A.; Mack, Elizabeth; Baranowska-Kortylewicz, Janina

    2011-01-01

    Pancreatic cancer does not respond to a single-agent imatinib therapy. Consequently, multimodality treatments are contemplated. Published data indicate that in colorectal cancer, imatinib and radioimmunotherapy synergize to delay tumor growth. In pancreatic cancer, the tumor response is additive. This disparity of outcomes merited further studies because interactions between these modalities depend on the imatinib-induced reduction of the tumor interstitial fluid pressure. The examination of human and murine PDGFr-β/PDGF-B pathways in SW1990 pancreatic cancer xenografts revealed that the human branch is practically dormant in untreated tumors but the insult on the stromal component produces massive responses of human cancer cells. Inhibition of the stromal PDGFr-β with imatinib activates human PDGFr-β/PDGF-B signaling loop, silent in untreated xenografts, via an apparent paracrine rescue pathway. Responses are treatment-and time-dependent. Soon after treatment, levels of human PDGFr-β, compared to untreated tumors, are 3.4×, 12.4×, and 5.7× higher in imatinib-, radioimmunotherapy + imatinib-, and radioimmunotherapy-treated tumors, respectively. A continuous 14-day irradiation of imatinib-treated xenografts reduces levels of PDGFr-β and phosphorylated PDGFr-β by 5.3× and 4×, compared to earlier times. Human PDGF-B is upregulated suggesting that the survival signaling via the autocrine pathway is also triggered after stromal injury. These findings indicate that therapies targeting pancreatic cancer stromal components may have unintended mitogenic effects and that these effects can be reversed when imatinib is used in conjunction with radioimmunotherapy

  9. Intrathecal opioids versus epidural local anesthetics for labor analgesia: a meta-analysis.

    Science.gov (United States)

    Bucklin, Brenda A; Chestnut, David H; Hawkins, Joy L

    2002-01-01

    Some anesthesiologists contend that intrathecal opioid administration has advantages over conventional epidural techniques during labor. Randomized clinical trials comparing analgesia and obstetric outcome using single-injection intrathecal opioids versus epidural local anesthetics suggest that intrathecal opioids provide comparable analgesia with few serious side effects. This meta-analysis compared the analgesic efficacy, side effects, and obstetric outcome of single-injection intrathecal opioid techniques versus epidural local anesthetics in laboring women. Relevant clinical studies were identified using electronic and manual searches of the literature covering the period from 1989 to 2000. Searches used the following descriptors: intrathecal analgesia, spinal opioids, epidural analgesia, epidural local anesthetics, and analgesia for labor. Data were extracted from 7 randomized clinical trials comparing analgesic measures, incidence of motor block, pruritus, nausea, hypotension, mode of delivery, and/or Apgar scores. Combined test results indicated comparable analgesic efficacy 15 to 20 minutes after injection with single-injection intrathecal opioid administration. Intrathecal opioid injections were associated with a greater incidence of pruritus (odds ratio, 14.01; 99% confidence interval, 6.9 to 28.3), but there was no difference in the incidence of nausea or in the method of delivery. Published studies suggest that intrathecal opioids provide comparable early labor analgesia when compared with epidural local anesthetics. Intrathecal opioid administration results in a greater incidence of pruritus. The choice of technique does not appear to affect the method of delivery.

  10. The radiolabeled monoclonal antibodies in immunoscintigraphy and radioimmunotherapy: current state and perspectives

    International Nuclear Information System (INIS)

    Chatal, J. F.

    2000-01-01

    The antibodies can be satisfactorily labelled with technitium-99 m or indium-111 for tumor immunoscintigraphy. The immunoscintigraphy is not useful for the primary tumor diagnosis. It can be useful for the diagnosis of the some cancer extension and for recurrent tumor visualization. The immunoscintigraphy is widely competed with Positron Emission Tomography (PET) which gives accurate results. In the future the immunoscintigraphy, in pre-therapeutic stage, contribute to the estimation of the dose delivered to the tumor and to normal organs for adopting or not a radioimmunotherapy. The antibodies can also be labeled with Iodine-131 for an application in radioimmunotherapy (RIT). The RIT is efficient in the non-Hodgkin's lymphoma treatment because of their great radiosensitivity. Until now the results have been very modest in solid tumor treatment but methodological and biotechnological progresses have to improve the efficiency especially for the small tumors. In the future iodine-131 which requires the confinement (very expensive) of patients will be substituted by yttrium-90 beta emitter, more energetic than iodine-131 and can be injected in walking case. In the long term, the alpha emitter radionuclides (astatine-211 or bismuth-213) can be used for hematologic cancer treatment. In conclusion the future of radiolabeled monoclonal antibodies is essentially therapeutic. The radioimmunotherapy associated to the chemotherapy give promising perspectives for the radiosensitive cancer treatment and in general small solid tumor treatment (F.M.)

  11. Development and evaluation of copper-67 and samarium-153 labeled conjugates for tumor radioimmunotherapy

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Mausner, L.F.; Mease, R.C.; Meinken, G.E.; Joshi, V.; Kolsky, K.; Sweet, M.; Steplewski, Z.

    1995-01-01

    The potential of utilizing receptor-specific agents such as monoclonal antibodies (MAb), and MAb-derived smaller molecules, as carriers of radionuclides for the selective destruction of tumors has stimulated much research activity. The success of such applications depends on many factors, especially the tumor binding properties of the antibody reagent, the efficiency of labeling and in-vivo stability of the radioconjugate and, on the careful choice of the radionuclide best suited to treat the tumor under consideration. The radiolabeled antibody technique for radioimmunotherapy (RIT), however, has experienced many limitations, and its success has not matched the expectations that were raised more than a decade ago. The problems that have been identified include: (i) degradation of antibody immunoreactivity resulting from chemical manipulations required for labeling; (ii) lack of suitable radioisotopes and methods for stable attachment of the radiolabel; (iii) in-vivo instability of the radioimmunoconjugates; (iv) excessive accumulation of activity in non-target locations; and (v) lack of radioimmunoconjugate accessibility to cells internal to a tumor mass. A careful choice of the radionuclide(s) best suited to treat the tumor under consideration is one of the most important requirements for successful radioimmunotherapy. This study evaluates copper 67 and samarium 153 for tumor radioimmunotherapy

  12. Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome. Conceptual chances

    International Nuclear Information System (INIS)

    Buchmann, I.; Helisch, A.; Bartenstein, P.; Meyer, R.G.; Herr, W.

    2005-01-01

    The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myelblative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand. (orig.)

  13. A comparison of intrathecal dexmedetomidine verses intrathecal fentanyl with epidural bupivacaine for combined spinal epidural labor analgesia

    OpenAIRE

    P K Dilesh; S Eapen; S Kiran; Vivek Chopra

    2014-01-01

    Context: Combined spinal epidural (CSE) analgesia technique is effective for labor analgesia and various concentrations of bupivacaine and lipophilic opioids like fentanyl have been studied. Dexmedetomidine is a highly selective alpha 2 adrenoreceptor agonist with analgesic properties and has been used intrathecally with bupivacaine for prolonged postoperative analgesia. Recent reviews have shown that it is highly lipophilic and does not cross placenta significantly. Aim: The aim of this s...

  14. Compartmentalization of prostaglandins in the canine kidney

    International Nuclear Information System (INIS)

    Morgan-Boyd, R.L.

    1986-01-01

    The kidney has been shown to synthesize all of the naturally occurring major prostaglandins which may be restricted to a discrete part of the kidney where their actions are physiologically important, such as the vascular compartment and the tubular compartment. In order to examine this concept of compartmentalization, the authors conducted a series of experiments to determine whether PGl 2 , measured as 6-keto-pGF/sub 1α/, produced in the kidney is restricted to the renal vascular compartment or whether it also has access to the tubular compartment. Experiments were performed in the pentobarbital-anesthetized dog. Increasing pre-glomerular levels of 6-keto-PFG/sub 1α/ caused marked increases in both the urinary excretion and the renal venous outflow to 6-keto-PGF/sub 1α/. When 3 H-6-keto-PGF/sub 1α/ was co-infused with inulin into the renal artery, 33% of the radioactivity and 23% of the inulin was recovered on first pass. With infusion of 3 H-PGl 2 and inulin, 20% of the radioactivity and 28% of the inulin reached the urine on first pass. Radioactive PGl 2 appeared to be less filterable at the glomeruli than either 3 H-6-keto-PGF/sub 1α/ or inulin. In the final set of experiments, in which dogs were prepared for a ureteral stopped-flow study, the PGE 2 /U/P/sub In/ ratio a peak was observed proximal to the Na + plateau but distal to the Na+ nadir. In light of the results from the stopped-flow study and the intrarenal infusion studies, they conclude that PGE 2 synthesized in the kidney enters both the renal and tubular compartments. In contrast, they find that 6-keto-PGF/sub 1α/ of renal origin enters only the renal origin enters only the renal vascular compartment and not the tubular compartment

  15. Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats

    OpenAIRE

    Birol Muhammet Er; İsmail Serhat Kocamanoğlu; Ayhan Bozkurt; Sırrı Bilge; Erhan Çetin Çetinoğlu

    2016-01-01

    Background: Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. Aims: The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Study Design: Animal experimentation. ...

  16. Comparison of the pharmacokinetics of imipenem after intravenous and intrathecal administration in rabbits.

    Science.gov (United States)

    Wang, Y; Qiu, L; Dong, J; Wang, B; Shi, Z; Liu, B; Wang, W; Zhang, J; Cai, S; Ye, G; Cai, X

    2013-03-01

    Intrathecal administration of antibiotics has potentially high effectiveness for the treatment for severe intracranial infections, particularly nosocomial meningitis. The use of intrathecal injection of antibiotics has been reported mostly in case reports. However, there is sparse data regarding the pharmacokinetics of antibiotics after intrathecal administration. This study investigated whether intrathecal injection is an effective method for the administration of imipenem. The pharmacokinetics of imipenem after intrathecal and intravenous administration of 1:1 imipenem: cilastatin (IMI/CIL) to rabbits were compared. The AUC0-t in the cerebrospinal fluid for intrathecal administration was approximately twice that of an equal dose of intravenous administration at doses of 0.35, 0.7, and 1.4 mg/kg. Brain concentrations of imipenem after intrathecal injection were three times greater than observed after intravenous injection and remained high for at least 8 hours post-injection. Elimination of imipenem after administration by either route was primarily via urine, but a transient surge of imipenem in bile and intestinal tissue was observed. Results indicate that there is a clinical potential for intrathecally administered IMI/CIL. Further studies are warranted to investigate the potential for seizure and to assess the translatability of the rabbit model to human treatment.

  17. Network thermodynamic approach compartmental analysis. Na+ transients in frog skin.

    Science.gov (United States)

    Mikulecky, D C; Huf, E G; Thomas, S R

    1979-01-01

    We introduce a general network thermodynamic method for compartmental analysis which uses a compartmental model of sodium flows through frog skin as an illustrative example (Huf and Howell, 1974a). We use network thermodynamics (Mikulecky et al., 1977b) to formulate the problem, and a circuit simulation program (ASTEC 2, SPICE2, or PCAP) for computation. In this way, the compartment concentrations and net fluxes between compartments are readily obtained for a set of experimental conditions involving a square-wave pulse of labeled sodium at the outer surface of the skin. Qualitative features of the influx at the outer surface correlate very well with those observed for the short circuit current under another similar set of conditions by Morel and LeBlanc (1975). In related work, the compartmental model is used as a basis for simulation of the short circuit current and sodium flows simultaneously using a two-port network (Mikulecky et al., 1977a, and Mikulecky et al., A network thermodynamic model for short circuit current transients in frog skin. Manuscript in preparation; Gary-Bobo et al., 1978). The network approach lends itself to computation of classic compartmental problems in a simple manner using circuit simulation programs (Chua and Lin, 1975), and it further extends the compartmental models to more complicated situations involving coupled flows and non-linearities such as concentration dependencies, chemical reaction kinetics, etc.

  18. MR cisternography after intrathecal Gd-DTPA application

    International Nuclear Information System (INIS)

    Reiche, Werner; Komenda, Yvonne; Steudel, Wolf-Ingo; Schick, Bernhard; Grunwald, Iris; Reith, Wolfgang

    2002-01-01

    The purpose of this study was to establish and to evaluate MR cisternography after intrathecal Gd-DTPA administration to detect rhinobasal cerebrospinal fluid (CSF) fistulae in patients with suspected CSF rhinorrhoea. Ten patients with suspected CSF rhinorrhoea were examined. The MR cisternography included the following investigation steps: acquisition of nonenhanced fat-suppressed T1-weighted spin-echo (SE) scans of the skull base and the paranasal sinuses, lumbar puncture with administration of 1 ml Gd-DTPA solute with 4 ml NaCl and performance of MR cisternography with the same fat-suppressed T1-weighted sequences as used initially. In 10 patients with suspected CSF rhinorrhoea Gd-DTPA enhanced MR cisternography detected 5 CSF fistulae. In 3 of 5 CSF leaks were located in the cribriform plate and in 2 of 5 sphenoidal. Whereas 4 of these depicted leaks were confirmed surgically, in 1 case the CSF fistula closed spontaneously. In another case, CSF leakage after severe head injury was clinically highly suspected but ceased prior to MR cisternography with inability to detect the temporary fistula. In the remaining 4 patients with serous rhinorrhoea MR cisternography did not provide any evidences for CSF fistulae. Intrathecal Gd-DTPA injection was tolerated excellently. Clinical and EEG examinations showed no gross behavioural or neurological disturbances and no seizure activity, respectively. The MR cisternography after intrathecal administration of Gd-DTPA represents a safe, promising and minimally invasive method for detection of CSF fistulae. This MR investigation provides excellent depiction of CSF spaces and pinpoints CSF fistulae. (orig.)

  19. Sonographic evaluation of epidural and intrathecal injections in cats.

    Science.gov (United States)

    Otero, Pablo E; Verdier, Natali; Zaccagnini, Andrea S; Fuensalida, Santiago E; Sclocco, Matias; Portela, Diego A; Waxman, Samanta

    2016-11-01

    To describe the ultrasonographic anatomy of the caudal lumbar spine in cats and to detect ultrasound (US) signs associated with epidural or intrathecal injection. Prospective, clinical study. Twenty-six client-owned cats. Transverse (position 1) and parasagittal (position 2) two-dimensional US scanning was performed over the caudal lumbar spine in all cats. Midline distances between the identified structures were measured. Cats assigned to epidural injection (group E, n = 16) were administered a bupivacaine-morphine combination confirmed by electrical stimulation. Cats assigned to intrathecal injection (group I, n = 10) were administered a morphine-iohexol combination injected at the lumbosacral level and confirmed by lateral radiography. The total volume injected (0.3 mL kg -1 ) was divided into two equal aliquots that were injected without needle repositioning, with the US probe in positions 1 and 2, respectively. The presence or absence of a burst of color [color flow Doppler test (CFDT)], dural sac collapse and epidural space enlargement were registered during and after both injections. US scanning allowed measurement of the distances between the highly visible structures inside the spinal canal. CFDT was positive for all animals in group E. In group I, intrathecal injection was confirmed in only two animals, for which the CFDT was negative; seven cats inadvertently and simultaneously were administered an epidural injection and showed a positive CFDT during the second aliquot injection, and the remaining animal was administered epidural anesthesia and was excluded from the CFDT data analysis. Dural sac collapse and epidural space enlargement were present in all animals in which an epidural injection was confirmed. US examination allowed an anatomical description of the caudal lumbar spine and real-time confirmation of epidural injection by observation of a positive CFDT, dural sac collapse and epidural space enlargement. © 2016 Association of Veterinary

  20. Radioimmunotherapy using 131I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

    International Nuclear Information System (INIS)

    Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L.; Srock, Stefanie; Pezzutto, Antonio

    2005-01-01

    The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using 131 I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with 131 I using the Iodogen method. The administered activity (2,200±600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of 131 I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8±2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

  1. Minimum effective local anesthetic dose of intrathecal hyperbaric ropivacaine and bupivacaine for cesarean section

    Institute of Scientific and Technical Information of China (English)

    GENG Zhi-yu; WANG Dong-xin; WU Xin-min

    2011-01-01

    Background Intrathecal anesthesia is commonly used for cesarean section. Bupivacaine and ropivacaine have all been used as intrathecal drugs. The minimum effective local anesthetic dose (MLAD) of intrathecal ropivacaine for nonobstetric patients has been reported. However, few data are available on the MLAD of hyperbaric ropivacine for obstetric patients and the relative potency to bupivacaine has not been fully determined. In this study, we sought to determine the MLAD of intrathecal ropivacaine and bupivacaine for elective cesarean section and to define their relative potency ratio.Methods We enrolled forty parturients undergoing elective cesarean section under combined spinal-epidural anesthesia and randomized them to one of two groups to receive intrathecal 0.5% hyperbaric ropivacaine or bupivacaine.The initial dose was 10 mg, and was increased in increments of 1 mg, using the technique of up-down sequential allocation. Efficacy was accepted if adequate sensory dermatomal anesthesia to pin prick to T7 or higher was attained within 20 minutes after intrathecal injection, and required no supplementary epidural injection for procedure until at least 50 minutes after the intrathecal injection.Results The intrathecal MLAD was 9.45 mg (95%confidence interval (CI), 8.45-10.56 mg) for ropivacaine and 7.53 mg (95%CI, 7.00-8.10 mg) for bupivacaine. The relative potency ratio was 0.80 (95% Cl, 0.74-0.85) for ropivacaine/bupivacaine when given intrathecally in cesarean section.Conclusion Ropivacaine is 20% less potent than bupivacaine during intrathecal anesthesia for cesarean delivery.

  2. Drivers of compartmentalization in a Mediterranean pollination network

    DEFF Research Database (Denmark)

    Gonzalez, Ana M. Martin; Allesina, Stefano; Rodrigo, Anselm

    2012-01-01

    We study compartmentalization in a Mediterranean pollination network using three different analytical approaches: unipartite modularity (UM), bipartite modularity (BM) and the group model (GM). Our objectives are to compare compartments obtained with these three approaches and to explore the role...... of several species attributes related to pollination syndromes, species phenology, abundance and connectivity in structuring compartmentalization. BM could not identify compartments in our network. By contrast, UM revealed four modules composed of plants and pollinators, and GM four groups of plants and five...... of pollinators. Phenology had a major influence on compartmentalization, and compartments (both UM and GM) had distinct phenophases. Compartments were also strongly characterized by species degree (number of connections) and betweenness centrality. These two attributes were highly related to each other...

  3. Does immunoscintigraphy serve clinical needs effectively? Is there a future for radioimmunotherapy?

    International Nuclear Information System (INIS)

    Chata, J.F.; Peltier, P.; Bardies, M.; Chetanneau, A.; Thedrez, P.; Faivre-Chauvet, A.; Gestin, J.F.

    1992-01-01

    Since 1980, immunoscintigraphy has been performed in thousands of patients, and its clinical value has been demonstrated for selective indications in malignant (early detection of recurrences of colorectal and ovarian carcinomas) and non-malignant (cardiovascular and inflammatory) pathology. However, many clinicians are not yet very convinced of its efficiency. Opinions range between favourable interest and marked scepticism. The causes of this inconclusive verdict include an often moderate target-to-background ratio in images, the immunogenicity of injected murine antibodies and the fact that a true benefit for the patient has not yet been clearly demonstrated in large series of patients. Future prospects could significantly improve this and involve the reduction of non-specific activity in normal tissues (to improve disease target contrast and thus make image interpretation easier) and the decreased immunogenicity of injected immunoconjugates (to permit repetition of examinations). Radioimmunotherapy, an innovative and promising approach, is still limited by numerous problems. The results of clinical studies are still inconclusive, being encouraging only for specific indications. In the future, pre-targetting techniques should allow the rapid elimination of radioactivity from normal tissues, resulting in a significant increase in tumour-to-normal tissue ratios. Progress is also required in the choice of radionuclides and labelling techniques and in methods for dosimetric estimations. The clinical indications of radioimmunotherapy after systemic injection will concern mainly radiosensitive tumours such as lymphomas, small-cell lung cancers and neuroblastomas. After endocavitary injection, radioimmunotherapy could prove efficient in the treatment of micrometastases of ovarian carcinomas. For all indications, this new approach should be combined with other therapeutic modalities. (orig.)

  4. Historical spirals of intrathecal therapy of bacterial meningoencephalites: from past to present

    Directory of Open Access Journals (Sweden)

    Сергей Петрович Борщев

    2015-10-01

    Full Text Available On the base of studying medical literature in the article was considered the history of using intrathecal methods of bacterial meningoencephalites therapy, using intrathecal methods in other medical fields, the modern state of problem.Aim of research: To study the history of using intrathecal methods of bacterial meningoencephalites therapy, the state of problem in the world, an experience of using intrathecal therapeutical methods in other medical fields and to define prospects and necessity of further scientific researches in this direction.Materials and methods: There were used scientometric data bases, available scientific medical printing editions, historical, analytical, philosophical methods, analysis and generalization, the cause-and-effect relations, logic, dialectic.Results of research: There were revealed regularities of growth and decline of interest of medical community to this problem. For today there is no unambiguous attitude to intrathecal therapy of bacterial meningoencephalites. There are contrary opinions about necessity of using this method. There were revealed objective factors that complicate the development of researches in the field of intrathecal therapy of bacterial meningoencephalites.Conclusions: 1. Intrathecal methods of administration preparations at treating patients with bacterial meningoencephalites were successfully used from the beginning of 20 century.2. The degree of interest of medical scientific community to intrathecal therapeutical methods depended on objective necessity of its use in different medical fields at the concrete historical stage.3. Attention to intrathecal methods of treatment decreased as an effect of discovery new antibacterial preparations4. From historical point of view the spread of intrathecal methods of treatment depends on toxicity and effectiveness of preparations for the system use: the higher toxicity and less effectiveness of the system therapy, the more spread use of intrathecal

  5. Intrathecal hypobaric versus hyperbaric bupivacaine with morphine for cesarean section.

    Science.gov (United States)

    Richardson, M G; Collins, H V; Wissler, R N

    1998-08-01

    Both hyper- and hypobaric solutions of bupivacaine are often combined with morphine to provide subarachnoid anesthesia for cesarean section. Differences in the baricity of subarachnoid solutions influence the intrathecal distribution of anesthetic drugs and would be expected to influence measurable clinical variables. We compared the effects of hyper- and hypobaric subarachnoid bupivacaine with morphine to determine whether one has significant advantages with regard to intraoperative anesthesia and postoperative analgesia in term parturients undergoing elective cesarean section. Thirty parturients were randomized to receive either hyper- or hypobaric bupivacaine (15 mg) with morphine sulfate (0.2 mg). Intraoperative outcomes compared included extent of sensory block, quality of anesthesia, and side effects. Postoperative outcomes, including pain visual analog scale scores, systemic analgesic requirements, and side effects, were monitored for 48 h. Sedation effects were quantified and compared using Trieger and digit-symbol substitution tests. We detected no differences in sensory or motor block, quality of anesthesia, quality of postoperative analgesia, incidence of side effects, or psychometric scores. Both preparations provide highly satisfactory anesthesia for cesarean section and effective postoperative analgesia. Dextrose alters the density of intrathecal bupivacaine solutions and is thought to influence subarachnoid distribution of the drug. We randomized parturients undergoing cesarean section to one of two often used spinal bupivacaine preparations, hypobaric and hyperbaric. We detected no differences in clinical outcomes between groups.

  6. Autologous Bone Marrow Mononuclear Cells Intrathecal Transplantation in Chronic Stroke

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2014-01-01

    Full Text Available Cell therapy is being widely explored in the management of stroke and has demonstrated great potential. It has been shown to assist in the remodeling of the central nervous system by inducing neurorestorative effect through the process of angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, the effect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs is analyzed on the recovery process of patients with chronic stroke. 24 patients diagnosed with chronic stroke were administered cell therapy, followed by multidisciplinary neurorehabilitation. They were assessed on functional independence measure (FIM objectively, along with assessment of standing and walking balance, ambulation, and hand functions. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. Further factor analysis was done. Patients of the younger groups showed higher percentage of improvement in all the areas. Patients who underwent cell therapy within 2 years after the stroke showed better changes. Ischemic type of stroke had better recovery than the hemorrhagic stroke. This study demonstrates the potential of autologous BMMNCs intrathecal transplantation in improving the prognosis of functional recovery in chronic stage of stroke. Further clinical trials are recommended. This trial is registered with NCT02065778.

  7. Intrathecal isobaric versus hyperbaric bupivacaine for elective caesarean section

    International Nuclear Information System (INIS)

    Aftab, S.; Ali, H.; Zafar, S.; Sheikh, M.; Sultan, T.

    2007-01-01

    To compare the results of isobaric bupivacaine (0.5%) with hyperbaric bupivacaine (0.75%) in cases of elective Caesarean Section, in respect of time to sensory analgesia, highest level of sensory block, haemodynamic effects, and complications. Sixty pregnant patients scheduled for elective Caesarean Section. The patients were randomly assigned to receive either 0.5% isobaric bupivacaine (Group-1B) or 0.75% hyperbaric bupivacaine (Group-HB) via intrathecal route. The time of onset of block, highest level of sensory block, cardio-respiratory data, duration of analgesia and complications were recorded during surgery. The time taken to reach T4 sensory analgesia in Group-1B was 6+-6.43 minutes as compared to 6.93+-7.8 minutes in Group-HB, while the highest sensory level achieved in Group-1B was T1 and in Group-HB T2. The lowest systolic blood pressure recorded in Group-1B was 83.27+-12.69 mmHg and in Group-HB 114.33+-13.83 mm Hg, the difference being significant (p<0.05). There was a higher incidence of complications in Group-1B as compared to Group-HB like high spinal analgesia, vomiting and discomfort. Intrathecal block showed a greater reduction in the systolic blood pressure, and associated complications, with Isobaric Bupivacaine as compared to Hyperbaric Bupivacaine. (author)

  8. Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy.

    Science.gov (United States)

    Kaushik, Mahesh K; Aritake, Kosuke; Imanishi, Aya; Kanbayashi, Takashi; Ichikawa, Tadashi; Shimizu, Tetsuo; Urade, Yoshihiro; Yanagisawa, Masashi

    2018-06-05

    Narcolepsy-cataplexy is a chronic neurological disorder caused by loss of orexin (hypocretin)-producing neurons, associated with excessive daytime sleepiness, sleep attacks, cataplexy, sleep paralysis, hypnagogic hallucinations, and fragmentation of nighttime sleep. Currently, human narcolepsy is treated by providing symptomatic therapies, which can be associated with an array of side effects. Although peripherally administered orexin does not efficiently penetrate the blood-brain barrier, centrally delivered orexin can effectively alleviate narcoleptic symptoms in animal models. Chronic intrathecal drug infusion through an implantable pump is a clinically available strategy to treat a number of neurological diseases. Here we demonstrate that the narcoleptic symptoms of orexin knockout mice can be reversed by lumbar-level intrathecal orexin delivery. Orexin was delivered via a chronically implanted intrathecal catheter at the upper lumbar level. The computed tomographic scan confirmed that intrathecally administered contrast agent rapidly moved from the spinal cord to the brain. Intrathecally delivered orexin was detected in the brain by radioimmunoassay at levels comparable to endogenous orexin levels. Cataplexy and sleep-onset REM sleep were significantly decreased in orexin knockout mice during and long after slow infusion of orexin (1 nmol/1 µL/h). Sleep/wake states remained unchanged both quantitatively as well as qualitatively. Intrathecal orexin failed to induce any changes in double orexin receptor-1 and -2 knockout mice. This study supports the concept of intrathecal orexin delivery as a potential therapy for narcolepsy-cataplexy to improve the well-being of patients.

  9. Integration through Compartmentalization? Pitfalls of “Poldering” in Bangladesh

    NARCIS (Netherlands)

    Warner, J.F.

    2010-01-01

    The article sketches the history of the Flood Action Plan 20 (FAP-20), an experiment with polder compartmentalization, seeking to integrate flood management, drainage, and irrigation, and make it more democratic in response to the destructive 1987 and 1988 floods in Bangladesh. As a transferred

  10. Macroanatomy of compartmentalization in fire scars of three western conifers

    Science.gov (United States)

    Kevin T. Smith; Elaine Sutherland; Estelle Arbellay; Markus Stoffel; Donald. Falk

    2013-01-01

    Fire scars are visible evidence of compartmentalization and closure processes that contribute to tree survival after fire injury. Preliminary observations of dissected fire scars from trees injured within the last decade showed centripetal development of wound-initiated discoloration (WID) through 2-3 decades of former sapwood in Larix occidentalis and Pseudotsuga...

  11. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Ihekwaba, Adoha

    2007-01-01

    A. Ihekwaba, R. Mardare. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems. Case study: NFkB system. In Proc. of International Conference of Computational Methods in Sciences and Engineering (ICCMSE), American Institute of Physics, AIP Proceedings, N 2...

  12. Integration through compartmentalization? Pitfalls of 'poldering' in Bangladesh

    NARCIS (Netherlands)

    Warner, J.F.

    2010-01-01

    The article sketches the history of the Flood Action Plan 20 (FAP-20), an experiment with polder compartmentalization, seeking to integrate flood management, drainage, and irrigation, and make it more democratic in response to the destructive 1987 and 1988 floods in Bangladesh. As a transferred

  13. Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

    Science.gov (United States)

    Sahin, Murat; Gullu, Huriye; Peker, Kemal; Sayar, Ilyas; Binici, Orhan; Yildiz, Huseyin

    2015-11-01

    The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

  14. Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?

    Directory of Open Access Journals (Sweden)

    Murat Sahin

    2015-01-01

    Full Text Available The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 µg was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

  15. The feasibility of 225Ac as a source of α-particles in radioimmunotherapy

    International Nuclear Information System (INIS)

    Geerlings, M.W.; Hout, R. van der; Kaspersen, F.M.; Apostolides, C.

    1993-01-01

    This paper proposes the utilization of 225 Ac for the α-radioimmunotherapy of cancer. The isotope decays with a radioactive half-life of 10 days into a cascade of short-lived α-and β-emitting isotopes. In addition, when indicated by the pharmacokinetic requirements of particular clinical applications, 213 Bi, with a radioactive half-life of 47 min, can be chosen as an alternative source of α-particles in radioimmunotherapy. This isotope is the last α emitter in the 225 Ac decay-cascade and can be extracted from a 225 Ac source at the bedside of the patient. 225 Ac can quasi ad infinitum be obtained from one of its precursors, 229 Th, which can be made available by various means. The indications for the use of α-particles as an alternative to more traditional classes of radiation are derived from the particle-kinetic characteristics and the radioactive half-life of their source isotope, as well as from the properties of the target-selective carrier moiety for the source isotope. It may be expected that useful applications, complementary to and/or in conjunction with other means of therapy will be identified. (author)

  16. Radiobiological comparison of external beam irradiation and radioimmunotherapy in renal cell carcinoma xenografts

    International Nuclear Information System (INIS)

    Wessels, B.W.; Vessella, R.L.; Palme, D.F. II; Berkopec, J.M.; Smith, G.K.; Bradley, E.W.

    1989-01-01

    Growth delay was measured in TK-82 renal cell carcinoma (RCC) xenografts implanted in nude mice receiving single fraction external beam irradiation (SF-XRT), multifraction external beam irradiation (MF-XRT), or radioimmunotherapy (RIT). Thermoluminescent dosimeter(s) (TLD) and autoradiography were used to ascertain the average absorbed dose delivered and the degree of heterogeneous uptake of radiolabeled antibody for the RIT irradiations. For intravenous administered activities of 100, 200, 400, and 600 microCi of I-131 labeled A6H antibody, volume doubling times (VDT) and TLD absorbed dose measurements for each administered activity were 7 days (341 cGy), 38 days (383 cGy), 85 days (886 cGy) and no regrowth (1034 cGy), respectively. For SF-XRT irradiations of 500, 1000, and 1500 cGy, VDT times were 11, 62, and 103 days, respectively. MF-XRT of 4 X 250 cGy over a 2-week period yielded a VDT of 25 days. Marked peripheral activity deposition was noted on most autoradiographs from multiple tumor samples. These data suggest that an equivalent to superior tumor growth delay is obtained for absorbed doses delivered by exponentially decaying low dose rate radioimmunotherapy RIT compared to similar doses of acute dose rate XRT as quantitated by the TLD method

  17. Radioimmunotherapy of human lymphoma in athymic, nude mice as monitored by 31P nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Adams, D.A.; DeNardo, G.L.; DeNardo, S.J.; Matson, G.B.; Epstein, A.L.; Bradbury, E.M.

    1985-01-01

    Human B cell lymphoma (Raji) growing in athymic, nude mice has been successfully treated with a single pulse dose of 131 I-labeled monoclonal antibody (Lym-1) specific for this tumor. Sequential in vivo measurements of phosphate metabolites in the tumors by 31 P surface coil nuclear magnetic resonance showed a significant initial decrease of phosphocreatine following radioimmunotherapy. Diminution of relative ATP to Pi peak area ratio suggesting tissue damage occurred within 3-4 days. The sequence of alterations of nuclear magnetic resonance spectra from tumors of treated mice were strikingly different from sequential nuclear magnetic resonance spectra obtained from tumors of control mice. These observations lead us to conclude that 31 P surface coil nuclear magnetic resonance is a promising non-invasive method for assessing and predicting the efficacy of radioimmunotherapy. Further spatial discrimination of the region of tissue observed by the surface coil nuclear magnetic resonance experiment is under exploration in an effort to increase the utility of these methods

  18. Kinetic compartmental analysis of carnitine metabolism in the dog

    International Nuclear Information System (INIS)

    Rebouche, C.J.; Engel, A.G.

    1983-01-01

    This study was undertaken to quantitate the dynamic parameters of carnitine metabolism in the dog. Six mongrel dogs were given intravenous injections of L-[methyl-3H]carnitine and the specific radioactivity of carnitine was followed in plasma and urine for 19-28 days. The data were analyzed by kinetic compartmental analysis. A three-compartment, open-system model [(a) extracellular fluid, (b) cardiac and skeletal muscle, (c) other tissues, particularly liver and kidney] was adopted and kinetic parameters (carnitine flux, pool sizes, kinetic constants) were derived. In four of six dogs the size of the muscle carnitine pool obtained by kinetic compartmental analysis agreed (+/- 5%) with estimates based on measurement of carnitine concentrations in different muscles. In three of six dogs carnitine excretion rates derived from kinetic compartmental analysis agreed (+/- 9%) with experimentally measured values, but in three dogs the rates by kinetic compartmental analysis were significantly higher than the corresponding rates measured directly. Appropriate chromatographic analyses revealed no radioactive metabolites in muscle or urine of any of the dogs. Turnover times for carnitine were (mean +/- SEM): 0.44 +/- 0.05 h for extracellular fluid, 232 +/- 22 h for muscle, and 7.9 +/- 1.1 h for other tissues. The estimated flux of carnitine in muscle was 210 pmol/min/g of tissue. Whole-body turnover time for carnitine was 62.9 +/- 5.6 days (mean +/- SEM). Estimated carnitine biosynthesis ranged from 2.9 to 28 mumol/kg body wt/day. Results of this study indicate that kinetic compartmental analysis may be applicable to study of human carnitine metabolism

  19. Treatment of neuropathic cancer pain with continuous intrathecal administration of S (+)-ketamine

    NARCIS (Netherlands)

    Vranken, J. H.; van der Vegt, M. H.; Kal, J. E.; Kruis, M. R.

    2004-01-01

    The effective treatment of patients suffering from neuropathic cancer pain remains a clinical challenge. When patients experience either insufficient analgesia or problematic side-effects after opioid administration, intrathecal administration of morphine and other medications such as bupivacaine

  20. Compartmental and dosimetric studies of anti-CD20 labelled with 188Re

    International Nuclear Information System (INIS)

    Kuramoto, Graciela Barrio

    2016-01-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β - emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β - emitters as 131 I, 90 Y, 188 Re 177 Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). 188 Re (E β = 2.12 MeV; E γ = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, 188 Re can be obtained from a radionuclide generator of 188 W/ 188 Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical 188 Re-Anti-CD20, where the radionuclide can be obtained from a generator system 188 W/ 188 Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with 188 Re with the marking of the antibody with 90 Y, 131 I, 177 Lu and 99m Tc (for their similar chemical characteristics) and 211 At, 213 Bi, 223 Ra and 225 Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for 188 Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of 188 Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β -131 I-labeled anti CD20, 177 Luanti- CD20, the γ emitter 99m Tc-Anti-CD20 and α emitter 211 At-Anti-CD20 presented a elimination constant of approximately 0.05 hours

  1. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... and insulin signalling transduction remain elusive. We believe that one of the reasons is that the role of intracellular compartmentalization as a regulator of metabolic pathways and signalling transduction has been rather ignored. This paper briefly reviews the literature to discuss the role of intracellular...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...

  2. A Novel Method for Performance Analysis of Compartmentalized Reservoirs

    Directory of Open Access Journals (Sweden)

    Shahamat Mohammad Sadeq

    2016-05-01

    Full Text Available This paper presents a simple analytical model for performance analysis of compartmentalized reservoirs producing under Constant Terminal Rate (CTR and Constant Terminal Pressure (CTP. The model is based on the well-known material balance and boundary dominated flow equations and is written in terms of capacitance and resistance of a production and a support compartment. These capacitance and resistance terms account for a combination of reservoir parameters which enable the developed model to be used for characterizing such systems. In addition to considering the properties contrast between the two reservoir compartments, the model takes into account existence of transmissibility barriers with the use of resistance terms. The model is used to analyze production performance of unconventional reservoirs, where the multistage fracturing of horizontal wells effectively creates a Stimulated Reservoir Volume (SRV with an enhanced permeability surrounded by a non-stimulated region. It can also be used for analysis of compartmentalized conventional reservoirs. The analytical solutions provide type curves through which the controlling reservoirs parameters of a compartmentalized system can be estimated. The contribution of the supporting compartment is modeled based on a boundary dominated flow assumption. The transient behaviour of the support compartment is captured by application of “distance of investigation” concept. The model shows that depletion of the production and support compartments exhibit two unit slopes on a log-log plot of pressure versus time for CTR. For CTP, however, the depletions display two exponential declines. The depletion signatures are separated by transition periods, which depend on the contribution of the support compartment (i.e. transient or boundary dominated flow. The developed equations can be implemented easily in a spreadsheet application, and are corroborated with the use of a numerical simulation. The study

  3. Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions

    Directory of Open Access Journals (Sweden)

    Marin de Mas Igor

    2011-10-01

    Full Text Available Abstract Background Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. Results The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate. The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. Conclusions The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose

  4. Field Testing of Compartmentalization Methods for Multifamily Construction

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, K. [Building Science Corporation, Westford, MA (United States); Lstiburek, J. [Building Science Corporation, Westford, MA (United States)

    2015-03-01

    The 2012 IECC has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure for both single-family and multifamily construction in Climate Zones 3-8. Other programs (LEED, ASHRAE 189, ASHRAE 62.2) have similar or tighter compartmentalization requirements, driving the need for easier and more effective methods of compartmentalization in multifamily buildings. Builders and practitioners have found that fire-resistance rated wall assemblies are a major source of difficulty in air sealing/compartmentalization, particularly in townhouse construction. This problem is exacerbated when garages are “tucked in” to the units and living space is located over the garages. In this project, Building Science Corporation examined the taping of exterior sheathing details to improve air sealing results in townhouse and multifamily construction, when coupled with a better understanding of air leakage pathways. Current approaches are cumbersome, expensive, time consuming, and ineffective; these details were proposed as a more effective and efficient method. The effectiveness of these air sealing methods was tested with blower door testing, including “nulled” or “guarded” testing (adjacent units run at equal test pressure to null out inter-unit air leakage, or “pressure neutralization”). Pressure diagnostics were used to evaluate unit-to-unit connections and series leakage pathways (i.e., air leakage from exterior, into the fire-resistance rated wall assembly, and to the interior).

  5. Development of 90Y-DOTA-nimotuzumab Fab fragment for radioimmunotherapy

    International Nuclear Information System (INIS)

    Alonso Martinez, L.M.; Marylaine Perez-Malo Cruz; Rene Leyva Montana; Calzada Falcon, V.N.; Minely Zamora Barrabi; Alejandro Arbesu Valdivia; Ignacio Hernandez Gonzalez; Mariela Leon Perez

    2014-01-01

    Yttrium-90-( 90 Y) labeled monoclonal antibodies prepared with a chelating agent, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), have been used for radioimmunotherapy of cancer. In the present work, the Fab fragment of anti-EGFR monoclonal antibody nimotuzumab was prepared with high purity, integrity and biological activity. The Fab fragment with high specific recognition of EGFR in NCI-H125 human lung adenocarcinoma cells was derivatized with DOTA-NHS applying a simple procedure. DOTA-nimotuzumab Fab fragment was successfully radiolabeled with 90 Y with high radiochemical yield. The in vitro stability of labeled product was optimal over 24 h in buffered solution at 37 deg C. Biodistribution and pharmacokinetic studies correctly evaluated the in vivo non-tumor uptake, dosage regimen and excretion pathway in normal Wistar rats. (author)

  6. Screening for sporadic or familial medullary thyroid carcinoma. Scintiscan s and radio-immunotherapy

    International Nuclear Information System (INIS)

    Rhmer, V.; Murat, A.

    2000-01-01

    The screening for sporadic medullary thyroid carcinoma relies upon calcitoninemia level, basal or during pentagastrine stimulation test. MEN2 are associated with nearly the third of medullary thyroid carcinoma. In these cases, prognosis of thyroid carcinoma is mainly driven by the tumor status at the time of surgery. Up to date, diagnosis relies upon the genetic screening. Prophylactic thyroidectomy indication may take account of calcitoninemia. Most of the molecules that have been suggested for scintiscan lack of accuracy and large use cannot be recommended. Promising results have been obtained with monoclonal antibodies anti-CEA, particularly with dual targeting antiCEA antiDTPA. This last technique may also be used for radio-guided surgery. Its use for radio-immunotherapy is under investigation. (authors)

  7. Positron emission tomography/computed tomography and radioimmunotherapy of prostate cancer

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Capala, Jacek; Oehr, Peter

    2009-01-01

    of a number of diagnostic and therapeutic strategies. J591, a monoclonal antibody, which targets the extracellular domain of prostate-specific membrane antigen, shows promising results. HER2 receptors may also have a potential as target for PET/CT imaging and RIT of advanced prostate cancer. SUMMARY: PET......PURPOSE OF REVIEW: Traditional morphologically based imaging modalities are now being complemented by positron emission tomography (PET)/computed tomography (CT) in prostate cancer. Metastatic prostate cancer is an attractive target for radioimmunotherapy (RIT) as no effective therapies...... are available. This review highlights the most important achievements within the last year in PET/CT and RIT of prostate cancer. RECENT FINDINGS: Conflicting results exist on the use of choline for detection of malignant disease in the prostate gland. The role of PET/CT in N-staging remains to be elucidated...

  8. Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells

    International Nuclear Information System (INIS)

    Friesen, Claudia; Lubatschofski, Annelie; Debatin, Klaus-Michael; Kotzerke, Joerg; Buchmann, Inga; Reske, Sven N.

    2003-01-01

    Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-x L , a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies. (orig.)

  9. Validation of a preclinical spinal safety model: effects of intrathecal morphine in the neonatal rat.

    Science.gov (United States)

    Westin, B David; Walker, Suellen M; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L

    2010-07-01

    Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long-term function after intrathecal morphine in the neonatal rat. Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P) 3, 10, and 21. The relationship between injectate volume and segmental spread was assessed postmortem and by in vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 min after intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis, and glial response were evaluated 1 and 7 days after P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally mediated analgesia at all ages with lower dose requirements in younger pups. High-dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. The therapeutic ratio for intrathecal morphine (toxic dose/antinociceptive dose) was at least 300 at P3 and at least 20 at P21 (latter doses limited by side effects). These data provide relative efficacy and safety for comparison with other analgesic preparations and contribute supporting evidence for the validity of this preclinical neonatal safety model.

  10. A mechanistic compartmental model for total antibody uptake in tumors.

    Science.gov (United States)

    Thurber, Greg M; Dane Wittrup, K

    2012-12-07

    Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Chronic intrathecal cannulation enhances nociceptive responses in rats

    Directory of Open Access Journals (Sweden)

    Almeida F.R.C.

    2000-01-01

    Full Text Available The influence of a chronically implanted spinal cannula on the nociceptive response induced by mechanical, chemical or thermal stimuli was evaluated. The hyperalgesia in response to mechanical stimulation induced by carrageenin or prostaglandin E2 (PGE2 was significantly increased in cannulated (Cn rats, compared with naive (Nv or sham-operated (Sh rats. Only Cn animals presented an enhanced nociceptive response in the first phase of the formalin test when low doses were used (0.3 and 1%. The withdrawal latency to thermal stimulation of a paw inflamed by carrageenin was significantly reduced in Cn rats but not in Nv or Sh rats. In contrast to Nv and Sh rats, injection in Cn animals of a standard non-steroid anti-inflammatory drug, indomethacin, either intraperitoneally or into the spinal cord via an implanted cannula or by direct puncture of the intrathecal space significantly blocked the intensity of the hyperalgesia induced by PGE2. Cannulated animals treated with indomethacin also showed a significant inhibition of second phase formalin-induced paw flinches. Histopathological analysis of the spinal cord showed an increased frequency of mononuclear inflammatory cells in the Cn groups. Thus, the presence of a chronically implanted cannula seems to cause nociceptive spinal sensitization to mechanical, chemical and thermal stimulation, which can be blocked by indomethacin, thus suggesting that it may result from the spinal release of prostaglandins due to an ongoing mild inflammation.

  12. Spinal conduction block by intrathecal ketamine in dogs.

    Science.gov (United States)

    Iida, H; Dohi, S; Tanahashi, T; Watanabe, Y; Takenaka, M

    1997-07-01

    In addition to its use for intravenous (I.V.) anesthesia, ketamine can provide pain relief in humans when administered spinally. To elucidate the mechanisms of intrathecal (I.T.) ketamine analgesia, we observed differences in the effects of I.V. and I.T. ketamine on intraspinal evoked potentials (ISEPs) in 28 dogs anesthetized with pentobarbital. Bipolar extradural electrodes were inserted at the cervical and lumbar regions of the spinal cord for recording descending ISEPs represented by the two negative deflections, Waves I and II. I.V. ketamine 2 and 10 mg/ kg did not affect the amplitude and latency of Wave I, whereas the large dose (10 mg/kg) significantly decreased the amplitude but not the latency of Wave II. I.T. ketamine 1 and 5 mg/kg caused significant dose-dependent decreases in both Wave I and II amplitudes and prolongations of both Wave I and II latencies. These I.T. effects on ISEPs are consistent with previous in vitro observations that ketamine blocks axonal conduction. We conclude that axonal conduction block may contribute to the analgesic mechanism of I.T. ketamine.

  13. Prophylaxis of meningosis leukemia via intrathecal radioactive colloid gold injection

    Energy Technology Data Exchange (ETDEWEB)

    Angelov, A; Uzunov, I; Marshavelova, J [Meditsinski Fakultet, Plovdiv (Bulgaria)

    1979-01-01

    Prophylaxis against meningosis leukemia (ML) via intrathecal radioactive colloid gold injection was carried out for a period of three years (January 1974 - September 1976) in 21 children with acute lymphoblast leukemia (ALL). The analysis of those patients after one relatively long period of observation (28 months after the last case) reveals that ML developed as a primary isolated manifestation of a recurrence in three children, i.e. in 14.2 per cent versus 68 per cent in the control group without prophylaxis. In another child ML development is in parallel with bone marrow recurrence. The reduction of ML incidence is accompanied with a prolongation of the first remission (in 24 per cent over 2 years and 6 months) and a lengthening of survival for 50 per cent of the patients (62 per cent of the treated patients are alive two years and 4 months during the period of observation). The advantages of the prophylaxis with radioactive colloid gold is emphasized in comparison with the other prophylactic programmes.

  14. Dose distribution to spinal structures from intrathecally administered yttrium-90

    Science.gov (United States)

    Mardirossian, George; Hall, Michael; Montebello, Joseph; Stevens, Patrick

    2006-01-01

    Previous treatment of cerebrospinal fluid (CSF) malignancies by intrathecal administration of 131I-radiolabelled monoclonal antibodies has led to the assumption that more healthy tissue will be spared when a pure beta-emitter such as 90Y replaces 131I. The purpose of this study is to compare and quantitatively evaluate the dose distribution from 90Y to the CSF space and its surrounding spinal structures to 131I. A 3D digital phantom of a section of the T-spine was constructed from the visible human project series of images which included the spinal cord, central canal, subarachnoid space, pia mater, arachnoid, dura mater, vertebral bone marrow and intervertebral disc. Monte Carlo N-particle (MCNP4C) was used to model the 90Y and 131I radiation distribution. Images of the CSF compartment were convolved with the radiation distribution to determine the dose within the subarachnoid space and surrounding tissues. 90Y appears to be a suitable radionuclide in the treatment of central nervous system (CNS) malignancies when attached to mAb's and the dose distribution would be confined largely within the vertebral foramen. This choice may offer favourable dose improvement to the subarachnoid and surface of spinal cord over 131I in such an application.

  15. Intrathecal delivery of protein therapeutics to the brain: a critical reassessment.

    Science.gov (United States)

    Calias, Pericles; Banks, William A; Begley, David; Scarpa, Maurizio; Dickson, Patricia

    2014-11-01

    Disorders of the central nervous system (CNS), including stroke, neurodegenerative diseases, and brain tumors, are the world's leading causes of disability. Delivery of drugs to the CNS is complicated by the blood-brain barriers that protect the brain from the unregulated leakage and entry of substances, including proteins, from the blood. Yet proteins represent one of the most promising classes of therapeutics for the treatment of CNS diseases. Many strategies for overcoming these obstacles are in development, but the relatively straightforward approach of bypassing these barriers through direct intrathecal administration has been largely overlooked. Originally discounted because of its lack of usefulness for delivering small, lipid-soluble drugs to the brain, the intrathecal route has emerged as a useful, in some cases perhaps the ideal, route of administration for certain therapeutic protein and targeted disease combinations. Here, we review blood-brain barrier functions and cerebrospinal fluid dynamics and their relevance to drug delivery via the intrathecal route, discuss animal and human studies that have investigated intrathecal delivery of protein therapeutics, and outline several characteristics of protein therapeutics that can allow them to be successfully delivered intrathecally. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Intrathecal ligaments and nerve root tension: possible sources of lumbar pain during spaceflight.

    Science.gov (United States)

    Kershner, David; Binhammer, Robert

    2004-04-01

    Lumbar intrathecal ligaments have recently been demonstrated to randomly bind dorsal nerve roots to the dura within the lumbar vertebral column. Lengthening of the vertebral column and associated lumbar back pain experienced by astronauts is common in microgravity. This study was designed to investigate the relationship of lumbar intrathecal ligaments in spinal lengthening as a possible mechanism for back pain. A two-part study was designed using 36 vertebral columns from embalmed cadavers. There were 12 vertebral columns studied in mid-sagittal section to demonstrate the possible movement of the spinal cord during lengthening of the vertebral column. The remainder were assessed for the amount of tension placed on a dorsal nerve root by the lumbar intrathecal ligament during lengthening of the vertebral column. The spinal cord moves in a cephalic direction approximately 2.8 mm with 4 cm lengthening of the vertebral column. During lengthening, a loss of thoracic and lordotic curvature was noted with an increase in disk height. Tension was significantly increased on the dorsal nerve roots being tethered by the lumbar intrathecal ligaments in comparison to non-tethered nerve roots during lengthening of the vertebral column. A significant amount of tension is placed on dorsal nerve roots tethered by intrathecal ligaments within the lumbar spine during spinal lengthening. These ligaments randomly bind dorsal nerve roots in the lumbar spine and may be involved in the back pain experienced by astronauts in microgravity.

  17. Intrathecal immunoglobulin synthesis in patients with symptomatic epilepsy and epilepsy of unknown etiology ('cryptogenic').

    Science.gov (United States)

    Fauser, S; Soellner, C; Bien, C G; Tumani, H

    2017-09-01

    To compare the frequency of intrathecal immunoglobulin (Ig) synthesis in patients with symptomatic epilepsy and epilepsy of unknown etiology ('cryptogenic'). Patients with epileptic (n = 301) and non-epileptic (n = 10) seizures were retrospectively screened for autochthonous intrathecal Ig synthesis and oligoclonal bands (OCBs) in the cerebrospinal fluid. Intrathecal IgG/OCBs were detected in 8% of patients with epilepsies of unknown etiology, 5% of patients with first seizures of unknown cause and 0-4% of patients with epilepsy due to brain tumors, cerebrovascular disease or other etiologies. Intrathecal IgG/OCBs were not seen in patients with psychogenic seizures. Identical OCBs in serum and cerebrospinal fluid were more common in all patient groups (10-40% depending on underlying etiology). Intrathecal IgG synthesis/OCBs were observed slightly more frequently in patients with 'cryptogenic' epilepsy and with first seizures of unknown etiology than in other patient groups. However, this remained an infrequent finding and thus we could not confirm humoral immunity as a leading disease mechanism in patients with epilepsy in general or with unknown etiology in particular. © 2017 EAN.

  18. Thoracic Nerve Root Entrapment by Intrathecal Catheter Coiling: Case Report and Review of the Literature.

    Science.gov (United States)

    Han, Jing L; Loriaux, Daniel B; Tybout, Caroline; Kinon, Merritt D; Rahimpour, Shervin; Runyon, Scott L; Hopkins, Thomas J; Boortz-Marx, Richard L; Lad, Shivanand P

    2016-03-01

    Intrathecal catheter placement has long-term therapeutic benefits in the management of chronic, intractable pain. Despite the diverse clinical applicability and rising prevalence of implantable drug delivery systems in pain medicine, the spectrum of complications associated with intrathecal catheterization remains largely understudied and underreported in the literature. To report a case of thoracic nerve root entrapment resulting from intrathecal catheter migration. Case report. Inpatient hospital service. A 60-year-old man status post implanted intrathecal (IT) catheter for intractable low back pain secondary to failed back surgery syndrome returned to the operating room for removal of IT pump trial catheter after experiencing relapse of preoperative pain and pump occlusion. Initial attempt at ambulatory removal of the catheter was aborted after the patient reported acute onset of lower extremity radiculopathic pain during the extraction. Noncontrast computed tomography (CT) subsequently revealed that the catheter had ascended and coiled around the T10 nerve root. The patient was taken back to the operating room for removal of the catheter under fluoroscopic guidance, with possible laminectomy for direct visualization. Removal was ultimately achieved with slow continuous tension, with complete resolution of the patient's new radicular symptoms. This report describes a single case report. This case demonstrates that any existing loops in the intrathecal catheter during initial implantation should be immediately re-addressed, as they can precipitate nerve root entrapment and irritation. Reduction of the loop or extrication of the catheter should be attempted under continuous fluoroscopic guidance to prevent further neurosurgical morbidity.

  19. The iDuo Bi-compartmental Knee Replacement: Our Early Experience.

    Directory of Open Access Journals (Sweden)

    Peter Jemmett

    2016-12-01

    Our early results suggest that the iDuo knee is a good option for those with isolated bi-compartmental disease and outcome scores are comparable with those reported for the BKA. This bi-compartmental design may bridge the gap between the uni-compartmental and total knee replacement. The choice between monolithic or modular designs remains in debate. We will continue to use this prosthesis for a carefully selected group of patients.

  20. Functional compartmentalization of the human superficial masseter muscle.

    Directory of Open Access Journals (Sweden)

    Rodrigo A Guzmán-Venegas

    Full Text Available Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM muscle's motor units using high-density surface electromyography (EMGs at different bite force levels. Twenty healthy natural dentate participants (men: 4; women: 16; age 20±2 years; mass: 60±12 kg, height: 163±7 cm were selected from 316 volunteers and included in this study. Using a gnathodynamometer, bites from 20 to 100% maximum voluntary bite force (MVBF were randomly requested. Using a two-dimensional grid (four columns, six electrodes located on the dominant SM, EMGs in the anterior, middle-anterior, middle-posterior and posterior portions were simultaneously recorded. In bite ranges from 20 to 60% MVBF, the EMG activity was higher in the anterior than in the posterior portion (p-value = 0.001.The center of mass of the EMG activity was displaced towards the posterior part when bite force increased (p-value = 0.001. The topographic distribution of EMGs was more homogeneous at high levels of MVBF (p-value = 0.001. The results of this study show that the superficial masseter is organized into three functional compartments: an anterior, a middle and a posterior compartment. However, this compartmentalization is only seen at low levels of bite force (20-60% MVBF.

  1. Analytical properties of a three-compartmental dynamical demographic model

    Science.gov (United States)

    Postnikov, E. B.

    2015-07-01

    The three-compartmental demographic model by Korotaeyv-Malkov-Khaltourina, connecting population size, economic surplus, and education level, is considered from the point of view of dynamical systems theory. It is shown that there exist two integrals of motion, which enables the system to be reduced to one nonlinear ordinary differential equation. The study of its structure provides analytical criteria for the dominance ranges of the dynamics of Malthus and Kremer. Additionally, the particular ranges of parameters enable the derived general ordinary differential equations to be reduced to the models of Gompertz and Thoularis-Wallace.

  2. Compartmental modeling approach to the radiation dosimetry of radiolabeled antibody

    International Nuclear Information System (INIS)

    Zanzonico, P.B.; Bigler, R.E.; Primus, F.J.; Alger, E.; DeJager, R.; Stowe, S.; Ford, E.; Brennan, K.; Goldenberg, D.M.

    1986-01-01

    Essential for the calculation of absorbed doses from systemically administered radiolabled antibody is the determination of the total number of nuclear transformations in specified source regions. Compartmental analysis (using biodistribution data augmented with a priori physiological information), unlike simply integrating empirical time-activity curves, may enable one to calculate the cumulated activity in unsampled as well as sampled source regions. These may include microscopic source regions (e.g. the intracellular space, cell surface, and extracellular space) important for microdosimetry calculations. Of particular importance is the interaction between the anti-tumor antibody and the tumor antigen. 30 references, 9 figures, 2 tables

  3. Immunoscintigraphy and radioimmunotherapy in Cuba: experiences with labeled monoclonal antibodies for cancer diagnosis and treatment (1993-2013).

    Science.gov (United States)

    Peña, Yamilé; Perera, Alejandro; Batista, Juan F

    2014-01-01

    INTRODUCTION The availability of monoclonal antibodies in Cuba has facilitated development and application of innovative techniques (immunoscintigraphy and radioimmunotherapy) for cancer diagnosis and treatment. Objective Review immunoscintigraphy and radioimmunotherapy techniques and analyze their use in Cuba, based on the published literature. In this context, we describe the experience of Havana's Clinical Research Center with labeled monoclonal antibodies for cancer diagnosis and treatment during the period 1993-2013. EVIDENCE ACQUISITION Basic concepts concerning cancer and monoclonal antibodies were reviewed, as well as relevant international and Cuban data. Forty-nine documents were reviewed, among them 2 textbooks, 34 articles by Cuban authors and 13 by international authors. All works published by the Clinical Research Center from 1993 through 2013 were included. Bibliography was obtained from the library of the Clinical Research Center and Infomed, Cuba's national health telematics network, using the following keywords: monoclonal antibodies, immunoscintigraphy and radioimmunotherapy. RESULTS Labeling the antibodies (ior t3, ior t1, ior cea 1, ior egf/r3, ior c5, h-R3, 14F7 and rituximab) with radioactive isotopes was a basic line of research in Cuba and has fostered their use as diagnostic and therapeutic tools. The studies conducted demonstrated the good sensitivity and diagnostic precision of immunoscintigraphy for detecting various types of tumors (head and neck, ovarian, colon, breast, lymphoma, brain). Obtaining different radioimmune conjugates with radioactive isotopes such as 99mTc and 188Re made it possible to administer radioimmunotherapy to patients with several types of cancer (brain, lymphoma, breast). The objective of 60% of the clinical trials was to determine pharmacokinetics, internal dosimetry and adverse effects of monoclonal antibodies, as well as tumor response; there were few adverse effects, no damage to vital organs, and a positive

  4. Severe neurotoxicity associated to the intrathecal of metotreaxate and cytanobina in patients with tenkenic or lymphoma

    International Nuclear Information System (INIS)

    Garcia Tena, J.; Lopez Andreu, J.A.; Verdeguer, A.; Menor, F.; Mulas, F.; Ferris, J.

    1995-01-01

    The prophylaxis and treatment of central nervous system leukemia and lymphoma with intrathecal chemotherapy have been related to severe neurotoxicity. At least 35 cases of subacute myeloencepthalopathy with transient a permanent paraplegia/quadriplegia have been reported. A comprehensive view of the literature and a description of a new case of intrathecal chemotherapy-related neurotoxicity is made. Among the cases reported in the literature, complete recovery was observed in 9 patients, partial recovery with variable sequelae in 6, no recovery in 8 and 13 patients died. Early cerebrospinal fluid exchange seems to be the only potentially effective approach although not universally accepted. The rarity of this toxicity and the proved efficacy of the intrathecal chemotherapy justify its use

  5. Intrathecal isobaric ropivacaine-fentanyl versus intrathecal isobaric bupivacaine-fentanyl for labor analgesia: A controlled comparative double-blinded study

    Directory of Open Access Journals (Sweden)

    Meenoti Pramod Potdar

    2014-01-01

    Full Text Available Context: Neuraxial analgesia and walking epidural is the popular method of practicing labor analgesia. The combination of local anesthetic and opioid is advantageous as it prolongs the duration of labor analgesia. Ropivacaine is the newer local anesthetic agent having lesser motor effects and toxic effects hence would be preferred for labor analgesia. Aims: The primary objective of the study was to assess the duration of analgesia of the intrathecal drug. The secondary objective was the assessment of onset, fixation of analgesia, motor weakness, ambulation, sedation, incidence of side-effects, maternal, and neonatal outcomes. Settings and Design: This is prospective, randomized, controlled, double-blinded, study of 120 patients consenting for labor analgesia. Subjects and Methods: A total of 120 primiparas with a singleton pregnancy in active labor who were given combined spinal epidural (CSE were included in the study. These patients were randomly allocated to three groups of 40 each and received CSE. Group F-received 25 μcg fentanyl intrathecally. Group BF-received 25 μcg fentanyl with 2.5 mg isobaric bupivacaine intrathecally. Group RF-received 25 μcg fentanyl with 2.5 mg isobaric ropivacaine intrathecally. Statistical Analysis Used: Correlations among different measurements were assessed using Pearson′s correlation coefficients, P <0.05 was considered to be statistically significant. Results: The three groups show comparable demographic data and obstetric parameters. The duration of spinal analgesia was significantly greater with Group RF 106.63 ± 17.99 min and Group BF 111.75 ± 23.58 min than the control Group F which was 60 ± 10.39 min with P = 0.001, but were comparable for Group BF and RF. The secondary outcome was comparable in all the three groups. Conclusions: The addition of bupivacaine or ropivacaine to fentanyl intrathecally increased duration and quality of analgesia, did not affect ambulation and bearing down. The

  6. Compartmentation and equilibration of abscisic acid in isolated Xanthium cells

    International Nuclear Information System (INIS)

    Bray, E.A.; Zeevaart, J.A.D.

    1986-01-01

    The compartmentation of endogenous abscisic acid (ABA), applied (+/-)-[ 3 H]ABA, and (+/-)-trans-ABA was measured in isolated mesophyll cells of the Chicago strain of Xanthium strumarium L. The release of ABA to the medium in the presence or absence of DMSO was used to determine the equilibration of ABA in the cells. It was found that a greater percentage of the (+/-)-[ 3 H]ABA and the (+/-)-trans-ABA was released into the medium than of the endogenous ABA, indicating that applied ABA did not equilibrate with the endogenous material. Therefore, in further investigations only the compartmentation of endogenous ABA was studied. Endogenous ABA was released from Xanthium cells according to the pH gradients among the various cellular compartments. Thus, darkness, high external pH, KNO 2 , and drought-stress all increased the efflux of ABA from the cells. Efflux of ABA from the cells in the presence of 0.6 M mannitol occurred within 30 seconds, but only 8% of the endogenous material was released during the 20 minute treatment

  7. The monitoring of relative changes in compartmental compliances of brain

    International Nuclear Information System (INIS)

    Kim, Dong-Joo; Carrera, Emmanuel; Castellani, Gianluca; Zweifel, Christian; Smielewski, Peter; Pickard, John D; Czosnyka, Marek; Kasprowicz, Magdalena; Lavinio, Andrea; Sutcliffe, Michael P F

    2009-01-01

    The study aimed to develop a computational method for assessing relative changes in compartmental compliances within the brain: the arterial bed and the cerebrospinal space. The method utilizes the relationship between pulsatile components in the arterial blood volume, arterial blood pressure (ABP) and intracranial pressure (ICP). It was verified by using clinical recordings of intracranial pressure plateau waves, when massive vasodilatation accompanying plateau waves produces changes in brain compliances of the arterial bed (C a ) and compliance of the cerebrospinal space (C i ). Ten patients admitted after head injury with a median Glasgow Coma Score of 6 were studied retrospectively. ABP was directly monitored from the radial artery. Changes in the cerebral arterial blood volume were assessed using Transcranial Doppler (TCD) ultrasonography by digital integration of inflow blood velocity. During plateau waves, ICP increased (P = 0.001), CPP decreased (P = 0.001), ABP remained constant (P = 0.532), blood flow velocity decreased (P = 0.001). Calculated compliance of the arterial bed C a increased significantly (P = 0.001); compliance of the CSF space C i decreased (P = 0.001). We concluded that the method allows for continuous monitoring of relative changes in brain compartmental compliances. Plateau waves affect the balance between vascular and CSF compartments, which is reflected by the inverse change of compliance of the cerebral arterial bed and global compliance of the CSF space

  8. Effects of intrathecal lidocaine on hyperalgesia and allodynia following chronic constriction injury in rats.

    Science.gov (United States)

    Tian, Jie; Gu, Yiwen; Su, Diansan; Wu, Yichao; Wang, Xiangrui

    2009-02-01

    The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain-relief effects, and the influence of this treatment on the body and tissues. Male Sprague-Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35 mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. Two animals in the group receiving 35 mg/kg lidocaine developed pulmonary oedema and died. Behavioral tests indicated that 6.5, 15, and 35 mg/kg intrathecal lidocaine showed different degrees of reversal of thermal hyperalgesia, and lasted for 2-8 days, while 2 mg/kg lidocaine did not. The inhibition of tactile allodynia was only observed in rats receiving 15 and 35 mg/kg lidocaine, and the anti-allodynic effects were identical in these two groups. Histopathologic examinations on the spinal cords revealed mild changes in rats receiving 2-15 mg/kg lidocaine. However, lesions were severe after administration of 35 mg/kg lidocaine. These findings indicate that intrathecal lidocaine has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35 mg/kg. Considering the ratio between useful effects and side effects, doses of 15 mg/kg are suitable for intrathecal injection for relief of neuropathic pain.

  9. Transdermal nitroglycerine enhances postoperative analgesia of intrathecal neostigmine following abdominal hysterectomies

    Directory of Open Access Journals (Sweden)

    Fareed Ahmed

    2010-01-01

    Full Text Available This study was carried out to assess the effect of nitroglycerine (transdermal on intrathecal neostigmine with bupivacaine on postoperative analgesia and note the incidence of adverse effects, if any. After taking informed consent, 120 patients of ASA Grade I and II were systematically randomised into four groups of 30 each. Patients were premedicated with midazolam 0.05 mg/kg intravenously and hydration with Ringer′s lactate solution 10ml/kg preoperatively in the holding room. Group I patients received Intrathecal injection of 15 mg bupivacaine with 1ml of normal saline and transdermal placebo patch. Group II patients received Intrathecal injection of 15 mg bupivacaine with 5 mcg of neostigmine and transdermal placebo patch. Group III patients received Intrathecal injection of 15 mg bupivacaine with 1ml of normal saline with transdermal nitroglycerine patch (5 mg/24 hours. Group IV patients received Intrathecal injection of 15 mg bupivacaine with 5mcg of neostigmine and transdermal nitroglycerine patch (5 mg/24 hours, applied on a non anaesthetised area after 20 minutes. Groups were demographically similar and did not differ in intraoperative characteristics like sensory block, motor block, haemodynamic parameters and SpO 2 . The mean duration of analgesia was 202.17 minutes, 407.20 minutes, 207.53 minutes and 581.63 minutes in control group (I, neostigmine group (II, nitroglycerine group (III and nitroglycerine neostigmine group (IV respectively (P< 0.01. To conclude, our results show that transdermal nitroglycerine itself does not show any analgesic potential but it enhances the analgesic potential of intrathecal neostigmine.

  10. Intrathecal Catheterization and Drug Delivery in Guinea Pigs: A Small-animal Model for Morphine-evoked Granuloma Formation.

    Science.gov (United States)

    Eddinger, Kelly A; Rondon, Eric S; Shubayev, Veronica I; Grafe, Marjorie R; Scadeng, Miriam; Hildebrand, Keith R; Page, Linda M; Malkmus, Shelle A; Steinauer, Joanne J; Yaksh, Tony L

    2016-08-01

    Intrathecal infusion of opioids in dogs, sheep, and humans produces local space-occupying masses. To develop a small-animal model, the authors examined effects of intrathecal catheterization and morphine infusion in guinea pigs. Under isoflurane, polyethylene or polyurethane catheters were advanced from the cisterna magna to the lumbar enlargement. Drugs were delivered as a bolus through the externalized catheter or continuously by subcutaneous minipumps. Hind paw withdrawal to a thermal stimulus was assessed. Spinal histopathology was systematically assessed in a blinded fashion. To assist in determining catheter placement, ex vivo images were obtained using magnetic resonance imaging in several animals. Canine spinal tissue from previous intrathecal morphine studies was analyzed in parallel. (1) Polyethylene (n = 30) and polyurethane (n = 25) catheters were implanted in the lumbar intrathecal space. (2) Bolus intrathecal morphine produced a dose-dependent (20 to 40 μg/10 μl) increase in thermal escape latencies. (3) Absent infusion, a catheter-associated distortion of the spinal cord and a fibrotic investment were noted along the catheter tract (polyethylene > polyurethane). (4) Intrathecal morphine infusion (25 mg/ml/0.5 μl/h for 14 days) resulted in intrathecal masses (fibroblasts, interspersed collagen, lymphocytes, and macrophages) arising from meninges proximal to the catheter tip in both polyethylene- and polyurethane-catheterized animals. This closely resembles mass histopathology from intrathecal morphine canine studies. Continuous intrathecal infusion of morphine leads to pericatheter masses that morphologically resemble those observed in dogs and humans. This small-animal model may be useful for studying spinal drug toxicology in general and the biology of intrathecal granuloma formation in particular.

  11. Practical considerations and patient selection for intrathecal drug delivery in the management of chronic pain

    Directory of Open Access Journals (Sweden)

    Saulino M

    2014-11-01

    Full Text Available Michael Saulino,1,2 Philip S Kim,3,4 Erik Shaw5 1MossRehab, Elkins Park, PA, USA; 2Department of Rehabilitation Medicine, Jefferson Medical College, Philadelphia, PA, USA; 3Helen F Graham Cancer Center, Christiana Care Health System, Newark, DE, USA; 4Center for Interventional Pain Spine, LLC., Bryn Mawr, PA, USA; 5Shepherd Pain Institute, Shepherd Center, Atlanta, GA, USA Abstract: Chronic pain continues to pose substantial and growing challenges for patients, caregivers, health care professionals, and health care systems. By the time a patient with severe refractory pain sees a pain specialist for evaluation and management, that patient has likely tried and failed several nonpharmacologic and pharmacologic approaches to pain treatment. Although relegated to one of the interventions of “last resort”, intrathecal drug delivery can be useful for improving pain control, optimizing patient functionality, and minimizing the use of systemic pain medications in appropriately selected patients. Due to its clinical and logistical requirements, however, intrathecal drug delivery may fit poorly into the classic pain clinic/interventional model and may be perceived as a "critical mass" intervention that is feasible only for large practices that have specialized staff and appropriate office resources. Potentially, intrathecal drug delivery may be more readily adopted into larger practices that can commit the necessary staff and resources to support patients' needs through the trialing, initiation, monitoring, maintenance, and troubleshooting phases of this therapy. Currently, two agents – morphine and ziconotide – are approved by the United States Food and Drug Administration for long-term intrathecal delivery. The efficacy and safety profiles of morphine have been assessed in long-term, open-label, and retrospective studies of >400 patients with chronic cancer and noncancer pain types. The efficacy and safety profiles of ziconotide have been

  12. Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Muriel, F.S.; Svarch, E.; Pavlovsky, S.

    1983-01-01

    In acute lymphoblastic leukemia, central nervous system prophylaxis with irradiation plus intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity was recognized mainly in children as CT scan abnormalities and neuropsychologic alterations. Two questions were analyzed: (1) Will further doses of i.t. methotraxate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse. (2) Is i.t. MTX-DMT given during induction and maintenance as effective as cranium irradiation plus i.t. MTX-DMT. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count 50,000, it was 16% in the treated group and 19% in the control group. These patients were compared with patients which had received 3 doses of i.t. MTX-DMT alone during induction, 3 doses weekly during the first month of remission, and quarterly thereafter. The incidence of leukemia at 60 mo in patients with a WBC count 50,000 at 48 mo was 28% and 42% in the irradiated and nonirradiated group respectively. Complete remission remained at 15% and 16% respectively of patients disease-free at 48 mo. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) use of i.t. MTX-DMT alone compares with cranial irradiation plus i.t. MTX-DMT in incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count < 50.000 were significantly longer in those without cranial irradiation

  13. Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Nestor, Marika, E-mail: marika.nestor@bms.uu.s [Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala (Sweden); Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, S-751 85 Uppsala (Sweden); Sundstroem, Magnus [Unit of Molecular Pathology, Department of Genetics and Pathology, Uppsala University (Sweden); Anniko, Matti [Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala (Sweden); Tolmachev, Vladimir [Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, S-751 85 Uppsala (Sweden)

    2011-01-15

    Aim: The monoclonal antibody cetuximab, targeting the epidermal growth factor receptor (EGFR), is a promising molecular targeting agent to be used in combination with radiation for anticancer therapy. In this study, effects of cetuximab in combination with alpha-emitting radioimmunotherapy (RIT) in a panel of cultured human squamous cell carcinomas (SCCs) were assessed. Methods: SCC cell lines were characterized and treated with cetuximab in combination with anti-CD44v6 RIT using the astatinated chimeric monoclonal antibody U36 ({sup 211}At-cMAb U36). Effects on {sup 211}At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells. Results: Cetuximab in combination with {sup 211}At-cMAb U36 mediated increased growth inhibition compared to RIT or cetuximab alone in two cell lines. However, cetuximab also mediated radioprotective effects compared to RIT alone in two cell lines. The radioprotective effects occurred in the cell lines in which cetuximab clearly inhibited cell growth during radiation exposure. Cetuximab treatment also influenced {sup 211}At-cMAb-U36 uptake and internalization, suggesting interactions between CD44v6 and EGFR. Conclusions: Results from this study demonstrate the vast importance of further clarifying the mechanisms of cetuximab and radiation response, and the relationship between EGFR and suitable RIT targets. This is important not only in order to avoid potential radioprotective effects, but also in order to find and utilize potential synergistic effects from these combinations.

  14. Radioimmunotherapy. Dose calculation and radionuclides used in treatment; Radioimmunoterapia. Hoidon radionuklidit ja annoslaskenta

    Energy Technology Data Exchange (ETDEWEB)

    Savolainen, S [Helsinki Univ. (Finland). Dept. of Physics; Kairemo, K [Helsinki Univ. (Finland). Dept. of Clinical Chemistry; Liewendahl, K [Helsinki Univ. Central Hospital (Finland). Dept. of Isotopes; Rannikko, S [Finnish Centre for Radiation and Nuclear Safety, Helsinki (Finland)

    1995-10-01

    In radioimmunotherapy (RIT) monoclonal antibodies to cancer-associated antigens can be utilized for the transport of therapeutic radioisotopes to cancer cells. Intravenous administration of radiolabelled antibody is a potentially curative form of therapy in hematological amignancies as circulating antibodies have easy access to tumour sites. Intravenous RIT is less effective in the treatment of solid tumours because of the low fractional uptake of the injected dose, particularly in the central parts of tumours. In solid tumours more promising results have been achieved by local RIT applications. The choice of radiation - {alpha}, {beta} or {gamma} - will depend of the characteristics of the tumour. The importance of radiation delivered by Auger electrons has been largely underestimated in the past, but recent research has resulted in a remarkable reassessment of this issue significantly influencing the selection of radioisotopes for RIT. Research is now being focused on the therapeutic aspects of different isotopes and microdosimetric problems. There are now good prospects of RIT becoming an important form of cancer treatment before year 2000. (orig.) (78 refs., 3 figs., 1 tab.).

  15. Development of dosimetric approaches to treatment planning for radioimmunotherapy. DOE annual report

    International Nuclear Information System (INIS)

    1998-01-01

    The objective of quantitative imaging is to Provide pharmacokinetic information for patients that is analogous to that provided by biodistribution studies in mice. Radio nuclide images depict the distribution of labeled antibodies in-vivo; thus the amount of radio nuclide in a specific organ or site can be estimated by relating the counts detected in a defined region of interest to the total radio nuclide content. This pharmacokinetic information can be used to obtain definitive and relevant answers to basic questions of importance for optimizing radioimmunoimaging and radioimmunotherapy and, in addition, can provide a data base from which to calculate the distribution of radiation absorbed doses. The projects supported by this program routinely employ quantitative imaging in evaluating therapies. Quantitative imaging is performed by a certified nuclear medicine technician using the Siemens gamma camera interfaced with the microVAX II. The technician processes the imaging data and obtains pharmacokinetic information from it using programs developed by us and others. During this grant period project staff have acquired and analyzed a large amount of data on the pharmacokinetics, dosimetry and toxicity of radiolabeled monoclonal therapy. Important dosimetry data on the whole body, marrow and tumor doses are available and all studies are archived so that they can be retrospectively analyzed

  16. Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas

    International Nuclear Information System (INIS)

    Nestor, Marika; Sundstroem, Magnus; Anniko, Matti; Tolmachev, Vladimir

    2011-01-01

    Aim: The monoclonal antibody cetuximab, targeting the epidermal growth factor receptor (EGFR), is a promising molecular targeting agent to be used in combination with radiation for anticancer therapy. In this study, effects of cetuximab in combination with alpha-emitting radioimmunotherapy (RIT) in a panel of cultured human squamous cell carcinomas (SCCs) were assessed. Methods: SCC cell lines were characterized and treated with cetuximab in combination with anti-CD44v6 RIT using the astatinated chimeric monoclonal antibody U36 ( 211 At-cMAb U36). Effects on 211 At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells. Results: Cetuximab in combination with 211 At-cMAb U36 mediated increased growth inhibition compared to RIT or cetuximab alone in two cell lines. However, cetuximab also mediated radioprotective effects compared to RIT alone in two cell lines. The radioprotective effects occurred in the cell lines in which cetuximab clearly inhibited cell growth during radiation exposure. Cetuximab treatment also influenced 211 At-cMAb-U36 uptake and internalization, suggesting interactions between CD44v6 and EGFR. Conclusions: Results from this study demonstrate the vast importance of further clarifying the mechanisms of cetuximab and radiation response, and the relationship between EGFR and suitable RIT targets. This is important not only in order to avoid potential radioprotective effects, but also in order to find and utilize potential synergistic effects from these combinations.

  17. Aptamer-based radioimmunotherapy. The feasibility and prospect in cancer therapy

    International Nuclear Information System (INIS)

    Li Li; Hui Wang; Shujie Liao; Wei Li; Weina Zhang; Dan Liu; Bo Cao; Shixuan Wang; Ding Ma; Wei Wang; Nanfang Hospital, Southern Medical University, Guangzhou; Xiangshang Xu; Keng Shen

    2011-01-01

    Radioimmunotherapy (RIT) has emerged as an attractive and promising strategy for the management of malignant diseases. It has been proven to be quite effective in the treatment of numerous tumors, such as non-Hodgkin lymphoma, metastatic prostate cancer, melanoma, thyroid cancer, colon cancer and so on. The RIT currently used is mainly based on monoclonal antibodies to recognize target antigens. As antibodies are large molecules, this method of RIT has some limitations in in vivo use, such as the immunogenicity, the high costs and low efficiency of production. Aptamer is discovered and selected by SELEX technology. As specific recognizers and binders, aptamers and antibodies have such a close similarity as to be interchangeable to some extent. But, aptamers have many advantages over antibodies: higher affinity and specificity, smaller molecular weight, more easily synthesized and modified, more rapidly penetrating into tumors, higher tumor-to-blood distribution ratio and more easily to be cleared. In addition, since aptamer has almost no immunogenicity in vivo, it can be repeatedly administered. Thus, we believe that aptamer-based RIT will be a feasible and promising way to treat human cancers, and it might display better results in cancer treatment than antibody-based RIT. In conclusion, aptamer-based RIT is hopeful to become a key therapeutics in cancer radiotherapy in the near future. (author)

  18. Development of dosimetric approaches to treatment planning for radioimmunotherapy. Annual report 1989--1990

    Energy Technology Data Exchange (ETDEWEB)

    DeNardo, S.J.

    1990-12-31

    The objective of quantitative imaging is to provide pharmacokinetic information for patients that is analogous to that provided by biodistribution studies in mice. Radionuclide images depict the distribution of labeled antibodies in-vivo; thus the amount of radionuclide in a specific organ or site can be estimated by relating the counts detected in a defined region of interest to the total radionuclide content. This pharmacokinetic information can be used to obtain definitive and relevant answers to basic questions of importance for optimizing radioimmunoimaging and radioimmunotherapy and, in addition, can provide a data base from which to calculate the distribution of radiation absorbed doses. The research employs quantitative imaging in evaluating therapies. Quantitative imaging is performed by a certified nuclear medicine technician using the Siemens gamma camera interfaced with the microVAX II. The technician processes the imaging data and obtains pharmacokinetic information from it using programs developed by the authors and others. A large amount of data has been acquired and analyzed on the pharmacokinetics, dosimetry and toxicity of radiolabeled monoclonal therapy. Important dosimetry data on the whole body, marrow and tumor doses are available and all studies are archived so that they can be retrospectively analyzed. Although the radiation absorbed doses delivered to tumor sites were modest, significant biological responses were found.

  19. Role of nuclear medicine in the treatment of malignant gliomas: the locoregional radioimmunotherapy approach

    International Nuclear Information System (INIS)

    Riva, P.; Franceschi, G.; Riva, N.; Casi, M.; Santimaria, M.; Adamo, M.

    2000-01-01

    The high-grade malignant gliomas (anaplastic astrocytomas and glioblastoma) have a very bad prognosis since the available methods of treatment (surgery, radiotherapy and chemotherapy) are unable to control the progression of the disease for long. The use of specific monoclonal antibodies labelled with a suitable isotope (iodine-131 or yttrium-90) represents an effective approach to hamper tumour regrowth. Some authors have injected the antibodies intravenously, or have tried to increase the tumour/background ratio with the avidin/ biotin system. In many cases the labelled monoclonal antibodies were injected directly into the tumoral bed after the operation. The authors' experiences concern a quite large locoregional radioimmunotherapy study which was performed by using antitenascin antibodies labelled initially with 131 I and more recently with 90 Y. The clinical results demonstrate the ability of this technique to control, for a long time, the growth of these tumours. The glioblastoma median survival was prolonged to 25 months ( 131 I group) or 31 months ( 90 Y group). The response rate (which comprises PR, CR and NED) was 47.1% (glioblastoma 131 I group) or 40% (glioblastoma 90 Y group). In many cases a significant tumour shrinking effect was radiologically demonstrated. The use of 90 Y proved more favourable in bulky lesions, and reduced the radioprotection problems. (orig.)

  20. Preparation and biological evaluation of {sup 177}Lu conjugated PR81 for radioimmunotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Salouti, Mojtaba, E-mail: saloutim@yahoo.com [Department of Biology, Faculty of Sciences, Zanjan Branch, Islamic Azad University, Zanjan 45156-58145 (Iran, Islamic Republic of); Babaei, Mohammad Hossein [Nuclear Biomolecule Laboratory, Radioisotope Department, Nuclear Science and Technology Research Institute, Tehran 14144-1339 (Iran, Islamic Republic of); Rajabi, Hossein [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111 (Iran, Islamic Republic of); Rasaee, Mohammad javad [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111 (Iran, Islamic Republic of)

    2011-08-15

    Aim: PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lutetium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer. Materials and Methods: The radiochemical purity and in vitro stability of {sup 177}Lu labeled PR81 was determined by instant thin layer chromatography. The immunoreactivity and cell toxicity of the complex were tested on MCF7 cell line. The biodistribution and scintigraphy studies were performed in BALB/c mice with breast tumor. Results: The radiochemical purity was 91.2{+-}3.8% after 2 h. The in vitro stabilities in phosphate buffer and human blood serum were 83.1{+-}3.4% and 76.2{+-}3.6% at 96 h, respectively. The immunoreactivity of the complex was 83.4{+-}2.4%. The cell toxicity study showed that the complex inhibited 85.2{+-}3.4% growth of MCF7 cells at a concentration of 2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity. Conclusion: The results showed that one may consider {sup 177}Lu-DOTA-PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which needs further investigations.

  1. Monoclonal antibodies to the pretargeting approach: Developments in the radiopharmaceuticals for radioimmunotherapy

    International Nuclear Information System (INIS)

    Chinol, M.

    2001-01-01

    In recent years, large experience has been accrued through the clinical application of radiolabelled monoclonal antibodies in the diagnosis and therapy of malignant disorders. While radioimmunoscintigraphy has established its role in the nuclear medicine practice, radioimmunotherapy has thus far gained limited acceptance mainly due to the low amount of radioactivity that can be targeted to the tumour and to the myelotoxicity which is typically the dose limiting factor. In an attempt to overcome the low uptake of label by the tumour and improve the tumour-to-blood ratio, various studies have examined the concept of tumour pretargeting based on the separate protocols, especially the 3-step approach, with respect to the use of directly labelled antibodies, lies in the lower toxicity observed which has allowed to administer high doses of therapeutic radionuclides, such as Y-90, without bone marrow toxicity. Pilot studies, applied to the treatment of advanced stage tumours, have shown that this approach interferes with the progression of tumours and produce tumours regression in patients no longer responsive to other conventional therapeutic modalities. The potency of pretargeting based on the avidin/biotin system may be exploited in the near future to convey a variety of cytotoxic substances, other than radioactivity, onto cancer cells. (author)

  2. Intrathecal nalbuphine versus intrathecal fentanyl as adjuvant to 0.5% hyperbaric bupivacaine for orthopedic surgery of lower limbs under subarachnoid block: A comparative evaluation

    Directory of Open Access Journals (Sweden)

    Kumkum Gupta

    2016-01-01

    Full Text Available Background: Subarachnoid block (SAB possesses many benefits with a drawback of short duration of anesthetic action. Intrathecal opioids have been used to enhance the clinical efficiency and duration of action of local anesthetic drugs. The present study was aimed to compare the clinical efficiency of intrathecal fentanyl with nalbuphine as adjuvant to 0.5% hyperbaric bupivacaine for orthopedic surgery of lower limbs. Patients and Methods: Sixty-eight adult patients of American Society of Anesthesiologist physical status I and II of both gender aged 25-65 years were randomized into two groups of 34 each to receive either fentanyl 25 μg (Group I or nalbuphine 2 mg (Group II with 3.5 mL 0.5% hyperbaric bupivacaine, making intrathecal drug volume to 4 mL in each group. Sensory and motor block characteristics and time to first rescue analgesic (intravenous tramadol 100 mg were recorded as the primary end points. Drug-related side effects of pruritus, nausea/vomiting, and respiratory depression were recorded as the secondary outcomes. Results: Both groups were comparable regarding the onset and cephalic extension of block. The time to two dermatome regressions and time for complete motor recovery were significantly prolonged in patients of Group II with statistical significant difference (P < 0.05. Duration of analgesia was also extended in patients of Group II (378.0 ± 35.72 min as compared to Group I (234.0 ± 24.10 min with highly significant difference (P < 0.001. No drug-related side effects were observed in either group. Conclusion: Intrathecal nalbuphine 2 mg as adjuvant to 0.5% bupivacaine was clinically more efficient than fentanyl for enhancing the postoperative analgesia.

  3. Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation

    Science.gov (United States)

    Li, Xiling; Goel, Pragya; Chen, Catherine; Angajala, Varun; Chen, Xun

    2018-01-01

    Postsynaptic compartments can be specifically modulated during various forms of synaptic plasticity, but it is unclear whether this precision is shared at presynaptic terminals. Presynaptic homeostatic plasticity (PHP) stabilizes neurotransmission at the Drosophila neuromuscular junction, where a retrograde enhancement of presynaptic neurotransmitter release compensates for diminished postsynaptic receptor functionality. To test the specificity of PHP induction and expression, we have developed a genetic manipulation to reduce postsynaptic receptor expression at one of the two muscles innervated by a single motor neuron. We find that PHP can be induced and expressed at a subset of synapses, over both acute and chronic time scales, without influencing transmission at adjacent release sites. Further, homeostatic modulations to CaMKII, vesicle pools, and functional release sites are compartmentalized and do not spread to neighboring pre- or post-synaptic structures. Thus, both PHP induction and expression mechanisms are locally transmitted and restricted to specific synaptic compartments. PMID:29620520

  4. The human NAD metabolome: Functions, metabolism and compartmentalization

    Science.gov (United States)

    Nikiforov, Andrey; Kulikova, Veronika; Ziegler, Mathias

    2015-01-01

    Abstract The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD+ and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools. PMID:25837229

  5. Compartmentalization of NO signaling cascade in skeletal muscles

    International Nuclear Information System (INIS)

    Buchwalow, Igor B.; Minin, Evgeny A.; Samoilova, Vera E.; Boecker, Werner; Wellner, Maren; Schmitz, Wilhelm; Neumann, Joachim; Punkt, Karla

    2005-01-01

    Skeletal muscle functions regulated by NO are now firmly established. However, the literature on the compartmentalization of NO signaling in myocytes is highly controversial. To address this issue, we examined localization of enzymes engaged in L-arginine-NO-cGMP signaling in the rat quadriceps muscle. Employing immunocytochemical labeling complemented with tyramide signal amplification and electron microscopy, we found NO synthase expressed not only in the sarcolemma, but also along contractile fibers, in the sarcoplasmic reticulum and mitochondria. The expression pattern of NO synthase in myocytes showed striking parallels with the enzymes engaged in L-arginine-NO-cGMP signaling (arginase, phosphodiesterase, and soluble guanylyl cyclase). Our findings are indicative of an autocrine fashion of NO signaling in skeletal muscles at both cellular and subcellular levels, and challenge the notion that the NO generation is restricted to the sarcolemma

  6. Imaging and compartmental classification of solid pelvic tumours in children

    International Nuclear Information System (INIS)

    Hugosson, C.; Nyman, R.; Jacobsson, B.; Jorulf, H.; McDonald, P.; Sackey, K.

    1996-01-01

    Thirty-five children aged from 1 day to 16 years (median 5 years) with solid pelvic tumours were investigated with US, CT and MR. All three methods gave similar estimates of tumour size. For defining location of the tumours, the pelvis was divided into three midline compartments (anterior, middle and posterior) and a right and left lateral compartment. CT and MR were accurate and equally reliable in determining the tumour location, US was less accurate. Evaluation of confinement to organ of origin was uncertain, regardless of imaging modality. Tissue characteristics with CT and MR did not contribute to the differentiation of the various tumour types, and contrast medium enhancement did not improve the discrimination. Compartmental localization was equally well assessed by CT and MR and, together with sex, was found to correlate with the tumour type. (orig.). With 7 figs., 5 tabs

  7. Compartmental analysis, imaging techniques and population pharmacokinetic. Experiences at CENTIS

    International Nuclear Information System (INIS)

    Hernández, Ignacio; León, Mariela; Leyva, Rene; Castro, Yusniel; Ayra, Fernando E.

    2016-01-01

    Introduction: In pharmacokinetic evaluation small rodents are used in a large extend. Traditional pharmacokinetic evaluations by the two steps approach can be replaced by the sparse data design which may also represent a complicated situation to evaluate satisfactorily from the statistical point of view. In this presentation different situations of sparse data sampling are analyzed based on practical consideration. Non linear mixed effect model was selected in order to estimate pharmacokinetic parameters in simulated data from real experimental results using blood sampling and imaging procedures. Materials and methods: Different scenarios representing several experimental designs of incomplete individual profiles were evaluated. Data sets were simulated based on real data from previous experiments. In all cases three to five blood samples were considered per time point. A combination of compartmental analysis with tumor uptake obtained by gammagraphy of radiolabeled drugs is also evaluated.All pharmacokinetic profiles were analyzed by means of MONOLIX software version 4.2.3. Results: All sampling schedules yield the same results when computed using the MONOLIX software and the SAEM algorithm. Population and individual pharmacokinetic parameters were accurately estimated with three or five determination per sampling point. According with the used methodology and software tool, it can be an expected result, but demonstrating the method performance in such situations, allow us to select a more flexible design using a very small number of animals in preclinical research. The combination with imaging procedures also allows us to construct a completely structured compartmental analysis. Results of real experiments are presented demonstrating the versatility of used methodology in different evaluations. The same sampling approach can be considered in phase I or II clinical trials. (author)

  8. Durable treatment response of relapsing CNS plasmacytoma using intrathecal chemotherapy, radiotherapy, and Daratumumab.

    Science.gov (United States)

    Elhassadi, Ezzat; Murphy, Maurice; Hacking, Dayle; Farrell, Michael

    2018-04-01

    CNS myelomatous involvement is a rare complication of multiple myeloma with dismal outcome. This disease's optimal treatment is unclear. Combined approach of systemic therapy, radiotherapy, and intrathecal injections chemotherapy should be considered and autologous stem cell transplant consolidation is offered to eligible patients. The role of Daratumumab in this disease deserves further evaluation.

  9. Positive experience with intrathecal baclofen treatment in children with severe cerebral palsy

    DEFF Research Database (Denmark)

    Overgård, Tinett Martesen; Kjærsgaard-Hansen, Lars; Søe, Morten

    2015-01-01

    INTRODUCTION: Treatment of severe spasticity and dystonia with intrathecal baclofen (ITB) in children has been shown to be effective and has therefore been employed in the Region of Southern Denmark. The aim of this retrospective study was to analyse the efficacy and adverse events since ITB was ...

  10. Comparison of Major Immunoglobulins Intrathecal Synthesis Patterns in Ecuadorian and Cuban Patients with Angiostrongyliasis

    Science.gov (United States)

    Padilla-Docal, Bárbara; Dorta-Contreras, Alberto J.; Moreira, Juan M.; Martini-Robles, Luiggi; Muzzio-Aroca, Jenny; Alarcón, Fernando; Magraner-Tarrau, María Esther; Bu-Coifiu-Fanego, Raisa

    2011-01-01

    Angiostrongylus cantonensis meningitis was first reported in Cuba in 1981, and it was recently reported in South America. The aim of this paper is to evaluate the intrathecal immunoglobulin synthesis patterns from Cuba's and Ecuador's patients with angiostrongyliasis; 8 Ecuadorian patients from two different outbreaks and 28 Cuban patients were studied. Simultaneous blood and cerebrospinal fluid simples were taken. Immunoglobulin (Ig) A, IgM, IgG, and albumin were quantified by radial immunodiffusion. Corresponding Reibergrams were applied. A three-Ig pattern was the most frequent in the two groups, but IgM was presented in all Ecuadorian young mature patients; however, in the Cuban children, only 12 of 28 patients had intrathecal IgM, but about 90% had an IgA and IgG synthesis at time of later puncture. This indicates that, with a larger amount of parasites ingested, clinical symptoms are more severe, and a higher frequency of intrathecal IgM synthesis could be observed. This is discussed as a similarity with the intrathecal IgM synthesis in African trypanosomiasis. PMID:21363978

  11. Intrathecal sufentanil versus fentanyl for lower limb surgeries - A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Poonam Motiani

    2011-01-01

    Full Text Available Background:To compare the efficacy and safety of intrathecal sufentanil or fentanyl as adjuvants to hyperbaric bupivacaine in patients undergoing major orthopaedic lower limb surgeries in terms of onset and duration of sensory block, motor block and post-operative pain relief. Patients & Methods: Ninety patients were recruited in this Prospective, randomized double blind study to receive either intrathecal sufentanil 5 μg (Group S, fentanyl 25 μg (Group F or normal saline 0.5 ml (Group C as adjuvants to 15 mg of 0.5% hyperbaric bupivacaine. The onset and duration of sensory and motor block were assessed intraoperatively. The pain scores were assessed postoperatively. Duration of complete and effective analgesia was recorded. The incidence of side effects such as nausea, vomiting, pruritus, shivering and PDPH was recorded. Results: The Demographic data, hemodynamic and respiratory parameters were comparable in the three groups. There was a significantly earlier onset and prolonged duration of sensory block in the sufentanil and fentanyl groups. The duration of complete and effective analgesia were also significantly prolonged in the fentanyl and sufentanil groups. Pruritus was noticed in the study groups (Groups S&F. Conclusions: Intrathecal sufentanil (5 μg and fentanyl (25 μg, as adjuvants lead to an earlier onset and prolonged duration of sensory block. The duration of effective analgesia with intrathecal sufentanil and fentanyl as adjuvants to hyperbaric bupivacaine is longer than that of bupivacaine alone.

  12. The effects of intrathecal midazolam on the duration of analgesia in ...

    African Journals Online (AJOL)

    This study was designed to evaluate the effect of 2 mg preservative-free intrathecal midazolam added to spinal bupivacaine during postoperative analgesia, and the incidence of adverse effects, if any, in patients undergoing knee arthroscopies. Method: Fifty consenting American Society of Anesthesiologists (ASA) physical ...

  13. Liposomal Cytarabine Induces Less Neurocognitive Dysfunction Than Intrathecal Methotrexate in an Animal Model

    DEFF Research Database (Denmark)

    Thomsen, Anna M; Gulinello, Maria E; Wen, Jing

    2018-01-01

    Liposomal cytarabine is currently being tested clinically as an alternative to intrathecal (IT) methotrexate (MTX) for preventing relapse within the central nervous system among patients with acute lymphoblastic leukemia. To compare the toxicity and cognitive deficits caused by IT MTX versus lipo...

  14. Catheter Migration After Implantationan Intrathecal Baclofen Infusion Pump for Severe Spasticity: A Case Report

    Directory of Open Access Journals (Sweden)

    Tung-Chou Li

    2008-09-01

    Full Text Available We report a case of intrathecal baclofen infusion pump implantation complicated by migration of the catheter tip. A 55-year-old man required an intrathecal baclofen infusion for severe spasticity 4 years after a cervical spinal cord injury with incomplete tetraparesis. Twelve months after initial implantation of the device, the patient began to experience a recurrence of trunk tightness and spasticity. Subsequent X-ray and computed tomography evaluations of the catheter system revealed pooling of contrast medium outside of the intrathecal distribution in the lumbar subcutaneous region of the back and therefore migration of the pump catheter tip. At surgical revision, emphasis was placed on minimizing the length of catheter outside of the spine and securing the catheter in the supraspinous fascia with a right-angled anchor. The distance between the anchors and the entry point of the catheter into the supraspinous fascia was also reduced to prevent slipping when the patient bends forward. After surgery, the patient's spasticity improved and, 1 year later, he has experienced no further complications during follow-up, requiring an average baclofen dose of 150 mg/day. Here, we describe several surgical methods intended to secure the intrathecal catheter and prevent catheter migration. Other complications related to catheter failure are also highlighted.

  15. Efficacy of intrathecal baclofen delivery in the management of severe spasticity in upper motor neuron syndrome

    NARCIS (Netherlands)

    Rietman, Johan Swanik; Geertzen, J.H.B.

    In the treatment of patients with severe spasticity, intrathecal administration of baclofen (ITB) was introduced in order to exert its effect directly at the receptor sites in the spinal cord, and have better therapeutic efficacy with smaller drug doses compared to oral antispasmodic medications.

  16. CT examination after intrathecal or intraventricular application of metrizamide in 110 patients for neurosurgery

    International Nuclear Information System (INIS)

    Krakow, D.

    1983-01-01

    The CT scans were done in 110 patients for examination of the liquor carrying cerebral brain compartments, especially the cisterns, after intrathecal application of the radiopaque medium metrizamide. The properties of the medium are explained in detail. (orig./MG) [de

  17. Tolerance to continuous intrathecal baclofen infusion can be reversed by pulsatile bolus infusion

    NARCIS (Netherlands)

    Heetla, H. W.; Staal, M. J.; van Laar, T.

    Study design: Pilot study. Objective: To study the effect of pulsatile bolus infusion of intrathecal baclofen (ITB) on daily ITB dose, in patients showing dose increases, probably due to tolerance. Setting: Department of neurology and neurosurgery, University Medical Center Groningen, the

  18. Intrathecal application of autologous bone marrow cell preparations in parkinsonian syndromes

    DEFF Research Database (Denmark)

    Storch, Alexander; Csoti, Ilona; Eggert, Karla

    2012-01-01

    A growing number of patients is treated with intrathecal application of autologous bone marrow cells (aBMCs), but clinical data are completely lacking in movement disorders. We provide first clinical data on efficacy and safety of this highly experimental treatment approach in parkinsonian...

  19. Comparative Study of Intrathecal Dexamethasone with Epinephrine as Adjuvants to Lidocaine in Cesarean Section

    Directory of Open Access Journals (Sweden)

    Fereshteh Naziri

    2013-09-01

    Full Text Available Background: Different additives have been used with local anesthetics to provide prolonged duration of sensory block in spinal anesthesia. The aim of present study was to evaluate the onset and duration of sensory block of intrathecal dexamethasone and epinephrine as adjuvants to lidocaine in patients who were candidate for cesarean section. Materials and Methods: This double-blind clinical trial research was conducted on 90 pregnant women candidate for cesarean section under spinal anesthesia. Patients were randomly allocated to receive intrathecally either 75 mg hyperbaric lidocaine plus 100 μg epinephrine or 75 mg hyperbaric lidocaine plus 4 mg dexamethasone or 75 mg hyperbaric lidocaine. The onset and duration of sensory block as well as postoperative analgesia were assessed. Results: The time to reach the peak sensory block in lidocaine group was shorter than that of other two groups (p<0.001. Duration of sensory block in the control group, dexamethasone group, and epinephrine group were 64.16±7.99 min, 74.79±12.78 min, and 99.30±10.93 min, respectively (p<0.001. Conclusion: The present research shows that intrathecal dexamethasone and intrathecal epinephrine as adjuvant to lidocaine increases sensory block duration in the women candidate for cesarean section.

  20. Intrathecal baclofen therapy in children with intractable spastic cerebral palsy: a cost-effectiveness analysis

    NARCIS (Netherlands)

    Hoving, M.A.; Evers, S.M.A.A.; Ament, A.J.H.A.; van Raak, E.P.M.; Becher, J.G.; Rotteveel, J.; Vles, J.S.H.

    2008-01-01

    In a Dutch national study, we recently established the effectiveness and safety of continuous intrathecal baclofen infusion (CITB) in children with intractable spastic cerebral palsy (CP). Because prospective studies on the cost-effectiveness of CITB in children with spastic CP are lacking, we

  1. Intrathecal baclofen therapy in children with intractable spastic cerebral palsy: a cost-effectiveness analysis.

    NARCIS (Netherlands)

    Hoving, M.A.; Evers, S.M.; Ament, A.J.; Raak, E.P. van; Vles, J.S.; Becher, J.G.; Vermeulen, R.; Brouwer, O.F.; Maathuis, C.G.B.; Catsman-Berrevoets, C.E.; Gerritsen, J.; Geerts, M.J.; Jongerius, P.H.; Nieuwenhuizen, O.F.; Rotteveel, J.J.; Speth, L.A.; Stroink, H.; Ziel, E.G. van der

    2008-01-01

    In a Dutch national study, we recently established the effectiveness and safety of continuous intrathecal baclofen infusion (CITB) in children with intractable spastic cerebral palsy (CP). Because prospective studies on the cost-effectiveness of CITB in children with spastic CP are lacking, we

  2. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Knee joint femorotibial (uni-compartmental) metal... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer porous-coated...

  3. Activities of AREVA Med. Extraction and purification of the 212Pb isotope from Thorium for radio-immunotherapy

    International Nuclear Information System (INIS)

    Miquel, Pierre

    2012-01-01

    After having recalled the definition of radio-immunotherapy (RIT) and the benefits of alpha RIT for the treatment of some cancers, this document explains the choice of the 212-Pb isotope instead of the 212-Bi isotope (the first one has a longer half-life than the second). The Pb isotope in fact progressively transforms itself into the Bi isotope. The production process is evoked with its important steps. A second part reports the first clinic tests performed in the Alabama Centre for the treatment of different cancer (breast, colon, ovarian, pancreas, stomach). Processes and doses are discussed

  4. MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain

    International Nuclear Information System (INIS)

    Eide, Per Kristian; Ringstad, Geir

    2015-01-01

    Recently, the “glymphatic system” of the brain has been discovered in rodents, which is a paravascular, transparenchymal route for clearance of excess brain metabolites and distribution of compounds in the cerebrospinal fluid. It has already been demonstrated that intrathecally administered gadolinium (Gd) contrast medium distributes along this route in rats, but so far not in humans. A 27-year-old woman underwent magnetic resonance imaging (MRI) with intrathecal administration of gadobutrol, which distributed throughout her entire brain after 1 and 4.5 h. MRI with intrathecal Gd may become a tool to study glymphatic function in the human brain

  5. Ultrasound Pulsed-Wave Doppler Detects an Intrathecal Location of an Epidural Catheter Tip: A Case Report.

    Science.gov (United States)

    Elsharkawy, Hesham; Saasouh, Wael; Patel, Bimal; Babazade, Rovnat

    2018-04-01

    Currently, no gold standard method exists for localization of an epidural catheter after placement. The technique described in this report uses pulsed-wave Doppler (PWD) ultrasound to identify intrathecal location of an epidural catheter. A thoracic epidural catheter was inserted after multiple trials with inconclusive aspiration and test dose. Ultrasound PWD confirmed no flow in the epidural space and positive flow in the intrathecal space. A fluid aspirate was positive for glucose, reconfirming intrathecal placement. PWD is a potential tool that can be used to locate the tip of an epidural catheter.

  6. MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain.

    Science.gov (United States)

    Eide, Per Kristian; Ringstad, Geir

    2015-11-01

    Recently, the "glymphatic system" of the brain has been discovered in rodents, which is a paravascular, transparenchymal route for clearance of excess brain metabolites and distribution of compounds in the cerebrospinal fluid. It has already been demonstrated that intrathecally administered gadolinium (Gd) contrast medium distributes along this route in rats, but so far not in humans. A 27-year-old woman underwent magnetic resonance imaging (MRI) with intrathecal administration of gadobutrol, which distributed throughout her entire brain after 1 and 4.5 h. MRI with intrathecal Gd may become a tool to study glymphatic function in the human brain.

  7. Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Muriel, F.S.; Svarch, E.; Pavlovsky, S.; Eppinger-Helft, M.; Braier, J.; Vergara, B.; Garay, G.; Kvicala, R.; Divito, J.M.; Failace, R.

    1983-08-01

    In acute lymphoblastic leukemia, central nervous system prophylaxis with irradiation plus intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity was recognized mainly in children as CT scan abnormalities and neuropsychologic alterations. Two questions were analyzed: (1) Will further doses of i.t. methotraxate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse. (2) Is i.t. MTX-DMT given during induction and maintenance as effective as cranium irradiation plus i.t. MTX-DMT. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count < 50,000 and in the untreated group was 11%. In patients with a WBC count > 50,000, it was 16% in the treated group and 19% in the control group. These patients were compared with patients which had received 3 doses of i.t. MTX-DMT alone during induction, 3 doses weekly during the first month of remission, and quarterly thereafter. The incidence of leukemia at 60 mo in patients with a WBC count < 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. The relapse-free survival at 60 mo was 26% and 41%, respectively, (p < 0.0005). The incidence in patients with a WBC count > 50,000 at 48 mo was 28% and 42% in the irradiated and nonirradiated group respectively. Complete remission remained at 15% and 16% respectively of patients disease-free at 48 mo. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) use of i.t. MTX-DMT alone compares with cranial irradiation plus i.t. MTX-DMT in incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count < 50.000 were significantly longer in those without cranial irradiation.

  8. Intrathecal Pump Exposure to Electromagnetic Interference: A Report of Device Interrogation following Multiple ECT Sessions.

    Science.gov (United States)

    Bicket, Mark C; Hanna, George M

    2016-02-01

    Intrathecal drug delivery systems represent an increasingly common treatment modality for patients with a variety of conditions, including chronic pain and spasticity. Pumps rely on electronic programming to properly control and administer highly concentrated medications. Electromagnetic interference (EMI) is a known exposure that may cause a potential patient safety issue stemming from direct patient injury, pump damage, or changes to pump operation or flow rate. The objective of our case report was to describe an approach to evaluating a patient with a pump prior to and following exposure to EMI from electroconvulsive therapy (ECT), as well as to document findings from device interrogations associated with this event. Case report. Academic university-based pain management center. We present the case of a patient with an intrathecal pump who underwent multiple exposures to EMI in the form of 42 ECT sessions. Interrogation of the intrathecal drug delivery system revealed no safety issues following ECT sessions. At no time were error messages, unintentional changes in event logs, unintentional changes in pump settings, or evidence of pump stall or over-infusion noted. Communication with multiple entities (patient, family, consulting physicians, and device manufacturer) and maintaining vigilance through device interrogation both before and after EMI exposure are appropriate safeguards to mitigate the risk and detect potential adverse events of EMI with intrathecal drug delivery systems. Given the infrequent reports of device exposure to ECT, best practices may be derived from experience with EMI exposure from magnetic resonance imaging (MRI). Although routine EMI exposure to intrathecal drug delivery systems should be avoided, we describe one patient with repeated exposure to ECT without apparent complication.

  9. Intrathecal baclofen in multiple sclerosis and spinal cord injury: complications and long-term dosage evolution.

    Science.gov (United States)

    Draulans, Nathalie; Vermeersch, Kristof; Degraeuwe, Bart; Meurrens, Tom; Peers, Koen; Nuttin, Bart; Kiekens, Carlotte

    2013-12-01

    To investigate the long-term dosage evolution and complication rate of intrathecal baclofen use in multiple sclerosis and spinal cord injury patients, based on a large population with a long follow-up. Retrospective data analysis. Academic hospital. Patients with multiple sclerosis (n = 81) or spinal cord injury (n = 49) having an intrathecal baclofen pump implanted at the University Hospitals Leuven between 1988 and 2009. Medical records review of included patients in August 2010. Complications linked to intrathecal baclofen therapy. Daily baclofen dosage after 3 and 6 months, and yearly thereafter. Data on dosage evolution were analysed using a mixed-effect linear model. In 130 patients with a mean follow-up of 63 months, comprising 797 pump years, 104 complications were recorded. This corresponds to a complication rate of 0.011 per month, equally divided among both groups. Seventy-eight of these complications were catheter related. The mean dosage of baclofen stabilizes two years after implantation at 323 µg/day in the multiple sclerosis population. In spinal cord injury patients the daily dose only stabilizes after five years at a significantly higher dosage (504 µg/day). No significant increase in dosage is seen in the long term. In multiple sclerosis and spinal cord injury patients, intrathecal baclofen therapy has a complication rate of 1% per month. Complications are mainly due to catheter-related problems (74%). The intrathecal baclofen dosage stabilizes in the long term, indicating that long-term tolerance, defined as progressive diminution of the susceptibility to the effects of a drug, is not present.

  10. Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer.

    Science.gov (United States)

    Yang, Lijun; Kress, Benjamin T; Weber, Harris J; Thiyagarajan, Meenakshisundaram; Wang, Baozhi; Deane, Rashid; Benveniste, Helene; Iliff, Jeffrey J; Nedergaard, Maiken

    2013-05-01

    Neurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30-180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.

  11. A new approach to the compartmental analysis in pharmacokinetics: fractional time evolution of diclofenac.

    Science.gov (United States)

    Popović, Jovan K; Atanacković, Milica T; Pilipović, Ana S; Rapaić, Milan R; Pilipović, Stevan; Atanacković, Teodor M

    2010-04-01

    This study presents a new two compartmental model and its application to the evaluation of diclofenac pharmacokinetics in a small number of healthy adults, during a bioequivalence trial. In the model the integer order derivatives are replaced by derivatives of real order often called fractional order derivatives. Physically that means that a history (memory) of a biological process, realized as a transfer from one compartment to another one with the mass balance conservation, is taken into account. This kind of investigations in pharmacokinetics is founded by Dokoumetzidis and Macheras through the one compartmental models while our contribution is the analysis of multi-dimensional compartmental models with the applications of the two compartmental model in evaluation of diclofenac pharmacokinetics. Two experiments were preformed with 12 healthy volunteers with two slow release 100 mg diclofenac tablet formulations. The agreement of the values predicted by the proposed model with the values obtained through experiments is shown to be good. Thus, pharmacokinetics of slow release diclofenac can be described well by a specific two compartmental model with fractional derivatives of the same order. Parameters in the model are determined by the least-squares method and the Particle Swarm Optimization (PSO) numerical procedure is used. The results show that the fractional order two compartmental model for diclofenac is superior in comparison to the classical two compartmental model. Actually this is true in general case since the classical one is a special case of the fractional one.

  12. Evaluating changes in stable chromosomal translocation frequency in patients receiving radioimmunotherapy

    International Nuclear Information System (INIS)

    Wong, Jeffrey Y.C.; Wang Jianyi; Liu An; Odom-Maryon, Tamara; Shively, John E.; Raubitschek, Andrew A.; Williams, Lawrence E.

    2000-01-01

    Purpose: The lack of any consistent correlation between radioimmunotherapy (RIT) dose and observed hematologic toxicity has made it difficult to validate RIT radiation dose estimates to marrow. Stable chromosomal translocations (SCT) which result after radiation exposure may be a biologic parameter that more closely correlates with RIT radiation dose. Increases in the frequency of SCT are observed after radiation exposure and are highly correlated with absorbed radiation dose. SCT are cumulative after multiple radiation doses and conserved through an extended number of cell divisions. The purpose of this study was to evaluate whether increases in SCT frequency were detectable in peripheral lymphocytes after RIT and whether the magnitude of these increases correlated with estimated radiation dose to marrow and whole body. Methods and Materials: Patients entered in a Phase I dose escalation therapy trial each received 1-3 intravenous cycles of the radiolabeled anti-carcinoembryonic antigen (CEA) monoclonal antibody, 90 Y-chimeric T84.66. Five mCi of 111 In-chimeric T84.66 was co-administered for imaging and biodistribution purposes. Blood samples were collected immediately prior to the start of therapy and 5-6 weeks after each therapy cycle. Peripheral lymphocytes were harvested after 72 hours of phytohemagglutinin stimulation and metaphase spreads prepared. Spreads were then stained by fluorescence in situ hybridization (FISH) using commercially available chromosome paint probes to chromosomes 3 and 4. Approximately 1000 spreads were evaluated for each chromosome sample. Red marrow radiation doses were estimated using the AAPM algorithm and blood clearance curves. Results: Eighteen patients were studied, each receiving at least one cycle of therapy ranging from 5-22 mCi/m 2 . Three patients received 2 cycles and two patients received 3 cycles of therapy. Cumulative estimated marrow doses ranged from 9.2 to 310 cGy. Increases in SCT frequencies were observed after

  13. Alpha radioimmunotherapy of multiple myeloma: study of feasibility of ex vivo medullary purge

    International Nuclear Information System (INIS)

    Couturier, O.; Filippovitch, I.V.; Sorokina, N.I.; Cherel, M.; Thedrez, P.; Faivre-Chauvet, A.; Chatal, J.F.

    1997-01-01

    The efficiency of the radioimmunotherapy (RIT) using beta emitters has been clinically proved in treatments of refractory forms of lymphoma. The alpha-emitting radioelements of short half-life are also good potential candidates for RIT, applicable to tumor targets accessible rapidly to the molecules of the radio-immuno-conjugates of size compatible with the short range of alpha particles (50 to 80 μm). The goal of this study is to demonstrate the feasibility of such an approach on a model of myeloma multiply targeted by specific antibodies (B-B4) coupled to bismuth-213 with a chelating agent (benzyl-DTPA). The efficiency of the alpha RIT was evaluated in vitro by means of different techniques analyzing the cellular mortality (the method of limited dilution), the effects on DNA (the testing of micro-nuclei), the analysis of radio-induced apoptosis (the test with acridine orange) and finally the study of non-specific irradiation on population of cells of hematopoietic system un-recognized by the B-B4 benzyl-DTPA) immuno-conjugate. The first results have shown besides the technical feasibility of the project a strong dose dependent cellular mortality with a survival falling rapidly from 28% to around 1 o/oo for a single doubling of the dose from 14.8 kBq / 10 5 cells (0.4 μCi) to 29.6 kBq/10 5 cells (0.8 μCi). The cellular mortality was total at 300 kBq/10 5 cells (8 μCi). The cells in an apoptosis state were evidenced at rates up to 40% for a dose of 7.4 kBq/10 5 cells (0.2 μ Ci). New experiments will permit confirming these first results and determining the irradiation range having in view a utilization in protocols of purging of the myeloma cells on pockets obtained after plasmaphereses

  14. Modern trends in radioimmunotherapy of cancer. Pre targeting strategies for the treatment of ovarian cancer

    International Nuclear Information System (INIS)

    Mcquarrie, S.A.; Xiao, Z.; Mercer, J. R.; Suresh, M. R.

    2001-01-01

    A review of published data on some of the problems associated in treating cancer using radioimmunotherapy is presented. Potential improvements for this type of therapy using pretargeting strategies are discussed and preliminary results on a novel multistep regimen to treat human ovarian cancer are presented. A pretargeting strategy using ovarian cancer are presented. A pretargeting strategy using a biotinylated, anti-CA 125 monoclonal antibody (MAb) to attract biotinylated long-circulating liposomes to the surface of CA 125-expressing ovarian cancer cells, was employed. Confocal laser scanning microscopy and fluorescent labels were used to establish the biodistribution patterns in NIH:OVCAR-3 (CA-125 positive) and SK-OV-3 (CA-125 negative) human ovarian cancer cells. Shedding kinetics of the pretargeted stage were measured using 125 I labeled MAbs. No significant internalization of the MAb used in the pretargeting step was observed by 4 hrs. The antibody was gradually internalized starting at 6 hrs, and most of the labelled MAb was detected in cytoplasm by 24 hrs. Shedding and exocytosis of the antigen-MAb complex was not significant for up to 6-hours following administration of the iodinated MAb. Biotinylated liposomes were shown to specifically target the biotinylated MAb/streptavidin complex on the cell surface. It has been demonstrated that by a three-step pretargeting approach, biotinylated liposomes can be specifically delivered to cells pretargeted with biotinylated MAb/SAv complex. The slow internalization and shedding properties of the two MAbs are ideal for multistep pretargeting methods. A successful multistep linkage was established with the biotinylated MAb B27.1, streptavidin and biotinylated liposomes to OVCAR-3 cells, but not to SK-OV-3 cells

  15. Preparation and characterization of a cysteine based DTPA derivative and its immunoconjugate for radioimmunotherapy

    International Nuclear Information System (INIS)

    Lee, S. Y.; Hong, Y. D.; Choi, S. J.

    2007-01-01

    Recently, radioimmunotherapy (RIT), which uses a monoclonal antibody in addition to a radionuclide to deliver radiation to the sites of a disease, has been extensively studied in this population. To label an antibody with radionuclides it is necessary to introduce a bifunctional chelating agent (BFCA) such a DTPA since it can not be directly labeled to a radionuclide. Therefore, developing a better BFCA for chelating biomolecule and radionuclide has been of major interest in developing radioimmunotherapeutic agents. Thereby, we describe the entantiospecific synthesis of a DTPA analogue which is derived from L-cysteine via bis N-alkylation. And the prepared DTPA derivative was conjugated with human Immunoglobulin G, and a characterization of the immunoconjugate was carried out. N, N-Bis[(tert-butoxycarbonyl)methyl]-2-ethanolamine, N, N-Bis[(tert-butoxycarbony)methyl]-2-bromoethyl-amine, 2-(4-N-Boc-aminophenyl) ethanol, 1-(4-N-Boc-aminophenyl)-2-bromoethane, S-((4-N-Boc-arninophenyl)-1-ethyl)-cysteine methylester, S-(N-Boc-aminophenyl)-Cys(tBu4-DTPA) methylester, -aminophenylethyl-Cys-DTPA, isothiocyanate-cysteine-DTPA, Immunoconjugation with IgG. The optimal molar DTPA derivative to IgG conjugation ratio was 1: 1. At higher amounts of DTPA derivative, amounts of unbounded DTPA derivative increased, and the immunoactivities of immunoconjugates reduced. Gel electrophoresis analysis of the immunoconjugates showed no degradation products or other impurities. This demonstrates the stability of the IgG in DTPA derivative. We established the preparation of an amino acid based DTPA by producing 4-Ethylaniline-DTPA-L-Cysteine. At the same molar this DTPA derivative to IgG, the immunoconjugate has stable molecular structure. In conclusion, 4-Ethylaniline-DTPA-L-Cysteine as a BFCA will show good properties for preparing a specific regional delivery system such as in radiopharmaceuticals, as a radiotracer, and NMR contrasting agents

  16. Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice

    International Nuclear Information System (INIS)

    Sato, Noriko; Saga, Tsuneo; Sakahara, Harumi; Nakamoto, Yuji; Zhao, Songji; Iida, Yasuhiko; Konishi, Junji; Kuroki, Masahide; Endo, Keigo

    2000-01-01

    Myelotoxicity is the main factor which decides the maximum tolerated dose (MTD) in radioimmunotherapy (RIT). Since bone marrow is mostly irradiated from blood radioactivity, enhancing the clearance of unbound circulating radiolabeled antibody is important to reduce myelotoxicity and to increase the MTD. We applied the avidin chase method, which was devised to obtain high tumor-to-background ratios in tumor-targeting, to RIT of experimental liver micrometastases and evaluated its influence on the side effects and therapeutic outcome. Seven days after intrasplenic injection of human colon cancer LS174T cells, nude mice were intravenously injected with biotinylated 131 I-labeled anti-CEA monoclonal antibody (MAb) (24-38 μg, 11.1 MBq). Mice of the chase group then received an intravenous injection of avidin twice (24 and 30 h, 72-115 μg each). Biodistribution, side effects (white blood cell counts and body weight change), and short- and long-term therapeutic effects were determined. Avidin chase markedly accelerated the clearance of radiolabeled MAb from the blood (P<0.0001) and normal tissues, resulting in milder leukocytopenia and body weight loss, both of which recovered earlier than in the non-chase group (P<0.01). The tumor uptake of radiolabeled MAb was also decreased by avidin chase, but the metastases-to-background ratios were increased. Avidin chase gave the therapeutic gain ratio of 1.89. Treated groups with and without avidin chase showed significant therapeutic effects compared to the non-treated group. There was no significant difference in the therapeutic effects between the two treated groups. Avidin chase effectively reduced the side effects of RIT and should increase the MTD. (author)

  17. Radioimmunotherapy for liver micrometastases in mice. Pharmacokinetics, dose estimation, and long-term effect

    International Nuclear Information System (INIS)

    Saga, Tsuneo; Sakahara, Harumi; Nakamoto, Yuji; Sato, Noriko; Zhao, Songji; Iida, Yasuhiko; Konishi, Junji; Kuroki, Masahide; Endo, Keigo

    1999-01-01

    The pharmacokinetics of a therapeutic dose of 131 I-labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nu/nu mice were investigated, along with the long-term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of 131 I-labeled anti-carcinoembryonic antigen (CEA) antibody F33-104 (8.88 MBq/40 μg). The biodistribution of the antibody was determined 1, 2, 4, 6, and 10 days later. The absorbed dose was estimated for three hypothetical tumor diameters; 1,000, 500, and 300 μm. Autoradiography showed a homogeneous distribution of radioactivity in the micrometastases, and a high uptake was maintained until day 6 (24.0% injected dose (ID)/g on day 1 to 17.8% ID/g on day 6), but decreased thereafter. The absorbed doses in the 1,000-, 500-, and 300-μm tumors were calculated to be 19.1, 12.0, and 8.2 Gy, respectively. The intravenous injection of the 131 I-labeled antibody also showed a dose-dependent therapeutic effect (all mice of the nontreated group died, with a mean survival period of 4 weeks; 3 of the 8 mice that received 9.25 MBq survived up to 120 days with no sign of liver metastasis). These data give further evidence that micrometastasis is a good target of radioimmunotherapy, and that an absorbed dose of less than 20 Gy can effectively control small metastatic lesions. (author)

  18. A Prototype {sup 212}Pb Medical Dose Calibrator for Alpha Radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, W.F.; Patil, A.; Russ, W.R.; Newman, J. [CANBERRA Industries, Inc. (United States); Torgue, J. [AREVA Med (United States)

    2015-07-01

    AREVA Med, an AREVA group subsidiary, is developing innovative cancer-fighting therapies involving the use of {sup 212}Pb for alpha radioimmunotherapy. Canberra Industries, the nuclear measurement subsidiary of AREVA, has been working with AREVA Med to develop a prototype measurement system to assay syringes containing a {sup 212}Pb solution following production by an elution system. The relative fraction of emitted radiation from the source associated directly with the {sup 212}Pb remains dynamic for approximately 6 hours after the parent is chemically purified. A significant challenge for this measurement application is that the short half-life of the parent nuclide requires assay prior to reaching equilibrium with progeny nuclides. A gross counting detector was developed to minimize system costs and meet the large dynamic range of source activities. Prior to equilibrium, a gross counting system must include the period since the {sup 212}Pb was pure to calculate the count rate attributable to the parent rather than the progeny. The dynamic state is determined by solving the set of differential equations, or Bateman equations, describing the source decay behavior while also applying the component measurement efficiencies for each nuclide. The efficiencies were initially estimated using mathematical modeling (MCNP) but were then benchmarked with source measurements. The goal accuracy of the system was required to be within 5%. Independent measurements of the source using a high resolution spectroscopic detector have shown good agreement with the prototype system results. The prototype design was driven by cost, compactness and simplicity. The detector development costs were minimized by using existing electronics and firmware with a Geiger-Mueller tube derived from Canberra's EcoGamma environmental monitoring product. The acquisition electronics, communications and interface were controlled using Python with the EcoGamma software development kit on a Raspberry

  19. Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

    International Nuclear Information System (INIS)

    Syme, A M; McQuarrie, S A; Middleton, J W; Fallone, B G

    2003-01-01

    A simple model has been developed to investigate the dosimetry of micrometastases in the peritoneal cavity during intraperitoneal targeted liposomal radioimmunotherapy. The model is applied to free-floating tumours with radii between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources: free liposomes in solution in the peritoneal cavity and liposomes bound to the surface of the micrometastases. It is assumed that liposomes do not penetrate beyond the surface of the tumours and that the total amount of surface antigen does not change over the course of treatment. Integrated tumour doses are expressed as a function of biological parameters that describe the rates at which liposomes bind to and unbind from the tumour surface, the rate at which liposomes escape from the peritoneal cavity and the tumour surface antigen density. Integrated doses are translated into time-dependent tumour control probabilities (TCPs). The results of the work are illustrated in the context of a therapy in which liposomes labelled with Re-188 are targeted at ovarian cancer cells that express the surface antigen CA-125. The time required to produce a TCP of 95% is used to investigate the importance of the various parameters. The relative contributions of surface-bound radioactivity and unbound radioactivity are used to assess the conditions required for a targeted approach to provide an improvement over a non-targeted approach during intraperitoneal radiation therapy. Using Re-188 as the radionuclide, the model suggests that, for microscopic tumours, the relative importance of the surface-bound radioactivity increases with tumour size. This is evidenced by the requirement for larger antigen densities on smaller tumours to affect an improvement in the time required to produce a TCP of 95%. This is because for the smallest tumours considered, the unbound radioactivity is often capable of exerting a tumouricidal effect before the targeting agent has time to accumulate

  20. A model for hematopoietic death in man from irradiation of bone marrow during radioimmunotherapy.

    Science.gov (United States)

    Scott, B R; Dillehay, L E

    1990-11-01

    There are numerous institutions worldwide performing clinical trials of radioimmunotherapy (RIT) for cancer. For RIT, an exponentially decaying radionuclide is attached by using a chelating agent to a specific monoclonal or polyclonal tumour antibody (e.g. antiferritin IgG). The major limitation to RIT is toxicity to normal tissue in organs other than the one containing the tumour (e.g. bone marrow). The focus of this manuscript is on modelling the risk (or probability) of hematopoietic death in man for exponentially decaying patterns of high-energy beta irradiation (e.g. 90Y) of bone marrow by radioimmunoglobulin injected into the blood. The analytical solutions presented are only applicable to protocols for which significant uptake of radioactivity by the bone marrow does not occur, and only for high energy beta emitters. However, the generic equation used to obtain the analytical solutions is applicable to any continuous pattern of high energy beta irradiation. A model called the "normalized dose model" was used to generate calculated values for the LD50 as a function of the effective half-time for the radioimmunoglobulin in the blood. A less complicated empirical model was used to describe the calculated values. This model is presumed to be valid for effective half-times in blood of up to about 20 days. For longer effective half-times, the LD50 can be estimated using the normalized-dose model presented. In this manuscript, we also provide a modified Weibull model that allows estimation of the risk of hematopoietic death for single or multiple injections (in one cycle) of radioimmunoglobulin, for patients with normal susceptibility to irradiation and for patients with heightened susceptibility. With the modified Weibull model, the risk of hematopoietic death depends on the level of medical treatment provided to mitigate radiation injuries.

  1. Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

    Directory of Open Access Journals (Sweden)

    Zaporowska-Stachowiak I

    2014-10-01

    Full Text Available Iwona Zaporowska-Stachowiak,1,2 Grzegorz Kowalski,3 Jacek Łuczak,2 Katarzyna Kosicka,4 Aleksandra Kotlinska-Lemieszek,3 Maciej Sopata,3 Franciszek Główka4 1Chair and Department of Pharmacology, Poznan University of Medical Sciences, Poznan, Poland; 2Palliative Medicine In-patient Unit, University Hospital of Lord's Transfiguration, Poznan University of Medical Sciences, Poznan, Poland; 3Palliative Medicine Chair and Department, Poznan University of Medical Sciences, Poznan, Poland; 4Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznan, Poland Background: Unacceptable adverse effects, contraindications to and/or ineffectiveness of World Health Organization step III "pain ladder" drugs causes needless suffering among a population of cancer patients. Successful management of severe cancer pain may require invasive treatment. However, a patient's refusal of an invasive procedure necessitates that clinicians consider alternative options. Objective: Intrathecal bupivacaine delivery as a viable treatment of intractable pain is well documented. There are no data on rectal bupivacaine use in cancer patients or in the treatment of cancer tenesmoid pain. This study aims to demonstrate that bupivacaine administered rectally could be a step in between the current treatment options for intractable cancer pain (conventional/conservative analgesia or invasive procedures, and to evaluate the effect of the mode of administration (intrathecal versus rectal on the bupivacaine plasma concentration.Cases: We present two Caucasian, elderly inpatients admitted to hospice due to intractable rectal/tenesmoid pain. The first case is a female with vulvar cancer, and malignant infiltration of the rectum/vagina. Bupivacaine was used intrathecally (0.25–0.5%, 1–2 mL every 6 hours. The second case is a female with ovarian cancer and malignant rectal infiltration. Bupivacaine was adminstered rectally (0.05–0.1%, 100 m

  2. Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Harila-Saari, Arja; Grell, Kathrine

    2016-01-01

    We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received...

  3. Compartmentation of sucrose during radial transfer in mature sorghum culm

    Directory of Open Access Journals (Sweden)

    Vietor Donald M

    2007-06-01

    Full Text Available Abstract Background The sucrose that accumulates in the culm of sorghum (Sorghum bicolor (L. Moench and other large tropical andropogonoid grasses can be of commercial value, and can buffer assimilate supply during development. Previous study conducted with intact plants showed that sucrose can be radially transferred to the intracellular compartment of mature ripening sorghum internode without being hydrolysed. In this study, culm-infused radiolabelled sucrose was traced between cellular compartments and among related metabolites to determine if the compartmental path of sucrose during radial transfer in culm tissue was symplasmic or included an apoplasmic step. This transfer path was evaluated for elongating and ripening culm tissue of intact plants of two semidwarf grain sorghums. The metabolic path in elongating internode tissue was also evaluated. Results On the day after culm infusion of the tracer sucrose, the specific radioactivity of sucrose recovered from the intracellular compartment of growing axillary-branch tissue was greater (nearly twice than that in the free space, indicating that sucrose was preferentially transferred through symplasmic routes. In contrast, the sucrose specific radioactivity in the intracellular compartment of the mature (ripening culm tissue was probably less (about 3/4's than that in free space indicating that sucrose was preferentially transferred through routes that included an apoplasmic step. In growing internodes of the axillary branch of sorghum, the tritium label initially provided in the fructose moiety of sucrose molecules was largely (81% recovered in the fructose moiety, indicating that a large portion of sucrose molecules is not hydrolysed and resynthesized during radial transfer. Conclusion During radial transfer of sucrose in ripening internodes of intact sorghum plants, much of the sucrose is transferred intact (without hydrolysis and resynthesis and primarily through a path that includes an

  4. Study of in vivo generators Pb-212/Bi--212 and U-230/Th-226 for alpha radioimmunotherapy

    International Nuclear Information System (INIS)

    Le Du, A.

    2011-01-01

    Alpha-radioimmunotherapy is a promising cancer therapy that uses a-particles vectorized by monoclonal antibody to break down cancerous tumors. The notion of in vivo generator was introduced in 1989 by Leonard Mausner. The concept involves labeling of various molecular carriers (antibodies, peptides, etc) with intermediate half-life generator parents, which after accumulation in the desired tissue generate much shorter half-life daughter radionuclide. This thesis focuses on the study of two in vivo generators potentially interesting for alpha-radioimmunotherapy: Pb-212 / Bi-212 generator and U-230 / Th-226 generator. The first part of this work presents the Pb-212 / Bi-212 generator, two approaches allowing the vectorization. Chelation approach on a protein and an approach by encapsulation in liposomes have been proposed. This last approach appears to be the most interesting. In vitro stability studies have been performed on these labeling. The second part of this work presents the U-230 / Th-226 generator. Studies have first been made to achieve a theoretical model to describe the speciation of Th(IV) in human serum. The efficacy of DTPA as chelating agent for complexation of Th(IV) in human serum could thus be estimated. (author)

  5. Comparative study of clindamycin concentration in the cerebrospinal fluid after intravenous and intrathecal administration in patients with toxoplasmic meningoencephalitis

    Directory of Open Access Journals (Sweden)

    Сергій Петрович Борщов

    2015-07-01

    Full Text Available Aim of the work: to study the difference of clindamycin concentration in CSF at the intravenous and combined (intrathecal + intravenous ways of administration of preparation.Materials and methods: study was carried out at the treatment of 11 HIV-positive patients 27-63 years old (men and women with toxoplasmic meningoencephalitises.There was measured the clindamycin concentration in CSF of every patient after intravenous and combined (intrathecal + intravenous ways of administration of preparation. The determinations of concentration were done by the way of the reverse-phase high-performance liquid chromatography (HPLC with ultraviolet (UV detection. Statistic processing of the received data was carried out using the Wilcoxon criterion.Results of research. There was received the statistically significant increase of clindamycin concentration in CSF of patients in a day after combined (intrathecal + intravenous administration of preparation comparing with an intravenous administration.Conclusions. 1. Intrathecal administration of 150 mg. of clindamycin with 8 mg. of dexamethasone is safe.2. Intrathecal administration of 150 mg. of clindamycin with 8 mg. of dexamethasone in combination with an intravenous administration of preparation leads to statistically significant increase of clindamycin concentration in CSF at least during a day after injection.3. Intrathecal administration of clindamycin with dexamethasone in offered doses can be recommended for treatment of meningoencephalitises that caused by microorganisms susceptible to clindamycin.4. If the therapy of toxoplasmic meningoencephalitis was started with an intravenous prescription of clindamycin it is recommended an additional treatment with an intrathecal administration of clindamycin with dexamethasone in offered doses to increase efficiency by creating an effective concentration of preparation in the nidus of infection.5. Intrathecal methods of therapy must be used by the specialists of

  6. The antinociceptive effects of Monechma ciliatum and changes in EEG waves following oral and intrathecal administration in rats

    Science.gov (United States)

    Meraiyebu, Ajibola B.; Adelaiye, Alexander B.; O, Odeh S.

    2010-02-01

    The research work was carried out to study the effect of Oral and Intrathecal Monechma Ciliatum on antinociception and EEG readings in Wistar Rats. Traditionally the extract is given to women in labour believed to reduce pain and ease parturition, though past works show that it has oesteogenic and oxytotic effects. The rats were divided into 5 major groups. Group 1 served as oral control group while groups 2 and 3 served as oral experimental groups and were treated with 500mg/kg and 1000mg/kg monechma ciliatum respectively. Group 4 served as intrathecal control group treated with intrathecal dextrose and group 5 received 1000mg/kg Monechma Ciliatrum intrathecally. The antinociceptive effect was analysed using a Von Frey's aesthesiometer. Monechma Ciliatum showed significant antinociceptive effect both orally and intrathecally, although it had a greater effect orally and during the first 15 minutes of intrathecal administration. EEG readings were also taken for all the groups and there was a decrease in amplitude and an increase in frequency for high dose (1000mg/ml) experimental groups and the mid brain electrodes produced a change from theta waves (3.5 - 7 waves per second) to alpha waves (7.5 - 13 waves per second) as seen in relaxed persons and caused decreased amplitudes and change in distribution seen in beta waves. Properties similarly accentuated by sedativehypnotic drugs.

  7. Inositol lipid turnover and compartmentation in canine trachealis smooth muscle

    International Nuclear Information System (INIS)

    Baron, C.B.; Pring, M.; Coburn, R.F.

    1989-01-01

    We established conditions for the study of metabolism and compartmentation of inositol phospholipids in canine trachealis muscle. Unstimulated muscle was incubated with myo-[3H]inositol for 30 min at 37 degrees C which resulted in labeling of the tissue free myo-inositol pool, whereas only a small amount of radioactivity was incorporated into inositol phospholipids or inositol phosphates. After addition of 5.5 microM carbachol, phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2), specific radioactivities increased exponentially, reaching apparent constant values in 180-240 min. Initial rates of increases in PI, PIP, and PIP2 specific radioactivities were 39, 32, and 66 times that measured in unstimulated muscle. Metabolic flux rates (nmol.100 nmol total lipid Pi-1.min-1) during development of force averaged 0.42 +/- 0.09 and during force maintenance averaged 0.14 +/- 0.01. Fractions of total PI, PIP, and PIP2 pools that were linked to muscarinic cholinergic activation were estimated to be 0.97, 0.85, and 0.65, respectively. Initial rates of increase in specific radioactivities and specific radioactivities during carbachol activation were similar in PI, PIP, and PIP2 fast active compartments, suggesting metabolic flux from PI to PIP to PIP2 was in near chemical equilibrium. Turnover times for PI, PIP, and PIP2 fast active compartments were estimated to be 21, 1.6, and 4.0 min, respectively

  8. The 4D Nucleome: Genome Compartmentalization in an Evolutionary Context.

    Science.gov (United States)

    Cremer, T; Cremer, M; Cremer, C

    2018-04-01

    4D nucleome research aims to understand the impact of nuclear organization in space and time on nuclear functions, such as gene expression patterns, chromatin replication, and the maintenance of genome integrity. In this review we describe evidence that the origin of 4D genome compartmentalization can be traced back to the prokaryotic world. In cell nuclei of animals and plants chromosomes occupy distinct territories, built up from ~1 Mb chromatin domains, which in turn are composed of smaller chromatin subdomains and also form larger chromatin domain clusters. Microscopic evidence for this higher order chromatin landscape was strengthened by chromosome conformation capture studies, in particular Hi-C. This approach demonstrated ~1 Mb sized, topologically associating domains in mammalian cell nuclei separated by boundaries. Mutations, which destroy boundaries, can result in developmental disorders and cancer. Nucleosomes appeared first as tetramers in the Archaea kingdom and later evolved to octamers built up each from two H2A, two H2B, two H3, and two H4 proteins. Notably, nucleosomes were lost during the evolution of the Dinoflagellata phylum. Dinoflagellate chromosomes remain condensed during the entire cell cycle, but their chromosome architecture differs radically from the architecture of other eukaryotes. In summary, the conservation of fundamental features of higher order chromatin arrangements throughout the evolution of metazoan animals suggests the existence of conserved, but still unknown mechanism(s) controlling this architecture. Notwithstanding this conservation, a comparison of metazoans and protists also demonstrates species-specific structural and functional features of nuclear organization.

  9. Pathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells

    Science.gov (United States)

    Nikiforov, Andrey; Dölle, Christian; Niere, Marc; Ziegler, Mathias

    2011-01-01

    NAD is a vital redox carrier, and its degradation is a key element of important regulatory pathways. NAD-mediated functions are compartmentalized and have to be fueled by specific biosynthetic routes. However, little is known about the different pathways, their subcellular distribution, and regulation in human cells. In particular, the route(s) to generate mitochondrial NAD, the largest subcellular pool, is still unknown. To visualize organellar NAD changes in cells, we targeted poly(ADP-ribose) polymerase activity into the mitochondrial matrix. This activity synthesized immunodetectable poly(ADP-ribose) depending on mitochondrial NAD availability. Based on this novel detector system, detailed subcellular enzyme localizations, and pharmacological inhibitors, we identified extracellular NAD precursors, their cytosolic conversions, and the pathway of mitochondrial NAD generation. Our results demonstrate that, besides nicotinamide and nicotinic acid, only the corresponding nucleosides readily enter the cells. Nucleotides (e.g. NAD and NMN) undergo extracellular degradation resulting in the formation of permeable precursors. These precursors can all be converted to cytosolic and mitochondrial NAD. For mitochondrial NAD synthesis, precursors are converted to NMN in the cytosol. When taken up into the organelles, NMN (together with ATP) serves as substrate of NMNAT3 to form NAD. NMNAT3 was conclusively localized to the mitochondrial matrix and is the only known enzyme of NAD synthesis residing within these organelles. We thus present a comprehensive dissection of mammalian NAD biosynthesis, the groundwork to understand regulation of NAD-mediated processes, and the organismal homeostasis of this fundamental molecule. PMID:21504897

  10. Nuclear Pore-Like Structures in a Compartmentalized Bacterium.

    Directory of Open Access Journals (Sweden)

    Evgeny Sagulenko

    Full Text Available Planctomycetes are distinguished from other Bacteria by compartmentalization of cells via internal membranes, interpretation of which has been subject to recent debate regarding potential relations to Gram-negative cell structure. In our interpretation of the available data, the planctomycete Gemmata obscuriglobus contains a nuclear body compartment, and thus possesses a type of cell organization with parallels to the eukaryote nucleus. Here we show that pore-like structures occur in internal membranes of G.obscuriglobus and that they have elements structurally similar to eukaryote nuclear pores, including a basket, ring-spoke structure, and eight-fold rotational symmetry. Bioinformatic analysis of proteomic data reveals that some of the G. obscuriglobus proteins associated with pore-containing membranes possess structural domains found in eukaryote nuclear pore complexes. Moreover, immunogold labelling demonstrates localization of one such protein, containing a β-propeller domain, specifically to the G. obscuriglobus pore-like structures. Finding bacterial pores within internal cell membranes and with structural similarities to eukaryote nuclear pore complexes raises the dual possibilities of either hitherto undetected homology or stunning evolutionary convergence.

  11. Compartmental transport model of microbicide delivery by an intravaginal ring

    Science.gov (United States)

    Geonnotti, Anthony R.; Katz, David F.

    2010-01-01

    Topical antimicrobials, or microbicides, are being developed to prevent HIV transmission through local, mucosal delivery of antiviral compounds. While hydrogel vehicles deliver the majority of current microbicide products, intravaginal rings (IVRs) are an alternative microbicide modality in preclinical development. IVRs provide a long-term dosing alternative to hydrogel use, and might provide improved user adherence. IVR efficacy requires sustained delivery of antiviral compounds to the entire vaginal compartment. A two-dimensional, compartmental vaginal drug transport model was created to evaluate the delivery of drugs from an intravaginal ring. The model utilized MRI-derived ring geometry and location, experimentally defined ring fluxes and vaginal fluid velocities, and biophysically relevant transport theory. Model outputs indicated the presence of potentially inhibitory concentrations of antiviral compounds along the entire vaginal canal within 24 hours following IVR insertion. Distributions of inhibitory concentrations of antiviral compounds were substantially influenced by vaginal fluid flow and production, while showing little change due to changes in diffusion coefficients or ring fluxes. Additionally, model results were predictive of in vivo concentrations obtained in clinical trials. Overall, this analysis initiates a mechanistic computational framework, heretofore missing, to understand and evaluate the potential of IVRs for effective delivery of antiviral compounds. PMID:20222027

  12. Adaptive and neuroadaptive control for nonnegative and compartmental dynamical systems

    Science.gov (United States)

    Volyanskyy, Kostyantyn Y.

    Neural networks have been extensively used for adaptive system identification as well as adaptive and neuroadaptive control of highly uncertain systems. The goal of adaptive and neuroadaptive control is to achieve system performance without excessive reliance on system models. To improve robustness and the speed of adaptation of adaptive and neuroadaptive controllers several controller architectures have been proposed in the literature. In this dissertation, we develop a new neuroadaptive control architecture for nonlinear uncertain dynamical systems. The proposed framework involves a novel controller architecture with additional terms in the update laws that are constructed using a moving window of the integrated system uncertainty. These terms can be used to identify the ideal system weights of the neural network as well as effectively suppress system uncertainty. Linear and nonlinear parameterizations of the system uncertainty are considered and state and output feedback neuroadaptive controllers are developed. Furthermore, we extend the developed framework to discrete-time dynamical systems. To illustrate the efficacy of the proposed approach we apply our results to an aircraft model with wing rock dynamics, a spacecraft model with unknown moment of inertia, and an unmanned combat aerial vehicle undergoing actuator failures, and compare our results with standard neuroadaptive control methods. Nonnegative systems are essential in capturing the behavior of a wide range of dynamical systems involving dynamic states whose values are nonnegative. A sub-class of nonnegative dynamical systems are compartmental systems. These systems are derived from mass and energy balance considerations and are comprised of homogeneous interconnected microscopic subsystems or compartments which exchange variable quantities of material via intercompartmental flow laws. In this dissertation, we develop direct adaptive and neuroadaptive control framework for stabilization, disturbance

  13. In or out? On the tightness of glycosomal compartmentalization of metabolites and enzymes in Trypanosoma brucei

    NARCIS (Netherlands)

    Haanstra, Jurgen R.; Bakker, Barbara M.; Michels, Paul A. M.

    Trypanosomatids sequester large parts of glucose metabolism inside specialised peroxisomes, called glycosomes. Many studies have shown that correct glycosomal compartmentalization of glycolytic enzymes is essential for bloodstream-form Trypanosoma brucel. The recent finding of pore-forming

  14. Compartmental models for assessing the fishery production in the Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Dalal, S.G.; Parulekar, A.H.

    Compartmental models for assessing the fishery production in the Indian Ocean is discussed. The article examines the theoretical basis on which modern fishery sciences is built. The model shows that, large changes in energy flux from one pathway...

  15. A Laminin-2, Dystroglycan, Utrophin Axis is Required for Compartmentalization and Elongation of Myelin Segments

    OpenAIRE

    Court, Felipe A.; Hewitt, Jane E.; Davies, Kay; Patton, Bruce L.; Uncini, Antonino; Wrabetz, Lawrence; Feltri, M. Laura

    2009-01-01

    Animal and plant cells compartmentalize to perform morphogenetic functions. Compartmentalization of myelin-forming Schwann cells may favor elongation of myelin segments to the size required for efficient conduction of nerve impulses. Compartments in myelinated fibers were described by Ramon-y-Cajal and depend on periaxin, mutated in the hereditary neuropathy Charcot-Marie-Tooth 4F. Lack of periaxin in mice causes loss of compartments, formation of short myelin segments (internodes) and reduce...

  16. Respiratory failure following delayed intrathecal morphine pump refill: a valuable, but costly lesson.

    Science.gov (United States)

    Ruan, Xiulu; Couch, J Patrick; Liu, HaiNan; Shah, Rinoo V; Wang, Frank; Chiravuri, Srinivas

    2010-01-01

    Spinal analgesia, mediated by opioid receptors, requires only a fraction of the opioid dose that is needed systemically. By infusing a small amount of opioid into the cerebrospinal fluid in close proximity to the receptor sites in the spinal cord, profound analgesia may be achieved while sparing some of the side effects due to systemic opioids. Intraspinal drug delivery (IDD) has been increasingly used in patients with intractable chronic pain, when these patients have developed untoward side effects with systemic opioid usage. The introduction of intrathecal opioids has been considered one of the most important breakthroughs in pain management in the past three decades. A variety of side effects associated with the long-term usage of IDD have been recognized. Among them, respiratory depression is the most feared. To describe a severe adverse event, i.e., respiratory failure, following delayed intrathecal morphine pump refill. A 65-year-old woman with intractable chronic low back pain, due to degenerative disc disease, and was referred to our clinic for an intraspinal drug delivery evaluation, after failing to respond to multidisciplinary pain treatment. Following a psychological evaluation confirming her candidacy, she underwent an outpatient patient-controlled continuous epidural morphine infusion trial. The infusion trial lasted 12 days and was beneficial in controlling her pain. The patient reported more than 90% pain reduction with improved distance for ambulation. She subsequently consented and was scheduled for permanent intrathecal morphine pump implantation. The intrathecal catheter was inserted at right paramedian L3-L4, with catheter tip advanced to L1, confirmed under fluoroscopy. Intrathecal catheter placement was confirmed by positive CSF flow and by myelogram. A non-programmable Codman 3000 constant-flow rate infusion pump was placed in the right mid quandrant between right rib cage and right iliac crest. The intrathecal infusion consisted of

  17. Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, T.L.; Sellebjerg, F; Jensen, C.V.

    2001-01-01

    leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9...... patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials....... Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls...

  18. Use of Intrathecal Fluorescein in Recurrent Meningitis after Cochlear Implantation-A Case Report

    Directory of Open Access Journals (Sweden)

    Swati Tandon

    2016-05-01

    Full Text Available Introduction: Congenital anomalies of the cochlea and labyrinth can be associated with meningitis and varying degrees of hearing loss or deafness. Despite antibiotics, meningitis remains a life threatening complication.   Case Report: We report a case of recurrent meningitis following episodes of otitis media in a cochlear implantee child with bilateral vestibulocochlear malformation, due to fistula in the stapes footplate. Intrathecal fluorescin was used to identify the leak site.   Conclusion:  Recurrent meningitis can indicate for possible immunological or anatomical abnormalities as well for chronic parameningeal infections. Intraoperative use of intrathecal fluorescin is an ideal investigative tool to demonstrate cerebrospinal fluid (CSF leak site in patients in whom other investigations fail to do so.

  19. Prolonged Survival of Acute Lymphoblastic Leukemia with Intrathecal Treatments for Isolated Central Nervous System Relapse

    Directory of Open Access Journals (Sweden)

    Elan Gorshein

    2018-01-01

    Full Text Available Acute lymphoblastic leukemia is commonly cured when diagnosed in the pediatric population. It portends a poorer prognosis if present in adult patients. Although adults frequently achieve complete remission, relapse rates are substantial, particularly among the elderly and high-risk populations. In the absence of prophylactic intrathecal chemotherapy, more than half of patients may develop CNS involvement or relapse, which is associated with significant risk for systemic illness. This report describes a patient with acute lymphoblastic leukemia with repeated isolated CNS relapses. This case should remind clinicians that isolated CNS disease in the absence of systemic recurrence could successfully respond to intrathecal therapy and offer patients a favorable quality of life.

  20. Single-dose volume regulation algorithm for a gas-compensated intrathecal infusion pump.

    Science.gov (United States)

    Nam, Kyoung Won; Kim, Kwang Gi; Sung, Mun Hyun; Choi, Seong Wook; Kim, Dae Hyun; Jo, Yung Ho

    2011-01-01

    The internal pressures of medication reservoirs of gas-compensated intrathecal medication infusion pumps decrease when medication is discharged, and these discharge-induced pressure drops can decrease the volume of medication discharged. To prevent these reductions, the volumes discharged must be adjusted to maintain the required dosage levels. In this study, the authors developed an automatic control algorithm for an intrathecal infusion pump developed by the Korean National Cancer Center that regulates single-dose volumes. The proposed algorithm estimates the amount of medication remaining and adjusts control parameters automatically to maintain single-dose volumes at predetermined levels. Experimental results demonstrated that the proposed algorithm can regulate mean single-dose volumes with a variation of 98%. © 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  1. Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats

    Directory of Open Access Journals (Sweden)

    Birol Muhammet Er

    2016-06-01

    Full Text Available Background: Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. Aims: The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Study Design: Animal experimentation. Methods: Forty rats were randomized into 4 groups 7 days after intrathecal catheterization; the following drugs were given through catheter lumens: Group Lidocaine (Group L: Lidocaine 20 μg; Group Lidocaine-Morphine (Group LM: Lidocaine 20 μg and morphine 0.5 μgr; Group Lidocaine-Dexketoprofen (Group LD: Lidocaine 20 μg and dexketoprofen trometamol 100 μg; and Group Dexketoprofen (Group D: Dexketoprofen trometamol 100 μg. Paw incision was achieved under ether inhalation. To measure analgesic potential, hot plate and tail immersion tests were used as nociceptive tests during the postoperative period. Results: The mean reaction times detected in groups during hot plate and tail immersion tests were shortest in Group L at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after start of surgery (p<0.01, all others. In the groups using dexketoprofen, as in the morphine group, longer reaction times were detected than in the lidocaine group at all measurement times except 120 minutes (p<0.01. Conclusion: Intrathecal dexketoprofen in the optimal perioperative pain management is effective, and can be administered as an adjuvant in clinics after neurotoxicity studies in animals, and effective dose studies in volunteers.

  2. Intrathecal antitetanus serum (horse) with steroid in the treatment of neonatal tetanus.

    OpenAIRE

    Singh, A K; Bansal, A; Goel, S P; Agarwal, V K

    1980-01-01

    107 patients with neonatal tetanus were studied and the value of intrathecal antitetanus serum with steroid was noted. The mortality rate in a control group (68%) was significantly higher than that of the test group (37%). Furthermore, a delay in antitetanus serum administration was found to have a strong positive linear correlation with the mortality rate. In fact, the mortality rate for neonates who were given antitetanus serum 24 hours after the onset of convulsions was found to be as high...

  3. Measured density and calculated baricity of custom-compounded drugs for chronic intrathecal infusion.

    Science.gov (United States)

    Hejtmanek, Michael R; Harvey, Tracy D; Bernards, Christopher M

    2011-01-01

    To minimize the frequency that intrathecal pumps require refilling, drugs are custom compounded at very high concentrations. Unfortunately, the baricity of these custom solutions is unknown, which is problematic, given baricity's importance in determining the spread of intrathecally administered drugs. Consequently, we measured the density and calculated the baricity of clinically relevant concentrations of multiple drugs used for intrathecal infusion. Morphine, clonidine, bupivacaine, and baclofen were weighed to within 0.0001 g and diluted in volumetric flasks to produce solutions of known concentrations (morphine 1, 10, 25, and 50 mg/mL; clonidine 0.05, 0.5, 1, and 3 mg/mL; bupivacaine 2.5, 5, 10, and 20 mg/mL; baclofen 1, 1.5, 2, and 4 mg/mL). The densities of the solutions were measured at 37°C using the mechanical oscillation method. A "best-fit" curve was calculated for plots of concentration versus density for each drug. All prepared solutions of clonidine and baclofen were hypobaric. Higher concentrations of morphine and bupivacaine were hyperbaric, whereas lower concentrations were hypobaric. The relationship between concentration and density is linear for morphine (r > 0.99) and bupivacaine (r > 0.99) and logarithmic for baclofen (r = 0.96) and clonidine (r = 0.98). This is the first study to examine the relationship between concentration and density for custom drug concentrations commonly used in implanted intrathecal pumps. We calculated an equation that defines the relationship between concentration and density for each drug. Using these equations, clinicians can calculate the density of any solution made from the drugs studied here.

  4. The effect of posture and baricity on the spread of intrathecal bupivacaine for elective cesarean delivery.

    Science.gov (United States)

    Hallworth, Stephen P; Fernando, Roshan; Columb, Malachy O; Stocks, Gary M

    2005-04-01

    Posture and baricity during induction of spinal anesthesia with intrathecal drugs are believed to be important in determining spread within the cerebrospinal fluid. In this double-blind prospective study, 150 patients undergoing elective cesarean delivery were randomized to receive a hyperbaric, isobaric, or hypobaric intrathecal solution of 10 mg bupivacaine during spinal anesthesia induced in either the sitting or right lateral position. After an intrathecal injection using a combined-spinal technique patients were placed in the supine wedged position. We determined the densities of the three intrathecal solutions from a previously validated formula and measured using a DMA-450 density meter. Data collection included sensory level, motor block, episodes of hypotension, and ephedrine use. Statistical analysis included analysis of variance and Cuzick's trend. In the lateral position, baricity had no effect on the spread of sensory levels for bupivacaine compared to the sitting position, where there was a statistically significant difference in spread with the hypobaric solution producing higher levels of analgesia than the hyperbaric solution (P = 0.002). However, the overall differences in maximal spread only differed by one dermatome, with the hyperbaric solution achieving a median maximum sensory level to T3 compared with T2 for the isobaric and hypobaric solutions. Motor block was significantly (P = 0.029) reduced with increasing baricity and this trend was significant (P = 0.033) for the lateral position only. Hypotension incidence and ephedrine use increased with decreasing baricity (P = 0.003 and 0.004 respectively), with the hypobaric sitting group having the most frequent incidence of hypotension (76%) as well as cervical blocks (24%; P = 0.032).

  5. Intrathecal Administration of Morphine Decreases Persistent Pain after Cesarean Section: A Prospective Observational Study.

    Directory of Open Access Journals (Sweden)

    Kumi Moriyama

    Full Text Available Chronic pain after cesarean section (CS is a serious concern, as it can result in functional disability. We evaluated the prevalence of chronic pain after CS prospectively at a single institution in Japan. We also analyzed perioperative risk factors associated with chronic pain using logistic regression analyses with a backward-stepwise procedure.Patients who underwent elective or emergency CS between May 2012 and May 2014 were recruited. Maternal demographics as well as details of surgery and anesthesia were recorded. An anesthesiologist visited the patients on postoperative day (POD 1 and 2, and assessed their pain with the Prince Henry Pain Scale. To evaluate the prevalence of chronic pain, we contacted patients by sending a questionnaire 3 months post-CS.Among 225 patients who questionnaires, 69 (30.7% of patients complained of persistent pain, although no patient required pain medication. Multivariate analyses identified lighter weight (p = 0.011 and non-intrathecal administration of morphine (p = 0.023 as determinant factors associated with persistent pain at 3 months. The adjusted odds ratio of intrathecal administration of morphine to reduce persistent pain was 0.424, suggesting that intrathecal administration of morphine could decrease chronic pain by 50%. In addition, 51.6% of patients had abnormal wound sensation, suggesting the development of neuropathic pain. Also, 6% of patients with abnormal wound sensation required medication, yet no patients with persistent pain required medication.Although no effect on acute pain was observed, intrathecal administration of morphine significantly decreased chronic pain after CS.

  6. Intrathecal morphine is superior to intravenous PCA in patients undergoing minimally invasive cardiac surgery

    Directory of Open Access Journals (Sweden)

    Chirojit Mukherjee

    2012-01-01

    Full Text Available Aim of our study was to evaluate the beneficial effect of low dose intrathecal morphine on postoperative analgesia, over the use of intravenous patient controlled anesthesia (PCA, in patients undergoing fast track anesthesia during minimally invasive cardiac surgical procedures. A randomized controlled trial was undertaken after approval from local ethical committee. Written informed consent was obtained from 61 patients receiving mitral or tricuspid or both surgical valve repair in minimal invasive technique. Patients were assigned randomly to 2 groups. Group 1 received general anesthesia and intravenous patient controlled analgesia (PCA pump with Piritramide (GA group. Group 2 received a single shot of intrathecal morphine (1.5 μg/kg body weight prior to the administration of general anesthesia (ITM group. Site of puncture was confined to lumbar (L1-2 or L2-3 intrathecal space. The amount of intravenous piritramide used in post anesthesia care unit (PACU and the first postoperative day was defined as primary end point. Secondary end points included: time for tracheal extubation, pain and sedation scores in PACU upto third postoperative day. For statistical analysis Mann-Whitney-U Test and Fishers exact test (SPSS were used. We found that the demand for intravenous opioids in PACU was significantly reduced in ITM group (P <0.001. Pain scores were significantly decreased in ITM group until second postoperative day (P <0.01. There was no time delay for tracheal extubation in ITM group, and sedation scores did not differ in either group. We conclude that low dose single shot intrathecal morphine provides adequate postoperative analgesia, reduces the intravenous opioid consumption during the early postoperative period and does not defer early extubation.

  7. Resolution of chronic migraine headaches with intrathecal ziconotide: a case report

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    Narain S

    2015-09-01

    Full Text Available Sachin Narain,1 Lama Al-Khoury,2 Eric Chang3–6 1Department of Anesthesiology and Perioperative Care, 2Department of Neurology, 3Department of Physical Medicine and Rehabilitation, 4Department of Neurosurgery, 5Department of Orthopedics, 6Reeve-Irvine Research Center for Spinal Cord Injury, University of California Irvine, Irvine, CA, USA Background: Migraine headaches are a common and functionally debilitating disorder affecting approximately 17% of women and 5.6% of men. Compared to episodic migraine patients, chronic migraineurs are more likely to be occupationally disabled, miss family activities, have comorbid anxiety and/or chronic pain disorders, and utilize significantly more health care dollars. Ziconotide is a calcium channel blocker used for the treatment of chronic severe pain without issues of tolerance or dependency found with opioid therapy. Case: A 59-year-old female had an intrathecal baclofen pump placed for spasticity secondary to multiple sclerosis. Her symptoms also included lower extremity neuropathic pain and severe migraine headaches with 22 migraine headache days per month. Prior treatments included nonsteroidal anti-inflammatory drugs, triptans, anticonvulsants, antihypertensives, and Botox injections which reduced her symptoms to four migraine days per month at best. While her spasticity had markedly improved with intrathecal baclofen, ziconotide was added to help her neuropathic pain complaints. Following initiation of low-dose ziconotide (1 µg/day, the patient noted both lower extremity pain improvement and complete resolution of migraine headaches resulting in zero migraine days per month. She has now been migraine free for 8 months. Conclusion: Upon review of the available literature, there are no published cases of migraine improvement with intrathecal ziconotide. This represents the first case describing resolution of migraine symptoms with low-dose ziconotide. Keywords: ziconotide, migraine, symptoms, chronic

  8. Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine in patients undergoing abdominal hysterectomy during spinal anesthesia.

    Science.gov (United States)

    Lauretti, G R; Mattos, A L; Gomes, J M; Pereira, N L

    1997-01-01

    Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine were investigated in a randomized, double-blind, placebo-controlled trial of 100 patients undergoing abdominal hysterectomy. The patients were assigned to one of five groups (n = 20), and received intravenous prior to the spinal block the antiemetic test drug (except propofol) and 0.05 mg/kg midazolam. The control group (group C), the neostigmine group (group N), and the propofol group (group P) received saline as the test drug. The droperidol group (group D) received 0.5 mg intravenous droperidol, and the metoclopramide group (group M) 10 mg intravenous metoclopramide. Group P was single-blinded and had an intravenous continuous propofol infusion (2-4 mg/kg/h) turned on 10 minutes after the spinal injection. The intrathecal drugs administered were 20 mg hyperbaric bupivacaine (0.5%) associated with either 100 microg neostigmine or saline (for group C). Nausea, emetic episodes, and the need for rescue medication were recorded for the first 24 hours postoperative and scored by the Visual Analog Scale (VAS). Time-to-first-rescue medication and rescue medications in 24 hours were similar among the groups (P = .2917 and P = .8780, respectively). Intrathecal 100 microg neostigmine was associated with a high incidence of nausea and vomiting perioperative, leading to a high consumption of antiemetics (P antiemetic test drugs were effective in preventing nausea and vomiting after 100 microg neostigmine. Intrathecal neostigmine (100 microg) was ineffective for postoperative analgesia after abdominal hysterectomy due to side effects of nausea and vomiting.

  9. Safety and efficacy of intrathecal ziconotide in the management of severe chronic pain

    Directory of Open Access Journals (Sweden)

    Howard S Smith

    2009-07-01

    Full Text Available Howard S Smith,1 Timothy R Deer21Albany Medical College, Department of Anesthesiology, Albany, New York, USA; 2The Center for Pain Relief, Clinical Professor, West Virginia, University, Charleston, West Virginia, USAAbstract: Ziconotide is a conopeptide intrathecal (IT analgesic which is approved by the US Food and Drug Administration (FDA for the management of severe chronic pain. It is a synthetic equivalent of a naturally occurring conopeptide found in the venom of the fish-eating marine cone snail and provides analgesia via binding to N-type voltage-sensitive calcium channels in the spinal cord. As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic enzymes widely located throughout the body, and not by other Phase I biotransformation processes (including the cytochrome P450 system or by Phase II conjugation reactions. Thus, IT administration, low plasma ziconotide concentrations, and metabolism by ubiquitous peptidases make metabolic interactions of other drugs with ziconotide unlikely. Side effects of ziconotide which tend to occur more commonly at higher doses may include: nausea, vomiting, confusion, postural hypotension, abnormal gait, urinary retention, nystagmus/amblyopia, drowsiness/somnolence (reduced level of consciousness, dizziness or lightheadedness, weakness, visual problems (eg, double vision, elevation of serum creatine kinase, or vestibular side effects. Initially, when ziconotide was first administered to human subjects, titration schedules were overly aggressive and led to an abundance of adverse effects. Subsequently, clinicians have gained appreciation for ziconotide’s relatively narrow therapeutic window. With appropriate usage multiple studies have shown ziconotide to be a safe and effective intrathecal analgesic alone or in combination with other intrathecal analgesics.Keywords: pain, ziconotide, intrathecal analgesics, safety, patient

  10. Combination of anti-retroviral drugs and radioimmunotherapy specifically kills infected cells from HIV infected individuals

    Directory of Open Access Journals (Sweden)

    Dina Tsukrov

    2016-09-01

    Full Text Available Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT, a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infect-ed cells. Since gp41 expression by infected cells is likely down-regulated in patients on an-tiretroviral therapy (ART, we evaluated the ability of RIT to kill ART-treated infected cells us-ing both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal anti-body to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. conjugated to the human monoclonal antibody 2556, which binds to HIV gp41. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: ten on ART and five ART-naive. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART, and supports continued development of 213Bi

  11. Targeting angiogenesis for radioimmunotherapy with a {sup 177}Lu-labeled antibody

    Energy Technology Data Exchange (ETDEWEB)

    Ehlerding, Emily B.; Hernandez, Reinier [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); Lacognata, Saige; Jiang, Dawei [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Ferreira, Carolina A. [University of Wisconsin - Madison, Department of Biomedical Engineering, Madison, WI (United States); Goel, Shreya [University of Wisconsin - Madison, Department of Materials Science and Engineering, Madison, WI (United States); Jeffery, Justin J. [University of Wisconsin - Madison, Small Animal Imaging Facility, Madison, WI (United States); Theuer, Charles P. [TRACON Pharmaceuticals, Inc., San Diego, CA (United States); Cai, Weibo [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin - Madison, Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin - Madison, Department of Materials Science and Engineering, Madison, WI (United States)

    2018-01-15

    Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy. The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with {sup 177}Lu (t{sub 1/2} 6.65 days). Balb/c mice were implanted with 4T1 mammary carcinoma cells, and five study groups were used: {sup 177}Lu only, TRC105 only, {sup 177}Lu-DTPA-IgG (a nonspecific antibody), {sup 177}Lu-DTPA-TRC105 low-dose, and {sup 177}Lu-DTPA-TRC105 high-dose. Toxicity of the agent was monitored by body weight measurements and analysis of blood markers. Biodistribution studies of {sup 177}Lu-DTPA-TRC105 were also performed at 1 and 7 days after injection. Ex vivo histology studies of various tissues were conducted at 1, 7, and 30 days after injection of high-dose {sup 177}Lu-DTPA-TRC105. Biodistribution studies indicated steady uptake of {sup 177}Lu-DTPA-TRC105 in 4T1 tumors between 1 and 7 days after injection (14.3 ± 2.3%ID/g and 11.6 ± 6.1%ID/g, respectively; n = 3) and gradual clearance from other organs. Significant inhibition of tumor growth was observed in the high-dose group, with a corresponding significant increase in survival (p < 0.001, all groups). In most study groups (all except the nonspecific IgG group), the body weights of the mice did not decrease by more than 10%, indicating the safety of the injected agents. Serum alanine transaminase levels remained nearly constant indicating no damage to the liver (a primary clearance organ of the agent), and this was confirmed by ex vivo histological analyses. {sup 177}Lu-DTPA-TRC105, when administered at a sufficient dose, is able to curtail tumor growth and provide a

  12. Intrathecal Versus Oral Baclofen: A Matched Cohort Study of Spasticity, Pain, Sleep, Fatigue, and Quality of Life.

    Science.gov (United States)

    McCormick, Zachary L; Chu, Samuel K; Binler, Danielle; Neudorf, Daniel; Mathur, Sunjay N; Lee, Jungwha; Marciniak, Christina

    2016-06-01

    Baclofen commonly is used to manage spasticity caused by central nervous system lesions or dysfunction. Although both intrathecal and oral delivery routes are possible, no study has directly compared clinical outcomes associated with these 2 routes of treatment. To compare spasticity levels, pain, sleep, fatigue, and quality of life between individuals receiving treatment with intrathecal versus oral baclofen. Cross-sectional matched cohort survey study. Urban academic rehabilitation outpatient clinics. Adult patients with spasticity, treated with intrathecal or oral baclofen for at least 1 year, matched 1:1 for age, gender, and diagnosis. Standardized surveys were administered during clinic appointments or by telephone. Surveys included the Penn Spasm Frequency Scale, Brief Pain Inventory, Epworth Sleepiness Scale, Fatigue Severity Scale, Life Satisfaction Questionnaire, and Diener Satisfaction with Life Scale. A total of 62 matched subjects were enrolled. The mean (standard deviation [SD]) age was 46 (11) years with a mean duration of intrathecal baclofen or oral baclofen treatment of 11 (6) and 13 (11) years, respectively. There were 40 (64%) male and 22 (36%) female subjects. Primary diagnoses included spinal cord injury (n = 38), cerebral palsy (n = 10), stroke (n = 10), and multiple sclerosis (n = 4). The mean (SD) dose of intrathecal and oral baclofen at the time of survey were 577 (1429) μg/day and 86 (50) mg/day, respectively. Patients receiving intrathecal compared with oral baclofen experienced significantly fewer (1.44 [0.92] versus 2.37 [1.12]) and less severe (1.44 [0.92] versus 2.16 [0.83]) spasms, respectively as measured by the Penn Spasm Frequency Scale (P life between groups. Subanalysis of patients with SCI mirrored results of the entire study sample, with significant decreases in spasm frequency and severity associated with intrathecal compared to oral baclofen (P < .01; P < .01), but no other between group differences. The mean (SD) percent

  13. Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab.

    Science.gov (United States)

    Oliveira, Mafalda; Braga, Sofia; Passos-Coelho, José Luís; Fonseca, Ricardo; Oliveira, João

    2011-06-01

    Trastuzumab, a monoclonal antibody against the HER2 receptor, is a major breakthrough in the treatment of HER2+ breast cancer. However, its high molecular weight precludes it from crossing the intact blood-brain barrier, making the central nervous system a sanctuary to HER2+ breast cancer metastases. We prospectively assessed functional outcome and toxicity of administering trastuzumab directly into the cerebrospinal fluid of a patient with leptomeningeal carcinomatosis (LC) and brain metastases from HER2+ breast cancer that had already been treated with other intrathecal chemotherapy, with no benefit. Upon signed informed consent, weekly lumbar puncture with administration of trastuzumab 25 mg was begun to a 44 year-old women with metastatic breast cancer (lymph node, bone, lung, and liver involvement) previously treated with tamoxifen, letrozole, anthracyclines, taxanes, capecitabine, intravenous trastuzumab, and lapatinib. She received 67 weekly administrations of intrathecal trastuzumab with marked clinical improvement and no adverse events. She survived 27 months after LC diagnosis. A complete leptomeningeal response, with no evidence of leptomeningeal metastasis at necropsy, was achieved. We believe that intrathecal trastuzumab administration should be prospectively evaluated to confirm clinical activity and optimize dose, schedule, and duration of treatment.

  14. Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats.

    Science.gov (United States)

    Birol Muhammet, Er; Kocamanoğlu, İsmail Serhat; Bozkurt, Ayhan; Bilge, Sırrı; Çetinoğlu, Erhan Çetin

    2016-05-01

    Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Animal experimentation. Forty rats were randomized into 4 groups 7 days after intrathecal catheterization; the following drugs were given through catheter lumens: Group Lidocaine (Group L): Lidocaine 20 μg; Group Lidocaine-Morphine (Group LM): Lidocaine 20 μg and morphine 0.5 μgr; Group Lidocaine-Dexketoprofen (Group LD): Lidocaine 20 μg and dexketoprofen trometamol 100 μg; and Group Dexketoprofen (Group D): Dexketoprofen trometamol 100 μg. Paw incision was achieved under ether inhalation. To measure analgesic potential, hot plate and tail immersion tests were used as nociceptive tests during the postoperative period. The mean reaction times detected in groups during hot plate and tail immersion tests were shortest in Group L at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after start of surgery (pdexketoprofen, as in the morphine group, longer reaction times were detected than in the lidocaine group at all measurement times except 120 minutes (pdexketoprofen in the optimal perioperative pain management is effective, and can be administered as an adjuvant in clinics after neurotoxicity studies in animals, and effective dose studies in volunteers.

  15. The effects of intrathecal administration of betamethasone over the dogs' spinal cord and meninges.

    Science.gov (United States)

    Barros, Guilherme Antonio Moreira de; Marques, Mariângela Esther Alencar; Ganem, Eliana Marisa

    2007-01-01

    To determinate the potential clinical and histological changes due the injection of betamethasone, when administered into the canine intrathecal space. Twenty one animals were included in a random and blind manner in the study. After general anesthesia, intrathecal puncture was performed and 1 ml of the random solution was injected. The G1 dogs received 0.9% saline solution, the G2 dogs received 1.75 mg betamethasone and the G3 dogs received 3.5 mg of betamethasone. The animals were clinically evaluated for 21 days and then sacrificed. The lumbar and sacral portions of the spinal cord were removed for light microscopy histological analyses. No clinical changes were observed in any of the animals included in this study. No histological changes were observed in G1 animals. Inflammatory infiltration was observed in two dogs, one in G2, another in G3. Hemorrhage and necrosis were also seen in the G2 dog which inflammatory infiltration was detected. In other two dogs, one from G2 and another from G3, there was discreet fibrosis and thickness of the arachnoid layer which was focal in one and diffuse in the other. Intrathecal administration of betamethasone caused histological changes in the spinal cord and meninges in some of the dogs involved in this study.

  16. Compartmental analysis to predict biodistribution in radiopharmaceutical design studies

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Marina F.; Pujatti, Priscilla B.; Araujo, Elaine B.; Mesquita, Carlos H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: mflima@ipen.br

    2009-07-01

    The use of compartmental analysis allows the mathematical separation of tissues and organs to determinate the concentration of activity in each fraction of interest. Although the radiochemical purity must observe Pharmacopoeia specification (values upper 95%), very lower contains of free radionuclides could contribute significantly as dose in the neighborhood organs and make tumor up take studies not viable in case of radiopharmaceutical on the basis of labeled peptides. Animal studies with a product of Lutetium-177 labeled Bombesin derivative ({sup 177}Lu-BBNP) developed in IPEN-CNEN/SP and free Lutetium-177 developed in CNEA/EZEIZA was used to show how subtract free {sup 177}Lu contribution over {sup 177}Lu-BBNP to estimate the radiopharmaceutical potential as diagnosis or therapy agent. The first approach of the studies included the knowledge of chemical kinetics and mimetism of the Lutetium and the possible targets of the diagnosis/therapy to choose the possible models to apply over the sampling standard methods used in experimental works. A model with only one physical compartment (whole body) and one chemical compartment ({sup 177}Lu-BBNP) generated with the compartmental analysis protocol ANACOMP showed high differences between experimental and theoretical values over 2.5 hours, in spite of the concentration of activity had been in a good statistics rang of measurement. The values used in this work were residence time from three different kinds of study with free {sup 177}Lu: whole body, average excretion and maximum excretion as a chemical compartment. Activity concentration values as time function in measurements of total whole body and activity measurement in samples of blood with projection to total circulating blood volume with {sup 177}Lu-BBNP. Considering the two sources of data in the same modeling a better consistence was obtained. The next step was the statistic treatment of biodistribution and dosimetry in mice (Balb C) considering three chemical

  17. Compartmentation and complexation of metals in hyperaccumulator plants

    Directory of Open Access Journals (Sweden)

    Barbara eLeitenmaier

    2013-09-01

    Full Text Available Hyperaccumulators are being intensely investigated. They are not only interesting in scientific context due to their strange behaviour in terms of dealing with high concentrations of metals, but also because of their use in phytoremediation and phytomining, for which understanding the mechanisms of hyperaccumulation is crucial. Hyperaccumulators naturally use metal accumulation as a defence against herbivores and pathogens, and therefore deal with accumulated metals in very specific ways of complexation and compartmentation, different from non-hyperaccumulator plants and also non-hyperaccumulated metals. For example, in contrast to non-hyperaccumulators, in hyperaccumulators even the classical phytochelatin-inducing metal, cadmium, is predominantly not bound by such sulfur ligands, but only by weak oxygen ligands. This applies to all hyperaccumulated metals investigated so far, as well as hyperaccumulation of the metalloid arsenic. Stronger ligands, as they have been shown to complex metals in non-hyperaccumulators, are in hyperaccumulators used for transient binding during transport to the storage sites. This confirmed that enhanced active metal transport, and not metal complexation, is the key mechanism of hyperaccumulation. Hyperaccumulators tolerate the high amount of accumulated heavy metals by sequestering them into vacuoles, usually in large storage cells of the epidermis. This is mediated by strongly elevated expression of specific transport proteins in various tissues from metal uptake in the shoots up to the storage sites in the leaf epidermis. However, this mechanism seems to be very metal specific. Non-hyperaccumulated metals in hyperaccumulators seem to be dealt with like in non-hyperaccumulator plants, i.e. detoxified by binding to strong ligands such as metallothioneins.

  18. Efficient Vaccine Distribution Based on a Hybrid Compartmental Model.

    Directory of Open Access Journals (Sweden)

    Zhiwen Yu

    Full Text Available To effectively and efficiently reduce the morbidity and mortality that may be caused by outbreaks of emerging infectious diseases, it is very important for public health agencies to make informed decisions for controlling the spread of the disease. Such decisions must incorporate various kinds of intervention strategies, such as vaccinations, school closures and border restrictions. Recently, researchers have paid increased attention to searching for effective vaccine distribution strategies for reducing the effects of pandemic outbreaks when resources are limited. Most of the existing research work has been focused on how to design an effective age-structured epidemic model and to select a suitable vaccine distribution strategy to prevent the propagation of an infectious virus. Models that evaluate age structure effects are common, but models that additionally evaluate geographical effects are less common. In this paper, we propose a new SEIR (susceptible-exposed-infectious šC recovered model, named the hybrid SEIR-V model (HSEIR-V, which considers not only the dynamics of infection prevalence in several age-specific host populations, but also seeks to characterize the dynamics by which a virus spreads in various geographic districts. Several vaccination strategies such as different kinds of vaccine coverage, different vaccine releasing times and different vaccine deployment methods are incorporated into the HSEIR-V compartmental model. We also design four hybrid vaccination distribution strategies (based on population size, contact pattern matrix, infection rate and infectious risk for controlling the spread of viral infections. Based on data from the 2009-2010 H1N1 influenza epidemic, we evaluate the effectiveness of our proposed HSEIR-V model and study the effects of different types of human behaviour in responding to epidemics.

  19. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation

    International Nuclear Information System (INIS)

    Buchmann, I.

    2008-01-01

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. 90 Y, 188 Re and 131 I are the most frequently used β - -particles. Of these, 90 Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate 90 Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The 90 Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow 90 Y-anti-CD45-mAb YAML568 are 6.4 ± 1.2 (bone marrow), 3.9 ± 1.4 (liver) and 1.1 ± 0.4 (kidneys). CD45 is expressed also on the extramedullar clonogenic myeloma progenitor cell that circulates in the peripheral blood. Thus, the conditioning of

  20. Compartmental and dosimetric studies of anti-CD20 labeled with 188Re

    International Nuclear Information System (INIS)

    Barrio Kuramoto Graciela; Mie Nakamura Matsuda Margareth; Osso Joao Jr, Alberto

    2016-01-01

    Radioimmunotherapy has the potential to deliver lethal radiation energy directly to malignant cells via targeting of radioisotope-conjugated monoclonal antibodies (MAbs) to specific antigens. Rituximab (RTX) is specifically targeted against CD20, a surface antigen expressed by B-lymphocytes. The use of 188 Re from a 188 W/ 188 Re generator system represents an alternative radionuclide for therapy. Rhenium has chemical properties similar to technetium and both can be conjugated to antibodies using similar chemistry methods. The objective of this work is to prove the usefulness of this radiopharmaceutical based on dosimetric and pharmacokinetic studies that are also required by the Brazilian Regulatory Agency. (author)

  1. Human-Mouse Dosimetry in Clinical Radioimmunotherapy - Special Emphasis on Pediatric Applications

    International Nuclear Information System (INIS)

    Kairemo, K.J.A.; Pyyry, J.; Heiskanen, T.; Flux, G.; Fisher, D.R.

    2009-01-01

    Monoclonal antibody ('MAB') has been developed for targeting secretory alpha-fetoprotein in hepatic tissue. We have used these MABs for radioimmunotherapy and dose planning of recurrent hepatoblastoma, a rare childhood malignancy This MAB has been labelled with In- 111 and Y-90 for clinical purposes, and can be applied for diagnosis and therapy of liver neoplasms. Physiology based pharmacokinetic (PBPK) modeling and simulation is a useful method for prediction of biodistribution of macromolecules, it can enhance our understanding of the underlying mechanisms and hence may help in rational design of diagnostic and therapeutic agents. Here we also discuss PBPK modeling and simulation of this MAB in mice without tumor and in a pediatric patient. In the clinical study, radiopharmacokinetic parameters for this MAB ( 111 In-DOTA-hAFP31 IgG) were calculated after serial quantitative whole body scans in a child with hepatoblastoma. A 3-D dose planning computer program was used to calculate tumor doses for In-111 and Y-90, the active tumor was delineated on PET/CT images and tumor dose calculation was done based on the In-111-MAB SPECT data using dose point kernel approach both for In-111 and Y-90. The results were compared with MIRD doses obtained for organs in SPECT imaging field, i.e. bone marrow, heart, kidneys, liver, spleen, lungs. The simulated results were fitted to experimental time series data by varying parameters which were not fixed a priori. From quantitative serial imaging based on 8 whole body images at 0-168 hrs using In-111- MAB, the half-lives of spleen, lungs, kidneys and whole body were 502 hrs, 230 hrs, 193 hrs and 490 hrs, respectively. The measured blood half-life was 132 hrs, after a total MAB dose of 50 mg and In-111 activity of 105 MBq. The presumed Y-90 dose based on this kinetic behavior was 43 MBq which should had given 0.3Gy bone marrow dose with assumption of bone marrow: blood ratio 0.4 for IgG. The calculated MIRD Y-90 doses were for

  2. Intrathecal Bupivacaine Monotherapy with a Retrograde Catheter for the Management of Complex Regional Pain Syndrome of the Lower Extremity.

    Science.gov (United States)

    McRoberts, W Porter; Apostol, Catalina; Haleem, Abdul

    2016-01-01

    Complex regional pain syndrome (CRPS) presents a therapeutic challenge due to its many presentations and multifaceted pathophysiology. There is no approved treatment algorithm and clinical interventions are often applied empirically. In cases of CRPS where symptoms are localized to an extremity, a targeted treatment is indicated. We describe the use of intrathecal bupivacaine monotherapy, delivered through a retrograde catheter, in the treatment of CRPS affecting the lower extremity. The patient, a 57-year-old woman with a history of failed foot surgery, was seen in our office after 2 years of ineffective treatments with local blocks and neurolytic procedures. We advanced therapy to moderately invasive procedures with an emphasis on neuromodulation. A combined central and peripheral stimulation technique that initially provided 75% pain relief, failed to provide lasting analgesia. We proceeded with an intrathecal pump implant. Based on the results of dorsal root ganglion (DRG) mapping, L5-S1 was identified as the optimal target for therapy and a retrograde catheter was placed at this level. Various intrathecal medications were tested individually. An intrathecal morphine trial was ineffective (visual analog scale [VAS] 7), while intrathecal clonidine provided excellent pain relief (VAS 0) that was limited by severe side effects. Bupivacaine provided 100% analgesia with tolerable side effects (lower extremity weakness and minor bladder incontinence) and was selected for intrathecal infusion. After 14 months, bupivacaine treatment continued to control pain exacerbations. We conclude that CRPS patients benefit from early identification of the predominant underlying symptoms and a targeted treatment with moderately invasive techniques when less invasive techniques fail. Intrathecal bupivacaine, bupivacaine monotherapy, retrograde catheter, complex regional pain syndrome (CRPS), dual stimulation, dosal root ganglion (DRG) testing.

  3. Intrathecal morphine for postoperative analgesia in patients with idiopathic scoliosis undergoing posterior spinal fusion.

    Science.gov (United States)

    Tripi, Paul A; Poe-Kochert, Connie; Potzman, Jennifer; Son-Hing, Jochen P; Thompson, George H

    2008-09-15

    A retrospective study of postoperative pain management with intrathecal morphine. Identify the dosing regimen of intrathecal morphine that safely and effectively provides postoperative analgesia with minimal complications in patients with idiopathic scoliosis undergoing posterior spinal fusion (PSF) and segmental spinal instrumentation (SSI). Postoperative pain after surgery for idiopathic scoliosis is a concern. Intrathecal morphine has been used to decrease pain. However, the most appropriate dose has not been determined. We retrospectively analyzed 407 consecutive patients with idiopathic scoliosis who underwent PSF and SSI at our institution from 1992 through 2006. Patients were divided into 3 groups based on the intrathecal morphine dose: no dose (n = 68); moderate dose of 9 to 19 microg/kg, mean 14 microg/kg (n = 293); and high dose of 20 microg/kg or greater, mean 24 microg/kg (n = 46). Data included demographics, Wong-Baker visual analog scale postoperative pain scores, postoperative intravenous morphine requirements, time to first rescue dose of intravenous morphine, and postoperative complications of pruritus, nausea/vomiting, respiratory depression, and pediatric intensive care unit (PICU) admission. The demographics of the 3 study groups showed no statistical differences. The mean Wong-Baker visual analog scale pain score in the post anesthesia care unit was 5.2, 0.5, and 0.2, and the mean time to first morphine rescue was 6.6, 16.7, and 22.9 hours, respectively. In the first 48 postoperative hours, respiratory depression occurred in 1 (1.5%), 8 (2.7%), and 7 (15.2%) patients, whereas PICU admission occurred in 0 (0%), 6 (2%), and 8 (17.4%) patients, respectively. The majority of PICU admissions were the result of respiratory depression. Frequency of pruritus and nausea/vomiting was similar in all 3 groups. Intrathecal morphine in the moderate dose range of 9 to 19 microg/kg (mean 14 microg/kg), provides safe and effective postoperative analgesia in the

  4. Radioimmunotherapy using {sup 131}I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L. [Charite - Universitaetsmedizin Berlin, Clinic for Nuclear Medicine, Berlin (Germany); Srock, Stefanie; Pezzutto, Antonio [Charite - Universitaetsmedizin Berlin, Department of Haematology and Oncology, Berlin (Germany)

    2005-10-01

    The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using {sup 131}I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with {sup 131}I using the Iodogen method. The administered activity (2,200{+-}600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of{sup 131}I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8{+-}2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

  5. Intrathecal pressure monitoring and cerebrospinal fluid drainage in acute spinal cord injury: a prospective randomized trial.

    Science.gov (United States)

    Kwon, Brian K; Curt, Armin; Belanger, Lise M; Bernardo, Arlene; Chan, Donna; Markez, John A; Gorelik, Stephen; Slobogean, Gerard P; Umedaly, Hamed; Giffin, Mitch; Nikolakis, Michael A; Street, John; Boyd, Michael C; Paquette, Scott; Fisher, Charles G; Dvorak, Marcel F

    2009-03-01

    Ischemia is an important factor in the pathophysiology of secondary damage after traumatic spinal cord injury (SCI) and, in the setting of thoracoabdominal aortic aneurysm repair, can be the primary cause of paralysis. Lowering the intrathecal pressure (ITP) by draining CSF is routinely done in thoracoabdominal aortic aneurysm surgery but has not been evaluated in the setting of acute traumatic SCI. Additionally, while much attention is directed toward maintaining an adequate mean arterial blood pressure (MABP) in the acute postinjury phase, little is known about what is happening to the ITP during this period when spinal cord perfusion pressure (MABP - ITP) is important. The objectives of this study were to: 1) evaluate the safety and feasibility of draining CSF to lower ITP after acute traumatic SCI; 2) evaluate changes in ITP before and after surgical decompression; and 3) measure neurological recovery in relation to the drainage of CSF. Twenty-two patients seen within 48 hours of injury were prospectively randomized to a drainage or no-drainage treatment group. In all cases a lumbar intrathecal catheter was inserted for 72 hours. Acute complications of headache/nausea/vomiting, meningitis, or neurological deterioration were carefully monitored. Acute Spinal Cord Injury motor scores were documented at baseline and at 6 months postinjury. On insertion of the catheter, mean ITP was 13.8 +/- 1.3 mm Hg (+/- SD), and it increased to a mean peak of 21.7 +/- 1.5 mm Hg intraoperatively. The difference between the starting ITP on catheter insertion and the observed peak intrathecal pressure after decompression was, on average, an increase of 7.9 +/- 1.6 mm Hg (p drainage group was 30.6 +/- 2.3 mm Hg, which was significantly higher than the peak intraoperative ITP (p = 0.0098). During the same period, the peak recorded ITP in patients randomized to receive drainage was 28.1 +/- 2.8 mm Hg, which was not statistically higher than the peak intraoperative ITP (p = 0.15). The

  6. Bivalent fragment of the ior-CEA1 antibody. A challenge to the positive CEA tumors radioimmunotherapy

    International Nuclear Information System (INIS)

    Ravelo, Rolando; Sanchez, Iradia; Pimentel, Gilmara; Oliva, Juan; Perez, Lincidio; Ayala, Marta; Bell, Hansell; Gavilondo, Jorge

    2006-01-01

    The directed radiotherapy of the solid tumors with fragments recombinants of radiolabelled antibodies is a topic of current investigation, so much at preclinical level as clinical. This work describes the preclinical characterization of a new fragment type diabody of the AcMo ior CEA1 that has been labelled with 131 I for their use in the diagnosis and the therapy of CEA positive tumors. The radiolabelling methodology used allows the incorporation of more than 90% of the radio iodine to the molecule without committing the capacity of recognition of its antigen significantly. The combination of the favourable properties pharmacy kinetic and high selective accumulation in the tumor, they make of the diabody anti CEA an appropriate candidate for the radioimmunodiagnosis and the radioimmunotherapy of tumors that expresses CEA (Author)

  7. Synthesis of Lutetium Phosphate/Apoferritin Core-Shell Nanoparticles for Potential Applications in Radioimmunoimaging and Radioimmunotherapy of Cancers

    International Nuclear Information System (INIS)

    Wu, Hong; Engelhard, Mark H.; Wang, Jun; Fisher, Darrell R.; Lin, Yuehe

    2008-01-01

    We report a novel approach for synthesizing LuPO4/apoferritin core-shell nanoparticles based on an apoferritin template, conjugated to the protein biotin. To prepare the nanoparticle conjugates, we used non-radioactive lutetium as a model target or surrogate for radiolutetium (177Lu). The central cavity, multi-channel structure, and chemical properties of apoferritin are well-suited for sequentially diffusing lutetium and phosphate ions into the cavity--resulting in a stable core-shell composite. We characterized the synthesized LuPO4/apoferritin nanoparticle using transmission electron microscopy (TEM) and x-ray photoelectron spectroscopy (XPS). We tested the pre-targeting capability of biotin-modified lutetium/apoferritin nanoparticle using streptavidin-modified magnetic beads and streptavidin-modified fluorescein isothiocyanate (FITC) tracer. This paper presents a simple, fast, and efficient method for synthesizing LuPO4/apoferritin nanoparticle conjugates with biotin for potential applications in radioimmunotherapy and radioimmunoimaging of cancer

  8. EANM procedure guideline for radio-immunotherapy for B-cell lymphoma with 90Y-radiolabelled ibritumomab tiuxetan (Zevalin)

    International Nuclear Information System (INIS)

    Tennvall, Jan; Fischer, Manfred; Brans, Boudewijn; Bischof Delaloye, Angelika; Bombardieri, Emilio; Bodei, Lisa; Giammarile, Francesco; Lassmann, Michael; Oyen, Wim

    2007-01-01

    In January 2004, EMEA approved 90 Y-radiolabelled ibritumomab tiuxetan, Zevalin, in Europe for the treatment of adult patients with rituximab-relapsed or -refractory CD20+ follicular B-cell non-Hodgkin's lymphoma. The number of European nuclear medicine departments using Zevalin is continuously increasing, since the therapy is often considered successful. The Therapy, Oncology and Dosimetry Committees have worked together in order to define some EANM guidelines on the use of Zevalin, paying particular attention to the problems related to nuclear medicine. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients who may be candidates for radio-immunotherapy. The guideline also stresses the need for close collaboration with the physician(s) treating the patient for the underlying disease. (orig.)

  9. 177Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

    International Nuclear Information System (INIS)

    Rasaneh, Samira; Rajabi, Hossein; Babaei, Mohammad Hossein; Daha, Fariba Johari

    2010-01-01

    Introduction: In the present study, Herceptin was labeled with lutetium-177 via DOTA, and the necessary preclinical quality control tests (in vitro and in vivo) were performed to evaluate its use as a radioimmunotherapy agent. Material and Methods: Herceptin was conjugated to DOTA as a chelator in three different conjugation buffers (ammonium acetate, carbonate and HEPES buffer); each of the resulting conjugates was compared with respect to in vitro characteristics such as number of chelates per antibody, incorporated activity, immunoreactivity and in vitro stability in PBS buffer and blood serum. The biodistribution study and gamma camera imaging were performed in mice bearing breast tumors. To assess the therapeutic effects of 177 Lu-Herceptin, cytotoxicity was investigated for 7 days in a SKBr3 breast cancer cell line. Results: Carbonate buffer was the best conjugation buffer (number of chelates per antibody: 6; incorporated activity: 81%; immunoreactivity: 87%; buffer stability: 86%; serum stability: 81%, after 4 days). The efficient tumor uptake observed in the biodistribution studies was consistent with the gamma camera image results. At a concentration of 4 μg ml -1 , 177 Lu-Herceptin (surviving cells: 5±0.6% of the total cells) of the total cells corresponded to an approximately eightfold increase in cytotoxicity in comparison to unmodified Herceptin (surviving cells: 43±3.9%). Conclusion: The new complex described herein could be considered for further evaluation in animals and potentially in humans as a radiopharmaceutical for use in the radioimmunotherapy of breast cancer. These results may be important for patients who cannot tolerate the therapeutic dosage of Herceptin currently used because of heart problems.

  10. 'Was it worth it?' Intrathecal analgesia for cancer pain: A qualitative study exploring the views of family carers.

    Science.gov (United States)

    Patel, Nishi; Huddart, Melanie; Makins, Helen; Mitchell, Theresa; Gibbins, Jane L; Graterol, Juan; Stevens, Deborah; Perkins, Paul

    2018-01-01

    Intrathecal drug delivery is known to reduce pain in patients where conventional systemic analgesia has been ineffective or intolerable. However, there is little information regarding the effects of intrathecal drug delivery on quality of life and function in those with advanced, incurable cancer. Retrospective exploration of the views of bereaved carers regarding the physical and psychosocial effects of external tunnelled intrathecal drug delivery in patients with advanced incurable cancer. Thematic analysis of qualitative interviews with carers of deceased individuals who received percutaneous external tunnelled intrathecal drug delivery as part of their pain management, within two UK centres. A total of 11 carers were recruited from two UK Palliative Care centres. Family carers of adult patients who had received external tunnelled intrathecal drug delivery analgesia for cancer pain and had died between 6 and 48 months prior to contact were included. Carer relatives who were considered likely to be too vulnerable or who had lodged a complaint about treatment within the recruiting department or who had been treated directly by the interviewer were excluded. In total, 11 interviews took place. The emerging themes were (1) making the decision to have the intrathecal - relatives described desperate situations with severe pain and/or sedation, meaning that the individual would try anything; (2) timing and knowing they were having the best - an increased access to pain and palliative care services, meant carers felt everything possible was being done, making the situation more bearable; (3) was it worth it? - the success of the external tunnelled intrathecal drug delivery was judged on its ability to enable the individual to be themselves through their final illness. Side effects were often considered acceptable, if the external tunnelled intrathecal drug delivery enabled improvements in quality of life. Carers perceived external tunnelled intrathecal drug delivery

  11. A Common Decision of Compartmental Models on the Base of Laplace Transform and Retain Function Concept

    International Nuclear Information System (INIS)

    Dimitrov, L.; Tzvetkova, A.; Nikolov, A.

    1997-01-01

    The compartmental models have a variety of applications in the analysis of the transport of radioactive and non-radioactive material in complex systems as atmosphere, hydrosphere, food chains, human body. The analysis of the biokinetic behaviour of the radioactive material into a human body gives a possibility for correct assessment of the dose from internal irradiation. Skrable has given a decision of non-cyclic linear compartmental models in case of a single intake of material in the compartments as an initial condition. The main purpose of our article is to write down a procedure for analysis of a general compartmental model in case of continuous intake of material into the compartments. This procedure is related to retain function concept and had developed on the base of Laplace transform. On the base on the proposed procedure a non-cyclic linear compartmental model decisions are given in case of both a single and a continuous intake. The Laplace images of cyclic and circular linear compartmental model decisions and their originals in some cases are given too. (author)

  12. Comparison between radioimmunotherapy and external beam radiation therapy for patients with hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Zhao-Chong [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032 (China); Tang, Zhao-You; Yang, Bing-Hui; Liu, Kang-Da; Wu, Zhi-Quan; Fan, Jia; Qin, Lun-Xiu; Sun, Hui-Chuan; Zhou, Jian [Liver Cancer Institute, Fudan University, Shanghai (China); Jiang, Guo-Liang [Department of Radiation Oncology, Cancer Hospital. Fudan University, Shanghai (China)

    2002-12-01

    It has previously been observed in animal studies that, at equivalent doses, radioimmunotherapy (RIT) is 2.5 times more effective than multiple fractions of external beam radiation therapy (EBRT) in inhibiting tumour growth. In this study, we compared the use of RIT and EBRT in patients with hepatocellular carcinoma (HCC), treated during the past 10 years. Of 67 patients without extrahepatic involvement, 32 were treated with hepatic artery ligation combined with RIT (the RIT group) while 35 were treated with a combination of hepatic arterial chemo-embolisation and EBRT (the EBRT group). The patients in the RIT group received {sup 131}I-Hepama-1 monoclonal antibody, which was infused through the hepatic artery catheter. The patients in the EBRT group received transcatheter arterial chemo-embolisation and limited-field EBRT using a linear accelerator. Parameters observed include tumour response, alpha-fetoprotein (AFP) level in serum, human anti-murine antibody (HAMA) assay, T lymphocyte subsets, survival rates, routine parameters, sequential resection rates and histopathological status of the resection specimens. The sequential resection rates were 53% (17/32) and 23% (8/35), and tumour response rates were 72% (23/32) and 86% (30/35) in the RIT and EBRT groups, respectively. The main side-effects in the RIT group were mild allergic reactions. The most common toxicity in the EBRT group was an increase in liver enzymes. The liver tissue in the target volume was injured by EBRT. The injured liver tissue revealed a low-attenuation area adjacent to the hepatic tumour within the target volume on follow-up computed tomography studies after EBRT. On pathological evaluation, the low-attenuation area revealed hyperaemia, distended hepatic sinusoids packed with erythrocytes and hepatic cell loss. The sequential resection specimens from both the RIT and the EBRT group showed residual cancer tissue located at the edge of the mass. The residual cancer cells presented as giant

  13. Radioimmunotherapy of Non-Hodgkin's Lymphoma. The interaction of radiation and antibody with lymphoma cells

    International Nuclear Information System (INIS)

    Illidge, T.M.

    1999-06-01

    Whilst many patients with indolent Non-Hodgkin's Lymphoma (NHL) can achieve clinical remissions to first-line chemotherapy and/or radiotherapy, most will relapse. Current treatment options for relapsing patients are limited since most patients become resistant to repeated chemotherapy. Death usually occurs within 10 years of diagnosis. Overall, these disappointing results have not changed significantly in a quarter of a century and clearly advocate the urgent priority to research into potential new therapeutic approaches into this diverse and increasingly prevalent group of human tumours. Radioimmunotherapy (RIT) is currently under investigation as a new approach for the treatment of this disease. In this form of treatment, radionuclide-labeled monoclonal antibodies are able to deliver selective systemic irradiation by recognising tumour-associated antigens. The use of RIT with radiolabeled anti-CD20 antibodies in patients with recurrent B-cell lymphoma has resulted in extremely high rates of durable complete remissions. The optimal approach and mechanisms of action of successful RIT remain however largely unknown. The work described in this thesis has focused on clarifying some of the important determinants and mechanisms of effective RIT of syngeneic B-cell lymphoma, both in vivo and in vitro. A successful animal model of RIT in B cell lymphomas was established by initially generating a panel of antibodies against mouse B cell antigens. The in vitro characteristics of these antibodies have been compared with their subsequent performance, in biodistribution studies and RIT in vivo. For the first time in an in vivo model the relative contributions of antibody and irradiation are described. Some antibodies including anti-MHC Class II were shown to be effective delivery vehicles of low doses of Iodine-131. These antibodies, which appear to be inactive delivery vehicles can cure animals with low burdens of tumour. However antibodies such as anti-idiotype and anti-CD40

  14. Fluconazole and intrathecal injection of amphotericin B for treating cryptococcal meningitis

    Institute of Scientific and Technical Information of China (English)

    Shiguang Wen; Jian Yin; Shaosen Qin; Meiping Wen; Xiaoyan Zhang; Dongke Chen

    2006-01-01

    BACKGROUND: At present, fiuconazole and intrathecal injection of amphotericin B has been widely used to treat cryptococcal meningitis. However, the application of amphotericin B can shorten course and has good effects on the treatment of cryptococcal meningitis.OBJECTIVE: To observe the effects and poor response of the intrathecal injection of amphotericin B on the treatment of cryptococcal meningitis.DESIGN: Retrospective-case analysis.SETTING: Department of Neurology, Beijing Hospital of Ministry of Public Health.PARTICIPANTS: Eight patients with cryptococcal meningitis were selected from Department of Neurology,Beijing Hospital of Ministry of Public Health from January 1995 to January 2006. Among them, there were 3 males and 5 females aged from 17 to 41 years and the course ranged from 21 days to 3 months. Patients who had symptoms of febrile and headache, positive meninges excitation, positive latex agglutination of cryptococcus of cerebrospinal fluid and positive ink smear were selected in this study. All patients provided informed consent.METHODS: Eight patients were treated with the fluconazole and intrathecal injection of amphotericin B. ①Intracranial hypertension of patients was controlled with flowing cerebrospinal fluid by repeatedly piercing waist;meanwhile, patients were taken the intrathecal injection of amphotericin B combining with flucytosine or fiuconazole treatment. The dosage of amphotericin B was 1-5 mg/d at the beginning of administration, and then, the samples were added with 2 mg dexasine and 500 mL 5% glucose solution. The dosage was increased 5.0 mg per day till 50 mg per day, and the total dosage was 3.0-4.0 g. In addition, 2 mg dexasine was mixed with 4.0-5.0 mL cerebrospinal fluid, and then the solution was gradually injected into sheath for once a week. Fluconazole was dripped into vein with the volume of 400 mg per day, and then, 14 days later,fluconazole was orally taken by patients. ② Other therapies, such as decreasing

  15. Radioimmunotherapy with an antibody to HPV16 E6 oncoprotein is effective in experimental cervical tumor expressing low levels of E6

    Science.gov (United States)

    Jiang, Zewei; Wang, Xing Guo; Einstein, Mark H; Goldberg, Gary L; Casadevall, Arturo

    2010-01-01

    Purpose HPV16 is associated with ∼50% of all cervical cancers worldwide. The E6 and E7 genes of oncogenic HPV types, such as HPV16, are necessary for the HPV transforming function and tumorogenesis making them ideal targets for novel treatments. Radioimmunotherapy employs systemically administered radiolabeled monoclonal antibodies (mAbs) that bind to tumor-associated antigens. Previously we demonstrated in mice that radioimmunotherapy targeting viral antigens with mAb to HPV16 E6 suppressed CasKi cervical tumors expressing high levels of E6 (∼600 copies of HPV per cell). However, that study opened the question whether radioimmunotherapy can suppress the growth of cervical tumors with low E6 and E7 expression, such as may be seen in patients. Experimental Design We evaluated the expression of E6 in patients' tumors and in the SiHa cell line expressing low levels of E6 and E7 (1–2 copies of HPV per cell) and found them comparable. We initiated SiHa tumors in nude mice, radiolabeled C1P5 mAb to E6 with a beta-emitter 188-Rhenium (188Re) and treated tumor-bearing mice with: (1) 200 µCi 188Re-C1P5 alone; (2) proteasome inhibitor MG132 alone; (3) MG132 followed by 200 µCi 188Re-C1P5; (4) unlabeled C1P5; (5) 200 µCi 188Re-18B7 (isotype-matching control mAb); (6) no treatment. 188Re-C1P5 alone and in combination with MG-132 significantly retarded tumor growth compared to all control groups. Conclusions Our data demonstrate the possibility to suppress tumor growth by targeting viral antigens even in cervical tumors with low E6 expression and provide additional evidence for the potential usefulness of radioimmunotherapy targeting HPV-related antigens in the clinic. PMID:20861673

  16. Global identifiability of linear compartmental models--a computer algebra algorithm.

    Science.gov (United States)

    Audoly, S; D'Angiò, L; Saccomani, M P; Cobelli, C

    1998-01-01

    A priori global identifiability deals with the uniqueness of the solution for the unknown parameters of a model and is, thus, a prerequisite for parameter estimation of biological dynamic models. Global identifiability is however difficult to test, since it requires solving a system of algebraic nonlinear equations which increases both in nonlinearity degree and number of terms and unknowns with increasing model order. In this paper, a computer algebra tool, GLOBI (GLOBal Identifiability) is presented, which combines the topological transfer function method with the Buchberger algorithm, to test global identifiability of linear compartmental models. GLOBI allows for the automatic testing of a priori global identifiability of general structure compartmental models from general multi input-multi output experiments. Examples of usage of GLOBI to analyze a priori global identifiability of some complex biological compartmental models are provided.

  17. Intrathecal administration of clonidine or yohimbine decreases the nociceptive behavior caused by formalin injection in the marsh terrapin (Pelomedusa subrufa)

    DEFF Research Database (Denmark)

    Makau, Christopher M; Towett, Philemon K; Abelson, Klas S P

    2014-01-01

    BACKGROUND: The role of noradrenergic system in the control of nociception is documented in some vertebrate animals. However, there are no data showing the role of this system on nociception in the marsh terrapins. METHODOLOGY: In this study, the antinociceptive action of intrathecal administration...... of the α 2-adrenoreceptor agonist clonidine and α 2-adrenoreceptor antagonist yohimbine was evaluated in the African marsh terrapin using the formalin test. The interaction of clonidine and yohimbine was also evaluated. RESULTS: Intrathecal administration of clonidine (37.5 or 65 μg/kg) caused...... a significant reduction in the mean time spent in pain-related behavior. Yohimbine, at a dose of 25 μg/kg, significantly blocked the effect of clonidine (65 μg/kg). However, administration of yohimbine (40 or 53 μg/kg) caused a significant reduction in the mean time spent in pain-related behavior. Intrathecal...

  18. A COMPARATIVE STUDY OF INTRATHECAL DEXMEDETOMIDINE AND FENTANYL AS ADJUVANTS TO BUPIVACAINE FOR LOWER ABDOMINAL SURGERIES

    Directory of Open Access Journals (Sweden)

    Hari Kishore

    2015-01-01

    Full Text Available INTRODUCTION: Various adjuvants have been used with local anesthetics in spinal anesthesia to improve the quality of block and to provide prolonged postoperative analgesia. Dexmedetomidine, the new highly selective α2 - agonist drug, is now being used as a neuraxial adju vant. AIM: The aim of this study was to evaluate the onset and duration of sensory and motor block, hemodynamic effect, postoperative analgesia, and adverse effects of dexmedetomidine or fentanyl given intrathecally with hyperbaric 0.5% bupivacaine. METHOD OLOGY: Fifty patients classified in American Society of Anesthesiologists classes I and II scheduled for lower abdominal surgeries were included in this prospective cohort study at Amala Institute of Medical Sciences. Patients received either 15 mg hyperba ric bupivacaine plus 25 μg fentanyl (group 1, n = 25 or 15 mg hyperbaric bupivacaine plus 5 μg dexmedetomidine (group 2, n = 25 intrathecally . RESULTS : Patients in dexmedetomidine group (2 had a significantly longer duration of motor and sensory block t han patients in fentanyl group . (1 The mean time regression of motor block to reach Bromage 0 was 17 6 . 2± 5.71 min in d exmeditomid ine group and 16 6 . 36 ± 5.97 min in fentanyl group (P<0.05. Duration of analgesia was 2 39.52 ± 9.05 min in D exmed i tomidine gro up and 189.96 ± 5.35 min in fentanyl group ( p< 0.05. A significant decrease in heart rate was noted in dexmedetomidine group. CONCLUSION : Intrathecal dexmedetomidine is associated with prolonged duration of analgesia and motor block along with significant dec rease in heart rate.

  19. Progression of scoliosis in patients with spastic quadriplegia after the insertion of an intrathecal baclofen pump.

    Science.gov (United States)

    Ginsburg, Glen M; Lauder, Anthony J

    2007-11-15

    Medical and radiographic review of 19 consecutive patients with spastic quadriplegia before and after intrathecal baclofen pump insertion with special attention paid to progression of scoliosis. Many orthopedic surgeons who treat spastic quadriplegic patients have noticed a trend of marked scoliosis progression after the administration of intrathecal baclofen (ITB) via subcutaneous pump and catheter. The purpose of this study is to quantify scoliosis progression in this patient population before and after baclofen administration and compare this to published natural history data. The authors had noted rapid progression of scoliosis in spastic quadriplegic patients after intrathecal baclofen pump insertion. This had been noted at other centers, but no significant statistical analysis had been done comparing prepump to postpump scoliosis progression in these patients. To document the magnitude and rate of scoliosis progressions after the placement of an ITB pump, the charts and radiographs of 19 consecutive nonambulatory patients with spastic quadriplegia and an ITB pump were reviewed. To document the rate of scoliosis progression, each patient had at least 2 pre and 2 postpump insertion spinal radiographs made. All radiographs were made with the patients in the supine position without orthoses. A board-certified orthopedic surgeon reviewed these radiographs. Skeletal maturity was assessed using Risser grading. Catheter tip location and rate of baclofen administration were recorded. For 19 patients with complete radiographic data, average Cobb angles were 10.2 degrees before pump insertion and 25 degrees at an average of 20.9 months after pump insertion (P quadriplegia and ITB pump. The authors are now performing spinal fusions for curves that exceed 40 degrees to 50 degrees in the presence of an ITB pump as recommended by previous reviews of scoliosis and accompanying quadriplegia.

  20. Cardiovascular effects of intrathecally administered bradykinin in the rat: characterization of receptors with antagonists.

    OpenAIRE

    Lopes, P.; Regoli, D.; Couture, R.

    1993-01-01

    1. The effects of intrathecal (i.t.) pretreatment with selective B1 or B2 kinin receptor antagonists were studied on the cardiovascular response to i.t. injection of bradykinin (BK) in conscious freely moving rats. 2. BK (81 pmol) produced an increase in mean arterial pressure (MAP: 9-13 mmHg) and decrease in heart rate (HR: 20-30 beats min-1) that reached a maximum 2 min after injection. 3. The BK-induced cardiovascular responses were dose-dependently and reversibly reduced by four antagonis...

  1. Leukoencephalopathy and cortical leminar necrosis associated with intrathecal methotrexate and cranial irridiation

    International Nuclear Information System (INIS)

    Iqbal, Yasir; Al-Sudairy, Reem; Abdullah, Mohammad F.

    2003-01-01

    With the advent of chemotherapy, mortality rates in children with acute lymphoblastic leukemia have decreased . Though prophylactic treatment of central nervous system (CNS) to prevent leukemic infiltration has reduced the incidence of CNS relapse and improved the survival in pediatric acute lymphoblastic leukemia. We studied a unique case of neurotoxicity associated with prophylactic cranial irradiation and intrathecal MTX. This is the first reported case of pure MTX-related CLN.Perhaps the combination of MTX along with cranial irradiation, can result in increased neurotoxic effects. (author)

  2. Tumor Lysis Syndrome (TLS following intrathecal chemotherapy in a child with acute myelogenous leukemia (AML

    Directory of Open Access Journals (Sweden)

    Chana L. Glasser, MD

    2017-01-01

    Full Text Available Tumor Lysis Syndrome (TLS is a well-known complication of induction therapy for hematologic malignancies. It is characterized by rapid breakdown of malignant white blood cells (WBCs leading to metabolic derangements and serious morbidity if left untreated. Most commonly, TLS is triggered by systemic chemotherapy, however, there have been case reports of TLS following intrathecal (IT chemotherapy, all in patients with acute lymphoblastic leukemia (ALL/lymphoma. Here, we report the first case of a patient with acute myelogenous leukemia (AML who developed TLS following a single dose of IT cytosine arabinoside (Ara-C.

  3. Dosimetry in intrathecal radiogold therapy. 5. Principles of gonad dose calculation

    Energy Technology Data Exchange (ETDEWEB)

    Hliscs, R; Doege, H [Medizinische Akademie, Dresden (German Democratic Republic). Nuklearmedizinische Klinik

    1980-10-01

    Basing on MIRD recommendations the absorbed dose per unit of accumulated activity in the ovaries and testes is calculated when radioactivity is accumulated in the spinal and cerebral liquor space as well as in the liver following instillation of /sup 198/Au colloid for intrathecal therapy of acute leukemia in childhood. The calculations were made for the IAEA standard man as well as for a 100 cm tall child. Besides that the maximum value of ovarian exposure for the child was determined which arises when the ovaries are close to the spinal column.

  4. Central neuraxial opioid analgesia after caesarean section: comparison of epidural diamorphine and intrathecal morphine.

    Science.gov (United States)

    Caranza, R; Jeyapalan, I; Buggy, D J

    1999-04-01

    In a prospective, randomized, double-blind study in 55 women undergoing elective caesarean section under spinal anaesthesia, we compared epidural diamorphine 3 mg (2 distinct boluses, group ED) with single-dose intrathecal morphine 0.2 mg (group SM), in terms of analgesic efficacy, patient satisfaction and side-effects at 2, 3, 4, 8, 12, 16, 24 and 28 h postoperatively. There were no significant differences between groups in pain (assessed by 100 mm visual analogue scale), incidence of pruritus, sedation or respiratory depression measured by continuous pulse oximetry. However, time to first request for supplementary oral analgesia was longer in SM than in ED (mean +/- SD: 22.3+/-12.0 h vs. 13.8+/-6.5 h, P=0.04). The incidence of nausea or vomiting was significantly higher in SM than ED (73% vs. 41%, P=0.01). In ED, the mean +/- SD time to requirement of the second bolus was 6.7+/-3.2 h. There was a high level of satisfaction in both groups. We conclude that two boluses of epidural diamorphine 3 mg and single-dose intrathecal morphine 0.2 mg provide satisfactory analgesia after caesarean section, but spinal morphine was associated with both delayed requirement for supplementary analgesia and a higher incidence of nausea and vomiting.

  5. Spinal cord distribution of sup 3 H-morphine after intrathecal administration: Relationship to analgesia

    Energy Technology Data Exchange (ETDEWEB)

    Nishio, Y.; Sinatra, R.S.; Kitahata, L.M.; Collins, J.G. (Yale Univ. School of Medicine, CT (USA))

    1989-09-01

    The distribution of intrathecally administered {sup 3}H-morphine was examined by light microscopic autoradiography in rat spinal cord and temporal changes in silver grain localization were compared with results obtained from simultaneous measurements of analgesia. After tissue processing, radio-activity was found to have penetrated in superficial as well as in deeper layers (Rexed lamina V, VII, and X) of rat spinal cord within minutes after application. Silver grain density reached maximal values at 30 min in every region of cord studied. Radioactivity decreased rapidly between 30 min and 2 hr and then more slowly over the next 24 hr. In rats tested for responses to a thermal stimulus (tail flick test), intrathecal administration of morphine (5 and 15 micrograms) resulted in significant dose dependent analgesia that peaked at 30 min and lasted up to 5 hr (P less than 0.5). There was a close relationship between analgesia and spinal cord silver grain density during the first 4 hr of the study. It is postulated that the onset of spinal morphine analgesia depends on appearance of molecules at sites of action followed by the activation of anti-nociceptive mechanisms.

  6. T2-weighted vs. intrathecal contrast-enhanced MR cisternography in the evaluation of CSF rhinorrhea

    International Nuclear Information System (INIS)

    Ecin, Gaye; Oner, A. Yusuf; Tokgoz, Nil; Ucar, Murat; Tali, Turgut; Aykol, Sukru

    2013-01-01

    Background: Endoscopic surgical approach is being more widely used in the treatment of cerebrospinal fluid (CSF) rhinorrhea. Accurate localization of CSF fistulas prior to surgery is essential in increasing the success of dural repair and in decreasing negative or recurrent explorations. Purpose: To evaluate and compare intrathecal contrast medium-enhanced magnetic resonance cisternography (CEMRC) with T2-weighted MR cisternography (T2MRC) in identifying the presence and site of CSF rhinorrhea. Material and Methods: Sixty patients with suspected CSF rhinorrhea underwent MR cisternography including intrathecally enhanced fat-suppressed T1WI in three orthogonal planes and T2WI in the coronal plane. Both set of images were reviewed by two blinded radiologists for the presence and location of CSF leakage. Imaging data were compared with surgical findings and/or beta-2 transferrin testing. Results: With surgery proven CSF leakage in 20 instances as reference, CEMRC detected 18 (90%), whereas T2MRC reported only 13 (65%) correctly. Overall, sensitivity, specificity, positive predictive value, and negative predictive value in detecting CSF fistulas were 92%, 80%, 76%, and 93% for CEMRC, and 56%, 77%, 64%, and 71% for T2MRC, respectively. Conclusion: The minimally invasive CEMRC is an effective method with higher sensitivity and specificity than T2MRC in the evaluation of CSF fistulas

  7. Effect of Single Shot Intrathecal Sufentanil on Delivery Time and Analgesia in Nuliparae

    Directory of Open Access Journals (Sweden)

    E. Khoshraftar

    2008-04-01

    Full Text Available Introduction & Objective : The objective of this study was to determine the evaluation of intrathecal sufentanil for labor analgesia with respect to duration of labor stages and relief of pain during labor.Materials & Methods : In a clinical trial 60 subjects with ASA class I were selected and randomly divided in two equal groups. 30 subjects had received sufentanil 10 gr in 1 ml of saline during active phase of first stage of labor. The other group as controls, did not receive anything for analgesia. Parturient visual analog scale (VAS , HR, RR, BP, sensory and motor block, FHR and complications such as nausea, vomiting, pruritus and duration of stage I been monitored recorded and compared among those two groups.Results : Comparison of results in two groups have showed that sufentanil does not prolong the duration of labor in stage 1 and 2. We observed lack of hypotension and respiratory depression in sufentanil group FHR changes that had been associated with adverse neonatal out come had not occurred. The apgar scores in two groups were identical. There was itching in majority of parturient who had received sufentanil (83.3%. The pruritus were defined as mild and moderate. Conclusion : Intrathecal sufentanil provide a good analgesia in stage I labor and does not prolong the duration of labor with minimum adverse effects on parturient and fetus.

  8. The hypoxic cytotoxin SR 4233 increases the effectiveness of radioimmunotherapy in mice with human non-Hodgkin's lymphoma xenografts.

    Science.gov (United States)

    Wilder, R B; McGann, J K; Sutherland, W R; Waller, E K; Minchinton, A I; Goris, M L; Knox, S J

    1994-01-01

    To determine if either the hypoxic cell radiosensitizer etanidazole (SR 2508) or the hypoxic cytotoxin SR 4233 could improve the effectiveness of radioimmunotherapy. LC4 (an IgG1 monoclonal antibody directed toward malignant T cells) and MB-1 (an irrelevant isotype-matched control antibody) were injected intraperitoneally into severe combined immunodeficient phenotype mice with human cutaneous T cell lymphoma xenografts in order to determine the distribution of the antibodies in the tumors and normal tissues as a function of time. Computerized-pO2-histography was used to measure the median oxygen tension in the tumors. Tumor-bearing mice were treated with: (a) LC4; (b) 90Y-LC4; (c) 90Y-MB-1; (d) whole body irradiation delivered via an external 137Cs source; (e) etanidazole and 90Y-LC4; (f) SR 4233 and 90Y-LC4; (g) etanidazole; and (h) SR 4233. An additional group of mice received no treatment and served as controls. A tumor growth delay assay was used to assess the effectiveness of the different treatment regimens. LC4 accumulated in the tumors to a significantly greater extent than MB-1 (p LC4 by itself was able to produce a minor decrease in tumor size (control vs. LC4; p = 0.001). 90Y-LC4 produced greater tumor growth delay than LC4 alone (LC4 vs. 90Y-LC4; p = 0.01); however, the Yttrium-90 caused neutropenia and weight loss. The 90Y-labeled tumor-specific and non-specific antibodies both exerted greater tumor growth delay than externally delivered whole body irradiation (p LC4 (90Y-LC4 vs etanidazole and 90Y-LC4, p = 0.13). SR 4233, on the other hand, did enhance the tumor growth delay produced by 90Y-LC4 (90Y-LC4 vs. SR 4233 and 90Y-LC4, p = 0.046). The neutropenia and weight loss caused by 90Y-LC4 were exacerbated slightly (< 10%) by the administration of SR 4233. A first generation hypoxic cytotoxin, SR 4233, was able to enhance the tumor growth delay produced by radioimmunotherapy in severe combined immunodeficient phenotype mice with human cutaneous T cell

  9. Macroanatomy and compartmentalization of recent fire scars in three North American conifers

    Science.gov (United States)

    Kevin T. Smith; Estelle Arbellay; Donald A. Falk; Elaine Kennedy Sutherland

    2016-01-01

    Fire scars are initiated by cambial necrosis caused by localized lethal heating of the tree stem. Scars develop as part of the linked survival processes of compartmentalization and wound closure. The position of scars within dated tree ring series is the basis for dendrochronological reconstruction of fire history. Macroanatomical features were described for western...

  10. Meningoencephalitis and Compartmentalization of the Cerebral Ventricles Caused by Enterobacter sakazakii

    Science.gov (United States)

    Kleiman, Martin B.; Allen, Stephen D.; Neal, Patricia; Reynolds, Janet

    1981-01-01

    A necrotizing meningoencephalitis complicated by ventricular compartmentalization and abscess formation caused by Enterobacter sakazakii in a previously healthy 5-week-old female is described. A detailed description of the isolate is presented. This communication firmly establishes the pathogenicity of E. sakazakii. PMID:7287892

  11. Sustainability of a Compartmentalized Host-Parasite Replicator System under Periodic Washout-Mixing Cycles

    Directory of Open Access Journals (Sweden)

    Taro Furubayashi

    2018-01-01

    Full Text Available The emergence and dominance of parasitic replicators are among the major hurdles for the proliferation of primitive replicators. Compartmentalization of replicators is proposed to relieve the parasite dominance; however, it remains unclear under what conditions simple compartmentalization uncoupled with internal reaction secures the long-term survival of a population of primitive replicators against incessant parasite emergence. Here, we investigate the sustainability of a compartmentalized host-parasite replicator (CHPR system undergoing periodic washout-mixing cycles, by constructing a mathematical model and performing extensive simulations. We describe sustainable landscapes of the CHPR system in the parameter space and elucidate the mechanism of phase transitions between sustainable and extinct regions. Our findings revealed that a large population size of compartments, a high mixing intensity, and a modest amount of nutrients are important factors for the robust survival of replicators. We also found two distinctive sustainable phases with different mixing intensities. These results suggest that a population of simple host–parasite replicators assumed before the origin of life can be sustained by a simple compartmentalization with periodic washout-mixing processes.

  12. Analysis of a compartmental model of amyloid beta production, irreversible loss and exchange in humans.

    Science.gov (United States)

    Elbert, Donald L; Patterson, Bruce W; Bateman, Randall J

    2015-03-01

    Amyloid beta (Aβ) peptides, and in particular Aβ42, are found in senile plaques associated with Alzheimer's disease. A compartmental model of Aβ production, exchange and irreversible loss was recently developed to explain the kinetics of isotope-labeling of Aβ peptides collected in cerebrospinal fluid (CSF) following infusion of stable isotope-labeled leucine in humans. The compartmental model allowed calculation of the rates of production, irreversible loss (or turnover) and short-term exchange of Aβ peptides. Exchange of Aβ42 was particularly pronounced in amyloid plaque-bearing participants. In the current work, we describe in much greater detail the characteristics of the compartmental model to two distinct audiences: physician-scientists and biokineticists. For physician-scientists, we describe through examples the types of questions the model can and cannot answer, as well as correct some misunderstandings of previous kinetic analyses applied to this type of isotope labeling data. For biokineticists, we perform a system identifiability analysis and a sensitivity analysis of the kinetic model to explore the global and local properties of the model. Combined, these analyses motivate simplifications from a more comprehensive physiological model to the final model that was previously presented. The analyses clearly demonstrate that the current dataset and compartmental model allow determination with confidence a single 'turnover' parameter, a single 'exchange' parameter and a single 'delay' parameter. When combined with CSF concentration data for the Aβ peptides, production rates may also be obtained. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. A new method to estimate parameters of linear compartmental models using artificial neural networks

    International Nuclear Information System (INIS)

    Gambhir, Sanjiv S.; Keppenne, Christian L.; Phelps, Michael E.; Banerjee, Pranab K.

    1998-01-01

    At present, the preferred tool for parameter estimation in compartmental analysis is an iterative procedure; weighted nonlinear regression. For a large number of applications, observed data can be fitted to sums of exponentials whose parameters are directly related to the rate constants/coefficients of the compartmental models. Since weighted nonlinear regression often has to be repeated for many different data sets, the process of fitting data from compartmental systems can be very time consuming. Furthermore the minimization routine often converges to a local (as opposed to global) minimum. In this paper, we examine the possibility of using artificial neural networks instead of weighted nonlinear regression in order to estimate model parameters. We train simple feed-forward neural networks to produce as outputs the parameter values of a given model when kinetic data are fed to the networks' input layer. The artificial neural networks produce unbiased estimates and are orders of magnitude faster than regression algorithms. At noise levels typical of many real applications, the neural networks are found to produce lower variance estimates than weighted nonlinear regression in the estimation of parameters from mono- and biexponential models. These results are primarily due to the inability of weighted nonlinear regression to converge. These results establish that artificial neural networks are powerful tools for estimating parameters for simple compartmental models. (author)

  14. Heterogeneity and compartmentalization of Pneumocystis carinii f. sp. hominis genotypes in autopsy lungs

    DEFF Research Database (Denmark)

    Helweg-Larsen, J; Lundgren, Bettina; Lundgren, Jens Dilling

    2001-01-01

    . Not all genotypes present in the lungs at autopsy were detected in the diagnostic respiratory samples. Compartmentalization of specific ITS and mtLSU rRNA sequence types was observed in different lung segments. In conclusion, the interpretation of genotype data and in particular ITS sequence types...

  15. The Contradictions and Compartmentalizing the Interactions between Integrated Business Structures: Aspect of Branding

    Directory of Open Access Journals (Sweden)

    Nifatova Olena M.

    2017-04-01

    Full Text Available The article is aimed at identifying contradictions and developing a compartmentalizing as to the interaction between integrated business structures, taking into consideration the branding approach to management. The main specific features and contradictions that arise in the process of integration in the domestic market of mergers and acquisitions have been allocated. The contradictions identified were systematized and substantiated at three economic levels: macro-, meso-, and microeconomic. A compartmentalizing of the business units interaction in a merge or an acquisition process has been proposed. This compartmentalizing takes account of the branding aspect through the introduction of «brands interaction» – cluster interaction, circular interaction, holding interaction, linear interaction, which enhances the scientific view of exploring the problem of business units interaction in the process of the formations becoming integrated. The development of a compartmentalizing as to the interaction between integrated business structures, taking into consideration the branding approach to management, would provide a more effective use of the fundamental nature of branding as synergistic force in terms of the system of integration of business structures at the current stage of development of the national economy. Further development of branding issues in this sphere will have a significant impact on the functioning of the integrated business structures with the participation of Ukrainian companies.

  16. Statistical properties of compartmental model parameters extracted from dynamic positron emission tomography experiments

    International Nuclear Information System (INIS)

    Mazoyer, B.M.; Huesman, R.H.; Budinger, T.F.; Knittel, B.L.

    1986-01-01

    Over the past years a major focus of research in physiologic studies employing tracers has been the computer implementation of mathematical methods of kinetic modeling for extracting the desired physiological parameters from tomographically derived data. A study is reported of factors that affect the statistical properties of compartmental model parameters extracted from dynamic positron emission tomography (PET) experiments

  17. Compartmental Model For Uptake Of 137cs By Pine In Forest Soil ...

    African Journals Online (AJOL)

    A compartmental model of soil to pine tree transfer of 137Cs following the Chernobyl nuclear accident is presented. The model was validated using data collected in 1996 at five sites in Northern Ukraine. The transfer constants of 137Cs between model compartments are estimated using a semi-empirical method.

  18. A compartmentalized out-of-equilibrium enzymatic reaction network for sustained autonomous movement

    NARCIS (Netherlands)

    Nijemeisland, M.; Abdelmohsen, L.K.E.A.; Huck, W.T.S.; Wilson, D.A.; van Hest, J.C.M.

    2016-01-01

    Every living cell is a compartmentalized out-ofequilibrium system exquisitely able to convert chemical energy into function. In order to maintain homeostasis, the flux of metabolites is tightly controlled by regulatory enzymatic networks. A crucial prerequisite for the development of lifelike

  19. SYNCHROTRON X-RAY ABSORPTION-EDGE COMPUTED MICROTOMOGRAPHY IMAGING OF THALLIUM COMPARTMENTALIZATION IN IBERIS INTERMEDIA

    Science.gov (United States)

    Thallium (TI) is an extremely toxic metal which, due to its similarities to K, is readily taken up by plants. Thallium is efficiently hyperaccumulated in Iberis intermedia as TI(I). Distribution and compartmentalization of TI in I. intermedia is highes...

  20. Compartmentalization: a conceptual framework for understanding how trees grow and defend themselves

    Science.gov (United States)

    Alex L. Shigo

    1984-01-01

    The purpose of this chapter is to describe a conceptual framework for understanding how trees grow and how they and other perennial plants defend themselves. The concept of compartmentalization has developed over many years, a synthesis of ideas from a number of investigators. It is derived from detailed studies of the gross morphology and cellular anatomy of the wood...

  1. Linear regressive model structures for estimation and prediction of compartmental diffusive systems

    NARCIS (Netherlands)

    Vries, D; Keesman, K.J.; Zwart, Heiko J.

    In input-output relations of (compartmental) diffusive systems, physical parameters appear non-linearly, resulting in the use of (constrained) non-linear parameter estimation techniques with its short-comings regarding global optimality and computational effort. Given a LTI system in state space

  2. Linear regressive model structures for estimation and prediction of compartmental diffusive systems

    NARCIS (Netherlands)

    Vries, D.; Keesman, K.J.; Zwart, H.

    2006-01-01

    Abstract In input-output relations of (compartmental) diffusive systems, physical parameters appear non-linearly, resulting in the use of (constrained) non-linear parameter estimation techniques with its short-comings regarding global optimality and computational effort. Given a LTI system in state

  3. Neuropathological findings after continuous intrathecal administration of S(+)-ketamine for the management of neuropathic cancer pain

    NARCIS (Netherlands)

    Vranken, J. H.; Troost, D.; Wegener, J. T.; Kruis, M. R.; van der Vegt, M. H.

    2005-01-01

    Questions have been raised about the potential neurotoxicity of the neuraxial use of ketamine although ketamine and its active enantiomer S(+)-ketamine have been used intrathecally and epidurally (caudally) for the management of perioperative pain and in a variety of chronic pain syndromes. Clinical

  4. Progressive increase in brain glucose metabolism after intrathecal administration of autologous mesenchymal stromal cells in patients with diffuse axonal injury.

    Science.gov (United States)

    Vaquero, Jesús; Zurita, Mercedes; Bonilla, Celia; Fernández, Cecilia; Rubio, Juan J; Mucientes, Jorge; Rodriguez, Begoña; Blanco, Edelio; Donis, Luis

    2017-01-01

    Cell therapy in neurological disability after traumatic brain injury (TBI) is in its initial clinical stage. We describe our preliminary clinical experience with three patients with diffuse axonal injury (DAI) who were treated with intrathecal administration of autologous mesenchymal stromal cells (MSCs). Three patients with established neurological sequelae due to DAI received intrathecally autologous MSCs. The total number of MSCs administered was 60 × 10 6 (one patient), 100 × 10 6 (one patient) and 300 × 10 6 (one patient). All three patients showed improvement after cell therapy, and subsequent studies with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) showed a diffuse and progressive increase in brain glucose metabolism. Our present results suggest benefit of intrathecal administration of MSCs in patients with DAI, as well as a relationship between this type of treatment and increase in brain glucose metabolism. These preliminary findings raise the question of convenience of assessing the potential benefit of intrathecal administration of MSCs for brain diseases in which a decrease in glucose metabolism represents a crucial pathophysiological finding, such as Alzheimer's disease (AD) and other dementias. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  5. Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies

    Directory of Open Access Journals (Sweden)

    Benedikt Grünewald

    2016-08-01

    Full Text Available Neuromyelitis Optica Spectrum Disorders (NMOSD are associated with autoantibodies (ABs targeting the astrocytic aquaporin-4 water channels (AQP4-ABs. These ABs have a direct pathogenic role by initiating a variety of immunological and inflammatory processes in the course of disease. In a recently-established animal model, chronic intrathecal passive-transfer of immunoglobulin G from NMOSD patients (NMO-IgG, or of recombinant human AQP4-ABs (rAB-AQP4, provided evidence for complementary and immune-cell independent effects of AQP4-ABs. Utilizing this animal model, we here tested the effects of systemically and intrathecally applied pooled human immunoglobulins (IVIg using a preventive and a therapeutic paradigm. In NMO-IgG animals, prophylactic application of systemic IVIg led to a reduced median disease score of 2.4 on a 0–10 scale, in comparison to 4.1 with sham treatment. Therapeutic IVIg, applied systemically after the 10th intrathecal NMO-IgG injection, significantly reduced the disease score by 0.8. Intrathecal IVIg application induced a beneficial effect in animals with NMO-IgG (median score IVIg 1.6 vs. sham 3.7 or with rAB-AQP4 (median score IVIg 2.0 vs. sham 3.7. We here provide evidence that treatment with IVIg ameliorates disease symptoms in this passive-transfer model, in analogy to former studies investigating passive-transfer animal models of other antibody-mediated disorders.

  6. Use of PET volume determination by fuzzy logic in the follow up of lymphomas treated by radio-immunotherapy

    International Nuclear Information System (INIS)

    Esnault, J.M.; Steinling, M.; Huglo, D.; Vermandel, M.; Vermandel, M.; Steinling, M.; Huglo, D.; Morschhauser, F.

    2007-01-01

    Purposes: the aim of this study was to assess if the evaluation of tumoral volumes by fuzzy logic was workable for clinical use. This study was performed with patients followed up for radio-immunotherapy of non-Hodgkin's lymphomas with a comparison of the respective contributions of this quantification and Standardized Uptake Value (S.U.V.). Materials and methods: thirty patients underwent 18 F-FDG PET before treatment and then in an iterative way. The analysis of 217 lesions allowed to evaluate their volumes and S.U.V.. The evolution of these parameters of quantification was compared. Results: these two quantitative parameters did not statistically differ but there were important discrepancies in some examinations. The determination of volumes was sometimes limited by tumoral localization or junction of lesions. Conclusion: this study proved the feasibility of the determination of tumoral volumes by fuzzy method in clinical use. Quantification supplemented the subjective visual analysis, which in most cases was sufficient to appreciate the progression of the disease. This quantification, usually given by the value of the S.U.V., could be improved by the volume data either in a separated way, or combining intensity and volume (total lesion glycolysis). Further work is necessary to specify the predictive value of these parameters in this particular indication. (authors)

  7. Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy

    International Nuclear Information System (INIS)

    Kinuya, Seigo; Yokoyama, Kunihiko; Bai, Jingming; Michigishi, Takatoshi; Tonami, Norihisa; Koshida, Kiyoshi; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki

    2004-01-01

    We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of 131 I-A7, an IgG1 anti-colorectal monoclonal antibody, or 131 I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P 131 I-A7 RIT displayed a marked therapeutic effect (n=8) (P 131 I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P 131 I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases. (orig.)

  8. Carrier-free 194Ir from an 194Os/194Ir generator - a new candidate for radioimmunotherapy

    International Nuclear Information System (INIS)

    Mirzadeh, S.; Rice, D.E.; Knapp, F.F. Jr.

    1992-01-01

    Iridium-194 (t 1/2 = 19.15 h) decays by beta-particle emission (E max = 2.236 MeV) and is a potential candidate for radioimmunotherapy. An important characteristic is availability of 194 Ir from decay of reactor-produced 194 Os (t 1/2 = 6y). We report the fabrication of the first 194 Os/ 194 Ir generator system using activated carbon. In addition, a novel gas thermochromatographic method was developed for the one step conversion of metallic Os to OsO 4 and subsequent separation and purification of OsO 4 . In this manner, the reactor irradiated enriched 192 Os target was converted to 194 OsO 4 , which was then converted to the K 2 OsCl 6 for generator loading. The yield and the elution profile of carrier-free 194 Ir, and 194 Os breakthrough were determined for a prototype generator which was evaluated over a 10-month period. (author)

  9. Radiolabeling of trastuzumab with {sup 177}Lu via DOTA, a new radiopharmaceutical for radioimmunotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira [Department of Medical Physics, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Rajabi, Hossein [Department of Medical Physics, Tarbiat Modares University, Tehran (Iran, Islamic Republic of)], E-mail: hrajabi@modares.ac.ir; Babaei, Mohammad Hossein; Daha, Fariba Johari [Department of Radioisotope, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Salouti, Mojtaba [Department of Biology, School of Sciences, Islamic Azad University - Zanjan Branch, Zanjan (Iran, Islamic Republic of)

    2009-05-15

    Aim: Trastuzumab is a monoclonal antibody that is used in treating breast cancer. We labeled this monoclonal antibody with lutetium-177 and performed in vitro quality control tests as a first step in the production of a new radiopharmaceutical. Material and Methods: Trastuzumab was labeled with lutetium-177 using DOTA as chelator. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Immunoreactivity and toxicity of the complex were tested on MCF7 breast cancer cell line. Results: The radiochemical purity of the complex was 96{+-}0.9%. The stabilities in phosphate buffer and in human blood serum at 96 h postpreparation were 93{+-}1.2% and 85{+-}3.5%, respectively. The immunoreactivity of the complex was 89{+-}1.4%. At a concentration of 1 nM, the complex killed 70{+-}3% of MCF7 cells. At 1.9 nM, 90{+-}5% of the cells were killed. Conclusions: The results showed that the new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy against breast cancer.

  10. RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

    Science.gov (United States)

    2010-01-01

    Background Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation) hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR)-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT) with the EGFR-inhibitor cetuximab. Methods Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant) and overall survival were calculated using Kaplan-Meier estimation. Results Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%); 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS) at 2 years and median overall survival were only 62,5% and 22,2 mo respectively. Conclusion While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial. PMID:21047402

  11. RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

    Directory of Open Access Journals (Sweden)

    Weichert Wilko

    2010-11-01

    Full Text Available Abstract Background Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT with the EGFR-inhibitor cetuximab. Methods Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant and overall survival were calculated using Kaplan-Meier estimation. Results Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%; 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS at 2 years and median overall survival were only 62,5% and 22,2 mo respectively. Conclusion While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial.

  12. Real-time, in vivo measurement of radiation dose during radioimmunotherapy in mice using a miniature MOSFET dosimeter probe

    International Nuclear Information System (INIS)

    Gladstone, D.J.; Chin, L.M.

    1995-01-01

    This report presents the first real-time measurement of absorbed radiation dose during radioimmunotherapy in mice. Dose rate and total dose at the center of the tumor were measured after administration of 90 Y-labeled antibodies using a miniature metal oxide semiconductor field-effect transistor radiation dosimeter probe which was inserted into the center of the tumor volume. Continuous real-time measurements were made for as long as 23 h after injection of the radiolabeled antibodies. Comparison of the real-time dose-rate measurements with estimates based on the MIRD formalism indicates good agreement. The real-time measurements are further compared to measurements made in a second experiment in which groups of mice were sacrificed at individual times after injection of the same radiolabeled antibodies. The real-time measurements agree well with the measurements in excised tumors. The real-time measurements have greater time resolution and are much more efficient than traditional uptake measurements. 17 refs., 2 figs

  13. Extensive scarring induced by chronic intrathecal tubing augmented cord tissue damage and worsened functional recovery after rat spinal cord injury.

    Science.gov (United States)

    Zhang, Shu-xin; Huang, Fengfa; Gates, Mary; White, Jason; Holmberg, Eric G

    2010-08-30

    Intrathecal infusion has been widely used to directly deliver drugs or neurotrophins to a lesion site following spinal cord injury. Evidence shows that intrathecal infusion is efficient for 7 days but is markedly reduced after 14 days, due to time dependent occlusion. In addition, extensive fibrotic scarring is commonly observed with intrathecal infusion. These anomalies need to be clearly elucidated in histology. In the present study, all adult Long-Evans rats received a 25 mm contusion injury on spinal cord T10 produced using the NYU impactor device. Immediately after injury, catheter tubing with an outer diameter of 0.38 mm was inserted through a small dural opening at L3 into the subdural space with the tubing tip positioned near the injury site. The tubing was connected to an Alzet mini pump, which was filled with saline solution and was placed subcutaneously. Injured rats without tubing served as control. Rats were behaviorally tested for 6 weeks using the BBB locomotor rating scale and histologically assessed for tissue scarring. Six weeks later, we found that the intrathecal tubing caused extensive scarring and inflammation, related to neutrophils, macrophages and plasma cells. The tubing's tip was occluded by scar tissue and inflammatory cells. The scar tissue surrounding the tubing consists of 20-70 layers of fibroblasts and densely compacted collagen fibers, seriously compressing and damaging the cord tissue. BBB scores of rats with intrathecal tubing were significantly lower than control rats (p<0.01) from 2 weeks after injury, implying serious impairment of functional recovery caused by the scarring. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  14. RELATIVE POTENCIES OF MOTOR BLOCKADE AFTER INTRATHECAL ROPIVACAINE, LEVOBUPIVACAINE AND BUPIVACAINE

    Directory of Open Access Journals (Sweden)

    Udayagiri Ravisankar

    2015-12-01

    Full Text Available AIM Ever since the times spinal anaesthesia has been introduced by August Bier, multiple drugs at different dosages, concentrations and differing baricities have been studied. This study was conducted to compare the anaesthetic efficacy of intrathecal isobaric 0.5% ropivacaine, isobaric 0.5% bupivacaine and isobaric levobupivacaine in lower abdominal and lower limb surgeries, in 150 ASA grade I and II patients of both sexes in the age group of 19-65 years undergoing elective surgery under spinal anaesthesia. MATERIALS & METHODS After getting ethical committee approval and informed written consent from the patients, 150 patients were allocated into three groups of 50 patients each. The baseline pulse rate and mean arterial pressure were recorded. The first group A received 3ml of isobaric 0.5% ropivacaine (5mg/ml, the second group received 3ml of isobaric 0.5% bupivacaine and the third group C received 3ml of isobaric levobupivacaine intrathecally. The onset of sensory and motor blocks, duration of sensory and motor blocks was recorded in three groups. RESULTS The results were analyzed statistically using epidemiologically information package. On comparison of data we have found that the intrathecal isobaric 0.5% ropivacaine produces delayed onset of both sensory and motor block but of shorter duration which is statistically significant when compared with that of isobaric 0.5% bupivacaine and levobupivacaine. There is no significant inter-group difference between bupivacaine and levobupivacaine except for the mean duration of sensory block, which is more in levobupivacaine group. The quality of motor block which was assessed by Bromage scale, shows relatively lesser degree of motor block for ropivacaine group, when compared with that of bupivacaine and levobupivacaine groups. The haemodynamics were also recorded. The incidence of hypotension and Bradycardia is more in bupivacaine group. The height of block (peak sensory level is higher for

  15. Chronopharmacodynamics of Intrathecal Co-injection of Sufentanyl and Bupivacaine in Orthopedic Surgery of Lower Extremities

    Directory of Open Access Journals (Sweden)

    B Sadri

    2012-05-01

    Full Text Available  

    Background and objectives: In chronopharmacology the biological rhythm variations caused by drug administration is assessed. Evaluation of the time of drug administration and the qualitative and quantitative effects of reactions to drugs is called chronopharmacodynamics. In this study, we assessed the chronopharmacodynamics of intrathecal co-administration of sufentanyl and bupivacaine in surgical operations of lower extremities.  

    Methods: In 2006, patients aged 20-50 with ASA physical status of I and II, who underwent surgical operation of lower extremities were entered into this prospective study. The patients received a slow intrathecal injection of 10 μg sufentanyl and 15 mg bupivacaine into subarachnoid of third and fourth lumbar spaces in 30 seconds. After the operation, the time of first pain sensation and the visual analogue scale (VAS score, as the measure of severity of pain, were recorded.  

    Results: 115 patients were studied in this project. The pain-free interval was considered as the time between injection and patient’s demand for pain relief. This interval was 746 (± 322 minutes. The average score of pain severity on VAS at the time of demand for pain relief was 24.7 (± 9.3. The average pain-free duration in patients injected about noon or at midnight was significantly longer than the pain-free interval of other patients. 

    Conclusion: The results show that intrathecal co-administration of sufentanyl and bupivacaine at noon or midnight (conforming to the circadian rhythm causes better pain-relief with longer duration in comparison with other times of the day or night. 

  16. In vitro stability of low-concentration ziconotide alone or in admixtures in intrathecal pumps.

    Science.gov (United States)

    Dupoiron, Denis; Richard, Hélène; Chabert-Desnot, Vincent; Devys, Catherine; Leynia, Pierre; Boisdron-Celle, Michèle

    2014-07-01

    Ziconotide is often administered in combination with other analgesics via an intrathecal pump. Studies have established that ziconotide is stable when delivered alone in high concentrations. No stability data are available, however, for ziconotide given in low concentrations and/or with other analgesics as usually occurs in clinical oncology practice. The objective of this study was to assess the in vitro stability of ziconotide alone and combined with other analgesics in intrathecal pumps at 37 °C, as well as in syringes at 5 °C, to evaluate conditions for storing and transporting preparations. Various ziconotide concentrations (0.1, 0.25, 0.5, and 0.75 μg/mL) were combined with an admixture of ropivacaine (7.5 mg/mL), morphine (7.5 mg/mL), and clonidine (15 μg/mL) in 20-mL intrathecal pumps at 37 °C and in syringes at 5 °C. Solutions of ziconotide alone in concentrations of 0.25, 0.5, 0.75, and 1 μg/mL were introduced into pumps at 37 °C and syringes at 5 °C. Assays were performed using ultra high pressure liquid chromatography. In admixtures, mean ziconotide concentrations decreased linearly to 53.4% (± 3.33%) of baseline after 35 days. When ziconotide was introduced alone in pumps at 37 °C, the residual concentration on day 31 was 35.54% (± 0.04%) with 0.25 μg/mL, 39.37% (± 0.15%) with 0.5 μg/mL, and 44.49% (± 0.18%) with 1 μg/mL. Ziconotide alone or combined with the other analgesics was stable in syringes stored at 5 °C. The preparations complied with the prescriptions, with a mean error of less than 10%, except with the lowest ziconotide concentration (0.1 μg/mL). At the low ziconotide concentrations studied, the degradation of ziconotide admixed with other drugs was linear and only weakly influenced by the baseline concentration. Linear regression with intrapolation to 30 days showed that the degradation of ziconotide admixed with other drugs was consistent with previously published data. © 2014 International Neuromodulation Society.

  17. Intrathecal volume changes in lumbar spinal canal stenosis following extension and flexion: An experimental cadaver study.

    Science.gov (United States)

    Teske, Wolfram; Schwert, Martin; Zirke, Sonja; von Schulze Pellengahr, Christoph; Wiese, Matthias; Lahner, Matthias

    2015-01-01

    The spinal canal stenosis is a common disease in elderly. The thecal sac narrowing is considered as the anatomical cause for the disease. There is evidence that the anatomical proportions of the lumbar spinal canal are influenced by postural changes. The liquor volume shift during these postural changes is a valuable parameter to estimate the dynamic qualities of this disease. The aim of this human cadaver study was the determination of intrathecal fluid volume changes during the lumbar flexion and the extension. A special measuring device was designed and built for the study to investigate this issue under controlled conditions. The measuring apparatus fixed the lumbar spine firmly and allowed only flexion and extension. The dural sac was closed water tight. The in vitro changes of the intrathecal volumes during the motion cycle were determined according to the principle of communicating vessels. Thirteen human cadaver spines from the Institute of Anatomy were examined in a test setting with a continuous adjustment of motion. The diagnosis of the lumbar spinal stenosis was confirmed by a positive computer tomography prior testing. The volume changes during flexion and extension cycles were measured stepwise in a 2 degree distance between 18° flexion and 18° extension. Three complete series of measurements were performed for each cadaver. Two specimens were excluded because of fluid leaks from further investigation. The flexion of the lumbar spine resulted in an intrathecal volume increase. The maximum volume effects were seen in the early flexion positions of 2° and 4°. The spine reclination resulted in a volume reduction. The maximum extension effect was seen between 14° and 16°. According to our results, remarkable volume effects were seen in the early movements of the lumbar spine especially for the flexion. The results support the concept of the spinal stenosis as a dynamic disease and allow a better understanding of the pathophysiology of this

  18. Long-term intrathecal baclofen: outcomes after more than 10 years of treatment.

    Science.gov (United States)

    Mathur, Sunjay N; Chu, Samuel K; McCormick, Zack; Chang Chien, George C; Marciniak, Christina M

    2014-06-01

    To report outcomes of intrathecal baclofen (ITB) therapy for spasticity management in a cohort of patients who had received this treatment for at least 10 years. A cross-sectional survey and retrospective chart review. An academic rehabilitation outpatient clinic. Adult patients with spasticity treated with ITB for at least 10 years. Surveys included the Brief Pain Inventory, Penn Spasm Frequency Scale, Epworth Sleepiness Scale, Fatigue Severity Scale, Diener Satisfaction with Life, Life Satisfaction Questionnaire, and Intrathecal Baclofen Survey. Twenty-four subjects completed the surveys. The subjects had been treated with ITB from 10.0-28.4 years, with a mean (standard deviation) of 14.7 ± 4.2 years. The mean (standard deviation) dose of ITB was 627.9 ± 306.7 μg/d, with only 6 subjects averaging daily dose changes of more than 10% compared with 3 years earlier. The mean (standard deviation) scores on outcomes surveys were the following: 2.6 ± 2.3 for pain severity on the Brief Pain Inventory, 1.4 ± 0.7 for spasm severity on the Penn Spasm Frequency Scale, 7.9 ± 5.4 on the Epworth Sleepiness Scale, 4.1 ± 1.6 on the Fatigue Severity Scale, 19.4 ± 8.1 on the Diener Satisfaction with Life, 3.9 ± 0.9 on the Life Satisfaction Questionnaire, and 8.8 ± 1.9 for overall satisfaction with ITB on the Intrathecal Baclofen Survey. On the Brief Pain Inventory, the mean scores for pain severity and interference of pain with life showed moderate inverse correlations with ITB dose (r = -0.386, P = .115; and r = -0.447, P = .062, respectively). On the Life Satisfaction Questionnaire, the mean scores for life satisfaction showed statistically significant positive correlation with ITB dose (r = 0.549, P = .021). The subjects reported low levels of pain, moderate levels of life satisfaction, normal levels of sleepiness, low-to-moderate levels of fatigue, infrequent spasms at mild-to-moderate severity, and high levels of satisfaction. The efficacy and favorable adverse

  19. Phylum Verrucomicrobia representatives share a compartmentalized cell plan with members of bacterial phylum Planctomycetes

    Directory of Open Access Journals (Sweden)

    Romeo Tony

    2009-01-01

    Full Text Available Abstract Background The phylum Verrucomicrobia is a divergent phylum within domain Bacteria including members of the microbial communities of soil and fresh and marine waters; recently extremely acidophilic members from hot springs have been found to oxidize methane. At least one genus, Prosthecobacter, includes species with genes homologous to those encoding eukaryotic tubulins. A significant superphylum relationship of Verrucomicrobia with members of phylum Planctomycetes possessing a unique compartmentalized cell plan, and members of the phylum Chlamydiae including human pathogens with a complex intracellular life cycle, has been proposed. Based on the postulated superphylum relationship, we hypothesized that members of the two separate phyla Planctomycetes and Verrucomicrobia might share a similar ultrastructure plan differing from classical prokaryote organization. Results The ultrastructure of cells of four members of phylum Verrucomicrobia – Verrucomicrobium spinosum, Prosthecobacter dejongeii, Chthoniobacter flavus, and strain Ellin514 – was examined using electron microscopy incorporating high-pressure freezing and cryosubstitution. These four members of phylum Verrucomicrobia, representing 3 class-level subdivisions within the phylum, were found to possess a compartmentalized cell plan analogous to that found in phylum Planctomycetes. Like all planctomycetes investigated, they possess a major pirellulosome compartment containing a condensed nucleoid and ribosomes surrounded by an intracytoplasmic membrane (ICM, as well as a ribosome-free paryphoplasm compartment between the ICM and cytoplasmic membrane. Conclusion A unique compartmentalized cell plan so far found among Domain Bacteria only within phylum Planctomycetes, and challenging our concept of prokaryote cell plans, has now been found in a second phylum of the Domain Bacteria, in members of phylum Verrucomicrobia. The planctomycete cell plan thus occurs in at least two

  20. Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

    DEFF Research Database (Denmark)

    Barbosa, Thales C; Vianna, Lauro C; Fernandes, Igor A

    2016-01-01

    . In the present study, we tested whether the attenuation of these neural signals in hypertensive patients could normalize their abnormal increase in blood pressure during physical activity. Attenuation of the neural signals from the leg muscles with intrathecal fentanyl injection reduced the blood pressure...... of fentanyl, a μ-opioid receptor agonist, aiming to attenuate the central projection of opioid-sensitive group III and IV muscle afferent nerves. The cardiovascular response to exercise of these subjects was compared with that of six normotensive men. During cycling, the hypertensive group demonstrated...... an exaggerated increase in blood pressure compared to the normotensive group (mean ± SEM: +17 ± 3 vs. +8 ± 1 mmHg, respectively; P 0.05). Fentanyl inhibited the blood pressure response to exercise...

  1. Clearance from cerebrospinal fluid of intrathecally administered beta-endorphin in monkeys

    International Nuclear Information System (INIS)

    Lee, V.C.; Burns, R.S.; Dubois, M.; Cohen, M.R.

    1984-01-01

    Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and [ 14 C]methoxy-inulin (50 microCi) in 400 microliters of normal saline intrathecally. Serial samples of cerebrospinal fluid were drawn through a previously positioned indwelling spinal catheter and were assayed for concentrations of beta-endorphin (determined by radioimmunoassay) and inulin (determined by liquid scintillation counter). Spinal fluid concentrations of beta-endorphin and inulin peaked and declined in a parallel manner. The clearance ratio (calculated from the reciprocal of the ratio of the areas under the respective curves of elimination of the two species) remained remarkably similar from animal to animal, giving a mean value of 1.060 +/- 0.090 (SEM). This ratio, being near unity, suggests that beta-endorphin is eliminated from spinal fluid in a fashion similar to that of inulin, which is removed exclusively by bulk absorption

  2. Clearance from cerebrospinal fluid of intrathecally administered beta-endorphin in monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Lee, V.C.; Burns, R.S.; Dubois, M.; Cohen, M.R.

    1984-05-01

    Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and (/sup 14/C)methoxy-inulin (50 microCi) in 400 microliters of normal saline intrathecally. Serial samples of cerebrospinal fluid were drawn through a previously positioned indwelling spinal catheter and were assayed for concentrations of beta-endorphin (determined by radioimmunoassay) and inulin (determined by liquid scintillation counter). Spinal fluid concentrations of beta-endorphin and inulin peaked and declined in a parallel manner. The clearance ratio (calculated from the reciprocal of the ratio of the areas under the respective curves of elimination of the two species) remained remarkably similar from animal to animal, giving a mean value of 1.060 +/- 0.090 (SEM). This ratio, being near unity, suggests that beta-endorphin is eliminated from spinal fluid in a fashion similar to that of inulin, which is removed exclusively by bulk absorption.

  3. Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain.

    Science.gov (United States)

    Li, Xiao; Li, Guoqi; Wu, Shaoling; Zhang, Baiyu; Wan, Qing; Yu, Ding; Zhou, Ruijun; Ma, Chao

    2014-07-08

    Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

  4. Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    Xiao Li

    2014-07-01

    Full Text Available Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l lysine-alginate (APA microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

  5. [Intrathecal baclofen therapy for spastic paraparesis due to aortic dissecting aneurysm; recent progress in treatment strategy].

    Science.gov (United States)

    Nakajima, T; Akagawa, H; Ochiai, T; Hayashi, M; Goto, S; Taira, T; Okada, Y

    2009-11-01

    A 48-year-old man suffered from acute dissection of thoracic aortic aneurysm which eventually led to replacement of the ascending aorta with a tube graft. During this clinical course, circulatory failure in intercostal artery resulted in spinal cord infarction followed by moto-sensory disturbance below Th7 dermatomic area. Seven months later, spasticity with pain in both lower extremities became conspicuous that was uncontrollable by any oral medication. Eventually the patient underwent the implantation of continuous infusion pump for intrathecal baclofen therapy (ITB). The clinical condition was remarkably improved and now has been well controlled. ITB, authorized by Japanese Ministry of Health Labour and Welfare in 2006, has notable therapeutic effects on spasticity derived from any sort of central nervous disorder. More promotive enlightenment if ITB is indispensable for enhancement of its medical benefit in Japan.

  6. Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

    International Nuclear Information System (INIS)

    Trigg, M.E.; Makuch, R.; Glaubiger, D.

    1985-01-01

    Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS

  7. Myeloablative radioimmunotherapy with 188Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-α

    International Nuclear Information System (INIS)

    Mutschler, J.; Reske, S.N.; Steinbach, G.; Bunjes, D.; Buchmann, I.

    2009-01-01

    Tumour necrosis factor-α (TNF-α) serum levels may increase due to intensive conditioning regimes with high-dose chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with 188 Re-CD-66-mAb on changes on TNF-α serum levels. Patients, methods: In 18 patients we measured TNF-α before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-α we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-α after conditioning with 188 Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 ± 6.6 pg/ml) and chemotherapy (10.8 ± 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with 188 Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-α. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD. (orig.)

  8. Compartmental and dosimetric studies of anti-CD20 labelled with {sup 188}Re; Estudo compartimental e dosimetrico do Anti-CD20 marcado com {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Kuramoto, Graciela Barrio

    2016-10-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β{sup -} emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β{sup -} emitters as {sup 131}I, {sup 90}Y, {sup 188}Re {sup 177}Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). {sup 188}Re (E{sub β} = 2.12 MeV; E{sub γ} = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, {sup 188}Re can be obtained from a radionuclide generator of {sup 188}W/{sup 188}Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical {sup 188}Re-Anti-CD20, where the radionuclide can be obtained from a generator system {sup 188}W/{sup 188}Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with {sup 188}Re with the marking of the antibody with {sup 90}Y, {sup 131}I, {sup 177}Lu and {sup 99m}Tc (for their similar chemical characteristics) and {sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for {sup 188}Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of {sup 188}Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β{sup -131}I-labeled anti CD20, {sup 177

  9. Analgesic and cardiopulmonary effects of intrathecally administered romifidine or romifidine and ketamine in goats (Capra hircus

    Directory of Open Access Journals (Sweden)

    H.P. Aithal

    2001-07-01

    Full Text Available The study was conducted to evaluate the effects of romifidine alone (50 µg/kg and a combination of romifidine (50 µg/kg and ketamine (2.5 mg/kg after intrathecal administration in goats. Ten adult goats of either sex weighing between 15 and 20 kg were randomly placed in 2 groups (groups I and II. The agents were administered at the lumbosacral subarachnoid space. Clinico-physiological parameters such as analgesia, motor incoordination, sedation, salivation, heart rate, respiratory rate, arterial pressure, central venous pressure and rectal temperature were studied. Other haematobiochemical parameters monitored were packed cell volume, haemoglobin, plasma proteins, glucose, urea and creatinine. The onset of analgesia was faster in group II (35.5 ±6.25 s compared to that of group I (5.2 ±0.54 min. Analgesia of the tail, perineum, hind limbs, flank and thorax was mild to moderate in group I, but complete analgesia of tail, perineum and hind limbs was recorded in group II. Motor incoordination was mild in group I and severe in group II. Significant reduction in heart rate (more pronounced in group I and respiratory rate (more pronounced in group II, and a significant increase in central venous pressure were recorded in both groups. Mean arterial pressure was reduced in both groups, but more markedly in group I. Sedation, electro-cardiogram, rectal temperature and haemato-biochemical parameters did not show significant differences between the 2 groups. The results of this study indicated a possible synergistic analgesic interaction between intrathecally administered romifidine and ketamine, without causing any marked systemic effects in goats.

  10. Comparative Study of Constant Dose Intrathecal Hypobaric Levobupivacaine with Varying Baricities in Lower Limb Surgeries.

    Science.gov (United States)

    Biji, K P; Sunil, M; Ramadas, K T

    2017-01-01

    Hypobaric spinal anesthesia is advantageous for unilateral lower extremity fractures as it obviates pain of lying on fractured limb for performing subarachnoid block. This study compares block characteristics and complications of three different baricities of constant dose intrathecal hypobaric levobupivacaine to determine an optimum baricity. One-twenty American Society of Anesthesiologists Physical Status 1 and 2 patients aged 18-65 years undergoing unilateral lower limb surgeries were divided into three equal groups for this prospective cohort study. To 2 mL intrathecal 0.5% isobaric levobupivacaine (10 mg), 0.4 mL, 0.6 mL, and 0.8 mL of distilled water were added in Groups A, B, and C, respectively. Baricities of Groups A, B, and C are 0.999294, 0.998945, and 0.998806, respectively. Development of sensory and motor block was assessed by the pinprick method and Bromage scale, respectively. The total duration of analgesia and complications were noted. Mean, standard error, one-way ANOVA, and Bonferroni were used to analyze quantitative variables; proportions and Chi-square tests for qualitative variables. Demographic parameters, motor block of operated limb, and complications were comparable. Group C had the fastest onset of sensory block (10.10 min) and maximum duration of analgesia (478.97 min; P < 0.001); but high sensory levels in 48.7%. Group B had T 10 sensory level in 92.5%; onset comparable to Group C ( P = 0.248), and reasonable duration of analgesia (332.50 min). Group A had inadequate sensory levels, slow onset, and early regression. Group B (baricity - 0.998945) has better block characteristics among three groups compared.

  11. Intrathecal tramadol as and adjuvant in subrachnoid block to prolong the duration of analgesia

    International Nuclear Information System (INIS)

    Zahid, F.; Tarar, H. M.; Tariq, M.; Nazir, H.; Zafar, I.; Munir, S.

    2017-01-01

    Objective: To assess the effect of intrathecal tramadol added to bupivacaine to prolong the duration of analgesia in subarachnoid block for lower limb orthopedic surgeries. Study Design: Randomized controlled trial. Place and Duration of Study: Anesthesia department of Combined Military Hospital Sialkot, from Nov 2015 to Apr 2016. Material and Methods: Patients were selected by non-probability consecutive sampling. One hundred and fifty patients from American Society of Anesthesiologists (ASA) I, II and III category fulfilling inclusion criteria undergoing various lower limb orthopedic surgeries were divided into two groups by lottery system. Group tramadol bupivacaine (TB) received 25mg (1 ml) of tramadol plus 2ml (10mg) of 0.5 percent bupivacaine while group bupivacaine alone (SB) received 1 ml normal saline plus 2ml (10mg) of 0.5 percent bupivacaine. Time to first analgesia request was noted as a measure of duration of analgesia. Time of onset of sensory block level and peak sensory block level and time to reach the peak sensory block level were also noted. Quality of anesthesia was compared among two groups. Data were analyzed by using SPSS version 22. Results: Four patients were excluded from the study. The duration of anesthesia was effectively prolonged in group TB 181.56 ± 12.42 mins as compared to group SB 120.93 ± 15.54 mins. VAS score was significantly lower in group TB. Higher peak sensory block levels (T6) were achieved in group TB as compared to group SB. However time to reach the peak sensory block levels were significantly longer in group TB. (4.5 ± 0.47mins vs 3.09 ± 0.54 mins). Conclusion: This study showed that intrathecal tramadol (25mg) can safely be used along with bupivacaine in subarachnoid blockade to prolong the duration of analgesia and improve the quality of anesthesia as well. (author)

  12. A COMPARATIVE STUDY OF INTRATHECAL DEXMEDETOMIDINE AND FENTANYL AS ADJUVANTS TO BUPIVACAINE

    Directory of Open Access Journals (Sweden)

    Gollapalli Hanumanth

    2016-02-01

    Full Text Available INTRODUCTION Uncontrolled postoperative pain may produce a range of detrimental acute and chronic effects. Spinal anaesthesia provided by bupivacaine may be too short for providing postoperative analgesia. This study is conducted to evaluate the efficacy of intrathecal fentanyl and intrathecal dexmedetomidine as an adjuvant to hyperbaric bupivacaine with regards to the onset and duration of sensory and motor blockade, as well as postoperative analgesia and adverse effects. Hundred patients aged 18-55 years were randomly divided into two groups, each group consisting of 50 patients of either sex belonging to ASA class I and II posted for elective lower abdominal surgeries were given spinal anaesthesia using bupivacaine 0.5%, heavy 2.5 ml with either fentanyl 25µg (group F or 5µg of preservative free dexmedetomidine (group D. Assessment of the sensory and motor blockade were done at the end of each minute till the maximum level achieved. Measurement of blood pressure, pulse rate, respiratory rate and arterial oxygen saturation were obtained. Postoperatively the patients were observed for the duration of analgesia, time taken for complete regression of sensory blockade to S1 and time taken for complete recovery of motor power. RESULTS Our results showed a statistically highly significant prolongation of sensory and motor blockade, and postoperative analgesia in the dexmedetomidine group compared to the fentanyl group. In dexmedetomidine group four out of fifty patients, and in fentanyl group two out of fifty patients developed hypotension. In dexmedetomidine group five out of fifty patients, and in fentanyl group two out of fifty patients developed bradycardia. Incidence of pruritis is significantly high in fentanyl group.

  13. The analgesic effects of intrathecal xylazine and detomidine in sheep and their antagonism with systemic atipamezole.

    Science.gov (United States)

    Christina Haerdi-Landerer, M; Schlegel, Urs; Neiger-Aeschbacher, Gina

    2005-09-01

    To evaluate the analgesic and adverse side effects of intrathecal (IT) xylazine (XYL) and detomidine (DET) and the subsequent effects of two doses of intravenous (IV) atipamezole (ATI). Prospective, randomized, cross-over. Five adult healthy female sheep with mean body mass of 55 +/- 2.3 kg. Material and methods Each sheep underwent four treatments: 1) 50 microg kg(-1) XYL IT and 5 microg kg(-1) ATI IV, 2) 50 microg kg(-1) XYL IT and 2.5 microg kg(-1) ATI IV, 3) 10 microg kg(-1) DET IT and 5 microg kg(-1) ATI IV, 4) 10 microg kg(-1) DET IT and 2.5 microg kg(-1) ATI IV. Pain threshold (TH) was tested by applying pulsed and stepwise incremental direct current to the skin overlying the pastern. The current at the point of foot lift was recorded as the TH. Heart rate (HR), mean arterial pressure, arterial oxygen (PO(2)) and carbon dioxide (PCO(2)) tensions were monitored. Outcomes were derived as differences between baseline assessment and measurements after treatment. Two-way anova was used to analyse drug effects, treatment differences between groups were examined with an F-test or Wilcoxon's rank sum test in case of non-parametric data distribution. p was set at 0.05. Both drugs increased the pain TH, caused small increases in PCO(2), and small decreases in HR, the latter was only significant for XYL recipients. Xylazine produced a significantly higher TH, more rapidly and for longer than DET. Atipamezole only significantly affected PaCO(2) in the XYL group 2. The pain TH was not affected in either group after IV ATI. At the doses used, IT XYL, and to a lesser extent DET, induced pastern analgesia. Atipamezole 5 microg kg(-1) IV antagonized some side effects without affecting analgesia. Intrathecal XYL may be useful as an analgesic in sheep. Its safety is increased because IV ATI antagonizes side effects, but not analgesia.

  14. Distribution of label after intrathecal administration of 125I-substance P in the rat

    International Nuclear Information System (INIS)

    Cridland, R.A.; Yashpal, K.; Romita, V.V.; Gauthier, S.; Henry, J.L.

    1987-01-01

    Despite the widespread use of the intrathecal route for the administration of neuroactive agents, little is known about the penetration of these agents into the spinal cord. In the present study, 125 I-substance P was injected via a spinal catheter to the thoracic or sacro-coccygeal spinal cord in the rat (350-400 g) anesthetized with urethane (2.5 g/kg). Spinal cords were removed rapidly at 1 or 10 min after injection and immediately frozen in CCl 2 F 2 . Frozen sections, 20 micron thick, were cut and mounted for autoradiography. Autoradiographs of transverse sections demonstrated that the label penetrated 700 to 1800 micron from the surface of the spinal cord at both levels. In longitudinal sections, this penetration extended about 0.5 cm rostrally and caudally from the site of injection. Serial autoradiographs of transverse sections showed a similar penetration rostro-caudally. In addition, venous blood samples were taken at 1, 6, 11 and 16 min after injection of the labelled peptide. Quantification of the radioactivity in the samples revealed that 0.8 to 3.5% of the total CPM injected had passed into the general circulation at these times. These data indicate that after intrathecal administration of radiolabelled substance P, the label penetrates into the grey matter of the spinal cord to presumed sites of action. They also suggest that the rostro-caudal extent of penetration is more localized than suggested from earlier studies which looked only at levels of radioactivity in pieces of whole spinal cord. Finally, our study has indicated that passage of label into the circulation is negligible at least for substance P

  15. Magnesium Sulphate and Dexmedetomidine used Intrathecally as Adjuvant to Bupivacaine: A Study

    Directory of Open Access Journals (Sweden)

    Zameer Farooq

    2017-08-01

    Full Text Available Background: Intrathecal adjuvants are used for prolongation of duration of subarachnoid block, and provide adequate analgesia. Aim: To evaluate the onset of sensory and motor block, level of sensory block, highest sensory level and Bromage grade at time of onset, induced by Dexmedetomidine and Magnesium sulphate when given intrathecally with 0.5% hyperbaric Bupivacaine for spinal anaesthesia. Materials and methods: 90 patients, of ASA grade I and grade II, age 18-65 years, of either gender, height 150 cm and above and weight 50 kg to 80 kg, scheduled for lower abdominal and lower limb surgery under spinal anaesthesia. They were randomly assigned according to table of randomization into three groups, 30 patients in each group. Patients in Group A were given 15 mg hyperbaric Bupivacaine and 10 μg (0.1 ml Dexmedetomidine and those in Group B were given 15 mg hyperbaric Bupivacaine and 50 mg (0.1 ml magnesium sulphate. Patients in Group C were given 15 mg hyperbaric Bupivacaine and normal saline (0.1 ml as control. The onset of sensory block, motor block, level of sensory and grade of motor block were recorded at the time of onset. Results: Onset of sensory and motor block was shorter in group Dexmed as compared to other two groups, and prolonged in group magnesium as compared to other two groups. The level of sensory block was higher at the time of onset and grade of motor block was more in group Dexmed than other two groups. Conclusion: Addition of Dexmedetomidine to Bupivacaine shortens the onset time whereas addition of Magnesium delays onset.

  16. A case of trigeminal hypersensitivity after administration of intrathecal sufentanil and bupivacaine for labor analgesia

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    Adriano Bechara de Souza Hobaika

    2014-01-01

    Full Text Available Rostral spread of intrathecal drugs and sensitization of supraspinal sites may provoke several adverse effects. This case describes a patient with right hemifacial paresthesia, trismus and dysphasia on the trigeminal nerve distribution after intrathecal sufentanil administration. Primigravida, 34 years, 39 weeks of pregnancy, with hypothyroidism and pregnancy induced hypertension. Allergic to latex. In the use of puran T4, 50 μg /day. When the patient presented cervical dilatation of 4 cm, she requested analgesia. She was placed in the sitting position and a spinal puncture was performed with a 27G needle pencil point in L4/L5 (1.5 mg of bupivacaine plus 7.5 μg of sufentanil. Next, was performed an epidural puncture in the same space. It was injected bupivacaine 0.065%, 10 ml, to facilitate the passage of the catheter. After 5 min lying down in the lateral upright position, she complained of perioral and right hemifacial paresthesia, mainly maxillary and periorbital, as well as trismus and difficulty to speak. The symptoms lasted for 30 min and resolved spontaneously. After 1 h, patient requested supplementary analgesia (12 ml of bupivacaine 0.125% and a healthy baby girl was born. Temporary mental alterations have been described with the use of fentanyl and sufentanil in combined epidural-spinal analgesia, such as aphasia, difficulty of swallowing, mental confusion and even unconsciousness. In this patient, facial areas with paresthesia indicated by patient appear in clear association with the ophthalmic and maxillary branches of the trigeminal nerve and the occurrence of trismus and dysphagia are in association with the mandibular motor branch. The exact mechanism of rostral spread is not known, but it is speculated that after spinal drug administration, a subsequent epidural dose may reduce the intratecal space and propel the drug into the supraspinal sites.

  17. Prilocaine hydrochloride 2% hyperbaric solution for intrathecal injection: a clinical review

    Directory of Open Access Journals (Sweden)

    Manassero A

    2017-03-01

    Full Text Available Alberto Manassero,1 Andrea Fanelli2 1Department of Emergency and Critical Care, Anesthesia and Intensive Care Unit, S. Croce e Carle Hospital, Cuneo, 2Department of Medical and Surgical Sciences, Anesthesia and Intensive Care Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy Abstract: Prilocaine is a local anesthetic characterized by intermediate potency and duration and fast onset of action. As hyperbaric formulation of 5% solution, it was introduced and has been successfully used for spinal anesthesia since 1960. A new formulation of 2% plain and hyperbaric solution is currently available in Europe. Because of its lower incidence of transient neurological symptoms, prilocaine is suggested as substitute to lidocaine and mepivacaine in spinal anesthesia for ambulatory surgery, as well as a suitable alternative to low doses of long-acting local anesthetics. The National Library of Medicine database, the Excerpta Medica database, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials database, were searched for the period 1970 to September 2016, with the aim to identify studies evaluating the intrathecal use of 2% prilocaine. A total of 13 randomized clinical trials (RCTs, 1 observational study, 2 dose finding, and 4 systematic reviews has been used for this review. The studies evaluated showed that 2% hyperbaric prilocaine due to a favorable anesthetic and safety profile is an alternative drug to lidocaine and mepivacaine for spinal anesthesia of intermediate or short duration. In comparison with plain solutions, hyperbaricity remarkably accelerates the onset and offset times of intrathecal 2% prilocaine. Literature suggests a dose ranging between 40 and 60 mg of prilocaine for lower extremities and lower abdominal procedures lasting up to 90 min, whereas a dose ranging from 10 to 30 mg is appropriate for perineal surgery. Readiness for discharge occurs in ~4 h from spinal administration. Keywords

  18. Experimental study on 211At labelled monoclonal antibody 3H11 and its Fab fragment radioimmunotherapy for human gastric cancer xenografts in nude mice

    International Nuclear Information System (INIS)

    Jin Jiannan; Liu Ning; Zhang Shuyuan; Zhang Shiyuan; Luo Deyuan; Zhou Maolun

    1996-01-01

    Experimental radioimmunotherapy investigation of α-emitting radionuclide 211 At labelled anti-gastric cancer monoclonal antibody 3H11 and its Fab fragment for nude mice carrying human gastric cancer xenografts was conducted. Three i.p. injections of 14.8 or 22.2 kBq/g mouse were given, once every 5 days. The results showed that the growth of tumor xenografts was inhibited efficiently. The most evident therapy effect was observed at 15 days after treatment, and the tumor inhibition rates were 65% and 72%, respectively. No radiation injury of important organs was found

  19. Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator.

    Science.gov (United States)

    Weitz, Maximilian; Kim, Jongmin; Kapsner, Korbinian; Winfree, Erik; Franco, Elisa; Simmel, Friedrich C

    2014-04-01

    In vitro compartmentalization of biochemical reaction networks is a crucial step towards engineering artificial cell-scale devices and systems. At this scale the dynamics of molecular systems becomes stochastic, which introduces several engineering challenges and opportunities. Here we study a programmable transcriptional oscillator system that is compartmentalized into microemulsion droplets with volumes between 33 fl and 16 pl. Simultaneous measurement of large populations of droplets reveals major variations in the amplitude, frequency and damping of the oscillations. Variability increases for smaller droplets and depends on the operating point of the oscillator. Rather than reflecting the stochastic kinetics of the chemical reaction network itself, the variability can be attributed to the statistical variation of reactant concentrations created during their partitioning into droplets. We anticipate that robustness to partitioning variability will be a critical challenge for engineering cell-scale systems, and that highly parallel time-series acquisition from microemulsion droplets will become a key tool for characterization of stochastic circuit function.

  20. Low intrathecal antibody production despite high seroprevalence of Epstein-Barr virus in multiple sclerosis: a review of the literature.

    Science.gov (United States)

    Ruprecht, Klemens; Wildemann, Brigitte; Jarius, Sven

    2018-02-01

    Patients with multiple sclerosis (MS) frequently have an intrathecal production of antibodies to different common viruses, which can be detected by elevated antiviral antibody indices (AIs). There is a strong and consistent association of MS and Epstein-Barr virus (EBV) infection. To systematically compare the frequencies of intrathecal antibody production to EBV, measles virus, rubella virus, varicella zoster virus (VZV) and herpes simplex virus (HSV) in patients with MS. Review of the English and German literature on the frequencies of intrathecal immunoglobulin (Ig)G antibody production, as defined by an elevated AI, to EBV, measles virus, rubella virus, VZV and HSV in adult and pediatric patients with MS. In nine original studies identified, the frequencies of an intrathecal production of antibodies to Epstein-Barr nuclear antigen-1 (33/340, 9.7%), EBV viral capsid antigen (12/279, 4.3%) and antigens from EBV-infected cell lines (14/90, 15.6%) in adult patients with MS were clearly lower (p ≤ 0.03 for all pairwise comparisons) than the frequencies of an intrathecal production of antibodies to measles virus (612/922, 66.4%), rubella virus (521/922, 56.5%), VZV (470/922, 51%; data from 17 original studies) and HSV (78/291, 26.8%; data from 6 original studies). Though based on a lower number of original studies and patients, findings in children with MS were essentially similar. As in adults and children with MS the seroprevalence of EBV is higher than the seroprevalences of the other investigated viruses, the lower frequency of elevated EBV AIs became even more pronounced after correction of the frequencies of elevated antiviral AIs for the seroprevalences of the respective viruses. Given the very high seroprevalence of EBV in MS, the frequency of intrathecally produced antibodies to EBV in patients with MS is paradoxically low compared to that of other common viruses. These findings are compatible with the recently proposed hypothesis that in individuals

  1. Abdominal girth and vertebral column length aid in predicting intrathecal hyperbaric bupivacaine dose for elective cesarean section.

    Science.gov (United States)

    Wei, Chang-Na; Zhou, Qing-He; Wang, Li-Zhong

    2017-08-01

    Currently, there is no consensus on how to determine the optimal dose of intrathecal bupivacaine for an individual undergoing an elective cesarean section. In this study, we developed a regression equation between intrathecal 0.5% hyperbaric bupivacaine volume and abdominal girth and vertebral column length, to determine a suitable block level (T5) for elective cesarean section patients.In phase I, we analyzed 374 parturients undergoing an elective cesarean section that received a suitable dose of intrathecal 0.5% hyperbaric bupivacaine after a combined spinal-epidural (CSE) was performed at the L3/4 interspace. Parturients with T5 blockade to pinprick were selected for establishing the regression equation between 0.5% hyperbaric bupivacaine volume and vertebral column length and abdominal girth. Six parturient and neonatal variables, intrathecal 0.5% hyperbaric bupivacaine volume, and spinal anesthesia spread were recorded. Bivariate line correlation analyses, multiple line regression analyses, and 2-tailed t tests or chi-square test were performed, as appropriate. In phase II, another 200 parturients with CSE for elective cesarean section were enrolled to verify the accuracy of the regression equation.In phase I, a total of 143 parturients were selected to establish the following regression equation: YT5 = 0.074X1 - 0.022X2 - 0.017 (YT5 = 0.5% hyperbaric bupivacaine volume for T5 block level; X1 = vertebral column length; and X2 = abdominal girth). In phase II, a total of 189 participants were enrolled in the study to verify the accuracy of the regression equation, and 155 parturients with T5 blockade were deemed eligible, which accounted for 82.01% of all participants.This study evaluated parturients with T5 blockade to pinprick after a CSE for elective cesarean section to establish a regression equation between parturient vertebral column length and abdominal girth and 0.5% hyperbaric intrathecal bupivacaine volume. This equation can accurately

  2. A Residual Approach for Balanced Truncation Model Reduction (BTMR of Compartmental Systems

    Directory of Open Access Journals (Sweden)

    William La Cruz

    2014-05-01

    Full Text Available This paper presents a residual approach of the square root balanced truncation algorithm for model order reduction of continuous, linear and time-invariante compartmental systems. Specifically, the new approach uses a residual method to approximate the controllability and observability gramians, whose resolution is an essential step of the square root balanced truncation algorithm, that requires a great computational cost. Numerical experiences are included to highlight the efficacy of the proposed approach.

  3. Individual optimization of therapeutic applications and dosimetry of radiopharmaceuticals with the help of compartmental analysis

    International Nuclear Information System (INIS)

    Augusto Ciussani

    2007-01-01

    Complete test of publication follows. The successful application of radiopharmaceuticals requires a patient-specific optimization of the activity to be administered, in order to deliver the desired therapeutic dose to the target organ while saving the healthy tissues. For a therapy specifically tailored on the characteristics of the patient, the correct knowledge of the morphology of the regions of interest, of the fractional uptake and of the related kinetics is necessary. Compartmental modelling can represent a powerful and simple tool for deriving the information of interest. In this presentation, the potentiality of compartmental analysis will be illustrated and two applications presented. The first study was conducted in patients with the autonomous functioning thyroid nodule (AFTN) syndrome treated with 131 I at the Ospedale Maggiore Policlinico of Milano (Milano, Italy). In these patients, the great challenge is represented by the healthy lobe surrounding the malignant nodule. A model was developed, where nodule and lobe are considered as separate entities in order to provide distinct dose estimates for the two tissues. The model has been also used for the optimization of the sampling schedule and for interpretation of biokinetic discrepancies observed between the diagnostic tests and the therapeutic application. The second study, carried out at Ospedali Riuniti di Bergamo (Bergamo, Italy), dealt with the application of [ 186 Re]-HEDP (hydroxyethyliden-diphosphonate disodium salt) for palliation of pain due to bone metastases of primary carcinomas. On the basis of the biodistribution studies and of chromatographic measurements, a compartmental model was suggested, taking into account the possible dissociation of the compound after injection into the patient. Also in this case, the compartmental model represents a valuable tool for individual optimization of the therapeutic procedure and for a more precise evaluation of the radiation dose the organs.

  4. A compartmentalized solute transport model for redox zones in contaminated aquifers: 1. Theory and development

    Science.gov (United States)

    Abrams , Robert H.; Loague, Keith

    2000-01-01

    This paper, the first of two parts [see Abrams and Loague, this issue], takes the compartmentalized approach for the geochemical evolution of redox zones presented by Abrams et al. [1998] and embeds it within a solute transport framework. In this paper the compartmentalized approach is generalized to facilitate the description of its incorporation into a solute transport simulator. An equivalent formulation is developed which removes any discontinuities that may occur when switching compartments. Rate‐limited redox reactions are modeled with a modified Monod relationship that allows either the organic substrate or the electron acceptor to be the rate‐limiting reactant. Thermodynamic constraints are used to inhibit lower‐energy redox reactions from occurring under infeasible geochemical conditions without imposing equilibrium on the lower‐energy reactions. The procedure used allows any redox reaction to be simulated as being kinetically limited or thermodynamically limited, depending on local geochemical conditions. Empirical reaction inhibition methods are not needed. The sequential iteration approach (SIA), a technique which allows the number of solute transport equations to be reduced, is adopted to solve the coupled geochemical/solute transport problem. When the compartmentalized approach is embedded within the SIA, with the total analytical concentration of each component as the dependent variable in the transport equation, it is possible to reduce the number of transport equations even further than with the unmodified SIA. A one‐dimensional, coupled geochemical/solute transport simulation is presented in which redox zones evolve dynamically in time and space. The compartmentalized solute transport (COMPTRAN) model described in this paper enables the development of redox zones to be simulated under both kinetic and thermodynamic constraints. The modular design of COMPTRAN facilitates the use of many different, preexisting solute transport and

  5. The Propeptide of the Metalloprotease of Listeria monocytogenes Controls Compartmentalization of the Zymogen during Intracellular Infection▿

    OpenAIRE

    O'Neil, Heather S.; Forster, Brian M.; Roberts, Kari L.; Chambers, Andrew J.; Bitar, Alan Pavinski; Marquis, Hélène

    2009-01-01

    Integral to the virulence of the intracellular bacterial pathogen Listeria monocytogenes is its metalloprotease (Mpl). Mpl regulates the activity and compartmentalization of the bacterial broad-range phospholipase C (PC-PLC). Mpl is secreted as a proprotein that undergoes intramolecular autocatalysis to release its catalytic domain. In related proteases, the propeptide serves as a folding catalyst and can act either in cis or in trans. Propeptides can also influence protein compartmentalizati...

  6. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

    DEFF Research Database (Denmark)

    Kreft, Marko; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2012-01-01

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy......-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation....

  7. Repurposing the Saccharomyces cerevisiae peroxisome for compartmentalizing multi-enzyme pathways

    Energy Technology Data Exchange (ETDEWEB)

    DeLoache, William [Univ. of California, Berkeley, CA (United States); Russ, Zachary [Univ. of California, Berkeley, CA (United States); Samson, Jennifer [Univ. of California, Berkeley, CA (United States); Dueber, John [Univ. of California, Berkeley, CA (United States)

    2017-09-25

    The peroxisome of Saccharomyces cerevisiae was targeted for repurposing in order to create a synthetic organelle that provides a generalizable compartment for engineered metabolic pathways. Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk, improving pathway efficiency, and ultimately modifying the chemical environment to be distinct from that of the cytoplasm. We focused on the Saccharomyces cerevisiae peroxisome, as this organelle is not required for viability when grown on conventional media. We identified an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly importing non-native cargo proteins. Additionally, we performed the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay and characterized the size dependency of metabolite trafficking. Finally, we applied these new insights to compartmentalize a two-enzyme pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titer. This work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.

  8. Robust global identifiability theory using potentials--Application to compartmental models.

    Science.gov (United States)

    Wongvanich, N; Hann, C E; Sirisena, H R

    2015-04-01

    This paper presents a global practical identifiability theory for analyzing and identifying linear and nonlinear compartmental models. The compartmental system is prolonged onto the potential jet space to formulate a set of input-output equations that are integrals in terms of the measured data, which allows for robust identification of parameters without requiring any simulation of the model differential equations. Two classes of linear and non-linear compartmental models are considered. The theory is first applied to analyze the linear nitrous oxide (N2O) uptake model. The fitting accuracy of the identified models from differential jet space and potential jet space identifiability theories is compared with a realistic noise level of 3% which is derived from sensor noise data in the literature. The potential jet space approach gave a match that was well within the coefficient of variation. The differential jet space formulation was unstable and not suitable for parameter identification. The proposed theory is then applied to a nonlinear immunological model for mastitis in cows. In addition, the model formulation is extended to include an iterative method which allows initial conditions to be accurately identified. With up to 10% noise, the potential jet space theory predicts the normalized population concentration infected with pathogens, to within 9% of the true curve. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Human Lsg1 defines a family of essential GTPases that correlates with the evolution of compartmentalization

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    Scheffzek Klaus

    2005-10-01

    Full Text Available Abstract Background Compartmentalization is a key feature of eukaryotic cells, but its evolution remains poorly understood. GTPases are the oldest enzymes that use nucleotides as substrates and they participate in a wide range of cellular processes. Therefore, they are ideal tools for comparative genomic studies aimed at understanding how aspects of biological complexity such as cellular compartmentalization evolved. Results We describe the identification and characterization of a unique family of circularly permuted GTPases represented by the human orthologue of yeast Lsg1p. We placed the members of this family in the phylogenetic context of the YlqF Related GTPase (YRG family, which are present in Eukarya, Bacteria and Archea and include the stem cell regulator Nucleostemin. To extend the computational analysis, we showed that hLsg1 is an essential GTPase predominantly located in the endoplasmic reticulum and, in some cells, in Cajal bodies in the nucleus. Comparison of localization and siRNA datasets suggests that all members of the family are essential GTPases that have increased in number as the compartmentalization of the eukaryotic cell and the ribosome biogenesis pathway have evolved. Conclusion We propose a scenario, consistent with our data, for the evolution of this family: cytoplasmic components were first acquired, followed by nuclear components, and finally the mitochondrial and chloroplast elements were derived from different bacterial species, in parallel with the formation of the nucleolus and the specialization of nuclear components.

  10. Self-concept structure and borderline personality disorder: evidence for negative compartmentalization.

    Science.gov (United States)

    Vater, Aline; Schröder-Abé, Michela; Weißgerber, Susan; Roepke, Stefan; Schütz, Astrid

    2015-03-01

    Borderline personality disorder (BPD) is characterized by an unstable and incongruent self-concept. However, there is a dearth of empirical studies investigating self-concept in BPD. In order to bridge this research gap, the purpose of this study was to apply an in-depth analysis of structural aspects of the self-concept in BPD. We examined the degree of compartmentalization, i.e., a tendency to organize knowledge about the self into discrete, extremely valenced (i.e., either positive or negative) categories (Showers, 1992). We hypothesized and found that BPD patients had the most compartmentalized self-concept structure and a higher proportion of negative self-attributes relative to both a non-clinical and a depressed control group. Moreover, BPD patients rated negative self-aspects as more important than positive ones relative to non-clinical controls. We cannot determine whether causal relationships exist between psychological symptoms and self-concept structure. Moreover, further comparisons to patients with other psychiatric disorders are necessary in order to further confirm the clinical specificity of our results. Our findings indicate that a negative compartmentalized self-concept is a specific feature of BPD. Implications for future research, psychological assessment, and psychotherapeutic treatment are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies

    International Nuclear Information System (INIS)

    Shen, Shang; Forero, Andres; LoBuglio, Albert F.; Breitz, H.; Khazaeli, M. B.; Fisher, Darrell R.; Wang, W. Q.; Meredith, Ruby F.

    2005-01-01

    Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies. Shen S, Forero A, Lobuglio AF, Breitz H, Khazaeli MB, Fisher DR, Wang W, Meredith RF. Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, and Radioisotopes Program at Pacific Northwest National Laboratory, Richland, Washington. Pretargeted radioimmunotherapy (RIT) using CC49 fusion protein, comprised of CC49-(scFv)(4) and streptavidin, in conjunction with (90)Y/(111)In-DOTA-biotin (DOTA = dodecanetetraacetic acid) provides a new opportunity to improve efficacy by increasing the tumor-to-normal tissue dose ratio. To our knowledge, the patient-specific dosimetry of pretargeted (90)Y/(111)In-DOTA-biotin after CC49 fusion protein in patients has not been reported previously. METHODS: Nine patients received 3-step pretargeted RIT: (a) 160 mg/m(2) of CC49 fusion protein, (b) synthetic clearing agent (sCA) at 48 or 72 h later, and (c) (90)Y/(111)In-DOTA-biotin 24 h after the sCA administration. Sequential whole-body (111)In images were acquired immediately and at 2-144 h after injection of (90)Y/(111)In-DOTA-biotin. Geometric-mean quantification with background and attenuation correction was used for liver and lung dosimetry. Effective point source quantification was used for spleen, kidneys, and tumors. Organ and tumor (90)Y doses were calculated based on (111)In imaging data and the MIRD formalism using patient-specific organ masses determined from CT images. Patient-specific marrow doses were determined based on radioactivity concentration in the blood. RESULTS: The (90)Y/(111)In-DOTA-biotin had a rapid plasma clearance, which was biphasic with <10% residual at 8 h. Organ masses ranged from 1,263 to 3,855 g for liver, 95 to 1,009 g for spleen, and 309 to 578 g for kidneys. The patient-specific mean (90)Y dose (cGy/37 MBq, or rad/mCi) was 0.53 (0.32-0.78) to whole body

  12. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

    Science.gov (United States)

    Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W; Swanstrom, Ronald

    2009-04-01

    Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2) mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2) range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+) T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

  13. Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia.

    Directory of Open Access Journals (Sweden)

    Gretja Schnell

    2009-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 invades the central nervous system (CNS shortly after systemic infection and can result in the subsequent development of HIV-1-associated dementia (HAD in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1-associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA, targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t(1/2 mean = 2.27 days. However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t(1/2 range = 9.85 days to no initial decay. The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4(+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD.

  14. Studies on the optimization of leukemia and non-Hodgkin lymphoma therapies using opioids, chemotherapy and radioimmunotherapy

    International Nuclear Information System (INIS)

    Roscher, Mareike

    2013-01-01

    Despite complex treatment schedules for cancer, the occurrence of resistances and relapses is a major concern in oncology. Hence, novel treatment options are needed. In this thesis, different approaches using radioimmunotherapy and the opioid D,L-methadone alone or in combination with doxorubicin were analyzed regarding their cytotoxic potential and the triggered signalling pathways in sensitive and resistant leukaemia and non-Hodgkin lymphoma (NHL). The radioimmunoconjugates [Bi-213]anti-CD33 and [Bi-213]anti-CD20 for treatment of acute myeloid leukaemia (AML) or NHL, respectively, were applied exemplary for the use of targeted alpha-therapies (TAT). Depending on the analyzed cell lines, the used activity concentrations and specific activities (MBq/μg antibody) apoptosis was induced abrogating radio- and chemo-cross-resistances specifically. The cell death was caspase-dependent activating the mitochondrial pathway and was executed by downregulation of the anti-apoptotic proteins XIAP and Bcl-xL. D,L-Methadone induces apoptosis in vitro and in vivo in opioid-receptor (OR) expressing cells depending on the OR density and the used concentrations. Resistances could be overcome and proliferation was inhibited. In combination with doxorubicin, a synergistic effect regarding cytotoxicity in ex vivo patient cells and cell lines was observed. This effect depends on the increase of doxorubicin uptake co-administering D,L-methadone whereas doxorubicin enhances OR expression. The activation of OR leads to the downregulation of cAMP playing a pivotal role in apoptosis induction. In vivo, the therapeutic potential of D,L-methadone alone or in combination with doxorubicin could be proven as mice transplanted with human T-ALL-cells could be identified as tumour free. In summary, these studies show that TAT using [Bi-213]anti-CD33 and [Bi-213]anti-CD20 as well as the opioid D,L-methadone harbour the potential to optimize conventional treatment modalities for leukaemia and NHL.

  15. Eradication of colon cancer cells before tumour formation in the peritoneal cavity of mice treated with intraperitoneal Re-186 radioimmunotherapy

    International Nuclear Information System (INIS)

    Kinuya, S.; Hiramatsu, T.; Michigishi, T.

    2006-01-01

    A treatment adjuvant to surgical resection of the primary lesion has been proven to be beneficial in improving the prognosis of patients with high risks of peritoneal dissemination of colon cancer. This study was performed to determine the comparative efficacy of intraperitoneal radioimmunotherapy (RIT) using Re-186 or I-131 labeled murine antibodies in the extermination of cancer cells. A murine anti-colorectal IgG1, A7 monoclonal antibody, was radio-labeled either with I-131 (by the chloramine-T method) or Re-186 (by the MAG3 pre-chelated method). A total number of 16 mice were subjected to RIT with Re-186 A7 (N=8) or I-131 A7 (N=8) at equitoxic doses in Balb/c bu/nu mice 10 min after intraperitoneal injection of LS180 human colon cancer cells. A third group of mice were subjected to chemotherapy with 5-fluorouracil at 30 mg/kg for 4 consecutive days following the intraperitoneal injection of the same LS180 human colon cancer cells. There were 19 mice in the control group who were not subjected to any form of therapy. The results revealed that the mean survival of mice in the control (N-19), I-131 A7 RIT (N=8) and Chemotherapy (N=6) groups were 33.8 ± 1.0, 80.1 ± 2.5 and 49.3 ± 5.3 days respectively. The eight mice who were subjected to Re-186 A7 RIT showed much better survival compared to the other groups. Two of the eight mice from this group died at 105 and 111 days following Re-186 A7 RIT. Other six mice were sacrificed at 172 days, and autopsy revealed no macroscopic peritoneal tumor growth. Based on this pilot study we concluded that individual tumor cells in the peritoneal cavity would be effectively exterminated by intraperitoneal RIT with Re-186 A7. (author)

  16. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orcutt, Kelly Davis; Slusarczyk, Adrian L. [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cieslewicz, Maryelise [Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ruiz-Yi, Benjamin [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Bhushan, Kumar R. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Frangioni, John V. [Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215 (United States); Wittrup, K. Dane, E-mail: wittrup@mit.ed [Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2011-02-15

    Introduction: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. Methods: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). Results: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2{+-}1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a {sup 111}In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.

  17. Use of Re-188 labelled anti-EGFr humanized monoclonal antibody h-R3 for radioimmunotherapy of gliomas

    International Nuclear Information System (INIS)

    Perera, A.; Torres, L.A.; Lopez, G.; Casaco, A.; Batista, J.F.; Pena, Y.; Coca, M.A.; Leyva, R.; Garcia, I.

    2007-01-01

    Full text: Locally administered monoclonal antibodies labelled with radioisotopes like 90Y, 131I, 186Re, 212Bi, 211At, 177Lu and others, constitute a viable and promising alternative for management different kind of malignancies. The development of 188W/188Re generator has given the possibility of having a radionuclide showing satisfactory features for radioimmunotherapy (Eb2.12 MeV, Eg155 keV, T1/2=16.9 h and easy to make labelling approaches, similar to used for 99mTc). Neuroepithelial-derived tumours show an increased expression of the EGF receptor with regard to adjacent normal tissue. This overexpression could be related with the autocrine stimulation of the neoplasm by EGF and TGFb. Humanized monoclonal antibody h-R3 has shown a high affinity for this EGF receptor, blocking the binding of EGF to it receptor and inducing apoptosis. Thus, it could be a good candidate for radioimmunotherapy of neuroepithelial malignancies. The aim of the present work was to label monoclonal antibody h-R3 with 188Re, to assess it in an animal model and evaluate its internal dosimetry and toxicity in patients with grade III-IV gliomas through a phase I clinical trial. Schwarz's direct labelling method was employed. Briefly, a 2000-fold molar excess of 2-mercaptoethanol was used to reduce bisulfide bonds of the antibody. The amount of sodium glucoheptonate, ascorbic acid and stannous fluoride were varied to achieve optimum labelling yield. 188Re-labeling yield was proportional to the volume of stannous glucoheptonate solution added to the formulation. Radiochemical purity of 188Re-h-R3 was 98.0±0.4%. Challenge against 300-fold molar excess of L-cysteine was made to assess the stability of the tracer. There was no significant difference between stability of 188Re-h-R3 and 99mTc-h-R3 against cysteine challenge up to 24 h. Animal biodistribution study was performed at 3 and 24 h after intravenous administration of 188Re-h-R3 through tale vein of Male Wistar rats. The results were

  18. Effects of massage therapy on pain and anxiety arising from intrathecal therapy or bone marrow aspiration in children with cancer.

    Science.gov (United States)

    Çelebioğlu, Ayda; Gürol, Ayşe; Yildirim, Zuhal Keskin; Büyükavci, Mustafa

    2015-12-01

    Cancer and its treatment are stressful and reduce the quality of life in children. The aim of this study was to investigate the effect of massage therapy on pain and anxiety arising from intrathecal therapy or bone marrow aspiration in children with cancer. We conducted a controlled pretest/posttest quasi-experimental study at a paediatric oncology unit in Turkey. Twenty-five children were enrolled in this study. Their pain and anxiety were determined using a visual analogue scale. When the pretest and posttest pain and anxiety levels of the groups were compared, no statistically significant difference was found (P > 0.05). It was determined that pain and anxiety levels in the experimental group decreased significantly. This study provides preliminary evidence for the effectiveness in children of massage in reducing pain and anxiety arising from intrathecal therapy or bone marrow aspiration. © 2014 Wiley Publishing Asia Pty Ltd.

  19. Bone marrow dosimetry using blood-based models for 131i-anti-cd20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Kwon, J. H.; Kim, H. G.; Choi, T. H.

    2005-01-01

    Accurate estimations of radiation absorbed dose are essential part of evaluating the risks and benefits associated with radiotherapy. Determination of red marrow dose is important because myelotoxicity is often dose limiting in radioimmunotherapy. The aim of this study is to set up the procedures of dosimetry with activities in the blood and whole-body and to estimate the dose of patients according to MIRD schema. Therapy activities of 131I (136, 185, 200 mCi) were administrated to patients (n=3). Blood activity concentrations and whole-body images by gamma camera were collected from patients with non-Hodgkin's lymphoma (5min, 6h, 24h, 48h, 72h, 2week). Two kinds of patient specific approaches based on Sgouros bone marrow dosimetry methodology were considered to estimate bone marrow dose. The mean effective half-life in blood and whole-body were 25.2h and 27.1h respectively and the mean absorbed dose to bone marrow was 0.48Gy (0.22∼0.93Gy). The dominant contribution of dose was found to be from bone marrow self-dose (over 60%). The procedures of dosimetry with blood and gamma camera image were established. These enable to estimate the radioimmunotherapy patient's dose retrospectively. Some parts of the procedures need to be elaborated to obtain more accurate dose in the near future

  20. Intrathecal Morphine for Laparoscopic Segmental Colonic Resection as Part of an Enhanced Recovery Protocol: A Randomized Controlled Trial.

    Science.gov (United States)

    Koning, Mark V; Teunissen, Aart Jan W; van der Harst, Erwin; Ruijgrok, Elisabeth J; Stolker, Robert Jan

    2018-02-01

    Management of postoperative pain after laparoscopic segmental colonic resections remains controversial. We compared 2 methods of analgesia within an Enhanced Recovery After Surgery (ERAS) program. The goal of the study was to investigate whether administration of intrathecal bupivacaine/morphine would lead to an enhanced recovery. A single-center, randomized, double-blind controlled trial was performed (NL43488.101.13). Patients scheduled for laparoscopic segmental intestinal resections were considered. Exclusion criteria were patients in whom contraindications to spinal anesthesia were present, conversion to open surgery, and gastric and rectal surgery. The intervention group received single-shot intrathecal bupivacaine/morphine (12.5 mg/300 μg), with an altered dose for older patients. The control group received a sham procedure and a bolus of piritramide (0.1 mg/kg). Both groups received standardized general anesthesia and a patient-controlled intravenous analgesia pump as postoperative analgesia. All patients were treated according to an ERAS protocol. A decrease in days to "fit for discharge" was the primary outcome. Fifty-six patients were enrolled. Intervention group patients were fit for discharge earlier (median of 3 vs 4 days, P = 0.044). Furthermore, there was a significant decrease in opioid use and lower pain scores on the first postoperative day in the intervention group. There were no differences in adverse events (except for more pruritus), time to mobilization, fluid administration, or patient satisfaction. This randomized controlled trial shows that intrathecal morphine is a more effective method of postoperative analgesia in laparoscopic surgery than intravenous opioids within an ERAS program. Recovery is faster and less painful with intrathecal morphine. Other studies have confirmed these results, although data on faster recovery are new and require confirmation in future trials. This study was registered at ClinicalTrials.gov, identifier NCT

  1. Electrophysiologic Study of a Method of Euthanasia Using Intrathecal Lidocaine Hydrochloride Administered during Intravenous Anesthesia in Horses.

    Science.gov (United States)

    Aleman, M; Davis, E; Williams, D C; Madigan, J E; Smith, F; Guedes, A

    2015-01-01

    An intravenous (IV) overdose of pentobarbital sodium is the most commonly used method of euthanasia in veterinary medicine. However, this compound is not available in many countries or rural areas resulting in usage of alternative methods such as intrathecal lidocaine administration after IV anesthesia. Its safety and efficacy as a method of euthanasia have not been investigated in the horse. To investigate changes in mean arterial blood pressure and electrical activity of the cerebral cortex, brainstem, and heart during intrathecal administration of lidocaine. Our hypothesis was that intrathecal lidocaine affects the cerebral cortex and brainstem before affecting cardiovascular function. Eleven horses requiring euthanasia for medical reasons. Prospective observational study. Horses were anesthetized with xylazine, midazolam, and ketamine; and instrumented for recording of electroencephalogram (EEG), electrooculogram (EOG), brainstem auditory evoked response (BAER), and electrocardiogram (ECG). Physical and neurological (brainstem reflexes) variables were monitored. Mean arterial blood pressure was recorded throughout the study. Loss of cerebro-cortical electrical activity occurred up to 226 seconds after the end of the infusion of lidocaine solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of BAER occurred subsequently. Undetectable heart sounds, nonpalpable arterial pulse, and extremely low mean arterial blood pressure supported cardiac death; a recordable ECG was the last variable to disappear after the infusion (300-1,279 seconds). Intrathecal administration of lidocaine is an effective alternative method of euthanasia in anesthetized horses, during which brain death occurs before cardiac death. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  2. Cautious Use of Intrathecal Baclofen in Walking Spastic Patients: Results on Long-term Follow-up.

    Science.gov (United States)

    Dones, Ivano; Nazzi, Vittoria; Tringali, Giovanni; Broggi, Giovanni

    2006-04-01

    Intrathecal baclofen is presently the most effective treatment for diffuse spasticity whatever the cause. The fact that both spasticity is always accompanied by a degree of muscle weakness and that any antispastic treatment causes a decrease in muscle strength indicate that major attention must be paid in treating spasticity in ambulant patients. Methods.  We present here a retrospective study, approved by the insitutional ethics committee, of 22 ambulant spastic patients, selected as homogeneous for disease and disease duration, who were treated with intrathecal baclofen at the Istituto Nazionale Neurologico "C.Besta" in Milan. These patients were followed-up for to 15 years of treatment and their clinical assessment was enriched by the evaluation of their functional independence measurement (FIM) before and during treatment. Results.  There was improvement in quality of life as measured by the FIM scale; however, an increase in the patient's motor performance could not be detected. Conclusion.  Although we did not show any improvement in muscle performance, intrathecal baclofen did improve daily quality of life, even in spastic patients who were able to walk.

  3. Perioperative analgesia after intrathecal fentanyl and morphine or morphine alone for cesarean section: A randomized controlled study.

    Science.gov (United States)

    Weigl, Wojciech; Bieryło, Andrzej; Wielgus, Monika; Krzemień-Wiczyńska, Świetlana; Kołacz, Marcin; Dąbrowski, Michał J

    2017-12-01

    Intrathecal morphine is used in the postoperative management of pain after caesarean section (CS), but might not be optimal for intraoperative analgesia. We hypothesized that intrathecal fentanyl could supplement intraoperative analgesia when added to a local anesthetic and morphine without affecting management of postoperative pain. This prospective, randomized, double-blind, parallel-group study included 60 parturients scheduled for elective CS. Spinal anesthesia consisted of bupivacaine with either morphine 100 μg (M group), or fentanyl 25 μg and morphine 100 μg (FM group). The frequency of intraoperative pain and pethidine consumption in the 24 hours postoperatively was recorded. Fewer patients in the FM group required additional intraoperative analgesia (P fentanyl and morphine may provide better perioperative analgesia than morphine alone in CS and could be useful when the time from anesthesia to skin incision is short. However, an increase in PONV and possible acute spinal opioid tolerance after addition of intrathecal fentanyl warrants further investigation using lower doses of fentanyl.

  4. Comparison of Spinal Block Levels between Laboring and Nonlaboring Parturients Using Combined Spinal Epidural Technique with Intrathecal Plain Bupivacaine

    Directory of Open Access Journals (Sweden)

    Yu-Ying Tang

    2012-01-01

    Full Text Available Background. It was suggested that labor may influence the spread of intrathecal bupivacaine using combined spinal epidural (CSE technique. However, no previous studies investigated this proposition. We designed this study to investigate the spinal block characteristics of plain bupivacaine between nonlaboring and laboring parturients using CSE technique. Methods. Twenty-five nonlaboring (Group NL and twenty-five laboring parturients (Group L undergoing cesarean delivery were enrolled. Following identification of the epidural space at the L3-4 interspace, plain bupivacaine 10 mg was administered intrathecally using CSE technique. The level of sensory block, degree of motor block, and hemodynamic changes were assessed. Results. The baseline systolic blood pressure (SBP and the maximal decrease of SBP in Group L were significantly higher than those in Group NL (=0.002 and =0.03, resp.. The median sensory level tested by cold stimulation was T6 for Group NL and T5 for Group L (=0.46. The median sensory level tested by pinprick was T7 for both groups (=0.35. The degree of motor block was comparable between the two groups (=0.85. Conclusion. We did not detect significant differences in the sensory block levels between laboring and nonlaboring parturients using CSE technique with intrathecal plain bupivacaine.

  5. Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

    Energy Technology Data Exchange (ETDEWEB)

    Hohloch, Karin; Lankeit, H.K.; Truemper, L. [Georg August University, Hematology and Oncology, Goettingen (Germany); Zinzani, P.L. [University of Bologna, Institute of Hematology and Medical Oncology ' ' L. e A. Seragnoli' ' , Bologna (Italy); Scholz, C.W. [Charite, University Berlin, Hematology, Oncology and Tumor Immunology, Berlin (Germany); Lorsbach, M.; Windemuth-Kieselbach, C. [Alcedis GmbH, Giessen (Germany)

    2014-08-15

    Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)

  6. Intrathecal morphine attenuates acute opioid tolerance secondary to remifentanil infusions during spinal surgery in adolescents

    Directory of Open Access Journals (Sweden)

    Tripi PA

    2015-09-01

    Full Text Available Paul A Tripi,1 Matthew E Kuestner,1 Connie S Poe-Kochert,2 Kasia Rubin,1 Jochen P Son-Hing,2 George H Thompson,2 Joseph D Tobias3 1Division of Pediatric Anesthesiology, 2Division of Pediatric Orthopaedic Surgery, Rainbow Babies and Children's Hospital, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, 3Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital, Columbus, OH, USA Introduction: The unique pharmacokinetic properties of remifentanil with a context-sensitive half-life unaffected by length of infusion contribute to its frequent use during anesthetic management during posterior spinal fusion in children and adolescents. However, its intraoperative administration can lead to increased postoperative analgesic requirements, which is postulated to be the result of acute opioid tolerance with enhancement of spinal N-methyl-D-aspartate receptor function. Although strategies to prevent or reduce tolerance have included the coadministration of longer acting opioids or ketamine, the majority of these studies have demonstrated little to no benefit. The current study retrospectively evaluates the efficacy of intrathecal morphine (ITM in preventing hyperalgesia following a remifentanil infusion.Methods: We retrospectively analyzed 54 patients undergoing posterior spinal fusion with segmental spinal instrumentation, to evaluate the effects of ITM on hyperalgesia from remifentanil. Patients were divided into two groups based on whether they did or did not receive remifentanil during the surgery: no remifentanil (control group (n=27 and remifentanil (study group (n=27. Data included demographics, remifentanil dose and duration, Wong–Baker visual analog scale postoperative pain scores, and postoperative intravenous morphine consumption in the first 48 postoperative hours.Results: The demographics of the two study groups were similar. There were no differences in the Wong–Baker visual analog

  7. In vivo kinematics of a robot-assisted uni- and multi-compartmental knee arthroplasty.

    Science.gov (United States)

    Watanabe, Toshifumi; Abbasi, Ali Z; Conditt, Michael A; Christopher, Jennifer; Kreuzer, Stefan; Otto, Jason K; Banks, Scott A

    2014-07-01

    There is great interest in providing reliable and durable treatments for one- and two-compartment arthritic degeneration of the cruciate-ligament intact knee. One approach is to resurface only the diseased compartments with discrete unicompartmental components, retaining the undamaged compartment(s). However, placing multiple small implants into the knee presents a greater surgical challenge than total knee arthroplasty, so it is not certain that the natural knee mechanics can be maintained or restored. The goal of this study was to determine whether near-normal knee kinematics can be obtained with a robot-assisted multi-compartmental knee arthroplasty. Thirteen patients with 15 multi-compartmental knee arthroplasties using haptic robotic-assisted bone preparation were involved in this study. Nine subjects received a medial unicompartmental knee arthroplasty (UKA), three subjects received a medial UKA and patellofemoral (PF) arthroplasty, and three subjects received medial and lateral bi-unicondylar arthroplasty. Knee motions were recorded using video-fluoroscopy an average of 13 months (6-29 months) after surgery during stair and kneeling activities. The three-dimensional position and orientation of the implant components were determined using model-image registration techniques. Knee kinematics during maximum flexion kneeling showed femoral external rotation and posterior lateral condylar translation. All knees showed femoral external rotation and posterior condylar translation with flexion during the step activity. Knees with medial UKA and PF arthroplasty showed the most femoral external rotation and posterior translation, and knees with bicondylar UKA showed the least. Knees with accurately placed uni- or bi-compartmental arthroplasty exhibited stable knee kinematics consistent with intact and functioning cruciate ligaments. The patterns of tibiofemoral motion were more similar to natural knees than commonly has been observed in knees with total knee

  8. DISTING: A web application for fast algorithmic computation of alternative indistinguishable linear compartmental models.

    Science.gov (United States)

    Davidson, Natalie R; Godfrey, Keith R; Alquaddoomi, Faisal; Nola, David; DiStefano, Joseph J

    2017-05-01

    We describe and illustrate use of DISTING, a novel web application for computing alternative structurally identifiable linear compartmental models that are input-output indistinguishable from a postulated linear compartmental model. Several computer packages are available for analysing the structural identifiability of such models, but DISTING is the first to be made available for assessing indistinguishability. The computational algorithms embedded in DISTING are based on advanced versions of established geometric and algebraic properties of linear compartmental models, embedded in a user-friendly graphic model user interface. Novel computational tools greatly speed up the overall procedure. These include algorithms for Jacobian matrix reduction, submatrix rank reduction, and parallelization of candidate rank computations in symbolic matrix analysis. The application of DISTING to three postulated models with respectively two, three and four compartments is given. The 2-compartment example is used to illustrate the indistinguishability problem; the original (unidentifiable) model is found to have two structurally identifiable models that are indistinguishable from it. The 3-compartment example has three structurally identifiable indistinguishable models. It is found from DISTING that the four-compartment example has five structurally identifiable models indistinguishable from the original postulated model. This example shows that care is needed when dealing with models that have two or more compartments which are neither perturbed nor observed, because the numbering of these compartments may be arbitrary. DISTING is universally and freely available via the Internet. It is easy to use and circumvents tedious and complicated algebraic analysis previously done by hand. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Regulation of NAD+ metabolism, signaling and compartmentalization in the yeast Saccharomyces cerevisiae

    Science.gov (United States)

    Kato, Michiko; Lin, Su-Ju

    2014-01-01

    Pyridine nucleotides are essential coenzymes in many cellular redox reactions in all living systems. In addition to functioning as a redox carrier, NAD+ is also a required co-substrate for the conserved sirtuin deacetylases. Sirtuins regulate transcription, genome maintenance and metabolism and function as molecular links between cells and their environment. Maintaining NAD+ homeostasis is essential for proper cellular function and aberrant NAD+ metabolism has been implicated in a number of metabolic- and age-associated diseases. Recently, NAD+ metabolism has been linked to the phosphate-responsive signaling pathway (PHO pathway) in the budding yeast Saccharomyces cerevisiae. Activation of the PHO pathway is associated with the production and mobilization of the NAD+ metabolite nicotinamide riboside (NR), which is mediated in part by PHO-regulated nucleotidases. Cross-regulation between NAD+ metabolism and the PHO pathway has also been reported; however, detailed mechanisms remain to be elucidated. The PHO pathway also appears to modulate the activities of common downstream effectors of multiple nutrient-sensing pathways (Ras-PKA, TOR, Sch9/AKT). These signaling pathways were suggested to play a role in calorie restriction-mediated beneficial effects, which have also been linked to Sir2 function and NAD+ metabolism. Here, we discuss the interactions of these pathways and their potential roles in regulating NAD+ metabolism. In eukaryotic cells, intracellular compartmentalization facilitates the regulation of enzymatic functions and also concentrates or sequesters specific metabolites. Various NAD+-mediated cellular functions such as mitochondrial oxidative phosphorylation are compartmentalized. Therefore, we also discuss several key players functioning in mitochondrial, cytosolic and vacuolar compartmentalization of NAD+ intermediates, and their potential roles in NAD+ homeostasis. To date, it remains unclear how NAD+ and NAD+ intermediates shuttle between different

  10. Regulation of NAD+ metabolism, signaling and compartmentalization in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Kato, Michiko; Lin, Su-Ju

    2014-11-01

    Pyridine nucleotides are essential coenzymes in many cellular redox reactions in all living systems. In addition to functioning as a redox carrier, NAD(+) is also a required co-substrate for the conserved sirtuin deacetylases. Sirtuins regulate transcription, genome maintenance and metabolism and function as molecular links between cells and their environment. Maintaining NAD(+) homeostasis is essential for proper cellular function and aberrant NAD(+) metabolism has been implicated in a number of metabolic- and age-associated diseases. Recently, NAD(+) metabolism has been linked to the phosphate-responsive signaling pathway (PHO pathway) in the budding yeast Saccharomyces cerevisiae. Activation of the PHO pathway is associated with the production and mobilization of the NAD(+) metabolite nicotinamide riboside (NR), which is mediated in part by PHO-regulated nucleotidases. Cross-regulation between NAD(+) metabolism and the PHO pathway has also been reported; however, detailed mechanisms remain to be elucidated. The PHO pathway also appears to modulate the activities of common downstream effectors of multiple nutrient-sensing pathways (Ras-PKA, TOR, Sch9/AKT). These signaling pathways were suggested to play a role in calorie restriction-mediated beneficial effects, which have also been linked to Sir2 function and NAD(+) metabolism. Here, we discuss the interactions of these pathways and their potential roles in regulating NAD(+) metabolism. In eukaryotic cells, intracellular compartmentalization facilitates the regulation of enzymatic functions and also concentrates or sequesters specific metabolites. Various NAD(+)-mediated cellular functions such as mitochondrial oxidative phosphorylation are compartmentalized. Therefore, we also discuss several key players functioning in mitochondrial, cytosolic and vacuolar compartmentalization of NAD(+) intermediates, and their potential roles in NAD(+) homeostasis. To date, it remains unclear how NAD(+) and NAD(+) intermediates

  11. Study of compartmentalization in the visna clinical form of small ruminant lentivirus infection in sheep

    Directory of Open Access Journals (Sweden)

    Ramírez Hugo

    2012-01-01

    Full Text Available Abstract Background A central nervous system (CNS disease outbreak caused by small ruminant lentiviruses (SRLV has triggered interest in Spain due to the rapid onset of clinical signs and relevant production losses. In a previous study on this outbreak, the role of LTR in tropism was unclear and env encoded sequences, likely involved in tropism, were not investigated. This study aimed to analyze heterogeneity of SRLV Env regions - TM amino terminal and SU V4, C4 and V5 segments - in order to assess virus compartmentalization in CNS. Results Eight Visna (neurologically affected sheep of the outbreak were used. Of the 350 clones obtained after PCR amplification, 142 corresponded to CNS samples (spinal cord and choroid plexus and the remaining to mammary gland, blood cells, bronchoalveolar lavage cells and/or lung. The diversity of the env sequences from CNS was 11.1-16.1% between animals and 0.35-11.6% within each animal, except in one animal presenting two sequence types (30% diversity in the CNS (one grouping with those of the outbreak, indicative of CNS virus sequence heterogeneity. Outbreak sequences were of genotype A, clustering per animal and compartmentalizing in the animal tissues. No CNS specific signature patterns were found. Conclusions Bayesian approach inferences suggested that proviruses from broncoalveolar lavage cells and peripheral blood mononuclear cells represented the common ancestors (infecting viruses in the animal and that neuroinvasion in the outbreak involved microevolution after initial infection with an A-type strain. This study demonstrates virus compartmentalization in the CNS and other body tissues in sheep presenting the neurological form of SRLV infection.

  12. Development and testing of a compartmentalized reaction network model for redox zones in contaminated aquifers

    Science.gov (United States)

    Abrams , Robert H.; Loague, Keith; Kent, Douglas B.

    1998-01-01

    The work reported here is the first part of a larger effort focused on efficient numerical simulation of redox zone development in contaminated aquifers. The sequential use of various electron acceptors, which is governed by the energy yield of each reaction, gives rise to redox zones. The large difference in energy yields between the various redox reactions leads to systems of equations that are extremely ill-conditioned. These equations are very difficult to solve, especially in the context of coupled fluid flow, solute transport, and geochemical simulations. We have developed a general, rational method to solve such systems where we focus on the dominant reactions, compartmentalizing them in a manner that is analogous to the redox zones that are often observed in the field. The compartmentalized approach allows us to easily solve a complex geochemical system as a function of time and energy yield, laying the foundation for our ongoing work in which we couple the reaction network, for the development of redox zones, to a model of subsurface fluid flow and solute transport. Our method (1) solves the numerical system without evoking a redox parameter, (2) improves the numerical stability of redox systems by choosing which compartment and thus which reaction network to use based upon the concentration ratios of key constituents, (3) simulates the development of redox zones as a function of time without the use of inhibition factors or switching functions, and (4) can reduce the number of transport equations that need to be solved in space and time. We show through the use of various model performance evaluation statistics that the appropriate compartment choice under different geochemical conditions leads to numerical solutions without significant error. The compartmentalized approach described here facilitates the next phase of this effort where we couple the redox zone reaction network to models of fluid flow and solute transport.

  13. 18F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

    International Nuclear Information System (INIS)

    Salaun, Pierre-Yves; Robin, Philippe; Campion, Loic; Ansquer, Catherine; Mathieu, Cedric; Frampas, Eric; Bournaud, Claire; Vuillez, Jean-Philippe; Taieb, David; Rousseau, Caroline; Drui, Delphine; Mirallie, Eric; Borson-Chazot, Francoise; Goldenberg, David M.; Chatal, Jean-Francois; Barbet, Jacques; Kraeber-Bodere, Francoise

    2014-01-01

    PET is a powerful tool for assessing targeted therapy. Since 18 F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated 18 F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV max , location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUV max (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC

  14. Predictive patient-specific dosimetry and individualized dosing of pretargeted radioimmunotherapy in patients with advanced colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schoffelen, Rafke; Woliner-van der Weg, Wietske; Visser, Eric P.; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, PO Box 9101, Nijmegen (Netherlands); Goldenberg, David M. [Garden State Cancer Center, Morris Plains, NJ (United States); Immunomedics, Inc., Morris Plains, NJ (United States); IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Sharkey, Robert M.; McBride, William J.; Chang, Chien-Hsing [Immunomedics, Inc., Morris Plains, NJ (United States); Rossi, Edmund A. [IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Graaf, Winette T.A. van der [Radboud University Medical Center, Department of Medical Oncology, Nijmegen (Netherlands)

    2014-08-15

    Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies (bsMAb) and a radiolabeled peptide reduces the radiation dose to normal tissues. Here we report the accuracy of an {sup 111}In-labeled pretherapy test dose for personalized dosing of {sup 177}Lu-labeled IMP288 following pretargeting with the anti-CEA x anti-hapten bsMAb, TF2, in patients with metastatic colorectal cancer (CRC). In 20 patients bone marrow absorbed doses (BMD) and doses to the kidneys were predicted based on blood samples and scintigrams acquired after {sup 111}In-IMP288 injection for individualized dosing of PRIT with {sup 177}Lu-IMP288. Different dose schedules were studied, varying the interval between the bsMAb and peptide administration (5 days vs. 1 day), increasing the bsMAb dose (75 mg vs. 150 mg), and lowering the peptide dose (100 μg vs. 25 μg). TF2 and {sup 111}In/{sup 177}Lu-IMP288 clearance was highly variable. A strong correlation was observed between peptide residence times and individual TF2 blood concentrations at the time of peptide injection (Spearman's ρ = 0.94, P < 0.0001). PRIT with 7.4 GBq {sup 177}Lu-IMP288 resulted in low radiation doses to normal tissues (BMD <0.5 Gy, kidney dose <3 Gy). Predicted {sup 177}Lu-IMP288 BMD were in good agreement with the actual measured doses (mean ± SD difference -0.0026 ± 0.028 mGy/MBq). Hematological toxicity was mild in most patients, with only two (10 %) having grade 3-4 thrombocytopenia. A correlation was found between platelet toxicity and BMD (Spearman's ρ = 0.58, P = 0.008). No nonhematological toxicity was observed. These results show that individual high activity doses in PRIT in patients with CEA-expressing CRC could be safely administered by predicting the radiation dose to red marrow and kidneys, based on dosimetric analysis of a test dose of TF2 and {sup 111}In-IMP288. (orig.)

  15. Benefits of combined radioimmunotherapy and anti-angiogenic therapy in a liver metastasis model of human colon cancer cells

    International Nuclear Information System (INIS)

    Li, Xiao-Feng; Kinuya, Seigo; Yokoyama, Kunihiko; Michigishi, Takatoshi; Tonami, Norihisa; Koshida, Kiyoshi; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki

    2002-01-01

    The combined use of anti-angiogenic therapy (AT) and radioimmunotherapy (RIT) may improve the therapeutic outcome in patients with cancer lesions. This hypothesis is based on the ability of AT to suppress tumour endothelial compartments and the direct action of RIT against tumour cells. We previously confirmed this hypothesis in an established subcutaneous xenograft model of colon cancer. The purpose of the current investigation was to determine the benefit of this combination within a liver metastasis model, which mimics treatment of minimal disease in an adjuvant setting. Liver metastases were established in nude mice by intrasplenic inoculation of LS180 colon cancer cells; following such inoculation, metastases of 131 I-A7, an IgG1 anti-colorectal monoclonal antibody, was conducted at 2 weeks. RIT employing an irrelevant IgG1, 131 I-HPMS-1, was implemented for comparison. The weight of liver metastases was measured 4 weeks after cell inoculation. The effect of AT on 131 I-A7 accumulation in metastases was also observed. Toxicity of treatment was monitored by blood cell counts. Monotherapy with 2-ME AT or 131 I-A7 RIT significantly suppressed metastasis growth (P 131 I-A7 RIT. Combination of AT and 131 I-A7 RIT more effectively suppressed the growth to 0.28±0.32 g (P 131 I-HPMS-1 RIT, which suppressed metastasis growth to 2.25±0.88 g, was significant in comparison with the control (P 131 I-HPMS-1 RIT (which suppressed growth to 1.41±0.68 g) was far less effective than the combination of AT and 131 I-A7 RIT. AT did not decrease 131 I-A7 accumulation in metastases. AT did not affect RIT myelotoxicity. The results of this study demonstrating the combined effects of AT and 131 I-A7 RIT in a small metastasis model indicate that such combination therapy may be suitable for the treatment of minimal disease. (orig.)

  16. SU-C-201-05: Imaging 212Pb-TCMC-Trastuzumab for Alpha Radioimmunotherapy for Ovarian Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shen, S; Meredith, R; Azure, M; Yoder, D [University of Alabama, Birmingham, AL (United States); Torgue, J; Banaga, E [AREVA Med LLC, Bethesda, MD (United States)

    2015-06-15

    Purpose: To support the phase I trial for toxicity, biodistribution and pharmacokinetics of intra-peritoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2 expressing malignancy. A whole body gamma camera imaging method was developed for estimating amount of 212Pb-TCMC-trastuzumab left in the peritoneal cavity. Methods: {sup 212}Pb decays to {sup 212}Bi via beta emission. {sup 212}Bi emits an alpha particle at an average of 6.1 MeV. The 238.6 keV gamma ray with a 43.6% yield can be exploited for imaging. Initial phantom was made of saline bags with 212Pb. Images were collected for 238.6 keV with a medium energy general purpose collimator. There are other high energy gamma emissions (e.g. 511keV, 8%; 583 keV, 31%) that penetrate the septae of the collimator and contribute scatter into 238.6 keV. An upper scatter window was used for scatter correction for these high energy gammas. Results: A small source containing 212Pb can be easily visualized. Scatter correction on images of a small 212Pb source resulted in a ∼50% reduction in the full width at tenth maximum (FWTM), while change in full width at half maximum (FWHM) was <10%. For photopeak images, substantial scatter around phantom source extended to > 5 cm outside; scatter correction improved image contrast by removing this scatter around the sources. Patient imaging, in the 1st cohort (n=3) showed little redistribution of 212Pb-TCMC-trastuzumab out of the peritoneal cavity. Compared to the early post-treatment images, the 18-hour post-injection images illustrated the shift to more uniform anterior/posterior abdominal distribution and the loss of intensity due to radioactive decay. Conclusion: Use of medium energy collimator, 15% width of 238.6 keV photopeak, and a 7.5% upper scatter window is adequate for quantification of 212Pb radioactivity inside peritoneal cavity for alpha radioimmunotherapy of ovarian cancer. Research Support: AREVA Med, NIH 1UL1RR025777-01.

  17. Pharmacokinetics and Dosimetry Studies for Optimization of Pretargeted Radioimmunotherapy in CEA-Expressing Advanced Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Caroline eBodet-Milin

    2015-11-01

    Full Text Available Objectives. A phase I pretargeted radioimmunotherapy trial (EudractCT 200800603096 was designed in patients with metastatic lung cancer expressing carcinoembryonic antigen (CEA to optimize bispecific antibody and labelled peptide doses, as well as the delay between their injections.Methods. Three cohorts of 3 patients received the anti-CEA x anti-histamine-succinyl-glycine (HSG humanized trivalent bispecific antibody (TF2 and the IMP288 bivalent HSG-peptide. Patients underwent a pre-therapeutic imaging session S1 (44 or 88 nmol/m2 of TF2 followed by 4.4 nmol/m2, 185 MBq, of 111In-labelled IMP288, and, 1-2 weeks later, a therapy session S2 (240 or 480 nmol/m2 of TF2 followed by 24 nmol/m2, 1.1 GBq/m2, 177Lu-labeled IMP288. The pretargeting delay was 24 or 48 hours. The dose schedule was defined based on pre-clinical TF2 pharmacokinetic studies, on our previous clinical data using the previous anti-CEA pretargeting system and on clinical results observed in the first patients injected using the same system in the Netherlands.Results. TF2 pharmacokinetics (PK was represented by a two-compartment model in which the central compartment volume was linearly dependent on the patient's surface area. PK were remarkably similar, with a clearance of 0.33 +/- 0.03 L/h per m2. 111In- and 177Lu-IMP288 PK were also well represented by a two-compartment model. IMP288 PK were faster (clearance 1.4 to 3.3 l/h. The central compartment volume was proportional to body surface area and IMP288clearance depended on the molar ratio of injected IMP288 to circulating TF2 at the time of IMP288 injection. Modelling of image quantification confirmed the dependence of IMP288 kinetics on circulating TF2, but tumour activity PK were variable. Organ absorbed doses were not significantly different in the 3 cohorts, but the tumour dose was significantly higher with the higher molar doses of TF2 (p < 0.002. S1 imaging predicted absorbed doses calculated in S2. Conclusion. The best

  18. {sup 18}F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Salaun, Pierre-Yves; Robin, Philippe [University Hospital, Nuclear Medicine Department, Brest (France); Campion, Loic [ICO-Gauducheau Cancer Institute, Statistical Department, Nantes (France); Ansquer, Catherine; Mathieu, Cedric [University Hospital, Nuclear Medicine Department, Nantes (France); Frampas, Eric [University Hospital, Radiology Department, Nantes (France); Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); Bournaud, Claire [University Hospital, Nuclear Medicine Department, Lyon (France); Vuillez, Jean-Philippe [University Hospital, Nuclear Medicine Department, Grenoble (France); Taieb, David [University Hospital, Nuclear Medicine Department, Marseille (France); Rousseau, Caroline [Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); ICO-Rene Gauducheau, Nuclear Medicine Department, Nantes (France); Drui, Delphine [University Hospital, Endocrinology Department, Nantes (France); Mirallie, Eric [University Hospital, Surgery Department, Nantes (France); Borson-Chazot, Francoise [University Hospital, Endocrinology Department, Lyon (France); Goldenberg, David M. [IBC Pharmaceuticals, Inc., and Immunomedics, Inc., Morris Plains, NJ (United States); Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, NJ (United States); Chatal, Jean-Francois [GIP ARRONAX, Saint-Herblain (France); Barbet, Jacques [Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); GIP ARRONAX, Saint-Herblain (France); Kraeber-Bodere, Francoise [University Hospital, Nuclear Medicine Department, Nantes (France); Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); ICO-Rene Gauducheau, Nuclear Medicine Department, Nantes (France); Hotel Dieu University Hospital, Nuclear Medicine Department, Nantes (France)

    2014-08-15

    PET is a powerful tool for assessing targeted therapy. Since {sup 18}F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated {sup 18}F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV{sub max}, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUV{sub max} (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the

  19. Intrathecal antibody production in two cases of yellow fever vaccine associated neurotropic disease in Argentina.

    Science.gov (United States)

    Pires-Marczeski, Fanny Clara; Martinez, Valeria Paula; Nemirovsky, Corina; Padula, Paula Julieta

    2011-12-01

    During the period 2007-2008 several epizootics of Yellow fever with dead of monkeys occurred in southeastern Brasil, Paraguay, and northeastern Argentina. In 2008 after a Yellow fever outbreak an exhaustive prevention campaign took place in Argentina using 17D live attenuated Yellow fever vaccine. This vaccine is considered one of the safest live virus vaccines, although serious adverse reactions may occur after vaccination, and vaccine-associated neurotropic disease are reported rarely. The aim of this study was to confirm two serious adverse events associated to Yellow fever vaccine in Argentina, and to describe the analysis performed to assess the origin of specific IgM against Yellow fever virus (YFV) in cerebrospinal fluid (CSF). Both cases coincided with the Yellow fever vaccine-associated neurotropic disease case definition, being clinical diagnosis longitudinal myelitis (case 1) and meningoencephalitis (case 2). Specific YFV antibodies were detected in CSF and serum samples in both cases by IgM antibody-capture ELISA. No other cause of neurological disease was identified. In order to obtain a conclusive diagnosis of central nervous system (CNS) infection the IgM antibody index (AI(IgM) ) was calculated. High AI(IgM) values were found in both cases indicating intrathecal production of antibodies and, therefore, CNS post-vaccinal YFV infection could be definitively associated to YFV vaccination. Copyright © 2011 Wiley Periodicals, Inc.

  20. Intrathecal injection of naked plasmid DNA provides long-term expression of secreted proteins.

    Science.gov (United States)

    Hughes, Travis S; Langer, Stephen J; Johnson, Kirk W; Chavez, Raymond A; Watkins, Linda R; Milligan, Erin D; Leinwand, Leslie A

    2009-01-01

    Therapeutic benefit has been reported to result from intrathecal (i.t.) injection of transgene vectors, including naked DNA. However, most studies using naked DNA have measured only the transgene expression of intracellular proteins. Here we demonstrate that i.t. injection of naked DNA can result in long-term expression of secreted proteins. Plasmids expressing either secreted alkaline phosphatase (SEAP) or human interleukin-10 (hIL-10) were injected into the i.t. space in rats, and transgene products were repeatedly measured in the cerebrospinal fluid (CSF). Both SEAP and hIL-10 were maximal at 1 and 2 days after the injection and still detectable at 4 months. The utilization of a plasmid having two features that are hypothesized to increase gene expression (matrix attachment regions (MARs) and lack of CpG dinucleotides) resulted in a significant increase in gene expression. Reinjection of SEAP or hIL-10 plasmids after 4 months significantly increased protein levels at 1 and 14 days after the reinjection. SEAP was uniformly distributed between the DNA delivery site (approximately vertebral level T13) and the lumbar puncture site (L5/L6 inter-vertebral space), was reduced at the cisterna magna, and was detectable, though at much lower levels, in serum. These data suggest that naked DNA has the potential to be used as a therapeutic tool for applications that require long-term release of transgenes into the CSF.

  1. Neurologic complications of intrathecal liposomal cytarabine administered prophylactically to patients with non-Hodgkin lymphoma.

    Science.gov (United States)

    Gállego Pérez-Larraya, Jaime; Palma, José Alberto; Carmona-Iragui, María; Fernández-Torrón, Roberto; Irimia, Pablo; Rodríguez-Otero, Paula; Panizo, Carlos; Martínez-Vila, Eduardo

    2011-07-01

    Central nervous system (CNS) prophylaxis is required during initial treatment of non-Hodgkin lymphoma (NHL) subtypes that carry a high risk of CNS involvement. Intrathecal (IT) liposomal cytarabine, a formulation with prolonged half-life, has been shown to be safe and effective in the treatment of meningeal disease in patients with high-grade lymphoma. We retrospectively reviewed all adult patients with high-grade NHL that received prophylactic therapy with IT liposomal cytarabine and developed neurologic complications in our institution between April 2007 and May 2009. We recorded information on hospital admission, chemotherapy regimens, clinical features, neuroimaging, cerebrospinal fluid, neurophysiology data, and outcome. Neurotoxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Four of fourteen patients (28%) developed moderate or severe neurotoxicity (grades 2 and 3 of the NCI-CTC), manifested as conus medullaris/cauda equine syndrome or pseudotumour cerebri-like syndrome, after a median of 3.5 IT courses of liposomal cytarabine. All patients had received corticosteroids to prevent arachnoiditis. Liposomal cytarabine given via the IT route, even with concomitant corticosteroid administration, can result in significant neurotoxicity in some patients. We discuss the potential pathogenesis of these effects and suggest hypothetical therapeutic measures to prevent these complications. Specialists should be aware of these possible complications when administering prophylactic IT liposomal cytarabine in high-grade NHL patients, and additional prospective studies should be conducted to more clearly delineate the frequency and characteristics of these complications.

  2. Treatment of severe spacticity in multiple sclerosis by continuous intrathecal baclofen

    Directory of Open Access Journals (Sweden)

    Perić Predrag

    2006-01-01

    Full Text Available Background. Successful treatment of severe spasticity represents an imperative of symptomatic therapy of multiple sclerosis (MS due to a significant improvement of physical, psychic and social rehabilitation of MS patients, as well as a longterm cost savings for the additional treatments of conditions arising from uncontrolled severe spasticity. Continuous intrathecal administration of baclofen (ITB, using a subcutaneously implanted programmable infusion pump, is a minimally invasive, reversible method for the treatment of severe diffuse spasticity of the spinal origin. Case report. The first two cases in our country, treated by ITB due to severe spasticity caused by MS, were reported. Despite the local complications of surgical wound healing above the implanted components of the ITB-system in one patient, the optimal reduction of spasticity the with complete elimination of spastic pain was obtained in both patients. Conclusion. Our initial experiences confirmed ITB as a safe and effective therapeutical option for the treatment of intractable spasticity in patients with MS. Major prerequisites for this were adequate patient selection and good control of the basic disease. The use of the minimal invasive implantation technique and the experience in choosing of the adequate ITB-system components, could successfully prevent the occurrence of local complications related to the impaired healing of the ITB-system implantation site.

  3. Efficacy of the Bilateral Ilioinguinal-Iliohypogastric Block with Intrathecal Morphine for Postoperative Cesarean Delivery Analgesia

    Directory of Open Access Journals (Sweden)

    Manuel C. Vallejo

    2012-01-01

    Full Text Available The ilioinguinal-iliohypogastric (IIIH block is frequently used as multimodal analgesia for lower abdominal surgeries. The aim of this study is to compare the efficacy of IIIH block using ultrasound visualization for reducing postoperative pain after caesarean delivery (CD in patients receiving intrathecal morphine (ITM under spinal anesthesia. Participants were randomly assigned to 1 of 3 treatment groups for the bilateral IIIH block: Group A = 10 mL of 0.5% bupivacaine, Group B = 10 mL of 0.5% bupivacaine on one side and 10 mL of a normal saline (NSS placebo block on the opposite side, and Group C = 10 mL of NSS placebo per side. Pain and nausea scores, treatment for pain and nausea, and patient satisfaction were recorded for 48 hours after CD. No differences were noted with respect to pain scores or treatment for pain over the 48 hours. There were no differences to the presence of nausea (P=0.64, treatment for nausea (P=0.21, pruritus (P=0.39, emesis (P=0.35, or patient satisfaction (P=0.29. There were no differences in pain and nausea scores over the measured time periods (MANOVA, P>0.05. In parturients receiving ITM for elective CD, IIIH block offers no additional postoperative benefit for up to 48 hours.

  4. Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Akira [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: yakira@kuhp.kyoto-u.ac.jp; Miki, Yukio [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: mikiy@kuhp.kyoto-u.ac.jp; Adachi, Souichi [Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: sadachi@kuhp.kyoto-u.ac.jp (and others)

    2006-03-15

    Background and purpose: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. Materials and methods: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. Results: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. Conclusions: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

  5. Comparison of intrathecal plain articaine and levobupivacaine with fentanyl for Caesarean section.

    Science.gov (United States)

    Demircioglu, Rüveyda I; Gozdemir, Muhammet; Usta, Burhanettin; Sert, Hüseyin; Karabayirli, Safinaz; Muslu, Bünyamin; Keskin, Esra A

    2016-12-01

    Articaine is used as a local anesthetic for outpatient surgery because it offers rapid onset of anesthesia and short duration motor block. Levobupivacaine is often preferred for Caesarean section. We evaluated the anesthetic characteristics of fentanyl-supplemented plain articaine and levobupivacaine for Caesarean section under combine spinal epidural anesthesia. Patients undergoing Caesarean section received in random order plain articaine 40 mg (Group A, n=50) or plain levobupivacaine 10 mg (Group L, n=50) mixed with fentanyl 20 µg intrathecally. The onset and duration of sensory and motor block, first analgesic request, and hemodynamic parameters were recorded. Onset times of maximum motor block were longer in Group L than Group A (P=0,001). Time to two-segment regression of sensory block were 70 min for Group A and 90 min group L (P=0.001). Times to complete regression of motor blockade were significantly longer in group L than group A (P =0,001). To have a faster onset and shorter duration of spinal anesthesia, we recommend the use of plain articaine for Caesarean section.

  6. Retrospective analysis of the financial break-even point for intrathecal morphine pump use in Korea.

    Science.gov (United States)

    Kim, Eun Kyoung; Shin, Ji Yeon; Castañeda, Anyela Marcela; Lee, Seung Jae; Yoon, Hyun Kyu; Kim, Yong Chul; Moon, Jee Youn

    2017-10-01

    The high cost of intrathecal morphine pump (ITMP) implantation may be the main obstacle to its use. Since July 2014, the Korean national health insurance (NHI) program began paying 50% of the ITMP implantation cost in select refractory chronic pain patients. The aims of this study were to investigate the financial break-even point and patients' satisfaction in patients with ITMP treatment after the initiation of the NHI reimbursement. We collected data retrospectively or via direct phone calls to patients who underwent ITMP implantation at a single university-based tertiary hospital between July 2014 and May 2016. Pain severity, changes in the morphine equivalent daily dosage (MEDD), any adverse events, and patients' satisfaction were determined. We calculated the financial break-even point of ITMP implantation via investigating the patient's actual medical costs and insurance information. During the studied period, 23 patients received ITMP implantation, and 20 patients were included in our study. Scores on an 11-point numeric rating scale (NRS) for pain were significantly reduced compared to the baseline value ( P break-even point was 28 months for ITMP treatment after the NHI reimbursement policy. ITMP provided effective chronic pain management with improved satisfaction and reasonable financial break-even point of 28 months with 50% financial coverage by NHI program.

  7. ANALGESIC EFFECT OF INTRATHECAL BACLOFEN BOLUS ON NEUROPATHIC PAIN IN SPINAL CORD INJURY PATIENTS.

    Science.gov (United States)

    Kumru, Hatice; Benito-Penalva, Jesus; Kofler, Markus; Vidal, Joan

    2018-05-18

    GABA-ergic neurons are widely distributed throughout the central nervous system, including the spinal cord which is important for the transmission of pain impulses to the brain. Here we hypothesized that intrathecal baclofen (ITB) which is a GABA analogue might exert analgesic effects on neuropathic pain, which could be related to subtypes of pain in spinal cord injury (SCI). SCI patients with a cervical or thoracic lesion and neuropathic pain were randomized to receive either a single ITB bolus or placebo. Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory (NPSI), and Brief Pain Inventory (BPI) were obtained for assessment of neuropathic pain. Spasticity was assessed using Modified Ashworth Scale and visual analogue scale. Evaluations were performed at baseline, and 4, 8, and 24 hours after application of ITB or placebo. Eight patients received ITB, 5 placebo. Neuropathic pain improved significantly in the ITB group based on NRS, BPI, and NPSI, which revealed an effect on all subtypes of pain. Spasticity declined significantly. In the placebo group, there was neither significant change in pain nor in spasticity. An ITB bolus exerted a significant analgesic effect on all subtypes of neuropathic pain in SCI patients. ITB has analgesic effects on all subtypes of neuropathic pain and can improve interference of neuropathic pain with activities of daily living. ITB might be a promising analgesic treatment to control neuropathic pain. Copyright © 2018. Published by Elsevier Inc.

  8. Multiple Sclerosis Patients with Markedly Low Intrathecal Antibody Response in Sri Lanka

    Directory of Open Access Journals (Sweden)

    S. M. K. Gamage

    2018-01-01

    Full Text Available Multiple sclerosis (MS is a heterogeneous disease which is poorly studied in Asia, where the disease is known to be rare with significant differences in clinical and radiological presentations and intrathecal antibody response. Therefore the objective of this study was to determine clinical presentation, radiological and neurophysiological characteristics, and oligoclonal band status in Sri Lankan MS patients, following careful exclusion of patients with neuromyelitis optica spectrum disorders and other conditions mimicking multiple sclerosis. Sixty-nine MS patients were recruited to the study adhering to McDonald 2010 criteria. Their clinical presentation, characteristics of central nervous system lesions in magnetic resonance imaging, visual evoked potential (VEP results, oligoclonal bands (OCB, and AQP4 antibody status were studied. Of 69 MS patients, 54%, 6%, and 1% were relapsing remitting, secondary progressive, and primary progressive, respectively, and 39% were patients with clinically isolated syndrome. The commonest clinical presentations were cerebral motor followed by cerebral sensory and optic neuritis. Majority had typical periventricular and infratentorial lesions in MRI. Though not clinically apparent, bilateral delay of P100 wave latency was present in 52%. OCB positivity was 42% and AQP4 antibody was positive in only one patient. In conclusion, this group of Sri Lankan MS patients shares most of the clinical and radiological features of Caucasian MS patients. However, the OCB positivity is lower in this group, when compared to the Caucasian MS populations.

  9. Hospitalization for partial nephrectomy was not associated with intrathecal opioid analgesia: Retrospective analysis.

    Science.gov (United States)

    Weingarten, Toby N; Del Mundo, Serena B; Yeoh, Tze Yeng; Scavonetto, Federica; Leibovich, Bradley C; Sprung, Juraj

    2014-10-01

    The aim of this retrospective study is to test the hypothesis that the use of spinal analgesia shortens the length of hospital stay after partial nephrectomy. We reviewed all patients undergoing partial nephrectomy for malignancy through flank incision between January 1, 2008, and June 30, 2011. We excluded patients who underwent tumor thrombectomy, used sustained-release opioids, or had general anesthesia supplemented by epidural analgesia. Patients were grouped into "spinal" (intrathecal opioid injection for postoperative analgesia) versus "general anesthetic" group, and "early" discharge group (within 3 postoperative days) versus "late" group. Association between demographics, patient physical status, anesthetic techniques, and surgical complexity and hospital stay were analyzed using multivariable logistic regression analysis. Of 380 patients, 158 (41.6%) were discharged "early" and 151 (39.7%) were "spinal" cases. Both spinal and early discharge groups had better postoperative pain control and used less postoperative systemic opioids. Spinal analgesia was associated with early hospital discharge, odds ratio 1.52, (95% confidence interval 1.00-2.30), P = 0.05, but in adjusted analysis was no longer associated with early discharge, 1.16 (0.73-1.86), P = 0.52. Early discharge was associated with calendar year, with more recent years being associated with early discharge. Spinal analgesia combined with general anesthesia was associated with improved postoperative pain control during the 1(st) postoperative day, but not with shorter hospital stay following partial nephrectomy. Therefore, unaccounted practice changes that occurred during more recent times affected hospital stay.

  10. Nuclear matrix and structural and functional compartmentalization of the eucaryotic cell nucleus.

    Science.gov (United States)

    Razin, S V; Borunova, V V; Iarovaia, O V; Vassetzky, Y S

    2014-07-01

    Becoming popular at the end of the 20th century, the concept of the nuclear matrix implies the existence of a nuclear skeleton that organizes functional elements in the cell nucleus. This review presents a critical analysis of the results obtained in the study of nuclear matrix in the light of current views on the organization of the cell nucleus. Numerous studies of nuclear matrix have failed to provide evidence of the existence of such a structure. Moreover, the existence of a filamentous structure that supports the nuclear compartmentalization appears to be unnecessary, since this function is performed by the folded genome itself.

  11. The kinetics of multi-compartmentalized systems, studied by radioactive tracers

    International Nuclear Information System (INIS)

    Gouveia, A.S. de.

    1978-01-01

    The use of compartmental models to investigate kinetic problems is presented. This use is restricted, however, to linear models. As an application of different methods, the kinetic behaviour of haemaccel labelled with iodine 131 is studied, the interval of the physically viable solutions being established. The existence of a class of solutions is explained as a result of lack of knowledge of a complete data set. The possibility of obtaining a single solution is also discussed. The formalism of the program SAAM (Simulation, Analysis and modelling) now judged very important for the study of multi-compartimental analysis is presented. (I.C.R) [pt

  12. Effects of Air Stacking Maneuver on Cough Peak Flow and Chest Wall Compartmental Volumes of Subjects With Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Sarmento, Antonio; Resqueti, Vanessa; Dourado-Júnior, Mario; Saturnino, Lailane; Aliverti, Andrea; Fregonezi, Guilherme; de Andrade, Armele Dornelas

    2017-11-01

    To assess the acute effects of air stacking on cough peak flow (CPF) and chest wall compartmental volumes of persons with amyotrophic lateral sclerosis (ALS) versus healthy subjects positioned at 45° body inclination. Cross-sectional study with a matched-pair design. University hospital. Persons (N=24) with ALS (n=12) and age-matched healthy subjects (n=12). CPF, chest wall compartmental inspiratory capacity, chest wall vital capacity, chest wall tidal volume and operational volumes, breathing pattern, and percentage of contribution of the compartments to the inspired volume were measured by optoelectronic plethysmography. Compared with healthy subjects, significantly lower CPF (P=.007), chest wall compartmental inspiratory capacity (Pprotocol in the healthy subjects, mainly because of end-inspiratory (P<.001) and abdominal volumes (P=.008). No significant differences were observed in percentage of contribution of the compartments to the inspired volume and end-expiratory volume of both groups. No significant differences were found in chest wall tidal volume, operational volume, and breathing pattern in persons with ALS. Air stacking is effective in increasing CPF, chest wall compartmental inspiratory capacity, and chest wall vital capacity of persons with ALS with no hyperinflation. Differences in compartmental volume contributions are probably because of lung and chest wall physiological changes. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  13. Posttranslational protein S-palmitoylation and the compartmentalization of signaling molecules in neurons

    Directory of Open Access Journals (Sweden)

    SEAN I PATTERSON

    2002-01-01

    Full Text Available Protein domains play a fundamental role in the spatial and temporal organization of intracellular signaling systems. While protein phosphorylation has long been known to modify the interactions that underlie this organization, the dynamic cycling of lipids should now be included amongst the posttranslational processes determining specificity in signal transduction. The characteristics of this process are reminiscent of the properties of protein and lipid phosphorylation in determining compartmentalization through SH2 or PH domains. Recent studies have confirmed the functional importance of protein S-palmitoylation in the compartmentalization of signaling molecules that support normal physiological function in cell division and apoptosis, and synaptic transmission and neurite outgrowth. In neurons, S-palmitoylation and targeting of proteins to rafts are regulated differentially in development by a number of processes, including some related to synaptogenesis and synaptic plasticity. Alterations in the S-palmitoylation state of proteins substantially affect their cellular function, raising the possibility of new therapeutic targets in cancer and nervous system injury and disease.

  14. Compartmentalized metabolic network reconstruction of microbial communities to determine the effect of agricultural intervention on soils

    Science.gov (United States)

    Álvarez-Yela, Astrid Catalina; Gómez-Cano, Fabio; Zambrano, María Mercedes; Husserl, Johana; Danies, Giovanna; Restrepo, Silvia; González-Barrios, Andrés Fernando

    2017-01-01

    Soil microbial communities are responsible for a wide range of ecological processes and have an important economic impact in agriculture. Determining the metabolic processes performed by microbial communities is crucial for understanding and managing ecosystem properties. Metagenomic approaches allow the elucidation of the main metabolic processes that determine the performance of microbial communities under different environmental conditions and perturbations. Here we present the first compartmentalized metabolic reconstruction at a metagenomics scale of a microbial ecosystem. This systematic approach conceives a meta-organism without boundaries between individual organisms and allows the in silico evaluation of the effect of agricultural intervention on soils at a metagenomics level. To characterize the microbial ecosystems, topological properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis (FBA) were considered. Furthermore, topological and optimization algorithms were implemented to carry out the curation of the models, to ensure the continuity of the fluxes between the metabolic pathways, and to confirm the metabolite exchange between subcellular compartments. The proposed models provide specific information about ecosystems that are generally overlooked in non-compartmentalized or non-curated networks, like the influence of transport reactions in the metabolic processes, especially the important effect on mitochondrial processes, as well as provide more accurate results of the fluxes used to optimize the metabolic processes within the microbial community. PMID:28767679

  15. [Compartmentalization of the cell nucleus and spatial organization of the genome].

    Science.gov (United States)

    Gavrilov, A A; Razin, S V

    2015-01-01

    The eukaryotic cell nucleus is one of the most complex cell organelles. Despite the absence of membranes, the nuclear space is divided into numerous compartments where different processes in- volved in the genome activity take place. The most important nuclear compartments include nucleoli, nuclear speckles, PML bodies, Cajal bodies, histone locus bodies, Polycomb bodies, insulator bodies, transcription and replication factories. The structural basis for the nuclear compartmentalization is provided by genomic DNA that occupies most of the nuclear volume. Nuclear compartments, in turn, guide the chromosome folding by providing a platform for the spatial interaction of individual genomic loci. In this review, we discuss fundamental principles of higher order genome organization with a focus on chromosome territories and chromosome domains, as well as consider the structure and function of the key nuclear compartments. We show that the func- tional compartmentalization of the cell nucleus and genome spatial organization are tightly interconnected, and that this form of organization is highly dynamic and is based on stochastic processes.

  16. Intracellular Redox Compartmentation and ROS-Related Communication in Regulation and Signaling.

    Science.gov (United States)

    Noctor, Graham; Foyer, Christine H

    2016-07-01

    Recent years have witnessed enormous progress in understanding redox signaling related to reactive oxygen species (ROS) in plants. The consensus view is that such signaling is intrinsic to many developmental processes and responses to the environment. ROS-related redox signaling is tightly wedded to compartmentation. Because membranes function as barriers, highly redox-active powerhouses such as chloroplasts, peroxisomes, and mitochondria may elicit specific signaling responses. However, transporter functions allow membranes also to act as bridges between compartments, and so regulated capacity to transmit redox changes across membranes influences the outcome of triggers produced at different locations. As well as ROS and other oxidizing species, antioxidants are key players that determine the extent of ROS accumulation at different sites and that may themselves act as signal transmitters. Like ROS, antioxidants can be transported across membranes. In addition, the intracellular distribution of antioxidative enzymes may be modulated to regulate or facilitate redox signaling appropriate to the conditions. Finally, there is substantial plasticity in organellar shape, with extensions such as stromules, peroxules, and matrixules playing potentially crucial roles in organelle-organelle communication. We provide an overview of the advances in subcellular compartmentation, identifying the gaps in our knowledge and discussing future developments in the area. © 2016 American Society of Plant Biologists. All Rights Reserved.

  17. Compartmental modeling alternatives for kinetic analysis of pet neurotransmitter receptor studies

    International Nuclear Information System (INIS)

    Koeppe, R.A.

    1991-01-01

    With the increased interest in studying neurotransmitter and receptor function in vivo, imaging procedures using positron emission tomography have presented new challenges for kinetic modeling and analysis of data. The in vivo behavior of radiolabeled markers for examining these neurotransmitter systems can be quite complex and, therefore, the implementation of compartmental models for data analysis is similarly complex. Often, the variability in the estimates of model parameters representing neurotransmitter or receptor densities, association and dissociation rates, or rates of incorporation or turnover does not permit reliable interpretation of the data. When less complex analyses are used, these model parameters may be biased and thus also do not yield the information being sought. Examination of trade-offs between uncertainty and bias in the parameters of interest may be used to select a compartmental model configuration with an appropriate level of complexity. Modeling alternatives will be discussed for radioligands with varying kinetic properties, such as those that bind reversibly and rapidly and others that bind nearly irreversibly. Specific problems, such as those occurring when a radioligand is open-quotes flow limitedclose quotes also will be discussed

  18. Estimation of Caesium-137 Intake in Dicentrarchus Labrax by Using Compartmental Model and Neural Network

    International Nuclear Information System (INIS)

    Yahaghi, E.; Movafeghi, A.; Askari, M. A.; Karimi Diba, G.; Mohammadzadeh, N.

    2012-01-01

    Cs-137 is one of the fission products that is usually released in environment after nuclear accidents. This contamination remains in environment for a long time due to long half life of Cs-137 (30 years) and can enter easily into the human food chain. A two-compartmental model was implemented to describe caesium intake and its distribution in Dicentrarchus Labrax, using a proposed differential equation model. The model included two compartments, the first compartment was the blood and the second one was the tissue. The activity of Cs-137 was undertaken in each compartment by means of a numerical method and the activity of Cs-137 was considered as an input of compartmental equations. We obtained the transfer coefficients between fish tissues by comparing the radiation curves with the actual data. In the light of the differences with the transfer coefficients, the calculation by the COMKAT software was found to be about 2%. Then, we provided the activity curves of Cs-137 and their characteristics (feature extractions) by changing the transfer coefficients and they were utilized to train the neural network. The network was trained for six data groups, and the results of the network testing had about 99% correct response, therefore it can be employed to estimate the transfer coefficients in fish tissue, the salinity range, and the activity of Cs-137 in water.

  19. Engineering of DNA polymerase I from Thermus thermophilus using compartmentalized self-replication.

    Science.gov (United States)

    Aye, Seaim Lwin; Fujiwara, Kei; Ueki, Asuka; Doi, Nobuhide

    2018-05-05

    Although compartmentalized self-replication (CSR) and compartmentalized partnered replication (CPR) are powerful tools for directed evolution of proteins and gene circuits, limitations remain in the emulsion PCR process with the wild-type Taq DNA polymerase used so far, including long run times, low amounts of product, and false negative results due to inhibitors. In this study, we developed a high-efficiency mutant of DNA polymerase I from Thermus thermophilus HB27 (Tth pol) suited for CSR and CPR. We modified the wild-type Tth pol by (i) deletion of the N-terminal 5' to 3' exonuclease domain, (ii) fusion with the DNA-binding protein Sso7d, (iii) introduction of four known effective point mutations from other DNA polymerase mutants, and (iv) codon optimization to reduce the GC content. Consequently, we obtained a mutant that provides higher product yields than the conventional Taq pol without decreased fidelity. Next, we performed four rounds of CSR selection with a randomly mutated library of this modified Tth pol and obtained mutants that provide higher product yields in fewer cycles of emulsion PCR than the parent Tth pol as well as the conventional Taq pol. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Proline accumulation, ions dynamics and sodium root-shoot partition and compartmentation

    Directory of Open Access Journals (Sweden)

    Jesus Emanuel eBojorquez Quintal

    2014-11-01

    Full Text Available Despite its economic relevance, little is known about salt tolerance mechanisms in pepper plants. To address this question, we compared differences in responses to NaCl in two Capsicum chinense varieties: Rex (tolerant and Chichen-Itza (sensitive. Under salt stress (150 mM NaCl over 7 days roots of Rex variety accumulated 50 times more compatible solutes such as proline compared to Chichen-Itza. Mineral analysis indicated that Na+ is restricted to roots by preventing its transport to leaves. Fluorescence analysis suggested an efficient Na+ compartmentalization in vacuole-like structures and in small intracellular compartments in roots of Rex variety. At the same time, Na+ in Chichen-Itza plants was compartmentalized in the apoplast, suggesting substantial Na+ extrusion. Rex variety was found to retain more K+ in its roots under salt stress according to a mineral analysis and microelectrode ion flux estimation (MIFE. Vanadate-sensitive H+ efflux was higher in Chichen-Itza variety plants, suggesting a higher activity of the plasma membrane H+-ATPase, which fuels the extrusion of Na+, and, possibly, also the re-uptake of K+. Our results suggest a combination of stress tolerance mechanisms, in order to alleviate the salt-induced injury. Furthermore, Na+ extrusion to apoplast does not appear to be an efficient strategy for salt tolerance in pepper plants.

  1. A compartmental model of the cAMP/PKA/MAPK pathway in Bio-PEPA

    Directory of Open Access Journals (Sweden)

    Federica Ciocchetta

    2009-11-01

    Full Text Available The vast majority of biochemical systems involve the exchange of information between different compartments, either in the form of transportation or via the intervention of membrane proteins which are able to transmit stimuli between bordering compartments. The correct quantitative handling of compartments is, therefore, extremely important when modelling real biochemical systems. The Bio-PEPA process algebra is equipped with the capability of explicitly defining quantitative information such as compartment volumes and membrane surface areas. Furthermore, the recent development of the Bio-PEPA Eclipse Plug-in allows us to perform a correct stochastic simulation of multi-compartmental models. Here we present a Bio-PEPA compartmental model of the cAMP/PKA/MAPK pathway. We analyse the system using the Bio-PEPA Eclipse Plug-in and we show the correctness of our model by comparison with an existing ODE model. Furthermore, we perform computational experiments in order to investigate certain properties of the pathway. Specifically, we focus on the system response to the inhibition and strengthening of feedback loops and to the variation in the activity of key pathway reactions and we observe how these modifications affect the behaviour of the pathway. These experiments are useful to understand the control and regulatory mechanisms of the system.

  2. Compartmentalized metabolic network reconstruction of microbial communities to determine the effect of agricultural intervention on soils.

    Directory of Open Access Journals (Sweden)

    María Camila Alvarez-Silva

    Full Text Available Soil microbial communities are responsible for a wide range of ecological processes and have an important economic impact in agriculture. Determining the metabolic processes performed by microbial communities is crucial for understanding and managing ecosystem properties. Metagenomic approaches allow the elucidation of the main metabolic processes that determine the performance of microbial communities under different environmental conditions and perturbations. Here we present the first compartmentalized metabolic reconstruction at a metagenomics scale of a microbial ecosystem. This systematic approach conceives a meta-organism without boundaries between individual organisms and allows the in silico evaluation of the effect of agricultural intervention on soils at a metagenomics level. To characterize the microbial ecosystems, topological properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis (FBA were considered. Furthermore, topological and optimization algorithms were implemented to carry out the curation of the models, to ensure the continuity of the fluxes between the metabolic pathways, and to confirm the metabolite exchange between subcellular compartments. The proposed models provide specific information about ecosystems that are generally overlooked in non-compartmentalized or non-curated networks, like the influence of transport reactions in the metabolic processes, especially the important effect on mitochondrial processes, as well as provide more accurate results of the fluxes used to optimize the metabolic processes within the microbial community.

  3. Compartmentalization of the gut viral reservoir in HIV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Grant Tannika

    2007-12-01

    Full Text Available Abstract Background Recently there has been an increasing interest and appreciation for the gut as both a viral reservoir as well as an important host-pathogen interface in human immunodefiency virus type 1 (HIV-1 infection. The gut associated lymphoid tissue (GALT is the largest lymphoid organ infected by HIV-1. In this study we examined if different HIV-1 quasispecies are found in different parts of the gut of HIV-1 infected individuals. Results Gut biopsies (esophagus, stomach, duodenum and colorectum were obtained from eight HIV-1 infected preHAART (highly active antiretroviral therapy patients. HIV-1 Nef and Reverse transcriptase (RT encoding sequences were obtained through nested PCR amplification from DNA isolated from the gut biopsy tissues. The PCR fragments were cloned and sequenced. The resulting sequences were subjected to various phylogenetic analyses. Expression of the nef gene and viral RNA in the different gut tissues was determined using real-time RT-PCR. Phylogenetic analysis of the Nef protein-encoding region revealed compartmentalization of viral replication in the gut within patients. Viral diversity in both the Nef and RT encoding region varied in different parts of the gut. Moreover, increased nef gene expression (p Conclusion Our results indicated that different HIV-1 quasispecies populate different parts of the gut, and that viral replication in the gut is compartmentalized. These observations underscore the importance of the gut as a host-pathogen interface in HIV-1 infection.

  4. Estimation of guinea pig tracheobronchial transport rates using a compartmental model

    International Nuclear Information System (INIS)

    Velasquez, D.J.; Morrow, P.E.

    1984-01-01

    Mucociliary clearance in the tracheobronchial tree of guinea pigs was examined using monodisperse 7.9 μm MMAD polystyrene particles. Animals were exposed for approximately 1 h by inhalation via an intratracheal tube to aerosols tagged with gold-198 and fluorescent dyes. Following exposure, animals were radioactively monitored and sacrificed at predetermined times. The lungs were removed, freeze-dried, sectioned completely, and examined with a fluorescent microscope. Measurements were made of airway diameters where particles were found. An anatomic model for guinea pig lung morphology was used to assign ranges of airway diameters to five zones, which were incorporated into a compartmental model for lung clearance. Kinetic analysis of particle distributions in the zones led to development of first-order equations describing the compartmental clearance. Rate constants obtained from the kinetic analysis were used to estimate mucociliary transport rates in specific bronchial generations, which ranged from approximately 0.001 mm/min in the distal bronchioles to approximately 8 mm/min in the trachea, and resulted in a calculated 24-h clearance time for tracheobronchial clearance in the guinea pig. No evidence for either bronchial penetration by particles or relatively prolonged bronchial retention of particles was found in this study. 22 references, 3 figures, 3 tables

  5. Sequential radioimmunotherapy with 177Lu- and 211At-labeled monoclonal antibody BR96 in a syngeneic rat colon carcinoma model

    DEFF Research Database (Denmark)

    Eriksson, Sophie E; Elgström, Erika; Bäck, Tom

    2014-01-01

    for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later. METHODS: Rats bearing solid colon...... carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96....... The rats suffered from reversible myelotoxicity after treatment. CONCLUSIONS: Sequential administration of 177Lu-BR96 and 211At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect....

  6. A radiolabeled antibody targeting CD123+ leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML

    Directory of Open Access Journals (Sweden)

    Jeffrey V. Leyton

    2015-01-01

    Full Text Available Radioimmunotherapy (RIT with anti-CD123 monoclonal antibody CSL360 modified with nuclear translocation sequence (NLS peptides and labeled with the Auger electron-emitter, 111In (111In-NLS-CSL360 was studied in the prevalent NOD/SCID mouse AML engraftment assay. Significant decreases in CD123+ leukemic cells and impairment of leukemic stem cell self-renewal were achieved with high doses of RIT. However, NOD/SCID mice were very radiosensitive to these doses. At low non-toxic treatment doses, 111In-NLS-CSL360 demonstrated a trend towards improved survival associated with decreased spleen/body weight ratio, an indicator of leukemia burden, and almost complete eradication of leukemia from the bone marrow in some mice.

  7. Utilization of stable isotopes for the study of in vivo compartmental metabolism of poly-insaturate fatty acids

    International Nuclear Information System (INIS)

    Brossard, N.; Croset, M.; Lecerf, J.; Lagarde, M.; Pachiaudi, C.; Normand, S.; Riou, J.P.; Chirouze, V.; Tayot, J.L.

    1994-01-01

    In order to study the compartmental metabolism of the 22:6n-3 fatty acid, and particularly the role of the transport plasmatic forms for the tissue uptake (especially brain), a technique is developed using carbon 13 stable isotope and an isotopic mass spectrometry coupled to gaseous chromatography technique. This method has been validated in rat with docosahexaenoic acid enriched in 13 C and esterified in triglycerides. The compartmental metabolism is monitored by measuring the variation of 22:6n-3 isotopic enrichment in the various lipoprotein lipidic fractions, in blood globules and in the brain. 1 fig., 1 tab., 12 refs

  8. Cerebrospinal fluid IL-12p40, CXCL13 and IL-8 as a combinatorial biomarker of active intrathecal inflammation.

    Directory of Open Access Journals (Sweden)

    Bibiana Bielekova

    Full Text Available Diagnosis and management of the neuroinflammatory diseases of the central nervous system (CNS are hindered by the lack of reliable biomarkers of active intrathecal inflammation. We hypothesized that measuring several putative inflammatory biomarkers simultaneously will augment specificity and sensitivity of the biomarker to the clinically useful range. Based on our pilot experiment in which we measured 18 inflammatory biomarkers in 10-fold concentrated cerebrospinal fluid (CSF derived from 16 untreated patients with highly active multiple sclerosis (MS we selected a combination of three CSF biomarkers, IL-12p40, CXCL13 and IL-8, for further validation.Concentrations of IL-12p40, CXCL13 and IL-8 were determined in a blinded fashion in CSF samples from an initial cohort (n = 72 and a confirmatory cohort (n = 167 of prospectively collected, untreated subjects presenting for a diagnostic work-up of possible neuroimmunological disorder. Diagnostic conclusion was based on a thorough clinical workup, which included laboratory assessment of the blood and CSF, neuroimaging and longitudinal follow-up. Receiver operating characteristic (ROC curve analysis in conjunction with principal component analysis (PCA, which was used to combine information from all three biomarkers, assessed the diagnostic value of measured biomarkers.Each of the three biomarkers was significantly increased in MS and other inflammatory neurological disease (OIND in comparison to non-inflammatory neurological disorder patients (NIND at least in one cohort. However, considering all three biomarkers together improved accuracy of predicting the presence of intrathecal inflammation to the consistently good to excellent range (area under the ROC curve = 0.868-0.924.Future clinical studies will determine if a combinatorial biomarker consisting of CSF IL-12p40, CXCL13 and IL-8 provides utility in determining the presence of active intrathecal inflammation in diagnostically

  9. Comparative study of intrathecal hyperbaric versus isobaric ropivacaine: A randomized control trial

    Directory of Open Access Journals (Sweden)

    Rajni Gupta

    2013-01-01

    Full Text Available Background: Hyperbaric ropivacaine produce more reliable sensory and motor block, with faster onset, better quality of muscles relaxation than isobaric ropivacaine. So, this study was designed to compare the efficacy of hyperbaric ropivacaine with isobaric ropivacaine in patients undergoing lower abdominal surgery. Methods: A randomized controlled double blind study in two groups of patients. group A (n=35 received 3 ml of isobaric ropivacaine 6 mg/ml (18 mg. Group B (n=35 received 3 ml of hyperbaric ropivacaine 6 mg/ml (18 mg. The onset and duration of sensory block at dermatome level T10, maximum upper and lower spread of sensory block, intensity, and duration of motor block were recorded. Statistical Analysis: Block characteristics were compared using the two-tailed Mann - Whitney U-test. The proportion of side effects was compared using the Chi-square test. Results: The median time of onset of sensory block at the T10 dermatome was 4.4±1.3 min in group B and 6.0±1.03 min in group A. The median time to maximum block height was 16.7±3.7 min in group A and 12.03±1.96 min in group B. The median duration of complete motor recovery (B0 was significantly shorter in the heavy ropivacaine group (166.5±11.7 min compared with the isobaric ropivacaine group (192.9±9.6 min. Conclusions: Intrathecal hyperbaric ropivacaine provides more rapid, adequate, and good quality of sensory and motor block with rapid post-operative recovery as compare to isobaric ropivacaine.

  10. Preventive Effect of Intrathecal Paracetamol on Spinal Cord Injury in Rats

    Science.gov (United States)

    Sahin, Murat; Sayar, Ilyas; Peker, Kemal; Gullu, Huriye; Yildiz, Huseyin

    2014-01-01

    Background: Ischemic injury of the spinal cord during the surgical repair of thoracoabdominal aortic aneurysms might lead to paraplegia. Although a number of different mechanisms have been proposed, the exact cause of paraplegia has remained unknown, hampering the development of effective pharmacologic or other strategies for prevention of this condition. A number of studies suggested that cyclooxygenases (COX) contribute to neural breakdown; thus, COX inhibitors might reduce injury. Objectives: We aimed to assess the preventive effect of intrathecal (IT) pretreatment with paracetamol on spinal cord injury in a rat model. Materials and Methods: This experimental study was performed in Ataturk University Animal Research Laboratory Center, Erzurum, Turkey. Adult male Wistar rats were randomly allocated to three experimental groups (n = 6) to receive IT physiologic saline (controls), 50 µg of paracetamol, or 100 µg paracetamol one hour before induction of spinal cord ischemia. Six other rats were considered as the sham group. For the assessment of ischemic injury, motor functions of the hind limbs and histopathologic changes of the lumbar spinal cord were evaluated. Additional 20 rats were divided into two equal groups for the second part of the study where the survival rates were recorded in controls and in animals receiving 100 µg of paracetamol during the 28-day observation period. Results: Pretreatment with 100 µg of paracetamol resulted in a significant improvement in motor functions and histopathologic findings (P < 0.05). Despite a higher rate of survival in 100 µg of paracetamol group (70%) at day 28, the difference was not statistically significant in comparison with controls. Conclusions: Our results suggest a protective effect of pretreatment with IT paracetamol on ischemic spinal cord injury during thoracolumbar aortic aneurysm surgery. PMID:25763224

  11. Intrathecal or intraventricular therapy for post-neurosurgical Gram-negative meningitis: matched cohort study.

    Science.gov (United States)

    Shofty, B; Neuberger, A; Naffaa, M E; Binawi, T; Babitch, T; Rappaport, Z H; Zaaroor, M; Sviri, G; Paul, M

    2016-01-01

    Gram-negative post-operative meningitis due to carbapenem-resistant bacteria (CR-GNPOM) is a dire complication of neurosurgical procedures. We performed a nested propensity-matched historical cohort study aimed at examining the possible benefit of intrathecal or intraventricular (IT/IV) antibiotic treatment for CR-GNPOM. We included consecutive adults with GNPOM in two centres between 2005 and 2014. Patients receiving combined systemic and IT/IV treatment were matched to patients receiving systemic treatment only. Matching was done based on the propensity of the patients to receive IT/IV treatment. We compared patient groups with 30-day mortality defined as the primary outcome. The cohort included 95 patients with GNPOM. Of them, 37 received IT/IV therapy in addition to systemic treatment (22 with colistin and 15 with amikacin), mostly as initial therapy, through indwelling cerebrospinal fluid drains. Variables associated with IT/IV therapy in the propensity score included no previous neurosurgery, time from admission to meningitis, presence of a urinary catheter and GNPOM caused by carbapenem-resistant Gram-negative bacteria. Following propensity matching, 23 patients given IT/IV therapy and 27 controls were analysed. Mortality was significantly lower with IT/IV therapy: 2/23 (8.7%) versus 9/27 (33.3%), propensity-adjusted OR 0.19, 95% CI 0.04-0.99. Death or neurological deterioration at 30 days, 14-day and in-hospital mortality were lower with IT/IV therapy (OR <0.4 for all) without statistically significant differences. Among patients discharged alive, those receiving IT/IV therapy did not experience more neurological deterioration. Serious adverse events with IT/IV therapy were not documented. Our results support the early use of IT antibiotic treatment for CR-GNPOM when a delivery method is available. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Detection of virus-specific intrathecally synthesised immunoglobulin G with a fully automated enzyme immunoassay system

    Directory of Open Access Journals (Sweden)

    Weissbrich Benedikt

    2007-05-01

    Full Text Available Abstract Background The determination of virus-specific immunoglobulin G (IgG antibodies in cerebrospinal fluid (CSF is useful for the diagnosis of virus associated diseases of the central nervous system (CNS and for the detection of a polyspecific intrathecal immune response in patients with multiple sclerosis. Quantification of virus-specific IgG in the CSF is frequently performed by calculation of a virus-specific antibody index (AI. Determination of the AI is a demanding and labour-intensive technique and therefore automation is desirable. We evaluated the precision and the diagnostic value of a fully automated enzyme immunoassay for the detection of virus-specific IgG in serum and CSF using the analyser BEP2000 (Dade Behring. Methods The AI for measles, rubella, varicella-zoster, and herpes simplex virus IgG was determined from pairs of serum and CSF samples of patients with viral CNS infections, multiple sclerosis and of control patients. CSF and serum samples were tested simultaneously with reference to a standard curve. Starting dilutions were 1:6 and 1:36 for CSF and 1:1386 and 1:8316 for serum samples. Results The interassay coefficient of variation was below 10% for all parameters tested. There was good agreement between AIs obtained with the BEP2000 and AIs derived from the semi-automated reference method. Conclusion Determination of virus-specific IgG in serum-CSF-pairs for calculation of AI has been successfully automated on the BEP2000. Current limitations of the assay layout imposed by the analyser software should be solved in future versions to offer more convenience in comparison to manual or semi-automated methods.

  13. Intrathecal trastuzumab in the management of HER2+ breast leptomeningeal disease: a single institution experience.

    Science.gov (United States)

    Figura, Nicholas B; Long, Wendy; Yu, Michael; Robinson, Timothy J; Mokhtari, Sepideh; Etame, Arnold B; Tran, Nam D; Diaz, Roberto; Soliman, Hatem; Han, Heather S; Sahebjam, Solmaz; Forsyth, Peter A; Ahmed, Kamran A

    2018-06-01

    Leptomeningeal disease is a rare and devastating presentation of advanced stage metastatic breast cancer with historically poor overall survival. We assessed the safety and feasibility of intrathecal (IT) trastuzumab in HER2+ leptomeningeal disease. A total of 13 patients were treated at our institution with IT trastuzumab beginning November 2012 and followed until November 2017. Outcomes including craniospinal progression as well as overall survival (OS) following initiation of IT trastuzumab were assessed from review of the clinical chart and radiologic examinations. The median age of patients was 48 (range 29-75). Median time from breast cancer diagnosis to development of brain metastases was 87.7 months with a median of 4.6 months from brain metastases diagnosis to the development of leptomeningeal disease. Previous whole brain radiotherapy was received by the majority of patients (92%) and prior surgery for brain metastases was performed in 23%. Median duration of IT trastuzumab treatment was 6.4 months. Median time from IT trastuzumab start to craniospinal progression was 5.7 months with 6- and 12-month Kaplan-Meier rates of 41 and 21%, respectively. Sustained responses > 6 months were achieved in 4 patients. Median survival from the start of IT trastuzumab was 10.6 months with 6- and 12-month OS rates of 68 and 47%, respectively. IT trastuzumab was well tolerated with one patient developing ventriculitis, which resolved with IV antibiotics. IT trastuzumab was well tolerated with prolongation of OS over historical controls. IT trastuzumab should be considered for management of HER2+ leptomeningeal disease patients.

  14. Fast Track Liver Resection: The Effect of a Comprehensive Care Package and Analgesia with Single Dose Intrathecal Morphine with Gabapentin or Continuous Epidural Analgesia

    Directory of Open Access Journals (Sweden)

    Jonathan B. Koea

    2009-01-01

    Full Text Available Background. A comprehensive care package for patients undergoing hepatectomy was developed with the aim of minimal physiological disturbance in the peri-operative period. Peri-operative analgesia with few gastrointestinal effects and reduced requirement for intravenous (IV fluid therapy was central to this plan. Methods. Data on 100 consecutive patients managed with continuous epidural infusion (n = 50; bupivicaine 0.125% and fentanyl 2 g/mL at 0.1 mL/kg/hr or intrathecal morphine (n = 50; 300 g in combination with oral gabapentin 1200 mg preoperatively and 400 mg bd postoperatively was compared. Results. The epidural and intrathecal morphine groups were equivalent in terms of patient demographics, procedures and complications. Patients receiving intrathecal morphine received less intra-operative IV fluids (median 1500 mL versus 2200 mL, =.06, less postoperative IV fluids (median 1200 mL versus 4300 mL, =.03 than patients receiving epidural infusion. Patients managed with intrathecal morphine established a normal dietary intake sooner (16 hours versus 20 hours, =.05 and had shorter hospital stays than those managed with epidural infusions (4.7 ± 0.9 days versus 6.8 ± 1.2 days, =.02. Conclusions. Single dose intrathecal morphine is a safe and effective means of providing peri-operative analgesia. Patients managed with intrathecal morphine have reduced peri-operative physiological disturbance and return home within a few days of hepatic resection.

  15. First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury.

    Science.gov (United States)

    Kucher, Klaus; Johns, Donald; Maier, Doris; Abel, Rainer; Badke, Andreas; Baron, Hagen; Thietje, Roland; Casha, Steven; Meindl, Renate; Gomez-Mancilla, Baltazar; Pfister, Christian; Rupp, Rüdiger; Weidner, Norbert; Mir, Anis; Schwab, Martin E; Curt, Armin

    2018-05-01

    Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery. This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia. Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks). ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining >10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia. ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.

  16. Intrathecal dexmedetomidine as adjuvant for spinal anaesthesia for perianal ambulatory surgeries: A randomised double-blind controlled study

    Directory of Open Access Journals (Sweden)

    S S Nethra

    2015-01-01

    Full Text Available Background and Aim: The newer trend in regional anaesthesia for ambulatory anorectal surgeries advocate use of lower dose of local anaesthetic, providing segmental block with adjuvants such as opioids and α2 agonists to prolong analgesia. The current study investigated effects of addition of 5 μg of dexmedetomidine to 6 mg of hyperbaric bupivacaine on duration of analgesia, sensory and motor block characteristics for perianal ambulatory surgeries. Methods: This study is a prospective randomised controlled double blind study. Forty adult patients between 18 and 55 years of age were divided into 2 groups. Group D received intrathecal 0.5% hyperbaric bupivacaine 6 mg (1.2 ml with injection dexmedetomidine 5 μg in 0.5 ml of normal saline and Group N received intrathecal 0.5% hyperbaric bupivacaine 6 mg (1.2 ml with 0.5 ml of normal saline. The parameters assessed were time to regression of sensory blockade, motor blockade, ambulation, time to void, first administration of analgesic. Statistical analysis was done using appropriate tests. Results: Time for regression of sensory level and time for first administration of analgesic were prolonged in Group D (430.05 ± 89.13 min, 459.8 ± 100.9 min, respectively in comparison to Group N (301.10 ± 94.86 min, 321.85 ± 95.08 min, respectively. However, the duration of motor blockade, time to ambulation, and time to void were also significantly prolonged in Group D (323.05 ± 54.58 min, 329.55 ± 54.06 min, 422.30 ± 87.59 min than in Group N (220.10 ± 63.61 min, 221.60 ± 63.84 min, 328.45 ± 113.38 min. Conclusion: Intrathecal dexmedetomidine 5 μg added to intrathecal bupivacaine 6 mg as adjuvant may not be suitable for ambulatory perianal surgeries due to prolongation of motor blockade.

  17. Relation of intrathecal oligoclonal band production to inflammatory mediator and immunotherapy response in 208 children with OMS.

    Science.gov (United States)

    Pranzatelli, Michael R; McGee, Nathan R; Tate, Elizabeth D

    2018-04-12

    In 208 children with opsoclonus-myoclonus syndrome (OMS), CSF IgG oligoclonal bands (OCB) and 22 immunomarkers in CSF and 21 in serum/blood were measured. In 36 untreated OMS, 58% were OCB(+), whereas 55% of treated OMS were OCB(-). OCB positivity or negativity did not alter concentrations or frequencies of immunomarkers. The phenotypes of OCB(+) and OCB(-) patients were not distinctive. CSF B cells were expanded in untreated OMS regardless of OCB positivity. These data reveal a much higher frequency of OCB positivity in untreated OMS than previously realized and a disconnect between intrathecal OCB and inflammatory mediator production. Copyright © 2018. Published by Elsevier B.V.

  18. Radioimmunotherapy of Non-Hodgkin's Lymphoma. The interaction of radiation and antibody with lymphoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Illidge, T.M

    1999-06-01

    Whilst many patients with indolent Non-Hodgkin's Lymphoma (NHL) can achieve clinical remissions to first-line chemotherapy and/or radiotherapy, most will relapse. Current treatment options for relapsing patients are limited since most patients become resistant to repeated chemotherapy. Death usually occurs within 10 years of diagnosis. Overall, these disappointing results have not changed significantly in a quarter of a century and clearly advocate the urgent priority to research into potential new therapeutic approaches into this diverse and increasingly prevalent group of human tumours. Radioimmunotherapy (RIT) is currently under investigation as a new approach for the treatment of this disease. In this form of treatment, radionuclide-labeled monoclonal antibodies are able to deliver selective systemic irradiation by recognising tumour-associated antigens. The use of RIT with radiolabeled anti-CD20 antibodies in patients with recurrent B-cell lymphoma has resulted in extremely high rates of durable complete remissions. The optimal approach and mechanisms of action of successful RIT remain however largely unknown. The work described in this thesis has focused on clarifying some of the important determinants and mechanisms of effective RIT of syngeneic B-cell lymphoma, both in vivo and in vitro. A successful animal model of RIT in B cell lymphomas was established by initially generating a panel of antibodies against mouse B cell antigens. The in vitro characteristics of these antibodies have been compared with their subsequent performance, in biodistribution studies and RIT in vivo. For the first time in an in vivo model the relative contributions of antibody and irradiation are described. Some antibodies including anti-MHC Class II were shown to be effective delivery vehicles of low doses of Iodine-131. These antibodies, which appear to be inactive delivery vehicles can cure animals with low burdens of tumour. However antibodies such as anti-idiotype and anti

  19. Radioimmunotherapy with Y-90-epratuzumab in patients with previously treated B-cell lymphoma. A fractionated dose-escalation study

    International Nuclear Information System (INIS)

    Linden, O.; Cavallin-Stahl, E.; Tennvall, J.; Hindorf, C.; Olsson, T.; Strand, S.E.; Stenberg, L.; Wingardh, K.

    2002-01-01

    unequivocal CD22 expression, as compared with one of four patients with weak expression, exhibited OR. Tumour CD22 assessments before and during therapy were made in three patients, indicating down regulation of CD22. Conclusion: Radioimmunotherapy using a 2-4 weekly injection schedule with 90 Y-epratuzumab can result in durable OR in patients with various subtypes of B-cell lymphoma. Three weekly infusions 185 MBq/m 2 resulted in only minor haematological toxicity. Unequivocally CD22 expressing lymphoma seems more responsive. Low toxicity as well as evidence of down regulation of CD22 expression during therapy make fractionated treatment with 90 Y-epratuzumab warrants further study

  20. Detection of endotoxins in radiopharmaceutical preparations--I. Comparison of rabbit hyperthermia after intravenous or intrathecal administration of reference endotoxin preparations

    Energy Technology Data Exchange (ETDEWEB)

    Merlin, L; Bruneau, J; Cohen, Y; Michaud, T

    1986-01-01

    The rise of the rabbit internal temperature after endotoxin injection is related to the route of administration. A rise of 1.71 +/- 0.411/sup 0/C is obtained after i.v. injection of 1 ng/kg Escherichia coli 0111.B.4 endotoxin. An increase of 1.93 +/- 0.236/sup 0/C is obtained after suboccipital intrathecal injection of 0.1 ng/kg of the same endotoxin; with the intrathecal route, the hyperthermia is induced by E. coli endotoxin after a dose ten times lower than with i.v. injection as shown by statistical analysis.

  1. Intrathecal application of /sup 198/Au colloid in acute leukemia and non-Hodgkin's lymphoma in chilhood. 2. Metaphylaxis of meningosis neoplastica

    Energy Technology Data Exchange (ETDEWEB)

    Metz, O; Unverricht, A; Stoll, W [Friedrich-Schiller-Universitaet, Jena (German Democratic Republic)

    1979-08-01

    7 children suffering from acute lymphatic leukemia (ALL) and non-Hodgkin's lymphoma, resp., were injected intrathecally with /sup 198/Au colloid for metaphylaxis. The children had been cured of 8 relapses of miningosis and received irregularly intrathecal injections of methotrexate for cerebral maintenance therapy. The median cerebral period of remission was 52 weeks. 1 child suffering from ALL had been free from meningosis relapses for 128 weeks. Continuous cytostatic therapy is necessary for methaphylaxis. However, despite of the good results presented, /sup 198/Au colloid can not be recommended for long-term therapy because radiation injuries are to be expected.

  2. Membrane Compartmentalization Reducing the Mobility of Lipids and Proteins within a Model Plasma Membrane.

    Science.gov (United States)

    Koldsø, Heidi; Reddy, Tyler; Fowler, Philip W; Duncan, Anna L; Sansom, Mark S P

    2016-09-01

    The cytoskeleton underlying cell membranes may influence the dynamic organization of proteins and lipids within the bilayer by immobilizing certain transmembrane (TM) proteins and forming corrals within the membrane. Here, we present coarse-grained resolution simulations of a biologically realistic membrane model of asymmetrically organized lipids and TM proteins. We determine the effects of a model of cytoskeletal immobilization of selected membrane proteins using long time scale coarse-grained molecular dynamics simulations. By introducing compartments with varying degrees of restraints within the membrane models, we are able to reveal how compartmentalization caused by cytoskeletal immobilization leads to reduced and anomalous diffusional mobility of both proteins and lipids. This in turn results in a reduced rate of protein dimerization within the membrane and of hopping of membrane proteins between compartments. These simulations provide a molecular realization of hierarchical models often invoked to explain single-molecule imaging studies of membrane proteins.

  3. A comprehensive compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Vahidi, O; Kwok, K E; Gopaluni, R B

    2016-01-01

    We have expanded a former compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects. The former model was a detailed physiological model which considered the interactions of three substances, glucose, insulin and glucagon on regulating the blood sugar. The main...... variations of blood glucose concentrations following an oral glucose intake. Another model representing the incretins production in the gastrointestinal tract along with their hormonal effects on boosting pancreatic insulin production is also added to the former model. We have used two sets of clinical data...... obtained during oral glucose tolerance test and isoglycemic intravenous glucose infusion test from both type 2 diabetic and healthy subjects to estimate the model parameters and to validate the model results. The estimation of model parameters is accomplished through solving a nonlinear optimization...

  4. Savannah River Laboratory DOSTOMAN code: a compartmental pathways computer model of contaminant transport

    International Nuclear Information System (INIS)

    King, C.M.; Wilhite, E.L.; Root, R.W. Jr.

    1985-01-01

    The Savannah River Laboratory DOSTOMAN code has been used since 1978 for environmental pathway analysis of potential migration of radionuclides and hazardous chemicals. The DOSTOMAN work is reviewed including a summary of historical use of compartmental models, the mathematical basis for the DOSTOMAN code, examples of exact analytical solutions for simple matrices, methods for numerical solution of complex matrices, and mathematical validation/calibration of the SRL code. The review includes the methodology for application to nuclear and hazardous chemical waste disposal, examples of use of the model in contaminant transport and pathway analysis, a user's guide for computer implementation, peer review of the code, and use of DOSTOMAN at other Department of Energy sites. 22 refs., 3 figs

  5. A dynamic compartmental food chain model of radiocaesium transfer to Apodemus sylvaticus in woodland ecosystems

    International Nuclear Information System (INIS)

    Toal, M.E.; Copplestone, D.; Johnson, M.S.; Jackson, D.; Jones, S.R.

    2001-01-01

    A study was undertaken to quantify the activity concentrations of 137Cs in Apodemus sylvaticus (the woodmouse) in two woodland sites, Lady Wood and Longrigg Wood, adjacent to British Nuclear Fuels Ltd. (BNFL) Sellafield, Cumbria, UK. A deterministic dynamic compartmental food chain model was also constructed to predict 137Cs activity concentration [Bq kg -1 dry weight (dw)] in A. sylvaticus on a seasonal basis given the activity concentrations in its diet. Within the coniferous woodland site (Lady Wood), significant differences were found between seasons (P x / 2.3 Bq kg -1 dw) being attributed to mycophagy. Fungal concentrations ranged from 2-3213 Bq kg -1 dw. The modelled activity concentrations fell between the confidence intervals of the observed data in four of the six seasonal cohorts sampled. Disparities between predicted and observed activity concentrations are attributed to uncertainties surrounding the fundamental feeding ecology of small mammals

  6. Measurement of renal glomerular filtration rate using labelled substances with compartmental analysis

    International Nuclear Information System (INIS)

    Eberstadt, P.L.

    1981-10-01

    Using a model for the two-compartmental open system and experiments on animals (rabbits and dogs) as well as on human healthy volunteers, an attempt was made to study the advantages and limitations of different radionuclide methods for glomerular filtration rate determination. Labelled compounds used in different combinations were: 3 H-inulin, sup(113m)In-EDTA, 131 I-iothalamate, sup(99m)Tc-DTPA and 14 C-creatinine. The results of the study lead to some working hypotheses concerning the value of creatinine and other labelled substances in the measurement of glomerular filtration rate in clinical practice. The advantages and disadvantages of individual methods summarized in the final report are generally in agreement with the present views of many research workers. Also the hypothesis can be justified that the different labelled compounds which have been studied might be handled independently by the membranes involved but at the long run produce similar homeostatic balance

  7. Geo-environmental zoning using physiographic compartmentalization: a proposal for supporting sustainable decision-making

    Directory of Open Access Journals (Sweden)

    CLAUDIA V.S. CORRÊA

    Full Text Available ABSTRACT The geo-environmental zoning represents an important strategy in the territorial management. However, it requires a logical and structured procedure. Therefore, an approach using physiographic compartmentalization is proposed and applied as case study in a region covered by the topographic maps of São José dos Campos and Jacareí, Brazil. This region has great geological and geomorphological peculiarities, beyond being a place with large human interventions because of its quickly economic growth. The methodology is based on photointerpretation techniques and remote sensing in GIS environment. As a result, seven geo-environmental zones were obtained from a weighted integration by multicriteria analysis of physiographic units with land-use classes. In conclusion, taking into account potentialities and limitations, the proposed approach can be considered able to support sustainable decision-making, being applicable in other regions.

  8. Fatigue in isometric contraction in a single muscle fibre: a compartmental calcium ion flow model.

    Science.gov (United States)

    Kothiyal, K P; Ibramsha, M

    1986-01-01

    Fatigue in muscle is a complex biological phenomenon which has so far eluded a definite explanation. Many biochemical and physiological models have been suggested in the literature to account for the decrement in the ability of muscle to sustain a given level of force for a long time. Some of these models have been critically analysed in this paper and are shown to be not able to explain all the experimental observations. A new compartmental model based on the intracellular calcium ion movement in muscle is proposed to study the mechanical responses of a muscle fibre. Computer simulation is performed to obtain model responses in isometric contraction to an impulse and a train of stimuli of long duration. The simulated curves have been compared with experimentally observed mechanical responses of the semitendinosus muscle fibre of Rana pipiens. The comparison of computed and observed responses indicates that the proposed calcium ion model indeed accounts very well for the muscle fatigue.

  9. [Effect of NaCl stress on ion compartmentation, photosynthesis and growth of Salicornia bigelovii Torr].

    Science.gov (United States)

    Wang, Li-Yan; Zhao, Ke-Fu

    2004-02-01

    Seedlings of Salicornia bigelovii Torr. were treated with different concentrations of NaCl (0, 100, 300, 600 mmol/L). Ion contents, Na(+) subcelluar localization, photosynthetic rate, ultrastructure of chloroplast and other parameters were measured. The data showed both fresh and dry weight of whole plant of Salicornia bigelovii Torr. under salinity were higher than the control. When NaCl concentration is about 300 mmol/L Salicornia bigelovii Torr. grow strongest. The contents of Na(+) and Cl(-) and c(Na)/c(K) in shoots increased with the salinity. Both Na(+) and Cl(-) were mainly transported to shoots. Ion X-ray microanalysis indicated Na(+) was mainly compartmentalized into vacuoles. Photosynthetic rate increased with the salinity under NaCl 100-300 mmol/L, but declined under NaCl 600 mmol/L. Ultrastructure of chloroplast was destroyed by NaCl 600 mmol/L.

  10. Dual regulation of muscle glycogen synthase during exercise by activation and compartmentalization

    DEFF Research Database (Denmark)

    Prats, Clara; Helge, Jørn W; Nordby, Pernille

    2009-01-01

    Glycogen synthase (GS) is considered the rate-limiting enzyme in glycogenesis but still today there is a lack of understanding on its regulation. We have previously shown phosphorylation-dependent GS intracellular redistribution at the start of glycogen re-synthesis in rabbit skeletal muscle (Prats......, C., Cadefau, J. A., Cussó, R., Qvortrup, K., Nielsen, J. N., Wojtaszewki, J. F., Wojtaszewki, J. F., Hardie, D. G., Stewart, G., Hansen, B. F., and Ploug, T. (2005) J. Biol. Chem. 280, 23165-23172). In the present study we investigate the regulation of human muscle GS activity by glycogen, exercise......, and insulin. Using immunocytochemistry we investigate the existence and relevance of GS intracellular compartmentalization during exercise and during glycogen re-synthesis. The results show that GS intrinsic activity is strongly dependent on glycogen levels and that such regulation involves associated...

  11. Estimation of pharmacokinetic parameters from non-compartmental variables using Microsoft Excel.

    Science.gov (United States)

    Dansirikul, Chantaratsamon; Choi, Malcolm; Duffull, Stephen B

    2005-06-01

    This study was conducted to develop a method, termed 'back analysis (BA)', for converting non-compartmental variables to compartment model dependent pharmacokinetic parameters for both one- and two-compartment models. A Microsoft Excel spreadsheet was implemented with the use of Solver and visual basic functions. The performance of the BA method in estimating pharmacokinetic parameter values was evaluated by comparing the parameter values obtained to a standard modelling software program, NONMEM, using simulated data. The results show that the BA method was reasonably precise and provided low bias in estimating fixed and random effect parameters for both one- and two-compartment models. The pharmacokinetic parameters estimated from the BA method were similar to those of NONMEM estimation.

  12. Cerebrospinal fluid analysis in the HIV infection and compartmentalization of HIV in the central nervous system

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2015-07-01

    Full Text Available The nervous system plays an important role in HIV infection. The purpose of this review is to discuss the indications for cerebrospinal fluid (CSF analysis in HIV infection in clinical practice. CSF analysis in HIV infection is indicated for the diagnosis of opportunistic infections and co-infections, diagnosis of meningitis caused by HIV, quantification of HIV viral load, and analysis of CNS HIV compartmentalization. Although several CSF biomarkers have been investigated, none are clinically applicable. The capacity of HIV to generate genetic diversity, in association with the constitutional characteristics of the CNS, facilitates the generation of HIV quasispecies in the CNS that are distinct from HIV in the systemic circulation. CSF analysis has a well-defined and valuable role in the diagnosis of CNS infections in HIV/AIDS patients. Further research is necessary to establish a clinically applicable biomarker for the diagnosis of HIV-associated neurocognitive disorders.

  13. Heterogeneity and compartmentalization of Pneumocystis carinii f. sp. hominis genotypes in autopsy lungs

    DEFF Research Database (Denmark)

    Helweg-Larsen, J; Lundgren, Bettina; Lundgren, Jens Dilling

    2001-01-01

    The extent and importance of genotype heterogeneity of Pneumocystis carinii f. sp. hominis within lungs have not previously been investigated. Two hundred forty PCR clones obtained from respiratory specimens and lung segments from three patients with fatal P. carinii pneumonia were investigated....... Not all genotypes present in the lungs at autopsy were detected in the diagnostic respiratory samples. Compartmentalization of specific ITS and mtLSU rRNA sequence types was observed in different lung segments. In conclusion, the interpretation of genotype data and in particular ITS sequence types...... in the assessment of epidemiological questions should be cautious since genotyping done on respiratory samples cannot a priori be assumed to represent all genotypes present within the lung....

  14. Sequence Stratigraphy of the Dakota Sandstone, Eastern San Juan Basin, New Mexico, and its Relationship to Reservoir Compartmentalization; FINAL

    International Nuclear Information System (INIS)

    Varney, Peter J.

    2002-01-01

    This research established the Dakota-outcrop sequence stratigraphy in part of the eastern San Juan Basin, New Mexico, and relates reservoir quality lithologies in depositional sequences to structure and reservoir compartmentalization in the South Lindrith Field area. The result was a predictive tool that will help guide further exploration and development

  15. Sequence Stratigraphy of the Dakota Sandstone, Eastern San Juan Basin, New Mexico, and its Relationship to Reservoir Compartmentalization

    Energy Technology Data Exchange (ETDEWEB)

    Varney, Peter J.

    2002-04-23

    This research established the Dakota-outcrop sequence stratigraphy in part of the eastern San Juan Basin, New Mexico, and relates reservoir quality lithologies in depositional sequences to structure and reservoir compartmentalization in the South Lindrith Field area. The result was a predictive tool that will help guide further exploration and development.

  16. Trial Watch: Anticancer radioimmunotherapy.

    Science.gov (United States)

    Vacchelli, Erika; Vitale, Ilio; Tartour, Eric; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-09-01

    Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in cancer patients.

  17. Cs-137 accumulation and elimination by Gracilaria caudata alga and Abudefduf saxatilis fish. Compartmental analysis

    International Nuclear Information System (INIS)

    Mattiolo-Marchese, Sandra Regina

    1998-01-01

    From the ecological point of view, 137 Cs is a critical radionuclide because its physical half-life is long (30 years), and it has a high fission yield. Besides, it presents similar characteristics to sodium and potassium, fundamental elements for the living organisms, in great concentration in all cells. This work has as aim to study the 137 Cs accumulation and elimination by the alga Gracilaria caudata and by the fish Abudefduf saxatilis as well as to obtain the transfer constants of the 137 Cs from the water into the organisms. The concentration factor found for the fish was 5.6 +- 0.2 and for the alga, 13.0 +- 0,6. With 7 and 22 days, the fish and alga respectively had already eliminated half of the accumulated radionuclide. The 137 Cs ingestion efficiency by the fish was also studied and it was verified that the fish assimilated only 47.6 % of the cesium content in the food; and within of 4 days it had eliminated more than half of ingested cesium. A compartmental model was proposed to explain the distribution of cesium in the compartments (water - alga and water - fish). Data obtained from the experiments of 137 Cs accumulation and elimination were applied in the Ana Comp Program. This program permits the compartmental analysis, and quantifies the cesium distribution from the sea-water to the organisms, and vice versa, through the transfer constants (k). The Ana Comp Program also allowed to calculate the dose that one would receive by the consumption of fish contaminated by cesium. Levels of 137 Cs from the global fallout in environmental samples, from Sao Sebastiao, northern coast of Sao Paulo, (where the 'Centro de Biologia Marinha da Universidade de Sao Paulo - CEBIMar - USP' is located), were verified. (author)

  18. PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling

    Science.gov (United States)

    Yang, Jason H.; Polanowska-Grabowska, Renata K.; Smith, Jeffrey S.; Shields, Charles W.; Saucerman, Jeffrey J.

    2014-01-01

    β-adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca2+ handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t50 = 10.60±0.68 min; EC50 = 89.00 nmol/L) than in the cytosol (t50 = 3.71±0.25 min; EC50 = 1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca2+ and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC50 = 1.84 nmol/L) over cell hypertrophy (EC50 = 85.88 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile β-adrenergic signaling responses. PMID:24225179

  19. The construction of next-generation matrices for compartmental epidemic models.

    Science.gov (United States)

    Diekmann, O; Heesterbeek, J A P; Roberts, M G

    2010-06-06

    The basic reproduction number (0) is arguably the most important quantity in infectious disease epidemiology. The next-generation matrix (NGM) is the natural basis for the definition and calculation of (0) where finitely many different categories of individuals are recognized. We clear up confusion that has been around in the literature concerning the construction of this matrix, specifically for the most frequently used so-called compartmental models. We present a detailed easy recipe for the construction of the NGM from basic ingredients derived directly from the specifications of the model. We show that two related matrices exist which we define to be the NGM with large domain and the NGM with small domain. The three matrices together reflect the range of possibilities encountered in the literature for the characterization of (0). We show how they are connected and how their construction follows from the basic model ingredients, and establish that they have the same non-zero eigenvalues, the largest of which is the basic reproduction number (0). Although we present formal recipes based on linear algebra, we encourage the construction of the NGM by way of direct epidemiological reasoning, using the clear interpretation of the elements of the NGM and of the model ingredients. We present a selection of examples as a practical guide to our methods. In the appendix we present an elementary but complete proof that (0) defined as the dominant eigenvalue of the NGM for compartmental systems and the Malthusian parameter r, the real-time exponential growth rate in the early phase of an outbreak, are connected by the properties that (0) > 1 if and only if r > 0, and (0) = 1 if and only if r = 0.

  20. Evaluation of a compartmental model for estimating tumor hypoxia via FMISO dynamic PET imaging

    International Nuclear Information System (INIS)

    Wang Wenli; Nehmeh, Sadek A; O'Donoghue, Joseph; Zanzonico, Pat B; Schmidtlein, C Ross; Lee, Nancy Y; Humm, John L; Georgi, Jens-Christoph; Paulus, Timo; Narayanan, Manoj; Bal, Matthieu

    2009-01-01

    This paper systematically evaluates a pharmacokinetic compartmental model for identifying tumor hypoxia using dynamic positron emission tomography (PET) imaging with 18 F-fluoromisonidazole (FMISO). A generic irreversible one-plasma two-tissue compartmental model was used. A dynamic PET image dataset was simulated with three tumor regions-normoxic, hypoxic and necrotic-embedded in a normal-tissue background, and with an image-based arterial input function. Each voxelized tissue's time activity curve (TAC) was simulated with typical values of kinetic parameters, as deduced from FMISO-PET data from nine head-and-neck cancer patients. The dynamic dataset was first produced without any statistical noise to ensure that correct kinetic parameters were reproducible. Next, to investigate the stability of kinetic parameter estimation in the presence of noise, 1000 noisy samples of the dynamic dataset were generated, from which 1000 noisy estimates of kinetic parameters were calculated and used to estimate the sample mean and covariance matrix. It is found that a more peaked input function gave less variation in various kinetic parameters, and the variation of kinetic parameters could also be reduced by two region-of-interest averaging techniques. To further investigate how bias in the arterial input function affected the kinetic parameter estimation, a shift error was introduced in the peak amplitude and peak location of the input TAC, and the bias of various kinetic parameters calculated. In summary, mathematical phantom studies have been used to determine the statistical accuracy and precision of model-based kinetic analysis, which helps to validate this analysis and provides guidance in planning clinical dynamic FMISO-PET studies.

  1. Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants

    Directory of Open Access Journals (Sweden)

    Mukae Takehiro

    2011-09-01

    Full Text Available Abstract Background Fibromyalgia (FM is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS. Results In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief. Conclusions These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.

  2. Intrathecal huperzine A increases thermal escape latency and decreases flinching behavior in the formalin test in rats.

    Science.gov (United States)

    Park, Paula; Schachter, Steven; Yaksh, Tony

    2010-02-05

    Huperzine A (HupA) is an alkaloid isolated from the Chinese club moss Huperzia serrata and has been used for improving memory, cognitive and behavioral function in patients with Alzheimer's disease in China. It has NMDA antagonist and anticholinesterase activity and has shown anticonvulsant and antinociceptive effects in preliminary studies when administered intraperitoneally to mice. To better characterize the antinociceptive effects of HupA at the spinal level, Holtzman rats were implanted with intrathecal catheters to measure thermal escape latency using Hargreaves thermal escape testing system and flinching behavior using the formalin test. Intrathecal (IT) administration of HupA showed a dose-dependent increase in thermal escape latency with an ED50 of 0.57 microg. Atropine reversed the increase in thermal escape latency produced by 10 microg HupA, indicating an antinociceptive mechanism through muscarinic cholinergic receptors. The formalin test showed that HupA decreased flinching behavior in a dose-dependent manner. Atropine also reversed the decrease in flinching behavior caused by 10 microg HupA. A dose-dependent increase of side effects including scratching, biting, and chewing tails was observed, although antinociceptive effects were observed in doses that did not produce any adverse effects. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  3. [In vitro study on intrathecal application of 5-fluoro-2'-deoxyuridine (FdUrd) for meningeal dissemination of malignant tumor].

    Science.gov (United States)

    Nakagawa, H; Yamada, M; Fukushima, M; Shimizu, K; Ikenaka, K

    1998-09-01

    To evaluate the possible clinical intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for malignant brain tumors, its anti-tumor activity and neurotoxicity were compared with that of 5-fluorouracil (5-FU) and 5-fluorouridine (FUrd) in vitro. FdUrd showed good tumoricidal activity against cultured mouse 203 glioma cells and rat Walker 256 carcinoma cells as well as A172 human glioblastoma cells. Daoy human medulloblastoma cells and CADO-LC4 human lung cancer cells. It also showed less toxicity for primary cultures of neurons from C57/BL6 mouse and human embryo compared to 5-FU and FUrd. Thymidine phosphorylase (TPase) and thymidine kinase (TK), key enzymes for metabolism of 5-FU derivatives, were measured in cerebrospinal fluid (CSF). TPase or TK activity was detected in the CSF of hardly any patients with malignant brain tumors including meningeal carcinomatosis. These data indicated that the CSF is a favorable site for FdUrd chemotherapy, because the rate of conversion of FdUrd injected to 5-FU would be minimal. In conclusion, FdUrd may be potentially useful for intrathecal treatment of meningeal carcinomatosis.

  4. A COMPARATIVE STUDY OF HEAMOD Y NAMIC PARAMETERS IN LSCS WITH INTRATHECAL FENTANYL - BUPIVACAINE COMBINATION AND BUPIVACAINE ALONE

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    Ramana Prasad

    2015-10-01

    Full Text Available BACKGROUND: Caesarean section is considered as a major abdominal surgery, which requires profound blockade of spinal segments. Spinal anaesthesia is the most elegant approach providing profound anaesthesia and excellent operative conditions. Hypotension, the most clinically significant effect of spinal anaesthesia can occur rapidly and have a significant impact on neonatal outcome. There has been interest in using analgesic additives to local anaesthetics to decrease the dose of local anaesthetics and reduce in incidence of hypotension without compromising intra - operative analgesia, enabling faster motor recovery and providing efficient post - operative analgesia. This study was conducted t o compare the incidence of hypotension between intrathecal fentanyl - bupivacaine combinations with bupivacaine alone in patients undergoing elective LSCS. INTRODUCTION: In Caesarean section, the surgery is major and profound blockade of many spinal segments is required. Strong visceral stimulation is present, sudden cardiovascular changes is compounded by posture and fetal wellbeing may be influenced by several physiologic variables and drugs. Spinal anaesthesia is perhaps the most efficient and elegant appr oach to this challenge. With a small needle and little amount of drug, profound anaesthesia and excellent operating conditions can be readily provided for this major intrabdominal surgery. Spinal hypotension, the most clinically significant aspect of spina l anaesthesia can occur rapidly and may have a significant impact on the neonatal outcome. Recently, there has been an interest in using analgesic additives to subarachnoid local anaesthetic dose so as to reduce the incidence and degree of hypotension but at the same time without compromising intraoperative analgesia and also to enable faster recovery and providing efficient post - operative analgesia. Opioids were the first clinically used selective spinal analgesics after the discovery of opioids

  5. Intrathecal hyperbaric versus isobaric bupivacaine for adult non-caesarean-section surgery: systematic review protocol.

    Science.gov (United States)

    Uppal, Vishal; Shanthanna, Harsha; Prabhakar, Christopher; McKeen, Dolores M

    2016-05-18

    Bupivacaine is the most commonly used local anaesthetic for spinal anaesthesia (SA). There are two forms of commercially available bupivacaine; isobaric bupivacaine (IB): a formulation with a specific gravity or density equal to cerebrospinal fluid, and hyperbaric bupivacaine (HB): a formulation with density heavier than cerebrospinal fluid. The difference in densities of the two available preparations is believed to affect the diffusion pattern that determines the effectiveness, spread and side-effect profile of bupivacaine. This systematic review will summarise the best available evidence regarding the effectiveness and safety on the use of HB compared with IB, when used to provide SA for surgery. Primarily, we will analyse the need for conversion to general anaesthesia. As secondary outcomes, we will compare the incidence of hypotension, incidence of nausea/vomiting, the onset time and duration of anaesthesia. We will search key electronic databases using search strategy (1) injections, spinal OR intrathecal OR subarachnoid; (2) bupivacaine OR levobupivacaine; (3) hypobaric OR isobaric OR plain; (4) baricity. We will search MEDLINE, EMBASE and Cochrane databases, from their inception for randomised controlled trials, with no restrictions on language. Caesarean section surgery will be excluded. 2 reviewers will independently extract the data using a standardised form. Extracted items will include study characteristics, risk of bias domains, as per modified Cochrane risk of bias, participant disposition and study outcomes. We will conduct a meta-analysis for variables that can be compared across the studies. We will evaluate clinical heterogeneity by qualitatively appraising differences in study characteristics in participants, interventions and the outcomes assessed. We will report our findings as relative risks (dichotomous), and weighted mean differences (continuous) for individual outcomes, along with their 95% CIs. We plan to submit, and will publish, our

  6. Intrathecal baclofen pumps do not accelerate progression of scoliosis in quadriplegic spastic cerebral palsy.

    Science.gov (United States)

    Rushton, Paul R P; Nasto, Luigi A; Aujla, Ranjit K; Ammar, Amr; Grevitt, Michael P; Vloeberghs, Michael H

    2017-06-01

    To compare scoliosis progression in quadriplegic spastic cerebral palsy with and without intrathecal baclofen (ITB) pumps. A retrospective matched cohort study was conducted. Patients with quadriplegic spastic cerebral palsy, GMFCS level 5, treated with ITB pumps with follow-up >1 year were matched to comparable cases by age and baseline Cobb angle without ITB pumps. Annual and peak coronal curve progression, pelvic obliquity progression and need for spinal fusion were compared. ITB group: 25 patients (9 female), mean age at pump insertion 9.4 and Risser 0.9. Initial Cobb angle 25.6° and pelvic tilt 3.2°. Follow-up 4.3 (1.0-7.8) years. Cobb angle at follow-up 76.1° and pelvic tilt 18.9°. Non-ITB group: 25 patients (14 female), mean age at baseline 9.2 and Risser 1.0. Initial Cobb angle 29.7° and pelvic tilt 7.1°. Follow-up 3.5 (1.0-7.5) years. Cobb angle at follow-up 69.1° and pelvic tilt 21.0°. The two groups were statistically similar for baseline age, Cobb angle and Risser grade. Mean curve progression was 13.6°/year for the ITB group vs 12.6°/year for the non-ITB group (p = 0.39). Peak curve progression was similar between the groups. Pelvic tilt progression was comparable; ITB group 4.5°/year vs non-ITB 4.6°/year (p = 0.97). During follow-up 5 patients in the ITB group and 9 in the non-ITB group required spinal fusion surgery for curve progression (p = 0.35). Patients with quadriplegic spastic cerebral palsy with and without ITB pumps showed significant curve progression over time. ITB pumps do not appear to alter the natural history of curve progression in this population.

  7. Long term effect (more than five years) of intrathecal baclofen on impairment, disability, and quality of life in patients with severe spasticity of spinal origin

    NARCIS (Netherlands)

    Zahavi, A; Geertzen, JHB; Middel, B; Staal, M; Rietman, JS

    2004-01-01

    Objectives: To evaluate long term change in impairment, disability, and health related functional status in patients with severe spasticity who received intrathecal baclofen. Methods: A long term ( more than five years) observational longitudinal follow up study assessing 21 patients who received

  8. Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.

    Science.gov (United States)

    Von Bergen, Nicholas H; Subieta, Alberto; Brennan, Timothy J

    2002-07-01

    Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia. Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 microl bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558. Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558. Drugs like LY293558 that block alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.

  9. Intrathecal Fentanyl for Labour Analgesia in a Patient with Severe Mitral Stenosis and Atrial Fibrillation in Advanced Stage of Labour-Case Report

    Directory of Open Access Journals (Sweden)

    Vaijayanti Nitin Gadre

    2013-12-01

    Full Text Available Labour is an intensely painful experience and puts considerable physiological stress on the circulation. A case of rheumatic valvular heart disease with severe mitral stenosis in atrial fibrillation is discussed here in which analgesia with intrathecal fentanyl proved beneficial given during the advanced first stage of labour.

  10. ED50 and ED95 of Intrathecal Bupivacaine Coadministered with Sufentanil for Cesarean Delivery Under Combined Spinal-epidural in Severely Preeclamptic Patients

    Institute of Scientific and Technical Information of China (English)

    Fei Xiao; Wen-Ping Xu; Xiao-Min Zhang; Yin-Fa Zhang; Li-Zhong Wang; Xin-Zhong Chen

    2015-01-01

    Background:Spinal anesthesia was considered as a reasonable anesthetic option in severe preeclampsia when cesarean delivery is indicated,and there is no indwelling epidural catheter or contraindication to spinal anesthesia.However,the ideal dose of intrathecal bupivacaine has not been quantified for cesarean delivery for severe preeclamptic patients.This study aimed to determine the ED50 and ED95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery.Methods:Two hundred severely preeclamptic patients are undergoing elective cesarean delivery under combined spinal-epidural anesthesia enrolled in this randomized,double-blinded,dose-ranging study.Patients received 4 mg,6 mg,8 mg,or 10 mg intrathecal hyperbaric bupivacaine with 2.5 μg sufentanil.Successful spinal anesthesia was defined as a T6 sensory level achieved within 10 minutes after intrathecal drug administration and/or no epidural supplement was required during the cesarean section.The ED50 and ED95 were calculated with a logistic regression model.Results:ED50 and ED95 ofintrathecal bupivacaine for successful spinal anesthesia were 5.67 mg (95% confidence interval [CI]:5.20-6.10 mg) and 8.82 mg (95% CI:8.14-9.87 mg) respectively.The incidence of hypotension in Group 8 mg and Group 10 mg was higher than that in Group 4 mg and Group 6 mg (P < 0.05).The sensory block was significantly different among groups 10 minutes after intrathecal injection (P < 0.05).The use of lidocaine in Group 4 mg was higher than that in other groups (P < 0.05).The use of phenylephrine in Group 8 mg and Group 10 mg was higher than that in the other two groups (P < 0.05).The lowest systolic blood pressure before the infant delivery of Group 8 mg and Group 10 mg was lower than the other two groups (P < 0.05).The satisfaction of muscle relaxation in Group 4 mg was lower than other groups (P < 0.05).There was no significant difference in patients' satisfaction and the newborns

  11. Intrathecal morphine plus general anesthesia in cardiac surgery: effects on pulmonary function, postoperative analgesia, and plasma morphine concentration

    Directory of Open Access Journals (Sweden)

    Luciana Moraes dos Santos

    2009-04-01

    Full Text Available OBJECTIVES: To evaluate the effects of intrathecal morphine on pulmonary function, analgesia, and morphine plasma concentrations after cardiac surgery. INTRODUCTION: Lung dysfunction increases morbidity and mortality after cardiac surgery. Regional analgesia may improve pulmonary outcomes by reducing pain, but the occurrence of this benefit remains controversial. METHODS: Forty-two patients were randomized for general anesthesia (control group n=22 or 400 µg of intrathecal morphine followed by general anesthesia (morphine group n=20. Postoperative analgesia was accomplished with an intravenous, patient-controlled morphine pump. Blood gas measurements, forced vital capacity (FVC, forced expiratory volume (FEV, and FVC/FEV ratio were obtained preoperatively, as well as on the first and second postoperative days. Pain at rest, profound inspiration, amount of coughing, morphine solicitation, consumption, and plasma morphine concentration were evaluated for 36 hours postoperatively. Statistical analyses were performed using the repeated measures ANOVA or Mann-Whiney tests (*p<0.05. RESULTS: Both groups experienced reduced FVC postoperatively (3.24 L to 1.38 L in control group; 2.72 L to 1.18 L in morphine group, with no significant decreases observed between groups. The two groups also exhibited similar results for FEV1 (p=0.085, FEV1/FVC (p=0.68 and PaO2/FiO2 ratio (p=0.08. The morphine group reported less pain intensity (evaluated using a visual numeric scale, especially when coughing (18 hours postoperatively: control group= 4.73 and morphine group= 1.80, p=0.001. Cumulative morphine consumption was reduced after 18 hours in the morphine group (control group= 20.14 and morphine group= 14.20 mg, p=0.037. The plasma morphine concentration was also reduced in the morphine group 24 hours after surgery (control group= 15.87 ng.mL-1 and morphine group= 4.08 ng.mL-1, p=0.029. CONCLUSIONS: Intrathecal morphine administration did not significantly alter

  12. Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory.

    Science.gov (United States)

    Havekes, Robbert; Park, Alan J; Tolentino, Rosa E; Bruinenberg, Vibeke M; Tudor, Jennifer C; Lee, Yool; Hansen, Rolf T; Guercio, Leonardo A; Linton, Edward; Neves-Zaph, Susana R; Meerlo, Peter; Baillie, George S; Houslay, Miles D; Abel, Ted

    2016-08-24

    Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular compartments. The

  13. Compartmental analysis of the disposition of benzo[a]pyrene in rats.

    Science.gov (United States)

    Bevan, D R; Weyand, E H

    1988-11-01

    We have previously reported the disposition of benzo[a]pyrene (B[a]P) and its metabolites in male Sprague-Dawley rats following intratracheal instillation of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1986) Cancer Res., 46, 5655-5661]. In some experiments, cannulas were implanted in the bile duct of the animals prior to administration of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1987) Drug Metab. Disposition, 15, 442-448]. Based on these data, we have developed a compartmental model of the distribution of radioactivity to provide a quantitative description of the fate of B[a]P and its metabolites in rats. Modeling of the distribution of radioactivity was performed using the Simulation, Analysis and Modeling (SAAM) and conversational SAAM (CONSAM) computer programs. Compartments in the model included organs into which the largest amounts of radioactivity were distributed as well as pathways for excretion of radioactivity from the animals. Data from animals with and without cannulas implanted in the bile duct were considered simultaneously during modeling. Radioactivity was so rapidly absorbed from the lungs that an absorption phase into blood was not apparent at the earliest sampling times. Using the model of extrapolate to shorter times, it was predicted that the maximum amount of radioactivity was present in blood within 2 min after administration. In addition, considerable recycling of radioactivity back to lungs from blood was predicted by the model. Transfer of radioactivity from blood to liver and carcass (skin, muscle, bones, fat and associated blood) also was extensive. Carcass was modeled as the sum of two compartments to obtain agreement between the model and experimental data. The model accounted for enterohepatic circulation of B[a]P metabolites; data also required that intestinal secretion be included in the model. Quantitative data obtained from compartmental analysis included rate constants for transfer of radioactivity among compartments as well as

  14. Intrathecal IgM index correlates with a severe disease course in multiple sclerosis: Clinical and MRI results.

    Science.gov (United States)

    Ozakbas, Serkan; Cinar, Bilge Piri; Özcelik, Pinar; Baser, Hatice; Kosehasanoğullari, Gorkem

    2017-09-01

    Intrathecally synthesized IgM can be seen not only in the cerebrospinal fluid (CSF) in infectious and inflammatory diseases of the central nervous system, but also in that of patients with multiple sclerosis (MS). Intrathecal IgM synthesis in MS seems to be correlated with an unfavorable disease course. In one cross-sectional study, intrathecal synthesis of IgM (IgM index) was found to be correlated with cranial magnetic resonance imaging (MRI) parameters. The purpose of this study was to determine the possible relationship between the IgM index and MRI and clinical parameters. Eighty-one patients with MS (58 female) undergoing lumbar puncture were included in the study. Fifty-one patients had a relapsing-remitting (RR) disease course, while 30 cases were secondary progressive MS (SPMS). IgM was detected in paired CSF and serum specimens using ELISA. The IgM index was calculated using the formula CSF IgM/serum IgM: CSF albumin/serum albumin. IgM indexes higher than 0.1 were considered "increased". All patients underwent brain and whole spinal cord MRI. The IgM index was normal in 43 of the 81 patients (53.1%) and increased in 38 (46.9%). A significant correlation was determined between the IgM index and Expanded Disability Status Scale (EDSS) (r=0.638, p=0.001). Most of the subjects with increased IgM indexes were SPMS patients, 28 having a SPMS course and 10 a RRMS course. Only two patients with SPMS courses had normal IgM indexes. EDSS scores were significantly higher in patients with increased IgM indexes (EDSS 4.3 vs EDSS 2.8, p=0.000). All patients with EDSS >3 had increased IgM indexes. All patients with IgM index values higher than 0.2 IgM had SPMS courses and EDSS >6. Time to onset of the secondary progressive phase of the disease was correlated with IgM index values (p=0.004). IgM index values were also correlated with T1 hypointense lesions (r=0.0431, p=0.008) and Gd enhancing lesions (r=0.0396, p=0.006). Patients with increased IgM indexes also had more

  15. Case with high cervical intramedullary hemangioblastoma associated with arteriovenous fistula. CT with simultaneous intravenous and intrathecal injection of contrast medium

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Takao; Shoji, Shin-ichi; Yanagisawa, Nobuo; Tada, Tsuyoshi; Kobayashi, Naoki

    1988-02-01

    A 34-year-old woman complained of right hemiparesis and pain in the right hand. Routine X-ray of the cervical portion failed to reveal abnormal findings. CT with intravenous contrast medium showed a large high-density mass in the spinal canal at the level of C2. Right vertebral angiography showed a hypervascular mass. With simultaneous intravenous and intrathecal injections of contrast medium, the tumor was shown as a moderately high-density area and the parenchyma of cord as a thin low-density area surrounding the tumor stain on CT. These CT appearances led to the final diagnosis of high cervical intramedullary hemangioblastoma associated with arteriovenous fistulae. Pathological findings are typical of hemangioblastoma. The usefulness of CT in detecting the localization of hypervascular spinal cord lesions is stressed. (Namekawa, K.).

  16. Micro-compartmentalized cultivation of cyanobacteria for mutant screening using glass slides with highly water-repellent mark

    Directory of Open Access Journals (Sweden)

    Sayuri Arai

    2014-12-01

    Full Text Available Photosynthetic microorganisms such as cyanobacteria have attracted attention for their potential to produce biofuels and biochemicals directly from CO2. Cell isolation by colony has conventionally been used for selecting target cells. Colony isolation methods require a significant amount of time for cultivation, and the colony-forming ratio is potentially low for cyanobacteria. Here, we overcome such limitations by encapsulating and culturing cells in droplets with an overlay of dodecane using glass slides printed with highly water-repellent mark. In the compartmentalized culture, the oil phase protects the small volume of culture medium from drying and increases the CO2 supply. Since a difference in cell growth was observed with and without the addition of antibiotics, this compartmentalized culture method could be a powerful tool for mutant selection.

  17. Mathematical basis for the measurement of absolute and fractional cardiac output with diffusible tracers by compartmental analysis methods

    International Nuclear Information System (INIS)

    Charkes, N.D.

    1984-01-01

    Using compartmental analysis methods, a mathematical basis is given for the measurement of absolute and fractional cardiac output with diffusible tracers. Cardiac output is shown to be the product of the blood volume and the sum of the rate constants of tracer egress from blood, modified by a factor reflecting transcapillary diffusibility, the transfer fraction. The return of tracer to the blood and distant (intracellular) events are shown to play no role in the solution. Fractional cardiac output is the ratio of the rate constant of tracer egress from blood to an organ, divided by the sum of the egress constants from blood. Predominantly extracellular ions such as sodium or bromide are best suited for this technique, although theoretically any diffusible tracer whose compartmental model can be solved may be used. It is shown that fractional cardiac output is independent of the transfer fraction, and therefore can be measured accurately by tracers which are not freely diffusible

  18. THE EFFECTS OF INTRATHECAL NEOSTIGMINE ADDED TO BUPIVACAINE ON POSTOPERATIVE ANALGESIC REQUIREMENT IN PATIENTS UNDERGOING LOWER LIMB ORTHOPEDIC SURGERY.

    Science.gov (United States)

    Kayalha, Hamid; Mousavi, Zinat; Sadat Barikani, Ameneh; Yaghoobi, Siamak; Khezri, Marzieh Beigom

    2015-06-01

    Several additives have been suggested to enhance analgesic effect of local anesthetic agents to decrease the adverse effects of them and increase the degree of satisfaction. We designed this randomized double-blind controlled study to evaluate the analgesic efficacy of the neostigmine added to bupivacaine using spinal anesthesia in patients undergoing lower limb orthopedic surgery. Sixty patients 18-80 yr old American Society of Anesthesiologists (ASA) physical status I or II, scheduled for femur surgery under spinal anesthesia, were recruited in a prospective, double-blinded, randomized way. The patients were randomly allocated to one of two groups of 30 each. The neostigmine group (group N) received bupivacaine 20 mg combined with 25 µg neostigmine, and the placebo group (group C) received bupivacaine 20 mg combined with 0.5ml distilled water (intrathecally) 5 minutes prior to surgery. The time to the first analgesic request, analgesic requirement in the first 12 hours after surgery, the duration of sensory and motor blockade, the incidence of adverse effects such as nausea,vomiting,hypotension, ephedrine requirements, bradycardia, and hypoxemia were recorded. Patients receiving neostigmine had a significantly prolonged duration of motor block (C95% CI 30.27 to 87.65; P < 0.001) and sensory block (C95% CI 101.04 to 224.64; P < 0.001) compared to the control group. The difference of the mean time to the first analgesic request was also significantly longer in neostigmine group (C95% CI 83.139 to 208.526; P < 0.001). The total analgesic consumption during the first 12 hours after surgery was devoid of any significant difference between groups N and C (p = 0.41).The two groups were not significantly different in terms of intraoperative and postoperative side effects. Intrathecal neostigmine 25 µg with bupivacaine caused a prolonged time to the first analgesic request and its use was not associated with any side effects.

  19. Comparative in Vivo Investigation of Intrathecal and Intracerebroventricular Administration with Melanocortin Ligands MTII and AGRP into Mice.

    Science.gov (United States)

    Adank, Danielle N; Lunzer, Mary M; Lensing, Cody J; Wilber, Stacey L; Gancarz, Amy M; Haskell-Luevano, Carrie

    2018-02-21

    Central administration of melanocortin ligands has been used as a critical technique to study energy homeostasis. While intracerebroventricular (ICV) injection is the most commonly used method during these investigations, intrathecal (IT) injection can be equally efficacious for the central delivery of ligands. Importantly, intrathecal administration can optimize exploration of melanocortin receptors in the spinal cord. Herein, we investigate comparative IT and ICV administration of two melanocortin ligands, the synthetic MTII (Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH 2 ) MC4R agonist and agouti-related peptide [AGRP(87-132)] MC4R inverse agonist/antagonist, on the same batch of age-matched mice in TSE metabolic cages undergoing a nocturnal satiated paradigm. To our knowledge, this is the first study to test how central administration of these ligands directly to the spinal cord affects energy homeostasis. Results showed, as expected, that MTII IT administration caused a decrease in food and water intake and an overall negative energy balance without affecting activity. As anticipated, IT administration of AGRP caused weight gain, increase of food/water intake, and increase respiratory exchange ratio (RER). Unexpectantly, the prolonged activity of AGRP was notably shorter (2 days) compared to mice given ICV injections of the same concentrations in previous studies (7 days or more).1-4 It appears that IT administration results in a more sensitive response that may be a good approach for testing synthetic compound potency values ranging in nanomolar to high micromolar in vitro EC 50 values. Indeed, our investigation reveals that the spine influences a different melanocortin response compared to the brain for the AGRP ligand. This study indicates that IT administration can be a useful technique for future metabolic studies using melanocortin ligands and highlights the importance of exploring the role of melanocortin receptors in the spinal cord.

  20. Evaluation of the effect of transdermal nitroglycerine patch on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy

    Directory of Open Access Journals (Sweden)

    Rama Chatterji

    2017-01-01

    Full Text Available Aim: The aim of this study is to evaluate the effect of transdermal nitroglycerin on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy. Materials and Methods: Totally 140 patients of the American Society of Anesthesiologists Grade I or II, posted for abdominal hysterectomy under spinal anesthesia, were randomized to four groups using computer-generated random number list. Group B received 3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml normal saline and placebo patch, Group BN received 3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml NS and transdermal nitroglycerin (t-NTG, Group BD received 3 ml of 0.5% hyperbaric bupivacaine with 5 mcg (0.5 ml dexmedetomidine and placebo patch and Group BDN received 3 ml of 0.5% hyperbaric bupivacaine with 5 μg (0.5 ml dexmedetomidine and t-NTG patch. Outcomes measured include the total duration of analgesia, onset, and duration of sensory and motor block and any adverse effects. Results: The total duration of analgesia was longest in Group BDN (349.9 ± 40.6 min. It was significantly longer than Group BD (252.3 ± 34.0 min and Group B and BN (130.5 ± 18.8, 138.3 ± 19.2 min. Time taken for two segment regression was comparable in Group B (79.9 ± 14.4 min and Group BN (87.1 ± 22.6 min, but it was significantly longer in Group BD (122.5 ± 17.2 min and Group BDN (136.4 ± 25.5 min. There was no significant difference in other variables between the groups. Conclusion: Transdermal nitroglycerine itself does not exhibit any analgesic potential of its own but, it enhances the analgesic potential of intrathecal dexmedetomidine.

  1. Association between change in normal appearing white matter metabolites and intrathecal inflammation in natalizumab-treated multiple sclerosis.

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    Johan Mellergård

    Full Text Available BACKGROUND: Multiple sclerosis (MS is associated not only with focal inflammatory lesions but also diffuse pathology in the central nervous system (CNS. Since there is no firm association between the amount of focal inflammatory lesions and disease severity, diffuse pathology in normal appearing white matter (NAWM may be crucial for disease progression. Immunomodulating treatments for MS reduce the number of focal lesions, but possible effects on diffuse white matter pathology are less studied. Furthermore, it is not known whether intrathecal levels of inflammatory or neurodegenerative markers are associated with development of pathology in NAWM. METHODS: Quantitative proton magnetic resonance spectroscopy ((1H-MRS was used to investigate NAWM in 27 patients with relapsing MS before and after one year of treatment with natalizumab as well as NAWM in 20 healthy controls at baseline. Changes in (1H-MRS metabolite concentrations during treatment were also correlated with a panel of intrathecal markers of inflammation and neurodegeneration in 24 of these 27 patients. RESULTS: The group levels of (1H-MRS metabolite concentrations were unchanged pre- to posttreatment, but a pattern of high magnitude correlation coefficients (r = 0.43-0.67, p<0.0005-0.03 were found between changes in individual metabolite concentrations (total creatine and total choline and levels of pro-inflammatory markers (IL-1β and CXCL8. CONCLUSIONS: Despite a clinical improvement and a global decrease in levels of inflammatory markers in cerebrospinal fluid during treatment, high levels of pro-inflammatory CXCL8 and IL-1β were associated with an increase in (1H-MRS metabolites indicative of continued gliosis development and membrane turnover in NAWM.

  2. Comparison of intrathecal clonidine and magnesium sulphate used as an adjuvant with hyperbaric bupivacaine in lower abdominal surgery

    Directory of Open Access Journals (Sweden)

    Mamta Khandelwal

    2017-01-01

    Full Text Available Background and Aims: Use of various adjuvants to spinal anaesthesia is a well-known modality to provide intra- and post-operative analgesia. This study was designed to evaluate and compare the analgesic efficacy of clonidine and magnesium when used as an additive to intrathecal 0.5% hyperbaric bupivacaine. Methods: Ninety patients of the American Society of Anesthesiologists' physical status grade I or II, scheduled for lower abdominal surgery under spinal anaesthesia, were randomly allocated into three groups. Group B received 3 mL of 0.5% hyperbaric bupivacaine with 1 mL of normal saline, Group C received 3 mL of 0.5% hyperbaric bupivacaine with 1 mL (30 μg of clonidine and Group M received 3 mL of 0.5% hyperbaric bupivacaine with 1 mL (50 mg magnesium sulphate. The primary outcome variable was duration of analgesia and secondary outcome variables included onset and duration of sensory and motor block, sedation level and adverse effects. Data were analysed with ANOVA, Kruskal–Wallis and Chi-square tests. Results: The time to first rescue analgesia was significantly (P < 0.01 longer in the Group C (330.7 ± 47.7 min than both Groups. Group M (246.3 ± 55.9 min showed significantly prolonged analgesia than Group B (134.4 ± 17.9 min. Group C and Group M showed significantly prolonged duration of both sensory and motor block compared to Group B. Conclusion: Intrathecal clonidine added to bupivacaine prolongs the duration of post-operative analgesia, and hastens the onset and prolongs the duration of sensory and motor block compared to magnesium or controls.

  3. Effects of intrathecal dexmedetomidine on shivering after spinal anesthesia for cesarean section: a double-blind randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Nasseri K

    2017-04-01

    Full Text Available Karim Nasseri,1,2 Negin Ghadami,1 Bijan Nouri2 1Department of Anesthesiology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran; 2Social Determinants of Health Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran Background: Shivering is among the common troublesome complications of spinal anesthesia (SA, and causes discomfort and discontentment in parturients undergoing cesarean sections (CSs. The aim of this study was to investigate the effects of intrathecal dexmedetomidine in the prevention of shivering in those who underwent CS under SA.Subjects and methods: Fifty parturients planned for elective CSs under SA were enrolled in this prospective, double-blinded, controlled study and randomly divided into two equal groups. Spinal block was achieved with 12.5 mg 0.5% heavy bupivacaine plus 5 µg dexmedetomidine (BD group or 0.5 mL 0.9% normal saline (BN group. The incidence and intensity of shivering, peripheral and core body temperature, hemodynamic parameters, and adverse events was recorded.Results: The incidence of shivering was significantly higher in the BN group (52% than the BD group (24% (P=0.04. Likewise, the intensity of shivering was significantly higher in the BN group than the BD group (P=0.04. The incidence of adverse events, such as hypotension, nausea/vomiting, and bradycardia, was not significantly different between the two groups, although the grade of sedation was higher in the BD group than the BN group (P=0.004.Conclusion: We conclude that intrathecal dexmedetomidine is effective in lowering the incidence and intensity of shivering in parturients undergoing CSs under SA without major adverse effects. Keywords: dexmedetomidine, shivering, spinal anesthesia, cesarean sections, bupivacaine

  4. The experimental study on the radioimmunotherapy of the hepatoma in nude mice model with intratumoral injection of 131I-human anti-HBsAg Fab

    International Nuclear Information System (INIS)

    Luo Rongcheng; Wu Guichen; Han Huanxing; You Changxuan; Ding Xuemei; Li Aimin; Wang Chuanbin; Zhang Mingjiang

    2001-01-01

    Objective: To study the therapeutic efficacy of radioimmunotherapy of 131 I-human anti-HBsAg Fab via different routes of administration. Methods: The human hepatoma bearing nude mice we reinjected with 131 I-human anti-HBsAg Fab intra-tumor (IT) and intra-peritoneum (IP). Biodistribution was measured on the 5th day. The tumor growth inhibition rate was determined by measurement of tumor volume. Results: In the IT-treated mice, tumor uptake of 131 I-human anti-HBsAg Fab was four-fold greater than in the IP-treated mice, and normal organ uptake was half of that in the IP-treated mice. At the 3rd week after the infusion, the tumor growth inhibition rate in IT-treated mice was higher than that in the IP-treated mice. Conclusions: Intratumoral administration of 131 I-human anti-HBsAg Fab makes high level of radioactivity retained in tumor with significantly lower radioactivity retained in normal tissues, and provides a more effective regional therapy

  5. Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19)

    International Nuclear Information System (INIS)

    Spaeth, Nicolas; Wyss, Matthias T.; Pahnke, Jens; Biollaz, Gregoire; Trachsel, Eveline; Drandarov, Konstantin; Treyer, Valerie; Weber, Bruno; Neri, Dario; Buck, Alfred

    2006-01-01

    Despite aggressive treatment protocols, patients suffering from glioblastoma multiforme still experience poor outcome. Therefore, new adjuvant therapeutic options such as radioimmunotherapy (RIT) have been studied and have resulted in significant survival benefit. In this study, we assessed the efficacy of a novel radioimmunotherapeutic approach targeting the extra domain B (EDB) of fibronectin, a marker of angiogenesis, in glioma-bearing rats. Methods: C6 gliomas were induced intracerebrally in Wistar rats. Ten to 11 days later, 220-360 MBq of iodine-131-labeled anti-EDB SIP(L19) ('small immunoprotein') was administered intravenously into nine animals, yielding a radiation dose of 13-21 Gy. Another nine rats served as controls. Then the following parameters were compared: median survival time, tumor size and histology. Results: Histological examination of the tumors revealed typical glioblastoma characteristics. Eleven of 18 rats developed a tumor size bigger than 150 mm 3 . When these animals were used for survival analysis, median survival did significantly differ between groups [22 days (therapy; n=7) vs. 16 days (control; n=4); P 131 I-SIP(L19)-RIT showed promising potential in treating C6 gliomas, warranting further studies. However, larger trials with preferentially higher doses are needed to confirm this finding and, potentially, to further increase the efficacy of this treatment

  6. Three-compartmental analysis of effects of D-propranolol on thyroid hormone kinetics

    International Nuclear Information System (INIS)

    Van Der Heijden, J.T.M.; Krenning, E.P.; Van Toor, H.; Hennemann, G.; Docter, R.

    1988-01-01

    Tracer thyroxine (T 4 ), 3,3',5-triiodothyronine (T 3 ), and 3,3',5'-triiodothyronine (rT 3 ) kinetic studies were performed in normal T 4 substituted subjects before and during oral D-propranolol treatment to determine whether changes in thyroid hormone metabolism in a propranolol-induced low-T 3 syndrome result from inhibition of 5'-deiodination or inhibition of transport of iodothyronines into tissues. Data were analyzed according to a three-compartmental model of distribution and metabolism. No changes were observed in size of the three T 4 compartments or in fractional and mass transfer rates of T 4 from plasma to the rapidly (REP) and slowly (SEP) equilibrating pools. Serum T 3 , free T 3 , T 3 plasma pool, T 3 mass transfer rate to REP and SEP, and the T 3 pool masses were all significantly decreased during propranolol to a similar extent as the T 3 plasma production rate (PR). It is concluded that the D-propranolol-induced changes in thyroid hormone metabolism, resulting in a low-T 3 syndrome, are due to inhibition of thyroid hormone deiodination. This is in contrast to the low-T 3 syndrome during caloric deprivation, which results from inhibition of transport of iodothyronines into the liver

  7. Synthesis, characterization and biological activity of symmetric dinuclear complexes derived from a novel macrocyclic compartmental ligand

    Energy Technology Data Exchange (ETDEWEB)

    Mruthyunjayaswamy, B.H.M.; Ijare, Omkar B.; Jadegoud, Y. [Gulbarga University (India). Dept. of Chemistry]. E-mail: bhmmswamy53@rediffmail.com

    2005-07-15

    A phenol based novel macrocyclic binucleating compartmental ligand N,N-bis(2,6-diiminomethyl-4-methyl-1-hydroxyphenyl)malonoyldicarboxamide was prepared. The complexes were prepared by template method by reacting 2,6-diformyl-4-methylphenol, malonoyl dihydrazide and the metal chlorides of Cu(II), Ni(II), Co(II), Cd(II), Zn(II) and Hg(II) in methanol to get a series of dinuclear complexes. The complexes were characterized by elemental analyses, conductivity measurements, magnetic susceptibility data, IR, UV-Vis, ESR, NMR and FAB mass spectral data. The dinuclear nature of the complexes was confirmed on the basis of elemental analyses, magnetic susceptibility, ESR and FAB mass spectral data. The ligand as well as Cu(II), Ni(II), Co(II) and Zn(II) complexes were tested for their antibacterial and antifungal properties against Escherichia coli, Staphyloccocus aureus, Aspergillus niger and Fusarium oxysporum. Magnetic susceptibility measurements of Cu(II), Ni(II) and Co(II) complexes reveal that these complexes exhibit antiferromagnetic coupling behavior due to the presence of two metal ions in close proximity. FAB mass spectrum of the Cu(II) complex gave a clear evidence for the dinuclear nature. The ligand and the complexes were found to be less active against the tested bacteria, but the ligand alone was found active against the fungus Fusarium oxysporum. (author)

  8. Dynamic PET scanning and compartmental model analysis to determine cellular level radiotracer distribution in vivo

    International Nuclear Information System (INIS)

    Smith, G.T.; Hubner, K.F.; Goodman, M.M.; Stubbs, J.B.

    1992-01-01

    Positron emission tomography (PET) has been used to measure tissue radiotracer concentration in vivo. Radiochemical distribution can be determined with compartmental model analysis. A two compartment model describes the kinetics of N-13 ammonia ( 13 NH 3 ) in the myocardium. The model consists of a vascular space, Q 1 and a space for 13 NH 3 bound within the tissue, Q 2 . Differential equations for the model can be written: X(t) = AX(t) + BU( t), Y(t)= CX(t)+ DU(t) (1) where X(t) is a column vector [Q 1 (t); Q 2 (t)], U(t) is the arterial input activity measured from the left ventricular blood pool, and Y(t) is the measured tissue activity using PET. Matrices A, B, C, and D are dependent on physiological parameters describing the kinetics of 13 NH 3 in the myocardium. Estimated parameter matrices in Equation 1 have been validated in dog experiments by measuring myocardial perfusion with dynamic PET scanning and intravenous injection of 13 NH 3 . Tracer concentrations for each compartment can be calculated by direct integration of Equation 1. If the cellular level distribution of each compartment is known, the concentration of tracer within the intracellular and extracellular space can be determined. Applications of this type of modeling include parameter estimation for measurement of physiological processes, organ level dosimetry, and determination of cellular radiotracer distribution

  9. Compartmental modelling of the pharmacokinetics of a breast cancer resistance protein.

    Science.gov (United States)

    Grandjean, Thomas R B; Chappell, Mike J; Yates, James T W; Jones, Kevin; Wood, Gemma; Coleman, Tanya

    2011-11-01

    A mathematical model for the pharmacokinetics of Hoechst 33342 following administration into a culture medium containing a population of transfected cells (HEK293 hBCRP) with a potent breast cancer resistance protein inhibitor, Fumitremorgin C (FTC), present is described. FTC is reported to almost completely annul resistance mediated by BCRP in vitro. This non-linear compartmental model has seven macroscopic sub-units, with 14 rate parameters. It describes the relationship between the concentration of Hoechst 33342 and FTC, initially spiked in the medium, and the observed change in fluorescence due to Hoechst 33342 binding to DNA. Structural identifiability analysis has been performed using two methods, one based on the similarity transformation/exhaustive modelling approach and the other based on the differential algebra approach. The analyses demonstrated that all models derived are uniquely identifiable for the experiments/observations available. A kinetic modelling software package, namely FACSIMILE (MPCA Software, UK), was used for parameter fitting and to obtain numerical solutions for the system equations. Model fits gave very good agreement with in vitro data provided by AstraZeneca across a variety of experimental scenarios. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Compartmental analysis and dosimetric aspects applied to cholesterol with 3H labeled

    International Nuclear Information System (INIS)

    Oliveira, Adriano dos Santos

    2015-01-01

    Cardiovascular diseases (CVDs) are one of the major reasons of death around the world according to the World Health Organization (WHO). It is well known that changes in levels of plasma lipoproteins, which are responsible for the transport of cholesterol into the bloodstream, are associated with cardiovascular diseases. For this reason to know the biokinetic parameters of plasma lipoproteins and quantifies them is important to correct and deep understanding about the diseases associated with these disorders. The main aim of this study is to provide a biokinetic model and estimate the radiometric doses for 3 H-Cholesterol, a radioactive tracer widely used in physiological and metabolic studies. The model was based on [Schwartz et al. 2004] about the distribution of cholesterol by the lipoprotein and gastrointestinal model [ICRP 30, 1979]. The doses distribution in compartments of the model and other organs and tissues of a standard adult described in [ICRP 106, 2008] was calculated using MIRD method (Medical Internal Radiation Dose) and compartmental analysis using the computer program Matlab®. The dose coefficients were estimated for a standard phantom man (73 kg) described in [ICRP 60, 1991]. The estimated doses for both model and for other organs were low and did not exceed the highest dose obtained that was in the upper large intestine, as 44,8 μGy these parameters will assist in ethics committee's opinions on the use of works that use the 3 H-cholesterol which radioactive tracer. (author)

  11. PGI2 synthesis and excretion in dog kidney: evidence for renal PG compartmentalization

    International Nuclear Information System (INIS)

    Boyd, R.M.; Nasjletti, A.; Heerdt, P.M.; Baer, P.G.

    1986-01-01

    To assess the concept of compartmentalization of renal prostaglandins (PG), we compared entry of PGE2 and the PGI2 metabolite 6-keto-PGF1 alpha into the renal vascular and tubular compartments, in sodium pentobarbital-anesthetized dogs. Renal arterial 6-keto-PGF1 alpha infusion increased both renal venous and urinary 6-keto-PGF1 alpha outflow. In contrast, renal arterial infusion of arachidonic acid (AA) or bradykinin (BK) increased renal venous 6-keto-PGF1 alpha outflow but had no effect on its urinary outflow. Both urinary and renal venous PGE2 outflows increased during AA or BK infusion. Ureteral stopped-flow studies revealed no postglomerular 6-keto-PGF1 alpha entry into tubular fluid. During renal arterial infusion of [3H]PGI2 and inulin, first-pass 3H clearance was 40% of inulin clearance; 35% of urinary 3H was 6-keto-PGF1 alpha, and two other urinary metabolites were found. During renal arterial infusion of [3H]6-keto-PGF1 alpha and inulin, first-pass 3H clearance was 150% of inulin clearance; 75% of urinary 3H was 6-keto-PGF1 alpha, and only one other metabolite was found. We conclude that in the dog PGE2 synthesized in the kidney enters directly into both the renal vascular and tubular compartments, but 6-keto-PGF1 alpha of renal origin enters directly into only the renal vascular compartment

  12. Linear least squares compartmental-model-independent parameter identification in PET

    International Nuclear Information System (INIS)

    Thie, J.A.; Smith, G.T.; Hubner, K.F.

    1997-01-01

    A simplified approach involving linear-regression straight-line parameter fitting of dynamic scan data is developed for both specific and nonspecific models. Where compartmental-model topologies apply, the measured activity may be expressed in terms of: its integrals, plasma activity and plasma integrals -- all in a linear expression with macroparameters as coefficients. Multiple linear regression, as in spreadsheet software, determines parameters for best data fits. Positron emission tomography (PET)-acquired gray-matter images in a dynamic scan are analyzed: both by this method and by traditional iterative nonlinear least squares. Both patient and simulated data were used. Regression and traditional methods are in expected agreement. Monte-Carlo simulations evaluate parameter standard deviations, due to data noise, and much smaller noise-induced biases. Unique straight-line graphical displays permit visualizing data influences on various macroparameters as changes in slopes. Advantages of regression fitting are: simplicity, speed, ease of implementation in spreadsheet software, avoiding risks of convergence failures or false solutions in iterative least squares, and providing various visualizations of the uptake process by straight line graphical displays. Multiparameter model-independent analyses on lesser understood systems is also made possible

  13. Reservoir compartmentalization and management strategies: Lessons learned in the Illinois basin

    Energy Technology Data Exchange (ETDEWEB)

    Grube, J.P.; Crockett, J.E.; Huff, B.G. [and others

    1997-08-01

    A research project jointly sponsored by the US Department of Energy and the Illinois State Geological Survey focused on the Cypress and Aux Vases Formations (Mississippian), major clastic reservoirs in the Illinois Basin. Results from the research showed that understanding the nature and distribution of reservoir compartments, and using effective reservoir management strategies, can significantly improve recovery efficiencies from oil fields in this mature basin. Compartments can be most effectively drained where they are geologically well defined and reservoir management practices are coordinated through unified, compartment-wide, development programs. Our studies showed that the Cypress and Aux Vases reservoirs contain lateral and vertical permeability barriers forming compartments that range in size from isolated, interlaminated sandstone and shale beds to sandstone bodies tens of feet in thickness and more than a mile in length. Stacked or shingled, genetically similar sandstone bodies are commonly separated by thin impermeable intervals that can be difficult to distinguish on logs and can, therefore, cause correlation problems, even between wells drilled on spacing of less than ten acres. Lateral separation of sandstone bodies causes similar problems. Reservoir compartmentalization reduces primary and particularly secondary recovery by trapping pockets of by-passed or banked oil. Compartments can be detected by comparing recovery factors of genetically similar sandstone bodies within a field; using packers to separate commingled intervals and analyzing fluid recoveries and pressures; making detailed core-to-log calibrations that identify compartment boundaries; and analyzing pressure data from waterflood programs.

  14. Bystander effects and compartmental stress response to X-ray irradiation in L929 cells.

    Science.gov (United States)

    Temelie, Mihaela; Stroe, Daniela; Petcu, Ileana; Mustaciosu, Cosmin; Moisoi, Nicoleta; Savu, Diana

    2016-08-01

    Bystander effects are indirect consequences of radiation and many other stress factors. They occur in cells that are not directly exposed to these factors, but receive signals from affected cells either by gap junctions or by molecules released in the medium. Characterizing these effects and deciphering the underlying mechanisms involved in radiation-induced bystander effects are relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation 0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei shortly after the treatment, through medium transfer and by co-cultures. Interestingly, bystander cells did not exhibit long-term adverse changes in viability. Evaluation of several compartmental stress markers (CHOP, BiP, mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at transcriptional level. We investigated the involvement of ROS and NO in this process by addition of specific scavengers of these molecules, DMSO or c-PTIO in the transferred medium. This approach proved that ROS but not NO is involved in the induction of lesions in the acceptor cells. These results indicate that L929 cells are susceptible to stress effects of radiation-induced bystander signaling.

  15. Effects of hypoxia on 13NH4+ fluxes in rice roots: kinetics and compartmental analysis

    International Nuclear Information System (INIS)

    Kronzucker, H.J.; Kirk, G.J.D.; Siddiqi, M.Y.; Glass, A.D.M.

    1998-01-01

    Techniques of compartmental (efflux) and kinetic influx analyses with the radiotracer 13NH4+ were used to examine the adaptation to hypoxia (15, 35, and 50% O2 saturation) of root N uptake and metabolism in 3-week-old hydroponically grown rice (Oryza sativa L., cv IR72) seedlings. A time-dependence study of NH4+ influx into rice roots after onset of hypoxia (15% O2) revealed an initial increase in the first 1 to 2.5 h after treatment imposition, followed by a decline to less than 50% of influx in control plants by 4 d. Efflux analyses conducted 0, 1, 3, and 5 d after the treatment confirmed this adaptation pattern of NH4+ uptake. Half-lives for NH4+ exchange with subcellular compartments, cytoplasmic NH4+ concentrations, and efflux (as percentage of influx) were unaffected by hypoxia. However, significant differences were observed in the relative amounts of N allocated to NH4+ assimilation and the vacuole versus translocation to the shoot. Kinetic experiments conducted at 100, 50, 35, and 15% O2 saturation showed no significant change in the K(m) value for NH4+ uptake with varying O2 supply. However, V(max) was 42% higher than controls at 50% O2 saturation, unchanged at 35%, and 10% lower than controls at 15% O2. The significance of these flux adaptations is discussed

  16. Synthesis, characterization and biological activity of symmetric dinuclear complexes derived from a novel macrocyclic compartmental ligand

    International Nuclear Information System (INIS)

    Mruthyunjayaswamy, B.H.M.; Ijare, Omkar B.; Jadegoud, Y.

    2005-01-01

    A phenol based novel macrocyclic binucleating compartmental ligand N,N-bis(2,6-diiminomethyl-4-methyl-1-hydroxyphenyl)malonoyldicarboxamide was prepared. The complexes were prepared by template method by reacting 2,6-diformyl-4-methylphenol, malonoyl dihydrazide and the metal chlorides of Cu(II), Ni(II), Co(II), Cd(II), Zn(II) and Hg(II) in methanol to get a series of dinuclear complexes. The complexes were characterized by elemental analyses, conductivity measurements, magnetic susceptibility data, IR, UV-Vis, ESR, NMR and FAB mass spectral data. The dinuclear nature of the complexes was confirmed on the basis of elemental analyses, magnetic susceptibility, ESR and FAB mass spectral data. The ligand as well as Cu(II), Ni(II), Co(II) and Zn(II) complexes were tested for their antibacterial and antifungal properties against Escherichia coli, Staphyloccocus aureus, Aspergillus niger and Fusarium oxysporum. Magnetic susceptibility measurements of Cu(II), Ni(II) and Co(II) complexes reveal that these complexes exhibit antiferromagnetic coupling behavior due to the presence of two metal ions in close proximity. FAB mass spectrum of the Cu(II) complex gave a clear evidence for the dinuclear nature. The ligand and the complexes were found to be less active against the tested bacteria, but the ligand alone was found active against the fungus Fusarium oxysporum. (author)

  17. Metabolic Compartmentation – A System Level Property of Muscle Cells

    Directory of Open Access Journals (Sweden)

    Theo Wallimann

    2008-05-01

    Full Text Available Problems of quantitative investigation of intracellular diffusion and compartmentation of metabolites are analyzed. Principal controversies in recently published analyses of these problems for the living cells are discussed. It is shown that the formal theoretical analysis of diffusion of metabolites based on Fick’s equation and using fixed diffusion coefficients for diluted homogenous aqueous solutions, but applied for biological systems in vivo without any comparison with experimental results, may lead to misleading conclusions, which are contradictory to most biological observations. However, if the same theoretical methods are used for analysis of actual experimental data, the apparent diffusion constants obtained are orders of magnitude lower than those in diluted aqueous solutions. Thus, it can be concluded that local restrictions of diffusion of metabolites in a cell are a system-level properties caused by complex structural organization of the cells, macromolecular crowding, cytoskeletal networks and organization of metabolic pathways into multienzyme complexes and metabolons. This results in microcompartmentation of metabolites, their channeling between enzymes and in modular organization of cellular metabolic networks. The perspectives of further studies of these complex intracellular interactions in the framework of Systems Biology are discussed.

  18. Compartmentalized Epidermal Activation of β-Catenin Differentially Affects Lineage Reprogramming and Underlies Tumor Heterogeneity

    Directory of Open Access Journals (Sweden)

    Kai Kretzschmar

    2016-01-01

    Full Text Available Wnt/β-catenin activation in adult epidermis can induce new hair follicle formation and tumor development. We used lineage tracing to uncover the relative contribution of different stem cell populations. LGR6+ and LRIG1+ stem cells contributed to ectopic hair follicles formed in the sebaceous gland upon β-catenin activation, whereas LGR5+ cells did not. Lgr6, but not Lrig1 or Lgr5, was expressed in a subpopulation of interfollicular epidermal cells that were competent to form new hair follicles. Oncogenic β-catenin expression in LGR5+ cells led to formation of pilomatricomas, while LRIG1+ cells formed trichoadenomas and LGR6+ cells formed dermatofibromas. Tumor formation was always accompanied by a local increase in dermal fibroblast density and transient extracellular matrix remodeling. However, each tumor had a distinct stromal signature in terms of immune cell infiltrate and expression of CD26 and CD44. We conclude that compartmentalization of epidermal stem cells underlies different responses to β-catenin and skin tumor heterogeneity.

  19. Characterization and subcellular compartmentation of recombinant 4-hydroxyphenylpyruvate dioxygenase from Arabidopsis in transgenic tobacco.

    Science.gov (United States)

    Garcia, I; Rodgers, M; Pepin, R; Hsieh, T F; Matringe, M

    1999-04-01

    4-Hydroxyphenylpyruvate dioxygenase (4HPPD) catalyzes the formation of homogentisate (2,5-dihydroxyphenylacetate) from p-hydroxyphenylpyruvate and molecular oxygen. In plants this enzyme activity is involved in two distinct metabolic processes, the biosynthesis of prenylquinones and the catabolism of tyrosine. We report here the molecular and biochemical characterization of an Arabidopsis 4HPPD and the compartmentation of the recombinant protein in chlorophyllous tissues. We isolated a 1508-bp cDNA with one large open reading frame of 1338 bp. Southern analysis strongly suggested that this Arabidopsis 4HPPD is encoded by a single-copy gene. We investigated the biochemical characteristics of this 4HPPD by overproducing the recombinant protein in Escherichia coli JM105. The subcellular localization of the recombinant 4HPPD in chlorophyllous tissues was examined by overexpressing its complete coding sequence in transgenic tobacco (Nicotiana tabacum), using Agrobacterium tumefaciens transformation. We performed western analyses for the immunodetection of protein extracts from purified chloroplasts and total leaf extracts and for the immunocytochemistry on tissue sections. These analyses clearly revealed that 4HPPD was confined to the cytosol compartment, not targeted to the chloroplast. Western analyses confirmed the presence of a cytosolic form of 4HPPD in cultured green Arabidopsis cells.

  20. Integrated compartmental model for describing the transport of solute in a fractured porous medium. [FRACPORT

    Energy Technology Data Exchange (ETDEWEB)

    DeAngelis, D.L.; Yeh, G.T.; Huff, D.D.

    1984-10-01

    This report documents a model, FRACPORT, that simulates the transport of a solute through a fractured porous matrix. The model should be useful in analyzing the possible transport of radionuclides from shallow-land burial sites in humid environments. The use of the model is restricted to transport through saturated zones. The report first discusses the general modeling approach used, which is based on the Integrated Compartmental Method. The basic equations of solute transport are then presented. The model, which assumes a known water velocity field, solves these equations on two different time scales; one related to rapid transport of solute along fractures and the other related to slower transport through the porous matrix. FRACPORT is validated by application to a simple example of fractured porous medium transport that has previously been analyzed by other methods. Then its utility is demonstrated in analyzing more complex cases of pulses of solute into a fractured matrix. The report serves as a user's guide to FRACPORT. A detailed description of data input, along with a listing of input for a sample problem, is provided. 16 references, 18 figures, 3 tables.

  1. A comprehensive compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects.

    Science.gov (United States)

    Vahidi, O; Kwok, K E; Gopaluni, R B; Knop, F K

    2016-09-01

    We have expanded a former compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects. The former model was a detailed physiological model which considered the interactions of three substances, glucose, insulin and glucagon on regulating the blood sugar. The main drawback of the former model was its restriction on the route of glucose entrance to the body which was limited to the intravenous glucose injection. To handle the oral glucose intake, we have added a model of glucose absorption in the gastrointestinal tract to the former model to address the resultant variations of blood glucose concentrations following an oral glucose intake. Another model representing the incretins production in the gastrointestinal tract along with their hormonal effects on boosting pancreatic insulin production is also added to the former model. We have used two sets of clinical data obtained during oral glucose tolerance test and isoglycemic intravenous glucose infusion test from both type 2 diabetic and healthy subjects to estimate the model parameters and to validate the model results. The estimation of model parameters is accomplished through solving a nonlinear optimization problem. The results show acceptable precision of the estimated model parameters and demonstrate the capability of the model in accurate prediction of the body response during the clinical studies.

  2. Proposing a Compartmental Model for Leprosy and Parameterizing Using Regional Incidence in Brazil.

    Science.gov (United States)

    Smith, Rebecca Lee

    2016-08-01

    Hansen's disease (HD), or leprosy, is still considered a public health risk in much of Brazil. Understanding the dynamics of the infection at a regional level can aid in identification of targets to improve control. A compartmental continuous-time model for leprosy dynamics was designed based on understanding of the biology of the infection. The transmission coefficients for the model and the rate of detection were fit for each region using Approximate Bayesian Computation applied to paucibacillary and multibacillary incidence data over the period of 2000 to 2010, and model fit was validated on incidence data from 2011 to 2012. Regional variation was noted in detection rate, with cases in the Midwest estimated to be infectious for 10 years prior to detection compared to 5 years for most other regions. Posterior predictions for the model estimated that elimination of leprosy as a public health risk would require, on average, 44-45 years in the three regions with the highest prevalence. The model is easily adaptable to other settings, and can be studied to determine the efficacy of improved case finding on leprosy control.

  3. cGMP Signaling in the Cardiovascular System—The Role of Compartmentation and Its Live Cell Imaging

    Science.gov (United States)

    Bork, Nadja I.; Nikolaev, Viacheslav O.

    2018-01-01

    The ubiquitous second messenger 3′,5′-cyclic guanosine monophosphate (cGMP) regulates multiple physiologic processes in the cardiovascular system. Its intracellular effects are mediated by stringently controlled subcellular microdomains. In this review, we will illustrate the current techniques available for real-time cGMP measurements with a specific focus on live cell imaging methods. We will also discuss currently accepted and emerging mechanisms of cGMP compartmentation in the cardiovascular system. PMID:29534460

  4. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

    OpenAIRE

    Rebouche, C J; Engel, A G

    1984-01-01

    The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine wa...

  5. Compartmentalized Human Immunodeficiency Virus Type 1 Originates from Long-Lived Cells in Some Subjects with HIV-1–Associated Dementia

    Science.gov (United States)

    Schnell, Gretja; Spudich, Serena; Harrington, Patrick; Price, Richard W.; Swanstrom, Ronald

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after systemic infection and can result in the subsequent development of HIV-1–associated dementia (HAD) in a subset of infected individuals. Genetically compartmentalized virus in the CNS is associated with HAD, suggesting autonomous viral replication as a factor in the disease process. We examined the source of compartmentalized HIV-1 in the CNS of subjects with HIV-1–associated neurological disease and in asymptomatic subjects who were initiating antiretroviral therapy. The heteroduplex tracking assay (HTA), targeting the variable regions of env, was used to determine which HIV-1 genetic variants in the cerebrospinal fluid (CSF) were compartmentalized and which variants were shared with the blood plasma. We then measured the viral decay kinetics of individual variants after the initiation of antiretroviral therapy. Compartmentalized HIV-1 variants in the CSF of asymptomatic subjects decayed rapidly after the initiation of antiretroviral therapy, with a mean half-life of 1.57 days. Rapid viral decay was also measured for CSF-compartmentalized variants in four HAD subjects (t1/2 mean = 2.27 days). However, slow viral decay was measured for CSF-compartmentalized variants from an additional four subjects with neurological disease (t1/2 range = 9.85 days to no initial decay). The slow decay detected for CSF-compartmentalized variants was not associated with poor CNS drug penetration, drug resistant virus in the CSF, or the presence of X4 virus genotypes. We found that the slow decay measured for CSF-compartmentalized variants in subjects with neurological disease was correlated with low peripheral CD4 cell count and reduced CSF pleocytosis. We propose a model in which infiltrating macrophages replace CD4+ T cells as the primary source of productive viral replication in the CNS to maintain high viral loads in the CSF in a substantial subset of subjects with HAD

  6. Human Immunodeficiency Viruses Appear Compartmentalized to the Female Genital Tract in Cross-Sectional Analyses but Genital Lineages Do Not Persist Over Time

    OpenAIRE

    Bull, Marta E.; Heath, Laura M.; McKernan-Mullin, Jennifer L.; Kraft, Kelli M.; Acevedo, Luis; Hitti, Jane E.; Cohn, Susan E.; Tapia, Kenneth A.; Holte, Sarah E.; Dragavon, Joan A.; Coombs, Robert W.; Mullins, James I.; Frenkel, Lisa M.

    2013-01-01

    Background. Whether unique human immunodeficiency type 1 (HIV) genotypes occur in the genital tract is important for vaccine development and management of drug resistant viruses. Multiple cross-sectional studies suggest HIV is compartmentalized within the female genital tract. We hypothesize that bursts of HIV replication and/or proliferation of infected cells captured in cross-sectional analyses drive compartmentalization but over time genital-specific viral lineages do not form; rather viru...

  7. Intrathecally enhanced spinal CT in the early diagnosis of cerebrospinal fluid-borne metastasis in pediatric patients with primary brain tumors

    International Nuclear Information System (INIS)

    Wang, H.; Rosenbaum, A.E.; Ahn, H.S.; Zinreich, S.J.; Diffley, D.M.; Killmond, T.A.; Strauss, L.C.

    1987-01-01

    Early diagnosis and treatment of asymptomatic intraspinal cerebrospinal fluid-borne metastases can obviate serious sequelae in pediatric patients with known intracranial tumors. MR imaging is a superior imaging modality; however, in very young patients who need general anesthesia for immobilization and also for evaluation of small subarachnoid seedings, the authors found CT to be a valuable alternative. Twelve patients ranging in age from 3 months to 13 years underwent CT screening of the entire spine after intrathecal enhancement with 3-5 ml of metrizamide (100 mg iodine per milliliter) via a lumbar puncture. Intrathecal spinal metastases were found in 67% of the studied patients and even in a patient whose MR imaging examination failed to disclose the lesion

  8. The effect of intrathecal delivery of bone marrow stromal cells on hippocampal neurons in rat model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Mina Eftekharzadeh

    2015-05-01

    Full Text Available Objective(s: Intracerebral injection of bone marrow stromal cells (BMSCs is being investigated as a therapeutic tool to prevent Alzheimer's disease (AD. Our aim was to investigate the effects of BMSCs by intrathecal injection in AD rat model. Materials and Methods: BMSCs were obtained from the bone marrow of Wistar rat and transplanted into AD rat model via intrathecal injection. The rat model had received an injection of β amyloid into the hippocampus for histological and immunohistochemical studies. Results: Histological examination of the brains in transplanted rats compared to controls demonstrated the migration of BrdU-labeled BMSCs from the site of delivery, confirmed the differentiation of BMSCs transplanted cells into the cholinergic neurons, and increased number of healthy and decreased number of dark neurons. Conclusion: Our results showed that BMSCs intratechal administration could be a promising method for treatment ofAlzheimer’s disease in rat model.

  9. Compartmentalized microbial composition, oxygen gradients and nitrogen fixation in the gut of Odontotaenius disjunctus.

    Science.gov (United States)

    Ceja-Navarro, Javier A; Nguyen, Nhu H; Karaoz, Ulas; Gross, Stephanie R; Herman, Donald J; Andersen, Gary L; Bruns, Thomas D; Pett-Ridge, Jennifer; Blackwell, Meredith; Brodie, Eoin L

    2014-01-01

    Coarse woody debris is an important biomass pool in forest ecosystems that numerous groups of insects have evolved to take advantage of. These insects are ecologically important and represent useful natural analogs for biomass to biofuel conversion. Using a range of molecular approaches combined with microelectrode measurements of oxygen, we have characterized the gut microbiome and physiology of Odontotaenius disjunctus, a wood-feeding beetle native to the eastern United States. We hypothesized that morphological and physiological differences among gut regions would correspond to distinct microbial populations and activities. In fact, significantly different communities were found in the foregut (FG), midgut (MG)/posterior hindgut (PHG) and anterior hindgut (AHG), with Actinobacteria and Rhizobiales being more abundant toward the FG and PHG. Conversely, fermentative bacteria such as Bacteroidetes and Clostridia were more abundant in the AHG, and also the sole region where methanogenic Archaea were detected. Although each gut region possessed an anaerobic core, micron-scale profiling identified radial gradients in oxygen concentration in all regions. Nitrogen fixation was confirmed by (15)N2 incorporation, and nitrogenase gene (nifH) expression was greatest in the AHG. Phylogenetic analysis of nifH identified the most abundant transcript as related to Ni-Fe nitrogenase of a Bacteroidetes species, Paludibacter propionicigenes. Overall, we demonstrate not only a compartmentalized microbiome in this beetle digestive tract but also sharp oxygen gradients that may permit aerobic and anaerobic metabolism to occur within the same regions in close proximity. We provide evidence for the microbial fixation of N2 that is important for this beetle to subsist on woody biomass.

  10. The subcellular compartmentalization of arginine metabolizing enzymes and their role in endothelial dysfunction

    Directory of Open Access Journals (Sweden)

    Feng eChen

    2013-07-01

    Full Text Available The endothelial production of nitric oxide (NO mediates endothelium-dependent vasorelaxation and restrains vascular inflammation, smooth muscle proliferation and platelet aggregation. Impaired production of NO is a hallmark of endothelial dysfunction and promotes the development of cardiovascular disease. In endothelial cells, NO is generated by endothelial nitric oxide synthase (eNOS through the conversion of its substrate, L-arginine to L-citrulline. Reduced access to L-arginine has been proposed as a major mechanism underlying reduced eNOS activity and NO production in cardiovascular disease. The arginases (Arg1 and Arg2 metabolize L-arginine to generate L-ornithine and urea and increased expression of arginase has been proposed as a mechanism of reduced eNOS activity secondary to the depletion of L-arginine. Indeed, supplemental L-arginine and suppression of arginase activity has been shown to improve endothelium-dependent relaxation and ameliorate cardiovascular disease. However, L-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis suggesting additional mechanisms. The compartmentalization of intracellular L-arginine into poorly interchangeable pools has been proposed to allow for the local depletion of L-arginine. Indeed the subcellular location of L-arginine metabolizing enzymes plays important functional roles. In endothelial cells, eNOS is found in discrete intracellular locations and the capacity to generate NO is heavily influenced by its localtion. Arg1 and Arg2 also reside in different subcellular environments and are thought to differentially influence endothelial function. The plasma membrane solute transporter, CAT-1 and the arginine recycling enzyme, ASL, co-localize with eNOS and facilitate NO release. This review highlights the importance of the subcellular location of eNOS and arginine transporting and metabolizing enzymes to NO release and cardiovascular disease.

  11. The Importance of Bank Storage in Supplying Baseflow to Rivers Flowing Through Compartmentalized, Alluvial Aquifers

    Science.gov (United States)

    Rhodes, Kimberly A.; Proffitt, Tiffany; Rowley, Taylor; Knappett, Peter S. K.; Montiel, Daniel; Dimova, Natasha; Tebo, Daniel; Miller, Gretchen R.

    2017-12-01

    As water grows scarcer in semiarid and arid regions around the world, new tools are needed to quantify fluxes of water and chemicals between aquifers and rivers. In this study, we quantify the volumetric flux of subsurface water to a 24 km reach of the Brazos River, a lowland river that meanders through the Brazos River Alluvium Aquifer (BRAA), with 8 months of high-frequency differential gaging measurements using fixed gaging stations. Subsurface discharge sources were determined using natural tracers and End-Member Mixing Analysis (EMMA). During a 4 month river stage recession following a high stage event, subsurface discharge decreased from 50 m3/s to 0, releasing a total of 1.0 × 108 m3 of water. Subsurface discharge dried up even as the groundwater table at two locations in the BRAA located 300-500 m from the river remained ˜4 m higher than the river stage. Less than 4% of the water discharged from the subsurface during the prolonged recession period resembled the chemical fingerprint of the alluvial aquifer. Instead, the chemistry of this discharged water closely resembled high stage "event" river water. Together, these findings suggest that the river is well connected to rechargeable bank storage reservoirs but disconnected from the broader alluvial aquifer. The average width of discrete bank storage zones on each side of the river, identified with Electrical Resistivity Tomography (ERT), was approximately 1.5 km. In such highly compartmentalized aquifers, groundwater pumping is unlikely to impact the exchange between the river and the alluvium.

  12. Ocular pharmacokinetics of a novel tetrahydroquinoline analog in rabbit: absorption, disposition, and non-compartmental analysis.

    Science.gov (United States)

    Pamulapati, Chandrasena R; Schoenwald, Ronald D

    2011-12-01

    The pharmacologically active compound (33% reduction in rabbit intraocular pressure recovery rate assay) 1-ethyl-6-fluoro-1,2,3,4-tetrahydroquinoline (MC4), which showed ocular hypotensive action and had optimum physicochemical properties, was characterized for its ocular absorption and distribution properties to better understand its in vivo potency in comparison with an inactive compound, N-ethyl-1,4-benzoxazine (MC1). Tissue distribution to various ocular tissues was determined after absorption by both corneal and conjunctival-scleral routes, following administration by the "topical infusion" technique. The rank order of penetration for both the compounds was cornea > iris-ciliary body > aqueous humor > lens > conjunctiva-sclera. Overall, MC4 had significantly higher concentrations than MC1 in various ocular tissues, but particularly in the iris-ciliary body, which is the site of action (biophase). Ocular disposition studies of the active compound MC4 were then conducted to characterize its elimination kinetics, and the pharmacokinetic parameters were determined by non-compartmental and moment analysis using equations specific to "topical infusion" technique: first-order absorption rate constant, 4.1 × 10(-4) min(-1) ; elimination rate constant, 0.012 min(-1) ; mean residence time, 39.6 min; steady-state volume of distribution, 0.721 mL; and aqueous humor ocular clearance, 8.44 µL/min. The results were consistent with the conclusion that MC4 is well absorbed and distributed to the active site. Copyright © 2011 Wiley-Liss, Inc.

  13. Validation of Bayesian analysis of compartmental kinetic models in medical imaging.

    Science.gov (United States)

    Sitek, Arkadiusz; Li, Quanzheng; El Fakhri, Georges; Alpert, Nathaniel M

    2016-10-01

    Kinetic compartmental analysis is frequently used to compute physiologically relevant quantitative values from time series of images. In this paper, a new approach based on Bayesian analysis to obtain information about these parameters is presented and validated. The closed-form of the posterior distribution of kinetic parameters is derived with a hierarchical prior to model the standard deviation of normally distributed noise. Markov chain Monte Carlo methods are used for numerical estimation of the posterior distribution. Computer simulations of the kinetics of F18-fluorodeoxyglucose (FDG) are used to demonstrate drawing statistical inferences about kinetic parameters and to validate the theory and implementation. Additionally, point estimates of kinetic parameters and covariance of those estimates are determined using the classical non-linear least squares approach. Posteriors obtained using methods proposed in this work are accurate as no significant deviation from the expected shape of the posterior was found (one-sided P>0.08). It is demonstrated that the results obtained by the standard non-linear least-square methods fail to provide accurate estimation of uncertainty for the same data set (P<0.0001). The results of this work validate new methods for a computer simulations of FDG kinetics. Results show that in situations where the classical approach fails in accurate estimation of uncertainty, Bayesian estimation provides an accurate information about the uncertainties in the parameters. Although a particular example of FDG kinetics was used in the paper, the methods can be extended for different pharmaceuticals and imaging modalities. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  14. Barcoding of GPCR trafficking and signaling through the various trafficking roadmaps by compartmentalized signaling networks.

    Science.gov (United States)

    Bahouth, Suleiman W; Nooh, Mohammed M

    2017-08-01

    Proper signaling by G protein coupled receptors (GPCR) is dependent on the specific repertoire of transducing, enzymatic and regulatory kinases and phosphatases that shape its signaling output. Activation and signaling of the GPCR through its cognate G protein is impacted by G protein-coupled receptor kinase (GRK)-imprinted "barcodes" that recruit β-arrestins to regulate subsequent desensitization, biased signaling and endocytosis of the GPCR. The outcome of agonist-internalized GPCR in endosomes is also regulated by sequence motifs or "barcodes" within the GPCR that mediate its recycling to the plasma membrane or retention and eventual degradation as well as its subsequent signaling in endosomes. Given the vast number of diverse sequences in GPCR, several trafficking mechanisms for endosomal GPCR have been described. The majority of recycling GPCR, are sorted out of endosomes in a "sequence-dependent pathway" anchored around a type-1 PDZ-binding module found in their C-tails. For a subset of these GPCR, a second "barcode" imprinted onto specific GPCR serine/threonine residues by compartmentalized kinase networks was required for their efficient recycling through the "sequence-dependent pathway". Mutating the serine/threonine residues involved, produced dramatic effects on GPCR trafficking, indicating that they played a major role in setting the trafficking itinerary of these GPCR. While endosomal SNX27, retromer/WASH complexes and actin were required for efficient sorting and budding of all these GPCR, additional proteins were required for GPCR sorting via the second "barcode". Here we will review recent developments in GPCR trafficking in general and the human β 1 -adrenergic receptor in particular across the various trafficking roadmaps. In addition, we will discuss the role of GPCR trafficking in regulating endosomal GPCR signaling, which promote biochemical and physiological effects that are distinct from those generated by the GPCR signal transduction

  15. DNA precursor compartmentation in mammalian cells: distribution and rates of equilibration between nucleus and cytoplasm

    International Nuclear Information System (INIS)

    Leeds, J.M.

    1986-01-01

    A rapid nuclear isolation technique was adapted in order to examine the question of DNA precursor compartmentation in mammalian cells. By using this method a reproducible proportion of the cellular nucleotides remained associated with the isolated nuclei. Examination, at several different cell densities, of exponentially growing HeLa cells showed that the nuclei contained a constant but distinct proportion of each dNTP. The nuclear dATP and dTTP concentrations were equal at all densities examined even though the dTTP pool was 150% of the dATP whole-cell pool. The nuclear portion of the whole-cell pools was roughly equal to the volume occupied by the nucleus. The nuclear-cytoplasmic dNTP pool distribution did not change throughout the cell cycle of synchronized Chinese hamster ovary (CHO) cells. The rates at which either radiolabeled cytidine or deoxycytidine equilibrated with the nuclear and whole-cell dCTP pools of G1 and S phase CHO cells were compared. Experiments comparing the labeling kinetics of 3 H-thymidine in G1, S phase, and exponentially growing cells revealed that the S phase dTTP pool equilibrated with exogenously added thymidine faster than the G1 phase pool. The rate of equilibration in exponentially growing cells appeared to be a combination of that seen in G1 and S phases. A linear rate of 3 H-thymidine incorporation into DNA occurred at the same rate in S phase and exponentially growing cells

  16. Relationships between metal compartmentalization and biomarkers in earthworms exposed to field-contaminated soils.

    Science.gov (United States)

    Beaumelle, Léa; Hedde, Mickaël; Vandenbulcke, Franck; Lamy, Isabelle

    2017-05-01

    Partitioning tissue metal concentration into subcellular compartments reflecting toxicologically available pools may provide good descriptors of the toxicological effects of metals on organisms. Here we investigated the relationships between internal compartmentalization of Cd, Pb and Zn and biomarker responses in a model soil organism: the earthworm. The aim of this study was to identify metal fractions reflecting the toxic pressure in an endogeic, naturally occurring earthworm species (Aporrectodea caliginosa) exposed to realistic field-contaminated soils. After a 21 days exposure experiment to 31 field-contaminated soils, Cd, Pb and Zn concentrations in earthworms and in three subcellular fractions (cytosol, debris and granules) were quantified. Different biomarkers were measured: the expression of a metallothionein gene (mt), the activity of catalase (CAT) and of glutathione-s-transferase (GST), and the protein, lipid and glycogen reserves. Biomarkers were further combined into an integrated biomarker index (IBR). The subcellular fractionation provided better predictors of biomarkers than the total internal contents hence supporting its use when assessing toxicological bioavailability of metals to earthworms. The most soluble internal pools of metals were not always the best predictors of biomarker responses. metallothionein expression responded to increasing concentrations of Cd in the insoluble fraction (debris + granules). Protein and glycogen contents were also mainly related to Cd and Pb in the insoluble fraction. On the other hand, GST activity was better explained by Pb in the cytosolic fraction. CAT activity and lipid contents variations were not related to metal subcellular distribution. The IBR was best explained by both soluble and insoluble fractions of Pb and Cd. This study further extends the scope of mt expression as a robust and specific biomarker in an ecologically representative earthworm species exposed to field-contaminated soils. The

  17. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse Nucleus Accumbens

    Directory of Open Access Journals (Sweden)

    Giuseppe eGangarossa

    2013-02-01

    Full Text Available The nucleus accumbens (NAc is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP or the Cre-recombinase (Cre under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific ERK phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist, quinpirole (a D2R-like agonist, apomorphine (a non-selective DA receptor agonist, raclopride (a D2R-like antagonist, and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study.

  18. An improved single cell ultrahigh throughput screening method based on in vitro compartmentalization.

    Directory of Open Access Journals (Sweden)

    Fuqiang Ma

    Full Text Available High-throughput screening is a key technique in discovery and engineering of enzymes. In vitro compartmentalization based fluorescence-activated cell sorting (IVC-FACS has recently emerged as a powerful tool for ultrahigh-throughput screening of biocatalysts. However, the accuracy of current IVC-FACS assays is severely limited by the wide polydispersity of micro-reactors generated by homogenizing. Here, an improved protocol based on membrane-extrusion technique was reported to generate the micro-reactors in a more uniform manner. This crucial improvement enables ultrahigh-throughput screening of enzymatic activity at a speed of >10⁸ clones/day with an accuracy that could discriminate as low as two-fold differences in enzymatic activity inside the micro-reactors, which is higher than similar IVC-FACS systems eve