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Sample records for low-dose rate prostate

  1. Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

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    Al-Qaisieh, Bashar [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Mason, Josh, E-mail: joshua.mason@nhs.net [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Bownes, Peter; Henry, Ann [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Dickinson, Louise [Division of Surgery and Interventional Science, University College London, London (United Kingdom); Department of Radiology, Northwick Park Hospital, London North West NHS Trust, London (United Kingdom); Ahmed, Hashim U. [Division of Surgery and Interventional Science, University College London, London (United Kingdom); University College London Hospital, London (United Kingdom); Emberton, Mark [University College London Hospital, London (United Kingdom); Langley, Stephen [St Luke' s Cancer Centre, Guildford (United Kingdom)

    2015-07-15

    Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable

  2. Current topics in the treatment of prostate cancer with low-dose-rate brachytherapy.

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    Stock, Richard G; Stone, Nelson N

    2010-02-01

    The treatment of prostate cancer with low dose rate prostate brachytherapy has grown rapidly in the last 20 years. Outcome analyses performed in this period have enriched understanding of this modality. This article focuses on the development of a real-time ultrasound-guided implant technique, the importance of radiation dose, trimodality treatment of high-risk disease, long-term treatment outcomes, and treatment-associated morbidity.

  3. Measurement uncertainty analysis of low-dose-rate prostate seed brachytherapy: post-implant dosimetry.

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    Gregory, Kent J; Pattison, John E; Bibbo, Giovanni

    2015-03-01

    The minimal dose covering 90 % of the prostate volume--D 90--is arguably the most important dosimetric parameter in low-dose-rate prostate seed brachytherapy. In this study an analysis of the measurement uncertainties in D 90 from low-dose-rate prostate seed brachytherapy was conducted for two common treatment procedures with two different post-implant dosimetry methods. The analysis was undertaken in order to determine the magnitude of D 90 uncertainty, how the magnitude of the uncertainty varied when D 90 was calculated using different dosimetry methods, and which factors were the major contributors to the uncertainty. The analysis considered the prostate as being homogeneous and tissue equivalent and made use of published data, as well as original data collected specifically for this analysis, and was performed according to the Guide to the expression of uncertainty in measurement (GUM). It was found that when prostate imaging and seed implantation were conducted in two separate sessions using only CT images for post-implant analysis, the expanded uncertainty in D 90 values were about 25 % at the 95 % confidence interval. When prostate imaging and seed implantation were conducted during a single session using CT and ultrasound images for post-implant analysis, the expanded uncertainty in D 90 values were about 33 %. Methods for reducing these uncertainty levels are discussed. It was found that variations in contouring the target tissue made the largest contribution to D 90 uncertainty, while the uncertainty in seed source strength made only a small contribution. It is important that clinicians appreciate the overall magnitude of D 90 uncertainty and understand the factors that affect it so that clinical decisions are soundly based, and resources are appropriately allocated.

  4. LOW-DOSE RATE BRACHYTHERAPY FOR PROSTATE CANCER: DIFFERENT INDICATIONS – DIFFERENT RESULTS

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    V. A. Biryukov

    2014-07-01

    Full Text Available In Russia, there is presently a growing interest in low-dose intratissue radiotherapy (brachytherapy for locally advanced prostate cancer (PC. Since its inception, current brachytherapy has undergone a number of significant changes in terms of improved visualization and better treatment planning and monitoring, which is sure to have affected the higher quality of their performance and better long-term results. The main purpose of the given paper is to generalize the data of foreign investigators who have the greatest experience with brachytherapy for its further use in the treatment of patients with locally advanced PC under the conditions of Russian clinics.

  5. An open-source genetic algorithm for determining optimal seed distributions for low-dose-rate prostate brachytherapy.

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    McGeachy, P; Madamesila, J; Beauchamp, A; Khan, R

    2015-01-01

    An open source optimizer that generates seed distributions for low-dose-rate prostate brachytherapy was designed, tested, and validated. The optimizer was a simple genetic algorithm (SGA) that, given a set of prostate and urethra contours, determines the optimal seed distribution in terms of coverage of the prostate with the prescribed dose while avoiding hotspots within the urethra. The algorithm was validated in a retrospective study on 45 previously contoured low-dose-rate prostate brachytherapy patients. Dosimetric indices were evaluated to ensure solutions adhered to clinical standards. The SGA performance was further benchmarked by comparing solutions obtained from a commercial optimizer (inverse planning simulated annealing [IPSA]) with the same cohort of 45 patients. Clinically acceptable target coverage by the prescribed dose (V100) was obtained for both SGA and IPSA, with a mean ± standard deviation of 98 ± 2% and 99.5 ± 0.5%, respectively. For the prostate D90, SGA and IPSA yielded 177 ± 8 Gy and 186 ± 7 Gy, respectively, which were both clinically acceptable. Both algorithms yielded reasonable dose to the rectum, with V100 open source SGA was validated that provides a research tool for the brachytherapy community. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  6. Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer: long-term results

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    Prada, Pedro J.; Anchuelo, Javier; Blanco, Ana Garcia; Paya, Gema; Cardenal, Juan; Acuña, Enrique; Ferri, Maria [Department of Radiation Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria (Spain); Vazquez, Andres; Pacheco, Maite; Sanchez, Jesica [Department of Radiation Physics, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria (Spain)

    2016-01-15

    Objectives: We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. Methods and Materials: From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the 'Phoenix consensus'. Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. Results: The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function. Conclusions: The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer. (author)

  7. SU-E-J-232: Feasibility of MRI-Based Preplan On Low Dose Rate Prostate Brachytherapy

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    Huang, Y; Tward, J; Rassiah-Szegedi, P; Zhao, H; Sarkar, V; Huang, L; Szegedi, M; Kokeny, K; Salter, B [University of Utah Huntsman Cancer Institute, Salt Lake City, UT (United States)

    2015-06-15

    Purpose: To investigate the feasibility of using MRI-based preplan for low dose rate prostate brachytherapy. Methods: 12 patients who received transrectal ultrasound (TRUS) guided prostate brachytherapy with Pd-103 were retrospectively studied. Our care-standard of the TRUS-based preplan served as the control. One or more prostate T2-weighted wide and/or narrow-field of view MRIs obtained within the 3 months prior to the implant were imported into the MIM Symphony software v6.3 (MIM Software Inc., Cleveland, OH) for each patient. In total, 37 MRI preplans (10 different image sequences with average thickness of 4.8mm) were generated. The contoured prostate volume and the seed counts required to achieve adequate dosimetric coverage from TRUS and MRI preplans were compared for each patient. The effects of different MRI sequences and image thicknesses were also investigated statistically using Student’s t-test. Lastly, the nomogram from the MRI preplan and TRUS preplan from our historical treatment data were compared. Results: The average prostate volume contoured on the TRUS and MRI were 26.6cc (range: 12.6∼41.3cc), and 27.4 cc (range: 14.3∼50.0cc), respectively. Axial MRI thicknesses (range: 3.5∼8.1mm) did not significantly affect the contoured volume or the number of seeds required on the preplan (R2 = 0.0002 and 0.0012, respectively). Four of the MRI sequences (AX-T2, AX-T2-Whole-Pelvis, AX-T2-FSE, and AXIALT2- Hi-Res) showed statistically significant better prostate volume agreement with TRUS than the other seven sequences (P <0.01). Nomogram overlay between the MRI and TRUS preplans showed good agreement; indicating volumes contoured on MRI preplan scan reliably predict how many seeds are needed for implant. Conclusion: Although MRI does not allow for determination of the actual implant geometry, it can give reliable volumes for seed ordering purposes. Our future work will investigate if MRI is sufficient to reliably replace TRUS preplanning in patients

  8. SU-E-T-34: An in Vivo Study On Pulsed Low Dose-Rate Radiotherapy for Prostate Cancer

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    Wang, B; Cvetkovic, D; Chen, L; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States); Chen, X [Fox Chase Cancer Center, Philadelphia, PA (United States); Virtua Fox Chase Cancer Center, Voorhees, NJ (United States); Zhang, P [Fox Chase Cancer Center, Philadelphia, PA (United States); Sichuan Cancer Hospital, Chengdu (China); Zhang, C [Fox Chase Cancer Center, Philadelphia, PA (United States); Qiqihar Medical University, Qiqihar (China)

    2014-06-01

    Purpose: Re-irradiation with conventional radiotherapy techniques (CRT) may pose significant risks due to high accumulative radiation doses. Pulsed low dose-rate radiotherapy (PLDR) has been used in clinical trials for recurrent cancer treatment. In our previous studies, PLDR irradiation showed significantly lower toxicity than CRT, resulting in much longer survival of mice after PLDR total body irradiation (TBI) than conventional TBI. The purpose of this study was to investigate tumor control efficacy of PLDR treatment for prostate cancer with an animal model of prostate cancer LNCaP. Methods: We used an orthotopic murine model of LNCaP cell line for this study. LNCaP cells were implanted into immune-suppressed male nude mice via surgery. We monitored the tumor growth with MRI. The tumor-bearing mice were allocated into a PLDR(n=9), CRT(n=7), and control group(n=7) randomly. The mice in the PLDR and CRT groups were irradiated with 2Gy dose for one time. For the CRT treatment, the mice received 2Gy at a dose-rate of 300 MU/minute. For the PLDR treatment, the 2Gy dose was further divided into ten pulses of 0.2Gy at the same dose-rate with an interval of 3 minutes between the pulses. Results: Sizable tumor growth delays were observed for the PLDR and CRT groups through weekly MRI scans. The mean values of the normalized tumor volumes (± standard deviation of the mean) were 1.53±0.07, 1.53±0.14, and 1.81±0.09 at one week after treatment, 2.28±0.13, 2.19±0.16, and 3.04±0.25 at two weeks after treatment, and 3.31±0.23, 3.14±0.24 and 4.62±0.49 at three weeks after treatment, for the PLDR, CRT, and control groups, respectively. Conclusion: The PLDR and CRT treatments showed comparable tumor control rates in this study. Our in vivo results indicate that PLDR may be a viable option for treating recurrent prostate cancer due to its equivalent tumor control but low normal tissue toxocities.

  9. Permanent interstitial low-dose-rate brachytherapy for patients with low risk prostate cancer. An interim analysis of 312 cases

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    Badakhshi, Harun; Graf, Reinhold; Budach, Volker; Wust, Peter [University Hospital Berlin, Department for Radiation Oncology of Charite School of Medicine, Berlin (Germany)

    2015-04-01

    The biochemical relapse-free survival (bRFS) rate after treatment with permanent iodine-125 seed implantation (PSI) or combined seeds and external beam radiotherapy (COMB) for clinical stage T1-T2 localized prostate cancer is a clinically relevant endpoint. The goal of this work was to evaluate the influence of relevant patient- and treatment-related factors. The study population comprised 312 consecutive patients treated with permanent seed implantation. All patients were evaluable for analysis of overall survival (OS) and disease-specific survival (DSS), 230 for bRFS, of which 192 were in the PSI group and 38 in the COMB group. The prescribed minimum peripheral dose was 145 Gy for PSI, for COMB 110 Gy implant and external beam radiotherapy of 45 Gy. The median follow-up time was 33 months (range 8-66 months). bRFS was defined as a serum prostate-specific antigen (PSA) level ≤ 0.2 ng/ml at last follow-up. Overall, the actuarial bRFS at 50 months was 88.4 %. The 50-month bRFS rate for PSI and COMB was 90.9 %, and 77.2 %, respectively. In the univariate analysis, age in the categories ≤ 63 and > 63 years (p < 0.00), PSA nadir (≤ 0.5 ng/ml and > 0.5 ng/ml) and PSA bounce (yes/no) were the significant predicting factors for bRFS. None of the other patient and treatment variables (treatment modality, stage, PSA, Gleason score, risk group, number of risk factors, D90 and various other dose parameters) were found to be a statistically significant predictor of 50-month bRFS. The biochemical failure rates were low in this study. As a proof of principle, our large monocenteric analysis shows that low-dose-rate brachytherapy is an effective and safe procedure for patients with early stage prostate cancer. (orig.) [German] Das biochemisch rezidivfreie Ueberleben (bRFS) nach der Brachytherapie mit permanenter Iod-125-Seed-Implantation (PSI) oder in Kombination mit externer Radiotherapie (COMB) ist beim Patienten mit fruehem Prostatakarzinom (T1/T2) ein relevanter

  10. Long-Term Efficacy and Toxicity of Low-Dose-Rate {sup 125}I Prostate Brachytherapy as Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer

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    Kittel, Jeffrey A.; Reddy, Chandana A.; Smith, Kristin L.; Stephans, Kevin L.; Tendulkar, Rahul D. [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States); Ulchaker, James; Angermeier, Kenneth; Campbell, Steven; Stephenson, Andrew; Klein, Eric A. [Department of Urology, Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, Ohio (United States); Wilkinson, D. Allan [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States); Ciezki, Jay P., E-mail: ciezkij@ccf.org [Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio (United States)

    2015-07-15

    Purpose/Objectives: To report long-term efficacy and toxicity for a single-institution cohort of patients treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy. Methods and Materials: From 1996 to 2007, 1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate-risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and followed up prospectively in a registry. All patients were treated with {sup 125}I monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), overall survival (OS), and prostate cancer–specific mortality (PCSM) were calculated. We identified factors associated with late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence. Results: The median age of the patients was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%, 97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1%, and 2.5%, respectively. The overall rates of late grade ≥3 GU and GI toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and prostate length were significantly associated with increased risk of late grade ≥3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI and post-PI transurethral resection of the prostate. Conclusions: Prostate brachytherapy as monotherapy is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy.

  11. Time-driven activity-based costing of low-dose-rate and high-dose-rate brachytherapy for low-risk prostate cancer.

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    Ilg, Annette M; Laviana, Aaron A; Kamrava, Mitchell; Veruttipong, Darlene; Steinberg, Michael; Park, Sang-June; Burke, Michael A; Niedzwiecki, Douglas; Kupelian, Patrick A; Saigal, Christopher

    Cost estimates through traditional hospital accounting systems are often arbitrary and ambiguous. We used time-driven activity-based costing (TDABC) to determine the true cost of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy for prostate cancer and demonstrate opportunities for cost containment at an academic referral center. We implemented TDABC for patients treated with I-125, preplanned LDR and computed tomography based HDR brachytherapy with two implants from initial consultation through 12-month followup. We constructed detailed process maps for provision of both HDR and LDR. Personnel, space, equipment, and material costs of each step were identified and used to derive capacity cost rates, defined as price per minute. Each capacity cost rate was then multiplied by the relevant process time and products were summed to determine total cost of care. The calculated cost to deliver HDR was greater than LDR by $2,668.86 ($9,538 vs. $6,869). The first and second HDR treatment day cost $3,999.67 and $3,955.67, whereas LDR was delivered on one treatment day and cost $3,887.55. The greatest overall cost driver for both LDR and HDR was personnel at 65.6% ($4,506.82) and 67.0% ($6,387.27) of the total cost. After personnel costs, disposable materials contributed the second most for LDR ($1,920.66, 28.0%) and for HDR ($2,295.94, 24.0%). With TDABC, the true costs to deliver LDR and HDR from the health system perspective were derived. Analysis by physicians and hospital administrators regarding the cost of care afforded redesign opportunities including delivering HDR as one implant. Our work underscores the need to assess clinical outcomes to understand the true difference in value between these modalities. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  12. Low-dose rate prostate brachytherapy is well tolerated in patients with a history of inflammatory bowel disease.

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    Peters, Christopher A; Cesaretti, Jamie A; Stone, Nelson N; Stock, Richard G

    2006-10-01

    We report on the follow-up of 24 patients with a prior history of inflammatory bowel disease (IBD) treated with brachytherapy for early-stage prostate cancer. Twenty-four patients with a history of inflammatory bowel disease (17 with ulcerative colitis (UC), 7 with Crohn's disease [CD]) underwent prostate brachytherapy between 1992 and 2004. Fifteen patients were treated with I-125 implantation and 6 patients were treated with Pd-103 alone or in combination with 45 Gy external beam radiation. Charts were reviewed for all patients, and all living patients were contacted by phone. National Cancer Institute common toxicity scores for proctitis were assigned to all patients. Actuarial risk of late toxicity was calculated by the Kaplan-Meier method. Statistical analysis was performed using SPSS software. Follow-up ranged from 3 to 126 months (median, 48.5 months; mean, 56.8 months). None of the patients experienced Grade 3 or 4 rectal toxicity. Four patients experienced Grade 2 late rectal toxicity. The 5-year actuarial freedom from developing late Grade 2 rectal toxicity was 81%. At a median follow-up of 48.5 months, 23 patients were alive and had no evidence of disease with a median prostate-specific antigen for the sample of 0.1 ng/mL (range, <0.05-0.88 ng/mL). One patient died of other causes unrelated to his prostate cancer. Prostate brachytherapy is well tolerated in patients with a history of controlled IBD. Therefore, brachytherapy should be considered a viable therapeutic option in this patient population.

  13. Radiation Leukemogenesis at Low Dose Rates

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    Weil, Michael; Ullrich, Robert

    2013-09-25

    The major goals of this program were to study the efficacy of low dose rate radiation exposures for the induction of acute myeloid leukemia (AML) and to characterize the leukemias that are caused by radiation exposures at low dose rate. An irradiator facility was designed and constructed that allows large numbers of mice to be irradiated at low dose rates for protracted periods (up to their life span). To the best of our knowledge this facility is unique in the US and it was subsequently used to study radioprotectors being developed for radiological defense (PLoS One. 7(3), e33044, 2012) and is currently being used to study the role of genetic background in susceptibility to radiation-induced lung cancer. One result of the irradiation was expected; low dose rate exposures are ineffective in inducing AML. However, another result was completely unexpected; the irradiated mice had a very high incidence of hepatocellular carcinoma (HCC), approximately 50%. It was unexpected because acute exposures are ineffective in increasing HCC incidence above background. This is a potential important finding for setting exposure limits because it supports the concept of an 'inverse dose rate effect' for some tumor types. That is, for the development of some tumor types low dose rate exposures carry greater risks than acute exposures.

  14. The investigation of prostatic calcifications using μ-PIXE analysis and their dosimetric effect in low dose rate brachytherapy treatments using Geant4

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    Pope, D. J.; Cutajar, D. L.; George, S. P.; Guatelli, S.; Bucci, J. A.; Enari, K. E.; Miller, S.; Siegele, R.; Rosenfeld, A. B.

    2015-06-01

    Low dose rate brachytherapy is a widely used modality for the treatment of prostate cancer. Most clinical treatment planning systems currently in use approximate all tissue to water, neglecting the existence of inhomogeneities, such as calcifications. The presence of prostatic calcifications may perturb the dose due to the higher photoelectric effect cross section in comparison to water. This study quantitatively evaluates the effect of prostatic calcifications on the dosimetric outcome of brachytherapy treatments by means of Monte Carlo simulations and its potential clinical consequences. Four pathological calcification samples were characterised with micro-particle induced x-ray emission (μ-PIXE) to determine their heavy elemental composition. Calcium, phosphorus and zinc were found to be the predominant heavy elements in the calcification composition. Four clinical patient brachytherapy treatments were modelled using Geant4 based Monte Carlo simulations, in terms of the distribution of brachytherapy seeds and calcifications in the prostate. Dose reductions were observed to be up to 30% locally to the calcification boundary, calcification size dependent. Single large calcifications and closely placed calculi caused local dose reductions of between 30-60%. Individual calculi smaller than 0.5 mm in diameter showed minimal dosimetric impact, however, the effects of small or diffuse calcifications within the prostatic tissue could not be determined using the methods employed in the study. The simulation study showed a varying reduction on common dosimetric parameters. D90 showed a reduction of 2-5%, regardless of calcification surface area and volume. The parameters V100, V150 and V200 were also reduced by as much as 3% and on average by 1%. These reductions were also found to relate to the surface area and volume of calcifications, which may have a significant dosimetric impact on brachytherapy treatment, however, such impacts depend strongly on specific factors

  15. External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer

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    Strom, Tobin J.; Hutchinson, Sean Z.; Shrinath, Kushagra; Cruz, Alex A.; Figura, Nicholas B.; Nethers, Kevin; Biagioli, Matthew C.; Fernandez, Daniel C.; Heysek, Randy V.; Wilder, Richard B., E-mail: richard.wilder@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States)

    2014-07-15

    Purpose: To assess outcomes with external beam radiation therapy (EBRT) and a low-dose-rate (LDR) brachytherapy boost without or with androgen deprivation therapy (ADT) for prostate cancer. Materials and Methods: From January 2001 through August 2011, 120 intermediate-risk or high-risk prostate cancer patients were treated with EBRT to a total dose of 4,500 cGy in 25 daily fractions and a palladium-103 LDR brachytherapy boost of 10,000 cGy (n = 90) or an iodine-125 LDR brachytherapy boost of 11,000 cGy (n = 30). ADT, consisting of a gonadotropin-releasing hormone agonist ± an anti-androgen, was administered to 29/92 (32%) intermediate-risk patients for a median duration of 4 months and 26/28 (93%) high-risk patients for a median duration of 28 months. Results: Median follow-up was 5.2 years (range, 1.1-12.8 years). There was no statistically-significant difference in biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), or overall survival (OS) without or with ADT. Also, there was no statistically-significant difference in bDFS, DMFS, or OS with a palladium-103 vs. an iodine-125 LDR brachytherapy boost. Conclusions: There was no statistically-significant difference in outcomes with the addition of ADT, though the power of the current study was limited. The Radiation Therapy Oncology Group 0815 and 0924 phase III trials, which have accrual targets of more than 1,500 men, will help to clarify the role ADT in locally-advanced prostate cancer patients treated with EBRT and a brachytherapy boost. Palladium-103 and iodine-125 provide similar bDFS, DMFS, and OS. (author)

  16. Incidence of Second Malignancies in Prostate Cancer Patients Treated With Low-Dose-Rate Brachytherapy and Radical Prostatectomy

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    Hamilton, Sarah Nicole; Tyldesley, Scott [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Hamm, Jeremy [Department of Population Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Jiang, Wei Ning [Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Keyes, Mira; Pickles, Tom [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Lapointe, Vince [Department of Medical Physics, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Kahnamelli, Adam [Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); McKenzie, Michael [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Miller, Stacy [Department of Radiation Oncology, British Columbia Cancer Agency–Centre for the North, Prince George, British Columbia (Canada); Morris, W. James, E-mail: jmorris@bccancer.bc.ca [Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia (Canada); Department of Radiation Oncology, British Columbia Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada)

    2014-11-15

    Purpose: To compare the second malignancy incidence in prostate cancer patients treated with brachytherapy (BT) relative to radical prostatectomy (RP) and to compare both groups with the cancer incidence in the general population. Methods and Materials: From 1998 to 2010, 2418 patients were treated with Iodine 125 prostate BT monotherapy at the British Columbia Cancer Agency, and 4015 referred patients were treated with RP. Cancer incidence was compared with the age-matched general population using standardized incidence ratios (SIRs). Pelvic malignancies included invasive and noninvasive bladder cancer and rectal cancer. Cox multivariable analysis was performed with adjustment for covariates to determine whether treatment (RP vs BT) was associated with second malignancy risk. Results: The median age at BT was 66 years and at RP 62 years. The SIR comparing BT patients with the general population was 1.06 (95% confidence interval [CI] 0.91-1.22) for second malignancy and was 1.53 (95% CI 1.12-2.04) for pelvic malignancy. The SIR comparing RP patients with the general population was 1.11 (95% CI 0.98-1.25) for second malignancy and was 1.11 (95% CI 0.82-1.48) for pelvic malignancy. On multivariable analysis, older age (hazard ratio [HR] 1.05) and smoking (HR 1.65) were associated with increased second malignancy risk (P<.0001). Radical prostatectomy was not associated with a decreased second malignancy risk relative to BT (HR 0.90, P=.43), even when excluding patients who received postprostatectomy external beam radiation therapy (HR 1.13, P=.25). Older age (HR 1.09, P<.0001) and smoking (HR 2.17, P=.0009) were associated with increased pelvic malignancy risk. Radical prostatectomy was not associated with a decreased pelvic malignancy risk compared with BT (HR 0.57, P=.082), even when excluding postprostatectomy external beam radiation therapy patients (HR 0.87, P=.56). Conclusions: After adjustment for covariates, BT patients did not have an increased second

  17. PARP inhibition sensitizes to low dose-rate radiation TMPRSS2-ERG fusion gene-expressing and PTEN-deficient prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Payel Chatterjee

    Full Text Available Exposure to genotoxic agents, such as irradiation produces DNA damage, the toxicity of which is augmented when the DNA repair is impaired. Poly (ADP-ribose polymerase (PARP inhibitors were found to be "synthetic lethal" in cells deficient in BRCA1 and BRCA2 that impair homologous recombination. However, since many tumors, including prostate cancer (PCa rarely have on such mutations, there is considerable interest in finding alternative determinants of PARP inhibitor sensitivity. We evaluated the effectiveness of radiation in combination with the PARP inhibitor, rucaparib in PCa cells. The combination index for clonogenic survival following radiation and rucaparib treatments revealed synergistic interactions in a panel of PCa cell lines, being strongest for LNCaP and VCaP cells that express ETS gene fusion proteins. These findings correlated with synergistic interactions for senescence activation, as indicated by β--galactosidase staining. Absence of PTEN and presence of ETS gene fusion thus facilitated activation of senescence, which contributed to decreased clonogenic survival. Increased radiosensitivity in the presence of rucaparib was associated with persistent DNA breaks, as determined by χ-H2AX, p53BP1, and Rad51 foci. VCaP cells, which harbor the TMPRSS2-ERG gene fusion and PC3 cells that stably express a similar construct (fusion III showed enhanced sensitivity towards rucaparib, which, in turn, increased the radiation response to a similar extent as the DNA-PKcs inhibitor NU7441. Rucaparib radiosensitized PCa cells, with a clear benefit of low dose-rate radiation (LDR administered over a longer period of time that caused enhanced DNA damage. LDR mimicking brachytherapy, which is used successfully in the clinic, was most effective when combined with rucaparib by inducing persistent DNA damage and senescence, leading to decreased clonogenic survival. This combination was most effective in the presence of the TMPRSS2-ERG and in the

  18. PARP inhibition sensitizes to low dose-rate radiation TMPRSS2-ERG fusion gene-expressing and PTEN-deficient prostate cancer cells.

    Science.gov (United States)

    Chatterjee, Payel; Choudhary, Gaurav S; Sharma, Arishya; Singh, Kamini; Heston, Warren D; Ciezki, Jay; Klein, Eric A; Almasan, Alexandru

    2013-01-01

    Exposure to genotoxic agents, such as irradiation produces DNA damage, the toxicity of which is augmented when the DNA repair is impaired. Poly (ADP-ribose) polymerase (PARP) inhibitors were found to be "synthetic lethal" in cells deficient in BRCA1 and BRCA2 that impair homologous recombination. However, since many tumors, including prostate cancer (PCa) rarely have on such mutations, there is considerable interest in finding alternative determinants of PARP inhibitor sensitivity. We evaluated the effectiveness of radiation in combination with the PARP inhibitor, rucaparib in PCa cells. The combination index for clonogenic survival following radiation and rucaparib treatments revealed synergistic interactions in a panel of PCa cell lines, being strongest for LNCaP and VCaP cells that express ETS gene fusion proteins. These findings correlated with synergistic interactions for senescence activation, as indicated by β--galactosidase staining. Absence of PTEN and presence of ETS gene fusion thus facilitated activation of senescence, which contributed to decreased clonogenic survival. Increased radiosensitivity in the presence of rucaparib was associated with persistent DNA breaks, as determined by χ-H2AX, p53BP1, and Rad51 foci. VCaP cells, which harbor the TMPRSS2-ERG gene fusion and PC3 cells that stably express a similar construct (fusion III) showed enhanced sensitivity towards rucaparib, which, in turn, increased the radiation response to a similar extent as the DNA-PKcs inhibitor NU7441. Rucaparib radiosensitized PCa cells, with a clear benefit of low dose-rate radiation (LDR) administered over a longer period of time that caused enhanced DNA damage. LDR mimicking brachytherapy, which is used successfully in the clinic, was most effective when combined with rucaparib by inducing persistent DNA damage and senescence, leading to decreased clonogenic survival. This combination was most effective in the presence of the TMPRSS2-ERG and in the absence of PTEN

  19. Patterns of Recurrence After Low-Dose-Rate Prostate Brachytherapy: A Population-Based Study of 2223 Consecutive Low- and Intermediate-Risk Patients

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Andrea C.; Morris, W. James, E-mail: JMorris@bccancer.bc.ca; Pickles, Tom; Keyes, Mira; McKenzie, Michael; Tyldesley, Scott

    2015-03-15

    Objectives: This study examined patterns of recurrence after low–dose-rate prostate brachytherapy (LDR-PB), estimated local recurrence rate and compared that rate to the estimated local recurrence rate after radical prostatectomy (RP). Methods and Materials: A prospective database was maintained with clinical, dosimetric, and outcome data for all LDR-PB implantation procedures performed at our institution. From 1998 to 2008, 2223 patients with prostate cancer received LDR-PB without supplemental external beam radiation therapy. Patients who developed Phoenix-defined biochemical failure were reviewed for sites of relapse and investigations completed. Results: At a median follow-up of 5 years, 108 of 2223 patients (4.8%) developed biochemical relapse. In 1 additional patient, local relapse was found on transurethral prostate resection, but his prostate-specific antigen concentration was well short of triggering Phoenix-defined failure. Of the 109 patients with disease relapse, 18 of 2223 (0.8%) had a proven local recurrence, and 30 of 2223 (1.3%) had a proven distant recurrence. The remaining 61 of 2223 patients (2.7%) had unidentified sites of recurrence; of these, 57 patients (93%) had digital rectal examinations (DREs), 18 (30%) had post-treatment biopsies, 45 (74%) had bone scans, and 34 (56%) had computed tomography imaging of the abdomen and pelvis. If every biochemical failure were local, the local recurrence rate would be as high as 4.9%; however, by excluding those with proven distant failure and those with both a negative DRE and biopsy, we estimate that the local recurrence rate is 2.7% or less. Conclusions: In the context of limitations of the study design, our population-based analysis indicates that the local recurrence rate after LDR-PB is as low or lower than that after RP in our jurisdiction.

  20. Late Urinary Side Effects 10 Years After Low-Dose-Rate Prostate Brachytherapy: Population-Based Results From a Multiphysician Practice Treating With a Standardized Protocol and Uniform Dosimetric Goals

    Energy Technology Data Exchange (ETDEWEB)

    Keyes, Mira, E-mail: mkeyes@bccancer.bc.ca; Miller, Stacy; Pickles, Tom; Halperin, Ross; Kwan, Winkle; Lapointe, Vincent; McKenzie, Michael; Spadinger, Ingrid; Pai, Howard; Chan, Elisa K.; Morris, W. James

    2014-11-01

    Purpose: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. Methods and Materials: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network–defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 ({sup 125}I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier and log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. Results: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower in patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. Conclusion: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer

  1. A comparative study of seed localization and dose calculation on pre- and post-implantation ultrasound and CT images for low-dose-rate prostate brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Imad; Algan, Ozer; Thompson, Spencer; Sindhwani, Puneet; Herman, Terence; Cheng, C.-Y.; Ahmad, Salahuddin [Department of Radiation Oncology, University of Oklahoma Health Sciences Center, 825 NE 10th Street, OUPB 1430, Oklahoma City, OK 73104 (United States)], E-mail: iali@ouhsc.edu

    2009-09-21

    This work investigates variation in the volume of the prostate measured at different stages through the prostate brachytherapy procedure for 30 patients treated with I-125 radioactive seeds. The implanted seeds were localized on post-implantation ultrasound (US) images and the effect of prostate enlargement due to edema on dose coverage for 15 patients was studied. The volume of the prostate was measured at four stages as follows: (a) 2-3 weeks prior to implantation using US imaging, (b) then at the start of the intra-operative prostate brachytherapy procedure on the day of the implant, (c) immediately post-implantation using US imaging in the operating room and (d) finally by CT imaging at nearly 4 weeks post-implantation. Comparative prostate volume studies were performed using US imaging stepper and twister modes. For the purpose of this study, the implanted seeds were localized successfully on post-implant ultrasound twister images, retrospectively. The plans using post-implant US imaging were compared with intra-operative plans on US and plans created on CT images. The prostate volume increases about 10 cm{sup 3} on average due to edema induced by needle insertion and seed loading during implantation. The visibility of the implanted seeds on US twister images acquired post-implantation is as good as those on CT images and can be localized and used for dose calculation. The dose coverage represented by parameters such as D90 (dose covering 90% of the volume) and V100 (volume covered by 100% dose) is poorer on plans performed on post-implantation twister US studies than on the intra-operative live plan or the CT scan performed 4 weeks post-operatively. For example, the mean D90 difference on post-implantation US is lower by more than 15% than that on pre-implantation US. The volume enlargement of the prostate due to edema induced by needle insertion and seed placement has a significant effect on the quality of dosimetric coverage in brachytherapy prostate seed

  2. A comparative study of seed localization and dose calculation on pre- and post-implantation ultrasound and CT images for low-dose-rate prostate brachytherapy

    Science.gov (United States)

    Ali, Imad; Algan, Ozer; Thompson, Spencer; Sindhwani, Puneet; Herman, Terence; Cheng, Chih-Yao; Ahmad, Salahuddin

    2009-09-01

    This work investigates variation in the volume of the prostate measured at different stages through the prostate brachytherapy procedure for 30 patients treated with I-125 radioactive seeds. The implanted seeds were localized on post-implantation ultrasound (US) images and the effect of prostate enlargement due to edema on dose coverage for 15 patients was studied. The volume of the prostate was measured at four stages as follows: (a) 2-3 weeks prior to implantation using US imaging, (b) then at the start of the intra-operative prostate brachytherapy procedure on the day of the implant, (c) immediately post-implantation using US imaging in the operating room and (d) finally by CT imaging at nearly 4 weeks post-implantation. Comparative prostate volume studies were performed using US imaging stepper and twister modes. For the purpose of this study, the implanted seeds were localized successfully on post-implant ultrasound twister images, retrospectively. The plans using post-implant US imaging were compared with intra-operative plans on US and plans created on CT images. The prostate volume increases about 10 cm3 on average due to edema induced by needle insertion and seed loading during implantation. The visibility of the implanted seeds on US twister images acquired post-implantation is as good as those on CT images and can be localized and used for dose calculation. The dose coverage represented by parameters such as D90 (dose covering 90% of the volume) and V100 (volume covered by 100% dose) is poorer on plans performed on post-implantation twister US studies than on the intra-operative live plan or the CT scan performed 4 weeks post-operatively. For example, the mean D90 difference on post-implantation US is lower by more than 15% than that on pre-implantation US. The volume enlargement of the prostate due to edema induced by needle insertion and seed placement has a significant effect on the quality of dosimetric coverage in brachytherapy prostate seed

  3. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    applications of NEOTRANS2, indicate that nonlinear threshold-type, dose-response relationships for excess stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected after exposure to low linear energy transfer (LET) gamma rays or gamma rays in combination with high-LET alpha radiation. Similar thresholds are expected for low-dose-rate low-LET beta irradiation. We attribute the thresholds to low-dose, low-LET radiation induced protection against spontaneous mutations and neoplastic transformations. The protection is presumed mainly to involve selective elimination of problematic cells via apoptosis. Low-dose, low-LET radiation is presumed to trigger wide-area cell signaling, which in turn leads to problematic bystander cells (e.g., mutants, neoplastically transformed cells) selectively undergoing apoptosis. Thus, this protective bystander effect leads to selective elimination of problematic cells (a tissue cleansing process in vivo). However, this protective bystander effects is a different process from low-dose stimulation of the immune system. Low-dose, low-LET radiation stimulation of the immune system may explain why thresholds for inducing excess cancer appear much larger (possibly more than 100-fold larger) than thresholds for inducing excess mutations and neoplastic transformations, when the dose rate is low. For ionizing radiation, the current risk assessment paradigm is such that the relative risk (RR) is always ¡Ý 1, no matter how small the dose. Our research results indicate that for low-dose or low-dose-rate, low-LET irradiation, RR < 1 may be more the rule than the exception. Directly tied to the current RR paradigm are the billion-dollar cleanup costs for radionuclide-contaminated DOE sites. Our research results suggest that continued use of the current RR paradigm for which RR ¡Ý 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low

  4. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    applications of NEOTRANS2, indicate that nonlinear threshold-type, dose-response relationships for excess stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected after exposure to low linear energy transfer (LET) gamma rays or gamma rays in combination with high-LET alpha radiation. Similar thresholds are expected for low-dose-rate low-LET beta irradiation. We attribute the thresholds to low-dose, low-LET radiation induced protection against spontaneous mutations and neoplastic transformations. The protection is presumed mainly to involve selective elimination of problematic cells via apoptosis. Low-dose, low-LET radiation is presumed to trigger wide-area cell signaling, which in turn leads to problematic bystander cells (e.g., mutants, neoplastically transformed cells) selectively undergoing apoptosis. Thus, this protective bystander effect leads to selective elimination of problematic cells (a tissue cleansing process in vivo). However, this protective bystander effects is a different process from low-dose stimulation of the immune system. Low-dose, low-LET radiation stimulation of the immune system may explain why thresholds for inducing excess cancer appear much larger (possibly more than 100-fold larger) than thresholds for inducing excess mutations and neoplastic transformations, when the dose rate is low. For ionizing radiation, the current risk assessment paradigm is such that the relative risk (RR) is always ¡Ý 1, no matter how small the dose. Our research results indicate that for low-dose or low-dose-rate, low-LET irradiation, RR < 1 may be more the rule than the exception. Directly tied to the current RR paradigm are the billion-dollar cleanup costs for radionuclide-contaminated DOE sites. Our research results suggest that continued use of the current RR paradigm for which RR ¡Ý 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low

  5. Low-dose or low-dose-rate ionizing radiation-induced bioeffects in animal models.

    Science.gov (United States)

    Tang, Feng Ru; Loke, Weng Keong; Khoo, Boo Cheong

    2017-03-01

    Animal experimental studies indicate that acute or chronic low-dose ionizing radiation (LDIR) (≤100 mSv) or low-dose-rate ionizing radiation (LDRIR) (radiation exposure (i.e. acute, fractionated or chronic radiation exposure), type of radiation, combination of radiation with other toxic agents (such as smoking, pesticides or other chemical toxins) or animal experimental designs. In this review paper, we aimed to update radiation researchers and radiologists on the current progress achieved in understanding the LDIR/LDRIR-induced bionegative and biopositive effects reported in the various animal models. The roles played by a variety of molecules that are implicated in LDIR/LDRIR-induced health effects will be elaborated. The review will help in future investigations of LDIR/LDRIR-induced health effects by providing clues for designing improved animal research models in order to clarify the current controversial/contradictory findings from existing studies. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  6. Dose to the Bladder Neck Is the Most Important Predictor for Acute and Late Toxicity After Low-Dose-Rate Prostate Brachytherapy: Implications for Establishing New Dose Constraints for Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Hathout, Lara; Folkert, Michael R.; Kollmeier, Marisa A.; Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Cohen, Gil' ad N. [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

    2014-10-01

    Purpose: To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT). Methods and Materials: From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area under the receiver operator curve (ROC) (AUC). Results: Grade ≥2 AUT and grade ≥2 LUT occurred in 520 patients (56%) and 154 patients (20%), respectively. No grade 4 toxicities were observed. Bladder neck D2cc retained a significant association with AUT (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.03-1.04; P<.0001) and LUT (HR, 1.01; 95% CI, 1.00-1.03; P=.014) on multivariable analysis. In a comparison of bladder neck with the standard dosimetric variables by use of ROC analysis (prostate V100 >90%, D90 >100%, V150 >60%, urethra D20 >130%), bladder neck D2cc >50% was shown to have the strongest prognostic power for AUT (AUC, 0.697; P<.0001) and LUT (AUC, 0.620; P<.001). Conclusions: Bladder neck D2cc >50% was the strongest predictor for grade ≥2 AUT and LUT in patients treated with LDR brachytherapy. These data support inclusion of bladder neck constraints into brachytherapy planning to decrease urinary toxicity.

  7. Dosimetric Considerations to Determine the Optimal Technique for Localized Prostate Cancer Among External Photon, Proton, or Carbon-Ion Therapy and High-Dose-Rate or Low-Dose-Rate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Georg, Dietmar, E-mail: Dietmar.Georg@akhwien.at [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Hopfgartner, Johannes [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Gòra, Joanna [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Kuess, Peter [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Kragl, Gabriele [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Berger, Daniel [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Hegazy, Neamat [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Goldner, Gregor; Georg, Petra [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria)

    2014-03-01

    Purpose: To assess the dosimetric differences among volumetric modulated arc therapy (VMAT), scanned proton therapy (intensity-modulated proton therapy, IMPT), scanned carbon-ion therapy (intensity-modulated carbon-ion therapy, IMIT), and low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy (BT) treatment of localized prostate cancer. Methods and Materials: Ten patients were considered for this planning study. For external beam radiation therapy (EBRT), planning target volume was created by adding a margin of 5 mm (lateral/anterior–posterior) and 8 mm (superior–inferior) to the clinical target volume. Bladder wall (BW), rectal wall (RW), femoral heads, urethra, and pelvic tissue were considered as organs at risk. For VMAT and IMPT, 78 Gy(relative biological effectiveness, RBE)/2 Gy were prescribed. The IMIT was based on 66 Gy(RBE)/20 fractions. The clinical target volume planning aims for HDR-BT ({sup 192}Ir) and LDR-BT ({sup 125}I) were D{sub 90%} ≥34 Gy in 8.5 Gy per fraction and D{sub 90%} ≥145 Gy. Both physical and RBE-weighted dose distributions for protons and carbon-ions were converted to dose distributions based on 2-Gy(IsoE) fractions. From these dose distributions various dose and dose–volume parameters were extracted. Results: Rectal wall exposure 30-70 Gy(IsoE) was reduced for IMIT, LDR-BT, and HDR-BT when compared with VMAT and IMPT. The high-dose region of the BW dose–volume histogram above 50 Gy(IsoE) of IMPT resembled the VMAT shape, whereas all other techniques showed a significantly lower high-dose region. For all 3 EBRT techniques similar urethra D{sub mean} around 74 Gy(IsoE) were obtained. The LDR-BT results were approximately 30 Gy(IsoE) higher, HDR-BT 10 Gy(IsoE) lower. Normal tissue and femoral head sparing was best with BT. Conclusion: Despite the different EBRT prescription and fractionation schemes, the high-dose regions of BW and RW expressed in Gy(IsoE) were on the same order of magnitude. Brachytherapy techniques

  8. Patient release criteria for low dose rate brachytherapy implants.

    Science.gov (United States)

    Boyce, Dale E; Sheetz, Michael A

    2013-04-01

    A lack of consensus regarding a model governing the release of patients following sealed source brachytherapy has led to a set of patient release policies that vary from institution to institution. The U.S. Nuclear Regulatory Commission has issued regulatory guidance on patient release in NUREG 1556, Volume 9, Rev. 2, Appendix U, which allows calculation of release limits following implant brachytherapy. While the formalism presented in NUREG is meaningful for the calculation of release limits in the context of relatively high energy gamma emitters, it does not estimate accurately the effective dose equivalent for the common low dose rate brachytherapy sources Cs, I, and Pd. NUREG 1556 states that patient release may be based on patient-specific calculations as long as the calculation is documented. This work is intended to provide a format for patient-specific calculations to be used for the consideration of patients' release following the implantation of certain low dose rate brachytherapy isotopes.

  9. Low-dose aspirin or other nonsteroidal anti-inflammatory drug use and prostate cancer risk

    DEFF Research Database (Denmark)

    Skriver, Charlotte; Dehlendorff, Christian; Borre, Michael

    2016-01-01

    Purpose Increasing evidence suggests that aspirin use may protect against prostate cancer. In a nationwide case–control study, using Danish high-quality registry data, we evaluated the association between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs......) and the risk of prostate cancer. Methods We identified 35,600 patients (cases) with histologically verified prostate cancer during 2000–2012. Cases were matched to 177,992 population controls on age and residence by risk-set sampling. Aspirin and nonaspirin NSAID exposure was defined by type, estimated dose......, duration, and consistency of use. We used conditional logistic regression to estimate odds ratios (ORs), with 95 % confidence intervals (CIs), for prostate cancer associated with low-dose aspirin (75–150 mg) or nonaspirin NSAID use, adjusted for potential confounders. Results Use of low-dose aspirin...

  10. Minimal percentage of dose received by 90% of the urethra (%UD90 is the most significant predictor of PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    Tanaka Nobumichi

    2012-09-01

    Full Text Available Abstract Background To clarify the significant clinicopathological and postdosimetric parameters to predict PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy for prostate cancer. Methods We studied 200 consecutive patients who received LDR-brachytherapy between July 2004 and November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant androgen deprivation therapy. One hundred and forty-two patients were treated with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in combination with external beam radiation therapy. The cut-off value of PSA bounce was 0.1 ng/mL. The incidence, time, height, and duration of PSA bounce were investigated. Clinicopathological and postdosimetric parameters were evaluated to elucidate independent factors to predict PSA bounce in hormone-naïve patients who underwent LDR-brachytherapy alone. Results Fifty patients (25% showed PSA bounce and 10 patients (5% showed PSA failure. The median time, height, and duration of PSA bounce were 17 months, 0.29 ng/mL, and 7.0 months, respectively. In 103 hormone-naïve patients treated with LDR-brachytherapy alone, and univariate Cox proportional regression hazard model indicated that age and minimal percentage of the dose received by 30% and 90% of the urethra were independent predictors of PSA bounce. With a multivariate Cox proportional regression hazard model, minimal percentage of the dose received by 90% of the urethra was the most significant parameter of PSA bounce. Conclusions Minimal percentage of the dose received by 90% of the urethra was the most significant predictor of PSA bounce in hormone-naïve patients treated with LDR-brachytherapy alone.

  11. Safety of ultrasound-guided transrectal extended prostate biopsy in patients receiving low-dose aspirin

    Directory of Open Access Journals (Sweden)

    Ioannis Kariotis

    2010-06-01

    Full Text Available PURPOSE: To determine whether the peri-procedural administration of low-dose aspirin increases the risk of bleeding complications for patients undergoing extended prostate biopsies. MATERIALS AND METHODS: From February 2007 to September 2008, 530 men undergoing extended needle biopsies were divided in two groups; those receiving aspirin and those not receiving aspirin. The morbidity of the procedure, with emphasis on hemorrhagic complications, was assessed prospectively using two standardized questionnaires. RESULTS: There were no significant differences between the two groups regarding the mean number of biopsy cores (12.9 ± 1.6 vs. 13.1 ± 1.2 cores, p = 0.09. No major biopsy-related complications were noted. Statistical analysis did not demonstrate significant differences in the rate of hematuria (64.5% vs. 60.6%, p = 0.46, rectal bleeding (33.6% vs. 25.9%, p = 0.09 or hemospermia (90.1% vs. 86.9%, p = 0.45. The mean duration of hematuria and rectal bleeding was significantly greater in the aspirin group compared to the control group (4.45 ± 2.7 vs. 2.4 ± 2.6, p = < 0.001 and 3.3 ± 1.3 vs. 1.9 ± 0.7, p < 0.001. Multivariate logistic regression analysis revealed that only younger patients (mean age 60.1 ± 5.8 years with a lower body mass index (< 25 kg/m2 receiving aspirin were at a higher risk (odds ratio = 3.46, p = 0.047 for developing hematuria and rectal bleeding after the procedure. CONCLUSIONS: The continuing use of low-dose aspirin in patients undergoing extended prostatic biopsy is a relatively safe option since it does not increase the morbidity of the procedure.

  12. EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.

    Science.gov (United States)

    Kitamura, Tadaichi; Nishimatsu, Hiroaki; Hamamoto, Toshiaki; Tomita, Kyoichi; Takeuchi, Takumi; Ohta, Nobutaka

    2002-02-01

    Many chemotherapeutic regimens combined with estramustine phosphate (EMP) have been elaborated for the treatment of hormone-refractory prostate cancer over 30 years. However, older EMP-based combination chemotherapies with vinblastine, vinorelbine, doxorubicin or cyclophosphamide showed relatively low PSA response rate (25-58%) accompanied with high toxicities. On the other hand, newly developed EMP-based combination regimens with etoposide, pacitaxel, carboplatin or docetaxel demonstrated promising PSA response rate (43-77%) with moderate to severe toxicity in the rate of thromboembolic event (5-18%) and of neutropenia (9-41%). Treatment-related death was less in the latter combination group (5/615, 0.8%) than that in the former group (3/234, 1.3%). Of note, in the docetaxel combination with EMP, PSA response rate is as high as 77% with high rate (41%) of neutropenia but no treatment-related death was observed. Docetaxel combination with EMP seems to be the best regimen, though not completely justified by randomized trials, to be selected in the modern era, which will be followed by paclitaxel, carboplatin and EMP combination with PSA response rate of 71%. In addition, an interim report in 83 patients was presented. They were not consecutively enrolled but were treated on low-dose EMP monotherapy for previously untreated advanced prostate cancer in Department of Urology of Tokyo University and our 21 affiliated hospitals. Overall PSA response rate was as high as 93.4% out of 76 assessable patients. However, overall toxicity rate was abnormally high (39.5%) with drug discontinuation rate of 32.1%. The reason of low drug compliance may be attributed to gastrointestinal symptoms. To overcome the low drug compliance, appropriate patients for EMP administration should be selected by using gene analysis on the basis of sophisticated tailor-made medicine.

  13. Genetic Factors Affecting Susceptibility to Low Dose & Low Dose-Rate Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bedford, Joel

    2014-04-18

    Our laboratory has, among other things, developed and used the gamma H2AX focus assay and other chromosomal and cell killing assays to show that differences in this DNA double strand break (dsb) related response can be clearly and distinctly demonstrated for cells which are mildly hyper-radiosensitive such as those associated with A-T heterozygosity. We have found this level of mild hypersensitivity for cells from some 20 to 30 % of apparently normal individuals and from apparently normal parents of Retinoblastoma patients. We found significant differences in gene expression in somatic cells from unaffected parents of Rb patients as compared with normal controls, suggesting that these parents may harbor some as yet unidentified genetic abnormality. In other experiments we sought to determine the extent of differences in normal human cellular reaponses to radiation depending on their irradiation in 2D monolayer vs 3D organized acinar growth conditions. We exmined cell reproductive death, chromosomal aberration induction, and the levels of γ-H2AX foci in cells after single acute gamma-ray doses and immediately after 20 hours of irradiation at a dose rate of 0.0017 Gy/min. We found no significant differences in the dose-responses of these cells under the 2D or 3D growth conditions. While this does not mean such differences cannot occur in other situations, it does mean that they do not generally or necessarily occur. In another series of studies in collaboration with Dr Chuan Li, with supprt from this current grant. We reported a role for apoptotic cell death in promoting wound healing and tissue regeneration in mice. Apoptotic cells released growth signals that stimulated the proliferation of progenitor or stem cells. In yet another collaboration with Dr, B. Chen with funds from this grant, the relative radiosensitivity to cell killing as well as chromosomal instability of 13 DNA-PKcs site-directed mutant cell lines (defective at phosphorylation sites or kinase

  14. Oral exposure to low-dose bisphenol A aggravates testosterone-induced benign hyperplasia prostate in rats.

    Science.gov (United States)

    Wu, Jian-Hui; Jiang, Xiu-Rong; Liu, Gui-Ming; Liu, Xiang-Yun; He, Gui-Lin; Sun, Zu-Yue

    2011-10-01

    The declining level of androgen during aging, associated with an inclining level of estrogen, has been hypothesized to be important in the development of benign prostatic hyperplasia (BPH). Within physiologic range, increasing estrogen levels can stimulate prostate to develop and permanently increase prostate size. As an estrogenic endocrine disruptor, bisphenol A (BPA) might be stimulatory to prostate development. We further hypothesized that low dose BPA could induce hyperplasia prostate to proliferate and aggravate the symptom of BPH in male SD rats. BPH was induced by testosterone and then treated with BPA (10, 30, or 90 μg/kg, i.g., daily), 17β-estradiol (E(2); 50.0 μg/kg, s.c., daily), or vehicle for 4 weeks. We found that weight and volume in rats treated with low dose BPA (10 μg/kg) was higher than that of model control, and BPA significantly increased the relative weight of prostate (p prostate lobes, BPA 10 μg/kg/day significantly increased relative weight of ventral prostate (VP), weight and relative weight of dorsolateral prostate (DLP) (p prostate-specific antigen level. E(2) treatment also showed an obvious effect on relative weight of VP and DLP, HEC, and hormone levels. We concluded that environment exposure to low dose of BPA may induce prostate to proliferate and aggravate testosterone-induced benign hyperplasia prostate in rats.

  15. Injury of the blood-testies barrier after low-dose-rate chronic radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Young Hoon; Bae Min Ji; Lee, Chang Geun; Yang, Kwang Mo; Jur, Kyu; Kim, Jong Sun [Dongnam Institute of Radiological and Medical Science, Busan (Korea, Republic of)

    2014-04-15

    The systemic effect of radiation increases in proportionally with the dose and dose rate. Little is known concerning the relationships between harmful effects and accumulated dose, which is derived from continuous low-dose rate radiation exposure. Recent our studies show that low-dose-rate chronic radiation exposure (3.49 mGy/h) causes adverse effects in the testis at a dose of 2 Gy (6 mGy/h). However, the mechanism of the low-dose-rate 2 Gy irradiation induced testicular injury remains unclear. The present results indicate that low-dose rate chronic radiation might affect the BTB permeability, possibly by decreasing levels of ZO-1, Occludin-1, and NPC-2. Furthermore, our results suggest that there is a risk of male infertility through BTB impairment even with low-dose-rate radiation if exposure is continuous.

  16. Modeling low-dose-rate effects in irradiated bipolar-base oxides

    Energy Technology Data Exchange (ETDEWEB)

    Graves, R.J.; Cirba, C.R.; Schrimpf, R.D.; Milanowski, R.J.; Saigne, F. [Vanderbilt Univ., Nashville, TN (United States); Michez, A. [Univ. Montpellier 2 (France); Fleetwood, D.M. [Sandia National Labs., Albuquerque, NM (United States); Witczak, S.C. [Aerospace Corp., Los Angeles, CA (United States)

    1997-02-01

    A physical model is developed to quantify the contribution of oxide-trapped charge to enhanced low-dose-rate gain degradation in BJTs. Simulations show that space charge limited transport is partially responsible for the low-dose-rate enhancement.

  17. Low doses effects and gamma radiations low dose rates; Les effets des faibles doses et des faibles debits de doses de rayons gamma

    Energy Technology Data Exchange (ETDEWEB)

    Averbeck, D. [Institut Curie, CNRS UMR 2027, 75 - Paris (France)

    1999-07-01

    This expose wishes for bringing some definitions and base facts relative to the problematics of low doses effects and low dose rates effects. It shows some already used methods and some actual experimental approaches by focusing on the effects of ionizing radiations with a low linear energy transfer. (N.C.)

  18. Modeling Low-Dose-Rate Effects in Irradiated Bipolar-Base Oxides

    Energy Technology Data Exchange (ETDEWEB)

    Cirba, C.R.; Fleetwood, D.M.; Graves, R.J.; Michez, A.; Milanowski, R.J.; Saigne, F.; Schrimpf, R.D.; Witczak, S.C.

    1998-10-26

    A physical model is developed to quantify the contribution of oxide-trapped charge to enhanced low-dose-rate gain degradation in bipolar junction transistors. Multiple-trapping simulations show that space charge limited transport is partially responsible for low-dose-rate enhancement. At low dose rates, more holes are trapped near the silicon-oxide interface than at high dose rates, resulting in larger midgap voltage shifts at lower dose rates. The additional trapped charge near the interface may cause an exponential increase in excess base current, and a resultant decrease in current gain for some NPN bipolar technologies.

  19. Enhanced charge trapping in bipolar spacer oxides during low-dose-rate irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Fleetwood, D.M.; Reber, R.A. Jr.; Winokur, P.S. [Sandia National Labs., Albuquerque, NM (United States); Kosier, S.L.; Schrimpf, R.D. [Arizona Univ., Tucson, AZ (United States). Dept. of Electrical and Computer Engineering; Nowlin, R.N. [Air Force Phillips Laboratory, Albuquerque, NM (United States); Pease, R.L. [RLP Research, Inc., Albuquerque, NM (United States); DeLaus, M. [Analog Devices, Wilmington, MA (United States)

    1994-03-01

    Thermally-stimulated-current and capacitance-voltage measurements reveal enhanced hole trapping in bipolar spacer-oxide capacitors irradiated at 0 V at low dose rates. Possible mechanisms and implications for bipolar low-rate response are discussed.

  20. Thermal-stress effects on enhanced low-dose-rate sensitivity of linear bipolar circuits

    Energy Technology Data Exchange (ETDEWEB)

    SHANEYFELT,MARTY R.; SCHWANK,JAMES R.; WITCZAK,STEVEN C.; RIEWE,LEONARD CHARLES; WINOKUR,PETER S.; HASH,GERALD L.; PEASE,R.L.; FLEETWOOD,D.M.

    2000-02-17

    Thermal-stress effects are shown to have a significant impact on the enhanced low-dose-rate sensitivity of linear bipolar circuits. Implications of these results on hardness assurance testing and mechanisms are discussed.

  1. Dose rate effect on low-dose hyper-radiosensitivity with cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Geon-Min; Kim, Eun-Hee [Seoul National University, Seoul (Korea, Republic of)

    2016-10-15

    Low-dose hyper-radiosensitivity (HRS) is the phenomenon that mammalian cells exhibit higher sensitivity to radiation at low doses (< 0.5 Gy) than expected by the linear-quadratic model. At doses above 0.5Gy, the cellular response is recovered to the level expected by the linear-quadratic model. This transition is called the increased radio-resistance (IRR). HRS was first verified using Chinese hamster V79 cells in vitro by Marples and has been confirmed in studies with other cell lines including human normal and tumor cells. HRS is known to be induced by inactivation of ataxia telangiectasia-mutated (ATM), which plays a key role in repairing DNA damages. Considering the connection between ATM and HRS, one can infer that dose rate may affect cellular response regarding HRS at low doses. In this study, we quantitated the effect of dose rate on HRS by clonogenic assay with normal and tumor cells. The HRS of cells at low dose exposures is a phenomenon already known. In this study, we observed HRS of rat normal diencephalon cells and rat gliosarcoma cells at doses below 1 Gy. In addition, we found that dose rate mattered. HRS occurred at low doses, but only when total dose was delivered at a rate below certain level.

  2. Low-dose prednisolone in first-line docetaxel for patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge Marie; Lindberg, Henriette;

    2015-01-01

    BACKGROUND: Randomized studies have shown improved survival with the combination of docetaxel (D) and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). We retrospectively investigated whether coadministration of low-dose glucocorticoids has clinical benefits.......001). P did not influence progression-free survival (P = 0.692, log-rank test) or overall survival when adjusting for baseline levels of hemoglobin, alkaline phosphatase, lactate dehydrogenase, prostate-specific antigen, and Eastern Cooperative Oncology Group performance status (hazard ratioP = 0.98, 95...

  3. Toxicity bioassay in mice exposed to low dose-rate radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joog Sun; Gong, Eun Ji; Heo, Kyu; Yang, Kwang Mo [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of)

    2013-04-15

    The systemic effect of radiation increases in proportion to the dose amount and rate. The association between accumulated radiation dose and adverse effects, which is derived according to continuous low dose-rate radiation exposure, is not clearly elucidated. Our previous study showed that low dose-rate radiation exposure did not cause adverse effects in BALB/c mice at dose levels of ≤2 Gy, but the testis weight decreased at a dose of 2 Gy. In this study, we studied the effects of irradiation at the low dose rate (3.49 mGy/h) in the testes of C57BL/6 mice. Mice exposed to a total dose of 0.02, 0.2, and 2 Gy were found to be healthy and did not show any significant changes in body weight and peripheral blood components. However, mice irradiated with a dose of 2 Gy had significantly decreased testis weight. Further, histological studies and sperm evaluation also demonstrated changes consistent with the findings of decreased testis weight. In fertile patients found to have arrest of sperm maturation, the seminiferous tubules lack the DNMT1 and HDAC1 protein. The decrease of DNMT1 and HDAC1 in irradiated testis may be the part of the mechanism via which low dose-rate irradiation results in teticular injury. In conclusion, despite a low dose-rate radiation, our study found that when mice testis were irradiated with 2 Gy at 3.49 mGy/h dose rate, there was significant testicular and sperm damage with decreased DNMT1 and HDAC1 expression.

  4. Measurement bias dependence of enhanced bipolar gain degradation at low dose rates

    Energy Technology Data Exchange (ETDEWEB)

    Witczak, S.C.; Lacoe, R.C.; Mayer, D.C. [Aerospace Corp., Los Angeles, CA (United States). Electronics Technology Center; Schrimpf, R.D.; Barnaby, H.J.; Galloway, K.F. [Vanderbilt Univ., Nashville, TN (United States). Dept. of Electrical and Computer Engineering; Pease, R.L. [RLP Research, Inc., Albuquerque, NM (United States); Fleetwood, D.M. [Sandia National Labs., Albuquerque, NM (United States)

    1998-03-01

    Oxide trapped charge, field effects from emitter metallization, and high level injection phenomena moderate enhanced gain degradation of lateral pnp transistors at low dose rates. Hardness assurance tests at elevated irradiation temperatures require larger design margins for low power measurement biases.

  5. Lack of high-dose radiation mediated prostate cancer promotion and low-dose radiation adaptive response in the TRAMP mouse model.

    Science.gov (United States)

    Lawrence, M D; Ormsby, R J; Blyth, B J; Bezak, E; England, G; Newman, M R; Tilley, W D; Sykes, P J

    2013-10-01

    Cancer of the prostate is a highly prevalent disease with a heterogeneous aetiology and prognosis. Current understanding of the biological mechanisms underlying the responses of prostate tissue to ionizing radiation exposure, including cancer induction, is surprisingly limited for both high- and low-dose exposures. As population exposure to radiation increases, largely through medical imaging, a better understanding of the response of the prostate to radiation exposure is required. Low-dose radiation-induced adaptive responses for increased cancer latency and decreased cancer frequency have been demonstrated in mouse models, largely for hematological cancers. This study examines the effects of high- and low-dose whole-body radiation exposure on prostate cancer development using an autochthonous mouse model of prostate cancer: TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP). TRAMP mice were exposed to single acute high (2 Gy), low (50 mGy) and repeated low (5 × 50 mGy) doses of X rays to evaluate both the potential prostate cancer promoting effects of high-dose radiation and low-dose adaptive response phenomena in this prostate cancer model. Prostate weights and histopathology were examined to evaluate gross changes in cancer development and, in mice exposed to a single 2 Gy dose, time to palpable tumor was examined. Proliferation (Ki-67), apoptosis, DNA damage (γ-H2AX) and transgene expression (large T-antigen) were examined within TRAMP prostate sections. Neither high- nor low-dose radiation-induced effects on prostate cancer progression were observed for any of the endpoints studied. Lack of observable effects of high- or low-dose radiation exposure suggests that modulation of tumorigenesis in the TRAMP model is largely resistant to such exposures. However, further study is required to better assess the effects of radiation exposure using alternative prostate cancer models that incorporate normal prostate and in those that are not driven by SV40 large T

  6. Method of simulation of low dose rate for total dose effect in 0.18 {mu}m CMOS technology

    Energy Technology Data Exchange (ETDEWEB)

    He Baoping; Yao Zhibin; Guo Hongxia; Luo Yinhong; Zhang Fengqi; Wang Yuanming; Zhang Keying, E-mail: baopinghe@126.co [Northwest Institute of Nuclear Technology, Xi' an 710613 (China)

    2009-07-15

    Three methods for simulating low dose rate irradiation are presented and experimentally verified by using 0.18 {mu}m CMOS transistors. The results show that it is the best way to use a series of high dose rate irradiations, with 100 {sup 0}C annealing steps in-between irradiation steps, to simulate a continuous low dose rate irradiation. This approach can reduce the low dose rate testing time by as much as a factor of 45 with respect to the actual 0.5 rad (Si)/s dose rate irradiation. The procedure also provides detailed information on the behavior of the test devices in a low dose rate environment.

  7. Efficacy of a Low Dose of Estrogen on Antioxidant Defenses and Heart Rate Variability

    Directory of Open Access Journals (Sweden)

    Cristina Campos

    2014-01-01

    Full Text Available This study tested whether a low dose (40% less than the pharmacological dose of 17-β estradiol would be as effective as the pharmacological dose to improve cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar rats (n=9/group were divided in three groups: (1 ovariectomized (Ovx, (2 ovariectomized animals treated for 21 days with low dose (LE; 0.2 mg, and (3 high dose (HE; 0.5 mg 17-β estradiol subcutaneously. Hemodynamic assessment and spectral analysis for evaluation of autonomic nervous system regulation were performed. Myocardial superoxide dismutase (SOD and catalase (CAT activities, redox ratio (GSH/GSSG, total radical-trapping antioxidant potential (TRAP, hydrogen peroxide, and superoxide anion concentrations were measured. HE and LE groups exhibited an improvement in hemodynamic function and heart rate variability. These changes were associated with an increase in the TRAP, GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and superoxide anion was also observed in the treated estrogen groups as compared to the Ovx group. Our results indicate that a low dose of estrogen is just as effective as a high dose into promoting cardiovascular function and reducing oxidative stress, thereby supporting the approach of using low dose of estrogen in clinical settings to minimize the risks associated with estrogen therapy.

  8. The enhanced low dose rate sensitivity of a linear voltage regulator with different biases

    Institute of Scientific and Technical Information of China (English)

    Wang Yiyuan; Lu Wu; Ren Diyuan; Guo Qi; Yu Xuefeng; Gao Bo

    2011-01-01

    A linear voltage regulator was irradiated by 60Co γ at high and low dose rates with two bias conditions to investigate the dose rate effect.The devices exhibit enhanced low dose rate sensitivity (ELDRS) under both biases.Comparing the enhancement factors between zero and working biases,it was found that the ELDRS is more severe under zero bias conditions.This confirms that the ELDRS is related to the low electric field in a bipolar structure.The reasons for the change in the line regulation and the maximum drive current were analyzed by combining the principle of linear voltage regulator with irradiation response of the transistors and error amplifier in the regulator.This may be helpful for designing radiation hardened devices.

  9. Brachytherapy for early oral tongue cancer. Low dose rate to high dose rate

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hideya [Toyonaka Municipal Hospital, Osaka (Japan); Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Inoue, Toshihiko [Osaka Univ., Suita (Japan). Graduate School of Medicine; Furukawa, Souhei; Kakimoto, Naoya [Osaka Univ., Suita (Japan). Graduate School of Dentistry

    2003-03-01

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n=341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer. (author)

  10. Brachytherapy for early oral tongue cancer: low dose rate to high dose rate.

    Science.gov (United States)

    Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Furukawa, Souhei; Kakimoto, Naoya; Shimizutani, Kimishige; Inoue, Toshihiko

    2003-03-01

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n = 341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer.

  11. Relationship of HepG2 cell sensitivity to continuous low dose-rate irradiation with ATM phosphorylation

    Institute of Scientific and Technical Information of China (English)

    Quelin Mei; Jianyong Yang; Duanming Du; Zaizhong Cheng; Pengcheng liu

    2008-01-01

    Objective: To investigate the change of ATM phosphorylation in HepG2 cells and its effect on HepG2 cell survival under a continuous low dose-rate irradiation.Methods: HepG2 cells were exposed to equivalent doses of irradiation delivered at either a continuous low dose-rate (7.76 cGy/h) or a high dose-rate (4500 cGy/h).The ATM phosphorylated proteins and surviving fraction of HepG2 cell after low dose-rate irradiation were compared with that after equivalent doses of high dose-rate irradiation.Results: The phosphorylation of ATM protein was maximal at 0.5 Gy irradiation delivered at either a high dose-rate or a continuous low dose-rate.As the radiation dose increased, the phosphorylation of ATM protein decreased under continuous low dose-rate irradiation.However, the phosphorylation of ATM protein was remained stable under high dose-rate irradiation.When the phosphorylation of ATM protein under continuous low dose-rate irradiation was equal to that under high dose-rate irradiation, there was no significant difference in the surviving fraction of HepG2 cells between two ir-radiation methods (P>0.05).When the phosphorylation of ATM protein significantly decreased after continuous low dose-rate irradiation compared with that after high dose-rate irradiation, increased amounts of cell killing was found in low dose-rate irradiation (P<0.01).Conclusion: Continuous low dose-rate irradiation increases HepG2 cells radiosensitivity compared with high dose-rate irradiation.The increased amounts of cell killing following continuous low dose-rate exposures are associated with reduced ATM phosphorylated protein.

  12. SU-E-T-546: Use of Implant Volume for Quality Assurance of Low Dose Rate Brachytherapy Treatment Plans

    Energy Technology Data Exchange (ETDEWEB)

    Wilkinson, D; Kolar, M [Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH (United States)

    2014-06-01

    Purpose: To analyze the application of volume implant (V100) data as a method for a global check of low dose rate (LDR) brachytherapy plans. Methods: Treatment plans for 335 consecutive patients undergoing permanent seed implants for prostate cancer and for 113 patients treated with plaque therapy for ocular melanoma were analyzed. Plaques used were 54 COMS (10 to 20 mm, notched and regular) and 59 Eye Physics EP917s with variable loading. Plots of treatment time x implanted activity per unit dose versus v100 ^.667 were made. V100 values were obtained using dose volume histograms calculated by the treatment planning systems (Variseed 8.02 and Plaque Simulator 5.4). Four different physicists were involved in planning the prostate seed cases; two physicists for the eye plaques. Results: Since the time and dose for the prostate cases did not vary, a plot of implanted activity vs V100 ^.667 was made. A linear fit with no intercept had an r{sup 2} = 0.978; more than 94% of the actual activities fell within 5% of the activities calculated from the linear fit. The greatest deviations were in cases where the implant volumes were large (> 100 cc). Both COMS and EP917 plaque linear fits were good (r{sup 2} = .967 and .957); the largest deviations were seen for large volumes. Conclusions: The method outlined here is effective for checking planning consistency and quality assurance of two types of LDR brachytherapy treatment plans (temporary and permanent). A spreadsheet for the calculations enables a quick check of the plan in situations were time is short (e.g. OR-based prostate planning)

  13. Multi-Level Effects of Low Dose Rate Ionizing Radiation on Southern Toad, Anaxyrus [Bufo] terrestris.

    Directory of Open Access Journals (Sweden)

    Karolina Stark

    Full Text Available Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad (Anaxyrus [Bufo] terrestris during its pre-terrestrial stages of development -embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later, to four low dose rates of 137Cs at 0.13, 2.4, 21, and 222 mGy d-1, resulting in total doses up to 15.8 Gy. Radiation treatments did not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay in red blood cells at a dose rate of 21 mGy d-1 and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.

  14. Regeneration of Murine Hair Follicles is Inhibited by Low-Dose-Rate Gamma Irradiation.

    Science.gov (United States)

    Sugaya, Kimihiko; Hirobe, Tomohisa; Ishihara, Yoshie; Inoue, Sonoe

    2016-10-01

    To determine whether the effects of low-dose-rate gamma (γ) irradiation are identifiable in the regeneration of murine hair follicles, we irradiated whole bodies of C57BL/10JHir mice in the first telogen phase of the hair cycle with (137)Cs γ-rays. The mice were examined for effects on hair follicles, including number, morphology, and pigmentation in the second anagen phase. Effects of γ-radiation on melanocyte stem cells were also investigated by the indirect immunolabeling of tyrosinase-related protein 2 (TRP2). Irradiated skin showed a decrease in hair follicle density and the induction of curved hair follicles along with the presence of white hairs and hypopigmented hair bulbs. There was a small, but not significant, change in the number of TRP2-positive melanocyte stem cells in the hair bulge region of the irradiated skin. These results suggest that low-dose rate γ-irradiation does not deplete melanocyte stem cells, but can damage stem cells and progenitors for both keratinocytes and melanocytes, thereby affecting the structure and pigmentation of regenerated hair follicles in the 2(nd) anagen phase.

  15. Success rates for computed tomography-guided musculoskeletal biopsies performed using a low-dose technique

    Energy Technology Data Exchange (ETDEWEB)

    Motamedi, Kambiz; Levine, Benjamin D.; Seeger, Leanne L.; McNitt-Gray, Michael F. [UCLA Health System, Radiology, Los Angeles, CA (United States)

    2014-11-15

    To evaluate the success rate of a low-dose (50 % mAs reduction) computed tomography (CT) biopsy technique. This protocol was adopted based on other successful reduced-CT radiation dose protocols in our department, which were implemented in conjunction with quality improvement projects. The technique included a scout view and initial localizing scan with standard dose. Additional scans obtained for further guidance or needle adjustment were acquired by reducing the tube current-time product (mAs) by 50 %. The radiology billing data were searched for CT-guided musculoskeletal procedures performed over a period of 8 months following the initial implementation of the protocol. These were reviewed for the type of procedure and compliance with the implemented protocol. The compliant CT-guided biopsy cases were then retrospectively reviewed for patient demographics, tumor pathology, and lesion size. Pathology results were compared to the ultimate diagnoses and were categorized as diagnostic, accurate, or successful. Of 92 CT-guided procedures performed during this period, two were excluded as they were not biopsies (one joint injection and one drainage), 19 were excluded due to non-compliance (operators neglected to follow the protocol), and four were excluded due to lack of available follow-up in our electronic medical records. A total of 67 compliant biopsies were performed in 63 patients (two had two biopsies, and one had three biopsies). There were 32 males and 31 females with an average age of 50 (range, 15-84 years). Of the 67 biopsies, five were non-diagnostic and inaccurate and thus unsuccessful (7 %); five were diagnostic but inaccurate and thus unsuccessful (7 %); 57 were diagnostic and accurate thus successful (85 %). These results were comparable with results published in the radiology literature. The success rate of CT-guided biopsies using a low-dose protocol is comparable to published rates for conventional dose biopsies. The implemented low-dose protocol

  16. An evaluation of a Low-Dose-Rate (LDR) brachytherapy procedure using a systems engineering & error analysis methodology for health care (SEABH) - (SAVE)

    LENUS (Irish Health Repository)

    Chadwick, Liam

    2012-03-12

    Health Care Failure Modes and Effects Analysis (HFMEA®) is an established tool for risk assessment in health care. A number of deficiencies have been identified in the method. A new method called Systems and Error Analysis Bundle for Health Care (SEABH) was developed to address these deficiencies. SEABH has been applied to a number of medical processes as part of its validation and testing. One of these, Low Dose Rate (LDR) prostate Brachytherapy is reported in this paper. The case study supported the validity of SEABH with respect to its capacity to address the weaknesses of (HFMEA®).

  17. Impact of learning curve and technical changes on dosimetry in low-dose brachytherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Le Fur, E. [CHU Brest (France). Radiation Therapy Dept.; Universite de Bretagne Occidentale, Brest (France). Faculte de Medecine et des Sciences de la Sante; Malhaire, J.P.; Baverez, D.; Schlurmann, F. [CHU Brest (France). Radiation Therapy Dept.; Delage, F.; Perrouin-Verbe, M.A. [CHU Brest (France). Urology Dept.; Guerif, S. [University Hospital La Miletrie, Poitiers (France). Radiation Therapy Dept.; Poitiers Univ. (France); Fournier, G.; Valeri, A. [CHU Brest (France). Urology Dept.; Universite de Bretagne Occidentale, Brest (France). Faculte de Medecine et des Sciences de la Sante; Universite Europeenne de Bretagne, Rennes (France); APHP, Hopital Tenon, Paris (France). CeRe.PP; Pradier, O. [CHU Brest (France). Radiation Therapy Dept.; Universite de Bretagne Occidentale, Brest (France). Faculte de Medecine et des Sciences de la Sante; Universite Europeenne de Bretagne, Rennes (France); CHU Brest (France). LaTIM, INSERM U650

    2012-12-15

    Purpose: To assess the impact of experience and technical changes on peri- and postimplantation (1 month later) dosimetry for permanent prostate brachytherapy (PPB). Patients and methods: From July 2003 to May 2010, 150 prostate cancer patients underwent low-dose, loose-seed I{sup 125} PPB as monotherapy with intraoperative planning. Patients were divided into three groups - P1 (n = 64), P2 (n = 45), P3 (n = 41) - according to the technical changes that occurred during the study period: use of an automatic stepper at the beginning of P2 and a high-frequency ultrasound probe in P3. Peri- and postimplantation dosimetric parameters (on day 30) were reported: D90 (dose received by 90% of prostate volume), V100 and V150 (prostate volume receiving, respectively, 100% and 150% of the prescribed dose), D2 cc and D0.1 cc (doses received by 2 cc and 0.1 cc of the rectum), R100 (rectum volume that received 100% of the prescribed dose), and D10 and D30 (doses received by 10% and 30% of the urethra, only during peri-implantation). Results: We observed a decrease in the number of needles and seeds used over time. The mean peri-implantation D90 was 187.52 Gy without a significant difference between the three periods (p = 0.48). The postimplantation D90, V100, and V150 parameters were, respectively, 168.3 Gy, 91.9%, and 55% with no significant difference between the three periods. The peri-implantation and postimplantation D0.1 cc and R100 significantly decreased over time; on day 30: D0.1 cc P1 = 223.1 Gy vs. D0.1 cc P3 = 190.4 Gy (p = 8.10- 5) and R100 P1 = 1.06 cc vs. R100 P3 = 0.53 cc (p = 0.0008). Conclusion: We observed a learning curve for the implantation parameters, which led to a significant decrease in the rectal doses without having any impact on the prostate dosimetric parameters. (orig.)

  18. The effects of low dose rate irradiation and thermal aging on reactor structural alloys

    Science.gov (United States)

    Allen, T. R.; Trybus, C. L.; Cole, J. I.

    As part of the EBR-II reactor materials surveillance program, test samples of fifteen different alloys were placed into EBR-II in 1965. The surveillance (SURV) program was intended to determine property changes in reactor structural materials caused by irradiation and thermal aging. In this work, the effect of low dose rate (approximately 2 × 10 -8 dpa/s) irradiation at 380-410°C and long term thermal aging at 371°C on the properties of 20% cold worked 304 stainless steel, 420 stainless steel, Inconel X750, 304/308 stainless weld material, and 17-4 PH steel are evaluated. Doses of up to 6.8 dpa and thermal aging to 2994 days did not significantly affect the density of these alloys. The strength of 304 SS, X750, 17-4 PH, and 304/308 weld material increased with irradiation. In contrast, the strength of 420 stainless steel decreased with irradiation. Irradiation decreased the impact energy in both Inconel X750 and 17-4 PH steel. Thermal aging decreased the impact energy in 17-4 PH steel and increased the impact energy in Inconel X750. Tensile property comparisons of 304 SURV samples with 304 samples irradiated in EBR-II at a higher dose rate show that the higher dose rate samples had greater increases in strength and greater losses in ductility.

  19. The effect of low dose rate on metabolomic response to radiation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Goudarzi, Maryam [Georgetown University, Biochemistry and Molecular and Cellular Biology, Washington, DC (United States); Mak, Tytus D. [Georgetown University, Lombardi Comprehensive Cancer Center, Washington, DC (United States); Chen, Congju; Smilenov, Lubomir B.; Brenner, David J. [Columbia University, Center for High-Throughput Minimally-Invasive Radiation Biodosimetry, New York, NY (United States); Fornace, Albert J. [Georgetown University, Biochemistry and Molecular and Cellular Biology, Washington, DC (United States); Georgetown University, Lombardi Comprehensive Cancer Center, Washington, DC (United States)

    2014-11-15

    Metabolomics has been shown to have utility in assessing responses to exposure by ionizing radiation (IR) in easily accessible biofluids such as urine. Most studies to date from our laboratory and others have employed γ-irradiation at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at relatively low dose rates (LDR). There are well-documented differences in the biologic responses to LDR compared to HDR, so an important question is to assess LDR effects at the metabolomics level. Our study took advantage of a modern mass spectrometry approach in exploring the effects of dose rate on the urinary excretion levels of metabolites 2 days after IR in mice. A wide variety of statistical tools were employed to further focus on metabolites, which showed responses to LDR IR exposure (0.00309 Gy/min) distinguishable from those of HDR. From a total of 709 detected spectral features, more than 100 were determined to be statistically significant when comparing urine from mice irradiated with 1.1 or 4.45 Gy to that of sham-irradiated mice 2 days post-exposure. The results of this study show that LDR and HDR exposures perturb many of the same pathways such as TCA cycle and fatty acid metabolism, which also have been implicated in our previous IR studies. However, it is important to note that dose rate did affect the levels of particular metabolites. Differences in urinary excretion levels of such metabolites could potentially be used to assess an individual's exposure in a radiobiological event and thus would have utility for both triage and injury assessment. (orig.)

  20. Gamma radiation at a human relevant low dose rate is genotoxic in mice

    Science.gov (United States)

    Graupner, Anne; Eide, Dag M.; Instanes, Christine; Andersen, Jill M.; Brede, Dag A.; Dertinger, Stephen D.; Lind, Ole C.; Brandt-Kjelsen, Anicke; Bjerke, Hans; Salbu, Brit; Oughton, Deborah; Brunborg, Gunnar; Olsen, Ann K.

    2016-09-01

    Even today, 70 years after Hiroshima and accidents like in Chernobyl and Fukushima, we still have limited knowledge about the health effects of low dose rate (LDR) radiation. Despite their human relevance after occupational and accidental exposure, only few animal studies on the genotoxic effects of chronic LDR radiation have been performed. Selenium (Se) is involved in oxidative stress defence, protecting DNA and other biomolecules from reactive oxygen species (ROS). It is hypothesised that Se deficiency, as it occurs in several parts of the world, may aggravate harmful effects of ROS-inducing stressors such as ionising radiation. We performed a study in the newly established LDR-facility Figaro on the combined effects of Se deprivation and LDR γ exposure in DNA repair knockout mice (Ogg1-/-) and control animals (Ogg1+/-). Genotoxic effects were seen after continuous radiation (1.4 mGy/h) for 45 days. Chromosomal damage (micronucleus), phenotypic mutations (Pig-a gene mutation of RBCCD24-) and DNA lesions (single strand breaks/alkali labile sites) were significantly increased in blood cells of irradiated animals, covering three types of genotoxic activity. This study demonstrates that chronic LDR γ radiation is genotoxic in an exposure scenario realistic for humans, supporting the hypothesis that even LDR γ radiation may induce cancer.

  1. Effects of orientation of substrate on the enhanced low-dose-rate sensitivity (ELDRS) in NPN transistors

    Institute of Scientific and Technical Information of China (English)

    LU Wu; ZHENG Yu-Zhan; WANG Yi-Yuan; REN Di-Yuan; GUO Qi; WANG Zhi-Kuan; WANG Jian-An

    2011-01-01

    The radiation effects and annealing characteristics of two types of domestic NPN bipolar junction transistors, fabricated with different orientations, were investigated under different dose-rate irradiation. The experimental results show that both types of the NPN transistors exhibit remarkable Enhanced Low-Dose-Rate Sensitivity (ELDRS). After irradiation at high or low dose rate, the excess base current of NPN transistors obviously increased, and the current gain would degrade rapidly. Moreover, the decrease of collector current was also observed. The NPN transistor with (111) orientation was more sensitive to ionizing radiation than that with (100) orientation. The underlying mechanisms of various experimental phenomena are discussed in detail in this paper.

  2. Effects of orientation of substrate on the enhanced low-dose-rate sensitivity (ELDRS) in NPN transistors

    Science.gov (United States)

    Lu, Wu; Zheng, Yu-Zhan; Wang, Yi-Yuan; Ren, Di-Yuan; Guo, Qi; Wang, Zhi-Kuan; Wang, Jian-An

    2011-02-01

    The radiation effects and annealing characteristics of two types of domestic NPN bipolar junction transistors, fabricated with different orientations, were investigated under different dose-rate irradiation. The experimental results show that both types of the NPN transistors exhibit remarkable Enhanced Low-Dose-Rate Sensitivity (ELDRS). After irradiation at high or low dose rate, the excess base current of NPN transistors obviously increased, and the current gain would degrade rapidly. Moreover, the decrease of collector current was also observed. The NPN transistor with orientation was more sensitive to ionizing radiation than that with orientation. The underlying mechanisms of various experimental phenomena are discussed in detail in this paper.

  3. Metronomic Treatment with Low-Dose Trofosfamide Leads to a Long-Term Remission in a Patient with Docetaxel-Refractory Advanced Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jochen Greiner

    2010-01-01

    Full Text Available The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11 C-Choline positron emission tomography/computerized tomography (PET/CT. After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 g/l. The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.

  4. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium at the EMS 2009 Annual Meeting - September 2006

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F.; von Borstel, Robert C.; Brenner,; Redpath, J. Leslie; Erickson, Barbra E.; Brooks,

    2009-11-12

    The low dose symposium thoughtfully addressed controversy of risk from low dose radiation exposure, hormesis and radon therapy. The stem cell symposium cogently considered the role of DNA damage and repair in hematopoietic stem cells underlying aging and malignancy and provocatively presented evidence that stem cells may have distinct morphologies and replicative properties, as well as special roles in cancer initiation. In the epigenetics symposium, studies illustrated the long range interaction of epigenetic mechanisms, the roles of CTCF and BORIS in region/specific regulation of epigenetic processes, the impact of DNA damage on epigenetic processes as well as links between epigenetic mechanisms and early nutrition and bystander effects.

  5. Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons.

    Science.gov (United States)

    Dionet, Claude; Müller-Barthélémy, Melanie; Marceau, Geoffroy; Denis, Jean-Marc; Averbeck, Dietrich; Gueulette, John; Sapin, Vincent; Pereira, Bruno; Tchirkov, Andrei; Chautard, Emmanuel; Verrelle, Pierre

    2016-09-01

    To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts. We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS. HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR). HRS does not seem to be due either to DSB or to apoptosis. Both phenomena (HRS and ICRR) appear to be related to ATP availability for triggering cell repair. Fibroblast survival after neutron irradiation is also dose rate-dependent but without HRS. Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation.

  6. Induction of chromosome aberrations is non-linear within the low dose region and depends on dose rate

    Energy Technology Data Exchange (ETDEWEB)

    Oudalova, A.A.; Geras' kin, S.A.; Dikarev, V.G.; Nesterov, Y.B.; Dikareva, N.S

    2002-07-01

    The low dose region was evaluated for meristem cells of spring barley. A study of the cytogenetic damage in the low dose range was carried out to determine the genuine shape of the dose curve. The relationship between the frequency of aberrant cells and the absorbed dose is shown to be non-linear with a site at low doses within which the cytogenetic damage exceeds the control level significantly and does not depend on dose value. Within the tested exposure region, the aberrant cell frequency is found to decrease with increasing dose rate, but the shape of the dose curve remained invariable. The piecewise linear model fits the experimental data much better than the linear one. (author)

  7. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lim Yiting [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Kastan, Michael B. [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States); Matsui, William, E-mail: matsuwi@jhmi.edu [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); DeWeese, Theodore L., E-mail: deweete@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2012-11-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  8. COMPROMISING EFFECT OF LOW DOSE-RATE TOTAL-BODY IRRADIATION ON ALLOGENEIC BONE-MARROW ENGRAFTMENT

    NARCIS (Netherlands)

    VANOS, R; KONINGS, AWT; DOWN, JD

    1993-01-01

    The protraction of total body irradiation (TBI) to a continuous low dose-rate has been investigated for its effect on donor marrow engraftment in murine bone marrow transplant (BMT) models of varying histocompatibility. Three different BMT combinations were used: syngeneic [B6-Gpi-1a --> B6-Gpi-1b],

  9. Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE−/− Alzheimer mouse model

    DEFF Research Database (Denmark)

    Kempf, Stefan; Janik, Dirk; Barjaktarovic, Zarko

    2017-01-01

    Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer´s. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days with cumula...

  10. Low-dose growth hormone supplementation increases clinical pregnancy rate in poor responders undergoing in vitro fertilisation.

    Science.gov (United States)

    Lattes, Karinna; Brassesco, Mario; Gomez, Manuel; Checa, Miguel A

    2015-07-01

    Poor ovarian response (POR) often means low success rates after in vitro fertilisation (IVF). We aim to study the impact of a low-dose growth hormone (GH) supplementation in pregnancy rates in poor responders in a prospective, self-controlled study of 64 poor responders to previous IVF cycles, who failed to achieve pregnancy and were supplemented with low-doses of GH in a subsequent cycle using the same gonadotropin dose and protocol. Our primary endpoint was the clinical pregnancy rate (CPR), considering secondary endpoints, the number of retrieved oocytes, embryos, embryo quality and the proportion of cycles with embryo transfer. CPR in the GH group was 34.4%. Significant differences were observed for the GH group both in the number of top quality embryos (0.64 ± 0.88 versus 1.03 ± 1.17, p < 0.05) and cryopreserved embryos (0.3 ± 0.81 versus 0.85 ± 1.49, p < 0.05). This is, to our knowledge, the first clinical trial to use a low dose of GH as a supplement for IVF in POR patients. Despite this low dose, we achieved excellent success rates in patients with a very poor prognosis, at a reasonable cost and without side effects, which makes this a safe and cost-effective alternative.

  11. COMPROMISING EFFECT OF LOW DOSE-RATE TOTAL-BODY IRRADIATION ON ALLOGENEIC BONE-MARROW ENGRAFTMENT

    NARCIS (Netherlands)

    VAN OS, R; KONINGS, A W T; DOWN, J D

    1993-01-01

    The protraction of total body irradiation (TBI) to a continuous low dose-rate has been investigated for its effect on donor marrow engraftment in murine bone marrow transplant (BMT) models of varying histocompatibility. Three different BMT combinations were used: syngeneic [B6-Gpi-1a --> B6-Gpi-1b],

  12. Risk of Low Dose/Low Dose Rate Ionizing Radiation to Humans Symposium Annual Meeting of the Environmental Mutagen Society: Agenda and Abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Veigl, Martina L. [Environmental Mutagen Society (EMS), Reston, VA (United States); Case Western Reserve Univ., Cleveland, OH (United States). Case Comprehensive Cancer Center; Morgan, William F. [Univ. of Maryland, College Park, MD (United States); Schwartz, Jeffrey L. [Univ. of Washington, Seattle, WA (United States)

    2009-11-11

    The low dose symposium thoughtfully addressed controversy of risk from low dose radiation exposure, hormesis and radon therapy. The stem cell symposium cogently considered the role of DNA damage and repair in hematopoietic stem cells underlying aging and malignancy and provocatively presented evidence that stem cells may have distinct morphologies and replicative properties, as well as special roles in cancer initiation. In the epigenetics symposium, studies illustrated the long range interaction of epigenetic mechanisms, the roles of CTCF and BORIS in region/specific regulation of epigenetic processes, the impact of DNA damage on epigenetic processes as well as links between epigenetic mechanisms and early nutrition and bystander effects. This report shows the agenda and abstracts for this symposium.

  13. CLINICAL USE OF LOW DOSE TADALAFIL IN COMBINATION WITH ALPHA BLOCKER IN THE MANAGEMENT OF BENIGN PROSTATIC HYPERPLASIA

    Directory of Open Access Journals (Sweden)

    Manish

    2016-02-01

    Full Text Available Benign Prostatic Hyperplasia associated with lower urinary tract symptoms is a common geriatric condition in males, which considerably impairs the quality of life due to the irritable and obstructive symptoms, decreased urinary flow and progression to bladder outlet obstruction. Tadalafil is a selective, reversible inhibitor of cyclic guanosine monophosphate (cGMP – specific phosphodiesterase type 5 (PDE5. PDE5 receptor is identified in the lower urinary tract – prostate, ureter and bladder and also identified in visceral smooth muscles, skeletal muscles, platelets, kidney, lungs and cerebellum. It is well established as the first line treatment for erectile dysfunction and approved for treatment of BPH and LUTS with or without ED. OBJECTIVE To evaluate the efficacy of low-dose Tadalafil (5mg along with alpha blocker in the management of Benign Prostatic Hyperplasia (BPH and Lower Urinary Tract Symptoms (LUTS. PATIENTS AND DURATION The study was conducted by the Dept. of Urology, Mahatma Gandhi Medical College and Hospital, Jaipur. In this retrospective study, we reviewed the records of 60 patients in the outpatient clinic from August 2014 to August 2015 with prostatomegaly and LUTS, who were subject to a single daily dose of tamsulosin 0.4mg or alfuzosin 10mg and a daily dose of 5mg Tadalafil. METHOD Patients with LUTS and BPH who were previously managed with alpha blockers (Tamsulosin 0.4mg or Alfuzosin 10mg and who developed progressively bothersome symptoms with stable or increasing IPSS were included in our study by addition of 5mg phosphodiesterase type 5 inhibitor (Tadalafil, which has been reported by various well designed studies to be useful in the management of ED, BPH and LUTS. We analysed the International Prostate Symptom Score (IPSS, BPH Impact Index (BII and Quality of Life (QoL. Mean age of inclusion was 45 to 80 years. RESULTS Before the inclusion of tadalafil in patients, patients exclusively on alpha blockers had a mean

  14. DNA repair and damage pathway related cancer suppressor genes in low-dose-rate irradiated AKR/J an IR mice

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Hyun Soon; Bong, Jin Jong; Kang, Yumi; Choi, Moo Hyun; Lee, Hae Un; Yoo, Jae Young; Choi, Seung Jin; Kim, Hee Sun [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd, Gyeongju (Korea, Republic of); Lee, Kyung Mi [Global Research Lab, BAERI Institute, Dept. of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2012-11-15

    It has been reported that low-dose-rate radiation stimulates the immune response, prolongs life span and inhibits carcinogenesis. The high dose-rate radiation influences the expression of DNA repair and damage-related genes. In contrast, DNA repair and damage signaling triggered by low-dose-rate irradiation remain unclear. In the present study, we investigated the differential expression of DNA repair and damage pathway related genes in the thymus of AKR/J and ICR mice after 100th day low-dose-rate irradiation. Our findings demonstrated that low-dose-rate γ -radiation suppressed tumorigenesis.

  15. Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE-/- Alzheimer's mouse model

    DEFF Research Database (Denmark)

    Kempf, S. J.; Janik, Dirk; Barjaktarovic, Zarko

    2016-01-01

    Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer's. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days...... that several molecular targets induced by chronic low-dose-rate radiation overlap with those of Alzheimer's pathology. It may suggest that ionising radiation functions as a contributing risk factor to this neurodegenerative disease....... with cumulative doses of 0.3 Gy and 6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an Alzheimer's model. Using mass spectrometry, a marked alteration in the phosphoproteome was found at both dose rates. The radiation-induced changes in the phosphoproteome were associated with the control...

  16. Risk of solid cancer in low dose-rate radiation epidemiological studies and the dose-rate effectiveness factor.

    Science.gov (United States)

    Shore, Roy; Walsh, Linda; Azizova, Tamara; Rühm, Werner

    2017-10-01

    Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF). We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR Gy(-1)) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF. The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta-analyses that included only cohorts in which the mean dose was radiation exposure. The LDR data provide direct evidence regarding risk from exposures at low dose rates as an important complement to the

  17. Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure.

    Directory of Open Access Journals (Sweden)

    Esther L Calderon-Gierszal

    Full Text Available Studies using rodent and adult human prostate stem-progenitor cell models suggest that developmental exposure to the endocrine disruptor Bisphenol-A (BPA can predispose to prostate carcinogenesis with aging. Unknown at present is whether the embryonic human prostate is equally susceptible to BPA during its natural developmental window. To address this unmet need, we herein report the construction of a pioneer in vitro human prostate developmental model to study the effects of BPA. The directed differentiation of human embryonic stem cells (hESC into prostatic organoids in a spatial system was accomplished with precise temporal control of growth factors and steroids. Activin-induced definitive endoderm was driven to prostate specification by combined exposure to WNT10B and FGF10. Matrigel culture for 20-30 days in medium containing R-Spondin-1, Noggin, EGF, retinoic acid and testosterone was sufficient for mature prostate organoid development. Immunofluorescence and gene expression analysis confirmed that organoids exhibited cytodifferentiation and functional properties of the human prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing and 10 nM BPA reducing the number of branched structures formed. While differentiation of branched structures to mature organoids seemed largely unaffected by BPA exposure, the stem-like cell population increased, appearing as focal stem cell nests that have not properly entered lineage commitment rather than the rare isolated stem cells found in normally differentiated structures. These findings provide the first direct evidence that low-dose BPA exposure targets hESC and perturbs morphogenesis as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by in utero BPA exposures.

  18. Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure.

    Science.gov (United States)

    Calderon-Gierszal, Esther L; Prins, Gail S

    2015-01-01

    Studies using rodent and adult human prostate stem-progenitor cell models suggest that developmental exposure to the endocrine disruptor Bisphenol-A (BPA) can predispose to prostate carcinogenesis with aging. Unknown at present is whether the embryonic human prostate is equally susceptible to BPA during its natural developmental window. To address this unmet need, we herein report the construction of a pioneer in vitro human prostate developmental model to study the effects of BPA. The directed differentiation of human embryonic stem cells (hESC) into prostatic organoids in a spatial system was accomplished with precise temporal control of growth factors and steroids. Activin-induced definitive endoderm was driven to prostate specification by combined exposure to WNT10B and FGF10. Matrigel culture for 20-30 days in medium containing R-Spondin-1, Noggin, EGF, retinoic acid and testosterone was sufficient for mature prostate organoid development. Immunofluorescence and gene expression analysis confirmed that organoids exhibited cytodifferentiation and functional properties of the human prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing and 10 nM BPA reducing the number of branched structures formed. While differentiation of branched structures to mature organoids seemed largely unaffected by BPA exposure, the stem-like cell population increased, appearing as focal stem cell nests that have not properly entered lineage commitment rather than the rare isolated stem cells found in normally differentiated structures. These findings provide the first direct evidence that low-dose BPA exposure targets hESC and perturbs morphogenesis as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by in utero BPA exposures.

  19. [Low-dose rate brachytherapy with locally integrated beta emitters after internal urethrotomy. A pilot project using an animal model].

    Science.gov (United States)

    Weidlich, P; Adam, C; Sroka, R; Lanzl, I; Assmann, W; Stief, C

    2007-09-01

    The treatment of urethral strictures represents an unsolved urological problem. The effect of a (32)P-coated urethral catheter in the sense of low-dose rate brachytherapy to modulate wound healing will be analyzed in an animal experiment. Unfortunately it is not possible to present any results because this is being studied for the first time and there are no experiences with low-dose rate brachytherapy and this form of application in the lower urinary tract. Furthermore the animal experiment will only start in the near future. Both decade-long experiences with radiotherapy to treat benign diseases and our own results of previous studies in otolaryngology and ophthalmology let us expect a significantly lower formation of urethral strictures after internal urethrotomy. This study will contribute to improving the treatment of urethral strictures as demanded in previous papers.

  20. A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer.

    Science.gov (United States)

    Noguchi, Masanori; Kakuma, Tatsuyuki; Uemura, Hirotsugu; Nasu, Yasutomo; Kumon, Hiromi; Hirao, Yasuhiko; Moriya, Fukuko; Suekane, Shigetaka; Matsuoka, Kei; Komatsu, Nobukazu; Shichijo, Shigeki; Yamada, Akira; Itoh, Kyogo

    2010-07-01

    Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.

  1. High dose rate versus low dose rate brachytherapy for oral cancer--a meta-analysis of clinical trials.

    Directory of Open Access Journals (Sweden)

    Zhenxing Liu

    Full Text Available OBJECTIVE: To compare the efficacy and safety of high dose rate (HDR and low dose rate (LDR brachytherapy in treating early-stage oral cancer. DATA SOURCES: A systematic search of MEDLINE, EMBASE and Cochrane Library databases, restricted to English language up to June 1, 2012, was performed to identify potentially relevant studies. STUDY SELECTION: Only randomized controlled trials (RCT and controlled trials that compared HDR to LDR brachytherapy in treatment of early-stage oral cancer (stages I, II and III were of interest. DATA EXTRACTION AND SYNTHESIS: Two investigators independently extracted data from retrieved studies and controversies were solved by discussion. Meta-analysis was performed using RevMan 5.1. One RCT and five controlled trials (607 patients: 447 for LDR and 160 for HDR met the inclusion criteria. The odds ratio showed no statistically significant difference between LDR group and HDR group in terms of local recurrence (OR = 1.12, CI 95% 0.62-2.01, overall mortality (OR = 1.01, CI 95% 0.61-1.66 and Grade 3/4 complications (OR = 0.86, CI 95% 0.52-1.42. CONCLUSIONS: This meta-analysis indicated that HDR brachytherapy was a comparable alternative to LDR brachytherapy in treatment of oral cancer. HDR brachytherapy might become a routine choice for early-stage oral cancer in the future.

  2. PRE-EXPOSURE OF MICE TO LOW DOSE OR LOW DOSE RATE IONIZING RADIATION REDUCES CHROMOSOME ABERRATIONS INDUCED BY SUBSEQUENT EXPOSURE TO HIGH DOSE OF RADIATION OR MITOMYCIN C

    Institute of Scientific and Technical Information of China (English)

    于文儒; 王明东; 蔡露; 金玉珂

    1995-01-01

    The phenomenon of cytogenetic adaptive and cross-adaptive response induced by low dose irradiation and chemical mutagen in mice is described. We found, firstly, that adapration can be induced by acute low dose X-irracliation (0—100 mGy). Secondly, a cross-adaptation can occur between X-irradiatlon and rrdto-mycin C (MMC). And finally, mice pre-exposed to chronic low dose rate 60Co-Gamma irradiation (0-226. 0 mGy/day) are less susceptible to chromosome aberration induced by subsequent acute higher X-irradiation. Therefore, our data suggest that radioadaptlve respotrse depends on dose, dose rate and time interval. Possible mechanisms are also discussed.

  3. SU-E-T-145: Beam Characteristics of Flattening Filter Free Beams Including Low Dose Rate Setting

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, K; Ogata, T; Nakayama, M; Shinji, T; Nishimura, H; Masutani, T [Kobe Minimally Invasive Cancer Center, Kobe, Hyogo (Japan); Ishihara, T; Ejima, Y; Sasaki, R [Kobe University Hospital, Kobe, Hyogo (Japan)

    2015-06-15

    Purpose: In commissioning of volumetric modulated arc therapy (VMAT), it is necessary to evaluate the beam characteristics of various dose rate settings with potential to use. The aim of this study is to evaluate the beam characteristics of flattened and flattening filter free (FFF) including low dose rate setting. Methods: We used a Varian TrueBeam with Millennium 120 MLC. Both 6 and 10 MV beams with or without flattening filter were used for this study. To evaluate low-dose rate FFF beams, specially-designed leaf sequence files control out-of-field MLC leaf pair at constant dose rate ranging from 80 to 400 MU/min. For dose rate from 80 MU/min to the maximum usable value of all energies, beam output were measured using ionization chamber (CC04, IBA). The ionization chamber was inserted into water equivalent phantom (RT3000-New, R-tech), and the phantom was set with SAD of 100cm. The beam profiles were performed using the 2D diode array (Profiler2, Sun Nuclear). The SSD was set to 90cm and a combined 30cmx30cmx9cm phantom which consisted of solid water slabs was put on the device. All measurement were made using 100MU irradiation for 10cmx10cm jaw-defined field size with a gantry angle of 0°. Results: In all energies, the dose rate dependences with beam output and variation coefficient were within 0.2% and 0.07%, respectively. The flatness and symmetry exhibited small variations (flatness ≤0.1 point and symmetry≤0.3 point at absolute difference). Conclusion: We had studied the characteristics of flattened and FFF beam over the 80 MU/min. Our results indicated that the beam output and profiles of FFF of TrueBeam linac were highly stable at low dose rate setting.

  4. Low dose rate caesium-137 implant time of intracavitary brachytherapy source of a selected oncology center in Ghana

    OpenAIRE

    John Owusu Banahene; Emmanuel Ofori Darko; Baffour Awuah

    2015-01-01

    Background: The treatment time taken for a radioactive source is found to be very important in intracavitary brachytherapy treatment. The duration of the treatment time depends on the prescribed dose requested to a reference point and the calculated dose rate to the same point. The duration of the treatment time of source is found to depend on the tumour stage. In this work, the treatment time of implant has been calculated for a Caesium-137 low dose rate brachytherapy source at an oncology f...

  5. Biological effects of long-term exposure to low dose-rate radiation -- Comparisons of WAM model and LQ model

    CERN Document Server

    Wada, Takahiro; Nakamura, Issei; Tsunoyama, Yuichi; Nakajima, Hiroo; Bando, Masako

    2015-01-01

    Newly proposed Whack-A-Mole (WAM) model which is to be used to estimate the biological effects of artificial radiations is compared with conventionally used Linear-Quadratic model. Basic properties of WAM model are discussed emphasizing on the dose-rate dependence. By adopting the parameters that are determined to fit the mega mouse experiments, biological effects of long-term exposure to extremely low dose-rate radiation are discussed. In WAM model, the effects of the long-term exposure show a saturation property, which makes a clear distinction from the LNT hypothesis which predicts a linear increase of the effects with time.

  6. Chromosome aberrations and micronucleus in continuously irradiated mice for a low dose rate of {sup 137}Cs {gamma}-rays

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, Jun; Yanai, Takanori; Shirata, Katsutoshi; Tanaka, Kimio; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan)

    2002-07-01

    Delayed chromosomal instability is developed by radiation after several cell divisions in cultured rodent and human cells. The genetic instability might be related to cancer development and it has been mainly found in cultured rodent and human cells irradiated at high dose rate. It has not been well studied whether the genetic instability is induced by prolonged irradiation with low dose rate in vivo or not. Mice irradiated with 20 mGy/day for 5-8 Gy were analyzed by FISH to estimate the chromosome aberration rate and micronucleus incidence in spleen and bone marrow cells. Spleen cells in mice exposed to 8 Gy have higher incidence of monosomy and trisomy than non-exposed mice. The number of cells with 2-4 micronuclei in 10,000 scored spleen cells is also higher in 5-8 Gy exposed mice. These numerical chromosome aberrations are not induced directly by radiation exposure. These results indicate that prolonged {sup 137}Cs {gamma} ray-irradiation with low dose rates of 20 mGy/day induces delayed chromosome instability in mice. (author)

  7. Pulsed-dose-rate and low-dose-rate brachytherapy : Comparison of sparing effects in cells of a radiosensitive and a radioresistant cell line

    NARCIS (Netherlands)

    Pomp, J; Woudstra, EC; Kampinga, HH

    Pulsed-dose-rate regimens are an attractive alternative to continuous low-dose-rate brachytherapy. However, apart from data obtained from modeling, only a few irt vitro results are available for comparing the biological effectiveness of both modalities. Cells of two human cell lines with survival

  8. Investigation of bias dependence on enhanced low dose rate sensitivity in SiGe HBTs for space application

    Science.gov (United States)

    Sun, Yabin; Fu, Jun; Xu, Jun; Wang, Yudong; Zhou, Wei; Zhang, Wei; Cui, Jie; Li, Gaoqing; Liu, Zhihong

    2014-02-01

    NPN silicon-germanium (SiGe) heterojunction bipolar transistors (HBTs) were exposed to 60Co gamma source at different dose rates under two bias conditions. Excess base currents and normalized current gains are used to quantify performance degradation. Experiment results demonstrate that the lower the dose rate, the more the irradiation damage, and some enhanced low dose rate sensitivity (ELDRS) exists in SiGe HBTs. The ELDRS effect is found to depend highly on the bias condition during exposure, and the transistors with forward active mode exhibit a more serious ELDRS effect compared to the floating case. The performance degradation at different dose rates and bias conditions is compared and discussed, and furthermore the underlying physical mechanisms are analyzed and investigated in detail.

  9. Effect of low dose oxytocin treatment on the pregnancy rate of the dairy cows

    Directory of Open Access Journals (Sweden)

    H. Hamali,

    2011-02-01

    Full Text Available It is well known that during the natural mating, stimulation of the female genital system by the bull causes oxytocin release from the caudal part of the female pituitary gland and this hormone enhances the sperm transport in the genital tract. During the artificial insemination (A.I, this hormone dose not release perfectly. For determine of the oxytocin effect on the pregnancy rates of the cows, a total 100 cows were chosen in a dairy herd located in a suburb of Tabriz (North-west of Iran. These cows were randomly divided into two groups. In the group A, during the A.I, 30 IU oxytocin (3cc Vetocin was injected to the cows intramuscularly. In the group of B, 3cc saline was injected intramuscularly to the control cows. After 45 days of A.I, all of the cows were examined by rectal palpation for pregnancy detection. The pregnancy rates were 58% and 54% in the groups of oxytocin treated and control respectively. The difference between two groups did not differ significantly. These results indicated that oxytocin administration during the A.I had not significant effect on the cow's pregnancy rates.

  10. Low doses of caffeine reduce heart rate during submaximal cycle ergometry

    Directory of Open Access Journals (Sweden)

    Wetter Thomas J

    2007-10-01

    Full Text Available Abstract Background The purpose of this study was to examine the cardiovascular effects of two low-levels of caffeine ingestion in non habitual caffeine users at various submaximal and maximal exercise intensities. Methods Nine male subjects (19–25 yr; 83.3 ± 3.1 kg; 184 ± 2 cm, underwent three testing sessions administered in a randomized and double-blind fashion. During each session, subjects were provided 4 oz of water and a gelatin capsule containing a placebo, 1.5 mg/kg caffeine, or 3.0 mg/kg caffeine. After thirty minutes of rest, a warm-up (30 Watts for 2 min the pedal rate of 60 rpm was maintained at a steady-state output of 60 watts for five minutes; increased to 120 watts for five minutes and to 180 watts for five minutes. After a 2 min rest the workload was 180 watts for one minute and increased by 30 watts every minute until exhaustion. Heart rate (HR was measured during the last 15-seconds of each minute of submaximal exercise. Systolic blood pressure (BP was measured at rest and during each of the three sub-maximal steady state power outputs. Minute ventilation (VE, Tidal volume (VT, Breathing frequency (Bf, Rating of perceived exertion (RPE, Respiratory exchange ratio (RER, and Oxygen consumption (VO2 were measured at rest and during each minute of exercise. Results Caffeine at 1.5 and 3.0 mg/kg body weight significantly lowered (p E, VT, VO2, RPE, maximal power output or time to exhaustion. Conclusion In non habitual caffeine users it appears that consuming a caffeine pill (1.5 & 3.0 mg/kg at a dose comparable to 1–3 cups of coffee lowers heart rate during submaximal exercise but not at near maximal and maximal exercise. In addition, this caffeine dose also only appears to affect systolic blood pressure at rest but not during cycling exercise.

  11. Repair of I-SceI induced DSB at a specific site of chromosome in human cells: influence of low-dose, low-dose-rate gamma-rays.

    Science.gov (United States)

    Yatagai, Fumio; Suzuki, Masao; Ishioka, Noriaki; Ohmori, Hitoshi; Honma, Masamitsu

    2008-11-01

    We investigated the influence of low-dose, low-dose-rate gamma-ray irradiation on DNA double strand break (DSB) repair in human lymphoblastoid TK6 cells. A single DSB was introduced at intron 4 of the TK+ allele (chromosome 17) by transfection with the I-SceI expression vector pCBASce. We assessed for DSB repair due to non-homologous end-joining (NHEJ) by determining the generation of TK-deficient mutants in the TK6 derivative TSCE5 (TK +/-) carrying an I-SceI recognition site. We similarly estimated DSB repair via homologous recombination (HR) at the same site in the derived compound heterozygote (TK-/-) cell line TSCER2 that carries an additional point mutation in exon 5. The NHEJ repair of DSB was barely influenced by pre-irradiation of the cells with 30 mGy gamma-rays at 1.2 mGy h(-1). DSB repair by HR, in contrast, was enhanced by approximately 50% after pre-irradiation of the cells under these conditions. Furthermore, when I-SceI digestion was followed by irradiation at a dose of 8.5 mGy, delivered at a dose rate of only 0.125 mGy h(-1), HR repair efficiency was enhanced by approximately 80%. This experimental approach can be applied to characterize DSB repair in the low-dose region of ionizing radiation.

  12. Characterizing low dose and dose rate effects in rodent and human neural stem cells exposed to proton and gamma irradiation

    Directory of Open Access Journals (Sweden)

    Bertrand P. Tseng

    2013-01-01

    Full Text Available Past work has shown that exposure to gamma rays and protons elicit a persistent oxidative stress in rodent and human neural stem cells (hNSCs. We have now adapted these studies to more realistic exposure scenarios in space, using lower doses and dose rates of these radiation modalities, to further elucidate the role of radiation-induced oxidative stress in these cells. Rodent neural stem and precursor cells grown as neurospheres and human neural stem cells grown as monolayers were subjected to acute and multi-dosing paradigms at differing dose rates and analyzed for changes in reactive oxygen species (ROS, reactive nitrogen species (RNS, nitric oxide and superoxide for 2 days after irradiation. While acute exposures led to significant changes in both cell types, hNSCs in particular, exhibited marked and significant elevations in radiation-induced oxidative stress. Elevated oxidative stress was more significant in hNSCs as opposed to their rodent counterparts, and hNSCs were significantly more sensitive to low dose exposures in terms of survival. Combinations of protons and γ-rays delivered as lower priming or higher challenge doses elicited radioadaptive changes that were associated with improved survival, but in general, only under conditions where the levels of reactive species were suppressed compared to cells irradiated acutely. Protective radioadaptive effects on survival were eliminated in the presence of the antioxidant N-acetylcysteine, suggesting further that radiation-induced oxidative stress could activate pro-survival signaling pathways that were sensitive to redox state. Data corroborates much of our past work and shows that low dose and dose rate exposures elicit significant changes in oxidative stress that have functional consequences on survival.

  13. Reductions in carotid chemoreceptor activity with low-dose dopamine improves baroreflex control of heart rate during hypoxia in humans.

    Science.gov (United States)

    Mozer, Michael T; Holbein, Walter W; Joyner, Michael J; Curry, Timothy B; Limberg, Jacqueline K

    2016-07-01

    The purpose of the present investigation was to examine the contribution of the carotid body chemoreceptors to changes in baroreflex control of heart rate with exposure to hypoxia. We hypothesized spontaneous cardiac baroreflex sensitivity (scBRS) would be reduced with hypoxia and this effect would be blunted when carotid chemoreceptor activity was reduced with low-dose dopamine. Fifteen healthy adults (11 M/4 F) completed two visits randomized to intravenous dopamine or placebo (saline). On each visit, subjects were exposed to 5-min normoxia (~99% SpO2), followed by 5-min hypoxia (~84% SpO2). Blood pressure (intra-arterial catheter) and heart rate (ECG) were measured continuously and scBRS was assessed by spectrum and sequence methodologies. scBRS was reduced with hypoxia (P dopamine (P dopamine (P dopamine did not attenuate the decrease in baroreflex sensitivity to falling pressures (scBRS "down-down"; P > 0.05). Present findings are consistent with a reduction in scBRS with systemic hypoxia. Furthermore, we show this effect is partially mediated by the carotid body chemoreceptors, given the fall in scBRS is attenuated when activity of the chemoreceptors is reduced with low-dose dopamine. However, the improvement in scBRS with dopamine appears to be specific to rising blood pressures. These results may have important implications for impairments in baroreflex function common in disease states of acute and/or chronic hypoxemia, as well as the experimental use of dopamine to assess such changes.

  14. Low dose rate caesium-137 implant time of intracavitary brachytherapy source of a selected oncology center in Ghana

    Directory of Open Access Journals (Sweden)

    John Owusu Banahene

    2015-01-01

    Full Text Available Background: The treatment time taken for a radioactive source is found to be very important in intracavitary brachytherapy treatment. The duration of the treatment time depends on the prescribed dose requested to a reference point and the calculated dose rate to the same point. The duration of the treatment time of source is found to depend on the tumour stage. In this work, the treatment time of implant has been calculated for a Caesium-137 low dose rate brachytherapy source at an oncology facility in Ghana. Objective: The objective was to determine how the treatment time of tumours depends on the dose rate to the reference point prescribed by the Oncologists and the dose rate determined by the dosimetrists at the facility. Materials and Method: Depending upon the stage of the cancer, the Oncologist determines the type of treatment modality, source configuration for the cancer patient and positions of both tandem and ovoids in the cervix. Depending also on the tumour stage, two orthogonal radiographic X-ray films are taken using a simulator machine. The treatment machine used in the study is AMRA-Curietron. The maximum activity of the source was 259GBq. It has five channels which is a manual remote afterloader. In clinical practice, the treatment time t is very short(only some few days for such low dose rate brachytherapy source like Cs-137 which lasts only for some few days in comparison with the half life of the Cs-137 source. The mathematical equation for the calculation of treatment time is written as t=D/D. Hence t is the treatment time of the radioactive source of patients undergoing intracavitary brachytherapy treatment, D is prescribed dose to a reference point and D is the dose rate to the same reference point. Results: The calculated treatment time of the Cs-137 brachytherapy source for different source arrangements or channels used in clinical practice at the brachytherapy Centre have been determined. Also provided, are the

  15. The effect of low dose rate irradiation on the swelling of 12% cold-worked 316 stainless steel.

    Energy Technology Data Exchange (ETDEWEB)

    Allen, T. R.

    1999-03-02

    In pressurized water reactors (PWRs), stainless steel components are irradiated at temperatures that may reach 400 C due to gamma heating. If large amounts of swelling (>10%) occur in these reactor internals, significant swelling related embrittlement may occur. Although fast reactor studies indicate that swelling should be insignificant at PWR temperatures, the low dose rate conditions experienced by PWR components may possibly lead to significant swelling. To address these issues, JNC and ANL have collaborated to analyze swelling in 316 stainless steel, irradiated in the EBR-II reactor at temperatures from 376-444 C, at dose rates between 4.9 x 10{sup {minus}8} and 5.8 x 10{sup {minus}7} dpa/s, and to doses of 56 dpa. For these irradiation conditions, the swelling decreases markedly at temperatures less than approximately 386 C, with the extrapolated swelling at 100 dpa being around 3%. For temperatures greater than 386 C, the swelling extrapolated to 100 dpa is around 9%. For a factor of two difference in dose rate, no statistically significant effect of dose rate on swelling was seen. For the range of dose rates analyzed, the swelling measurements do not support significant (>10%) swelling of 316 stainless steel in PWRs.

  16. Low-Dose-Rate Californium-252 Neutron Intracavitary Afterloading Radiotherapy Combined With Conformal Radiotherapy for Treatment of Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Min [Department of Oncology, Armed Police Hospital of Hangzhou, Hangzhou, Zhejiang Province (China); Xu Hongde [Cancer Center, Armed Police Hospital of Hangzhou, Hangzhou, Zhejiang Province (China); Pan Songdan; Lin Shan; Yue Jianhua [Department of Oncology, Armed Police Hospital of Hangzhou, Hangzhou, Zhejiang Province (China); Liu Jianren, E-mail: liujianren0571@hotmail.com [Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province (China)

    2012-07-01

    Purpose: To study the efficacy of low-dose-rate californium-252 ({sup 252}Cf) neutron intracavitary afterloading radiotherapy (RT) combined with external pelvic RT for treatment of cervical cancer. Methods and Materials: The records of 96 patients treated for cervical cancer from 2006 to 2010 were retrospectively reviewed. For patients with tumors {<=}4 cm in diameter, external beam radiation was performed (1.8 Gy/day, five times/week) until the dose reached 20 Gy, and then {sup 252}Cf neutron intracavitary afterloading RT (once/week) was begun, and the frequency of external beam radiation was changed to four times/week. For patients with tumors >4 cm, {sup 252}Cf RT was performed one to two times before whole-pelvis external beam radiation. The tumor-eliminating dose was determined by using the depth limit of 5 mm below the mucosa as the reference point. In all patients, the total dose of the external beam radiation ranged from 46.8 to 50 Gy. For {sup 252}Cf RT, the dose delivered to point A was 6 Gy/fraction, once per week, for a total of seven times, and the total dose was 42 Gy. Results: The mean {+-} SD patient age was 54.7 {+-} 13.7 years. Six patients had disease assessed at stage IB, 13 patients had stage IIA, 49 patients had stage IIB, 3 patients had stage IIIA, 24 patients had stage IIIB, and 1 patient had stage IVA. All patients obtained complete tumor regression (CR). The mean {+-} SD time to CR was 23.5 {+-} 3.4 days. Vaginal bleeding was fully controlled in 80 patients within 1 to 8 days. The mean {+-} SD follow-up period was 27.6 {+-} 12.7 months (range, 6-48 months). Five patients died due to recurrence or metastasis. The 3-year survival and disease-free recurrence rates were 89.6% and 87.5 %, respectively. Nine patients experienced mild radiation proctitis, and 4 patients developed radiocystitis. Conclusions: Low-dose-rate {sup 252}Cf neutron RT combined with external pelvic RT is effective for treating cervical cancer, with a low incidence of

  17. Macroarray analysis of gene expression in hematopoietic tissues from mice continuously irradiated by low dose-rate ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Saitou, Mikio; Nakamura, Shingo; Shirata, Katsutoshi; Yanai, Takanori; Izumi, Jun; Sugihara, Takashi; Tanaka, Satoshi; Tanaka, Kimio; Otsu, Hiroshi; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan)

    2002-07-01

    We found that the number of hematopoietic progenitor cells in bone marrow and spleen from 4 - 8 Gy-irradiated mice decreased about 50%, in spite of no change in the number of peripheral blood cells. To evaluate the effects of chronic irradiation by low dose-rate ionizing radiation on the gene expression in mice hematopoietic cells from bone marrow and spleen, the RNA expressions of more than 500 genes such as cytokine genes and oncogenes were measured on the membranes by the RNA macroarray analysis method at accumulated doses at 4.7 and 8 Gy in specific-pathogen-free (SPF) C3H/HeN female mice irradiated by {sup 137}Cs {gamma}-rays with the dose rate of 20 mGy/day. The RNA macroarray analysis in spleens from 8 Gy-irradiated mice showed that the expressions in 16 genes including noggin were more than 1.5 times larger than that of control, while those in 64 genes including shh (sonic hedgehog) and BMP-4 (bone morphogenesis protein 4) were more than 1.5 times smaller than that of control. (author)

  18. Monte Carlo validation and optimisation of detector packaging for spectroscopic dosimetry for in vivo urethral dosimetry during low dose rate brachytherapy.

    Science.gov (United States)

    Nourbehesht, L K; Cutajar, D L; Guatelli, S; Rosenfeld, A B

    2015-09-01

    The urethral mini-dosimeter, developed by the Centre for Medical Radiation Physics, University of Wollongong, uses spectroscopic dosimetry to provide real time point dose measurements along the urethra during low dose rate prostate brachytherapy. Spectroscopic dosimetry uses the measured spectrum of the treatment isotope to estimate the dose rate at the point of measurement, however, the silicon mini-detectors employed in the urethral mini-dosimeter require water proof encapsulation which must be capable of providing electromagnetic shielding without greatly increasing the size of the probe. The introduction of non-tissue equivalent materials within the encapsulation can change the spectrum of radiation incident on the detector, which may influence the application of spectroscopic dosimetry within the urethral dosimeter. The Monte Carlo code Geant4 was adopted to study the effect of encapsulation on the operation of the urethral mini-dosimeter, as well as to determine whether an appropriate thickness of aluminium shielding was possible for electromagnetic screening. The depth dose response and angular dependence of the urethral mini-dosimeter with three thicknesses of aluminium shielding (20, 50, 100 µm) was compared with the urethral mini-dosimeter without aluminium shielding. The aluminium shielding had the effect of increasing the depth dose response (up to 3% within 30 mm and up to 5% within 50 mm), slightly reduced the azimuth angular dependence and slightly increased the polar angular dependence. The 100 µm thick shielding provided the least azimuth angular dependence (±2 %) and provided a polar angular dependence of ±1.4 % within the angles of -45° to 45°.

  19. Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart.

    Science.gov (United States)

    Seawright, John W; Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A; Hauer-Jensen, Martin; Boerma, Marjan

    2017-01-01

    Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and

  20. Possible use of EPDM in radioactive waste disposal: Long term low dose rate and short term high dose rate irradiation in aquatic and atmospheric environment

    Science.gov (United States)

    Hacıoğlu, Fırat; Özdemir, Tonguç; Çavdar, Seda; Usanmaz, Ali

    2013-02-01

    In this study, changes in the properties of ethylene propylene diene terpolymer (EPDM) irradiated with different dose rates in ambient atmosphere and aqueous environment were investigated. Irradiations were carried out both with low dose and high dose rate irradiation sources. EPDM samples which were differentiated from each other by peroxide type and 5-ethylidene 2-norbornene (ENB) contents were used. Long term low dose rate irradiations were carried out for the duration of up to 2.5 years (total dose of 1178 kGy) in two different irradiation environments. Dose rates (both high and low), irradiation environments (in aquatic and open to atmosphere), and peroxide types (aliphatic or aromatic) were the parameters studied. Characterization of irradiated EPDM samples were performed by hardness, compression, tensile, dynamic mechanical analysis (DMA), TGA-FTIR, ATR-FTIR, XRD and SEM tests. It was observed that the irradiation in water environment led to a lower degree of degradation when compared to that of irradiation open to atmosphere for the same irradiation dose. In addition, irradiation environment, peroxide type and dose rate had effects on the extent of change in the properties of EPDM. It was observed that EPDM is relatively radiation resistant and a candidate polymer for usage in radioactive waste management.

  1. The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

    Institute of Scientific and Technical Information of China (English)

    Rui-Yi Wu; Guo-Min Wang; Lei Xu; Bo-Heng Zhang; Ye-Qing Xu; Zhao-Chong Zeng; Bing Chen

    2011-01-01

    The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound (HIFU) combined with (+) low-dose external beam radiotherapy (LRT) as supplemental therapy for advanced prostate cancer (PCa) following hormonal therapy (HT). Our definition of HIFU+LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy (CRT). We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU+LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU+LRT treatment. There were significant differences among four groups with regard to overall survival (OS) and disease-specific survival (DSS) curves (P=0.018 and 0.015). Further comparison between each pair of groups suggested that the long-term DSS of the HIFU+LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU+LRT group and the CRT group. Multivariable Cox's proportional hazard model showed that both HIFU+LRT and CRT were independently associated with DSS (P=0.001 and 0.035) and had protective effects with regard to the risk of death. Compared with CRT, HIFU+LRT significantly decreased incidences of radiation-related late gastrointestinal (GI) and genitourinary (GU) toxicity grade ≥II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and regional lymph node metastases after HT. As an alternative to CRT, HIFU+LRT showed good efficacy and better safety.

  2. Local Tumor Control and Normal Tissue Toxicity of Pulsed Low-Dose Rate Radiotherapy for Recurrent Lung Cancer

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    2015-05-01

    Full Text Available Objectives: This study investigates (1 local tumor control and (2 normal tissue toxicity of pulsed low-dose rate radiotherapy (PLDR for recurrent lung cancer. Methods: For study 1, nude mice were implanted with A549 tumors and divided into the following 3 groups: (1 control (n = 10, (2 conventional radiotherapy (RT; n = 10, and (3 PLDR (n = 10. Tumor-bearing mice received 2 Gy daily dose for 2 consecutive days. Weekly magnetic resonance imaging was used for tumor growth monitoring. For study 2, 20 mice received 8 Gy total body irradiation either continuously (n = 10 or 40 × 0.2 Gy pulses with 3-minute intervals (n = 10. Results: For study 1, both conventional RT and PLDR significantly inhibited the growth of A549 xenografts compared with the control group (>35% difference in the mean tumor volume; P .05. For study 2, the average weight was 20.94 ± 1.68 g and 25.69 ± 1.27 g and the survival time was 8 days and 12 days for mice treated with conventional RT and PLDR (P < .05, respectively. Conclusion: This study showed that PLDR could control A549 tumors as effectively as conventional RT, and PLDR induced much less normal tissue toxicity than conventional RT. Thus, PLDR would be a good modality for recurrent lung cancers. Advances in Knowledge: This article reports our results of an in vivo animal investigation of PLDR for the treatment of recurrent cancers, which may not be eligible for treatment because of the dose limitations on nearby healthy organs that have been irradiated in previous treatments. This was the first in vivo study to quantify the tumor control and normal tissue toxicities of PLDR using mice with implanted tumors, and our findings provided evidence to support the clinical trials that employ PLDR treatment techniques.

  3. Health effects of prolonged low-dose rate gamma-irradiation of a human population in Taiwan, 1983-2003

    Energy Technology Data Exchange (ETDEWEB)

    Chang, W. P.; Hsieh, W. A.; Lin, Y. P.; Huang, S.; Hwang, B. F.; Lee, S. D.; Chen, J. C.; Tsai, M.; Yen, N. P.

    2004-07-01

    Health effects of low dose-rate , low LET irradiation on large numbers of human population have been rare and less well known and studied. However, the standards for safety and health regulation for radiation exposure depend on solid observations of related studies. during 1983 to mid 1990s, an unusual contamination occurred that was derived from several lost Co-60 orphan sources and un-intentionally recycled into thousands tons construction steels, eventually employed for construction in several cities in Taiwan. Continuous studies on the immediate and prolonged health effects of these 7,000 subjects, with more than 60% have been exposed during prenatal, childhood, and adolescents periods, have been able to form a stron scientific avenue to provide evidences for unusual observation on a human population in natural environments. Moreover, an exposure reconstruction program, co-joined with scientists in National Institute of Occupational Safety and Health and Oregan State University in the U. S.; were initiated and continued throughout the study program that critically provided dose response analysis feasible. These studies include bone marrow/hematological changes, lens opacities, thyroid function and thyroid glands abnormalities, growth and development in physical parameters, helper and suppressor T cell populations, serum p53 protein levels, and cancer incidences and risks. Moreover, several cytogenetic markers have been employed to analyze the subtle changes in the somatic tissues. These include frequencies of micronuclei formation, chromosomal aberrations and chromosomal translocations on circulating T-lymphocytes. Functional studies including IQ testing on prenatally exposed children and the reproductive potential as time-to-pregnancy, TTP, were also observed in married couples with offspring. The observations, published in more than 20 manuscripts, will be summarized and presented for future collaborative studies, based on the established database, case

  4. Characterization of the neutron irradiation system for use in the Low-Dose-Rate Irradiation Facility at Sandia National Laboratories.

    Energy Technology Data Exchange (ETDEWEB)

    Franco, Manuel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-08-01

    The objective of this work was to characterize the neutron irradiation system consisting of americium-241 beryllium (241AmBe) neutron sources placed in a polyethylene shielding for use at Sandia National Laboratories (SNL) Low Dose Rate Irradiation Facility (LDRIF). With a total activity of 0.3 TBq (9 Ci), the source consisted of three recycled 241AmBe sources of different activities that had been combined into a single source. The source in its polyethylene shielding will be used in neutron irradiation testing of components. The characterization of the source-shielding system was necessary to evaluate the radiation environment for future experiments. Characterization of the source was also necessary because the documentation for the three component sources and their relative alignment within the Special Form Capsule (SFC) was inadequate. The system consisting of the source and shielding was modeled using Monte Carlo N-Particle transport code (MCNP). The model was validated by benchmarking it against measurements using multiple techniques. To characterize the radiation fields over the full spatial geometry of the irradiation system, it was necessary to use a number of instruments of varying sensitivities. First, the computed photon radiography assisted in determining orientation of the component sources. With the capsule properly oriented inside the shielding, the neutron spectra were measured using a variety of techniques. A N-probe Microspec and a neutron Bubble Dosimeter Spectrometer (BDS) set were used to characterize the neutron spectra/field in several locations. In the third technique, neutron foil activation was used to ascertain the neutron spectra. A high purity germanium (HPGe) detector was used to characterize the photon spectrum. The experimentally measured spectra and the MCNP results compared well. Once the MCNP model was validated to an adequate level of confidence, parametric analyses was performed on the model to optimize for potential

  5. Impact of low-dose acetylsalicylic acid on kidney function in type 2 diabetic patients with elevated urinary albumin excretion rate

    DEFF Research Database (Denmark)

    Gaede, Peter; Hansen, Henrik Post; Parving, Hans-Henrik

    2003-01-01

    Low-dose treatment with acetylsalicylic acid (ASA) is widely recommended to type 2 diabetic patients as primary prevention against cardiovascular disease. High-dose treatment with cyclooxygenase inhibitors reduces urinary albumin excretion rate (AER) in type 1 diabetic patients with micro...

  6. Radiation Leukemogenesis: Applying Basic Science of Epidemiological Estimates of Low Dose Risks and Dose-Rate Effects

    Energy Technology Data Exchange (ETDEWEB)

    Hoel, D. G.

    1998-11-01

    The next stage of work has been to examine more closely the A-bomb leukemia data which provides the underpinnings of the risk estimation of CML in the above mentioned manuscript. The paper by Hoel and Li (Health Physics 75:241-50) shows how the linear-quadratic model has basic non-linearities at the low dose region for the leukemias including CML. Pierce et. al., (Radiation Research 123:275-84) have developed distributions for the uncertainty in the estimated exposures of the A-bomb cohort. Kellerer, et. al., (Radiation and Environmental Biophysics 36:73-83) has further considered possible errors in the estimated neutron values and with changing RBE values with dose and has hypothesized that the tumor response due to gamma may not be linear. We have incorporated his neutron model and have constricted new A-bomb doses based on his model adjustments. The Hoel and Li dose response analysis has also been applied using the Kellerer neutron dose adjustments for the leukemias. Finally, both Pierce's dose uncertainties and Kellerer neutron adjustments are combined as well as the varying RBE with dose as suggested by Rossi and Zaider and used for leukemia dose-response analysis. First the results of Hoel and Li showing a significantly improved fit of the linear-quadratic dose response by the inclusion of a threshold (i.e. low-dose nonlinearity) persisted. This work has been complete for both solid tumor as well as leukemia for both mortality as well as incidence data. The results are given in the manuscript described below which has been submitted to Health Physics.

  7. In vitro studies on the modification of low-dose hyper-radiosensitivity in prostate cancer cells by incubation with genistein and estradiol

    Directory of Open Access Journals (Sweden)

    Thelen Paul

    2008-07-01

    Full Text Available Abstract Background As the majority of prostate cancers (PC express estrogen receptors, we evaluated the combination of radiation and estrogenic stimulation (estrogen and genistein on the radiosensitivity of PC cells in vitro. Methods PC cells LNCaP (androgen-sensitive and PC-3 (androgen-independent were evaluated. Estrogen receptor (ER expression was analyzed by means of immunostaining. Cells were incubated in FCS-free media with genistein 10 μM and estradiol 10 μM 24 h before irradiation and up to 24 h after irradiation. Clonogenic survival, cell cycle changes, and expression of p21 were assessed. Results LNCaP expressed both ER-α and ER-β, PC-3 did not. Incubation of LNCaP and PC-3 with genistein resulted in a significant reduction of clonogenic survival. Incubation with estradiol exhibited in low concentrations (0.01 μM stimulatory effects, while higher concentrations did not influence survival. Both genistein 10 μM and estradiol 10 μM increased low-dose hyper-radiosensitivity [HRS] in LNCaP, while hormonal incubation abolished HRS in PC-3. In LNCaP cells hormonal stimulation inhibited p21 induction after irradiation with 4 Gy. In PC-3 cells, the proportion of cells in G2/M was increased after irradiation with 4 Gy. Conclusion We found an increased HRS to low irradiation doses after incubation with estradiol or genistein in ER-α and ER-β positive LNCaP cells. This is of high clinical interest, as this tumor model reflects a locally advanced, androgen dependent PC. In contrast, in ER-α and ER-β negative PC-3 cells we observed an abolishing of the HRS to low irradiation doses by hormonal stimulation. The effects of both tested compounds on survival were ER and p53 independent. Since genistein and estradiol effects in both cell lines were comparable, neither ER- nor p53-expression seemed to play a role in the linked signalling. Nevertheless both compounds targeted the same molecular switch. To identify the underlying molecular

  8. Treatment Outcome of Medium-Dose-Rate Intracavitary Brachytherapy for Carcinoma of the Uterine Cervix: Comparison With Low-Dose-Rate Intracavitary Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kaneyasu, Yuko, E-mail: kaneyasu@hiroshima-u.ac.jp [Department of Radiation Oncology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima (Japan); Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan); Kita, Midori [Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan); Department of Clinical Radiology, Tokyo Metropolitan Tama Medical Center, Tokyo (Japan); Okawa, Tomohiko [Evaluation and Promotion Center, Utsunomiya Memorial Hospital, Tochigi (Japan); Maebayashi, Katsuya [Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan); Kohno, Mari [Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women' s Medical University Hospital, Tokyo (Japan); Sonoda, Tatsuo; Hirabayashi, Hisae [Department of Radiology, Tokyo Women' s Medical University Hospital, Tokyo (Japan); Nagata, Yasushi [Department of Radiation Oncology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima (Japan); Mitsuhashi, Norio [Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan)

    2012-09-01

    Purpose: To evaluate and compare the efficacy of medium-dose-rate (MDR) and low-dose-rate (LDR) intracavitary brachytherapy (ICBT) for uterine cervical cancer. Methods and Materials: We evaluated 419 patients with squamous cell carcinoma of the cervix who were treated by radical radiotherapy with curative intent at Tokyo Women's Medical University from 1969 to 1999. LDR was used from 1969 to 1986, and MDR has been used since July 1987. When compared with LDR, fraction dose was decreased and fraction size was increased (1 or 2 fractions) for MDR to make the total dose of MDR equal to that of LDR. In general, the patients received a total dose of 60 to 70 Gy at Point A with external beam radiotherapy combined with brachytherapy according to the International Federation of Gynecology and Obstetrics stage. In the LDR group, 32 patients had Stage I disease, 81 had Stage II, 182 had Stage III, and 29 had Stage IVA; in the MDR group, 9 patients had Stage I disease, 19 had Stage II, 55 had Stage III, and 12 had Stage IVA. Results: The 5-year overall survival rates for Stages I, II, III, and IVA in the LDR group were 78%, 72%, 55%, and 34%, respectively. In the MDR group, the 5-year overall survival rates were 100%, 68%, 52%, and 42%, respectively. No significant statistical differences were seen between the two groups. The actuarial rates of late complications Grade 2 or greater at 5 years for the rectum, bladder, and small intestine in the LDR group were 11.1%, 5.8%, and 2.0%, respectively. The rates for the MDR group were 11.7%, 4.2%, and 2.6%, respectively, all of which were without statistical differences. Conclusion: These data suggest that MDR ICBT is effective, useful, and equally as good as LDR ICBT in daytime (about 5 hours) treatments of patients with cervical cancer.

  9. Immunological network activation by low-dose rate irradiation. Analysis of cell populations and cell surface molecules in whole body irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Ina, Yasuhiro; Sakai, Kazuo [Central Research Inst. of Electric Power Industry, Low Dose Radiation Research Center, Komae, Tokyo (Japan)

    2003-07-01

    The effects of low-dose rate whole body irradiation on biodefense and immunological systems were investigated using female C57BL/6 (B6) mice. These B6 mice were exposed continuously to {gamma}-rays from a {sup 137}Cs source in the long-term low-dose rate irradiation facility at CRIEPI for 0 - 12 weeks at a dose rate of 0.95 mGy/hr. In the bone marrow, thymus, spleen, lymph nodes, and peripheral blood of the irradiated mice, changes in cell populations and cell surface molecules were examined. The cell surface functional molecules (CD3, CD4, CD8, CD19, CD45R/B220, ICAM-1, Fas, NK-1.1, CXCR4, and CCR5), and activation molecules (THAM, CD28, CD40, CD44H, CD70, B7-1, B7-2, OX-40 antigen, CTLA-4, CD30 ligand, and CD40 ligand) were analyzed by flow cytometry. The percentage of CD4{sup +} T cells and cell surface CD8 molecule expressions on the CD8{sup +} T cells increased significantly to 120-130% after 3 weeks of the irradiation, compared to non-irradiated control mice. On the other hand, the percentage of CD45R/B220{sup +} CD40{sup +} B cells, which is one of the immunological markers of inflammation, infection, tumor, and autoimmune disease, decreased significantly to 80-90% between the 3rd to 5th week of irradiation. There was no significant difference in other cell population rates and cell surface molecule expression. Furthermore, abnormal T cells bearing mutated T cell receptors induced by high-dose rate irradiation were not observed throughout this study. These results suggest that low-dose rate irradiation activates the immunological status of the whole body. (author)

  10. Enhancement of viability of radiosensitive (PBMC) and resistant (MDA-MB-231) clones in low-dose-rate cobalt-60 radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Falcao, Patricia Lima, E-mail: patricialfalcao@gmail.com [Universidade Federal do Amazonas (UFAM), Manaus, AM (Brazil); Motta, Barbara Miranda; Lima, Fernanda Castro de; Lima, Celso Vieira; Campos, Tarcisio Passos Ribeiro [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2015-05-15

    Objective: in the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231) cells line and radiosensitive peripheral blood mononuclear cells (PBMC), as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and methods: the cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min{sup -1} and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results: radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB-231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48-72 hours post-radiation. Conclusion: low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer. (author)

  11. Enhancement of viability of radiosensitive (PBMC and resistant (MDA-MB-231 clones in low-dose-rate cobalt-60 radiation therapy

    Directory of Open Access Journals (Sweden)

    Patrícia Lima Falcão

    2015-06-01

    Full Text Available Abstract Objective: In the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231 cells line and radiosensitive peripheral blood mononuclear cells (PBMC, as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and Methods: The cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min–1 and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results: Radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB- 231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48–72 hours post-radiation. Conclusion: Low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer.

  12. Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders.

    Science.gov (United States)

    Griffin, Daniel; Benadiva, Claudio; Kummer, Nicole; Budinetz, Tara; Nulsen, John; Engmann, Lawrence

    2012-06-01

    To compare live birth rates after dual trigger of oocyte maturation with GnRH agonist (GnRHa) and low-dose hCG versus GnRHa alone in high responders with peak E(2) triggered with GnRHa alone or GnRHa plus 1,000 IU hCG (dual trigger) for oocyte maturation. GnRHa alone versus dual trigger. Live birth, implantation, and clinical pregnancy rates and OHSS. The dual-trigger group had a significantly higher live birth rate (52.9% vs. 30.9%), implantation rate (41.9% vs. 22.1%), and clinical pregnancy rate (58.8% vs. 36.8%) compared with the GnRHa trigger group. One case of mild OHSS occurred in the dual-trigger group, and there were no cases of OHSS in the GnRHa trigger group. Dual trigger of oocyte maturation with GnRHa and low-dose hCG in high responders with peak E(2) birth without increasing the risk of significant OHSS. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Effects of orientation of substrate on the enhanced low-dose-rate sensitivity (ELDRS) in NPN transistors

    Institute of Scientific and Technical Information of China (English)

    LU Wu; ZHENG Yu-Zhan; WANG Yi-Yuan; REN Di-Yuan; GUO Qi; WANG Zhi-Kuan; WANG Jian-An

    2011-01-01

    The radiation effects and annealing characteristics of two types of domestic NPN bipolar junction transistors, fabricated with different orientations, were investigated under different dose-rate irradiation. The experimental results show that both types o

  14. High and low dose rate irradiation have opposing effects on cytokine gene expression in human glioblastoma cell lines.

    Science.gov (United States)

    Ross, H J; Canada, A L; Antoniono, R J; Redpath, J L

    1997-01-01

    Effects of radiation on five cytokine expressing human glioblastoma cell lines were studied. In comparison to unirradiated controls, IL-1 beta and IL-6 mRNAs were generally reduced after low (LDR, 1.0 cGy/min) and very low (VLDR, 0.35 cGy/min) dose rate irradiation. In contrast, high (HDR, 200 cGy/min) and intermediate (IDR, 4.1 cGy/min) dose rates increased steady-state levels of IL-1 beta and IL-6 mRNAs. The surviving fraction was generally inversely proportional to the dose rate; however, these glioma cells were unusually susceptible to LDR. In the two cell lines tested, IDR was less cytotoxic than either HDR or LDR irradiation. Although cytokine gene expression had no clear effect on radiation survival in vitro, autologous cytokines could be important to radiation response in vivo by affecting immune response, tumour stroma, vasculature or surrounding tissues. Adjusting dose rates to account for inverse dose rate effects and altered gene expression may be a useful strategy in optimising radiation therapy of glioblastomas.

  15. High and low dose rate irradiation have opposing effects on cytokine gene expression in human glioblastoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Ross, H.J.; Canada, A.L.; Antoniono, R.J.; Redpath, J.L. [California Univ., Irvine, CA (United States)

    1997-01-01

    Effects of radiation on five cytokine expressing human glioblastoma cell lines were studied. In comparison to unirradiated controls, IL-1{beta} and IL-6 mRNAs were generally reduced after low (LDR, 1.0 cGy/min) and very low (VLDR, 0.35 cGy/min) dose rate irradiation. In contrast, high (HDR, 200 cGy/min) and intermediate (IDR, 4.1 cGy/min) dose rates increased steady-state levels of IL-1{beta} and IL-6 mRNAs. The surviving fraction was generally inversely proportional to the dose rate; however, these glioma cells were unusually to susceptible LDR. In the two cell lines tested, IDR was less cytotoxic than either HDR or LDR irradiation. Although cytokine gene expression had no clear effect on radiation survival in vitro, autologous cytokines could be important to radiation response in vivo by affecting immune response, tumour stroma, vasculature or surrounding tissues. Adjusting dose rates to account for inverse dose rate effects and altered gene expression may be a useful strategy in optimising radiation therapy of gliobastomas. (Author).

  16. Low-dose-rate high-let radiation cytogenetic effects on mice in vivo as model of space radiation action on mammalian

    Science.gov (United States)

    Sorokina, Svetlana; Zaichkina, Svetlana; Rozanova, Olga; Aptikaeva, Gella; Romanchenko, Sergei; Smirnova, Helene; Dyukina, Alsu; Peleshko, Vladimir

    At present time little is known concerning the biological effects of low-dose-rate high-LET radiation exposure in space. The currently available experimental data on the biological effect of low doses of chronic radiation with high-LET values, which occur under the conditions of aircraft and space flights, have been primarily obtained in the examinations of pilots and astronauts after flights. Another way of obtaining this kind of evidence is the simulation of irradiation conditions during aircraft and space flights on high-energy accelerators and the conduction of large-scale experiments on animals under these conditions on Earth. In the present work, we investigated the cytogenetic effects of low-dose-rate high-LET radiation in the dose ranges of 0.2-30 cGy (1 cGy/day) and 0.5-16 cGy (0.43 cGy/day) in the radiation field behind the concrete shield of the Serpukhov accelerator of 70 GeV protons that simulates the spectral and component composition of radiation fields formed in the conditions of high-altitude flights on SHK mice in vivo. The dose dependence, adaptive response (AR) and the growth of solid tumor were examined. For induction of AR, two groups of mice were exposed to adapting doses of 0.2-30 cGy and the doses of 0.5-16 cGy of high-LET radiation. For comparison, third group of mice from unirradiated males was chronically irradiated with X-rays at adapting doses of 10 cGy (1 cGy/day). After a day, the mice of all groups were exposed to a challenging dose of 1.5 Gy of X-rays (1 Gy/min). After 28 h, the animals of all groups were killed by the method of cervical dislocation. Bone marrow specimens for calculating micronuclei (MN) in polychromatic erythrocytes (PCE) were prepared by a conventional method with minor modifications. The influence of adapting dose of 16 cGy on the growth of solid tumor of Ehrlich ascite carcinoma was estimated by measuring the size of the tumor at different times after the inoculation of ascitic cells s.c. into the femur. It was

  17. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Olga Loseva

    2014-07-01

    Full Text Available The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR exposure (5 or 15 mGy/h of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

  18. Solar Variability and the Near-Earth Environment: Mining Enhanced Low Dose Rate Sensitivity Data From the Microelectronics and Photonics Test Bed Space Experiment

    Science.gov (United States)

    Turflinger, T.; Schmeichel, W.; Krieg, J.; Titus, J.; Campbell, A.; Reeves, M.; Marshall (P.); Hardage, Donna (Technical Monitor)

    2004-01-01

    This effort is a detailed analysis of existing microelectronics and photonics test bed satellite data from one experiment, the bipolar test board, looking to improve our understanding of the enhanced low dose rate sensitivity (ELDRS) phenomenon. Over the past several years, extensive total dose irradiations of bipolar devices have demonstrated that many of these devices exhibited ELDRS. In sensitive bipolar transistors, ELDRS produced enhanced degradation of base current, resulting in enhanced gain degradation at dose rates 1 rd(Si)/s. This Technical Publication provides updated information about the test devices, the in-flight experiment, and both flight-and ground-based observations. Flight data are presented for the past 5 yr of the mission. These data are compared to ground-based data taken on devices from the same date code lots. Information about temperature fluctuations, power shutdowns, and other variables encountered during the space flight are documented.

  19. Evidence That Lifelong Low Dose Rates of Ionizing Radiation Increase Lifespan in Long- and Short-Lived Dogs.

    Science.gov (United States)

    Cuttler, Jerry M; Feinendegen, Ludwig E; Socol, Yehoshua

    2017-01-01

    After the 1956 radiation scare to stop weapons testing, studies focused on cancer induction by low-level radiation. Concern has shifted to protecting "radiation-sensitive individuals." Since longevity is a measure of health impact, this analysis reexamined data to compare the effect of dose rate on the lifespans of short-lived (5% and 10% mortality) dogs and on the lifespans of dogs at 50% mortality. The data came from 2 large-scale studies. One exposed 10 groups to different γ dose rates; the other exposed 8 groups to different lung burdens of plutonium. Reexamination indicated that normalized lifespans increased more for short-lived dogs than for average dogs, when radiation was moderately above background. This was apparent by interpolating between the lifespans of nonirradiated dogs and exposed dogs. The optimum lifespan increase appeared at 50 mGy/y. The threshold for harm (decreased lifespan) was 700 mGy/y for 50% mortality dogs and 1100 mGy/y for short-lived dogs. For inhaled α-emitting particulates, longevity was remarkably increased for short-lived dogs below the threshold for harm. Short-lived dogs seem more radiosensitive than average dogs and they benefit more from low radiation. If dogs model humans, this evidence would support a change to radiation protection policy. Maintaining exposures "as low as reasonably achievable" (ALARA) appears questionable.

  20. Evidence That Lifelong Low Dose Rates of Ionizing Radiation Increase Lifespan in Long- and Short-Lived Dogs

    Science.gov (United States)

    Feinendegen, Ludwig E.; Socol, Yehoshua

    2017-01-01

    After the 1956 radiation scare to stop weapons testing, studies focused on cancer induction by low-level radiation. Concern has shifted to protecting “radiation-sensitive individuals.” Since longevity is a measure of health impact, this analysis reexamined data to compare the effect of dose rate on the lifespans of short-lived (5% and 10% mortality) dogs and on the lifespans of dogs at 50% mortality. The data came from 2 large-scale studies. One exposed 10 groups to different γ dose rates; the other exposed 8 groups to different lung burdens of plutonium. Reexamination indicated that normalized lifespans increased more for short-lived dogs than for average dogs, when radiation was moderately above background. This was apparent by interpolating between the lifespans of nonirradiated dogs and exposed dogs. The optimum lifespan increase appeared at 50 mGy/y. The threshold for harm (decreased lifespan) was 700 mGy/y for 50% mortality dogs and 1100 mGy/y for short-lived dogs. For inhaled α-emitting particulates, longevity was remarkably increased for short-lived dogs below the threshold for harm. Short-lived dogs seem more radiosensitive than average dogs and they benefit more from low radiation. If dogs model humans, this evidence would support a change to radiation protection policy. Maintaining exposures “as low as reasonably achievable” (ALARA) appears questionable.

  1. Neutron dosimetry for low dose rate Cf-252 AT sources and adherence to recent clinical dosimetry protocol for brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Rivard, M.J.; Wierzbicki, J.G.; Van den Heuvel, F. [Wayne State Univ., Detroit, MI (United States). Dept. of Radiation Oncology; Martin, R.C. [Oak Ridge National Lab., TN (United States). Chemical Technology Div.

    1997-12-01

    In 1995, the American Association of Physicists in Medicine Task Group 43 (AAPM TG-43) published a protocol obsoleting all mixed-field radiation dosimetry for Cf-252. Recommendations for a new brachytherapy dosimetry formalism made by this Task Group favor quantification of source strength in terms of air kerma rather than apparent Curies or other radiation units. Additionally, representation of this dosimetry data in terms of radial dose functions, anisotropy functions, geometric factors, and dose rate constants are in an angular and radial (spherical) coordinate system as recommended, rather than the along-away dosimetry data (Cartesian coordinate system) currently available. This paper presents the initial results of calculated neutron dosimetry in a water phantom for a Cf-252 applicator tube (AT) type medical source soon available from Oak Ridge National Laboratory (ORNL).

  2. Effects of low-dose candesartan on the rate of re-endothelialisation following vascular wound healing

    Directory of Open Access Journals (Sweden)

    Prakash Koshy

    2001-03-01

    Full Text Available The wound healing response of the vascular wall to injury involves re-endothelialisation of the denuded luminal surface and thickening of the intimal area (intimal hyperplasia, as expressed by the intimal-to-medial area ratio (I/M. Candesartan, at doses of 1 mg/kg/day or higher, has been reported to attenuate the intimal hyperplastic response. We tested the hypothesis that candesartan, at doses lower than those associated with attenuation of intimal hyperplasia, may affect re-endothelialisation. New Zealand White rabbits were subjected to balloon catheter injury to the thoracic aorta. Candesartan, at doses of 50, 100, and 500 µg/kg/day, was delivered via an Alzet pump placed in the abdomen one week prior to aortic injury. There was no attenuation of the hyperplastic response of the aortic wall. However, at 50 µg/kg/day the rate of reendothelialisation was significantly increased. These data suggest that candesartan may exhibit pleiotropic effects on vascular wound healing, in addition to the well-known effect of attenuating the development of intimal hyperplasia.

  3. Separation of two sub-groups with different DNA content after treatment of T-47D breast cancer cells with low dose-rate irradiation and intermittent hypoxia.

    Science.gov (United States)

    Mikalsen, Stine Gyland; Jeppesen Edin, Nina; Sandvik, Joe Alexander; Pettersen, Erik Olai

    2017-01-01

    Background Previous studies have shown that combined treatment with internal ultra-low dose-rate irradiation selectively inactivated hypoxic T-47D breast cancer cells after three to five weeks of treatment. However, 2-3% of the hypoxic cells were found to survive and restart proliferation upon re-oxygenation. Purpose To investigate the metastatic potential and characteristics of radiosensitivity of these surviving cells, named T - 47 DS. Material and Methods The T - 47 DS cells were grown in ambient air without irradiation. A cloning experiment identified two sub-groups with different DNA content ([Formula: see text] and [Formula: see text]). Furthermore, radiosensitivity and presence of hyper-radiosensitivity (HRS) was measured by Co-60 challenge irradiation and relative migration was determined by scratch assays. Results The two subpopulations of T - 47 DS had different DNA content; one had abnormally high DNA content ([Formula: see text]) and one had DNA content similar to wild-type T-47D cells ([Formula: see text]). HRS was surprisingly present in cells of the cloned population [Formula: see text], but was absent in cells of both [Formula: see text] and T - 47 DS. The radio response of T - 47 DS, [Formula: see text] at higher radiation doses were similar to that of T-47D cells, and neither subpopulation showed increased migration compared with wild-type T-47D. Conclusion No increase in the risk of metastasis was found and only slight changes in radiosensitivity in response to conventional clinical doses was observed. Thus, the data suggest that if ultra-low dose-rate irradiation is used for targeting the hypoxic tumor fraction, conventional high dose-rate irradiation can be used to eradicate eventual surviving cells as well as cells in the well oxygenated areas of the tumor.

  4. γ-H2AX responds to DNA damage induced by long-term exposure to combined low-dose-rate neutron and γ-ray radiation.

    Science.gov (United States)

    Zhang, Junlin; He, Ying; Shen, Xianrong; Jiang, Dingwen; Wang, Qingrong; Liu, Qiong; Fang, Wen

    2016-01-01

    Risk estimates for low-dose radiation (LDR) remain controversial. The possible involvement of DNA repair-related genes in long-term low-dose-rate neutron-gamma radiation exposure is poorly understood. In this study, 60 rats were divided into control groups and irradiated groups, which were exposed to low-dose-rate n-γ combined radiation (LDCR) for 15, 30, or 60 days. The effects of different cumulative radiation doses on peripheral blood cell (PBC), subsets of T cells of peripheral blood lymphocytes (PBL) and DNA damage repair were investigated. Real-time PCR and immunoblot analyses were used to detect expression of DNA DSB-repair-related genes involved in the NHEJ pathway, such as Ku70 and Ku80, in PBL. The mRNA level of H2AX and the expression level of γ-H2AX were detected by real-time PCR, immunoblot, and flow cytometry. White blood cells (WBC) and platelets (PLT) of all ionizing radiation (IR) groups decreased significantly, while no difference was seen between the 30 day and 60 day exposure groups. The numbers of CD3(+), CD4(+) T cells and CD4(+)/CD8(+) in the PBL of IR groups were lower than in the control group. In the 30 day and 60 day exposure groups, CD8(+) T cells decreased significantly. Real-time PCR and immunoblot results showed no significant difference in the mRNA and protein expression of Ku70 and Ku80 between the control groups and IR groups. However, the mRNA of H2AX increased significantly, and there was a positive correlation with dose. There was no difference in the protein expression of γ-H2AX between 30 day and 60 day groups, which may help to explain the damage to PBL. In conclusion, PBL damage increased with cumulative dose, suggesting that γ-H2AX, but neither Ku70 nor Ku80, plays an important role in PBL impairment induced by LDCR. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Fukushima simulation experiment: assessing the effects of chronic low-dose-rate internal 137Cs radiation exposure on litter size, sex ratio, and biokinetics in mice

    Science.gov (United States)

    Nakajima, Hiroo; Yamaguchi, Yoshiaki; Yoshimura, Takashi; Fukumoto, Manabu; Todo, Takeshi

    2015-01-01

    To investigate the transgenerational effects of chronic low-dose-rate internal radiation exposure after the Fukushima Daiichi Nuclear Power Plant accident in Japan, 18 generations of mice were maintained in a radioisotope facility, with free access to drinking water containing 137CsCl (0 and 100 Bq/ml). The 137Cs distribution in the organs of the mice was measured after long-term ad libitum intake of the 137CsCl water. The litter size and the sex ratio of the group ingesting the 137Cs water were compared with those of the control group, for all 18 generations of mice. No significant difference was noted in the litter size or the sex ratio between the mice in the control group and those in the group ingesting the 137Cs water. The fixed internal exposure doses were ∼160 Bq/g and 80 Bq/g in the muscles and other organs, respectively. PMID:26825299

  6. Effect of irradiation temperature and strain rate on the mechanical properties of V-4Cr-4Ti irradiated to low doses in fission reactors

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J.; Snead, L.L.; Rowcliffe, A.F.; Alexander, D.J.; Gibson, L.T. [Oak Ridge National Lab., TN (United States)

    1998-09-01

    Tensile tests performed on irradiated V-(3-6%)Cr-(3-6%)Ti alloys indicate that pronounced hardening and loss of strain hardening capacity occurs for doses of 0.1--20 dpa at irradiation temperatures below {approximately}330 C. The amount of radiation hardening decreases rapidly for irradiation temperatures above 400 C, with a concomitant increase in strain hardening capacity. Low-dose (0.1--0.5 dpa) irradiation shifts the dynamic strain aging regime to higher temperatures and lower strain rates compared to unirradiated specimens. Very low fracture toughness values were observed in miniature disk compact specimens irradiated at 200--320 C to {approximately}1.5--15 dpa and tested at 200 C.

  7. Low dose rate vaginal brachytherapy of endometrial adenocarcinomas; Curietherapie vaginale postoperatoire des adenocarcinomes de l`endometre a bas debit de dose

    Energy Technology Data Exchange (ETDEWEB)

    Charra-Brumaud, C.; Peiffert, D.; Hoffstetter, S.; Luporsi, E.; Guillemin, F.; Bey, P. [Centre Alexis-Vautrin, 54 - Vandoeuvre-les-Nancy (France)

    1998-01-01

    Surgery is the primary treatment for endometrial carcinoma. Methods of complementary treatment are still debated, with the potential association of external radiotherapy and/or brachytherapy before or after surgery. This study was aimed at evaluating local control and complication rates in a series of patients treated by hysterectomy followed by postoperative vaginal low-dose rate brachytherapy (BT) combined with pelvic irradiation in case of poor prognosis factors. From 1978 to 1993, 101 patients were treated at the Centre Alexis-Vautrin, France according to this scheme. Forty five had deep myometrial invasion, and thirteen cervical involvement. Fifty patients received pelvic irradiation (median dose 46 Gy) combined with BT (dose 14 Gy, median volume 127 cm{sup 3}); 51 patients had BT alone (dose 60 Gy, median volume 71 cm{sup 3}). The 5-year overall survival rate was 83 % and the local control rate 97 % with a median follow-up of 7 years. Multivariate analysis showed two factors of bad prognosis, i.e. deep myometrial invasion and cervical involvement. Three severe complications occurred in two patients for whom the treated volume was larger than the theoretical target volume. Eleven patients developed metastases. Results obtained from this series are comparable with those of previous studies, particularly in regard to pre-operative BT. The complication rate is also satisfactory and depends on the irradiation precision and the definition of the target volume. (authors)

  8. Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats

    Energy Technology Data Exchange (ETDEWEB)

    Stanko, Jason [National Institute of Environmental Health Sciences (NIEHS); Enoch, Rolondo [North Carolina Central University, Durham; Rayner, Jennifer L [ORNL; Davis, Christine [U.S. Environmental Protection Agency; Wolf, Douglas [U.S. Environmental Protection Agency; Malarkey, David [University of North Carolina, Chapel Hill; Fenton, Suzanne [National Institute of Environmental Health Sciences (NIEHS)

    2010-12-01

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73 mg AMM/kg body weight (BW), vehicle, or 100 mg ATR/kg BW positive control, on gestation days 15 19. Preputial separation was significantly delayed in 0.87 mg and 8.73 mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.

  9. Reducing infection rates after prostate biopsy.

    Science.gov (United States)

    Wagenlehner, Florian M E; Pilatz, Adrian; Waliszewski, Przemyslaw; Weidner, Wolfgang; Johansen, Truls E Bjerklund

    2014-02-01

    Over the years, prostate biopsy has become the gold-standard technique for diagnosing prostate carcinoma. Worldwide, several million prostate biopsies are performed every year, most commonly using the transrectal approach. Preoperative antibiotic prophylaxis with fluoroquinolones has been shown to be effective for reducing infection rates. However, in recent years, an increase in febrile infection rates after transrectal prostate biopsy (from 1% to 4%) has been reported in retrospective and prospective studies. The predominant risk factor for infection seems to be the presence of fluoroquinolone-resistant bacteria in faeces. Patients at risk of fluoroquinolone resistance should receive carefully selected antibiotics at sufficient concentrations to be effective. Targeted prophylaxis after rectal flora swabbing has been shown to be efficacious compared with empirical antibiotic prophylaxis. Several forms of bowel preparations are under investigation, although none have yet been shown to significantly reduce infection rates. Perineal prostate biopsy is currently being evaluated as a strategy for preventing the inoculation of rectal flora, but limited data support this approach at present.

  10. Accelerated Partial Breast Irradiation With Low-Dose-Rate Interstitial Implant Brachytherapy After Wide Local Excision: 12-Year Outcomes From a Prospective Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hattangadi, Jona A. [Harvard Radiation Oncology Program, Boston, MA (United States); Powell, Simon N. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); MacDonald, Shannon M.; Mauceri, Thomas; Ancukiewicz, Marek [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Freer, Phoebe [Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); Lawenda, Brian [21st Century Oncology, Las Vegas, NV (United States); Alm El-Din, Mohamed A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Department of Clinical Oncology, Tanta University Hospital, Tanta (Egypt); Gadd, Michele A.; Smith, Barbara L. [Department of Surgical Oncology, Massachusetts General Hospital, Boston, MA (United States); Taghian, Alphonse G., E-mail: ataghian@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)

    2012-07-01

    Purpose: To evaluate the long-term toxicity, cosmesis, and local control of accelerated partial breast irradiation with implant brachytherapy after wide local excision for Stage T1N0 breast cancer (BCa). Materials and Methods: Between 1997 and 2001, 50 patients with Stage T1N0M0 BCa were treated in a Phase I-II protocol using low-dose-rate accelerated partial breast irradiation with implant brachytherapy after wide local excision and lymph node surgery. The total dose was escalated in three groups: 50 Gy (n = 20), 55 Gy (n = 17), and 60 Gy (n = 13). Patient- and physician-assessed breast cosmesis, patient satisfaction, toxicity, mammographic abnormalities, repeat biopsies, and disease status were prospectively evaluated at each visit. Kendall's tau ({tau}{sub {beta}}) and logistic regression analyses were used to correlate outcomes with dose, implant volume, patient age, and systemic therapy. Results: The median follow-up period was 11.2 years (range, 4-14). The patient satisfaction rate was 67%, 67% reported good-excellent cosmesis, and 54% had moderate-severe fibrosis. Higher dose was correlated with worse cosmetic outcome ({tau}{sub {beta}} 0.6, p < .0001), lower patient satisfaction ({tau}{sub {beta}} 0.5, p < .001), and worse fibrosis ({tau}{sub {beta}} 0.4, p = .0024). Of the 50 patients, 35% had fat necrosis and 34% developed telangiectasias {>=}1 cm{sup 2}. Grade 3-4 late skin and subcutaneous toxicities were seen in 4 patients (9%) and 6 patients (13%), respectively, and both correlated with higher dose ({tau}{sub {beta}} 0.3-0.5, p {<=} .01). One patient had Grade 4 skin ulceration and fat necrosis requiring surgery. Mammographic abnormalities were seen in 32% of the patients, and 30% underwent repeat biopsy, of which 73% were benign. Six patients had ipsilateral breast recurrence: five elsewhere in the breast, and one at the implant site. One patient died of metastatic BCa after recurrence. The 12-year actuarial local control, recurrence

  11. Molecular biological study-effects of prolonged irradiation by low dose-rate ionizing radiation on the production of growth factors in murine bone marrow cells

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Mikio; Yamada, Yutaka; Nakamura, Shingo [Inst. for Environmental Sciences, Dept. of Radiobiology, Rokkasho, Aomori (JP)] [and others

    2001-07-01

    To evaluate effects of prolonged irradiation by low dose-rate ionizing radiation on the production of growth factors of cells, the gene expression of five cytokines, interleukin-1{alpha} (IL-1{alpha}), IL-6, IL-11 stem cell factor (SCF) and granulocyte-macrophage colony stimulating factor (GM-CSF), of mice was measured at accumulated doses between 1 and 8 Gy, with the dose interval of 1 Gy. Ten specific-pathogen-free (SPF) C3H/HeN female mice (8 w.o.) per experimental group were irradiated with {sup 137}Cs {gamma}-rays with the doses of 5 - 8 Gy at the dose rate of 20 mGy/(22 h-day), and the gene expression of five cytokines (IL-1{alpha}, IL-6, IL-11, SCF and GM-CSF) in bone marrow and two cytokines (IL-6 and GM-CSF) in spleen cells from the mice was measured semiquantitatively by both the reverse transcriptase-polymerase chain reaction (RT-PCR) and TaqMan Real-Time PCR method. (author)

  12. Effect of a vitamin D{sub 3}-based nutritional supplement ('Videchol') on carbohydrate metabolism of rats following chronic low dose-rate irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Starikovich, L.S.; Vernikovska, Ya.I.; Vigovska, T.V.; Veliky, M.M. [Lviv Ivan Franko National University, Department of Biochemistry, Lviv (Ukraine); Becerril Aragon, G.A. [Lviv Ivan Franko National University, Department of Biochemistry, Lviv (Ukraine)]. E-mail: gabriel_aragon@mail.ru

    2001-09-01

    In this study we evaluated the effects of the administration of a vitamin D{sub 3} preparation 'Videchol' to chronically irradiated rats (1 cGy day{sup -1}) by the assessment of the activities of several glycolytic enzymes: lactic dehydrogenase (LDH) (EC 1.1.1.28), pyruvate kinase (PK) (EC 2.7.1.40) and hexokinase (HK) (EC 2.7.1.1), in populations of erythroid and myeloid bone marrow cells. Videchol treatment of irradiated rats led to the normalisation of HK and LDH activity at cumulative doses of around 30 cGy in granulocyte-monocyte cells and to normalisation of LDH and PK activities in erythroid cells starting at 20 cGy in comparison with irradiated rats who did not receive Videchol. The reaction kinetic parameters of LDH in erythrocytes changed according to the redistribution pattern of the isozymes throughout the different stages of the experiment. The administration of Videchol to irradiated rats led to a rearrangement of the LDH isozymes ratio characterised by kinetic properties more comparable to those of the controls. Thus, vitamin D{sub 3} appears to induce a normalisation of carbohydrate metabolism in rats chronically irradiated with low dose-rate ionising radiation. (author)

  13. [Searching Radiation Countermeasures using the Model of Prolonged Irradiation of Mice with Low Dose Rate and Evaluation of Their Influence on Heat Shock Protein Genes Expression].

    Science.gov (United States)

    Rozhdestvensky, L M; Mikhailov, V F; Schlyakova, T G; Shagirova, J M; Shchegoleva, R A; Raeva, N F; Lisina, N I; Shulenina, L V; Zorin, V V; Pchelka, A V; Trubitsina, K Y

    2015-01-01

    Different radiomodificators (cytokine betaleukine, antioxidant phenoxan, antigipoksant limontar and nucleoside riboxin) were investigated on mice for evaluating their radiation protective capacity against prolonged (21 h) exposure at a dose of 12.6 Gy at a low dose rate of 10 mGy/min. Bone marrow cellularity and endogenic CFUs were used as evaluation criteria 9 days after exposure. Simultaneously, expression of the heat shock proteins of 25, 70 and 90 kDa in unexposed mice bone marrow was studied 2, 24 and 48 h after injections. Betaleukine only had a positive significant effect in both tests in the variants of 50 mcg/kg and 3 mcg/kg when administered 2 h and 22 h before exposure, correspondingly. Effects of betaleukine HSPs on expression were both stimulating and inhibiting, that was in contradiction with a constant positive effect in 5 experiments on exposed mice for each betaleukine variant. It argues against the vital role of HSPs in the betaleukine antiradiation effect. In 2 experiments with high temperatures betaleukine administered at a dose of 50 mcg/kg evoked a very high HSP-70 gene expression after 24 h, and mice exposed to irradiation at that time in a parallel experiment showed an increased radiation effect. It corresponds to the idea that HSPs serve a stress indicator.

  14. Low-dose effects of hormones and endocrine disruptors.

    Science.gov (United States)

    Vandenberg, Laura N

    2014-01-01

    Endogenous hormones have effects on tissue morphology, cell physiology, and behaviors at low doses. In fact, hormones are known to circulate in the part-per-trillion and part-per-billion concentrations, making them highly effective and potent signaling molecules. Many endocrine-disrupting chemicals (EDCs) mimic hormones, yet there is strong debate over whether these chemicals can also have effects at low doses. In the 1990s, scientists proposed the "low-dose hypothesis," which postulated that EDCs affect humans and animals at environmentally relevant doses. This chapter focuses on data that support and refute the low-dose hypothesis. A case study examining the highly controversial example of bisphenol A and its low-dose effects on the prostate is examined through the lens of endocrinology. Finally, the chapter concludes with a discussion of factors that can influence the ability of a study to detect and interpret low-dose effects appropriately.

  15. SU-E-T-501: Normal Tissue Toxicities of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy: An in Vivo Total Body Irradiation Study

    Energy Technology Data Exchange (ETDEWEB)

    Cvetkovic, D; Zhang, P; Wang, B; Chen, L; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2014-06-01

    Purpose: Pulsed low dose rate radiotherapy (PLDR) is a re-irradiation technique for therapy of recurrent cancers. We have previously shown a significant difference in the weight and survival time between the mice treated with conventional radiotherapy (CRT) and PLDR using total body irradiation (TBI). The purpose of this study was to investigate the in vivo effects of PLDR on normal mouse tissues.Materials and Methods: Twenty two male BALB/c nude mice, 4 months of age, were randomly assigned into a PLDR group (n=10), a CRT group (n=10), and a non-irradiated control group (n=2). The Siemens Artiste accelerator with 6 MV photon beams was used. The mice received a total of 18Gy in 3 fractions with a 20day interval. The CRT group received the 6Gy dose continuously at a dose rate of 300 MU/min. The PLDR group was irradiated with 0.2Gyx20 pulses with a 3min interval between the pulses. The mice were weighed thrice weekly and sacrificed 2 weeks after the last treatment. Brain, heart, lung, liver, spleen, gastrointestinal, urinary and reproductive organs, and sternal bone marrow were removed, formalin-fixed, paraffin-embedded and stained with H and E. Morphological changes were observed under a microscope. Results: Histopathological examination revealed atrophy in several irradiated organs. The degree of atrophy was mild to moderate in the PLDR group, but severe in the CRT group. The most pronounced morphological abnormalities were in the immune and hematopoietic systems, namely spleen and bone marrow. Brain hemorrhage was seen in the CRT group, but not in the PLDR group. Conclusions: Our results showed that PLDR induced less toxicity in the normal mouse tissues than conventional radiotherapy for the same dose and regimen. Considering that PLDR produces equivalent tumor control as conventional radiotherapy, it would be a good modality for treatment of recurrent cancers.

  16. mBAND analysis of chromosome aberrations in human epithelial cells induced by gamma-rays and secondary neutrons of low dose rate.

    Science.gov (United States)

    Hada, M; Gersey, B; Saganti, P B; Wilkins, R; Cucinotta, F A; Wu, H

    2010-08-14

    Human risks from chronic exposures to both low- and high-LET radiation are of intensive research interest in recent years. In the present study, human epithelial cells were exposed in vitro to gamma-rays at a dose rate of 17 mGy/h or secondary neutrons of 25 mGy/h. The secondary neutrons have a broad energy spectrum that simulates the Earth's atmosphere at high altitude, as well as the environment inside spacecrafts like the Russian MIR station and the International Space Station (ISS). Chromosome aberrations in the exposed cells were analyzed using the multicolor banding in situ hybridization (mBAND) technique with chromosome 3 painted in 23 colored bands that allows identification of both inter- and intrachromosome exchanges including inversions. Comparison of present dose responses between gamma-rays and neutron irradiations for the fraction of cells with damaged chromosome 3 yielded a relative biological effectiveness (RBE) value of 26+/-4 for the secondary neutrons. Our results also revealed that secondary neutrons of low dose rate induced a higher fraction of intrachromosome exchanges than gamma-rays, but the fractions of inversions observed between these two radiation types were indistinguishable. Similar to the previous findings after acute radiation exposures, most of the inversions observed in the present study were accompanied by other aberrations. The fractions of complex type aberrations and of unrejoined chromosomal breakages were also found to be higher in the neutron-exposed cells than after gamma-rays. We further analyzed the location of the breaks involved in chromosome aberrations along chromosome 3, and observed hot spots after gamma-ray, but not neutron, exposures.

  17. Image fusion analysis of volumetric changes after interstitial low-dose-rate iodine-125 irradiation of supratentorial low-grade gliomas.

    Science.gov (United States)

    Julow, Jeno; Major, Tibor; Mangel, László; Bajzik, Gábor; Viola, Arpad

    2007-04-01

    The aim of this study was to compare the volumes of tumor necrosis, reactive zone and edema with the three-dimensional dose distributions after brachytherapy treatments of gliomas. The investigation was performed an average of 14.2 months after low-dose-rate (125)I interstitial irradiation of 25 inoperable low-grade gliomas. The prescribed dose was 50-60 Gy to the tumor surface. Dose planning and image fusion were performed with the BrainLab-Target 1.19 software. In the CT/ MRI images, the "triple ring" (tumor necrosis, reactive ring and edema) developing after the interstitial irradiation of the brain tumors was examined. The images with the triple ring were fused with the planning images, and the isodose curves were superimposed on them. The volumes of the three regions were measured. The average dose at the necrosis border was determined from the isodose distribution. For quantitative assessment of the dose distributions, the dose nonuniformity ratio (DNR), homogeneity index (HI), coverage index (CI) and conformal index (COIN) were calculated. The relative volumes of the different parts of the triple ring after the interstitial irradiation compared to the reference dose volume were the following: necrosis, 40.9%, reactive zone, 47.1%, and edema, 367%. The tumor necrosis developed at 79.1 Gy on average. The average DNR, HI, CI and COIN were 0.45, 0.24, 0.94 and 0.57, respectively. The image fusion analysis of the volume of tumor necrosis, reactive ring and edema caused by interstitial irradiation and their correlation with the dose distribution provide valuable information for patient follow-up, treatment options, and effects and side effects of radio therapy.

  18. SU-E-T-620: Planning and Dosimetry for Pulsed Low Dose Rate RT for Recurrent Lung, Spine, GYN and Head and Neck Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Tong, X; Luo, F; Liu, Y; Zhang, W; Xu, Q; Zhang, T; Li, J [3rd Affiliated Hospital of Qiqihar Medical University, Qiqihar (China); Chen, L; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2015-06-15

    Purpose: Extensive in vitro and in vivo studies have shown that pulsed low dose rate (PLDR) radiotherapy has potential to provide significant local tumor control and to reduce normal tissue toxicities. This work investigated the planning and dosimetry of PLDR re-irradiation for recurrent cancers. Methods: We analyzed the treatment plans and dosimetry for 13 recurrent patients who were treated with the PLDR technique in this study. All cases were planned with the 3DCRT technique with optimal beam angle selection. The treatment was performed on a Siemens accelerator using 6MV beams. The target volume ranged between 161 and 703cc. The previous RT dose was 40–60Gy while the re-irradiation dose was 16–60Gy. The interval between previous RT and re-irradiation was 13–336 months, and the follow-up time was up to 27months. The total prescription dose was administered in 2Gy/day fractions with the daily dose delivered in 10 sub-fractions (pulses) of 20cGy with a 3min interval between the pulses to achieve an effective dose rate of 6.7cGy/min. Results: The clinical outcome was analyzed based on the treatment plans. All pulses were kept with Dmax<40cGy. The PLDR treatments were effective (CR: 3 patients, PR: 10 patients). The acute and late toxicities were all acceptable (generally grade II or under). Two patients died three months after the PLDR re-irradiation, one due to massive cerebral infarction and the other due to acute cardiac failure. All others survived more than 8 months. Five patients showed good conditions at the last follow-up. Among them two recurrent lung cancer patients had survived 23 months and one nasopharyngeal cancer patient had survived 27 months. Conclusion: The PLDR technique was effective for the palliative treatment of head and neck, lung, spine and GYN cancers. Further phase II and III studies are warranted to quantify the efficacy of PLDR for recurrent cancers.

  19. Total body irradiation (TBI) in pediatric patients. A single-center experience after 30 years of low-dose rate irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Linsenmeier, Claudia; Thoennessen, Daniel; Negretti, Laura; Streller, Tino; Luetolf, Urs Martin [University Hospital Zurich (Switzerland). Dept. of Radiation-Oncology; Bourquin, Jean-Pierre [University Children' s Hospital Zurich (Switzerland). Dept. of Hemato-Oncology; Oertel, Susanne [University Hospital Zurich (Switzerland). Dept. of Radiation-Oncology; Heidelberg Univ. (Germany). Dept. of Radiation Oncology

    2010-11-15

    TBI at the low-dose rate that was generally used here. Conditioning for bone marrow transplantation without radiation is an attractive option, but is not sufficiently effective to completely replace TBI for the most common pediatric indications. (orig.)

  20. Effects of very low dose-rate (90)Sr/(90)Y exposure on the acute moist desquamation response of pig skin.

    Science.gov (United States)

    Millar, W T; Hopewell, J W

    2007-05-01

    Previous data, predominantly involving high dose-rate fractionated irradiation with incomplete repair intervals, had indicated that the kinetics of repair of sublethal damage for acute radiation reactions in pig skin could best be defined by a biphasic repair model with half-times for repair of 0.2 and 5.4 h, partition coefficient 0.5. To further test the validity of this finding and obtain a better estimate of the repair rate of the slow component of repair, the acute response of pig skin to very low dose-rates (VLDR), originally estimated to be 0.0067-0.0244 Gy/min, was investigated as part of a 4 fraction irradiation protocol involving an overall treatment time of VLDR fraction. The total doses administered were originally planned to represent the dose associated with the predicted ED(20), ED(50) and ED(80) (75% of total biological dose given at high dose-rate and 25% at VLDR) calculated on the basis of the repair kinetic parameters obtained from earlier studies. However, during the analysis a revision to the physical dosimetry was identified; this had been overlooked prior to the start of the study. Following completion of irradiation the irradiated sites were examined weekly and the presence or absence of moist desquamation recorded. The incidence of moist desquamation was slightly higher than expected on the basis of the parameters used to calculate iso-effective doses, at least in part as a consequence of the change to the dosimetry. Using likelihood methods and the original dose estimates, the best model based estimate of the dose-rate correction factor for the LDR and VLDR plaques was 1.29. This was comparable with the physical calibration factor, median value 1.23. The VLDR fraction associated with a 50% incidence of moist desquamation, based on experimental observation, was 23.2+/-0.84, 27+/-2.6 and 30.1+/-3.2 Gy, for corrected VLDRs of 0.0247, 0.0093 and 0.0068 Gy/min, respectively. A biphasic model, which incorporated a dose-rate correction factor

  1. [{sup 131}I]Iodoazomycin arabinoside for low-dose-rate isotope radiotherapy: radiolabeling, stability, long-term whole-body clearance and radiation dosimetry estimates in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Piyush [Department of Oncologic Imaging, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada); McQuarrie, Steven A. [Department of Oncologic Imaging, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada); Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada); Zhou, Aihya [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada); McEwan, Alexander J.B. [Department of Oncologic Imaging, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada); Wiebe, Leonard I. [Department of Oncologic Imaging, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada) and Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2N8 (Canada)]. E-mail: leonard.wiebe@ualberta.ca

    2005-08-01

    activities. Based on measured radioactivity burdens during the week following injection and on published animal ([{sup 125}I]IAZA) and clinical ([{sup 123}I]IAZA) dosimetry data, the current dose estimates point to selective tumor irradiation at low dose rates.

  2. Early effects comparison of X-rays delivered at high-dose-rate pulses by a plasma focus device and at low dose rate on human tumour cells.

    Science.gov (United States)

    Virelli, A; Zironi, I; Pasi, F; Ceccolini, E; Nano, R; Facoetti, A; Gavoçi, E; Fiore, M R; Rocchi, F; Mostacci, D; Cucchi, G; Castellani, G; Sumini, M; Orecchia, R

    2015-09-01

    A comparative study has been performed on the effects of high-dose-rate (DR) X-ray beams produced by a plasma focus device (PFMA-3), to exploit its potential medical applications (e.g. radiotherapy), and low-DR X-ray beams produced by a conventional source (XRT). Experiments have been performed at 0.5 and 2 Gy doses on a human glioblastoma cell line (T98G). Cell proliferation rate and potassium outward currents (IK) have been investigated by time lapse imaging and patch clamp recordings. The results showed that PFMA-3 irradiation has a greater capability to reduce the proliferation rate activity with respect to XRT, while it does not affect IK of T98G cells at any of the dose levels tested. XRT irradiation significantly reduces the mean IK amplitude of T98G cells only at 0.5 Gy. This work confirms that the DR, and therefore the source of radiation, is crucial for the planning and optimisation of radiotherapy applications.

  3. Conditioned instrumental behaviour in the rat: Effects of prenatal irradiation with various low dose-rate doses. Instrumentelle Verhaltensuntersuchungen an der Ratte: Ueber die Wirkung verschiedener Dosen einer praenatalen Bestrahlung niedriger Dosisleistung

    Energy Technology Data Exchange (ETDEWEB)

    Klug, H.

    1986-01-01

    4 groups of rats of the Wistar-strain were subjected to ..gamma..-irradiation on the 16th day of gestation. 5 rats received 0,6 Gy low dose rate irradiation, 5 animals received 0,9 Gy low dose and 6 high dose irradiation, 3 females were shamirradiated. The male offspring of these 3 irradiation groups and 1 control group were tested for locomotor coordination on parallel bars and in a water maze. The female offspring were used in an operant conditioning test. The locomotor test showed slight impairment of locomotor coordination in those animals irradiated with 0,9 Gy high dose rate. Swimming ability was significantly impaired by irradiation with 0,9 Gy high dose rate. Performance in the operant conditioning task was improved by irradiation with 0,9 Gy both low and high dose rate. The 0,9 Gy high dose rate group learned faster than all the other groups. For the dose of 0,9 Gy a significant dose rate effect could be observed. For the dose of 0,6 Gy a similar tendency was observed, differences between 0,6 Gy high and low dose rate and controls not being significant.

  4. Health effects of low doses at low dose rates: dose-response relationship modeling in a cohort of workers of the nuclear industry; Effets sanitaires des faibles doses a faibles debits de dose: modelisation de la relation dose-reponse dans une cohorte de travailleurs du nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Metz-Flamant, Camille

    2011-09-19

    The aim of this thesis is to contribute to a better understanding of the health effects of chronic external low doses of ionising radiation. This work is based on the French cohort of CEA-AREVA NC nuclear workers. The mains stages of this thesis were (1) conducting a review of epidemiological studies on nuclear workers, (2) completing the database and performing a descriptive analysis of the cohort, (3) quantifying risk by different statistical methods and (4) modelling the exposure-time-risk relationship. The cohort includes monitored workers employed more than one year between 1950 and 1994 at CEA or AREVA NC companies. Individual annual external exposure, history of work, vital status and causes of death were reconstructed for each worker. Standardized mortality ratios using French national mortality rates as external reference were computed. Exposure-risk analysis was conducted in the cohort using the linear excess relative risk model, based on both Poisson regression and Cox model. Time dependent modifying factors were investigated by adding an interaction term in the model or by using exposure time windows. The cohort includes 36, 769 workers, followed-up until age 60 in average. During the 1968- 2004 period, 5, 443 deaths, 2, 213 cancers, 62 leukemia and 1, 314 cardiovascular diseases were recorded. Among the 57% exposed workers, the mean cumulative dose was 21.5 milli-sieverts (mSv). A strong Healthy Worker Effect is observed in the cohort. Significant elevated risks of pleura cancer and melanoma deaths were observed in the cohort but not associated with dose. No significant association was observed with solid cancers, lung cancer and cardiovascular diseases. A significant dose-response relationship was observed for leukemia excluding chronic lymphatic leukemia, mainly for doses received less than 15 years before and for yearly dose rates higher than 10 mSv. This PhD work contributes to the evaluation of risks associated to chronic external radiation

  5. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G;

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  6. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G;

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  7. Determination of the survival curve of the cell irradiated with low dose rate neutrons; Determinacao da curva de sobrevivencia de celulas irradiadas com neutrons a baixa taxa de dose

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Bruno M.; Freitas, Marcelo H.A. de; Campos, Tarcisio P.R. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear; Silva, Luciana M.; Dias, Consuelo L.F. [Fundacao Ezequiel Dias, Belo Horizonte, MG (Brazil). Dept. de Pesquisa. Lab. de Bioquimica

    2000-07-01

    The effect of the radiation in tissue and cells are a theme of extreme importance and that is receiving large attention more and more now. This work purposes to evaluate the deleterious effects of the neutrons radiation at low dose rate in lineages of human cancerous cells through the analysis of survival curves. Deleterious effects due to radiation of low dose rate (3.8 mSv/hr) were observed in cells of the lineage HeLa S3. Previous studies, in lineage HN5 of tongue carcinoma, showed survive level to 0.2Sv of 80%, compatible to the value of 88,57% 0.4 Sv obtained for HeLa S3. In a close future, with the molecular biology characterization of a great number or possibly all cancer types (that will be accelerated largely with the conclusion of the human genome project), studies like this, can be much more specific, and could determine the efficiency of the neutrons or any other radiation type for each one of those types. Those data would have of great value for the medicine and they would help to plan the treatments better. (author)

  8. Low-dose adaptive sequential scan for dual-source CT coronary angiography in patients with high heart rate: Comparison with retrospective ECG gating

    Energy Technology Data Exchange (ETDEWEB)

    Xu Lei, E-mail: leixu2001@hotmail.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Yang Lin, E-mail: anna7949@163.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Zhang Zhaoqi, E-mail: zhaoqi5000@vip.sohu.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Li Yu, E-mail: athen06@hotmail.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Fan Zhanming, E-mail: fanzm120@tom.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Ma Xiaohai, E-mail: maxi8238@gmail.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Lv Biao, E-mail: biao_lu2007@sina.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Yu Wei, E-mail: yuwei02@gmail.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China)

    2010-11-15

    Purpose: To explore feasibility of dual-source CT (DS-CT) prospective ECG-gated coronary angiography in patients with heart rate (HR) higher than 70 beat per minute (bpm), and evaluate image quality and radiation dose with comparison to retrospective ECG-gated spiral scan. Materials and methods: One hundred patients who underwent DS-CT coronary angiography (DS-CTCA) with mean HR higher than 70 bpm but below 110 bpm were enrolled in the study, 50 were scanned by adaptive sequential scan and another 50 were analyzed by retrospectively gated CT scan. The imaging quality of coronary artery segments in the two groups was evaluated using a four-point grading scale by two independent reviewers. Patient radiation dose was calculated by multiplying dose length product by conversion coefficient of 0.017. Results: There was no significant difference between the two groups for mean HR (p = 0.305), HR variability (p = 0.103), body mass index (p = 0.472), and scan length (p = 0.208). There was good agreement for image quality scoring between the two reviewers (Kappa = 0.72). Coronary evaluability of adaptive sequential scan was 99.7% (608 of 610 segments), while that of retrospective gated scan was 98.7% (614 of 622 segments), showing similar coronary evaluability (p = 0.061). Effective doses of adaptive sequential scan and retrospective gated scan were 5.1 {+-} 1.6 and 11.8 {+-} 4.5 mSv, respectively (p < 0.001), showing that adaptive sequential scan reduced radiation dose by 57% compared with that of retrospective gated scan. Conclusions: In patients with 70-110 bpm HR, DS-CTCA adaptive sequential scan shows similar image quality as retrospective ECG-gated spiral scan with 57% reduction of radiation dose.

  9. EFFECT OF LOW DOSES OF THE MYCOTOXIN FUMONISIN B1 ON THE BODY MASS GAIN, FEED INTAKE AND FEED CONVERSION RATE OF PIGS

    Directory of Open Access Journals (Sweden)

    Akos Toth

    2000-06-01

    Full Text Available The fumonisin group of mycotoxins produced by Fusariun moniliforme is a rather newly discovered contaminant of some agricultural products, especially maize based food and animal feed. Fumonisin was discovered in 1988 of mouldy maize inspected since 1993 has shown FB1 contamination, the degree of this contamination increasing from year to year. Problems of mycotoxins cause significant economic losses due to the reduced feed intake, body weight gain and feed efficiency. We have very few informations about the effect of FB1 on these in South Africa, where high evidence was found between the occurrence of human oesophageal cancer and the rate of FB1 contamination. The discovery of this toxin lead to the explanation of equine leucoencephalomalacia (ELEM, porcine pulmonary oedema (PPC and possibly liver cancer in rats. In Hungary almost 70 % parameters – especially in farm animals. Three experiments were carried out with weaned piglets, in order to study the dose and time dependent effect of FB1. Fungal culture of Fusariun moniliforme was added to the diet so that the FB1 exposure was: 0, 10, 20 and 40 ppm for 4 weeks, 0, 1, 5 and 10 ppm for 8 weeks and 0, 1, 5 and 10 ppm for 5 months. In none of the experiments and the periods examined had FB1 any significant effect on feed consumption, body weight gain and feed conversion of weaned pigs. In spite of these findings mild or severe pulmonary oedema caused by the toxin was found in the animals by dissection carried out at the end of the experiment. Our results draw the attention to human health concerns of FB1. The toxin consumed by the animals without any clinical signs can cumulate in the animals and then enter the human organism by means of products of animal origin (meat, milk, etc..

  10. Low Dose Suppression of Neoplastic Transformation in Vitro

    Energy Technology Data Exchange (ETDEWEB)

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  11. Pregnancy rates after fixed-time artificial insemination of Brahman heifers treated to synchronize ovulation with low-dose intravaginal progesterone releasing devices, with or without eCG.

    Science.gov (United States)

    Butler, S A A; Atkinson, P C; Boe-Hansen, G B; Burns, B M; Dawson, K; Bo, G A; McGowan, M R

    2011-11-01

    The objective was to determine whether eCG in an ovulation synchronization protocol with an intravaginal progesterone (P(4))-releasing device (IPRD) containing a low dose of P(4) improves pregnancy rate (PR) to fixed-time AI (FTAI) in Bos indicus heifers. Day 0, 2 y old Brahman heifers were allocated to either eCG+ (n = 159) or eCG- (n = 157) treatment groups. All heifers were weighed, body condition scored (BCS), and ultrasonographically examined to measure uterine horn diameter and presence of a CL. On Day 0, all heifers received a low-dose IPRD (0.78 g P(4)) and 1 mg of estradiol benzoate (EB) im. On Day 8, the IPRD was removed, all heifers received 500 μg cloprostenol im, and those in the eCG+ treatment group received 300 IU of eCG im. On Day 9, all heifers received 1 mg EB im. All heifers were FTAI 52 to 56 h after IPRD removal. Ten days after FTAI, heifers were exposed to bulls. Heifers were diagnosed as pregnant to FTAI, natural mating, or not detectably pregnant (NDP) 65 d after FTAI. Treatment with eCG+ as compared to eCG- did not affect PR to FTAI (28.9 vs 30.6%; P = 0.590), natural mating (51.3 vs 47.7%; P = 0.595), or overall (65.4 vs 63.7%; P = 0.872). Mean live weight gain from Days 0 to 65 d post-FTAI was higher in heifers pregnant to FTAI (72.29 ± 4.26 kg; P = 0.033) and overall (66.83 ± 3.65 kg; P = 0.021), compared to heifers that were NDP (60.03 ± 3.16 kg). Uterine diameter group, 9-11, 12-13, and 14-20 mm (26.2, 31.3, and 33.3%; P = 0.256), presence and absence of CL (29.8 vs 29.4%; P = 0.975), AI technicians 1, 2, and 3 (32.6, 28.8, and 22.4%; P = 0.293) and sires A, B, and C (23.9, 36.0 and 27.0%; P = 0.122) had no effect on PR to FTAI, natural mating, or overall. In conclusion, treatment of primarily cycling Brahman heifers with 300 IU eCG in conjunction with a low P(4)-dose (0.78 g) IPRD and EB to synchronize ovulation, did not improve PR after FTAI, natural mating, or overall. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Preparation and determination of kerma for Iridium 192 sources of low dose rate for brachytherapy; Preparacion y determinacion del kerma de fuentes de iridio-192 de baja tasa de dosis para braquiterapia

    Energy Technology Data Exchange (ETDEWEB)

    Tendilla, J.I.; Tovar M, V.; Mitsoura, E.; Aguilar H, F.; Alanis M, J. [Instituto Nacional de Investigaciones Nucleares, C.P. 52045-1, Salazar, Esrado de Mexico, D.F. (Mexico)

    2000-07-01

    The practice of Brachytherapy with Iridium-192 sources of low dose rate (0.4 - 0.8 Gy/h) is a technique used in the treatment of diverse illnesses. in this work the preparation, quality control and calibration are presented in terms of kerma in air of Iridium-192 using as target these recycled Iridium-Platinum wires. The targets were obtained as decayed sources of different radio therapeutical centers in the country and they were characterized by Scanning electron microscopy in order to determine their chemical composition. Subsequently it was developed an experimental design to establish the effect of neutron flux, geometrical array and irradiation time over the activity and percentage of the sources homogeneity. The homogeneity was determined by auto radiography and by Gamma spectroscopy. Once the optimal irradiation conditions were established, it is determined the apparent activity and kerma in air using a well type ionization chamber with traceability to a primary laboratory. Iridium-192 sources were obtained with an average homogeneity 96 %, apparent activity 282.129 {+-} 0.531 M Bq and kerma in air 0.03200 {+-} 0.00006 m Gy m/h A. (Author)

  13. Detection rate of prostate cancer using prostate specific antigen in patients presenting with lower urinary tract symptoms: A retrospective study

    Directory of Open Access Journals (Sweden)

    Chavan P

    2009-01-01

    Full Text Available Background: Need for undertaking prostate biopsies for detection of prostate cancer is often decided on the basis of serum levels of prostate specific antigen (PSA. Aim: To evaluate the case detection rate of prostate cancer among patients presenting with lower urinary tract symptoms (LUTS on the basis of PSA levels and to assess the scope of prostate biopsy in these patients. Setting and Design: A retrospective study from a tertiary care center. Materials and Methods: The clinical and histopathological data of 922 patients presenting with LUTS in the last five years was obtained from the medical record section. They had been screened for prostate cancer using PSA and /or digital rectal examination examination followed by confirmation with prostate biopsy. Statistical Analysis Used: Detection rate and receiver operating characteristic curve were performed using SPSS 16 and Medcalc softwares. Results: The detection rate of prostate cancer according to the PSA levels was 0.6%, 2.3%, 2.5%, 34.1% and 54.9% in the PSA range of 0-4, 4-10, 10-20, 20-50 and> 50 ng/ml, respectively. Maximum prostate cancer cases were detected beyond a PSA value of 20 ng/ml whereas no significant difference in the detection rate was observed in the PSA range of 0-4, 4-10 and 10-20 ng/ml. Conclusion: A low detection rate of prostate cancer observed in the PSA range of 4-20 ng/ml in LUTS patients indicates the need for use of higher cutoff values of PSA in such cases. Therefore we recommend a cutoff of 20 ng/ml of PSA for evaluation of detection rate of prostate cancer among patients presenting with LUTS.

  14. Low-dose hormone therapy in postmenopausal women in China.

    Science.gov (United States)

    Zang, H; Shi, H; Speroff, L

    2010-12-01

    To review the experience of menopausal symptoms and low-dose hormone therapy (HT) in postmenopausal women in China. Literature review and critical summaries of available prospective, clinical trials (randomized, controlled trials, RCTs). Chinese women experience menopausal symptoms less frequently compared with women in developed countries, and the prevalence of menopausal symptoms is less in women of southern China than in women of northern China. The majority of postmenopausal Chinese women lack knowledge about HT, and the usage rate of HT is low in these women compared to that in women of developed countries. Some RCTs investigated the efficacy and safety of low- or ultra-low-dose HT, including conjugated equine estrogen, estradiol valerate, transdermal estradiol, nylestriol alone or in combination with progesterone, and tibolone in postmenopausal Chinese women. These RCTs reported that low- or ultra-low-dose HT relieved menopausal symptoms and prevented bone loss as well as standard-dose HT and was less likely to induce side-effects, including irregular vaginal bleeding and breast tenderness; there may be dose-dependent effects of HT. No study evaluated the effects of low-dose HT on cardiovascular events or breast mammographic density/risk of breast cancer. More RCTs are required to confirm efficacy and to assess the safety of low- or ultra-low-dose HT for a long-term period in a large group of postmenopausal women.

  15. The effect of low-dose β-blocker on heart rate and heart rate variability in health subjects wth a resting heart rate of less than 65 beats per minute: Effect on the quality of prospective electrocardiography-gated coronary CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chul Hwan; Kim, Tae Hoon [Dept. of Radiology and Research Institute of Radiological Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Sang Min [Dept. of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Hong, Yoo Jin [Dept. of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-02-15

    We assessed the effect of a low-dose β-blocker on heart rate (HR), HR variability (HRV) and image quality of prospective electrocardiography-gated coronary CT angiography (CCTA) in healthy subjects with low HR. CCTA was performed with a 64-slice CT in 75 subjects with a HR of less than 65 beats per minute (bpm). Subjects were divided into 2 groups: Group 1 (G1), 35 with a low dose β-blocker; and Group 2 (G2), 40 without pre-medication. The image quality (IQ) of the CCTA was assessed on a 4-point grading scale (1, poor; 4, excellent). Initial HR (bpm) was not different between the 2 groups. HR during CCTA was lower in G1 than G2 (50.3 ± 5.6 vs. 53.3 ± 4.8, p = 0.016). HRV was not different between the 2 groups. Per-segment analysis showed better IQ at the mid-segment of the right coronary artery (3.0 ± 0.9 vs. 2.5 ± 1.1, p = 0.039) and the first diagonal branch (3.4 ± 0.6 vs. 3.1 ± 0.7, p = 0.024), in the G1 than the G2 group, respectively. The IQ was negatively correlated with HR, but no correlation was found between HRV and IQ. The IQs in the per-vessel analysis were not different between the 2 groups. Low-dose β-blocker reduced HR and improved the IQ of CCTA in a few segments, even at a HR of less than 65 bpm. However the effect was limited.

  16. Low dose metoprolol in acute myocardial infarction.

    Science.gov (United States)

    Kumar, K P; Krishnaswami, S; Prasad, N K; Rath, P C; Jose, J

    1989-01-01

    A study of the effects of low dose Metoprolol was undertaken in 37 patients with acute myocardial infarction. These patients were randomly divided into three groups depending on the dose of the drug per kg body weight. Group I, consisting of 18 patients, received 0.36 to 0.65 mg per kg per day, Group II (10 patients) received 0.66 to 0.99 mg/kg/day, and Group III (9 patients) 1 to 1.81 mg/kg/day. To assess the degree of beta blockade achieved, the parameters that were evaluated were the fall in blood pressure and heart rate. There was a fall in systolic blood pressure which ranged from 7 to 17%, and fall in heart rate of 6.6 to 12.8% in the 3 groups over the 48-hour study period. These observations were compared with the results obtained from the Goteberg Metoprolol trial and Metoprolol in acute myocardial infarction (MIAMI) trials wherein 200 mg of Metoprolol per day were used. Our preliminary observations suggest that Indian patients may not need such a high dose, and Metoprolol at 50-100 mg per day would probably be sufficient to get the desired effect.

  17. Screening for lung cancer with low-dose CT.

    Science.gov (United States)

    Coche, E

    2008-01-01

    Lung cancer represents the leading cause of cancer-related mortality in the world. In the past, many attempts were made to detect the disease at an early stage and subsequently reduce its mortality. Chest X-ray was abandoned for this purpose. For several years low-dose computed tomography has been introduced as a potential tool for early screening in a high-risk population. As demonstrated in several papers, the task is not easy and researchers are faced with many difficulties. This paper reviews mainly the role of low-dose CT for early cancer screening. Results of past and current trials, controversies related to the high rate of lung nodules, cost-effectiveness, and delivered radiation dose to the patient are presented. Finally some limitations of low dose CT for lung cancer detection are explained.

  18. Low dose aspirin after ischemic stroke associated with antiphospholipid syndrome

    NARCIS (Netherlands)

    Derksen, RHWM; de Groot, PG; Kappelle, LJ

    2003-01-01

    The authors describe course and outcome of eight patients with ischemic stroke as the first thrombotic manifestation of antiphospholipid syndrome who received low-dose aspirin as prophylactic treatment. During 8.9 years of follow-up, two patients had a recurrent stroke. Recurrent stroke rate per 100

  19. Study of the radiation levels in low dose rate brachytherapy zones of the National Institute of Neoplastic Illnesses; Estudio de los Niveles de Radiacion en Zonas de Braquiterapia de Baja Tasa de Dosis del Instituto Nacional de Enfermedades Neoplasicas

    Energy Technology Data Exchange (ETDEWEB)

    Figueroa J, N.; Mora Y, B. [Instituto Nacional de Enfermedades Neoplasicas, Lima (Peru)]. e-mail: navorf01@yahoo.es

    2006-07-01

    The present study has as objective to evaluate the radiation levels of the Brachytherapy work areas of low dose rate (Gammateque, nurses station and of hospitalization rooms of patients RIC of 4th, 5th Floor-East) and to estimate the effective dose of the occupationally exposed personnel and the public in general. The measurements of the dose rate in these areas, were registered with a radiations monitor Inspector trademark, during a period of 60 days, without altering the routinary work conditions. The more high levels of environmental dose equivalent rate registered in the different work areas its are of 1.41 and 47.78 {mu}Sv/h rooms 1 and 2 in the Gammateque environments, in the hospitalization rooms of the 4th and 5th floor in the point 1 are of 40.77 and 23.67, {mu}Sv/h respectively and in the point 2 are of 129.19 and 39.93, {mu}Sv/h respectively, and in the nurses station of the 4th and 5th floor its are respectively of 7.62 u Sv/h and 0.45 u Sv/h. According to the carried out measurements and the permanency in the work place is possible to estimate the effective dose involved to the occupationally exposed personnel. The personnel that works in Gammateque could be receiving respectively as maximum dose 0.61 mSv/month, and the personnel that works in the nurses station of 13.17 and 0.78 mSv/year in the 4th and 5th floor. These registered differences among the two floors are due to that the 5th floor counts with the shielding systems (screen) contrary to the 4th, another of the factors is the distribution form of the patient beds RIC. We should have present that the radiation levels although in some cases it is very high, however, they are below of the permissible limits according to standards, but it is still possible to reduce even more, the radiation levels in the critical points fulfilling with the ALARA principle. (Author)

  20. Perineal recurrence of prostate cancer six years after trans-perineal brachytherapy

    NARCIS (Netherlands)

    Eppinga, Wietse; Vijverberg, Peter; Moerland, Rien; Brand, Eric; van der Voort van Zyp, Jochem; Noteboom, Juus; van Vulpen, Marco

    2015-01-01

    We report a case of perineal recurrence of prostate cancer 6 years after low-dose-rate (LDR) brachytherapy for localized prostate cancer. The most common approach to treat such perineal masses, including those occurring after prior biopsy or surgery, is local excision. We report the use of stereotac

  1. LOW DOSE MAGNESIUM SULPHATE REGIME FOR ECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Bangal V

    2009-09-01

    Full Text Available Pre- eclampsia is one of the commonest medical complications seen during pregnancy. It contributes significantly to maternal and perinatal morbidity and mortality. Dr.J.A.Pritchard in 1955, introduced magnesium sulphate for control of convulsions in eclampsia and is used worldwide. Considering the low body mass index of indian women, a low dose magnesium sulphate regime has been introduced by some authors. Present study was carried out at tertiary care centre in rural area. Fifty cases of eclampsia were randomly selected to find out the efficacy of low dose magnesium sulphate regime to control eclamptic convulsions. Maternal and perinatal outcome and magnesium toxicity were analyzed. It was observed that 86% cases responded to initial intravenous dose of 4 grams of 20% magnesium sulphate . Eight percent cases, who got recurrence of convulsion, were controlled by additional 2 grams of 20% magnesium sulphate. Six percent cases required shifting to standard Pritchard regime, as they did not respond to low dose magnesium sulphate regime. The average total dose of magnesium sulphate required for control of convulsions was 20 grams ie. 54.4% less than that of standard Pritchard regime. The maternal and perinatal morbidity and mortality in the present study werecomparable to those of standard Pritchard regime. The study did not find a single case of magnesium related toxicity with low dose magnesium sulphate regime. Low dose magnesium sulphate regime was found to be safe and effective in eclampsia.

  2. The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis

    Science.gov (United States)

    Ochieng, Josiah; Nangami, Gladys N.; Ogunkua, Olugbemiga; Miousse, Isabelle R.; Koturbash, Igor; Odero-Marah, Valerie; McCawley, Lisa; Nangia-Makker, Pratima; Ahmed, Nuzhat; Luqmani, Yunus; Chen, Zhenbang; Papagerakis, Silvana; Wolf, Gregory T.; Dong, Chenfang; Zhou, Binhua P.; Brown, Dustin G.; Colacci, Annamaria; Hamid, Roslida A.; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P.; Woodrick, Jordan; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Al-Temaimi, Rabeah; Al-Mulla, Fahd; Bisson, William H.; Eltom, Sakina E.

    2015-01-01

    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial–mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. PMID:26106135

  3. Tardive dyskinesia with low dose amisulpride.

    Science.gov (United States)

    Tharoor, Hema; Padmavati, R

    2013-01-01

    In recent years, there has been an increasing trend to use amisulpride in the treatment of dysthymia and also as an adjunct treatment in patients with major depression. At low doses (50 mg), amisulpride preferentially blocks presynaptic auto receptors, enhances dopamine release, and therefore acts as a dopaminergic compound able to resolve the dopaminergic hypo activity that characterizes depression. Based on experimental data, amisulpride is the drug of choice for dopaminergic transmission disorders, both in depression and in schizophrenia. This case highlights the development of dyskinesia in a depressed patient treated with low dose amisulpride and fluvoxamine.

  4. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Engelward, Bevin P

    2009-09-16

    The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy

  5. Prostatitis

    OpenAIRE

    Domingue, Gerald J.; Hellstrom, Wayne J.G.

    1998-01-01

    The laboratory diagnosis of acute bacterial prostatitis is straightforward and easily accomplished in clinical laboratories. Chronic bacterial prostatitis, and especially chronic idiopathic prostatitis (most often referred to as abacterial prostatitis), presents a real challenge to the clinician and clinical microbiologist. Clinically, the diagnosis of chronic idiopathic prostatitis is differentiated from that of acute prostatitis by a lack of prostatic inflammation and no “significant” (cont...

  6. 小剂量氯胺酮对老年患者经尿道前列腺切除术术后疼痛及认知功能的影响%Effect of low dose ketamine on postoperative pain and cognitive function in elderly patients with transurethrue resection of prostate

    Institute of Scientific and Technical Information of China (English)

    赵海蕊; 殷积慧; 赵洋; 衣选龙; 王桂娥

    2014-01-01

    目的:研究小剂量氯胺酮在经尿道前列腺电切术(TURP)中的应用,观察其对老年患者术后疼痛及认知功能的影响。方法选择择期在连续硬膜外麻醉下行TURP的患者60例,随机分为两组:对照组(N)和氯胺酮组(K),每组30例。两组患者分别在硬膜外阻滞完善手术开始前给予生理盐水5 ml 和氯胺酮0.3 mg/kg(用生理盐水稀释至5 ml),手术开始后泵注丙泊酚3~4 mg·kg-1·h-1,手术结束前10 min停注丙泊酚,观察并记录两组患者入室(T0)、给药后3 min(T1)、手术开始前(T2)、给药30 min(T3)、术毕(T4)的平均动脉压(MAP)、心率(HR)、脉搏氧饱和度(SpO2);并随访记录术后4、8、12、24 h视觉模拟评分(VAS);同时记录两组患者术前1 d、术后1 d及术后3 d简易智能精神状态检查量表(MMSE)评分;观察术后平均每小时膀胱痉挛次数以及术后需应用镇痛药物的例数。结果两组患者一般情况及手术时间差异无统计学意义(P>0.05);两组MAP及HR在T1时氯胺酮组高于对照组(P<0.05),其余各时间点HR、MAP、SpO2组间比较差异无统计学意义,组内比较对照组T1~T3各时点MAP 较T0时低,氯胺酮组T2、T3时MAP低于T0时,氯胺酮组中T1时HR高于T0时;两组患者术后VAS评分各时点氯胺酮组低于对照组(P<0.05);两组患者术后每小时膀胱痉挛次数,氯胺酮组少于对照组(P<0.01);两组术前及术后1 d、术后3 d MMSE评分组间及组内比较均无统计学意义(P>0.05)。结论小剂量氯胺酮可以减轻老年患者TURP术后疼痛并对老年患者术后认知功能无影响。%Objective To study the application of low dose of ketamine in transurethral resection of the prostate(TURP), and observe the influence on postoperative pain and cognitive function of elderly patients. Methods Sixty elderly patients with TURP by

  7. Low dose rate gamma ray induced loss and data error rate of multimode silica fibre links; Affaiblissement et taux d`erreur de transmission de fibres optiques multimodes soumises a une irradiation gamma a faible debit de dose

    Energy Technology Data Exchange (ETDEWEB)

    Breuze, G.; Fanet, H.; Serre, J. [CEA Centre d`Etudes de Saclay, 91 - Gif-sur-Yvette (France). Dept. d`Electronique et d`Instrumentation Nucleaire; Colas, D.; Garnero, E.; Hamet, T. [Electricite de France (EDF), 77 - Ecuelles (France)

    1993-12-31

    Fiber optics data transmission from numerous multiplexed sensors, is potentially attractive for nuclear plant applications. Multimode silica fiber behaviour during steady state gamma ray exposure is studied as a joint programme between LETI CE/SACLAY and EDF Renardieres: transmitted optical power and bit error rate have been measured on a 100 m optical fiber.

  8. Relationship of blood pressure variability and heart rate variability with prostatic volume in patients with benign prostatic hyperplasia

    Institute of Scientific and Technical Information of China (English)

    金江丽

    2014-01-01

    Objective To investigate the relationship of blood pressure variability(BPV)and heart rate variability(HRV)with prostatic volume(PV)in patients with benign prostatic hyperplasia(BPH).Methods A total of133 patients admitted to our department between January2011 and April 2013 were analyzed retrospectively.The patients were divided into BPH group and non-BPH group according to the PV value.The ambulatory blood

  9. Effects of low doses; Effet des faibles doses

    Energy Technology Data Exchange (ETDEWEB)

    Le Guen, B. [Electricite de France (EDF-LAM-SCAST), 93 - Saint-Denis (France)

    2001-07-01

    Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

  10. Epigenomic Adaptation to Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gould, Michael N. [Univ. of Wisconsin, Madison, WI (United States)

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  11. Low doses of glyphosate change the response of soybean to later glyphosate exposures

    Science.gov (United States)

    The stimulatory effect of low doses of toxic substances is known as hormesis. Many herbicides that cause severe injury to plants at recommended rates, promote growth or have other stimulatory effects at very low doses. The objective of this study was to evaluate glyphosate-induced hormesis in soyb...

  12. Complications and prostate cancer diagnosis rate of TRUS prostate biopsies using 16 and 18G needles by Clavien scoring.

    Science.gov (United States)

    Ozcan, Serkan; Akif Diri, Mehmet; Bagcioglu, Murat; Karakan, Tolga; Aydın, Arif

    2017-05-16

    We aimed to compare the 18 and 16-Gauge (G) needles used in transrectal ultrasonography (TRUS)-guided needle biopsy for cancer detection rates and complications using the Clavien Scoring System. The 80 patients who were included in the study were randomized and divided into two groups. Group 1 (n = 36) had a TRUS-guided prostate biopsy with an 18G needle and Group 2 had a 16G needle (n = 44). The hematuria, bleeding assessment, and infection events were evaluated on a daily basis. These complications were graded according to the Clavien Scoring. In Group 1, only five (13%) patients were diagnosed with prostate cancer, and three patients were reported to have atypical small acinar proliferation (ASAP). In Group 2, 16 (36%) patients were diagnosed with prostate cancer and one patient was reported to have ASAP. The difference in the prostate cancer detection rate between the groups was statistically significant. According to the Clavien grading system, the complications were at the Grade 1 level in 25 people in Group 1 in 29 people in Group 2. Grade 2 level complications were not observed in either group. While one person was Grade 3 in Group 1, two people in Group 2 had this rate. There were no significant differences between the groups. We found that cancer detection rate increased by increasing the thickness of the needle used in TRUS-guided prostate biopsy without any increase in the complications.

  13. Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, Niraj H., E-mail: nmehta@mednet.ucla.edu [University of California, Los Angeles, Los Angeles, California (United States); Kamrava, Mitchell; Wang, Pin-Chieh; Steinberg, Michael; Demanes, Jeffrey [University of California, Los Angeles, Los Angeles, California (United States)

    2013-07-15

    Purpose: To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce. Methods and Materials: Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL). Results: A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged <55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045). Conclusions: A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from <1 in 28% of cases to ≥1 in 15%. The median duration of bounce is <1 year. More bounces were identified in patients with lower Gleason score and age <55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way.

  14. The role of brachytherapy in the definitive management of prostate cancer; Place de la curietherapie dans le traitement du cancer prostatique localise

    Energy Technology Data Exchange (ETDEWEB)

    Crook, J. [British Columbia Cancer Agency, Center for the Southern Interior, 399, Royal Avenue, Kelowna, British Columbia, V1Y 5L33 (Canada)

    2011-06-15

    Over the past two decades, brachytherapy has played an ever expanding role in the definitive radiotherapy of prostate cancer. Brachytherapy surpasses external beam radiotherapy in its ability to deliver intense intra-prostatic dose escalation. Although initially low dose rate permanent seed brachytherapy was favored for favorable risk prostate cancers, and high dose rate temporary brachytherapy for intermediate and advanced disease, both types of brachytherapy now have a place across all the risk groups of localized prostate cancer. This article will review indications and patient selection, planning and technical aspects, toxicity and efficacy for both low and high dose rate prostate brachytherapy. (author)

  15. Incidence of intracranial bleeds in new users of low-dose aspirin

    DEFF Research Database (Denmark)

    Cea Soriano, Lucía; Gaist, David; Soriano-Gabarró, Montse

    2017-01-01

    BACKGROUND: Low-dose aspirin protects against ischemic cardiovascular (CV) events as well as colorectal cancer (CRC). However, low-dose aspirin may be associated with a small increased risk of intracranial bleeds (ICB). OBJECTIVES: To obtain incidence rates of ICB overall and by patient subgroups...... among new users of low-dose aspirin. PATIENTS/METHODS: Using The Health Improvement Network (THIN) UK primary care database (2000-2012), we identified a cohort of new users of low-dose aspirin aged 40-84 years (N=199,079; mean age at start of follow-up, 63.9 years) and followed them, for up to 14 years...... estimates of the absolute risk of ICB for incorporation into risk-benefit assessments of low-dose aspirin use. This article is protected by copyright. All rights reserved....

  16. Low dose spinal anesthesia for knee arthroscopy

    Directory of Open Access Journals (Sweden)

    Lakhin R.E.

    2015-06-01

    Full Text Available Objective: to evaluate the nature of unilateral spinal anesthesia using various modes of administration of low doses of hyperbaric bupivacaine. Materials and Methods. Prospectively, the randomized study included 56 patients undergoing knee arthroscopy. In the control group bupivacaine of 5mg was administered simultaneously, in the main group — fractionally by 2.5 mg. The development of thermal and pain blocks from different sides was investigated. The data were statistically processed. Results. In the control group, the positioning of the patient usually began after the entire dose of anesthetic had been administered. In the case of temperature paresthesia in the area of the sacral segments of the full anesthesia throughout underlying limb was not always achieved. In 6 cases of block was not sufficient. In the main group patient positioning was performed after the administration of 2.5 mg of anesthetic and evaluate temperature paresthesia and in 2 cases the total dose was increased to 7.5 mg. The successful development of sensory block at fractional administration was significantly higher than in the single-step introduction. Conclusion. Temperature paresthesia occurs within the first minute and is an early predictor of developing spinal anesthesia. The area of arising paresthesia shows preferential distribution of the anesthetic. In the application of low dose local anesthetic the desired upper level of anesthesia via the patient positioning and dose adjustment may be achieved.

  17. Detection rate of clinically insignificant prostate cancer increases with repeat prostate biopsies

    Institute of Scientific and Technical Information of China (English)

    Bumsoo Park; Seong-Soo Jeon; Sung-Ho Ju; Byong-Chang Jeong; Seong-Il Seo; Hyun-Moo Lee; Han-Yong Choi

    2013-01-01

    To analyze if clinically insignificant prostate cancer (ClPC) is more frequently detected with repeat prostate biopsies,we retrospectively analyzed the records of 2146 men diagnosed with prostate cancer after one or more prostate biopsies.The patients were divided into five groups according to the number of prostate biopsies obtained,e.g.group 1 had one biopsy,group 2 had two biopsies and group 3 had three biopsies.Of the 2146 patients diagnosed with prostate cancer,1956 (91.1%),142 (6.6%),38 (1.8%),9 (0.4%) and 1 (0.1%) men were in groups 1,2,3,4 and 5,respectively.Groups 4 and 5 were excluded because of the small sample sizes.The remaining three groups (groups 1,2 and 3) were statistically analyzed.There were no differences in age or prostate-specific antigen level among the three groups.ClPC was detected in 201 (10.3%),28 (19.7%) and 9 (23.7%) patients in groups 1,2 and 3,respectively (P<0.001).A multivariate analysis showed that the number of biopsies was an independent predictor to detect CIPC (0R=2.688 for group 2; 0R=4.723 for group 3).In conclusion,patients undergoing multiple prostate biopsies are more likely to be diagnosed with CIPC than those who only undergo one biopsy.However,the risk still exists that the patient could have clinically significant prostate cancer.Therefore,when counseling patients with regard to serial repeat biopsies,the possibility of prostate cancer overdiagnosis and overtreatment must be balanced with the continued risk of clinically significant disease.

  18. Long-term results of exclusive low-dose rate curie-therapy for a high-grade vaginal intraepithelial neoplasia; Resultats a long terme de la curietherapie exclusive de bas debit de dose pour neoplasie vaginale intraepitheliale de haut grade

    Energy Technology Data Exchange (ETDEWEB)

    Blanchard, P.; Monnier, L.; Dumas, I.; Azoury, F.; Mazeron, R.; Haie-Meder, C. [Institut Gustave-Roussy, 94 - Villejuif (France)

    2010-10-15

    The authors report the results of an exclusive low dose rate curie therapy for female patients treated for a grade 3 vaginal intraepithelial neoplasia. They reviewed the medical files of patients treated since 1983, i.e. 28 women. They analysed demographic characteristics, the clinic description of lesions, possible treatments which occurred before this high-grade vaginal intraepithelial neoplasia, possible previous history of cervical or endometrial cancer, curie therapy detailed data, presence of tumorous relapse. According to that, they conclude that a 60 Gy exclusive low- vaginal dose-rate curie-therapy is an efficient and well tolerated treatment for high-grade vaginal intraepithelial neoplasia. Short communication

  19. Cervical ripening with low-dose prostaglandins in planned vaginal birth after cesarean

    National Research Council Canada - National Science Library

    Schmitz, Thomas; Pourcelot, Anne-Gaelle; Moutafoff, Constance; Biran, Valérie; Sibony, Olivier; Oury, Jean-François

    2013-01-01

    To compare uterine rupture, maternal and perinatal morbidity rates in women with one single previous cesarean after spontaneous onset of labor or low-dose prostaglandin-induced cervical ripening for unfavourable cervix...

  20. Cervical Ripening with Low-Dose Prostaglandins in Planned Vaginal Birth after Cesarean: e80903

    National Research Council Canada - National Science Library

    Thomas Schmitz; Anne-Gaelle Pourcelot; Constance Moutafoff; Valérie Biran; Olivier Sibony; Jean-François Oury

    2013-01-01

      Objectives To compare uterine rupture, maternal and perinatal morbidity rates in women with one single previous cesarean after spontaneous onset of labor or low-dose prostaglandin-induced cervical...

  1. Biological Effects of Low-Dose Exposure

    CERN Document Server

    Komochkov, M M

    2000-01-01

    On the basis of the two-protection reaction model an analysis of stochastic radiobiological effects of low-dose exposure of different biological objects has been carried out. The stochastic effects are the results published in the last decade: epidemiological studies of human cancer mortality, the yield of thymocyte apoptosis of mice and different types of chromosomal aberrations. The results of the analysis show that as dependent upon the nature of biological object, spontanous effect, exposure conditions and radiation type one or another form dose - effect relationship is realized: downwards concave, near to linear and upwards concave with the effect of hormesis included. This result testifies to the incomplete conformity of studied effects of 1990 ICRP recomendations based on the linear no-threshold hypothesis about dose - effect relationship. Because of this the methodology of radiation risk estimation recomended by ICRP needs more precisian and such quantity as collective dose ought to be classified into...

  2. Low Dose Ionizing Radiation Modulates Immune Function

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Gregory A. [Loma Linda Univ., CA (United States)

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the

  3. Detection Rate of Prostate Cancer on the Basis of the Vienna Nomogram: A Singapore Study

    Science.gov (United States)

    Poh, Beow Kiong; Ng, Foo Cheong; Fong, Yan Kit

    2014-01-01

    Purpose The purpose of this study was to determine the efficacy of the Vienna nomogram prostate biopsy model in the detection of prostate cancer in our local population. We also assessed the incidence of complications from using such a template. Materials and Methods From January 2006 to June 2007, 120 men with either elevated prostate-specific antigen (PSA) scores (>4 ng/mL) and/or abnormal digital rectal examination were enrolled prospectively to undergo extraction of 6 to 18 cores for transrectal ultrasound-guided prostate biopsy, as indicated by the Vienna nomogram. Results The mean age was 62.6±8.3 years (range, 40-86 years). The mean PSA score was 13.42 ng/mL. The mean number of cores obtained was 9.68±3.1. According to the Vienna nomogram, 27 out of a total of 120 patients had prostate cancer, for a detection rate of 22.5%. In the group of patients with PSA scores 10 ng/mL had a detection rate of 50% (13 of 26). The complication rate in our study was 7.5%. Conclusions With the use of the Vienna nomogram, our prostate cancer detection rate is comparable to previously published data for Asian patients. This nomogram offers an easy tool with which to select the optimal number of prostate biopsy cores to be taken on the basis of patient age and total prostate volume. With this biopsy strategy, we also have found that the complication rate from prostate biopsy is low. PMID:24741412

  4. SU-E-T-647: Quality Assurance of VMAT by Gamma Analysis Dependence On Low-Dose Threshold

    Energy Technology Data Exchange (ETDEWEB)

    Song, J; Kim, M; Lee, S; Lee, M; Suh, T [Department of Biomedical Engineering, Reasearch Institute of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of); Park, S [Department of Biomedical Engineering, Reasearch Institute of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of); Department of Radiation Oncology, Uijeongbu St. Mary’s Hospital, Gyeonggi-do (Korea, Republic of)

    2015-06-15

    Purpose: The AAPM TG-119 instructed institutions to use low-dose threshold (LDT) of 10% or a ROI determined by the jaw when they collected gamma analysis QA data of planar dose distribution. Also, based on a survey by Nelms and Simon, more than 70% of institutions use a LDT between 0% and 10% for gamma analysis. However, there are no clinical data to quantitatively demonstrate the impact of the LDT on the gamma index. Therefore, we performed a gamma analysis with LDTs of 0% to 15% according to both global and local normalization and different acceptance criteria: 3%/3 mm, 2%/2 mm, and 1%/1 mm. Methods: A total of 30 treatment plans—10 head and neck, 10 brain, and 10 prostate cancer cases—were randomly selected from the Varian Eclipse TPS, retrospectively. For the gamma analysis, a predicted portal image was acquired through a portal dose calculation algorithm in the Eclipse TPS, and a measured portal image was obtained using a Varian Clinac iX and an EPID. Then, the gamma analysis was performed using the Portal Dosimetry software. Results: For the global normalization, the gamma passing rate (%GP) decreased as the LDT increased, and all cases of low-dose thresholds exhibited a %GP above 95% for both the 3%/3 mm and 2%/2 mm criteria. However, for local normalization, the %GP increased as LDT increased. The gamma passing rate with LDT of 10% increased by 6.86%, 9.22% and 6.14% compared with the 0% in the case of the head and neck, brain and prostate for 3%/3 mm criteria, respectively. Conclusion: Applying the LDT in the global normalization does not have critical impact to judge patient-specific QA results. However, LDT for the local normalization should be carefully selected because applying the LDT could affect the average of the %GP to increase rapidly.

  5. Prostate cancer incidence rates have started to decrease in central Italy.

    Science.gov (United States)

    Crocetti, Emanuele; Ciatto, Stefano; Buzzoni, Carlotta; Zappa, Marco

    2010-01-01

    The widespread use of prostate-specific antigen (PSA) testing has dramatically changed the epidemiology of prostate cancer. Growing incidence rates have been documented in almost all western countries following the increased usage of PSA screening. In the United States after a period of huge increase in incidence, rates have decreased to values lower than those of the pre-PSA era. Similar changes have been documented also in the area of the Tuscany Cancer Registry, central Italy, where prostate cancer incidence rates doubled from the early 1990s to 2003 and afterwards decreased. This is the first evidence, to our knowledge, of a decline in prostate cancer incidence in Italy following the screening-related increase.

  6. Harderian Gland Tumorigenesis: Low-Dose and LET Response

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Polly Y. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cucinotta, Francis A. [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Bjornstad, Kathleen A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Bakke, James [SRI International, Menlo Park, CA (United States). Biosciences Div.; Rosen, Chris J. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Du, Nicholas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Fairchild, David G. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cacao, Eliedonna [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Blakely, Eleanor A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

    2016-04-19

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  7. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    Science.gov (United States)

    Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

    2016-05-01

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ∼70 keV/μm) and 1,000 MeV/u titanium (LET ∼100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  8. Low Dose Intermittent Isotretinoin Therapy in Moderate Acne Vulgaris

    Directory of Open Access Journals (Sweden)

    Belçın İzol

    2012-03-01

    Full Text Available Objective: In this study, we aimed to investigate the efficiency and side effects of intermittent low dose isotretinoin therapy in moderate acne. Materials and Methods: Patients followed up at our acne outpatient clinic between September 2007 and April 2009 were evaluated. Those treated with 20 mg/day isotretinoin three times a week were included in the study. Relevant data were recorded from patient files. We recorded the age and weight of the cases, duration of acne, previous treatments, acne grading based on global acne scoring system, side effects and pretreatment and posttreatment Dermatology Life Quality Index scores. Hemogram, liver function tests, lipid profiles at baseline and monthly follow-ups were noted. Results: Global acne scoring of complete response rate in 94.3% of 35 patients was achieved after one year of therapy. The partial response rate was 5.7%. The earliest clinical response was observed after four weeks. The Dermatology Life Quality Index was 7.8 at baseline and 1.8 at the end of the treatment. Cheilitis was the only side effect observed. We observed mild degree relapses in 5 cases in the evaluation 17 months after the end of the treatment.Conclusion: Our results show that low dose intermittent isotretinoin therapy is an effective and tolerable treatment in moderate acne.

  9. Contraception. Low-dose pill launched.

    Science.gov (United States)

    1993-01-01

    At a vibrant ceremony in Kampala, Uganda, the Minister of Women in Development, Youth and Culture launched the new low-dose oral contraceptive Pilplan which provides women more options for birth spacing. Diplomats, physicians, government officials, and business leaders attended the ceremony at the Sheraton Hotel Kampala. A dance group did an interpretation of "Women in Uganda: Gaining Momentum." The Minister considered the introduction of this new pill as a turning point for reproductive rights. A baseline survey among Ugandan women has shown that although almost all women were familiar with the pill, only 36% have ever used it and only 15% were currently using it. 80% thought that pill use was preferable to having an unplanned pregnancy. These findings convinced the Minister that ignorance and misconception keep women from using the pill. The government, health providers, and others need to educate women about Pilplan and how to use it correctly. A bilateral agreement between the Ministry of Health and USAID set in motion a social marketing project which has now launched two contraceptive methods: Pilplan in 1993 and the Protector condom in 1990. USAID vowed to continue to support Pilplan, particularly if men could also help in supporting birth spacing. A Uganda-based pharmaceutical firm will distribute Pilplan in Uganda through pharmacies, clinics, and health facilities. Pilplan targets all middle- to low-income women.

  10. A combination of high dose rate (10X FFF/2400 MU/min/10 MV X-rays) and total low dose (0.5 Gy) induces a higher rate of apoptosis in melanoma cells in vitro and superior preservation of normal melanocytes.

    Science.gov (United States)

    Sarojini, Sreeja; Pecora, Andrew; Milinovikj, Natasha; Barbiere, Joseph; Gupta, Saakshi; Hussain, Zeenathual M; Tuna, Mehmet; Jiang, Jennifer; Adrianzen, Laura; Jun, Jaewook; Catello, Laurice; Sanchez, Diana; Agarwal, Neha; Jeong, Stephanie; Jin, Youngjin; Remache, Yvonne; Goy, Andre; Ndlovu, Alois; Ingenito, Anthony; Suh, K Stephen

    2015-10-01

    The aim of this study was to determine the apoptotic effects, toxicity, and radiosensitization of total low dose irradiation delivered at a high dose rate in vitro to melanoma cells, normal human epidermal melanocytes (HEM), or normal human dermal fibroblasts (HDF) and to study the effect of mitochondrial inhibition in combination with radiation to enhance apoptosis in melanoma cells. Cells irradiated using 10X flattening filter-free (FFF) 10 MV X-rays at a dose rate of 400 or 2400 MU/min and a total dose of 0.25-8 Gy were analyzed by cell/colony counting, MitoTracker, MTT, and DNA-damage assays, as well as by quantitative real-time reverse transcriptase PCR in the presence or absence of mitochondrial respiration inhibitors. A dose rate of 2400 MU/min killed on average five-fold more melanoma cells than a dose rate 400 MU/min at a total dose of 0.5 Gy and preserved 80% survival of HEM and 90% survival of HDF. Increased apoptosis at the 2400 MU/min dose rate is mediated by greater DNA damage, reduced cell proliferation, upregulation of apoptotic genes, and downregulation of cell cycle genes. HEM and HDF were relatively unharmed at 2400 MU/min. Radiation induced upregulation of mitochondrial respiration in both normal and cancer cells, and blocking the respiration with inhibitors enhanced apoptosis only in melanoma cells. A high dose rate with a low total dose (2400 MU/min, 0.5 Gy/10X FFF 10 MV X-rays) enhances radiosensitivity of melanoma cells while reducing radiotoxicity toward HEM and HDF. Selective cytotoxicity of melanoma cells is increased by blocking mitochondrial respiration.

  11. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses.

    Directory of Open Access Journals (Sweden)

    Hae Mi Joo

    Full Text Available Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6 and LAD2 cells, mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6 and LAD2 cells that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i. The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13, and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro.

  12. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses.

    Science.gov (United States)

    Joo, Hae Mi; Kang, Su Jin; Nam, Seon Young; Yang, Kwang Hee; Kim, Cha Soon; Lee, In Kyung; Kim, Ji Young

    2015-01-01

    Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6) and LAD2 cells), mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6) and LAD2 cells) that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i). The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13), and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro.

  13. Low-dose endotoxemia and human neuropsychological functions.

    Science.gov (United States)

    Krabbe, Karen Suárez; Reichenberg, Abraham; Yirmiya, Raz; Smed, Annelise; Pedersen, Bente Klarlund; Bruunsgaard, Helle

    2005-09-01

    Epidemiological data demonstrate an association between systemic low-grade inflammation defined as 2- to 3-fold increases in circulating inflammatory mediators and age-related decline in cognitive function. However, it is not known whether small elevations of circulating cytokine levels cause direct effects on human neuropsychological functions. We investigated changes in emotional, cognitive, and inflammatory parameters in an experimental in vivo model of low-grade inflammation. In a double-blind crossover study, 12 healthy young males completed neuropsychological tests before as well as 1.5, 6, and 24 h after an intravenous injection of Escherichia coli endotoxin (0.2 ng/kg) or saline in two experimental sessions. Endotoxin administration had no effect on body temperature, cortisol levels, blood pressure or heart rate, but circulating levels of tumor necrosis factor (TNF) and interleukin (IL)-6 increased 2- and 7-fold, respectively, reaching peak values at 3 h, whereas soluble TNF-receptors and IL-1 receptor antagonist peaked at 4.5 h. The neutrophil count increased and the lymphocyte count declined. In this model, low-dose endotoxemia did not affect cognitive performance significantly but declarative memory performance was inversely correlated with cytokine increases. In conclusion, our findings demonstrate a negative association between circulating IL-6 and memory functions during very low-dose endotoxemia independently of physical stress symptoms, and the hypothalamo-pituitary-adrenal axis.

  14. State-of-the-art: prostate LDR brachytherapy.

    Science.gov (United States)

    Voulgaris, S; Nobes, J P; Laing, R W; Langley, S E M

    2008-01-01

    This article on low dose rate (LDR) prostate brachytherapy reviews long-term results, patient selection and quality of life issues. Mature results from the United States and United Kingdom are reported and issues regarding definitions of biochemical failure are discussed. Latest data comparing brachytherapy with radical prostatectomy or no definitive treatment and also the risk of secondary malignancies after prostate brachytherapy are presented. Urological parameters of patient selection and quality of life issues concerning urinary, sexual and bowel function are reviewed. The position of prostate brachytherapy next to surgery as a first-line treatment modality is demonstrated.

  15. Photoacoustic imaging of prostate brachytherapy seeds in ex vivo prostate

    Science.gov (United States)

    Kuo, Nathanael; Kang, Hyun Jae; DeJournett, Travis; Spicer, James; Boctor, Emad

    2011-03-01

    The localization of brachytherapy seeds in relation to the prostate is a key step in intraoperative treatment planning (ITP) for improving outcomes in prostate cancer patients treated with low dose rate prostate brachytherapy. Transrectal ultrasound (TRUS) has traditionally been the modality of choice to guide the prostate brachytherapy procedure due to its relatively low cost and apparent ease of use. However, TRUS is unable to visualize seeds well, precluding ITP and producing suboptimal results. While other modalities such as X-ray and magnetic resonance imaging have been investigated to localize seeds in relation to the prostate, photoacoustic imaging has become an emerging and promising modality to solve this challenge. Moreover, photoacoustic imaging may be more practical in the clinical setting compared to other methods since it adds little additional equipment to the ultrasound system already adopted in procedure today, reducing cost and simplifying engineering steps. In this paper, we demonstrate the latest efforts of localizing prostate brachytherapy seeds using photoacoustic imaging, including visualization of multiple seeds in actual prostate tissue. Although there are still several challenges to be met before photoacoustic imaging can be used in the operating room, we are pleased to present the current progress in this effort.

  16. Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Gniadecki, Robert; Iversen, Lars

    2015-01-01

    is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. METHODS AND MATERIALS: In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over ...: Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong...... the beneficial effects of low-dose TSEBT....

  17. In vivo determination of very-low-density lipoprotein-apolipoprotein B100 secretion rates in humans with a low dose of L-[1-C-13]valine and isotope ratio mass spectrometry

    NARCIS (Netherlands)

    de Sain-van der Velden, MGM; Rabelink, TJ; Gadellaa, MM; Elzinga, H; Reijngoud, DJ; Kuipers, F; Stellaard, F

    1998-01-01

    The aim of the present study was to determine the rate of very-low-density lipoprotein (VLDL)-apolipoprotein (apo) B100 secretion in humans with a minimized amount of L-[1-C-13]valine infusion in combination with the use of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) an

  18. Characteristics of changes in the number of yH2AX and Rad51 protein foci in human skin fibroblasts after prolonged exposure to low-dose rate X-ray radiation

    Directory of Open Access Journals (Sweden)

    Ozerov I.V.

    2014-12-01

    Full Text Available Aim: to compare the repair process of DNA double-strand breaks in mammalian cells after acute versus prolonged exposure to X-ray irradiation with different dose rates. Material and methods. Studies were performed on primary human fibroblasts isolated from skin biopsies of healthy volunteers (women, 29 and 30 years. Cells were irradiated using an X-ray machine RUB RUST-M1 (JSC "Ruselectronics", Moscow, Russia at 37°C temperature with a dose rate of 400 mGy/min (200 kV, 2*2.4 mA, a filter of 1.5mm AI or 4 mGy/min (50 kV, 2*0.4 mA, a filter of 1.5 mm AI. Immuno-cytochemical protein staining was utilized for yH2AX and Rad51 foci analysis. Results. Phosphorylated histone H2AX (yH2AX and the key protein of homologous recombination Rad51 foci formation and disappearance kinetics were investigated simultaneously in primary human dermal fibroblasts after acute and prolonged exposure to X-ray radiation at a same dose. It was shown that the relative yield of yH2AX foci per dose reduces with decrease in dose rate, while the relative yield of Rad51 foci conversely increases. Conclusion. Our findings suggest the fundamental differences in the ratio of non-homologous end joining and homologous recombination DNA repair in acute versus prolonged irradiated cells.

  19. Amphotericin B for cryptococcal meningitis in HIV positive patients: Low dose versus high dose

    Directory of Open Access Journals (Sweden)

    Rajeshwari S

    2007-01-01

    Ondansetran, Domperidone, Diclofenac, Mannitol, Dexamethazone and Pheniramine. Comparison between the groups showed that the cure rate is similar in both the groups ( P =0.440, where as over all mortality was higher in low dose group than in high dose group which was statistically significant ( P =0.03. Adverse effects were higher in high dose group than in low dose group such as hypokalemia ( P =0.04, facial puffiness ( P =0.01. Other adverse effects were comparable in both the groups. Conclusion: High dose of amphotericin B therapy is more efficacious. However hypokalemia and clinical features of nephrotoxicity was higher with patients on high dose therapy, which can be managed by proper monitoring.

  20. New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies

    Directory of Open Access Journals (Sweden)

    Noriyuki Yanagida

    2016-04-01

    With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods.

  1. Characterization of Staphylococcus aureus Strains Isolated from Czech Cystic Fibrosis Patients: High Rate of Ribosomal Mutation Conferring Resistance to MLS(B) Antibiotics as a Result of Long-Term and Low-Dose Azithromycin Treatment.

    Science.gov (United States)

    Tkadlec, Jan; Vařeková, Eva; Pantůček, Roman; Doškař, Jiří; Růžičková, Vladislava; Botka, Tibor; Fila, Libor; Melter, Oto

    2015-08-01

    Staphylococcus aureus is one of the most frequent pathogens infecting the respiratory tract of patients with cystic fibrosis (CF). This study was the first to examine S. aureus isolates from CF patients in the Czech Republic. Among 100 S. aureus isolates from 92 of 107 observed patients, we found a high prevalence of resistance to macrolide-lincosamide-streptogramin B (MLS(B)) antibiotics (56%). More than half of the resistant strains (29 of 56) carried a mutation in the MLS(B) target site. The emergence of MLS(B) resistance and mutations conferring resistance to MLS(B) antibiotics was associated with azithromycin treatment (p=0.000000184 and p=0.000681, respectively). Methicillin resistance was only detected in 3% of isolates and the rate of resistance to other antibiotics did not exceed 12%. The prevalence of small-colony variant (SCV) strains was relatively low (9%) and eight of nine isolates with the SCV phenotype were thymidine dependent. The study population of S. aureus was heterogeneous in structure and both the most prevalent community-associated and hospital-acquired clonal lineages were represented. Of the virulence genes, enterotoxin genes seg (n=52), sei (n=49), and sec (n=16) were the most frequently detected among the isolates. The PVL genes (lukS-PV and lukF-PV) have not been revealed in any of the isolates.

  2. RELATIONSHIP BETWEEN THE INCIDENCE RATES OF TESTICULAR AND PROSTATIC CANCERS AND FOOD CONSUMPTIONS

    Institute of Scientific and Technical Information of China (English)

    李湘鸣; 刘秀梵; 佐藤·章夫

    2002-01-01

    Objective: To determine the relationships between the incidence rates of testicular and prostatic cancers and food consumptions in order to study the etiologic cause and the mechanism of the development of male genital organ cancer. Methods: The incidence rates of testicular and prostatic cancers in 42 countries (region) were correlated with the dietary practices in these countries. These data came from the cancer rate database (1988-1992) and the food supply database (1961-1990) provided by the Department of Environmental Health, Medical University of Yamanashi, Japan. Results: The incidence rates of testicular and prostatic cancers varied greatly from country to country but in China the rates of the both malignancies were lower than that of USA and Japan. This may be due to the difference in lifestyle, especially in dietary practices. Among the food items weexamined, cheese was most closely correlated with the incidence of testicular cancer at ages 20-39, followed by animal fats and milk. The correlation coefficient (r) was the highest (r= 0.804) when calculated for cheese consumed during the period of 1961-1965 (maternal or prepubertal consumption). Stepwise- multiple-regression analysis revealed that cheese (1961-1965) made a significant contribution to the incidence of testicular cancer. Multiple coefficient ( r) is 0.920. As far as prostatic cancer was concerned, milk was most closely correlated (r=0.711) with its incidence, followed by meat and coffee. Stepwise-multiple-regression analysis identified milk, meat, butter and coffee as significant factors contributing to the incidence of prostatic cancer (R=0.993).The results of our study suggest a role of milk and dairy practices in the development of testicular and prostatic cancers.

  3. Low dose radiation and plant growth

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Jae; Lee, Hae Youn; Park, Hong Sook

    2001-03-01

    Ionizing radiation includes cosmic radiation, earth radiation, radionuclides for the medical purpose and nuclear industry, fallout radiation. From the experimental results of various radiation effects on seeds or seedlings, it was found that germination rate, development, respiration rate, reproduction and blooming were accelerated compared with the control. In mammal, hormesis phenomenon manifested itself in increased disease resistance, lifespan, and decreased rate of tumor incidence. In plants, it was shown that germination, sprouting, growth, development, blooming and resistance to disease were accelerated.

  4. [Indications for low-dose CT in the emergency setting].

    Science.gov (United States)

    Poletti, Pierre-Alexandre; Andereggen, Elisabeth; Rutschmann, Olivier; de Perrot, Thomas; Caviezel, Alessandro; Platon, Alexandra

    2009-08-19

    CT delivers a large dose of radiation, especially in abdominal imaging. Recently, a low-dose abdominal CT protocol (low-dose CT) has been set-up in our institution. "Low-dose CT" is almost equivalent to a single standard abdominal radiograph in term of dose of radiation (about one sixth of those delivered by a standard CT). "Low-dose CT" is now used routinely in our emergency service in two main indications: patients with a suspicion of renal colic and those with right lower quadrant pain. It is obtained without intravenous contrast media. Oral contrast is given to patients with suspicion of appendicitis. "Low-dose CT" is used in the frame of well defined clinical algorithms, and does only replace standard CT when it can reach a comparable diagnostic quality.

  5. What can be learned from epidemiologic studies of persons exposed to low doses of radiation?

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, E.S.

    1993-04-01

    The main objective of radiation risk assessment is to determine the risk of various adverse health effects associated with exposure to low doses and low dose rates. Extrapolation of risks from studies of persons exposed at high doses (generally exceeding 1 Sv) and dose rates has been the primary approach used to achieve this objective. The study of Japanese atomic bomb survivors in Hiroshima and Nagasaki has played an especially important role in risk assessment efforts. A direct assessment of the dose-response function based on studies of persons exposed at low doses and dose rates is obviously desirable. This paper focuses on the potential of both current and future nuclear workers studies for investigating the dose-response functions at low doses, and also discusses analyses making use of the low dose portion of the atomic bomb survivor data. Difficulties in using these data are the statistical imprecision of estimated dose-response parameters, and potential bias resulting from confounding factors and from uncertainties in dose estimates.

  6. PREOPERATIVE THERAPY OF LOW-DOSE ASPIRIN IN INTERNAL MAMMARY ARTERY BYPASS OPERATIONS WITH AND WITHOUT LOW-DOSE APROTININ

    NARCIS (Netherlands)

    SCHONBERGER, JPAM; BREDEE, JJ; VANOEVEREN, W; VANZUNDERT, AAJ; VERKROOST, M; TERWOORST, J; BAVINCK, JH; BERREKLOUW, E; WILDEVUUR, CRH

    1993-01-01

    The effect of preoperative low-dose aspirin (1 mg/kg of body weight) and intraoperative low-dose aprotinin (2 million kallikrein inactivator units) treatment on perioperative blood loss and blood requirements in patients who undergo internal mammary artery bypass operations is unknown. Therefore, we

  7. Toward a better understanding of the comparatively high prostate cancer incidence rates in Utah

    Directory of Open Access Journals (Sweden)

    Wiggins Charles L

    2003-04-01

    Full Text Available Abstract Background This study assesses whether comparatively high prostate cancer incidence rates among white men in Utah represent higher rates among members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormons, who comprise about 70% of the state's male population, and considers the potential influence screening has on these rates. Methods Analyses are based on 14,693 histologically confirmed invasive prostate cancer cases among men aged 50 years and older identified through the Utah Cancer Registry between 1985 and 1999. Cancer records were linked to LDS Church membership records to determine LDS status. Poisson regression was used to derive rate ratios of LDS to nonLDS prostate cancer incidence, adjusted for age, disease stage, calendar time, and incidental detection. Results LDS men had a 31% (95% confidence interval, 26% – 36% higher incidence rate of prostate cancer than nonLDS men during the study period. Rates were consistently higher among LDS men over time (118% in 1985–88, 20% in 1989–92, 15% in 1993–1996, and 13% in 1997–99; age (13% in ages 50–59, 48% in ages 60–69, 28% in ages 70–79, and 16% in ages 80 and older; and stage (36% in local/regional and 17% in unstaged. An age- and stage-shift was observed for both LDS and nonLDS men, although more pronounced among LDS men. Conclusions Comparatively high prostate cancer incidence rates among LDS men in Utah are explained, at least in part, by more aggressive screening among these men.

  8. An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern

    NARCIS (Netherlands)

    Borot, Maxence; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.

    2015-01-01

    Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance.

  9. Low-dose adenosine stress echocardiography: Detection of myocardial viability

    Directory of Open Access Journals (Sweden)

    Nedeljkovic Milan

    2003-06-01

    Full Text Available Abstract Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability.

  10. Low-dose CT denoising with convolutional neural network

    CERN Document Server

    Chen, Hu; Zhang, Weihua; Liao, Peixi; Li, Ke; Zhou, Jiliu; Wang, Ge

    2016-01-01

    To reduce the potential radiation risk, low-dose CT has attracted much attention. However, simply lowering the radiation dose will lead to significant deterioration of the image quality. In this paper, we propose a noise reduction method for low-dose CT via deep neural network without accessing original projection data. A deep convolutional neural network is trained to transform low-dose CT images towards normal-dose CT images, patch by patch. Visual and quantitative evaluation demonstrates a competing performance of the proposed method.

  11. Low-Dose CT via Deep Neural Network

    CERN Document Server

    Chen, Hu; Zhang, Weihua; Liao, Peixi; Li, Ke; Zhou, Jiliu; Wang, Ge

    2016-01-01

    In order to reduce the potential radiation risk, low-dose CT has attracted more and more attention. However, simply lowering the radiation dose will significantly degrade the imaging quality. In this paper, we propose a noise reduction method for low-dose CT via deep learning without accessing the original projection data. An architecture of deep convolutional neural network was considered to map the low-dose CT images into its corresponding normal-dose CT images patch by patch. Qualitative and quantitative evaluations demonstrate a state-the-art performance of the proposed method.

  12. High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Demanes, D. Jeffrey, E-mail: jdemanes@mednet.ucla.edu [California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine of University of California at Los Angeles, Los Angeles, CA (United States); Martinez, Alvaro A.; Ghilezan, Michel [William Beaumont Hospital, Royal Oak, MI (United States); Hill, Dennis R.; Schour, Lionel; Brandt, David [California Endocurietherapy, Oakland, CA (United States); Gustafson, Gary [William Beaumont Hospital, Royal Oak, MI (United States)

    2011-12-01

    Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

  13. Irradiation with low-dose gamma ray enhances tolerance to heat stress in Arabidopsis seedlings.

    Science.gov (United States)

    Zhang, Liang; Zheng, Fengxia; Qi, Wencai; Wang, Tianqi; Ma, Lingyu; Qiu, Zongbo; Li, Jingyuan

    2016-06-01

    Gamma irradiation at low doses can stimulate the tolerance to environmental stress in plants. However, the knowledge regarding the mechanisms underlying the enhanced tolerance induced by low-dose gamma irradiation is far from fully understood. In this study, to investigate the physiological and molecular mechanisms of heat stress alleviated by low-dose gamma irradiation, the Arabidopsis seeds were exposed to a range of doses before subjected to heat treatment. Our results showed that 50-Gy gamma irradiation maximally promoted seedling growth in response to heat stress. The production rate of superoxide radical and contents of hydrogen peroxide and malondialdehyde in the seedlings irradiated with 50-Gy dose under heat stress were significantly lower than those of controls. The activities of antioxidant enzymes, glutathione (GSH) content and proline level in the gamma-irradiated seedlings were significantly increased compared with the controls. Furthermore, transcriptional expression analysis of selected genes revealed that some components related to heat tolerance were stimulated by low-dose gamma irradiation under heat shock. Our results suggest that low-dose gamma irradiation can modulate the physiological responses as well as gene expression related to heat tolerance, thus alleviating the stress damage in Arabidopsis seedlings.

  14. Health risks associated with low dose diagnostic or therapeutic radiation exposures

    Energy Technology Data Exchange (ETDEWEB)

    Boreham, D.R. [McMaster Univ., Dept. of Medical Physics and Applied Radiation Sciences, Hamilton, Ontario (Canada)

    2007-07-01

    The health risks to humans associated with exposure to low doses of ionizing radiation have been extrapolated from effects observed at high doses, dose rates, and mixed radiation qualities using a linear no threshold model. Based on this approach, it has been argued that human exposure to low doses of diagnostics X-rays and gamma-rays increase an individual's risk of developing cancer throughout their life-time. Also, repeated medical diagnostic procedures involving low dose exposures will have an additive effect and consequently further increase health risk. The specific aim of this seminar will be to address the relative risk associated with diagnostic X-rays from CT scans and gamma-rays from positron emission tomography (PET) scans. Objectives of the talk will include: 1) Defining low dose exposures at a cellular level and relate that to diagnostic or therapeutic exposures, 2) Describing modern tools in molecular cytogenetics to estimate radiation exposure and assess radiation risk, 3) Identifying the different cellular mechanisms that influence radiation risk at high and low dose exposures and relate that to individual radiation risk. (author)

  15. Bronchiolitis obliterans organizing pneumonia during low-dose amiodarone therapy

    NARCIS (Netherlands)

    Jessurun, GAJ; Hoogenberg, K; Crijns, HJGM

    1997-01-01

    Two cases of amiodarone-induced pulmonary toxicity during a relatively short period of low-dose amiodarone treatment are reported. The toxicity risk of amiodarone is determined by cumulative factors in individual patients.

  16. Bronchiolitis obliterans organizing pneumonia during low-dose amiodarone therapy

    NARCIS (Netherlands)

    Jessurun, GAJ; Hoogenberg, K; Crijns, HJGM

    Two cases of amiodarone-induced pulmonary toxicity during a relatively short period of low-dose amiodarone treatment are reported. The toxicity risk of amiodarone is determined by cumulative factors in individual patients.

  17. Responses to low doses of ionizing radiation in biological systems.

    Science.gov (United States)

    Feinendegen, Ludwig E; Pollycove, Myron; Sondhaus, Charles A

    2004-07-01

    Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems.To examine tissue effects specific for low-dose radiation, (1) absorbed dose in tissue is replaced by the sum of the energies deposited by each track event, or hit, in a cell-equivalent tissue micromass (1 ng) in all micromasses exposed, that is, by the mean energy delivered by all microdose hits in the exposed micromasses, with cell dose expressing the total energy per micromass from multiple microdoses; and (2) tissue effects are related to cell damage and protective cellular responses per average microdose hit from a given radiation quality for all such hits in the exposed micromasses.The probability of immediate DNA damage per low-linear-energy-transfer (LET) average micro-dose hit is extremely small, increasing over a certain dose range in proportion to the number of hits. Delayed temporary adaptive protection (AP) involves (a) induced detoxification of reactive oxygen species, (b) enhanced rate of DNA repair, (c) induced removal of damaged cells by apoptosis followed by normal cell replacement and by cell differentiation, and (d) stimulated immune response, all with corresponding changes in gene expression. These AP categories may last from less than a day to weeks and be tested by cell responses against renewed irradiation. They operate physiologically against nonradiogenic, largely endogenous DNA damage, which occurs abundantly and continually. Background radiation damage caused by rare microdose hits per micromass is many orders of magnitude less frequent. Except for apoptosis, AP increasingly fails above about 200 mGy of low-LET radiation, corresponding to about 200 microdose hits per exposed micromass. This ratio appears to exceed approximately

  18. Development of Plant Application Technique of Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Byung Yeoup; Kim, Jae Sung; Lim, Yong Taek (and others)

    2007-07-15

    The project was carried out to achieve three aims. First, development of application techniques of cell-stimulating effects by low-dose radiation. Following irradiation with gamma-rays of low doses, beneficial effects in crop germination, early growth, and yield were investigated using various plant species and experimental approaches. For the actual field application, corroborative studies were also carried out with a few concerned experimental stations and farmers. Moreover, we attempted to establish a new technique of cell cultivation for industrial mass-production of shikonin, a medicinal compound from Lithospermum erythrorhizon and thereby suggested new application fields for application techniques of low-dose radiation. Second, elucidation of action mechanisms of ionizing radiation in plants. By investigating changes in plant photosynthesis and physiological metabolism, we attempted to elucidate physiological activity-stimulating effects of low-dose radiation and to search for radiation-adaptive cellular components. Besides, analyses of biochemical and molecular biological mechanisms for stimulus-stimulating effects of low-dose radiation were accomplished by examining genes and proteins inducible by low-dose radiation. Third, development of functional crop plants using radiation-resistant factors. Changes in stress-tolerance of plants against environmental stress factors such as light, temperature, salinity and UV-B stress after exposed to low-dose gamma-rays were investigated. Concerned reactive oxygen species, antioxidative enzymes, and antioxidants were also analyzed to develop high value-added and environment-friendly functional plants using radiation-resistant factors. These researches are important to elucidate biological activities increased by low-dose radiation and help to provide leading technologies for improvement of domestic productivity in agriculture and development of high value-added genetic resources.

  19. Long term/low dose formalin exposure to small-scale recirculation aquaculture systems

    DEFF Research Database (Denmark)

    Pedersen, Lars-Flemming; Pedersen, Per Bovbjerg; Nielsen, Jeppe L.

    2010-01-01

    Repetitive long term formalin application at low dose was investigated to determine the effect on formaldehyde removal rate, biofilter nitrification and the microbial composition in small-scale recirculation aquaculture biofilters. Six pilot-scale recirculation aquaculture systems holding rainbow...... Nitrobacter sp. was not detected. The relative abundances of AOB and NOB in the untreated system were generally higher compared to the system exposed to formalin. Low dose formalin in recirculated aquaculture systems proved to be a possible treatment strategy, as the effect on nitrification was minimal. Since...

  20. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Suk Chul [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Lee, Kyung-Mi [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kang, Yu Mi [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Kwanghee [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Chong Soon [Department of Nuclear Medicine, Haeundae Paik Hospital, Inje University, Busan 612-030 (Korea, Republic of); Kim, Hee Sun, E-mail: hskimdvm@khnp.co.kr [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of)

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  1. Low-Dose Radiation Exposure and Atherosclerosis in ApoE(-/-) Mice

    NARCIS (Netherlands)

    Mitchel, R. E. J.; Hasu, M.; Bugden, M.; Wyatt, H.; Little, M. P.; Gola, A.; Hildebrandt, G.; Priest, N. D.; Whitman, S. C.

    2011-01-01

    The hypothesis that single low-dose exposures (0.025-0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE(-/-)). Mice were exposed eithe

  2. Low-dose acarbose does not delay digestion of starch but reduces its bioavailability

    NARCIS (Netherlands)

    Wachters-Hagedoorn, R. E.; Priebe, M. G.; Heimweg, J. A. J.; Heiner, A. M.; Elzinga, H.; Stellaard, F.; Vonk, R. J.

    2007-01-01

    Aims Slowly digestible starch is associated with beneficial health effects. The glucose-lowering drug acarbose has the potential to retard starch digestion since it inhibits alpha-amylase and alpha-glucosidases. We tested the hypothesis that a low dose of acarbose delays the rate of digestion of rap

  3. Low-Dose Radiation Exposure and Atherosclerosis in ApoE(-/-) Mice

    NARCIS (Netherlands)

    Mitchel, R. E. J.; Hasu, M.; Bugden, M.; Wyatt, H.; Little, M. P.; Gola, A.; Hildebrandt, G.; Priest, N. D.; Whitman, S. C.

    The hypothesis that single low-dose exposures (0.025-0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE(-/-)). Mice were exposed

  4. Stereoscopic interpretation of low-dose breast tomosynthesis projection images.

    Science.gov (United States)

    Muralidhar, Gautam S; Markey, Mia K; Bovik, Alan C; Haygood, Tamara Miner; Stephens, Tanya W; Geiser, William R; Garg, Naveen; Adrada, Beatriz E; Dogan, Basak E; Carkaci, Selin; Khisty, Raunak; Whitman, Gary J

    2014-04-01

    The purpose of this study was to evaluate stereoscopic perception of low-dose breast tomosynthesis projection images. In this Institutional Review Board exempt study, craniocaudal breast tomosynthesis cases (N = 47), consisting of 23 biopsy-proven malignant mass cases and 24 normal cases, were retrospectively reviewed. A stereoscopic pair comprised of two projection images that were ±4° apart from the zero angle projection was displayed on a Planar PL2010M stereoscopic display (Planar Systems, Inc., Beaverton, OR, USA). An experienced breast imager verified the truth for each case stereoscopically. A two-phase blinded observer study was conducted. In the first phase, two experienced breast imagers rated their ability to perceive 3D information using a scale of 1-3 and described the most suspicious lesion using the BI-RADS® descriptors. In the second phase, four experienced breast imagers were asked to make a binary decision on whether they saw a mass for which they would initiate a diagnostic workup or not and also report the location of the mass and provide a confidence score in the range of 0-100. The sensitivity and the specificity of the lesion detection task were evaluated. The results from our study suggest that radiologists who can perceive stereo can reliably interpret breast tomosynthesis projection images using stereoscopic viewing.

  5. Low-dose adenosine stress echocardiography: Detection of myocardial viability

    Science.gov (United States)

    Djordjevic-Dikic, Ana; Ostojic, Miodrag; Beleslin, Branko; Nedeljkovic, Ivana; Stepanovic, Jelena; Stojkovic, Sinisa; Petrasinovic, Zorica; Nedeljkovic, Milan; Saponjski, Jovica; Giga, Vojislav

    2003-01-01

    Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals) echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months) were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p < 0.001). Of the 257 segments with baseline dyssynergy, adenosine echocardiography identified 122 segments as positive for viability, and 135 as necrotic since no improvement of systolic thickening was observed. Follow-up wall motion score index was 1.31 ± 0.30 (p < 0.001 vs. rest). The sensitivity of adenosine echo test for identification of viable segments was 87%, while specificity was 95%, and diagnostic accuracy 90%. Positive and negative predictive values were 97% and 80%, respectively. Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability. PMID:12812523

  6. Low Dose Radiation Hypersensitivity is Caused by p53-dependent Apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Enns, L; Bogen, K; Wizniak, J; Murtha, A; Weinfeld, M

    2004-04-08

    Exposure to environmental radiation and the application of new clinical modalities, such as radioimmunotherapy, have heightened the need to understand cellular responses to low dose and low-dose rate ionizing radiation. Many tumor cell lines have been observed to exhibit a hypersensitivity to radiation doses below 50 cGy, which manifests as a significant deviation from the clonogenic survival response predicted by a linear-quadratic fit to higher doses. However, the underlying processes for this phenomenon remain unclear. Using a gel microdrop/flow cytometry assay to monitor single cell proliferation at early times post irradiation, we examined the response of human A549 lung carcinoma, T98G glioma and MCF7 breast carcinoma cell lines exposed to gamma radiation doses from 0 to 200 cGy delivered at 0.18 and 22 cGy/min. The A549 and T98G cells, but not MCF7 cells, showed the marked hypersensitivity at doses <50 cGy. To further characterize the low-dose hypersensitivity, we examined the influence of low-dose radiation on cell cycle status and apoptosis by assays for active caspase-3 and phosphatidylserine translocation (annexin-V binding). We observed that caspase-3 activation and annexin-V binding mirrored the proliferation curves for the cell lines. Furthermore, the low-dose hypersensitivity and annexin-V binding to irradiated A549 and T98G cells were eliminated by treating the cells with pifithrin, an inhibitor of p53. When p53-inactive cell lines (2800T skin fibroblasts and HCT116 colorectal carcinoma cells) were examined for similar patterns, we found that there was no HRS and apoptosis was not detectable by annexin-V or caspase-3 assays. Our data therefore suggest that low-dose hypersensitivity is associated with p53-dependent apoptosis.

  7. Prostate Cancer Biochemical Recurrence Rates After Robotic-Assisted Laparoscopic Radical Prostatectomy

    Science.gov (United States)

    Ginzburg, Serge; Nevers, Thomas; Staff, Ilene; Tortora, Joseph; Champagne, Alison; Kesler, Stuart S.; Laudone, Vincent P.

    2012-01-01

    Background and Objectives: To determine prostate cancer biochemical recurrence rates with respect to surgical margin (SM) status for patients undergoing robotic-assisted laparoscopic radical prostatectomy (RALP). Methods: IRB-approved radical prostatectomy database was queried. Patients were stratified as low, intermediate, and high risk according to D’Amico's risk classification. Postoperative prostate-specific antigen (PSA) values were obtained every 3 mo for the first year, then biannually and annually thereafter. Biochemical recurrence was defined as ≥0.2ng/mL. Patients receiving adjuvant or salvage treatment were included. Positive surgical margin was defined as presence of cancer cells at inked resection margin in the final specimen. Margin presence (negative/positive), margin multiplicity (single/multiple), and margin length (≤3mm focal and >3mm extensive) were noted. Kaplan-Meier curves of biochemical recurrence-free survival (BRFS) as a function of SM were generated. Forward stepwise multivariate Cox regression was performed, with preoperative PSA, Gleason score, pathologic stage, prostate gland weight, and SM as covariates. Results: At our institution, 1437 patients underwent RALP (2003-2009). Of these, 1159 had sufficient data and were included in our analysis. Mean follow-up was 16 mo. Kaplan-Meier curves demonstrated significant increase in BRFS in low-risk and intermediate-risk groups with negative SM. Overall BRFS at 5 y was 72%. Gleason score, pathologic stage, and SM status were significant prognostic factors in multivariate analysis. Conclusions: Negative surgical margins resulted in lower biochemical recurrence rates for low-risk and intermediate-risk groups. Multifocal and longer positive margins were associated with higher biochemical recurrence rates compared with unifocal and shorter positive margins. Documenting biochemical recurrence rates for RALP is important, because this treatment for localized prostate cancer is validated. PMID

  8. High-Dose-Rate Prostate Brachytherapy Consistently Results in High Quality Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    White, Evan C.; Kamrava, Mitchell R.; Demarco, John; Park, Sang-June; Wang, Pin-Chieh; Kayode, Oluwatosin; Steinberg, Michael L. [California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine of University of California at Los Angeles, Los Angeles, California (United States); Demanes, D. Jeffrey, E-mail: jdemanes@mednet.ucla.edu [California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine of University of California at Los Angeles, Los Angeles, California (United States)

    2013-02-01

    Purpose: We performed a dosimetry analysis to determine how well the goals for clinical target volume coverage, dose homogeneity, and normal tissue dose constraints were achieved with high-dose-rate (HDR) prostate brachytherapy. Methods and Materials: Cumulative dose-volume histograms for 208 consecutively treated HDR prostate brachytherapy implants were analyzed. Planning was based on ultrasound-guided catheter insertion and postoperative CT imaging; the contoured clinical target volume (CTV) was the prostate, a small margin, and the proximal seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100, V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were evaluated by the dose to 0.1 cm{sup 3}, 1 cm{sup 3}, and 2 cm{sup 3} of each organ, expressed as a percentage of the prescribed dose. Analysis was stratified according to prostate size. Results: The mean prostate ultrasound volume was 38.7 {+-} 13.4 cm{sup 3} (range: 11.7-108.6 cm{sup 3}). The mean CTV was 75.1 {+-} 20.6 cm{sup 3} (range: 33.4-156.5 cm{sup 3}). The mean D90 was 109.2% {+-} 2.6% (range: 102.3%-118.4%). Ninety-three percent of observed D90 values were between 105 and 115%. The mean V90, V100, V150, and V200 were 99.9% {+-} 0.05%, 99.5% {+-} 0.8%, 25.4% {+-} 4.2%, and 7.8% {+-} 1.4%. The mean dose to 0.1 cm{sup 3}, 1 cm{sup 3}, and 2 cm{sup 3} for organs at risk were: Urethra: 107.3% {+-} 3.0%, 101.1% {+-} 14.6%, and 47.9% {+-} 34.8%; bladder wall: 79.5% {+-} 5.1%, 69.8% {+-} 4.9%, and 64.3% {+-} 5.0%; bladder balloon: 70.3% {+-} 6.8%, 59.1% {+-} 6.6%, and 52.3% {+-} 6.2%; rectum: 76.3% {+-} 2.5%, 70.2% {+-} 3.3%, and 66.3% {+-} 3.8%. There was no significant difference between D90 and V100 when stratified by prostate size. Conclusions: HDR brachytherapy allows the physician to consistently achieve complete prostate target coverage and maintain normal tissue dose constraints for organs at risk over a wide range of target volumes.

  9. Low dose Mifepristone (100 mg for medical termination of pregnancy

    Directory of Open Access Journals (Sweden)

    Shikha Seth

    2011-02-01

    Full Text Available Background: Abortion is the most common entity in the practice of obstetrics and gynaecology. Different methods and modes have been opted for until now to find an effective regimen with the least complications. We have tried the minimal dose (100 mg of Mifepristone (PO instead of the presently recommended 200 mg for medical abortion in early first trimester cases. Objectives: The objective of the study was to determine the efficacy of low dose (100 mg Mifepristone for medical termination of early pregnancy with oral Misoprostol 800 μg, 24 hours later.Design: A prospective analytical study was conducted on a population of 82 early-pregnant patients who have requested medical abortions.Method: Pregnant women of less than 56 days gestation age from their last menstrual period, requesting medical abortion were selected over a period of 14 months from January 2007 to March 2008. They were given 100 mg Mifepristone orally on Day-1, followed by 800 μg Misoprostol orally 24 hours later on Day-2, keeping the patient in the ward for at least 6 hours. Abortion interval, success rate, post-abortion bleeding and side-effects were noted. Success was defined as complete uterine evacuation without the need for surgical intervention.Results: The total success rate of this minimal dose Mifepristone regimen was 96.25%. Pain and nausea were the predominant side-effects noted. In total 72 (90% women had completely aborted within 5 hours of taking Misoprostol. Three (3.75% women only required suction aspiration, hence termed as failed medical abortion. The abortion interval increased with the gestation age. All three failures were of the more-than-42-day gestational age group. The overall mean abortion interval was 4.68 ± 5.32 hours.Conclusion: Mifepristone 100 mg, followed 24 hours later by Misoprostol 800 μg orally, is a safe and effective regimen for medical abortion.

  10. Lung cancer risk at low doses of alpha particles.

    Science.gov (United States)

    Hofmann, W; Katz, R; Zhang, C X

    1986-10-01

    A survey of inhabitant exposures arising from the inhalation of 222Rn and 220Rn progeny, and lung cancer mortality has been carried out in two adjacent areas in Guangdong Province, People's Republic of China, designated as the "high background" and the "control" area. Annual exposure rates are 0.38 working level months (WLM) per year in the high background, and 0.16 WLM/yr in the control area. In 14 yr of continuous study, from 1970 to 1983, age-adjusted mortality rates were found to be 2.7 per 10(5) living persons of all ages in the high background area, and 2.9 per 10(5) living persons in the control area. From this data, we conclude that we are unable to determine excess lung cancers over the normal fluctuations below a cumulative exposure of 15 WLM. This conclusion is supported by lung cancer mortality data from Austrian and Finnish high-background areas. A theoretical analysis of epidemiological data on human lung cancer incidence from inhaled 222Rn and 220Rn progeny, which takes into account cell killing as competitive with malignant transformation, leads to the evaluation of a risk factor which is either a linear-exponential or a quadratic-exponential function of the alpha-particle dose. Animal lung cancer data and theoretical considerations can be supplied to support either hypothesis. Thus we conclude that at our current stage of knowledge both the linear-exponential and the quadratic-exponential extrapolation to low doses seem to be equally acceptable for Rn-induced lung cancer risk, possibly suggesting a linear-quadratic transformation function with an exponential cell-killing term, or the influence of risk-modifying factors such as repair or proliferation stimuli.

  11. High-Dose-Rate Brachytherapy Boost for Prostate Cancer: Comparison of Two Different Fractionation Schemes

    Energy Technology Data Exchange (ETDEWEB)

    Kaprealian, Tania [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Weinberg, Vivian [Biostatistics and Computational Biology Core, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Speight, Joycelyn L. [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Gottschalk, Alexander R. [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Shinohara, Katsuto [Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Hsu, I.-Chow, E-mail: IHsu@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States)

    2012-01-01

    Purpose: This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy Multiplication-Sign 3 fractions (patient group 1) and 950 cGy Multiplication-Sign 2 fractions (patient group 2). Methods and Materials: A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy Multiplication-Sign 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy Multiplication-Sign 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score {>=}7, and/or clinical stage T3 disease. Results: Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. Conclusions: Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

  12. High-resolution low-dose scanning transmission electron microscopy.

    Science.gov (United States)

    Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

  13. Unusual specificity of the androgen receptor in the human prostate tumor cell line LNCaP: High affinity for progestagenic and estrogenic steroids

    NARCIS (Netherlands)

    J. Veldscholte (Jos); M.M. Voorhorst-Ogink (M.); J. Bolt-de Vries (Joan); H.C.J. van Rooij (Henri); J. Trapman (Jan); E. Mulder (Eppo)

    1990-01-01

    textabstractAbstract LNCaP tumor cells, derived from a metastatic lesion of a human prostatic carcinoma, are androgen-sensitive in cell culture. Although increase in growth rate is observed with low doses of progestagens or estradiol, these cells contain exclusively androgen receptors. In the presen

  14. Cancer detection rates of different prostate biopsy regimens in patients with renal failure.

    Science.gov (United States)

    Hoşcan, Mustafa Burak; Özorak, Alper; Oksay, Taylan; Perk, Hakkı; Armağan, Abdullah; Soyupek, Sedat; Serel, Tekin Ahmet; Koşar, Alim

    2014-07-01

    We aimed to evaluate the cancer detection rates of 6-, 10-, 12-core biopsy regimens and the optimal biopsy protocol for prostate cancer diagnosis in patients with renal failure. A total of 122 consecutive patients with renal failure underwent biopsy with age-specific prostate-specific antigen (PSA) levels up to 20 ng/mL. The 12-core biopsy technique (sextant biopsy + lateral base, lateral mid-zone, lateral apex, bilaterally) performed to all patients. Pathology results were examined separately for each sextant, 10-core that exclude parasagittal mid-zones from 12-cores (10a), 10-core that exclude apex zones from 12-cores (10b) and 12-core biopsy regimens. Of 122 patients, 37 (30.3%) were positive for prostate cancer. The cancer detection rates for sextant, 10a, 10b and 12 cores were 17.2%, 29%, 23.7% and 30.7%, respectively. Biopsy techniques of 10a, 10b and 12 cores increased the cancer detection rates by 40%, 27.5% and 43.2% among the sextant technique, respectively. Biopsy techniques of 10a and 12 cores increased the cancer detection rates by 17.1% and 21.6% among 10b biopsy technique, respectively. There were no statistical differences between 12 core and 10a core about cancer detection rate. Adding lateral cores to sextant biopsy improves the cancer detection rates. In our study, 12-core biopsy technique increases the cancer detection rate by 5.4% among 10a core but that was not statistically different. On the other hand, 12-core biopsy technique includes all biopsy regimens. We therefore suggest 12-core biopsy or minimum 10-core strategy incorporating six peripheral biopsies with elevated age- specific PSA levels up to 20 ng/mL in patients with renal failure.

  15. Clofarabine plus Low-Dose Cytarabine Followed by Clofarabine plus Low-Dose Cytarabine Alternating with Decitabine in AML Frontline Therapy of Older Patients

    Science.gov (United States)

    Faderl, Stefan; Ravandi, Farhad; Huang, Xuelin; Wang, Xuemei; Jabbour, Elias; Garcia-Manero, Guillermo; Kadia, Tapan; Ferrajoli, Alessandra; Konopleva, Marina; Borthakur, Gautam; Burger, Jan; Feliu, Jennie; Kantarjian, Hagop M.

    2014-01-01

    Background Standard therapy for older patients with AML has a poor outcome. We have designed a combination of clofarabine plus low-dose cytarabine followed by a prolonged consolidation alternating with decitabine. Methods Sixty patients with a median age of 70 years (range 60-81) with newly diagnosed AML were included. They received clofarabine 20mg/m2 intravenously daily × 5 days plus cytarabine 20mg subcutaneously twice daily × 10 days. Responding patients continued for up to 17 courses of consolidation therapy including decitabine. Results Forty of 59 evaluable patients responded (66%). Complete remission rate was 58%. Median relapse-free survival (RFS) was 14.1 (95% CI: 6.9-not estimable) and median overall survival (OS) 12.7 months (95% CI: 8.8-not estimable). Median OS of responding patients (CR/CRp) was 24.2 months (95% CI: 17-not estimable). Compared to a historical group of patients who received clofarabine plus low-dose cytarabine with a shorter consolidation, RFS was not statistically different. Induction mortality was low (7% at 8 weeks) and toxicities manageable. Conclusions Clofarabine plus low-dose cytarabine alternating with decitabine in consolidation is active in older patients with newly diagnosed AML. The benefits of a prolonged consolidation remain unproven. PMID:22282348

  16. Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

    Science.gov (United States)

    Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

    2014-05-01

    Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.

  17. The debate on the use of linear no threshold for assessing the effects of low doses

    Energy Technology Data Exchange (ETDEWEB)

    Tubiana, M; Aurengo, A; Averbeck, D; Masse, R [Centre Antoine Beclere, 45 rue des Saints-Peres, 75006 Paris (France)

    2006-09-15

    From December 2004 to July 2005, three reports on the effects of low doses of ionising radiation were released: ICRP (2004), the joint report of the French Academies of Science and Medicine (Tubiana et al 2005), and a report from the American Academy of Sciences (BEIR VII 2005). These reports quote the same recent articles on the biological effects of low doses, yet their conclusions diverge. The French report concludes that recent biological data show that the efficacy of defense mechanisms is modulated by dose and dose rate and that linear no threshold (LNT) is no longer plausible. The ICRP and the BEIR VII reports recognise that there are biologic arguments against LNT but feel that there are not sufficient biological proofs against it to change risk assessment methodology and subsequent regulatory policy based on LNT. They point out the remaining uncertainties and the lack of mechanistic explanations of phenomena such as low dose hyperlethality or the adaptive response. In this context, a critical analysis of the available data is necessary. The epidemiological data and the experimental data challenge the validity of the LNT hypothesis for assessing the carcinogenic effect of low doses, but do not allow its exclusion. Therefore, the main criteria for selecting the most reliable dose-effect relationship from a scientific point of view should be based on biological data. Their analysis should help one to understand the current controversy. (opinion)

  18. The debate on the use of linear no threshold for assessing the effects of low doses.

    Science.gov (United States)

    Tubiana, M; Aurengo, A; Averbeck, D; Masse, R

    2006-09-01

    From December 2004 to July 2005, three reports on the effects of low doses of ionising radiation were released: ICRP (2004), the joint report of the French Academies of Science and Medicine (Tubiana et al 2005), and a report from the American Academy of Sciences (BEIR VII 2005). These reports quote the same recent articles on the biological effects of low doses, yet their conclusions diverge. The French report concludes that recent biological data show that the efficacy of defense mechanisms is modulated by dose and dose rate and that linear no threshold (LNT) is no longer plausible. The ICRP and the BEIR VII reports recognise that there are biologic arguments against LNT but feel that there are not sufficient biological proofs against it to change risk assessment methodology and subsequent regulatory policy based on LNT. They point out the remaining uncertainties and the lack of mechanistic explanations of phenomena such as low dose hyperlethality or the adaptive response. In this context, a critical analysis of the available data is necessary. The epidemiological data and the experimental data challenge the validity of the LNT hypothesis for assessing the carcinogenic effect of low doses, but do not allow its exclusion. Therefore, the main criteria for selecting the most reliable dose-effect relationship from a scientific point of view should be based on biological data. Their analysis should help one to understand the current controversy.

  19. Mammalian Tissue Response to Low Dose Ionizing Radiation: The Role of Oxidative Metabolism and Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Azzam, Edouard I

    2013-01-16

    The objective of the project was to elucidate the mechanisms underlying the biological effects of low dose/low dose rate ionizing radiation in organs/tissues of irradiated mice that differ in their susceptibility to ionizing radiation, and in human cells grown under conditions that mimic the natural in vivo environment. The focus was on the effects of sparsely ionizing cesium-137 gamma rays and the role of oxidative metabolism and intercellular communication in these effects. Four Specific Aims were proposed. The integrated outcome of the experiments performed to investigate these aims has been significant towards developing a scientific basis to more accurately estimate human health risks from exposures to low doses ionizing radiation. By understanding the biochemical and molecular changes induced by low dose radiation, several novel markers associated with mitochondrial functions were identified, which has opened new avenues to investigate metabolic processes that may be affected by such exposure. In particular, a sensitive biomarker that is differentially modulated by low and high dose gamma rays was discovered.

  20. Exposure of luminous marine bacteria to low-dose gamma-radiation.

    Science.gov (United States)

    Kudryasheva, N S; Petrova, A S; Dementyev, D V; Bondar, A A

    2017-04-01

    The study addresses biological effects of low-dose gamma-radiation. Radioactive (137)Cs-containing particles were used as model sources of gamma-radiation. Luminous marine bacterium Photobacterium phosphoreum was used as a bioassay with the bioluminescent intensity as the physiological parameter tested. To investigate the sensitivity of the bacteria to the low-dose gamma-radiation exposure (≤250 mGy), the irradiation conditions were varied as follows: bioluminescence intensity was measured at 5, 10, and 20°С for 175, 100, and 47 h, respectively, at different dose rates (up to 4100 μGy/h). There was no noticeable effect of gamma-radiation at 5 and 10°С, while the 20°С exposure revealed authentic bioluminescence inhibition. The 20°С results of gamma-radiation exposure were compared to those for low-dose alpha- and beta-radiation exposures studied previously under comparable experimental conditions. In contrast to ionizing radiation of alpha and beta types, gamma-emission did not initiate bacterial bioluminescence activation (adaptive response). As with alpha- and beta-radiation, gamma-emission did not demonstrate monotonic dose-effect dependencies; the bioluminescence inhibition efficiency was found to be related to the exposure time, while no dose rate dependence was found. The sequence analysis of 16S ribosomal RNA gene did not reveal a mutagenic effect of low-dose gamma radiation. The exposure time that caused 50% bioluminescence inhibition was suggested as a test parameter for radiotoxicity evaluation under conditions of chronic low-dose gamma irradiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Combined low dose local anesthetics and opioids versus single use ...

    African Journals Online (AJOL)

    2014-09-24

    Sep 24, 2014 ... it allows early recognition of symptoms caused by ... postoperative pain score, less demand for analgesics ... Combined low dose LA and opioids for transurethral surgery. 257 ..... blocks after the intrathecal administration of an LA. .... organ blood volume during spinal anesthesia in elderly men with cardiac.

  2. Malignant melanoma of the tongue following low-dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  3. Low-Dose Pyridoxine Masks Pyridoxine-Dependent Seizures

    OpenAIRE

    2001-01-01

    A 4-month-old male infant with pyridoxine dependency and seizures from birth was controlled with extremely low-dose pyridoxine (0.5 mg/day) given as a vitamin supplement, in a report from Joana de Gusmao Children’s Hospital, Florianopolis, Brazil.

  4. Topics on study of low dose-effect relationship

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Takeshi [Toho Univ., School of Medicine, Tokyo (Japan); Ohyama, Harumi

    1999-09-01

    It is not exceptional but usually observed that a dose-effect relationship in biosystem is not linear. Sometimes, the low dose-effect relationship appears entirely contrary to the expectation from high dose-effect. This is called a 'hormesis' phenomena. A high dose irradiation inflicts certainly an injury on biosystem. No matter how low the dose may be, an irradiation might inflict some injury on biosystem according to Linear Non-Threshold hypothesis(LNT). On the contrary to the expectation, a low dose irradiation stimulates immune system, and promotes cell proliferation. This is called 'radiation hormesis'. The studies of the radiation hormesis are made on from four points of view as follows: (1) radiation adaptive response, (2) revitalization caused by a low dose stimulation, (3) a low dose response unexpected from the LNT hypothesis, (4) negation of the LNT hypothesis. The various empirical proofs of radiation hormesis are introduced in the report. (M . Suetake)

  5. Low dose computed tomography of the chest : Applications and limitations

    NARCIS (Netherlands)

    Gietema, H.A.

    2007-01-01

    In areas with a high intrinsic contrast such as the chest, radiation dose can be reduced for specific indications. Low dose chest CT is feasible and cannot only be applied for lung cancer screening, but also in daily routine and for early detection of lung destruction. We showed in a small sample of

  6. [Clinical study of a low-dose contraceptive--Femodene].

    Science.gov (United States)

    Rachev, E; Damianov, L; Dukovski, A; Katsarova, M

    1995-01-01

    The authors present their clinical experience with a low-dose monophasic contraceptive consisting of 30 mcg ethinylestradiol and 75 mcg a gestagen--gestodene (Femoden, Schering). 112 menstrual cycles of 22 women in fertile age were followed. The results show 100% contraception, a good control of the menstrual cycle and tolerance of the preparation.

  7. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    Science.gov (United States)

    Carcinogenic Effects of Low Doses of Ionizing RadiationR Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711The form of the dose-response curve for radiation-induced cancers, particu...

  8. Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes

    Energy Technology Data Exchange (ETDEWEB)

    Yang, George; Strom, Tobin J.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Wilder, Richard B., E-mail: mcbiagioli@yahoo.com [Cancer Treatment Centers of America, Newnan, GA (United States)

    2015-05-15

    Purpose: to evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and methods: one hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results: median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p-0.04). There was no ≥ Grade 3 acute toxicity. Conclusions: dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. (author)

  9. Dosimetric Coverage of the Prostate, Normal Tissue Sparing, and Acute Toxicity with High-Dose-Rate Brachytherapy for Large Prostate Volumes

    Directory of Open Access Journals (Sweden)

    George Yang

    2015-06-01

    Full Text Available ABSTRACTPurposeTo evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes.Materials and MethodsOne hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL were treated with high-dose-rate (HDR brachytherapy ± intensity modulated radiation therapy (IMRT to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38% unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.ResultsMedian follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3% patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17% patients developed Grade 2 acute urinary retention. American Urological Association (AUA symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p=0.04. There was no ≥ Grade 3 acute toxicity.ConclusionsDosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes.

  10. National Prostate Cancer Screening Rates After the 2012 US Preventive Services Task Force Recommendation Discouraging Prostate-Specific Antigen-Based Screening.

    Science.gov (United States)

    Drazer, Michael W; Huo, Dezheng; Eggener, Scott E

    2015-08-01

    In 2012, the US Preventive Services Task Force (USPSTF) discouraged prostate-specific antigen (PSA) -based prostate cancer screening. Previous USPSTF recommendations did not appreciably alter prostate cancer screening. Therefore, we designed a trend analysis to determine the population-based impact of the 2012 recommendation. The nationally representative National Health Interview Survey was used to estimate the proportion of men age 40 years and older who saw a physician and were screened for prostate cancer in 2013. An externally validated 9-year mortality index was used to analyze screening rates based on remaining life expectancy. Screening rates from 2005, 2010, and 2013 were compared using logistic regression. PSA-based screening did not significantly change from 2010 to 2013 among 40- to 49-year-old men (from 12.5% to 11.2%; P = .4). Screening rates significantly declined in men age 50 to 59 years (from 33.2% to 24.8%; P screened for prostate cancer despite a high risk (> 52%) of 9-year mortality, including approximately one third of men older than age 75 years. Approximately 1.4 million men age 65 years or older with a high risk (> 52%) of 9-year mortality were screened in 2013. Prostate cancer screening significantly declined among men older than age 50 years after the 2012 USPSTF guideline discouraging PSA-based screening. A significant proportion of men continue to be screened despite a high risk of 9-year mortality, including one third of men age 75 years and older. © 2015 by American Society of Clinical Oncology.

  11. AT cells are not radiosensitive for simple chromosomal exchanges at low dose

    Energy Technology Data Exchange (ETDEWEB)

    Hada, Megumi; Huff, Janice L.; Patel, Zarana S. [USRA Division of Life Sciences, Houston, TX 77058 (United States); Kawata, Tetsuya [Department of Radiology, School of Medicine, Keio University, Tokyo (Japan); Pluth, Janice M. [Lawrence Berkeley National Laboratory, Life Sciences Division, One Cyclotron Road, Building 74, Berkeley, CA 94720 (United States); George, Kerry A. [Wyle, 1290 Hercules Drive, Houston, TX 77058 (United States); Cucinotta, Francis A., E-mail: Francis.A.Cucinotta@nasa.gov [NASA, Lyndon B. Johnson Space Center, 2101 NASA Parkway, Houston, TX 77058 (United States)

    2011-11-01

    Cells deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome) show increased yields of both simple and complex chromosomal aberrations after high doses (>0.5 Gy) of ionizing radiation (X-rays or {gamma}-rays), however less is known on how these cells respond at low dose. Previously we had shown that the increased chromosome aberrations in ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex exchanges. The linear dose-response term for simple exchanges was significantly higher in NBS cells compared to wild type cells, but not for AT cells. However, AT cells have a high background level of exchanges compared to wild type or NBS cells that confounds the understanding of low dose responses. To understand the sensitivity differences for high to low doses, chromosomal aberration analysis was first performed at low dose-rates (0.5 Gy/d), and results provided further evidence for the lack of sensitivity for exchanges in AT cells below doses of 1 Gy. Normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, showed increased numbers of exchanges at a dose of 1 Gy and higher, but were similar to wild type cells at 0.5 Gy or below. These results were confirmed using siRNA knockdown of ATM. The present study provides evidence that the increased radiation sensitivity of AT cells for chromosomal exchanges found at high dose does not occur at low dose.

  12. Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

    Science.gov (United States)

    Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

    2017-03-22

    The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

  13. Activation of chemical biological defense mechanisms and remission of vital oxidative injury by low dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yamaoka, K. [Okayama University Medical School, Okayama (Japan); Nomura, T. [Central Research Institute of Electric Power Industry, Tokyo (Japan); Kojima, S. [Science University of Tokyo, Chiba (Japan)

    2000-05-01

    still be evaluated. Hence, we studied the effect of low-dose X-ray irradiation on the synthesis of glutathione peroxidase (GSHP{sub x}), which is an antioxidant that catalyzes this reaction. The results suggest that H{sub 2}O{sub 2} produced by increased SOD activity can be detoxicated into H{sub 2}O and O{sub 2} due to simultaneous enhancement of the GSHP{sub x} activity by X-ray irradiation at 20 cGy, in contrast to irradiation at 400 cGy. The results also show the enhancement in enzyme activities by induction of their synthesis shortly after irradiation at 20 cGy. Moreover, as this phenomenon was observed in BALB/c mice (which are more radiation sensitive compared to other mouse strains) and radiation-resistant C57BL/6NJcl mice, it was considered to be a common phenomenon in the rat spleen. Remission of vital oxidative injury by low dose radiation: (1) We studied the effects of a single post whole-body low-dose radiation (50 cGy of {gamma}-ray) on mice with ferric nitrilotriacetate (Fe{sup 3+} - NTA)-induced transient hepatopathy. As a result, low-dose radiation accelerated the rate of recovery. Based on the changes in glutamic oxaloacetic transaminase activities, glutamic pyruvic transaminase activities and liquid peroxide levels, it was shown that hepatopathy improved by low dose radiation 3 hours after Fe{sup 3+} - NTA administration. This may be because of the enhancement of antioxidant agents such as total glutathione (GSH+GSSG), glutathione peroxidase, glutathione reductase and {gamma}-glutamylcysteine synthetase by low-dose radiation. These findings suggest that low-dose radiation relieved functional disorder at least in the livers of mice with active oxygen species related diseases. (2) Indications for treatment at the Misasa Hot Spring, a radon producing radioactive spring, include hypertension, diabetes mellitus and pain. To clarify its mechanisms of action on these conditions, we evaluated dynamic changes in blood components such as vasoactive substances

  14. Low dose intravesical heparin as prophylaxis against recurrent noninvasive (stage Ta) bladder cancer

    DEFF Research Database (Denmark)

    Bitsch, M; Hermann, G G; Andersen, J P;

    1990-01-01

    A controlled randomized clinical trial was conducted to examine the efficacy of topical low dose heparin (0.125 gm./l., 25,000 units per l.) as prophylaxis against recurrent noninvasive (stage Ta) transitional cell bladder cancer. Transurethral tumor resection was done with irrigation fluid...... containing either 1.5% glycine with heparin or glycine solution alone. Tumor recurrence was determined by cystoscopy 4 to 6 months later. There were 70 patients evaluated: 38 in the heparin and 32 in the control group, respectively. The recurrence rate (heparin 74%, control 66%) and the median number...... of recurrences (heparin 3, range 1 to 15 and control 3, range 1 to 30) were similar (p greater than 0.05) in the 2 groups of patients. These observations show that low dose heparin administered in the irrigation fluid during transurethral resection does not decrease the recurrence rate of noninvasive (stage Ta...

  15. [Treatment of diabetic ketoacidosis and hyperosmolality with low dose insulin infusion (author's transl)].

    Science.gov (United States)

    Duclos, F; François, P; Dumon, P; Altmann, J J

    1978-06-03

    Fifteen patients were treated with low-dose (5 u/hour) insulin infusion, including 10 cases of ketoacidosis, 3 cases of hyperglycemia without acidosis in severely affected diabetics, and 2 cases with hyperosmolality. The treatment was successful in all cases. Insulin was infused at a constant rate, during 12 hours as a mean value. Blood glucose fell regularly and no hypoglycemia occured. Serum potassium varied within narrow limits, and no accident related to hypokalemia was observed. The correction of ketoacidosis was delayed, as compared to that of hyperglycemia. The two elderly patients with hyperosmolality recovered quickly and completely. The method of low-dose insulin infusion seems thus effective and easily applicable, at least in an intensive care unit. Our experience prompted us to increase (10 u/h) rather than to decrease the insulin infusion rate, with the aim to obtain a faster correction of ketoacidosis.

  16. A Paradigm Shift in Low Dose Radiation Biology

    Directory of Open Access Journals (Sweden)

    Z. Alatas

    2015-08-01

    Full Text Available When ionizing radiation traverses biological material, some energy depositions occur and ionize directly deoxyribonucleic acid (DNA molecules, the critical target. A classical paradigm in radiobiology is that the deposition of energy in the cell nucleus and the resulting damage to DNA are responsible for the detrimental biological effects of radiation. It is presumed that no radiation effect would be expected in cells that receive no direct radiation exposure through nucleus. The risks of exposure to low dose ionizing radiation are estimated by extrapolating from data obtained after exposure to high dose radiation. However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose radiation than they do to high dose radiation. Moreover, recent experimental evidences from many laboratories reveal the fact that radiation effects also occur in cells that were not exposed to radiation and in the progeny of irradiated cells at delayed times after radiation exposure where cells do not encounter direct DNA damage. Recently, the classical paradigm in radiobiology has been shifted from the nucleus, specifically the DNA, as the principal target for the biological effects of radiation to cells. The universality of target theory has been challenged by phenomena of radiation-induced genomic instability, bystander effect and adaptive response. The new radiation biology paradigm would cover both targeted and non-targeted effects of ionizing radiation. The mechanisms underlying these responses involve biochemical/molecular signals that respond to targeted and non-targeted events. These results brought in understanding that the biological response to low dose radiation at tissue or organism level is a complex process of integrated response of cellular targets as well as extra-cellular factors. Biological understanding of

  17. Low Dose Gamma Irradiation Potentiates Secondary Exposure to Gamma Rays or Protons in Thyroid Tissue Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Green, Lora M

    2006-05-25

    We have utilized our unique bioreactor model to produce three-dimensional thyroid tissue analogs that we believe better represent the effects of radiation in vivo than two-dimensional cultures. Our thyroid model has been characterized at multiple levels, including: cell-cell exchanges (bystander), signal transduction, functional changes and modulation of gene expression. We have significant preliminary data on structural, functional, signal transduction and gene expression responses from acute exposures at high doses (50-1000 rads) of gamma, protons and iron (Green et al., 2001a; 2001b; 2002a; 2002b; 2005). More recently, we used our DOE funding (ending Feb 06) to characterize the pattern of radiation modulated gene expression in rat thyroid tissue analogs using low-dose/low-dose rate radiation, plus/minus acute challenge exposures. Findings from these studies show that the low-dose/low-dose rate “priming” exposures to radiation invoked changes in gene expression profiles that varied with dose and time. The thyrocytes transitioned to a “primed” state, so that when the tissue analogs were challenged with an acute exposure to radiation they had a muted response (or an increased resistance) to cytopathological changes relative to “un-primed” cells. We measured dramatic differences in the primed tissue analogs, showing that our original hypothesis was correct: that low dose gamma irradiation will potentiate the repair/adaptation response to a secondary exposure. Implications from these findings are that risk assessments based on classical in vitro tissue culture assays will overestimate risk, and that low dose rate priming results in a reduced response in gene expression to a secondary challenge exposure, which implies that a priming dose provides enhanced protection to thyroid cells grown as tissue analogs. If we can determine that the effects of radiation on our tissue analogs more closely resemble the effects of radiation in vivo, then we can better

  18. Animal Studies of Residual Hematopoietic and Immune System Injury from Low Dose/Low Dose Rate Radiation and Heavy Metals.

    Science.gov (United States)

    1998-09-01

    exposed to background over, LDR radiation causes activation of the DNA repair amounts of electromagnetic (e.g., ionizing) radiation as system, thus...decrease in the subpopulations of rhythm, which formed the basic wave of proliferation, but granulocytes or on a regular increase in the subpopulations also...fission products as other common genotoxic factors present in the environ- ment (e.g., cancerogenic chemicals, toxic metal ions). " Nuclear fuel operators

  19. Implementation of High-Dose-Rate Brachytherapy and Androgen Deprivation in Patients With Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lilleby, Wolfgang, E-mail: wolfgang.lilleby@ous-hf.no [Cancer Clinic, Oslo University Hospital, Norwegian Radiumhospital, Department of Radiotherapy and Oncology, Oslo (Norway); Tafjord, Gunnar; Raabe, Nils K. [Cancer Clinic, Oslo University Hospital, Norwegian Radiumhospital, Department of Radiotherapy and Oncology, Oslo (Norway)

    2012-07-01

    Purpose: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims. Methods: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy Multiplication-Sign 25) combined with HDR-BT (iridium 192; prostate 10 Gy Multiplication-Sign 2) with long-term androgen deprivation therapy (ADT). Results: After a median observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had relapsed clinically and/or biochemically and 10 patients were dead, of which 2 patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients with either Gleason score <8 or with intermediate risk profile had relapsed. The number of HDR-BT treatments was not related to outcome. Despite of age (median, 65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39 of 275 patients, Genitourinary treatment-related morbidity was moderate with long-lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2 for gastrointestinal at follow-up. Complications during implantations were related to pubic arch interference (4 patients) and lithotomy time, causing 2 patients to develop compartment syndrome. Conclusion: Despite still preliminary observations, our 5-year outcome estimates favor the implementation of high-dose-rate brachytherapy in high-risk patients combined with conformal

  20. Cystoid Macular Edema Induced by Low Doses of Nicotinic Acid

    Directory of Open Access Journals (Sweden)

    Daniela Domanico

    2013-01-01

    Full Text Available Cystoid macular edema (CME is a condition that involves the macula, causing painless vision loss. In this paper, we report a case of niacin-induced bilateral cystoid macular edema (CME in a middle-age woman taking low dose of niacin (18 mg of nicotinic acid. Optical coherence tomography (OCT showed retinal thickening and cystoid spaces in both eyes, whereas fluorescein angiography (FA; HRA 2, Heidelberg Engineering revealed the absence of fluorescein leakage also in later phases. Four weeks after discontinuation of therapy there were a complete disappearance of macular edema at funduscopic examination and an improvement of visual acuity in both eyes. Furthermore OCT showed a normal retinal profile in both eyes. In our opinion considering the wide availability of niacin, medical monitoring and periodical examination should be considered during niacin administration. To our knowledge, this is the first report in the literature that described the very low-dose niacin-induced bilateral niacin maculopathy.

  1. A Case of Lichen Amyloidosis Treated with Low Dose Acitretin

    Directory of Open Access Journals (Sweden)

    Fatma Pelin Cengiz

    2014-12-01

    Full Text Available Primary localized cutaneous amyloidosis (PCA is a rare disorder characterized by amyloid deposition in dermis without systemic involvement. There are three different types of primary localized cutaneous amyloidosis: Lichen amyloidosis, macular amyloidosis and nodular amyloidosis. The lesions of lichen amyloidosis are characterized by pruritic papules. Although, topical or intralesional treatment with corticosteroids, topical dimethyl sulfoxide, ultraviolet B, oral psoralen plus ultraviolet A, retinoic acid derivatives are the recommended treatment for lichen amyloidosis, the results are often unsatisfactory. In the literature, there have been only a few reports evaluating the efficacy of low dose acitretin in the treatment of lichen amiloidosis. In this article, we report a case of lichen amyloidosis with pruritic hyperkeratotic papules on the back and chest of 5 years’ duration, successfully treated with low dose acitretin.

  2. Low dose ionizing radiation induced acoustic neuroma: A putative link?

    Directory of Open Access Journals (Sweden)

    Sachin A Borkar

    2012-01-01

    Full Text Available Although exposure to high dose ionizing radiation (following therapeutic radiotherapy has been incriminated in the pathogenesis of many brain tumors, exposure to chronic low dose ionizing radiation has not yet been shown to be associated with tumorigenesis. The authors report a case of a 50-year-old atomic reactor scientist who received a cumulative dose of 78.9 mSv over a 10-year period and was detected to have an acoustic neuroma another 15 years later. Although there is no proof that exposure to ionizing radiation was the cause for the development of the acoustic neuroma, this case highlights the need for extended follow-up periods following exposure to low dose ionizing radiation.

  3. Treatment of refractory catatonic schizophrenia with low dose aripiprazole

    Directory of Open Access Journals (Sweden)

    Sasaki Tsuyoshi

    2012-05-01

    Full Text Available Abstract This case is of 54-year-old female with catatonic schizophrenia, characterized by treatment resistance to the pharmacotherapy with olanzapine, risperidone, flunitrazepam, and ECT. Olanzapine and risperidone and flunitrazepam did not improve her catatonic and psychotic symptoms, and induced the extrapyramidal symptoms. The effects of ECT did not continue even for a month. However, the treatment with low-dose aripiprazole dramatically improved the patient’s psychotic symptoms and extrapyramidal symptoms. The mechanisms underlying the effects of low-dose aripiprazole in this case remain unclear, but unlike other antipsychotics, aripiprazole is a dopamine D2 partial agonist. In this regard, our results suggest that aripiprazole has numerous advantages, especially in cases of stuporous catatonia and a defective general status.

  4. Low doses of radiation reduce risks in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Mitchel, R.E.J. [Atomic Energy of Canada Ltd., Chalk River, Ontario (Canada)

    2004-05-01

    The 'Linear No Threshold' hypothesis, used in all radiation protection practices, assumes that all doses, no matter how low, increase risk. The protective effects of adaptive responses to radiation, shown to exist in lower organisms and in human and other mammalian cells, are inconsistent with this hypothesis. An in vivo test of the hypothesis in mice showed that a 100-mGy dose of {gamma}-radiation protected the mice by increasing latency for acute myeloid leukemia initiated by a subsequent large dose. A similar result was observed in cancer prone mice, where a 10-mGy adapting exposure prior to a large acute dose increased latency for lymphomas without altering frequency. Increasing the adapting dose to 100-mGy eliminated the protective effect. In the cancer prone mice, a 10-mGy dose alone, without a subsequent high dose, increased latency for spontaneous osteosarcomas and lymphomas without altering frequency. Increasing the dose to 100-mGy decreased latency for spontaneous osteosarcomas but still increased latency for lymphomas, indicating that this higher dose was in a transition zone between reduced and increased risk, and that the transition dose from protective to detrimental effects is tumor type specific. In genetically normal fetal mice, prior low doses also protected against radiation induced teratogenic effects. In genetically normal adult male mice, high doses induce mutations in sperm stem cells, detectable as heritable mutations in the offspring of these mice. A prior 100 mGy dose protected the male mice from induction of these heritable mutations by the large dose. We conclude that adaptive responses are induced by low doses in normal or cancer prone mice, and that these responses can reduce the risk of cancer, teratogenesis and heritable mutations. At low doses in vivo, the relationship between dose and risk is not linear, and low doses can reduce risk. (author)

  5. Effect of low dose ionizing radiation upon concentration of

    Energy Technology Data Exchange (ETDEWEB)

    Viliae, M.; Kraljeviae, P.; Simpraga, M.; Miljaniae, S.

    2004-07-01

    It is known that low dose ionizing radiation might have stimulating effects (Luckey, 1982, Kraljeviae, 1988). This fact has also been confirmed in the previous papers of Kraljeviae et al. (2000-2000a; 2001). Namely, those authors showed that irradiation of chicken eggs before incubation by a low dose of 0.15 Gy gamma radiation increases the activity aspartateaminotrasferases (AST) and alanine-aminotransferases (ALT) in blood plasma of chickens hatched from irradiated eggs, as well as growth of chickens during the fattening period. Low doses might also cause changes in the concentration of some biochemical parameters in blood plasma of the same chickens such as changes in the concentration of total proteins, glucose and cholesterol. In this paper, an attempt was made to investigate the effects of low dose gamma radiation upon the concentration of sodium and potassium in the blood plasma of chickens which were hatched from eggs irradiated on the 19th day of incubation by dose of 0.15 Gy. Obtained results were compared with the results from the control group (chickens hatched from nonirradiated eggs). After hatching, all other conditions were the same for both groups. Blood samples were drawn from heart, and later from the wing vein on days 1, 3, 5, 7, 10, 20, 30 and 42. The concentration of sodium and potassium was determined spectrophotometrically by atomic absorbing spectrophotometer Perkin-Elmer 1100B. The concentration of sodium and potassium in blood plasma of chickens hatched from eggs irradiated on the 19th day of incubation by dose of 0.15 Gy indicated a statistically significant increase (P>0.01) only on the first day of the experiment. Obtained results showed that irradiation of eggs on the 19th day of incubation by dose of 0.15 Gy gamma radiation could have effects upon the metabolism of electrolytes in chickens. (Author)

  6. Cytogenetic damage at low doses and the problem of bioindication of chronic low level radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' kin, S.A.; Dikarev, V.G.; Nesterov, E.B.; Vasiliev, D.V.; Dikareva, N.S. [Russian Inst. of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2000-05-01

    The analysis undertaken by us of the experimentally observed cellular responses to low dose irradiation has shown that the relationship between the yield of induced cytogenetic damage and radiation dose within low dose range is non-linear and universal in character. Because of the relationship between the yield of cytogenetic damage and dose within low dose range is non-linear, the aberration frequency cannot be used in biological dosimetry in the most important in terms of practical application case. The cytogenetic damage frequency cannot be used in biological dosimetry also because of the probability of synergistic and antagonistic interaction effects of the different nature factors simultaneously acting on test-object in real conditions is high within low dose (concentration) range. In our experimental study of the regularities in the yield of structural mutations in conditions of combined influence of ionizing radiation, heavy metals and pesticides it was found that synergistic and antagonistic effects are mainly induced in conditions of combined action of low exposure injuring agents. Experiments on agricultural plants were carried out in 1986-1989 at the 30-km zone around Chernobyl NPP. It was shown that chronic low dose exposure could cause an inheritable destabilization of genetic structures expressing in increase of cytogenetic damage and yield karyotypic variability in offspring's of irradiated organisms. Obviously exactly this circumstance is the reason of the phenomenon found in our researches of significant time delay of cytogenetic damage reduction rate from radioactive pollution reduction rate from time past from the accident moment. Research of cytogenetic damage of reproductive (seeds) and vegetative (needles) plant organs of the Pinus sylvestris tree micropopulations growing in contrast by radioactive pollution level sites of the 30-km ChNPP zone and also in the vicinity of the industrial plant <> for processing and temporary storage

  7. Exercise and sport performance with low doses of caffeine.

    Science.gov (United States)

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis.

  8. Evaluation of a combination of low-dose ketamine and low-dose midazolam in terminal dyspnea-attenuation of "double-effect"

    Directory of Open Access Journals (Sweden)

    Abhijit Kanti Dam

    2008-01-01

    Full Text Available Aim: Of all symptoms in palliative medicine those concerning respiration are most excruciating and difficult to treat. Reticence about the use of morphine for palliation of dyspnea is common, especially in nonmalignant diseases, as there is a fear of causing respiratory depression, particularly where Chronic Obstructive Pulmonary Disease (COPD exists. This factor is also compounded by the lack of availability of morphine in parts of developing countries. Ketamine has excellent anesthetic and analgesic effects in addition to being easily available. It produces bronchodilatation and does not produce respiratory or cardiovascular depression. The author seeks to evaluate the role of low-dose (0.2 mg/kg ketamine and midazolam (0.02 mg/kg in the attenuation of terminal dyspnea. Methods: Sixteen patients with terminal dyspnea, admitted to the Critical Care Unit (CCU with cancer and other noncancer diagnoses were recruited. The subjective component of dyspnea was assessed using the Graphic Rating Scale (GRS, which has values from 0 - 10, 10 being maximum dyspnea. Each patient received a low-dose of ketamine and midazolam for relief of dyspnea. All the patients received low-flow (2 L/min. oxygen therapy via nasal cannula. Immediately after admission, all the patients were reassured and nursed in a decubitus position of their choice. The GRS was recorded at the point of admission, 10 minutes after starting oxygen therapy, and ten minutes after administration of low-dose ketamine and midazolam. Hemodynamic parameters were also recorded at these three points. Result: All the patients who enrolled in our study had significant dyspnea at admission, as was evident from the GRS scores of 8.250 (SD 0.91, respiratory rate of 28.56 (SD 5.0, mean arterial blood pressure (MABP of 102.7 (SD 14.63, pulse rate of 115.62 (SD 23.3, and SpO2 of 92.43 (SD 2.38. All the patients benefited from the combination of ketamine and midazolam, as evidenced by the statistically

  9. Long term outcome and side effects in patients receiving low-dose I125 brachytherapy: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Pieter Logghe

    Full Text Available ABSTRACT Objectives: To retrospectively evaluate the disease free survival (DFS, disease specific survival (DSS,overall survival (OS and side effects in patients who received low-dose rate (LDR brachytherapy with I125 stranded seeds. Materials and methods: Between july 2003 and august 2012, 274 patients with organ confined prostate cancer were treated with permanent I125 brachytherapy. The median follow-up, age and pretreatment prostate specific antigen (iPSA was 84 months (12-120, 67 years (50-83 and 7.8 ng/mL (1.14-38, respectively. Median Gleason score was 6 (3-9. 219 patients (80% had stage cT1c, 42 patients (15.3% had stage cT2a, 3 (1.1% had stage cT2b and 3 (1.1% had stage cT2c. The median D90 was 154.3 Gy (102.7-190.2. Results: DSS was 98.5%.OS was 93.5%. 13 patients (4.7% developed systemic disease, 7 patients (2.55% had local progression. In 139 low risk patients, the 5 year biochemical freedom from failure rate (BFFF was 85% and 9 patients (6.4% developed clinical progression. In the intermediate risk group, the 5 year BFFF rate was 70% and 5 patients (7.1% developed clinical progression. Median nPSA in patients with biochemical relapse was 1.58 ng/mL (0.21 – 10.46, median nPSA in patients in remission was 0.51 ng/mL (0.01 – 8.5. Patients attaining a low PSA nadir had a significant higher BFFF (p<0.05. Median D90 in patients with biochemical relapse was 87.2 Gy (51 – 143,1. Patients receiving a high D90 had a significant higher BFFF (p<0.05. Conclusion: In a well selected patient population, LDR brachytherapy offers excellent outcomes. Reaching a low PSA nadir and attaining high D90 values are significant predictors for a higher DFS.

  10. The effect of low dose steroid (Physiologic dose and Chloroquine in the treatment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Gharibdoost F

    1999-06-01

    Full Text Available Introduction: The regulation of neuroendocrine axis is one of the most important goals in the treatment of Rheumatoid Arthritis. Disease modifying drugs such as chloroquine with low dose steroid is the first choice in clinical practice by some physicians. This combination therapy is evaluated by this study. Methods: This survey is a prospective study on furty patients. Variables for determining the activity index of disease were joint tenderness, joint swelling, morning stiffness and erythrocytes sedimentation rate in two years follow up. Results: Decrementation of disease activity index was statistically significant before and after treatment, joint tenderness (X²=7.205, P=0.007, morning stiffness (X²=19.253, P=0.00001, joint swelling (X²=14.107, P=0.0001, ESR (T=2.428, P=0.02. Conclusion: The combination of chloroquine with low dose steroid is beneficial in the treatment of Rheumatoid arthritis

  11. Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs.

    Science.gov (United States)

    Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki

    2013-03-01

    This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH.

  12. Mortality from diseases other than cancer following low doses of ionizing radiation

    DEFF Research Database (Denmark)

    Vrijheid, M; Cardis, E; Ashmore, P

    2007-01-01

    , whether such effects also occur following the lower doses and dose rates of public health concern. METHODS: We used data from an international (15-country) nuclear workers cohort study to evaluate whether mortality from diseases other than cancer is related to low doses of external ionizing radiation...... workers (attained age radiation, random variation or residual confounding. CONCLUSIONS: The most informative low-dose radiation......BACKGROUND: Ionizing radiation at very high (radio-therapeutic) dose levels can cause diseases other than cancer, particularly heart diseases. There is increasing evidence that doses of the order of a few sievert (Sv) may also increase the risk of non-cancer diseases. It is not known, however...

  13. Transperineal in vivo fluence-rate dosimetry in the canine prostate during SnET2-mediated PDT

    Energy Technology Data Exchange (ETDEWEB)

    Lilge, Lothar [Ontario Cancer Institute, Princess Margaret Hospital, Toronto, ON (Canada); Pomerleau-Dalcourt, Natalie [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Douplik, Alexander [Ontario Cancer Institute, Princess Margaret Hospital, Toronto, ON (Canada); Selman, Steven H [Urology Research Center, Department of Urology, Medical College of Ohio, Toledo, OH (United States); Keck, Rick W [Urology Research Center, Department of Urology, Medical College of Ohio, Toledo, OH (United States); Szkudlarek, Maria [Urology Research Center, Department of Urology, Medical College of Ohio, Toledo, OH (United States); Pestka, Maciej [Urology Research Center, Department of Urology, Medical College of Ohio, Toledo, OH (United States); Jankun, Jerzy [Urology Research Center, Department of Urology, Medical College of Ohio, Toledo, OH (United States)

    2004-07-21

    Advances in photodynamic therapy (PDT) treatment for prostate cancer can be achieved either by improving selectivity of the photosensitizer towards prostate gland tissue or improving the dosimetry by means of individualized treatment planning using currently available photosensitizers. The latter approach requires the ability to measure, among other parameters, the fluence rate at different positions within the prostate and the ability to derive the tissue optical properties. Here fibre optic probes are presented capable of measuring the fluence rate throughout large tissue volumes and a method to derive the tissue optical properties for different volumes of the prostate. The responsivity of the sensors is sufficient to detect a fluence rate of 0.1 mW cm{sup -2}. The effective attenuation coefficient in the canine prostate at 660 nm is higher at the capsule (2.15 {+-} 0.19 cm{sup -1}) than in proximity of the urethra (1.84 {+-} 0.36 cm{sup -1}). Significant spatial and temporal intra- and inter-canine variability in the tissue optical properties was noted, highlighting the need for individualized monitoring of the fluence rate for improved dosimetry.

  14. Low-dose photons modify liver response to simulated solar particle event protons.

    Science.gov (United States)

    Gridley, Daila S; Coutrakon, George B; Rizvi, Asma; Bayeta, Erben J M; Luo-Owen, Xian; Makinde, Adeola Y; Baqai, Farnaz; Koss, Peter; Slater, James M; Pecaut, Michael J

    2008-03-01

    The health consequences of exposure to low-dose radiation combined with a solar particle event during space travel remain unresolved. The goal of this study was to determine whether protracted radiation exposure alters gene expression and oxidative burst capacity in the liver, an organ vital in many biological processes. C57BL/6 mice were whole-body irradiated with 2 Gy simulated solar particle event (SPE) protons over 36 h, both with and without pre-exposure to low-dose/low-dose-rate photons ((57)Co, 0.049 Gy total at 0.024 cGy/h). Livers were excised immediately after irradiation (day 0) or on day 21 thereafter for analysis of 84 oxidative stress-related genes using RT-PCR; genes up or down-regulated by more than twofold were noted. On day 0, genes with increased expression were: photons, none; simulated SPE, Id1; photons + simulated SPE, Bax, Id1, Snrp70. Down-regulated genes at this same time were: photons, Igfbp1; simulated SPE, Arnt2, Igfbp1, Il6, Lct, Mybl2, Ptx3. By day 21, a much greater effect was noted than on day 0. Exposure to photons + simulated SPE up-regulated completely different genes than those up-regulated after either photons or the simulated SPE alone (photons, Cstb; simulated SPE, Dctn2, Khsrp, Man2b1, Snrp70; photons + simulated SPE, Casp1, Col1a1, Hspcb, Il6st, Rpl28, Spnb2). There were many down-regulated genes in all irradiated groups on day 21 (photons, 13; simulated SPE, 16; photons + simulated SPE, 16), with very little overlap among groups. Oxygen radical production by liver phagocytes was significantly enhanced by photons on day 21. The results demonstrate that whole-body irradiation with low-dose-rate photons, as well as time after exposure, had a great impact on liver response to a simulated solar particle event.

  15. Effects of low dose gamma-ray radiation on the seed germination and physiological activity of vegetable crops

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J. S.; Baek, M. H.; Lee, Y. G. [KAERI, Taejon (Korea, Republic of); Jung, K. H. [Kyunghee Univ., Yongin (Korea, Republic of)

    2000-10-01

    To determine the effect of low dose gamma-ray radiation on the germination rate and physiology of germinative seeds of Chinese cabbage(Brassica campestris L. cv. Hanyoreum) and radish(Raphanus sativus L. cv. Chungsukoungzoung). The germination rate of irradiation group was higher than that of the control. Especially it was highest at the early stage of induction. The germination rate of Chinese cabbage increased at 4 Gy-, 10 Gy- and 50 Gy irradiation group and that of radish increased at 2 Gy-, 6 Gy- and 10 Gy irradiation group. The seedling height of Chinese cabbage and radish increased positively in low dose irradiation group. The seedling height of Chinese cabbage was noticeably higher at 4 Gy and 10 Gy irradiation group and that of radish at 6 Gy irradiation group. The protein contents of seeds irradiated with low dose gamma-ray radiation was increased compared to that of the control especially at the early stage of induction. The enzyme activity of seeds irradiated with low dose of gamma-ray radiation was increased at 4 Gy and 10 Gy irradiation group. These results suggest that the germination and physiological activity of old seeds could be stimulated promisingly by the low dose gamma-ray radiation.

  16. New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies.

    Science.gov (United States)

    Yanagida, Noriyuki; Okada, Yu; Sato, Sakura; Ebisawa, Motohiro

    2016-04-01

    A number of studies have suggested that a large subset of children (approximately 70%) who react to unheated milk or egg can tolerate extensively heated forms of these foods. A diet that includes baked milk or egg is well tolerated and appears to accelerate the development of regular milk or egg tolerance when compared with strict avoidance. However, the indications for an oral food challenge (OFC) using baked products are limited for patients with high specific IgE values or large skin prick test diameters. Oral immunotherapies (OITs) are becoming increasingly popular for the management of food allergies. However, the reported efficacy of OIT is not satisfactory, given the high frequency of symptoms and requirement for long-term therapy. With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods.

  17. Repurposing Itraconazole as a Treatment for Advanced Prostate Cancer: A Noncomparative Randomized Phase II Trial in Men With Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Heath, Elisabeth I.; Smith, David C.; Rathkopf, Dana; Blackford, Amanda L.; Danila, Daniel C.; King, Serina; Frost, Anja; Ajiboye, A. Seun; Zhao, Ming; Mendonca, Janet; Kachhap, Sushant K.; Rudek, Michelle A.; Carducci, Michael A.

    2013-01-01

    Background. The antifungal drug itraconazole inhibits angiogenesis and Hedgehog signaling and delays tumor growth in murine prostate cancer xenograft models. We conducted a noncomparative, randomized, phase II study evaluating the antitumor efficacy of two doses of oral itraconazole in men with metastatic prostate cancer. Patients and Methods. We randomly assigned 46 men with chemotherapy-naïve metastatic castration-resistant prostate cancer (CRPC) to receive low-dose (200 mg/day) or high-dose (600 mg/day) itraconazole until disease progression or unacceptable toxicity. The primary endpoint was the prostate-specific antigen (PSA) progression-free survival (PPFS) rate at 24 weeks; a 45% success rate in either arm was prespecified as constituting clinical significance. Secondary endpoints included the progression-free survival (PFS) rate and PSA response rate (Prostate Cancer Working Group criteria). Exploratory outcomes included circulating tumor cell (CTC) enumeration, serum androgen measurements, as well as pharmacokinetic and pharmacodynamic analyses. Results. The high-dose arm enrolled to completion (n = 29), but the low-dose arm closed early (n = 17) because of a prespecified futility rule. The PPFS rates at 24 weeks were 11.8% in the low-dose arm and 48.0% in the high-dose arm. The median PFS times were 11.9 weeks and 35.9 weeks, respectively. PSA response rates were 0% and 14.3%, respectively. In addition, itraconazole had favorable effects on CTC counts, and it suppressed Hedgehog signaling in skin biopsy samples. Itraconazole did not reduce serum testosterone or dehydroepiandrostenedione sulfate levels. Common toxicities included fatigue, nausea, anorexia, rash, and a syndrome of hypokalemia, hypertension, and edema. Conclusion. High-dose itraconazole (600 mg/day) has modest antitumor activity in men with metastatic CRPC that is not mediated by testosterone suppression. PMID:23340005

  18. Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006 and Mortality Rates (1997–2009

    Directory of Open Access Journals (Sweden)

    Chantal Babb

    2014-01-01

    Full Text Available Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA from the pathology based National Cancer Registry (1986–2006 and data on mortality (1997–2009 from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma. There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

  19. Prostate cancer in South Africa: pathology based national cancer registry data (1986-2006) and mortality rates (1997-2009).

    Science.gov (United States)

    Babb, Chantal; Urban, Margaret; Kielkowski, Danuta; Kellett, Patricia

    2014-01-01

    Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986-2006) and data on mortality (1997-2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

  20. Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006) and Mortality Rates (1997–2009)

    Science.gov (United States)

    Babb, Chantal; Urban, Margaret; Kielkowski, Danuta; Kellett, Patricia

    2014-01-01

    Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986–2006) and data on mortality (1997–2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA. PMID:24955252

  1. Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements

    Science.gov (United States)

    Whitaker, May

    2016-01-01

    Purpose Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. Material and methods This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. Results The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. Conclusions The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected. PMID:27504129

  2. An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern

    Science.gov (United States)

    Borot de Battisti, M.; Maenhout, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; van Vulpen, M.; Moerland, M. A.

    2015-10-01

    Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR-guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm3to 23.3 cm3) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions.

  3. Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment plans to catheter displacements.

    Science.gov (United States)

    Poder, Joel; Whitaker, May

    2016-06-01

    Inverse planning simulated annealing (IPSA) optimized brachytherapy treatment plans are characterized with large isolated dwell times at the first or last dwell position of each catheter. The potential of catheter shifts relative to the target and organs at risk in these plans may lead to a more significant change in delivered dose to the volumes of interest relative to plans with more uniform dwell times. This study aims to determine if the Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be optimized to improve the robustness of high-dose-rate (HDR) prostate brachytherapy plans to catheter displacements. A set of 10 clinically acceptable prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and the change in dose volume histogram (DVH) indices and conformity indices analyzed. The robustness of clinically acceptable prostate plans to catheter displacements in the caudal direction was found to be dependent on the DTDC parameter. A DTDC value of 0 improves the robustness of planning target volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4 improves the robustness of the plans to changes in hotspots. The results indicate that if used in conjunction with a pre-treatment catheter displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may produce clinically superior plans. However, the effect of the DTDC parameter in plan robustness was not observed to be as strong as initially suspected.

  4. A Commentary on: "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008".

    Science.gov (United States)

    Brooks, Antone L

    2015-04-01

    This commentary provides a very brief overview of the book "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008" ( http://lowdose.energy.gov ). The book summarizes and evaluates the research progress, publications and impact of the U.S. Department of Energy Low Dose Radiation Research Program over its first 10 years. The purpose of this book was to summarize the impact of the program's research on the current thinking and low-dose paradigms associated with the radiation biology field and to help stimulate research on the potential adverse and/or protective health effects of low doses of ionizing radiation. In addition, this book provides a summary of the data generated in the low dose program and a scientific background for anyone interested in conducting future research on the effects of low-dose or low-dose-rate radiation exposure. This book's exhaustive list of publications coupled with discussions of major observations should provide a significant resource for future research in the low-dose and dose-rate region. However, because of space limitations, only a limited number of critical references are mentioned. Finally, this history book provides a list of major advancements that were accomplished by the program in the field of radiation biology, and these bulleted highlights can be found in last part of chapters 4-10.

  5. Uncommon toxicity of low-dose methotrexate: case report

    Directory of Open Access Journals (Sweden)

    Zohreh Yousefi

    2015-10-01

    Full Text Available Background: Standard treatment of Gestational Trophoblastic Disease (GTD is chemotherapy. Single-agent chemotherapy regime including Methotrexate (MTX or Actinomycin. Single-agent is widely used in treatment of persistent trophoblastic disease. We reported an uncommon toxicity of low-dose single-agent methotrexate in a patient. Case Presentation: A 20-year-old woman, primary gravid after two months missed period and spotting with diagnosis of incomplete abortion with uterine size equivalent of ten weeks pregnancy (8-10 cm underwent evacuation curettage. In serial follow-up, based on rise of beta-hCG titer and absence of metastatic disease, it was categorized as low-risk persistent trophoblastic disease. She was referred to gynecology oncology center of Ghaem Hospital, Mashhad University of Medical Sciences in May 2014. Because of rise of beta-hCG titer, after complete metastatic work-up and lack of disease in other sites, persistent disease was diagnosed and candidate for chemotherapy (single agent low-dose. The patient received first course of therapy with MTX (50 mg/m², intra muscular. Unfortunately, after two days of treatment she developed uncommon severe toxicity, fever, severe nausea and vomiting, tachycardia, and generalized weakness. Also, we found hematologic abnormality (WBC: -14000-15000 µI, platelet- 540 µI and sever neutropenia, and abnormal rising in liver function test (SGOT, SGPT (three to four times and renal function test (BUN and Creatinine (two times. In addition, she had disseminated erosive lesion in all of body especially in face. Due to the fatal side effects of chemotherapy, she was admitted to intensive care unit (ICU. Fortunately, after two to three weeks, she was improved by conservative management. After few weeks beta-hCG titer was in normal limit. However she had normal serial beta-hCG in one year of follow-up. Conclusion: It is important to emphasis unpredictable side effects of chemotherapy with low-dose

  6. Role of low dose cytarabine in elderly patients with acute myeloid leukemia: An experience

    Directory of Open Access Journals (Sweden)

    Yasir Bashir

    2015-01-01

    Full Text Available Purpose: To highlight the acceptable results seen after use of low dose cytarabine in elderly patients of acute myeloid leukemia (AML with comorbidities. Materials and Methods: This was a prospective study carried on 30 newly diagnosed patients of AML over 60 years of age who were unfit for standard treatment regimens. We did not use azacytidine and decitabine in our patients because these therapeutic modalities being extremely costly and our patient affordability being poor. After taking patient consent and institutional ethical clearance these patients were treated with 20 mg/m 2 cytarabine subcutaneously in two divided doses 12 h apart for 4 days every week for 4 weeks which constituted a cycle before disease, re-assessment was done. A repeat cycle was administered where ever needed and after attainment of remission, we continued low dose cytarabine for 2 days/week as maintenance after complete or partial response was documented. Results: In our study, we found that around 20% of patients achieved complete remission and 30% partial remission. The remission rates were definitely influenced by counts at presentation, performance at presentation, comorbidities, underlying myelodysplastic syndrome and baseline cytogenetics. Conclusion: Low dose cytarabine is effective treatment option for elderly patients with AML when standard treatment options are not warranted.

  7. [The effect of extremely low doses of the novel regulatory plant proteins ].

    Science.gov (United States)

    Krasnov, M S; Margasiuk, D V; Iamskov, I A; Iamskova, V P

    2003-01-01

    Searching and study on regulatory proteins, which can keep under control the scope of important processes as like as cell adhesion, proliferation, differentiation and morphogenesis, is an actual aim of the current biochemistry. Recently we have identified S-100 proteins in plants of following species: plantain (Plantago major L.), aloe (Aloe arborescens L.), and bilberry (Vaccinum myrtillus L.). Extraction and purification of S-100 proteins gotten from these plants were performed by the method we developed earlier for adhesion proteins of animal tissues. Homogeneity of the studied plant proteins was evaluated and confirmed by HPLC and SDS-electrophoresis in PAAG. Both, plant and animal proteins have appeared to be biologically active at extremely low doses. The tests were performed by adhesiometrical method in short-term tissue culture of mouse's liver in vitro. As a result it was established that the plant proteins insert a membranotropic effect being added in extremely low doses, corresponding to 10(-10)-10(-13) mg/ml. Keeping in mind that the plantain is well known remedy for wound protection and healing, in several experiments we studied the biological effect of plant S-100 proteins on animal cells. It was found that S-100 proteins obtained from plantain influences proliferation of human fibroblasts in vitro. It was found that after the treatment with this protein in low doses the cell growth rate increases essentially.

  8. Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Joris D. Veltman

    2010-01-01

    Full Text Available Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.

  9. Effects of low dose rate 60Co γ ray combined with 252Cf neutron irradiation on hematopoietic and antioxidation systems in rats%低剂量率60Co γ射线和252Cf裂变中子混合照射对大鼠造血及抗氧化系统的影响

    Institute of Scientific and Technical Information of China (English)

    莫琳芳; 何颖; 侯登勇; 钱甜甜; 蒋定文; 王岩; 刘玉明; 李珂娴; 王庆蓉

    2013-01-01

    Objective To study the effects of low dose rate 60Co γ ray combined with 252Cf neutron irradiation on hematopoietic and antioxidation systems in rats.Methods Sixteen SD male rats were randomly divided into the irradiation group and the control group,each consisting of 8 rats.The irradiation group was exposed to whole-body 60 Co γray (with daily dose rate of 0.072 Gy) for 1 hour and to 252 Cf neutron (with daily dose rate of 0.085 mGy/h) for 20 hours,for a total of 7 successive days.Peripheral blood cell counts,main organ indices,bone marrow DNA contents,SOD activity and MDA content of rats were monitored,at day 8 after irradiation.Results Compared with those of the control group [(6.2 ± 2.4) × 109/L],WBC of the irradiation group decreased significantly following irradiation [(3.4 ± 1.2) × 109/L],(P < O.05),but no statistical significance could be noted in the changes of various organ indices (P > O.05).Bone marrow DNA contents and serum SOD activity all decreased significantly (P < 0.05),while organ indices and MDA contents seemed to increase,but without statistical significance (P > 0.05).Conclusions 60 Co γirradiation combined with 252Cf neutron irradiation could obviously damage the hemopoietic and anti-oxidation systems of rats.%目的 探讨低剂量率60Co γ射线与252Cf裂变中子混合照射对大鼠的生物效应.方法 16只雄性SD大鼠按数字表法随机分成实验组和对照组,每组8只.实验组每天依次暴露于60Co γ射线1h(剂量率为0.072 Gy/h),252Cf裂变中子20 h(剂量率为0.085 mGy/h),连续7d.照后第8天检测大鼠外周血细胞计数、主要脏器指数、骨髓DNA含量、血清超氧化物歧化酶(SOD)活力及丙二醛(MDA)含量.结果 与对照组[(6.2 ±2.4)×109/L]相比,实验组大鼠外周血白细胞数[(3.4±1.2)×109/L](WBC)显著降低(P<0.05),各项脏器指数变化组间差异无统计学意义(P>0.05),骨髓DNA含量显著降低(P<0.05);血清SOD活力显著降低(P<0

  10. Chronic low-dose radiation protects cells from high-dose radiation via increase of AKT expression by NF-{sub k}B

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyung Sun; Seong, Ki Moon; Kim, Ji Young; Kim, Cha Soon; Yang, Kwang Hee; Nam, Seon Young [Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., LTD., Gyeongju (Korea, Republic of)

    2013-04-15

    Exposure to low-dose and low-dose rate of ionizing radiation is an important issue in radiation protection. Low-dose ionizing radiation has been observed to elicit distinctly different responses compared to high-dose radiation, in various biological systems including the reproductive, immune, and hematopoietic systems (Liu et al. 2006). Some data were reported that low-dose radiation could initiate beneficial effects by stimulating cell growth, DNA repair, activation of transcription factors and gene expression (Calabrese et al., 2004). Cells exposed to low-dose radiation can develop adaptive resistance to subsequent high-dose radiation induced DNA damage, gene mutation, and cell death. We previously reported that low-dose of ionizing radiation induced cell survival through the activation of AKT (protein kinase B, PKB) pathway (Park et al., 2009). AKT has been shown to be potently activated in response to a wide variety of growth factors and ionizing radiation. Cell survival against ionizing radiation seems to be associated with the activation of AKT pathway via phosphorylation of its downstream nuclear target molecules. In the present study, we examined the effects of chronic low-dose irradiation in human lung fibroblast cells. The aim was to explore the possibility of a low-dose radiation-induced adaptive cellular response against subsequent challenging high-dose irradiation. In the present study, we examined the regulatory mechanism responsible for cellular response induced by chronic low-dose of ionizing radiation in normal human cells. We found that the level of AKT protein was closely associated with cell survival. In addition, NF-{sub k}B activation by chronic low-dose radiation regulates AKT activation via gene expression and acinus expression. In conclusion, our data demonstrate that chronic low-dose radiation could inhibit the cell death induced by cytotoxic high-dose radiation through the modulation of the level of AKT and acinus proteins via NF-{sub k

  11. Low Dose IR Creates an Oncogenic Microenvironment by Inducing Premature

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Zhi-Min [Harvard School of Public Health

    2013-04-28

    Introduction Much of the work addressing ionizing radiation-induced cellular response has been carried out mainly with the traditional cell culture technique involving only one cell type, how cellular response to IR is influenced by the tissue microenvironment remains elusive. By use of a three-dimensional (3D) co-culture system to model critical interactions of different cell types with their neighbors and with their environment, we recently showed that low-dose IR-induced extracellular signaling via the tissue environment affects profoundly cellular responses. This proposal aims at determining the response of mammary epithelial cells in a tissue-like setting.

  12. Exposure to low dose ionising radiation: Molecular and clinical consequences.

    LENUS (Irish Health Repository)

    Martin, Lynn M

    2014-07-10

    This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HRS and the impact of HRS on the cellular response to radiation in mammalian cells. Particular attention is paid to the balance of evidence suggesting a role for DNA repair processes in the response, evidence suggesting a role for the cell cycle checkpoint processes, and evidence investigating the clinical implications\\/relevance of the effect.

  13. Extrapyramidal side effects with low doses of amisulpride.

    Science.gov (United States)

    Mandal, Nikhiles; Singh, Om P; Sen, Subrata

    2014-04-01

    Amisulpride, the newly introduced antipsychotic in India, is claimed to be effective in both positive and negative symptom schizophrenia and related disorders, though it has little or no action on serotonergic receptors. Limbic selectivity and lower striatal dopaminergic receptor binding capacity causes very low incidence of EPS. But, in clinical practice, we are getting EPS with this drug even at lower doses. We have reported three cases of akathisia, acute dystonia, and drug-induced Parkinsonism with low doses of amisulpride. So, we should keep this side effect in mind when using amisulpride. In fact, more studies are required in our country to find out the incidence of EPS and other associated mechanism.

  14. Low dose aspirin therapy and renal function in elderly patients

    Directory of Open Access Journals (Sweden)

    Akinwusi PO

    2013-01-01

    Full Text Available Patience Olayinka Akinwusi,1,2 Rotimi Oluyombo,2 Paul Sunday Ogunro,3 Adetunji Oladeni Adeniji,4 Oluyomi Olusola Okunola,5 Olugbenga Edward Ayodele21Department of Medicine, Osun State University, Osogbo, Osun State, Nigeria; 2Department of Medicine, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 3Department of Chemical Pathology, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 4Department of Obstetrics and Gynecology, LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria; 5Department of Medicine, Obafemi Awolowo University, Ile-Ife, Osun State, NigeriaPurpose: To determine whether low dose aspirin has any deleterious effects on renal function in elderly patients.Methods: We conducted a prospective pilot study of 30 Nigerians older than 60 years with various chronic ailments necessitating the use of low dose aspirin. Patients gave their consent, and institutional ethical clearance was obtained. Each patient's baseline samples at enrolment (before commencing aspirin use served as a control, and subsequent weekly samples were compared. The weekly mean of each parameter was calculated, and the differences of means from baseline were determined, and values were compared for statistical differences with the Statistical Package for the Social Sciences, version 16.Results: We found that a majority of patients (86.67% had basal renal functions at chronic kidney disease stages 1 and 2. When compared with the corresponding baseline parameters, the mean weekly serum and urinary electrolytes, urea, creatinine, and uric acid parameters did not change, and the P-value did not show any statistical significance. However, there was positive statistical significance for the creatinine clearance (P = 0.025. Also, unlike in previous studies, anemia and hypoalbuminemia did not affect the renal function parameters.Conclusion: This study did not show any deleterious effects with short-term, low dose (75 mg daily aspirin use on kidney functions in

  15. Low doses controversy; La controverse des faibles doses

    Energy Technology Data Exchange (ETDEWEB)

    Masse, R. [Office de Protection contre les Rayonnements Ionisants, 78 -le Vesinet (France); Carde, C. [EDF, 75 - Paris (France)

    1997-12-31

    In this article is studied the question of low dose irradiation. From this question, the risk assessment and how it is perceived in public opinion is studied. Then, it is more generally, the question of public opinion and the information made by the media which is discussed. Different events and how they were related in press are reviewed: leukemia around La Hague, human guinea-pigs for plutonium, Chernobyl consequences, survivors from Hiroshima, nuclear nomads ( for temporary workers and their bad medical surveillance ), radioactive effluents releases from La Hague, Valduc or Cattenom. (N.C.).

  16. 3D versus 2D Systematic Transrectal Ultrasound-Guided Prostate Biopsy: Higher Cancer Detection Rate in Clinical Practice

    Directory of Open Access Journals (Sweden)

    Alexandre Peltier

    2013-01-01

    Full Text Available Objectives. To compare prostate cancer detection rates of extended 2D versus 3D biopsies and to further assess the clinical impact of this method in day-to-day practice. Methods. We analyzed the data of a cohort of 220 consecutive patients with no prior history of prostate cancer who underwent an initial prostate biopsy in daily practice due to an abnormal PSA and/or DRE using, respectively, the classical 2D and the new 3D systems. All the biopsies were done by a single experienced operator using the same standardized protocol. Results. There was no significant difference in terms of age, total PSA, or prostate volume between the two groups. However, cancer detection rate was significantly higher using the 3D versus the 2D system, 50% versus 34% (P<0.05. There was no statistically significant difference while comparing the 2 groups in term of nonsignificant cancer detection. Conclusion. There is reasonable evidence demonstrating the superiority of the 3D-guided biopsies in detecting prostate cancers that would have been missed using the 2D extended protocol.

  17. Diagnostic and predictive value of voiding diary data versus prostate volume, maximal free urinary flow rate, and Abrams-Griffiths number in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia

    NARCIS (Netherlands)

    van Venrooij, Ger E. P. M.; van Melick, Harm H. E.; Eckhardt, Mardy D.; Boon, Tom A.

    2008-01-01

    OBJECTIVES To investigate the information of voiding data in relation to symptoms and well-being in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and to compare this information with that of prostate volume (Vprostate), maximal free urinary flow rate (

  18. Transfer of Low Dose Aspirin Into Human Milk.

    Science.gov (United States)

    Datta, Palika; Rewers-Felkins, Kathleen; Kallem, Raja Reddy; Baker, Teresa; Hale, Thomas W

    2017-05-01

    Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry. Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

  19. Locoregional IL-2 low dose applications for gastrointestinal tumors

    Institute of Scientific and Technical Information of China (English)

    Zachary Krastev; Willem Den Otter; V Koltchakov; R Tomova; S Deredjian; A Alexiev; D Popov; B Tomov; Jan-Willem Koten; John Jacobs

    2005-01-01

    AIM: To explore the feasibility of local interleukin 2 (IL-2)in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of application.METHODS: Sixteen patients with stages Ⅲ and Ⅳ of gastrointestinal malignancies (primary or metastatic) who were admitted to our Department of Gastroenterology were treated with locoregionally applied IL-2 in low doses.RESULTS: No major problems applying locoregional IL-2 were encountered. In 6 out of 16 patients, a modest but clinically worthwhile improvement was obtained. Adverse effects were minimal, The therapeutic scheme was well tolerated, even in patients in a poor condition.CONCLUSION: This study demonstrates the feasibility of low dose locoregional IL-2 application in advanced abdominal cancer. Local IL-2 therapy gives only negligible adverse effects. The results suggest that it is important to apply intratumorally. Local IL-2 may be given adjunct to standard therapeutic regimes and does not imply complex surgical interventions. These initial results are encouraging.

  20. Low-dose computed tomography to diagnose fetal bone dysplasias.

    Science.gov (United States)

    Montoya Filardi, A; Guasp Vizcaíno, M; Gómez Fernández-Montes, J; Llorens Salvador, R

    We present a case of cleidocranial dysplasia diagnosed by low-dose fetal computed tomography (CT) in the 25th week of gestation. Severe bone dysplasia was suspected because of the fetus' low percentile in long bones length and the appearance of craniosynostosis on sonography. CT found no abnormalities incompatible with life. The effective dose was 5 mSv, within the recommended range for this type of examination. Low-dose fetal CT is a new technique that makes precision study of the bony structures possible from the second trimester of pregnancy. In Spain, abortion is legal even after the 22nd week of gestation in cases of severe fetal malformations. Therefore, in cases in which severe bone dysplasia is suspected, radiologists must know the strategies for reducing the dose of radiation while maintaining sufficient diagnostic quality, and they must also know which bony structures to evaluate. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Is a low dose of hepatitis B vaccine enough for a rapid vaccination scheme?

    Institute of Scientific and Technical Information of China (English)

    Ru-Xiang Wang; Jan van Hattum; Gijsbert C. de Gast; Greet Boland; Ying Guo; Shao-Ping Lei; Chang-Hong Yang; Juan Chen; Jie Tian; Jin-Ying Wen; Ke-Hong Du

    2003-01-01

    AIM: To determine whether or not a low dose of HB vaccine can be effectively used in the rapid vaccination.METHODS: Rapid vaccination (0, 1, 2 months) with low dose (5 μg) or routine dose (10 μg) HB vaccine was studied in 250 subjects (130 school children and 120 university students). Serum from all the participants was tested for HBsAg, anti-HBs and anti-HBc at 1, 3 and 7 months after the first dose of vaccination and all subjects were serum HBV marks negative before the vaccination. Non-responders to a complete initial vaccination from university students were given an additional vaccination with 10 μg of HB vaccine and their serum anti-HBs was tested again one month later.RESULTS: One month after the third dose of vaccination (third month) sero-conversion rates and geometric mean titer (GMTs) were significantly (P<0.01) higher in the routine dose (resp. 89 % and 106.8) than in the low dose group (resp. 72 % and 59.5). Sero-conversion rates and GMTs were maintained stable for another 4 months in both groups.After an additional vaccination to non-responders with 10 μg HB vaccine, 17/23 subjects (13/15 from those vaccinated with 5 μg vaccine and 4/8 from those vaccinated with 10 μg vaccine) became anti-HBs positive, yielding similar seroconversion rates for both dose groups.CONCLUSION: Higher sero-conversion rates and GMTs were reached in those vaccinated with 10 μg HB vaccine than in those vaccinated with 5 μg HB vaccine after a comp~te vaccination with a 0, 1, 2 month scheme. But the subjects vaccinated with 5 μg vaccine can also reach the similar sero-conversion rate after an additional vaccination.

  2. Retrospective study comparing low-dose versus standard dose of bortezomib in patients with multiple myeloma

    Directory of Open Access Journals (Sweden)

    Marcela Espinoza Zelada

    2015-03-01

    Full Text Available INTRODUCTION Bortezomib is a selective inhibitor of the proteosoma that is used in multiple myeloma. In combination with other antineoplastic drugs, it has a well-documented impact in progression-free survival rates and overall survival rates with standard doses (1.3-1.5 mg/m2. However, up to 88% of patients on standard doses have unwanted side effects (neutropenia, neuropathy or anemia. Standard dose (1.3 mg/m2 is used in almost all patients and low dose (0.7-0.8 mg/m2 is reserved for patients with kidney disease and neuropathy. OBJECTIVE We aim to describe clinical, cytological, and cytometric outcomes, as well as overall survival and side effects of low dose versus standard dose of bortezomib in our institution. METHODS Retrospective, descriptive study based on data recovered from clinical charts of 48 multiple myeloma patients treated in our hospital between 2011 and 2013. We included data on age, gender, type of multiple myeloma, serum albumin, serum creatinine, beta 2 microglobulin, calcemia, imaging studies, disease stage, pre-and post-therapy bone marrow studies, adverse events and rate of progression. We also recorded events like date of death or of the last medical appointment. RESULTS Forty-eight multiple myeloma patients were treated with bortezomib-cyclophosphamide-dexamethasone. Twenty-one patients received low dose and 27 patients were treated with the standard dose. No statistical differences between the two groups were found for clinical response (p=0.6, cytological response (p=0.28, flow cytometric response (p= 0.3, rate of adverse effects and overall survival rates. CONCLUSION This retrospective analysis suggests that lower doses of bortezomib have similar effects in disease control measured by flow cytometry and cytology compared to standard doses in multiple myeloma patients.

  3. A comparative population-based study of prostate cancer incidence and mortality rates in Singapore, Sweden and Geneva, Switzerland from 1973 to 2006

    Directory of Open Access Journals (Sweden)

    Chen Cynthia

    2012-06-01

    Full Text Available Abstract Background Prostate cancer is the most commonly diagnosed malignancy in men in Sweden and Geneva, and the third most common in men in Singapore. This population-based study describes trends in the incidence and mortality rates of prostate cancer in Singapore, Sweden and Geneva (Switzerland from 1973 to 2006 and explores possible explanations for these different trends. Methods Data from patients diagnosed with prostate cancer were extracted from national cancer registries in Singapore (n = 5,172, Sweden (n = 188,783 and Geneva (n = 5,755 from 1973 to 2006. Trends of incidence and mortality were reported using the Poisson and negative binomial regression models. The age, period and birth-cohort were tested as predictors of incidence and mortality rates of prostate cancer. Results Incidence rates of prostate cancer increased over all time periods for all three populations. Based on the age-period-cohort analysis, older age and later period of diagnosis were associated with a higher incidence of prostate cancer, whereas older age and earlier period were associated with higher mortality rates for prostate cancer in all three countries. Conclusions This study demonstrated an overall increase in incidence rates and decrease in mortality rates in Singapore, Sweden and Geneva. Both incidence and mortality rates were much lower in Singapore. The period effect is a stronger predictor of incidence and mortality of prostate cancer than the birth-cohort effect.

  4. Incidence rate of prostate cancer in men treated for erectile dysfunction with phosphodiesterase type 5 inhibitors: retrospective analysis

    Institute of Scientific and Technical Information of China (English)

    Anthony H Chavez; K Scott Coffield; M Hasan Rajab; Chanhee Jo

    2013-01-01

    The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction (ED) treated with phosphodiesterase type 5 inhibitors (PDE-5i) over a 7-year period vs.men with ED of the same age and with similar risk factors who were not treated with PDE-5i.In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006,men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified.These individuals were divided into two groups:2362 men who had treatment with PDE-5i,and 2612 men who did not have treatment.Demographic data in each group were compared.During the study period,97 (4.1%) men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 (9.9%) men with ED in the non-treated group (P<00001).A higher percentage of African Americans were treated with PDE-5i vs.those who were not (10.5% vs.7.1%; P<0.0001).The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen (10.0% vs.13.1%; P=0.0008) and higher percentage of benign prostatic hyperplasia (38.4% vs.35.1%; P=0.0149).Men with ED treated with PDE-5i tended to have less chance (adjusted odds ratio:0.4; 95% confidence intervals:0.3-0.5; P<0.0001) of having prostate cancer.Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of being diagnosed with prostate cancer.Further research is warranted.

  5. Adaptive planning strategy for high dose rate prostate brachytherapy—a simulation study on needle positioning errors

    NARCIS (Netherlands)

    Borot, Maxence; Denis de Senneville, B; Maenhout, M; Hautvast, G; Binnekamp, D; Lagendijk, J J W; van Vulpen, M; Moerland, M A

    2016-01-01

    The development of magnetic resonance (MR) guided high dose rate (HDR) brachytherapy for prostate cancer has gained increasing interest for delivering a high tumor dose safely in a single fraction. To support needle placement in the limited workspace inside the closed-bore MRI, a single-needle MR-co

  6. High-dose-rate prostate brachytherapy based on registered transrectal ultrasound and in-room cone-beam CT images

    NARCIS (Netherlands)

    Even, Aniek J.G.; Nuver, Tonnis T.; Westendorp, Hendrik; Hoekstra, Carel J.; Slump, C.H.; Minken, Andre W.

    2014-01-01

    Purpose To present a high-dose-rate (HDR) brachytherapy procedure for prostate cancer using transrectal ultrasound (TRUS) to contour the regions of interest and registered in-room cone-beam CT (CBCT) images for needle reconstruction. To characterize the registration uncertainties between the two ima

  7. Human cardiac beta1- or beta2-adrenergic receptor stimulation and the negative chronotropic effect of low-dose pirenzepine.

    Science.gov (United States)

    Jakubetz, J; Schmuck, S; Wochatz, G; Ruhland, B; Poller, U; Radke, J; Brodde, O E

    2000-05-01

    The M1-muscarinic receptor antagonist pirenzepine in low doses (pirenzepine differ in volunteers with activated cardiac beta1-adrenergic receptors versus activated cardiac beta2-adrenergic receptors. In 17 male volunteers (25 +/- 1 years) we studied effects of pirenzepine infusion (0.5 mg intravenous bolus followed by continuous infusion of 0.15 microg/kg/min) on heart rate and heart rate-corrected duration of electromechanical systole (QS2c, as a measure of inotropism) that had been stimulated by activation of cardiac beta1-adrenergic receptors (bicycle exercise in the supine position for 60 minutes at 25 W) or cardiac beta2-adrenergic receptors (continuous intravenous infusion of 100 ng/kg/min terbutaline). Bicycle exercise and terbutaline infusion significantly increased heart rate and shortened QS2c. When pirenzepine was infused 20 minutes after the beginning of the exercise or terbutaline infusion, heart rate decreased in both settings by approximately the same extent (approximately -10 to -14 beats/min), although exercise and terbutaline infusion continued; however, QS2c was not affected. Pirenzepine (0.05 to 1 mg intravenous bolus)-induced decrease in heart rate was abolished after 6 days of transdermal scopolamine treatment of volunteers. Low-dose pirenzepine decreased heart rate by muscarinic receptor stimulation, because this was blocked by scopolamine. Moreover, low-dose pirenzepine did not differentiate between cardiac beta1- or beta2-adrenergic receptor stimulation; however, low-dose pirenzepine did not affect cardiac contractility as measured by QS2c. Low-dose pirenzepine therefore exerted a unique pattern of action in the human heart: it decreased heart rate (basal and beta1- and/or beta2-adrenergic receptor-stimulated) without affecting contractility.

  8. Quantifying exploratory low dose compounds in humans with AMS.

    Science.gov (United States)

    Dueker, Stephen R; Vuong, Le T; Lohstroh, Peter N; Giacomo, Jason A; Vogel, John S

    2011-06-19

    Accelerator Mass Spectrometry is an established technology whose essentiality extends beyond simply a better detector for radiolabeled molecules. Attomole sensitivity reduces radioisotope exposures in clinical subjects to the point that no population need be excluded from clinical study. Insights in human physiochemistry are enabled by the quantitative recovery of simplified AMS processes that provide biological concentrations of all labeled metabolites and total compound related material at non-saturating levels. In this paper, we review some of the exploratory applications of AMS (14)C in toxicological, nutritional, and pharmacological research. This body of research addresses the human physiochemistry of important compounds in their own right, but also serves as examples of the analytical methods and clinical practices that are available for studying low dose physiochemistry of candidate therapeutic compounds, helping to broaden the knowledge base of AMS application in pharmaceutical research.

  9. Transcriptome profiling of mice testes following low dose irradiation

    DEFF Research Database (Denmark)

    Belling, Kirstine C.; Tanaka, Masami; Dalgaard, Marlene Danner;

    2013-01-01

    cell types of the adult testis. We observed large expression changes in the somatic cell profile, which mainly could be attributed to changes in cellularity, but hyperplasia of Leydig cells may also play a role. We speculate that the possible hyperplasia may be caused by lower testosterone production......ABSTRACT: BACKGROUND: Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types...... in the adult testis. METHODS: Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were...

  10. Restless Legs Syndrome After Single Low Dose Quetiapine Administration.

    Science.gov (United States)

    Soyata, Ahmet Z; Celebi, Fahri; Yargc, Lutfi I

    2016-01-01

    Restless legs syndrome is an underdiagnosed sensori-motor disorder and psychotropic drugs are one of the main secondary causes of the illness. The most common psychotropic agents that cause restless legs syndrome are antidepressants; however, antipsychotics have also been reported to induce restless legs syndrome. The prevalence, vulnerability factors and the underlying mechanism of antipsychotic-induced restless legs syndrome are unclear. A possible explanation is that dopaminergic blockade is the main precipitator of the syndrome. Quetiapine-induced restless legs syndrome is another point of interest because of its low binding to D2 receptors. We herein report the case of a restless legs syndrome that emerged after a single low dose quetiapine administration.

  11. Optical fiber sensor for low dose gamma irradiation monitoring

    Science.gov (United States)

    de Andrés, Ana I.; Esteban, Ã.`scar; Embid, Miguel

    2016-05-01

    An optical fiber gamma ray detector is presented in this work. It is based on a Terbium doped Gadolinium Oxysulfide (Gd2O2S:Tb) scintillating powder which cover a chemically etched polymer fiber tip. This etching improves the fluorescence gathering by the optical fiber. The final diameter has been selected to fulfill the trade-off between light gathering and mechanical strength. Powder has been encapsulated inside a microtube where the fiber tip is immersed. The sensor has been irradiated with different air Kerma doses up to 2 Gy/h with a 137Cs source, and the spectral distribution of the fluorescence intensity has been recorded in a commercial grade CCD spectrometer. The obtained signal-to-noise ratio is good enough even for low doses, which has allowed to reduce the integration time in the spectrometer. The presented results show the feasibility for using low cost equipment to detect/measure ionizing radiation as gamma rays are.

  12. Low-Dose Naltrexone for Pruritus in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Tracy Frech

    2011-01-01

    Full Text Available Pruritus is a common symptom in systemic sclerosis (SSc, an autoimmune disease which causes fibrosis and vasculopathy in skin, lung, and gastrointestinal tract (GIT. Unfortunately, pruritus has limited treatment options in this disease. Pilot trials of low-dose naltrexone hydrochloride (LDN for pruritus, pain, and quality of life (QOL in other GIT diseases have been successful. In this case series we report three patients that had significant improvement in pruritus and total GIT symptoms as measured by the 10-point faces scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0 questionnaire. This small case series suggests LDN may be an effective, highly tolerable, and inexpensive treatment for pruritus and GIT symptoms in SSc.

  13. The spectrum of mutation produced by low dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Morley,Alexander,A; Turner, David,R

    2004-10-31

    Inherited mutations are the basis of evolution and acquired mutations in humans are important in ageing, cancer and possibly various forms of tissue degeneration. Mutations are responsible for many of the long-term effects of radiation. However, sensitive direct detection of mutations in humans has been difficult. The aims of the project were to develop methods for the sensitive enumeration of mutations in DNA, to measure mutation frequencies in a wide variety of tissue types and to quantify the mutational effect of direct oxidative damage produced by radiation, at both high and low doses. The project was successful in developing a sensitive method which could detect mutations directly in the genetic material, DNA at a sensitivity of 1 mutated molecule in 1000000000 unmutated molecules. However a number of methodological problems had to be overcome and lack of ongoing funding made it impossible to fulfill all of the aims of the project

  14. Porous hydroxyapatite tablets as carriers for low-dosed drugs.

    Science.gov (United States)

    Cosijns, A; Vervaet, C; Luyten, J; Mullens, S; Siepmann, F; Van Hoorebeke, L; Masschaele, B; Cnudde, V; Remon, J P

    2007-09-01

    The present study evaluated an innovative technique for the manufacturing of low-dosed tablets. Tablets containing hydroxyapatite and a pore forming agent (50% (w/w) Avicel PH 200/20, 37.5% and 50% corn starch/37.5% sorbitol) were manufactured by direct compression followed by sintering. The influence of pore forming agent (type and concentration), sinter temperature and sinter time on tablet properties was investigated. Sintering (1250 degrees C) revealed tablets with an acceptable friability (manufactured using a modified gelcasting technique yielding tablets with a median pore size of 60 and 80 microm. Release from these tablets was drastically increased indicating that the permeability of the tablets was influenced by the pore size, shape and connectivity of the porous network. Changing and controlling these parameters made it possible to obtain drug delivery systems providing different drug delivery behaviour.

  15. Dosimetric Evaluation of High-Dose-Rate Interstitial Brachytherapy Boost Treatments for Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Froehlich, Georgina [Semmelweis Univ., Budapest (Hungary); Dept. of Radiotherapy, National Inst. of Oncology, Budapest (Hungary); Agoston, Peter; Loevey, Jozsef; Somogyi, Andras; Fodor, Janos; Polgar, Csaba; Major, Tibor [Dept. of Radiotherapy, National Inst. of Oncology, Budapest (Hungary)

    2010-07-15

    Purpose: to quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. Material and methods: treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D{sub min}) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D{sub r}) and urethra (D{sub u}), dose to volume of 2 cm{sup 3} of the rectum (D{sub 2ccm}), and 0.1 cm{sup 3} and 1% of the urethra (D{sub 0.1ccm} and D1) were determined. Nonparametric correlation analysis was performed between these parameters. Results: the median number of needles was 16, the mean prostate volume (V{sub p}) was 27.1 cm{sup 3}. The mean V90, V100, V150, and V200 were 90%, 97%, 39% and 13%, respectively. The mean D90 was 109%, and the D{sub min} was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D{sub 2ccm} = 49% for the rectum, D{sub 0.1ccm} = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D{sub r}, D{sub 2ccm}) = 0.69, R(D{sub u}, D{sub 0.1ccm}) = 0.64, R(D{sub u}, D1) = 0.23. Conclusion: US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose

  16. Low dose mTHPC photodynamic therapy for cholangiocarcinoma

    Science.gov (United States)

    Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

    2013-06-01

    Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

  17. Cardiovascular risks associated with low dose ionizing particle radiation.

    Directory of Open Access Journals (Sweden)

    Xinhua Yan

    Full Text Available Previous epidemiologic data demonstrate that cardiovascular (CV morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ((1H; 0.5 Gy, 1 GeV and iron ion ((56Fe; 0.15 Gy, 1GeV/nucleon irradiation with and without an acute myocardial ischemia (AMI event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in (56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  18. Low dose radiation enhances the Locomotor activity of D. melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Ki Moon; Lee, Buyng Sub; Nam Seon Young; Kim, Ji Young; Yang, Kwang Hee; Choi, Tae In; Kim, Cha Soon [Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., Gyeongju (Korea, Republic of)

    2013-04-15

    Mild stresses at low level including radiation can induce the beneficial effects in many vertebrate and invertebrate species. However, a large amount of studies in radiation biology have focused on the detrimental effects of high dose radiation (HDR) such as the increased incidence of cancers and developmental diseases. Low dose radiation (LDR) induces biologically favorable effects in diverse fields, for example, cancer development, genomic instability, immune response, and longevity. Our previous data indicated that LDR promotes cells proliferation of which degree is not much but significant, and microarray data explained that LDR irradiated fruit flies showing the augmented immunity significantly changed the program for gene expression of many genes in Gene Ontology (GO) categories related to metabolic process. Metabolic process in development one of major contributors in organism growth, interbreeding, motility, and aging. Therefore, it is valuable to examine whether LDR change the physiological parameters related to metabolism, and how LDR regulates the metabolism in D. melanogaster. In this study, to investigate that LDR influences change of the metabolism, a representative parameter, locomotor activity. In addition, the activation of several cellular signal molecules was determined to investigate the specific molecular mechanism of LDR effects on the metabolism. We explored whether ionizing radiation affects the motility activity. We performed the RING assays to evaluate the locomotor activity, a representative parameter presenting motility of fruit flies. HDR dramatically decreased the motor activity of irradiated flies. Surprisingly, the irradiated flies at low dose radiation in both acute and chronic showed the significantly increased locomotor activity, compared to non-irradiated flies. Irradiation would induce change of the several signal pathways for flies to respond to it. The activation of some proteins involved in the cells proliferation and stress

  19. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kleiman, Norman Jay [Columbia University

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9

  20. Varicose Vein Stripping Under Low-Dose Spinal Anaesthesia

    Directory of Open Access Journals (Sweden)

    Nalan Muhammedoğlu

    2014-03-01

    Full Text Available Aim: Spinal anesthesia is frequently used for procedures involving the lower limbs. Compared with general anesthesia, low-dose spinal anesthesia is a cost-effective method and has advantages such as avoiding hypotension, longer duration of anesthesia and increased length of hospitalization. The aim of this trial was to compare two different low-dose bupivacaine drug regimens. Methods: Sixty unpremedicated patients were randomly allocated into two groups (n=30. There were no differences between the groups in age, weight, the American Society of Anesthesiologists (ASA physical status classification, gender, and duration of surgery. We performed spinal anesthesia at the L3-4 interspace with the patient in the lateral decubitus position. We administered 6.5 mg (group 1 and 8 mg (group 2 0.5% heavy bupivacaine into the subarachnoid space. We positioned the patient laterally to the operation side for 15 minutes, then, turned to supine position. Motor and sensory block was assessed by the Bromage scale and pinprick test. Results: There were significant differences between the two groups in duration of motor block, but no significant differences in hemodynamic response to spinal anesthesia. None of the patients had intraoperative pain. Five patients in group 1 and 2 patients in group 2 had urinary retention. Conclusion: Our observations suggest that 6.5 mg heavy bupivacaine is efficient and suitable for unilateral varicose veins stripping operation. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 25-8

  1. Prostatitis: Inflammation of the Prostate

    Science.gov (United States)

    ... the Prostate Prostate Enlargement (Benign Prostatic Hyperplasia) Prostatitis: Inflammation of the Prostate What is prostatitis? Prostatitis is a frequently painful condition that involves inflammation of the prostate and sometimes the areas around ...

  2. Ultra-low-dose continuous combined estradiol and norethisterone acetate: improved bleeding profile in postmenopausal women

    DEFF Research Database (Denmark)

    Sturdee, D.W.; Archer, D.F.; Rakov, V.;

    2008-01-01

    OBJECTIVE: To evaluate the effect of two ultra-low-dose hormone treatments containing estradiol (E2) 0.5 mg and norethisterone acetate (NETA) 0.1 or 0.25 mg on the endometrium and bleeding. METHODS: A prospective, randomized, placebo-controlled trial of 6 months. Local Ethics Committee approval...... at baseline and on completion. An endometrial biopsy was obtained when indicated clinically. RESULTS: In months 1-6, the amenorrhea rates with E2/NETA 0.1 were 89%, 89%, 86%, 85%, 89% and 89%, respectively and the no-bleeding rates were correspondingly high: 95%, 94%, 93%, 90%, 95% and 95%. The amenorrhea...... and spotting-only rates were similar with both ultra-low-dose combinations. The withdrawal rates due to bleeding were very low and the same in all three treatment arms (n = 1; 1%). There was a slight increase in the mean endometrial thickness in all three groups, which remained less than 5 mm. CONCLUSIONS...

  3. Cervical ripening with low-dose prostaglandins in planned vaginal birth after cesarean.

    Directory of Open Access Journals (Sweden)

    Thomas Schmitz

    Full Text Available OBJECTIVES: To compare uterine rupture, maternal and perinatal morbidity rates in women with one single previous cesarean after spontaneous onset of labor or low-dose prostaglandin-induced cervical ripening for unfavourable cervix. STUDY DESIGN: This was a retrospective cohort study of 4,137 women with one single previous cesarean over a 22-year period. Inpatient prostaglandin administration consisted in single daily local applications. RESULTS: Vaginal delivery was planned for 3,544 (85.7% patients, 2,704 (76.3% of whom delivered vaginally (vaginal birth after Cesarean (VBAC rate = 65.4%. Among women receiving prostaglandins (n=515, 323 (62.7% delivered vaginally. Uterine rupture (0.7% compared with 0.8%, OR 1.1, 95% CI 0.4-3.4, p=0.88, maternal (0.9% compared with 1.2%, OR 1.3, 95% CI 0.5-3.2, p=0.63 and perinatal (0.3% compared with 0.8%, OR 2.4, 95% CI 0.7-8.5, p=0.18 morbidity rates did not differ significantly between patients with spontaneous onset of labor and those receiving prostaglandins, nor did these rates differ according to the planned mode of delivery. CONCLUSION: In comparison with patients with spontaneous labor, inducing cervical ripening with low-dose prostaglandins in case of unfavourable cervix is not associated with appreciable increase in uterine rupture, maternal or perinatal morbidity.

  4. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information

  5. Serum metabonomics of rats irradiated by low-dose γ-rays

    OpenAIRE

    HE, YING; Xian-rong SHEN; Deng-yong HOU; Yu-ming LIU; Ding-wen JIANG; Qing-rong WANG; Ke-xian LI; Chen, Wei; Tian-tian QIAN

    2014-01-01

    Objective To explore the effect of low-dose γ-rays on the metabolites in rat serum. Methods Sixteen healthy male SD rats were randomly divided into control group and irradiated group (n=8). The rats in irradiated group were irradiated by 60Co γ-rays with a dose rate of 72mGy/h for 7 days (1 hour per day). At the 7th day after irradiation, blood samples were taken from abdominal aorta to obtain the serum. The metabolic fingerprints of serum were obtained from the two groups of rats, and 1H nuc...

  6. Assessment of a low dose of IV midazolam used orally for conscious sedation in pediatric dentistry

    OpenAIRE

    M. Mortazavi; Pourhashemi SJ; Khosravi, M. B.; S Ashtari; F. Ghaderi

    2009-01-01

    Background and the purpose of the study: Midazolam is preferably used in pediatric dentistry for quick onset of action and recovery. The aim of this prospective, observer-blind and placebo-controlled study was to assess the efficacy of a low dose of oral midazolam in modification of  the behavior of young pediatric dental patients. Methods: Forty children aged 3 to 5 years who displayed ratings 1 or 2 on the Frankl Scale and  were healthy by the American Society of Anesthesi...

  7. Brachytherapy for prostate cancer: Comparative characteristics of procedures

    Directory of Open Access Journals (Sweden)

    S. V. Kanaev

    2015-01-01

    Full Text Available The introduction of interstitial radiation sources is the «youngest» of the radical method of treatment of patients with prostate cancer (PC. The high level of efficiency comparable to prostatectomy at a significantly lower rate of complications causes rapid growth of clinical use of brachytherapy (BT. Depending on the radiation source and the mode of administration into the prostate gland are two types BT – high-dose rate (temporary (HDR-BT and low-dose rate (permanent (LDR-BT brachytherapy. At the heart of these two methods are based on a single principle of direct effect of the quantum gamma radiation on the area of interest. However, the differences between the characteristics of isotopes used and technical aspects of the techniques cause the difference in performance and complication rates for expression HDR-BT and LDR-BT.

  8. Treatment of cryptococcal meningitis with low-dose amphotericin B and flucytosine

    Institute of Scientific and Technical Information of China (English)

    YAN Dong; HUANG Jian-rong; LIAN Jiang-shan; LI Lan-juan

    2012-01-01

    Background Amphotericin B (0.7 mg/kg) with flucytosine is the standard treatment for cryptococcal meningitis.However,the long treatment course can induce adverse reactions in patients; therefore,reducing the dose may decrease such reactions.We performed a retrospective analysis of treatment effects and adverse reactions when amphotericin B (0.4 mg/kg or 0.7 mg/kg per day) and flucytosine were used together to treat HIV-negative patients with cryptococcal meningitis.Methods Retrospective analysis was conducted on inpatients at the First Affiliated Hospital,College of Medicine,Zhejiang University (January 2005 to December 2009).Low- or high-dose amphotericin B (0.4 or 0.7 mg/kg per day,respectively) plus flucytosine was used.The negative conversion rate of Cryptococcus in the cerebrospinal fluid (CSF),patient mortality,and the incidence of side effects for the two groups (low- vs.high-dose) were compared immediately after treatment and 2 and 10 weeks later.Data were analyzed by the Student's t test,chi-square tests using SPSS 12.0 statistical soitware.Results Two weeks post-treatment,Cryptococcus negative CSF rates were 78% (18/23) in the low-dose group and 87% (13/15) in the high-dose group (P=0.28).Ten weeks post-treatment,both groups were negative.The mortality rate was 8% (2/25) in the low-dose group and 17% (3/18) in the high-dose group (P=-0.25).There was a statistically significant difference in the incidence of adverse events between the groups,48% (12/25) and 78% (14/18) in the low- and high-dose groups,respectively (P=0.04).Adverse events that required a change in treatment program in the low-dose group were 12% (3/25) compared to 39% (7/18) in the high-dose group (P=-0.04).Conclusion Low-dose treatment regimens were better tolerated than high-dose ones.

  9. Low-dose norfloxacin and ciprofloxacin therapy worsen leptospirosis in hamster.

    Science.gov (United States)

    Wu, Dianjun; Zhang, Wenlong; Wang, Tingting; Lin, Tao; Jin, Xuemin; Xie, Xufeng; Guo, Jian; Cao, Yongguo; Wu, Rui

    2017-01-01

    Antibiotics play an important role in the treatment of leptospirosis. Many antibiotics at appropriate concentrations improved the survival rate and alleviated tissue injury, while, when dosing strategies fall below subtherapeutic levels, worse therapeutic effects are seen. In the present study, we investigated the efficacy of low-dose norfloxacin (10, 20 and 30 mg/kg) and ciprofloxacin (1, 2 and 5 mg/kg) against leptospirosis in a hamster model using Leptospira interrogans serovar Icterohaemorrhagiae. The histopathology and bacterial loads of target organs (liver, kidney and lung) were also studied by treatment with norfloxacin at the dose of 10 mg/kg in this model. Using RT-PCR, the expression of inflammatory factor IL-1β and TNF-α was analyzed by comparing the norfloxacin and untreated group. All untreated animals, serving as a negative control, displayed 50% survival rate, while hamsters treated with norfloxacin at the dose of 10 and 20 mg/kg and ciprofloxacin at the dose of 1 and 2 mg/kg showed a lower survival rate than the untreated group. Furthermore, norfloxacin at the dose of 10 mg/kg increased bacterial loads and aggravated tissue injury of target organs. The delayed induction of IL-1β and TNF-α was found in tissues of norfloxacin group. Our study indicates an increased risk associated with low-dose norfloxacin and ciprofloxacin in leptospirosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Risk Factors for Upper GI Damage in Low-Dose Aspirin Users and the Interaction Between H. pylori Infection and Low-Dose Aspirin Use.

    Science.gov (United States)

    Iijima, Katsunori; Shimosegawa, Tooru

    2015-01-01

    Nowadays, low-dose aspirin is widely administered at low dose as an antithrombotic drug for the prevention of cerebrovascular and cardiovascular diseases. However, aspirin, even at a low dose, can induce varying degrees of gastroduodenal mucosal injury (erosion, ulcer, ulcer bleeding). Hence, co-prescription of proton pump inhibitors with low-dose aspirin is recommended for those at high risk for adverse gastroduodenal events. At present, a history of peptic ulcer, especially that of complicated ulcer, is the most important risk factor for low-dose aspirin-associated gastroduodenal adverse events. Additionally, concomitant use of non-steroidal anti-inflammatory drugs including COX-2 selective inhibitors, anti-platelet agents, anti-coagulants, and oral corticosteroid is recognized to increase the risk for adverse gastroduodenal events in low-dose aspirin users. H. pylori infection could also be associated with the increased risk for adverse gastroduodenal events in low-dose aspirin users, especially in patients with histories of peptic ulcers. Therefore, eradication therapy for such patients can prevent ulcer recurrence. However, the efficacy of eradication therapy on low-dose aspirin-related gastroduodenal lesions in unselected H. pylori-positive lowdose aspirin users without histories of peptic ulcers remains to be clarified.

  11. HIGH AND LOW DOSE IVIG THERAPY IN GUILLAIN-BARRE SYNDROME CHILDREN: A COMPARISON

    Directory of Open Access Journals (Sweden)

    P. KARIMZADEH MD

    2009-05-01

    Full Text Available Objective:Acute inflammatory demyelinating peripheral neuropathy (Guillain-Barre-Syndrome is by far the most common cause of immune-medicated peripheral nervous system disease in children; with the near disappearance of poliomyelitis, GBS is responsible for the great majority of cases of acute flaccid paralysis. So far, in several controlled studies, corticosteroids, plasmapheresis and IVIG have been utilized in pediatric patients, afflicted with GBS. Regarding IVIG therapy, two methods have been used; the high dose (1 gr/kg/day for 2 days, and the low dose (400mg/kg/day for 5 days. Review of literature shows that a faster rate of recovery can be accomplished in patients who receive total dose of IVIG in 2 days as compared to the dose being given over 5 days.Materials & Methods:In this study we have compared these two types of treatment in an investigation, conducted in the Mofid Children Hospital on pediatric patients who had sudden onset of acute flaccid  paralysis, and were diagnosed as having GBS. Based on histories, physical examination and electrodiagnosis, subjects were divided in two groups, the high dose IVIG treatment, 1gr/kg/day for 2 days (experimental group, and the low dose IVIG treatment, 400 mg/kg/day for 5 days (control group. Statistical analyses were then carried out using the appropriate software.Results:Result of this study showed a faster rate of recovery for patients in the high dose IVIG group; in this group duration of weakness of limbs was shorter and returning of DTR was faster than in controls. In fact, in this type of treatment, the relationship between high dose IVIG therapy and drug side effects was not significant.Conclusion:Base upon the finding in the present study, we conclude that the high dose IVIG therapy is superior to low dose, in view of faster duration of recovery and shorter hospital stay. Also we may infer that shorter hospital stay could be a factor in reducing of more nasocomial infection. In

  12. Fricke gel dosimeter with improved sensitivity for low-dose-level measurements.

    Science.gov (United States)

    Vaiente, Mauro; Molina, Wladimir; Silva, Lila Carrizales; Figueroa, Rodolfo; Malano, Francisco; Pérez, Pedro; Santibañez, Mauricio; Vedelago, José

    2016-07-01

    Fricke solution has a wide range of applications as radiation detector and dosimetry. It is particularly appreciated in terms of relevant comparative advantages, like tissue-equivalence when prepared in aqueous media like gel matrix, continuous mapping capability, independence of dose rate and incident direction, as well as linear dose response. This work presents the development and characterization of an improved Fricke gel system, based on modified chemical compositions, making possible its application in clinical radiology due to its improved sensitivity. Properties of standard Fricke gel dosimeter for high-dose levels are used as a starting point, and suitable chemical modifications are introduced and carefully investigated in order to attain high resolution for low-dose ranges, like those corresponding to radiology interventions. The developed Fricke gel radiation dosimeter system achieves the expected typical dose-dependency, showing linear response in the dose range from 20 up to 4000 mGy. Systematic investigations including several chemical compositions are carried out in order to obtain an adequate dosimeter response for low-dose levels. A suitable composition from among those studied is selected as a good candidate for low-dose-level radiation dosimetry consisting of a modified Fricke solution fixed to a gel matrix containing benzoic acid along with sulfuric acid, ferrous sulfate, Xylenol orange, and tridistilled water. Dosimeter samples are prepared in standard vials for in-phantom irradiation and further characterization by spectrophotometry measuring visible light transmission and absorbance before and after irradiation. Samples are irradiated using typical X-ray tubes for radiology and calibrated Farmer-type ionization chamber is used as reference to measure dose rates inside phantoms at vial locations. Once sensitive material composition is optimized, dose-response curves show significant improvement regarding overall sensitivity for low dose levels

  13. Prostate; Prostate

    Energy Technology Data Exchange (ETDEWEB)

    Rouviere, O.; Valette, O.; Grivolat, S.; Colin-Pangaud, C.; Bouvier, R.; Chapelon, J.Y.; Gelet, A.; Lyonnet, D.; Rouviere, O.; Mege-Lechevallier, F.; Chapelon, J.Y.; Gelet, A.; Bouvier, R.; Boutitie, F.; Lyonnet, D. [69 - Lyon (France)

    2005-10-15

    Two methods to detect recurrence of prostate cancer are presented. Dynamic magnetic resonance imaging after radiotherapy and color doppler after high intensity focused ultrasounds (but with patients that have not received a hormones therapy). These two methods presents an useful contribution. (N.C.)

  14. Low-dose ionizing radiation limitations to seed germination: Results from a model linking physiological characteristics and developmental-dynamics simulation strategy.

    Science.gov (United States)

    Liu, Hui; Hu, Dawei; Dong, Chen; Fu, Yuming; Liu, Guanghui; Qin, Youcai; Sun, Yi; Liu, Dianlei; Li, Lei; Liu, Hong

    2017-08-01

    There is much uncertainty about the risks of seed germination after repeated or protracted environmental low-dose ionizing radiation exposure. The purpose of this study is to explore the influence mechanism of low-dose ionizing radiation on wheat seed germination using a model linking physiological characteristics and developmental-dynamics simulation. A low-dose ionizing radiation environment simulator was built to investigate wheat (Triticum aestivum L.) seeds germination process and then a kinetic model expressing the relationship between wheat seed germination dynamics and low-dose ionizing radiation intensity variations was developed by experimental data, plant physiology, relevant hypotheses and system dynamics, and sufficiently validated and accredited by computer simulation. Germination percentages were showing no differences in response to different dose rates. However, root and shoot lengths were reduced significantly. Plasma governing equations were set up and the finite element analysis demonstrated H2O, CO2, O2 as well as the seed physiological responses to the low-dose ionizing radiation. The kinetic model was highly valid, and simultaneously the related influence mechanism of low-dose ionizing radiation on wheat seed germination proposed in the modeling process was also adequately verified. Collectively these data demonstrate that low-dose ionizing radiation has an important effect on absorbing water, consuming O2 and releasing CO2, which means the risk for embryo and endosperm development was higher. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Limits of Ultra-Low Dose CT Attenuation Correction for PET/CT.

    Science.gov (United States)

    Xia, Ting; Alessio, Adam M; Kinahan, Paul E

    2010-01-29

    We present an analysis of the effects of ultra-low dose X-ray computerized tomography (CT) based attenuation correction for positron emission tomography (PET). By ultra low dose we mean less than approximately 5 mAs or 0.5 mSv total effective whole body dose. The motivation is the increased interest in using respiratory motion information acquired during the CT scan for both phase-matched CT-based attenuation correction and for motion estimation. Since longer duration CT scans are desired, radiation dose to the patient can be a limiting factor. In this study we evaluate the impact of reducing photon flux rates in the CT data on the reconstructed PET image by using the CATSIM simulation tool for the CT component and the ASIM simulation tool for the PET component. The CT simulation includes effects of the x-ray tube spectra, beam conditioning, bowtie filter, detector noise, and bean hardening correction. The PET simulation includes the effect of attenuation and photon counting. Noise and bias in the PET image were evaluated from multiple realizations of test objects. We show that techniques can be used to significantly reduce the mAs needed for CT based attenuation correction if the CT is not used for diagnostic purposes. The limiting factor, however, is not the noise in the CT image but rather the bias introduced by CT sinogram elements with no detected flux. These results constrain the methods that can be used to lower CT dose in a manner suitable for attenuation correction of PET data. We conclude that ultra-low-dose CT for attenuation correction of PET data is feasible with current PET/CT scanners.

  16. Analysis of ionic mobilities in liquid isooctane with low dose radiotherapy pulsed photon beams

    Science.gov (United States)

    Pardo-Montero, J.; Tegami, S.; Gago-Arias, A.; González-Castaño, D. M.; Holzscheiter, M. H.; Gómez, F.

    2012-09-01

    In this work we present a model of signal temporal development in ionization chambers and we use it to determine ionic mobilities and relative densities of charge carriers in non-ultrapure liquid isooctane using a liquid-filled ionization chamber dosimeter. The detector has been irradiated with a low dose rate, short pulsed photon beam generated with a medical LINAC. Ionic mobilities have been obtained by studying the temporal development of the readout signal and fitting it to a model for low dose rate beams where recombination is negligible. The best fit has been obtained for 3 ionic species with mobilities k1 = (2.22±0.22) × 10-8, k2 = (3.37±0.43) × 10-8, k3 = (19.69±2.59) × 10-8 m2 V-1 s-1 and relative densities n1 = 0.5 (n1 is not a fitting parameter), n2 = 0.23±0.03 and n3 = 0.27±0.03.

  17. Automated detection and classification of interstitial lung diseases from low-dose CT images

    Science.gov (United States)

    Zheng, Bin; Leader, Joseph K.; Fuhrman, Carl R.; Sciurba, Frank C.; Gur, David

    2004-05-01

    We developed a computer-aided diagnosis (CAD) scheme to detect and quantitatively assess interstitial lung diseases (ILD) depicted on low-dose and multi-slice helical high-resolution computed tomography (CT) examinations. Eighteen CT cases acquired from patients who underwent routine low-dose whole-lung screening examinations for the detection of lung cancer were used to test the scheme. ILD was identified in all of these cases. The CAD scheme involves multiple steps to segment lung areas, identify suspicious ILD regions depicted on each CT slice, and generate volumetric ILD lesions by grouping and matching ILD regions detected on multiple adjacent slices. The scheme computes five "global" features for each identified ILD region, which include size (or volume), contrast, average local pixel value fluctuation, mean of stochastic fractal dimension, and geometric fractal dimension. Two sets of classification rules are applied to remove false-positive detections. The severity of ILD in each case was rated by one experienced chest radiologist into one of the three categories (mild, moderate, and severe). A distance-weighted k-nearest neighbor algorithm and round-robin validation method was applied to classify each testing case into one of the three categories of severity. In this experiment, the CAD scheme classified 78% (14 out of 18) cases into the same categories as rated by the radiologist.

  18. Nuclear energy and health: and the benefits of low-dose radiation hormesis.

    Science.gov (United States)

    Cuttler, Jerry M; Pollycove, Myron

    2009-01-01

    Energy needs worldwide are expected to increase for the foreseeable future, but fuel supplies are limited. Nuclear reactors could supply much of the energy demand in a safe, sustainable manner were it not for fear of potential releases of radioactivity. Such releases would likely deliver a low dose or dose rate of radiation, within the range of naturally occurring radiation, to which life is already accustomed. The key areas of concern are discussed. Studies of actual health effects, especially thyroid cancers, following exposures are assessed. Radiation hormesis is explained, pointing out that beneficial effects are expected following a low dose or dose rate because protective responses against stresses are stimulated. The notions that no amount of radiation is small enough to be harmless and that a nuclear accident could kill hundreds of thousands are challenged in light of experience: more than a century with radiation and six decades with reactors. If nuclear energy is to play a significant role in meeting future needs, regulatory authorities must examine the scientific evidence and communicate the real health effects of nuclear radiation. Negative images and implications of health risks derived by unscientific extrapolations of harmful effects of high doses must be dispelled.

  19. Methods for prostate stabilization during transperineal LDR brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Podder, Tarun; Yu Yan [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Sherman, Jason [Department of Medical Physics, University of Buffalo, Buffalo, NY 14260 (United States); Rubens, Deborah; Strang, John [Departments of Imaging Science and Surgery, University of Rochester, Rochester, NY 14642 (United States); Messing, Edward [Departments of Urology and Surgery, University of Rochester, Rochester, NY 14642 (United States); Ng, Wan-Sing [School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

    2008-03-21

    In traditional prostate brachytherapy procedures for a low-dose-rate (LDR) radiation seed implant, stabilizing needles are first inserted to provide some rigidity and support to the prostate. Ideally this will provide better seed placement and an overall improved treatment. However, there is much speculation regarding the effectiveness of using regular brachytherapy needles as stabilizers. In this study, we explored the efficacy of two types of needle geometries (regular brachytherapy needle and hooked needle) and several clinically feasible configurations of the stabilization needles. To understand and assess the prostate movement during seed implantation, we collected in vivo data from patients during actual brachytherapy procedures. In vitro experimentation with tissue-equivalent phantoms allowed us to further understand the mechanics behind prostate stabilization. We observed superior stabilization with the hooked needles compared to the regular brachytherapy needles (more than 40% in bilateral parallel needle configuration). Prostate movement was also reduced significantly when regular brachytherapy needles were in an angulated configuration as compared to the parallel configuration (more than 60%). When the hooked needles were angulated for stabilization, further reduction in prostate displacement was observed. In general, for convenience of dosimetric planning and to avoid needle collision, all needles are desired to be in a parallel configuration. In this configuration, hooked needles provide improved stabilization of the prostate. On the other hand, both regular and hooked needles appear to be equally effective in reducing prostate movement when they are in angulated configurations, which will be useful in seed implantation using a robotic system. We have developed nonlinear spring-damper model for the prostate movement which can be used for adapting dosimetric planning during brachytherapy as well as for developing more realistic haptic devices and

  20. Pb low doses induced genotoxicity in Lactuca sativa plants.

    Science.gov (United States)

    Silva, S; Silva, P; Oliveira, H; Gaivão, I; Matos, M; Pinto-Carnide, O; Santos, C

    2017-03-01

    Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L(-1). In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO3)2 up to 20 mg L(-1). The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used. However, for doses higher than 5 mg L(-1) significant DNA damage was detected: Comet assay detected DNA fragmentation at ≥ 5 mg L(-1) and presence of micronuclei (MN) were detected for 20 mg L(-1). Also, cell cycle impairment was observed for doses as low as 0.05 mg L(-1) and 0.5 mg L(-1) (mostly G2 arrest). Our data show that for the low doses of Pb used, the OECD endpoints were not able to detect toxicity, while more sensitive endpoints (related with DNA damage and mitotic/interphase disorders) identified genotoxic and cytostatic effects. Furthermore, the nature of the genotoxic effect was dependent on the concentration. Finally, we recommend that MN test and the comet assay should be included as sensitive endpoints in (eco)toxicological assays.

  1. Information content of low-dose radiographs: Part 2

    Energy Technology Data Exchange (ETDEWEB)

    Morris, R.A.

    1997-10-01

    The previous paper described the concept of using the net number of information bits transmitted in a radiographic image as a measure of the contrast parameter of image quality. The concept is particularly useful when the image contrast is limited by the statistics of the photon fluence incident on the detector (low doses). The Wolfram Research Mathematica program (described in Ref. 1) that was used to simulate a noisy image of an object with two thicknesses and to calculate the resulting IC (information content). The only noise source in the simulation was fluctuations in the photon fluence incident on the detector. The results from the simulation were compared to data obtained from actual radiographs of a copper step wedge radiographed with 10 and 50 pulses from a 150-p, V x-ray machine. Good agreement between the simulation and experiment was obtained when the photon fluence was considered a free, adjustable parameter. This report extends the simulation described in Ref. 1 and shows how IC varies as the following radiographic parameters change: object thickness; object Z number; x-ray energy; and incident x-ray fluence.

  2. Low dose radiation damage effects in silicon strip detectors

    Science.gov (United States)

    Wiącek, P.; Dąbrowski, W.

    2016-11-01

    The radiation damage effects in silicon segmented detectors caused by X-rays have become recently an important research topic driven mainly by development of new detectors for applications at the European X-ray Free Electron Laser (E-XFEL). However, radiation damage in silicon strip is observed not only after extreme doses up to 1 GGy expected at E-XFEL, but also at doses in the range of tens of Gy, to which the detectors in laboratory instruments like X-ray diffractometers or X-ray spectrometers can be exposed. In this paper we report on investigation of radiation damage effects in a custom developed silicon strip detector used in laboratory diffractometers equipped with X-ray tubes. Our results show that significant degradation of detector performance occurs at low doses, well below 200 Gy, which can be reached during normal operation of laboratory instruments. Degradation of the detector energy resolution can be explained by increasing leakage current and increasing interstrip capacitance of the sensor. Another observed effect caused by accumulation of charge trapped in the surface oxide layer is change of charge division between adjacent strips. In addition, we have observed unexpected anomalies in the annealing process.

  3. Personalized low dose CT via variable kVp

    Science.gov (United States)

    Wang, Hui; Jin, Yannan; Yao, Yangyang; Wu, Mingye; Yan, Ming; Tao, Kun; Yin, Zhye; De Man, Bruno

    2015-03-01

    Computerized Tomography (CT) is a powerful radiographic imaging technology but the health risk due to the exposure of x-ray radiation has drawn wide concern. In this study, we propose to use kVp modulation to reduce the radiation dose and achieve the personalized low dose CT. Two sets of simulation are performed to demonstrate the effectiveness of kVp modulation and the corresponding calibration. The first simulation used the helical body phantom (HBP) that is an elliptical water cylinder with high density bone inserts. The second simulation uses the NCAT phantom to emulate the practical use of kVp modulation approach with region of interest (ROI) selected in the cardiac region. The kVp modulation profile could be optimized view by view based on the knowledge of patient attenuation. A second order correction is applied to eliminate the beam hardening artifacts. To simplify the calibration process, we first generate the calibration vectors for a few representative spectra and then acquire other calibration vectors with interpolation. The simulation results demonstrate the beam hardening artifacts in the images with kVp modulation can be eliminated with proper beam hardening correction. The results also show that the simplification of calibration did not impair the image quality: the calibration with the simplified and the complete vectors both eliminate the artifacts effectively and the results are comparable. In summary, this study demonstrates the feasibility of kVp modulation and gives a practical way to calibrate the high order beam hardening artifacts.

  4. Benzodiazepine dependence and its treatment with low dose flumazenil.

    Science.gov (United States)

    Hood, Sean David; Norman, Amanda; Hince, Dana Adelle; Melichar, Jan Krzysztof; Hulse, Gary Kenneth

    2014-02-01

    Globally benzodiazepines remain one of the most prescribed medication groups, especially in the primary care setting. With such high levels of prescribing it is not surprising that benzodiazepine dependence is common, cutting across all socioeconomic levels. Despite recognition of the potential for the development of iatrogenic dependence and the lack of any effective treatment, benzodiazepines continue to be widely prescribed in general practice. Conventional dependence management, benzodiazepine tapering, is commonly a protracted process over several weeks or months. It is often associated with significant withdrawal symptoms and craving leading to patient drop out and return to use. Accordingly, there is a worldwide need to find effective pharmacotherapeutic interventions for benzodiazepine dependence. One drug of increasing interest is the GABAA benzodiazepine receptor antagonist/partial agonist, flumazenil. Multiple bolus intravenous infusions of low dose flumazenil used either with or without benzodiazepine tapering can reduce withdrawal sequelae, and/or longer term symptoms in the months following withdrawal. Preliminary data suggest that continuous intravenous or subcutaneous flumazenil infusion for 4 days significantly reduces acute benzodiazepine withdrawal sequelae. The subcutaneous infusion was shown to be tissue compatible so the development of a longer acting (i.e. several weeks) depot flumazenil formulation has been explored. This could be capable of managing both acute and longer term benzodiazepine withdrawal sequelae. Preliminary in vitro water bath and in vivo biocompatibility data in sheep show that such an implant is feasible and so is likely to be used in clinical trials in the near future.

  5. Low dose CT perfusion using k-means clustering

    Science.gov (United States)

    Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc

    2016-03-01

    We aim at improving low dose CT perfusion functional parameters maps and CT images quality, preserving quantitative information. In a dynamic CT perfusion dataset, each voxel is measured T times, where T is the number of acquired time points. In this sense, we can think about a voxel as a point in a T-dimensional space, where the coordinates of the voxels would be the values of its time attenuation curve (TAC). Starting from this idea, a k-means algorithm was designed to group voxels in K classes. A modified guided time-intensity profile similarity (gTIPS) filter was implemented and applied only for those voxels belonging to the same class. The approach was tested on a digital brain perfusion phantom as well as on clinical brain and body perfusion datasets, and compared to the original TIPS implementation. The TIPS filter showed the highest CNR improvement, but lowest spatial resolution. gTIPS proved to have the best combination of spatial resolution and CNR improvement for CT images, while k-gTIPS was superior to both gTIPS and TIPS in terms of perfusion maps image quality. We demonstrate k-means clustering analysis can be applied to denoise dynamic CT perfusion data and to improve functional maps. Beside the promising results, this approach has the major benefit of being independent from the perfusion model employed for functional parameters calculation. No similar approaches were found in literature.

  6. Low-dose techniques in CT-guided interventions.

    Science.gov (United States)

    Sarti, Marc; Brehmer, William P; Gay, Spencer B

    2012-01-01

    Computed tomography (CT)-guided interventions such as biopsy, drainage, and ablation may be significant sources of radiation exposure in both patients and radiologists. Simple CT techniques to reduce radiation dose may be employed without increasing the procedure time or significantly degrading image quality. To develop low-dose protocols, it is important to understand the key concepts of delivered radiation dose to patients and physicians during CT-guided interventions. Patient dose estimates are easily followed and are provided at CT workstations. Familiarity with dose estimates, which are expressed as CT dose index and dose-length product, is also important. Methods to reduce radiation exposure in patients and physicians include performing proper preprocedure planning and paying careful attention to technique during the planning stage, making use of personal protective equipment, performing CT fluoroscopy intermittently instead of in real time, and optimizing needle visualization. Representative examples of these techniques have resulted in dose reductions of as much as 89%. Alternative imaging technologies that do not use ionizing radiation, such as virtual and ultrasonographic guidance, may also be used to reduce radiation dose. Understanding dose contribution strategies to reduce radiation dose provides a safer, more efficient environment for patients and the radiology team.

  7. Prostate cancer in Denmark

    DEFF Research Database (Denmark)

    Brasso, K; Friis, S; Kjaer, S K

    1998-01-01

    To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period.......To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period....

  8. Prostate cancer in Denmark

    DEFF Research Database (Denmark)

    Brasso, K; Friis, S; Kjaer, S K

    1998-01-01

    To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period.......To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period....

  9. High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding: a meta-analysis.

    Science.gov (United States)

    Wu, Liu-Cheng; Cao, Yun-Fei; Huang, Jia-Hao; Liao, Cun; Gao, Feng

    2010-05-28

    To evaluate the efficacy of high-dose proton pump inhibitors (PPIs) vs low-dose PPIs for patients with upper gastrointestinal bleeding. PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify relevant randomized controlled trials (RCTs). Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis. The primary endpoint was rebleeding; secondary endpoints were patient numbers that needed surgery, and mortality. The meta-analysis was performed with a fixed effects model or random effects model. Nine eligible RCTs including 1342 patients were retrieved. The results showed that high-dose intravenous PPI was not superior to low-dose intravenous PPI in reducing rebleeding [odds ratio (OR) = 1.091, 95% confidential interval (CI): 0.777-1.532], need for surgery (OR = 1.522, 95% CI: 0.643-3.605) and mortality (OR = 1.022, 95% CI: 0.476-2.196). Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients (OR = 0.831, 95% CI, 0.467-1.480) and European patients (OR = 1.263, 95% CI: 0.827-1.929). Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

  10. Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF

    Directory of Open Access Journals (Sweden)

    Gomaa Hala

    2012-08-01

    Full Text Available Abstract Background To compare the outcome of IVF cycles in women receiving controlled ovarian stimulation with recFSH or recFSH plus low dose hCG. Methods A retrospective case control study, performed at a private practice affiliated with an academic institute. Patients were infertile women who were treated with IVF/ICSI and controlled ovarian stimulation in a long GnRH agonist protocol using either low dose hCG in addition to recFSH [N = 88] or recFSH alone [N = 99]. Primary outcomes were mean FSH dose, number of mature eggs, number of fertilized eggs, and serum levels of estradiol. Secondary outcomes were endometrial thickness, cycle cancellations and pregnancy rates. Results A significant increase in number of mature and fertilized eggs was observed in women over 40 years of age using low dose hCG in addition to recFSH. The estradiol level was significantly higher on the day of hCG administration and the serum level of FSH on cycle day 7 and on the day of hCG administration were lower. Conclusion Addition of low dose hCG to recFSH compared with recFSH alone significantly modified cycle characteristics in patients >/= 40 years and could be of potential benefit for IVF cycles in older infertile women.

  11. Low-Dose Decitabine-Based Chemoimmunotherapy for Patients with Refractory Advanced Solid Tumors: A Phase I/II Report

    Directory of Open Access Journals (Sweden)

    Hui Fan

    2014-01-01

    Full Text Available Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083.

  12. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, Francis A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

  13. EFFICIENT ACTIVATION OF ANTITUMOR IMMUNITY BY IL-6 GENE-MODIFIED LEUKEMIA VACCINE IN COMBINATION WITH LOW DOSE CYCLOPHOSPHAMIDE AND LOW DOSE IL-2

    Institute of Scientific and Technical Information of China (English)

    Cao Xuetao; Ge Lingfu; Ju Dianwen; Tao Qun; Yu Yizhi

    1998-01-01

    Objective:To investigate the antitumor effect of the IL-6 gene-modified erythroleukemia cells combined with low dose cyclophosphamide (Cy) and low dose IL-2.Methods: Mice inoculated with FBL-3-IL-6 in combination with low dose IL-2 and low dose cyclophosphamide (Cy). Results: Mice received combined therapy of FBL-3-IL-6, IL-2 and Cy developed tumors most slowly and survived much longer when compared with mice in control groups, with 5 out of 8leukemia-bearing mice being tumor free 100 days after the combined treatment. To further explain the mechanism of the antitumor effects by the combined therapy. It was found that combined therapy with low dose Cy, low dose IL-2 and FBL-3-IL-6 achieved maximal cytotoxic effects of nature killer cells and specific cytotoxic T lymphocytes, increased production IL-2, TNF and GM-CSF from spleen lymphocytes in tumor-bearing mice. Vaccination with the FBL3-IL-6 also enhanced the cytotoxic activity of the peritoneal macrophages. The results demonstrated that administration of low dose Cy and low dose IL-2 in combination with IL-6 genemodified leukemia vaccine could elicit potent antileukemia effects, and the mechanisms involved in the antitumor process may include the induction of specific and nonspecific antitumor immunity, reversal of T suppressor cells that mediated local immuno-suppression in tumor bearing mice. Conclusion: The combined therapy with cytokine gene-modified tumor vaccine, low dose of Cy and IL-2 might be a promising approach for the treatment of leukemia.

  14. Low dose X -ray effects on catalase activity in animal tissue

    Science.gov (United States)

    Focea, R.; Nadejde, C.; Creanga, D.; Luchian, T.

    2012-12-01

    This study was intended to investigate the effect of low-dose X ray-irradiation upon the activity of catalase (CAT) in freshly excised chicken tissues (liver, kidney, brain, muscle). The tissue samples were irradiated with 0.5Gy and 2Gy respectively, in a 6 MV photon beam produced by a clinical linear accelerator (VARIAN CLINAC 2100SC). The dose rate was of 260.88cGy/min. at 100 cm source to sample distance. The catalase level was assayed spectrophotometrically, based on reaction kinetics, using a catalase UV assay kit (SIGMA). Catalase increased activity in various tissue samples exposed to the studied X ray doses (for example with 24 % in the liver cells, pantioxidant enzyme biosynthesis within several hours after exposure at doses of 0.5 Gy and 2 Gy; the putative enzyme inactivation could also occur (due to the injuries on the hydrogen bonds that ensure the specificity of CAT active site) but the resulted balance of the two concurrent processes indicates the cell ability of decomposing the hydrogen peroxide-with benefits for the cell physiology restoration for the chosen low dose radiation.

  15. Consequences of peripheral chemoreflex inhibition with low-dose dopamine in humans

    Science.gov (United States)

    Niewinski, Piotr; Tubek, Stanislaw; Banasiak, Waldemar; Paton, Julian F R; Ponikowski, Piotr

    2014-01-01

    Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg–1 min–1) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function. PMID:24396060

  16. Consequences of peripheral chemoreflex inhibition with low-dose dopamine in humans.

    Science.gov (United States)

    Niewinski, Piotr; Tubek, Stanislaw; Banasiak, Waldemar; Paton, Julian F R; Ponikowski, Piotr

    2014-03-15

    Low-dose dopamine inhibits peripheral chemoreceptors and attenuates the hypoxic ventilatory response (HVR) in humans. However, it is unknown: (1) whether it also modulates the haemodynamic reactions to acute hypoxia, (2) whether it also modulates cardiac baroreflex sensitivity (BRS) and (3) if there is any effect of dopamine withdrawal. We performed a double-blind, placebo-controlled study on 11 healthy male volunteers. At sea level over 2 days every subject was administered low-dose dopamine (2 μg kg(-1) min(-1)) or saline infusion, during which we assessed both ventilatory and haemodynamic responses to acute hypoxia. Separately, we evaluated effects of initiation and withdrawal of each infusion and BRS. The initiation of dopamine infusion did not affect minute ventilation (MV) or mean blood pressure (MAP), but increased both heart rate (HR) and cardiac output. Concomitantly, it decreased systemic vascular resistance. Dopamine blunted the ventilatory, MAP and HR reactions (hypertension, tachycardia) to acute hypoxia. Dopamine attenuated cardiac BRS to falling blood pressure. Dopamine withdrawal evoked an increase in MV. The magnitude of the increment in MV due to dopamine withdrawal correlated with the size of the HVR and depended on the duration of dopamine administration. The ventilatory reaction to dopamine withdrawal constitutes a novel index of peripheral chemoreceptor function.

  17. Effect of low-dose fenvalerate on semen quality capacitation in adult mice

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-dan; BI Huan-jing; FU He-ling; LI Liang-yun; LIU De-kang; LI Jian-min

    2011-01-01

    Background Fenvalerate (FEN) has been demonstrated to be a reproductive toxicant in humans and rodents. However,little is known about whether short-term exposure to low-dose FEN produces reproductive toxicity.Methods We administered FEN (0.009 375, 0.1875, 3.750, or 45.00 mg·kg-1d-1 by gavage for 30 days) to male ICR mice and compared reproductive toxicity parameters between groups receiving different concentrations of FEN.Reproductive toxicity was evaluated by computer-assisted semen quality analysis (CASA), chlortetracycline (CTC) assay,and histopathology.Results The sperm morphology and testis histology of FEN-exposed mice (all doses) were similar to that in controlling mice. Exposure to FEN at a concentration of 0.1875 mg·kg-1d-1 decreased sperm path straightness (STR) and linearity (LIN) (both P< 0.05), but had no significant impact on average path velocity (VAP), straight line velocity (VSL), curvilinear velocity (VCL), lateral amplitude (ALH), beat cross frequency (BCF), or progressive motility (MOT). FEN reduced the rate of mouse sperm capacitation in a dose-dependent manner.Conclusion The present results demonstrate that exposure to low-dose FEN for 30 days reduces semen quality and sperm capacitation in adult mice.

  18. Efficacy of rebamipide for low-dose aspirin-related gastrointestinal symptoms.

    Science.gov (United States)

    Mizukami, Kazuhiro; Murakami, Kazunari; Hirashita, Yuka; Hisamatsu, Akari; Ogawa, Ryo; Uchida, Masahiro; Nakagawa, Yoshifumi; Okimoto, Tadayoshi; Kodama, Masaaki; Fujioka, Toshio

    2012-11-01

    Gastrointestinal symptoms are a problematic issue for patients who take low-dose aspirin for long time. We conducted a pilot study to investigate the efficacy of combination therapy with proton pump inhibitor and rebamipide. This was a prospective, randomized, double-blind, placebo-controlled cross-over study. All the subjects received aspirin 100 mg and omeprazole 20 mg. The subjects were divided into two groups and received either rebamipide 300 mg or placebo, which was prescribed for 4 weeks. The subjects were instructed to record their gastrointestinal symptom rating scale before the study and 1 and 4 weeks after beginning the protocol. These scores of the groups were compared before and after the treatment to evaluate the severity of their symptoms and the number of symptom items present in each group. For the subjects receiving rebamipide, the total prevalence of lower gastrointestinal symptoms was significantly different from the placebo group (p=0.0093) at week 4. No troublesome symptoms were observed in the rebamipide group. Inconclusion, the administration of rebamipide prevented the occurrence of troublesome symptoms, especially lower gastrointestinal symptoms, in patients taking aspirin and omeprazole. Rebamipide is a candidate drug for combination therapy with proton pump inhibitors to prevent low-dose aspirin-induced gastrointestinal symptoms.

  19. LOW-DOSE RADIOACTIVE ENDOVASCULAR STENTS PREVENT NEOINTIMAL HYPERPLASIA IN RABBITS RESTENOSIS MODEL

    Institute of Scientific and Technical Information of China (English)

    任晓庆; 黄定九; 黄刚; 毛家亮

    2002-01-01

    Objective To evaluate the effects of low-dose radioactive stents on the prevention of restenosis in rabbit model. Methods The stents were bombarded with suitable charged particles of adapted energy in the cyclotron to create a proper mixture of the radionuclides 59Fe, 60Co, 58Co, 51Cr, and 54Mn. The radioactive stents were implanted in the iliac arteries of rabbits. The effects of radioactive stents on prevention of restenosis were assessed by angiography, histomorphometry and immunocytochemistry. Results All the iliac arteries that had been implanted with radioactive stents were patent on angiography and had no radiation complication during the 1~2 months of follow-up. There was a significant reduction in neointimal area (0.37±0.14mm2 vs. 0.81±0.10mm2, P<0.01), percent area stenosis (6.7±2.9% vs. 13.2±1.4%, P<0.01) and PCNA immunoreactive rate (2.00±1.58% vs. 10.88±6.98%, P<0.05) in the radioactive stent group compared with the control stent group. Conclusion Radioactive stents with an active of 0.91~1.65 μCi could inhibit SMC proliferation and neointimal hyperplasia in animal restenosis model. The low-dose radioactive stents are safe and feasible for prevention of restenosis.

  20. Effects of low dose ketamine on tourniquet-induced haemodynamic responses during general anaesthesia.

    Science.gov (United States)

    Park, J-W; Jung, Y-H; Baek, C-W; Kang, H; Cha, S-M

    2007-01-01

    This study investigated the effect of a pre-operative low dose of intravenous ketamine on tourniquet-induced haemodynamic changes. Ten minutes after induction of general anaesthesia, 0.1 mg/kg ketamine in 10 ml of saline (ketamine group, n = 14) or 10 ml of normal saline (control group, n = 14) were administered intravenously. Systolic and diastolic blood pressures, and heart rate relative to tourniquet inflation and deflation were recorded and compared within and between groups. Systolic and diastolic blood pressures in the control group significantly increased relative to baseline during the observation period following tourniquet inflation, but generally did not significantly increase in the ketamine group. The control group had a greater percentage of patients with a 30% rise in blood pressure at 60 min after tourniquet inflation compared with the ketamine group (28.6% vs 7.1%), but this was not statistically significant. We conclude that a pre-operative low dose (0.1 mg/kg) of intravenous ketamine can prevent a systemic arterial pressure increase for at least 60 min after tourniquet inflation under general anaesthesia.

  1. Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients

    Energy Technology Data Exchange (ETDEWEB)

    Tschirch, Frank T.C.; Goepfert, Kerstin; Brunner, Genevieve; Weishaupt, Dominik [University Hospital Zuerich, Institute of Diagnostic Radiology, Zuerich (Switzerland); Froehlich, Johannes M. [Klus-Apotheke, Zuerich (Switzerland)

    2007-06-15

    The purpose of this study was to assess prospectively the potential of low-dose intranasal midazolam compared to oral midazolam in claustrophobic patients undergoing routine body magnetic resonance imaging (MRI). Seventy-two adult claustrophobic patients referred for body MRI were randomly assigned to one of two treatment groups (TG1 and TG2). The 36 patients of TG1 received 7.5 mg midazolam orally 15 min before MRI, whereas the 36 patients of TG2 received one (or, if necessary, two) pumps of a midazolam nasal spray into each nostril immediately prior to MRI (in total, 1 or 2 mg). Patients' tolerance, anxiety and sedation were assessed using a questionnaire and a visual analogue scale immediately before and after MRI. Image quality was evaluated using a five-point-scale. In TG1, 18/36 MRI examinations (50%) had to be cancelled, the reduction of anxiety was insufficient in 12/18 remaining patients (67%). In TG2, 35/36 MRI examinations (97%) were completed successfully, without relevant adverse effects. MRI image quality was rated higher among patients of TG2 compared to TG1 (p<0.001). Low-dose intranasal midazolam is an effective and patient-friendly solution to overcome anxiety in claustrophobic patients in a broad spectrum of body MRI. Its anxiolytic effect is superior to that of the orally administrated form. (orig.)

  2. Perioperative low-dose ketamine improves postoperative analgesia following Cesarean delivery with general anesthesia.

    Science.gov (United States)

    Haliloglu, Murat; Ozdemir, Mehtap; Uzture, Neslihan; Cenksoy, Pinar Ozcan; Bakan, Nurten

    2016-03-01

    In this study, the effect of perioperative uses of low dose ketamine on post-operative wound pain and analgesic consumption in patients undergoing elective Cesarean section was evaluated. In randomized, double blind clinical trial, 52 women with American Society of Anesthesiologists (ASA) class I-II identification undergoing elective Cesarean section in general anesthesia were enrolled. In the ketamine group (group K), a ketamine bolus of 0.5 mg kg(-1) IV was administered at the time of induction of general anesthesia. After induction, a ketamine infusion of 0.25 mg kg(-1) h(-1) was started and discontinued at the end of surgery. Patients allocated to the control group (group C) were given identical volumes of saline. The cumulative dose of morphine consumption after surgery was measured as the primary outcome of this study. Secondary outcomes were pain control assessed by numeric rating scale (NRS) and need for rescue analgesia and incidence of side effects. The mean 24-h morphine consumption was lower in group K (p = 0,001). At 15 min postoperatively, NRS values were lower in group K than group C (p = 0,001). There was no difference among groups regarding the need for supplemental analgesia (rescue diclofenac doses) (p > 0.05). Perioperative uses of low dose ketamine decreased post-operative opioid requirements, which was observed long after the normal expected duration of ketamine.

  3. Efficacy of low dose spironolactone in chronic kidney disease with resistant hypertension

    Directory of Open Access Journals (Sweden)

    Rozita Abolghasmi

    2011-01-01

    Full Text Available To determine the antihypertensive benefit of adding low dose sprinolactone to multi-drug regimens that included a diuretic, a calcium channel blocker and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in patients with moderately severe chronic kidney disease (CKD [glomerular filtration rate (GFR 25-50 mL/min] and resistant hyper-tension, we studied 41 patients randomly divided into two groups: group 1: patients who received placebo as spironolactone and group 2: patients who received spironolactone 25-50 mg/day. The patients were evaluated during follow-up at the 6th and 12th weeks. The mean decrease in systolic and diastolic blood pressure after 6 weeks of spironolactone was 33 ± 8 and 13 ± 2 mmHg, respectively, and it was maintained after 12 weeks of spironolactone wherein the values were 36 ± 10 and 12 ± 2 mmHg, respectively, while there was no change in the blood pressure in the control group. Hyperkalemia (serum potassium >5.5 meq/L occurred in one subject in the spironolactone group. We conclude that low-dose spironolactone may provide a significant additive blood pressure reduction in CKD patients (stage 2 and 3 with resistant hypertension.

  4. Low-dose radiation modifies skin response to acute gamma-rays and protons.

    Science.gov (United States)

    Mao, Xiao Wen; Pecaut, Michael J; Cao, Jeffrey D; Moldovan, Maria; Gridley, Daila S

    2013-01-01

    The goal of the present study was to obtain pilot data on the effects of protracted low-dose/low-dose-rate (LDR) γ-rays on the skin, both with and without acute gamma or proton irradiation (IR). Six groups of C57BL/6 mice were examined: a) 0 Gy control, b) LDR, c) Gamma, d) LDR+Gamma, e) Proton, and f) LDR+Proton. LDR radiation was delivered to a total dose of 0.01 Gy (0.03 cGy/h), whereas the Gamma and Proton groups received 2 Gy (0.9 Gy/min and 1.0 Gy/min, respectively). Assays were performed 56 days after exposure. Skin samples from all irradiated groups had activated caspase-3, indicative of apoptosis. The significant (pGamma and Proton groups were not present when LDR pre-exposure was included. However, the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay for DNA fragmentation and histological examination of hematoxylin and eosin-stained sections revealed no significant differences among groups, regardless of radiation regimen. The data demonstrate that caspase-3 activation initially triggered by both forms of acute radiation was greatly elevated in the skin nearly two months after whole-body exposure. In addition, LDR γ-ray priming ameliorated this response.

  5. Effect of low-dose gaseous ozone on pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Fontes Belchor

    2012-12-01

    Full Text Available Abstract Background Treatment of chronically infected wounds is a challenge, and bacterial environmental contamination is a growing issue in infection control. Ozone may have a role in these situations. The objective of this study was to determine whether a low dose of gaseous ozone/oxygen mixture eliminates pathogenic bacteria cultivated in Petri dishes. Methods A pilot study with 6 bacterial strains was made using different concentrations of ozone in an ozone-oxygen mixture to determine a minimally effective dose that completely eliminated bacterial growth. The small and apparently bactericidal gaseous dose of 20 μg/mL ozone/oxygen (1:99 mixture, applied for 5min under atmospheric pressure was selected. In the 2nd phase, eight bacterial strains with well characterized resistance patterns were evaluated in vitro using agar-blood in adapted Petri dishes (105 bacteria/dish. The cultures were divided into 3 groups: 1- ozone-oxygen gaseous mixture containing 20 μg of O3/mL for 5 min; 2- 100% oxygen for 5 min; 3- baseline: no gas was used. Results The selected ozone dose was applied to the following eight strains: Escherichia coli, oxacillin-resistant Staphylococcus aureus, oxacillin-susceptible Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, Acinetobacter baumannii susceptible only to carbapenems, and Pseudomonas aeruginosa susceptible to imipenem and meropenem. All isolates were completely inhibited by the ozone-oxygen mixture while growth occurred in the other 2 groups. Conclusion A single topical application by nebulization of a low ozone dose completely inhibited the growth of all potentially pathogenic bacterial strains with known resistance to antimicrobial agents.

  6. Low dose CT perfusion in acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Amanda; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I. [Sunnybrook Health Sciences Centre, Toronto, ON (Canada); So, Aaron; Lee, Ting-Yim [Robarts Research Institute, London, Ontario (Canada)

    2014-12-15

    The purpose of this investigation is to determine if CT perfusion (CTP) measurements at low doses (LD = 20 or 50 mAs) are similar to those obtained at regular doses (RD = 100 mAs), with and without the addition of adaptive statistical iterative reconstruction (ASIR). A single-center, prospective study was performed in patients with acute ischemic stroke (n = 37; 54 % male; age = 74 ± 15 years). Two CTP scans were performed on each subject: one at 100 mAs (RD) and one at either 50 or 20 mAs (LD). CTP parameters were compared between the RD and LD scans in regions of ischemia, infarction, and normal tissue. Differences were determined using a within-subjects ANOVA (p < 0.05) followed by a paired t test post hoc analysis (p < 0.01). At 50 mAs, there was no significant difference between cerebral blood flow (CBF), cerebral blood volume (CBV), or time to maximum enhancement (Tmax) values for the RD and LD scans in the ischemic, infarcted, or normal contralateral regions (p < 0.05). At 20 mAs, there were significant differences between the RD and LD scans for all parameters in the ischemic and normal tissue regions (p > 0.05). CTP-derived CBF and CBV are not different at 50 mAs compared to 100 mAs, even without the addition of ASIR. Current CTP protocols can be modified to reduce the effective dose by 50 % without altering CTP measurements. (orig.)

  7. Low dose TBT exposure decreases amphipod immunocompetence and reproductive fitness.

    Science.gov (United States)

    Jacobson, Therese; Sundelin, Brita; Yang, Gongda; Ford, Alex T

    2011-01-17

    The antifouling agent tributyltin (TBT) is a highly toxic pollutant present in many aquatic ecosystems. Despite of regulations on the usage of TBT, it remains in high concentrations in sediments both in harbors and in off-shore sites. The toxicity of TBT in mollusks is well documented. However, adverse effects in other aquatic organisms, such as crustaceans, are less well known. This study is an effort to assess the effects of environmentally realistic concentrations of TBT on an ecologically important species in Swedish fresh and brackish water ecosystems, the benthic amphipod Monoporeia affinis. Field collected animals were exposed during gonad maturation to TBT (70 and 170 ng/g sediment d wt) for five weeks in static microcosms with natural sediment. Exposure concentrations were chosen to reflect effects at concentrations found in Swedish coastal sediment, but below expected effects on survival. TBT exposure resulted in a statistically significant adverse effect on oocyte viability and a doubling of the prevalence of microsporidian parasites in females, from 17% in the control to 34% in the 170 ng TBT/g sediment d wt exposure. No effects on survival were observed. Borderline significant effects were observed on male sexual maturation in the 70 ng TBT/g d wt exposure and on ecdysteroid levels in the 170 ng/g sediment d wt exposure. Both reproduction and parasite infection effects are of ecological importance since they have the potential to affect population viability in the field. This study gives further evidence to the connection between low dose contaminant exposure and increases in microsporidian parasite infection.

  8. [Prostate cancer boost using high-dose-rate brachytherapy: impact of the learning curve on the dosimetry].

    Science.gov (United States)

    Benhaïm, C; Chand, M-È; Gal, J; Hijazi, H; Gautier, M; Hannoun-Lévi, J-M

    2014-11-01

    To analyse the influence of the learning curve on dosimetric data for high-dose-rate brachytherapy prostate cancer boost. From February 2009 to May 2012, after a first course of external beam radiation therapy (46Gy/23 fractions), 124 patients underwent high-dose-rate brachytherapy boost using Plato™ (Nucletron, an Elekta company, Elekta AB, Stockholm, Sweden). The impact of the learning curve on the dosimetric quality of the prostate implant was assessed. The dosimetric data have been analysed: clinical target volume (CTV), D90 (dose to 90 % of CTV), D100, V100 (part on the CTV receiving 100 % of the dose), V150, V200 and DHI (dose non-homogeneity index). The doses delivered to 0.1, 1 and 2 cm(3) of the rectum and urethra were calculated. During the study period (39 months), a significant reduction of V150 (PD100 (P=0.3). This study confirms that the dosimetric quality of high-dose-rate brachytherapy prostate implant is significantly improved during the learning curve period. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  9. Exisulind in combination with celecoxib modulates epidermal growth factor receptor, cyclooxygenase-2, and cyclin D1 against prostate carcinogenesis: in vivo evidence.

    Science.gov (United States)

    Narayanan, Bhagavathi A; Reddy, Bandaru S; Bosland, Maarten C; Nargi, Dominick; Horton, Lori; Randolph, Carla; Narayanan, Narayanan K

    2007-10-01

    Nonsteroidal anti-inflammatory drugs mediate anticancer effects by modulating cyclooxygenase-2 (COX-2)-dependent and/or COX-2-independent mechanism(s); however, the toxicity issue is a concern with single agents at higher doses. In this study, we determined the combined effect of celecoxib, a COX-2 inhibitor, along with exisulind (sulindac sulfone/Aptosyn) at low doses in prostate cancer. We used a sequential regimen of N-methyl-N-nitrosourea + testosterone to induce prostate cancer in Wistar-Unilever rats. Following carcinogen treatment, celecoxib and exisulind individually and their combination at low doses were given in NIH-07 diet for 52 weeks. We determined the incidence of prostatic intraepithelial neoplasia, adenocarcinomas, rate of tumor cell proliferation, and apoptosis. Immunohistochemical and Western blot analysis were done to determine COX-2, epidermal growth factor receptor (EGFR), Akt, androgen receptor, and cyclin D1 expression. Serum prostaglandin E2 and tumor necrosis factor-alpha levels were determined using enzyme immunoassay/ELISA assays. The rats that received celecoxib in combination with exisulind at low doses showed a significant decrease in prostatic intraepithelial neoplasia and adenocarcinomas as well as an enhanced rate of apoptosis. An overall decrease in COX-2, EGFR, Akt, androgen receptor, and cyclin D1 expression was found associated with tumor growth inhibition. Reduced serum levels of COX-2 protein, prostaglandin E2, and tumor necrosis factor-alpha indicated anti-inflammatory effects. A strong inhibition of total and phosphorylated form of EGFR (Tyr(992) and Tyr(845)) and Akt (Ser(473)) was significant in rats given with these agents in combination. In this study, we show for the first time that the combination of celecoxib with exisulind at low doses could prevent prostate carcinogenesis by altering key molecular events.

  10. High-Dose-Rate Brachytherapy as a Monotherapy for Favorable-Risk Prostate Cancer: A Phase II Trial

    Energy Technology Data Exchange (ETDEWEB)

    Barkati, Maroie [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Williams, Scott G., E-mail: scott.williams@petermac.org [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Foroudi, Farshad; Tai, Keen Hun; Chander, Sarat [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia); Dyk, Sylvia van [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); See, Andrew [Ballarat Austin Radiation Oncology Centre, Ballarat (Australia); Duchesne, Gillian M. [Division of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Pathology, University of Melbourne, Melbourne (Australia)

    2012-04-01

    Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer. Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time. Conclusions: HDR brachytherapy as a monotherapy for favorable

  11. A pilot study of low-dose L-deprenyl in Alzheimer's disease.

    Science.gov (United States)

    Schneider, L S; Pollock, V E; Zemansky, M F; Gleason, R P; Palmer, R; Sloane, R B

    1991-01-01

    The use of low-dose L-deprenyl, a selective MAO-B inhibitor, in Alzheimer's disease patients has been associated previously with improvements in agitation and episodic learning and memory. Behavioral, cognitive, and regional electroencephalogram (EEG) measures were obtained in a 4-week open pilot study of 14 patients with probable Alzheimer's disease by NINCDS criteria who were administered 10 mg L-deprenyl per day. L-Deprenyl administration was associated with significant improvements on the agitation and depression factors of the Brief Psychiatric Rating Scale, the Cornell Scale for Depression in Dementia, and spouses' blind ratings. Recall improved on the Buschke Selective Reminding Task, but intrusions also tended to increase; verbal fluency decreased. Absolute EEG delta measures were selectively suppressed in the right frontal region. The pattern of changes suggests that L-deprenyl may be associated with improvement in behavioral and cognitive performance, in part through a mild behavioral disinhibiting effect.

  12. Low-dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern.

    Science.gov (United States)

    Meerwaldt, J H; Carde, P; Burgers, J M; Monconduit, M; Thomas, J; Somers, R; Sizoo, W; Glabbeke, M V; Duez, N; de Wolf-Peeters, C

    1991-10-01

    The treatment of Non-Hodgkin's lymphomas with follicular growth pattern and advanced stage of disease remains controversial. Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated. The EORTC Lymphoma Cooperative Group has performed a randomized prospective trial comparing short duration low dose total body irradiation (TBI) vs combination chemotherapy (CHVmP) + consolidation radiotherapy. Ninety-three patients were entered; of 84 evaluable patients, 44 received TBI and 40 CHVmP. Complete remission (CR) rates were 36%--TBI and 55%--CHVmP, but overall response rates were identical, 76 versus 69%. No significant difference in freedom from progression or survival was observed. No unexpected toxicity was seen. Although numbers are small, we cannot conclude that aggressive combination chemo-radiotherapy resulted in a better survival. Our analysis confirms that there is a constant risk of relapse. Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population.

  13. Low dose dynamic myocardial CT perfusion using advanced iterative reconstruction

    Science.gov (United States)

    Eck, Brendan L.; Fahmi, Rachid; Fuqua, Christopher; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

    2015-03-01

    Dynamic myocardial CT perfusion (CTP) can provide quantitative functional information for the assessment of coronary artery disease. However, x-ray dose in dynamic CTP is high, typically from 10mSv to >20mSv. We compared the dose reduction potential of advanced iterative reconstruction, Iterative Model Reconstruction (IMR, Philips Healthcare, Cleveland, Ohio) to hybrid iterative reconstruction (iDose4) and filtered back projection (FBP). Dynamic CTP scans were obtained using a porcine model with balloon-induced ischemia in the left anterior descending coronary artery to prescribed fractional flow reserve values. High dose dynamic CTP scans were acquired at 100kVp/100mAs with effective dose of 23mSv. Low dose scans at 75mAs, 50mAs, and 25mAs were simulated by adding x-ray quantum noise and detector electronic noise to the projection space data. Images were reconstructed with FBP, iDose4, and IMR at each dose level. Image quality in static CTP images was assessed by SNR and CNR. Blood flow was obtained using a dynamic CTP analysis pipeline and blood flow image quality was assessed using flow-SNR and flow-CNR. IMR showed highest static image quality according to SNR and CNR. Blood flow in FBP was increasingly over-estimated at reduced dose. Flow was more consistent for iDose4 from 100mAs to 50mAs, but was over-estimated at 25mAs. IMR was most consistent from 100mAs to 25mAs. Static images and flow maps for 100mAs FBP, 50mAs iDose4, and 25mAs IMR showed comparable, clear ischemia, CNR, and flow-CNR values. These results suggest that IMR can enable dynamic CTP at significantly reduced dose, at 5.8mSv or 25% of the comparable 23mSv FBP protocol.

  14. Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma

    OpenAIRE

    Gay, Francesca; Rajkumar, S. Vincent; Coleman, Morton; Kumar, Shaji; Mark, Tomer; Dispenzieri, Angela; Pearse, Roger; Gertz, Morie A.; Leonard, John; Lacy, Martha Q.; Cheng-Kiang, Selina; Roy, Vivek; Jayabalan, David S.; Lust, John A.; Witzig, Thomas E.

    2010-01-01

    The objective of this case–matched study was to compare the efficacy and the toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low-dose dexamethasone (BiRd) vs lenalidomide/low-dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital–Cornell Medical Center were retrospectively compared to an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blin...

  15. Mitochondrial-Derived Oxidants and Cellular Responses to Low Dose/Low LET Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Spitz, Douglas R.

    2009-11-09

    that could be mitigated by over expression of the H2O2 metabolizing enzyme, catalase, and/or the mitochondrial form of superoxide dismutase (MnSOD). Furthermore, using radiation-induced genomically unstable cells, it was shown that steady-state levels of H2O2 were significantly elevated for many cell generations following exposure, catalase suppressed the radiation-induced mutator phenotype when added long after radiation exposure, unstable clones showed evidence of mitochondrial dysfunction some of which was characterized by improper assembly of SDH subunits (particularly subunit B), and chemical inhibitors of SDH activity could decrease steady-state levels of H2O2 as well as mutation frequency. These results support the hypotheses that 1) SDH mutations could contribute to transformation by inducing genomic instability and a mutator phenotype via increasing steady-state levels of ROS; 2) metabolic sources of O2•- and H2O2 play a significant role in low dose radiation induced injury and genomic instability; and 3) increased mutation rates in irradiated mammal cells can be suppressed by scavengers of H2O2 (particularly catalase) long after radiation exposure. Overall the results obtained during this period of support provide clear evidence in support of the hypothesis that abnormal oxidative metabolism in mitochondria that result in increases in steady-sate levels of H2O2 and other ROS are capable of significantly contributing to radiation-induced mutator phenotypes in mammalian cells.

  16. Low dose irradiation creep of pure nickel. [17 or 15 MeV deuterons

    Energy Technology Data Exchange (ETDEWEB)

    Henager, C.H. Jr.

    1984-10-01

    A detailed climb-controlled glide model of low dose irradiation creep has been developed to rationalize irradiation creep data of pure nickel irradiated in a light ion irradiation creep apparatus. Experimental irradiation creep data were obtained to study the effects of initial microstructure and stress on low dose irradiation creep in pure nickel. Pure nickel specimens (99.992% Ni), with three different microstructures, were irradiated with 17 or 15 MeV deuterons at 473 K and stresses ranging from 0.35 to 0.9 of the unirradiated yield stress. Transmission electron microscopy revealed that the microstructure following irradiation to 0.05 dpa consisted of a high density of small dislocation loops, some small voids and network dislocations. The creep model predicted creep rates proportional to the mobile dislocation density and a comparison of experimental irradiation creep rates as a function of homologous stress revealed a dependence on initial microstructure of the magnitude predicted by the measured dislocation densities. The three microstructures that were irradiated consisted of 85% and 25% cold-worked Ni specimens and well-annealed Ni specimens. A weak stress dependence of irradiation creep was observed in 85% cold-worked Ni in agreement with experimental determinations of the stress dependence of irradiation creep by others. The weak stress dependence was shown to be a consequence of the stress independence of the dislocation climb velocity and the weak stress dependence of the barrier removal process. The irradiation creep rate was observed to be proportional to the applied stress. This linear stress dependence was suggested to be due to the stress dependence of the mobile dislocation density. 101 references, 27 figures, 11 tables.

  17. Revisiting Low-Dose Total Skin Electron Beam Therapy in Mycosis Fungoides

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Cameron, E-mail: cameronh@stanford.edu [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Young, James; Navi, Daniel [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Riaz, Nadeem [Department of Radiation Oncology, Stanford Cancer Center, Stanford, California (United States); Lingala, Bharathi; Kim, Youn [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Hoppe, Richard [Department of Radiation Oncology, Stanford Cancer Center, Stanford, California (United States)

    2011-11-15

    Purpose: Total skin electron beam therapy (TSEBT) is a highly effective treatment for mycosis fungoides (MF). The standard course consists of 30 to 36 Gy delivered over an 8- to 10-week period. This regimen is time intensive and associated with significant treatment-related toxicities including erythema, desquamation, anhydrosis, alopecia, and xerosis. The aim of this study was to identify a lower dose alternative while retaining a favorable efficacy profile. Methods and Materials: One hundred two MF patients were identified who had been treated with an initial course of low-dose TSEBT (5-<30 Gy) between 1958 and 1995. Patients had a T stage classification of T2 (generalized patch/plaque, n = 51), T3 (tumor, n = 29), and T4 (erythrodermic, n = 22). Those with extracutaneous disease were excluded. Results: Overall response (OR) rates (>50% improvement) were 90% among patients with T2 to T4 disease receiving 5 to <10 Gy (n = 19). In comparison, OR rates between the 10 to <20 Gy and 20 to <30 Gy subgroups were 98% and 97%, respectively. There was no significant difference in median progression free survival (PFS) in T2 and T3 patients when stratified by dose group, and PFS in each was comparable to that of the standard dose. Conclusions: OR rates associated with low-dose TSEBT in the ranges of 10 to <20 Gy and 20 to <30 Gy are comparable to that of the standard dose ({>=} 30 Gy). Efficacy measures including OS, PFS, and RFS are also favorable. Given that the efficacy profile is similar between 10 and <20 Gy and 20 and <30 Gy, the utility of TSEBT within the lower dose range of 10 to <20 Gy merits further investigation, especially in the context of combined modality treatment.

  18. Dosimetric effect by the low-dose threshold levels in gamma analysis on VMAT QA

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ji Hye; Kim, Min Joo; Park, So Hyun; Lee, Seu Ran; Lee, Min Young; Suh, Tae Suk [Dept. of Biomedical Engineering and Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Lee, Dong Soo [Dept. of Radiation Oncology, Uijeongbu St. Mary' s Hospital, Uijeongbu (Korea, Republic of)

    2015-10-15

    Based on a survey by Nelms and Simon, more than 70% of institutions use a low-dose threshold between 0% and 10% for gamma analysis. However, there are no clinical data to quantitatively demonstrate the impact of the low-dose threshold on the gamma index. Therefore, we performed a gamma analysis with low-dose thresholds of 0%, 5%, 10%, and 15% according to both global and local normalization and different acceptance criteria: 3%/3 mm, 2%/2 mm, and 1%/1 mm. Applying low-dose threshold in the global normalization does not have critical effect to judge patient-specific QA results.

  19. A High-Fat Diet Containing Lard Accelerates Prostate Cancer Progression and Reduces Survival Rate in Mice: Possible Contribution of Adipose Tissue-Derived Cytokines

    Directory of Open Access Journals (Sweden)

    Han Jin Cho

    2015-04-01

    Full Text Available To examine the effects of high-fat diet (HFD containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.

  20. Differential Response and Priming Dose Effect on the Proteome of Human Fibroblast and Stem Cells Induced by Exposure to Low Doses of Ionizing Radiation.

    Science.gov (United States)

    Hauptmann, Monika; Haghdoost, Siamak; Gomolka, Maria; Sarioglu, Hakan; Ueffing, Marius; Dietz, Anne; Kulka, Ulrike; Unger, Kristian; Babini, Gabriele; Harms-Ringdahl, Mats; Ottolenghi, Andrea; Hornhardt, Sabine

    2016-03-01

    It has been suggested that a mechanistic understanding of the cellular responses to low dose and dose rate may be valuable in reducing some of the uncertainties involved in current risk estimates for cancer- and non-cancer-related radiation effects that are inherited in the linear no-threshold hypothesis. In this study, the effects of low-dose radiation on the proteome in both human fibroblasts and stem cells were investigated. Particular emphasis was placed on examining: 1. the dose-response relationships for the differential expression of proteins in the low-dose range (40-140 mGy) of low-linear energy transfer (LET) radiation; and 2. the effect on differential expression of proteins of a priming dose given prior to a challenge dose (adaptive response effects). These studies were performed on cultured human fibroblasts (VH10) and human adipose-derived stem cells (ADSC). The results from the VH10 cell experiments demonstrated that low-doses of low-LET radiation induced unique patterns of differentially expressed proteins for each dose investigated. In addition, a low priming radiation dose significantly changed the protein expression induced by the subsequent challenge exposure. In the ADSC the number of differentially expressed proteins was markedly less compared to VH10 cells, indicating that ADSC differ in their intrinsic response to low doses of radiation. The proteomic results are further discussed in terms of possible pathways influenced by low-dose irradiation.

  1. Effect of low dose gamma irradiation on plant and grain nutrition of wheat

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Bhupinder, E-mail: bhupindersinghiari@yahoo.co [Nuclear Research Laboratory, Indian Agricultural Research Institute, New Delhi 110 012 (India); Datta, Partha Sarathi [Nuclear Research Laboratory, Indian Agricultural Research Institute, New Delhi 110 012 (India)

    2010-08-15

    We recently reported the use of low dose gamma irradiation to improve plant vigor, grain development and yield attributes of wheat (). Further, we report here the results of a field experiment conducted to assess the effect of gamma irradiation at 0, 0.01, 0.03, 0.05, 0.07 and 0.1 kGy on flag leaf area, stomatal conductance, transpiration and photosynthetic rate and plant and grain nutritional quality. Gamma irradiation improved plant nutrition but did not improve the nutritional quality of grains particularly relating to micronutrients. Grain carotene, a precursor for vitamin A, was higher in irradiated grains. Low grain micronutrients seem to be caused by a limitation in the source to sink nutrient translocation rather than in the nutrient uptake capacity of the plant root.

  2. [Rapid dicentric assay of human blood lymphocytes after exposure to low doses of ionizing radiation].

    Science.gov (United States)

    Repin, M V; Repina, L A

    2011-01-01

    The probability of losses of different chromosome aberrations during the dicentric chromosome assay of metaphase cells with incomplete sets of chromosome centromeres was estimated using a mathematical model for low doses of ionizing radiation. A dicentric assay of human blood lymphocytes without determination of the total amount of chromosome centromeres in cells without chromosome aberrations (rapid dicentric assay) has been proposed. The rapid dicentric analysis allows to register chromosome aberrations in full compliance with the conventional classification. The experimental data have shown no statistically significant difference between the frequencies of dicentric chromosomes detected by rapid and classical dicentric chromosome assays of human lymphocytes exposed to 0.5 Gy of 60Co gamma-rays. The rate of the rapid dicentric assay was almost twice as high as that of the classical dicentric assay.

  3. Revealing low-dose radiation damage using single-crystal spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Owen, Robin L., E-mail: robin.owen@diamond.ac.uk [Diamond Light Source Ltd, Diamond House, Harwell Science and Innovation Campus, Didcot, OX11 0DE (United Kingdom); Yorke, Briony A.; Gowdy, James A.; Pearson, Arwen R. [University of Leeds, Leeds (United Kingdom)

    2011-05-01

    Data on the rapid reduction of haem proteins in the X-ray beam at synchrotron sources are presented. The use of single-crystal spectroscopy to detect these changes and their implication for diffraction data collection from oxidized species is also discussed. The structural information and functional insight obtained from X-ray crystallography can be enhanced by the use of complementary spectroscopies. Here the information that can be obtained from spectroscopic methods commonly used in conjunction with X-ray crystallography and best-practice single-crystal UV-Vis absorption data collection are briefly reviewed. Using data collected with the in situ system at the Swiss Light Source, the time and dose scales of low-dose X-ray-induced radiation damage and solvated electron generation in metalloproteins at 100 K are investigated. The effect of dose rate on these scales is also discussed.

  4. Single-ion microbeam as a tool for low-dose radiation effects investigations

    Energy Technology Data Exchange (ETDEWEB)

    Gerardi, Silvia [INFN - Laboratori Nazionali di Legnaro, Legnaro, Padova (Italy); Galeazzi, Giuseppe [INFN - Laboratori Nazionali di Legnaro, Legnaro, Padova (Italy); Cherubini, Roberto [INFN - Laboratori Nazionali di Legnaro, Legnaro, Padova (Italy)

    2006-05-15

    Practical assessment of human radiation exposure risk deserves particular attention especially for low doses (and low dose rates), which concern environmental and occupational exposure. At these dose levels ionizing radiation exposures involve mainly isolated charged particle tracks, which strike individual cells at time intervals averaging from weeks to several years apart. Accelerator-based microbeam irradiation technique offers a unique tool to mimic such an exposure, allowing irradiating single cells individually with micrometer precision and with a preset number of charged particles down to one particle per cell. A horizontal single-ion microbeam facility for single-cell irradiations has been designed and set up at the INFN-LNL 7MV CN Van de Graaff accelerator. The light ion beam is collimated in air down to a section of 2-3{mu}m in diameter by means of appropriate pinholes. Semi-automatic cell visualization and automatic cell positioning and revisiting system, based on an inverted phase contrast optical microscope and on X-Y translation stages with 0.1{mu}m positioning precision, has been developed. An in-house-written software allows to control remotely the irradiation protocol. As a distinctive feature of the facility, cell recognition is performed without using fluorescent staining and UV light. Particle detection in air, behind the biological sample, is based on a silicon detector while in-air beam profile and precise hit position measurements are accomplished by a custom-made cooled-CCD camera and Solid State Nuclear Track detectors, respectively. A particle counting rate of less than 1 ion/sec can be reached.

  5. Assessment of a low dose of IV midazolam used orally for conscious sedation in pediatric dentistry

    Directory of Open Access Journals (Sweden)

    M Mortazavi

    2009-08-01

    Full Text Available Background and the purpose of the study: Midazolam is preferably used in pediatric dentistry for quick onset of action and recovery. The aim of this prospective, observer-blind and placebo-controlled study was to assess the efficacy of a low dose of oral midazolam in modification of  the behavior of young pediatric dental patients. Methods: Forty children aged 3 to 5 years who displayed ratings 1 or 2 on the Frankl Scale and  were healthy by the American Society of Anesthesiologists-I status were randomly divided into two experimental and control groups of 20 each. All children required pulpotomy and restoration of D and E teeth and received either 0.25mg/kg of a 15mg/3ml IV midazolam mixed in black cherry syrup or the syrup alone. Subjects were continuously observed and monitored with pulse oximetry. Houpt's Behavioral Ratings was used to determine the overall behavior, the degree of crying and movement during treatment. Mann-Whitney U test was used for statistical analysis. Results and major conclusion: Patients who received 0.25mg/kg of the prepared oral midazolam significantly behaved better during treatment than the placebo controls (P<0.05. In comparison with the placebo group, reduced movement and crying were observed in the midazolam group (P<0.05. No adverse effects were observed and treatments were completed successfully. A low dose of 0.25mg/kg of a 15mg/3ml IV midazolam mixed in black cherry syrup was found to be effective in conscious sedation of young pediatric dental patients.

  6. Axillary block duration and related hemodynamic changes: high versus low dose Adrenaline addition to Lidocaine

    Directory of Open Access Journals (Sweden)

    Shariat Moharari R

    2009-03-01

    Full Text Available "nBackground: Axillary block is used for inducing anesthesia in outpatient hand and forearm surgeries. Few researches have studied hemodynamic and blockade effects of low doses of Epinephrine. The aim of the present study was to compare the duration of analgesia and hemodynamic changes following the injection of high/low epinephrine doses in such surgeries. "nMethods: The present randomized clinical trial study was conducted on healthy individuals (ASA I-II who were candidates for hand and forearm surgeries. The patients were randomly divided into three groups. The first two groups were allocated to receive lidocaine with low (0.6µg/cc and high (5µg/cc doses of epinephrine whereas lidocaine plus normal saline was injected in the third group. The hemodynamic changes (Mean arterial blood pressure and heart rate and the occurance of any side-effects along with the duration of analgesia and motor block were recorded. "nResults: From among the total of 75 patients, 15 cases were excluded due to incomplete blockade or failure needing general anesthesia. The duration of analgesia and the motor block were longer in the high dose epinephrine group, the difference, however, was not statistically significant. Heart rate changes within the groups was significant in the 4th-7th and 10th minutes. Mean arterial blood pressure changes was only significant in the 4th minute, within the groups. "nConclusions: Administering low doses of epinephrine plus lidocaine as a local anesthetic not only provides acceptable analgesia compared to higher doses of the medication, but also is associated with fewer side effects.

  7. MRI-guided biopsy of the prostate: correlation between the cancer detection rate and the number of previous negative TRUS biopsies.

    Science.gov (United States)

    Durmuş, Tahir; Reichelt, Uta; Huppertz, Alexander; Hamm, Bernd; Beyersdorff, Dirk; Franiel, Tobias

    2013-01-01

    We aimed to investigate prostate cancer detection rate of magnetic resonance imaging (MRI)-guided biopsy and to elucidate possible relations to the number of prior negative transrectal ultrasonography (TRUS)-guided biopsies. Eighty-seven consecutive patients (mean age, 65.0 years; mean prostate-specific antigen, 13.3 ng/mL) with at least one prior negative TRUS-guided biopsy and persistent suspicion of prostate cancer were included in this study. All patients underwent MRI-guided biopsy after a diagnostic multiparametric MRI examination at 1.5 Tesla. Specimens were immediately fixated and subsequently evaluated by an experienced uropathologist. Prostate cancer detection rates were calculated. Prostate cancer-positive and -negative cores were compared. Correlation between number of prior biopsies and presence of prostate cancer was evaluated. Cancer detection rates for patients with one (n=24), two (n=25), three (n=18), and four or more (n=20) negative TRUS-guided biopsies were 29.2%, 40.0%, 66.7%, and 35.0%, respectively (P = 0.087). The median number of removed cores per patient was 3 (range, 1-8) without a significant difference between patients with and without cancer (P = 0.48). 
Thirty of 36 cancer patients were at intermediate or high risk according to the D´Amico clinical risk score. Eleven of 15 high risk cancers were localized in the transition zone (P = 0.002). This study demonstrates high cancer detection rates of MRI-guided biopsy independent of the number of previous TRUS-guided biopsies and the number of taken prostate cores. MRI-guided biopsy therefore represents a less invasive and effective diagnostic tool for patients with prostate cancer suspicion and previous negative TRUS-guided biopsies.

  8. Radiation therapy for localized prostate cancer. For high-dose rate conformal brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kinugawa, Keigo; Jo, Yoshimasa; Morioka, Masaaki; Tanaka, Hiroyoshi; Hiratsuka, Junichi; Imajo, Yoshinari [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    1999-05-01

    Sixteen patients with localized prostate cancer were referred to our clinic for radiation therapy in combination with HDR brachytherapy using Ir-192 pellets between October 1997 and August 1998. The patients were given external beam radiation of 45 Gy to the whole pelvis in combination with an interstitial HDR brachytherapy implant of 3 fractions each delivering 5.5 Gy during two days. Using an implanting device especially designed for HDR, 10-18 applicator needles (17 gauge) were implanted into the prostate using transrectal ultrasound (TRUS) with perineal template guidance under spinal anesthesia. Pathological evaluation was performed at 6 months after treatment. This technique of external beam radiation combined with HDR brachytherapy was well tolerated. Serum prostatic antigen (PSA) levels became normalized in 87.5% of the patients (14 out of 16) within 1-14 months (median 2 months) after the irradiation. No significant intraoperative or perioperative complications occurred, however one patient (6.25%) experienced Grade 3 hematuria. Most of the early complications were otherwise Grade 1 or 2. From prospectively planned prostatic rebiopsies performed at 6 months, we can observe the radiation effects in the pathological findings such as fibrosis, basal cell hyperplasia, bizarre cells and intraductal calcifications. (K.H.)

  9. Low-dose modified-release prednisone in axial spondyloarthritis: 3-month efficacy and tolerability

    Directory of Open Access Journals (Sweden)

    Bandinelli F

    2016-11-01

    Full Text Available Francesca Bandinelli,1 Francesco Scazzariello,1 Emanuela Pimenta da Fonseca,2 Mittermayer Barreto Santiago,2 Claudio Marcassa,3 Francesca Nacci,1 Marco Matucci Cerinic1 1Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 2Service of Rheumatology, Hospital Santa Isabel, Escola de Medicina e Saúde Pública, Bahia, Brazil; 3Maugeri Clinical and Scientific Institutes, IRCCS, Veruno, Novara, Italy Background: Oral glucocorticoids (GCs have been shown to be effective in reducing the inflammatory symptoms of rheumatoid arthritis, but their use is not supported by evidence in spondyloarthritis (SpA. Modified-release (MR oral prednisone taken at bedtime has been shown to be more effective than immediate-release prednisone taken in the morning. The efficacy of low-dose MR prednisolone in patients with SpA is unknown. Patients and methods: This single-center cohort study retrospectively assessed the effectiveness and safety of 12-week low-dose MR prednisone (5 mg daily, bedtime administration in GC-naïve adult patients with symptomatic axial SpA. A 50% improvement of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI or a final BASDAI score of <4 according to disease activity at baseline was chosen as the primary outcome parameter after MR prednisone. Results: Fifty-seven patients were evaluated; of them, 41 had an active disease (BASDAI score of ≥4 at baseline. MR prednisone significantly reduced BASDAI (from 5.5±2.6 to 3.0±2.8, P<0.001 as well as inflammatory symptoms, pain, fatigue and morning stiffness. The overall response rate after MR prednisone was 52.6% (53.7% in patients with active SpA and 50.0% in patients with low-active disease; nonsignificant. At multivariable analysis, none of the considered clinical findings independently predicted the response to MR prednisone in subjects with active SpA. Overall, seven patients (11.8% had nonserious adverse drug reactions after MR prednisone

  10. TH-C-12A-07: Implementation of a Pulsed Low Dose Date Radiotherapy (PLRT) Protocol for Recurrent Cancers Using Advanced Beam Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Ma, C; Lin, M; Chen, L; Price, R [Fox Chase Cancer Center, Philadelphia, PA (United States); Li, J; Kang, S; Wang, P; Lang, J [Sichuan Provincial Cancer Hospital, Chengdu (China)

    2014-06-15

    Purpose: Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT. Methods: Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategies were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H and N, breast, lung, pancreas and prostate patients and compared. Results: All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Conclusion: IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.

  11. A COMPARISON OF PROGRESSION OF CHRONIC RENAL FAILURE: LOW DOSE VS STANDARD DOSE KETOACIDS

    Directory of Open Access Journals (Sweden)

    Jin-Bor Chen

    2012-06-01

    Conclusions: The 6-month observation study showed low dose ketoacid analogues combined with LPD had a beneficial effect to slow down renal function deterioration in CKD stage 4,5. However, the slope of 1/Cr levels in low dose ketoacid analogues was less than that in standard dose ketoacid analogues.

  12. [Risk and prevention of gastrointestinal complications due to low-dose aspirin and other antiplatelet agents].

    Science.gov (United States)

    Bretagne, Jean-François

    2008-09-15

    Upper and lower gastrointestinal (GI) haemorrhages are the main complications associated with low-dose aspirin or anti-thrombotic drugs. In France, low-dose aspirin or anti-thrombotic agents use has been found in 30% of upper GI and 40% of lower GI bleeding episodes. Main causes of GI bleeding with low-dose aspirin are gastroduodenal peptic ulcer and colonic diverticulosis. Recent cohort studies have shown that the relative risk of GI bleeding with low-dose aspirin was comprised between 2 and 4 and the absolute risk comprised between 1 per 100 and 1 per 1000 aspirin users per year. Main risk factors for upper GI bleeding with low-dose aspirin are concomitant antiplatelet agents, anticoagulants, non steroidal anti-inflammatory drugs or steroids use, and recent history of complicated or non-complicated gastroduodenal ulcer. Helicobacter pylori infection increases the risk for upper GI bleeding with low-dose aspirin, but infection should be searched and treated only in patients with peptic ulcer. Despite eradication of H. pylori in the latter patients, gastroprotection with PPI is strongly recommended. In patients presenting with peptic ulcer bleeding with low-dose aspirin, aspirin should be continued in association with PPI rather than replaced with clopidogrel. Discontinuation of low-dose aspirin which exposes to increased cardiovascular complications and mortality should be avoided, even in cases of peptic ulcer bleeding.

  13. Coronary artery calcification scoring in low-dose ungated CT screening for lung cancer: interscan agreement.

    NARCIS (Netherlands)

    Jacobs, P.C.; Isgum, I.; Gondrie, M.J.; Mali, W.P.Th.; Ginneken, B. van; Prokop, M.; Graaf, Y. van der

    2010-01-01

    OBJECTIVE: In previous studies detection of coronary artery calcification (CAC) with low-dose ungated MDCT performed for lung cancer screening has been compared with detection with cardiac CT. We evaluated the interscan agreement of CAC scores from two consecutive low-dose ungated MDCT examinations.

  14. Coronary Artery Calcification Scoring in Low-Dose Ungated CT Screening for Lung Cancer : Interscan Agreement

    NARCIS (Netherlands)

    Jacobs, Peter C. A.; Isgum, Ivana; Gondrie, Martijn J. A.; Mali, Willem P. Th. M.; van Ginneken, Bram; Prokop, Mathias; van der Graaf, Yolanda

    2010-01-01

    OBJECTIVE. In previous studies detection of coronary artery calcification (CAC) with low-dose ungated MDCT performed for lung cancer screening has been compared with detection with cardiac CT. We evaluated the interscan agreement of CAC scores from two consecutive low-dose ungated MDCT examinations.

  15. Response of patients in mixed state of anxiety and depression to low dose sulpiride.

    Science.gov (United States)

    Kato, K

    1993-02-01

    Two cases with mixed symptoms of anxiety and depression are described. In both cases, a low dose of sulpiride was effective, improving patients anxious and depressive symptoms without severe side effects. These findings suggest that a low dose sulpiride treatment can be useful in the treatment of anxious and depressive patients.

  16. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chuan-Yaun

    2009-01-27

    “Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  17. Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease

    Energy Technology Data Exchange (ETDEWEB)

    Littley, M.D.; Shalet, S.M.; Beardwell, C.G.; Ahmed, S.R.; Sutton, M.L. (Christie Hospital, Manchester (UK))

    1990-10-01

    Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. In this series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy. (author).

  18. James V. Neel and Yuri E. Dubrova: Cold War debates and the genetic effects of low-dose radiation.

    Science.gov (United States)

    Goldstein, Donna M; Stawkowski, Magdalena E

    2015-01-01

    This article traces disagreements about the genetic effects of low-dose radiation exposure as waged by James Neel (1915-2000), a central figure in radiation studies of Japanese populations after World War II, and Yuri Dubrova (1955-), who analyzed the 1986 Chernobyl nuclear power plant accident. In a 1996 article in Nature, Dubrova reported a statistically significant increase in the minisatellite (junk) DNA mutation rate in the children of parents who received a high dose of radiation from the Chernobyl accident, contradicting studies that found no significant inherited genetic effects among offspring of Japanese A-bomb survivors. Neel's subsequent defense of his large-scale longitudinal studies of the genetic effects of ionizing radiation consolidated current scientific understandings of low-dose ionizing radiation. The article seeks to explain how the Hiroshima/Nagasaki data remain hegemonic in radiation studies, contextualizing the debate with attention to the perceived inferiority of Soviet genetic science during the Cold War.

  19. Ultra-low-dose recombinant human bone morphogenetic protein-2 for 3-level anterior cervical diskectomy and fusion.

    Science.gov (United States)

    Pourtaheri, Sina; Hwang, Ki; Faloon, Michael; Issa, Kimona; Mease, Samuel J; Mangels, Daniel; Sinha, Kumar; Emami, Arash

    2015-04-01

    This study evaluated the safety of 3-level anterior cervical diskectomy and fusion (ACDF) with ultra-low-dose recombinant bone morphogenetic protein-2 (rhBMP-2). Thirty-seven consecutive patients with cervical spondylotic myelopathy who were treated with 3-level ACDF and rhBMP-2 were evaluated. Complications such as airway or cervical swelling or hematoma were not observed. The rate of dysphagia was no different at 1, 2, and 6 months postoperatively compared with reports in the literature without rhBMP-2. There were significant improvements in VAS neck/arm pain, Oswestry Neck Disability Index, and cervical lordosis. The use of ultra-low-dose rhBMP-2 for 3-level ACDF may be efficacious for surgically addressing 3-level spondylotic myelopathy.

  20. Effects of low dose gamma irradiation on the germination and physiological activity of old red pepper (Capsicum annuum L.) seed

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Sung; Back, Myung Hwa; Lee, Hae Youn; Lee, Young Keun [KAERI, Daejeon (Korea, Republic of)

    2001-12-15

    To observe the stimulating effects of low dose gamma radiation on the germination and physiological activity of germinating seeds of old red pepper (Capsicum annuum L. cv, Jokwang and cv. Hongkwang), seeds were irradiated at the dose of 2{approx}50 Gy. The germination rate of irradiation group was higher than that of the control. Especially it was highest at the early stage of induction. The germination rate at 7 days after sowing in Jokwang and Hongkwang cultivar was high as 74% and 11% at 4 Gy and 8 Gy irradiation group, respectively. The seedling height of Jokwang cultivar was noticeably high at 4 Gy irradiation group and that of Hongkwang cultivar at 8 Gy Irradiation group. The protein contents of seedlings from seeds irradiated with low dose gamma radiation of Jokwang cultivar increased at the late stage of induction and that of Hongkwang cultivar at the early stage of induction. Catalase and peroxidase activities of seedlings from seeds irradiated with low dose gamma radiation of Jokwang cultivar increased at 4 Gy irradiation group and that of Hongkwang cultivar at 8 Gy irradiation group.

  1. Evaluation of low-dose dual energy computed tomography for in vivo assessment of renal/ureteric calculus composition.

    Science.gov (United States)

    Mahalingam, Harshavardhan; Lal, Anupam; Mandal, Arup K; Singh, Shrawan Kumar; Bhattacharyya, Shalmoli; Khandelwal, Niranjan

    2015-08-01

    This study aimed to assess the accuracy of low-dose dual-energy computed tomography (DECT) in predicting the composition of urinary calculi. A total of 52 patients with urinary calculi were scanned with a 128-slice dual-source DECT scanner by use of a low-dose protocol. Dual-energy (DE) ratio, weighted average Hounsfield unit (HU) of calculi, radiation dose, and image noise levels were recorded. Two radiologists independently rated study quality. Stone composition was assessed after extraction by Fourier transform infrared spectroscopy (FTIRS). Analysis of variance was used to determine if the differences in HU values and DE ratios between the various calculus groups were significant. Threshold cutoff values to classify the calculi into separate groups were identified by receiver operating characteristic curve analysis. A total of 137 calculi were detected. FTIRS analysis differentiated the calculi into five groups: uric acid (n=17), struvite (n=3), calcium oxalate monohydrate and dihydrate (COM-COD, n=84), calcium oxalate monohydrate (COM, n=28), and carbonate apatite (n=5). The HU value could differentiate only uric acid calculi from calcified calculi (p80% sensitivity and specificity to differentiate them. The DE ratio could not differentiate COM from COM-COD calculi. No study was rated poor in quality by either of the observers. The mean radiation dose was 1.8 mSv. Low-dose DECT accurately predicts urinary calculus composition in vivo while simultaneously reducing radiation exposure without compromising study quality.

  2. Efficacy and safety of low-dose lenalidomide plus dexamethasone in patients with relapsed or refractory POEMS syndrome.

    Science.gov (United States)

    Cai, Qian-Qian; Wang, Chen; Cao, Xin-Xin; Cai, Hao; Zhou, Dao-Bin; Li, Jian

    2015-10-01

    Although autologous stem cell transplantation or melphalan-based chemotherapy has significantly improved the prognosis of POEMS syndrome, a few patients will relapse or be refractory to primary therapy, and there is a lack of studies regarding these patients. In this study, we used low-dose lenalidomide (10 mg daily) and dexamethasone (40 mg, once weekly) to treat twelve patients with relapsed (n = 8) or refractory (n = 4) POEMS syndrome. After a median follow-up time of 20 months, the overall hematologic response rate was 77% with 44% having a complete response. Eight (67%) patients had neurological response, and the median overall neuropathy limitation scale score was reduced from 3 (range, 1-9) to 2 (range, 0-6). Serum vascular endothelial growth factor response rate was 91% and 46% of patients had normal serum VEGF levels. One patient had progression of the disease 3 months after the end of treatment and subsequently died from the disease. Therefore, the estimated 2 year overall survival and progression-free survival were 92%. The low-dose lenalidomide and dexamethasone regimen was well tolerated, with no treatment-related death or any grade 3 or 4 toxicity. In conclusion, low-dose lenalidomide plus dexamethasone therapy is an effective and safe regimen for patients with relapsed or refractory POEMS syndrome.

  3. Korean Society of Thoracic Radiology Guideline for Lung Cancer Screening with Low-Dose CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Ju [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Jin Hwan [Dept. of Radiology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon (Korea, Republic of); Kim, Yoon Kyung [Dept. of Radiology, Gachon University Gil Medical Center, Incheon (Korea, Republic of); Park, Chang Min [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Jeong, Yeon Joo [Dept. of Radiology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan (Korea, Republic of)

    2012-09-15

    The National Lung Screening Trial (NLST), a nation-wide randomized controlled trial involving more than 50,000 current and former heavy smokers ages 55 to 74, compared the effects of two screening procedures (low-dose helical CT and standard chest radiography) on lung cancer mortality and found 20 percent fewer lung cancer deaths among trial participants screened with low-dose CT. Korean Society of Thoracic Radiology (KSTR) planned to establish an effective guideline for lung cancer screening with low-dose CT to improve health of Korean people and to reduce harms from misuse of lung cancer screening with low-dose CT. KSTR guideline for lung cancer screening with low-dose CT established based on objective medical evidences obtained by NLST.

  4. An exploratory study of responses to low-dose lithium in African Americans and Hispanics.

    Science.gov (United States)

    Gonzalez Arnold, Jodi; Salcedo, Stephanie; Ketter, Terrence A; Calabrese, Joseph R; Rabideau, Dustin J; Nierenberg, Andrew A; Bazan, Melissa; Leon, Andrew C; Friedman, Edward S; Iosifescu, Dan; Sylvia, Louisa G; Ostacher, Michael; Thase, Michael; Reilly-Harrington, Noreen A; Bowden, Charles L

    2015-06-01

    Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder. This exploratory study examines differences in lithium response and treatment outcomes in Hispanics, African Americans, and non-Hispanic whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study (LiTMUS). LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment (OPT; personalized, evidence-based pharmacotherapy) vs. OPT alone in outpatients with bipolar disorder. Of 283 participants, 47 African Americans, 39 Hispanics, and 175 non-Hispanic whites were examined. We predicted minority groups would have more negative medication attitudes and higher attrition rates, but better clinical outcomes. African Americans in the lithium group improved more on depression and life functioning compared to whites over the 6 month study. African Americans in the OPT only group had marginal improvement on depression symptoms. For Hispanics, satisfaction with life did not significantly improve in the OPT only group, in contrast to whites and African Americans who improved over time on all measures. Attitudes toward medications did not differ across ethnic/racial groups. African Americans show some greater improvements with lithium than non-Hispanic whites, and Hispanics showed more consistent improvements in the lithium group. The impact of low-dose lithium should be studied in a larger sample as there may be particular benefit for African Americans and Hispanics. Given that the control group (regardless of ethnicity/race) had significant improvements, optimized treatment may be beneficial for any ethnic group. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Serum metabonomics of rats irradiated by low-dose γ-rays

    Directory of Open Access Journals (Sweden)

    Ying HE

    2014-08-01

    Full Text Available Objective To explore the effect of low-dose γ-rays on the metabolites in rat serum. Methods Sixteen healthy male SD rats were randomly divided into control group and irradiated group (n=8. The rats in irradiated group were irradiated by 60Co γ-rays with a dose rate of 72mGy/h for 7 days (1 hour per day. At the 7th day after irradiation, blood samples were taken from abdominal aorta to obtain the serum. The metabolic fingerprints of serum were obtained from the two groups of rats, and 1H nuclear magnetic resonance (NMR spectroscopy, principal component analysis (PCA and orthogonal signal correction-partial least squares (OSC-PLS method were used for pattern recognition, and the difference in metabolite profile between two groups was identified by SIMCA-P software. Results The rat serum 1H NMR spectra revealed a significant difference between control group and irradiated group, the OSC-PLS plots of the serum samples presented marked clustering between two groups. Compared with the control group, the content of lipid, glucose, creatine, glycine/glucose, high density lipoprotein, low density lipoprotein, very low density lipoprotein/low density lipoprotein and unsaturated fatty acid increased, while the content of lactic acid, threonine/lipid, alanine, N-acetyl glycoprotein 1, N-acetyl glycoprotein 2, saturated fatty acid and phosphatidyl choline decreased in irradiated group. Conclusion Irradiation with low-dose γ-ray could induce changes in metabolites in rat serum, concerning mainly immune function, energy metabolism, carbohydrate metabolism and lipid metabolism. DOI: 10.11855/j.issn.0577-7402.2014.07.02

  6. Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Hisato Igarashi; Tetsuhide Ito; Ken Kawabe; Terumasa Hisano; Yoshiyuki Arita; Toyoma Kaku; Ryoichi Takayanagi

    2008-01-01

    AIM:To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly.METHODS:We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2.After that,maintenance systemic chemotherapy with gemcitabine,at a dose of 1000 mg/m2,was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed.RESULTS:Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled.Three of those patients could not continue with the therapy;one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy.The median survival was 15.0 mo and the overall 1-year survival rate was 60%,while the median progression-free survival was 8.0 too.The subgroup which showed the reduction of tumor development,more than 50% showed a tendency for a better prognosis;however,other parameters including age,gender and performance status did not correlate with survival.The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo,respectively.CONCLUSION:Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer;however,patients developing liver metastases had a worse prognosis.Another chemoradiotherapy strategy might be needed for those patients,such as administrating one or two cycles of chemotherapy initially,followed by chemoradiotherapy for the cases with no distant metastases.

  7. Comparison of conventional and low dose steroid in the treatment of PFAPA syndrome: preliminary study.

    Science.gov (United States)

    Yazgan, Hamza; Gültekin, Erhan; Yazıcılar, Osman; Sagun, Ömer Faruk; Uzun, Lokman

    2012-11-01

    Steroids have been widely used to relief symptoms in the patients with PFAPA syndrome. This study was constructed to show the effectiveness of low-dose steroid therapy in patients diagnosed with PFAPA syndrome. 41 patients (86 febrile attacks) who were diagnosed using the criteria suggested by Thomas et al. were involved in the study. The cases were classified into two groups and the selection of patients in groups was made randomly. Twenty patients received prednisolone at a dose of 2 mg/kg/day (first group: 40 attacks) and 21 patients received a dose of 0.5 mg/kg/day (second group: 46 attacks). The effectiveness of the treatment was especially determined by the time needed to reduce the fever and the effect on the duration between the two attacks. The patients were re-examined 24 hours later, after a steroid treatment. The patients who were in the first group received 2mg/kg/day dose of prednisolone and their fever was dramatically decreased in 6-8 hours (7.6 ± 0.9 hours). The second group received 0.5mg/kg/day dose and 19 of these patients' fever was decreased in 8-12 hours. Two patients whose temperature did not decrease, received another dose of prednisolone 24 hours after the first dose and their fever was reduced 12 hours after the second dose (11.3 ± 6.4 hours). A comparison of the rate of fever reduction and the interval between the attacks (Group I: 5.11 ± 1.01 week and Group II: 5.2 ± 1.13 week) in the two groups did not show any statistical significance (p=0.104). Low-dose steroid treatment is as effective as normal dose in PFAPA syndrome but there is need to study with a larger group. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Plants ecotoxicology. A case of low doses and multi pollutant exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' Kin, S.; Kim, J.; Evseeva, T.; Oudalova, A.; Dikarev, V. [Russian Institute of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2004-07-01

    In this report, results of long-term laboratory, 'green-house' and field experiments carried out on different species of wild and agricultural plants (spring barley, Scots pine, spider wort, bulb onion and others) to study toxic and genotoxic effects of low doses and concentrations of such common pollutants as acute and chronic {gamma}-radiation, heavy natural radionuclides, compounds of heavy and alkaline earth metals, pesticides are presented for the first time. Special attention is paid to eco-toxic effects of chronic low dose exposures, the dose-rate effect, synergistic and antagonistic effects of different factors' combined exposures and biological effects of incorporated radionuclides. The results of long-term field experiments in the 30-km Chernobyl NPP zone, in the vicinity of the facility for the processing and storage of radioactive wastes (Leningrad region), in the vicinity of the radium production industry storage cell (Komi Republic), at the site of an underground nuclear explosion (Perm region) are discussed. These findings suggest that the further evolution of investigations in this field would issue in the development of a theoretical bases and practical procedures for environmental protection against radioactivity, taking into account the new experimentally confirmed facts about the presence of such essentially important singularities of the biological effect of low ionizing radiation doses as the nonlinearity of a dose-effect relationship, radiation-induced genomic instability, phenomenon of radio-adaptation, increased probability of synergetic and antagonistic effects of the combined action of different nature factors. A development of a new concept of radiation protection for a human and biota should be based on the clear understanding of these effects and their contribution to the response of biological objects. (author)

  9. Heart region segmentation from low-dose CT scans: an anatomy based approach

    Science.gov (United States)

    Reeves, Anthony P.; Biancardi, Alberto M.; Yankelevitz, David F.; Cham, Matthew D.; Henschke, Claudia I.

    2012-02-01

    Cardiovascular disease is a leading cause of death in developed countries. The concurrent detection of heart diseases during low-dose whole-lung CT scans (LDCT), typically performed as part of a screening protocol, hinges on the accurate quantification of coronary calcification. The creation of fully automated methods is ideal as complete manual evaluation is imprecise, operator dependent, time consuming and thus costly. The technical challenges posed by LDCT scans in this context are mainly twofold. First, there is a high level image noise arising from the low radiation dose technique. Additionally, there is a variable amount of cardiac motion blurring due to the lack of electrocardiographic gating and the fact that heart rates differ between human subjects. As a consequence, the reliable segmentation of the heart, the first stage toward the implementation of morphologic heart abnormality detection, is also quite challenging. An automated computer method based on a sequential labeling of major organs and determination of anatomical landmarks has been evaluated on a public database of LDCT images. The novel algorithm builds from a robust segmentation of the bones and airways and embodies a stepwise refinement starting at the top of the lungs where image noise is at its lowest and where the carina provides a good calibration landmark. The segmentation is completed at the inferior wall of the heart where extensive image noise is accommodated. This method is based on the geometry of human anatomy and does not involve training through manual markings. Using visual inspection by an expert reader as a gold standard, the algorithm achieved successful heart and major vessel segmentation in 42 of 45 low-dose CT images. In the 3 remaining cases, the cardiac base was over segmented due to incorrect hemidiaphragm localization.

  10. An Exploratory Study of Responses to Low-Dose Lithium in African Americans and Hispanics

    Science.gov (United States)

    Arnold, Jodi Gonzalez; Salcedo, Stephanie; Ketter, Terrence A.; Calabrese, Joseph R.; Rabideau, Dustin J.; Nierenberg, Andrew A.; Bazan, Melissa; Leon, Andrew C.; Friedman, Edward S.; Iosifescu, Dan; Sylvia, Louisa G.; Ostacher, Michael; Thase, Michael; Reilly-Harrington, Noreen A.; Bowden, Charles L.

    2015-01-01

    Objectives Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder. This exploratory study examines differences in lithium response and treatment outcomes in Hispanics, African Americans, and non-Hispanic Whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study (LiTMUS). Methods LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment (OPT; personalized, evidence-based pharmacotherapy) versus OPT alone in outpatients with bipolar disorder. Of 283 participants, 47 African Americans, 39 Hispanics, and 175 non-Hispanic whites were examined. We predicted minority groups would have more negative medication attitudes and higher attrition rates, but better clinical outcomes. Results African Americans in the lithium group improved more on depression and life functioning compared to whites over the 6 month study. African Americans in the OPT only group had marginal improvement on depression symptoms. For Hispanics, satisfaction with life did not significantly improve in the OPT only group, in contrast to whites and African Americans who improved over time on all measures. Attitudes toward medications did not differ across ethnic/racial groups. Conclusions African Americans show some greater improvements with lithium than non-Hispanic whites, and Hispanics showed more consistent improvements in the lithium group. The impact of low-dose lithium should be studied in a larger sample as there may be particular benefit for African Americans and Hispanics. Given that the control group (regardless of ethnicity/race) had significant improvements, optimized treatment may be beneficial for any ethnic group. PMID:25827507

  11. Low-dose effect of ethanol on locomotor activity induced by activation of the mesolimbic system.

    Science.gov (United States)

    Milton, G V; Randall, P K; Erickson, C K

    1995-06-01

    Four experiments were designed to study the ability of 0.5 g/kg ethanol (EtOH) intraperitoneally to modify locomotor activity induced by drugs that interact with different sites in the mesolimbic system (MLS) of male Sprague-Dawley rats. Locomotor activity was measured in a doughnut-shaped circular arena after various treatments. EtOH alone did not alter locomotor activity in any of the experiments. Amphetamine (AMP, intraperitoneally or intraaccumbens) increased locomotor activity in a dose-dependent manner, and the presence of EtOH attenuated AMP-induced locomotor activity. Bilateral infusion of GABAA antagonist picrotoxin (PIC) into the ventral tegmental area also increased locomotor activity in a dose-dependent manner, and the presence of EtOH attenuated PIC-induced locomotor activity. On the other hand, the interaction between bilateral infusion of mu-receptor agonist Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO) and EtOH on locomotor activity is complex. The highest dose of DAGO that significantly increased locomotor activity was not affected by the presence of EtOH. But, with lower doses of DAGO that either had no effect or a small increase in locomotor activity, the combination of EtOH and DAGO increased and attenuated locomotor activity, respectively. Results from this study support our hypothesis that a low dose of EtOH that does not modify behavior can interact with neurotransmitter systems in the brain and modify drug-induced locomotor activity. Modification of this drug-induced locomotor activity by a low dose of EtOH is dependent on the rate of ongoing locomotor behavior induced by drug and the neurotransmitter substrate that the drug modified to induce locomotor behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. A novel adaptive needle insertion sequencing for robotic, single needle MR-guided high-dose-rate prostate brachytherapy

    Science.gov (United States)

    Borot de Battisti, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; Maenhout, M.; Moerland, M. A.

    2017-05-01

    MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The

  13. Comparison of plasmakinetic transurethral resection of the prostate with monopolar transurethral resection of the prostate in terms of urethral stricture rates in patients with comorbidities

    Directory of Open Access Journals (Sweden)

    Orhun Sinanoglu

    2014-09-01

    Conclusions: The risk of urethral stricture increases with PK-TURP in elderly patients with a large prostate and concomitant hypertension and/or coronary artery disease and/or diabetes mellitus. Therefore, PK-TURP should be performed cautiously in this group of benign prostatic hyperplasia patients.

  14. New use of low-dose aspirin and risk of colorectal cancer by stage at diagnosis: a nested case-control study in UK general practice.

    Science.gov (United States)

    García Rodríguez, Luis A; Soriano-Gabarró, Montse; Bromley, Susan; Lanas, Angel; Cea Soriano, Lucía

    2017-09-07

    Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease. We investigated the risk of CRC among new-users of low-dose aspirin (75-300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case-control analysis. Two cohorts (N = 170,336 each) aged 40-89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified 'as-treated' independent from baseline exposure status to account for changes in exposure during follow-up. Current users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60-0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63-0·79) and 0.60 (0.53-0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66-1.33) for Dukes Stage A CRC, 0.54 (0.42-0.68) for Dukes B, 0.71 (0.56-0.91) for Dukes C, and 0.60 (0.48-0.74) for Dukes D. After 5 years' therapy, the RR for Dukes Stage A CRC was 0.53 (0.24-1.19). Patients starting low-dose aspirin therapy have a reduced

  15. High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

    Energy Technology Data Exchange (ETDEWEB)

    Zamboglou, Nikolaos [Department of Radiation Oncology, Klinikum Offenbach, Offenbach (Germany); Tselis, Nikolaos, E-mail: ntselis@hotmail.com [Department of Radiation Oncology, Klinikum Offenbach, Offenbach (Germany); Baltas, Dimos [Department of Medical Physics and Engineering, Klinikum Offenbach, Offenbach (Germany); Buhleier, Thomas [Department of Radiation Oncology, Klinikum Offenbach, Offenbach (Germany); Martin, Thomas [Department of Radiation Oncology, Klinikum Bremen-Mitte, Bremen (Germany); Milickovic, Natasa; Papaioannou, Sokratis [Department of Medical Physics and Engineering, Klinikum Offenbach, Offenbach (Germany); Ackermann, Hanns [Institute of Biostatistics, J.W. Goethe University of Frankfurt, Frankfurt (Germany); Tunn, Ulf W. [Department of Urology, Klinikum Offenbach, Offenbach (Germany)

    2013-03-01

    Purpose: To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. Methods and Materials: Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. Conclusion: Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

  16. Brachytherapy for the treatment of prostate cancer.

    Science.gov (United States)

    Cesaretti, Jamie A; Stone, Nelson N; Skouteris, Vassilios M; Park, Janelle L; Stock, Richard G

    2007-01-01

    Low-dose rate brachytherapy has become a mainstream treatment option for men diagnosed with prostate cancer because of excellent long-term treatment outcomes in low-, intermediate-, and high-risk patients. Largely due to patient lead advocacy for minimally invasive treatment options, high-quality prostate implants have become widely available in the US, Europe, and Japan. The reason that brachytherapy results are reproducible in several different practice settings is because numerous implant quality factors have been defined over the last 20 years, which can be applied objectively to judge the success of the intervention both during and after the procedure. In addition, recent long-term follow-up studies have clarified that the secondary cancer incidence of brachytherapy is not clinically meaningful. In terms of future directions, the study of radiation repair genetics may allow for the counseling physician to better estimate any given patients risk for side effects, thereby substantially reducing the therapeutic uncertainties faced by patients choosing a prostate cancer intervention.

  17. Pregnancy course in patients with intrahepatic cholestasis of pregnancy treated with very low doses of ursodeoxycholic acid.

    Science.gov (United States)

    Grymowicz, Monika; Czajkowski, Krzysztof; Smolarczyk, Roman

    2016-01-01

    Ursodeoxycholic acid (UDCA) has been proposed as the optimal pharmacological treatment for intrahepatic cholestasis of pregnancy (ICP). The lowest effective dosage of UDCA in women with ICP has not been established. The objective is to determine the risk of adverse pregnancy outcomes resulting from ICP and to measure changes in liver function parameters and pruritus severity in ICP patients treated with low doses of UDCA. ICP was diagnosed in 203 patients on the basis of pruritus and elevated liver biochemical parameters. Patients with total bile acids (TBA) ≥ 10 μmol/l (n = 157) received UDCA (300-450 mg/day; 4-6 mg/kg/day) until delivery. Maternal and fetal outcomes of women with ICP were compared with 100 patients without cholestasis. Patients with ICP were hospitalized for treatment and fetal surveillance. There was no correlation between fetal and neonatal complication rates in ICP patients and biochemical markers of cholestasis. Significant declines in serum TBA (p = 0.003), bilirubin concentration (p = 0.026) and aminotransferase activity (p < 0.001) were observed during treatment with low doses of UDCA. Moreover, severity of pruritus was ameliorated during the 2 weeks of therapy (p = 0.037). A total of 17 patients (10.9%) did not respond to treatment. UDCA at low doses improved biochemical markers and clinical symptoms in almost 90% of ICP patients.

  18. Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

    Science.gov (United States)

    Sokolov, Mykyta; Neumann, Ronald

    2015-01-01

    Exposure to ionizing radiation (IR) is inevitable to humans in real-life scenarios; the hazards of IR primarily stem from its mutagenic, carcinogenic, and cell killing ability. For many decades, extensive research has been conducted on the human cell responses to IR delivered at a low dose/low dose (LD) rate. These studies have shown that the molecular-, cellular-, and tissue-level responses are different after low doses of IR (LDIR) compared to those observed after a short-term high-dose IR exposure (HDIR). With the advent of high-throughput technologies in the late 1990s, such as DNA microarrays, changes in gene expression have also been found to be ubiquitous after LDIR. Very limited subset of genes has been shown to be consistently up-regulated by LDIR, including CDKN1A. Further research on the biological effects and mechanisms induced by IR in human cells demonstrated that the molecular and cellular processes, including transcriptional alterations, activated by LDIR are often related to protective responses and, sometimes, hormesis. Following LDIR, some distinct responses were observed, these included bystander effects, and adaptive responses. Changes in gene expression, not only at the level of mRNA, but also miRNA, have been found to crucially underlie these effects having implications for radiation protection purposes. PMID:26729107

  19. Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Mykyta Sokolov

    2015-12-01

    Full Text Available Exposure to ionizing radiation (IR is inevitable to humans in real-life scenarios; the hazards of IR primarily stem from its mutagenic, carcinogenic, and cell killing ability. For many decades, extensive research has been conducted on the human cell responses to IR delivered at a low dose/low dose (LD rate. These studies have shown that the molecular-, cellular-, and tissue-level responses are different after low doses of IR (LDIR compared to those observed after a short-term high-dose IR exposure (HDIR. With the advent of high-throughput technologies in the late 1990s, such as DNA microarrays, changes in gene expression have also been found to be ubiquitous after LDIR. Very limited subset of genes has been shown to be consistently up-regulated by LDIR, including CDKN1A. Further research on the biological effects and mechanisms induced by IR in human cells demonstrated that the molecular and cellular processes, including transcriptional alterations, activated by LDIR are often related to protective responses and, sometimes, hormesis. Following LDIR, some distinct responses were observed, these included bystander effects, and adaptive responses. Changes in gene expression, not only at the level of mRNA, but also miRNA, have been found to crucially underlie these effects having implications for radiation protection purposes.

  20. Effects of low dose gamma radiation on the growth, enzyme and photosynthetic activities of gourd (lagenaria siceraria)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J. S.; Beak, M. H.; Lee, H. Y.; Lee, Y. K. [KAERI, Taejon (Korea, Republic of)

    2001-10-01

    Gourd seeds were irradiated with the doses of 0 {approx} 20 Gy to investigate the effect of the low lose gamma radiation on the early growth and physiological activity. The stimulating effects of the low dose gamma radiation on the early growth were not noticeably high, but were increased generally 4 {approx} 16 Gy irradiation group. The catalase and peroxidase activity of cotylendon from seeds irradiated with gamma radiation were increased at 8 Gy irradiation group and peroxidase activity of leaf was noticeably high at 4 Gy irradiation group. The photochemical yield of PSII, estimated as Fv/Fm, was decreased with increasing illumination time by 50% after 4 hours while Fo did not change. Interestingly, Fv/Fm in plants of 4 Gy irradiation group was decreased less showing 40% of inhibition after 4 hr, indicating that the low dose gamma radiation increased resistance of plants to photoinhibition. Changes in the effective quantum yield of PSII(1-F/Fm'), {phi}{sub PSII} and I/Fo-1/Fm, a measure of the rate constant of excitation trapping by the PSII reaction center, showed similar pattern as Fv/Fm. These results showed the positive effect of low dose gamma radiation on the seedling growth or physiological activities gourd via increasing photoprotective capacities of photosynthetic apparatus.

  1. Combined administration of the GPVI-Fc fusion protein Revacept with low-dose thrombolysis in the treatment of stroke

    Directory of Open Access Journals (Sweden)

    Andreas Reimann

    2016-04-01

    Full Text Available Background Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA remains the only approved medication for acute ischemic stroke, but incurs significant bleeding risks. Therefore, approaches to combine lower doses of thrombolytic therapy with other effective drugs aim at improving efficacy and reducing bleeding rates. We examined the safety and therapeutic effects of various dosings of rtPA, either alone or combined with glycoprotein VI-Fc fusion protein (GPVI-Fc, Revacept on experimental stroke in mice. Methods and results The effect of filament-induced intracerebral thrombus formation and embolization was investigated after a one-hour occlusion of the middle cerebral artery. In accordance with previous studies, treatment with 10 mg/kg rtPA significantly improved functional outcome, cerebral infarct size and edema, but also resulted in markedly increased intracranial bleeding volumes. In contrast, low doses of rtPA (0.1 or 0.35 mg/kg body weight did not change outcome parameters. However, addition of 1 mg/kg Revacept to 0.35 mg/kg rtPA led to improved reperfusion compared to rtPA alone. Moreover, these combined treatments resulted in improved grip strength, compared to the respective dose of rtPA alone. Infarct-surrounding edema improved after combined treatments, but not after respective single rtPA dosings. Intracranial bleeding volumes were below controls after all low-dose rtPA therapies, given either alone or combined with Revacept. Conclusions In contrast to using the equally effective full dose of rtPA, intracranial bleeding was not increased by low-dose rtPA combined with Revacept. Therefore, addition of Revacept to low-dose rtPA does not incur safety risks, but improves efficacy of treatment.

  2. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

    Science.gov (United States)

    Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

  3. Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation.

    Science.gov (United States)

    Kim, Rae-Kwon; Kim, Min-Jung; Seong, Ki Moon; Kaushik, Neha; Suh, Yongjoon; Yoo, Ki-Chun; Cui, Yan-Hong; Jin, Young Woo; Nam, Seon Young; Lee, Su-Jae

    2015-10-30

    Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen.

  4. Impact of penile rehabilitation with low-dose vardenafil on recovery of erectile function in Japanese men following nerve-sparing radical prostatectomy

    Directory of Open Access Journals (Sweden)

    Yuzo Nakano

    2014-12-01

    Full Text Available Erectile dysfunction (ED is a major complication after radical prostatectomy (RP; however, debate continues regarding the efficacy of penile rehabilitation in the recovery of the postoperative erectile function (EF. This study included a total of 103 consecutive sexually active Japanese men with localized prostate cancer undergoing nerve-sparing RP, and analyzed the postoperative EF, focusing on the significance of penile rehabilitation. In this series, 24 and 79 patients underwent bilateral and unilateral nerve-sparing RPs, respectively, and 10 or 20 mg of vardenafil was administered to 35 patients at least once weekly, who agreed to undergo penile rehabilitation. Twelve months after RP, 48 (46.6% of the 103 patients were judged to have recovered EF sufficient for sexual intercourse without any assistance. The proportion of patients who recovered EF in those undergoing penile rehabilitation (60.0% was significantly greater than that in those without penile rehabilitation (38.2%. Of several parameters examined, the preoperative International Index of Erectile Function-5 (IIEF-5 score and nerve-sparing procedure were significantly associated with the postoperative EF recovery rates in patients with and without management by penile rehabilitation, respectively. Furthermore, univariate analysis identified the preoperative IIEF-5 score, nerve-sparing procedure and penile rehabilitation as significant predictors of EF recovery, among which the preoperative IIEF-5 score and nerve-sparing procedure appeared to be independently associated with EF recovery. Considering these findings, despite the lack of independent significance, penile rehabilitation with low-dose vardenafil could exert a beneficial effect on EF recovery in Japanese men following nerve-sparing RP.

  5. Unintended clinical consequences of the implementation of a checklist-based, low-dose oxytocin protocol.

    Science.gov (United States)

    Rohn, Amanda E; Bastek, Jamie A; Sammel, Mary D; Wang, Eileen; Srinivas, Sindhu K

    2015-03-01

    Standardized oxytocin protocols have been used to improve the safety and quality of obstetric care. We examined rates of chorioamnionitis and labor dystocia requiring cesarean delivery as unintended consequences of the implementation of a low-dose, checklist-based oxytocin protocol. We performed a retrospective cohort study of live singleton deliveries that underwent a trial of labor in two 15-month periods, comparing outcomes in those who delivered before to after protocol implementation. Patients and outcomes were identified using a combination of electronic medical records and International Classification of Diseases, 9th Revision, Clinical Modification codes. Time trend analysis was performed to evaluate for secular trends. A total of 8,717 women were included; 5,077 received oxytocin. Despite an unchanged rate of cesarean deliveries from before to after initiation of the protocol (15.15 vs. 14.75%, p = 0.60), deliveries after protocol implementation were generally characterized by higher rates of chorioamnionitis (7.48 vs. 5.97%, p labor dystocia (50.62 vs. 40.92%, p oxytocin protocols are intended to increase safety, but they may have unintended consequences related to prolonged labor, and should be studied before widespread use. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    Science.gov (United States)

    Chen, Yang; Yin, Xindao; Shi, Luyao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis; Toumoulin, Christine

    2013-08-01

    In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors.

  7. Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial

    DEFF Research Database (Denmark)

    Marchetti, Monia; Barosi, Giovanni; Balestri, Francesca

    2004-01-01

    daily and increasing to 400 mg as tolerated. RESULTS: Half of the patients sustained daily doses more than 100 mg and the drop-out rate was 51% at 6 months: the drop-out rate was lower in patients with high baseline fatigue score. At efficacy analysis, anemia was ameliorated in 22% of the patients...... score occurred in 31% of patients and was associated with a significant reduction of fatigue. Disease severity amelioration was independently predicted by a high baseline myeloproliferative index (ie, large splenomegaly, thrombocytosis, or leukocytosis). CONCLUSION: Low-dose thalidomide displays...

  8. Prostate Ultrasound

    Medline Plus

    Full Text Available ... the prostate is enlarged, also known as benign prostatic hyperplasia (BPH) , with measurements acquired as needed for any ... size with caption Related Articles and Media Benign Prostatic Hyperplasia (BPH) Prostate Cancer Ultrasound- and MRI-Guided Prostate ...

  9. Prostate Ultrasound

    Medline Plus

    Full Text Available ... prostate is enlarged, also known as benign prostatic hyperplasia (BPH) , with measurements acquired as needed for any ... with caption Related Articles and Media Benign Prostatic Hyperplasia (BPH) Prostate Cancer Ultrasound- and MRI-Guided Prostate ...

  10. Low-Dose Gamma Radiation Does Not Induce an Adaptive Response for Micronucleus Induction in Mouse Splenocytes.

    Science.gov (United States)

    Bannister, L A; Serran, M L; Mantha, R R

    2015-11-01

    Low-dose ionizing radiation is known to induce radioadaptive responses in cells in vitro as well as in mice in vivo. Low-dose radiation decreases the incidence and increases latency for spontaneous and radiation-induced tumors in mice, potentially as a result of enhanced cellular DNA repair efficiency or a reduction in genomic instability. In this study, the cytokinesis-block micronucleus (CBMN) assay was used to examine dose response and potential radioadaptive response for cytogenetic damage and cell survival in C57BL/6 and BALB/c spleen cells exposed in vitro or in vivo to low-dose 60Co gamma radiation. The effects of genetic background, radiation dose and dose rate, sampling time and cell cycle were investigated with respect to dose response and radioadaptive response. In C57BL/6 mice, a linear-quadratic dose-response relationship for the induction of micronuclei (MN) was observed for doses between 100 mGy and 2 Gy. BALB/c mice exhibited increased radiosensitivity for MN induction compared to C57BL/6 mice. A 20 mGy dose had no effect on MN frequencies in splenocytes of either mouse strain, however, increased spleen weight and a reduced number of dead cells were noted in the C57BL/6 strain only. Multiple experimental parameters were investigated in radioadaptive response studies, including dose and dose rate of the priming dose (20 mGy at 0.5 mGy/min and 100 mGy at 10 mGy/min), time interval (4 and 24 h) between priming and challenge doses, cell cycle stage (resting or proliferating) at exposure and kinetics after the challenge dose. Radioadaptive responses were not observed for MN induction for either mouse strain under any of the experimental conditions investigated. In contrast, a synergistic response for radiation-induced micronuclei in C57BL/6 spleen was detected after in vivo 20 mGy irradiation. This increase in the percentage of cells with cytogenetic damage was associated with a reduction in the number of nonviable spleen cells, suggesting that low-dose

  11. Prostate Specific Antigen (PSA as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT in Combination with Additional External Beam Radiation Therapy (EBRT for High Risk Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Thorsten H. Ecke

    2016-11-01

    Full Text Available High-dose-rate brachytherapy (HDR-BT with external beam radiation therapy (EBRT is a common treatment option for locally advanced prostate cancer (PCa. Seventy-nine male patients (median age 71 years, range 50 to 79 with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index, Gleason score, D’Amico risk classification for PCa, digital rectal examination (DRE, PSA value after one/three/five year(s follow-up (FU, time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis (p = 0.009, PSA on date of first HDR-BT (p = 0.033, and PSA on date of first follow-up after one year (p = 0.025 have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

  12. Validation study of ultrasound-based high-dose-rate prostate brachytherapy planning compared with CT-based planning.

    Science.gov (United States)

    Batchelar, Deidre; Gaztañaga, Miren; Schmid, Matt; Araujo, Cynthia; Bachand, François; Crook, Juanita

    2014-01-01

    The use of transrectal ultrasound (TRUS) to both guide and plan high-dose-rate (HDR) brachytherapy (BT) for prostate is increasing. Studies using prostate phantoms have demonstrated the accuracy of ultrasound (US) needle tip reconstruction compared with CT imaging standard. We have assessed the in vivo accuracy of needle tip localization by TRUS using cone-beam CT (CBCT) as our reference standard. Needle positions from 37 implants have been analyzed. A median of 16 needles (range, 16-18) per implant were inserted, advanced to the prostate base, and their tips identified using live TRUS images and real-time planning BT software. Needle protrusion length from the template was recorded to allow for reverification before capturing images for planning. The needles remained locked in the template, which was fixed to the stepper, while a set of three-dimensional TRUS images was acquired for needle path reconstruction and HDR-BT treatment planning. Following treatment, CBCT images were acquired for subsequent needle reconstruction using a BT Treatment Planning System. The coordinates of each needle tip were recorded from the Treatment Planning System for CT and US and compared. A total of 574 needle tip positions have been compared between TRUS and CBCT. Of these, 59% agreed within 1 mm, 27% within 1-2 mm, and 11% agreed within 2-3 mm. The discrepancy between tip positions in the two modalities was greater than 3 mm for only 20 needles (3%). The US needle tip identification in vivo is at least as accurate as CT identification, while providing all the advantages of a one-step procedure. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  13. Adaptive planning strategy for high dose rate prostate brachytherapy—a simulation study on needle positioning errors.

    Science.gov (United States)

    Borot de Battisti, M; Denis de Senneville, B; Maenhout, M; Hautvast, G; Binnekamp, D; Lagendijk, J J W; van Vulpen, M; Moerland, M A

    2016-03-01

    The development of magnetic resonance (MR) guided high dose rate (HDR) brachytherapy for prostate cancer has gained increasing interest for delivering a high tumor dose safely in a single fraction. To support needle placement in the limited workspace inside the closed-bore MRI, a single-needle MR-compatible robot is currently under development at the University Medical Center Utrecht (UMCU). This robotic device taps the needle in a divergent way from a single rotation point into the prostate. With this setup, it is warranted to deliver the irradiation dose by successive insertions of the needle. Although robot-assisted needle placement is expected to be more accurate than manual template-guided insertion, needle positioning errors may occur and are likely to modify the pre-planned dose distribution.In this paper, we propose a dose plan adaptation strategy for HDR prostate brachytherapy with feedback on the needle position: a dose plan is made at the beginning of the interventional procedure and updated after each needle insertion in order to compensate for possible needle positioning errors. The introduced procedure can be used with the single needle MR-compatible robot developed at the UMCU. The proposed feedback strategy was tested by simulating complete HDR procedures with and without feedback on eight patients with different numbers of needle insertions (varying from 4 to 12). In of the cases tested, the number of clinically acceptable plans obtained at the end of the procedure was larger with feedback compared to the situation without feedback. Furthermore, the computation time of the feedback between each insertion was below 100 s which makes it eligible for intra-operative use.

  14. Effects of verbenalin on prostatitis mouse model

    Science.gov (United States)

    Miao, Mingsan; Guo, Lin; Yan, Xiaoli; Wang, Tan; Li, Zuming

    2015-01-01

    The aim of this study was to observe the treatment characteristics of verbenalin on a prostatitis mouse model. Give Xiaozhiling injection in the prostate locally to make a prostatitis mouse model. High, medium and low doses of verbenalin were each given to different mouse groups. The amount of water was determined in 14th, 28th. The number of white cells and lecithin corpuscle density in prostatic fluid were determined. Morphological changes in the prostate, testis, epididymis and kidney were detected. Compared with the model control group, the mice treated with high, medium and low doses of verbenalin had significantly increased amounts of water, and prostate white blood cell count and prostate volume density (Vv) were decreased significantly, the density of lecithin corpuscle score increased, and pathologic prostatitis changes were significantly reduced. Pathological change in the testis was significantly reduced and the change in the epididymis was obviously reduced. The thymic cortex thickness and the number of lymphocytes increased significantly and could reduce the renal pathological changes in potential. Verbenalin has a good therapeutic effect on the prostatitis mouse model. PMID:26858560

  15. Gamma ray radiation induced visible light absorption in P-doped silica fibers at low dose levels

    CERN Document Server

    Lu Ping; Kulkarni, N S; Brown, K

    1999-01-01

    A CCD Fiber Optic Spectrometer has been used to monitor the gamma ray radiation induced loss in P-doped fibers at different dopant concentrations (1, 5 and 10 mol%) with a light source (an incandescent bulb with a temperature of 2800-3000 K). The range of dose rates is limited to that used in medical applications (cancer treatments), that is 0.1 to 1.0 Gray per minute (Gy/min). At low integral dose level (<2.0 Gy) four absorption peaks were observed (470, 502, 540 and 600 nm) within the visible region. It has been observed that the radiation induced loss at 470 and 600 nm depends strongly on dose rate. At dose rates of 0.2 and 0.5 Gy/min the induced loss shows nonlinear relation to the total dose. However, at high dose rate (1.0 Gy/min) and low dose rate (0.1 Gy/min) it seems to have a linear dependence with total dose. The conversion from NBOHCs to GeX centers was observed during gamma radiation at low dose rates (0.1-0.5 Gy/min). At the wavelength of 502 and 540 nm, the radiation induced losses show exce...

  16. EXACERBATION OF ANKYLOSING SPONDYLITIS AFTER LOW-DOSE METHOTREXATE THERAPY

    Directory of Open Access Journals (Sweden)

    A. V. Orlov-Morozov

    2014-01-01

    Full Text Available Background: Efficacy of methotrexate in ankylosing spondylitis (AS is disputable. Nevertheless, methotrexate is still used for disease-modifying therapy of AS. Aim: To assess efficacy and safety of methotrexate in AS patients. Materials and methods: It was an open comparative study of efficacy of methotrexate (n=12 versus standard therapy (n=12 in AS patients. Results: Negative results of methotrexate therapy were obtained. In the majority of patients methotrexate therapy was associated with increased joint pain, swelling and morning stiffness as well as elevation of erythrocyte sedimentation rate, fever and visceritis. Worsening of symptoms was regarded as exacerbation of inflammatory process. The study was terminated prematurely. Conclusion: Methotrexate demonstrated no therapeutic effect in AS patients. In AS, methotrexate should be administrated under close physician control in order to ensure treatment safety

  17. Learning curve of MRI-based planning for high-dose-rate brachytherapy for prostate cancer

    DEFF Research Database (Denmark)

    Buus, Simon; Rylander, Susanne; Hokland, Steffen

    2016-01-01

    –D as treatment planning time, and D to E as treatment delivery time. Dose-volume parameters were retrieved from the dose planning system. Results from the first 21 patients were compared with the last 21 patients. Results Total procedure time, operating room time, MRI procedure time, and treatment planning time...... decreased significantly from average 7.6 to 5.3 hours (p delivery time remained unchanged at 0.5 hours. Clinical target volume prostate+3mmD90 fulfilled planning aim in 92% of procedures...

  18. 20 percent lower lung cancer mortality with low-dose CT vs chest X-ray

    Science.gov (United States)

    Scientists have found a 20 percent reduction in deaths from lung cancer among current or former heavy smokers who were screened with low-dose helical computed tomography (CT) versus those screened by chest X-ray.

  19. The Effect of Low-Dose Oxytocin Infusion on Cerebral Hemodynamics in Pregnant Women

    NARCIS (Netherlands)

    van Veen, Teelkien R.; Belfort, Michael A.; Zeeman, Gerda G.

    We investigated the cerebrovascular effects of continuous infusion of low-dose oxytocin in normal pregnant women undergoing induction of labor. In our prospective observational study, middle cerebral artery velocity was measured with transcranial Doppler ultrasound in 25 healthy, normotensive,

  20. Low-dose helical computed tomography (CT) in the perioperative workup of adolescent idiopathic scoliosis

    Energy Technology Data Exchange (ETDEWEB)

    Abul-Kasim, Kasim; Overgaard, Angelica; Maly, Pavel [Malmoe University Hospital, Department of Radiology, Section of Neuroradiology, University of Lund, Malmoe (Sweden); Ohlin, Acke [Malmoe University Hospital, Department of Orthopaedic Surgery, University of Lund, Malmoe (Sweden); Gunnarsson, Mikael [Malmoe University Hospital, Department of Radiation Physics, University of Lund, Malmoe (Sweden); Sundgren, Pia C. [University of Michigan Health Systems, Department of Radiology, Division of Neuroradiology, Ann Arbor (United States)

    2009-03-15

    The study aims were to estimate the radiation dose in patients examined with low dose spine CT and to compare it with that received by patients undergoing standard CT for trauma of the same region, as well as to evaluate the impact of dose reduction on image quality. Radiation doses in 113 consecutive low dose spine CTs were compared with those in 127 CTs for trauma. The inter- and intraobserver agreement in measurements of pedicular width, and vertebral rotation, measurements of signal-to-noise ratio and assessment of hardware status were the indicators in the evaluation of image quality. The effective dose of the low dose spine CT (0.37 mSv) was 20 times lower than that of a standard CT for trauma (13.09 mSv). This dose reduction conveyed no impact on image quality. This low dose spine CT protocol allows detailed evaluation that is necessary for preoperative planning and postoperative evaluation. (orig.)

  1. Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery

    Science.gov (United States)

    A low dose of radioactive iodine given after surgery for thyroid cancer destroyed (ablated) residual thyroid tissue as effectively as a higher dose, with fewer side effects and less exposure to radiation, according to two randomized controlled trials.

  2. CANCER RISKS ATTRIBUTABLE TO LOW DOSES OF IONIZING RADIATION - ASSESSING WHAT WE REALLY KNOW?

    Science.gov (United States)

    Cancer Risks Attributable to Low Doses of Ionizing Radiation - What Do We Really Know?AbstractHigh doses of ionizing radiation clearly produce deleterious consequences in humans including, but not exclusively, cancer induction. At very low radiation doses the situatio...

  3. Microdose acquisition in adolescent leg length discrepancy using a low-dose biplane imaging system

    DEFF Research Database (Denmark)

    Jensen, Janni; Mussmann, Bo Redder; Hjarbæk, John

    2017-01-01

    Background Children with leg length discrepancy often undergo repeat imaging. Therefore, every effort to reduce radiation dose is important. Using low dose preview images and noise reduction software rather than diagnostic images for length measurements might contribute to reducing dose. Purpose...... To compare leg length measurements performed on diagnostic images and low dose preview images both acquired using a low-dose bi-planar imaging system. Material and Methods Preview and diagnostic images from 22 patients were retrospectively collected (14 girls, 8 boys; mean age, 12.8 years; age range, 10...... strongly imply that leg length measurements performed on preview images from a low-dose bi-planar imaging system are comparable to measurements performed on diagnostic images....

  4. Brachytherapy optimization using radiobiological-based planning for high dose rate and permanent implants for prostate cancer treatment

    Science.gov (United States)

    Seeley, Kaelyn; Cunha, J. Adam; Hong, Tae Min

    2017-01-01

    We discuss an improvement in brachytherapy--a prostate cancer treatment method that directly places radioactive seeds inside target cancerous regions--by optimizing the current standard for delivering dose. Currently, the seeds' spatiotemporal placement is determined by optimizing the dose based on a set of physical, user-defined constraints. One particular approach is the ``inverse planning'' algorithms that allow for tightly fit isodose lines around the target volumes in order to reduce dose to the patient's organs at risk. However, these dose distributions are typically computed assuming the same biological response to radiation for different types of tissues. In our work, we consider radiobiological parameters to account for the differences in the individual sensitivities and responses to radiation for tissues surrounding the target. Among the benefits are a more accurate toxicity rate and more coverage to target regions for planning high-dose-rate treatments as well as permanent implants.

  5. Combined low-dose ipilimumab and pembrolizumab after sequential ipilimumab and pembrolizumab failure in advanced melanoma.

    Science.gov (United States)

    Kirchberger, Michael C; Hauschild, Axel; Schuler, Gerold; Heinzerling, Lucie

    2016-09-01

    With the wide use of anti-PD-1 therapy, an increasing number of patients progress under treatment. Combined immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies induces higher response rates as first-line treatment in comparison to single-agent therapy, however, with substantial toxicity since the combination of ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) induced 55% grade 3/4 treatment-related adverse events and treatment discontinuation rates of 39%. In this case series, we investigated the efficacy and toxicity of the combined immunotherapy with low-dose ipilimumab (1 mg/kg) plus pembrolizumab (2 mg/kg) in patients with metastatic melanoma with progressive disease under sequential monotherapy with both agents. All patients had received at least three lines of treatment, 78% of patients were M1c, and 67% had brain metastases. Stable disease was observed in 3 out of 9 patients with a median overall survival of 8 months after double checkpoint inhibition. No treatment-related grade 3/4 adverse events occurred, and none of the patients needed to discontinue the treatment due to toxicity. Further trials are needed to investigate combined immunotherapy as rescue treatment in heavily pretreated melanoma patients to find optimal dosage in regard to outcome and toxicity.

  6. Concurrent chemoradiotherapy with daily low dose CDDP/5FU for locally unresectable head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kohno, Naoyuki; Kitahara, Satoshi; Tamura, Etsuyo; Tanabe, Tetsuya [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine; Murata, Yasuhiro [National Defence Medical Coll., Tokorozawa, Saitama (Japan)

    2002-07-01

    To improve the local control rate and the prognosis of locally unresectable head and neck cancer patients, we studied the concurrent chemoradiotherapy. Between September 1996 and September 2000, thirty-eight patients with locally unresectable head and neck cancer were administered concurrent chemoradiotherapy consisting of low-dose and long-term treatment with cisplatin (CDDP) plus 5-fluorouracil (5FU), or (L-CF); the L-CF regimen consisted of CDDP, 3 mg/m{sup 2} on 5 days of the week and 5FU, 150 mg/m{sup 2} as a 24-hour infusion on 5 days of the week. Concurrently, conventional radiotherapy was given up to total dose of around 60 Gy. In the 36 patients evaluable for response, 19 complete and 10 partial responses were noted, with an overall response rate of 81%. Oral mucositis and myelosuppression were the major side effects and dose limiting toxicity. This study demonstrates increase in survival among the responders (complete+partial) in the concurrent chemoradiotherapy setting. We concluded that this treatment strategy was beneficial. Further studies for patients with locally unresectable head and neck cancer are warranted. (author)

  7. Low-dose acetylsalicylic acid and bleeding risks with ventriculoperitoneal shunt placement.

    Science.gov (United States)

    Kamenova, Maria; Croci, Davide; Guzman, Raphael; Mariani, Luigi; Soleman, Jehuda

    2016-09-01

    OBJECTIVE Ventriculoperitoneal (VP) shunt placement is a common procedure for the treatment of hydrocephalus following diverse neurosurgical conditions. Most of the patients present with other comorbidities and receive antiplatelet therapy, usually acetylsalicylic acid (ASA). Despite its clinical relevance, the perioperative management of these patients has not been sufficiently investigated. The aim of this study was to compare the peri- and postoperative bleeding complication rates associated with ASA intake in patients undergoing VP shunt placement. METHODS Of 172 consecutive patients undergoing VP shunt placement between June 2009 and December 2015, 40 (23.3%) patients were receiving low-dose ASA treatment. The primary outcome measure was bleeding events in ASA users versus nonusers, whereas secondary outcome measures were postoperative cardiovascular events, hematological findings, morbidity, and mortality. A subgroup analysis was conducted in patients who discontinued ASA treatment for < 7 days (n = 4, ASA Group 1) and for ≥ 7 days (n = 36, ASA Group 2). RESULTS No statistically significant difference for bleeding events was observed between ASA users and nonusers (p = 0.30). Cardiovascular complications, surgical morbidity, and mortality did not differ significantly between the groups either. Moreover, there was no association between ASA discontinuation regimens (< 7 days and ≥ 7 days) and hemorrhagic events. CONCLUSIONS Given the lack of guidelines regarding perioperative management of neurosurgical patients with antiplatelet therapy, these findings elucidate one issue, showing comparable bleeding rates in ASA users and nonusers undergoing VP shunt placement.

  8. HIGH AND LOW DOSE IVIG THERAPY IN GUILLAIN-BARRE SYNDROME CHILDREN: A COMPARISON

    Directory of Open Access Journals (Sweden)

    P. KARIMZADEH

    2006-06-01

    Full Text Available Introduction:Acute inflammatory demyelinating peripheral neuropathy (GuillainBarre-Syndrome is by far the most common cause of immune-medicatedperipheral nervous system disease in children; with the near disappearanceof poliomyelitis, GBS is responsible for the great majority of cases ofacute flaccid paralysis. So far, in several controlled studies, corticosteroids,plasmapheresis and IVIG have been utilized in pediatric patients, afflictedwith GBS. Regarding IVIG therapy, two methods have been used; thehigh dose (1 gr/kg/day for 2 days, and the low dose (400mg/kg/day for5 days. Review of literature shows that a faster rate of recovery can beaccomplished in patients who receive total dose of IVIG in 2 days ascompared to the dose being given over 5 days.Materials & Methods: In this study we have compared these two types of treatment in aninvestigation, conducted in the Mofid Children Hospital on pediatricpatients who had sudden onset of acute flaccid paralysis, and werediagnosed as having GBS. Based on histories, physical examination andelectrodiagnosis, subjects were divided in two groups, the high doseIVIG treatment, 1gr/kg/day for 2 days (experimental group, and the lowdose IVIG treatment, 400 mg/kg/day for 5 days (control group. Statisticalanalyses were then carried out using the appropriate software.Results: Result of this study showed a faster rate of recovery for patients in thehigh dose IVIG group; in this group duration of weakness of limbs wasshorter and returning of DTR was faster than in controls. In fact, in thistype of treatment, the relationship between high dose IVIG therapy anddrug side effects was not significant.Conclusion: Base upon the finding in the present study, we conclude that the highdose IVIG therapy is superior to low dose, in view of faster duration ofrecovery and shorter hospital stay.Also we may infer that shorter hospital stay could be a factor in reducingof more nasocomial infection.In conclusion, we suggest using

  9. Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy.

    Science.gov (United States)

    Iwamoto, Junichi; Saito, Yoshifumi; Honda, Akira; Matsuzaki, Yasushi

    2013-03-21

    Low-dose aspirin (LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society. On the other hand, a very low dose of aspirin (10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage. The incidence of LDA-induced gastrointestinal mucosal injury and bleeding has increased. It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug (NSAID)-induced lesions. The pathogenesis related to inhibition of cyclooxygenase (COX)-1 includes reduced mucosal flow, reduced mucus and bicarbonate secretion, and impaired platelet aggregation. The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence. The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation. The factors associated with an increased risk of upper gastrointestinal (GI) complications in subjects taking LDA are aspirin dose, history of ulcer or upper GI bleeding, age > 70 years, concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs, and Helicobacter pylori (H. pylori) infection. Moreover, no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea, acid regurgitation, heartburn, and bloating. It has been shown that the ratios of ulcers located in the body, fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA. Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers. In contrast to NSAID-induced gastrointestinal ulcers, a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers. The eradication of H. pylori is equivalent to treatment with

  10. Optimizing prostate biopsy for repeat transrectal prostate biopsies patients

    Institute of Scientific and Technical Information of China (English)

    Xiaojun Deng; Jianwei Cao; Feng Liu; Weifeng Wang; Jidong Hao; Jiansheng Wan; Hui Liu

    2014-01-01

    Objective:Diagnosis of patients with negative prostate biopsy and persistent suspicion of prostate cancer re-mains a serious problem. In this study, we investigated the application of optimizing prostate biopsy for patients who need repeat prostate biopsy. Methods:In this prospective, non-randomized phase-I clinical trial, the prostate cancer detection rate of initial detection scheme was compared with optimizing prostate biopsy scheme. The number of punctures of initial detection scheme was the same as that of optimizing prostate biopsy scheme. The puncture direction of optimizing prostate biopsy was a 4