Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

International Nuclear Information System (INIS)

Minsky, B.D.; Cohen, A.M.; Kemeny, N.; Enker, W.E.; Kelsen, D.P.; Schwartz, G.; Saltz, L.; Dougherty, J.; Frankel, J.; Wiseberg, J.

1993-01-01

The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs

Standard and Low-dose Hormone Therapy for Postmenopausal Women—Focus on the Breast

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Peng-Hui Wang

2007-06-01

Full Text Available Menopause occurs naturally when the ovary ceases folliculogenesis, or artificially by surgical and/or medical ablation of the ovarian function. Menopause is a hypoestrogenic state, which may adversely affect estrogen target tissues, such as the brain, skeleton and skin, as well as the cardiovascular and genitourinary systems, with resultant frequency and severity of climacteric symptoms. The climacteric symptoms, however, vary significantly among women. For decades, hormone therapy (HT has been the mainstay and is considered the most effective for managing menopausal symptoms. The prolonged use of either single estrogen therapy or a combination therapy of estrogen and progestogen (EPT might be associated with a slightly increased risk of breast cancer and many resultant adverse events, such as coronary heart disease, stroke and venous thromboembolism. Perhaps because the clear benefits are limited to these end points of HT in treating menopausal women, the relatively significant adverse event profiles of these women may not be enough to trigger primary care physicians to be more aggressive than they have been to date in treating climacteric symptoms of postmenopausal women. However, severe climacteric symptoms really disturb the woman's life. Some epidemiologic studies have shown that the increased risk for breast cancer after 5 years of combined EPT is similar in magnitude to other lifestyle variables, such as 10-year delayed menopause, fewer pregnancies and reduced breastfeeding, postmenopausal obesity, excessive alcohol or cigarette use, and lack of regular exercise. Furthermore, elevated serum concentrations of either endogenous or exogenous (replaced by HT sex hormone in either pre- or postmenopausal women are associated with an increased risk of breast cancer. Finally, the increased breast cancer risk diminishes soon after discontinuing hormones, and largely disappears by 5 years after cessation. Taken together, low-dose conventional HT

Low-dose cholecalciferol supplementation and dual vitamin D therapy in haemodialysis patients.

Science.gov (United States)

Dusilová-Sulková, Sylvie; Šafránek, Roman; Vávrová, Jaroslava; Horáček, Jiří; Pavlíková, Ladislava; Palička, Vladimír

2015-01-01

Traditionally, secondary hyperparathyroidism (SHPT) due to low calcitriol synthesis in failing kidneys has been treated with synthetic vitamin D receptor (VDR) activators. Recently, also the importance of low native vitamin D status beyond the issue of SHPT has been recognized in these patients. The aim of this work was to evaluate the effect of cholecalciferol supplementation in haemodialysis patients with low vitamin D serum levels. Another aim was to evaluate dual vitamin D therapy (cholecalciferol supplementation plus paricalcitol) in haemodialysis patients with vitamin D deficiency and concomitant SHPT. Ninety clinically stable maintenance haemodialysis patients were included. Supervised cholecalciferol supplementation was administered due to low vitamin D status. Patients with SHPT were also treated with synthetic VDR activator. Two pre hoc subgroups for statistical analysis were formed: patients treated solely with cholecalciferol (N=34; 5,000 IU once weekly) and patients treated with a combination of cholecalciferol (identical dose, i.e. 5,000 IU/week) plus paricalcitol (N=34, median dose 10 μg/week). Follow-up visit was scheduled 15 weeks later. Serum concentrations of calcidiol (25-D), parathyroid hormone (PTH) and beta-cross laps (CTX) were assessed at baseline and at follow-up. Serum calcium, phosphate and alkaline phosphatase (ALP) were monitored monthly. Only non-calcium gastrointestinal phosphate binders were administered. Dialysate calcium was 1.5 mmol/L in all patients, and no oral calcium-containing preparations were prescribed. Depending on data distribution, parametric or nonparametric statistical methods were used for comparison within each group (i.e. baseline vs. follow-up data) as well as between groups. In the whole group of 90 patients, mean baseline 25-D serum level was 20.3 (standard deviation 8.7) nmol/L, and it increased to 66.8 (19) nmol/L (pvitamin D supplementation was almost identical. In cholecalciferol monotherapy, 25-D levels

Comparison of dose-volume histograms for Tomo therapy, linear accelerator-based 3D conformal radiation therapy, and intensity-modulated radiation therapy

International Nuclear Information System (INIS)

Ji, Youn-Sang; Dong, Kyung-Rae; Kim, Chang-Bok; Choi, Seong-Kwan; Chung, Woon-Kwan; Lee, Jong-Woong

2011-01-01

Highlights: → Evaluation of DVH from 3D CRT, IMRT and Tomo therapy was conducted for tumor therapy. → The doses of GTV and CTV were compared using DVHs from 3D CRT, IMRT and Tomo therapy. → The GTV was higher when Tomo therapy was used, while the doses of critical organ were low. → They said that Tomo therapy satisfied the goal of radiation therapy more than the others. - Abstract: Evaluation of dose-volume histograms from three-dimensional conformal radiation therapy (3D CRT), intensity-modulated radiation therapy (IMRT), and Tomo therapy was conducted. These three modalities are among the diverse treatment systems available for tumor therapy. Three patients who received tumor therapy for a malignant oligodendroglioma in the cranium, nasopharyngeal carcinoma in the cervical neck, and prostate cancer in the pelvis were selected as study subjects. Therapy plans were made for the three patients before dose-volume histograms were obtained. The doses of the gross tumor volume (GTV) and the clinical target volume (CTV) were compared using the dose-volume histograms obtained from the LINAC-based 3D CRT, IMRT planning station (Varian Eclipse-Varian, version 8.1), and Tomo therapy planning station. In addition, the doses of critical organs in the cranium, cervix, and pelvis that should be protected were compared. The GTV was higher when Tomo therapy was used compared to 3D CRT and the LINAC-based IMRT, while the doses of critical organ tissues that required protection were low. These results demonstrated that Tomo therapy satisfied the ultimate goal of radiation therapy more than the other therapies.

High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.

Science.gov (United States)

Taguchi, Isao; Iimuro, Satoshi; Iwata, Hiroshi; Takashima, Hiroaki; Abe, Mitsuru; Amiya, Eisuke; Ogawa, Takanori; Ozaki, Yukio; Sakuma, Ichiro; Nakagawa, Yoshihisa; Hibi, Kiyoshi; Hiro, Takafumi; Fukumoto, Yoshihiro; Hokimoto, Seiji; Miyauchi, Katsumi; Yamazaki, Tsutomu; Ito, Hiroshi; Otsuji, Yutaka; Kimura, Kazuo; Takahashi, Jun; Hirayama, Atsushi; Yokoi, Hiroyoshi; Kitagawa, Kazuo; Urabe, Takao; Okada, Yasushi; Terayama, Yasuo; Toyoda, Kazunori; Nagao, Takehiko; Matsumoto, Masayasu; Ohashi, Yasuo; Kaneko, Tetsuji; Fujita, Retsu; Ohtsu, Hiroshi; Ogawa, Hisao; Daida, Hiroyuki; Shimokawa, Hiroaki; Saito, Yasushi; Kimura, Takeshi; Inoue, Teruo; Matsuzaki, Masunori; Nagai, Ryozo

2018-05-08

Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group ( P Japanese patients with stable coronary artery disease. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730. © 2018 The Authors.

Clinical trial of combination therapy using systemic interleukin-2 infusion and low-dose tumor irradiation for advanced hepatocellular carcinoma

International Nuclear Information System (INIS)

Tsuchida, Tetsuo; Hiragushi, Junji; Asano, Yoshihide

1995-01-01

Although recent progress in surgical techniques and interventional radiology enables patients with hepatocellular carcinoma (HCC) to survive longer, there are still many who cannot receive them due to disease progression. We are currently investigating the therapeutic efficacy of the combination of systemic recombinant interleukin-2 (IL-2) administration and local tumor irradiation for HCC patients in the advanced stage. First, the results of the basic experiment to analyze the optimal dose and timing of IL-2 infusion were demonstrated. Intensive administration of high-dose IL-2 caused acute death, whereas intermittent low-dose IL-2 administration resulted in complete tumor regression followed by the acquisition of tumor-specific immunity. Our data suggested that the tumor-bearing state increased the responsiveness to IL-2 treatment, and that an excessively high-dose regimen is not prerequisite for the optimal IL-2 treatment. With regard to the effectiveness of radiotherapy for HCC, human hepatoma cells exhibited apoptotic death when hepatoma cells were cocultured with LAK cells, or were irradiated in vitro with relatively low-dose irradiation. These results suggested the possible synergistic effect of killer cells and low-dose irradiation. Finally, we presented six eligible cases of advanced HCC treated by combination therapy of IL-2 infusion and local low-dose tumor irradiation. Direct anti-tumor effects were one CR, one MR, two NC, and two PD. One CR case and a NC case have survived now for longer than 40 months. In all cases, NK cell activity increased prominently, and side effects wee mild flu-like symptoms except macroscopic hematuria and moderate VLS-like symptoms in two cases in which therapy was continued for longer than 2 years. Hepatic reserve function like prothrombin time or hepaplastic time improved. The apparent clinical effectiveness of the combination therapy presented here might give promising hints for a new therapeutic strategy for HCC. (author)

Emerging therapies in multiple myeloma.

Science.gov (United States)

El-Amm, Joelle; Tabbara, Imad A

2015-06-01

The treatment of multiple myeloma has evolved significantly over the past 2 decades due to the use of high-dose chemotherapy and autologous stem cell transplantation, and the subsequent introduction of the immunomodulatory agents (thalidomide and lenalidomide) and the proteasome inhibitor (bortezomib). The median overall survival of multiple myeloma patients has increased significantly with patients younger than age 50 years experiencing a 10-year survival rate of around 40%. However, despite the increased effectiveness of the first-line agents, the majority of patients will eventually relapse and become drug resistant. Promising novel therapies have recently emerged and are being used to treat relapsed and refractory patients. This review will cover the clinical data regarding these emergent therapies that include new generation of proteasome inhibitors (carfilzomib, ixazomib, oprozomib, and marizomib), immunomodulatory drugs (pomalidomide), monoclonal antibodies (elotuzumab and daratumumab), signal transduction modulator (perifosine), and histone deacetylase inhibitors (vorinostat and panobinostat).

Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

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Chung, Eugene [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Corbett, James R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Moran, Jean M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Ficaro, Edward C. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Pierce, Lori J., E-mail: ljpierce@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

2013-03-15

Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

Stereotactic body radiation therapy for low- and low-intermediate risk prostate cancer: Is there a dose effect?

Directory of Open Access Journals (Sweden)

Alan Jay Katz

2011-12-01

Full Text Available This study examines the efficacy and toxicity of two stereotactic body radiation therapy (SBRT dose regimens for treatment of early prostate cancer. Forty-one patients treated with 35 Gy were matched with 41 patients treated with 36.25 Gy. Both patient groups received SBRT in 5 fractions over 5 consecutive days using the CyberKnife. Each group had 37 low-risk patients and 4 intermediate-risk patients. No statistically significant differences were present for age, prostate volume, PSA, Gleason score, stage, or risk between the groups. The dose was prescribed to the 83-87% isodose line to cover the prostate and a 5-mm margin all around, except 3 mm posteriorly. The overall median follow-up is 51 months (range, 45-58 months with a median 54 months and 48 months follow-up for the 35-Gy and 36.25-Gy dose groups, respectively. One biochemical failure occurred in each group yielding a 97.5% freedom from biochemical failure. The PSA response has been favorable for all patients with a mean PSA of 0.1 ng/ml at 4-years. Overall toxicity has been mild with 5% late grade 2 rectal toxicity in both dose groups. Late grade 1 urinary toxicity was equivalent between groups; grade 2 urinary toxicity was 5% (2/41 patients and 10% (4/41 patients in the 35-Gy and 36.25-Gy dose groups (p = 0.6969, respectively. Overall, the highly favorable PSA response, limited biochemical failures, limited toxicity, and limited impact on quality of life in these low- to low-intermediate-risk patients are supportive of excellent long-term results for CyberKnife delivered SBRT.

Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy

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Berbeco, Ross I., E-mail: rberbeco@partners.org; Detappe, Alexandre [Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Tsiamas, Panogiotis [Department of Radiation Oncology, St. Jude Children’s Hospital, Memphis, Tennessee 38105 (United States); Parsons, David; Yewondwossen, Mammo; Robar, James [Department of Radiation Oncology and Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia B3H 1V7 (Canada)

2016-01-15

Purpose: Previous studies have introduced gold nanoparticles as vascular-disrupting agents during radiation therapy. Crucial to this concept is the low energy photon content of the therapy radiation beam. The authors introduce a new mode of delivery including a linear accelerator target that can toggle between low Z and high Z targets during beam delivery. In this study, the authors examine the potential increase in tumor blood vessel endothelial cell radiation dose enhancement with the low Z target. Methods: The authors use Monte Carlo methods to simulate delivery of three different clinical photon beams: (1) a 6 MV standard (Cu/W) beam, (2) a 6 MV flattening filter free (Cu/W), and (3) a 6 MV (carbon) beam. The photon energy spectra for each scenario are generated for depths in tissue-equivalent material: 2, 10, and 20 cm. The endothelial dose enhancement for each target and depth is calculated using a previously published analytic method. Results: It is found that the carbon target increases the proportion of low energy (<150 keV) photons at 10 cm depth to 28% from 8% for the 6 MV standard (Cu/W) beam. This nearly quadrupling of the low energy photon content incident on a gold nanoparticle results in 7.7 times the endothelial dose enhancement as a 6 MV standard (Cu/W) beam at this depth. Increased surface dose from the low Z target can be mitigated by well-spaced beam arrangements. Conclusions: By using the fast-switching target, one can modulate the photon beam during delivery, producing a customized photon energy spectrum for each specific situation.

Pancytopenia after low dose methotrexate therapy in a hemodialysis patient: case report and review of literature.

Science.gov (United States)

Yang, Ching-Ping; Kuo, Mei-Chuan; Guh, Jinn-Yuh; Chen, Hung-Chun

2006-01-01

Methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis (RA) with a side effect of pancytopenia. However, only a few cases of severe pancytopenia caused by low-dose MTX therapy have been reported, and the condition is rarely reported in uremic patients on dialysis therapy. We thereby report a hemodialysis patient who developed severe pancytopenia after oral treatment with low-dose MTX for RA. A 55-year-old woman who had been on regular hemodialysis treatment for 7 yr suffered from RA for 10 yr. She was regularly treated with celecoxib, prednisolone, and sulfasalazine in the past year. Because of the increasing arthralgia, 7.5 mg per week MTX was prescribed 3 months before admission. Stomatitis, fever, general fatigue, multiple skin carbuncles, and easy bruising developed after a cumulative dose of 90 mg. Pancytopenia was found at admission and the nadir of white blood cell count was 250/microL with 28% neutrophils, hematocrit was 22%, and platelet count was 6000/microL. Eosinophil counts increased from 11.5% initially to 26.1% on the sixth admission day. Transfusion with red blood cells and platelets, and appropriate antibiotics and folic acid were prescribed. She continued receiving regular hemodialysis and eventually recovered within 3 weeks.

Intracranial germinomas: a case for low dose radiation therapy alone

International Nuclear Information System (INIS)

Harrigan, Patricia M.; Loeffler, Jay S.; Shrieve, Dennis; Tarbell, Nancy J.

1995-01-01

Purpose: To determine the optimal dose and treatment outcome of patients treated with radiation for intracranial germinoma. Materials and Methods: Between 1975 and 1995, 39 patients with a diagnosis of intracranial germinoma were treated with radiation (RT) to the central nervous system. All but one pt received whole brain (WB) RT, (median dose: 3240 cGy range: 1500-4437 cGy) and a boost to the tumor volume (median total tumor volume dose: 5200 cGy, range: 3960-5950 cGy). Thirty-one pts received RT to the spine (median dose: 2500, range: 1875-3750). Eleven pts were treated with low dose RT and a tumor volume boost, (WB dose ≤ 2550 cGy, and spine dose ≤ 2160 cGy). Five pts were treated with cisplatin-based chemotherapy and low dose WB RT. Fifteen pts were biopsy-proven and 18 presented with multiple midline germinomas (MMG). Among all pts, 33% had serum or CSF positive for low levels of HCG and none of 19 (9 biopsy-proven) germinomas measured positive for AFP tumor marker. Six of 22 (27%) pts who had spine imaging or CSF cytology had evidence of tumor seeding. The male-to female-ratio was 1.4. Median age at diagnosis was 14 yrs for male pts and 9.5 yrs for females (p=.02, overall age range: 1-31 yrs). Median follow-up for survivors is 64 months (range: 1-226 months). Toxicity of treatment relative to dose was assessed. Results: The 5-yr. actuarial rate of disease-free survival (DFS) and overall survival for presumed germinomas was 97%. No pts died of germinoma. One pt died of a shunt infection who had received concurrent chemotherapy and low dose whole brain RT. Among the low dose RT alone group 6 pts received whole brain RT of ≤ 2550 cGy and 9 pts were treated with spinal RT of ≤ 2160 cGy without chemotherapy. Two of these pts had CSF cytology positive for tumor seeding. Additionally, 8 pts received a total dose to the tumor volume of ≤ 4800 cGy without chemotherapy. The 5-yr DFS was 100%. Five pts were treated with cisplatin-based chemotherapy followed

Intracranial germinomas: a case for low dose radiation therapy alone

Energy Technology Data Exchange (ETDEWEB)

Harrigan, Patricia M; Loeffler, Jay S; Shrieve, Dennis; Tarbell, Nancy J

1995-07-01

Purpose: To determine the optimal dose and treatment outcome of patients treated with radiation for intracranial germinoma. Materials and Methods: Between 1975 and 1995, 39 patients with a diagnosis of intracranial germinoma were treated with radiation (RT) to the central nervous system. All but one pt received whole brain (WB) RT, (median dose: 3240 cGy range: 1500-4437 cGy) and a boost to the tumor volume (median total tumor volume dose: 5200 cGy, range: 3960-5950 cGy). Thirty-one pts received RT to the spine (median dose: 2500, range: 1875-3750). Eleven pts were treated with low dose RT and a tumor volume boost, (WB dose {<=} 2550 cGy, and spine dose {<=} 2160 cGy). Five pts were treated with cisplatin-based chemotherapy and low dose WB RT. Fifteen pts were biopsy-proven and 18 presented with multiple midline germinomas (MMG). Among all pts, 33% had serum or CSF positive for low levels of HCG and none of 19 (9 biopsy-proven) germinomas measured positive for AFP tumor marker. Six of 22 (27%) pts who had spine imaging or CSF cytology had evidence of tumor seeding. The male-to female-ratio was 1.4. Median age at diagnosis was 14 yrs for male pts and 9.5 yrs for females (p=.02, overall age range: 1-31 yrs). Median follow-up for survivors is 64 months (range: 1-226 months). Toxicity of treatment relative to dose was assessed. Results: The 5-yr. actuarial rate of disease-free survival (DFS) and overall survival for presumed germinomas was 97%. No pts died of germinoma. One pt died of a shunt infection who had received concurrent chemotherapy and low dose whole brain RT. Among the low dose RT alone group 6 pts received whole brain RT of {<=} 2550 cGy and 9 pts were treated with spinal RT of {<=} 2160 cGy without chemotherapy. Two of these pts had CSF cytology positive for tumor seeding. Additionally, 8 pts received a total dose to the tumor volume of {<=} 4800 cGy without chemotherapy. The 5-yr DFS was 100%. Five pts were treated with cisplatin-based chemotherapy

Immunomodulatory effects of macrolide antibiotics - part 2: advantages and disadvantages of long-term, low-dose macrolide therapy.

Science.gov (United States)

Altenburg, J; de Graaff, C S; van der Werf, T S; Boersma, W G

2011-01-01

The available evidence for long-term, low-dose treatment with 14- and 15-membered ring macrolides in non-cystic fibrosis (CF) bronchiectasis, COPD, chronic sinusitis, and asthma is reviewed with special attention to possible adverse effects and the emergence of resistance during long-term macrolide treatment. Macrolide maintenance therapy has been proven to be of benefit in diffuse panbronchiolitis and CF, presumably due to an anti-inflammatory mechanism of action in addition to its direct antimicrobial effect. Solid evidence to justify this treatment regimen for non-CF bronchiectasis, asthma, or sinusitis is still lacking, although a beneficial effect of long-term macrolide therapy has been found in small clinical trials on these subjects. Data from randomized trials of long-term macrolide treatment in COPD are conflicting. A sufficiently long duration of treatment and the careful selection of patients appears to be crucial. Aside from its beneficial effects, possible side effects of macrolide treatment should be taken into account, the most important of these being gastrointestinal upset and cardiac arrhythmias. Development of macrolide resistance among respiratory pathogens is very common during long-term macrolide treatment. Whether this finding is clinically significant is a matter of debate. Copyright © 2010 S. Karger AG, Basel.

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.

Immunomodulatory Effects of Macrolide Antibiotics - Part 2 : Advantages and Disadvantages of Long-Term, Low-Dose Macrolide Therapy

NARCIS (Netherlands)

Altenburg, J.; de Graaff, C. S.; van der Werf, T. S.; Boersma, W. G.

2011-01-01

The available evidence for long-term, low-dose treatment with 14- and 15-membered ring macrolides in non-cystic fibrosis (CF) bronchiectasis, COPD, chronic sinusitis, and asthma is reviewed with special attention to possible adverse effects and the emergence of resistance during long-term macrolide

A model for inverse dose-rate effects - low dose-rate hyper-sensibility in response to targeted radionuclide therapy

International Nuclear Information System (INIS)

Murray, I.; Mather, S.J.

2015-01-01

Full text of publication follows. The aim of this work was to test the hypothesis that the Linear-Quadratic (LQ) model of cell survival, developed for external beam radiotherapy (EBRT), could be extended to targeted radionuclide therapy (TRT) in order to predict dose-response relationships in a cell line exhibiting low dose hypersensitivity (LDH). Methods: aliquots of the PC-3 cancer cell line were treated with either EBRT or an in-vitro model of TRT (Irradiation of cell culture with Y-90 EDTA over 24, 48, 72 or 96 hours). Dosimetry for the TRT was calculated using radiation transport simulations with the Monte Carlo PENELOPE code. Clonogenic as well as functional biological assays were used to assess cell response. An extension of the LQ model was developed which incorporated a dose-rate threshold for activation of repair mechanisms. Results: accurate dosimetry for in-vitro exposures of cell cultures to radioactivity was established. LQ parameters of cell survival were established for the PC-3 cell line in response to EBRT. The standard LQ model did not predict survival in PC-3 cells exposed to Y 90 irradiation over periods of up to 96 hours. In fact cells were more sensitive to the same dose when irradiation was carried out over 96 hours than 24 hours. I.e. at a lower dose-rate. Deviations from the LQ predictions were most pronounced below a threshold dose-rate of 0.5 Gy/hr. These results led to an extension of the LQ model based upon a dose-rate dependent sigmoid model of single strand DNA repair. This extension to the model resulted in predicted cell survival curves that closely matched the experimental data. Conclusion: the LQ model of cell survival to radiation has been shown to be largely predictive of response to low dose-rate irradiation. However, in cells displaying LDH, further adaptation of the model was required. (authors)

Low-dose total skin electron beam therapy for cutaneous lymphoma. Minimal risk of acute toxicities

Energy Technology Data Exchange (ETDEWEB)

Kroeger, Kai; Elsayad, Khaled; Moustakis, Christos; Haverkamp, Uwe; Eich, Hans Theodor [University Hospital of Muenster, Department of Radiation Oncology, Muenster (Germany)

2017-12-15

Low-dose total skin electron beam therapy (TSEBT) is attracting increased interest for the effective palliative treatment of primary cutaneous T-cell lymphoma (pCTCL). In this study, we compared toxicity profiles following various radiation doses. We reviewed the records of 60 patients who underwent TSEBT for pCTCL between 2000 and 2016 at the University Hospital of Munster. The treatment characteristics of the radiotherapy (RT) regimens and adverse events (AEs) were then analyzed and compared. In total, 67 courses of TSEBT were administered to 60 patients. Of these patients, 34 (51%) received a standard dose with a median surface dose of 30 Gy and 33 patients (49%) received a low dose with the median surface dose of 12 Gy (7 salvage low-dose TSEBT courses were administered to 5 patients). After a median follow-up of 15 months, the overall AE rate was 100%, including 38 patients (57%) with grade 2 and 7 (10%) with grade 3 AEs. Patients treated with low-dose TSEBT had significantly fewer grade 2 AEs than those with conventional dose regimens (33 vs. 79%, P < 0.001). A lower grade 3 AE rate was also observed in patients who had received the low-dose regimen compared to those with the conventional dose regimens (6 vs. 15%, P = 0.78). Multiple/salvage low-dose TSEBT courses were not associated with an increased risk of acute AEs. Low-dose TSEBT regimens are associated with significantly fewer grade 2 acute toxicities compared with conventional doses of TSEBT. Repeated/Salvage low-dose TSEBT, however, appears to be tolerable and can even be applied safely in patients with cutaneous relapses. (orig.) [German] Eine niedrigdosierte Ganzhautelektronenbestrahlung (TSEBT) wird vermehrt zur effektiven palliativen Behandlung von Patienten mit primaer kutanen T-Zell-Lymphomen (pCTCL) eingesetzt. In dieser Studie vergleichen wir die Toxizitaetsprofile verschiedener Dosiskonzepte. Untersucht wurden 60 zwischen 2000 und 2016 am Universitaetsklinikum Muenster mittels TSEBT

Combination effect of low dose fentanyl and propofol on emergence agitation in children following sevoflurane anesthesia

International Nuclear Information System (INIS)

Bakhamees, Hassan S; Mercan, Arzu; ElHalafawy, Yasser M

2009-01-01

To investigate the combination effect of low dose fentanyl and subhypnotic dose of propofol on emergence agitation in children receiving sevoflurane for adenotonsillectomy procedure.After ethical approval, a prospective, randomized, clinical study was performed in Saad Specialist Hospital, Al-Khobar, Kingdom of Saudi Arabia in 2007-2008. One hundred and twenty children in physical status of I according to the American Society of Anesthesiologists, aged 2-6 years, scheduled for adentonsillectomy under general anesthesia were allocated into 3 groups randomly. Anesthesia was induced and maintained by sevoflurane in all groups. Children received 0.1 ml.kg-1 normal saline at the end of surgery in group C (n=40), 1.5 mcg.kg-1 fentanyl during induction, and 0.1 ml.kg-1 normal saline at the end of surgery in group F (n=40), and 1.5 mcg.kg-1 fentanyl during induction and 1 mg.kg-1 propofol at the end of surgery in group FP (n=40). Postoperative agitation was recorded, if any, for the first postoperative hour.Three groups were comparable with regard to demographic data. Twenty-one patients (53%) in the control group, 14 patients (35%) in group F and 7 (18%) patients in group FP experienced postoperative agitation.The combination of low dose fentanyl before surgery and propofol at the end of surgery decreases the incidence and level of emergence agitation in children after adenotonsillectomy procedure under sevoflurane anesthesia. (author)

Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

Directory of Open Access Journals (Sweden)

Ning Ma

Full Text Available OBJECTIVES: To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. METHODS: From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. RESULTS: Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5% with acute thrombosis, 5 patients (1.8% with subacute thrombosis, 17 patients (6.2% with stroke, and 2 death (0.7% in low-dose aspirin group, compared with no patient (0% with acute thrombosis, 2 patient (2.1% with subacute thrombosis, 6 patients (6.2% with stroke, and 2 death (2.1% in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. CONCLUSION: Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

Low-dose antibiotics: current status and outlook for the future

DEFF Research Database (Denmark)

Antimicrobial therapy is a key factor in our success against pathogens poised to ravage at risk or infected individuals. However, we are currently at a watershed point as we face a growing crisis of antibiotic resistance among diverse pathogens. One area of intense interest is the impact of the a......Antimicrobial therapy is a key factor in our success against pathogens poised to ravage at risk or infected individuals. However, we are currently at a watershed point as we face a growing crisis of antibiotic resistance among diverse pathogens. One area of intense interest is the impact...... of the application of antibiotics for uses other than the treatment of patients and the association with such utilization with emerging drug resistance. This Research Topic “Low- dose antibiotics: current status and outlook for the future” in Frontiers in Microbiology: Antimicrobials, Resistance and Chemotherapy...

Local superficial hyperthermia in combination with low-dose radiation therapy for palliation of superficially localized metastases

International Nuclear Information System (INIS)

Owczarek, G.; Miszczyk, L.

2005-01-01

Full text: The aim of this study is to evaluate the response of superficially located metastases and local toxicity to microwave hyperthermia combined with radiation therapy. From May 2003 through December 2004 58 patients (33 male, 25 female; mean age 60 years) with lymph nodes or skin metastases were treated with microwave superficial hyperthermia combined with low-dose radiation therapy. Hyperthermia was administered twice weekly with high frequency applicator (∼900 Mhz) with water bolus. The temperature was set to 43 o C for 45 minutes. Radiotherapy was performed daily with dose 2 Gy or 4 Gy per fraction, to a total dose 20 Gy. There were 47 patients with carcinoma, 4 with sarcoma, 7 with melanoma. Treated regions were: head and neck (37 patients), chest wall 8, abdomen wall and groins 4, upper and lower limb 2 and 8 patients respectively. Primary tumor sites were: head and neck region (9 patients), lung 15, alimentary tract 8, breast 5, soft tissue 8, urogenital 4 and 9 patients with primary tumor site unknown. The toxicity was evaluated using 6 step scale: 0-no skin reaction, 1-faint red mark, 2-distinct red mark, 3-blisters, 4-brown mark, 5-necrosis. Presence of pain and its intensity were also analyzed. Diameter of tumor after the treatment was observed. Complete response was achieved in 5 patients (8.5 %), and partial response in 29 patients (50 %), no response was observed in 12 patients (20 %) and progression of tumor in 7 patients (12 %). No skin reaction was observed in 3 patients, faint red mark in 14 patients, distinct red mark in 28 patients, blisters in 8 patients, brown mark in 4 patients and necrosis in 1 patient. The pain occurred in 9 patients but it was no the cause of stopping treatment. Local superficial hyperthermia combined with low-dose radiation therapy is an effective method of treatment in a proportion of patients with superficial metastases. This combination of treatment modalities is well tolerated and is useful for palliation

Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis.

Science.gov (United States)

Kamstrup, Maria R; Gniadecki, Robert; Iversen, Lars; Skov, Lone; Petersen, Peter Meidahl; Loft, Annika; Specht, Lena

2015-05-01

Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments 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. In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over dose of 10 Gy in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (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. Copyright © 2015 Elsevier Inc. All rights reserved.

Multidisciplinary European Low Dose Initiative (MELODI). Strategic research agenda for low dose radiation risk research

Energy Technology Data Exchange (ETDEWEB)

Kreuzer, M. [Federal Office for Radiation Protection, BfS, Department of Radiation Protection and Health, Neuherberg (Germany); Auvinen, A. [University of Tampere, Tampere (Finland); STUK, Helsinki (Finland); Cardis, E. [ISGlobal, Barcelona Institute for Global Health, Barcelona (Spain); Durante, M. [Institute for Fundamental Physics and Applications, TIFPA, Trento (Italy); Harms-Ringdahl, M. [Stockholm University, Centre for Radiation Protection Research, Stockholm (Sweden); Jourdain, J.R. [Institute for Radiological Protection and Nuclear Safety, IRSN, Fontenay-aux-roses (France); Madas, B.G. [MTA Centre for Energy Research, Environmental Physics Department, Budapest (Hungary); Ottolenghi, A. [University of Pavia, Physics Department, Pavia (Italy); Pazzaglia, S. [Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Rome (Italy); Prise, K.M. [Queens University Belfast, Belfast (United Kingdom); Quintens, R. [Belgian Nuclear Research Centre, SCK-CEN, Mol (Belgium); Sabatier, L. [French Atomic Energy Commission, CEA, Paris (France); Bouffler, S. [Public Health England, PHE, Chilton (United Kingdom)

2018-03-15

MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website (http://www.melodi-online.eu/sra.html). (orig.)

The observation of curative effects by therapy with low-dose 131I in younger with Graves' disease

International Nuclear Information System (INIS)

Cui Liqun; Li Lingling; Zhang Chenggang

2007-01-01

Objective: To observe the the curative effects in younger with Graves disease therapied by 131 I. Methods: The dose of 131 I is administrated with 1480-2220kBq/g of thyroid tissue which was decided by many factors that include the paticnt's Age, volume of thyroid, course and if antihyroid drug is administrated. The curative effects was classfide into four groups: complete remission, excellence, parts of remission, no effect. Results: 47 were complete remission, 34 were excellence, 10 were the parts of remission and 0 was no effects. The total effective power was 100%. Conclusions: Therapy with low-dose of mi for younger with Graves' disease is an effect, simple and safe method. Repeating treatment with 131 I will improve the curative rate of Graves' disease in younger, and the incidence of hypothyroidism cannot be increased. (authors)

Treatment results by uneven fractionated irradiation, low-dose rate telecobalt therapy as a boost, and intraoperative irradiation for malignant glioma

Energy Technology Data Exchange (ETDEWEB)

Yamada, Shogo; Takai, Yoshihiro; Nemoto, Kenji; Ogawa, Yoshihiro; Kakuto, Yoshihisa; Hoshi, Akihiko; Sakamoto, Kiyohiko; Kayama, Takamasa; Yoshimoto, Takashi (Tohoku Univ., Sendai (Japan). School of Medicine)

1992-08-01

The prognosis of malignant glioma is extremely poor. We applied conventionally fractionated irradiation combined with 1-(4-aminio-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), uneven fractionated irradiation with ACNU, low dose rate telecobalt therapy as a boost, and intraoperative irradiation against 110 malignant gliomas to investigate the efficacy of these methods as alternative treatments for malignant glioma. Although local tumor control by uneven fractionated irradiation was better than that by the other methods, no significant improvement was obtained in survival rates. As a result of multiple regression analysis, age and histology were major factors for survival rates, and the difference of treatment methods was not important. Both low-dose rate telecobalt therapy as a boost and intraoperative irradiation showed little advantage because of the high risk of brain necrosis associated with them. (author).

Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer

International Nuclear Information System (INIS)

Minsky, Bruce D.; Cohen, Alfred M.; Enker, Warren E.; Saltz, Leonard; Guillem, Jose G.; Paty, Philip B.; Kelsen, David P.; Kemeny, Nancy; Ilson, David; Bass, Joanne; Conti, John

1997-01-01

Purpose: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer. Methods and Materials: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU. Results: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%). Conclusion: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response

Dose, time and volume effects in interstitial radiation therapy

International Nuclear Information System (INIS)

Burgers, J.M.V.

1982-01-01

This study presents the main features and uncertainties of interstitial therapy and was undertaken to examine whether differences could be found in different clinical situations treated by interstitial implants with removable sources, that were not simply related to dose. In chapter 2, dating from 1978, continuous low dose rate irradiation is discussed from the radiobiological point of view together with some points related to variation in dose rate. A benefit of continuous low dose rate irradiation could be surmised in a few situations with special cell-kinetic properties. The problem of dose specification, the sharp dose gradient and other volume characteristics are discussed in chapter 3. Possible adjustments to variations in dose rate are discussed in chapter 4. The clinical material is reviewed in chapter 5, including aspects of dose specification, dose fall-off and variation in dose rate. The general discussion and conclusions are given in chapter 6. (Auth.)

Low-dose thiopurine with allopurinol co-therapy overcomes thiopurine intolerance and allows thiopurine continuation in inflammatory bowel disease.

Science.gov (United States)

Vasudevan, Abhinav; Beswick, Lauren; Friedman, Antony B; Moltzen, Alicia; Haridy, James; Raghunath, Ajay; Sparrow, Miles; van Langenberg, Daniel

2018-02-10

To assess the utility and tolerability of thiopurine-allopurinol co-therapy in inflammatory bowel disease (IBD) patients with intolerance to thiopurine monotherapy. A retrospective observational study assessed cases of thiopurine intolerance then switched to thiopurine allopurinol co-therapy between 2011 and 2015 at two centres. Indications for switch, dosing and subsequent clinical outcomes (including thiopurine persistence) were recorded. Of 767 patients on thiopurines for IBD, 89 (12%) were switched to co-therapy for intolerance. 64/89 (72%) had Crohn's disease, 38 (43%) were males, median age at switch was 40y (range 17-78), median IBD duration 6y (0-29). Median follow-up was 1.9y (0-5). Reasons for switching to co-therapy included fatigue (37%), hepatotoxicity (23%), nausea (23%), arthralgia (10%), headache (12%) and hypersensitivity reaction (4%). Overall, 66 (74%) patients remained on co-therapy until most recent review and achieved a clinical response. High rates of overcoming intolerance (62-100%) occurred with co-therapy for all reasons above, although fatigue was less amenable to switching than non-fatigue indications (62% vs 91%, p = <0.001). Of 34 patients not escalated to biologics with endoscopic data, 15 were in remission (44%) at most recent review. Low-dose thiopurine combined with allopurinol appears safe and effective in overcoming intolerances to thiopurine monotherapy in many cases. Copyright © 2018. Published by Elsevier Ltd.

Low-Dose (10-Gy) Total Skin Electron Beam Therapy for Cutaneous T-Cell Lymphoma: An Open Clinical Study and Pooled Data Analysis

Energy Technology Data Exchange (ETDEWEB)

Kamstrup, Maria R., E-mail: mkam0004@bbh.regionh.dk [Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen (Denmark); Gniadecki, Robert [Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen (Denmark); Iversen, Lars [Department of Dermatology, Aarhus University Hospital, Aarhus (Denmark); Skov, Lone [Department of Dermatology, Gentofte Hospital, University of Copenhagen, Copenhagen (Denmark); Petersen, Peter Meidahl [Department of Oncology and Hematology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Loft, Annika [Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Specht, Lena [Department of Oncology and Hematology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark)

2015-05-01

Purpose: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments 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 <2.5 weeks, receiving a total dose of 10 Gy in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. Results: The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (<1% skin involvement with patches or plaques) documented in 57% of the patients. Median duration of overall cutaneous response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. Conclusions: 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.

Financial impact of outpatient clinic radioiodine therapy with sodium iodide I-131 for the treatment of patients with differentiated low-risk thyroid carcinoma in relation to hospital doses

International Nuclear Information System (INIS)

Berenguer, P.F.; Chang, T.M.C.; Silva, R.A.M.; Neto, A.H.D.; Belo, I.B.; Santos, M.A.P.

2017-01-01

Differential thyroid carcinoma (CDT) is the most prevalent endocrine malignancy in the world, with an excellent prognosis and a 10-year survival rate of over 95%. By 2013, the lowest activity of I-131 authorized by the Brazilian Unified Health System (SUS) in the therapy of patients with low-risk CDT was 3,700 MBq, requiring hospitalization. Recent studies have shown similar effectiveness between low and high doses of I-131 in the treatment of low-risk CDT. In 2014, the Ministry of Health included in the list of SUS procedures the use of lower activities (1,110 MBq and 1,850 MBq) for this purpose. The Brazilian National Nuclear Energy Commission (CNEN) also authorized the outpatient use of activity up to 1,850 MBq of I-131. Objective: To evaluate the financial impact of the adoption of ambulatory radioiodine therapy in patients with CDT of low-risk when compared to the hospital dose. Methods: Analysis of patients with CDT low-risk who were treated with an outpatient dose of I-131 from August / 2014 to January / 2017 at a nuclear medicine service in Recife, PE, Brazil. The cost of outpatient versus hospital doses was calculated. Results: A total of 289 patients underwent low doses of iodine therapy were evaluated, resulting in a savings of R$227,793.80. Conclusion: Outpatient radioiodine therapy in the treatment of patients with CDT of low-risk resulted in a 61.10% reduction in SUS expense, in addition to enabling faster care

Suppression of experimental tractional retinal detachment by low-dose radiation therapy

International Nuclear Information System (INIS)

Meredith, T.A.; Ficker, L.; Stevens, R.; Olkowski, Z.; Anderson, M.; Hartmann, J.; Crocker, I.

1988-01-01

We used a standardized model of traction retinal detachment (TRD) created by cellular membranes in the rabbit to test the effects of low-dose radiation therapy in suppressing TRD. The vitreous and lens were removed from pigmented rabbits, and homologous conjunctival fibroblasts were grown in cell culture. After resolution of postoperative inflammation, 50,000 fibroblasts in 0.1 mL of culture fluid were injected into the vitreous cavity. Ten eyes were maintained as controls. Nineteen eyes received 6 Gy (600 rad) of x-ray irradiation one to three hours after cellular injection. Eyes were monitored weekly for three weeks with indirect ophthalmoscopy. Seven (70%) of ten control eyes developed TRD at one week; no additional TRDs were noted at weeks 2 and 3. Significantly smaller numbers of irradiated eyes developed TRD: at week 1, two (11%) of 19; at week 2, five (28%) of 18; and at week 3, five (29%) of 17

Gastrointestinal Dose-Histogram Effects in the Context of Dose-Volume–Constrained Prostate Radiation Therapy: Analysis of Data From the RADAR Prostate Radiation Therapy Trial

Energy Technology Data Exchange (ETDEWEB)

Ebert, Martin A., E-mail: Martin.Ebert@health.wa.gov.au [Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia (Australia); School of Physics, University of Western Australia, Perth, Western Australia (Australia); Foo, Kerwyn [Sydney Medical School, University of Sydney, Sydney, New South Wales (Australia); Haworth, Annette [Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria (Australia); Gulliford, Sarah L. [Joint Department of Physics, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, Sutton, Surrey (United Kingdom); Kennedy, Angel [Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia (Australia); Joseph, David J. [Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia (Australia); School of Surgery, University of Western Australia, Perth, Western Australia (Australia); Denham, James W. [School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales (Australia)

2015-03-01

Purpose: To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma. Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint. Methods and Materials: Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with a comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose. Results: Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding. Conclusions: Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for

Gastrointestinal Dose-Histogram Effects in the Context of Dose-Volume–Constrained Prostate Radiation Therapy: Analysis of Data From the RADAR Prostate Radiation Therapy Trial

International Nuclear Information System (INIS)

Ebert, Martin A.; Foo, Kerwyn; Haworth, Annette; Gulliford, Sarah L.; Kennedy, Angel; Joseph, David J.; Denham, James W.

2015-01-01

Purpose: To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma. Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint. Methods and Materials: Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with a comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose. Results: Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding. Conclusions: Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for

Effects of low dose mitomycin C on experimental tumor radiotherapy

International Nuclear Information System (INIS)

Yang Jianzheng; Liang Shuo; Qu Yaqin; Pu Chunji; Zhang Haiying; Wu Zhenfeng; Wang Xianli

2001-01-01

Objective: To evaluate the possibility of low dose mitomycin C(MMC) as an adjunct therapy for radiotherapy. Methods: Change in tumor size tumor-bearing mice was measured. Radioimmunoassay was used to determine immune function of mice. Results: Low dose Mac's pretreatment reduced tumor size more markedly than did radiotherapy only. The immune function in mice given with low dose MMC 12h before radiotherapy was obviously higher than that in mice subjected to radiotherapy only (P<0.05), and was close to that in the tumor-bearing mice before radiotherapy. Conclusion: Low dose MMC could improve the radiotherapy effect. Pretreatment with low dose MMC could obviously improve the immune suppression state in mice caused by radiotherapy. The mechanism of its improvement of radiotherapeutic effect by low dose of MMC might be due to its enhancement of immune function and induction of adaptive response in tumor-bearing mice

Low dose ketamine use in the emergency department, a new direction in pain management.

Science.gov (United States)

Pourmand, A; Mazer-Amirshahi, M; Royall, C; Alhawas, R; Shesser, R

2017-06-01

There is a need for alternative non-opioid analgesics for the treatment of acute, chronic, and refractory pain in the emergency department (ED). Ketamine is a fast acting N-methyl-d-aspartate (NMDA) receptor antagonist that provides safe and effective analgesia. The use of low dose ketamine (LDK) (Ketamine was shown to be efficacious at treating a variety of painful conditions. It has a favorable adverse effect profile when given at sub-dissociative doses. Studies have also compared LDK to opioids in the ED. Although ketamine's analgesic effects were not shown to be superior, they were comparable to opioids. LDK has the benefit of causing less respiratory depression. It likely has less wide spread potential for abuse. Nursing protocols for the administration of LDK have been studied. We believe that LDK has the potential to be a safe and effective alternative and/or adjunct to opioid analgesics in the ED. Additional studies are needed to expand upon and determine the optimal use of LDK in the ED. Copyright © 2017 Elsevier Inc. All rights reserved.

Biological influence from low dose and low-dose rate radiation

International Nuclear Information System (INIS)

Magae, Junji

2007-01-01

Although living organisms have defense mechanisms for radioadaptive response, the influence is considered to vary qualitatively and quantitatively for low dose and high dose, as well as for low-dose rate and high-dose rate. This article describes the bioresponse to low dose and low-dose rate. Among various biomolecules, DNA is the most sensitive to radiation, and accurate replication of DNA is an essential requirement for the survival of living organisms. Also, the influence of active enzymes resulted from the effect of radiation on enzymes in the body is larger than the direct influence of radiation on the body. After this, the article describes the carcinogenic risk by low-dose radiation, and then so-called Hormesis effect to create cancer inhibition effect by stimulating active physiology. (S.K.)

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

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

International Nuclear Information System (INIS)

Georg, Dietmar; Hopfgartner, Johannes; Gòra, Joanna; Kuess, Peter; Kragl, Gabriele; Berger, Daniel; Hegazy, Neamat; Goldner, Gregor; Georg, Petra

2014-01-01

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 ( 192 Ir) and LDR-BT ( 125 I) were D 90% ≥34 Gy in 8.5 Gy per fraction and D 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 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 were clearly superior in

Microfluidic thrombosis under multiple shear rates and antiplatelet therapy doses.

Directory of Open Access Journals (Sweden)

Melissa Li

Full Text Available The mainstay of treatment for thrombosis, the formation of occlusive platelet aggregates that often lead to heart attack and stroke, is antiplatelet therapy. Antiplatelet therapy dosing and resistance are poorly understood, leading to potential incorrect and ineffective dosing. Shear rate is also suspected to play a major role in thrombosis, but instrumentation to measure its influence has been limited by flow conditions, agonist use, and non-systematic and/or non-quantitative studies. In this work we measured occlusion times and thrombus detachment for a range of initial shear rates (500, 1500, 4000, and 10000 s(-1 and therapy concentrations (0-2.4 µM for eptifibatide, 0-2 mM for acetyl-salicylic acid (ASA, 3.5-40 Units/L for heparin using a microfluidic device. We also measured complete blood counts (CBC and platelet activity using whole blood impedance aggregometry. Effects of shear rate and dose were analyzed using general linear models, logistic regressions, and Cox proportional hazards models. Shear rates have significant effects on thrombosis/dose-response curves for all tested therapies. ASA has little effect on high shear occlusion times, even at very high doses (up to 20 times the recommended dose. Under ASA therapy, thrombi formed at high shear rates were 4 times more prone to detachment compared to those formed under control conditions. Eptifibatide reduced occlusion when controlling for shear rate and its efficacy increased with dose concentration. In contrast, the hazard of occlusion from ASA was several orders of magnitude higher than that of eptifibatide. Our results show similar dose efficacy to our low shear measurements using whole blood aggregometry. This quantitative and statistically validated study of the effects of a wide range of shear rate and antiplatelet therapy doses on occlusive thrombosis contributes to more accurate understanding of thrombosis and to models for optimizing patient treatment.

Dose specification for radiation therapy: dose to water or dose to medium?

International Nuclear Information System (INIS)

Ma, C-M; Li Jinsheng

2011-01-01

The Monte Carlo method enables accurate dose calculation for radiation therapy treatment planning and has been implemented in some commercial treatment planning systems. Unlike conventional dose calculation algorithms that provide patient dose information in terms of dose to water with variable electron density, the Monte Carlo method calculates the energy deposition in different media and expresses dose to a medium. This paper discusses the differences in dose calculated using water with different electron densities and that calculated for different biological media and the clinical issues on dose specification including dose prescription and plan evaluation using dose to water and dose to medium. We will demonstrate that conventional photon dose calculation algorithms compute doses similar to those simulated by Monte Carlo using water with different electron densities, which are close (<4% differences) to doses to media but significantly different (up to 11%) from doses to water converted from doses to media following American Association of Physicists in Medicine (AAPM) Task Group 105 recommendations. Our results suggest that for consistency with previous radiation therapy experience Monte Carlo photon algorithms report dose to medium for radiotherapy dose prescription, treatment plan evaluation and treatment outcome analysis.

Low-dose megavoltage cone-beam CT for radiation therapy

International Nuclear Information System (INIS)

Pouliot, Jean; Bani-Hashemi, Ali; Chen, Josephine; Svatos, Michelle; Ghelmansarai, Farhad; Mitschke, Matthias; Aubin, Michele; Xia Ping; Morin, Olivier; Bucci, Kara; Roach, Mack; Hernandez, Paco; Zheng Zirao; Hristov, Dimitre; Verhey, Lynn

2005-01-01

Purpose: The objective of this work was to demonstrate the feasibility of acquiring low-exposure megavoltage cone-beam CT (MV CBCT) three-dimensional (3D) image data of sufficient quality to register the CBCT images to kilovoltage planning CT images for patient alignment and dose verification purposes. Methods and materials: A standard clinical 6-MV Primus linear accelerator, operating in arc therapy mode, and an amorphous-silicon (a-Si) flat-panel electronic portal-imaging device (EPID) were employed. The dose-pulse rate of a 6-MV Primus accelerator beam was windowed to expose an a-Si flat panel by using only 0.02 to 0.08 monitor units (MUs) per image. A triggered image-acquisition mode was designed to produce a high signal-to-noise ratio without pulsing artifacts. Several data sets were acquired for an anthropomorphic head phantom and frozen sheep and pig cadaver heads, as well as for a head-and-neck cancer patient on intensity-modulated radiotherapy (IMRT). For each CBCT image, a set of 90 to 180 projection images incremented by 1 deg to 2 deg was acquired. The two-dimensional (2D) projection images were then synthesized into a 3D image by use of cone-beam CT reconstruction. The resulting MV CBCT image set was used to visualize the 3D bony anatomy and some soft-tissue details. The 3D image registration with the kV planning CT was performed either automatically by application of a maximization of mutual information (MMI) algorithm or manually by aligning multiple 2D slices. Results: Low-noise 3D MV CBCT images without pulsing artifacts were acquired with a total delivered dose that ranged from 5 to 15 cGy. Acquisition times, including image readout, were on the order of 90 seconds for 180 projection images taken through a continuous gantry rotation of 180 deg . The processing time of the data required an additional 90 seconds for the reconstruction of a 256 3 cube with 1.0-mm voxel size. Implanted gold markers (1 mm x 3 mm) were easily visible for all exposure

Low-Dose Adefovir-Induced Hypophosphatemic Osteomalacia on Whole-Body Bone Scintigraphy

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Kim, Sung Hoon; Won, Kyoung Sook; Song, Bongil; Jo, Il; Zeon, Seok Kil [Keimyung Univ., Daegu (Korea, Republic of)

2013-12-15

While adefovir dipivoxil (ADV) effectively suppresses the hepatitis B virus, it can cause proximal renal tubular dysfunction leading to phosphate wasting. The safety of low-dose ADV (a dose of 10 mg/day), which does not induce clinically significant nephrotoxicity, is well recognized, but a few cases of hypophosphatemic osteomalacia (HO) caused by low-dose ADV therapy have recently been reported. Although HO induced by low-dose ADV therapy is rare, the presence of bone pain in patients treated with ADV should be monitored. Bone scintigraphy can be performed to confirm the occurrence of osteomalacia and to determine the disease extent. Bone scintigraphic and radiological image findings with a brief review of the literature are presented in this article. We report two cases of HO induced by low-dose ADV therapy that showed multifocal increased radiotracer uptakes in the bilateral bony ribs, spines, pelvic bones and lower extremities on whole-body bone scintigraphy. Bone pain gradually improved after phosphate supplementation and by changing the antiviral agent. Whole-body bone scintigraphy is a highly sensitive imaging tool and can show disease extent at once in the setting of the wide range of the clinical spectrum with nonspecific radiological findings. Furthermore, frequent involvement of the lower extremities, as a result of maximum weight bearing, could be an additional scintigraphic clue for the diagnosis of HO. These cases could be helpful for both clinicians prescribing ADV and nuclear physicians to prevent delayed diagnosis and plan further appropriate treatment.

Low-Dose Adefovir-Induced Hypophosphatemic Osteomalacia on Whole-Body Bone Scintigraphy

International Nuclear Information System (INIS)

Kim, Sung Hoon; Won, Kyoung Sook; Song, Bongil; Jo, Il; Zeon, Seok Kil

2013-01-01

While adefovir dipivoxil (ADV) effectively suppresses the hepatitis B virus, it can cause proximal renal tubular dysfunction leading to phosphate wasting. The safety of low-dose ADV (a dose of 10 mg/day), which does not induce clinically significant nephrotoxicity, is well recognized, but a few cases of hypophosphatemic osteomalacia (HO) caused by low-dose ADV therapy have recently been reported. Although HO induced by low-dose ADV therapy is rare, the presence of bone pain in patients treated with ADV should be monitored. Bone scintigraphy can be performed to confirm the occurrence of osteomalacia and to determine the disease extent. Bone scintigraphic and radiological image findings with a brief review of the literature are presented in this article. We report two cases of HO induced by low-dose ADV therapy that showed multifocal increased radiotracer uptakes in the bilateral bony ribs, spines, pelvic bones and lower extremities on whole-body bone scintigraphy. Bone pain gradually improved after phosphate supplementation and by changing the antiviral agent. Whole-body bone scintigraphy is a highly sensitive imaging tool and can show disease extent at once in the setting of the wide range of the clinical spectrum with nonspecific radiological findings. Furthermore, frequent involvement of the lower extremities, as a result of maximum weight bearing, could be an additional scintigraphic clue for the diagnosis of HO. These cases could be helpful for both clinicians prescribing ADV and nuclear physicians to prevent delayed diagnosis and plan further appropriate treatment

Dose monitoring in nuclear emergency

International Nuclear Information System (INIS)

Nan Hongjie; Yang Zhongping; Lei Xin

2012-01-01

In order to protect people from irradiation sickness and rebuild the radiation filed in nuclear emergency, personal and environmental dose need to be monitored. The application of TLD in dose monitoring is discussed in this paper. (authors)

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis.

Science.gov (United States)

Lee, Eun Nam; Lee, Jae Hoon

2016-01-01

Currently ketamine is not used often as an analgesic in the emergency department (ED). Nonetheless, it can increase the efficiency of opioids and decrease their side effects. The purpose of this systematic review and meta-analysis was to evaluate whether low-dose ketamine in the ED provides better analgesia with fewer adverse effects. The PubMed, EMBASE, and Cochrane Library databases were searched by two reviewers independently (last search performed on January 2016). Data were also extracted independently. A total of 6 trials involving 438 patients were included in the current analysis. Our subgroup analysis of pain reduction indicates that the favorable effects of ketamine were similar or superior to those of placebo or opioids, although these effects were heterogeneous. However, low-dose ketamine was associated with a higher risk of neurological (relative risk [RR] = 2.17, 95% confidence interval [CI] = 1.37-3.42, P ketamine varies depending on the pain site, but low-dose ketamine may be a key agent for pain control in the ED, as it has no side effects. It may also help to reduce the side effects of opioids.

Combination therapy with rituximab, low-dose cyclophosphamide, and prednisone for idiopathic membranous nephropathy: a case series.

Science.gov (United States)

Cortazar, Frank B; Leaf, David E; Owens, Charles T; Laliberte, Karen; Pendergraft, William F; Niles, John L

2017-02-01

Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted.

Palliation by Low-Dose Local Radiation Therapy for Indolent Non-Hodgkin Lymphoma

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Chan, Elisa K. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Fung, Sharon [Department of Clinical Study Coordination and Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Gospodarowicz, Mary; Hodgson, David; Wells, Woodrow; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Pintile, Melania [Department of Clinical Study Coordination and Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Southlake Regional Health Centre, Newmarket, Ontario (Canada); Tsang, Richard W., E-mail: richard.tsang@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)

2011-12-01

Purpose: The purpose of this study was to assess the efficacy of a 2 Multiplication-Sign 2 Gy (total dose, 4 Gy) palliative radiation therapy (RT) regimen for treating patients with indolent non-Hodgkin lymphoma (NHL) in terms of response rate, response duration, and symptom relief. Methods and Materials: A retrospective chart review was conducted. Between 2003 and 2007, 54 patients with NHL were treated to 85 anatomical sites with a 2 Multiplication-Sign 2 Gy palliative regimen. Local response was assessed by clinical and/or radiographic data. Symptoms before and after treatment for each site treated were obtained from clinical notes in patient medical records. Median follow-up time was 1.3 years. Results: For the 54 patients, the median age at time of treatment was 71.1 years old, and 57% of them were male. Of the 85 disease sites treated, 56% of sites had indolent histology, 28% of sites were diagnosed with chronic lymphocytic leukemia (CLL), 13% of sites had aggressive histology, and 2% of sites were shown to have other histology. Overall response rate (ORR) was 81% (49% complete response [CR], 32% partial response [PR]). The 2-year rate for freedom from local progression was 50% (95% CI, 37%-61%). The ORR for follicular lymphoma, Mucosa associated lymphoid tissue (MALT), and marginal zone lymphoma (MZL) histology was 88%, compared with a 59% rate for CLL histology (p = 0.005). While the ORR was similar for tumors of different sizes, the CR rate for patients with tumors <5 cm tended to be higher than those with tumors >10 cm (CR rate of 57% vs. 27%, respectively; p = 0.06). For the 48 sites with clearly documented symptoms at pretreatment, 92% of sites improved after low-dose RT. Conclusions: Short-course low-dose palliative radiotherapy (2 Multiplication-Sign 2 Gy) is an effective treatment that results in high response rates for indolent non-Hodgkin lymphoma. This treatment regimen provides effective symptomatic relief for tumor bulk of all sizes.

Sevoflurane-emergence agitation: Effect of supplementary low-dose oral ketamine premedication in preschool children undergoing dental surgery

Directory of Open Access Journals (Sweden)

Khattab Ahmed

2009-01-01

Full Text Available Background and Objectives: The use of sevoflurane in pediatric anesthesia, which could enable a more rapid emergence and recovery, is complicated by the frequent occurrence of post-anesthesia agitation. This study aims to test the efficacy of adding a low dose of ketamine orally, as a supplement to the midazolam-based oral premedication for reducing sevoflurane-related emergence agitation. Materials and Methods: Ninety-two preschool children, aged between two and six years, with an American Society of Anesthesiologists physical status I or II, scheduled for elective dental filling and extractions under general anesthesia were included. The patients were allocated into two groups: Group M (46 patients received oral midazolam 0.5 mg/kg, mixed with ibuprofen 10 mg/kg, while group KM (46 patients received a similar premedication mixture, in addition to ketamine 2 mg/kg. The acceptance of the drug mixture, the onset of action, and the occurrence of vomiting were monitored over the next 30 minutes. Induction of anesthesia was carried out using sevoflurane 8 Vol% in 100% oxygen via face mask. Anesthesia was maintained with sevoflurane 1.5-2 Vol% in an oxygen-nitrous oxide mixture. After extubation, the standard scoring scale was used for assessing the quality of emergence. Agitation parameters were measured using a five-point scale. Agitated children were managed by giving intravenous increments of fentanyl 1 μg/ kg. The time of hospital discharge allowance was recorded. Results: Drug palatability, vomiting, and onset of action of premedication; showed no significant differences between both groups. Time of eye opening after discontinuation of sevoflurane showed no significant differences between both groups. Postoperative agitation score and rescue fentanyl consumption were higher in group M than in group KM on admission to the PACU ( P < 0.01. The time of hospital discharge allowance in group M was longer than in group KM ( P< 0.05. Conclusion

Low dose rate and high dose rate intracavitary treatment for cervical cancer

International Nuclear Information System (INIS)

Hareyama, Masato; Oouchi, Atsushi; Shidou, Mitsuo

1997-01-01

From 1984 through 1993, 144 previous untreated patients with carcinoma of uterine cervix were treated with either low dose rate 137 Cs therapy (LDR) or high dose rate 60 Co therapy (HDR). The local failure rates for more than 2-years for the primary lesions were 11.8% (8 of 63 patients) for LDR and 18.0% (11 of 61 patients). Rectal complication rates were significantly lower for HDR versus LDR (14.3% VS. 32.8%. p<0.01). Also, bladder complication rates were significantly lower for HDR versus LDR (0% VS. 10.4%, p<0.005). Treatment results in term of local control were equivalent for HDR and LDR treatment. However, the incidence of complications was higher for the LDR group than for the HDR group. (author)

The Comparison of Two Types of Treatment (High Dose and Low Dose IVIG in Children with GBS in Mofid Hospital

Directory of Open Access Journals (Sweden)

Parvaneh Karim-Zadeh

2003-12-01

Full Text Available Objective: Acute inflammatory demyelinating peripheral neuropathy (Guillain-Barre-Syndrome is by far the most common cause of immune–mediated peripheral nerve disease in children and with the near disappearance of poliomyelitis, is responsible for the great majority of cases of acute flaccid paralysis. Several controlled studies have done with corticosteroids, plasma pheresis and IVIG in pediatric patients. IVIG treatment can be done in two types of treatment: 1- High dose that means 1gr/kg/day for 2 days. 2- Low dose that means 400mg/kg/day for 5 days. Several studies in other countries have shown faster rate of recovery in patients who received total dose of IVIG in 2 days as opposed to 5 days. Materials & Methods: Because we have not any study about this two types of treatment in IRAN we decided to comparison this two types of IVIG treatment. So the patients that referred to Mofid children hospital for weakness and we diagnosed GBS (with history, physical examination, laboratories and EMG-NCV are divided in two groups: 1- High dose IVIG treatment (experimental group. 2- Low dose IVIG treatment (control group Then the results evaluated. Results: Our findings included that in high dose IVIG therapy we have faster rate of recovery and the Hospital stay is shorter than low dose IVIG-therapy. Also in this type of treatment “because the patients cure faster” , so complications are decreased in them. In the group of high dose IVIG therapy, lower and upper extremities weakness decreased in time. Conclusion: We did not receive any relationship between side effects of drugs and the type of treatment. The relationship between high dose IVIG therapy and drug side effects was not significant.

Optimal dose-response relationships in voice therapy.

Science.gov (United States)

Roy, Nelson

2012-10-01

Like other areas of speech-language pathology, the behavioural management of voice disorders lacks precision regarding optimal dose-response relationships. In voice therapy, dosing can presumably vary from no measurable effect (i.e., no observable benefit or adverse effect), to ideal dose (maximum benefit with no adverse effects), to doses that produce toxic or harmful effects on voice production. Practicing specific vocal exercises will inevitably increase vocal load. At ideal doses, these exercises may be non-toxic and beneficial, while at intermediate or high doses, the same exercises may actually be toxic or damaging to vocal fold tissues. In pharmacology, toxicity is a critical concept, yet it is rarely considered in voice therapy, with little known regarding "effective" concentrations of specific voice therapies vs "toxic" concentrations. The potential for vocal fold tissue damage related to overdosing on specific vocal exercises has been under-studied. In this commentary, the issue of dosing will be explored within the context of voice therapy, with particular emphasis placed on possible "overdosing".

Low dose versus high dose anti-snake venom therapy in the treatment of haematotoxic snake bite in South India.

Science.gov (United States)

Joseph, Imanto M; Kuriakose, Cijoy K; Dev, Anand Vimal; Philip, George A

2017-10-01

Most of the studies on the appropriate dose of anti-snake venom (ASV) are from tertiary hospitals and the guidelines are unclear. Our observational study compared the outcomes of two prevalent treatment regimes for haematotoxic snake bite in a secondary care hospital in South India. The time to normalisation of whole blood clotting time, mortality and complications were not different between the groups. The average dose of ASV required in the low and high dose groups were 106 mL and 246 mL, respectively. Consequently, patients who received low dose ASV incurred approximately 50% less expense. Urticarial rashes were also significantly fewer in the low dose group.

Low dose irradiation reduces cancer mortality rates

International Nuclear Information System (INIS)

Luckey, T.D.

2000-01-01

. Increased production of many molecules (interleukins, interferons, leukotrienes, chemotactic agents, and mitogens) related to immunity are found in mice exposed to low dose irradiation (Lim, S.-Z., Biologic Effects of Low Level Exposures to Radiation and Related Agents, pp.15-16, 1993). Those plus many enzymes and cofactors are inter- and intra-cellular agents involved in gene expression, T-cell maturation, phagocytosis, signal transduction, antigen reception and antibody production. This basic science information has been utilized for cancer therapy in Japanese and United States clinics. With the usual radio-, chemo- and surgical therapy, the 10 year survival of non-Hodgkin's lymphoma was 59%; when this was augmented by low dose irradiation, survival was 80% (Sakamoto, K., ICONE-7 Abstracts, p 50-51, 1999). Low dose irradiation of the mid-section of the body was effective. This area includes many elements of the immune system: the spleen with its germinal centers and lymphoid follicles, the liver with its phagocytosing Kupffer cells, kidney phagocytes, and the lamina propria and Peyer's patches of the intestinal wall. Irradiation of either the head and chest or the groin-legs area was unresponsive. Chronic low dose irradiation redness premature cancer mortality 51%. Standards should be revised with health, not risks, as the goal. Safe supplementation with ionizing radiation would provide a new plateau of health for people and wealth for nations. (author)

Touch screen man machine interfere for emergency dose calculations

International Nuclear Information System (INIS)

Woodard, K.; Abrams, M.

1987-01-01

Emergency dose calculation systems generally use a keyboard to provide the interface between the user and the computer. This interface is preferred by users who work daily with computers; however, for many plant personnel who are not continuously involved with computer operations, the use of a keyboard can be cumbersome and time consuming. This is particularly true when the user is under pressure during a drill or an actual emergency. Experience in many applications of Pickard, Lowe and Garrick's PLG's Meteorological Information and Dose Assessment System (MIDAS) has shown that user friendliness is a key ingredient toward achieving acceptance of computerized systems. Hardware to support to touch screen interface is now available and has been implemented in MIDAS. Recent experience has demonstrated that selection times for dose calculations are reduced, data entry errors have been minimized, and confusion over appropriate entries has been avoided due to the built-in logic. A 10-yr search for an acceptable keyboard replacement has ended

Low-dose insulin therapy and nursing of children with diabetic ketoacidosis%小剂量胰岛素治疗儿童糖尿病酮症酸中毒及护理

Institute of Scientific and Technical Information of China (English)

王九珍

2011-01-01

目的 探讨小剂量胰岛素持续滴注治疗儿童糖尿病酮症酸中毒的护理方法.方法 对8例1型糖尿病酮症酸中毒患儿,在积极抢救治疗的基础上,注意严密观察病情变化,给予正确的液体治疗、小剂量胰岛素等治疗及护理.结果 8例患儿均好转,原发病病情稳定,血糖控制满意.结论 小剂量胰岛素法治疗糖尿病酮症酸中毒易于掌握,安全有效.护士熟练掌握儿童糖尿病酮症酸中毒抢救治疗护理的程序,对抢救患儿的生命起着重要的作用,做好监测、液体治疗、胰岛素的正确、精确的应用等都是控制本病的关键.%Objective To explore the nursing measures for the low - dose insulin continuous infusion therapy in children with diabetic ketoacidosis. Methods Being kept a strict watch over to note the slightest change in them, 8 cases of type 1 diabetic ketoacidosis in children were given correct fluid therapy, low - dose insulin treatment and nursing methods on the basis of active emergency treatment. Results The state of illness in all patients was improved, the primary disease in stable condition, the serum glucose controlled satisfactorily. Conclusions It is manageable, safe and effective to take low dose insulin treatment on diabetic ketoacidosis patients. Nurses' mastering of nursing procedure in emergency treatment of children with diabetic ketoacidosis plays an important role in saving patients' lives, and the key to control the disease is careful monitoring, fluid therapy,sophisticated use of insulin.

Low doses effects and gamma radiations low dose rates

International Nuclear Information System (INIS)

Averbeck, D.

1999-01-01

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.)

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

Energy Technology Data Exchange (ETDEWEB)

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)

Total Skin Electron Beam Therapy in the Treatment of Mycosis Fungoides: A Review of Conventional and Low-Dose Regimens.

Science.gov (United States)

Chowdhary, Mudit; Chhabra, Arpit M; Kharod, Shivam; Marwaha, Gaurav

2016-12-01

Mycosis fungoides (MF) is the most prevalent subtype of cutaneous T-cell lymphoma, which is characterized by the proliferation of CD4 + T cells. While often an indolent disease, most patients eventually develop progression from isolated patches to tumors and finally nodal or visceral involvement. Treatment choice is largely based on disease burden, though prognostic factors such as disease stage, patient age, and extracutaneous involvement must be taken into consideration. Radiotherapy represents one of the most effective therapeutic modalities in the treatment of MF. Lymphocytes are exquisitely radiosensitive, and excellent responses are observed even with low doses of radiation. Total skin electron beam therapy (TSEBT) is a special technique that allows for the homogenous irradiation of the entire skin. There are well-documented radiation dose-response relationships for achieving a complete response. As such, TSEBT doses ≥ 30 Gy comprise the current standard of care. Although highly effective, most patients experience recurrent disease even after conventional-dose (≥ 30 Gy) TSEBT. In addition, toxicity is cumulatively dose dependent, and there is reluctance to administer multiple courses of conventional-dose TSEBT. Consequently, there has been renewed interest in determining the utility of TSEBT at lower total (≤ 30 Gy) doses. Advantages of low-total-dose (with standard dose per fraction) TSEBT include a shortened treatment course, the potential to minimize the risk of adverse events, and the opportunity to allow for retreatment in cases of disease recurrence. This comprehensive review compares the impact of different TSEBT dosing schemes on clinical outcomes of MF. Copyright © 2016 Elsevier Inc. All rights reserved.

Low-dose narrow-band UVB phototherapy combined with topical therapy is effective in psoriasis and does not inhibit systemic T-cell activation

NARCIS (Netherlands)

de Rie, M. A.; Out, T. A.; Bos, J. D.

1998-01-01

Psoriasis is a chronic T-cell-mediated inflammatory skin disease which can be treated with topical medication, phototherapy or systemic medication. A subgroup of psoriatic patients does not respond to monotherapy and needs combination therapy. We used low-dose narrow-band UVB phototherapy, combined

Health effect of low dose/low dose rate radiation

International Nuclear Information System (INIS)

Kodama, Seiji

2012-01-01

The clarified and non-clarified scientific knowledge is discussed to consider the cause of confusion of explanation of the title subject. The low dose is defined roughly lower than 200 mGy and low dose rate, 0.05 mGy/min. The health effect is evaluated from 2 aspects of clinical symptom/radiation hazard protection. In the clinical aspect, the effect is classified in physical (early and late) and genetic ones, and is classified in stochastic (no threshold value, TV) and deterministic (with TV) ones from the radioprotection aspect. Although the absence of TV in the carcinogenic and genetic effects has not been proved, ICRP employs the stochastic standpoint from the safety aspect for radioprotection. The lowest human TV known now is 100 mGy, meaning that human deterministic effect would not be generated below this dose. Genetic deterministic effect can be observable only in animal experiments. These facts suggest that the practical risk of exposure to <100 mGy in human is the carcinogenesis. The relationship between carcinogenic risk in A-bomb survivors and their exposed dose are found fitted to the linear no TV model, but the epidemiologic data, because of restriction of subject number analyzed, do not always mean that the model is applicable even below the dose <100 mGy. This would be one of confusing causes in explanation: no carcinogenic risk at <100 mGy or risk linear to dose even at <100 mGy, neither of which is scientifically conclusive at present. Also mentioned is the scarce risk of cancer in residents living in the high background radiation regions in the world in comparison with that in the A-bomb survivors exposed to the chronic or acute low dose/dose rate. Molecular events are explained for the low-dose radiation-induced DNA damage and its repair, gene mutation and chromosome aberration, hypothesis of carcinogenesis by mutation, and non-targeting effect of radiation (bystander effect and gene instability). Further researches to elucidate the low dose

Validation of GPU based TomoTherapy dose calculation engine.

Science.gov (United States)

Chen, Quan; Lu, Weiguo; Chen, Yu; Chen, Mingli; Henderson, Douglas; Sterpin, Edmond

2012-04-01

The graphic processing unit (GPU) based TomoTherapy convolution/superposition(C/S) dose engine (GPU dose engine) achieves a dramatic performance improvement over the traditional CPU-cluster based TomoTherapy dose engine (CPU dose engine). Besides the architecture difference between the GPU and CPU, there are several algorithm changes from the CPU dose engine to the GPU dose engine. These changes made the GPU dose slightly different from the CPU-cluster dose. In order for the commercial release of the GPU dose engine, its accuracy has to be validated. Thirty eight TomoTherapy phantom plans and 19 patient plans were calculated with both dose engines to evaluate the equivalency between the two dose engines. Gamma indices (Γ) were used for the equivalency evaluation. The GPU dose was further verified with the absolute point dose measurement with ion chamber and film measurements for phantom plans. Monte Carlo calculation was used as a reference for both dose engines in the accuracy evaluation in heterogeneous phantom and actual patients. The GPU dose engine showed excellent agreement with the current CPU dose engine. The majority of cases had over 99.99% of voxels with Γ(1%, 1 mm) engine also showed similar degree of accuracy in heterogeneous media as the current TomoTherapy dose engine. It is verified and validated that the ultrafast TomoTherapy GPU dose engine can safely replace the existing TomoTherapy cluster based dose engine without degradation in dose accuracy.

Dose and volume specification for reporting interstitial therapy

International Nuclear Information System (INIS)

1997-01-01

The ICRU has previously published reports dealing with Dose Specification for Reporting External Beam Therapy with Photons and Electrons (ICRU Report 29, ICRU, 1978), Dose Specification for Reporting External Beam Therapy (ICRU Report 50, ICRU, 1993) and Dose and Volume Specification for Reporting Intracavitary Therapy in Gynecology (ICRU Report 38, ICRU, 1985). The present report addresses the problem of absorbed dose specification for report interstitial therapy. Although specific to interstitial therapy, many of the concepts developed in this report are also applicable to certain other kinds of brachytherapy applications. In particular, special cases of intraluminal brachytherapy and plesio-brachytherapy via surface molds employing x or gamma emitters are addressed in this report

High-dose radioiodine therapy of Graves disease

International Nuclear Information System (INIS)

Solodky, V.; Fomin, D.; Pestritskaya, E.

2015-01-01

Full text of publication follows. Objectives: to estimate the effectiveness and safety of the disease treatment under different modes of applying RIT. Materials and methods: 67 patients with the thyrotoxicosis condition associated with Graves disease were researched. The patients were divided into 2 groups: a control group with 25 people (18 women and 7 men), who underwent a low-dose therapy of 150-500 MBq; and a main group of 42 people (32 women and 10 men), who underwent a high-dose therapy of 550 and 800 MBq. The volume of thyroid prior to the treatment made up 23.8 ± 20 ml in the main group and 30.2 ± 23 ml in the control one. The average age in the high-dose group was 44.6 ±23 years old and in the low-dose -47.2 ± 24 years old. In terms of the hormone level before the RIT, 52% of the main group patients experienced euthyroidism, while 48% - thyrotoxicosis. The corresponding indices in the control group were 42% and 58% respectively. The cessation of the thyreostatic therapy came on 5. to 21. day prior to the treatment, with the average of 14 ±7 days in both groups. The diagnosis of the disease was based on ultrasonography, planar scintigraphy, the hormone level and antibody titer. The performance was assessed through the attainment of hypo-thyrosis and the transition to a substitutive hormonal therapy with L-thyroxine in 6 months or more. The attainment of euthyroidism was seen as a partial effect due to a possibility of relapse. Results: in 6 months a positive result in the form of hypo-thyrosis was achieved for 39 patients in the main group, which accounted for 93%, and 3 patients (7%) experienced euthyroidism. No symptomatic thyrotoxicosis relapses were revealed. In the control group, hypo-thyrosis was achieved by 18 patients, which accounted for 72%; euthyroidism came up to 12%; 4 patients needed a refresher course of RIT, which made up 16% of the group. 93% of the main group patients tolerated the treatment favourably. 3 patients complained of the

Research on low radiation doses - A better understanding of low doses

International Nuclear Information System (INIS)

2016-01-01

Radiation doses below 100 mSv are called low doses. Epidemiological research on the health hazards of low doses are difficult to do because numerous pathologies, particularly cancer, appear lifelong for genetical or environmental causes without any link with irradiation and it is very difficult to identify the real cause of a cancer. Another concern is that the impact on human health is weak and are observed only after a long period after irradiation. These features make epidemiological studies cumbersome to implement since they require vast cohorts and a very long-term follow-up. The extrapolation of the effects of higher doses to the domain of low doses does not meet reality and it is why the European Union takes part into the financing of such research. In order to gain efficiency, scientists work together through various European networks among them: HLEG (High Level Expert Group On European Low Dose Risk Research) or MELODI (Multidisciplinary European Low Dose Initiative). Several programs are underway or have been recently launched: -) the impact of Cesium contamination on children's health (Epice program), -) the study of the impact of medical imaging on children, -) the study of the health of children living near nuclear facilities, -) the relationship between radon and lung cancer, -) the effect of occupational low radiation doses, -) the effect of uranium dissolved in water on living organisms (Envirhom program). (A.C.)

Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in non-obese adolescents and women.

Science.gov (United States)

Ibáñez, Lourdes; de Zegher, Francis

2006-01-01

Polycystic ovary syndrome (PCOS) is a variable disorder that is characterized in adolescents and young women by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity and low-grade inflammation. At present, there is no approved therapy for PCOS. Recent studies indicate that a low-dose combination of flutamide (Flu; a generic androgen-receptor blocker) and metformin (Met; a generic insulin-sensitizer) normalizes the adolescent PCOS spectrum more than an oral contraceptive (OC); in young women, the PCOS spectrum was found to be more normalized by OC plus Flu-Met than by OC alone. Within the pathophysiological cascade of PCOS, Flu-Met seems to counter upstream anomalies like hyperinsulinemia or hyperandrogenism, thereby preventing or reversing downstream effects. In contrast, an OC essentially masks downstream symptoms like hirsutism, acne or irregular menses, whereas the upstream aberrations remain unaltered or may even be worsened. The available experience with Flu-Met is limited but promising. We emphasize that Flu-Met may (as part of its efficacy) induce ovulation but is contra-indicated post-conception because of potential embryotoxicity; therefore, it seems wise to combine Flu-Met with an oral or a transdermal oestro-progestagen or with a non-endocrine method of contraception. May this update prompt further research into Flu-Met's therapeutic potential in patients with PCOS. Until the abovementioned effects have been broadly confirmed, Flu-Met should not be regarded as a standard therapy for widespread clinical practice.

LOW-DOSE BROMOCRIPTINE-INDUCED PLEURAL EFFUSION AND PLEUROPULMONARY FIBROSIS

NARCIS (Netherlands)

BRUNT, ERP; BOEREE, MJ

We describe a parkinsonian patient who developed a slight asymptomatic pleural effusion during prolonged therapy with low dose bromocriptine (BCR) in addition to levodopa, following prior treatment with CQA 206-291. A moderate increase of BCR dosage prompted a severe pleuropulmonary inflammatory

Low-Dose Consolidation Radiation Therapy for Early Stage Unfavorable Hodgkin Lymphoma

Energy Technology Data Exchange (ETDEWEB)

Torok, Jordan A., E-mail: jordan.torok@dm.duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Wu, Yuan [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Prosnitz, Leonard R.; Kim, Grace J. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Beaven, Anne W.; Diehl, Louis F. [Division of Hematologic Malignancy and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Kelsey, Chris R. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

2015-05-01

Purpose: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. Methods and Materials: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achieve a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. Results: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. Conclusions: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.

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. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Malignant melanoma of the tongue following low-dose radiation

International Nuclear Information System (INIS)

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

1985-01-01

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

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.

Maximal safe dose therapy of I-131 after failure of standard fixed dose therapy in patients with differentiated thyroid carcinoma

International Nuclear Information System (INIS)

Lee, Jong Jin; Seok, Ju Won; Uh, Jae Sun

2005-01-01

In patients with recurrent or metastatic differentiated thyroid carcinoma, residual disease despite repetitive fixed dose I-131 therapy presents an awkward situation in terms of treatment decision making. Maximal safe dose (MSD) administration base on bone marrow radiation allows the delivery of a large amount I-131 to thyroid cancer tissue within the safety margin. We investigated the efficacy of MSD in differentiated thyroid cancers, which had persisted after conventional fixed dose therapy. Forty-six patients with differentiated thyroid carcinoma who had non-responsible residual disease despite repetitive fixed dose I-131 therapy were enrolled in this study. The postoperative pathology consisted of 43 papillary carcinomas and 3 follicular carcinomas. MSD was calculated according the Memorial Sloan Kettering Cancer Center protocol using blood samples. MSDs were administered at intervals of at least 6 months. Treatment responses were evaluated using I-131 whole body scan (WBS) and serum thyroglobulin measurements. Mean calculated MSD was 12.5±2.1 GBq. Of the 46 patients, 6 (13.0%) showed complete remission, 15 (32.6%) partial response, 19 (41.3%) stable disease, and 6 (13.0%) disease progression. Thus, about a half of the patients showed complete or partial remission, and of these patients, 14 (67%) showed response after a single MSD administration and 6 (29%) showed response after the second dose of MSD administrations. Twenty-nine patients (63%) experienced transient cytopenia after therapy, and recovered spontaneously with the exception of one. MSD administration is an effective method even in the patients who failed to be treated by conventional fixed dose therapy. MSD therapy of I-131 can be considered in the patients who failed by fixed dose therapy

Role of human recombinant activated protein C and low dose corticosteroid therapy in sepsis

Directory of Open Access Journals (Sweden)

Aparna Shukla

2010-01-01

Full Text Available Despite advances in modern medicine, sepsis remains a complex syndrome that has been associated with significant morbidity and mortality. Multiple organ failure associated with sepsis leads to high mortality and morbidity. About 28 - 50% deaths have been reported in patients with sepsis. The number of sepsis patients is increasing, with considerable burden on healthcare facilities. Various factors leading to a rise in the incidence of sepsis are (1 Improvement of diagnostic procedures (2 Increase in the number of immunocompromised patients taking treatment for various autoimmune disease, carcinomas, organ transplantation (3 Advances in intensive procedures (4 Nosocomial infections (5 Extensive use of antibiotics. With the better understanding of sepsis various modalities to modify pathophysiological response of septic patients have developed. Activated protein C and low-dose corticosteroid therapy have been tried in patients, with variable results.

Scalp Dose Evaluation According Radiation Therapy Technique of Whole Brain Radiation Therapy

International Nuclear Information System (INIS)

Jang, Joon Yung; Park, Soo Yun; Kim, Jong Sik; Choi, Byeong Gi; Song, Gi Won

2011-01-01

Opposing portal irradiation with helmet field shape that has been given to a patient with brain metastasis can cause excess dose in patient's scalp, resulting in hair loss. For this reason, this study is to quantitatively analyze scalp dose for effective prevention of hair loss by comparing opposing portal irradiation with scalp-shielding shape and tomotherapy designed to protect patient's scalp with conventional radiation therapy. Scalp dose was measured by using three therapies (HELMET, MLC, TOMO) after five thermo-luminescence dosimeters were positioned along center line of frontal lobe by using RANDO Phantom. Scalp dose and change in dose distribution were compared and analyzed with DVH after radiation therapy plan was made by using Radiation Treatment Planning System (Pinnacle3, Philips Medical System, USA) and 6 MV X-ray (Clinac 6EX, VARIAN, USA). When surface dose of scalp by using thermo-luminescence dosimeters was measured, it was revealed that scalp dose decreased by average 87.44% at each point in MLC technique and that scalp dose decreased by average 88.03% at each point in TOMO compared with HELMET field therapy. In addition, when percentage of volume (V95%, V100%, V105% of prescribed dose) was calculated by using Dose Volume Histogram (DVH) in order to evaluate the existence or nonexistence of hotspot in scalp as to three therapies (HELMET, MLC, TOMO), it was revealed that MLC technique and TOMO plan had good dose coverage and did not have hot spot. Reducing hair loss of a patient who receives whole brain radiotherapy treatment can make a contribution to improve life quality of the patient. It is expected that making good use of opposing portal irradiation with scalp-shielding shape and tomotherapy to protect scalp of a patient based on this study will reduce hair loss of a patient.

Scalp Dose Evaluation According Radiation Therapy Technique of Whole Brain Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Jang, Joon Yung; Park, Soo Yun; Kim, Jong Sik; Choi, Byeong Gi; Song, Gi Won [Dept. of Radiation Oncology, Samsung Medical Center, Seoul (Korea, Republic of)

2011-09-15

Opposing portal irradiation with helmet field shape that has been given to a patient with brain metastasis can cause excess dose in patient's scalp, resulting in hair loss. For this reason, this study is to quantitatively analyze scalp dose for effective prevention of hair loss by comparing opposing portal irradiation with scalp-shielding shape and tomotherapy designed to protect patient's scalp with conventional radiation therapy. Scalp dose was measured by using three therapies (HELMET, MLC, TOMO) after five thermo-luminescence dosimeters were positioned along center line of frontal lobe by using RANDO Phantom. Scalp dose and change in dose distribution were compared and analyzed with DVH after radiation therapy plan was made by using Radiation Treatment Planning System (Pinnacle3, Philips Medical System, USA) and 6 MV X-ray (Clinac 6EX, VARIAN, USA). When surface dose of scalp by using thermo-luminescence dosimeters was measured, it was revealed that scalp dose decreased by average 87.44% at each point in MLC technique and that scalp dose decreased by average 88.03% at each point in TOMO compared with HELMET field therapy. In addition, when percentage of volume (V95%, V100%, V105% of prescribed dose) was calculated by using Dose Volume Histogram (DVH) in order to evaluate the existence or nonexistence of hotspot in scalp as to three therapies (HELMET, MLC, TOMO), it was revealed that MLC technique and TOMO plan had good dose coverage and did not have hot spot. Reducing hair loss of a patient who receives whole brain radiotherapy treatment can make a contribution to improve life quality of the patient. It is expected that making good use of opposing portal irradiation with scalp-shielding shape and tomotherapy to protect scalp of a patient based on this study will reduce hair loss of a patient.

Low Dose I-131 MIBG therapy as an adjunct for bone pain palliation in pediatric patients with end-stage neuroblastoma: a pilot study

International Nuclear Information System (INIS)

Pascual, Thomas; Herbert, Anthony; Howman-Giles, Robert

2009-01-01

Full text: Objective: This study describes the initial experience in the use of low-dose 1-131 MIBG in patients with metastaticl refractory Neuroblastoma given at 18.5 Mbql Kg (0.5 mCi/Kg )to (1) achieve disease palliation (i.e., pain I symptom control) and improvement in the quality of life, through subjective response from patient/carers and (2) allow day-admission to minimize hospital stay providing more quality time between the patients and carers. Methods: Patients with refractory and metastatic Neuroblastoma whose primary treatment goal at that particular stage is pain palliation were given low-dose 1-131 M IBG at a dose of 18.5 Mbql Kg ( 0.5 mCil Kg)l. Assessment of subjective pain relief following 1-131 MIBG was done through interviews from hospital visits of the patient and home visits by the team. Results: Four patients underwent Low-Dose 1-131 MIBG Therapy for pain palliation between May 2007- March 2008. Median age was 5.75 years old and median total dose given was 539 Mbql patient (14.5 mCil patient). All patients at a cenain time had relief from disease pain allowing them to communicate with family and participate in physical activities not priyiledged before. Observations gathered from carersl parents revealed that the overall quality-of-life improved after the 1-131 MIBG therapy with concurrent pain medication protocol. Conclusion: This initial I pilot study described achievement of disease palliation (i.e., pain and symptom control) and improvement in the quality of life of Stage IV Neuroblastoma patients and allows day-admissions providing more quality time between the patient and the family and reduces patient anxiety.

Low dose radiation and ALARA: the potential risks to patients and staff from alpha-therapy

International Nuclear Information System (INIS)

Priest, N.D.

2014-01-01

This year a new drug containing radium-223, an alpha-emitting radionuclide, was approved for use by the US Food and Drug Administration for the palliative treatment of advanced prostate cancer metastases. Other drugs containing short-lived alpha-emitters are on clinical trial in Europe. Commonly, these employ a radionuclide attached to an antibody that specifically targets tumor cells to produce a highly localized radio-therapeutic dose to the tumor. However, normal tissues within the body will also be irradiated, albeit sometimes at low dose, and the question arises as to whether this presents a significant additional risk to the patient. Similarly, medical staff that handle these radionuclides could receive intakes of the radionuclides. What is the risk to staff? To assess the risk resulting from small tissue alpha-doses the toxicological, both human and animal, database was re-examined. The results of 20 epidemiological and toxicological studies with alpha-emitting radionuclides were analysed. In all cases a polynomial function provided a better fit to the data than a linear, no thresholds function. Also, in 19 cases a threshold dose below which no cancer is seen was indicated. The position of this threshold varied according to cancer type, but was typically in the range 0.1 to 1.0Gy of tissue dose - with a mean of 0.5Gy. It is concluded that alpha-radiation induced tumorogenesis is a threshold response and that as long as tissue doses are kept below these thresholds no additional cancers would be seen in either patients receiving alpha-therapy or in staff exposed to 'spilt' radionuclide. The presence of thresholds questions the appropriateness of current ALARA practices that are mostly used to drive occupational alpha-radiation exposures to as close to zero as possible. (author)

Low dose radiation and ALARA: the potential risks to patients and staff from alpha-therapy

Energy Technology Data Exchange (ETDEWEB)

Priest, N.D. [Atomic Energy of Canada Limited, Chalk River, ON (Canada)

2014-07-01

This year a new drug containing radium-223, an alpha-emitting radionuclide, was approved for use by the US Food and Drug Administration for the palliative treatment of advanced prostate cancer metastases. Other drugs containing short-lived alpha-emitters are on clinical trial in Europe. Commonly, these employ a radionuclide attached to an antibody that specifically targets tumor cells to produce a highly localized radio-therapeutic dose to the tumor. However, normal tissues within the body will also be irradiated, albeit sometimes at low dose, and the question arises as to whether this presents a significant additional risk to the patient. Similarly, medical staff that handle these radionuclides could receive intakes of the radionuclides. What is the risk to staff? To assess the risk resulting from small tissue alpha-doses the toxicological, both human and animal, database was re-examined. The results of 20 epidemiological and toxicological studies with alpha-emitting radionuclides were analysed. In all cases a polynomial function provided a better fit to the data than a linear, no thresholds function. Also, in 19 cases a threshold dose below which no cancer is seen was indicated. The position of this threshold varied according to cancer type, but was typically in the range 0.1 to 1.0Gy of tissue dose - with a mean of 0.5Gy. It is concluded that alpha-radiation induced tumorogenesis is a threshold response and that as long as tissue doses are kept below these thresholds no additional cancers would be seen in either patients receiving alpha-therapy or in staff exposed to 'spilt' radionuclide. The presence of thresholds questions the appropriateness of current ALARA practices that are mostly used to drive occupational alpha-radiation exposures to as close to zero as possible. (author)

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

Directory of Open Access Journals (Sweden)

Marcella Goetz MORO

Full Text Available Abstract The consumption of low-dose aspirin (LDA to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib and a non-selective COX-2 inhibitor (ibuprofen nonsteroidal anti-inflammatory drug (NSAID in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p 0.05. These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.

Cancer risk of low dose/low dose rate radiation: a meta-analysis of cancer data of mammals exposed to low doses of radiation

International Nuclear Information System (INIS)

Ogata, Hiromitsu; Magae, Junji

2008-01-01

Full text: Linear No Threshold (LNT) model is a basic theory for radioprotection, but the adaptability of this hypothesis to biological responses at low doses or at low dose rates is not sufficiently investigated. Simultaneous consideration of the cumulative dose and the dose rate is necessary for evaluating the risk of long-term exposure to ionizing radiation at low dose. This study intends to examine several numerical relationships between doses and dose rates in biological responses to gamma radiation. Collected datasets on the relationship between dose and the incidence of cancer in mammals exposed to low doses of radiation were analysed using meta-regression models and modified exponential (MOE) model, which we previously published, that predicts irradiation time-dependent biological response at low dose rate ionizing radiation. Minimum doses of observable risk and effective doses with a variety of dose rates were calculated using parameters estimated by fitting meta-regression models to the data and compared them with other statistical models that find values corresponding to 'threshold limits'. By fitting a weighted regression model (fixed-effects meta-regression model) to the data on risk of all cancers, it was found that the log relative risk [log(RR)] increased as the total exposure dose increased. The intersection of this regression line with the x-axis denotes the minimum dose of observable risk. These estimated minimum doses and effective doses increased with decrease of dose rate. The goodness of fits of MOE-model depended on cancer types, but the total cancer risk is reduced when dose rates are very low. The results suggest that dose response curve for cancer risk is remarkably affected by dose rate and that dose rate effect changes as a function of dose rate. For scientific discussion on the low dose exposure risk and its uncertainty, the term 'threshold' should be statistically defined, and dose rate effects should be included in the risk

Emerging therapies for Parkinson's disease: from bench to bedside.

Science.gov (United States)

Tarazi, F I; Sahli, Z T; Wolny, M; Mousa, S A

2014-11-01

The prevalence of Parkinson's disease (PD) increases with age and is projected to increase in parallel to the rising average age of the population. The disease can have significant health-related, social, and financial implications not only for the patient and the caregiver, but for the health care system as well. While the neuropathology of this neurodegenerative disorder is fairly well understood, its etiology remains a mystery, making it difficult to target therapy. The currently available drugs for treatment provide only symptomatic relief and do not control or prevent disease progression, and as a result patient compliance and satisfaction are low. Several emerging pharmacotherapies for PD are in different stages of clinical development. These therapies include adenosine A2A receptor antagonists, glutamate receptor antagonists, monoamine oxidase inhibitors, anti-apoptotic agents, and antioxidants such as coenzyme Q10, N-acetyl cysteine, and edaravone. Other emerging non-pharmacotherapies include viral vector gene therapy, microRNAs, transglutaminases, RTP801, stem cells and glial derived neurotrophic factor (GDNF). In addition, surgical procedures including deep brain stimulation, pallidotomy, thalamotomy and gamma knife surgery have emerged as alternative interventions for advanced PD patients who have completely utilized standard treatments and still suffer from persistent motor fluctuations. While several of these therapies hold much promise in delaying the onset of the disease and slowing its progression, more pharmacotherapies and surgical interventions need to be investigated in different stages of PD. It is hoped that these emerging therapies and surgical procedures will strengthen our clinical armamentarium for improved treatment of PD. Copyright © 2014 Elsevier Inc. All rights reserved.

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis.

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Eun Nam Lee

Full Text Available Currently ketamine is not used often as an analgesic in the emergency department (ED. Nonetheless, it can increase the efficiency of opioids and decrease their side effects. The purpose of this systematic review and meta-analysis was to evaluate whether low-dose ketamine in the ED provides better analgesia with fewer adverse effects.The PubMed, EMBASE, and Cochrane Library databases were searched by two reviewers independently (last search performed on January 2016. Data were also extracted independently.A total of 6 trials involving 438 patients were included in the current analysis. Our subgroup analysis of pain reduction indicates that the favorable effects of ketamine were similar or superior to those of placebo or opioids, although these effects were heterogeneous. However, low-dose ketamine was associated with a higher risk of neurological (relative risk [RR] = 2.17, 95% confidence interval [CI] = 1.37-3.42, P < 0.001 and psychological events (RR = 13.86, 95% CI = 4.85-39.58, P < 0.001. In contrast, the opioid group had a higher risk of major cardiopulmonary events (RR = 0.22, 95% CI = 0.05-1.01, P = 0.05.The efficiency of ketamine varies depending on the pain site, but low-dose ketamine may be a key agent for pain control in the ED, as it has no side effects. It may also help to reduce the side effects of opioids.

Antibiotic Dosing in Continuous Renal Replacement Therapy.

Science.gov (United States)

Shaw, Alexander R; Mueller, Bruce A

2017-07-01

Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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

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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.

Low-Dose Total Skin Electron Beam Therapy as a Debulking Agent for Cutaneous T-Cell Lymphoma: An open-label prospective phase II study

DEFF Research Database (Denmark)

Kamstrup, M R; Lindahl, Lise Maria; Gniadecki, R

2012-01-01

Background: Total skin electron beam therapy (TSEBT) is a powerful treatment for cutaneous T-cell lymphomas (CTCL). Based on the occurrence of relapses with low radiation doses, doses of 30-36 Gy are commonly used but most patients still eventually relapse and repeat treatment courses are limited...... due to the cumulative toxicity. Complete response rates are about 60-90% for T2-4 stages with a 5-year relapse-free survival of 10-25% for stages IB-III. Objectives: To evaluate prospectively the efficacy of low-dose TSEBT (10 Gy) in terms of complete cutaneous response rate, overall response rate...... and response duration in CTCL. Methods: Ten patients with stage IB-IV mycosis fungoides (MF) were treated in an open-label manner with 4 fractions of 1 Gy/week TSEB to a total skin dose of 10 Gy. Treatment responses were assessed at 1 and 3 months after treatment and subsequently at least every 6 months...

Comparative study of low dose 131I treatment in patients with Graves' disease

International Nuclear Information System (INIS)

Qin Lan; Shan Menglin; Wang Junqi

2005-01-01

Objective: To investigate the low dose 131 I therapy for Graves' disease we compared the results of 277 patients in our department with the report of Howarth D et al. Methods: 277 patients were classified as 45 Gy group and 77 Gy group according to the dose level. The results of these two groups were compared separately with results of 60 Gy group and 90 Gy group reported by Howarth D et al. Results: The euthyroidism rate and hypothyroidism rate among these four groups had no significant statistical difference after 6 months of 131 I therapy, but there were high significant statistical difference between our study and Howarth D research about euthyroidism rate and hypothyroidism rate 24 months later. Conclusion: The low dose 131 i management refered by Howarth D et al was an effective method for Graves' disease which could reduce or delay the incidence of hypothyroidism. Our study show that subsection on the foundation of this low dose procedure could further reduce the incidence of hypothyroidism and improve the euthyroidism rate. (authors)

Low doses effects

International Nuclear Information System (INIS)

Tubiana, M.

1997-01-01

In this article is asked the question about a possible carcinogens effect of low dose irradiation. With epidemiological data, knowledge about the carcinogenesis, the professor Tubiana explains that in spite of experiments made on thousand or hundred of thousands animals it has not been possible to bring to the fore a carcinogens effect for low doses and then it is not reasonable to believe and let the population believe that low dose irradiation could lead to an increase of neoplasms and from this point of view any hardening of radiation protection standards could in fact, increase anguish about ionizing radiations. (N.C.)

Radiation therapy tolerance doses for treatment planning

International Nuclear Information System (INIS)

Lyman, J.T.

1987-01-01

To adequately plan acceptable dose distributions for radiation therapy treatments it is necessary to ensure that normal structures do not receive unacceptable doses. Acceptable doses are generally those that are below a stated tolerance dose for development of some level of complication. To support the work sponsored by the National Cancer Institute, data for the tolerance of normal tissues or organs to low-LET radiation has been compiled from a number of sources. These tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD 5 ) or 50% (TD 50 ) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represent doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same end point. 20 refs., 1 fig., 1 tab

High-dose myeloablative versus conventional low-dose radioimmunotherapy (RIT) of mantle cell lymphoma (MCL) with the chimeric anti-CD20 antibody C2B8

International Nuclear Information System (INIS)

Behr, T.M.; Gotthardt, M.; Schipperm, M.L.; Gratz, S.; Behe, M.P.; Brittinger, G.; Woermann, B.; Becker, W.

2002-01-01

CD20 has been used as target molecule for low-dose as well as high-dose, myeloablative RIT of B-cell NHL. MCL is an especially aggressive, prognostically unfavorable form of B-cell NHL. The aim of this study was to investigate whether high-dose, myeloablative RIT with the 131 I-labeled chimeric anti-CD20 antibody C2B8 (rituxan, Mabthera, Roche) may be therapeutically more effective than conventional low-dose therapy in MCL. A total of twelve patients with chemorefractory or relapsed mantle cell lymphoma were studied so far (all of them having relapsed after high-dose chemotherapy, seven of them combined with 12 Gy TBI). A diagnostic-dosimetric study was performed with 10 mCi of 131 I-C2B8 at a protein dose of 2.5 mg/kg. In case of splenic pooling, the protein dose was increased until a more 'favorable' biodistribution was obtained. Therapy was performed with conventional (30-75 mCi; n=4) or myeloablative activities (261-515 mCi; n=8) of 131 I-C2B8 at the previously optimized protein dose, aiming at whole-body doses of ≤ 0.8 Gy (for low-dose RIT) or lung doses of ≤ 27 Gy (for high-dose RIT). Clinical follow-up was obtained for up to 42 months. Overall, in 11 patients the 2.5 mg/kg protein dose was used, whereas in one patient with marked splenomegaly, 10 mg/kg were necessary to overcome the splenic antigenic sink. In the high-dose patients, non-hematologic toxicity was restricted to mild to moderate nausea, fever, transient bilirubin or liver enzyme elevations. Despite thyroid blocking, 6/8 high-dose (in contrast to 0/4 low-dose) patients developed hypothyroidism, requiring thyroxine substitution at 6-18 months after RIT. The response rate in the low-dose arm was only 1(PR)/4, whereas 7/8 high-dose patients experienced complete and the remainder a partial remission. 6 high-dose patients are still in CR (one of them relapsed locally at 3 months, one systemically at 26 months after RIT), and 7 are still alive for up to 42+ months. In contrast to low-dose therapy

Biological effects of low doses of radiation at low dose rate

International Nuclear Information System (INIS)

1996-05-01

The purpose of this report was to examine available scientific data and models relevant to the hypothesis that induction of genetic changes and cancers by low doses of ionizing radiation at low dose rate is a stochastic process with no threshold or apparent threshold. Assessment of the effects of higher doses of radiation is based on a wealth of data from both humans and other organisms. 234 refs., 26 figs., 14 tabs

Factors Associated with Myelosuppression Related to Low-Dose Methotrexate Therapy for Inflammatory Rheumatic Diseases

Science.gov (United States)

Mori, Shunsuke; Hidaka, Michihiro; Kawakita, Toshiro; Hidaka, Toshihiko; Tsuda, Hiroyuki; Yoshitama, Tamami; Migita, Kiyoshi; Ueki, Yukitaka

2016-01-01

Objective Severe myelosuppression is a serious concern in the management of rheumatic disease patients receiving methotrexate (MTX) therapy. This study was intended to explore factors associated with the development of MTX-related myelosuppression and its disease severity. Methods We retrospectively examined a total of 40 cases of MTX-related myelosuppression that had been filed in the registries of participating rheumatology and hematology divisions. Data before onset were compared with those of 120 controls matched for age and sex. Cytopenia was graded according to the National Cancer Institute criteria for adverse events. Data before and at onset were compared between the severe and non-severe groups. Results Non-use of folic acid supplements, concurrent medications, and low renal function were significantly associated with the development of myelosuppression (p disease severity was not dependent on MTX doses. Serum albumin levels and folic acid supplementation are the important factors affecting the severity of MTX-related pancytopenia and neutropenia. PMID:27128679

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

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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

Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer

International Nuclear Information System (INIS)

Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi

2002-01-01

We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m 2 /day) was continuously infused over 24 hours, and CDDP (3-7 mg/m 2 /day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer. (author)

G2 arrest and apoptosis of cultured Raji cells by continuous low dose rate beta irradiation therapy with 188Re-perrhenate

International Nuclear Information System (INIS)

Yim, S. J.; Kim, E. H.; Lee, T. S.; Woo, K. S.; Jeong, W. S.; Choi, C. W.; Yim, S. M.

2001-01-01

Beta emitting radionuclide therapy gives exponentially decreasing radiation dose rate and results in cell death presumably by apoptosis. We observed changes in DNA content and apoptosis in relatively low dose rate beta irradiation. Raji cells were cultured and incubated with 188Re-perrhenate (3.7MBq, or 370MBq/ml) for 4 hours to give irradiation dose of 0.4, 4, or 40 Gy. After changing the culture media, cells were cultured for 2,4,8,16, and 24 hours. The cells were stained with Trypan blue, Annexin-V and Propidium Iodide (PI) to observe cell viability, cell membrane alternation by apoptosis and changes in DNA content respectively. Flowcytometry was done for Annexin-V and PI to quantitate apoptosis and necrosis in the irradiated cells. DAPI(4,6-diamidino-2-phenylindole) stain was also done to observe the damage in the nucleus. Cell viability decreased with an increasing radiation dose. Cells irradiated in 40 Gy showed early uptake of both Annexin-V and PI suggesting cell death by necrosis. Cells irradiated in 0.4 Gy showed delayed uptake of Annexin-V only, and later on PI uptake suggesting cell death mainly by apoptosis. The cells irradiated in 0.4 Gy showed G2 arrest in 16 hours after irradiation, but the cells irradiated in 40 Gy showed early DNA fragmentation within 2 hours after irradiation. In DAPI stain, early nucleus damage was observed in the cells irradiated in 40 Gy. On the other hand, slowly increasing apoptotic bodies were observed in the cells irradiated in 0.4 Gy. These results suggest that continuous low-dose irradiation induces G2 arrest and progressive apoptosis in cells while continuous high-dose irradiation induces rapid necrosis. Therefore, we expect therapeutic effect by continuous low-dose rate irradiation with beta emitting radiopharmaceuticals

Biological evidence of low ionizing radiation doses

International Nuclear Information System (INIS)

Mirsch, Johanna

2017-01-01

experiments with mice confirmed the physiological relevance of our cellular studies and suggests that the cellular radical level is critical for efficient DSB repair after low doses. In the third project, the inhomogeneous distribution of radon within the body of the mouse was investigated using a biological approach for the first time. To determine the distribution of radon, the DSBs induced by the decay of radon and its daughter nucleotides were quantified in several tissues. Radon is a naturally occurring noble gas, which can be found all over the world in different concentrations and contributes significantly to the natural radiation exposure of the population. Although the exposure to radon is a well-characterized risk factor for the development of lung cancer, radon is a popular remedy for the treatment of patients suffering from painful inflammatory diseases. Since conditions for the animal experiments were comparable to radon therapy sessions, the experimentally detected doses in the organs reflect their therapy-associated radiation exposure. Knowledge of the inhomogeneous radon distribution within the body and its resulting biological effects will help to shed light on the underlying mechanism that results in the therapeutic effect during the treatment of inflammatory diseases. The extensive biological data obtained here generally provides the unique possibility to verify and optimise mathematical models for risk assessment of radon exposures. Collectively, the three projects of this thesis investigated consequences of the exposure to low radiation doses. The controversy surrounding the effects of low doses is still standing and the presented results support the view that every exposure leads to non-negligible biological effects. Therefore, detailed knowledge of radiation effects is essential for the therapeutic application as well as for radiation protection.

Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Yang, Ruijie, E-mail: ruijyang@yahoo.com; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

2016-10-01

To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5 mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78 Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D{sub 90} of 34 Gy in 8.5 Gy per fraction, and 145 Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2 Gy per fraction, EQD{sub 2}) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The D{sub mean} (EQD{sub 2}) of rectum decreased 22.36 Gy in HDR and 17.01 Gy in LDR from 30.24 Gy in VMAT, respectively. The D{sub mean} (EQD{sub 2}) of bladder decreased 6.91 Gy in HDR and 2.53 Gy in LDR from 13.46 Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD{sub 2}) was 80.26, 70.23, and 104.91 Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR.

Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer

International Nuclear Information System (INIS)

Yang, Ruijie; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

2016-01-01

To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5 mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78 Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D 90 of 34 Gy in 8.5 Gy per fraction, and 145 Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2 Gy per fraction, EQD 2 ) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The D mean (EQD 2 ) of rectum decreased 22.36 Gy in HDR and 17.01 Gy in LDR from 30.24 Gy in VMAT, respectively. The D mean (EQD 2 ) of bladder decreased 6.91 Gy in HDR and 2.53 Gy in LDR from 13.46 Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD 2 ) was 80.26, 70.23, and 104.91 Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR.

Effect of Low-Dose Triple Therapy Using Gabapentin, Amitriptyline, and a Nonsteroidal Anti-Inflammatory Drug for Overactive Bladder Symptoms in Patients With Bladder Pain Syndrome

Directory of Open Access Journals (Sweden)

Whi-An Kwon

2013-06-01

Full Text Available Purpose: Patients with bladder pain syndrome/interstitial cystitis (BPS/IC can have pain as a main symptom and overactive bladder (OAB symptoms that are directly or indirectly related to a major mechanism that causes pain. The primary purpose of this study is firstly to identify the prevalence rate of OAB symptoms in patients with BPS/IC, secondly to identify changes in OAB symptoms after low-dose triple therapy, and thirdly to build a theoretical foundation to improve quality of life for patients. Methods: Patients who met the inclusion criteria of BPS/IC through basic tests including the O’Leary-Sant symptom index, overactive bladder symptom score (OABSS, and visual analog scale (VAS were identified. Treatment-based changes in OAB symptoms were identified using the IC Symptom Index and IC Problem Index (ICSI/ICPI, OABSS, and VAS before, and 4 and 12 weeks after low-dose triple therapy. Results: The patients consisted of 3 men and 20 women, and their mean age was 61.9 years (41.0–83.2 years. Comparing values before treatment, and 4 and 12 weeks after treatment (baseline vs. 4 weeks to baseline vs. 12 weeks, the rates of improvement were as follows: ICSI, 44.2% to 63.7%; ICPI, 46.9% to 59.4%; OABSS, 34.3% to 58.2%; and VAS, 53.6% to 75.0%, which showed statistically significant differences (P0.05. Conclusions: Low-dose triple therapy in BPS/IC results in a clear decrease in OAB symptoms in the first 4 weeks after treatment, and additional treatment for 8 weeks had a partial effect with varied statistical significances depending on the questionnaires.

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

OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

Neutrons in active proton therapy. Parameterization of dose and dose equivalent

Energy Technology Data Exchange (ETDEWEB)

Schneider, Uwe; Haelg, Roger A. [Univ. of Zurich (Switzerland). Dept. of Physics; Radiotherapy Hirslanden AG, Aarau (Switzerland); Lomax, Tony [Paul Scherrer Institute, Villigen (Switzerland). Center for Proton Therapy

2017-08-01

One of the essential elements of an epidemiological study to decide if proton therapy may be associated with increased or decreased subsequent malignancies compared to photon therapy is an ability to estimate all doses to non-target tissues, including neutron dose. This work therefore aims to predict for patients using proton pencil beam scanning the spatially localized neutron doses and dose equivalents. The proton pencil beam of Gantry 1 at the Paul Scherrer Institute (PSI) was Monte Carlo simulated using GEANT. Based on the simulated neutron dose and neutron spectra an analytical mechanistic dose model was developed. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed model in order to calculate the neutron component of the delivered dose distribution for each treated patient. The neutron dose was estimated for two patient example cases. The analytical neutron dose model represents the three-dimensional Monte Carlo simulated dose distribution up to 85 cm from the proton pencil beam with a satisfying precision. The root mean square error between Monte Carlo simulation and model is largest for 138 MeV protons and is 19% and 20% for dose and dose equivalent, respectively. The model was successfully integrated into the PSI treatment planning system. In average the neutron dose is increased by 10% or 65% when using 160 MeV or 177 MeV instead of 138 MeV. For the neutron dose equivalent the increase is 8% and 57%. The presented neutron dose calculations allow for estimates of dose that can be used in subsequent epidemiological studies or, should the need arise, to estimate the neutron dose at any point where a subsequent secondary tumour may occur. It was found that the neutron dose to the patient is heavily increased with proton energy.

Successful treatment of chronic recurrent multifocal osteomyelitis using low-dose radiotherapy. A case report

International Nuclear Information System (INIS)

Dietzel, Christian T.; Vordermark, Dirk; Schaefer, Christoph

2017-01-01

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, which lacks an infectious genesis and predominantly involves the metaphysis of long bones. Common treatments range from nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids at first onset of disease, to immunosuppressive drugs and bisphosphonates in cases of insufficient remission. The therapeutic use of low-dose radiotherapy for CRMO constitutes a novelty. A 67-year-old female patient presented with radiologically proven CRMO affecting the right tibia/talus and no response to immunosuppressive therapy. Two treatment series of radiation therapy were applied with an interval of 6 weeks. Each series contained six fractions (three fractions per week) with single doses of 0.5 Gy, thus the total applied dose was 6 Gy. Ten months later, pain and symptoms of osteomyelitis had completely vanished. Radiotherapy seems to be an efficient and feasible complementary treatment option for conventional treatment refractory CRMO in adulthood. The application of low doses per fraction is justified by the inflammatory pathomechanism of disease. (orig.) [de

Low-Dose Dexamethasone Therapy from Infancy of Virilizing Congenital Adrenal Hyperplasia

Directory of Open Access Journals (Sweden)

Stephenson Kerry

2009-12-01

Full Text Available Objective. To assess the growth and control of adrenal androgen secretion in children with virilizing congenital adrenal hyperplasia (CAH treated with dexamethasone. Method. We examined doses used, control of adrenal androgen secretion, and growth and skeletal maturation of 8 children with CAH treated with dexamethasone beginning in infancy. Results. 3 boys and 5 girls with classical CAH (17-hydroxyprogesterone at diagnosis >20,000 ng/dL were treated with dexamethasone beginning at diagnosis ( ; all doses were given in the morning using a dosing syringe to administer a 0.1 mg/mL elixir. The children were treated for years over which time the change in bone age to chronological age ratio (BA/CA was . Most recent height Z' scores were , and body mass index (BMI scores were . Late afternoon levels of 17-hydroxyprogesterone, androstenedione, and testosterone were  ng/dL ( nmol/L,  ng/dL ( nmol/L, and  ng/dL; ( nmol/L, respectively. Conclusions. These observations show that low doses of dexamethasone can be used to effectively treat CAH beginning in infancy.

Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

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Fasola, Carolina E. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Jones, Jennifer C. [Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (United States); Huang, Derek D. [Department of Internal Medicine, University of California-Los Angeles Olive View, Sylmar, California (United States); Le, Quynh-Thu; Hoppe, Richard T. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Donaldson, Sarah S., E-mail: sarah2@stanford.edu [Department of Radiation Oncology, Stanford University, Stanford, California (United States)

2013-08-01

Purpose: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). Results: At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. Conclusions: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.

Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

International Nuclear Information System (INIS)

Fasola, Carolina E.; Jones, Jennifer C.; Huang, Derek D.; Le, Quynh-Thu; Hoppe, Richard T.; Donaldson, Sarah S.

2013-01-01

Purpose: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). Results: At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. Conclusions: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse

Gynecological brachytherapy - from low-dose-rate to high-tech. Gynaekologische Brachytherapie - von Low-dose-rate zu High-tech

Energy Technology Data Exchange (ETDEWEB)

Herrmann, T. (Abt. Strahlenthgerapie, Klinik und Poliklinik fuer Radiologie, Medizinische Akademie ' Carl Gustav Carus' , Dresden (Germany)); Christen, N. (Abt. Strahlenthgerapie, Klinik und Poliklinik fuer Radiologie, Medizinische Akademie ' Carl Gustav Carus' , Dresden (Germany)); Alheit, H.D. (Abt. Strahlenthgerapie, Klinik und Poliklinik fuer Radiologie, Medizinische Akademie ' Carl Gustav Carus' , Dresden (Germany))

1993-03-01

The transition from low-dose-rate (LDR) brachytherapy to high-dose-rate (HDR) afterloading treatment is in progress in most centres of radiation therapy. First reports of studies comparing HDR and LDR treatment in cervix cancer demonstrate nearly equal local control. In our own investigations on 319 patients with primary irradiated carcinoma of the cervix (125 HDR/194 LDR) we found the following control rates: Stage FIGO I 95.4%/82.9% (HDR versus LDR), stage FIGO II 71.4%/73.7%, stage FIGO III 57.9%/38.5%. The results are not significant. The side effects - scored after EORT/RTOG criteria - showed no significant differences between both therapies for serious radiogenic late effects on intestine, bladder and vagina. The study and findings from the literature confirm the advantage of the HDR-procedure for patient and radiooncologist and for radiation protection showing at least the same results as in the LDR-area. As for radiobiolgical point of view it is important to consider that the use of fractionation in the HDR-treatment is essential for the sparing of normal tissues and therefore a greater number of small fractionation doses in the brachytherapy should be desirable too. On the other hand the rules, which are true for fractionated percutaneous irradiation therapy (overall treatment time as short as possible to avoid reppopulation of tumor cells) should be taken into consideration in combined brachy-teletherapy regime in gynecologic tumors. The first step in this direction may be accelerated regime with a daily application of both treatment procedures. The central blocking of the brachytherapy region from the whole percutaneous treatment target volume should be critically reflected, especially in the case of advanced tumors. (orig.)

Low-dose radiation therapy for choroidal neovascularization in age-related macular degeneration

International Nuclear Information System (INIS)

Matsuhashi, Hideaki; Takahashi, Daisuke; Mariya, Yasushi; Tarusawa, Nobuko; Yoshimoto, Hiroshi; Matsuyama, Shuichi; Noda, Yasuko.

1996-01-01

The efficacy of low-dose radiation was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. Ten eyes of ten patients received a total dose of 14 Gy of 10 MV X-rays in seven fractions and the mean follow-up time was 12 months (range 9-18 months). Thirteen control eyes of thirteen patients were followed for an average of 18 months (range 12-24 months). Visual acuity was improved in 2 eyes (20%), unchanged in 3 eyes (30%), and deteriorated in 5 eyes (50%) of treated patients, and it was improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients at their last follow-up examinations. Funduscopic and angiographic findings were improved in 3 eyes (30%), unchanged in 2 eyes (20%), and deteriorated in 5 eyes (50%) of treated patients, and they were improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients. These results suggested that low-dose radiation is beneficial for the management of subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. (author)

Low-dose radiation therapy for choroidal neovascularization in age-related macular degeneration

Energy Technology Data Exchange (ETDEWEB)

Matsuhashi, Hideaki; Takahashi, Daisuke; Mariya, Yasushi; Tarusawa, Nobuko; Yoshimoto, Hiroshi; Matsuyama, Shuichi [Hirosaki Univ., Aomori (Japan). School of Medicine; Noda, Yasuko

1996-10-01

The efficacy of low-dose radiation was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. Ten eyes of ten patients received a total dose of 14 Gy of 10 MV X-rays in seven fractions and the mean follow-up time was 12 months (range 9-18 months). Thirteen control eyes of thirteen patients were followed for an average of 18 months (range 12-24 months). Visual acuity was improved in 2 eyes (20%), unchanged in 3 eyes (30%), and deteriorated in 5 eyes (50%) of treated patients, and it was improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients at their last follow-up examinations. Funduscopic and angiographic findings were improved in 3 eyes (30%), unchanged in 2 eyes (20%), and deteriorated in 5 eyes (50%) of treated patients, and they were improved in no eyes (0%), unchanged in 5 eyes (32%), and deteriorated in 8 eyes (50%) of the control patients. These results suggested that low-dose radiation is beneficial for the management of subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration. (author)

Effects of low-dose preoperative irradiation on low anterior anastomosis in dogs

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Schauer, R.M.; Bubrick, M.P.; Feeney, D.A.; Johnston, G.R.; Rolfsmeyer, E.S.; Strom, R.L.; Hitchcock, C.R.

Twenty mongrel dogs underwent preoperative radiation therapy to the colon and rectum using the Nominal Standard Dose Equation to simulate treatment with 2000 rads. Each dog then underwent anterior resection of the rectosigmoid, and reconstruction was randomized into two groups consisting of either handsewn or EEA-stapled anastomoses. Anastomoses were examined digitally and radiographically on the day of surgery and on the seventh postoperative day. There were three radiographic leaks among the ten dogs having the handsewn anastomoses and one radiographic leak among the ten dogs having the EEA-stapled anastomoses. There was one clinically significant leak which occurred in a dog having an EEA-stapled anastomosis and was associated with peritonitis and death. The overall leak rate was 30 per cent among dogs having handsewn anastomoses and 20 per cent among dogs with stapled anastomoses. The data suggest that an anterior resection in low colorectal anastomosis can be done safely after low-dose radiation using either handsewn or stapling techniques.

Effects of low-dose preoperative irradiation on low anterior anastomosis in dogs.

Science.gov (United States)

Schauer, R M; Bubrick, M P; Feeney, D A; Johnston, G R; Rolfsmeyer, E S; Strom, R L; Hitchcock, C R

1982-01-01

Twenty mongrel dogs underwent preoperative radiation therapy to the colon and rectum using the Nominal Standard Dose Equation to simulate treatment with 2000 rads. Each dog then underwent anterior resection of the rectosigmoid, and reconstruction was randomized into two groups consisting of either handsewn or EEA-stapled anastomoses. Anastomoses were examined digitally and radiographically on the day of surgery and on the seventh postoperative day. There were three radiographic leaks among the ten dogs having the handsewn anastomoses and one radiographic leak among the ten dogs having the EEA-stapled anastomoses. There was one clinically significant leak which occurred in a dog having an EEA-stapled anastomosis and was associated with peritonitis and death. The overall leak rate was 30 per cent among dogs having handsewn anastomoses and 20 per cent among dogs with stapled anastomoses. The data suggest that an anterior resection in low colorectal anastomosis can be done safely after low-dose radiation using either handsewn or stapling techniques.

Effects of low-dose preoperative irradiation on low anterior anastomosis in dogs

International Nuclear Information System (INIS)

Schauer, R.M.; Bubrick, M.P.; Feeney, D.A.; Johnston, G.R.; Rolfsmeyer, E.S.; Strom, R.L.; Hitchcock, C.R.

1982-01-01

Twenty mongrel dogs underwent preoperative radiation therapy to the colon and rectum using the Nominal Standard Dose Equation to simulate treatment with 2000 rads. Each dog then underwent anterior resection of the rectosigmoid, and reconstruction was randomized into two groups consisting of either handsewn or EEA-stapled anastomoses. Anastomoses were examined digitally and radiographically on the day of surgery and on the seventh postoperative day. There were three radiographic leaks among the ten dogs having the handsewn anastomoses and one radiographic leak among the ten dogs having the EEA-stapled anastomoses. There was one clinically significant leak which occurred in a dog having an EEA-stapled anastomosis and was associated with peritonitis and death. The overall leak rate was 30 per cent among dogs having handsewn anastomoses and 20 per cent among dogs with stapled anastomoses. The data suggest that an anterior resection in low colorectal anastomosis can be done safely after low-dose radiation using either handsewn or stapling techniques

Single dose planning for radioiodine-131 therapy of Graves' disease

International Nuclear Information System (INIS)

Kita, Tamotsu; Yokoyama, Kunihiko; Kinuya, Seigo; Taki, Junichi; Michigishi, Takatoshi; Tonami, Norihisa

2004-01-01

Patients with Graves' disease were studied one year after radioiodine-131 therapy to assess the relationship between the effectiveness of the therapy and the radioiodine doses used. Patients were classified into three groups according to thyroid function as hyperthyroidism, euthyroidism and hypothyroidism at one year after I-131 therapy. In these groups we compared the mean values of dose, dose per thyroid weight calculated with I-123 uptake before the therapy (pre D/W), dose per thyroid weight calculated with therapeutic I-131 uptake (post D/W), and absorbed dose. No significant differences were found between the three groups in terms of dose or pre D/W. The mean values of post D/W and absorbed dose in the non-hyperthyroid (euthyroid and hypothyroid) group were significantly greater than those in the hyperthyroid group. Post D/W of 6.3 MBq/g was a threshold separating the non-hyperthyroid group from the hyperthyroid group. There was no correlation between pre D/W and post D/W; however, the mean post D/W was significantly greater than the mean pre D/W. All patients with pre D/W above 6.3 MBq/g showed non-hyperthyroidism at one year after the radioiodine treatment. No indicators before the radioiodine therapy had significant relationships with the effectiveness of the therapy at one year after the treatment. However, the single therapy planned for setting the pre D/W above 6.3 MBq/g will certainly make the patients non-hyperthyroid. As this proposal of dose planning is based on a small number of patients, further study is needed. (author)

Dose distribution following selective internal radiation therapy

International Nuclear Information System (INIS)

Fox, R.A.; Klemp, P.F.; Egan, G.; Mina, L.L.; Burton, M.A.; Gray, B.N.

1991-01-01

Selective Internal Radiation Therapy is the intrahepatic arterial injection of microspheres labelled with 90Y. The microspheres lodge in the precapillary circulation of tumor resulting in internal radiation therapy. The activity of the 90Y injected is managed by successive administrations of labelled microspheres and after each injection probing the liver with a calibrated beta probe to assess the dose to the superficial layers of normal tissue. Predicted doses of 75 Gy have been delivered without subsequent evidence of radiation damage to normal cells. This contrasts with the complications resulting from doses in excess of 30 Gy delivered from external beam radiotherapy. Detailed analysis of microsphere distribution in a cubic centimeter of normal liver and the calculation of dose to a 3-dimensional fine grid has shown that the radiation distribution created by the finite size and distribution of the microspheres results in an highly heterogeneous dose pattern. It has been shown that a third of normal liver will receive less than 33.7% of the dose predicted by assuming an homogeneous distribution of 90Y

SPEEDI: system for prediction of environmental emergency dose information

International Nuclear Information System (INIS)

Chino, Masamichi; Ishikawa, Hirohiko; Kai, Michiaki

1984-03-01

In this report a computer code system for prediction of environmental emergency dose information , i.e., SPEEDI for short, is presented. In case of an accidental release of radioactive materials from a nuclear plant, it is very important for an emergency planning to predict the concentration and dose caused by the materials. The SPEEDI code system has been developed for this purpose and it has features to predict by calculation the released nuclides, wind fields, concentrations and dose based on release information, actual weather and topographical data. (author)

Treatment of Complex Regional Pain Syndrome (CRPS) using low dose naltrexone (LDN).

Science.gov (United States)

Chopra, Pradeep; Cooper, Mark S

2013-06-01

Complex Regional Pain Syndrome (CRPS) is a neuropathic pain syndrome, which involves glial activation and central sensitization in the central nervous system. Here, we describe positive outcomes of two CRPS patients, after they were treated with low-dose naltrexone (a glial attenuator), in combination with other CRPS therapies. Prominent CRPS symptoms remitted in these two patients, including dystonic spasms and fixed dystonia (respectively), following treatment with low-dose naltrexone (LDN). LDN, which is known to antagonize the Toll-like Receptor 4 pathway and attenuate activated microglia, was utilized in these patients after conventional CRPS pharmacotherapy failed to suppress their recalcitrant CRPS symptoms.

Efficiency analysis of using tailored individual doses of radioiodine and fine tuning using a low-dose antithyroid drug in the treatment of Graves' disease.

Science.gov (United States)

Liu, Chang-Jiang; Dong, Yan-Yu; Wang, Yi-Wei; Wang, Kai-Hua; Zeng, Qun-Yan

2011-03-01

To evaluate the effect of using tailored individual doses of radioiodine (¹³¹I) and fine tuning using low-dose antithyroid drug (ATD) in the treatment of Graves' disease, and an attempt to establish a therapeutic strategy that can keep both high rate of euthyroidism and low incidence of hypothyroidism. The dose of radioiodine was calculated using the calculated dose formula, and low-dose ATD was used as a way of fine tuning during follow-up. The intended dose of radioiodine was modified according to the patient's age at radioiodine therapy, thyroid size, and duration of hyperthyroidism before radioiodine therapy in the study group; it was set as 2.96 MBq/g of thyroid in the control group. Twenty patients with Graves' disease were nonrandomly assigned to the control group and 98 patients with Graves' disease to the study group. The outcomes, which included euthyroidism, hypothyroidism, and persistent hyperthyroidism, were determined according to the patients' states at the end of follow-up. In the study group, 74 patients (75.5%) achieved the euthyroid state, six patients (6.1%) became hypothyroid, and 18 patients (18.4%) remained hyperthyroid. The rate of euthyroidism was statistically different between the study group and the control group (75.5 vs. 50%, P=0.03). Of 98 patients with Graves' disease in the study group, 19 patients were additionally treated with ATD during follow-up, and 12 patients achieved euthyroidism. In different age groups or duration of hyperthyroidism groups, the rate of euthyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). Similarly, in different age groups or duration of hyperthyroidism groups, the incidence of hypothyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). However, binary logistic regression analysis showed that thyroid size was associated with overtreatment and undertreatment in our study. Individual doses of

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

a total dose of 10 Gy in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. RESULTS: The overall response rate was 95% with a complete cutaneous response......PURPOSE: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments...... or a very good partial response rate (response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. CONCLUSIONS...

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 BackgroundThrombolytic 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 resultsThe 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.ConclusionsIn 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.

Low-Dose Dexamethasone Therapy from Infancy of Virilizing Congenital Adrenal Hyperplasia

Directory of Open Access Journals (Sweden)

Scott A. Rivkees

2009-01-01

Full Text Available Objective. To assess the growth and control of adrenal androgen secretion in children with virilizing congenital adrenal hyperplasia (CAH treated with dexamethasone. Method. We examined doses used, control of adrenal androgen secretion, and growth and skeletal maturation of 8 children with CAH treated with dexamethasone beginning in infancy. Results. 3 boys and 5 girls with classical CAH (17-hydroxyprogesterone at diagnosis >20,000 ng/dL were treated with dexamethasone beginning at diagnosis (<10 days of age. Patients were also treated with fludrocortisone and sodium chloride. The average initial medication dose was 0.1 mg (0.28±0.015 mg/m2; all doses were given in the morning using a dosing syringe to administer a 0.1 mg/mL elixir. The children were treated for 6.5±2.0 years over which time the change in bone age to chronological age ratio (ΔBA/ΔCA was 0.9±0.06. Most recent height Z' scores were +0.5±0.2, and body mass index (BMI scores were 18±0.2. Late afternoon levels of 17-hydroxyprogesterone, androstenedione, and testosterone were 780±238 ng/dL (23.4±7 nmol/L, 42±10 ng/dL (1.4±0.3 nmol/L, and 11.5±3 ng/dL; (0.4±0.1 nmol/L, respectively. Conclusions. These observations show that low doses of dexamethasone can be used to effectively treat CAH beginning in infancy.

Treatment of symptomatic splenomegaly with low doses of radiotherapy: Retrospective analysis and review of the literature

Directory of Open Access Journals (Sweden)

Carolina de la Pinta

2017-09-01

Conclusion: Low doses of radiation therapy for treatment of symptomatic splenomegaly were effective, with a low rate of side effects. Splenic pain and abdominal discomfort completely improved and cytopenias rised to secure levels.

An international intercomparison of absorbed dose measurements for radiation therapy

International Nuclear Information System (INIS)

Taiman Kadni; Noriah Mod Ali

2002-01-01

Dose intercomparison on an international basis has become an important component of quality assurance measurement i.e. to check the performance of absorbed dose measurements in radiation therapy. The absorbed dose to water measurements for radiation therapy at the SSDL, MINT have been regularly compared through international intercomparison programmes organised by the IAEA Dosimetry Laboratory, Seibersdorf, Austria such as IAEA/WHO TLD postal dose quality audits and the Intercomparison of therapy level ionisation chamber calibration factors in terms of air kerma and absorbed dose to water calibration factors. The results of these intercomparison in terms of percentage deviations for Cobalt 60 gamma radiation and megavoltage x-ray from medical linear accelerators participated by the SSDL-MINT during the year 1985-2001 are within the acceptance limit. (Author)

Studies of health effects of low dose radiation and its application to medicare

International Nuclear Information System (INIS)

Yamaoka, Kiyonori; Ishida, Kenji; Iwasaki, Toshiyasu; Koana, Takao; Magae, Junji; Watanabe, Masami; Sakamoto, Kiyohiko

2008-01-01

The articles contain following 7 topics of low dose radiation effects. Studies of Health Effects of Low dose Radiation and Its Application to Medicare'', describes the indication of Rn therapy and investigations of its usefulness mechanism mainly in Misasa Spa, Okayama Pref. ''Challenges for the Paradigm Shift (CRIEPI Studies)'', introduces studies against the paradigm that radiation dose is linearly and proportionally hazardous. ''Studies of High Background Radiation Area (CRIEPI Studies)'', describes global HBRA studies on chromosome affection and effect of smoking in HBRA. ''Is the Radiation Effect on Man Proportional to Dose? (CRIEPI Studies)'', describes studies of immature sperm irradiated at low dose against Linear-Non-threshold Theory (LNT) hypothesis. ''Induction of Radiation Resistance by Low Dose Radiation and Assessment of Its Effect in Models of Human Diseases (CRIEPI Studies)'', explains the adoptive response in radiation effect, suppression of carcinogenesis and immune regulation by previous low dose radiation in the mouse, and improvement of diabetes in the db/db mouse. ''Modulation of Biological Effects of Low Dose Radiation: Adoptive Response, Bystander Effect, Genetic Instability and Radiation Hormesis'', summarizes findings of each item. ''Cancer Treatment with Low dose Radiation to the Whole Body'', describes basic studies in the mouse tumor in relation to suppression of carcinogenesis and metastasis, immune activation and treatment, and successful clinical studies in patients with ovary, colon cancers and malignant lymphoma where survival has been significantly improved: a base of recent European Organization for Research and Treatment of Cancer (EORTC) clinical trials. The mechanism is essentially based on immune activation of patients to cure the disease. (R.T.)

Improved growth velocity of a patient with Noonan-like syndrome with loose anagen hair (NS/LAH) without growth hormone deficiency by low-dose growth hormone therapy.

Science.gov (United States)

Takasawa, Kei; Takishima, Shigeru; Morioka, Chikako; Nishioka, Masato; Ohashi, Hirofumi; Aoki, Yoko; Shimohira, Masayuki; Kashimada, Kenichi; Morio, Tomohiro

2015-10-01

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) is caused by a heterozygous c.4A>G mutation in SHOC2. Most cases exhibit both growth hormone deficiency (GHD) and growth hormone insensitivity (GHI) and thus require a high dose of growth hormone (GH) therapy (e.g., 35-40 µg/kg/day). We report on a genetically diagnosed NS/LAH patient manifesting severe short stature (-3.85 SDs) with low serum level of IGF1, 30 ng/ml. The peak levels of GH stimulation tests were within the normal range, and GHI was not observed in the IGF1 generation test. However, with low-dose GH therapy (25 µg/kg/day) for two years, IGF1 level and height were remarkably improved (IGF1: 117 ng/ml, height SDs: -2.20 SDs). Further, catch-up of motor development and improvement of the proportion of extending limbs to trunk were observed (the Developmental Quotient score increased from 68 to 98 points, and the relative sitting height ratio decreased from 0.62 to 0.57). Our results suggest that endocrinological causes for short stature are variable in NS/LAH and that GH therapy should be considered as a possible treatment for delayed development in NS/LAH. © 2015 Wiley Periodicals, Inc.

Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease

NARCIS (Netherlands)

Heitner, Rene; Elstein, Deborah; Aerts, Johannes; Weely, Sonja van; Zimran, Ari

2002-01-01

The objective of this study was to evaluate the efficacy and safety of low-dose substrate balance therapy with OGT 918 for the treatment of adults with Gaucher disease. Eighteen patients with Gaucher disease from two centers were enrolled in an open-label 6-month study of OGT 918, 50 mg taken three

Repair and dose-response at low doses

International Nuclear Information System (INIS)

Totter, J.R.; Weinberg, A.M.

1977-04-01

The DNA of each individual is subject to formation of some 2-4 x 10 14 ion pairs during the first 30 years of life from background radiation. If a single hit is sufficient to cause cancer, as is implicit in the linear, no-threshold theories, it is unclear why all individuals do not succumb to cancer, unless repair mechanisms operate to remove the damage. We describe a simple model in which the exposed population displays a distribution of repair thresholds. The dose-response at low dose is shown to depend on the shape of the threshold distribution at low thresholds. If the probability of zero threshold is zero, the response at low dose is quadratic. The model is used to resolve a longstanding discrepancy between observed incidence of leukemia at Nagasaki and the predictions of the usual linear hypothesis

Responses of epithelial cells to low and very low doses of low let radiation

International Nuclear Information System (INIS)

Mothersill, Carmel; Seymour, Colin

2003-01-01

Recent advances in our knowledge of the biological effects of low doses of ionizing radiation have shown unexpected phenomena. These vary in the endpoint used to detect them and in the dose range examined but all occur as high-frequency events in cell populations. They include: 1. a 'bystander effect' which can be demonstrated at low doses as a transferable.factor(s) causing radiobiological effects in unexposed cells, 2. an assortment of delayed effects' occurring in progeny of cells exposed to low doses, 3. Low-dose Hypersensitivity (HRS) and Increased radioresistance (IRR) which can collectively be demonstrated as a change in the dose-effect relationship, occurring around 0.5-1 Gy of low LET radiation and 4. adaptive responses where cells exposed to very low doses followed by higher doses, exhibit an induced relatively resistant response to the second dose. In all cases, the effect of very low doses is greater than would be predicted by extrapolation of high dose data and is inconsistent with conventional DNA break/repair-based radiobiology. In practical risk assessment terms, the relative importance of the effects are high at low doses where they dominate the response, and small at high doses. This paper reviews these assorted phenomena and in particular seeks to explore whether related or distinct mechanisms underlie these various effects Understanding the mechanistic basis of these phenomena may suggest new approaches to controlling death or survival sectoring at low radiation doses. The key question is whether these low dose phenomena necessitate a new approach to risk assessment. (author)

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.)

Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial.

Science.gov (United States)

Jo, Young-Il; Na, Ha-Young; Moon, Ju-Young; Han, Sang-Woong; Yang, Dong-Ho; Lee, Sang-Ho; Park, Hyeong-Cheon; Choi, Hoon-Young; Lim, So-Dug; Kie, Jeong-Hae; Lee, Yong-Kyu; Shin, Sug-Kyun

2016-03-01

Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% ± 26.1% (p valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.

Emerging pharmaceutical therapies for COPD

Science.gov (United States)

Lakshmi, Sowmya P; Reddy, Aravind T; Reddy, Raju C

2017-01-01

COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations. Among these are compounds that inhibit the CXCR2 receptor, mitogen-activated protein kinase/Src kinase, myristoylated alanine-rich C kinase substrate, selectins, and the endothelin receptor. Activation of certain transcription factors may also be relevant, as a large retrospective cohort study of COPD patients with diabetes found that the peroxisome proliferator-activated receptor γ (PPARγ) agonists rosiglitazone and pioglitazone were associated with reduced COPD exacerbation rate. Notably, several therapies have shown efficacy only in identifiable subgroups of COPD patients, suggesting that subgroup identification may become more important in future treatment strategies. This review summarizes the status of emerging therapeutic pharmaceuticals for COPD and highlights those that appear most promising. PMID:28790817

Low and very low doses, new recommendations?

International Nuclear Information System (INIS)

Foucher, N.

1999-01-01

The topic of the seminar organized by the world council of nuclear workers (WONUC) was the effects of low or very low doses on human health. Discussions centred round the linearity of the relation between dose and effect in the evaluation and management of the health hazard. The recommendations proposed by ICPR (international commission for radiological protection) are based on this linearity as a precaution. On the one hand it is remembered that low dose irradiation might be beneficial. It has been proved that the irradiation of the whole body is efficient in case of Hodgkin lymphoma. On the other hand it is remembered that doses as low as 10 mSv in utero have led to an excess of cancer in children. Studies based on experimentally radio-induced cancers have been carried out in Japan, China, Canada and France.Their results seem to be not consistent with the hypothesis of linearity. During the last decade a lot of work has been made but a conclusion is far to be reached, it is said that the American department of energy (DOE) has invited bids in 1999 to launch research programs in order to clarify the situation. (A.C.)

Effect of low dose 131I-MIBG therapy in metastatic neural crest tumors: Evaluation by RECIST and quality of life questionnaire

International Nuclear Information System (INIS)

Basu, S.; Joseph, J.K.

2004-01-01

were available in 4 cases, all of whom showed a biochemical response in the form of normal urinary VMA level at the third follow up visit. Hypertension control and improved quality of life was achieved by two therapies in all. These cases had stable disease at the end of 2 years following first therapy. One case had a disease unrelated death. Eleven therapies were at a median follow up of 9 months. Disease related death was observed in three patients. In two treated cases of paraganglioma, follow up information was available in one case, which had shown disease stabilization, biochemical response as well as improved quality of life at the end of two years. In conclusion, a fixed low dose (∼ 100 mCi) of 131IMIBG may be equally effective in metastatic pheochromocytoma and paraganglioma in disease stabilization and improving quality of life. This has an advantage of better tolerability as well as provision of therapeutic reserve for future recurrence. However, this does not seem to be suitable in cases of neuroblastoma, especially those refractory to the conventional therapy where the aggressive tumor biology invariably leads to disease progression after some time. Hence, a higher dose with curative intent followed by assessment for feasibility of surgery may be more preferable option in this group. (author)

Intermittent Preventive Therapy for Malaria During Pregnancy Using 2 vs 3 or More Doses of Sulfadoxine-Pyrimethamine and Risk of Low Birth Weight in Africa

Science.gov (United States)

Kayentao, Kassoum; Garner, Paul; van Eijk, Anne Maria; Naidoo, Inbarani; Roper, Cally; Mulokozi, Abdunoor; MacArthur, John R.; Luntamo, Mari; Ashorn, Per; Doumbo, Ogobara K.; ter Kuile, Feiko O.

2015-01-01

Importance Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a pivotal period for fetal weight gain. Objective To perform a systematic review and meta-analysis of trials to determine whether regimens containing 3 or more doses of sulfadoxine-pyrimethamine for intermittent preventive therapy during pregnancy are associated with a higher birth weight or lower risk of low birth weight (LBW) (<2500 g) than standard 2-dose regimens. Data Sources and Study Selection ISI Web of Knowledge, EMBASE, SCOPUS, PubMed, LILACS, the Malaria in Pregnancy Library, Cochrane CENTRAL, and trial registries from their inception to December 2012, without language restriction. Eligible studies included randomized and quasi-randomized trials of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine monotherapy. Data Extraction Data were independently abstracted by 2 investigators. Relative risk (RR), mean differences, and 95% CIs were calculated with random-effects models. Results Of 241 screened studies, 7 trials of 6281 pregnancies were included. The median birth weight in the 2-dose group was 2870 g (range, 2722–3239 g) and on average 56 g higher (95% CI, 29–83 g; I2=0%) in the ≥3-dose group. Three or more doses were associated with fewer LBW births (RR,0.80; 95% CI, 0.69–0.94; I2=0%), with a median LBW risk per 1000 women in the 2-dose group (assumed control group risk) of 167 per 1000 vs 134 per 1000 in the ≥3-dose group (absolute risk reduction, 33 per 1000 [95% CI, 10–52]; number needed to treat=31). The association was consistent across a wide range of sulfadoxine-pyrimethamine resistance (0% to 96% dihydropteroate-synthase K540E mutations). There was no evidence of small-study bias. The ≥3-dose group had

Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

International Nuclear Information System (INIS)

Nomura, Takaharu

2008-01-01

Living organisms have developed complex biological system which protects themselves against environmental radiation, and irradiation with proper dose, dose-rate and irradiation time can stimulate their biological responses against oxidative stress evoked by the irradiation. Because reactive oxygen species are involved in various human diseases, non-toxic low dose/low dose-rate radiation can be utilized for the amelioration of such diseases. In this study, we used mouse experimental models for fatty liver, nephritis, diabetes, and ageing to elucidate the ameliorative effect of low dose/low dose-rate radiation in relation to endogenous antioxidant activity. Single irradiation at 0.5 Gy ameliorates carbon tetrachloride-induced fatty liver. The irradiation increases hepatic anti-oxidative system involving glutathione and glutathione peroxidase, suggesting that endogenous radical scavenger is essential for the ameliorative effect of low dose radiation on carbon tetrachloride-induced fatty liver. Single irradiation at 0.5 Gy ameliorates ferric nitrilotriacetate-induced nephritis. The irradiation increases catalase and decreases superoxide dismutase in kidney. The result suggests that low dose radiation reduced generation of hydroxide radical generation by reducing cellular hydroperoxide level. Single irradiation at 0.5 Gy at 12 week of age ameliorates incidence of type I diabetes in non-obese diabetic (NOD) mice through the suppression of inflammatory activity of splenocytes, and resultant apoptosis of β-cells in pancreas. The irradiation activities of superoxide dismutase and catalase, which coordinately diminish intracellular reactive oxygen species. Continuous irradiation at 0.70 mGy/hr from 10 week of age elongates life span, and suppresses alopecia in type II diabetesmice. The irradiation improved glucose clearance without affecting insulin-resistance, and increased pancreatic catalase activity. The results suggest that continuous low dose-rate irradiation protect

Dose Recalculation and the Dose-Guided Radiation Therapy (DGRT) Process Using Megavoltage Cone-Beam CT

International Nuclear Information System (INIS)

Cheung, Joey; Aubry, Jean-Francois; Yom, Sue S.; Gottschalk, Alexander R.; Celi, Juan Carlos; Pouliot, Jean

2009-01-01

Purpose: At University of California San Francisco, daily or weekly three-dimensional images of patients in treatment position are acquired for image-guided radiation therapy. These images can be used for calculating the actual dose delivered to the patient during treatment. In this article, we present the process of performing dose recalculation on megavoltage cone-beam computed tomography images and discuss possible strategies for dose-guided radiation therapy (DGRT). Materials and Methods: A dedicated workstation has been developed to incorporate the necessary elements of DGRT. Patient image correction (cupping, missing data artifacts), calibration, completion, recontouring, and dose recalculation are all implemented in the workstation. Tools for dose comparison are also included. Examples of image correction and dose analysis using 6 head-and-neck and 2 prostate patient datasets are presented to show possible tracking of interfraction dosimetric endpoint variation over the course of treatment. Results: Analysis of the head-and-neck datasets shows that interfraction treatment doses vary compared with the planning dose for the organs at risk, with the mean parotid dose and spinal cord D 1 increasing by as much as 52% and 10%, respectively. Variation of the coverage to the target volumes was small, with an average D 5 dose difference of 1%. The prostate patient datasets revealed accurate dose coverage to the targeted prostate and varying interfraction dose distributions to the organs at risk. Conclusions: An effective workflow for the clinical implementation of DGRT has been established. With these techniques in place, future clinical developments in adaptive radiation therapy through daily or weekly dosimetric measurements of treatment day images are possible.

Monte Carlo calculations of lung dose in ORNL phantom for boron neutron capture therapy

International Nuclear Information System (INIS)

Krstic, D.; Markovic, V.M.; Jovanovic, Z.; Milenkovic, B.; Nikezic, D.; Atanackovic, J.

2014-01-01

Monte Carlo simulations were performed to evaluate dose for possible treatment of cancers by boron neutron capture therapy (BNCT). The computational model of male Oak Ridge National Laboratory (ORNL) phantom was used to simulate tumours in the lung. Calculations have been performed by means of the MCNP5/X code. In this simulation, two opposite neutron beams were considered, in order to obtain uniform neutron flux distribution inside the lung. The obtained results indicate that the lung cancer could be treated by BNCT under the assumptions of calculations. The difference in evaluated dose in cancer and normal lung tissue suggests that BNCT could be applied for the treatment of cancers. The difference in exposure of cancer and healthy tissue can be observed, so the healthy tissue can be spared from damage. An absorbed dose ratio of metastatic tissue-to-the healthy tissue was ∼5. Absorbed dose to all other organs was low when compared with the lung dose. Absorbed dose depth distribution shows that BNC therapy can be very useful in the treatments for tumour. The ratio of the tumour absorbed dose and irradiated healthy tissue absorbed dose was also ∼5. It was seen that an elliptical neutron field was better irradiation choice. (authors)

Impact of Penicillin Allergy on Time to First Dose of Antimicrobial Therapy and Clinical Outcomes.

Science.gov (United States)

Conway, Erin L; Lin, Ken; Sellick, John A; Kurtzhalts, Kari; Carbo, James; Ott, Michael C; Mergenhagen, Kari A

2017-11-01

The objective of this study was to evaluate the impact of a listed penicillin allergy on the time to first dose of antibiotic in a Veterans Affairs hospital. Additional clinical outcomes of patients with penicillin allergies were compared with those of patients without a penicillin allergy. A retrospective chart review of veterans admitted through the emergency department with a diagnosis of pneumonia, urinary tract infection, bacteremia, and sepsis from January 2006 to December 2015 was conducted. The primary outcome was time to first dose of antibiotic treatment, defined as the time from when the patient presented to the emergency department to the medication administration time. Secondary outcomes included total antibiotic therapy duration and treatment outcomes, including mortality, length of stay, and 30-day readmission rate. A total of 403 patients were included in the final analysis; 57 patients (14.1%) had a listed penicillin allergy. The average age of the population was 75 years and 99% of the population was male. The mean time to first dose of antibiotic treatment for patients with a penicillin allergy was prolonged compared with those without a penicillin allergy (236.1 vs 186.6 minutes; P = 0.03), resulting in an approximately 50-minute delay. Penicillin-allergic patients were more likely to receive a carbapenem or fluoroquinolone antibiotic (P penicillin allergy had a prolonged time to first dose of antibiotic therapy. No significant differences were found in total antibiotic duration, length of stay, or 30-day readmission rate. The small sample size, older population, and single-center nature of this study may limit the generalizability of the present findings to other populations. Published by Elsevier Inc.

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.

SU-E-T-566: Neutron Dose Cloud Map for Compact ProteusONE Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Syh, J; Patel, B; Syh, J; Rosen, L; Wu, H [Willis-Knighton Medical Center, Shreveport, LA (United States)

2015-06-15

Purpose: To establish the base line of neutron cloud during patient treatment in our new compact Proteus One proton pencil beam scanning (PBS) system with various beam delivery gantry angles, with or without range shifter (RS) at different body sites. Pencil beam scanning is an emerging treatment technique, for the concerns of neutron exposure, this study is to evaluate the neutron dose equivalent per given delivered dose under various treatment conditions at our proton therapy center. Methods: A wide energy neutron dose equivalent detector (SWENDI-II, Thermo Scientific, MA) was used for neutron dose measurements. It was conducted in the proton therapy vault during beam was on. The measurement location was specifically marked in order to obtain the equivalent dose of neutron activities (H). The distances of 100, 150 and 200 cm at various locations are from the patient isocenter. The neutron dose was measured of proton energy layers, # of spots, maximal energy range, modulation width, field radius, gantry angle, snout position and delivered dose in CGE. The neutron dose cloud is reproducible and is useful for the future reference. Results: When distance increased the neutron equivalent dose (H) reading did not decrease rapidly with changes of proton energy range, modulation width or spot layers. For cranial cases, the average mSv/CGE was about 0.02 versus 0.032 for pelvis cases. RS will induce higher H to be 0.10 mSv/CGE in average. Conclusion: From this study, neutron per dose ratio (mSv/CGE) slightly depends upon various treatment parameters for pencil beams. For similar treatment conditions, our measurement demonstrates this value for pencil beam scanning beam has lowest than uniform scanning or passive scattering beam with a factor of 5. This factor will be monitored continuously for other upcoming treatment parameters in our facility.

Perinatal exposure to low-dose BDE-47, an emergent environmental contaminant, causes hyperactivity in rat offspring.

Science.gov (United States)

Suvorov, Alexander; Girard, Sylvie; Lachapelle, Sophie; Abdelouahab, Nadia; Sebire, Guillaume; Takser, Larissa

2009-01-01

Polybrominated diphenyl ethers (PBDE) are a group of environmental contaminants increasing in North America. Few data are available on neurobehavioral effects at low-dose exposure. Our goal in the present study was to evaluate whether low-dose BDE-47, which is the most abundant PBDE in human samples, affects the neurobehavioral development of rats. Dams were exposed to vehicle or low-dose BDE-47 (0.002, 0.02 and 0.2 mg/kg body weight) each 5 days from gestational day 15 to postnatal day (PND) 20 by intravenous injections. Spontaneous locomotor activity of pups was assessed using the open field test on PND 15, 20 and 25. Sensorimotor coordination was assessed using a RotaRod on PND 30. Exposure to BDE-47 increased locomotor activity of pups. Developmental landmarks and sensorimotor coordination were not influenced by exposure to BDE-47. BDE-47 content in adipose tissue of exposed rats was similar to that known for human populations. These results indicate neurodevelopmental disruption induced in rats by BDE-47 at levels found in the human population.

Indications for suboptimal low-dose direct oral anticoagulants for non-valvular atrial fibrillation patients

Directory of Open Access Journals (Sweden)

Masahiko Umei, MD

2017-10-01

Conclusions: With good adherence, the clinical course associated with DOACs is comparatively good. In the future, suboptimal low-dose DOAC therapy may serve as an appropriate choice for some patients with a high risk of stroke and bleeding.

Impact of Drug Therapy, Radiation Dose, and Dose Rate on Renal Toxicity Following Bone Marrow Transplantation

International Nuclear Information System (INIS)

Cheng, Jonathan C.; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

2008-01-01

Purpose: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). Methods and Materials: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age ≥18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. Results: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. Conclusion: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function

Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial.

Science.gov (United States)

Beaudoin, Francesca L; Lin, Charlie; Guan, Wentao; Merchant, Roland C

2014-11-01

Low-dose ketamine has been used perioperatively for pain control and may be a useful adjunct to intravenous (IV) opioids in the control of acute pain in the emergency department (ED). The aim of this study was to determine the effectiveness of low-dose ketamine as an adjunct to morphine versus standard care with morphine alone for the treatment of acute moderate to severe pain among ED patients. A double-blind, randomized, placebo-controlled trial with three study groups was conducted at a large, urban academic ED over a 10-month period. Eligible patients were 18 to 65 years old with acute moderate to severe pain (score of at least 5 out of 10 on the numerical pain rating scale [NRS] and pain duration ketamine (group 1), or 3) morphine and 0.3 mg/kg ketamine (group 2). Participants were assessed at 30, 60, and 120 minutes after study medication administration and received rescue analgesia as needed to target a 50% reduction in pain. The primary outcome measure of pain relief, or pain intensity reduction, was derived using the NRS and calculated as the summed pain-intensity (SPID) difference over 2 hours. The amount and timing of rescue opioid analgesia was evaluated as a secondary outcome. The occurrence of adverse events was also measured. Sixty patients were enrolled (n = 20 in each group). There were no differences between study groups with respect to age, sex, race/ethnicity, preenrollment analgesia, or baseline NRS. Over the 2-hour poststudy medication administration period, the SPIDs were higher (greater pain relief) for the ketamine study groups than the control group (standard care 4.0, interquartile range [IQR] = 1.8 to 6.5; group 1 7.0, IQR = 4.3 to 10.8; and group 2 7.8, IQR = 4.8 to 12.8; p ketamine groups were similar (p pain intensity up to 2 hours, whereas group 1 was similar to standard care by 2 hours. Similar numbers of patients received rescue analgesia: standard care group, seven of 20, 35%; group 1, four of 20, 20%; and group 2, four of 20, 20

Low dose ionizing radiation responses and knockdown of ATM kinase activity in glioma stem cells

International Nuclear Information System (INIS)

Lim, Y.C.; Roberts, T.; Day, B.; Kozlov, S.; Walker, D.; Lavin, M.; Harding, A.

2009-01-01

Genesis of new cells in the mammalian brain has previously been regarded as a negligible event; an assumption that long limited our understanding in the development of neoplasias. The recent discovery of perpetual lineages derived from neural stem cells has resulted in a new approach to studying the cellular behaviour of potential cancer stem cells in the brain. Glioblastoma multiforme (GBM), the most aggressive and lethal brain tumour is derived from a group of cancerous stem cells known as glioma stem cells. GBM cells are impervious to conventional therapies such as surgical resection and ionizing radiation because of their pluripotent and radioresistant properties. Thus in our study, we aim to investigate whether a combination of chemo- and radio- therapies is an effective treatment for glioma stem cells. The study utilizes a specific kinase inhibitor (ATMi) of the ATM (Ataxia-telangiectasia mutated) protein which is an essential protein in DNA-damage responses. In the presence of both low dose radiation and ATMi, glioma stem cells have rapid onset of cell death and reduction in growth. Since DNA damage can be inherited through cell division, accumulated DNA breaks in later generations may also lead to cell death. The limitation of conventional radiation therapy is that administration of fractionated (low) doses to reduce any potential harm to the surrounding healthy cells in the brain outweighs the benefits of high radiation doses to induce actual arrest in the propagation of malignant cells. Our study demonstrates a benefit in using low dose radiation combined with chemotherapy resulting in a reduction in malignancy of glioma stem cells. (author)

Molecular mechanisms of macrophage activation induced by the synergistic effects of low dose irradiation and adoptive T cell therapy

Energy Technology Data Exchange (ETDEWEB)

Bender, Noemi

2016-12-19

The detection of cancerous cells by the immune system elicits spontaneous antitumour immune responses. Still, during their progression, tumours acquire characteristics that enable them to escape immune surveillance. Cancer immunotherapy aims to reverse tumour immune evasion by activating and directing the immune system against transformed tumour cells. However, the tumours' intrinsic resistance mechanisms limit the success of many immunotherapeutic approaches. The functionally and morphologically abnormal tumour vasculature forms a physical barrier and prevents the entry of tumour-reactive immune effector cells, while the immunosuppressive tumour microenvironment impairs their function. To block tumour immune evasion, therapeutic strategies are being developed that combine cancer immunotherapy with treatment modalities, such as radiotherapy, that reprogram the tumour microenvironment to increase treatment efficacies and improve clinical outcome. In various preclinical models radiotherapy was shown to enhance the efficacy of adoptive T cell therapy. Our group showed that in the RIP1-TAg5 mouse model of spontaneous insulinoma, the transfer of in vitro-activated tumour-specific T cells induces T cell infiltration and promotes long-term survival only in combination with neoadjuvant local low dose irradiation (LDI). These treatment effects were mediated by iNOS+ macrophages. In this thesis, we investigated the mechanisms underlying the improved T cell infiltration and prolonged survival upon combination therapy with adoptive T cell transfer and local LDI. We demonstrate that combination therapy leads to a normalization of the aberrant tumour vasculature and endothelial activation, an increase in intratumoural macrophages, a reduction of intratumoural myeloid derived suppressor cells and, most importantly, to tumour regression. These findings suggest that this treatment inhibits tumour immune suppression but also facilitates immune effector cell infiltration through

Molecular mechanisms of macrophage activation induced by the synergistic effects of low dose irradiation and adoptive T cell therapy

International Nuclear Information System (INIS)

Bender, Noemi

2016-01-01

The detection of cancerous cells by the immune system elicits spontaneous antitumour immune responses. Still, during their progression, tumours acquire characteristics that enable them to escape immune surveillance. Cancer immunotherapy aims to reverse tumour immune evasion by activating and directing the immune system against transformed tumour cells. However, the tumours' intrinsic resistance mechanisms limit the success of many immunotherapeutic approaches. The functionally and morphologically abnormal tumour vasculature forms a physical barrier and prevents the entry of tumour-reactive immune effector cells, while the immunosuppressive tumour microenvironment impairs their function. To block tumour immune evasion, therapeutic strategies are being developed that combine cancer immunotherapy with treatment modalities, such as radiotherapy, that reprogram the tumour microenvironment to increase treatment efficacies and improve clinical outcome. In various preclinical models radiotherapy was shown to enhance the efficacy of adoptive T cell therapy. Our group showed that in the RIP1-TAg5 mouse model of spontaneous insulinoma, the transfer of in vitro-activated tumour-specific T cells induces T cell infiltration and promotes long-term survival only in combination with neoadjuvant local low dose irradiation (LDI). These treatment effects were mediated by iNOS+ macrophages. In this thesis, we investigated the mechanisms underlying the improved T cell infiltration and prolonged survival upon combination therapy with adoptive T cell transfer and local LDI. We demonstrate that combination therapy leads to a normalization of the aberrant tumour vasculature and endothelial activation, an increase in intratumoural macrophages, a reduction of intratumoural myeloid derived suppressor cells and, most importantly, to tumour regression. These findings suggest that this treatment inhibits tumour immune suppression but also facilitates immune effector cell infiltration through the

Occupational therapy practice in emergency care: Occupational therapists' perspectives.

Science.gov (United States)

Spang, Lisa; Holmqvist, Kajsa

2015-01-01

Emergency care takes place in a complex work environment that is characterized by critically ill patients, short hospital stays, and a wide variety of different healthcare professionals. Studies of occupational therapists' (OTs) experiences of working within emergency care have shown that they often experience difficulties in explaining the essence of occupational therapy and have to justify their approaches. Much effort has been made in Sweden to help OTs dispel the notion that occupational therapy is difficult to explain, and the aim of this study was to describe how Swedish OTs perceive their work in emergency care. A qualitative descriptive approach was taken, and 14 interviews were conducted with OTs working in emergency care. Qualitative content analysis was used to analyse the data. The overall theme that emerged was "Feeling established through deliberate occupation-based work". The underlying categories showed different strategies used by the OTs to provide occupational therapy in an emergency care context. Deliberate strategies were used to demonstrate the effectiveness of occupational therapy and its approaches to patients and other health care professionals, and this resulted in the OTs feeling both established and needed. Unlike the OTs in previous studies, the Swedish OTs experienced no difficulties in explaining occupational therapy and could make convincing arguments for their interventions. Parallel to their clinical work, the OTs worked with on-going development to find ways to improve their approaches. In summary, these Swedish OTs seem to have been provided with a professional language and the knowledge required to establish themselves in an emergency care setting.

Low-dose irradiation for controlling prostate cancer

International Nuclear Information System (INIS)

Cuttler, J.M.

2003-01-01

Prostate cancer is the second most commonly diagnosed cancer among North American men and the second leading cause of death in those aged 65 and over. The American Cancer Society recommends testing those over age 50 who are expected to live at least 10 years, even though the ability of early detection to decrease prostate cancer mortality has not been demonstrated. So controversy exists about the appropriateness of screening because of the considerable economic and social burden of diagnosing and treating prostate cancer, coupled with the projected large increase in the number of new cases as the population ages. This very important public health issue could be addressed at low cost by total-body low-dose irradiation therapy to stimulate the patient's own defences to prevent and control most cancers, including prostate cancer, with no symptomatic side effects. (author)

Low-dose ionizing radiation alleviates Aβ42-induced defective phenotypes in Drosophila Alzheimer's disease models

International Nuclear Information System (INIS)

Hwang, SooJin; Jeong, Hae Min; Nam, Seon Young

2017-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disease that is characterized by amyloid plaques, progressive neuronal loss, and gradual deterioration of memory. Amyloid imaging using positron emission tomography (PET) radiotracers have been developed and approved for clinical use in the evaluation of suspected neurodegenerative disease, including AD. Particularly, previous studies involving low-dose ionizing radiation on Aβ 42-treated mouse hippocampal neurons have suggested a potential role for low-dose ionizing radiation in the treatment of AD. However, associated in vivo studies involving the therapy effects of low-dose ionizing radiation on AD are still insufficient. As a powerful cell biological system, Drosophila AD models have been generated and established a useful model organism for study on the etiology of human AD. In this study, we investigated the hormesis effects of low-dose ionizing radiation on Drosophila AD models. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation.

Carcinogenesis induced by low-dose radiation

Directory of Open Access Journals (Sweden)

Piotrowski Igor

2017-11-01

Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

adverse effects of low dose methotrexate in rheumatoid arthritis patients

International Nuclear Information System (INIS)

Gilani, S.T.; Khan, D.A.; Khan, F.A.; Ahmed, M.

2012-01-01

To determine the frequency of adverse effects attributed to Methotrexate (MTX) toxicity and serum minimum toxic concentration with low dose MTX in Rheumatoid Arthritis (RA) patients. Study Design: Cross-sectional observational study. Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from March 2010 to March 2011. Methodology: One hundred and forty adult patients of RA receiving low dose MTX (10 mg/week) for at least 3 months, ere included by consecutive sampling. Blood samples were collected 2 hours after the oral dose of MTX. Serum alanine transaminase and creatinine were analyzed on Hitachi and blood counts on Sysmex analyzer. Serum MTX concentration was measured on TDX analyzer. Results: Out of one hundred and forty patients; 68 males (49%) and 72 females (51%), 38 developed MTX toxicity (27%), comprising of hepatotoxicity in 12 (8.6%), nephrotoxicity in 3 (2.1%), anaemia in 8 (5.7%), leucopenia in 2 (1.4%), thrombocytopenia in 3 (2.1%), pancytopenia in 2 (1.4%), gastrointestinal adverse effects in 5 (3.6%) and mucocutaneous problems in 3 (2.1%). Receiver operating characteristic curve revealed serum minimum toxic concentration of MTX at cutoff value of 0.71 mu mol/l with a sensitivity of 71% and specificity of 76%. Conclusion: Adverse effects of low dose MTX were found in 27% of RA patients, mainly comprising of hepatotoxicity and haematological problems. MTX toxicity can be detected by therapeutic drug monitoring of serum concentration of 0.71 mu mol/l with sensitivity of 71% and specificity of 76% in the patients on low dose MTX maintenance therapy. (author)

Iodine 131 therapy patients: radiation dose to staff

International Nuclear Information System (INIS)

Castronovo, F.P. Jr.; Beh, R.A.; Veilleux, N.M.

1986-01-01

Metastasis to the skeletal system from follicular thyroid carcinoma may be treated with an oral dose of 131 I-NaI. Radiation exposures to hospital personnel attending these patients were calculated as a function of administered dose, distance from the patient and time after administration. Routine or emergency patient handling tasks would not exceed occupational radiation protection guidelines for up to 30 min immediately after administration. The emergency handling of several patients presents the potential for exceeding these guidelines. (author)

Biological responses to low dose rate gamma radiation

International Nuclear Information System (INIS)

Magae, Junji; Ogata, Hiromitsu

2003-01-01

Linear non-threshold (LNT) theory is a basic theory for radioprotection. While LNT dose not consider irradiation time or dose-rate, biological responses to radiation are complex processes dependent on irradiation time as well as total dose. Moreover, experimental and epidemiological studies that can evaluate LNT at low dose/low dose-rate are not sufficiently accumulated. Here we analyzed quantitative relationship among dose, dose-rate and irradiation time using chromosomal breakage and proliferation inhibition of human cells as indicators of biological responses. We also acquired quantitative data at low doses that can evaluate adaptability of LNT with statistically sufficient accuracy. Our results demonstrate that biological responses at low dose-rate are remarkably affected by exposure time, and they are dependent on dose-rate rather than total dose in long-term irradiation. We also found that change of biological responses at low dose was not linearly correlated to dose. These results suggest that it is necessary for us to create a new model which sufficiently includes dose-rate effect and correctly fits of actual experimental and epidemiological results to evaluate risk of radiation at low dose/low dose-rate. (author)

Effects of low-level laser therapy on wound healing

Directory of Open Access Journals (Sweden)

Fabiana do Socorro da Silva Dias Andrade

Full Text Available OBJECTIVE: To gather and clarify the actual effects of low-level laser therapy on wound healing and its most effective ways of application in human and veterinary medicine.METHODS: We searched original articles published in journals between the years 2000 and 2011, in Spanish, English, French and Portuguese languages, belonging to the following databases: Lilacs, Medline, PubMed and Bireme; Tey should contain the methodological description of the experimental design and parameters used.RESULTS: doses ranging from 3 to 6 J/cm2 appear to be more effective and doses 10 above J/cm2 are associated with deleterious effects. The wavelengths ranging from 632.8 to 1000 nm remain as those that provide more satisfactory results in the wound healing process.CONCLUSION: Low-level laser can be safely applied to accelerate the resolution of cutaneous wounds, although this fact is closely related to the election of parameters such as dose, time of exposure and wavelength.

Effects of low doses

International Nuclear Information System (INIS)

Le Guen, B.

2001-01-01

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.)

Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

DEFF Research Database (Denmark)

Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas

2015-01-01

High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue ...

Low-dose radiation epidemiological studies: an assessment of methodological problems

International Nuclear Information System (INIS)

Modan, B.

1991-01-01

The present report attempts to assess the problems inherent in the analysis of low dose radiation studies, with emphasis on possible sources of methodological errors in the published data, and the consequent relevance to risk estimates. The published data examined concerned populations exposed to nuclear sources such as fallout, weapons' test or in the vicinity of nuclear reactors, occupational exposure, intra-uterine diagnostic X-rays, scattered radiation following X-ray therapy and background irradiation. (UK)

Maximal safe dose of I-131 after failure of standard fixed dose therapy in patients with differentiated thyroid carcinoma

International Nuclear Information System (INIS)

Lee, Jong-Jin; Chung, June-Key; Kim, Sung-Eun; Kang, Won-Jun; Park, Do-Joon; Lee, Dong-Soo; Cho, Bo-Youn; Lee, Myung-Chul

2008-01-01

The maximal safe dose (MSD) on the basis of bone marrow irradiation levels allows the delivery of a large amount of I-131 to thyroid cancer tissue. The efficacy of MSD therapy in differentiated metastatic thyroid cancers that persisted after conventional fixed dose therapy is investigated. Forty-seven differentiated thyroid carcinoma patients with non-responsive residual disease despite repetitive fixed dose I-131 therapy were enrolled in this study. Their postoperative pathologies were 43 papillary carcinomas and 4 follicular carcinomas. The MSD was calculated with the Memorial Sloan-Kettering Cancer Center protocol using serial blood samples. The MSDs were administered at intervals of 6 months. Treatment responses were evaluated using I-131 whole-body scans and serum thyroglobulin measurements. The mean calculated MSD was 12.5±2.1 GBq (339.6±57.5 mCi). Of the 46 patients, 7 (14.9%) showed complete remission, 15 (31.9%) partial remission, 19 (40.4%) stable disease, and 6 (12.8%) disease progression. Of the patients who showed complete or partial remission, 15 (65%) showed response after the first MSD session and 6 (26%) showed response after the second session. Twenty-nine patients (62%) experienced transient cytopenia after therapy, but three did not recover to the baseline level. The maximal safe dose provides an effective means of treatment in patients who failed to respond adequately to conventional fixed dose therapy. I-131 MSD therapy can be considered in patients who fail fixed dose therapy. (author)

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.

Doses to Carotid Arteries After Modern Radiation Therapy for Hodgkin Lymphoma

DEFF Research Database (Denmark)

Maraldo, M.V.; Brodin, Nils Patrik; Aznar, Marianne Camille

2013-01-01

Hodgkin lymphoma (HL) survivors are at an increased risk of stroke because of carotid artery irradiation. However, for early-stage HL involved node radiation therapy (INRT) reduces the volume of normal tissue exposed to high doses. Here, we evaluate 3-dimensional conformal radiation therapy (3D......-CRT), volumetric-modulated arc therapy (VMAT), and proton therapy (PT) delivered as INRT along with the extensive mantle field (MF) by comparing doses to the carotid arteries and corresponding risk estimates....

Mammography-oncogenecity at low doses

International Nuclear Information System (INIS)

Heyes, G J; Mill, A J; Charles, M W

2009-01-01

Controversy exists regarding the biological effectiveness of low energy x-rays used for mammography breast screening. Recent radiobiology studies have provided compelling evidence that these low energy x-rays may be 4.42 ± 2.02 times more effective in causing mutational damage than higher energy x-rays. These data include a study involving in vitro irradiation of a human cell line using a mammography x-ray source and a high energy source which matches the spectrum of radiation observed in survivors from the Hiroshima atomic bomb. Current radiation risk estimates rely heavily on data from the atomic bomb survivors, and a direct comparison between the diagnostic energies used in the UK breast screening programme and those used for risk estimates can now be made. Evidence highlighting the increase in relative biological effectiveness (RBE) of mammography x-rays to a range of x-ray energies implies that the risks of radiation-induced breast cancers for mammography x-rays are potentially underestimated by a factor of four. A pooled analysis of three measurements gives a maximal RBE (for malignant transformation of human cells in vitro) of 4.02 ± 0.72 for 29 kVp (peak accelerating voltage) x-rays compared to high energy electrons and higher energy x-rays. For the majority of women in the UK NHS breast screening programme, it is shown that the benefit safely exceeds the risk of possible cancer induction even when this higher biological effectiveness factor is applied. The risk/benefit analysis, however, implies the need for caution for women screened under the age of 50, and particularly for those with a family history (and therefore a likely genetic susceptibility) of breast cancer. In vitro radiobiological data are generally acquired at high doses, and there are different extrapolation mechanisms to the low doses seen clinically. Recent low dose in vitro data have indicated a potential suppressive effect at very low dose rates and doses. Whilst mammography is a low

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.)

An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis

Directory of Open Access Journals (Sweden)

Martin-Martin LS

2017-03-01

Full Text Available LS Martin-Martin,1 F Giovannangeli,2 E Bizzi,2 U Massafra,2 E Ballanti,2 M Cassol,3 A Migliore2 1Department of Internal Medicine, Regina Apostolorum Hospital, 2Operative Unit of Rheumatology, 3Department of Internal Medicine, San Pietro Fatebenefratelli Hospital, Rome, Italy Background: Biologic agents are currently the strongest immunosuppressive drugs able to induce remission in rheumatoid arthritis (RA. One of the objectives of the medical scientific community now is how to maintain remission or low disease activity (LDA. The aim of this trial is to evaluate the contribution of low-dose sequential kinetic activation (SKA IL-4, IL-10, and anti-IL-1 antibodies (10 fg/mL in patients affected by RA in maintaining LDA or remission obtained after biological therapy. Method: This is a randomized, open, active-controlled, prospective, Phase IV trial. Disease activity score (DAS28, clinical disease activity index, simplified disease activity index, erythrocyte sedimentation rate and C-reactive protein levels, global health assessment, and pain visual analog scale were evaluated at baseline visit and then every 3 months together with an assessment of side effects till 12 months. Thirty-nine RA patients were enrolled and randomized to continue disease-modifying antirheumatic drugs (DMARDs therapy or to receive a combination of SKA low-dose cytokines formulated in concentration of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive months. Results: The rate of maintenance of LDA at 12 months was superior in the group treated with low-dose cytokines compared with patients treated with DMARDs, 66.7% and 42.1%, respectively; however, the difference between the groups was not statistically significant. No side effects were reported in both groups. Conclusion: This is the first study using a combination of three low-dose cytokines in RA, after data published on psoriasis. These data suggest that the use of a combination of low-dose SKA

Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Davidson, Sean R H; Gertner, Mark R; Bogaards, Arjen; Sherar, Michael D; Wilson, Brian C [Division of Biophysics and Bioimaging, Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada); Weersink, Robert A; Giewercer, David [Laboratory for Applied Biophysics, Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada); Haider, Masoom A [Joint Department of Medical Imaging, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada); Scherz, Avigdor [Department of Plant Science, Weizmann Institute of Science, PO Box 26, Rehovot 76100 (Israel); Elhilali, Mostafa [Department of Surgery, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6 (Canada); Chin, Joseph L [Department of Oncology, University of Western Ontario, 800 Commissioners Road East, PO Box 5010, London, Ontario N6A 5W9 (Canada); Trachtenberg, John [Department of Urology, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada)], E-mail: wilson@uhnres.utoronto.ca

2009-04-21

With the development of new photosensitizers that are activated by light at longer wavelengths, interstitial photodynamic therapy (PDT) is emerging as a feasible alternative for the treatment of larger volumes of tissue. Described here is the application of PDT treatment planning software developed by our group to ensure complete coverage of larger, geometrically complex target volumes such as the prostate. In a phase II clinical trial of TOOKAD vascular targeted photodynamic therapy (VTP) for prostate cancer in patients who failed prior radiotherapy, the software was used to generate patient-specific treatment prescriptions for the number of treatment fibres, their lengths, their positions and the energy each delivered. The core of the software is a finite element solution to the light diffusion equation. Validation against in vivo light measurements indicated that the software could predict the location of an iso-fluence contour to within approximately {+-}2 mm. The same software was used to reconstruct the treatments that were actually delivered, thereby providing an analysis of the threshold light dose required for TOOKAD-VTP of the post-irradiated prostate. The threshold light dose for VTP-induced prostate damage, as measured one week post-treatment using contrast-enhanced MRI, was found to be highly heterogeneous, both within and between patients. The minimum light dose received by 90% of the prostate, D{sub 90}, was determined from each patient's dose-volume histogram and compared to six-month sextant biopsy results. No patient with a D{sub 90} less than 23 J cm{sup -2} had complete biopsy response, while 8/13 (62%) of patients with a D{sub 90} greater than 23 J cm{sup -2} had negative biopsies at six months. The doses received by the urethra and the rectal wall were also investigated.

Transperineal high-dose-rate interstitial radiation therapy in the management of gynecologic malignancies

Energy Technology Data Exchange (ETDEWEB)

Itami, Jun; Hara, Ryuseke; Kozuka, Takuyou; Yamashita, Hideomi; Nakajima, Kaori; Shibata, Kouji; Abe, Yoshihisa; Fuse, Masashi; Ito, Masashi [International Medical Center of Japan, Tokyo (Japan). Dept. of Radiation Therapy and Oncology

2003-11-01

Background: High-dose-rate interstitial radiation therapy is a newly introduced modality, and its role in the management of gynecologic malignancies remains to be studied. Clinical experience in high-dose-rate interstitial radiation therapy was retrospectively investigated. Patients and Methods: Eight patients with primary and nine with recurrent gynecologic malignancies underwent high-dose-rate interstitial radiation therapy with/without external-beam irradiation. Fractional dose of the high-dose-rate interstitial radiation therapy ranged between 4 and 6 Gy with total doses of 15-54 Gy. Interstitial irradiation was performed twice daily with an interval of > 6 h. Results: 2-year local control rate was 75% for primary treatment and 47% for treatment of recurrence (p = 0.46). Maximum tumor size had a statistically significant impact on local control (p < 0.002). Grade 2 and 4 late complications were seen in five patients, and the incidence was significantly higher in patients with a larger volume enclosed by the prescribed fractional dose of high-dose-rate interstitial radiation therapy. The incidence of grade 2 and 4 complications at 18 months was 78% and 0% with a volume > 100 cm{sup 3} and {<=} 100 cm{sup 3}, respectively (p < 0.04). Conclusion: Although high-dose-rate interstitial radiation therapy is a promising modality, it must be applied cautiously to patients with bulky tumors because of the high incidence of serious complications. (orig.)

Low-dose computed tomography image restoration using previous normal-dose scan

International Nuclear Information System (INIS)

Ma, Jianhua; Huang, Jing; Feng, Qianjin; Zhang, Hua; Lu, Hongbing; Liang, Zhengrong; Chen, Wufan

2011-01-01

Purpose: In current computed tomography (CT) examinations, the associated x-ray radiation dose is of a significant concern to patients and operators. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) or kVp parameter (or delivering less x-ray energy to the body) as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and the noise would propagate into the CT image if no adequate noise control is applied during image reconstruction. Since a normal-dose high diagnostic CT image scanned previously may be available in some clinical applications, such as CT perfusion imaging and CT angiography (CTA), this paper presents an innovative way to utilize the normal-dose scan as a priori information to induce signal restoration of the current low-dose CT image series. Methods: Unlike conventional local operations on neighboring image voxels, nonlocal means (NLM) algorithm utilizes the redundancy of information across the whole image. This paper adapts the NLM to utilize the redundancy of information in the previous normal-dose scan and further exploits ways to optimize the nonlocal weights for low-dose image restoration in the NLM framework. The resulting algorithm is called the previous normal-dose scan induced nonlocal means (ndiNLM). Because of the optimized nature of nonlocal weights calculation, the ndiNLM algorithm does not depend heavily on image registration between the current low-dose and the previous normal-dose CT scans. Furthermore, the smoothing parameter involved in the ndiNLM algorithm can be adaptively estimated based on the image noise relationship between the current low-dose and the previous normal-dose scanning protocols. Results: Qualitative and quantitative evaluations were carried out on a physical phantom as well as clinical abdominal and brain perfusion CT scans in terms of accuracy and resolution properties. The gain by the use

Hypophosphatemic osteomalacia induced by low-dose adefovir therapy: focus on manifestations in the skeletal system and literature review.

Science.gov (United States)

Kim, Du Hwan; Sung, Duk Hyun; Min, Yong Ki

2013-03-01

Osteomalacia is a metabolic bone disease that leads to softening of the bones and can be caused by hypophosphatemia. Large clinical studies of low-dose adefovir dipivoxil (adefovir) have found no evidence of renal tubular dysfunction leading to hypophosphatemia after 48 weeks of treatment. We report two cases of low-dose adefovir-induced hypophosphatemic osteomalacia that initially presented with diffuse musculoskeletal pain. The first patient was a 62-year-old man with a 2-year history of bone pain involving the dorsal mid-thorax, lower anterior chest wall, right sacroiliac joint area, and both knees. The patient had been receiving adefovir for 5 years before confirmation of hypophosphatemia and urinary phosphate wasting. Bone scintigraphy revealed multifocal lesions including multiple ribs, costochondral junctions, costovertebral junctions, sacrum, both posterior iliac bones, both proximal tibia, right calcaneus, and the left second metatarsophalangeal joint area, which were suggestive of metabolic bone disorder. Bone pain was significantly reduced within 3 months after supplementation with phosphate and calcitriol. The second patient was a 54-year-old male who presented with an 18-month history of severe bone pain of the right medial knee and low back. The patient had been taking adefovir for approximately 40 months before the development of bone pain. Laboratory data revealed hypophosphatemia and vitamin D deficiency. Bone scintigraphy showed increased uptake in bilateral ribs, sternum, both scapulae, both costovertebral junctions, both pelvic bones, medial cortex of the right proximal femur, right proximal tibia, and the left lateral tarsal bone. The symptoms improved by changing the antiviral agent from adefovir to entecavir. Because osteomalacia often presents with diffuse bone pain, non-specific radiologic findings and non-characteristic routine serum biochemical changes, the disease can be confused with various musculoskeletal diseases and a high index

High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth

International Nuclear Information System (INIS)

Inoue, Takehiro; Inoue, Toshihiko; Yamazaki, Hideya; Koizumi, Masahiko; Kagawa, Kazufumi; Yoshida, Ken; Shiomi, Hiroya; Imai, Atsushi; Shimizutani, Kimishige; Tanaka, Eichii; Nose, Takayuki; Teshima, Teruki; Furukawa, Souhei; Fuchihata, Hajime

1998-01-01

Purpose: Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth. Methods and Materials: From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using 198 Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. Results: Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with 198 Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR. Conclusion: HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff

Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

Science.gov (United States)

Madas, Balázs G

2016-07-01

Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

The effect of low-dose spironolactone on resistant hypertension

DEFF Research Database (Denmark)

Engbaek, Mette; Hjerrild, Mette; Hallas, Jesper

2010-01-01

with three classes of antihypertensive drugs. The effect on blood pressure was estimated by office measurements together with serum potassium and adverse effects. The data were analyzed retrospectively. A total of 544 patients were identified; 200 were excluded because of secondary hypertension, other......Our objective was to estimate the effect of addition of low-dose spironolactone to previous antihypertensive therapy in patients with resistant hypertension. Patients had 25 to 50 mg of spironolactone once daily added to the treatment of hypertension that was uncontrolled despite previous treatment...... indications for spironolactone than hypertension, previous antihypertensive therapy with less than three drugs unless demonstrated intolerance to a third drug, insufficient compliance, and lack of follow-up data. Thus, 344 cases were included in the analysis. The population was 62.1 ± 12.8 years old, 45...

A Novel Simple Phantom for Verifying the Dose of Radiation Therapy

Directory of Open Access Journals (Sweden)

J. H. Lee

2015-01-01

Full Text Available A standard protocol of dosimetric measurements is used by the organizations responsible for verifying that the doses delivered in radiation-therapy institutions are within authorized limits. This study evaluated a self-designed simple auditing phantom for use in verifying the dose of radiation therapy; the phantom design, dose audit system, and clinical tests are described. Thermoluminescent dosimeters (TLDs were used as postal dosimeters, and mailable phantoms were produced for use in postal audits. Correction factors are important for converting TLD readout values from phantoms into the absorbed dose in water. The phantom scatter correction factor was used to quantify the difference in the scattered dose between a solid water phantom and homemade phantoms; its value ranged from 1.084 to 1.031. The energy-dependence correction factor was used to compare the TLD readout of the unit dose irradiated by audit beam energies with 60Co in the solid water phantom; its value was 0.99 to 1.01. The setup-condition factor was used to correct for differences in dose-output calibration conditions. Clinical tests of the device calibrating the dose output revealed that the dose deviation was within 3%. Therefore, our homemade phantoms and dosimetric system can be applied for accurately verifying the doses applied in radiation-therapy institutions.

Are low radiation doses Dangerous?

International Nuclear Information System (INIS)

Garcia Lima, O.; Cornejo, N.

1996-01-01

In the last few years the answers to this questions has been affirmative as well as negative from a radiation protection point of view low doses of ionizing radiation potentially constitute an agent causing stochasting effects. A lineal relation without threshold is assumed between dose and probability of occurrence of these effects . Arguments against the danger of probability of occurrence of these effects. Arguments again the danger of low dose radiation are reflected in concepts such as Hormesis and adaptive response, which are phenomena that being studied at present

Effects of low-dose IV ketamine on peripheral and central pain from major limb injuries sustained in combat.

Science.gov (United States)

Polomano, Rosemary C; Buckenmaier, Chester C; Kwon, Kyung H; Hanlon, Alexandra L; Rupprecht, Christine; Goldberg, Cynthia; Gallagher, Rollin M

2013-07-01

Examine response patterns to low-dose intravenous (IV) ketamine continuous infusions on multiple pain outcomes, and demonstrate effectiveness, safety, and tolerability of ketamine administration on general wards. Retrospective case series of consecutive patients given low-dose IV ketamine continuous infusions. Walter Reed Army Medical Center, Washington, DC. Nineteen eligible inpatients with neuropathic pain from major limb injuries sustained in combat with inadequate pain control from multimodal analgesia. A 3-day IV infusion of ketamine at doses ≤ 120 μg/kg/h. Daily present (PPI), average (API), and worst (WPI) pain intensity (0-10), global pain relief (GPR) (1 "no relief" to 5 "complete relief"), daily assessments of adverse events, and daily opioid requirements measured during therapy. A significant reduction in PPI (P pain (PLP) (N = 10; P = 0.0436) were observed. Mean percent increase in overall GPR was better for those reporting GPR scores ≤ 3 (N = 13) in the first 24 hours of therapy (P = 0.0153). While not significant, mean opioid requirement (IV morphine equivalents) decreased from 129.9 mgs ± 137.3 on day 1 to 112.14 ± 86.3 24 hours after therapy. Low-dose ketamine infusions for complex combat injury pain were safe and effective, and demonstrated response patterns over time and by baseline pain score stratification and presence or absence of PLP. Wiley Periodicals, Inc.

Nonrandomized study comparing the effects of preoperative radiotherapy and daily administration of low-dose cisplatin with those radiotherapy alone for oral cancer

International Nuclear Information System (INIS)

Kurita, Hiroshi; Azegami, Takuya; Kobayashi, Hirokazu; Kurashina, Kenji; Tanaka, Kouichi; Kotani, Akira; Oguchi, Masahiko; Tamura, Minoru.

1997-01-01

The purpose of this study was to compare the effect of preoperative radiotherapy and daily administration of low-dose cisplatin with those of radiotherapy alone for oral cancer. Ten patients underwent preoperative radiotherapy of 30 to 40 Gy with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten patients received external radiotherapy alone. The locoregional response rates (complete response and partial response) did not differ significantly between the two groups (80% for combined therapy and 60% for radiotherapy alone). On histopathologic evaluation of surgical specimens, however, the combined-therapy group (80%) had a higher response rate than did the radiotherapy-alone group (10%; p<0.01). We conclude that daily administration of low-dose cisplatin enhances the efficacy of radiotherapy against primary tumors. We also suggested that combined therapy may be beneficial as an initial treatment for oral cancer before a planned operation. (author)

Evaluation of the Effect of Different Doses of Low Energy Shock Wave Therapy on the Erectile Function of Streptozotocin (STZ-Induced Diabetic Rats

Directory of Open Access Journals (Sweden)

Zhong-Cheng Xin

2013-05-01

Full Text Available To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT on the erectile dysfunction (ED in streptozotocin (STZ induced diabetic rats. SD rats (n = 75 were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups. Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment.

Emerging biologic therapies for hypercholesterolaemia.

Science.gov (United States)

Pucci, Giacomo; Cicero, Arrigo F; Borghi, Claudio; Schillaci, Giuseppe

2017-09-01

LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy. Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions. The discontinuation in the development of bococizumab due to efficacy and safety concerns, and the initial promising data about inclisiran, a long-acting small inhibiting RNA molecule against PCSK9 synthesis, is also discussed. Expert opinion: Initial data about cardiovascular (CV) outcomes in large scale, long-term studies suggest a possible further therapeutic pathway for LDL-C reduction, and currently support the notion that further LDL-C reduction, obtained with PCSK9 inhibition on top of best available therapy, provides increased CV protection in subjects at very high CV risk. The development and marketing of mAbs against PCSK9 could help to redefine current therapeutic strategies aimed at reducing cardiovascular (CV) morbidity and risk, through the reduction of LDL-C concentrations. The cost-effectiveness of these emerging drugs is yet to be established.

Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

Energy Technology Data Exchange (ETDEWEB)

Willegaignon, J., E-mail: j.willegaignon@gmail.com; Sapienza, M. T.; Coura-Filho, G. B.; Buchpiguel, C. A. [Cancer Institute of São Paulo State (ICESP), Clinical Hospital, School of Medicine, University of São Paulo, São Paulo 01246-000 (Brazil); Nuclear Medicine Service, Department of Radiology, School of Medicine, University of São Paulo, Sao Paulo 01246-000 (Brazil); Watanabe, T. [Nuclear Medicine Service, Department of Radiology, School of Medicine, University of São Paulo, São Paulo 01246-000 (Brazil); Traino, A. C. [Unit of Medical Physics, Azienda Ospedaliero-Universitaria Pisana, Pisa 56126 (Italy)

2014-01-15

Purpose: The precise determination of organ mass (m{sub th}) and total number of disintegrations within the thyroid gland (A{sup ~}) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose–response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves’ disease (GD) treatment planning were calculated using different approaches to estimating the m{sub th} and the A{sup ~}. Methods: Fifty patients were included in the study. Thyroid{sup 131}I uptake measurements were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (T{sub eff}) of {sup 131}I in the thyroid; the thyroid cumulated activity was then estimated using the T{sub eff} thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA/EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. Results: The average ratio (±1 standard deviation) betweenm{sub th} estimated by SCTG and USG was 1.74 (±0.64) and that between A{sup ~} obtained by T{sub eff} and the integration of measured activity in the gland was 1.71 (±0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when m{sub th} was measured by either USG or SCTG and A

Cystoid Macular Edema Induced by Low Doses of Nicotinic Acid

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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.

Dose-response relationships and risk estimates for the induction of cancer due to low doses of low-LET radiation

International Nuclear Information System (INIS)

Elaguppillai, V.

1981-01-01

Risk estimates for radiation-induced cancer at low doses can be obtained only by extrapolation from the known effects at high doses and high dose rates, using a suitable dose-response model. The applicability of three different models, linear, sublinear and supralinear, are discussed in this paper. Several experimental studies tend to favour a sublinear dose-response model (linear-quadratic model) for low-LET radiation. However, human epidemiological studies do not exclude any of the dose-response relationships. The risk estimates based on linear and linear quadratic dose-response models are compared and it is concluded that, for low-LET radiation, the linear dose-response model would probably over-estimate the actual risk of cancer by a factor of two or more. (author)

Dose-volume considerations in stereotaxic brain radiation therapy

International Nuclear Information System (INIS)

Houdek, P.V.; Schwade, J.G.; Pisciotta, V.J.; Medina, A.J.; Lewin, A.A.; Abitbol, A.A.; Serago, C.F.

1988-01-01

Although brain radiation therapy experience suggests that a gain in the therapeutic ratio may be achieved by optimizing the dose-volume relationship, no practical system for quantitative assessment of dose-volume data has been developed. This presentation describes the rationale for using the integral dose function for this purpose and demonstrates that with the use of a conventional treatment planning computer and a series of computed tomographic scans, first-order optimization of the dose-volume function can be accomplished in two steps: first, high-dose volume is minimized by selecting an appropriate treatment technique and tumor margin, and then dosage is maximized by calculating the brain tolerance dose as a function of the irradiated volume

Emerging pharmaceutical therapies for COPD

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Lakshmi SP

2017-07-01

Full Text Available Sowmya P Lakshmi,1,2 Aravind T Reddy,1,2 Raju C Reddy1,2 1Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, 2Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA Abstract: COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations. Among these are compounds that inhibit the CXCR2 receptor, mitogen-activated protein kinase/Src kinase, myristoylated alanine-rich C kinase substrate, selectins, and the endothelin receptor. Activation of certain transcription factors may also be relevant, as a large retrospective cohort study of COPD patients with diabetes found that the peroxisome proliferator-activated receptor γ (PPARγ agonists rosiglitazone and pioglitazone were associated with reduced COPD exacerbation rate. Notably, several therapies have shown efficacy only in identifiable subgroups of COPD patients, suggesting that subgroup identification may become more important in future treatment strategies. This review summarizes the status of emerging therapeutic pharmaceuticals for COPD and highlights those that appear most promising. Keywords: pulmonary, PPAR, phosphodiesterase, emphysema, cigarette, mucus 

Reactor emergency preparedness: lifesaving or as low as reasonable achievable

International Nuclear Information System (INIS)

Hull, A.P.

1981-01-01

An emergency is defined as an unforseen combination of circumstances or the resultant state that calls for immediate action. Although not explicitly indicated, the implication is that the action is intended to protect life, limb and or property from extreme peril. For the most part, the kind and extent of the emergency planning required under current regulations of the USNRC do not appear to be so much related to emergencies (within the above definition) as they do toward the reduction of the off-site radiation doses from uncontrolled releases during reactor accident conditions to as low as reasonably achievable levels. Not only do the latter appear to be of questionable cost-effectiveness, but in their extent and complexity beyond normal disaster planning they may in fact be counter productive to optimum public safety

Reactor emergency preparedness: lifesaving or as low as reasonable achievable

Energy Technology Data Exchange (ETDEWEB)

Hull, A.P.

1981-01-01

An emergency is defined as an unforseen combination of circumstances or the resultant state that calls for immediate action. Although not explicitly indicated, the implication is that the action is intended to protect life, limb and or property from extreme peril. For the most part, the kind and extent of the emergency planning required under current regulations of the USNRC do not appear to be so much related to emergencies (within the above definition) as they do toward the reduction of the off-site radiation doses from uncontrolled releases during reactor accident conditions to as low as reasonably achievable levels. Not only do the latter appear to be of questionable cost-effectiveness, but in their extent and complexity beyond normal disaster planning they may in fact be counter productive to optimum public safety.

Pilot website to support international collaboration for dose assessments in a radiation emergency

International Nuclear Information System (INIS)

Livingston, G.K.; Wilkins, R.C.; Ainsbury, E.A.

2011-01-01

Nuclear terrorism has emerged as a significant threat which could require timely medical interventions to reduce potential radiation casualties. Early dose assessments are critical since optimal care depends on knowing a victim's radiation dose. The dicentric chromosome aberration assay is considered the 'gold standard' to estimate the radiation dose because the yield of dicentrics correlates positively with the absorbed dose. Dicentrics have a low background frequency, are independent of age and gender and are relatively easy to identify. This diagnostic test for radiation exposure, however, is labor intensive and any single or small group of laboratories could easily be overwhelmed by a mass casualty event. One solution to this potential problem is to link the global WHO BioDoseNet members via the Internet so multiple laboratories could work cooperatively to screen specimens for dicentric chromosomes and generate timely dose estimates. Inter-laboratory comparison studies have shown that analysis of electronic chromosome images viewed on the computer monitor produces scoring accuracy equivalent to viewing live images in the microscope. This functional equivalence was demonstrated during a comparative study involving five laboratories constructing 60 Co gamma ray calibration curves and was further confirmed when comparing results of blind dose estimates submitted by each laboratory. It has been further validated in two recent WHO BioDoseNet trial exercises where 20 metaphase images were shared by e-mail and 50 images were shared on a test website created for this purpose. The Internet-based exercise demonstrated a high level of concordance among 20 expert scorers who evaluated the same 50 metaphase spreads selected to exhibit no, low, moderate and severe radiation damage. Nineteen of 20 scorers produced dicentric equivalent counts within the 95% confidence limits of the mean. The Chi-squared test showed strong evidence of homogeneity in the data (p = 0

Pilot website to support international collaboration for dose assessments in a radiation emergency

Energy Technology Data Exchange (ETDEWEB)

Livingston, G.K., E-mail: Gordon.Livingston@orise.orau.gov [Oak Ridge Associated Universities, REAC/TS, Radiation Emergency Medicine (REM), P.O. Box 117, Oak Ridge, TN 37831 (United States); Wilkins, R.C., E-mail: Ruth.Wilkins@hc-sc.gc.ca [Health Canada, Consumer and Clinical Radiation Protection Bureau, Ottawa, ON K1A 1C1 (Canada); Ainsbury, E.A., E-mail: liz.ainsbury@hpa.org.uk [Health Protection Agency, Radiation Protection Division, Chilton, Didcot, Oxfordshire OX11 0RQ (United Kingdom)

2011-09-15

Nuclear terrorism has emerged as a significant threat which could require timely medical interventions to reduce potential radiation casualties. Early dose assessments are critical since optimal care depends on knowing a victim's radiation dose. The dicentric chromosome aberration assay is considered the 'gold standard' to estimate the radiation dose because the yield of dicentrics correlates positively with the absorbed dose. Dicentrics have a low background frequency, are independent of age and gender and are relatively easy to identify. This diagnostic test for radiation exposure, however, is labor intensive and any single or small group of laboratories could easily be overwhelmed by a mass casualty event. One solution to this potential problem is to link the global WHO BioDoseNet members via the Internet so multiple laboratories could work cooperatively to screen specimens for dicentric chromosomes and generate timely dose estimates. Inter-laboratory comparison studies have shown that analysis of electronic chromosome images viewed on the computer monitor produces scoring accuracy equivalent to viewing live images in the microscope. This functional equivalence was demonstrated during a comparative study involving five laboratories constructing {sup 60}Co gamma ray calibration curves and was further confirmed when comparing results of blind dose estimates submitted by each laboratory. It has been further validated in two recent WHO BioDoseNet trial exercises where 20 metaphase images were shared by e-mail and 50 images were shared on a test website created for this purpose. The Internet-based exercise demonstrated a high level of concordance among 20 expert scorers who evaluated the same 50 metaphase spreads selected to exhibit no, low, moderate and severe radiation damage. Nineteen of 20 scorers produced dicentric equivalent counts within the 95% confidence limits of the mean. The Chi-squared test showed strong evidence of homogeneity in the data

Cytogenetic effects of low-dose radiation

International Nuclear Information System (INIS)

Metalli, P.

1983-01-01

The effects of ionizing radiation on chromosomes have been known for several decades and dose-effect relationships are also fairly well established in the mid- and high-dose and dose-rate range for chromosomes of mammalian cells. In the range of low doses and dose rates of different types of radiation few data are available for direct analysis of the dose-effect relationships, and extrapolation from high to low doses is still the unavoidable approach in many cases of interest for risk assessment. A review is presented of the data actually available and of the attempts that have been made to obtain possible generalizations. Attention is focused on some specific chromosomal anomalies experimentally induced by radiation (such as reciprocal translocations and aneuploidies in germinal cells) and on their relevance for the human situation. (author)

Estimation dose of secondary neutrons in proton therapy

International Nuclear Information System (INIS)

Urban, T.

2014-01-01

Most of proton therapy centers for cancer treatment are still based on the passive scattering, in some of them there is system of the active scanning installed as well. The aim of this study is to compare secondary neutron doses in and around target volumes in proton therapy for both treatment techniques and for different energies and profile of incident proton beam. The proton induced neutrons have been simulated in the very simple geometry of tissue equivalent phantom (imitate the patient) and scattering and scanning nozzle, respectively. In simulations of the scattering nozzle, different types of scattering filters and brass collimators have been used as well. 3D map of neutron doses in and around the chosen/potential target volume in the phantom/patient have been evaluated and compared in the context of the dose deposited in the target volume. Finally, the simulation results have been compared with published data. (author)

Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity

International Nuclear Information System (INIS)

Crépeaux, Guillemette; Eidi, Housam; David, Marie-Odile; Baba-Amer, Yasmine; Tzavara, Eleni; Giros, Bruno; Authier, François-Jérôme; Exley, Christopher; Shaw, Christopher A.; Cadusseau, Josette

2017-01-01

Aluminium (Al) oxyhydroxide (Alhydrogel ® ), the main adjuvant licensed for human and animal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concerns about its safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations. Mouse experiments have documented its capture and slow transportation by monocyte-lineage cells from the injected muscle to lymphoid organs and eventually the brain. The present study aimed at evaluating mouse brain function and Al concentration 180 days after injection of various doses of Alhydrogel ® (200, 400 and 800 μg Al/kg of body weight) in the tibialis anterior muscle in adult female CD1 mice. Cognitive and motor performances were assessed by 8 validated tests, microglial activation by Iba-1 immunohistochemistry, and Al level by graphite furnace atomic absorption spectroscopy. An unusual neuro-toxicological pattern limited to a low dose of Alhydrogel ® was observed. Neurobehavioural changes, including decreased activity levels and altered anxiety-like behaviour, were observed compared to controls in animals exposed to 200 μg Al/kg but not at 400 and 800 μg Al/kg. Consistently, microglial number appeared increased in the ventral forebrain of the 200 μg Al/kg group. Cerebral Al levels were selectively increased in animals exposed to the lowest dose, while muscle granulomas had almost Completely disappeared at 6 months in these animals. We conclude that Alhydrogel ® injected at low dose in mouse muscle may selectively induce long-term Al cerebral accumulation and neurotoxic effects. To explain this unexpected result, an avenue that could be explored in the future relates to the adjuvant size since the injected suspensions corresponding to the lowest dose

Effect of ultra-low dose whole-body-irradiation on severe patients with myasthenia gravis

International Nuclear Information System (INIS)

Arimori, Shigeru; Koriyama, Kenji

1982-01-01

An ultra-low dose whole body irradiation therapy was given to 5 patients with intractable bulbar syndrome, in a dose of 10 rad/fraction, 2 times a week for 5 weeks, with a total of 100 rad; and effects of this therapy on their clinical symptoms and immunological ability were discussed. In 3 of them, bulbar syndrome was improved, and the other one, the first irradiation was effective. The peripheral leukocyte count and lymphocyte count became lowest immediately after completion of the irradiation, and returned to the normal level within 1 to 2 months. The function of T-cells, especially suppressive T-cells, was recovered; and decrease in B-cells, resulted in a decrease in the AChR antibody titer. (Ueda, J.)

Effect of ultra-low dose whole-body-irradiation on patients with severe myasthenia gravis

Energy Technology Data Exchange (ETDEWEB)

Arimori, Shigeru; Koriyama, Kenji (Tokai Univ., Isehara, Kanagawa (Japan). School of Medicine)

1982-12-01

An ultra-low dose whole body irradiation therapy was given to 5 patients with intractable bulbar syndrome, in a dose of 10 rad/fraction, 2 times a week for 5 weeks, with a total of 100 rad; and effects of this therapy on their clinical symptoms and immunological ability were discussed. In 3 of them, bulbar syndrome was improved, and the other one, the first irradiation was effective. The peripheral leukocyte count and lymphocyte count became lowest immediately after completion of the irradiation, and returned to the normal level within 1 to 2 months. The function of T-cells, especially suppressive T-cells, was recovered; and decrease in B-cells, resulted in a decrease in the AChR antibody titer.

Dose prescription in boron neutron capture therapy

International Nuclear Information System (INIS)

Gupta, N.M.S.; Gahbauer, R.A.; Blue, T.E.; Wambersie, A.

1994-01-01

The purpose of this paper is to address some aspects of the many considerations that need to go into a dose prescription in boron neutron capture therapy (BNCT) for brain tumors; and to describe some methods to incorporate knowledge from animal studies and other experiments into the process of dose prescription. Previously, an algorithm to estimate the normal tissue tolerance to mixed high and low linear energy transfer radiations in BNCT was proposed. The authors have developed mathematical formulations and computational methods to represent this algorithm. Generalized models to fit the central axis dose rate components for an epithermal neutron field were also developed. These formulations and beam fitting models were programmed into spreadsheets to simulate two treatment techniques which are expected to be used in BNCT: a two-field bilateral scheme and a single-field treatment scheme. Parameters in these spreadsheets can be varied to represent the fractionation scheme used, the 10 B microdistribution in normal tissue, and the ratio of 10 B in tumor to normal tissue. Most of these factors have to be determined for a given neutron field and 10 B compound combination from large animal studies. The spreadsheets have been programmed to integrate all of the treatment-related information and calculate the location along the central axis where the normal tissue tolerance is exceeded first. This information is then used to compute the maximum treatment time allowable and the maximum tumor dose that may be delivered for a given BNCT treatment. The effect of different treatment variables on the treatment time and tumor dose has been shown to be very significant. It has also been shown that the location of D max shifts significantly, depending on some of the treatment variables-mainly the fractionation scheme used. These results further emphasize the fact that dose prescription in BNCT is very complicated and nonintuitive. 11 refs., 6 figs., 3 tabs

Safety and efficacy of low-dose isotretinoin in the treatment of moderate to severe acne vulgaris

Directory of Open Access Journals (Sweden)

Parinitha K Rao

2014-01-01

Full Text Available Background: Isotretinoin is indicated for moderate to severe cases of acne which are unresponsive to conventional therapy. The classical recommended dose is 0.5 to 1.0 mg/kg/day. As the side effects are dose related, low-dose isotretinoin therapy for acne is an attractive option; however, but little data exists on the safety and efficacy of this strategy. Materials and Methods: In this prospective, non-comparative study, 50 participants, both male and female, having moderate to severe acne vulgaris were enrolled and treated with isotretinoin at a dose of 20 mg/day (approximately 0.3-0.4 mg/kg/day, for a period of 3 months. Participants were evaluated by means of clinical and laboratory investigations before starting isotretinoin. Investigations were repeated at the end of the first and third months following completion of treatment, and participants were followed up for 6 months to look for any relapse. Results: At the end of the treatment, very good results were observed in 90% of participants. Cheilitis was the most common among the side effects observed and was seen in 98% of the participants. One participant developed vitiligo as a side effect, which is a new finding, and has not reported in literature before. Elevated serum lipid levels were observed in 6% of the participants, and relapse occurred in 4% of the participants over a 6 month follow up period. Conclusion: Three months of treatment with low-dose isotretinoin (20 mg/day was found to be effective in the treatment of moderate to severe acne vulgaris, with a low incidence of serious side effects. This dose also was more economical than the higher doses.

High dose therapy with autologous stem cell support in malignant disorders

International Nuclear Information System (INIS)

Holte, H.; Kvaloey, S.O.; Engan, T.

1996-01-01

New biomedical knowledge may improve the diagnostic procedures and treatment provided by the Health Services, but at additional cost. In a social democratic health care system, the hospital budgets have no room for expensive, new procedures or treatments, unless these are funded through extra allocation from the central authorities. High dose therapy with autologous stem cell support in malignant disorders is an example of a new and promising, but rather expensive treatment, but its role in cancer therapy has yet to be established. The indications for testing high dose therapy with autologous stem cell support in various malignancies are discussed, with emphasis on the principles for deciding which categories of disease should have priority. The authors suggest some malignant disorder for which high dose therapy with stem cell support should be explored versus conventional treatment in randomized prospective trials. 8 refs., 1 tab

Methodology for Estimating Ingestion Dose for Emergency Response at SRS

CERN Document Server

Simpkins, A A

2002-01-01

At the Savannah River Site (SRS), emergency response models estimate dose for inhalation and ground shine pathways. A methodology has been developed to incorporate ingestion doses into the emergency response models. The methodology follows a two-phase approach. The first phase estimates site-specific derived response levels (DRLs) which can be compared with predicted ground-level concentrations to determine if intervention is needed to protect the public. This phase uses accepted methods with little deviation from recommended guidance. The second phase uses site-specific data to estimate a 'best estimate' dose to offsite individuals from ingestion of foodstuffs. While this method deviates from recommended guidance, it is technically defensibly and more realistic. As guidance is updated, these methods also will need to be updated.

Persistent Sexual Dysfunction and Suicidal Ideation in Young Men Treated with Low-Dose Finasteride: A Pharmacovigilance Study.

Science.gov (United States)

Ali, Ayad K; Heran, Balraj S; Etminan, Mahyar

2015-07-01

Finasteride, a 5α-reductase inhibitor, is marketed in a low dose (1 mg) as a popular therapy for androgenic alopecia in young men. As case reports and small surveys have suggested a link between persistent sexual dysfunction (SD) and suicidal ideation (SI) with low-dose finasteride, the aim of this study was to detect signals of SD and SI secondary to low-dose finasteride use in young men. Retrospective pharmacovigilance disproportionality analysis. United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Low-dose finasteride-related adverse event reports for men aged 18-45 years that were submitted to the FAERS between 1998 and 2013 were retrieved. Multi-item Gamma Poisson Shrinker disproportionality analysis was applied to calculate the empirical Bayes geometric mean (EBGM) and corresponding 95% confidence interval (CI) as an association metric between low-dose finasteride and the events of interest. Signals were defined as associations with thresholds of a CI lower limit of 2.0 or greater. Medical Dictionary for Regulatory Activities Preferred Terms denoting to SD and SI were identified to reflect the outcome of interest. In total, of 4910 reports, 577 persistent SD and 39 SI adverse event reports (11.8% and 7.9%, respectively) were identified for young men using low-dose finasteride; 34 (87.2%) of the 39 men with SI also experienced SD. The majority of these events were serious (e.g., contributed to the patient's death, hospitalization, or disability). Low-dose finasteride was associated with more than expected reporting of SD in young men compared with reporting of these events with all other drugs within the database (EBGM 28.0, 95% CI 26.1-30.0). Disproportional reporting in SI events was noted, although it did not reach signal threshold (EBGM 1.72; 95% CI 1.31-2.23). Among serious SD events, 43% led to disability; 28% required medical intervention, including hospitalization; and 5% were life-threatening. Six fatal SD

Influence of low- and high-dose radioiodine therapy on oxidative modification of fibrinogen

International Nuclear Information System (INIS)

Schweeger-Exeli, I.J.

2001-10-01

levels were significantly elevated above 300 mg/dl (p 0.05) and did not change to a significant extent after treatment in both subgroups. Conclusion: Purification of fibrinogen out of small volumes of plasma is feasible in a short period of time and requires only little technical effort. High - dose radioiodine therapy, applied in differentiated thyroid cancer, leads to significantly increased incorporation of carbonyl groups into the fibrinogen molecule. It remains to be elucidated, whether thyroid hormone status itself influences oxidative damage of fibrinogen. Key words: fibrinogen; radioiodine therapy; oxidative modification; isolation techniques; 2,4-dinitrophenylhydrazine. (author)

Assessments for high dose radionuclide therapy treatment planning

International Nuclear Information System (INIS)

Fisher, D.R.

2003-01-01

Advances in the biotechnology of cell specific targeting of cancer and the increased number of clinical trials involving treatment of cancer patients with radiolabelled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high dose radionuclide therapy procedures. Optimised radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be the lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential timepoints using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organ tissues of concern, for the whole body and sometimes for selected tumours. Patient specific factors often require that dose estimates be customised for each patient. In the United States, the Food and Drug Administration regulates the experimental use of investigational new drugs and requires 'reasonable calculation of radiation absorbed dose to the whole body and to critical organs' using the methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high dose studies shows that some are conducted with minimal dosimetry, that the marrow dose is difficult to establish and is subject to large uncertainties. Despite the general availability of software, internal dosimetry methods often seem to be inconsistent from one clinical centre to another. (author)

Dosing of Appropriate Antibiotics and Time to Administration of First Doses in the Pediatric Emergency Department.

Science.gov (United States)

Bailey, Abby M; Stephan, Maria; Weant, Kyle A; Justice, Stephanie Baker

2015-01-01

Emergency department (ED) providers are faced with the challenge of diagnosing and treating patients in a timely fashion given many obstacles including limited patient information, complex disease states, and high patient turnover. Time delays in administration or selection of appropriate drug therapies have been associated with negative outcomes in severe infections. This study was conducted to assess the impact of an emergency medicine pharmacist (EPh) on the selection of appropriate antibiotics and the timeliness of administration in pediatric patients in the ED. Patients younger than 18 years were evaluated who were admitted through the ED and received 1 dose of intravenous antibiotic for the following conditions: community-acquired pneumonia, complicated skin and soft tissue infection (SSTI), meningitis, and sepsis. To evaluate the impact of the presence of an EPh, patients with orders placed during the EPh's hours of 1 pm and 11 pm were compared to those with an order placed between 11 pm and 1 pm. A total of 142 patients were included in the study. Patients seen during EPh hours received an appropriate first antibiotic 93.4% of the time (p = 0.157) and second antibiotic 96.8% of the time (p = 0.023). Time from order to verification was significantly shorter for the first 2 antimicrobials in the EPh group (10.5 minutes [p = 0.003] and 11.4 minutes [p = 0.047], respectively). The days from discharge to return to readmission to the ED were also significantly different (17.5 days vs. 62.4 days, p = 0.008). The available data suggest that patients are more likely to receive appropriate doses of antimicrobials, and in a more timely fashion, whenever the EPh is present. Areas for future investigation include whether the presence of EPhs at the bedside has the potential to impact areas of patient care, including readmission rates, drug costs, and medication errors.

Financial impact of outpatient clinic radioiodine therapy with sodium iodide I-131 for the treatment of patients with differentiated low-risk thyroid carcinoma in relation to hospital doses; Impacto financeiro da radioiodoterapia ambulatorial com iodeto de sódio I-131 para tratamento de pacientes com carcinoma diferenciado da tireóide de baixo risco em relação às doses hospitalares

Energy Technology Data Exchange (ETDEWEB)

Berenguer, P.F.; Chang, T.M.C.; Silva, R.A.M.; Neto, A.H.D.; Belo, I.B., E-mail: pricilaberenguer@gmail.com [Instituto de Medicina Integral Professor Fernando Figueira, Recife, PE (Brazil). Serviço de Medicina Nuclear; Santos, M.A.P. [Centro Regional de Ciências Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife (Brazil). Coordenação de Radioproteção

2017-07-01

Differential thyroid carcinoma (CDT) is the most prevalent endocrine malignancy in the world, with an excellent prognosis and a 10-year survival rate of over 95%. By 2013, the lowest activity of I-131 authorized by the Brazilian Unified Health System (SUS) in the therapy of patients with low-risk CDT was 3,700 MBq, requiring hospitalization. Recent studies have shown similar effectiveness between low and high doses of I-131 in the treatment of low-risk CDT. In 2014, the Ministry of Health included in the list of SUS procedures the use of lower activities (1,110 MBq and 1,850 MBq) for this purpose. The Brazilian National Nuclear Energy Commission (CNEN) also authorized the outpatient use of activity up to 1,850 MBq of I-131. Objective: To evaluate the financial impact of the adoption of ambulatory radioiodine therapy in patients with CDT of low-risk when compared to the hospital dose. Methods: Analysis of patients with CDT low-risk who were treated with an outpatient dose of I-131 from August / 2014 to January / 2017 at a nuclear medicine service in Recife, PE, Brazil. The cost of outpatient versus hospital doses was calculated. Results: A total of 289 patients underwent low doses of iodine therapy were evaluated, resulting in a savings of R$227,793.80. Conclusion: Outpatient radioiodine therapy in the treatment of patients with CDT of low-risk resulted in a 61.10% reduction in SUS expense, in addition to enabling faster care.

The treatment of autism with low-dose phenytoin: a case report.

Science.gov (United States)

Bird, Philip D

2015-01-16

The drug treatment of autism spectrum disorders is often poorly tolerated and has traditionally targeted associated conditions (such as inattention or irritability) that frequently coexist, with limited benefit for the core social deficits. Here, I describe the novel use of a low dose of the anti-epileptic phenytoin to enhance social functioning in a patient with an autism spectrum disorder. I present the case of a 19-year-old Caucasian man with autism spectrum disorder treated with stimulant medication since early childhood. He experienced long-standing difficulties in establishing and maintaining relationships and reading social cues, and was socially isolated. Within 10 minutes of a single sublingual low dose of phenytoin there was an immediate observable improvement in his eye contact and integration of both verbal and non-verbal communication. This enhanced social functioning associated with his adherence to the low-dose phenytoin therapy was maintained for over 18 months of follow-up. These clinical observations were supported by ratings using the Autism-Spectrum Quotient and the Depression, Anxiety and Stress Scales, recorded pre-treatment and after seven months on 5mg phenytoin. This case report provides the first potential evidence that a low dose of phenytoin, a widely used and well tolerated anti-epileptic medication, may be capable of modifying the core social cognitive deficits associated with autism spectrum disorders. While acknowledging this is a single case study, the lack of availability of safe and effective treatments to address the important core deficits associated with autism spectrum disorders makes this case noteworthy.

A consideration of low dose radiation effects on human health

International Nuclear Information System (INIS)

Shimada, Yoshiya; Nishimura, Mayumi; Imaoka, Tatsuhiko; Kakinuma, Shizuko

2011-01-01

On March 11, 2011, an earthquake categorized as 9 Mw occurred off the northeast coast of Japan. The subsequent destructive tsunami disabled emergency units of Fukushima Dai'ichi Nuclear Power Plant and caused partial meltdown of reactors and explosions. Resulting radiation releases forced large evacuations, bore concerns about food and water and fears against human health. In this manuscript, we described the effect of radiation, especially low dose radiation below 100 mSv, on cancer risk, focusing on fetuses and children. (author)

Low-dose ionizing radiation alleviates Aβ42-induced defective phenotypes in Drosophila Alzheimer's disease models

Energy Technology Data Exchange (ETDEWEB)

Hwang, SooJin; Jeong, Hae Min; Nam, Seon Young [Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd., Daejeon (Korea, Republic of)

2017-04-15

Alzheimer's disease (AD) is the most common neurodegenerative disease that is characterized by amyloid plaques, progressive neuronal loss, and gradual deterioration of memory. Amyloid imaging using positron emission tomography (PET) radiotracers have been developed and approved for clinical use in the evaluation of suspected neurodegenerative disease, including AD. Particularly, previous studies involving low-dose ionizing radiation on Aβ 42-treated mouse hippocampal neurons have suggested a potential role for low-dose ionizing radiation in the treatment of AD. However, associated in vivo studies involving the therapy effects of low-dose ionizing radiation on AD are still insufficient. As a powerful cell biological system, Drosophila AD models have been generated and established a useful model organism for study on the etiology of human AD. In this study, we investigated the hormesis effects of low-dose ionizing radiation on Drosophila AD models. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation.

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. © 2014 Elsevier Inc. All rights reserved.

Low dose irradiation and biological defense mechanisms

International Nuclear Information System (INIS)

Sugahara, Tsutomu; Sagan, L.A.; Aoyama, Takashi

1992-01-01

It has been generally accepted in the context of radiation protection that ionizing radiation has some adverse effect even at low doses. However, epidemiological studies of human populations cannot definitively show its existence or absence. Furthermore, recent studies of populations living in areas of different background radiation levels reported some decrease in adverse health effects at high background levels. Genetic studies of atomic bomb survivors failed to produce statistically significant findings on the mutagenic effects of ionizing radiation. A British study however, suggests that a father's exposure to low dose radiation on the job may increase his children's risk of leukemia. On the other hand, many experimental studies have raised the possibility that low doses of ionizing radiation may not be harmful or may even produce stimulating or adaptive responses. The term 'hormesis' has come to be used to describe these phenomena produced by low doses of ionizing radiation when they were beneficial for the organisms studied. At the end of the International Conference on Low Dose Irradiation one conclusion appeared to be justified: radiation produces an adaptive response, though it is not universally detected yet. The conference failed to obtain any consensus on risk assessment at low doses, but raised many problems to be dealt with by future studies. The editors therefore believe that the Proceedings will be useful for all scientists and people concerned with radiation protection and the biological effects of low-dose irradiation

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)

Topics on study of low dose-effect relationship

International Nuclear Information System (INIS)

Yamada, Takeshi; Ohyama, Harumi

1999-01-01

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)

Can radiation therapy treatment planning system accurately predict surface doses in postmastectomy radiation therapy patients?

International Nuclear Information System (INIS)

Wong, Sharon; Back, Michael; Tan, Poh Wee; Lee, Khai Mun; Baggarley, Shaun; Lu, Jaide Jay

2012-01-01

Skin doses have been an important factor in the dose prescription for breast radiotherapy. Recent advances in radiotherapy treatment techniques, such as intensity-modulated radiation therapy (IMRT) and new treatment schemes such as hypofractionated breast therapy have made the precise determination of the surface dose necessary. Detailed information of the dose at various depths of the skin is also critical in designing new treatment strategies. The purpose of this work was to assess the accuracy of surface dose calculation by a clinically used treatment planning system and those measured by thermoluminescence dosimeters (TLDs) in a customized chest wall phantom. This study involved the construction of a chest wall phantom for skin dose assessment. Seven TLDs were distributed throughout each right chest wall phantom to give adequate representation of measured radiation doses. Point doses from the CMS Xio® treatment planning system (TPS) were calculated for each relevant TLD positions and results correlated. There were no significant difference between measured absorbed dose by TLD and calculated doses by the TPS (p > 0.05 (1-tailed). Dose accuracy of up to 2.21% was found. The deviations from the calculated absorbed doses were overall larger (3.4%) when wedges and bolus were used. 3D radiotherapy TPS is a useful and accurate tool to assess the accuracy of surface dose. Our studies have shown that radiation treatment accuracy expressed as a comparison between calculated doses (by TPS) and measured doses (by TLD dosimetry) can be accurately predicted for tangential treatment of the chest wall after mastectomy.

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

Science.gov (United States)

Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

2016-01-01

Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

Estimation of radiation risks at low dose

International Nuclear Information System (INIS)

1990-04-01

The report presents a review of the effects caused by radiation in low doses, or at low dose rates. For the inheritable (or ''genetic''), as well as for the cancer producing effects of radiation, present evidence is consistent with: (a) a non-linear relationship between the frequency of at least some forms of these effects, with comparing frequencies caused by doses many times those received annually from natural sources, with those caused by lower doses; (b) a probably linear relationship, however, between dose and frequency of effects for dose rates in the region of that received from natural sources, or at several times this rate; (c) no evidence to indicate the existence of a threshold dose below which such effects are not produced, and a strong inference from the mode of action of radiation on cells at low dose rates that no such thresholds are likely to apply to the detrimental, cancer-producing or inheritable, effects resulting from unrepaired damage to single cells. 19 refs

Establishment of exposure dose assessment laboratory in National Radiation Emergency Medical Center (NREMC)

Energy Technology Data Exchange (ETDEWEB)

Yoo, Jae Ryong; Ha, Wi Ho; Yoon, Seok Won; Han, Eun Ae; Lee, Seung Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2011-10-15

As unclear industry grown, 432 of the nuclear power plants are operating and 52 of NPPs are under construction currently. Increasing use of radiation or radioisotopes in the field of industry, medical purpose and research such as non-destructive examination, computed tomography and x-ray, etc. constantly. With use of nuclear or radiation has incidence possibility for example the Fukushima NPP incident, the Goiania accident and the Chernobyl Nuclear accident. Also the risk of terror by radioactive material such as Radiological Dispersal Device(RDD) etc. In Korea, since the 'Law on protection of nuclear facilities and countermeasure for radioactive preparedness was enacted in 2003, the Korean institute of Radiological and Medical Sciences(KIRAMS) was established for the radiation emergency medical response in radiological disaster due to nuclear accident, radioactive terror and so on. Especially National Radiation Emergency Medical Center(NREMC) has the duty that is protect citizens from nuclear, radiological accidents or radiological terrors through the emergency medical preparedness. The NREMC was established by the 39-article law on physical protection of nuclear material and facilities and measures for radiological emergencies. Dose assessment or contamination survey should be performed which provide the radiological information for medical response. For this reason, the NREMC establish and re-organized dose assessment system based on the existing dose assessment system of the NREMC recently. The exposure dose could be measured by physical and biological method. With these two methods, we can have conservative dose assessment result. Therefore the NREMC established the exposure dose assessment laboratory which was re-organized laboratory space and introduced specialized equipment for dose assessment. This paper will report the establishment and operation of exposure dose assessment laboratory for radiological emergency response and discuss how to enhance

High-dose ibuprofen therapy associated with esophageal ulceration after pneumonectomy in a patient with cystic fibrosis: a case report

Directory of Open Access Journals (Sweden)

Anbar Ran D

2004-09-01

Full Text Available Abstract Background Lung disease in patients with cystic fibrosis is thought to develop as a result of airway inflammation, infection, and obstruction. Pulmonary therapies for cystic fibrosis that reduce airway inflammation include corticosteroids, rhDNase, antibiotics, and high-dose ibuprofen. Despite evidence that high-dose ibuprofen slows the progression of lung disease in patients with cystic fibrosis, many clinicians have chosen not to use this therapy because of concerns regarding potential side effects, especially gastrointestinal bleeding. However, studies have shown a low incidence of gastrointestinal ulceration and bleeding in patients with cystic fibrosis who have been treated with high-dose ibuprofen. Case presentation The described case illustrates a life-threatening upper gastrointestinal bleed that may have resulted from high-dose ibuprofen therapy in a patient with CF who had undergone a pneumonectomy. Mediastinal shift post-pneumonectomy distorted the patient's esophageal anatomy and may have caused decreased esophageal motility, which led to prolonged contact of the ibuprofen with the esophagus. The concentrated effect of the ibuprofen, as well as its systemic effects, probably contributed to the occurrence of the bleed in this patient. Conclusions This report demonstrates that gastrointestinal tract anatomical abnormalities or dysmotility may be contraindications for therapy with high-dose ibuprofen in patients with cystic fibrosis.

Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

International Nuclear Information System (INIS)

Rödel, Franz; Frey, Benjamin; Manda, Katrin; Hildebrandt, Guido; Hehlgans, Stephanie; Keilholz, Ludwig; Seegenschmiedt, M. Heinrich; Gaipl, Udo S.; Rödel, Claus

2012-01-01

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

Energy Technology Data Exchange (ETDEWEB)

Rödel, Franz [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany); Frey, Benjamin [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen (Germany); Manda, Katrin; Hildebrandt, Guido [Department of Radiotherapy and Radiation Oncology, University of Rostock, Rostock (Germany); Hehlgans, Stephanie [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany); Keilholz, Ludwig [Department of Radiotherapy, Clinical Center Bayreuth, Bayreuth (Germany); Seegenschmiedt, M. Heinrich [Strahlenzentrum Hamburg Medizinisches Versorgungszentrum, Hamburg (Germany); Gaipl, Udo S. [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen (Germany); Rödel, Claus, E-mail: franz.roedel@kgu.de [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany)

2012-09-25

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

The incidence of breast cancer following mantle field radiation therapy as a function of dose and technique

International Nuclear Information System (INIS)

Tinger, Alfred; Wasserman, Todd H.; Klein, Eric E.; Miller, Elizabeth A.; Roberts, Tracy; Piephoff, James V.; Kucik, Nancy A.

1997-01-01

Purpose: There is an increased incidence of breast cancer following mantle field radiation therapy for Hodgkin's disease (HD). We reviewed the experience at the Mallinckrodt Institute of Radiology (MIR) for radiation factors related to the development of breast cancer after mantle field radiation therapy for HD. Methods: The radiation therapy records of 152 women treated with mantle field irradiation for HD at MIR between 1966-1985 were reviewed for the development of breast cancer and treatment-related factors. All patients had a minimum of 5 years of follow-up. The treatment era (1966-1974 vs. 1975-1985), stage of HD, mediastinal dose, axillary dose, maximum dose from the anterior field (anterior d max dose), the anterior-posterior:posterior-anterior (AP:PA) ratio, age at the time of treatment, length of follow-up, and history of splenectomy were analyzed as possible contributing factors for the development of breast cancer. The observed number of breast cancers was compared to the expected number based on age-adjusted incidences from the Connecticut Tumor Registry. Results: Ten breast cancers occurred in the population. Eight involved an upper outer quadrant. In a multivariate analysis, the development of breast cancer was significantly associated with axillary dose. Patients in the early treatment era were at an increased risk for the development of breast cancer due to high anterior d max and breast doses from weighting the fields anteriorly on a low energy linear accelerator. The use of current radiation therapy techniques was not related to an increased risk of breast cancer with a median follow-up of 13 years. Conclusions: A high dose to the axilla and the anterior d max point is significantly associated with the development of breast cancer after mantle field irradiation for HD. Efforts to protect the breast from high doses will likely lessen the increased risk of breast cancer in women treated with radiation therapy for HD

Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

Science.gov (United States)

Niesvizky, Ruben; Martínez-Baños, Déborah; Jalbrzikowski, Jessica; Christos, Paul; Furst, Jessica; De Sancho, Maria; Mark, Tomer; Pearse, Roger; Mazumdar, Madhu; Zafar, Faiza; Pekle, Karen; Leonard, John; Jayabalan, David; Coleman, Morton

2007-12-01

Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

Systematic measurements of whole-body imaging dose distributions in image-guided radiation therapy

International Nuclear Information System (INIS)

Hälg, Roger A.; Besserer, Jürgen; Schneider, Uwe

2012-01-01

Purpose: The full benefit of the increased precision of contemporary treatment techniques can only be exploited if the accuracy of the patient positioning is guaranteed. Therefore, more and more imaging modalities are used in the process of the patient setup in clinical routine of radiation therapy. The improved accuracy in patient positioning, however, results in additional dose contributions to the integral patient dose. To quantify this, absorbed dose measurements from typical imaging procedures involved in an image-guided radiation therapy treatment were measured in an anthropomorphic phantom for a complete course of treatment. The experimental setup, including the measurement positions in the phantom, was exactly the same as in a preceding study of radiotherapy stray dose measurements. This allows a direct combination of imaging dose distributions with the therapy dose distribution. Methods: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The dose distributions from imaging devices used with treatment machines from the manufacturers Accuray, Elekta, Siemens, and Varian and from computed tomography scanners from GE Healthcare were determined and the resulting effective dose was calculated. The list of investigated imaging techniques consisted of cone beam computed tomography (kilo- and megavoltage), megavoltage fan beam computed tomography, kilo- and megavoltage planar imaging, planning computed tomography with and without gating methods and planar scout views. Results: A conventional 3D planning CT resulted in an effective dose additional to the treatment stray dose of less than 1 mSv outside of the treated volume, whereas a 4D planning CT resulted in a 10 times larger dose. For a daily setup of the patient with two planar kilovoltage images or with a fan beam CT at the TomoTherapy unit, an additional effective dose outside of the treated volume of less than 0.4 mSv and 1

Low-dose multislice CT in febrile neutropenic patients

International Nuclear Information System (INIS)

Wendel, F.; Jenett, M.; Hahn, D.; Sandstede, J.; Geib, A.

2005-01-01

Purpose: to define the value of low-dose multislice CT in a clinical setting for early detection of pneumonia in neutropenic patients with fever of unknown origin. Materials and methods: thirty-five neutropenic patients suffering from fever of unknown origin with normal chest X-ray underwent unenhanced low-dose CT of the chest (120 kV, 10 eff. mAs, collimation 4 x 1 mm) using a multislice CT scanner. Axial und frontal slices with a thickness of 5 mm were calculated. If no pneumonia was found, standard antibiotics were given and a repeated examination was performed if fever continued. In case of pneumonia, antimycotic therapy was added and a follow-up CT was performed within one week. Regression or progression of pneumonia at follow-up served as evidence of pneumonia; lowering of fever within 48 h or inconspicuous follow-up CT was regarded as absence of pneumonia. Results: ten of 35 patients had pneumonic infiltration, which decreased or increased on follow-up CT in 3 and 6 patients, respectively. One patient revealed leucemic infiltration by bronchoalveolar lavage. Twenty-five of 35 patients had no evidence of pneumonia. Twenty of these patients were free of fever within 48 h under antibiotics; one patient died due to his basic illness. Out of 4 patients with persisting fever, 3 patients had no pneumonia on repeated examination; one patient showed disseminated micronodular infiltration. Frontal reconstructions helped to differentiate infiltration from atelectasis in 4 patients. Sensitivity and specificity for the detection of pneumonia at the first examination were 90% and 96%, negative predictive value was 96%. Conclusion: low-dose multislice CT should be performed in neutropenic patients having a fever of unknown origin and normal chest X-ray. (orig.)

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.

Science.gov (United States)

Moreau, Philippe; Dimopoulos, Meletios A; Richardson, Paul G; Siegel, David S; Cavo, Michele; Corradini, Paolo; Weisel, Katja; Delforge, Michel; O'Gorman, Peter; Song, Kevin; Chen, Christine; Bahlis, Nizar; Oriol, Albert; Hansson, Markus; Kaiser, Martin; Anttila, Pekka; Raymakers, Reinier; Joao, Cristina; Cook, Gordon; Sternas, Lars; Biyukov, Tsvetan; Slaughter, Ana; Hong, Kevin; Herring, Jennifer; Yu, Xin; Zaki, Mohamed; San-Miguel, Jesus

2017-09-01

Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Successful Outcome of Low-Dose S-1 Used to Treat Buccal Squamous Cell Carcinoma

Directory of Open Access Journals (Sweden)

Kazuyuki Yusa

2017-01-01

Full Text Available This case report describes an 86-year-old woman with dormant right buccal squamous cell carcinoma who was able to maintain a reasonable quality of life after being treated with oral low-dose S-1 (80 mg/day. The treatment regimen started in April 2014 and consisted of two weeks of S-1 followed by a one-week interval. The patient remains on this regimen while maintaining her quality of life and she has been under follow-up as an outpatient for 36 months. The outcomes for this patient indicated that low-dose S-1 is a valid anticancer therapy that may help maintain quality of life for some patients with incurable or dormant cancers.

Low-Dose Ketamine Infusion for Adjunct Management during Vaso-occlusive Episodes in Adults with Sickle Cell Disease: A Case Series.

Science.gov (United States)

Palm, Nicole; Floroff, Catherine; Hassig, Tanna B; Boylan, Alice; Kanter, Julie

2018-05-23

The optimal management of recurrent painful episodes in individuals living with sickle cell disease (SCD) remains unclear. Currently, the primary treatment for these episodes remains supportive, using fluids and intravenous opioid and anti-inflammatory medications. Few reports have described the use of adjunct subanesthetic doses of ketamine to opioids for treatment of refractory pain in SCD. This article reports a retrospective case series of five patients admitted to the intensive care unit (ICU) with prolonged vaso-occlusive episodes (VOEs). Patients were treated with a continuous-infusion of low-dose ketamine (up to 5 µg/kg/min) after insufficient pain control with opioid analgesic therapy. Outcomes studied included impact on opioid analgesic use, a description of ketamine dosing strategy, and an analysis of adverse events due to opioid or ketamine analgesia. Descriptive statistics are provided. During ketamine infusion, patients experienced a lower reported pain score (mean numeric rating scale [NRS] score 7.2 vs. 6.4), reduced opioid-induced adverse effects, and decreased opioid dosing requirements (median reduction of 90 mg morphine equivalents per patient). The average duration of severe pain during admission prior to ketamine therapy was 8 days. Only one of five patients reported an adverse effect (vivid dreams) secondary to ketamine infusion. The Richmond Agitation Sedation Scale (RASS) was assessed throughout therapy, with only one patient experiencing light drowsiness. Low-dose ketamine infusion may be considered as an adjunct analgesic agent in patients with vaso-occlusive episodes who report continued severe pain despite high-dose opioid therapy, particularly those experiencing opioid-induced adverse effects.

Influence of high-dose lipid lowering treatment compared to low-dose lipid lowering treatment on plaque composition assessed by intravascular ultrasound virtual histology in patients with ST-segment elevation acute myocardial infarction

DEFF Research Database (Denmark)

Egede, Rasmus; Jensen, Lisette Okkels; Hansen, Henrik Steen

2013-01-01

Aims: The aim of this study was to evaluate the effect of low-dose versus high-dose rosuvastatin therapy on the necrotic core content in coronary plaques of angiographic non-significant lesions as assessed by intravascular ultrasound - virtual histology. Methods and results: Eighty-seven statin...

Late effects of low doses and dose rates

International Nuclear Information System (INIS)

Paretzke, H.G.

1980-01-01

This paper outlines the spectrum of problems and approaches used in work on the derivation of quantitative prognoses of late effects in man of low doses and dose rates. The origins of principal problems encountered in radiation risks assessments, definitions and explanations of useful quantities, methods of deriving risk factors from biological and epidemiological data, and concepts of risk evaluation and problems of acceptance are individually discussed

Total-dose hardness assurance for low earth orbit

International Nuclear Information System (INIS)

Maurer, R.H.; Suter, J.J.

1987-01-01

The Low Earth Orbit radiation environment has two significant characteristics that make laboratory simulation exposures difficult: (1) a low dose rate and (2) many cycles of low dose accumulation followed by dose-free annealing. Hardness assurance considerations for this environment are discussed and related to data from the testing of Advanced Low Power Schottky and High-speed CMOS devices

Estimation of four-dimensional dose distribution using electronic portal imaging device in radiation therapy

International Nuclear Information System (INIS)

Mizoguchi, Asumi; Arimura, Hidetaka; Shioyama, Yoshiyuki

2013-01-01

We are developing a method to evaluate four-dimensional radiation dose distribution in a patient body based upon the animated image of EPID (electronic portal imaging device) which is an image of beam-direction at the irradiation. In the first place, we have obtained the image of the dose which is emitted from patient body at therapy planning using therapy planning CT image and dose evaluation algorism. In the second place, we have estimated the emission dose image at the irradiation using EPID animated image which is obtained at the irradiation. In the third place, we have got an affine transformation matrix including respiratory movement in the body by performing linear registration on the emission dose image at therapy planning to get the one at the irradiation. In the fourth place, we have applied the affine transformation matrix on the therapy planning CT image and estimated the CT image 'at irradiation'. Finally we have evaluated four-dimensional dose distribution by calculating dose distribution in the CT image 'at irradiation' which has been estimated for each frame of the EPID animated-image. This scheme may be useful for evaluating therapy results and risk management. (author)

Recalculation of dose for each fraction of treatment on TomoTherapy.

Science.gov (United States)

Thomas, Simon J; Romanchikova, Marina; Harrison, Karl; Parker, Michael A; Bates, Amy M; Scaife, Jessica E; Sutcliffe, Michael P F; Burnet, Neil G

2016-01-01

The VoxTox study, linking delivered dose to toxicity requires recalculation of typically 20-37 fractions per patient, for nearly 2000 patients. This requires a non-interactive interface permitting batch calculation with multiple computers. Data are extracted from the TomoTherapy(®) archive and processed using the computational task-management system GANGA. Doses are calculated for each fraction of radiotherapy using the daily megavoltage (MV) CT images. The calculated dose cube is saved as a digital imaging and communications in medicine RTDOSE object, which can then be read by utilities that calculate dose-volume histograms or dose surface maps. The rectum is delineated on daily MV images using an implementation of the Chan-Vese algorithm. On a cluster of up to 117 central processing units, dose cubes for all fractions of 151 patients took 12 days to calculate. Outlining the rectum on all slices and fractions on 151 patients took 7 h. We also present results of the Hounsfield unit (HU) calibration of TomoTherapy MV images, measured over an 8-year period, showing that the HU calibration has become less variable over time, with no large changes observed after 2011. We have developed a system for automatic dose recalculation of TomoTherapy dose distributions. This does not tie up the clinically needed planning system but can be run on a cluster of independent machines, enabling recalculation of delivered dose without user intervention. The use of a task management system for automation of dose calculation and outlining enables work to be scaled up to the level required for large studies.

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

International Nuclear Information System (INIS)

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

2014-01-01

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 (1) the presence of a threshold that varied with organ, gender and age at exposure, and (2) 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. (author)

A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition.

Science.gov (United States)

Schiffmann, L M; Brunold, M; Liwschitz, M; Goede, V; Loges, S; Wroblewski, M; Quaas, A; Alakus, H; Stippel, D; Bruns, C J; Hallek, M; Kashkar, H; Hacker, U T; Coutelle, O

2017-02-28

Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy. Collagen IV expression was analysed in response to VEGF inhibition in liver metastasis of colorectal cancer (CRC) patients, in syngeneic (Panc02) and xenograft tumours of human colorectal cancer cells (LS174T). The xenograft tumours were treated with low (0.5 mg kg -1 body weight) or high (5 mg kg -1 body weight) doses of the anti-VEGF antibody bevacizumab with or without the tyrosine kinase inhibitor imatinib. Changes in tumour growth, and vascular parameters, including microvessel density, pericyte coverage, leakiness, hypoxia, perfusion, fraction of vessels with an open lumen, and type IV collagen deposition were compared. ECM deposition was increased after standard VEGF inhibition in patients and tumour models. In contrast, treatment with low-dose bevacizumab and imatinib produced similar growth inhibition without inducing detrimental collagen IV deposition, leading to superior vascular normalisation, reduced leakiness, improved oxygenation, more open vessels that permit perfusion and access for therapy. Low-dose bevacizumab augmented by imatinib selects a mature, highly normalised and well perfused tumour vasculature without inducing incremental ECM deposition that normally limits the effectiveness of VEGF targeting drugs.

Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project.

Science.gov (United States)

Popowicz, Natalia; Bintcliffe, Oliver; De Fonseka, Duneesha; Blyth, Kevin G; Smith, Nicola A; Piccolo, Francesco; Martin, Geoffrey; Wong, Donny; Edey, Anthony; Maskell, Nick; Lee, Y C Gary

2017-06-01

Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22-58] to 16% [8-31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247-2,984] over 72 h of therapy; P <  0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent

Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

Energy Technology Data Exchange (ETDEWEB)

Feinendegen, L.E

2003-07-01

In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

International Nuclear Information System (INIS)

Feinendegen, L.E.

2003-01-01

In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

Multifocal Electroretinography after High Dose Chloroquine Therapy for Malaria

Directory of Open Access Journals (Sweden)

Aline Correa de Carvalho

2013-01-01

Full Text Available Purpose: To investigate changes in multifocal electroretinography (mfERG parameters associated with high dose chloroquine therapy for treatment of malaria in the Amazonia region of Brazil. Methods: Forty-eight subjects who had received chloroquine treatment for single or multiple malaria infections with a cumulative dose ranging from 1,050 to 27,000mg were included. The control group consisted of 37 healthy aged-matched subjects. Data was collected on amplitude and implicit time of the N1, P1 and N2 waves in the central macular hexagon (R1 and in five concentric rings at different retinal eccentricities (R2-R6. Results: No significant difference was observed in any mfERG parameter between chloroquine treated patients and control subjects. A comparison with previous data obtained from patients with rheumatologic disorders in the same region of Brazil who had received larger cumulative doses of chloroquine and had displayed mfERG changes, indicated that retinal toxicity seems to be dependent on cumulative dose. Conclusion: Lack of mfERG changes in the current study suggests that intensive high dose chloroquine therapy for treatment of malaria is not associated with retinal toxicity.

High-dose preoperative radiation for cancer of the rectum: Impact of radiation dose on patterns of failure and survival

International Nuclear Information System (INIS)

Ahmad, N.R.; Mohiuddin, M.; Marks, G.

1993-01-01

A variety of dose-time schedules are currently used for preoperative radiation therapy of rectal cancer. An analysis of patients treated with high-dose preoperative radiation therapy was undertaken to determine the influence of radiation dose on the patterns of failure, survival, and complications. Two hundred seventy-five patients with localized rectal cancer were treated with high-dose preoperative radiation therapy. One hundred fifty-six patients received 45 Gy (low-dose group). Since 1985, 119 patients with clinically unfavorable cancers were given a higher dose, 55 Gy using a shrinking field technique (high-dose group). All patients underwent curative resection. Median follow-up was 66 months in the low-dose group and 28 months in the high-dose group. Patterns of failure, survival, and complications were analyzed as a function of radiation dose. Fourteen percent of the total group developed a local recurrence; 20% in the low-dose group as compared with 6% in the high-dose group. The actuarial local recurrence rate at 5 years was 20% for the low-dose group and 8% for the high-dose group, and approached statistical significance with p = .057. For tethered/fixed tumors the actuarial local recurrence rates at 5 years were 28% and 9%, respectively, with p = .05. Similarly, for low-lying tumors (less than 6 cm from the anorectal junction) the rates were 24% and 9%, respectively, with p = .04. The actuarial rate of distant metastasis was 28% in the low-dose group and 20% in the high-dose group and was not significantly different. Overall actuarial 5-year survival for the total group of patients was 66%. No significant difference in survival was observed between the two groups, despite the higher proportion of unfavorable cancers in the high-dose group. The incidence of complications was 2%, equally distributed between the two groups. High-dose preoperative radiation therapy for rectal cancer results in excellent local control rates. 27 refs., 2 figs., 8 tabs

Spine stereotactic body radiation therapy plans: Achieving dose coverage, conformity, and dose falloff

International Nuclear Information System (INIS)

Hong, Linda X.; Shankar, Viswanathan; Shen, Jin; Kuo, Hsiang-Chi; Mynampati, Dinesh; Yaparpalvi, Ravindra; Goddard, Lee; Basavatia, Amar; Fox, Jana; Garg, Madhur; Kalnicki, Shalom; Tomé, Wolfgang A.

2015-01-01

We report our experience of establishing planning objectives to achieve dose coverage, conformity, and dose falloff for spine stereotactic body radiation therapy (SBRT) plans. Patients with spine lesions were treated using SBRT in our institution since September 2009. Since September 2011, we established the following planning objectives for our SBRT spine plans in addition to the cord dose constraints: (1) dose coverage—prescription dose (PD) to cover at least 95% planning target volume (PTV) and 90% PD to cover at least 99% PTV; (2) conformity index (CI)—ratio of prescription isodose volume (PIV) to the PTV < 1.2; (3) dose falloff—ratio of 50% PIV to the PTV (R 50% ); (4) and maximum dose in percentage of PD at 2 cm from PTV in any direction (D 2cm ) to follow Radiation Therapy Oncology Group (RTOG) 0915. We have retrospectively reviewed 66 separate spine lesions treated between September 2009 and December 2012 (31 treated before September 2011 [group 1] and 35 treated after [group 2]). The χ 2 test was used to examine the difference in parameters between groups. The PTV V 100% PD ≥ 95% objective was met in 29.0% of group 1 vs 91.4% of group 2 (p < 0.01) plans. The PTV V 90% PD ≥ 99% objective was met in 38.7% of group 1 vs 88.6% of group 2 (p < 0.01) plans. Overall, 4 plans in group 1 had CI > 1.2 vs none in group 2 (p = 0.04). For D 2cm , 48.3% plans yielded a minor violation of the objectives and 16.1% a major violation for group 1, whereas 17.1% exhibited a minor violation and 2.9% a major violation for group 2 (p < 0.01). Spine SBRT plans can be improved on dose coverage, conformity, and dose falloff employing a combination of RTOG spine and lung SBRT protocol planning objectives

Spine stereotactic body radiation therapy plans: Achieving dose coverage, conformity, and dose falloff

Energy Technology Data Exchange (ETDEWEB)

Hong, Linda X., E-mail: lhong0812@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY (United States); Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY (United States); Shankar, Viswanathan [Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (United States); Shen, Jin [Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY (United States); Kuo, Hsiang-Chi [Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY (United States); Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY (United States); Mynampati, Dinesh [Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY (United States); Yaparpalvi, Ravindra [Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY (United States); Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY (United States); Goddard, Lee [Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY (United States); Basavatia, Amar; Fox, Jana; Garg, Madhur; Kalnicki, Shalom; Tomé, Wolfgang A. [Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY (United States); Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY (United States)

2015-10-01

We report our experience of establishing planning objectives to achieve dose coverage, conformity, and dose falloff for spine stereotactic body radiation therapy (SBRT) plans. Patients with spine lesions were treated using SBRT in our institution since September 2009. Since September 2011, we established the following planning objectives for our SBRT spine plans in addition to the cord dose constraints: (1) dose coverage—prescription dose (PD) to cover at least 95% planning target volume (PTV) and 90% PD to cover at least 99% PTV; (2) conformity index (CI)—ratio of prescription isodose volume (PIV) to the PTV < 1.2; (3) dose falloff—ratio of 50% PIV to the PTV (R{sub 50%}); (4) and maximum dose in percentage of PD at 2 cm from PTV in any direction (D{sub 2cm}) to follow Radiation Therapy Oncology Group (RTOG) 0915. We have retrospectively reviewed 66 separate spine lesions treated between September 2009 and December 2012 (31 treated before September 2011 [group 1] and 35 treated after [group 2]). The χ{sup 2} test was used to examine the difference in parameters between groups. The PTV V{sub 100%} {sub PD} ≥ 95% objective was met in 29.0% of group 1 vs 91.4% of group 2 (p < 0.01) plans. The PTV V{sub 90%} {sub PD} ≥ 99% objective was met in 38.7% of group 1 vs 88.6% of group 2 (p < 0.01) plans. Overall, 4 plans in group 1 had CI > 1.2 vs none in group 2 (p = 0.04). For D{sub 2cm}, 48.3% plans yielded a minor violation of the objectives and 16.1% a major violation for group 1, whereas 17.1% exhibited a minor violation and 2.9% a major violation for group 2 (p < 0.01). Spine SBRT plans can be improved on dose coverage, conformity, and dose falloff employing a combination of RTOG spine and lung SBRT protocol planning objectives.

Modification of damage following low doses

International Nuclear Information System (INIS)

Braby, L.A.; Nelson, J.M.; Metting, N.F.

1988-01-01

At very low doses the damage-interaction mechanism is responsible for very little lethal or potentially lethal damage, and repair of the latter should essentially disappear. An alternative model suggests that potentially lethal damage is either repaired with a constant half time or misrepaired at a rate which is proportional to the square of the damage concentration. In this case, as the dose decreases, the probability of misrepair decreases faster than the probability of repair, and repair becomes a more pronounced feature of the cell response. Since the consequence of unrepaired damage is an important question in determining the effects of low doses of radiation delivered at low dose rates, we have attempted to determine which of these two types of models is consistent with the response of plateau-phase CHO cells. In the earlier experiments, there was no indication of repair after a 50-rad exposure with a 24-hour split dose or plating delay; in fact, immediate plating resulted in survival slightly above control and delayed plating in survival slightly below the control value

Dose-projection considerations for emergency conditions at nuclear power plants

International Nuclear Information System (INIS)

Stoetzel, G.A.; Ramsdell, J.V.; Poeton, R.W.; Powell, D.C.; Desrosiers, A.E.

1983-05-01

The purpose of this report is to review the problems and issues associated with making environmental radiation-dose projections during emergencies at nuclear power plants. The review is divided into three areas: source-term development, characterization of atmospheric dispersion and selection of appropriate dispersion models, and development of dosimetry calculations for determining thyroid dose and whole-body dose for ground-level and elevated releases. A discussion of uncertainties associated with these areas is also provided

Dose-projection considerations for emergency conditions at nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Stoetzel, G.A.; Ramsdell, J.V.; Poeton, R.W.; Powell, D.C.; Desrosiers, A.E.

1983-05-01

The purpose of this report is to review the problems and issues associated with making environmental radiation-dose projections during emergencies at nuclear power plants. The review is divided into three areas: source-term development, characterization of atmospheric dispersion and selection of appropriate dispersion models, and development of dosimetry calculations for determining thyroid dose and whole-body dose for ground-level and elevated releases. A discussion of uncertainties associated with these areas is also provided.

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

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

Science.gov (United States)

Shuryak, Igor; Sachs, Rainer K.; Hlatky, Lynn; Mark P. Little; Hahnfeldt, Philip; Brenner, David J.

2006-01-01

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose

Fetus dose estimation in thyroid cancer post-surgical radioiodine therapy

International Nuclear Information System (INIS)

Mianji, Fereidoun A.; Karimi Diba, Jila; Babakhani, Asad

2015-01-01

Unrecognised pregnancy during radioisotope therapy of thyroid cancer results in hardly definable embryo/fetus exposures, particularly when the thyroid gland is already removed. Sources of such difficulty include uncertainty in data like pregnancy commencing time, amount and distribution of metastasized thyroid cells in body, effect of the thyroidectomy on the fetus dose coefficient etc. Despite all these uncertainties, estimation of the order of the fetus dose in most cases is enough for medical and legal decision-making purposes. A model for adapting the dose coefficients recommended by the well-known methods to the problem of fetus dose assessment in athyrotic patients is proposed. The model defines a correction factor for the problem and ensures that the fetus dose in athyrotic pregnant patients is less than the normal patients. A case of pregnant patient undergone post-surgical therapy by I-131 is then studied for quantitative comparison of the methods. The results draw a range for the fetus dose in athyrotic patients using the derived factor. This reduces the concerns on under- or over-estimation of the embryo/fetus dose and is helpful for personal and/or legal decision-making on abortion. (authors)

The emergence of devastating impulse control disorders during dopamine agonist therapy of the restless legs syndrome.

Science.gov (United States)

Dang, Dien; Cunnington, David; Swieca, John

2011-01-01

The Restless Legs Syndrome is a common sensorimotor disorder, typically amenable to treatment with dopamine agonist therapy. Dopamine agonists have been associated with emergent impulse control disorders (ICDs) when used in patients with Parkinson disease, and ICDs have now been reported in individuals with RLS on dopamine agonist therapy. Our aim was to characterize cases of emergent ICDs in Australian patients with focus on the dopamine agonists implicated and the social significance of ICDs. A series of RLS patients on dopamine agonist therapy were identified with ICDs over a 2-year period. Additional cases of ICDs were found using a mailout questionnaire designed to capture those with high impulsivity. These patients were assessed using the Barratt Impulsiveness Scale, Version 11, and a modified Minnesota Impulse Disorders Interview. Case records and medication schedules were evaluated. Twelve cases of patients with de novo ICDs were found with a range of impulsive behaviors including pathological gambling, kleptomania, compulsive shopping, and hypersexuality. Criminality, suicidality, and marital discord also were featured. These occurred over a wide range of latencies and l-dopa exposures. This group of Australian RLS patients with ICDs display high levels of impulsivity and is the first to use the BIS-11 questionnaire in this setting. Impulse control disorders can occur over a wide range of dopamine agonist therapy types and dose exposures. Impulse control disorder tendencies may persist, despite withdrawal of dopamine agonists. The emergence of ICDs needs careful consideration in light of their potentially devastating financial, social, and marital consequences.

MELODI - Multidisciplinary European Low dose Initiative - First Draft of Strategic Research Agenda (SRA)

International Nuclear Information System (INIS)

Averbeck, D.; Lloyd, D.; O'Neill, P.

2010-01-01

The SRA Working Group of MELODI (Multidisciplinary European Low Dose Initiative) was tasked to develop a long-term strategic research agenda (SRA) to guide the coherent integration of national low dose research programmes. Priorities that need to be addressed concern fundamental mechanistic research ranging from radiation track structure and the deposition of energy in biologically important molecules; the resultant homeostatic perturbations and the steps in the cellular and tissue metabolic pathways that eventually lead to disease pathologies. In fact, the main priorities are here the step-wise elucidation of the mechanisms of radiation-induced (oxidative) stress responses and their impact on radiation-induced cancers and non cancer diseases. To achieve this a holistic approach is proposed staring with radiation-specific effects, radiation-induced molecular, biological and pathological effects involving a systems biology approach as well as molecular epidemiology and mathematical modelling in order to come up with more solid low dose health risk assessments. The pathologies considered are outlined in the report where the need is stressed for the MELODI platform to involve a constellation of classical and emerging technologies in a highly multidisciplinary approach. Elucidating the shapes of low-dose response relationships and resolving the question of thresholds is paramount to resolving questions of risk for both populations and individuals. Much is known about radiation-induced cancer in humans and animal models but this needs to be pursued particularly at low doses. More recently, the scientific community has realised that low radiation-induced health effects range well beyond cancer. The priority non-cancer areas that need to be brought into focus are cardiovascular, neurological and ophthalmic. (A.C.)

Low-dose vaporized cannabis significantly improves neuropathic pain.

Science.gov (United States)

Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

Low dose radiation exposure and atherosclerosis in ApoE-/- mice

International Nuclear Information System (INIS)

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

2010-01-01

The hypothesis that single low dose exposures (0.025-0.5 Gy) to low LET radiation, given at either high (240 mGy/min) or low (1 mGy/min) dose rate, would promote aortic atherosclerosis was tested in female C57BI/6 mice genetically predisposed to this disease (ApoE-/-). Mice were exposed either at early stage disease (2 months of age) and examined 3 or 6 months later, or at late stage disease (8 months of age) and examined 2 or 4 months later. Compared to unexposed controls, all doses given at low or high dose rate at early stage disease had significant inhibitory effects on lesion growth and, at 25 or 50 mGy, on lesion frequency. No dose given at low dose rate had any effect on total serum cholesterol, but this was elevated by every dose given at high dose rate. Exposures at low dose rate had no effect on the percentage of lesion lipids contained within macrophages, and, at either high or low dose rate, had no significant effect on lesion severity. Exposure at late stage disease, to any dose at high dose rate, had no significant effect on lesion frequency, but at low dose rate some doses produced a small transient increase in this frequency. Exposure to low doses at low, but not high dose rate, significantly, but transiently reduced average lesion size, and at either dose rate transiently reduced lesion severity. Exposure to any dose at low dose rate (but not high dose rate) resulted in large and persistent decreases in serum cholesterol. These data indicate that a single low dose exposure, depending on dose and dose rate, generally protects against various measures of atherosclerosis in genetically susceptible mice. This result contrasts with the known, generally detrimental effects of high doses on this disease in the same mice, suggesting that a linear extrapolation of risk from high doses is not appropriate. (author)

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

Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen.

LENUS (Irish Health Repository)

Cassidy, Eugene M

2012-10-01

The aim of the study was to compare symptom-triggered and standard benzodiazepine regimens for the treatment of alcohol withdrawal syndrome in an emergency department clinical decision unit. The authors found that the symptom-triggered approach reduced cumulative benzodiazepine dose and length of stay.

Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Munck af Rosenschöld, Per; Oh, Jung Hun; Hunt, Margie [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kollmeier, Marisa [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Happersett, Laura; Yorke, Ellen; Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jackson, Andrew, E-mail: jacksona@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

2014-02-01

Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the

Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

Science.gov (United States)

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-01-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

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.

Science.gov (United States)

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

2011-05-01

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.

Low dose epidemiologic studies

International Nuclear Information System (INIS)

Anon.

1990-01-01

In this chapter the BEIR committee has reviewed low-dose irradiation studies since the BEIR III report. They have considered the carcinogenic effectiveness of low-LET in populations exposed to radiation from a number of different sources: diagnostic radiography; fallout from nuclear weapons testing; nuclear installations; radiation in the workplace and high levels of natural background radiation

Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

Science.gov (United States)

Li, Yuan; Ge, Chang; Feng, Guoxing; Xiao, Huiwen; Dong, Jiali; Zhu, Changchun; Jiang, Mian; Cui, Ming; Fan, Saijun

2018-03-24

Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings. © 2018 Wiley Periodicals, Inc.

Low-dose effect on blood chromosomes

International Nuclear Information System (INIS)

Pohl-Rueling, J.

1992-01-01

Linear dose response relationships of biological effects at low doses are experimentally and theoretically disputed. Structural chromosome aberration rates at doses ranging from normal background exposures up to about 30 mGy/yr in vivo and up to 50 mGy in vitro were investigated by the author and other scientists. Results are comparable and dose effect curves reveal following shapes; within the normal burden and up to 2-10 mGy/yr in vivo rates they increase sharply to about 3-6 times the lowest values; subsequent doses either from natural, occupational or accidental exposures up to about 30 mGy/yr yield either constant aberration rates, assuming a plateau, or perhaps even a decrease. In vitro experiments show comparable results up to 50 mGy. Other biological effects seem to have similar dose dependencies. The non-linearity of low-dose effects can be explained by induction of repair enzymes at certain damage to the DNA. This hypothesis is sustained experimentally and theoretically by several papers in literature. (author). 14 refs., 5 figs

Monte Carlo simulation of secondary neutron dose for scanning proton therapy using FLUKA.

Directory of Open Access Journals (Sweden)

Chaeyeong Lee

Full Text Available Proton therapy is a rapidly progressing field for cancer treatment. Globally, many proton therapy facilities are being commissioned or under construction. Secondary neutrons are an important issue during the commissioning process of a proton therapy facility. The purpose of this study is to model and validate scanning nozzles of proton therapy at Samsung Medical Center (SMC by Monte Carlo simulation for beam commissioning. After the commissioning, a secondary neutron ambient dose from proton scanning nozzle (Gantry 1 was simulated and measured. This simulation was performed to evaluate beam properties such as percent depth dose curve, Bragg peak, and distal fall-off, so that they could be verified with measured data. Using the validated beam nozzle, the secondary neutron ambient dose was simulated and then compared with the measured ambient dose from Gantry 1. We calculated secondary neutron dose at several different points. We demonstrated the validity modeling a proton scanning nozzle system to evaluate various parameters using FLUKA. The measured secondary neutron ambient dose showed a similar tendency with the simulation result. This work will increase the knowledge necessary for the development of radiation safety technology in medical particle accelerators.

Risk of radiation-induced cancer at low doses and low dose rates for radiation protection purposes

International Nuclear Information System (INIS)

1995-01-01

The aim of this report is to provide an updated, comprehensive review of the data available for assessing the risk of radiation-induced cancer for radiation protection purposes. Particular emphasis is placed on assessing risks at low doses and low dose rates. The review brings together the results of epidemiological investigations and fundamental studies on the molecular and cellular mechanisms involved in radiation damage. Additionally, this information is supplemented by studies with experimental animals which provide further guidance on the form of the dose-response relationship for cancer induction, as well as on the effect of dose rate on the tumour yield. The emphasis of the report is on cancer induction resulting from exposure to radiations with a low linear energy transfer (LET). The work was performed under contract for the Institut de Protection et de Surete Nucleaire, Fontenay-aux-Roses, Paris, France, whose agreement to publish is gratefully ackowledged. It extends the advice on radiation risks given in Documents of the NRPB, 4 No. 4 (1993). (Author)

Cancer and non-cancer risk at low doses of radiation: biological basis of radiation-environment interplay

International Nuclear Information System (INIS)

Sasaki, Masao S.

2013-01-01

Cancer and non-cancer risk at low doses of ionizing radiation remains poorly defined due to ambiguity at low doses caused by limitations in statistical power and information available on interplay with environment. To deal with these problems, a novel non-parametric statistics was developed based on artificial neural networks theorem and applied to cancer and non-cancer risk in A-bomb survivors. The analysis revealed several unique features at low doses that could not be accounted for by nominal radiation dose alone. They include (1) threshold that varies with organ, gender and age, including cardiovascular diseases, (2) prevalence of infectious diseases, and (3) suppression of pathogenesis of HTLV1. The threshold is unique as it is manifested as negative excess relative risk, a reduction of spontaneous rate at low doses. The response is consistent with currently emerging laboratory data on DNA double-strand break (DSB) repair pathway choice and its sustainability as epigenetic memory in accordance with histone code theory. In response to DSB, of radiation or DNA replication arrest origin, distinct and competitively operating repair pathways are instigated. Activation by low doses of restitution-directed canonical non-homologous end-joining (C-NHEJ) suppresses both error-prone alternative end-joining (Alt-NHEJ) and homologous recombination (HR). The latter two present major pathways to mutagenesis at stalled replication folk associated with endogenous and exogenous genotoxin such as tobacco smoke metabolites and AID-associated somatic hypermutation and class switch recombination in Ig gene. Suppression of these error-prone pathways by low doses of low LET radiation is consistent with the reduction of cancer occurrence by environmental genotoxin, immunodiversity and stable integration of retrovirus DNA, providing a significant modulator of dose linearity at low doses. Whole picture may bring about a new landscape of cancer and non-cancer molecular epidemiology which

Low doses of gamma radiation in soybean

International Nuclear Information System (INIS)

Franco, José G.; Franco, Suely S.H.; Villavicencio, Anna L.C.; Arthur, Valter; Arthur, Paula B.; Franco, Caio H.

2017-01-01

The degree of radiosensitivity depends mostly on the species, the stage of the embryo at irradiation, the doses employed and the criteria used to measure the effect. One of the most common criteria to evaluate radiosensitivity in seeds is to measure the average plant production. Dry soya seeds were exposed to low doses of gamma radiation from source of Cobalt-60, type Gammecell-220, at 0.210 kGy dose rate. In order to study stimulation effects of radiation on germination, plant growth and production. A treatment with four radiation doses was applied as follows: 0 (control); 12.5; 25.0 and 50.0 Gy. Seed germination and harvested of number of seeds and total production were assessed to identify occurrence of stimulation. Soya seeds number and plants were handled as for usual seed production in Brazil. The low doses of gamma radiation in the seeds that stimulate the production were the doses of 12.5 and 50.0 Gy. The results show that the use of low doses of gamma radiation can stimulate germination and plant production. (author)

Low doses of gamma radiation in soybean

Energy Technology Data Exchange (ETDEWEB)

Franco, José G.; Franco, Suely S.H.; Villavicencio, Anna L.C., E-mail: zegilmar60@gmail.com, E-mail: gilmita@uol.com.br, E-mail: villavic@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil); Arthur, Valter; Arthur, Paula B., E-mail: arthur@cena.usp.br [Centro de Energia Nuclear na Agricultura (CENA/USP), Piracicaba, SP (Brazil); Franco, Caio H. [Universidade Federal de São Paulo (UNIFESP), SP (Brazil). Departamento de Microbiologia, Imunologia e Parasitologia

2017-07-01

The degree of radiosensitivity depends mostly on the species, the stage of the embryo at irradiation, the doses employed and the criteria used to measure the effect. One of the most common criteria to evaluate radiosensitivity in seeds is to measure the average plant production. Dry soya seeds were exposed to low doses of gamma radiation from source of Cobalt-60, type Gammecell-220, at 0.210 kGy dose rate. In order to study stimulation effects of radiation on germination, plant growth and production. A treatment with four radiation doses was applied as follows: 0 (control); 12.5; 25.0 and 50.0 Gy. Seed germination and harvested of number of seeds and total production were assessed to identify occurrence of stimulation. Soya seeds number and plants were handled as for usual seed production in Brazil. The low doses of gamma radiation in the seeds that stimulate the production were the doses of 12.5 and 50.0 Gy. The results show that the use of low doses of gamma radiation can stimulate germination and plant production. (author)

Low-level laser therapy for the prevention of low salivary flow rate after radiotherapy and chemotherapy in patients with head and neck cancer

International Nuclear Information System (INIS)

Gonnelli, Fernanda Aurora Stabile; Palma, Luiz Felipe; Giordani, Adelmo Jose; Dias, Rodrigo Souza; Segreto, Roberto Araujo; Segreto, Helena Regina Comodo; Deboni, Aline Lima Silva

2016-01-01

Objective: to determine whether low-level laser therapy can prevent salivary hypofunction after radiotherapy and chemotherapy in head and neck cancer patients. Materials and methods: ee evaluated 23 head and neck cancer patients, of whom 13 received laser therapy and 10 received clinical care only. An InGaAlP laser was used intra-orally (at 660 nm and 40 mW) at a mean dose of 10.0 J/cm 2 and extra-orally (at 780 nm and 15 mW) at a mean dose of 3.7 J/cm 2 , three times per week, on alternate days. Stimulated and unstimulated sialometry tests were performed before the first radiotherapy and chemotherapy sessions (NO) and at 30 days after the end of treatment (N30). Results: At N30, the mean salivary flow rates were significantly higher among the laser therapy patients than among the patients who received clinical care only, in the stimulated and unstimulated sialometry tests (p = 0.0131 and p = 0.0143, respectively). Conclusion: low-level laser therapy, administered concomitantly with radiotherapy and chemotherapy, appears to mitigate treatment induced salivary hypofunction in patients with head and neck cancer. (author)

Low-level laser therapy for the prevention of low salivary flow rate after radiotherapy and chemotherapy in patients with head and neck cancer

Energy Technology Data Exchange (ETDEWEB)

Gonnelli, Fernanda Aurora Stabile [Faculdades Metropolitanas Unidas (FMU), Sao Paulo, SP (Brazil); Palma, Luiz Felipe; Giordani, Adelmo Jose; Dias, Rodrigo Souza; Segreto, Roberto Araujo; Segreto, Helena Regina Comodo [Universidade Federal de Sao Paulo (EPM/UNIFESP), Sao Paulo, SP (Brazil). Escola Paulista de Medicina; Deboni, Aline Lima Silva

2016-03-15

Objective: to determine whether low-level laser therapy can prevent salivary hypofunction after radiotherapy and chemotherapy in head and neck cancer patients. Materials and methods: ee evaluated 23 head and neck cancer patients, of whom 13 received laser therapy and 10 received clinical care only. An InGaAlP laser was used intra-orally (at 660 nm and 40 mW) at a mean dose of 10.0 J/cm{sup 2} and extra-orally (at 780 nm and 15 mW) at a mean dose of 3.7 J/cm{sup 2} , three times per week, on alternate days. Stimulated and unstimulated sialometry tests were performed before the first radiotherapy and chemotherapy sessions (NO) and at 30 days after the end of treatment (N30). Results: At N30, the mean salivary flow rates were significantly higher among the laser therapy patients than among the patients who received clinical care only, in the stimulated and unstimulated sialometry tests (p = 0.0131 and p = 0.0143, respectively). Conclusion: low-level laser therapy, administered concomitantly with radiotherapy and chemotherapy, appears to mitigate treatment induced salivary hypofunction in patients with head and neck cancer. (author)

Fixed-dose combination therapy for the prevention of cardiovascular disease

Science.gov (United States)

de Cates, Angharad N; Farr, Matthew RB; Rees, Karen; Casas, Juan P; Huffman, Mark

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of fixed-dose combination therapy on optimising CVD risk factors and reducing CVD fatal and non-fatal events for both primary and secondary prevention of CVD. Details of CVD events and risk factors included are listed in the methods. We will also determine any adverse events associated with taking fixed-dose combination therapy. This will include studies conducted in both developed and developing regions of the world. PMID:25267903

Is It All about the Higher Dose? Why Psychoanalytic Therapy Is an Effective Treatment for Major Depression.

Science.gov (United States)

Zimmermann, Johannes; Löffler-Stastka, Henriette; Huber, Dorothea; Klug, Günther; Alhabbo, Sarah; Bock, Astrid; Benecke, Cord

2015-01-01

Empirical evidence for the effectiveness of long-term psychodynamic psychotherapy (LTPP) in patients with mood disorders is growing. However, it is unclear whether the effectiveness of LTPP is due to distinctive features of psychodynamic/psychoanalytic techniques or to a higher number of sessions. We tested these rival hypotheses in a quasi-experimental study comparing psychoanalytic therapy (i.e., high-dose LTPP) with psychodynamic therapy (i.e., low-dose LTPP) and cognitive-behavioural therapy (CBT) for depression. Analyses were based on a subsample of 77 subjects, with 27 receiving psychoanalytic therapy, 26 receiving psychodynamic therapy and 24 receiving CBT. Depressive symptoms, interpersonal problems and introject affiliation were assessed prior to treatment, after treatment and at the 1-, 2- and 3-year follow-ups. Psychoanalytic techniques were assessed from three audiotaped middle sessions per treatment using the Psychotherapy Process Q-Set. Subjects receiving psychoanalytic therapy reported having fewer interpersonal problems, treated themselves in a more affiliative way directly after treatment and tended to improve in depressive symptoms and interpersonal problems during follow-up as compared with patients receiving psychodynamic therapy and/or CBT. Multilevel mediation analyses suggested that post-treatment differences in interpersonal problems and introject affiliation were mediated by the higher number of sessions, and follow-up differences in depressive symptoms were mediated by the more pronounced application of psychoanalytic techniques. We also found some evidence for indirect treatment effects via psychoanalytic techniques on changes in introject affiliation during follow-up. These results provide support for the prediction that both a high dose and the application of psychoanalytic techniques facilitate therapeutic change in patients with major depression. Psychoanalytic therapy is an effective treatment for major depression, especially in the

Assessment of internal doses in emergency situations

Energy Technology Data Exchange (ETDEWEB)

Rahola, T.; Muikku, M. [Radiation and Nuclear Safety Authority - STUK (Finland); Falk, R.; Johansson, J. [Swedish Radiation Protection Authority - SSI (Sweden); Liland, A.; Thorshaug, S. [NRPA (Norway)

2006-04-15

The need for assessing internal radiation doses in emergency situations was demonstrated after accidents in Brazil, Ukraine and other countries. Lately more and more concern has been expressed regarding malevolent use of radiation and radioactive materials. The scenarios for such use are more difficult to predict than for nuclear power plant or weapons accidents. Much of the results of the work done in the IRADES project can be adopted for use in various accidental situations involving radionuclides that are not addressed in this report. If an emergency situation occurs in only one or a few of the Nordic countries, experts from the other countries could be called upon to assist in monitoring. A big advantage is then our common platform. In the Nordic countries much work has been put down on quality assurance of measurements and on training of dose assessment calculations. Attention to this was addressed at the internal dosimetry course in October 2005. Nordic emergency preparedness exercises have so far not included training of direct measurements of people in the early phase of an emergency. The aim of the IRADES project was to improve the preparedness especially for thyroid measurements. The modest financial support did not enable the participants to make big efforts but certainly acted as a much appreciated reminder of the importance of being prepared also to handle situations with malevolent use of radioactive materials. It was left to each country to decide to which extent to improve the practical skills. There is still a need for detailed national implementation plans. Measurement strategies need to be developed in each country separately taking into account national regulations, local circumstances and resources. End users of the IRADES report are the radiation protection authorities. (au)

Assessment of internal doses in emergency situations

International Nuclear Information System (INIS)

Rahola, T.; Muikku, M.; Falk, R.; Johansson, J.; Liland, A.; Thorshaug, S.

2006-04-01

The need for assessing internal radiation doses in emergency situations was demonstrated after accidents in Brazil, Ukraine and other countries. Lately more and more concern has been expressed regarding malevolent use of radiation and radioactive materials. The scenarios for such use are more difficult to predict than for nuclear power plant or weapons accidents. Much of the results of the work done in the IRADES project can be adopted for use in various accidental situations involving radionuclides that are not addressed in this report. If an emergency situation occurs in only one or a few of the Nordic countries, experts from the other countries could be called upon to assist in monitoring. A big advantage is then our common platform. In the Nordic countries much work has been put down on quality assurance of measurements and on training of dose assessment calculations. Attention to this was addressed at the internal dosimetry course in October 2005. Nordic emergency preparedness exercises have so far not included training of direct measurements of people in the early phase of an emergency. The aim of the IRADES project was to improve the preparedness especially for thyroid measurements. The modest financial support did not enable the participants to make big efforts but certainly acted as a much appreciated reminder of the importance of being prepared also to handle situations with malevolent use of radioactive materials. It was left to each country to decide to which extent to improve the practical skills. There is still a need for detailed national implementation plans. Measurement strategies need to be developed in each country separately taking into account national regulations, local circumstances and resources. End users of the IRADES report are the radiation protection authorities. (au)

The elementary discussion of volumetric modulated arc therapy using the orthogonal plane dose verification

International Nuclear Information System (INIS)

Shi Jinping; Chen Lixin; Xie Qiuying; Zhang Liwen; Teng Jianjian

2012-01-01

Objective: This study was to explore the feasibility of using the orthogonal plane dose formed by the coronal and sagittal plane to verify the volumetric modulated arc therapy (VMAT) plan. Methods: The VMAT plans of 12 patients were included in this study. The orthogonal plane dose formed by the coronal and sagittal plane were measured based on the combination of 2D ionization chamber array and multicube phantom, and the point dose were measured based on a multiple hole cylindrical phantom attached with two 0.125 cm 3 ionization chamber probes. Results: In the measurement of the point dose, the average error was 1.5% in high dose area (more than 80% of maximum), and 1.7% in low dose area (less than 80% of maximum), respectively. The discrepancy of point dose measurement was 1.3% between the 2D ionization chamber array and the VMAT planning system. In the measurement of the orthogonal plane dose, the pass rate of γ were 93.7% for 2%/2 mm and 97.2% for 3%/3 mm. Conclusion: It is reliable for using the orthogonal plane dose formed by the coronal and sagittal plane to verify the VMAT plan. (authors)

Conformal proton radiation therapy for pediatric low-grade astrocytomas

International Nuclear Information System (INIS)

Hug, E.B.; Loma Linda Univ. Medical Center, Loma Linda, CA; Darthmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Muenter, M.W.; Archambeau, J.O.; DeVries, A.; Loredo, L.N.; Grove, R.I.; Slater, J.D.; Liwnicz, B.

2002-01-01

Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Patients and Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephatic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (cobalt gray equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. Results: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. Conclusions: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment

High-dose steroid therapy for idiopathic optic perineuritis: a case series

Directory of Open Access Journals (Sweden)

Mimura Tatsuya

2010-12-01

Full Text Available Abstract Introduction It has been reported that the prognosis of optic perineuritis may be poor when initiation of treatment is delayed. Here we report the successful treatment of three patients with idiopathic optic perineuritis, including two in whom initiation of therapy was delayed. Case presentation Three Japanese patients (two women aged 73 and 66 years, and one man aged 27 years presented with loss of vision (for five months, several months, and two months respectively and pain on eye movement in the third case only, and were diagnosed as having idiopathic optic perineuritis. Fat-suppressed T2-weighted magnetic resonance images showed high signal intensity areas around the affected optic nerves, suggesting the presence of optic perineuritis. Two patients received steroid pulse therapy and the third was given high-dose steroid therapy. The visual acuity improved in all three cases. Conclusion High-dose steroid therapy may be effective for idiopathic perineuritis in patients without optic nerve atrophy, even if initial treatment (including moderate-dose steroids has failed.

[Effect of low-dose or standard-dose conjugated equine estrogen combined with different progesterone on bone density in menopause syndrome women].

Science.gov (United States)

Zuo, H L; Deng, Y; Wang, Y F; Gao, L L; Xue, W; Zhu, S Y; Ma, X; Sun, A J

2018-04-25

Objective: To explore the effect of low-dose or standard-dose conjugated equine estrogen (CEE) combined with natural progesterone or dydrogesterone on bone density in menopause syndrome women. Methods: Totally 123 patients with menopause syndrome were recruited and randomly assigned to 3 treatment groups: group A (low-dose CEE+progesterone) , group B (standard-dose CEE+progesterone) , group C (standard-dose CEE+dydrogesterone) . Using continuous sequential regimen, the duration of intervention was 12 cycles. The bone mineral density of lumbar 2-4 and neck of femur, the bone metabolic markers, the level of FSH and estradiol were examined just before the drug administration and 12 months after the beginning of experiment. Results: There were 107 cases completed the one year trial. (1) Bone density: after 12 cycles of treatment, there was no significant change in bone density in group A ( P> 0.05) ; lumbar vertebrae of group B and C increased significantly, at 3.0% and 2.1%respectively (all Pdensity of left femoral neck of group C significantly increased by 2.9% ( P= 0.029) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . (2) Bone metabolic markers: after 12 cycles of treatment, the levels of calcium, phosphorus, alkaline phosphatase, Ca/Cr decreased significantly, the difference were statistically significant (all P 0.05) . (3) Levels of FSH and estradiol: after 12 cycles of treatment, the levels of FSH in three groups were decreased significantly (all P 0.05) . Conclusions: Both low-dose and standard-dose menopause hormone therapy (MHT) could elevate the level of estradiol, reduce bone turnover, prevent bone loss of postmenopausal women effectively. The standard dose of MHT could also increase the density of vertebrae and femoral neck, and generate more clinical benefits.

Low-dose topical 5-aminolevulinic acid photodynamic therapy in the treatment of different severity of acne vulgaris.

Science.gov (United States)

Ma, Li; Xiang, Lei-Hong; Yu, Bo; Yin, Rui; Chen, Lei; Wu, Yan; Tan, Zhi-Jian; Liu, Yong-Bin; Tian, Hong-Qing; Li, Hui-Zhong; Lin, Tong; Wang, Xiu-Li; Li, Yuan-Hong; Wang, Wei-Zheng; Yang, Hui-Lan; Lai, Wei

2013-12-01

To investigate the efficacy and safety of low-concentration 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of different severity of acne vulgaris and optimize the treatment regimen. A self-controlled multicenter clinical trial was carried out in 15 centers throughout China. A total of 397 acne patients of grade II-IV received 3- or 4-session PDT treatment. 5% ALA gel was applied topically to acne lesions for 1h incubation. The lesions were irradiated by a LED light of 633 nm at dose levels of 96-120 J/cm(2). Clinical assessment was conducted before and after every treatment up to 8 weeks. The effective rate overall and of grade II, III and IV are 82.1%, 71.6%, 79.6% and 88.2%, respectively. The effective rate rises significantly proportionally to the severity of acne (P0.05). The count of inflammatory and non-inflammatory acne lesions gradually decrease after each treatment (Pacne vulgaris in Chinese patients. Superior efficacy is found in severe cystic acne of grade IV with mild side effects. Copyright © 2013 Elsevier B.V. All rights reserved.

The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

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Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

2017-09-01

We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Dose reporting in ion beam therapy. Proceedings of a meeting

International Nuclear Information System (INIS)

2007-06-01

Following the pioneering work in Berkeley, USA, ion beam therapy for cancer treatment is at present offered in Chiba and Hyogo in Japan, and Darmstadt in Germany. Other facilities are coming close to completion or are at various stages of planning in Europe and Japan. In all these facilities, carbon ions have been selected as the ions of choice, at least in the first phase. Taking into account this fast development, the complicated technical and radiobiological research issues involved, and the hope it raises for some types of cancer patients, the IAEA and the International Commission on Radiation Units and measurements (ICRU) jointly sponsored a technical meeting held in Vienna, 23-24 June 2004. That first meeting was orientated mainly towards radiobiology: the relative biological effectiveness (RBE) of carbon ions versus photons, and related issues. One of the main differences between ion beam therapy and other modern radiotherapy techniques (such as proton beam therapy or intensity modulated radiation therapy) is related to radiobiology and in particular the increased RBE of carbon ions compared to both protons and photons (i.e., high linear energy transfer (LET) versus low LET radiation). Another important issue for international agencies and commissions, such as the IAEA and the ICRU, is a worldwide agreement and harmonisation for reporting the treatments. In order to evaluate the merits of ion beam therapy, it is essential that the treatments be reported in a similar/comparable way in all centres so that the clinical reports and protocols can be understood and interpreted without ambiguity by the radiation therapy community in general. For the last few decades, the ICRU has published several reports containing recommendations on how to report external photon beam or electron beam therapy, and brachytherapy. A report on proton beam therapy, jointly prepared by the ICRU and the IAEA, is now completed and is being published in the ICRU series. In line with this

Lateral topography for reducing effective dose in low-dose chest CT.

Science.gov (United States)

Bang, Dong-Ho; Lim, Daekeon; Hwang, Wi-Sub; Park, Seong-Hoon; Jeong, Ok-man; Kang, Kyung Wook; Kang, Hohyung

2013-06-01

The purposes of this study were to assess radiation exposure during low-dose chest CT by using lateral topography and to compare the lateral topographic findings with findings obtained with anteroposterior topography alone and anteroposterior and lateral topography combined. From November 2011 to February 2012, 210 male subjects were enrolled in the study. Age, weight, and height of the men were recorded. All subjects were placed into one of three subgroups based on the type of topographic image obtained: anteroposterior topography, lateral topography, and both anteroposterior and lateral topography. Imaging was performed with a 128-MDCT scanner. CT, except for topography, was the same for all subjects. A radiologist analyzed each image, recorded scan length, checked for any insufficiencies in the FOV, and calculated the effective radiation dose. One-way analysis of variance and multiple comparisons were used to compare the effective radiation exposure and scan length between groups. The mean scan length in the anteroposterior topography group was significantly greater than that of the lateral topography group and the combined anteroposterior and lateral topography group (p topography group (0.735 ± 0.033 mSv) was significantly lower than that for the anteroposterior topography group (0.763 ± 0.038 mSv) and the combined anteroposterior and lateral topography group (0.773 ± 0.038) (p < 0.001). Lateral topographic low-dose CT was associated with a lower effective radiation dose and scan length than either anteroposterior topographic low-dose chest CT or low-dose chest CT with both anteroposterior and lateral topograms.

Ion therapy of prostate cancer: daily rectal dose reduction by application of spacer gel

International Nuclear Information System (INIS)

Rucinski, Antoni; Brons, Stephan; Richter, Daniel; Habl, Gregor; Debus, Jürgen; Bert, Christoph; Haberer, Thomas; Jäkel, Oliver

2015-01-01

Ion beam therapy represents a promising approach to treat prostate cancer, mainly due to its high conformity and radiobiological effectiveness. However, the presence of prostate motion, patient positioning and range uncertainties may deteriorate target dose and increase exposure of organs at risk. Spacer gel injected between prostate and rectum may increase the safety of prostate cancer (PC) radiation therapy by separating the rectum from the target dose field. The dosimetric impact of the application of spacer gel for scanned carbon ion therapy of PC has been analyzed at Heidelberg Ion-Beam Therapy Center (HIT). The robustness of ion therapy treatment plans was investigated by comparison of two data sets of patients treated with and without spacer gel. A research treatment planning system for ion therapy was used for treatment plan optimization and calculation of daily dose distributions on 2 to 9 Computed Tomography (CT) studies available for each of the 19 patients. Planning and daily dose distributions were analyzed with respect to target coverage, maximal dose to the rectum (excluding 1 ml of the greatest dose; Dmax-1 ml) and the rectal volume receiving dose greater than 90% of prescribed target dose (V90 Rectum ), respectively. The application of spacer gel did substantially diminish rectum dose. Dmax-1 ml on the treatment planning CT was on average reduced from 100.0 ± 1.0% to 90.2 ± 4.8%, when spacer gel was applied. The robustness analysis performed with daily CT studies demonstrated for all analyzed patient cases that application of spacer gel results in a decrease of the daily V90 Rectum index, which calculated over all patient cases and CT studies was 10.2 ± 10.4 [ml] and 1.1 ± 2.1 [ml] for patients without and with spacer gel, respectively. The dosimetric benefit of increasing the distance between prostate and rectum using spacer gel for PC treatment with carbon ion beams has been quantified. Application of spacer gel substantially reduced rectal

Effects of low dose radiation and epigenetic regulation

International Nuclear Information System (INIS)

Jiao Benzheng; Ma Shumei; Yi Heqing; Kong Dejuan; Zhao Guangtong; Gao Lin; Liu Xiaodong

2010-01-01

Purpose: To conclude the relationship between epigenetics regulation and radiation responses, especially in low-dose area. Methods: The literature was examined for papers related to the topics of DNA methylation, histone modifications, chromatin remodeling and non-coding RNA modulation in low-dose radiation responses. Results: DNA methylation and radiation can regulate reciprocally, especially in low-dose radiation responses. The relationship between histone methylation and radiation mainly exists in the high-dose radiation area; histone deacetylase (HDAC) inhibitors show a promising application to enhance radiation sensitivity, no matter whether in low-dose or high-dose areas; the connection between γ-H2AX and LDR has been remained unknown, although γ-H2AX has been shown no radiation sensitivities with 1-15 Gy irradiation; histone ubiquitination play an important role in DNA damage repair mechanism. Moreover, chromatin remodeling has an integral role in DSB repair and the chromatin response, in general, may be precede DNA end resection. Finally, the effect of radiation on miRNA expression seems to vary according to cell type, radiation dose, and post-irradiation time point. Conclusion: Although the advance of epigenetic regulation on radiation responses, which we are managing to elucidate in this review, has been concluded, there are many questions and blind blots deserved to investigated, especially in low-dose radiation area. However, as progress on epigenetics, we believe that many new elements will be identified in the low-dose radiation responses which may put new sights into the mechanisms of radiation responses and radiotherapy. (authors)

In vitro therapy study combined with low doses of radiation (Rn-222) and chemotherapy (taxol)

International Nuclear Information System (INIS)

Soto, J.; Sainz, C.; Cos, S.; Gonzalez-Lamuno, D.

2004-01-01

A study was carried out to test the possibility that breast cancer cells show increased sensitivity to the chemotherapeutic agent taxol when they have been treated with low radiation doses from the gas radon. To this end, the cells were cultivated in a medium containing dissolved radon and then in a second medium containing a concentration of taxol. After the culture phase the surviving cells were counted and their viability was assessed. The results obtained indicate that the cells treated with low doses of radon exhibit increased sensitivity when treated with certain concentrations of taxol; in particular a lower survival rate and lower viability were observed in cells treated with radon and 50 nM of taxol in cells treated with the same concentration of taxol alone. These effects seem to result from the influence of the radon on the expression of apoptosis -related genes, which is complementary to the action of taxol on bcl-x related genes. (author)

Biochemical and cellular mechanisms of low-dose effects

International Nuclear Information System (INIS)

Feinendegen, L.E.; Booz, J.; Muehlensiepen, H.

1988-01-01

The question of health effects from small radiation doses remains open. Individual cells, when being hit by single elemental doses - in low-dose irradiation - react acutely and temporarily by altering control of enzyme activity, as is demonstrated for the case of thymidine kinase. This response is not constant in that it provides a temporary protection of enzyme activity against a second irradiation, by a mechanism likely to be via improved detoxification of intracellular radicals. It must be considered that in the low-dose region radiation may also exert protection against other challenges involving radicals, causing a net beneficial effect by temporarily shielding the hit cell against radicals produced by metabolism. Since molecular alterations leading to late effects are considered a consequence of the initial cellular response, late effects from small radiation doses do not necessarily adhere to a linear dose-effect relationship. The reality of the linear relationship between the risk of late effects from high doses to small doses is an assumption, for setting dose limits, but it must not be taken for predicting health detriment from low doses. (author)

Fully automated bone mineral density assessment from low-dose chest CT

Science.gov (United States)

Liu, Shuang; Gonzalez, Jessica; Zulueta, Javier; de-Torres, Juan P.; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

2018-02-01

A fully automated system is presented for bone mineral density (BMD) assessment from low-dose chest CT (LDCT). BMD assessment is central in the diagnosis and follow-up therapy monitoring of osteoporosis, which is characterized by low bone density and is estimated to affect 12.3 million US population aged 50 years or older, creating tremendous social and economic burdens. BMD assessment from DXA scans (BMDDXA) is currently the most widely used and gold standard technique for the diagnosis of osteoporosis and bone fracture risk estimation. With the recent large-scale implementation of annual lung cancer screening using LDCT, great potential emerges for the concurrent opportunistic osteoporosis screening. In the presented BMDCT assessment system, each vertebral body is first segmented and labeled with its anatomical name. Various 3D region of interest (ROI) inside the vertebral body are then explored for BMDCT measurements at different vertebral levels. The system was validated using 76 pairs of DXA and LDCT scans of the same subject. Average BMDDXA of L1-L4 was used as the reference standard. Statistically significant (p-value correlation is obtained between BMDDXA and BMDCT at all vertebral levels (T1 - L2). A Pearson correlation of 0.857 was achieved between BMDDXA and average BMDCT of T9-T11 by using a 3D ROI taking into account of both trabecular and cortical bone tissue. These encouraging results demonstrate the feasibility of fully automated quantitative BMD assessment and the potential of opportunistic osteoporosis screening with concurrent lung cancer screening using LDCT.

What happens at very low levels of radiation exposure ? Are the low dose exposures beneficial ?

International Nuclear Information System (INIS)

Deniz, Dalji

2006-01-01

Full text: Radiation is naturally present in our environment and has been since the birth of this planet. The human population is constantly exposed to low levels of natural background radiation, primarily from environmental sources, and to higher levels from occupational sources, medical therapy, and other human-mediated events. Radiation is one of the best-investigated hazardous agents. The biological effects of ionizing radiation for radiation protection consideration are grouped into two categories: The deterministic and the stochastic ones. Deterministic radiation effects can be clinically diagnosed in the exposed individual and occur when above a certain t hreshold a n appropriately high dose is absorbed in the tissues and organs to cause the death of a large number of cells and consequently to impair tissue or organ functions early after exposure. A clinically observable biological effect (Acute Radiation Sendromes, ARS) occurs days to months after an acute radiation dose. Stochastic radiation effects are the chronic effects of radiation result from relatively low exposure levels delivered over long periods of time. These are sort of effects that might result from occupational exposure, or to the background exposure levels. Such late effects might be the development of malignant (cancerous) disease and of the hereditary consequences. These effects may be observed many years after the radiation exposure. There is a latent period between the initial radiation exposure and the development of the biological effect. For this reason, a stochastic effect is called a Linear or Zero-Threshold (LNT) Dose-Response Effect. There is a stochastic correlation between the number of cases of cancers or genetic defects developed inside a population and the dose received by the population at relatively large levels of radiation. These changes in gene activation seem to be able to modify the response of cells to subsequent radiation exposure, termed the a daptive response

Technology Assessment and Roadmap for the Emergency Radiation Dose Assessment Program

International Nuclear Information System (INIS)

Turteltaub, K W; Hartman-Siantar, C; Easterly, C; Blakely, W

2005-01-01

A Joint Interagency Working Group (JIWG) under the auspices of the Department of Homeland Security Office of Research and Development conducted a technology assessment of emergency radiological dose assessment capabilities as part of the overall need for rapid emergency medical response in the event of a radiological terrorist event in the United States. The goal of the evaluation is to identify gaps and recommend general research and development needs to better prepare the Country for mitigating the effects of such an event. Given the capabilities and roles for responding to a radiological event extend across many agencies, a consensus of gaps and suggested development plans was a major goal of this evaluation and road-mapping effort. The working group consisted of experts representing the Departments of Homeland Security, Health and Human Services (Centers for Disease Control and the National Institutes of Health), Food and Drug Administration, Department of Defense and the Department of Energy's National Laboratories (see appendix A for participants). The specific goals of this Technology Assessment and Roadmap were to: (1) Describe the general context for deployment of emergency radiation dose assessment tools following terrorist use of a radiological or nuclear device; (2) Assess current and emerging dose assessment technologies; and (3) Put forward a consensus high-level technology roadmap for interagency research and development in this area. This report provides a summary of the consensus of needs, gaps and recommendations for a research program in the area of radiation dosimetry for early response, followed by a summary of the technologies available and on the near-term horizon. We then present a roadmap for a research program to bring present and emerging near-term technologies to bear on the gaps in radiation dose assessment and triage. Finally we present detailed supporting discussion on the nature of the threats we considered, the status of technology

Technology Assessment and Roadmap for the Emergency Radiation Dose Assessment Program

Energy Technology Data Exchange (ETDEWEB)

Turteltaub, K W; Hartman-Siantar, C; Easterly, C; Blakely, W

2005-10-03

A Joint Interagency Working Group (JIWG) under the auspices of the Department of Homeland Security Office of Research and Development conducted a technology assessment of emergency radiological dose assessment capabilities as part of the overall need for rapid emergency medical response in the event of a radiological terrorist event in the United States. The goal of the evaluation is to identify gaps and recommend general research and development needs to better prepare the Country for mitigating the effects of such an event. Given the capabilities and roles for responding to a radiological event extend across many agencies, a consensus of gaps and suggested development plans was a major goal of this evaluation and road-mapping effort. The working group consisted of experts representing the Departments of Homeland Security, Health and Human Services (Centers for Disease Control and the National Institutes of Health), Food and Drug Administration, Department of Defense and the Department of Energy's National Laboratories (see appendix A for participants). The specific goals of this Technology Assessment and Roadmap were to: (1) Describe the general context for deployment of emergency radiation dose assessment tools following terrorist use of a radiological or nuclear device; (2) Assess current and emerging dose assessment technologies; and (3) Put forward a consensus high-level technology roadmap for interagency research and development in this area. This report provides a summary of the consensus of needs, gaps and recommendations for a research program in the area of radiation dosimetry for early response, followed by a summary of the technologies available and on the near-term horizon. We then present a roadmap for a research program to bring present and emerging near-term technologies to bear on the gaps in radiation dose assessment and triage. Finally we present detailed supporting discussion on the nature of the threats we considered, the status of

Transcutaneous electrical nerve stimulation reduces acute low back pain during emergency transport.

Science.gov (United States)

Bertalanffy, Alexander; Kober, Alexander; Bertalanffy, Petra; Gustorff, Burkhard; Gore, Odette; Adel, Sharam; Hoerauf, Klaus

2005-07-01

Patients with acute low back pain may require emergency transport because of pain and immobilization. Transcutaneous electrical nerve stimulation (TENS) is a nonpharmaceutical therapy for patients with low back pain. To evaluate the efficacy of paramedic-administered TENS in patients with acute low back pain during emergency transport. This was a prospective, randomized study involving 74 patients transported to hospital. The patients were randomly assigned to two groups: group 1 (n = 36) was treated with true TENS, while group 2 (n = 36) was treated with sham TENS. The authors recorded pain and anxiety as the main outcome variables using a visual analog scale (VAS). The authors recorded a significant (p pain reduction (mean +/- standard deviation) during transport in group 1 (79.2 +/- 6.5 mm VAS to 48.9 +/- 8.2 mm VAS), whereas pain scores remained unchanged in group 2 (75.9 +/- 16.4 mm VAS and 77.1 +/- 11.2 mm VAS). Similarly, the scores for anxiety were significantly reduced (p TENS was found to be effective and rapid in reducing pain during emergency transport of patients with acute low back pain and should be considered due to its ease of use and lack of side effects in the study population.

Systemic effects of low-dose dopamine during administration of cytarabine.

Science.gov (United States)

Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

2017-09-01

Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

Modulation of inflammation by low and high doses of ionizing radiation: Implications for benign and malign diseases.

Science.gov (United States)

Frey, Benjamin; Hehlgans, Stephanie; Rödel, Franz; Gaipl, Udo S

2015-11-28

Inflammation is a homeostatic mechanism aiming to maintain tissue integrity. The underlying immunological mechanisms and the interrelationship between ionizing radiation and inflammation are complex and multifactorial on cellular and chemical levels. On the one hand, radiation with single doses exceeding 1 Gy might initiate inflammatory reactions and thereby impact on tumor development. On the other hand, radiation is capable of attenuating an established inflammatory process, which is clinically used for the treatment of inflammatory and degenerative diseases with low-dose radiotherapy (single dose modulates inflammatory events in benign inflammatory and in malign diseases. A special focus is set on the role of tumor infiltrating lymphocytes and macrophages as biomarkers to predict treatment response and anti-tumor immunity and on mechanisms implicated in the anti-inflammatory effects of low-dose radiation therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reduced oxygen enhancement ratio at low doses

International Nuclear Information System (INIS)

Palcic, B.; Skarsgard, L.D.

1984-01-01

The oxygen depletion rate in cell suspensions was measured using a Clark electrode. It was found that under experimental conditions used in this laboratory for hypoxic irradiations, the oxygen levels before the start of irradiation are always below 0.1μm, the levels which could give any significant enhancement to radiation inactivation by x-rays. The measured O/sub 2/ depletion rates were comparable to those reported in the literature. Chinese hamster cells (CHO) were made hypoxic by gas exchange, combined with metabolic consumption of oxygen by cells at 37 0 C. Full survival curves were determined in the dose range 0 to 3Gy using the low dose survival assay. The results confirmed the authors' earlier finding that the OER decreases at low doses. The authors therefore believe that the dose-dependent OER is a true radiobiological phenomenon and not an artifact of the experimental method used in the low dose survival assay

Dose Response Model of Biological Reaction to Low Dose Rate Gamma Radiation

International Nuclear Information System (INIS)

Magae, J.; Furikawa, C.; Hoshi, Y.; Kawakami, Y.; Ogata, H.

2004-01-01

It is necessary to use reproducible and stable indicators to evaluate biological responses to long term irradiation at low dose-rate. They should be simple and quantitative enough to produce the results statistically accurate, because we have to analyze the subtle changes of biological responses around background level at low dose. For these purposes we chose micronucleus formation of U2OS, a human osteosarcoma cell line, as indicators of biological responses. Cells were exposed to gamma ray in irradiation rom bearing 50,000 Ci 60Co. After irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and prospidium iodide, respectively. the number of binuclear cells bearing micronuclei was counted under a fluorescence microscope. Dose rate in the irradiation room was measured with PLD. Dose response of PLD is linear between 1 mGy to 10 Gy, and standard deviation of triplicate count was several percent of mean value. We fitted statistically dose response curves to the data, and they were plotted on the coordinate of linearly scale response and dose. The results followed to the straight line passing through the origin of the coordinate axes between 0.1-5 Gy, and dose and does rate effectiveness factor (DDREF) was less than 2 when cells were irradiated for 1-10 min. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose above 0.1 Gy when 5,000 binuclear cells were analyzed. In contrast, dose response curves never followed LNT, when cells were irradiated for 7 to 124 days. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose below 6 Gy, when cells were continuously irradiated for 124 days. These results suggest that dose response curve of biological reaction is remarkably affected by exposure

Is High Dose Therapy Superior to Conventional Dose Therapy as Initial Treatment for Relapsed Germ Cell Tumors? The TIGER Trial

Directory of Open Access Journals (Sweden)

Darren R. Feldman, Robert Huddart, Emma Hall, Jörg Beyer, Thomas Powles

2011-01-01

Full Text Available Metastatic germ cell tumours (GCTs are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses, standard treatment is much more uncertain. Both conventional dose therapy (CDT and high dose therapy (HDT are widely used, due to the lack of conclusive data supporting one specific approach. A recent retrospective analysis focusing on this population suggested a significant benefit for HDT. Retrospective analyses are prone to bias, and therefore while this data is provocative it is by no mean conclusive. For this reason the international community is supporting a prospective randomised trial in this area comparing CDT(TIP with sequential HDT (TICE. The planned open labelled randomised phase III study (TIGER is due to open in 2011 and will recruit 390 patients to detect a 13% difference in 2 year progression free survival (primary endpoint. It is hoped that this large study will conclusively resolve the uncertainty which currently exists.

Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term low-dose aspirin therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial.

Science.gov (United States)

Sugano, Kentaro; Matsumoto, Yasushi; Itabashi, Tsukasa; Abe, Sumihisa; Sakaki, Nobuhiro; Ashida, Kiyoshi; Mizokami, Yuji; Chiba, Tsutomu; Matsui, Shigeyuki; Kanto, Tatsuya; Shimada, Kazuyuki; Uchiyama, Shinichiro; Uemura, Naomi; Hiramatsu, Naoki

2011-06-01

The efficacy of low-dose lansoprazole has not been established for the prevention of recurrent gastric or duodenal ulcers in those receiving long-term low-dose aspirin (LDA) for cardiovascular and cerebrovascular protection. This study sought to examine the efficacy of low-dose lansoprazole (15 mg once daily) for the secondary prevention of LDA-associated gastric or duodenal ulcers. Patients were randomized to receive lansoprazole 15 mg daily (n = 226) or gefarnate 50 mg twice daily (n = 235) for 12 months or longer in a prospective, multicenter, double-blind, randomized active-controlled trial, followed by a 6-month follow-up study with open-label lansoprazole treatment. The study utilized 94 sites in Japan and 461 Japanese patients with a history of gastric or duodenal ulcers who required long-term LDA therapy for cardiovascular and cerebrovascular disease. The primary endpoint was the development of gastric or duodenal ulcers. The cumulative incidence of gastric or duodenal ulcers on days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 1.5, 2.1, and 3.7%, respectively, in the lansoprazole group versus 15.2, 24.0, and 31.7%, respectively, in the gefarnate group. The risk of ulcer development was significantly (log-rank test, P lansoprazole group than in the gefarnate group, with the hazard ratio being 0.099 (95% confidence interval [CI] 0.042-0.230). Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term LDA therapy.

Comparison of 3-Factor Prothrombin Complex Concentrate and Low-Dose Recombinant Factor VIIa for Warfarin Reversal

OpenAIRE

Chapman, Scott A; Irwin, Eric D; Abou-Karam, Nada M; Rupnow, Nichole M; Hutson, Katherine E; Vespa, Jeffrey; Roach, Robert M

2014-01-01

Introduction Prothrombin complex concentrate (PCC) and recombinant Factor VIIa (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few clinical studies have compared these agents in warfarin reversal. We compared warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation. Methods Data were collected from medical charts of patients who received at least one dose of PCC3 (20 units/kg) or LDr...

High-dose methylprednisolone pulse therapy for treatment of refractory intestinal involvement caused by Henoch-Schönlein purpura: a case report.

Science.gov (United States)

Kang, Hyun Sik; Chung, Hee Sup; Kang, Ki-Soo; Han, Kyoung Hee

2015-03-24

Henoch-Schönlein purpura is an immunoglobulin A-mediated, small vascular inflammatory disease that can be associated with palpable purpura, arthralgia, abdominal pain, or nephritis. The presence of purpura facilitates the diagnosis of Henoch-Schönlein purpura at the onset of associated symptoms, whereas the absence of purpura makes the diagnosis challenging. It is important to diagnose Henoch-Schönlein purpura with delayed-onset skin purpura to avoid unnecessary surgery for acute abdomen. Most cases of Henoch-Schönlein purpura with severe abdominal pain are treated with low-dose steroids and intravenous immunoglobulin. A 15-year-old Korean girl complained of severe abdominal pain and delayed-onset purpura on admission. Henoch-Schönlein purpura was diagnosed based on endoscopic findings of hemorrhagic duodenitis and duodenal vasculitis and abdominal computed tomography findings of edematous bowels. Two common initial treatments, a low-dose steroid and intravenous immunoglobulin, were administered, but there was no improvement for 1 month. Subsequently, we used high-dose intravenous methylprednisolone pulse therapy (30 mg/kg/day, with a maximum of 1g/day), which dramatically alleviated her abdominal symptoms. High-dose intravenous methylprednisolone pulse therapy can be used as the ultimate treatment for delayed-onset Henoch-Schönlein purpura with severe abdominal pain when symptoms do not improve after low-dose steroid and intravenous immunoglobulin treatments.

Low dose radiation enhance the anti-tumor effect of high dose radiation on human glioma cell U251

International Nuclear Information System (INIS)

Wang Chang; Wang Guanjun; Tan Yehui; Jiang Hongyu; Li Wei

2008-01-01

Objective: To detect the effect on the growth of human glioma cell U251 induced by low dose irradiation and low dose irradiation combined with large dose irradiation. Methods: Human glioma cell line U251 and nude mice carried with human glioma were used. The tumor cells and the mice were treated with low dose, high dose, and low dose combined high dose radiation. Cells growth curve, MTT and flow cytometry were used to detect the proliferation, cell cycle and apoptosis of the cells; and the tumor inhibition rate was used to assess the growth of tumor in vivo. Results: After low dose irradiation, there was no difference between experimental group and control group in cell count, MTT and flow cytometry. Single high dose group and low dose combined high dose group both show significantly the suppressing effect on tumor cells, the apoptosis increased and there was cell cycle blocked in G 2 period, but there was no difference between two groups. In vivo apparent anti-tumor effect in high dose radiation group and the combining group was observed, and that was more significant in the combining group; the prior low dose radiation alleviated the injury of hematological system. There was no difference between single low dose radiation group and control. Conclusions: There is no significant effect on human glioma cell induced by low dose radiation, and low dose radiation could not induce adaptive response. But in vivo experience, low dose radiation could enhance the anti-tumor effect of high dose radiation and alleviated the injury of hematological system. (authors)

Detection of lung nodules with low-dose spiral CT: comparison with conventional dose CT

International Nuclear Information System (INIS)

Zhu Tianzhao; Tang Guangjian; Jiang Xuexiang

2004-01-01

Objective: To investigate the effect of reducing scan dose on the lung nodules detection rate by scanning a lung nodule model at low dose and conventional dose. Methods: The lung and the thoracic cage were simulated by using a cyst filled with water surrounded by a roll bandage. Flour, butter, and paraffin wax were mixed together by a certain ratio to simulate lung nodules of 10 mm and 5 mm in diameter with the CT values ranging from -10 to 50 HU. Conventional-dose scan (240 mA, 140 kV) and low-dose scan of three different levels (43 mA, 140 kV; 50 mA, 120 kV; 75 mA, 80 kV) together with three different pitches (1.0, 1.5, and 2.0) were performed. The images of the simulated nodules were combined with the CT images of a normal adult's upper, middle, and inferior lung. Three radiologists read the images and the number of the nodules they detected including both the real ones and the false-positive ones was calculated to investigate weather there was any difference among different doses, pitch groups, and different locations. Results: The detection rate of the 10 mm and 5 mm nodules was 100% and 89.6% respectively by the low-dose scan. There was no difference between low-dose and conventional-dose CT (χ 2 =0.6907, P>0.70). The detection rate of 5 mm nodules declined when large pitch was used. Conclusion: The detection rates of 10 mm and 5 mm nodules had no difference between low-dose CT and conventional-dose CT. As the pitch augmented, the detection rate for the nodules declined

Mutation process at low or high radiation doses

International Nuclear Information System (INIS)

Abrahamson, S.; Wisconsin Univ., Madison

1976-01-01

A concise review is given of the status of research on the genetic effects of low-level radiation in general. The term ''low dose'' is defined and current theories on low dose are set out. Problems and their solutions are discussed. (author)

''Low dose'' and/or ''high dose'' in radiation protection: A need to setting criteria for dose classification

International Nuclear Information System (INIS)

Sohrabi, M.

1997-01-01

The ''low dose'' and/or ''high dose'' of ionizing radiation are common terms widely used in radiation applications, radiation protection and radiobiology, and natural radiation environment. Reading the title, the papers of this interesting and highly important conference and the related literature, one can simply raise the question; ''What are the levels and/or criteria for defining a low dose or a high dose of ionizing radiation?''. This is due to the fact that the criteria for these terms and for dose levels between these two extreme quantities have not yet been set, so that the terms relatively lower doses or higher doses are usually applied. Therefore, setting criteria for classification of radiation doses in the above mentioned areas seems a vital need. The author while realizing the existing problems to achieve this important task, has made efforts in this paper to justify this need and has proposed some criteria, in particular for the classification of natural radiation areas, based on a system of dose limitation. (author)

Comparison of high dose rate (HDR) and low dose rate (LDR) brachytherapy in the treatment of stage IIIB cervix cancer with radiation therapy alone. The preliminary results

International Nuclear Information System (INIS)

Trippe, Nivaldo; Novaes, P.E.; Ferrigno, R.; Pellizzon, A.C.; Salvajoli, J.V.; Fogaroli, R.C.; Maia, M.A.C.; Baraldi, H.E.

1996-01-01

Purpose/Objective: To compare the results between HDR and LDR brachytherapy in the treatment of stage IIIB cervix cancer with radiation therapy alone through a prospective and randomized trial. Materials and Methods: From September 1992 to December 1993, 65 patients with stage IIIB cervical cancer were randomized to one of the following treatment schedule according to the brachytherapy used to complement the dose of external beam radiotherapy (EBRT): 1 - High dose rate (HDR) - 36 patients - 4 weekly insertions of 6,0 Gy at point A 2 - Low dose rate (LDR) - 29 patients - 2 insertions two weeks apart of 17,5 Gy at point A The External Beam radiotherapy was performed through a Linac 4MV, in box arrangement for whole pelvis and in AP-PA fields for parametrial complementation of dose. The dose at the whole pelvis was 45 Gy in 25 fractions of 1,8 Gy and the parametrial dose was 16 Gy. The brachytherapy was realized with Fletcher colpostats and intrauterine tandem, in both arms. The HDR brachytherapy was realized through a Micro-Selectron device, working with Iridium-192 with initial activity of 10 Ci and started ten days after the beginning of EBRT. The total treatment time was shortened in two weeks for this group. The LDR brachytherapy started only after the end of EBRT. Results: With the minimum follow up of 24 months and medium of 31 months, the disease free survival was 50% among the 36 patients in HDR group and 47,8% among the 29 patients in LDR group. Local failures occurred in 50% and 52,8% respectively. Grade I and II complications were restricted to rectites and cistites and the incidence of them was 8,3% for HDR group and 13% for LDR group. Until the time of evaluation there were no grade III complications in any group. Conclusions: Although the number of patients is small and the time of follow up still short, these preliminary results suggest that the HDR brachytherapy has an equivalent efficiency in local control as the LDR in the treatment of stage IIIB

Radiation exposure for 'caregivers' during high-dose outpatient radioiodine therapy

International Nuclear Information System (INIS)

Marriott, C. J.; Webber, C. E.; Gulenchyn, K. Y.

2007-01-01

On 27 occasions, radiation doses were measured for a family member designated as the 'caregiver' for a patient receiving high-dose radioiodine outpatient therapy for differentiated thyroid carcinoma. For 25 of the administrations, patients received 3.7 GBq of 131 I. Radiation doses for the designated caregivers were monitored on an hourly basis for 1 week using electronic personal dosemeters. The average penetrating dose was 98±64 μSv. The maximum penetrating dose was 283 μSv. Measured dose rate profiles showed that, on average, one-third of the caregiver dose was received during the journey home from hospital. The mean dose rate profile showed rapid clearance of 131 I with three distinct phases. The corresponding clearance half-times were 131 I contaminating the home. (authors)

Concomitant Imaging Dose and Cancer Risk in Image Guided Thoracic Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yibao; Wu, Hao [Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University Cancer Hospital & Institute, Beijing (China); Chen, Zhe [Department of Therapeutic Radiology, Yale University, New Haven, Connecticut (United States); Knisely, Jonathan P.S. [Department of Radiation Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, New York (United States); Nath, Ravinder [Department of Therapeutic Radiology, Yale University, New Haven, Connecticut (United States); Feng, Zhongsu [Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University Cancer Hospital & Institute, Beijing (China); Bao, Shanglian [Beijing Key Laboratory of Medical Physics and Engineering, Peking University, Beijing (China); Deng, Jun, E-mail: jun.deng@yale.edu [Department of Therapeutic Radiology, Yale University, New Haven, Connecticut (United States)

2015-11-01

Purpose: Kilovoltage cone beam computed tomography (CT) (kVCBCT) imaging guidance improves the accuracy of radiation therapy but imposes an extra radiation dose to cancer patients. This study aimed to investigate concomitant imaging dose and associated cancer risk in image guided thoracic radiation therapy. Methods and Materials: The planning CT images and structure sets of 72 patients were converted to CT phantoms whose chest circumferences (C{sub chest}) were calculated retrospectively. A low-dose thorax protocol on a Varian kVCBCT scanner was simulated by a validated Monte Carlo code. Computed doses to organs and cardiac substructures (for 5 selected patients of various dimensions) were regressed as empirical functions of C{sub chest}, and associated cancer risk was calculated using the published models. The exposures to nonthoracic organs in children were also investigated. Results: The structural mean doses decreased monotonically with increasing C{sub chest}. For all 72 patients, the median doses to the heart, spinal cord, breasts, lungs, and involved chest were 1.68, 1.33, 1.64, 1.62, and 1.58 cGy/scan, respectively. Nonthoracic organs in children received 0.6 to 2.8 cGy/scan if they were directly irradiated. The mean doses to the descending aorta (1.43 ± 0.68 cGy), left atrium (1.55 ± 0.75 cGy), left ventricle (1.68 ± 0.81 cGy), and right ventricle (1.85 ± 0.84 cGy) were significantly different (P<.05) from the heart mean dose (1.73 ± 0.82 cGy). The blade shielding alleviated the exposure to nonthoracic organs in children by an order of magnitude. Conclusions: As functions of patient size, a series of models for personalized estimation of kVCBCT doses to thoracic organs and cardiac substructures have been proposed. Pediatric patients received much higher doses than did the adults, and some nonthoracic organs could be irradiated unexpectedly by the default scanning protocol. Increased cancer risks and disease adverse events in the

Biological effects of low-dose ionizing radiation exposure

International Nuclear Information System (INIS)

Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst

2009-01-01

The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

Comparison of hyperuricemia in type 2 diabetics on low dose aspirin and not on low dose aspirin

International Nuclear Information System (INIS)

Malik, M.I.

2013-01-01

Objective: To compare the frequency of hyperuricemia in type 2 diabetes patients who are taking low dose aspirin with those patients who are not taking low dose aspirin. Study design: Quasi experimental study. Place and duration of study: This study was carried out at Military Hospital Rawalpindi for a period of two years (June 2006-May 2008). Patients and Methods: Sixty diabetic patients were selected who were taking low dose aspirin comparing group A and sixty diabetic patients who were not taking aspirin were placed in group B. These patients were selected from the OPD through non probability convenience sampling. All these patients were being followed up in medical outpatient quite regularly on fort-nightly basis. Data had been collected through a carefully designed questionnaire. Results: In group A, 90% of the patients had uric acid less than 445 micro mol/l and 10% of the patients had uric acid more than 445micro mol/l. Whereas in group B 100% of the patients had uric acid less than 445umol/l, there was a statistically significant difference between the two groups (p< 0.05). Conclusion: Aspirin in low doses cause hyperuricemia and regular monitoring of uric acid is mandatory to prevent its adverse effects. (author)

Study of dose effect relationship at low doses for non quantitative reactions of skin intestinal mucosa and lung

International Nuclear Information System (INIS)

Dutreix, J.; Wambersie, A.

1977-01-01

Most of the biological reactions observed in animal experiments or in clinical studies are non quantitative and they only allow assessing an inequality between the effects produced by different irradiations. The method used in non quantitative studies is actually based on the relative contribution of irreparable events and reparable to the cell killing. It provides for the cell population involved in non quantitative biological effects some data which can be expressed in term of a cell survival curve. Such data can be useful in Radiation therapy particularly for maximizing the difference between biological effects by a proper choice of the fraction size. The initial part of the cell survival curve, within the range of doses actually used appears to be a straight exponential. This should allow the extrapolation to very low doses in the range of interest to Radiation Protection

Changes in tumor cell response due to prolonged dose delivery times in fractionated radiation therapy

International Nuclear Information System (INIS)

Paganetti, Harald

2005-01-01

Purpose: Dynamic radiation therapy, such as intensity-modulated radiation therapy, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The cellular damage after a full treatment may depend on the dose rate, because sublethal radiation damage can be repaired more efficiently during prolonged dose delivery. The goal of this study was to investigate the significance of this effect in fractionated radiation therapy. Methods and Materials: The lethal/potentially lethal model was used to calculate lesion induction rates for repairable and nonrepairable lesions. Dose rate effects were analyzed for 9 different cell lines (8 human tumor xenografts and a C3H10T1/2 cell line). The effects of single-fraction as well as fractionated irradiation for different dose rates were studied. Results: Significant differences can be seen for dose rates lower than about 0.1 Gy/min for all cell lines considered. For 60 Gy delivered in 30 fractions, the equivalent dose is reduced by between 1.3% and 12% comparing 2 Gy delivery over 30 min per fraction with 2 Gy delivery over 1 min per fraction. The effect is higher for higher doses per fraction. Furthermore, the results show that dose rate effects do not show a simple correlation with the α/β ratio for ratios between 3 Gy and 31 Gy. Conclusions: If the total dose delivery time for a treatment fraction in radiation therapy increases to about 20 min, a correction for dose rate effects may have to be considered in treatment planning. Adjustments in effective dose may be necessary when comparing intensity-modulated radiation therapy with conventional treatment plans

Successful treatment of chronic recurrent multifocal osteomyelitis using low-dose radiotherapy. A case report

Energy Technology Data Exchange (ETDEWEB)

Dietzel, Christian T.; Vordermark, Dirk [Klinikum der Martin-Luther-Universitaet Halle-Wittenberg, Universitaetslinik und Poliklinik fuer Strahlentherapie, Halle (Saale) (Germany); Schaefer, Christoph [Klinikum der Martin-Luther-Universitaet Halle-Wittenberg, Universitaetsklinik und Poliklinik fuer Innere Medizin II, Halle (Saale) (Germany)

2017-03-15

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, which lacks an infectious genesis and predominantly involves the metaphysis of long bones. Common treatments range from nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids at first onset of disease, to immunosuppressive drugs and bisphosphonates in cases of insufficient remission. The therapeutic use of low-dose radiotherapy for CRMO constitutes a novelty. A 67-year-old female patient presented with radiologically proven CRMO affecting the right tibia/talus and no response to immunosuppressive therapy. Two treatment series of radiation therapy were applied with an interval of 6 weeks. Each series contained six fractions (three fractions per week) with single doses of 0.5 Gy, thus the total applied dose was 6 Gy. Ten months later, pain and symptoms of osteomyelitis had completely vanished. Radiotherapy seems to be an efficient and feasible complementary treatment option for conventional treatment refractory CRMO in adulthood. The application of low doses per fraction is justified by the inflammatory pathomechanism of disease. (orig.) [German] Die chronisch rekurrierende multifokale Osteomyelitis (CRMO) ist eine seltene autoimmunologische Erkrankung und befaellt vorzugsweise die Metaphysen der langen Roehrenknochen. Die Therapie umfasst nichtsteroidale Antirheumatika (NSAIDs) und Kortikosteroide bei Erstbefall und reicht bis hin zu Immunsuppressiva und Bisphosphonaten bei insuffizientem Ansprechen. Die Anwendung einer niedrigdosierten Radiatio stellt ein therapeutisches Novum dar. Eine 67-jaehrige Patientin stellte sich mit einem radiologisch gesicherten Befall im Sinne einer CRMO im Bereich des rechten Talus und der Tibia vor. Eine initiale Behandlung mit Immunsuppressiva verblieb erfolglos. Wir fuehrten zwei Bestrahlungsserien im Intervall von 6 Wochen durch. Jede Serie bestand aus 6 Fraktionen (3 Fraktionen/Woche), mit einer Einzeldosis von jeweils 0,5 Gy. Die

The use of low dose methotrexate in children with chronic anterior and intermediate uveitis.

Science.gov (United States)

Malik, A R; Pavesio, C

2005-07-01

To assess the efficacy of low dose methotrexate (MTX) therapy for children with chronic anterior and intermediate uveitis. A retrospective case review of 10 children who received MTX for chronic uveitis at a tertiary referral centre was performed. The following data were recorded for each patient: age, sex, race, duration of uveitis, primary diagnosis, anatomical localisation of uveitis, corticosteroid therapy, dose range of MTX, duration of MTX therapy, and side effects of MTX therapy. Several clinical parameters were evaluated to study the effect of MTX. These included visual acuity, anterior chamber inflammation, and topical and oral corticosteroid requirement. After MTX VA of 6/6 or better was present in 100% right eyes and 80% left eyes (p = 0.055 and p = 0.016, respectively). Anterior chamber inflammation decreased in 60% of children after MTX (p = 0.0168). The requirement of topical steroid decreased from a mean of 5.6 times a day before MTX to 1.5 times a day after MTX (p = 0.005). The dose of oral steroid decreased from a mean of 18 mg per day to 2.85 mg per day (p = 0.012). The most common adverse effect was nausea (20%). No patient required discontinuation of MTX because of side effects. MTX is effective and safe for chronic anterior and intermediate uveitis in children. An increase awareness of its efficacy is required among paediatricians and ophthalmologists to prevent sight threatening complication of chronic uveitis and its treatment with long term use of steroids.

Dose calculation methods in photon beam therapy using energy deposition kernels

International Nuclear Information System (INIS)

Ahnesjoe, A.

1991-01-01

The problem of calculating accurate dose distributions in treatment planning of megavoltage photon radiation therapy has been studied. New dose calculation algorithms using energy deposition kernels have been developed. The kernels describe the transfer of energy by secondary particles from a primary photon interaction site to its surroundings. Monte Carlo simulations of particle transport have been used for derivation of kernels for primary photon energies form 0.1 MeV to 50 MeV. The trade off between accuracy and calculational speed has been addressed by the development of two algorithms; one point oriented with low computional overhead for interactive use and one for fast and accurate calculation of dose distributions in a 3-dimensional lattice. The latter algorithm models secondary particle transport in heterogeneous tissue by scaling energy deposition kernels with the electron density of the tissue. The accuracy of the methods has been tested using full Monte Carlo simulations for different geometries, and found to be superior to conventional algorithms based on scaling of broad beam dose distributions. Methods have also been developed for characterization of clinical photon beams in entities appropriate for kernel based calculation models. By approximating the spectrum as laterally invariant, an effective spectrum and dose distribution for contaminating charge particles are derived form depth dose distributions measured in water, using analytical constraints. The spectrum is used to calculate kernels by superposition of monoenergetic kernels. The lateral energy fluence distribution is determined by deconvolving measured lateral dose distributions by a corresponding pencil beam kernel. Dose distributions for contaminating photons are described using two different methods, one for estimation of the dose outside of the collimated beam, and the other for calibration of output factors derived from kernel based dose calculations. (au)

Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

DEFF Research Database (Denmark)

Appelt, A. L.; Ploen, J.; Vogelius, I. R.

2013-01-01

estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination...... of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect...... of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D-50,D-i, and the normalized dose-response gradient, gamma(50,i). Results: A highly...

Low dose radiation exposure and atherosclerosis in ApoE{sup -/-} mice

Energy Technology Data Exchange (ETDEWEB)

Mitchel, R.E.J. [Atomic Energy of Canada Limited, Chalk River, ON (Canada); Hasu, M. [Univ. of Ottawa, Department of Pathology and Lab. Medicine, and Cellular and Molecular Medicine, Ottawa, ON (Canada); Univ. of Ottawa Heart Inst., Vascular Biology Group, Ottawa, ON (Canada); Bugden, M.; Wyatt, H. [Atomic Energy of Canada Limited, Chalk River, ON (Canada); Little, M. [Imperial Coll., Faculty of Medicine, St. Marys Campus, London (United Kingdom); Hildebrandt, G. [Univ. Hospital, Dept. of Radiotherapy, Rostock (Germany); Priest, N.D. [Atomic Energy of Canada Limited, Chalk River, ON (Canada); Whitman, S.C. [Univ. of Ottawa, Department of Pathology and Lab. Medicine, and Cellular and Molecular Medicine, Ottawa, ON (Canada); Univ. of Ottawa Heart Inst., Vascular Biology Group, Ottawa, ON (Canada)

2010-07-01

The hypothesis that single low dose exposures (0.025-0.5 Gy) to low LET radiation, given at either high (240 mGy/min) or low (1 mGy/min) dose rate, would promote aortic atherosclerosis was tested in female C57BI/6 mice genetically predisposed to this disease (ApoE-/-). Mice were exposed either at early stage disease (2 months of age) and examined 3 or 6 months later, or at late stage disease (8 months of age) and examined 2 or 4 months later. Compared to unexposed controls, all doses given at low or high dose rate at early stage disease had significant inhibitory effects on lesion growth and, at 25 or 50 mGy, on lesion frequency. No dose given at low dose rate had any effect on total serum cholesterol, but this was elevated by every dose given at high dose rate. Exposures at low dose rate had no effect on the percentage of lesion lipids contained within macrophages, and, at either high or low dose rate, had no significant effect on lesion severity. Exposure at late stage disease, to any dose at high dose rate, had no significant effect on lesion frequency, but at low dose rate some doses produced a small transient increase in this frequency. Exposure to low doses at low, but not high dose rate, significantly, but transiently reduced average lesion size, and at either dose rate transiently reduced lesion severity. Exposure to any dose at low dose rate (but not high dose rate) resulted in large and persistent decreases in serum cholesterol. These data indicate that a single low dose exposure, depending on dose and dose rate, generally protects against various measures of atherosclerosis in genetically susceptible mice. This result contrasts with the known, generally detrimental effects of high doses on this disease in the same mice, suggesting that a linear extrapolation of risk from high doses is not appropriate. (author)

Update on electroconvulsive therapy dosing strategies : review article

African Journals Online (AJOL)

Electroconvulsive Therapy (ECT) remains a controversial treatment modality, with a wide range of clinical practice and application. Recently significant advances in the technique of application of ECT have been made. These new approaches incorporate a variety of advances in ECT dosing strategies and techniques, ...

Physiological and immunological changes following exposure to low versus high-dose ionizing irradiation; comparative analysis with dose rate and cumulative dose

International Nuclear Information System (INIS)

Heesun, Kim; Heewon, Jang; Soungyeon, Song; Shinhye, Oh; Cukcheul, Shin; Meeseon, Jeong; Chasoon, Kim; Kwnaghee, Yang; Seonyoung, Nam; Jiyoung, Kim; Youngwoo, Jin; Changyoung, Cha

2008-01-01

Full text: While high-dose of ionizing radiation is generally harmful and causes damage to living organisms some reports suggest low-dose of radiation may not be as damaging as previously thought. Despite increasing evidence regarding the protective effect of low-dose radiation, no studies have directly compared the exact dose-response pattern by high- and low-dose of radiation exposed at high-and low-dose rate. This study aims to explore the cellular and molecular changes in mice exposed to low- and high-dose of radiation exposed at low- and high-dose rate. When C57BL/6 mice (Female, 6 weeks) were exposed at high-dose rate, 0.8 Gy/min, no significant change on the level of WBC, RBC, or platelets was observed up to total dose of 0.5 Gy. However, 2 Gy of radiation caused dramatic reduction in the level of white blood cells (WBC) and platelets. This reduction was accompanied by increased DNA damage in hematopoietic environments. The reduction of WBC was mainly due to the reduction in the number of CD4+ T cells and CD19+ B cells. CD8+ T cells and NK cells appeared to be relatively resistant to high-dose of radiation. This change was also accompanied by the reduction of T- and B- progenitor cells in the bone marrow. In contrast, no significant changes of the number of CD4+ T, CD8+ T, NK, and B cells were observed in the spleen of mice exposed at low-dose-rate (0.7 m Gy/h or 3.95 mGy/h) for up to 2 Gy, suggesting that low-dose radiation does not alter cellular distribution in the spleen. Nevertheless, mice exposed to low-dose radiation exhibited elevation of VEGF, MCP-1, IL-4, Leptin, IL-3, and Tpo in the peripheral blood and slight increases in MIP-2, RANTES, and IL-2 in the spleen. This suggests that chronic γ-radiation can stimulate immune function without causing damage to the immune components of the body. Taken together, these data indicate hormesis of low-dose radiation, which could be attributed to the stimulation of immune function. Dose rate rather than total

Regulatory aspects of low doses control in Albania

International Nuclear Information System (INIS)

Dollani, K.; Kushe, R.

1997-01-01

In the present paper are described the status of regulatory aspects of low doses control as well as the existing procedures for their implementation in Albania. According to new Radiological Protection Act, approved by Parliament in 1995, the establishment of the infrastructures in radiation protection area is in course, accompanied by the installation and functioning of new equipment for low dose control. Based in many years experience it is concluded that personal doses of the workers added by practices in Albania are 1/10 of dose Emits. Some particular cases of overexposured workers were investigated. Last times the elements of the optimisation procedures (QA and QC) are outlined in the frame of improving regulatory aspects of low doses control. (author)

Low-dose hydrocortisone (HC) replacement therapy is associated with improved bone remodeling balance in hypopituitary subjects

LENUS (Irish Health Repository)

Behan, L A

2011-06-01

The effect of commonly used glucocorticoid replacement regimens on bone health in hypopituitary subjects is not well known. We aimed to assess the effect of 3 hydrocortisone (HC) replacement dose regimens on bone turnover in this group.10 hypopituitary men with severe ACTH deficiency were randomised in a crossover design to 3 HC dose regimens, Dose A (20mg mane, 10mg tarde), Dose B (10mg twice daily) and Dose C (10mg mane, 5mg tarde). Following 6 weeks of each regimen participants underwent fasting sampling of bone turnover markers.Data from matched controls were used to produce a Z score for subject bone formation and resorption markers and to calculate the bone remodeling balance (formation Z score-resorption Z score) and turnover index ((formation Z + resorption Z)\\/2). A positive bone remodeling balance with increased turnover is consistent with a favourable bone cycle. Data are expressed as median (range).The Pro Collagen Type 1 Peptide (PINP) bone formation Z-score was significantly increased in Dose C, (1.805 (-0.6-10.24)) compared to Dose A (0.035 (-1.0-8.1)) p<0.05 while there was no difference in the C-terminal crosslinking telopeptide (CTx) resorption Z score. The bone remodeling balance was significantly lower for dose A -0.02 (-1.05-4.12) compared to dose C 1.13 (0.13-6.4) (p<0.05). Although there was a trend to an increased bone turnover index with the lower dose regimen, this was not statistically significant.Low dose HC replacement (10mg mane\\/5 mg tarde) was associated with increased bone formation and improved bone remodeling balance which is associated with a more favourable bone cycle. This may have a long term beneficial effect on bone health.

Exposure to low doses of ionizing radiations

International Nuclear Information System (INIS)

Le Guen, B.

2008-01-01

The author discusses the knowledge about the effects of ionizing radiations on mankind. Some of them have been well documented (skin cancer and leukaemia for the pioneer scientists who worked on radiations, some other types of cancer for workers who handled luminescent paints, rock miners, nuclear explosion survivors, patients submitted to radiological treatments). He also evokes the issue of hereditary cancers, and discusses the issue of low dose irradiation where some surveys can now be performed on workers. He discusses the biological effects of these low doses. He outlines that many questions remain about these effects, notably the influence of dose level and of dose rate level on the biological reaction

Bioavailability of diclofenac potassium at low doses

Science.gov (United States)

Hinz, Burkhard; Chevts, Julia; Renner, Bertold; Wuttke, Henrike; Rau, Thomas; Schmidt, Andreas; Szelenyi, Istvan; Brune, Kay; Werner, Ulrike

2005-01-01

Aim Diclofenac-K has been recently launched at low oral doses in different countries for over-the-counter use. However, given the considerable first-pass metabolism of diclofenac, the degree of absorption of diclofenac-K at low doses remained to be determined. The aim of this study was to determine the bioavailability of low-dose diclofenac-K. Methods A randomized, three-way, cross-over study was performed in 10 subjects. Each received diclofenac-K, 22.5 mg via short-term i.v. infusion and orally at single doses of 12.5 mg and 25 mg. Results Mean (± SD) times to maximal plasma concentration (tmax) of diclofenac were 0.48 ± 0.28 h (12.5 mg) and 0.93 ± 0.96 h (25 mg). The absolute bioavailability of diclofenac-K after oral administration did not differ significantly in the 12.5-mg and 25-mg dose group (63.1 ± 12.6% vs. 65.1 ± 19.4%, respectively). The 90% confidence intervals for the AUC∞ and AUCt ratios for the two oral regimes were 82.6, 103.4% (point estimate 92.4%) and 86.2, 112.9% (point estimate 98.6%), respectively. These values were within the acceptance criteria for bioequivalence (80–125%). Conclusions Our data indicate that diclofenac-K is rapidly and well absorbed at low dose, and are consistent with a rapid onset of action of the drug. Abbreviations AUC, area under plasma concentraton-time curve; Cmax, peak plasma concentration; CI, confidence interval; COX, cyclooxygenase; D, dose; F, absolute bioavailability; tmax, time to reach Cmax. PMID:15606444

Carcinogenesis in mice after low doses and dose rates

International Nuclear Information System (INIS)

Ullrich, R.L.

1979-01-01

The results from the experimental systems reported here indicate that the dose-response curves for tumor induction in various tissues cannot be described by a single model. Furthermore, although the understanding of the mechanisms involved in different systems is incomplete, it is clear that very different mechanisms for induction are involved. For some tumors the mechanism of carcinogenesis may be mainly a result of direct effects on the target cell, perhaps involving one or more mutations. While induction may occur, in many instances, through such direct effects, the eventual expression of the tumor can be influenced by a variety of host factors including endocrine status, competence of the immune system, and kinetics of target and interacting cell populations. In other tumors, indirect effects may play a major role in the initiation or expression of tumors. Some of the hormone-modulated tumors would fall into this class. Despite the complexities of the experimental systems and the lack of understanding of the types of mechanisms involved, in nearly every example the tumorigenic effectiveness per rad of low-LET radiation tends to decrease with decreasing dose rate. For some tumor types the differences may be small or may appear only with very low dose rates, while for others the dose-rate effects may be large

Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy

Directory of Open Access Journals (Sweden)

F. A. Zeiler

2015-01-01

Full Text Available Background. Treatment of symptomatic delayed cerebral ischemia (DCI after subarachnoid hemorrhage (SAH is difficult. Recent studies suggest intravenous (IV high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm.

Review of time-dose effects in radiation therapy

International Nuclear Information System (INIS)

Peschel, R.E.; Fischer, J.J.

1980-01-01

A historical review of conventional fractionation offers little confidence that such treatment is optimal for all tumors. Thus manipulation of time-dose schedules may provide a relatively inexpensive yet potentially useful technique for improving therapeutic results in radiation therapy. Consideration of basic radiobiological principles and animal model data illustrates the complex and heterogeneous nature of normal tissue and tumor response to time-dose effects and supports the hypothesis that better time-dose prescriptions can be found in clinical practice. The number of possible time-dose prescriptions is very large, and a review of the clinical trials using nonconventional fractionation demonstrates that the sampled portion of the total three-dimensional space of time, fraction number, and dose has been very small. Only carefully designed clinical trials can establish the therapeutic advantage of a new treatment schedule, and methods for selecting the most promising schedules are discussed. The use of simple data reduction formulas for time-dose effects should be discarded since they ignore the very complexity and heterogeneity of tissues and tumors which may form the basis of improved clinical results

Some remarks on the significance of low doses

International Nuclear Information System (INIS)

Cigna, A.A.

1989-12-01

The criteria of the present system of individual dose limitation are considered as well as the evolution of the limiting values. The assumption of the linearity of the dose-effect relationship without any threshold is probably the best approach to adopt for recommendations in radiation protection and for accounting the doses acquired by exposure to ionizing radiation. On the other hand the present evaluation of the natural background could imply a different dose-effect relationship in the low doses region and perhaps the existence of a threshold. Therefore the extrapolations which are usually made after exposures of different groups of people to low doses cannot be considered as scientifically sound. (author)

Mutation induction in cultured human cells after low-dose and low-dose-rate γ-ray irradiation. Detection by LOH analysis

International Nuclear Information System (INIS)

Umebayashi, Yukihiro; Iwaki, Masaya; Yatagai, Fumio; Honma, Masamitsu; Suzuki, Masao; Suzuki, Hiromi; Shimazu, Toru; Ishioka, Noriaki

2007-01-01

To study the genetic effects of low-doses and low-dose-rate ionizing radiation (IR), human lymphoblastoid TK6 cells were exposed to 30 mGy of γ-rays at a dose-rate of 1.2 mGy/hr. The frequency of early mutations (EMs) in the thymidine kinase (TK) gene locus was determined to be 1.7 x 10 -6 , or 1.9-fold higher than the level seen in unirradiated controls. These mutations were analyzed with a loss of heterozygosity (LOH) detection system, a methodology which has been shown to be sensitive to the effects of radiation. Among the 15 EMs observed after IR exposure, 8 were small interstitial-deletion events restricted to the TK gene locus. However, this specific type of event was not found in unirradiated controls. Although these results were observed under the limited conditions, they strongly suggest that the LOH detection system can be used for estimating the genetic effects of a low-dose IR exposure delivered at a low-dose-rate. (author)

Prevention of murine cerebral malaria by low-dose cyclosporin A.

Science.gov (United States)

Grau, G E; Gretener, D; Lambert, P H

1987-08-01

The effects of cyclosporin A (CsA) were investigated in an experimental model of cerebral malaria. In this model, Plasmodium berghei ANKA-infected CBA/Ca mice develop a clinically and histologically characterized neurological syndrome which is considered to be the result of immunopathological reactions mediated by L3T4+ T cells. It was shown that CsA displayed a strong protective effect on neurological complications when given at a dose 1 mg/kg/day for 5 consecutive days (Days 4-8), which had no effect on the parasite. Paradoxically, this protection against neurological complications was not seen when parasiticidal doses were used during this limited 5-day period. A similar protective effect was observed with two CsA derivatives, C5-34 and H7-94. The mechanisms by which CsA and the two derivatives could prevent murine cerebral malaria are unknown but can be related to exquisite effects on some lymphocyte functions. In view of these results, it might be conceivable to investigate the benefits of using low doses of CsA in man, in conjunction with the classical antiparasite therapy, for the management of cerebral malaria.

Validity of the linear no-threshold theory of radiation carcinogenesis at low doses

International Nuclear Information System (INIS)

Cohen, B.L.

1999-01-01

A great deal is known about the cancer risk of high radiation doses from studies of Japanese A-bomb survivors, patients exposed for medical therapy, occupational exposures, etc. But the vast majority of important applications deal with much lower doses, usually accumulated at much lower dose rates, referred to as 'low-level radiation' (LLR). Conventionally, the cancer risk from LLR has been estimated by the use of linear no-threshold theory (LNT). For example, it is assumed that the cancer risk from 0 01 Sr (100 mrem) of dose is 0 01 times the risk from 1 Sv (100 rem). In recent years, the former risk estimates have often been reduced by a 'dose and dose rate reduction factor', which is taken to be a factor of 2. But otherwise, the LNT is frequently used for doses as low as one hundred-thousandth of those for which there is direct evidence of cancer induction by radiation. It is the origin of the commonly used expression 'no level of radiation is safe' and the consequent public fear of LLR. The importance of this use of the LNT can not be exaggerated and is used in many applications in the nuclear industry. The LNT paradigm has also been carried over to chemical carcinogens, leading to severe restrictions on use of cleaning fluids, organic chemicals, pesticides, etc. If the LNT were abandoned for radiation, it would probably also be abandoned for chemical carcinogens. In view of these facts, it is important to consider the validity of the LNT. That is the purpose of this paper. (author)

Dose-Related Effect of Extracorporeal Shock Wave Therapy for Plantar Fasciitis

Science.gov (United States)

Lee, Su-Jin; Kang, Jung-Ho; Kim, Ja-Young; Kim, Jin-Hong; Jung, Kwang-Ik

2013-01-01

Objective To examine the dose-related effect of extracorporeal shock wave therapy (ESWT) for plantar fasciitis. Methods Sixty patients with plantar fasciitis despite conservative treatment were enrolled. The patients were divided into a low-energy group (group L: n=30, 1,000 shocks/session, energy flux density [EFD] per shock 0.08 mJ/mm2) and a medium-energy group (group M: n=30, 1,000 shocks/session, EFD 0.16 mJ/mm2). The main outcome measures were visual analogue scale (VAS), Roles and Maudsley (RM) score, and thickness of plantar fascia (PF). To compare the effects between each group, follow-up was carried out 1 week after 3 and 6 sessions, and 1 and 3 months after ESWT. Results Significant VAS and RM score improvement, and PF thickness reduction were observed in both groups (p0.05). Conclusion Therapeutic effect might disclose a dose-related relationship; therefore, EFD and the times of the session are considerable factors when treating with ESWT. PMID:23869336

Electron arc therapy: Influence of heterogeneities on dose to blood-forming organs

International Nuclear Information System (INIS)

Leavitt, D.D.; Gibbs, F.A.; Moeller, J.H.

1986-01-01

Electron arc therapy has been used successfully to treat extended chest wall surfaces after mastectomy. Treatment is frequently given simultaneously with chemotherapy. Although the primary electron arc treatment volume consists only of the chest wall and mediastinum, dose is accumulated at the isocenter of rotation due to the photon contamination of the arcing electron beam. Additionally, higher energy electron fields which are occasionally used over segments of the arc may contribute to the dose at isocenter if the electron range has been extended due to passage through a low-density heterogeneity such as lung. In some patient setups, the isocenter may intersect blood-forming organs, such as the vertebral bodies. Thermoluminescent dosimetry has been used to measure the dose at isocenter for the following setups: polystyrene phantom, polystyrene phantom covered by 1-cm-thick lead cast, polystyrene phantom with cork insert to simulate lung, and phantom plus cork insert plus lead cast. For the 9-MeV treatment mode, dose at isocenter per 90 0 of arc (as a percentage of maximum tumor dose) is as follows: phantom, 6.5%; phantom plus lead, 5%; phantom plus cork, 8%; and phantom plus cork plus lead, 6%. These values must be scaled by the size of the arc to estimate dose at isocenter in actual treatments. Computer calculation showed good agreement with these measured values, indicating that the computerized treatment plans can be used as a predictor of electron arc dose to blood-forming organs

Therapy with low-dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG-MDS study group.

Science.gov (United States)

Cseh, Annamaria M; Niemeyer, Charlotte M; Yoshimi, Ayami; Catala, Albert; Frühwald, Michael C; Hasle, Henrik; van den Heuvel-Eibrink, Mary M; Lauten, Melchior; De Moerloose, Barbara; Smith, Owen P; Bernig, Toralf; Gruhn, Bernd; Kulozik, Andreas E; Metzler, Markus; Olcay, Lale; Suttorp, Meinolf; Furlan, Ingrid; Strahm, Brigitte; Flotho, Christian

2016-03-01

Low-dose azacitidine is efficient and safe in the therapy of malignant myeloid disorders in adults but data in children are lacking. We present a retrospective analysis of 24 children and young adults with myelodysplastic syndrome (MDS) who received azacitidine at the time of first diagnosis or relapse after allotransplant (2 children were treated with azacitidine both initially and for relapse). Diagnoses were refractory cytopenia of childhood (N = 4), advanced primary MDS (N = 9) and secondary MDS (N = 11). The median duration of treatment was four cycles. Azacitidine was well tolerated, but cytopenias led to dose reduction in five cases. Treatment was discontinued in one child because of impaired renal function. Sixteen MDS patients were treated with azacitidine at first diagnosis. One complete clinical remission was observed and one child showed complete marrow remission; six children experienced stable disease with haematological improvement. Ten children received azacitidine for relapsed MDS after transplant: of these, seven experienced stable disease for 2-30 cycles (median 3), including one patient with haematological improvement for seven cycles. In summary, azacitidine is effective in some children with MDS and appears to be a non-toxic option in palliative situations to prolong survival. © 2016 John Wiley & Sons Ltd.

Thyrotoxicosis and radioiodine therapy: Does the dose matter?

Directory of Open Access Journals (Sweden)

Andrew Collier

2012-01-01

Full Text Available There are 3 treatment options for thyrotoxicosis: Antithyroid drugs, Surgery and radioiodine. The choice of treatment varies geographically. Radioiodine therapy is preferred in the United States. The aim of radioiodine is to destroy sufficient thyroid tissue to cure the hyperthyroidism. There is a lack of consensus towards what dose of radioiodine should be used. Several methods are used to determine the dose. In our practice we administer 400 MBq to patients with Graves and in patients with large multinodular goiter, we would administer 800 MBq.

Deep learning for low-dose CT

Science.gov (United States)

Chen, Hu; Zhang, Yi; Zhou, Jiliu; Wang, Ge

2017-09-01

Given the potential risk of X-ray radiation to the patient, low-dose CT has attracted a considerable interest in the medical imaging field. Currently, the main stream low-dose CT methods include vendor-specific sinogram domain filtration and iterative reconstruction algorithms, but they need to access raw data whose formats are not transparent to most users. Due to the difficulty of modeling the statistical characteristics in the image domain, the existing methods for directly processing reconstructed images cannot eliminate image noise very well while keeping structural details. Inspired by the idea of deep learning, here we combine the autoencoder, deconvolution network, and shortcut connections into the residual encoder-decoder convolutional neural network (RED-CNN) for low-dose CT imaging. After patch-based training, the proposed RED-CNN achieves a competitive performance relative to the-state-of-art methods. Especially, our method has been favorably evaluated in terms of noise suppression and structural preservation.

Learning from agriculture: understanding low-dose antimicrobials as drivers of resistome expansion

Directory of Open Access Journals (Sweden)

Yaqi eYou

2014-06-01

Full Text Available Antimicrobial resistance is a growing public health challenge worldwide, with agricultural use of antimicrobials being one major contributor to the emergence and dissemination of antimicrobial resistance. Globally, most antimicrobials are used in industrial food animal production, a major context for microbiomes encountering low-doses or subtherapeutic-levels of antimicrobial agents from all mechanistic classes. This modern practice exerts broad eco-evolutionary effects on the gut microbiome of food animals, which is subsequently transferred to animal waste. This waste contains complex constituents that are challenging to treat, including antimicrobial resistance determinants and low-dose antimicrobials. Unconfined storage or land deposition of a large volume of animal waste causes its wide contact with the environment and drives the expansion of the environmental resistome through mobilome facilitated horizontal genet transfer. The expanded environmental resistome, which encompasses both natural constituents and anthropogenic inputs, can persist under multiple stressors from agriculture and may re-enter humans, thus posing a public health risk to humans. For these reasons, this review focuses on agricultural antimicrobial use as a laboratory for understanding low-dose antimicrobials as drivers of resistome expansion, briefly summarizes current knowledge on this topic, highlights the importance of research specifically on environmental microbial ecosystems considering antimicrobial resistance as environmental pollution, and calls attention to the needs for longitudinal studies at the systems level.

Learning from agriculture: understanding low-dose antimicrobials as drivers of resistome expansion.

Science.gov (United States)

You, Yaqi; Silbergeld, Ellen K

2014-01-01

Antimicrobial resistance is a growing public health challenge worldwide, with agricultural use of antimicrobials being one major contributor to the emergence and dissemination of antimicrobial resistance (AMR). Globally, most antimicrobials are used in industrial food animal production, a major context for microbiomes encountering low-doses or subtherapeutic-levels of antimicrobial agents from all mechanistic classes. This modern practice exerts broad eco-evolutionary effects on the gut microbiome of food animals, which is subsequently transferred to animal waste. This waste contains complex constituents that are challenging to treat, including AMR determinants and low-dose antimicrobials. Unconfined storage or land deposition of a large volume of animal waste causes its wide contact with the environment and drives the expansion of the environmental resistome through mobilome facilitated horizontal genet transfer. The expanded environmental resistome, which encompasses both natural constituents and anthropogenic inputs, can persist under multiple stressors from agriculture and may re-enter humans, thus posing a public health risk to humans. For these reasons, this review focuses on agricultural antimicrobial use as a laboratory for understanding low-dose antimicrobials as drivers of resistome expansion, briefly summarizes current knowledge on this topic, highlights the importance of research specifically on environmental microbial ecosystems considering AMR as environmental pollution, and calls attention to the needs for longitudinal studies at the systems level.

Assessment of low absorbed dose with a MOSFET detector

International Nuclear Information System (INIS)

Butson, M.J.; Cancer Services, Wollongong, NSW; Cheung, T.; Yu, P.K.N.

2004-01-01

Full text: The ability of a MOSFET dosimetry system to measure low therapeutic doses has been evaluated for accuracy for high energy x-ray radiotherapy applications. The MOSFET system in high sensitivity mode produces a dose measurement reproducibility of within 10%, 4% and 2.5% for 2 cGy, 5 cGy and 10cGy dose assessment respectively. This is compared to 7%, 4% and 2% for an Attix parallel plate ionisation chamber and 20%, 7% and 3.5% for a Wellhofer IC4 small volume ionisation chamber. Results for our dose standard thimble ionisation chamber and low noise farmer dosemeter were 2%, 0.5% and 0.25% respectively for these measurements. The quoted accuracy of the MOSFET dosimetry system is partially due to the slight non linear dose response (reduced response) with age of the detector but mainly due to the intrinsic variations in measured voltage differential per applied dose. Results have shown that the MOSFET dosimetry system provides an adequate measure of dose at low dose levels and is comparable in accuracy to the Attix parallel plate ionisation chambers for relative dose assessment at levels of 2cGy to 10cGy. The use of the MOSFET dosimeter at low doses can extend the life expectancy of the device and may provide useful information for areas where low dose assessment is required. Copyright (2004) Australasian College of Physical Scientists and Engineers in Medicine

Hearing loss due to concurrent daily low-dose cisplatin chemoradiation for locally advanced head and neck cancer

International Nuclear Information System (INIS)

Zuur, Charlotte L.; Simis, Yvonne J.W.; Verkaik, Roxanna S.; Schornagel, Jan H.; Balm, Alfons J.M.; Dreschler, Wouter A.; Rasch, Coen R.N.

2008-01-01

Background and purpose: Cisplatin-based chemo-irradiation (CRT) is increasingly used for head and neck squamous cell carcinoma (HNSCC). We aimed to assess hearing deterioration due to low-dose cisplatin chemoradiation and to compare the observed hearing loss with hearing loss in our previously described high-dose cisplatin CRT cohort. Materials and methods: A prospective analysis of hearing thresholds at low and (ultra)-high frequencies obtained before and after treatment in 60 patients. Patients received low-dose cisplatin (6 mg/m 2 , daily infusions, 20-25 days) with concomitant accelerated radiotherapy (70 Gy). Results: Audiometry up to 16 kHz was performed before therapy and 31 days (median) post-treatment. The total incidence of ototoxicity in CTCAEv3.0 was 31% in audiograms up to 8 kHz, and 5% of ears tested qualified for HAs due to treatment. The mean hearing loss at speech frequencies was 2.6 dB (SD 5.7) and 2.3 dB (SD 9.2) at PTA 1-2-4 kHz air-conduction and bone-conduction, respectively. The mean hearing loss at ultra-high frequencies (PTA AC 8-10-12.5 kHz) was 9.0 dB (SD 8.1). Low-dose cisplatin CRT caused less acute hearing loss (CTCAE 31%), compared to high-dose cisplatin CRT (CTCAE 78%). Conclusions: Low-dose cisplatin chemo-irradiation for HNSCC is a relatively safe treatment protocol with respect to ototoxicity

Analytical probabilistic modeling of RBE-weighted dose for ion therapy

Science.gov (United States)

Wieser, H. P.; Hennig, P.; Wahl, N.; Bangert, M.

2017-12-01

Particle therapy is especially prone to uncertainties. This issue is usually addressed with uncertainty quantification and minimization techniques based on scenario sampling. For proton therapy, however, it was recently shown that it is also possible to use closed-form computations based on analytical probabilistic modeling (APM) for this purpose. APM yields unique features compared to sampling-based approaches, motivating further research in this context. This paper demonstrates the application of APM for intensity-modulated carbon ion therapy to quantify the influence of setup and range uncertainties on the RBE-weighted dose. In particular, we derive analytical forms for the nonlinear computations of the expectation value and variance of the RBE-weighted dose by propagating linearly correlated Gaussian input uncertainties through a pencil beam dose calculation algorithm. Both exact and approximation formulas are presented for the expectation value and variance of the RBE-weighted dose and are subsequently studied in-depth for a one-dimensional carbon ion spread-out Bragg peak. With V and B being the number of voxels and pencil beams, respectively, the proposed approximations induce only a marginal loss of accuracy while lowering the computational complexity from order O(V × B^2) to O(V × B) for the expectation value and from O(V × B^4) to O(V × B^2) for the variance of the RBE-weighted dose. Moreover, we evaluated the approximated calculation of the expectation value and standard deviation of the RBE-weighted dose in combination with a probabilistic effect-based optimization on three patient cases considering carbon ions as radiation modality against sampled references. The resulting global γ-pass rates (2 mm,2%) are > 99.15% for the expectation value and > 94.95% for the standard deviation of the RBE-weighted dose, respectively. We applied the derived analytical model to carbon ion treatment planning, although the concept is in general applicable to other

Low dose epidemiology

International Nuclear Information System (INIS)

Tirmarche, M.; Hubert, P.

1992-01-01

Actually, epidemiological studies have to establish if the assessment of cancer risk can be verified at low chronic radiation doses. The population surveillance must be very long, the side effects and cancers of such radiation appearing much later. In France, this epidemiological study on nuclear workers have been decided recently. Before describing the experiment and french projects in epidemiology of nuclear workers, the authors present the main english and american studies

Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

International Nuclear Information System (INIS)

Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E.

2015-01-01

Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm

Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

Energy Technology Data Exchange (ETDEWEB)

Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E., E-mail: claudia.ruebe@uks.eu

2015-08-01

Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

SU-F-J-194: Development of Dose-Based Image Guided Proton Therapy Workflow

Energy Technology Data Exchange (ETDEWEB)

Pham, R; Sun, B; Zhao, T; Li, H; Yang, D; Grantham, K; Goddu, S; Santanam, L; Bradley, J; Mutic, S; Kandlakunta, P; Zhang, T [Washington University School of Medicine, Saint Louis, MO (United States)

2016-06-15

Purpose: To implement image-guided proton therapy (IGPT) based on daily proton dose distribution. Methods: Unlike x-ray therapy, simple alignment based on anatomy cannot ensure proper dose coverage in proton therapy. Anatomy changes along the beam path may lead to underdosing the target, or overdosing the organ-at-risk (OAR). With an in-room mobile computed tomography (CT) system, we are developing a dose-based IGPT software tool that allows patient positioning and treatment adaption based on daily dose distributions. During an IGPT treatment, daily CT images are acquired in treatment position. After initial positioning based on rigid image registration, proton dose distribution is calculated on daily CT images. The target and OARs are automatically delineated via deformable image registration. Dose distributions are evaluated to decide if repositioning or plan adaptation is necessary in order to achieve proper coverage of the target and sparing of OARs. Besides online dose-based image guidance, the software tool can also map daily treatment doses to the treatment planning CT images for offline adaptive treatment. Results: An in-room helical CT system is commissioned for IGPT purposes. It produces accurate CT numbers that allow proton dose calculation. GPU-based deformable image registration algorithms are developed and evaluated for automatic ROI-delineation and dose mapping. The online and offline IGPT functionalities are evaluated with daily CT images of the proton patients. Conclusion: The online and offline IGPT software tool may improve the safety and quality of proton treatment by allowing dose-based IGPT and adaptive proton treatments. Research is partially supported by Mevion Medical Systems.

A unique manual method for emergency offsite dose calculations

International Nuclear Information System (INIS)

Wildner, T.E.; Carson, B.H.; Shank, K.E.

1987-01-01

This paper describes a manual method developed for performance of emergency offsite dose calculations for PP and L's Susquehanna Steam Electric Station. The method is based on a three-part carbonless form. The front page guides the user through selection of the appropriate accident case and inclusion of meteorological and effluent data data. By circling the applicable accident descriptors, the user circles the dose factors on pages 2 and 3 which are then simply multiplied to yield the whole body and thyroid dose rates at the plant boundary, two, five, and ten miles. The process used to generate the worksheet is discussed, including the method used to incorporate the observed terrain effects on airflow patterns caused by the Susquehanna River Valley topography

Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

International Nuclear Information System (INIS)

Appelt, Ane L.; Pløen, John; Vogelius, Ivan R.; Bentzen, Søren M.; Jakobsen, Anders

2013-01-01

Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D 50,i , and the normalized dose-response gradient, γ 50,i . Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D 50,TRG1 = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), γ 50,TRG1 = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D 50,TRG1 and 2 = 72.1 Gy (CI 65.3-94.0 Gy), γ 50,TRG1 and 2 = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.

Risks to health from radiation at low dose rates

International Nuclear Information System (INIS)

Gentner, N.E.; Osborne, R.V.

1997-01-01

Our focus is on whether, using a balance-of-evidence approach, it is possible to say that at a low enough dose, or at a sufficiently low dose rate, radiation risk reduces to zero in a population. We conclude that insufficient evidence exists at present to support such a conclusion. In part this reflects statistical limitations at low doses, and in part (although mechanisms unquestionably exist to protect us against much of the damage induced by ionizing radiation) the biological heterogeneity of human populations, which means these mechanisms do not act in all members of the population at all times. If it is going to be possible to demonstrate that low doses are less dangerous than we presently assume, the evidence, paradoxically, will likely come from studies of higher dose and dose rate scenarios than are encountered occupationally. (author)

Super-low dose endotoxin pre-conditioning exacerbates sepsis mortality.

Science.gov (United States)

Chen, Keqiang; Geng, Shuo; Yuan, Ruoxi; Diao, Na; Upchurch, Zachary; Li, Liwu

2015-04-01

Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditionings with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in opposite to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a novel mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

Super-low Dose Endotoxin Pre-conditioning Exacerbates Sepsis Mortality

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Keqiang Chen

2015-04-01

Full Text Available Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditioning with super-low or low dose endotoxin lipopolysaccharide (LPS cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP. This is in contrast to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

Colchicine triggered severe rhabdomyolysis after long-term low-dose simvastatin therapy: a case report.

Science.gov (United States)

Frydrychowicz, Clara; Pasieka, Bastian; Pierer, Matthias; Mueller, Wolf; Petros, Sirak; Weidhase, Lorenz

2017-01-04

Rhabdomyolysis is a widely recognized yet rare complication in statin use. Rhabdomyolysis might be triggered by the prescription of high doses of statins or by statin accumulation due to interactions with concomitant medication. Muscle cell destruction as evidenced by myoglobin elevation can induce potentially life-threatening acute renal failure. We report a case of a 70-year-old obese white man with sudden onset of severe rhabdomyolysis with consecutive renal failure. His medication included low-dose simvastatin, which he had taken for 6 years up until the event. The statin was withdrawn immediately. After 3 days of veno-venous hemofiltration his renal function was completely restored. Clinicians in both primary and special care might be unaware that side effects of statins do occur even after a long uneventful statin medication; they should be advised not to exclude that possibility upfront, even if a patient has tolerated the medication for years.

Immediate Dose-Response Effect of High-Energy Versus Low-Energy Extracorporeal Shock Wave Therapy on Cutaneous Microcirculation.

Science.gov (United States)

Kraemer, Robert; Sorg, Heiko; Forstmeier, Vinzent; Knobloch, Karsten; Liodaki, Eirini; Stang, Felix Hagen; Mailaender, Peter; Kisch, Tobias

2016-12-01

Elucidation of the precise mechanisms and therapeutic options of extracorporeal shock wave therapy (ESWT) is only at the beginning. Although immediate real-time effects of ESWT on cutaneous hemodynamics have recently been described, the dose response to different ESWT energies in cutaneous microcirculation has never been examined. Thirty-nine Sprague-Dawley rats were randomly assigned to three groups that received either focused high-energy shock waves (group A: total of 1000 impulses, 10 J) to the lower leg of the hind limb, focused low-energy shock waves (group B: total of 300 impulses, 1 J) or placebo shock wave treatment (group C: 0 impulses, 0 J) using a multimodality shock wave delivery system (Duolith SD-1 T-Top, Storz Medical, Tägerwilen, Switzerland). Immediate microcirculatory effects were assessed with the O2C (oxygen to see) system (LEA Medizintechnik, Giessen, Germany) before and for 20 min after application of ESWT. Cutaneous tissue oxygen saturation increased significantly higher after high-energy ESWT than after low-energy and placebo ESWT (A: 29.4% vs. B: 17.3% vs. C: 3.3%; p = 0.003). Capillary blood velocity was significantly higher after high-energy ESWT and lower after low-energy ESWT versus placebo ESWT (group A: 17.8% vs. group B: -22.1% vs. group C: -5.0%, p = 0.045). Post-capillary venous filling pressure was significantly enhanced in the high-energy ESWT group in contrast to the low-energy ESWT and placebo groups (group A: 25% vs. group B: 2% vs. group C: -4%, p = 0.001). Both high-energy and low-energy ESWT affect cutaneous hemodynamics in a standard rat model. High-energy ESWT significantly increases parameters of cutaneous microcirculation immediately after application, resulting in higher tissue oxygen saturation, venous filling pressure and blood velocity, which suggests higher tissue perfusion with enhanced oxygen saturation, in contrast to low-energy as well as placebo ESWT. Low-energy ESWT also increased tissue oxygen

Ageing effects of polymers at very low dose-rates

International Nuclear Information System (INIS)

Chenion, J.; Armand, X.; Berthet, J.; Carlin, F.; Gaussens, G.; Le Meur, M.

1987-10-01

The equipment irradiation dose-rate into the containment is variable from 10 -6 to 10 -4 gray per second for the most exposed materials. During qualification, safety equipments are submitted in France to dose-rates around 0.28 gray per second. This study purpose is to now if a so large irradiation dose-rate increase is reasonable. Three elastomeric materials used in electrical cables, o'rings seals and connectors, are exposed to a very large dose-rates scale between 2.1.10 -4 and 1.4 gray per second, to 49 KGy dose. This work was carried out during 3.5 years. Oxygen consumption measurement of the air in contact with polymer materials, as mechanical properties measurement show that: - at very low dose-rate, oxygen consumption is maximum at the same time (1.4 year) for the three elastomeric samples. Also, mechanical properties simultaneously change with oxygen consumption. At very low dose-rate, for the low irradiation doses, oxygen consumption is at least 10 times more important that it is showed when irradiation is carried out with usual material qualification dose-rate. At very low dose-rate, oxygen consumption decreases when absorbed irradiation dose by samples increases. The polymer samples irradiation dose is not still sufficient (49 KGy) to certainly determine, for the three chosen polymer materials, the reasonable irradiation acceleration boundary during nuclear qualification tests [fr

Absorbed Doses and Risk Estimates of (211)At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients

DEFF Research Database (Denmark)

Cederkrantz, Elin; Andersson, Håkan; Bernhardt, Peter

2015-01-01

dose associated with i.p. administration of (211)At-MX35 F(ab')2. METHODS AND MATERIALS: Patients in clinical remission after salvage chemotherapy for peritoneal recurrence of ovarian cancer underwent i.p. infusion of (211)At-MX35 F(ab')2. Potassium perchlorate was given to block unwanted accumulation...... 100 MBq/L, organ equivalent doses were less than 10% of the estimated tolerance dose. CONCLUSION: Intraperitoneal (211)At-MX35 F(ab')2 treatment is potentially a well-tolerated therapy for locally confined microscopic ovarian cancer. Absorbed doses to normal organs are low, but because the effective...

Addition of low-dose ketamine to midazolam and low-dose bupivacaine improves hemodynamics and postoperative analgesia during spinal anesthesia for cesarean section

Directory of Open Access Journals (Sweden)

Ahmed Sobhy Basuni

2016-01-01

Conclusion: Intrathecal low-dose ketamine combined with midazolam and low-dose bupivacaine stabilizes hemodynamics and prolongs postoperative analgesia without significant side-effects in parturients undergoing CS.

Acoustic neuromas: single dose vs fractionated therapy

Energy Technology Data Exchange (ETDEWEB)

Fuss, M; Debus, J; Lohr, F; Engenhart-Cabillic, R; Wannenmacher, M

1997-07-01

patients (18%) in the RS group, none of them requiring therapy, but none in the FT group. Hearing impairment improved in 1 case (RS) and 4 cases (FT). Complete hearing loss was diagnosed in 1 case in the FT group but in 3 cases in the RS group (all these patients were treated with 16 Gy or more). One temporary facial nerve weakness was found after FT. Among the RS group treated with {>=}16 Gy, 4 permanent facial nerve lesions were observed with complete facial nerve paresis in 2 patients. Improvement of vertigo or tinnitus was found in 1 patient after FT and in 3 patients treated with RS. If radiosurgical doses were <15 Gy, no severe side effects were observed. Among this group, 6 patients (54%) showed a significant reduction of preexisting neurological dysfunction. Conclusion: Radiosurgical treatment of small acoustic neuromas with doses <15 Gy prescribed to a volume <10 ccm results in excellent tumor control with no relevant toxicity. For fractionated therapy, results are comparable, even if the tumor volume exceeded 10 ccm. Single dose treatment with doses >15 Gy may cause higher toxicity. Fractionated conformal radiotherapy offers effective tumor control and low morbidity especially after contralateral neurosurgical resection of an acoustic neuroma with consecutive hearing loss and/or facial paresis.