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Sample records for emerging low-dose therapy

  1. Low dose iodine-131 therapy in solitary toxic thyroid nodules

    International Nuclear Information System (INIS)

    Prakash, Rajeev

    1999-01-01

    Forty patients with solitary hyperfunctioning thyroid nodules were treated with relatively low dose radioiodine therapy, 131 I doses were calculated taking into account thyroid mass and radioiodine kinetics to deliver 100 μCi/g of estimated nodule weight corrected for uptake. Patients remaining persistently hyperthyroid at four months after the initial therapy were retreated with a similarly calculated dose. Cure of the hyperthyroid state was achieved in all patients, total administered dose in individual cases ranging from 3-17 mCi. 28 of the 40 patients required a single therapy dose. 36 patients were euthyroid after a 4.5 year mean follow-up period. Four cases developed post therapy hypothyroidism requiring replacement therapy. Nodules regressed completely in nine cases following 131 I treatment, with partial regression in size in 19 patients. Control of hyperthyroid state in cases of solitary toxic thyroid nodules can be satisfactorily achieved using relatively low dose radioiodine therapy with low incidence of post therapy hypothyroidism. (author)

  2. Low-dose add-back therapy during postoperative GnRH agonist treatment

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Tsai

    2016-02-01

    Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

  3. 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

  4. Intracranial germinomas: a case for low dose radiation therapy alone

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    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

  5. Rational hemochromatosis therapy with erythrocytapheresis under low doses of erythropoietin

    OpenAIRE

    Brückl, Dorothea

    2016-01-01

    Summary: Hereditary hemochromatosis with an incidence of 1:200 – 1:400 is the most common hereditary disease. It is characterized by increased iron absorption and deposition in various organs, leading to organ damage and even death. To date, phlebotomy (bloodletting) is the standard therapy of iron-overload in hemochromatosis. However, this treatment is long lasting, frequently intolerable and/or remains limited due the development of significant anemia. All these difficulties might be ov...

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

    Science.gov (United States)

    Kroeger, Kai; Elsayad, Khaled; Moustakis, Christos; Haverkamp, Uwe; Eich, Hans Theodor

    2017-12-01

    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 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.

  7. Clinical investigation of 131I therapy combined with low-dose lithium carbonate for Graves disease

    International Nuclear Information System (INIS)

    Xu Haiqing; Wu Bian

    2006-01-01

    Objective: To investigate the clinical curative effects of 131 I therapy combined with low-dose lithium carbonate for Graves disease. Methods: Patients with Graves disease took lithium carbonate (250 mg, once per day) orally for 5 weeks. Then they were treated with 131 I (doses=3.15 MBq(80 uCi)/g, based on 60%-70% of the thyroid size). We kept track from 6 to 24 months (averaging 14 months) and classified the results into three: cured, improved or no effect. Results: After a single cycle of 131 I therapy combined with low-dose lithium carbonate, 106 patients with Graves disease were cured, 28 were improved and 8 saw no effects, respectively 74.6%, 19.7% and 5.6% among the 142 patients. We then treated 23 of them with another 131 I therapy (without lithium carbonate). 10 of such were cured (43.5%), 8 were improved (34.8%) and the other 5 saw no effects. Among all patients, hypothyroidism was observed from 25(17.6%), 6 months after the first 131 I therapy. Conclusions: Notable curative results were observed from 131 I therapy combined with low-dose lithium carbonate for Graves disease. Moreover, the dosage of 131 I was therefore decreased, which also lowered the toxicity response. (authors)

  8. Low-Dose Ketamine Infusion for Emergency Department Patients with Severe Pain.

    Science.gov (United States)

    Ahern, Terence L; Herring, Andrew A; Miller, Steve; Frazee, Bradley W

    2015-07-01

    Use of low-dose ketamine infusions in the emergency department (ED) has not previously been described, despite routine use in perioperative and other settings. Our hypothesis was that a low-dose ketamine bolus followed by continuous infusion would 1) provide clinically significant and sustained pain relief; 2) be well tolerated; and 3) be feasible in the ED. We prospectively administered 15 mg intravenous ketamine followed immediately by continuous ketamine infusion at 20 mg/h for 1 hour. Optional morphine (4 mg) was offered at 20, 40, and 60 minutes. Pain intensity, vitals signs, level of sedation, and adverse reactions were assessed for 120 minutes. A total of 38 patients were included with a median initial numerical rating scale (NRS) pain score of 9. At 10 minutes, the median reduction in pain score was 4, with 7 patients reporting a score of 0. At 60 and 120 minutes, 25 and 26 patients, respectively, reported clinically significant pain reduction (decrease NRS score > 3). Heart rate, blood pressure, respiratory rate, and oxygen saturation remained stable. Mild or moderate side effects including dizziness, fatigue, and headache were common. Patient satisfaction was high; 85% reported they would have this medication again for similar pain. A low-dose ketamine infusion protocol provided significant pain relief with mostly mild side effects and no severe adverse events. Wiley Periodicals, Inc.

  9. 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)

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

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    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

  11. 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.

  12. Low-dose radiation potentiates the therapeutic efficacy of folate receptor-targeted hapten therapy.

    Science.gov (United States)

    Sega, Emanuela I; Lu, Yingjuan; Ringor, Michael; Leamon, Christopher P; Low, Philip S

    2008-06-01

    Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm(3) before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Mice bearing 300-mm(3) subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon alpha) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm(3). More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

  13. Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

    International Nuclear Information System (INIS)

    Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael; Leamon, Christopher P.; Low, Philip S.

    2008-01-01

    Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm 3 before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm 3 subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon α) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm 3 . More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice

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

    Directory of Open Access Journals (Sweden)

    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

  15. 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.

  16. 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.

  17. 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

  18. Revisiting Low-Dose Total Skin Electron Beam Therapy in Mycosis Fungoides

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Cameron, E-mail: cameronh@stanford.edu [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Young, James; Navi, Daniel [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Riaz, Nadeem [Department of Radiation Oncology, Stanford Cancer Center, Stanford, California (United States); Lingala, Bharathi; Kim, Youn [Department of Dermatology, Stanford Cancer Center, Stanford, California (United States); Hoppe, Richard [Department of Radiation Oncology, Stanford Cancer Center, Stanford, California (United States)

    2011-11-15

    Purpose: Total skin electron beam therapy (TSEBT) is a highly effective treatment for mycosis fungoides (MF). The standard course consists of 30 to 36 Gy delivered over an 8- to 10-week period. This regimen is time intensive and associated with significant treatment-related toxicities including erythema, desquamation, anhydrosis, alopecia, and xerosis. The aim of this study was to identify a lower dose alternative while retaining a favorable efficacy profile. Methods and Materials: One hundred two MF patients were identified who had been treated with an initial course of low-dose TSEBT (5-<30 Gy) between 1958 and 1995. Patients had a T stage classification of T2 (generalized patch/plaque, n = 51), T3 (tumor, n = 29), and T4 (erythrodermic, n = 22). Those with extracutaneous disease were excluded. Results: Overall response (OR) rates (>50% improvement) were 90% among patients with T2 to T4 disease receiving 5 to <10 Gy (n = 19). In comparison, OR rates between the 10 to <20 Gy and 20 to <30 Gy subgroups were 98% and 97%, respectively. There was no significant difference in median progression free survival (PFS) in T2 and T3 patients when stratified by dose group, and PFS in each was comparable to that of the standard dose. Conclusions: OR rates associated with low-dose TSEBT in the ranges of 10 to <20 Gy and 20 to <30 Gy are comparable to that of the standard dose ({>=} 30 Gy). Efficacy measures including OS, PFS, and RFS are also favorable. Given that the efficacy profile is similar between 10 and <20 Gy and 20 and <30 Gy, the utility of TSEBT within the lower dose range of 10 to <20 Gy merits further investigation, especially in the context of combined modality treatment.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. 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.

  1. Pharmacokinetics of and short-term virologic response to low-dose 400-milligram once-daily raltegravir maintenance therapy.

    NARCIS (Netherlands)

    Ananworanich, J.; Gorowara, M.; Avihingsanon, A.; Kerr, S.J.; Heesch, N. van; Khongpetch, C.; Uanithirat, A.; Hill, A.; Ruxrungtham, K.; Burger, D.M.

    2012-01-01

    Because studies showed similar viral suppression with lower raltegravir doses and because Asians usually have high antiretroviral concentrations, we explored low-dose raltegravir therapy in Thais. Nineteen adults on raltegravir at 400 mg twice daily (BID) with HIV RNA loads of <50 copies/ml were

  2. 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

  3. 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)

  4. 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)

  5. 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

    increased from 18.4 (8.2) to 68.6 (21.2) and in dual vitamin D therapy from 18.4 (5.0) to 67.6 (17.7) nmol/L (both pimportantly: from 21.7 (interquartile range 17.3; 35.4) to 18.1 pmol/L (15.3; 24.7) in monotherapy (p=0.05) and from 38.6 (31.8; 53.3) to 33.9 pmol/L (26.1; 47.5) in dual vitamin D therapy (p=0.01). Serum calcium, phosphate, ALP and CTX did not change. We have not observed any episode of hypercalcemia in any subject during the whole period of follow-up. At baseline, slightly lower 25-D levels were observed in diabetic than in non-diabetic patients. This difference disappeared after substitution. Vitamin D status and its changes were not related to the patient's age. Low 25-D levels were very common in haemodialysis patients. They were safely and effectively corrected with supervised low-dose cholecalciferol supplementation. In patients with higher baseline PTH levels, dual vitamin D therapy (cholecalciferol plus paricalcitol) was safely and effectively used.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. 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

  9. A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Specht, Lena; Skovgaard, Gunhild L

    2008-01-01

    causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. CONCLUSION: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration......PURPOSE: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. METHODS AND MATERIALS: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years......]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4...

  10. 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)

  11. 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)

  12. 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)

  13. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients

    Directory of Open Access Journals (Sweden)

    Ellebaek Eva

    2012-08-01

    Full Text Available Abstract Background Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL, in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. Methods This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625 including patients with metastatic melanoma, PS ≤1, age Results Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3–4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months, 2 patients had stable disease (4 and 5 months and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. Conclusion Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.

  14. The outcome of clinical parameters in adults with severe Type I Gaucher disease using very low dose enzyme replacement therapy.

    Science.gov (United States)

    Wilson, Callum; Spearing, Ruth; Teague, Lochie; Robertson, Patsy; Blacklock, Hilary

    2007-01-01

    Enzyme replacement therapy is now well established as the treatment of choice in Type I Gaucher disease. Historically higher dosage regimens have been used in preference to lower doses despite the little clinical evidence in the way of large controlled clinical trials to support this. Moreover, the extraordinary cost of therapy means that not all eligible patients are able to be treated at the higher dose. Twelve type I adult patients with relatively severe disease were commenced on a very low dose of 7.5U of alglucerase/imiglucerase per kg every two weeks (initially given thrice weekly and later weekly). Follow-up 5 year data reveal a good visceral and haematological response with outcomes consistent with recently published treatment guidelines. Satisfactory clinical and radiological skeletal improvement was also demonstrated in most patients. Three patients had an inadequate overall skeletal response to therapy. Biomarkers also steadily improved although perhaps not quite at the same rate as that seen in higher doses. Very low dose enzyme replacement therapy may be appropriate for adult type I Gaucher patients with mild-moderate skeletal disease.

  15. 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.

  16. 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)

  17. Cardiac autonomic tone during trandolapril-irbesartan low-dose combined therapy in hypertension: a pilot project.

    Science.gov (United States)

    Franchi, F; Lazzeri, C; Foschi, M; Tosti-Guerra, C; Barletta, G

    2002-08-01

    Pharmacological and clinical studies on the effects of angiotensin-converting enzyme (ACE) inhibitors support the idea of a central role played Angiotensin II which is able to cause cardiovascular and renal diseases also independently of its blood pressure elevating effects. The present investigation was aimed at evaluating the effect(s) of three different pharmacological regimens on both blood pressure and sympathetic drive in uncomplicated essential hypertension, by means of blood pressure laboratory measurements and ambulatory monitoring, 24-h heart rate variability and plasma noradrenaline levels. Thus, an ACE-inhibitor monotherapy (trandolapril, 2 mg/day), an AT(1)-receptor antagonist monotherapy (irbesartan, 300 mg/day), their low-dose combination (0.5 mg/day plus 150 mg/day, respectively) and placebo were given, in a randomised, single-blind, crossover fashion for a period of 3 weeks each to 12 mild essential hypertensives. Power spectral analysis (short recordings) and noradrenaline measurements were also performed in the supine position and after a postural challenge (60 degrees head-up tilting test: HUT). The low-dose combination therapy induced the greatest reduction in LF component and in LF/HF ratio, both in the resting and tilted positions, as well as in blood pressure. However, the physiological autonomic response to HUT was maintained. Noradrenaline plasma levels were lower after the combined therapy than after each drug alone. Our data demonstrate that in mild and uncomplicated essential hypertension, the chronic low-dose combination therapy with an ACE-inhibitor and an AT(1)-antagonist is more effective than the recommended full-dose monotherapy with either drug in influencing the autonomic regulation of the heart, suggesting a relative reduction in sympathetic drive both at cardiac and systemic levels.

  18. Low-dose ion-based transmission radiography and tomography for optimization of carbon ion-beam therapy

    Energy Technology Data Exchange (ETDEWEB)

    Magallanes Hernandez, Lorena

    2017-02-21

    In the last few decades, ion-beam radiotherapy has emerged as a highly effective tumor treatment modality. Its success relies on the capability to precisely confine the prescribed dose within the target volume, due to the inverted depth-dose profile and the finite range featured by charged particles. However, to fully exploit the physical and biological advantages of ion-beams, it is necessary to prioritize on innovative imaging techniques to monitor the ion-range inside the patient. Main range uncertainties result from X-ray-based calibration of the ion relative Water Equivalent Path Length (rWEPL) during the planning phase, and patient anatomical or positioning variation during the treatment. In this thesis, low-dose carbon-ion transmissionimaging performed with a Residual Range Detector (RRD) is proposed as imaging strategy for actively scanned beam delivery facilities. It enables the verification of the beam range and the patient positioning with ion-radiographies (iRAD), and ion computed tomographies (iCT) can directly provide the ion stopping-power of the traversed tissue for treatment planning purposes. First experimental investigations aiming to minimize the imaging dose to the object are presented. The performance of the integration-mode multi-channel array of 61 parallel-plate ionization chambers (PPICs), interleaved with 3 mm thickness PMMA slabs, was thoroughly investigated for low-fluence irradiation. This characterization has been pursued in terms of beam-monitoring performance at the Heidelberg Ion-beam Therapy Center (HIT, Heidelberg, Germany), RRD signal-to-noise ratio (SNR), RRD charge-collection efficiency and drift voltage applied to the PPICs. Pixel-wise metrics for signal quality evaluation based on specific channel-charge features have been developed to support the visual assessment of the acquired images. Phantoms of different complexity and tissue-equivalent composition were imaged with high (5000 primaries per raster-scanning point (RP

  19. Low-dose ion-based transmission radiography and tomography for optimization of carbon ion-beam therapy

    International Nuclear Information System (INIS)

    Magallanes Hernandez, Lorena

    2017-01-01

    In the last few decades, ion-beam radiotherapy has emerged as a highly effective tumor treatment modality. Its success relies on the capability to precisely confine the prescribed dose within the target volume, due to the inverted depth-dose profile and the finite range featured by charged particles. However, to fully exploit the physical and biological advantages of ion-beams, it is necessary to prioritize on innovative imaging techniques to monitor the ion-range inside the patient. Main range uncertainties result from X-ray-based calibration of the ion relative Water Equivalent Path Length (rWEPL) during the planning phase, and patient anatomical or positioning variation during the treatment. In this thesis, low-dose carbon-ion transmissionimaging performed with a Residual Range Detector (RRD) is proposed as imaging strategy for actively scanned beam delivery facilities. It enables the verification of the beam range and the patient positioning with ion-radiographies (iRAD), and ion computed tomographies (iCT) can directly provide the ion stopping-power of the traversed tissue for treatment planning purposes. First experimental investigations aiming to minimize the imaging dose to the object are presented. The performance of the integration-mode multi-channel array of 61 parallel-plate ionization chambers (PPICs), interleaved with 3 mm thickness PMMA slabs, was thoroughly investigated for low-fluence irradiation. This characterization has been pursued in terms of beam-monitoring performance at the Heidelberg Ion-beam Therapy Center (HIT, Heidelberg, Germany), RRD signal-to-noise ratio (SNR), RRD charge-collection efficiency and drift voltage applied to the PPICs. Pixel-wise metrics for signal quality evaluation based on specific channel-charge features have been developed to support the visual assessment of the acquired images. Phantoms of different complexity and tissue-equivalent composition were imaged with high (5000 primaries per raster-scanning point (RP

  20. 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.

  1. Long-term follow-up study of compensated low-dose 131I therapy for Graves' disease

    International Nuclear Information System (INIS)

    Sridama, V.; McCormick, M.; Kaplan, E.L.; Fauchet, R.; DeGroot, L.J.

    1984-01-01

    We treated 187 patients who had Graves' disease with low-dose radioactive iodide ( 131 I), using a protocol that included a compensation for thyroid size. The incidence of early hypothyroidism (12 per cent) was acceptably low in the first year after 131 I treatment, but we found a cumulative high incidence (up to 76 per cent) at the end of the 11th year. In contrast, the incidence of permanent hypothyroidism was relatively stable in 166 surgically treated patients, increasing from 19 to 27 per cent at the end of 11 years. Among 122 medically treated patients, only 40 per cent entered remission, and hypothyroidism developed in 2 per cent during the same period of follow-up. The long-term incidence of hypothyroidism in our patients treated with low-dose 131 I therapy was much higher than that found in earlier studies using a comparable dose. Our study suggests that it will be difficult to modify therapy with 131 I alone to produce both early control of thyrotoxicosis and a low incidence of hypothyroidism

  2. 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

  3. 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.

  4. 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)

  5. 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.

  6. 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.

  7. 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

  8. 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...

  9. Therapy of CNS leukemia with intraventricular chemotherapy and low-dose neuraxis radiotherapy

    International Nuclear Information System (INIS)

    Steinherz, P.; Jereb, B.; Galicich, J.

    1985-01-01

    Successful treatment of CNS leukemic relapse has been frustrated by frequent local recurrence and eventual marrow relapse. The authors describe the treatment of meningeal leukemia in 39 children with intrathecal remission induction followed by the placement of an Ommaya reservoir to facilitate the administration and distribution of chemotherapeutic agents into the CSF. Six hundred or 900 rad of craniospinal radiation and maintenance intraventricular and intrathecal chemotherapy was then administered. Systemic reinduction therapy was added in the later cases. Sixteen children (41%) experienced no further events, with 17+ months to 13+ years (median, 25 months) follow-up . Eleven patients (28%) had CNS recurrence, nine (23%) bone marrow (BM) relapse, and two (5%) testicular relapse as the next adverse event. The course of patients with first isolated CNS relapse differed from that of the others. Eleven (69%) of 16 patients treated for first isolated CNS relapse are alive and 9 are event free, while only 35% of patients whose CNS relapse occurred simultaneously or after recurrent disease at other sites are alive (P = .04). Seven of 23 in the later group are event free. The difference is due to the increased incidence of BM relapse in the later group (30% v 6%; P = .04). For patients with first isolated CNS relapse, the life-table median CNS remission duration is 42 months. The projected CNS relapse-free survival and event-free survival 8 to 10 years after CNS relapse are 40% and 32%, respectively. Headache, nausea, and emesis of short duration were frequent during therapy. In three patients, the reservoir had to be removed for infection. No patient suffered neurologic deficit related to the reservoir. The therapy described can reduce the CNS relapse rate with manageable toxicity

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Long-term results of exclusive low-dose rate curie-therapy for a high-grade vaginal intraepithelial neoplasia

    International Nuclear Information System (INIS)

    Blanchard, P.; Monnier, L.; Dumas, I.; Azoury, F.; Mazeron, R.; Haie-Meder, C.

    2010-01-01

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

  5. 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).

  6. Comparison of fixed low dose versus high dose radioactive iodine for the treatment of hyperthyroidism: retrospective multifactorial analysis impacting the outcome of therapy

    International Nuclear Information System (INIS)

    Suresh Kumar, A.C.; Malhotra, G.; Basu, S.; Asopa, R.V.

    2010-01-01

    Full text: Radioactive iodine ( 131 I) as a fixed dose protocol is widely used for treatment of hyperthyroidism. However, there is no consensus on the best optimum dose for an individual patient. The objectives of this study were to observe the outcome of 131 I therapy in patients of primary hyperthyroidism in relation to fixed low dose versus high dose regimen, impact of antithyroid drugs and influence of thyroid gland size on therapy outcome. Materials and Methods: Study design: Retrospective analysis. Study group included 287 diagnosed patients of primary hyperthyroidism who had undergone 131 I therapy for the first time (68 M, 219 F; Mean age ± S.D.: 43.84 ± 12.53). All patients with low RAIU, thyrocardiac disease were excluded. Details of antithyroid (ATD) drug treatment were recorded. Analysis was done from 2002 till patients became euthyroid/hypothyroid or until January 2010. Each patient's response was evaluated initially at 6 weeks and thereafter every three months. Appropriate statistical tests were applied to compare treatment response between the groups. A P value<0.05 was considered significant. Results: Of 287 patients, 209 patients had been administered low dose (Mean ± S.D.: 4.68 ± 0.62 mCi) while 78 patients had received high dose (Mean ± S.D.: 9.15 ± 1.05 mCi) of radioiodine. 57.9% (121/ 209) patients in the low dose group responded as compared to 75.6% (59/78) in high dose group after a follow up of more than 36 months. Similarly, among patients with and without antithyroid drug treatment, grade II and above goiters the response rates were significantly higher for high dose group as compared to low dose group. Conclusion: We suggest that high dose radioiodine treatment with 8 to 10 mCi is effective in treating hyperthyroidism in patients with a better success rate than the low dose treatment with 3 to 5 mCi. This is also likely to be helpful in patients who have not received antithyroid drugs. It appears that clinically relevant

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. 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.

  10. Emergency assessment of patients with acute abdominal pain using low-dose CT with iterative reconstruction: a comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Poletti, Pierre-Alexandre; Becker, Minerva; Becker, Christoph D.; Zaidi, Habib; Platon, Alexandra [University Hospital of Geneva, Department of Radiology, Geneva (Switzerland); Halfon Poletti, Alice; Rutschmann, Olivier T. [University Hospital of Geneva, Department of Community, Primary Care and Emergency Medicine, Geneva (Switzerland); Perneger, Thomas [University Hospital of Geneva, Division of Clinical Epidemiology, Geneva (Switzerland)

    2017-08-15

    To determine if radiation dose delivered by contrast-enhanced CT (CECT) for acute abdominal pain can be reduced to the dose administered in abdominal radiography (<2.5 mSv) using low-dose CT (LDCT) with iterative reconstruction algorithms. One hundred and fifty-one consecutive patients requiring CECT for acute abdominal pain were included, and their body mass index (BMI) was calculated. CECT was immediately followed by LDCT. LDCT series was processed using 1) 40% iterative reconstruction algorithm blended with filtered back projection (LDCT-IR-FBP) and 2) model-based iterative reconstruction algorithm (LDCT-MBIR). LDCT-IR-FBP and LDCT-MBIR images were reviewed independently by two board-certified radiologists (Raters 1 and 2). Abdominal pathology was revealed on CECT in 120 (79%) patients. In those with BMI <30, accuracies for correct diagnosis by Rater 1 with LDCT-IR-FBP and LDCT-MBIR, when compared to CECT, were 95.4% (104/109) and 99% (108/109), respectively, and 92.7% (101/109) and 100% (109/109) for Rater 2. In patients with BMI ≥30, accuracies with LDCT-IR-FBP and LDCT-MBIR were 88.1% (37/42) and 90.5% (38/42) for Rater 1 and 78.6% (33/42) and 92.9% (39/42) for Rater 2. The radiation dose delivered by CT to non-obese patients with acute abdominal pain can be safely reduced to levels close to standard radiography using LDCT-MBIR. (orig.)

  11. Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) as an alternative therapy for ovarian cancer in an octogenarian patient.

    Science.gov (United States)

    Giger-Pabst, Urs; Solass, Wiebke; Buerkle, Bernd; Reymond, Marc-André; Tempfer, Clemens B

    2015-04-01

    Octogenarians with ovarian cancer limited to the abdomen may not be willing or able to undergo systemic chemotherapy. Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin is a form of intra-abdominal chemotherapy which can be applied repeatedly and potentially prevents from the systemic side-effects of chemotherapy. We present the case of an 84-year-old woman with laparoscopically and histologically confirmed ovarian cancer who refused to undergo systemic chemotherapy. She was treated with eight courses q 28-104 days of low-dose PIPAC with cisplatin at 7.5 mg/m(2) and doxorubicin at 1.5 mg/m(2) at 12 mmHg and 37 °C for 30 min. Objective tumor response was noted, defined as tumor regression on histology, and stable disease noted by peritoneal carcinomatosis index on repeated video-laparoscopy and abdominal computed tomographic scan. The treatment was well-tolerated with no Common Terminology Criteria for Adverse Events (CTCAE) CTCAE >2. With a follow-up of 15 months, the patient is alive and clinically stable. The quality of life measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 demonstrated improvement over 5-6 months (global physical score, global health score, global quality of live) without cumulative increase of gastrointestinal toxicity. Low-dose PIPAC is a new form of intraperitoneal chemotherapy which may be applied repeatedly in octogenarian patients. PIPAC may be an alternative and well-tolerated treatment for selected octogenarian patients with ovarian cancer limited to the abdomen who cannot be treated with systemic chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. 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.

  13. 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)

  14. 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.

  15. 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.)

  16. 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

  17. 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.

  18. 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.

  19. [A case of advanced gastric cancer with carcinomatosa peritonitis effectively treated by 5-FU and low-dose CDDP therapy].

    Science.gov (United States)

    Saito, E; Kunii, Y; Wada, G; Tsuchiya, S; Yamasaki, T; Sakakibara, N

    1997-07-01

    A 66-year-old woman was admitted to our clinic for appetite loss and abdominal distension in August 1995. Endoscopic study revealed an advanced gastric cancer in the upper body of her stomach. Abdominal CT study revealed massive ascites and para-aortic lymph nodal involvement. Cytological study of the ascites revealed class V. She was diagnosed to be in the terminal stage of gastric cancer with carcinomatosa peritonitis. Combination chemotherapy with 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) was given by continuous intravenous injection of 5-FU 500 mg/day, and intermittent intravenous injection of CDDP 30 mg/week was performed for reduction of the ascites and her complaint. Endoscopic study 6 weeks after starting chemotherapy could not find crater of the gastric cancer but only a shallow ulcerative lesion. The biopsy specimen of that lesion was group III. No ascites and over 50% reduction of the para-aortic lymph node were found by the abdominal CT study. This state persisted over 4 weeks. No myelo-suppression, renal dysfunction or any severe side effect were observed during chemotherapy. Her performance status improved from 3 to 1.

  20. 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.

  1. 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.

  2. Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

    DEFF Research Database (Denmark)

    Warming, Lise; Ravn, Pernille; Spielman, Danièle

    2004-01-01

    bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy...

  3. 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.

  4. Long term control of a maxillary sinus mucoepidermoid carcinoma with low dose radiation therapy: a case report

    International Nuclear Information System (INIS)

    Vulpe, Horia; Giuliani, Meredith; Goldstein, David; Perez-Ordonez, Bayardo; Dawson, Laura A; Hope, Andrew

    2013-01-01

    Mucoepidermoid carcinoma of the maxillary sinus is a rare malignancy of the head and neck. The location of this tumour near vital structures and its large size at presentation makes surgical resection with negative margins challenging. In incurable cases, relief from symptoms such as epistaxis may be achieved with radiation therapy. We present a case of mucoepidermoid carcinoma of the maxillary sinus that was effectively palliated with a short course of radiation therapy, achieving complete cessation of bleeding, decrease in tumour size, and long term control. We surveyed the literature on mucoepidermoid carcinomas and propose that some tumours may be particularly radiosensitive, benefiting from even short courses of radiation therapy

  5. 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

  6. Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

    Science.gov (United States)

    Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-08-01

    Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (ppain to chronic low back pain.

  7. 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

  8. 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.

  9. Low-Dose Gene Therapy for Murine PKU Using Episomal Naked DNA Vectors Expressing PAH from Its Endogenous Liver Promoter

    Directory of Open Access Journals (Sweden)

    Hiu Man Grisch-Chan

    2017-06-01

    Full Text Available Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH by delivery of naked DNA/minicircle (MC-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU. Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3.6-kb native Pah promoter/enhancer sequence. This vector, delivered via hydrodynamic injection, yielded therapeutic liver PAH activity and sustained correction of blood phenylalanine comparable to viral or synthetic liver promoters. Therapeutic efficacy was seen with vector copy numbers of 95% loss of vector genomes and PAH activity in liver, demonstrating that MC vectors had not integrated into the liver genome. In conclusion, MC vectors, which do not have a defined size-limitation, offer a favorable safety profile for hepatic gene therapy due to their non-integration in combination with native promoters.

  10. 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.

  11. 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.)

  12. Effects of a soy-based dietary supplement compared with low-dose hormone therapy on the urogenital system: a randomized, double-blind, controlled clinical trial.

    Science.gov (United States)

    Carmignani, Lucio O; Pedro, Adriana Orcesi; Montemor, Eliana B; Arias, Victor A; Costa-Paiva, Lucia H; Pinto-Neto, Aarão M

    2015-07-01

    This study aims to compare the effects of a soy-based dietary supplement, low-dose hormone therapy (HT), and placebo on the urogenital system in postmenopausal women. In this double-blind, randomized, placebo-controlled trial, 60 healthy postmenopausal women aged 40 to 60 years (mean time since menopause, 4.1 y) were randomized into three groups: a soy dietary supplement group (90 mg of isoflavone), a low-dose HT group (1 mg of estradiol plus 0.5 mg of norethisterone), and a placebo group. Urinary, vaginal, and sexual complaints were evaluated using the urogenital subscale of the Menopause Rating Scale. Vaginal maturation value was calculated. Transvaginal sonography was performed to evaluate endometrial thickness. Genital bleeding pattern was assessed. Statistical analysis was performed using χ(2) test, Fisher's exact test, paired Student's t test, Kruskal-Wallis test, Kruskal-Wallis nonparametric test, and analysis of variance. For intergroup comparisons, Kruskal-Wallis nonparametric test (followed by Mann-Whitney U test) was used. Vaginal dryness improved significantly in the soy and HT groups (P = 0.04). Urinary and sexual symptoms did not change with treatment in the three groups. After 16 weeks of treatment, there was a significant increase in maturation value only in the HT group (P < 0.01). Vaginal pH decreased only in this group (P < 0.01). There were no statistically significant differences in endometrial thickness between the three groups, and the adverse effects evaluated were similar. This study shows that a soy-based dietary supplement used for 16 weeks fails to exert estrogenic action on the urogenital tract but improves vaginal dryness.

  13. 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)

  14. 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)

  15. 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)

  16. 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...

  17. Comparison of PSA value at last follow-up of patients who underwent low-dose rate brachytherapy and intensity-modulated radiation therapy for prostate cancer.

    Science.gov (United States)

    Tanaka, Nobumichi; Asakawa, Isao; Nakai, Yasushi; Miyake, Makito; Anai, Satoshi; Fujii, Tomomi; Hasegawa, Masatoshi; Konishi, Noboru; Fujimoto, Kiyohide

    2017-08-25

    To compare the PSA value at the last follow-up of patients who underwent prostate low-dose rate brachytherapy (LDR-BT) with that of patients who underwent intensity-modulated radiation therapy (IMRT). A total of 610 prostate cancer patients (cT1c-3bN0M0) were enrolled, and 445 of them underwent LDR-BT, while 165 received IMRT (74-76 Gy). The median follow-up period of these two groups was 75 months (LDR-BT) and 78 months (IMRT), respectively. We also evaluated the biochemical recurrence (BCR)-free rate using two definitions (Phoenix definition and PSA ≥ 0.2 ng/mL). The percentage of patients who achieved PSA LDR-BT group and 49.7% in the IMRT group (p LDR-BT group and 32.1% in the IMRT group (p LDR-BT groups was 89.5 and 95.0% (p LDR-BT groups, respectively (p LDR-BT was significantly lower than that of IMRT, and this result was particularly marked in patients with a normal testosterone level at the last follow-up.

  18. 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.

  19. Time Course and Accumulated Risk of Severe Urinary Adverse Events After High- Versus Low-Dose-Rate Prostate Brachytherapy With or Without External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tward, Jonathan D., E-mail: Jonathan.Tward@hci.utah.edu [Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (United States); Jarosek, Stephanie; Chu, Haitao [University of Minnesota, Minneapolis, Minnesota (United States); Thorpe, Cameron; Shrieve, Dennis C. [Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah (United States); Elliott, Sean [University of Minnesota, Minneapolis, Minnesota (United States)

    2016-08-01

    Purpose: Severe urinary adverse events (UAEs) include surgical treatment of urethral stricture, urinary incontinence, and radiation cystitis. We compared the incidence of grade 3 UAEs, according to the Common Terminology Criteria for Adverse Events, after low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy, as well as after LDR plus external beam radiation therapy (EBRT) and HDR plus EBRT. Methods and Materials: Men aged >65 years with nonmetastatic prostate cancer were identified from the Surveillance, Epidemiology, and End Results–Medicare database who were treated with LDR (n=12,801), HDR (n=685), LDR plus EBRT (n=8518), or HDR plus EBRT (n=2392). The populations were balanced by propensity weighting, and the Kaplan-Meier incidence of severe UAEs was compared. Propensity-weighted Cox proportional hazards models were used to compare the adjusted hazard of UAEs. These UAEs were compared with those in a cohort of men not treated for prostate cancer. Results: Median follow-up was 4.3 years. At 8 years, the propensity-weighted cumulative UAE incidence was highest after HDR plus EBRT (26.6% [95% confidence interval, 23.8%-29.7%]) and lowest after LDR (15.7% [95% confidence interval, 14.8%-16.6%]). The absolute excess risk over nontreated controls at 8 years was 1.9%, 3.8%, 8.4%, and 12.9% for LDR, HDR, LDR plus EBRT, and HDR plus EBRT, respectively. These represent numbers needed to harm of 53, 26, 12, and 8 persons, respectively. The additional risk of development of a UAE related to treatment for LDR, LDR plus EBRT, and HDR plus EBRT was greatest within the 2 years after treatment and then continued to decline over time. Beyond 4 years, the risk of development of a new severe UAE matched the baseline risk of the control population for all treatments. Conclusions: Toxicity differences were observed between LDR and HDR, but the differences did not meet statistical significance. However, combination radiation therapy (either HDR plus EBRT or LDR plus

  20. Time Course and Accumulated Risk of Severe Urinary Adverse Events After High- Versus Low-Dose-Rate Prostate Brachytherapy With or Without External Beam Radiation Therapy

    International Nuclear Information System (INIS)

    Tward, Jonathan D.; Jarosek, Stephanie; Chu, Haitao; Thorpe, Cameron; Shrieve, Dennis C.; Elliott, Sean

    2016-01-01

    Purpose: Severe urinary adverse events (UAEs) include surgical treatment of urethral stricture, urinary incontinence, and radiation cystitis. We compared the incidence of grade 3 UAEs, according to the Common Terminology Criteria for Adverse Events, after low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy, as well as after LDR plus external beam radiation therapy (EBRT) and HDR plus EBRT. Methods and Materials: Men aged >65 years with nonmetastatic prostate cancer were identified from the Surveillance, Epidemiology, and End Results–Medicare database who were treated with LDR (n=12,801), HDR (n=685), LDR plus EBRT (n=8518), or HDR plus EBRT (n=2392). The populations were balanced by propensity weighting, and the Kaplan-Meier incidence of severe UAEs was compared. Propensity-weighted Cox proportional hazards models were used to compare the adjusted hazard of UAEs. These UAEs were compared with those in a cohort of men not treated for prostate cancer. Results: Median follow-up was 4.3 years. At 8 years, the propensity-weighted cumulative UAE incidence was highest after HDR plus EBRT (26.6% [95% confidence interval, 23.8%-29.7%]) and lowest after LDR (15.7% [95% confidence interval, 14.8%-16.6%]). The absolute excess risk over nontreated controls at 8 years was 1.9%, 3.8%, 8.4%, and 12.9% for LDR, HDR, LDR plus EBRT, and HDR plus EBRT, respectively. These represent numbers needed to harm of 53, 26, 12, and 8 persons, respectively. The additional risk of development of a UAE related to treatment for LDR, LDR plus EBRT, and HDR plus EBRT was greatest within the 2 years after treatment and then continued to decline over time. Beyond 4 years, the risk of development of a new severe UAE matched the baseline risk of the control population for all treatments. Conclusions: Toxicity differences were observed between LDR and HDR, but the differences did not meet statistical significance. However, combination radiation therapy (either HDR plus EBRT or LDR plus

  1. Time Course and Accumulated Risk of Severe Urinary Adverse Events After High- Versus Low-Dose-Rate Prostate Brachytherapy With or Without External Beam Radiation Therapy.

    Science.gov (United States)

    Tward, Jonathan D; Jarosek, Stephanie; Chu, Haitao; Thorpe, Cameron; Shrieve, Dennis C; Elliott, Sean

    2016-08-01

    Severe urinary adverse events (UAEs) include surgical treatment of urethral stricture, urinary incontinence, and radiation cystitis. We compared the incidence of grade 3 UAEs, according to the Common Terminology Criteria for Adverse Events, after low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy, as well as after LDR plus external beam radiation therapy (EBRT) and HDR plus EBRT. Men aged >65 years with nonmetastatic prostate cancer were identified from the Surveillance, Epidemiology, and End Results-Medicare database who were treated with LDR (n=12,801), HDR (n=685), LDR plus EBRT (n=8518), or HDR plus EBRT (n=2392). The populations were balanced by propensity weighting, and the Kaplan-Meier incidence of severe UAEs was compared. Propensity-weighted Cox proportional hazards models were used to compare the adjusted hazard of UAEs. These UAEs were compared with those in a cohort of men not treated for prostate cancer. Median follow-up was 4.3 years. At 8 years, the propensity-weighted cumulative UAE incidence was highest after HDR plus EBRT (26.6% [95% confidence interval, 23.8%-29.7%]) and lowest after LDR (15.7% [95% confidence interval, 14.8%-16.6%]). The absolute excess risk over nontreated controls at 8 years was 1.9%, 3.8%, 8.4%, and 12.9% for LDR, HDR, LDR plus EBRT, and HDR plus EBRT, respectively. These represent numbers needed to harm of 53, 26, 12, and 8 persons, respectively. The additional risk of development of a UAE related to treatment for LDR, LDR plus EBRT, and HDR plus EBRT was greatest within the 2 years after treatment and then continued to decline over time. Beyond 4 years, the risk of development of a new severe UAE matched the baseline risk of the control population for all treatments. Toxicity differences were observed between LDR and HDR, but the differences did not meet statistical significance. However, combination radiation therapy (either HDR plus EBRT or LDR plus EBRT) increases the risk of severe UAEs compared with HDR

  2. 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.

  3. Preliminary results of pre-operative 5-FU, low dose leucovorin (LV), and concurrent radiation therapy (RT) for resectable T3 rectal cancer

    International Nuclear Information System (INIS)

    Grann, Alison; Minsky, Bruce D.; Cohen, Alfred M.; Saltz, Leonard; Kelsen, David P.; Kemeny, Nancy; Ilson, David; Guillem, Jose G.; Paty, Philip B.; Bass, Joanne

    1996-01-01

    foci of tumor in the bowel wall (clinical complete response) Therefore, the total complete response rate (clinical + pathologic) was 22% ((7(32))). Operative procedures included LAR: 16, LAR/Coloanal anastomosis: 8, APR: 8. All margins were negative. Of the 25 pts thought to initially require an APR, 17 (68%) were able to undergo sphincter preserving surgery. Of the 25 pts, 5 had involvement of the anal sphincter at initial presentation and pre-op therapy was not performed with the goal of sphincter preservation since an APR was planned regardless of the degree of downstaging. Excluding those 5 pts, the incidence of sphincter preservation would have been (17(20)) (85%). The crude incidence of failure as a component of failure was local: 0%, abdominal: 10% and distant: 3%. The 2 yr actuarial disease free survival was 86% and the overall survival was 100%. CONCLUSION: Our preliminary data reveal encouraging downstaging, acute toxicity, local control, and survival rates. Additional experience is needed in order to assess the long term results. The concurrent low dose LV regimen remains our standard pre-op combined modality approach for pts with clinically resectable T3 rectal cancer

  4. 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.)

  5. Influence of low-dose daily cisplatin on the distant metastasis-free survival of patients with locally advanced nonmetastatic head and neck cancer treated with radiation therapy

    International Nuclear Information System (INIS)

    Jeremic, Branislav; Milicic, Biljana

    2008-01-01

    We investigated the impact of low dose daily cisplatin on distant metastasis-free survival (DMFS) in locally advanced head and neck cancer treated with hyperfractionated radiotherapy (77 Gy in 70 fractions in 35 treatment days). In locally controlled tumors cisplatin led to better DMFS (p = 0.0272); Cisplatin may have acted independently of micrometastasis in locally advanced H and N cancer

  6. 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

  7. 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.

  8. Prepubertal ultra-low-dose estrogen therapy is associated with healthier lipid profile than conventional estrogen replacement for pubertal induction in adolescent girls with Turner syndrome: preliminary results.

    Science.gov (United States)

    Ruszala, Anna; Wojcik, Malgorzata; Zygmunt-Gorska, Agata; Janus, Dominika; Wojtys, Joanna; Starzyk, Jerzy B

    2017-08-01

    The metabolic effects of prepubertal low-dose estrogen replacement (LE) therapy in Turner syndrome (TS) have not been fully investigated to date. The present study aimed to compare glucose and lipids metabolism in adolescents with TS on LE and conventional estrogen replacement (CE). In 14 TS (mean age 13.8), LE (17β-estradiol, 62.5 μg daily) was introduced before age 12 (mean age 10.5), and followed by a pubertal induction regimen after age 12, and in 14 CE was started after age 12 (mean 14, SD 1.96). Before, and 3 years after starting 17β-estradiol growth velocity, bone age, BMI, and selected parameters of glucose and lipids metabolism were assessed. There were no significant differences between LE and CE in the mean levels of any parameter before introduction of 17β-estradiol [total cholesterol (TC): 4.1 vs 4.3 mmol/L, LDL cholesterol (LDLc): 2.2 vs 2.4 mmol/L, HDL cholesterol (HDLc): 1.6 vs 1.4 mmol/L, triglycerides: 0.9 vs 1.0 mmol/L, fasting glucose: 4.2 vs 4.4 mmol/L, post-load glucose: 4.8 vs 5.5 mmol/L; fasting insulin: 6.8 vs 8.0 post-load insulin: 21.3 vs 67.0 μIU/mL, HOMA-IR 1.3 vs 1.6]. After three years of treatment, TC and LDLc levels were significantly lower in LE group (3.8 vs 4.4 mmol/L, p = 0.004; 1.9 vs 2.4 mmol/L, p = 0.03). The other parameters did not differ significantly. There was no negative impact on growth course and bone age advancement nor on BMI in LE group. Prepubertal LE is associated with healthier lipid profile than CE in girls with TS.

  9. Association between low-dose pulsed intravenous cyclophosphamide therapy and amenorrhea in patients with systemic lupus erythematosus: A case-control study

    Science.gov (United States)

    2011-01-01

    Background The risk for amenorrhea following treatment of systemic lupus erythematosus (SLE) patients with low-dose intravenous cyclophosphamide (IVCY) has not been fully explored. Our objective was to ascertain the incidence of amenorrhea following treatment with low-dose IVCY and the association between amenorrhea and the clinical parameters of SLE. Methods A case-control retrospective study of premenopausal women ≤ 45 years old who had been treated for SLE with low-dose IVCY (500 mg/body/pulse) plus high-dose glucocorticoids (0.8-1.0 mg/kg/day of prednisolone; IVCY group) or glucocorticoids alone (0.8-1.0 mg/kg/day of prednisolone; steroid group) in our hospital from 2000 through 2009 was conducted using a questionnaire survey and medical record review. Results Twenty-nine subjects in the IVCY group and 33 subjects in the steroid group returned the questionnaire. A multivariate analysis revealed that age at initiation of treatment ≥ 40 years old was significantly associated with amenorrhea [p = 0.009; odds ratio (OR) 10.2; 95% confidence interval (CI) 1.8-58.7]. IVCY treatment may display a trend for association with amenorrhea (p = 0.07; OR 2.9; 95% CI 0.9-9.4). Sustained amenorrhea developed in 4 subjects in the IVCY group and 1 subject in the steroid group; all of these patients were ≥ 40 years old. Menses resumed in all subjects amenorrhea, our data suggest that patients amenorrhea with low-dose IVCY treatment. A higher risk for sustained amenorrhea following treatment with IVCY is a consideration for patients ≥ 40 years old. PMID:21663683

  10. 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).

  11. 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

  12. 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

  13. Emerging pharmaceutical therapies for COPD

    Directory of Open Access Journals (Sweden)

    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 

  14. Emerging therapies for thyroid carcinoma.

    LENUS (Irish Health Repository)

    Walsh, S

    2012-02-01

    Thyroid carcinoma is the most commonly diagnosed endocrine malignancy. Its incidence is currently rising worldwide. The discovery of genetic mutations associated with the development of thyroid cancer, such as BRAF and RET, has lead to the development of new drugs which target the pathways which they influence. Despite recent advances, the prognosis of anaplastic thyroid carcinoma is still unfavourable. In this review we look at emerging novel therapies for the treatment of well-differentiated and medullary thyroid carcinoma, and advances and future directions in the management of anaplastic thyroid carcinoma.

  15. 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)

  16. 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.

  17. 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.

  18. 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

  19. Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus.

    Science.gov (United States)

    Fasano, Serena; Pierro, Luciana; Pantano, Ilenia; Iudici, Michele; Valentini, Gabriele

    2017-07-01

    Systemic lupus erythematosus (SLE) is associated with an increased risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin (ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE. Patients consecutively admitted to our center who, at admission, satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus Collaborating Clinics classification criteria for SLE, and had not experienced any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c-HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ associated with a lower incidence of CVE. Cox regression analysis served to identify factors associated with a first CVE. For the study, 189 patients with SLE were enrolled and monitored for 13 years (median). Ten CVE occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g (log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047, respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR 18.054) increased the risk of a first CVE. Our results suggest that prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional evidence for its continued use in patients with SLE.

  20. The anti-inflammatory effect of low-dose radiation therapy involves a diminished CCL20 chemokine expression and granulocyte/endothelial cell adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, F. [Dept. of Radiotherapy and Oncology, Univ. of Frankfurt/Main (Germany); Hofmann, D.; Auer, J.; Roellinghoff, M.; Beuscher, H.U. [Inst. of Microbiology and Immunology, Univ. of Erlangen-Nuremberg, Erlangen (Germany); Keilholz, L. [Dept. of Radiotherapy, Clinical Center Bayreuth (Germany); Sauer, R. [Dept. of Radiooncology, Univ. of Erlangen-Nuremberg, Erlangen (Germany)

    2008-01-15

    Background and purpose: low-dose radiotherapy (LD-RT) is known to exert an anti-inflammatory effect, however, the underlying molecular mechanisms are not fully understood. The manipulation of polymorphonuclear neutrophil (PMN) function and/or recruitment may be one mechanism. Chemokines contribute to this process by creating a chemotactic gradient and by activating integrins. This study aimed to characterize the effect of LD-RT on CCL20 chemokine production and PMN/endothelial cell (EC) adhesion. Material and methods: the EC line EA.hy.926 was irradiated with doses ranging from 0 to 3 Gy and was co-cultured with PMNs from healthy donors either by direct cell contact or separated by transwell membrane chambers. CXCL8, CCL18, CCL20 chemokine and tumor necrosis factor-(TNF-){alpha} cytokine levels in supernatants were determined by ELISA and adhesion assays were performed. The functional impact of the cytokines transforming growth factor-(TGF-){beta}{sub 1} and TNF-{alpha} and of the intercellular adhesion molecule-(ICAM-)1 on CCL20 expression was analyzed by using neutralizing antibodies. Results: as compared to CXCL8 and CCL18, CCL20 chemokine secretion was found to be exclusively induced by a direct cell-cell contact between PMNs and EA.hy.926 ECs in a TNF-{alpha}-dependent, but ICAM-1-independent manner. Furthermore, irradiation with doses between 0.5 and 1 Gy resulted in a significant reduction of CCL20 release which was dependent on TGF-{beta}{sub 1} (p < 0.01). The decrease of CCL20 paralleled with a significant reduction in PMN/EA.hy.926 EC adhesion (p < 0.001). Conclusion: the modulation of CCL20 chemokine expression and PMN/EC adhesion adds a further facet to the plethora of mechanisms contributing to the anti-inflammatory efficacy of LD-RT. (orig.)

  1. The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta.

    Science.gov (United States)

    Biggin, Andrew; Zheng, Linda; Briody, Julie N; Coorey, Craig P; Munns, Craig F

    2015-01-01

    Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy. A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods. Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI. © 2015 S. Karger AG, Basel.

  2. Comparison of one and two low dose rate brachytherapy insertions in the treatment of stage IIB cervix cancer with radiation therapy alone

    International Nuclear Information System (INIS)

    Ferrigno, Robson; Faria, S.L.C.O.

    1996-01-01

    Purpose/Objective: To compare one and two intracavitary brachytherapy with low dose rate in the management of stage IIB cervix cancer through a prospective and randomized trial. Materials and Methods: From September 1989 to December 1992, 81 patients with stage IIB cervix cancer were randomized in two arms according to the number of intracavitary brachytherapy insertion to be realized. Of these, 34 were treated by two intracavitary insertions (group A) and 47 by one insertion (group B). The external beam radiotherapy (EBRT) was realized through a Cobalt unit at whole pelvis with total dose of 40Gy in 20 fractions of 2,0Gy, in box arrangement, followed by parametrial complementation of 10Gy. The brachytherapy was realized right after the end of EBRT. The patients from group A were underwent to two insertions of 25Gy, calculated at point A, defined by the Manchester system. The interval between each insertions was 2 weeks. The patients from group B were underwent to one insertion of 40 Gy at point A. The average dose rate was 60cGy per hour at point A. Results: With the follow up ranging from 36 to 75 months and medium of 55 months, the disease free survival of the patients from group A was not statistically different of those from group B, 70,6% and 72,3% respectively (p=0,711). Local recurrence occurred in four patients from group A (11,7%) and in eight from group B (17%). Distant metastasis occurred in one patient from group A (2,9%) and in two from group B (4,2%). Three patients from group A (8,8%) and three from group B (6,4%) were lost to follow up and considered as dead. The causes of death among patients from group A were progression of local disease in four, distant metastasis in one, complicated diabetes mellitus in one and actinic intestinal complications in other one. The cause of deaths among patients from group B were progression of local disease in eight and distant metastasis in two. The grade I and II rectal complications rate was 5,9% and 6,3% at

  3. Statistical and low dose response

    International Nuclear Information System (INIS)

    Thorson, M.R.; Endres, G.W.R.

    1981-01-01

    The low dose response and the lower limit of detection of the Hanford dosimeter depend upon may factors, including the energy of the radiation, whether the exposure is to be a single radiation or mixed fields, annealing cycles, environmental factors, and how well various batches of TLD materials are matched in the system. A careful statistical study and sensitivity analysis were performed to determine how these factors influence the response of the dosimeter system. Estimates have been included in this study of the standard deviation of calculated dose for various mixed field exposures from 0 to 1000 mrem

  4. A Comparison Between Low-Dose-Rate Brachytherapy With or Without Androgen Deprivation, External Beam Radiation Therapy With or Without Androgen Deprivation, and Radical Prostatectomy With or Without Adjuvant or Salvage Radiation Therapy for High-Risk Prostate Cancer

    International Nuclear Information System (INIS)

    Ciezki, Jay P.; Weller, Michael; Reddy, Chandana A.; Kittel, Jeffrey; Singh, Harguneet; Tendulkar, Rahul; Stephans, Kevin L.; Ulchaker, James; Angermeier, Kenneth; Stephenson, Andrew; Campbell, Steven; Haber, Georges-Pascal; Klein, Eric A.

    2017-01-01

    Purpose: We compare the efficacy and toxicity among the 3 major modalities available used to treat high-risk prostate cancer (HRCaP). Methods and Materials: From 1996 to 2012, 2557 HRCaP patients were treated: 734 received external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT), 515 received low-dose-rate prostate brachytherapy (LDR) with or without ADT, and 1308 received radical prostatectomy (RP) with or without EBRT. Biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and prostate cancer–specific mortality (PCSM) were assessed. Toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.03. The log-rank test compared bRFS and cRFS among the modalities, and Cox regression identified factors associated with bRFS and cRFS. Gray's test compared differences in late toxicity and PSCM among the modalities. Competing risk regression identified factors associated with PCSM. Results: The median follow-up time and age were 63.5 months and 65 years, respectively. The bRFS at 5 and 10 years, respectively, was 74% and 53% for EBRT, 74% and 52% for LDR, and 65% and 47% for RP (P=.0001). The cRFS at 5 and 10 years, respectively, was 85% and 73% for EBRT, 90% and 76% for LDR, and 89% and 75% for RP (P=.121). The PCSM at 5 and 10 years, respectively, was 5.3% and 11.2% for EBRT, 3.2% and 3.6% for LDR, and 2.8% and 6.8% for RP (P=.0004). The 10-year cumulative incidence of ≥grade 3 genitourinary toxicity was 8.1% for EBRT, 7.2% for LDR, and 16.4% for RP (P<.0001). The 10-year cumulative incidence of ≥grade 3 gastrointestinal toxicity was 4.6% for EBRT, 1.1% for LDR, and 1.0% for RP (P<.0001). Conclusion: HRCaP treated with EBRT, LDR, or RP yields efficacy showing better bRFS for LDR and EBRT relative to RP, equivalence for cRFS, and a PCSM advantage of LDR and RP over EBRT. The toxicity is lowest for LDR.

  5. A Comparison Between Low-Dose-Rate Brachytherapy With or Without Androgen Deprivation, External Beam Radiation Therapy With or Without Androgen Deprivation, and Radical Prostatectomy With or Without Adjuvant or Salvage Radiation Therapy for High-Risk Prostate Cancer.

    Science.gov (United States)

    Ciezki, Jay P; Weller, Michael; Reddy, Chandana A; Kittel, Jeffrey; Singh, Harguneet; Tendulkar, Rahul; Stephans, Kevin L; Ulchaker, James; Angermeier, Kenneth; Stephenson, Andrew; Campbell, Steven; Haber, Georges-Pascal; Klein, Eric A

    2017-04-01

    We compare the efficacy and toxicity among the 3 major modalities available used to treat high-risk prostate cancer (HRCaP). From 1996 to 2012, 2557 HRCaP patients were treated: 734 received external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT), 515 received low-dose-rate prostate brachytherapy (LDR) with or without ADT, and 1308 received radical prostatectomy (RP) with or without EBRT. Biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and prostate cancer-specific mortality (PCSM) were assessed. Toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.03. The log-rank test compared bRFS and cRFS among the modalities, and Cox regression identified factors associated with bRFS and cRFS. Gray's test compared differences in late toxicity and PSCM among the modalities. Competing risk regression identified factors associated with PCSM. The median follow-up time and age were 63.5 months and 65 years, respectively. The bRFS at 5 and 10 years, respectively, was 74% and 53% for EBRT, 74% and 52% for LDR, and 65% and 47% for RP (P=.0001). The cRFS at 5 and 10 years, respectively, was 85% and 73% for EBRT, 90% and 76% for LDR, and 89% and 75% for RP (P=.121). The PCSM at 5 and 10 years, respectively, was 5.3% and 11.2% for EBRT, 3.2% and 3.6% for LDR, and 2.8% and 6.8% for RP (P=.0004). The 10-year cumulative incidence of ≥grade 3 genitourinary toxicity was 8.1% for EBRT, 7.2% for LDR, and 16.4% for RP (PLDR, and 1.0% for RP (PLDR, or RP yields efficacy showing better bRFS for LDR and EBRT relative to RP, equivalence for cRFS, and a PCSM advantage of LDR and RP over EBRT. The toxicity is lowest for LDR. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. A Comparison Between Low-Dose-Rate Brachytherapy With or Without Androgen Deprivation, External Beam Radiation Therapy With or Without Androgen Deprivation, and Radical Prostatectomy With or Without Adjuvant or Salvage Radiation Therapy for High-Risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-04-01

    Purpose: We compare the efficacy and toxicity among the 3 major modalities available used to treat high-risk prostate cancer (HRCaP). Methods and Materials: From 1996 to 2012, 2557 HRCaP patients were treated: 734 received external beam radiation therapy (EBRT) with or without androgen deprivation therapy (ADT), 515 received low-dose-rate prostate brachytherapy (LDR) with or without ADT, and 1308 received radical prostatectomy (RP) with or without EBRT. Biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and prostate cancer–specific mortality (PCSM) were assessed. Toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.03. The log-rank test compared bRFS and cRFS among the modalities, and Cox regression identified factors associated with bRFS and cRFS. Gray's test compared differences in late toxicity and PSCM among the modalities. Competing risk regression identified factors associated with PCSM. Results: The median follow-up time and age were 63.5 months and 65 years, respectively. The bRFS at 5 and 10 years, respectively, was 74% and 53% for EBRT, 74% and 52% for LDR, and 65% and 47% for RP (P=.0001). The cRFS at 5 and 10 years, respectively, was 85% and 73% for EBRT, 90% and 76% for LDR, and 89% and 75% for RP (P=.121). The PCSM at 5 and 10 years, respectively, was 5.3% and 11.2% for EBRT, 3.2% and 3.6% for LDR, and 2.8% and 6.8% for RP (P=.0004). The 10-year cumulative incidence of ≥grade 3 genitourinary toxicity was 8.1% for EBRT, 7.2% for LDR, and 16.4% for RP (P<.0001). The 10-year cumulative incidence of ≥grade 3 gastrointestinal toxicity was 4.6% for EBRT, 1.1% for LDR, and 1.0% for RP (P<.0001). Conclusion: HRCaP treated with EBRT, LDR, or RP yields efficacy showing better bRFS for LDR and EBRT relative to RP, equivalence for cRFS, and a PCSM advantage of LDR and RP over EBRT. The toxicity is lowest for LDR.

  7. 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.)

  8. High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Pan, J; Yang, J F; Deng, B P; Zhao, X J; Zhang, X; Lin, Y H; Wu, Y N; Deng, Z L; Zhang, Y L; Liu, S H; Wu, T; Lu, P H; Lu, D P; Chang, A H; Tong, C R

    2017-12-01

    Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD + ) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 10 5 /kg and were eventually settled at 1 × 10 5 /kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD + patients achieved MRD - . All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD - with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 10 5 /kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

  9. 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.

  10. Half-Fan-Based Intensity-Weighted Region-of-Interest Imaging for Low-Dose Cone-Beam CT in Image-Guided Radiation Therapy.

    Science.gov (United States)

    Yoo, Boyeol; Son, Kihong; Pua, Rizza; Kim, Jinsung; Solodov, Alexander; Cho, Seungryong

    2016-10-01

    With the increased use of computed tomography (CT) in clinics, dose reduction is the most important feature people seek when considering new CT techniques or applications. We developed an intensity-weighted region-of-interest (IWROI) imaging method in an exact half-fan geometry to reduce the imaging radiation dose to patients in cone-beam CT (CBCT) for image-guided radiation therapy (IGRT). While dose reduction is highly desirable, preserving the high-quality images of the ROI is also important for target localization in IGRT. An intensity-weighting (IW) filter made of copper was mounted in place of a bowtie filter on the X-ray tube unit of an on-board imager (OBI) system such that the filter can substantially reduce radiation exposure to the outer ROI. In addition to mounting the IW filter, the lead-blade collimation of the OBI was adjusted to produce an exact half-fan scanning geometry for a further reduction of the radiation dose. The chord-based rebinned backprojection-filtration (BPF) algorithm in circular CBCT was implemented for image reconstruction, and a humanoid pelvis phantom was used for the IWROI imaging experiment. The IWROI image of the phantom was successfully reconstructed after beam-quality correction, and it was registered to the reference image within an acceptable level of tolerance. Dosimetric measurements revealed that the dose is reduced by approximately 61% in the inner ROI and by 73% in the outer ROI compared to the conventional bowtie filter-based half-fan scan. The IWROI method substantially reduces the imaging radiation dose and provides reconstructed images with an acceptable level of quality for patient setup and target localization. The proposed half-fan-based IWROI imaging technique can add a valuable option to CBCT in IGRT applications.

  11. 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

  12. 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

  13. Emerging therapies in neurorehabilitation II

    CERN Document Server

    Raya, Rafael; González, José

    2016-01-01

    This book reports on the latest technological and clinical advances in the field of neurorehabilitation. It is, however, much more than a conventional survey of the state-of-the-art in neurorehabilitation technologies and therapies. It was written on the basis of a week of lively discussions between PhD students and leading research experts during the Summer School on Neurorehabilitation (SSNR2014), held September 15-19 in Baiona, Spain. Its unconventional format makes it a perfect guide for all PhD students, researchers and professionals interested in gaining a multidisciplinary perspective on current and future neurorehabilitation scenarios.  The book addresses various aspects of neurorehabilitation research and practice, including a selection of common impairments affecting CNS function, such as stroke and spinal cord injury, as well as cutting-edge rehabilitation and diagnostics technologies, including robotics, neuroprosthetics, brain-machine interfaces and neuromodulation.

  14. Incremental cost and cost-effectiveness of low-dose, high-frequency training in basic emergency obstetric and newborn care as compared to status quo: part of a cluster-randomized training intervention evaluation in Ghana.

    Science.gov (United States)

    Willcox, Michelle; Harrison, Heather; Asiedu, Amos; Nelson, Allyson; Gomez, Patricia; LeFevre, Amnesty

    2017-12-06

    Low-dose, high-frequency (LDHF) training is a new approach best practices to improve clinical knowledge, build and retain competency, and transfer skills into practice after training. LDHF training in Ghana is an opportunity to build health workforce capacity in critical areas of maternal and newborn health and translate improved capacity into better health outcomes. This study examined the costs of an LDHF training approach for basic emergency obstetric and newborn care and calculates the incremental cost-effectiveness of the LDHF training program for health outcomes of newborn survival, compared to the status quo alternative of no training. The costs of LDHF were compared to costs of traditional workshop-based training per provider trained. Retrospective program cost analysis with activity-based costing was used to measure all resources of the LDHF training program over a 3-year analytic time horizon. Economic costs were estimated from financial records, informant interviews, and regional market prices. Health effects from the program's impact evaluation were used to model lives saved and disability-adjusted life years (DALYs) averted. Uncertainty analysis included one-way and probabilistic sensitivity analysis to explore incremental cost-effectiveness results when fluctuating key parameters. For the 40 health facilities included in the evaluation, the total LDHF training cost was $823,134. During the follow-up period after the first LDHF training-1 year at each participating facility-approximately 544 lives were saved. With deterministic calculation, these findings translate to $1497.77 per life saved or $53.07 per DALY averted. Probabilistic sensitivity analysis, with mean incremental cost-effectiveness ratio of $54.79 per DALY averted ($24.42-$107.01), suggests the LDHF training program as compared to no training has 100% probability of being cost-effective above a willingness to pay threshold of $1480, Ghana's gross national income per capita in 2015. This

  15. 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.

  16. 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

  17. Growth hormone therapy: emerging dilemmas.

    Science.gov (United States)

    Laron, Zvi

    2011-06-01

    The history of pituitary growth hormone (GH) started 100 years ago but the isolation purification and determination of the chemical structure of the human GH (hGH) took another 50 years. Starting in 1957 hGH was extracted from cadaver pituitaries and its clinical use was restricted to severe GH deficient patient. With the invention of recombinant biosynthetic hGH in 1985; the indications for its use were extended. The major approved medications are GH deficiency and short statured children of various etiologies. This is a critical review of present and future use of human GH. To evaluate the effectiveness of the hGH treatment several pharmaceutical companies established postmarketing follow-up programs which are based on the reliability and cooperation of the treating physicians. Unfortunately they stop when the treatment is terminated and most studies refer to growth stimulation effectiveness during initial years but do not follow the children until final height. The long-term experience enabled to evaluate adverse effects (AE), the majority being due to large dosage. The most serious AE reported are increases in malignancies and early or late mortality in adult age. There is consensus that GH deficient children need replacement therapy. As long-term hGH treatment is expensive and the final height gains in non-GH deficient children small the cost-benefit indications to treat short children without a disease has been questioned. To avoid the need of daily injections, long-acting hGH preparations undergo clinical trials. The future will show their effectiveness and eventual adverse effects.

  18. Low Dose Risk, Decisions, and Risk Communication

    International Nuclear Information System (INIS)

    Flynn, James

    2002-01-01

    The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation

  19. 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

  20. Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer

    Science.gov (United States)

    Warner, Andrew; Pickles, Tom; Crook, Juanita; Martin, Andre-Guy; Souhami, Luis; Catton, Charles; Lukka, Himu

    2015-01-01

    Purpose: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II “Phoenix” definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database. Methods and Materials: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy  (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates. Results: Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT. Conclusions: Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and

  1. Therapy Dogs in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Nickolas Nahm

    2012-09-01

    Full Text Available Introduction: This study examined acceptance by staff and patients of a therapy dog (TD in the emergency department (ED.Methods: Immediately after TD visits to a University Hospital ED, all available ED staff, patients, and their visitors were invited to complete a survey.Results: Of 125 ‘‘patient’’ and 105 staff responses, most were favorable. Ninety-three percent of patients and 95% of staff agreed that TDs should visit EDs; 87.8% of patients and 92% of staff approved of TDs for both adult and pediatric patients. Fewer than 5% of either patients or staff were afraid of the TDs. Fewer than 10% of patients and staff thought the TDs posed a sanitary risk or interfered with staff work.Conclusion: Both patients and staff approve of TDs in an ED. The benefits of animal-assisted therapy should be further explored in the ED setting.

  2. Occupation emerges in the process of therapy.

    Science.gov (United States)

    Price, Pollie; Miner, Stephanie

    2007-01-01

    The current literature offers no cohesive definition of occupation-based practice. Current definitions emphasize intervention forms and contexts, which do not reflect the complexity of practice. This article demonstrates that the therapeutic relationship and the meanings that are created in the therapy process are central aspects of occupation-based practice. Occupation, as an idea that emerges in the therapeutic process, has aspects of both doing and becoming. The authors conducted observation sessions and interviews with an occupational therapist, Nancy, who used multiple therapeutic strategies with one child, Hannah, as they worked toward Hannah's goals of going to preschool and becoming a friend. Strategies include changing therapeutic conditions, using cognitive strategies, bridging the person-task-social context, pushing participation, and engaging in narrative micronegotiations. Occupation emerged in the therapeutic processes as the occupational therapist and client co-created meaning about the client moving toward or away from who she wanted to become.

  3. 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

  4. LOW DOSE RISK, DECISIONS, and RISK COMMUNICATION

    International Nuclear Information System (INIS)

    Flynn, James

    2002-01-01

    The objective of this project is to conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low-dose exposures. Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low-dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

  5. 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

  6. Stem Cell Therapy: An emerging science

    International Nuclear Information System (INIS)

    Khan, Muhammad M.

    2007-01-01

    The research on stem cells is advancing knowledge about the development of an organism from a single cell and to how healthy cells replace damaged cells in adult organisms. Stem cell therapy is emerging rapidly nowadays as a technical tool for tissue repair and replacement. The purpose of this review to provide a framework of understanding for the challenges behind translating fundamental stem cell biology and its potential use into clinical therapies, also to give an overview on stem cell research to the scientists of Saudi Arabia in general. English language MEDLINE publications from 1980 through January 2007 for experimental, observational and clinical studies having relation with stem cells with different diseases were reviewed. Approximately 85 publications were reviewed based on the relevance, strength and quality of design and methods, 36 publications were selected for inclusion. Stem cells reside in a specific area of each tissue where they may remain undivided for several years until they are activated by disease or tissue injury. The embryonic stem cells are typically derived from four or five days old embryos and they are pluripotent. The adult tissues reported to contain stem cells brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin and liver. The promise of stem cell therapies is an exciting one, but significant technical hurdles remain that will only be overcome through years of intensive research. (author)

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

    Directory of Open Access Journals (Sweden)

    Daniela Domanico

    2013-01-01

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

  8. 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...

  9. 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.

  10. 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.

  11. 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.)

  12. 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.

  13. Stimulation of seeds by low dose irradiation

    International Nuclear Information System (INIS)

    Lawson, Helen

    1976-05-01

    The first section of the bibliography lists materials on the stimulation of seeds by low dose irradiation, with particular reference to stimulation of germination and yield. The second section contains a small number of selected references on seed irradiation facilities. (author)

  14. Emerging therapies for the treatment of osteoporosis

    Directory of Open Access Journals (Sweden)

    Garima Bhutani

    2013-01-01

    Full Text Available Osteoporosis is a chronic disease of the osseous system characterized by decreased bone strength and increased fracture risk. It is due to an imbalance in the dynamic ongoing processes of bone formation and bone resorption. Currently available osteoporosis therapies like bisphosphonates, selective estrogen receptor modulators (SERMs, and denosumab are anti-resorptive agents. Parathyroid hormone analogs like teriparatide are the only anabolic agents currently approved for osteoporosis treatment. The side-effects and limited efficacy of the presently available therapies has encouraged extensive research into the pathophysiology of the disease and newer drug targets for its treatment. The novel anti-resorptive agents being developed are newer SERMs, osteoprotegerin, c-src (cellular-sarcoma kinase inhibitors, αVβ3 integrin antagonists, cathepsin K inhibitors, chloride channel inhibitors, and nitrates. Upcoming anabolic agents include calcilytics, antibodies against sclerostin and Dickkopf-1, statins, matrix extracellular phosphoglycoprotein fragments activin inhibitiors, and endo-cannabinoid agonists. Many of these new drugs are still in development. This article provides an insight into the emerging drugs for the treatment of osteoporosis.

  15. 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

  16. Combination therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea and low dose rate radiation in the 9L rat brain tumor and spheroid models: implications for brain tumor brachytherapy

    International Nuclear Information System (INIS)

    Gutin, P.H.; Bernstein, M.; Sano, Y.; Deen, D.F.

    1984-01-01

    The effects of combination treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and low dose rate radiation were studied in the 9L rat brain tumor in vivo model and the 9L multicellular tumor spheroid model. F-344 rats bearing intracerebral 9L gliosarcomas were implanted with removable 125 I sources. Minimal (peripheral) tumor doses of 6387 rad produced an increased life-span (ILS) of 28% over that of control rats implanted with dummy sources, BCNU alone (13.3 mg/kg) produced in an ILS of 67%, and combination treatment with BCNU and implanted 125 I sources produced an ILS of 167%. As measured by a colony-forming efficiency assay, the greatest cell kill in 9L spheroids occurred when BCNU was administered 24 hours before irradiation from a 137 Cs source at a low dose rate of 5 rad/minute. At a higher dose rate of 210 rad/minute, the time dependence of the effects of combination treatment was identical and therefore independent of dose rate

  17. 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)

  18. New risk estimates at low doses

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1992-01-01

    The age of molecular radiation epidemiology may be at hand. The techniques are available to establish with the degree of precision required to determine whether agent-specific mutations can be identified consistently. A concerted effort to examine radiation-induced changes in as many relevant genes as possible appears to be justified. Cancers in those exposed to low doses of ionizing radiation should be chosen for the investigation. Parallel studies of radiation-induced cancers in experimental animals would not only complement the human studies, but perhaps reveal approaches to extrapolation of risk estimates across species. A caveat should be added to this optimistic view of what molecular studies might contribute to the knotty problem of risk estimates at low doses. The suggestions are made by one with no expertise in the field of molecular biology

  19. 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)

  20. Epigenomic Adaptation to Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-30

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

  1. Radiation effects of high and low doses

    International Nuclear Information System (INIS)

    El-Naggar, A.M.

    1998-01-01

    The extensive proliferation of the uses and applications of atomic and nuclear energy resulted in possible repercussions on human health. The prominent features of the health hazards that may be incurred after exposure to high and low radiation doses are discussed. The physical and biological factors involved in the sequential development of radiation health effects and the different cellular responses to radiation injury are considered. The main criteria and features of radiation effects of high and low doses are comprehensively outlined

  2. 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

  3. 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.

  4. 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)

  5. 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

  6. 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)

  7. 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.

  8. 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.

  9. 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

  10. 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)

  11. Insulin Therapy in Diabetic Hyperglycemic Emergencies

    Directory of Open Access Journals (Sweden)

    Diana Machado Ramírez

    2014-09-01

    Full Text Available Background: diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state are two of the most serious metabolic emergencies in diabetic patients. Objective: to identify the type of metabolic complications (diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state in order to analyze the patients’ outcome considering the plasma pH levels, as well as the mode of insulin administration. Method: a cross-sectional descriptive study was conducted in 52 patients admitted to the intensive care unit of the Enrique Cabrera Hospital from 2000 to 2007. The variables analyzed included: type of diabetes mellitus, type of acute complication, mode of insulin administration, blood gas analysis and outcome. Results: diabetic ketoacidosis occurred in 57.5 % of the type 1 diabetic patients and in the 42.5 % of the type 2 diabetics. None of the type 1 diabetics developed hyperglycemic hyperosmolar nonketotic state and this complication was observed in 23.0 % of the patients with diabetes type 2. Microdosing was the mode of insulin administration that predominated in both ketoacidosis and hyperglycemic state cases. Mortality was higher in the hyperglycemic state (67 % and using microdoses in the insulin therapy. Conclusions: diabetic ketoacidosis was the major complication. Mortality from diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state was high and the mode of insulin administration was inadequate in some patients.

  12. 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

  13. Effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Anon.

    2008-01-01

    Ionizing radiation of cosmic or terrestrial origin is part of the environment in which all living things have evolved since the creation of the universe. The artificial radioactivity generated by medical diagnostic and treatment techniques, some industrial activities, radioactive fallout, etc. has now been added to this natural radioactivity. This article reviews the biological effects of the low doses of ionizing radiation to which the population is thus exposed. Their carcinogenic risk cannot simply be extrapolated from what we know about high-dose exposure. (author)

  14. Low dose radiation and diabetes mellitus

    International Nuclear Information System (INIS)

    Zhao Hongguang; Gong Shouliang; Cai Lu

    2006-01-01

    Induction of hormesis and adaptive response by low-dose radiatio (LDR) has been extensively indicated. It's mechanism may be related with the protective protein and antioxidants that LDR induced, which take effects on the diabetes mellitus (DM) and other diseases. This review will summarize available dat with emphasis on three points: the preventive effect of LDR on the development of diabetes, the therapeutic effect of LDR on diabetic complications and possible mechanisms by which LDR prevents the development of diabetes and diabetic complications. Finally, the perspectives of LDR clinical, diabetes-related implication are discussed. (authors)

  15. 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

  16. 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.)

  17. 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...

  18. 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.)

  19. 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

  20. Chiral analysis of amphetamines in hair by liquid chromatography-tandem mass spectrometry: compliance-monitoring of attention deficit hyperactivity disorder (ADHD) patients under Elvanse® therapy and identification after controlled low-dose application.

    Science.gov (United States)

    Binz, Tina M; Williner, Elena; Strajhar, Petra; Dolder, Patrick C; Liechti, Matthias E; Baumgartner, Markus R; Kraemer, Thomas; Steuer, Andrea E

    2018-02-01

    Amphetamine (AMP) is used as an illicit drug and also for the treatment of attention deficit hyperactivity disorder (ADHD). Respective drugs most often contain the enantiomer (S)-AMP as active compound or (S)-AMP is formed from the prodrug lisdexamfetamine (Elvanse®) whereas the illicit drug is usually traded as racemate ((R/S)-AMP). A differentiation between the use of the medically prescribed drug and the abuse of illicit street amphetamine is of great importance, for example in retrospective consumption monitoring by hair analysis. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the chiral separation and quantitation of (S)- and (R)-AMP in hair was developed. For this purpose, 20 mg hair was extracted and derivatized with N-(2,4-dinitro-5-fluorophenyl)-L(S)-valinamide L(S)-(DNPV) to yield amphetamine diastereomers. Baseline separation of the resulting diastereomers was achieved on a high-pressure liquid-chromatography system (HPLC) coupled to a Sciex QTRAP® 5500 linear ion trap quadrupole mass spectrometer. The method was successfully validated. Analysis of hair samples from nine Elvanse® patients revealed only (S)-AMP in eight cases; one subject showed both enantiomers indicating a (side-) consumption of street amphetamine. The analysis of the 16 amphetamine users' samples showed only racemic amphetamine. Furthermore, it could be shown in a controlled study that (S)-AMP can be detected after administration of even very low doses of lisdexamfetamine and dexamphetamine, which can be of interest in forensic toxicology and especially in drug-facilitated crime (DFC). The method now enables the retrospective compliance-monitoring of ADHD patients and the differentiation between medically prescribed intake of (S)-amphetamine and abuse of illicit street amphetamine. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Biological Effects of Low-Dose Exposure

    CERN Document Server

    Komochkov, M M

    2000-01-01

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

  2. Low Dose Ionizing Radiation Modulates Immune Function

    International Nuclear Information System (INIS)

    Nelson, Gregory A.

    2016-01-01

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a 'Th2 polarized' immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in

  3. Low Dose Ionizing Radiation Modulates Immune Function

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-12

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

  4. Fluid therapy in the emergency unit

    African Journals Online (AJOL)

    Senior Specialist Paediatrician, Department of Ambulatory and Emergency Paediatrics, Red Cross War Memorial Children's Hospital, Cape. Town. Dr Diedericks is currently head of the Paediatric Emergency Service at Red Cross Hospital. He has previous experience ... intravenous fluid administration. Choosing the correct ...

  5. 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

  6. 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)

  7. 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.

  8. low dose irradiation growth in zirconium

    International Nuclear Information System (INIS)

    Fortis, A.M.

    1987-01-01

    Low dose neutron irradiation growth in textured and recrystallized zirconium, is studied, at the Candu Reactors Calandria temperature (340 K) and at 77 K. It was necessary to design and build 1: A facility to irradiate at high temperatures, which was installed in the Argentine Atomic Energy Commission's RA1 Reactor; 2: Devices to carry out thermal recoveries, and 3: Devices for 'in situ' measurements of dimensional changes. The first growth kinetics curves were obtained at 365 K and at 77 K in a cryostat under neutron fluxes of similar spectra. Irradiation growth experiments were made in zirconium doped with fissionable material (0,1 at % 235 U). In this way an equivalent dose two orders of magnitude greater than the reactor's fast neutrons dose was obtained, significantly reducing the irradiation time. The specimens used were bimetallic couples, thus obtaining a great accuracy in the measurements. The results allow to determine that the dislocation loops are the main cause of irradiation growth in recrystallized zirconium. Furthermore, it is shown the importance of 'in situ' measurements as a way to avoid the effect that temperature changes have in the final growth measurement; since they can modify the residual stresses and the overconcentrations of defects. (M.E.L.) [es

  9. Emerging pharmacological therapy for functional dyspepsia.

    Science.gov (United States)

    Hojo, Mariko; Nagahara, Akihito; Asaoka, Daisuke; Watanabe, Sumio

    2013-10-01

    Functional dyspepsia (FD) is a multifactorial disease with complex underlying pathophysiology. To date, there is no established treatment for FD. This review summarizes recent progress in pharmacological therapy for the disease. A newly developed drug, acotiamide, is expected to improve symptoms of postprandial distress syndrome. Herbal medicines are also expected to become options for FD treatment.

  10. Emerging Therapies in Metastatic Prostate Cancer.

    Science.gov (United States)

    Sonnenburg, Daniel W; Morgans, Alicia K

    2018-04-11

    In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy. A single-arm phase 2 study of the PARP inhibitor olaparib demonstrated high response rates and more favorable progression-free and overall survival for men with metastatic castration-resistant prostate cancer and DNA repair defects treated with olaparib compared with men without DNA repair defects. Multiple ongoing clinical trials are investigating novel hormonal therapies and combinations of chemotherapy, targeted small molecules, immunotherapy, and radiopharmaceuticals. Progress continues to be made in the treatment of metastatic prostate cancer, and ongoing clinical trials continue to investigate novel agents and approaches to treatment.

  11. Current and emerging therapies for Addison's disease.

    Science.gov (United States)

    Napier, Catherine; Pearce, Simon H S

    2014-06-01

    The purpose of this article is to review the current therapy of Addison's disease and to highlight recent developments in this field. Conventional steroid replacement for Addison's disease consists of twice or three-times daily oral hydrocortisone and once-daily fludrocortisone; however, new treatment modalities such as modified-released hydrocortisone and continuous subcutaneous hydrocortisone infusion have recently been developed. These offer the potential for closer simulation of the physiological serum cortisol rhythm. Two studies have also looked at modifying the natural history of adrenal failure using adrenocorticotropic hormone (ACTH) stimulation and immunomodulatory therapies, leading to the concept of residual adrenal function in some Addison's disease patients. Following more than 60 years with no significant innovation in the management of Addison's disease, these new approaches hold promise for improved patient health and better quality of life in the future.

  12. Effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Masse, R.

    2006-01-01

    Several groups of human have been irradiated by accidental or medical exposure, if no gene defect has been associated to these exposures, some radioinduced cancers interesting several organs are observed among persons exposed over 100 to 200 mSv delivered at high dose rate. Numerous steps are now identified between the initial energy deposit in tissue and the aberrations of cell that lead to tumors but the sequence of events and the specific character of some of them are the subject of controversy. The stake of this controversy is the risk assessment. From the hypothesis called linear relationship without threshold is developed an approach that leads to predict cancers at any tiny dose without real scientific foundation. The nature and the intensity of biological effects depend on the quantity of energy absorbed in tissue and the modality of its distribution in space and time. The probability to reach a target (a gene) associated to the cancerating of tissue is directly proportional to the dose without any other threshold than the quantity of energy necessary to the effect, its probability of effect can be a more complex function and depends on the quality of the damage produced as well as the ability of the cell to repair the damage. These two parameters are influenced by the concentration of initial injuries in the target so by the quality of radiation and by the dose rate. The mechanisms of defence explain the low efficiency of radiation as carcinogen and then the linearity of effects in the area of low doses is certainly the least defensible scientific hypothesis for the prediction of the risks. (N.C.)

  13. Characteristics of repair following very low doses

    International Nuclear Information System (INIS)

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

    1987-01-01

    The effects of ionizing radiation on living systems being with the physical processes of energy deposition and develop through many stages of chemical reaction and biological response. The modeling effort attempts to organize the available data and theories of all of these stages into self-consistent models that can be compared and tested. In some cases, important differences among models result in only small differences in cell survival within the ranges of dose and dose rate that are normally investigated. To overcome this limitation, new ways of irradiating cells at extremes of dose rate, or ways of evaluating the effects of very small doses, are developed. Mathematical modeling and cellular studies complement each other. It has recently been found that some mechanisms are not adequate to account for the interaction of dose and repair time as they affect the reproductive survival of plateau-phase Chinese hamster ovary (CHO) cells. Repair of radiation-induced cellular damage plays a central role in the survival of cells exposed to doses of 1 Gy or more. This repair is responsible for the dose rate, split-dose and delayed plating effect and can be evaluated. Because split-dose and dose-rate experiments involve repair during irradiation and delayed plating experiments involve repair after irradiation is completed, it was originally thought that different repair processes were involved. It is now clear that this is not necessarily the case. Appropriately designed models can account for observed effects at conventional doses (1 Gy or more) whether they assume all damage is lethal unless repaired or some damage is innocuous unless it interacts with additional damage. The fact that the survival following a plating delay is always less than the survival following immediate plating at low doses indicates that the damage produced is probably not potentially lethal

  14. Emerging technologies for enabling proangiogenic therapy

    International Nuclear Information System (INIS)

    Roy, Rituparna Sinha; Roy, Bhaskar; Sengupta, Shiladitya

    2011-01-01

    Ischemic disease causes a large number of deaths and significant clinical problems worldwide. Therapeutic angiogenesis, strengthened by advances in growth-factor-based therapies, is a promising solution to ischemic pathologies. Major challenges in therapeutic angiogenesis are the lack of stability of native angiogenic proteins and also providing sustained delivery of biologically active proteins at the ischemic sites. This paper will discuss various protein engineering strategies to develop stabilized proangiogenic proteins and several biomaterial technologies used to amplify the angiogenic outcome by delivering biologically active growth factors in a sustained manner.

  15. Emerging technologies for enabling proangiogenic therapy

    Science.gov (United States)

    Sinha Roy, Rituparna; Roy, Bhaskar; Sengupta, Shiladitya

    2011-12-01

    Ischemic disease causes a large number of deaths and significant clinical problems worldwide. Therapeutic angiogenesis, strengthened by advances in growth-factor-based therapies, is a promising solution to ischemic pathologies. Major challenges in therapeutic angiogenesis are the lack of stability of native angiogenic proteins and also providing sustained delivery of biologically active proteins at the ischemic sites. This paper will discuss various protein engineering strategies to develop stabilized proangiogenic proteins and several biomaterial technologies used to amplify the angiogenic outcome by delivering biologically active growth factors in a sustained manner.

  16. The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Maghsoudi, S; Fisker, S

    2000-01-01

    The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. Glucose metabolism was evaluated by an oral glucose tolerance test and an iv...... (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P ... in glucose tolerance, beta-cell response was still inappropriate. Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound changes in kinetics of C-peptide, and insulin and prehepatic insulin secretion, despite...

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.)

  3. Current and emerging therapy for celiac disease

    Directory of Open Access Journals (Sweden)

    Govind K Makharia

    2014-03-01

    Full Text Available AbstractAt present, strict and lifelong gluten free diet is the only effective treatment for celiac disease. Even small amounts of gluten (50mg/day can be immunogenic; therefore all food and food items and drugs that contain gluten and its derivatives must be eliminated completely from the diet. While prescribing gluten free diet is easy; the key to the success is the dietary counseling by a nutrition specialist and maintenance of compliance by the patient. In recent times, a number of targets to halt the process of immunological injury have been explored to find out alternative treatment for celiac disease. These targets include exploration of ancient wheat if they are less immunogenic, intra-luminal digestion of gluten using prolylendopeptidases, pretreatment of whole gluten with bacterial-derived peptidase before ingestion; prevention of passage of immunogenic peptides through the tight junctions such as zonulin antagonists, Blocking of HLA-DQ2 to prevent binding of immunogenic peptides, inhibition of transglutaminase-2, immune-modulation and induction of tolerance to gluten using gluten tolerizing vaccines, use of gluten-sequestering polymers, use of anti-inflammatory drugs (glucocorticoides, budesonides and anti-cytokines such as anti TNF-α, and anti-interleukin-15. While many of these targets are still in the pre-clinical phase, some of them including zonulin antagonist and endopeptidases have already reached phase II and phase III clinical trials. Furthermore, while these targets appears very exciting; they at best are likely to be used as adjunctive therapy rather than a complete replacement for gluten free diet.

  4. Current and emerging therapy for celiac disease.

    Science.gov (United States)

    Makharia, Govind K

    2014-01-01

    At present, strict and lifelong gluten-free diet is the only effective treatment for celiac disease. Even small amounts of gluten (50 mg/day) can be immunogenic; therefore all food and food items and drugs that contain gluten and its derivatives must be eliminated completely from the diet. While prescribing gluten-free diet is easy; the key to the success is the dietary counseling by a nutrition specialist and maintenance of adherence to GFD by the patient. In recent times, a number of targets to halt the process of immunological injury have been explored to find out alternative treatment for celiac disease. These targets include exploration of ancient wheat if they are less immunogenic, intra-luminal digestion of gluten using prolylendopeptidases, pretreatment of whole gluten with bacterial-derived peptidase before ingestion; prevention of passage of immunogenic peptides through the tight junctions such as zonulin antagonists, Blocking of HLA-DQ2 to prevent binding of immunogenic peptides, inhibition of transglutaminase 2, immune-modulation, and induction of tolerance to gluten using gluten tolerizing vaccines, use of gluten-sequestering polymers, use of anti-inflammatory drugs (glucocorticoids, budesonides) and anti-cytokines such as anti TNF-α, and anti-interleukin-15. While many of these targets are still in the pre-clinical phase, some of them including zonulin antagonist and endopeptidases have already reached phase II and phase III clinical trials. Furthermore, while these targets appear very exciting; they at best are likely to be used as adjunctive therapy rather than a complete replacement for gluten-free diet.

  5. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. 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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  10. Study of genomic instability induced by low dose ionizing radiation

    International Nuclear Information System (INIS)

    Seoane, A.; Crudeli, C.; Dulout, F.

    2006-01-01

    The crews of commercial flights and services staff of radiology and radiotherapy from hospitals are exposed to low doses of ionizing radiation. Genomic instability includes those adverse effects observed in cells, several generations after the exposure occurred. The purpose of this study was to analyze the occurrence of genomic instability by very low doses of ionizing radiation [es

  11. 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.

  12. DNA repair in cancer: emerging targets for personalized therapy

    International Nuclear Information System (INIS)

    Abbotts, Rachel; Thompson, Nicola; Madhusudan, Srinivasan

    2014-01-01

    Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Interestingly, in established tumors, DNA repair activity is required to counteract oxidative DNA damage that is prevalent in the tumor microenvironment. Emerging clinical data provide compelling evidence that overexpression of DNA repair factors may have prognostic and predictive significance in patients. More recently, DNA repair inhibition has emerged as a promising target for anticancer therapy. Synthetic lethality exploits intergene relationships where the loss of function of either of two related genes is nonlethal, but loss of both causes cell death. Exploiting this approach by targeting DNA repair has emerged as a promising strategy for personalized cancer therapy. In the current review, we focus on recent advances with a particular focus on synthetic lethality targeting in cancer

  13. 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)

  14. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-11-11

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

  16. An Emerging Theoretical Model of Music Therapy Student Development.

    Science.gov (United States)

    Dvorak, Abbey L; Hernandez-Ruiz, Eugenia; Jang, Sekyung; Kim, Borin; Joseph, Megan; Wells, Kori E

    2017-07-01

    Music therapy students negotiate a complex relationship with music and its use in clinical work throughout their education and training. This distinct, pervasive, and evolving relationship suggests a developmental process unique to music therapy. The purpose of this grounded theory study was to create a theoretical model of music therapy students' developmental process, beginning with a study within one large Midwestern university. Participants (N = 15) were music therapy students who completed one 60-minute intensive interview, followed by a 20-minute member check meeting. Recorded interviews were transcribed, analyzed, and coded using open and axial coding. The theoretical model that emerged was a six-step sequential developmental progression that included the following themes: (a) Personal Connection, (b) Turning Point, (c) Adjusting Relationship with Music, (d) Growth and Development, (e) Evolution, and (f) Empowerment. The first three steps are linear; development continues in a cyclical process among the last three steps. As the cycle continues, music therapy students continue to grow and develop their skills, leading to increased empowerment, and more specifically, increased self-efficacy and competence. Further exploration of the model is needed to inform educators' and other key stakeholders' understanding of student needs and concerns as they progress through music therapy degree programs. © the American Music Therapy Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  17. 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

  18. High versus low-dose rate brachytherapy for cervical cancer.

    Science.gov (United States)

    Patankar, Sonali S; Tergas, Ana I; Deutsch, Israel; Burke, William M; Hou, June Y; Ananth, Cande V; Huang, Yongmei; Neugut, Alfred I; Hershman, Dawn L; Wright, Jason D

    2015-03-01

    Brachytherapy plays an important role in the treatment of cervical cancer. While small trials have shown comparable survival outcomes between high (HDR) and low-dose rate (LDR) brachytherapy, little data is available in the US. We examined the utilization of HDR brachytherapy and analyzed the impact of type of brachytherapy on survival for cervical cancer. Women with stages IB2-IVA cervical cancer treated with primary (external beam and brachytherapy) radiotherapy between 2003-2011 and recorded in the National Cancer Database (NCDB) were analyzed. Generalized linear mixed models and Cox proportional hazards regression were used to examine predictors of HDR brachytherapy use and the association between HDR use and survival. A total of 10,564 women including 2681 (25.4%) who received LDR and 7883 (74.6%) that received HDR were identified. Use of HDR increased from 50.2% in 2003 to 83.9% in 2011 (Puse of HDR. While patients in the Northeast were more likely to receive HDR therapy, there were no other clinical or socioeconomic characteristics associated with receipt of HDR. In a multivariable Cox model, survival was similar between the HDR and LDR groups (HR=0.93; 95% CI 0.83-1.03). Similar findings were noted in analyses stratified by stage and histology. Kaplan-Meier analyses demonstrated no difference in survival based on type of brachytherapy for stage IIB (P=0.68), IIIB (P=0.17), or IVA (P=0.16) tumors. The use of HDR therapy has increased rapidly. Overall survival is similar for LDR and HDR brachytherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Thyroid emergencies following radioiodine therapy - Two case reports

    International Nuclear Information System (INIS)

    Tasmine, Sufia; Haque, Fatema Sultana; Karim, M. A.

    2002-01-01

    Thyrotoxicosis and well differentiated thyroid carcinomas are the two most common pathological conditions where radioiodine is used. Patients with well differentiated thyroid carcinomas are the candidates for post operative radio iodine therapy. It is currently the most popular and frequently used method of treatment. Its use is safe and cost effective. The results are usually eventless but in some exceptional cases emergencies that occurred after administration of I-131. One emergency occurred after I-131 administration for Graves' disease and the second case happened after therapeutic application of I-131 for treatment of local recurrences of thyroid cancer.(author)

  20. Risk of cancer subsequent to low-dose radiation

    International Nuclear Information System (INIS)

    Warren, S.

    1980-01-01

    The author puts low dose irradiation risks in perspective using average background radiation doses for standards. He assailed irresponsible media coverage during the height of public interest in the Three-Mile Island Reactor incident

  1. Radiation effects after low dose chronic long-term exposure

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Friesecke, I.

    1997-01-01

    This document approaches the radiation effects after low dose chronic long-term exposure, presenting examples occurred, the pathophysiologic mechanisms for cell system tolerance in elevated radiation fields, and the diagnostic and therapeutic possibilities

  2. 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)

  3. Development of Plant Application Technique of Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-07-15

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

  4. Low dose rate Ir-192 interstitial brachytherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oki, Yosuke; Dokiya, Takushi; Yorozu, Atsunori; Suzuki, Takayuki; Saito, Shiro; Monma, Tetsuo; Ohki, Takahiro [National Tokyo Medical Center (Japan); Murai, Masaru; Kubo, Atsushi

    2000-04-01

    From December 1997 through January 1999, fifteen prostatic cancer patients were treated with low dose rate Ir-192 interstitial brachytherapy using TRUS and perineal template guidance without external radiotherapy. Up to now, as no apparent side effects were found, the safety of this treatment is suggested. In the future, in order to treat prostatic cancer patients with interstitial brachytherapy using I-125 or Pd-103, more investigation for this low dose rate Ir-192 interstitial brachytherapy is needed. (author)

  5. Development of Plant Application Technique of Low Dose Radiation

    International Nuclear Information System (INIS)

    Chung, Byung Yeoup; Kim, Jae Sung; Lim, Yong Taek

    2007-07-01

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

  6. Review of European research trends of low dose radiation risk

    International Nuclear Information System (INIS)

    Iwasaki, Toshiyasu; Yoshida, Kazuo

    2010-01-01

    Large research projects on low dose radiation effects in Europe and US over the past decade have provided limited scientific knowledge which could underpin the validation of radiation protection systems. Recently in Europe, there have been repeated discussions and dialogues to improve the situation, and as the consequence, the circumstances surrounding low dose radiation risks are changing. In 2009, Multidisciplinary European Low Dose Initiative (MELODI) was established as a trans-national organization capable of ensuring appropriate governance of research in the pursuit of a long term shared vision, and Low Dose Research towards Multidisciplinary Integration (DoReMi) network was launched in 2010 to achieve fairly short term results in order to prove the validity of the MELODI approach. It is expected to be very effective and powerful activities to facilitate the reduction of uncertainties in the understanding of low dose risks, but the regulatory requests rushing the reinforcement of radiological protection regulations based on the precautional principles are more increasing. To develop reasonable radiological protection systems based on scientific evidences, we need to accelerate to collect scientific evidences which could directly underpin more appropriate radiation protection systems even in Japan. For the purpose, we Japan need to develop from an independent standpoint and share as a multidisciplinary vision a long term and holistic research strategy which enables to enhance Japanese advantages such as low dose rate facilities and animal facilities, as soon as possible. (author)

  7. 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

  8. 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)

  9. Low-dose Ketamine Versus Morphine for Acute Pain In the ED: A Randomized Controlled Trial

    Science.gov (United States)

    2015-03-01

    pain [18,27,30,31]. Another unique aspect of this study was the use of the RASS score to capture the cognitive and behavioral effects of the study...pregnant or breast-feeding, history of chronic oxygen-dependent pulmonary disease, hepatic cirrhosis, or dialysis dependent, presence of intracranial...studies have evaluated low-dose ketamine as an adjunct to opioid therapy [29,30], as the sole agent without comparison[27], and in a retrospective

  10. 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)

  11. 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.

  12. Effects of low dose radiation on tumor-bearing mice

    International Nuclear Information System (INIS)

    Feng Li; Hou Dianjun; Huang Shanying; Deng Daping; Wang Linchao; Cheng Yufeng

    2007-01-01

    Objective: To explore the effects of low-dose radiation on tumor-bearing mice and radiotherapy induced by low-dose radiation. Methods: Male Wistar mice were implanted with Walker-256 sarcoma cells in the right armpit. On day 4, the mice were given 75 mGy whole-body X-ray radiation. From the fifth day, tumor volume was measured, allowing for the creation of a graph depicting tumor growth. Lymphocytes activity in mice after whole-body X-ray radiation with LDR was determinned by FCM. Cytokines level were also determined by ELISA. Results: Compared with the radiotherapy group, tumor growth was significantly slower in the mice pre-exposed to low-dose radiation (P<0.05), after 15 days, the average tumor weight in the mice pre- exposed to low-dose radiation was also significantly lower (P<0.05). Lymphocytes activity and the expression of the CK in mice after whole-body y-ray radiation with LDR increased significantly. Conclusions: Low-dose radiation can markedly improve the immune function of the lymphocyte, inhibit the tumor growth, increase the resistant of the high-dose radiotherapy and enhance the effect of radiotherapy. (authors)

  13. 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

  14. Pharmacotherapy for uveitis: current management and emerging therapy

    Science.gov (United States)

    Barry, Robert J; Nguyen, Quan Dong; Lee, Richard W; Murray, Philip I; Denniston, Alastair K

    2014-01-01

    Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual function for patients with the minimum possible side effects. PMID:25284976

  15. Emerging therapies for Clostridium difficile infection – focus on fidaxomicin

    Directory of Open Access Journals (Sweden)

    Chaparro-Rojas F

    2013-06-01

    Full Text Available Fredy Chaparro-Rojas, Kathleen M MullaneDepartment of Medicine, Section of Infectious Diseases, University of Chicago, Chicago, IL, USAAbstract: The epidemiology of Clostridium difficile infections (CDI has evolved during the last decades, with an increase in the reported incidence, severity of cases, and rate of mortality and relapses. These increases have primarily affected some special populations including the elderly, patients requiring concomitant antibiotic therapy, patients with renal failure, and patients with cancer. Until recently, the treatment of CDI was limited to either metronidazole or vancomycin. New therapeutic options have emerged to address the shortcomings of current antibiotic therapy. Fidaxomicin stands out as the first-in-class oral macrocyclic antibiotic with targeted activity against C. difficile and minimal collateral damage on the normal colonic flora. Fidaxomicin has demonstrated performance not inferior to what is considered the “gold standard” available therapy for CDI, vancomycin, in two separate Phase III clinical trials, but with significant advantages, including fewer recurrences and higher rates of sustained clinical cures. Fidaxomicin constitutes an important development in targeted antibiotic therapy for CDI and must be considered as a first-line agent for patients with risk factors known to portend relapse and severe infection.Keywords: fidaxomicin, Clostridium difficile-associated diarrhea, CDAD, Clostridium difficile infection (CDI, vancomycin, metronidazole

  16. Emergency interventional therapy of peripheral arterial stenosis and thrombosis

    International Nuclear Information System (INIS)

    Cai Fengquan; Yu Xixiang

    2004-01-01

    Objective: To evaluate the clinical value of emergency interventional therapy of stenosis and thrombosis of peripheral arteries. Methods: 26 patients suffered from stenosis and thrombosis of peripheral arteries including, 3 subclavical arteries, 5 iliac arteries, 7 femoral arteries, 4 popliteal arteries, 4 posterior or anterior tibial arteries, 2 graft vessels and 1 instent restenosis were undertaken interventional ATD or urokinase infusion thrombolysis, percutanous transluminal angioplasty (PTA) and stent placement. Results: The stenotic arteries were recanalized after PTA or stent placement and the thrombosis vanished after thrombolysis with distal flowes improved or resumed. Clinical symptom was ameliorated. No more complication occurred except one patient with alimentary hemorrhage after thrombolysis. The patients were followed up from 1 to 20 months with all the involved arteries keeping in constant patency without any amputation. Conclusions: Emergency thrombolysis by machine or drug along with PTA or stent placement can effectively cure the stenosis or thrombosis of peripheral artery with recanalization and no amputation. (authors)

  17. 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)

  18. 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.

  19. Low doses of arsenic, via perturbing p53, promotes tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ganapathy, Suthakar, E-mail: s.ganapathy@neu.edu [Center for Drug Development, Northeastern University, Boston (United States); Li, Ping [The First Affiliated Hospital, Zhengzhou University, Zhengzhou (China); The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden); Fagman, Johan [The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden); Yu, Tianqi; Lafontant, Jean [Center for Drug Development, Northeastern University, Boston (United States); Zhang, Guojun [The First Affiliated Hospital, Zhengzhou University, Zhengzhou (China); Chen, Changyan [Center for Drug Development, Northeastern University, Boston (United States); The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg (Sweden)

    2016-09-01

    In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.

  20. Low doses of arsenic, via perturbing p53, promotes tumorigenesis

    International Nuclear Information System (INIS)

    Ganapathy, Suthakar; Li, Ping; Fagman, Johan; Yu, Tianqi; Lafontant, Jean; Zhang, Guojun; Chen, Changyan

    2016-01-01

    In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.

  1. 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)

  2. Low-Dose Risk, Decisions, and Risk Communication

    International Nuclear Information System (INIS)

    Flynn, James; Slovic, Paul

    2001-01-01

    To conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low dose exposures. This involves the study of existing knowledge and the evaluation of science information presented within a variety of formats, as educational information, news media stories, and alternative communication methods (personal contact, small group interaction, email and internet, etc.). Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low- dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

  3. 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.)

  4. 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)

  5. 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.

  6. The researches on the effects of low doses irradiation

    International Nuclear Information System (INIS)

    2009-02-01

    All research conducted as part of 'Risc-Rad' and those conducted by actors in international programs on low doses allow progress in understanding mechanisms of carcinogenesis associated with irradiation. The data do not question the use in radiation protection, risk estimation models based on a linear increase of the risk with the dose of radiation. Nevertheless, they show that the nature of biological responses induced by low doses of radiation has differences with the responses induced by high doses of radiation. They also show the diversity of effects/dose relationships as the mechanism observed and the importance of genetic predisposition in the individual sensitivity to low doses of radiation. It is therefore essential to continue to bring new data to better understand the complex biological effects and their impact on the establishment of radiation protection standards. In addition, the results have often been at the cellular level. The diversity of responses induced by radiations is also a function of cell types observed, the aging of cells and tissue organization. It is essential to strengthen researches at the tissue and body level, involving in vitro and in vivo approaches while testing the hypothesis in epidemiology with a global approach to systems biology. Over the past four years, the collaboration between partners of 'Risc-Rad' using experimental biology approaches and those using mathematical modeling techniques aimed at developing a new model describing the carcinogenesis induced by low radiation doses. On an other hand, The High level expert group on European low dose risk research (H.L.E.G.) develop programmes in the area of low dose irradiation (Germany, Finland, France, Italy and United Kingdom). It proposed a structure of trans national government called M.E.L.O.D.I. ( multidisciplinary european low dose initiative). Its objective is to structure and integrate European research by gathering around a common programme of multidisciplinary

  7. 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)

  8. 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)

  9. Low-dose budesonide treatment improves lung function in patients with infrequent asthma symptoms at baseline

    DEFF Research Database (Denmark)

    Reddel, H. K.; Busse, W. W.; Pedersen, Søren

    2015-01-01

    symptom frequency groups (Figure). CONCLUSIONS: Long-term, once-daily, low-dose budesonide treatment plus usual asthma medication improves lung function in patients with mild, recent-onset asthma. These beneficial effects were seen even in patients with the lowest baseline asthma symptom frequency (0......RATIONALE: Inhaled corticosteroids (ICS) are highly effective in low doses for improving asthma outcomes, including lung function. In the past, ICS treatment was recommended for patients with 'persistent' asthma, defined by symptoms >2 days/week.1 However, evidence is lacking for the benefit of ICS...... in patients with less frequent symptoms at presentation. This was investigated in a post-hoc analysis of the multinational inhaled Steroid Treatment As Regular Therapy in early asthma (START) study.2 METHODS: Patients aged 4-66 years (median 21 years) with a history of recent-onset mild asthma (11 years...

  10. 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.

  11. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Morris, W. James, E-mail: jmorris@bccancer.bc.ca [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Tyldesley, Scott [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Rodda, Sree [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Halperin, Ross [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Centre for the Southern Interior, Vancouver, British Columbia (Canada); Pai, Howard [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Island Centre, Vancouver, British Columbia (Canada); McKenzie, Michael; Duncan, Graeme [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Morton, Gerard [Department of Radiation Oncology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Hamm, Jeremy [Department of Population Oncology, BC Cancer Agency, Vancouver, British Columbia (Canada); Murray, Nevin [BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Department of Medicine, University of British Columbia, Vancouver, British Columbia (Canada)

    2017-06-01

    Purpose: To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer. Methods and Materials: ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Of the 398 trial subjects, 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost. The median follow-up was 6.5 years. Results: In an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (multivariable analysis [MVA] hazard ratio [HR] 2.04; P=.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86%, and 83% for the LDR-PB boost versus 84%, 75%, and 62% for the DE-EBRT boost (log-rank P<.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Because the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow-up. On MVA, the only variables correlated with reduced overall survival were age (MVA HR 1.06/y; P=.004) and biochemical failure (MVA HR 6.30; P<.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant overall survival difference was observed between the treatment arms (MVA HR 1.13; P=.62). Conclusions: Compared with 78 Gy EBRT, men randomized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years.

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

    International Nuclear Information System (INIS)

    Yamaoka, K.; Nomura, T.; Kojima, S.

    2000-01-01

    -like analgesic effects were observed, suggesting that these change constitute part of the mechanisms of the radon spring therapy on the above conditions. In conclusion, we clarified that adequate oxygen stress induced by low dose radiation activates chemical biological protective function, such as induction of the synthesis of SOD and GSHP x . It is possible that activation of these mechanisms alleviates in vivo oxidation injuries resulting in alleviation of pathologic condition, such as symptoms of diabetes mellitus. Namely, adequate activation of the functions of the living body by low dose radiation can contribute to suppressing aging and to preventing or reducing diseases which are thought to involve peroxidation and have been regarded as diseases for which radon spring water is an effective treatment. (author)

  13. Emerging genetic therapies to treat Duchenne muscular dystrophy

    Science.gov (United States)

    Nelson, Stanley F.; Crosbie, Rachelle H.; Miceli, M. Carrie; Spencer, Melissa J.

    2010-01-01

    Purpose of review Duchenne muscular dystrophy is a progressive muscle degenerative disease caused by dystrophin mutations. The purpose of this review is to highlight two emerging therapies designed to repair the primary genetic defect, called `exon skipping' and `nonsense codon suppression'. Recent findings A drug, PTC124, was identified that suppresses nonsense codon translation termination. PTC124 can lead to restoration of some dystrophin expression in human Duchenne muscular dystrophy muscles with mutations resulting in premature stops. Two drugs developed for exon skipping, PRO051 and AVI-4658, result in the exclusion of exon 51 from mature mRNA. They can restore the translational reading frame to dystrophin transcripts from patients with a particular subset of dystrophin gene deletions and lead to some restoration of dystrophin expression in affected boys' muscle in vivo. Both approaches have concluded phase I trials with no serious adverse events. Summary These novel therapies that act to correct the primary genetic defect of dystrophin deficiency are among the first generation of therapies tailored to correct specific mutations in humans. Thus, they represent paradigm forming approaches to personalized medicine with the potential to lead to life changing treatment for those affected by Duchenne muscular dystrophy. PMID:19745732

  14. Late effects of low-dose ionizing radiation on man

    International Nuclear Information System (INIS)

    Brilliant, M.D.; Vorob'ev, A.I.; Gogin, E.E.

    1987-01-01

    One of the most important problems, being stated before the medicine by the accident, which took place in Chernobyl in 1986- the problem of the so-called ionizing radiation low dose effect on a man's organism, is considered because a lot of people were subjected to low dose action. The concept of low doses of radiaion action and specificity of its immediate action in comparison with high dose action is considered. One of the most important poit while studying low dose action is the necessity to develop a system including all irradiated people and dosimetry, and espicially to study frequencies and periods of tumor appearance in different irradiated tissues. The results obtained when examining people who survived the atomic explosion in Japan and on the Marshall islands are analyzed. They testify to the fact that radiation affets more tissues than the clinical picture about the acute radiation sickness tells, and that tumors developing in them many years after radiation action tell about radiosensitivity in some tissues

  15. Use of combined paracetamol and low dose ketamine in pain ...

    African Journals Online (AJOL)

    Objective: To determine the effectiveness of Paracetamol and low dose Ketamine in controlling burn pain during dressings. Setting: The burns ward of Moi Teaching and Referral Hospital, a 750 bed capacity tertiary centre in Western Kenya. Subjects: Consenting patients were recruited to the study on admission. Babies and ...

  16. Low-dose aspirin and risk of intracranial bleeds

    DEFF Research Database (Denmark)

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

    2017-01-01

    cohort of nonusers of low-dose aspirin at baseline were followed (maximum 14 years, median 5.4 years) to identify incident cases of ICB, with validation by manual review of patient records or linkage to hospitalization data. Using 10,000 frequency-matched controls, adjusted rate ratios (RRs) with 95...

  17. Biological effects of very low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Evseev, V.S.

    1987-01-01

    The paper deals with a qualitative microdosimetric analysis of a new radiobiological phenomenon (physiological reaction of the cell as a whole to very low doses of ionizing radiations). The analysis is aimed at identifying the type of the primary interaction of radiation with the cell and finding its place in the cell

  18. Advance of study on hormesis of low dose radiation

    International Nuclear Information System (INIS)

    Su Liaoyuan

    2003-01-01

    There have been growing interests in recent years over the effects of low doses of ionizing radiation on human. The paper gives a brief review on the LDR studies, which include LDR-induced hormesis and adaptive response, LDR experiments in vivo or in vitro and epidemiologic investigation, and clinical applications of LDR as well

  19. Low dose CT simulation using experimental noise model

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Satori; Zamyatin, Alexander A. [Toshiba Medical Systems Corporation, Tochigi, Otawarashi (Japan); Silver, Michael D. [Toshiba Medical Research Institute, Vernon Hills, IL (United States)

    2011-07-01

    We suggest a method to obtain system noise model experimentally without relying on assumptions on statistical distribution of the noise; also, knowledge of DAS gain and electronic noise level are not required. Evaluation with ultra-low dose CT data (5 mAs) shows good match between simulated and real data noise. (orig.)

  20. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    Science.gov (United States)

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

  1. 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)

  2. Health hazards of low doses of ionizing radiations. Vo. 1

    International Nuclear Information System (INIS)

    El-Naggar, M.A.

    1996-01-01

    Exposure to high doses of ionizing radiation results in clinical manifestations of several disease entities that may be fatal. The onset and severity of these acute radiation syndromes are deterministic in relation to dose magnitude. Exposure to ionizing radiations at low doses and low dose rates could initiate certain damage in critical molecules of the cell, that may develop in time into serious health effects. The incidence of such delayed effects in low, and is only detectable through sophisticated epidemiological models carried out on large populations. The radiation damage induced in critical molecules of cells may develop by stochastic biochemical mechanisms of repair, residual damage, adaptive response, cellular transformation, promotion and progression into delayed health effects, the most important of which is carcinogenesis. The dose response relationship of probabilistic stochastic delayed effects of radiation at low doses and low dose rates, is very complex indeed. The purpose of this review is to provide a comprehensive understanding of the underlying mechanisms, the factors involved, and the uncertainties encountered. Contrary to acute deterministic effects, the occurrence of probabilistic delayed effects of radiation remains to be enigmatic. 7 figs

  3. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Engelward, Bevin P. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2009-09-16

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

  5. 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.

  6. Personal dosimetry statistics and specifics of low dose evaluation

    International Nuclear Information System (INIS)

    Avila, R.E.; Gómez Salinas, R.A.; Oyarzún Cortés, C.H.

    2015-01-01

    The dose statistics of a personal dosimetry service, considering 35,000+ readings, display a sharp peak at low dose (below 0.5 mSv) with skewness to higher values. A measure of the dispersion is that approximately 65% of the doses fall below the average plus 2 standard deviations, an observation which may prove helpful to radiation protection agencies. Categorizing the doses by the concomitant use of a finger ring dosimeter, that skewness is larger in the whole body, and ring dosimeters. The use of Harshaw 5500 readers at high gain leads to frequent values of the glow curve that are judged to be spurious, i.e. values not belonging to the roughly normal noise over the curve. A statistical criterion is shown for identifying those anomalous values, and replacing them with the local behavior, as fit by a cubic polynomial. As a result, the doses above 0.05 mSv which are affected by more than 2% comprise over 10% of the data base. The low dose peak of the statistics, above, has focused our attention on the evaluation of LiF(Mg,Ti) dosimeters exposed at low dose, and read with Harshaw 5500 readers. The standard linear procedure, via an overall reader calibration factor, is observed to fail at low dose, in detailed calibrations from 0.02 mSv to 1 Sv. A significant improvement is achieved by a piecewise polynomials calibration curve. A cubic, at low dose is matched, at ∼10 mSv, in value and first derivative, to a linear dependence at higher doses. This improvement is particularly noticeable below 2 mSv, where over 60% of the evaluated dosimeters are found. (author)

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

    Directory of Open Access Journals (Sweden)

    Abhijit Kanti Dam

    2008-01-01

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

  8. 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)

  9. A Paradigm Shift in Low Dose Radiation Biology

    Directory of Open Access Journals (Sweden)

    Z. Alatas

    2015-08-01

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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Response of human fibroblasts to low dose rate gamma irradiation

    International Nuclear Information System (INIS)

    Dritschilo, A.; Brennan, T.; Weichselbaum, R.R.; Mossman, K.L.

    1984-01-01

    Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to γ radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase inthe terminal slope (D 0 ) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury

  18. Low dose CT in early lung cancer diagnosis: prevalence data

    International Nuclear Information System (INIS)

    Cardinale, Luciano; Cortese, Giancarlo; Ferraris, Fabrizio; Perotto, Fabio; Fava, Cesare; Borasio, Piero; Dogliotti, Luigi; Novello, Silvia; Scagliotti, Giorgio

    2005-01-01

    Purpose. Lung cancer has a high mortality rate and its prognosis largely depends on early detection. We report the prevalence data of the study on early detection of lung cancer with low-dose spiral CT underway at our hospital. Materials and methods. Since the beginning of 2001, 519 asymptomatic volunteers have undergone annual blood tests, sputum tests, urinalyses and low-dose spiral CT. The inclusion criteria were age (55 years old), a history of cigarette smoking and a negative history for previous neoplastic disease. The diagnostic workup varied depending on the size and CT features of the nodules detected. Results. At baseline, the CT scan detected nodules> 5 mm in 22% of subjects; the nodules were single in 42 and multiple in 71. In 53% of cases the findings were completely negative, while in 122 (23.4%) nodules with a diameter [it

  19. Low-Dose Aspirin for the Prevention of Preeclampsia.

    Science.gov (United States)

    Fantasia, Heidi Collins

    2018-02-01

    Preeclampsia is a hypertensive disorder specific to pregnancy that remains a significant cause of maternal and neonatal morbidity and mortality. Identification of women who are most at risk for preeclampsia is imprecise. Because of the potential negative health consequences of preeclampsia for women and newborns and the lack of effective screening mechanisms preventing preeclampsia is an important component of prenatal care. Researchers have documented that low-dose aspirin, taken daily after the first trimester, can decrease the development of preeclampsia and reduce the incidence of preterm birth and birth of small-for-gestational-age infants. This column includes an overview of low-dose aspirin in pregnancy and a review of current recommendations from leading national organizations. © 2018 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

  20. The assessment of the carcinogenic effects of low dose radiation

    International Nuclear Information System (INIS)

    Tubiana, M.; Lafuma, J.; Masse, R.; Latarjet, R.

    1991-01-01

    It is concluded that the exclusion of patients for the purposes of risk estimation, the choice of a particular relative risk projection model and of a dose reduction factor equal to 2 are all decisions which result in an overestimation of the actual risk. These choices can be understood when the aim is radiation protection and when it is safer to overestimate the risk; however, they are open to criticism if the aim is a realistic assessment of the risk. For low doses, below 50 mSv/year, and when all causes of uncertainty are added, the actual risk might be markedly lower than the risk estimated with the ICRP (1991) carcinogenic risk coefficient and the DRF estimated by ICRP. Future studies should aim at providing direct and more precise assessments of risk coefficients in the low dose region. (Author)

  1. Gamma regularization based reconstruction for low dose CT

    International Nuclear Information System (INIS)

    Zhang, Junfeng; Chen, Yang; Hu, Yining; Luo, Limin; Shu, Huazhong; Li, Bicao; Liu, Jin; Coatrieux, Jean-Louis

    2015-01-01

    Reducing the radiation in computerized tomography is today a major concern in radiology. Low dose computerized tomography (LDCT) offers a sound way to deal with this problem. However, more severe noise in the reconstructed CT images is observed under low dose scan protocols (e.g. lowered tube current or voltage values). In this paper we propose a Gamma regularization based algorithm for LDCT image reconstruction. This solution is flexible and provides a good balance between the regularizations based on l 0 -norm and l 1 -norm. We evaluate the proposed approach using the projection data from simulated phantoms and scanned Catphan phantoms. Qualitative and quantitative results show that the Gamma regularization based reconstruction can perform better in both edge-preserving and noise suppression when compared with other norms. (paper)

  2. Low-dose effects hypothesis and observations on NPP personal

    Energy Technology Data Exchange (ETDEWEB)

    Georgieva, R.; Acheva, A.; Boteva, R.; Chobanova, N.; Djounova, J.; Gyuleva, I.; Ivanova, K.; Kurchatova, G.; Milchev, A.; Negoicheva, K.; Nikolov, V.; Panova, D.; Pejankov, I.; Rupova, I.; Stankova, K.; Zacharieva, E. [Radiobiology Department, National Centre of Radiobiology and Radiation Protection, Sofia (Bulgaria)

    2013-07-01

    In the modern world the use of various sources of ionizing radiation is nearly ubiquitous. They have numerous applications in industry, medicine, science, agriculture, etc. Radiation doses to workers nevertheless are commensurable to the natural background exposure. Published data on the health effects of occupational radiation exposure are often contradictory. Addressing the issue of „negative” (bystander effects, genomic instability) and „positive” (adaptive response, radiation hormesis) effects of low doses is important and has a significant social and economic impact. In this paper we summarize the results of our extensive monitoring of nuclear power plant (NPP) staff. We believe it is a cohort suitable for analysis of health effects at low doses, because of their good medical and dosimetric control. Our results rather support the idea of absence of adverse health effects in NPP workers. (author)

  3. Effect of low-dose radiation on ocular circulation

    International Nuclear Information System (INIS)

    Baba, Keiko; Hiroishi, Goro; Honda, Masae; Yoshikawa, Hiroshi; Fujisawa, Kimihiko; Ishibashi, Tatsuro

    1999-01-01

    We treated 6 eyes of unilateral age-related macular degeneration by low-dose radiation. Each eye received daily dose of 2 Gy by 4MV lineac totalling 20 Gy over 2 weeks. Color doppler flowmetry was used to determine the mean blood flow velocity (Vmean) and vascular resistive index (RI) in the short posterior ciliary artery, central retinal artery and ophthalmic artery in the treated and fellow eyes before and up to 6 months of treatment. There were no significant differences in Vmean and RI before and after treatment. The findings show the absence of apparent influence of low-dose radiation on the ocular circulation in age-related macular degeneration. (author)

  4. Effect of low-dose radiation on ocular circulation

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Keiko; Hiroishi, Goro; Honda, Masae; Yoshikawa, Hiroshi; Fujisawa, Kimihiko; Ishibashi, Tatsuro [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1999-05-01

    We treated 6 eyes of unilateral age-related macular degeneration by low-dose radiation. Each eye received daily dose of 2 Gy by 4MV lineac totalling 20 Gy over 2 weeks. Color doppler flowmetry was used to determine the mean blood flow velocity (Vmean) and vascular resistive index (RI) in the short posterior ciliary artery, central retinal artery and ophthalmic artery in the treated and fellow eyes before and up to 6 months of treatment. There were no significant differences in Vmean and RI before and after treatment. The findings show the absence of apparent influence of low-dose radiation on the ocular circulation in age-related macular degeneration. (author)

  5. Low-dose radiation-induced endothelial cell retraction

    International Nuclear Information System (INIS)

    Kantak, S.S.; Onoda, J.M.; Diglio, C.A.; Harper Hospital, Detroit, MI

    1993-01-01

    The data presented here are representative of a series of studies designed to characterize low-dose radiation effects on pulmonary microvascular endothelium. Data suggest that post-irradiation lung injuries (e.g. oedema) may be induced with only a single fraction of therapeutic radiation, and thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than would be suggested by the time course for clinically-detectable oedema. (author)

  6. 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

  7. 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.)

  8. Fruit-flies in low-dose exposure experiments

    International Nuclear Information System (INIS)

    Zajnullin, V.G.; Moskalev, A.A.; Shaposhnikov, M.V.; Sheptyakova, A.I.

    2002-01-01

    In vivo exposure of fruit-flies of Drosophila melanogaster line to low doses provided new data indicating that mechanisms of induced genetic instability are involved in radiation-induced alteration of genotype. It is true for increase of genetic variance due to change in transposition number, for change in adaptation capabilities due to modification of gene expression, and for mutability-associated reparation and apoptosis. (author)

  9. Transportable, Low-Dose Active Fast-Neutron Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mihalczo, John T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wright, Michael C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); McConchie, Seth M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Archer, Daniel E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Palles, Blake A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-08-01

    This document contains a description of the method of transportable, low-dose active fast-neutron imaging as developed by ORNL. The discussion begins with the technique and instrumentation and continues with the image reconstruction and analysis. The analysis discussion includes an example of how a gap smaller than the neutron production spot size and detector size can be detected and characterized depending upon the measurement time.

  10. Biological effects of low doses of ionising radiation

    International Nuclear Information System (INIS)

    Osmak, M.

    1998-01-01

    A study was performed with the aim to examine whether the progeny of cells that had been repeatedly irradiated with low doses of gamma rays will change their sensitivity to cytotoxic agents. Four mammalian cell lines were used in the experiment. It was found that the progeny of cells irradiated in this way do not change their sensitivity to gamma rays but would change their sensitivity to various cytostatics drugs. (A.K.)

  11. Effect of low dose ionizing radiation upon concentration of

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  12. Low dose monitoring by double implant technique in IC fabrication

    International Nuclear Information System (INIS)

    Ahmad, I.B.; Weidemann, J.

    1995-01-01

    The utilisation of low dose implant monitoring (using Boron) in a manufacturing line has been discussed. The utilisation of phosphorus ions as the second implant dose were also studied as comparison. The technique relies on the fact that the sheet resistant of doped layer will increase significantly when damaged by relatively low implant dose. The technique is very sensitive and applicable for adjusting the channel dose so that an accurate threshold voltage in MOS device could be achieved

  13. Global DNA methylation responses to low dose radiation exposure

    International Nuclear Information System (INIS)

    Newman, M.R.; Ormsby, R.J.; Blyth, B.J.; Sykes, P.J.; Bezak, E.

    2011-01-01

    Full text: High radiation doses cause breaks in the DNA which are considered the critical lesions in initiation of radiation-induced cancer. However, at very low radiation doses relevant for the general public, the induction of such breaks will be rare, and other changes to the DNA such as DNA methylation which affects gene expression may playa role in radiation responses. We are studying global DNA methylation after low dose radiation exposure to determine if low dose radiation has short- and/or long-term effects on chromatin structure. We developed a sensitive high resolution melt assay to measure the levels of DNA methylation across the mouse genome by analysing a stretch of DNA sequence within Long Interspersed Nuclear Elements-I (LINE I) that comprise a very large proportion of the mouse and human genomes. Our initial results suggest no significant short-term or longterm) changes in global NA methylation after low dose whole-body X-radiation of 10 J1Gyor 10 mGy, with a significant transient increase in NA methylation observed I day after a high dose of I Gy. If the low radiation doses tested are inducing changes in bal DNA methylation, these would appear to be smaller than the variation observed between the sexes and following the general stress of the sham-irradiation procedure itself. This research was funded by the Low Dose Radiation Research Program, Biological and Environmental Research, US DOE, Grant DE-FG02-05ER64104 and MN is the recipient of the FMCF/BHP Dose Radiation Research Scholarship.

  14. Exercise and Sport Performance with Low Doses of Caffeine

    OpenAIRE

    Spriet, Lawrence L.

    2014-01-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5–13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (

  15. Total Risk Management for Low Dose Radiation Exposures

    International Nuclear Information System (INIS)

    Simic, Z.; Mikulicic, V.; Sterc, D.

    2012-01-01

    Our civilization is witnessing about century of nuclear age mixed with enormous promises and cataclysmic threats. Nuclear energy seems to encapsulate both potential for pure good and evil or at least we humans are able to perceive that. These images are continuously with us and they are both helping and distracting from making best of nuclear potentials for civilization. Today with nuclear use significantly present and with huge potential to further improve our life with energy and medical use it is of enormous importance to try to have calmed, rational, and objective view on potential risks and certain benefits. Because all use of nuclear energy proved that their immediate risks are negligible (i.e., Three Mile Island and Fukushima) or much smaller than from the other alternatives (i.e., Chernobyl) it seems that the most important issue is the amount of risk from the long term effects to people from exposure to small doses of radiation. A similar issue is present in the increased use of modern computational tomography and other radiation sources use in medicine for examination and therapy. Finally, extreme natural exposures are third such potential risk sources. Definition of low doses varies depending on the way of delivery (i.e., single, multiple or continuous exposures), and for this paper usual dose of 100 mSv is selected as yearly upper amount. There are three very different scientifically supported views on the potential risks from the low doses exposure. The most conservative theory is that all radiation is harmful, and even small increments from background levels (i.e., 2-3 mSv) present additional risk. This view is called linear no threshold theory (LNT) and it is accepted as a regulatory conservative simple approach which guarantees safety. Risk is derived from the extrapolation of the measured effects of high levels of radiation. Opposite theory to LNT is hormesis which assumes that in fact small doses of radiation are helpful and they are improving our

  16. 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

  17. MELODI: The 'Multidisciplinary European Low-Dose Initiative'

    International Nuclear Information System (INIS)

    Belli, M.; Salomaa, S.; Ottolenghi, A.

    2011-01-01

    The importance of research to reduce uncertainties in risk assessment of low and protracted exposures is now recognised globally. In Europe a new initiative, called 'Multidisciplinary European Low Dose Initiative' (MELODI), has been proposed by a 'European High Level and Expert Group on low-dose risk research' (www.hleg.de), aimed at integrating national and EC (Euratom) efforts. Five national organisations: BfS (DE), CEA (FR), IRSN (FR), ISS (IT) and STUK (FI), with the support of the EC, have initiated the creation of MELODI by signing a letter of intent. In the forthcoming years, MELODI will integrate in a step-by-step approach EU institutions with significant programmes in the field and will be open to other scientific organisations and stakeholders. A key role of MELODI is to develop and maintain over time a strategic research agenda (SRA) and a road map of scientific priorities within a multidisciplinary approach, and to transfer the results for the radiation protection system. Under the coordination of STUK a network has been proposed in the 2009 Euratom Programme, called DoReMi (Low-Dose Research towards Multidisciplinary Integration), which can help the integration process within the MELODI platform. DoReMi and the First MELODI Open Workshop, organised by BfS in September 2009, are now important inputs for the European SRA. (authors)

  18. Low dose effects detected by micronucleus assay in lymphocytes

    International Nuclear Information System (INIS)

    Koeteles, G.J.; Bojtor, I.; Kubasova, T.; Horvath, G.

    1997-01-01

    The effects of low doses of X-rays between 0.01 and 1 Gy were studied on whole blood samples of various individuals using the cytokinesis-blocked lymphocyte micronucleus assay as an endpoint. The adaptive response could be induced in G 0 cells by 0.01 Gy followed by 1 Gy challenging dose within a time period of 8 hours, in vitro. The probability distribution of micronucleus increments in those samples which had received very low doses in the range 0.01-0.05 Gy proved to be of asymmetrical type (i.e. lognormal) -very likely to the same shape which has been verified for unirradiated (control) population - while the variable turned to be normally distributed at or above 1 Gy. Profound changes have been experienced in the main characteristics of the linear dose - response relationship and in regression parameters, as well, when successively lessened dose ranges were studied toward 0.01 Gy. In the range below ∼ 0.2 Gy the response were found to be unrelated to the absorbed dose. These findings suggest that in (very) low dose range a higher attention should be needed to biological parameters like repair, protective mechanisms and antioxidant capacities, rather than to the absorbed radiation energy only. (author)

  19. Problems linked to effects of ionizing radiations low doses

    International Nuclear Information System (INIS)

    Anon.

    1995-10-01

    The question of exposure to ionizing radiations low doses and risks existing for professional and populations has been asked again, with the recommendations of the International Commission of Radiation Protection (ICRP) to lower the previous standards and agreed as guides to organize radiation protection, by concerned countries and big international organisms. The sciences academy presents an analysis which concerned on epidemiological and dosimetric aspects in risk estimation, on cellular and molecular aspects of response mechanism to irradiation. The observation of absence of carcinogen effects for doses inferior to 200 milli-sieverts and a re-evaluation of data coming from Nagasaki and Hiroshima, lead to revise the methodology of studies to pursue, to appreciate more exactly the effects of low doses, in taking in part, particularly, the dose rate. The progress of molecular and cellular biology showed that the extrapolation from high doses to low doses is not in accordance with actual data. The acknowledge of DNA repair and carcinogenesis should make clearer the debate. (N.C.). 61 refs., 9 annexes

  20. Thermoluminescent dosimeters for low dose X-ray measurements

    International Nuclear Information System (INIS)

    Del Sol Fernández, S.; García-Salcedo, R.; Sánchez-Guzmán, D.; Ramírez-Rodríguez, G.; Gaona, E.; León-Alfaro, M.A. de; Rivera-Montalvo, T.

    2016-01-01

    The response of TLD-100, CaSO_4:Dy and LiF:Mg,Cu,P for a range of X-ray low dose was measured. For calibration, the TLDs were arranged at the center of the X-ray field. The dose output of the X-ray machine was determined using an ACCU-Gold. All dosimeters were exposed at the available air kerma values of 14.69 mGy within a field 10×10 cm"2 at 80 cm of SSD. Results of LiF:Mg,Cu,P X-ray irradiated showed 4.8 times higher sensitivity than TLD-100. Meanwhile, TL response of CaSO_4:Dy exposed at the same dose was 5.6 time higher than TLD-100. Experimental results show for low dose X-ray measurements a better linearity for LiF:Mg,Cu,P compared with that of TLD-100. CaSO_4:Dy showed a linearity from 0.1 to 60 mGy - Highlights: • Low dose X-ray doses for personal dosimetry were measured. • Radiation dose (µGy ) for environmental dosimetry were determined. • Scattering radiation dose were measured by TLDs. • Linearity of pair TLD system was successful in the range of microgray. • Pair TLDs composed by CaSO_4:Dy and by LiF:Mg,Cu,P. is suggested for clinical dosimetry.

  1. Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma

    International Nuclear Information System (INIS)

    Schoenfeld, Gordon O.; Amdur, Robert J.; Schmalfuss, Ilona M.; Morris, Christopher G.; Keole, Sameer R.; Mendenhall, William M.; Marcus, Robert B.

    2006-01-01

    Purpose: To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. Methods and Materials: Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. Results: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. Conclusions: Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element

  2. 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

  3. 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)

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

    Science.gov (United States)

    Spriet, Lawrence L

    2014-11-01

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

  5. 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)

  6. Low dose combined chemotherapy/radiotherapy in the management of locally advanced urethral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Johnson, D.W.; Kessler, J.F.; Ferrigni, R.G.; Anderson, J.D.

    1989-01-01

    The successful treatment of a patient with bulky squamous cell carcinoma of the urethra using low dose preoperative radiation therapy and concurrent chemotherapy is described. Dramatic rapid tumor response facilitated surgical resection of the remaining microscopic disease. This clinical behavior is remarkably similar to that seen with squamous cell carcinoma of the anal canal and esophagus when a similar regimen is used. At the latter tumor sites the successful use of combination radiotherapy and chemotherapy has reduced the morbidity of subsequent surgery, and in selected cases has obviated the need for a radical operation. Further investigation of such combination treatment is warranted for urethral carcinoma

  7. Plants as warning signal for exposure to low dose radiation

    International Nuclear Information System (INIS)

    Rusli Ibrahim; Norhafiz Talib

    2012-01-01

    The stamen-hair system of Tradescantia for flower colour has proven to be one of the most suitable materials to study the frequency of mutations induced by low doses of various ionizing radiations and chemical mutagens. The system has also been used successfully for detecting mutagenic synergisms among chemical mutagens and ionizing radiations as well as for studying the variations of spontaneous mutation frequency. In this study of radiobiology, the main objective is to observe somatic mutation (occurrence of pink cells from blue cells) induced on stamen hairs of five Tradescantia sp. available in Malaysia after exposure to low doses of chronic gamma irradiation using Gamma Green House. Pink cells appeared only on Tradescantia Pallida Purpurea stamen hairs after 13 days of exposure to irradiation with different doses of gamma rays. The highest number of stamens with pink cells was recorded from flowers irradiated with the highest dose of 6.37 Gy with 0.07 Gy/ h of dose rate. The lowest number of stamens with pink cells was recorded with an average of 0.57, irradiated with the lowest dose of 0.91 Gy with 0.01 Gy/ h of dose rate. There were no pink cells observed on Tradescantia Spathaceae Discolor after exposure to different doses of gamma rays. Similar negative results were observed for the control experiments. The principal cells in this assay are the mitotic stamen hair cells developing in the young flower buds. After exposure to radiation, the heterozygous dominant blue character of the stamen hair cell is prevented, resulting in the appearance of the recessive pink color. Furthermore, no pink cell appears on all species of Tradescantia spathaceae after irradiated with different doses of gamma rays. The sensitivity of the Tradescantia has been used widely and has demonstrated the relation between radiation dose and frequency of mutation observed at low doses which can contribute to the effects of low doses and their consequences for human health. This system

  8. Investigations on the effects of low dose irradiation on different bulbous plants

    International Nuclear Information System (INIS)

    Bors, J.; Fendrik, I.

    1983-01-01

    Dormant bulbs, and bulbs with the first emergent leaf, of species of tulip, crocus, iris, scilla, eranthus, galanthus and muscari, were irradiated with low doses of X-rays. Four parameters were investigated when the plants flowered:-plant height, flower number, fresh weight and dry weight. The effects of irradiation of dormant bulbs and one-leaf plants on these four parameters were tabulated for the different species. Results agree with previous experiments and indicate greater radiation effects on plant compared to bulb irradiation. (U.K.)

  9. Nano-aggregates: emerging delivery tools for tumor therapy.

    Science.gov (United States)

    Sharma, Vinod Kumar; Jain, Ankit; Soni, Vandana

    2013-01-01

    A plethora of formulation techniques have been reported in the literature for site-specific targeting of water-soluble and -insoluble anticancer drugs. Along with other vesicular and particulate carrier systems, nano-aggregates have recently emerged as a novel supramolecular colloidal carrier with promise for using poorly water-soluble drugs in molecular targeted therapies. Nano-aggregates possess some inherent properties such as size in the nanometers, high loading efficiency, and in vivo stability. Nano-aggregates can provide site-specific drug delivery via either a passive or active targeting mechanism. Nano-aggregates are formed from a polymer-drug conjugated amphiphilic block copolymer. They are suitable for encapsulation of poorly water-soluble drugs by covalent conjugation as well as physical encapsulation. Because of physical encapsulation, a maximum amount of drug can be loaded in nano-aggregates, which helps to achieve a sufficiently high drug concentration at the target site. Active transport can be achieved by conjugating a drug with vectors or ligands that bind specifically to receptors being overexpressed in the tumor cells. In this review, we explore synthesis and tumor targeting potential of nano-aggregates with active and passive mechanisms, and we discuss various characterization parameters, ex vivo studies, biodistribution studies, clinical trials, and patents.

  10. An update on emerging therapies for urinary tract infections.

    Science.gov (United States)

    Majeed, Aneela; Alarfaj, Sumaiah; Darouiche, Rabih; Mohajer, Mayar

    2017-03-01

    Urinary tract infections (UTIs) are the most common healthcare-acquired infections, and are associated with high morbidity and mortality. Worldwide use of antibiotics has led to a significant rise in resistant uropathogens emanating from both hospitals and communities. The huge concern of multidrug resistance (MDR) has led the Food and Drug Administration (FDA) to encourage drug companies to invest in the development of new antibiotics. Area covered: In this review we summarized data on already approved antibiotics, and selected emerging therapies that are currently in phase II and III trials with emphasis on complicated urinary tract infections (cUTIs). We performed our search using PubMed, ClinicalTrials.gov, Google Scholar and Pharmaprojects. Expert opinion: Efficacious antimicrobials are needed to overcome MDR organisms. There are several dugs in initial and later stages of development, but most of them lack full spectrum of activity against some Gram-negative organisms, particularly against MDR Pseudomonas aeruginosa. Better understanding of the pathogenesis of UTI and genetic engineering of pathogens can provide new drugs to combat resistance in the future.

  11. Low-dose CT: new tool for screening lung cancer?

    International Nuclear Information System (INIS)

    Diederich, S.; Wormanns, D.; Heindel, W.

    2001-01-01

    Lung cancer is the leading cause of death from malignant tumours as it is very common and has a poor prognosis at advanced tumour stages. Prognosis could be improved by treatment at early stages. As these stages are usually asymptomatic, a diagnostic test that would allow detection of early tumour stages in a population at risk could potentially reduce mortality from lung cancer. Previous approaches using chest radiography and sputum cytology in smokers have been disappointing. Fluorescent bronchoscopy and molecular markers are not yet applicable in clinical routine. Because of its high sensitivity for small pulmonary nodules, which are the most common manifestation of early lung cancer, CT appears suitable as a screening test. Low-dose examination parameters can and should be used for this purpose. From clinical practice it is well known that chest CT often demonstrates small pulmonary nodules, which do not represent lung cancer. Therefore, non-invasive diagnostic algorithms are required to avoid unnecessary biopsies in benign lesions. In preliminary studies of low-dose CT using algorithms based on size and density of detected nodules a large proportion of asymptomatic lung cancers and a large proportion of early, resectable tumour stages were found with a small proportion of invasive procedures for benign nodules. Before this technology can be recommended for broad application, however, further information is required regarding appropriate inclusion criteria (smoking habits, age groups) and screening intervals. Most importantly, further data are required to clarify whether lung cancer screening using low-dose CT can actually reduce mortality from lung cancer. (orig.)

  12. Development of new chemical dosimeter for low dose range

    International Nuclear Information System (INIS)

    Mhatre, Sachin G.V.; Adhikari, S.

    2012-01-01

    Accurate measurement of low dose radiation in complex systems is of utmost importance in radiation biology and related areas. Ferrous Benzoic acid Xylenol orange (FBX) system is being widely used for measurement of low dose gamma radiation because of its reproducibility and precision. However, an additional step, i.e., dissolution of benzoic acid in water at higher temperature followed by cooling at room temperature is involved for the preparation of this dosimeter. This makes it inconvenient as a ready to use dosimeter. In the present work, the organic molecule, sorbitol has been used for measurement of low doses of radiation. The advantages of using sorbitol are its ready availability and instantaneous water solubility. Owing to its dissolution at room temperature, possible errors those are involved in calculation of dose due to thermal oxidation of ferrous ions during preparation of the FBX dosimetric solution could be made insignificant in the proposed dosimeter. In the present system, sorbitol acts as radiolytic sensitizer for the oxidation of ferrous ion, and xylenol orange forms a 1:1 complex specifically with ferric ions. Thus, the analytical detection limit of ferric ions is enhanced compared to other systems. Final composition of the dosimetric solution is; 0.5 mol/m 3 xylenol orange, 10 mol/m 3 sorbitol and 0.2 mol/m 3 ferrous ion in 50 mol/m 3 sulfuric acid. Radiolytic sensitization in combination with analytical enhancement of the ferrous based system, allows us to measure radiation dose in the range of 0.05 Gy–12 Gy with ease and high reproducibility.

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

    LENUS (Irish Health Repository)

    Martin, Lynn M

    2014-07-10

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-19

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

  15. Effect of low doses of ionizing radiation on human health

    International Nuclear Information System (INIS)

    Kovalenko, A.N.

    1990-01-01

    Data are reported on the possible mechanism of biological effects of low doses of ionizing radiation on the human body. The lesioning effect of this radiation resulted in some of the persons in the development of disorders of the function of information and vegetative-regulatory systems determined as a desintegration syndrome. This syndrome is manifested in unspecific neuro-vegetative disorders of the function of most important physiological and homeostatic system of the body leading to weakening of the processes of compensation and adaptation. This condition is characterized by an unspecific radiation syndrome as distinct from acute or chronic radiation disease which is a specific radiation syndrome

  16. Low-Dose Radiation Induces Genes Promoting Cell Survival

    International Nuclear Information System (INIS)

    Liu, Shu-Zheng; Chen, Dong; Mu, Ying

    1999-01-01

    Apoptosis is an important process controlling homeostasis of the body. It is influenced by stimuli constantly arising from the external and internal environment of the organism. It is well known that radiation could induce apoptosis of cells in vitro and in vivo. However, the dose-effect relationship of apoptosis extending to the low-dose range has scarcely been studied. Here, the molecular basis of the phenomenon is explored by examining the changes in expression of some of the proapoptotic and antiapoptotic genes

  17. Anti-tumor effect of low dose radiation in mice

    International Nuclear Information System (INIS)

    Fan Zhengping; Lu Jiaben; Zhu Bingchai

    1997-01-01

    The author reports the effects of the total body irradiation of low dose radiation (LDR) and/or the local irradiation of large dose on average tumor weights and tumor inhibitory rates in 170 mice inoculated S 180 sarcoma cell, and the influence of LDR on average longevity in 40 tumor-bearing animals. Results show (1) LDR in the range of 75∼250 mGy can inhibit tumor growth to some extent; (2) fractionated irradiation of 75 mGy and local irradiation of 10 Gy may produce a synergism in tumor growth inhibition; and (3)LDR may enhance average longevity in ascitic tumor-bearing mice

  18. Uterine malignant degeneration after low-dose endometrial irradiation

    International Nuclear Information System (INIS)

    Nikkanen, V.; Salmi, T.; Groenroos, M.

    1980-01-01

    The effectiveness of low-dose intrauterine irradiation for benign diseases and its possible carcinogenic effect on the uterus was studied in 190 patients who were treated during the years 1952-1974. The indications for irradiation were premenopausal functional bleeding, leukemia, hemophilia, fibroids, endometriosis or other benign reason. Radiation was also performed on patients with severe neurologic diseases that contraindicated surgery and on some mentally retarded patients whose restlessness and epileptic seizures were aggravated premenstrually and during menstruation. The mean follow-up period was 15 years. Uterine bleeding recurred in 21 percent of the patients. No cases of uterine malignant degeneration were found. (author)

  19. From Chernobyl to Fukushima: the effect of low doses

    International Nuclear Information System (INIS)

    Aurengo, A.

    2011-01-01

    This Power Point presentation describes the Fukushima's reactors, recalls some data about the earthquake and tsunami, and indicates their consequences for the operation of the power station (notably the loss of cooling means). It identifies some design errors for the Chernobyl's and Fukushima's power stations, outlines differences between these two cases. It gives assessment of doses receives by external irradiation around Fukushima, of the dose rate evolution, of the sea contamination. It gives some data about the Chernobyl accident (radioactivity evolution). After some data about health consequences of Chernobyl, health risks and more particularly biological risks associated to low doses are described. Protection measures are evoked, as well as psycho-social impacts

  20. Application of low dose radiation for preservation of sea foods

    International Nuclear Information System (INIS)

    Venugopal, V.; Nair, P.M.

    1994-01-01

    Treatment of food with low doses of gamma radiation has been recognized to have two main advantages. These consist of: (1) improvement of food safety by elimination of pathogens and (2) reduction of microbial spoilage and extension of shelf life of perishable items by reducing the number of viable spoilage organisms. Studies during the last few decades have conclusively proved the beneficial effects of radiation with respect to fishery products. The three potential areas of application to fish products include: (i) radurization for shelf life extension (ii) radicidation to eliminate food borne pathogens in the products and (iii) radiation treatment to dried products to control insects

  1. 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

  2. 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.

  3. 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

  4. Randomized Controlled Trial of Low-Dose Estradiol and the SNRI Venlafaxine for Vasomotor Symptoms

    Science.gov (United States)

    Joffe, Hadine; Guthrie, Katherine A.; LaCroix, Andrea Z.; Reed, Susan D.; Ensrud, Kristine E.; Manson, JoAnn E.; Newton, Katherine M.; Freeman, Ellen W.; Anderson, Garnet L.; Larson, Joseph C.; Hunt, Julie; Shifren, Jan; Rexrode, Kathryn M.; Caan, Bette; Sternfeld, Barbara; Carpenter, Janet S.; Cohen, Lee

    2014-01-01

    Importance Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine is used widely as a non-hormonal treatment. While clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial. Objective To determine the efficacy and tolerability of low-dose oral 17-beta-estradiol and low-dose venlafaxine XR in alleviating vasomotor symptoms. Design and Participants 339 peri- and postmenopausal women with ≥2 bothersome vasomotor symptoms per day (mean 8.1, SD 5.3/day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites November 2011—October 2012. Interventions Participants were randomized to double-blinded treatment with low-dose oral 17-beta-estradiol 0.5-mg/day (n=97), low-dose venlafaxine XR 75-mg/day (n=96), or placebo (n=146) for 8 weeks. Main Outcomes Primary outcome was the mean daily frequency of vasomotor symptoms after 8 weeks of treatment. Secondary outcomes were vasomotor symptom severity, bother and interference. Intent-to-treat analyses compared change in vasomotor symptom frequency between each active intervention and placebo and between the two active treatments. Results Compared to baseline, mean vasomotor symptom frequency at week 8 decreased by 53% with estradiol, 48% with venlafaxine, and 29% with placebo. Estradiol reduced the frequency of symptoms by 2.3 (95% CI 1.3–3.4) more per day than placebo (p<0.001), and venlafaxine by 1.8 (95% CI 0.8–2.7) more per day than placebo (p=0.005). Results were consistent for VMS severity, bother and interference. Low-dose estradiol reduced symptom frequency by 0.6 more per day than venlafaxine (95% CI, 1.8 more per day to 0.6 fewer per day than

  5. Biologically based modelling and simulation of carcinogenesis at low doses

    International Nuclear Information System (INIS)

    Ouchi, Noriyuki B.

    2003-01-01

    The process of the carcinogenesis is studied by computer simulation. In general, we need a large number of experimental samples to detect mutations at low doses, but in practice it is difficult to get such a large number of data. To satisfy the requirements of the situation at low doses, it is good to study the process of carcinogenesis using biologically based mathematical model. We have mainly studied it by using as known as 'multi-stage model'; the model seems to get complicated, as we adopt the recent new findings of molecular biological experiments. Moreover, the basic idea of the multi-stage model is based on the epidemiologic data of log-log variation of cancer incidence with age, it seems to be difficult to compare with experimental data of irradiated cell culture system, which has been increasing in recent years. Taking above into consideration, we concluded that we had better make new model with following features: 1) a unit of the target system is a cell, 2) the new information of the molecular biology can be easily introduced, 3) having spatial coordinates for checking a colony formation or tumorigenesis. In this presentation, we will show the detail of the model and some simulation results about the carcinogenesis. (author)

  6. Low-dose aripiprazole for refractory burning mouth syndrome

    Directory of Open Access Journals (Sweden)

    Umezaki Y

    2016-05-01

    Full Text Available Yojiro Umezaki,1 Miho Takenoshita,2 Akira Toyofuku2 1Psychosomatic Dentistry Clinic, Dental Hospital, 2Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan Abstract: We report a case of refractory burning mouth syndrome (BMS ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. Keywords: burning mouth syndrome, low-dose aripiprazole, chronic pain

  7. Low doses of neutrons induce changes in gene expression

    International Nuclear Information System (INIS)

    Woloschak, G.E.; Chang-Liu, C.M.; Panozzo, J.; Libertin, C.R.

    1993-01-01

    Studies were designed to identify genes induced following low-dose neutron but not following γ-ray exposure in fibroblasts. Our past work had shown differences in the expression of β-protein kinase C and c-fos genes, both being induced following γ-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not γ-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to γ rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure

  8. Development of microcontroller based instrumentation for low dose implantation

    International Nuclear Information System (INIS)

    Suresh, K.; Saravanan, K.; Panigrahi, B.K.; Nair, K.G.M.

    2011-01-01

    In experiments like ion implantation based ion track formations, the sample is implanted to low doses of the order of 10 10 ions/cm 2 , limiting the ion beam currents to be less than 1-5 x 10 -12 A. However the standard current integrators available are not sensitive to very low currents, causing an unacceptable high level of error in dose measurement. Hence a low dose implantation measurement system has been developed. It consists of a very sensitive low current preamplifier with full scale input 1nA/100pA, a standard current integrator, a microcontroller based interface circuit, which are connected to a personal computer(PC) through USB. Two types of the software are developed for the system: the microcontroller firmware using C and windows based virtual instrument programs using LabVIEW 7.0. Necessary precautions associated with pA level measurement like rigidly fastened good quality cables, low ripple DC power supply, shielding, close mounting of the preamplifier to the sample are adopted. After necessary calibrations with an ECIL make low current source, the system has been put into regular use. Design and development details, salient features are discussed in this paper. (author)

  9. Exposures at low doses and biological effects of ionizing radiations

    International Nuclear Information System (INIS)

    Masse, R.

    2000-01-01

    Everyone is exposed to radiation from natural, man-made and medical sources, and world-wide average annual exposure can be set at about 3.5 mSv. Exposure to natural sources is characterised by very large fluctuations, not excluding a range covering two orders of magnitude. Millions of inhabitants are continuously exposed to external doses as high as 10 mSv per year, delivered at low dose rates, very few workers are exposed above the legal limit of 50 mSv/year, and referring to accidental exposures, only 5% of the 116 000 people evacuated following the Chernobyl disaster encountered doses above 100 mSv. Epidemiological survey of accidentally, occupationally or medically exposed groups have revealed radio-induced cancers, mostly following high dose-rate exposure levels, only above 100 mSv. Risk coefficients were derived from these studies and projected into linear models of risk (linear non-threshold hypothesis: LNT), for the purpose of risk management following exposures at low doses and low dose-rates. The legitimacy of this approach has been questioned, by the Academy of sciences and the Academy of medicine in France, arguing: that LNT was not supported by Hiroshima and Nagasaki studies when neutron dose was revisited; that linear modelling failed to explain why so many site-related cancers were obviously nonlinearly related to the dose, and especially when theory predicted they ought to be; that no evidence could be found of radio-induced cancers related to natural exposures or to low exposures at the work place; and that no evidence of genetic disease could be shown from any of the exposed groups. Arguments were provided from cellular and molecular biology helping to solve this issue, all resulting in dismissing the LNT hypothesis. These arguments included: different mechanisms of DNA repair at high and low dose rate; influence of inducible stress responses modifying mutagenesis and lethality; bystander effects allowing it to be considered that individual

  10. The successful treatment of vocal cord dysfunction with low-dose amitriptyline – including literature review

    Directory of Open Access Journals (Sweden)

    VA Varney

    2009-11-01

    Full Text Available VA Varney1, H Parnell1, J Evans1, NT Cooke1, J Lloyd2, J Bolton31Department of Respiratory Medicine, 2Department of Speech and Language Therapy, 3Department of Liaison Psychiatry, St Helier Hospital, Carshalton, Surrey, UKAbstract: Vocal cord dysfunction is an asthma mimic. Diagnosis of this condition requires a high index of suspicion if unnecessary treatments are to be avoided. We describe the findings from our case series of 62 patients (age range 18 to 90 years in whom the diagnosis was confirmed. Our findings show low-dose amitriptyline to be very effective in 90% of cases, with rapid benefit for those patients whose symptoms had been present for less than 12 months. This treatment, in conjunction with psycho-therapeutic and behavioral therapies may reduce unnecessary hospital admissions. Future studies may show whether this treatment regimen may reduce demands on the speech and language therapists.Keywords: vocal cord dysfunction, asthma, amitriptyline, wheeze, anxiety

  11. 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)

  12. 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.)

  13. 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.

  14. State of research and perspective on adaptive response to low doses of ionizing radiation in Japan

    International Nuclear Information System (INIS)

    Sadao Hattori

    1997-01-01

    In a review article entitled ''Physical Benefits from Low Levels of Ionizing Radiation,'' published in Health Physics in December of 1982, Professor T.D. Luckey of the University of Missouri, asserted the ''radiation hormesis'' with 200 references. This resulted in the first International Symposium on Radiation Hormesis in Oakland, California (August 1985). CRIEPI consulted many specialists about Luckey's paper and studied many other papers such as Lorenz, 1954; Luckey, 1980, Liu et al., 1985. Radiation hormesis research in Japan has been based on the rationale that if Luckey's claim were to be true, radiation management in Japan has been extremely erroneous. CRIEPI organized a Hormesis Research Steering Committee composed of leading specialists in the field concerned, and began research in cooperation with a number of universities, as well as the National Cancer Research Institute, and the National Institute of Radiological Sciences. After obtaining interesting results in various experiments on the health effects of exposure to low doses of radiation, we have proceeded on an expanded program, which involves fourteen universities and two research institutes throughout Japan. The interesting results we obtained can be categorized in five groups. 1. Enhancement of immune systems such as lymphocytes and suppression of cancer, 2. Radio-adaptive response relating to the activation of DNA repair and adoptosis, 3. Rejuvenation of cells such as increase of SOD and cell membrane permeability, 4. Radiation effect on neuro-transmitting system through increase of key enzymes, 5. Others, including the therapy of adult-disease such as diabetes and hypertension. We are now carrying out experimental activities on the effects of low-dose radiation on mammals. After several years of research activities, we are recognizing Luckey's claim. Some basic surveys including Hiroshima Nagasaki and animal experiments in Japan have brought us valuable informations on the health effects of low-dose

  15. 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)

  16. The health effects of low-dose ionizing radiation

    International Nuclear Information System (INIS)

    Dixit, A.N.; Dixit, Nishant

    2012-01-01

    It has been established by various researches, that high doses of ionizing radiation are harmful to health. There is substantial controversy regarding the effects of low doses of ionizing radiation despite the large amount of work carried out (both laboratory and epidemiological). Exposure to high levels of radiation can cause radiation injury, and these injuries can be relatively severe with sufficiently high radiation doses. Prolonged exposure to low levels of radiation may lead to cancer, although the nature of our response to very low radiation levels is not well known at this time. Many of our radiation safety regulations and procedures are designed to protect the health of those exposed to radiation occupationally or as members of the public. According to the linear no-threshold (LNT) hypothesis, any amount, however small, of radiation is potentially harmful, even down to zero levels. The threshold hypothesis, on the other hand, emphasizes that below a certain threshold level of radiation exposure, any deleterious effects are absent. At the same time, there are strong arguments, both experimental and epidemiological, which support the radiation hormesis (beneficial effects of low-level ionizing radiation). These effects cannot be anticipated by extrapolating from harmful effects noted at high doses. Evidence indicates an inverse relationship between chronic low-dose radiation levels and cancer incidence and/or mortality rates. Examples are drawn from: 1) state surveys for more than 200 million people in the United States; 2) state cancer hospitals for 200 million people in India; 3) 10,000 residents of Taipei who lived in cobalt-60 contaminated homes; 4) high-radiation areas of Ramsar, Iran; 5) 12 million person-years of exposed and carefully selected control nuclear workers; 6) almost 300,000 radon measurements of homes in the United States; and 7) non-smokers in high-radon areas of early Saxony, Germany. This evidence conforms to the hypothesis that

  17. The spectrum of mutation produced by low dose radiation

    International Nuclear Information System (INIS)

    Morley, Alexander A.; Turner, David R.

    2004-01-01

    Inherited mutations are the basis of evolution and acquired mutations in humans are important in ageing, cancer and possibly various forms of tissue degeneration. Mutations are responsible for many of the long-term effects of radiation. However, sensitive direct detection of mutations in humans has been difficult. The aims of the project were to develop methods for the sensitive enumeration of mutations in DNA, to measure mutation frequencies in a wide variety of tissue types and to quantify the mutational effect of direct oxidative damage produced by radiation, at both high and low doses. The project was successful in developing a sensitive method which could detect mutations directly in the genetic material, DNA at a sensitivity of 1 mutated molecule in 1000000000 unmutated molecules. However a number of methodological problems had to be overcome and lack of ongoing funding made it impossible to fulfill all of the aims of the project

  18. Low dose response analysis through a cytogenetic end-point

    International Nuclear Information System (INIS)

    Bojtor, I.; Koeteles, G.J.

    1998-01-01

    The effects of low doses were studied on human lymphocytes of various individuals. The frequency of micronuclei in cytokinesis-blocked cultured lymphocytes was taken as end-point. The probability distribution of radiation-induced increment was statistically proved and identified as to be asymmetric when the blood samples had been irradiated with doses of 0.01-0.05 Gy of X-rays, similarly to that in unirradiated control population. On the contrary, at or above 1 Gy the corresponding normal curve could be accepted only reflecting an approximately symmetrical scatter of the increments about their mean value. It was found that the slope as well as the closeness of correlation of the variables considerably changed when lower and lower dose ranges had been selected. Below approximately 0.2 Gy even an unrelatedness was found betwen the absorbed dose and the increment

  19. Metabolomics: new prospects in low-dose radio-toxicology

    International Nuclear Information System (INIS)

    Souidi, Maamar; Grison, Stephane

    2014-01-01

    There is recurring public concern regarding the health impact of chronic exposure to low-dose ionizing radiation. This concern is further heightened when possible sources of exposure are identified, such as disused mines, the operation of nuclear facilities and radioactive waste disposal facilities, accidental release from fuel cycle facilities or the possible return of residents to areas contaminated following a reactor accident, such as the one that occurred at Fukushima. In keeping with the guidelines set out in the European strategic research agenda for MELODI, IRSN is conducting an extensive, largely experiment-based, research program to acquire scientific data to respond to this concern. The program has already revealed that chronic ingestion of cesium-137 or uranium induces many subtle, generally slight, metabolic changes, the overall biological effects of which remain to be studied. A recent 'broad-spectrum' analytical technique known as metabolomics was used to pinpoint these metabolic changes. (authors)

  20. Transcriptome profiling of mice testes following low dose irradiation

    DEFF Research Database (Denmark)

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

    2013-01-01

    ABSTRACT: BACKGROUND: Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types...... in the adult testis. METHODS: Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were...... selected for further analysis. These transcripts were separated into clusters and their cellular origin was determined. Immunohistochemistry and in silico quantification was further used to study cellular changes post-irradiation (pi). RESULTS: We identified a subset of transcripts (n = 988) where changes...

  1. Low-dose aripiprazole for refractory burning mouth syndrome.

    Science.gov (United States)

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS.

  2. 'Reasonable' regulation of low doses in the Netherlands?

    International Nuclear Information System (INIS)

    Zuur, Ciska

    2002-01-01

    As long as it is not clear exactly what the risks of low doses are, exposures should be regulated to be 'as low as reasonably achievable' (ALARA). In radiation protection, for normal situations, this means that a projected dose reduction can only be obligatory when the efforts needed to achieve the reduction are 'reasonable' in comparison with it, economical and social aspects being taken into account. In the recent Dutch regulations, 'reasonable' values have been established for the relevant parameters used in the ALARA concept and the paper discusses the values required to calculate the doses for the critical group due to a source. In some cases, the effort expended in making the ALARA dose assessments might not be reasonable in comparison with the dose reduction to be expected. The system which has been developed in the Netherlands to avoid these 'unreasonable' dose calculations, measurements and assessments is explained. (author)

  3. State of human genome at low-doses ecological influences

    International Nuclear Information System (INIS)

    Mel'nov, S.B.; Rytik, P.G.; Kruchinskij, N.G.; Kovalev, V.A.; Palamar, L.A.; Senyuk, O.F.

    2005-01-01

    The results of analysis of the state of genome (amounts of single strand breaks in DNA) of the persons exposed to influence of complex 'Chernobyl factor' in remote terms after a failure on ChNPP are resulted. Findings allowed to expose the increase of level of single strand breaks in DNA at the chronically irradiated persons mainly carry adaptive character and probably can be related to instability of genome. Thus at organism level growth of mutational pressure and strengthening of instability of cellular genome is related to the change of spectrum of biological characteristics, in particular individual reaction of somatic cells of victims on additional mutagens influences. The indicated changes can testify to existence of potential risk of remote genetic consequences of long-term irradiation influence in low doses

  4. Optical fiber sensor for low dose gamma irradiation monitoring

    Science.gov (United States)

    de Andrés, Ana I.; Esteban, Ã.`scar; Embid, Miguel

    2016-05-01

    An optical fiber gamma ray detector is presented in this work. It is based on a Terbium doped Gadolinium Oxysulfide (Gd2O2S:Tb) scintillating powder which cover a chemically etched polymer fiber tip. This etching improves the fluorescence gathering by the optical fiber. The final diameter has been selected to fulfill the trade-off between light gathering and mechanical strength. Powder has been encapsulated inside a microtube where the fiber tip is immersed. The sensor has been irradiated with different air Kerma doses up to 2 Gy/h with a 137Cs source, and the spectral distribution of the fluorescence intensity has been recorded in a commercial grade CCD spectrometer. The obtained signal-to-noise ratio is good enough even for low doses, which has allowed to reduce the integration time in the spectrometer. The presented results show the feasibility for using low cost equipment to detect/measure ionizing radiation as gamma rays are.

  5. Effect of low dose radiation on apoptosis in mouse spleen

    International Nuclear Information System (INIS)

    Chen Dong; Liu Jiamei; Chen Aijun; Liu Shuzheng

    1999-01-01

    Objective: To study the effect of whole body irradiation (WBI) with different doses of X-ray on apoptosis in mouse spleen. Methods: Time course changes and dose-effect relationship of apoptosis in mouse spleen induced by WBI were observed with transmission electron microscopy (TEM) qualitatively and TUNEL method semi-quantitatively. Results: Many typical apoptotic lymphocytes were found by TEM in mouse spleen after WBI with 2 Gy. No marked alterations of ultrastructure were found following WBI with 0.075 Gy. It was observed by TUNEL that the apoptosis of splenocytes increased after high dose radiation and decreased following low dose radiation (LDR). The dose-effect relationship of radiation-induced apoptosis showed a J-shaped curve. Conclusion: The effect of different doses of ionizing radiation on apoptosis in mouse spleen was distinct. And the decrease of apoptosis after LDR is considered a manifestation of radiation hormesis

  6. The effects of chronic low dose irradiation on drosophila melanogaster

    International Nuclear Information System (INIS)

    Zajnullin, V.G.; Moskalev, A.A.; Shaposhnikov, M.V.; Yuraneva, I.N.; Taskaev, A.I.

    2001-01-01

    It was investigated the influence of the chronic gamma-irradiation in the dose rate of 0.17 cGy/h on the rate of genetic variability and on the life-span in the laboratory strains of Drosophila melanogaster with genotypic distinguishes in mobile genetic elements and defects in the DNA repair processes. It is shown that the radiation-induced alteration of the traits under study depends from genotype of investigated strains. In the different strains we have observed an increase as well as a decrease of the mutation rate and life-span. Also it was established that irradiation leads to the frequencies of the GD-sterility and mutability of the snw and h(w+) in the P-M and H-E dysgenic crosses. The obtained results suggest that mobile genetic elements play an important role in the forming of genetic effects in response to low dose irradiation. (author)

  7. Genetic effects of low-dose irradiation in Drosophila Melanogaster

    International Nuclear Information System (INIS)

    Zajnulin, V.G.; Shaposhnikov, M.V.; Yuraneva, I.N.

    2000-01-01

    Influence of chronic γ-irradiation at the dose rate of 0.17 cGy/h on the rate of genetic variability in the laboratory strains of Drosophila Melanogaster with genotypic distinguishes by families of mobile genetic elements and of systems of hybrid disgenesis and also violations in reparation processes control mechanisms. It was shown that the rates of induction of recessive lethal mutations depended on genotype of investigated strains. In the different strains an increase as well as a decrease of the mutation rate were observed. Also in was established that irradiation leads to the increase in frequencies of the gonads sterility and mutability of the sn w and h(w + ) in the P-M and H-E dysgenic crosses. Obtained results suggest that mobile genetic elements play an important role in the forming of genetic effects in response to low dose irradiation [ru

  8. Low dose preoperative radiotherapy for carcinoma of the oesophagus

    International Nuclear Information System (INIS)

    Arnott, S.J.; Duncan, W.; Kerr, G.R.; Jack, W.J.L.; Mackillop, W.J.; Walbaum, P.R.; Cameron, E.

    1992-01-01

    Patients (176) with potentially operable squamous cell carcinoma or adenocarcinoma of middle or lower thirds of oesophagus were randomly assigned to preoperative radiotherapy or surgery alone. Patients assigned to the radiotherapy arm received 20 Gy in 10 treatments over 2 weeks, using parallel opposed 4 MV beams. The preoperative radiotherapy was not associated with any significant acute morbidity or any increase in operative complications. The median survival of the overall group of 176 patients was 8 moths, and the 5-year survival was 13%. There was no significant difference in the survival of the 90 patients who received preoperative radiotherapy and the 86 who were managed by surgery alone. Proportional hazards analysis identified lymph node involvement, high tumor grade and male sex as significant adverse prognostic features, but the treatment option assigned had no prognostic significance. It was concluded that low dose preoperative radiotherapy offered no advantage over surgery alone. (author). 9 refs.; 3 figs.; 6 tabs

  9. High and low dose-rate brachytherapy for cervical carcinoma

    International Nuclear Information System (INIS)

    Orton, C.G.

    1998-01-01

    For the brachytherapy component of the r[iation treatment of cervical carcinoma, high dose rate (HDR) is slowly replacing conventional low dose rate (LDR) due primarily to r[iation safety and other physical benefits attributed to the HDR modality. Many r[iation oncologists are reluctant to make this change because of perceived r[iobiological dis[vantages of HDR. However, in clinical practice HDR appears to be as effective as LDR but with a lower risk of late complications, as demonstrated by one randomized clinical trial and two comprehensive literature and practice surveys. The reason for this appears to be that the r[iobiological dis[vantages of HDR are outweighed by the physical [vantages. (orig.)

  10. Lung cancer screening with low-dose CT

    International Nuclear Information System (INIS)

    Diederich, S.; Wormanns, D.; Heindel, W.

    2003-01-01

    Screening for lung cancer is hoped to reduce mortality from this common tumour, which is characterised by a dismal overall survival, relatively well defined risk groups (mainly heavy cigarette smokers and workers exposed to asbestos) and a lack of early symptoms. In the past studies using sputum cytology and chest radiography have failed to demonstrate any reduction in lung cancer mortality through screening. One of the reasons is probably the relatively poor sensitivity of both these tests in early tumours. Low radiation dose computed tomography (CT) has been shown to have a much higher sensitivity for small pulmonary nodules, which are believed to be the most common presentation of early lung cancer. As, however, small pulmonary nodules are common and most are not malignant, non-invasive diagnostic algorithms are required to correctly classify the detected lesions and avoid invasive procedures in benign nodules. Nodule density, size and the demonstration of growth at follow-up have been shown to be useful in this respect and may in the future be supplemented by contrast-enhanced CT and positron emission tomography. Based on these diagnostic algorithms preliminary studies of low-dose CT in heavy smokers have demonstrated a high proportion of asymptomatic, early, resectable cancers with good survival. As, however, several biases could explain these findings in the absence of the ultimate goal of cancer screening, i.e. mortality reduction, most researchers believe that randomised controlled trials including several 10000 subjects are required to demonstrate a possible mortality reduction. Only then general recommendations to screen individuals at risk of lung cancer with low-dose CT should be made. It can be hoped that international cooperation will succeed in providing results as early as possible

  11. Low dose radiation enhances the Locomotor activity of D. melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Ki Moon; Lee, Buyng Sub; Nam Seon Young; Kim, Ji Young; Yang, Kwang Hee; Choi, Tae In; Kim, Cha Soon [Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., Gyeongju (Korea, Republic of)

    2013-04-15

    Mild stresses at low level including radiation can induce the beneficial effects in many vertebrate and invertebrate species. However, a large amount of studies in radiation biology have focused on the detrimental effects of high dose radiation (HDR) such as the increased incidence of cancers and developmental diseases. Low dose radiation (LDR) induces biologically favorable effects in diverse fields, for example, cancer development, genomic instability, immune response, and longevity. Our previous data indicated that LDR promotes cells proliferation of which degree is not much but significant, and microarray data explained that LDR irradiated fruit flies showing the augmented immunity significantly changed the program for gene expression of many genes in Gene Ontology (GO) categories related to metabolic process. Metabolic process in development one of major contributors in organism growth, interbreeding, motility, and aging. Therefore, it is valuable to examine whether LDR change the physiological parameters related to metabolism, and how LDR regulates the metabolism in D. melanogaster. In this study, to investigate that LDR influences change of the metabolism, a representative parameter, locomotor activity. In addition, the activation of several cellular signal molecules was determined to investigate the specific molecular mechanism of LDR effects on the metabolism. We explored whether ionizing radiation affects the motility activity. We performed the RING assays to evaluate the locomotor activity, a representative parameter presenting motility of fruit flies. HDR dramatically decreased the motor activity of irradiated flies. Surprisingly, the irradiated flies at low dose radiation in both acute and chronic showed the significantly increased locomotor activity, compared to non-irradiated flies. Irradiation would induce change of the several signal pathways for flies to respond to it. The activation of some proteins involved in the cells proliferation and stress

  12. Varicose Vein Stripping Under Low-Dose Spinal Anaesthesia

    Directory of Open Access Journals (Sweden)

    Nalan Muhammedoğlu

    2014-03-01

    Full Text Available Aim: Spinal anesthesia is frequently used for procedures involving the lower limbs. Compared with general anesthesia, low-dose spinal anesthesia is a cost-effective method and has advantages such as avoiding hypotension, longer duration of anesthesia and increased length of hospitalization. The aim of this trial was to compare two different low-dose bupivacaine drug regimens. Methods: Sixty unpremedicated patients were randomly allocated into two groups (n=30. There were no differences between the groups in age, weight, the American Society of Anesthesiologists (ASA physical status classification, gender, and duration of surgery. We performed spinal anesthesia at the L3-4 interspace with the patient in the lateral decubitus position. We administered 6.5 mg (group 1 and 8 mg (group 2 0.5% heavy bupivacaine into the subarachnoid space. We positioned the patient laterally to the operation side for 15 minutes, then, turned to supine position. Motor and sensory block was assessed by the Bromage scale and pinprick test. Results: There were significant differences between the two groups in duration of motor block, but no significant differences in hemodynamic response to spinal anesthesia. None of the patients had intraoperative pain. Five patients in group 1 and 2 patients in group 2 had urinary retention. Conclusion: Our observations suggest that 6.5 mg heavy bupivacaine is efficient and suitable for unilateral varicose veins stripping operation. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 25-8

  13. Cardiovascular risks associated with low dose ionizing particle radiation.

    Directory of Open Access Journals (Sweden)

    Xinhua Yan

    Full Text Available Previous epidemiologic data demonstrate that cardiovascular (CV morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ((1H; 0.5 Gy, 1 GeV and iron ion ((56Fe; 0.15 Gy, 1GeV/nucleon irradiation with and without an acute myocardial ischemia (AMI event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in (56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  14. Clinical application of low-dose spiral CT for orthodontics

    International Nuclear Information System (INIS)

    Xie Na; Gan Yungen; Shu Huang; Lin FeiFei; Li Zhiyong; Sun Jie

    2009-01-01

    Objective: To determine the effect of reducing the value of mA or kV on the image quality and the radiation dose of the patients undergoing low-dose spiral CT for orthodontics. Methods: Thirty patients were divided into three groups, each group has 10 patients. They were group 1 (80 kV and 200 mA), group 2 (120 kV and 80 mA), group 3 (120 kV and 200 mA) The volume CT dose index (CTDI) was recorded and the average dose-length produce (DLP) was calculated in three groups,respectively. Image quality of three groups were compared and scored by two radiologists, and the results were statistically analysed. Results: The CTDI and DLP of 80 kV group (group 2) were 8.7 mGy and (36.80 ± 3.60) mGy · cm, respectively, those of 80 mA group (group 3) were 19.6 mGy and (82.14 ± 7.18) mGy · cm, respectively, and those of conventional-dose group (group 1) were 19.6 mGy and (82.14 ± 7.18) mGy · cm, respectively. There was no significant difference among three groups in diagnostic image quality. Conclusions: Low-dose spiral CT for orthodontics, especially the low-kV scan, may decrease the radiation exposure and guarantee the image quality. (authors)

  15. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kleiman, Norman Jay [Columbia University

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9

  16. Progress of research on activation function of NK cell exposed to low dose radiation in adoptive cellular immunotherapy

    International Nuclear Information System (INIS)

    Pan Xiaosong; Shi Yujia; Yao Yimin; Xu Hong; Liu Fenju

    2009-01-01

    Natural killer cells is an important immunological factor in killing malignant cells. Low dose radiation can enhance proliferation and biological activity of NK cell. The involvement of P38MAPK signal pathway and endogenous glutathione induced by LDR may be the probable mechanism. Natural killer cell, especially adherent natural killer cell, is the preferential choice for adoptive cellular immunotherapy, which has a remarkable foreground in malignancy therapy.(authors)

  17. Implications of effects ''adaptive response'', ''low-dose hypersensitivity'' und ''bystander effect'' for cancer risk at low doses and low dose rates

    International Nuclear Information System (INIS)

    Jacob, P

    2006-01-01

    A model for carcinogenesis (the TSCE model) was applied in order to examine the effects of ''Low-dose hypersensitivity (LDH)'' and the ''Bystander effect (BE)'' on the derivation of radiation related cancer mortality risks. LDH has been discovered to occur in the inactivation of cells after acute exposure to low LET radiation. A corresponding version of the TSCE model was applied to the mortality data on the Abomb survivors from Hiroshima and Nagasaki. The BE has been mainly observed in cells after exposure to high LET radiation. A Version of the TSCE model which included the BE was applied to the data on lung cancer mortality from the workers at the Mayak nuclear facilities who were exposed to Plutonium. In general an equally good description of the A-bomb survivor mortality data (for all solid, stomach and lung tumours) was found for the TSCE model and the (conventional) empirical models but fewer parameters were necessary for the TSCE model. The TSCE model which included the effects of radiation induced cell killing resulted in non-linear dose response curves with excess relative risks after exposure at young ages that were generally lower than in the models without cell killing. The main results from TSCE models which included cell killing described by either conventional survival curves or LDH were very similar. A sub multiplicative effect from the interaction of smoking and exposure to plutonium was found to result from the analysis of the Mayak lung cancer mortality data. All models examined resulted in the predominant number of Mayak lung cancer deaths being ascribed to smoking. The interaction between smoking and plutonium exposures was found to be the second largest effect. The TSCE model resulted in lower estimates for the lung cancer excess relative risk per unit plutonium dose than the empirical risk model, but this difference was not found to be statistically significant. The excess relative risk dose responses were linear in the empirical model and

  18. Toxicity risk of non-target organs at risk receiving low-dose radiation: case report

    International Nuclear Information System (INIS)

    Shueng, Pei-Wei; Lin, Shih-Chiang; Chang, Hou-Tai; Chong, Ngot-Swan; Chen, Yu-Jen; Wang, Li-Ying; Hsieh, Yen-Ping; Hsieh, Chen-Hsi

    2009-01-01

    The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT), a new image-guided intensity modulated radiotherapy (IMRT), delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs) occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy

  19. Stimulatory effect of low dose radiation on the immune function in tumor-bearing mice

    International Nuclear Information System (INIS)

    Zhang Ying; Li Xiujuan; Li Xiuyi; Liu Shuzheng

    1999-01-01

    Objective: The author aims at investigating the effect of whole body irradiation (WBI) with low dose radiation on immune function in tumor-bearing mice. Methods: C57BL/6J mine implanted with Lewis lung carcinoma cells in the right thighs were used as an experimental animal model. WBI with 75 mGy X-rays was given at the 10 th day after implantation and immunological parameters were detected 18 hours after irradiation. The immunological parameters included the spontaneous incorporation of 3 H-TdR into thymocytes, the number of splenocytes, the reaction of splenocytes to ConA and LPS, the splenic production of IL-2, the cytotoxic activities of natural killer (NK) and lymphokine activated killer cells (LAK) as well as specific cytotoxic T lymphocytes (CTL). Results: The immunological parameters of irradiated tumor-bearing mice were significantly increased compared with those of sham-irradiated tumor-bearing mice (P<0.05∼0.01). Conclusion: Low dose radiation could significantly increase the immune function of tumor-bearing mice, and this stimulatory effect may be of some potential significance in tumor therapy

  20. 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.

  1. 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.

  2. Bolus versus continuous low dose of enalaprilat in congestive heart failure with acute refractory decompensation.

    Science.gov (United States)

    Podbregar, M; Voga, G; Horvat, M; Zuran, I; Krivec, B; Skale, R; Pareznik, R

    1999-01-01

    The first dose of angiotensin-converting enzyme (ACE) inhibitors may trigger a considerable fall of blood pressure in chronic heart failure. The response may be dose-related. To determine hemodynamic and systemic oxygenation effects of low-dose enalaprilat, we administered intravenous enalaprilat (0.004 mg/kg) as bolus (group B) or continuous 1-hour infusion (group C) in 20 patients with congestive heart failure due to ischemic heart disease with acute decompensation refractory to inotropic, vasodilator and diuretic therapy. Hemodynamic and systemic oxygenation variables were recorded at baseline (+0 min), +30, +60, +120, +180, and +360 min after the start of intervention. Mean arterial pressure (MAP) (p < 0. 001), mean pulmonary artery pressure (MPAP) (p < 0.001), pulmonary artery occlusion pressure (PAOP) (p < 0.001), oxygen extraction ratio (ER) (p < 0.026) decreased regardless of enalaprilat application. Compared to group B, there was in group C prolonged decrease of MAP, MPAP, PAOP, ER and increase of pulmonary artery oxyhemoglobin saturation in regard to baseline values. Cardiac index, heart rate, central venous pressure and oxygen consumption index did not change. A low dose of intravenous enalaprilat (0.004 mg/kg) can be used to safely improve hemodynamics and systemic oxygenation in congestive heart failure due to ischemic heart disease with acute refractory decompensation.

  3. Concurrent chemoradiation with daily low dose cisplatin for advanced stage head and neck carcinoma

    International Nuclear Information System (INIS)

    Hoebers, Frank J.P.; Heemsbergen, Wilma; Balm, Alfons J.M.; Zanten, Mathilde van; Schornagel, Jan H.; Rasch, Coen R.N.

    2007-01-01

    Background and purpose: To evaluate treatment results of concurrent chemoradiation with daily low dose cisplatin. Materials and methods: 121 patients with advanced stage HNSCC were treated with RT (35 x 2 Gy) and cisplatin (6 mg/m 2 i.v. x20, daily before RT). After 47 patients, the treatment protocol (Standard Group) was changed: Daily i.v. prehydration and accelerated RT were given to the subsequent 74 patients (Hydr-Ac-RT Group). Results: Mean follow-up was 29 months (range 7-62). More chemotherapy could be administered in the Hydr-Ac-RT Group (maximum no. of 20 cisplatin-infusions increased from 59% to 91% of patients, p = 0.008), with less renal toxicity (p < 0.001) and less hospital admissions (p < 0.02). However, mucositis was more pronounced and tubefeeding more frequent in the Hydr-Ac-RT Group. The CR rate of the primary tumor increased from 74% (Standard Group) to 90% (Hydr-Ac-RT Group) (p = 0.06), although this did not lead to an improvement in loco-regional control. Conclusions: Concurrent chemoradiation with daily low dose cisplatin is feasible and effective for selected patients with advanced HNSCC. Although the addition of accelerated RT resulted in more mucositis and tubefeeding, the introduction of prehydration led to better compliance to therapy with more chemotherapy administered and less hospital admissions

  4. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cheryl G. Burrell, Ph.D.

    2012-05-14

    The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

  5. COMPARISON OF EFFICACY AND FETOMATERNAL OUTCOME WITH LOW DOSE AND STANDARD PRITCHARD’S REGIMEN OF MAGNESIUM SULPHATE IN ECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Nirmala Chamakuri

    2017-11-01

    Full Text Available BACKGROUND Eclampsia, a hypertensive disorder of pregnancy is a common obstetric emergency, which leads to significant maternal morbidity, perinatal morbidity and mortality. The Pritchard’s regimen of magnesium sulphate remains as the standard regimen worldwide. The aim of this study is to compare the effectiveness, side effects and fetomaternal outcome using low-dose magnesium sulphate with the results of Pritchard regime. MATERIALS AND METHODS A comparative prospective study including 120 eclampsia patients designed into group I and group II treated with low-dose magnesium sulphate and Pritchard’s regimen was conducted in the Department of Obstetrics and Gynaecology for a period of 18 months between January 2015 to June 2016. RESULTS In the present study, there was 100% control of seizures in both the groups. No recurrence of seizures were seen in 57 (95% of cases in group II (low-dose regimen and 3 (5% cases showed recurrence, which were controlled by giving additional doses. In group II, loss of patellar reflexes was seen in 6 (10%, reduced urine output was seen in 3 (5% of cases, mild PPH was observed in 3 (5% cases and perinatal mortality in 18 (30% cases, which were lower than that of group I (Pritchard’s regimen. CONCLUSION Low-dose magnesium sulphate is effective in controlling convulsions in eclampsia. This regimen is highly suitable for use in Indian women who are known to have low body mass index

  6. 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)

  7. 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.

  8. A framework to measure myocardial extracellular volume fraction using dual-phase low dose CT images

    International Nuclear Information System (INIS)

    Liu, Yixun; Summers, Ronald M.; Yao, Jianhua; Liu, Songtao; Sibley, Christopher T.; Bluemke, David A.; Nacif, Marcelo S.

    2013-01-01

    Purpose: Myocardial extracellular volume fraction (ECVF) is a surrogate imaging biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular remodeling. Low dose cardiac CT is emerging as a promising modality to detect diffuse interstitial myocardial fibrosis due to its fast acquisition and low radiation; however, the insufficient contrast in the low dose CT images poses great challenge to measure ECVF from the image. Methods: To deal with this difficulty, the authors present a complete ECVF measurement framework including a point-guided myocardial modeling, a deformable model-based myocardium segmentation, nonrigid registration of pre- and post-CT, and ECVF calculation. Results: The proposed method was evaluated on 20 patients by two observers. Compared to the manually delineated reference segmentations, the accuracy of our segmentation in terms of true positive volume fraction (TPVF), false positive volume fraction (FPVF), and average surface distance (ASD), were 92.18% ± 3.52%, 0.31% ± 0.10%, 0.69 ± 0.14 mm, respectively. The interobserver variability measured by concordance correlation coefficient regarding TPVF, FPVF, and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement. Bland-Altman method showed 95% limits of agreement between ECVF at CT and ECVF at MR. Conclusions: The proposed framework demonstrates its efficiency, accuracy, and noninvasiveness in ECVF measurement and dramatically advances the ECVF at cardiac CT toward its clinical use

  9. A framework to measure myocardial extracellular volume fraction using dual-phase low dose CT images

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yixun; Summers, Ronald M.; Yao, Jianhua, E-mail: JYao@cc.nih.gov [Clinical Image Processing Service, Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, Maryland 20892 (United States); Liu, Songtao; Sibley, Christopher T.; Bluemke, David A. [Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, Maryland 20892-1182 and Molecular Biomedical Imaging Laboratory, National Institute of Biomedical Imaging and Bioengineering, NIH Clinical Center, Bethesda, Maryland 20892 (United States); Nacif, Marcelo S. [Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, Maryland 20892-1182 (United States)

    2013-10-15

    Purpose: Myocardial extracellular volume fraction (ECVF) is a surrogate imaging biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular remodeling. Low dose cardiac CT is emerging as a promising modality to detect diffuse interstitial myocardial fibrosis due to its fast acquisition and low radiation; however, the insufficient contrast in the low dose CT images poses great challenge to measure ECVF from the image. Methods: To deal with this difficulty, the authors present a complete ECVF measurement framework including a point-guided myocardial modeling, a deformable model-based myocardium segmentation, nonrigid registration of pre- and post-CT, and ECVF calculation. Results: The proposed method was evaluated on 20 patients by two observers. Compared to the manually delineated reference segmentations, the accuracy of our segmentation in terms of true positive volume fraction (TPVF), false positive volume fraction (FPVF), and average surface distance (ASD), were 92.18% ± 3.52%, 0.31% ± 0.10%, 0.69 ± 0.14 mm, respectively. The interobserver variability measured by concordance correlation coefficient regarding TPVF, FPVF, and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement. Bland-Altman method showed 95% limits of agreement between ECVF at CT and ECVF at MR. Conclusions: The proposed framework demonstrates its efficiency, accuracy, and noninvasiveness in ECVF measurement and dramatically advances the ECVF at cardiac CT toward its clinical use.

  10. Collaboration around Facilitating Emergent Literacy: Role of Occupational Therapy

    Science.gov (United States)

    Asher, Asha; Nichols, Joy D.

    2016-01-01

    The article uses a case study to illustrate transdisciplinary perspectives on facilitating emergent literacy skills of Elsa, a primary grade student with autism. The study demonstrates how a professional learning community implemented motor, sensory, and speech/language components to generate a classroom model supporting emergent literacy skills.…

  11. 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.)

  12. Low doses effects of ionizing radiation on Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Durand, J.; Broock, M. van; Gillette, V.H.

    2000-01-01

    The exposure of living cells to low doses of ionizing radiation induce in response the activation of cellular protection mechanisms against subsequent larger doses of radiation. This cellular adaptive response may vary depending on radiation intensity and time of exposure, and also on the testing probes used whether they were mammalian cells, yeast, bacteria and other organisms or cell types. The mechanisms involved are the genome activation, followed by DNA repair enzymes synthesis. Due to the prompt cell response, the cell cycle can be delayed, and the secondary detoxification of free radicals and/or activation of membrane bound receptors may proceed. All these phenomena are submitted to intense scientific research nowadays, and their elucidation will depend on the complexity of the organism under study. In the present work, the effects of low doses of ionizing radiation (gamma rays) over a suspension of the yeast Saccharomyces cerevisiae (Baker's yeast) was studied, mainly in respect to survival rate and radio-adaptive response. At first, the yeast surviving curve was assessed towards increasing doses, and an estimation of Lethal Dose 50 (LD50) was made. The irradiation tests were performed at LINAC (electrons Linear Accelerator) where electron energy reached approximately 2.65 MeV, and gamma-radiation was produced for bremsstrahlung process over an aluminium screen target. A series of experiments of conditioning doses was performed and an increment surviving fraction was observed when the dose was 2.3 Gy and a interval time between this and a higher dose (challenging dose) of 27 Gy was 90 minutes. A value of 58 ± 4 Gy was estimated for LD50, at a dose rate of 0.44 ± 0.03 Gy/min These quantities must be optimized. Besides data obtained over yeast survival, an unusual increasing amount of tiny yeast colonies appeared on the agar plates after incubation, and this number increased as increasing the time exposure. Preliminary results indicate these colonies as

  13. 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.

  14. SU-F-18C-15: Model-Based Multiscale Noise Reduction On Low Dose Cone Beam Projection

    International Nuclear Information System (INIS)

    Yao, W; Farr, J

    2014-01-01

    Purpose: To improve image quality of low dose cone beam CT for patient positioning in radiation therapy. Methods: In low dose cone beam CT (CBCT) imaging systems, Poisson process governs the randomness of photon fluence at x-ray source and the detector because of the independent binomial process of photon absorption in medium. On a CBCT projection, the variance of fluence consists of the variance of noiseless imaging structure and that of Poisson noise, which is proportional to the mean (noiseless) of the fluence at the detector. This requires multiscale filters to smoothen noise while keeping the structure information of the imaged object. We used a mathematical model of Poisson process to design multiscale filters and established the balance of noise correction and structure blurring. The algorithm was checked with low dose kilo-voltage CBCT projections acquired from a Varian OBI system. Results: From the investigation of low dose CBCT of a Catphan phantom and patients, it showed that our model-based multiscale technique could efficiently reduce noise and meanwhile keep the fine structure of the imaged object. After the image processing, the number of visible line pairs in Catphan phantom scanned with 4 ms pulse time was similar to that scanned with 32 ms, and soft tissue structure from simulated 4 ms patient head-and-neck images was also comparable with scanned 20 ms ones. Compared with fixed-scale technique, the image quality from multiscale one was improved. Conclusion: Use of projection-specific multiscale filters can reach better balance on noise reduction and structure information loss. The image quality of low dose CBCT can be improved by using multiscale filters

  15. BET 2: Low-dose ketamine for acute pain in the ED.

    Science.gov (United States)

    Duncan, Colby; Riley, Brad

    2016-12-01

    A short cut review was carried out to establish whether low-dose ketamine is better than morphine at safely and effectively reducing pain scores in ED patients with acute pain who do not respond to conventional therapies. One hundred and thirty-two papers were found using the reported searches, of these three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that the evidence is limited, but that ketamine can be an effective alternative or adjunct to intravenous opioid pain medications and in some instances may provide more effective pain relief when compared with opioids. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Low-dose aspirin in polycythaemia vera: a pilot study. Gruppo Italiano Studio Policitemia (GISP).

    Science.gov (United States)

    1997-05-01

    In this pilot study, aimed at exploring the feasibility of a large-scale trial of low-dose aspirin in polycythaemia vera (PV), 112 PV patients (42 females, 70 males. aged 17-80 years) were selected for not having a clear indication for, or contraindication to, aspirin treatment and randomized to receive oral aspirin (40 mg/d) or placebo. Follow-up duration was 16 +/- 6 months. Measurements of thromboxane A2 production during whole blood clotting demonstrated complete inhibition of platelet cyclooxygenase activity in patients receiving aspirin. Aspirin administration was not associated with any bleeding complication. Within the limitations of the small sample size, this study indicates that a biochemically effective regimen of antiplatelet therapy is well tolerated in patients with polycythaemia vera and that a large-scale placebo-controlled trial is feasible.

  17. Evaluation of chemoradiotherapy of low dose nedaplatin (NDP) for head and neck cancer

    International Nuclear Information System (INIS)

    Semba, Osamu; Nagahara, Masamitsu; Miyazaki, Nobuo; Adachi, Osamu; Fukuda, Kazuyasu; Watanabe, Yusuke

    2002-01-01

    There were 21 evaluable cases (22 lesions) who received concurrent chemotherapy with low dose Nedaplatin and radiotherapy, and the diagnosis was head and neck cancer at our institute during the 3 years and 3 months from March 1997 to June 2000. Approximately 77.3% had advanced cancer, and all cases involved squamous cell carcinoma (SCC) except for one case involving undifferentiated carcinoma of the maxillary sinus. The 21 lesions of SCC which could be assessed by TNM classification showed clinical or pathological CR at the primary lesions (T). In consideration of the metastatic lymph nodes (N), 11 for 14 lesions (78.6%) showed CR. From the results, it is believed that this treatment is an excellent therapy in functional preservation and QOL, though further observation and more cases are necessary. (author)

  18. Virtual Colonoscopy Screening With Ultra Low-Dose CT and Less-Stressful Bowel Preparation: A Computer Simulation Study

    Science.gov (United States)

    Wang, Jing; Wang, Su; Li, Lihong; Fan, Yi; Lu, Hongbing; Liang, Zhengrong

    2008-10-01

    Computed tomography colonography (CTC) or CT-based virtual colonoscopy (VC) is an emerging tool for detection of colonic polyps. Compared to the conventional fiber-optic colonoscopy, VC has demonstrated the potential to become a mass screening modality in terms of safety, cost, and patient compliance. However, current CTC delivers excessive X-ray radiation to the patient during data acquisition. The radiation is a major concern for screening application of CTC. In this work, we performed a simulation study to demonstrate a possible ultra low-dose CT technique for VC. The ultra low-dose abdominal CT images were simulated by adding noise to the sinograms of the patient CTC images acquired with normal dose scans at 100 mA s levels. The simulated noisy sinogram or projection data were first processed by a Karhunen-Loeve domain penalized weighted least-squares (KL-PWLS) restoration method and then reconstructed by a filtered backprojection algorithm for the ultra low-dose CT images. The patient-specific virtual colon lumen was constructed and navigated by a VC system after electronic colon cleansing of the orally-tagged residue stool and fluid. By the KL-PWLS noise reduction, the colon lumen can successfully be constructed and the colonic polyp can be detected in an ultra low-dose level below 50 mA s. Polyp detection can be found more easily by the KL-PWLS noise reduction compared to the results using the conventional noise filters, such as Hanning filter. These promising results indicate the feasibility of an ultra low-dose CTC pipeline for colon screening with less-stressful bowel preparation by fecal tagging with oral contrast.

  19. [Low-dose flutamide in the treatment of hyperandrogenism in adolescents].

    Science.gov (United States)

    Pizzo, A; Borrielli, I; Mastroeni, M T; Fattori, A; Dugo, C; Dugo, N; Dinatale, A

    2008-12-01

    The aim of the study was to evaluate the results of the use of flutamide at low doses for the therapy of the iperandrogenism in adolescents. The study enrolled 35 young women with acne and irsutism; 31 had polycystic ovary syndrome (PCOS) and 4 periferic iperandrogenism. In other 8 young women, sexually active, the flutamide has been associated with the hormonal contraceptive. On the three young women with iperinsulinism it has been decided to associate the flutamide with the metformina. All the young women were checked each month for the liver functional. Before the beginning of the therapy the menstrual situation, the Body Mass Index (BMI), the Ferriman' s and Cremoncini's score, the ovary's ultrasound aspect, and the hormonal order were evaluated. Follow-up was made after three months and after six months after the beginning of the therapy with flutamide 62.5 mg/die. Only in 4 cases the therapy has been suspended due to collateral effects, soon regressed after one week of the treatment interruption. The results have demonstrated a overwhelming improvement of the peripheral symptoms of iperandrogenism in all patients. The authors hope that flutamide could enter in the list of medicines normally used to treat the beauty flaws of policistic acne and to restore a hormonal order associated to an effective contraception.

  20. 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

  1. 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.)

  2. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    Science.gov (United States)

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals.

  3. Effect of low doses gamma irradiation of cotton seeds

    International Nuclear Information System (INIS)

    Al-Oudat, M.; Khalifa, Kh.

    1996-01-01

    Field experiments and then large scale application of irradiated cotton seeds (C.V. Aleppo-40) were carried out during three seasons (1986, 1987 and 1988) for field experiment at ACSAD Station in Dier-Ezzor and 1988, 1989 and 1990 for large scale application at Euphrate's Basin, Al-Ghab and Salamia, farmers farms. The above areas were selected as they represent major cotton production areas in Syria. The aims of the experiments were to study the effect of low doses of gamma irradiation 0, 5, 10, 20, 30, 40 and 50 Gy on cotton yield and to look for the optimum dose of gamma irradiation to obtain best results. The results show that, there were positive effect (P<0.95) for doses 5-30 Gy in increasing cotton yield. The highest increase was at dose of 10 Gy. which as 19.5% higher than control. For the large scale application using 10 Gy the increase in cotton yield varied from 10-39% compared to control. (author). 11 refs., 6 figs

  4. Sensitivity to low-dose radiation in radiosensitive ''wasted'' mice

    International Nuclear Information System (INIS)

    Paunesku, T.; Protic, M.; Woloschak, G. E.

    1999-01-01

    Mice homozygous for the autosomal recessive wasted mutation (wst/wst) have abnormalities in T-lymphocytes and in the anterior motor neuron cells of the spinal cord, leading to sensitivity to low doses of ionizing radiation, hind limb paralysis, and immunodeficiency. This defect results in a failure to gain weight by 20 days and death at 28 days of age. The wasted mutation (previously mapped to mouse chromosome 2) is shown to be a 3-bp deletion in a T-cell-specific (and perhaps motor-neuron-specific) regulatory region (promoter) of the proliferating cell nuclear antigen (PCNA) gene on mouse chromosome 2. A regulatory element is also shown to be important in PCNA expression in T-lymphocytes and motor neuron cells afflicted by the 3-bp deletion in the PCNA promoter. The model is as follows: Absence of PCNA expression in the thymuses (and motor neurons) of wasted mice causes cellular apoptosis; this absence of expression is mediated by a positive transactor that can bind to the wild-type but not the wasted mutant PCNA promoter; the bound protein induces late expression of PCNA in T-lymphocytes and prevents onset of radiation sensitivity in the cells

  5. Medical effects of low doses of ionising radiation

    International Nuclear Information System (INIS)

    Coggle, J.E.

    1990-01-01

    Ionising radiation is genotoxic and causes biological effects via a chain of events involving DNA strand breaks and 'multiply damaged sites' as critical lesions that lead to cell death. The acute health effects of radiation after doses of a few gray, are due to such cell death and consequent disturbance of cell population kinetics. Because of cellular repair and repopulation there is generally a threshold dose of about 1-2 Gy below which such severe effects are not inducible. However, more subtle, sub-lethal mutational DNA damage in somatic cells of the body and the germ cells of the ovary and testis cause the two major low dose health risks -cancer induction and genetic (heritable) effects. This paper discusses some of the epidemiological and experimental evidence regarding radiation genetic effects, carcinogenesis and CNS teratogenesis. It concludes that current risk estimates imply that about 3% of all cancers; 1% of genetic disorders and between 0% and 0.3% of severe mental subnormality in the UK is attributable to the ubiquitous background radiation. The health risks associated with the medical uses of radiation are smaller, whilst the nuclear industry causes perhaps 1% of the health detriment attributable to background doses. (author)

  6. 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

  7. Fully automated gynecomastia quantification from low-dose chest CT

    Science.gov (United States)

    Liu, Shuang; Sonnenblick, Emily B.; Azour, Lea; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

    2018-02-01

    Gynecomastia is characterized by the enlargement of male breasts, which is a common and sometimes distressing condition found in over half of adult men over the age of 44. Although the majority of gynecomastia is physiologic or idiopathic, its occurrence may also associate with an extensive variety of underlying systemic disease or drug toxicity. With the recent large-scale implementation of annual lung cancer screening using low-dose chest CT (LDCT), gynecomastia is believed to be a frequent incidental finding on LDCT. A fully automated system for gynecomastia quantification from LDCT is presented in this paper. The whole breast region is first segmented using an anatomyorientated approach based on the propagation of pectoral muscle fronts in the vertical direction. The subareolar region is then localized, and the fibroglandular tissue within it is measured for the assessment of gynecomastia. The presented system was validated using 454 breast regions from non-contrast LDCT scans of 227 adult men. The ground truth was established by an experienced radiologist by classifying each breast into one of the five categorical scores. The automated measurements have been demonstrated to achieve promising performance for the gynecomastia diagnosis with the AUC of 0.86 for the ROC curve and have statistically significant Spearman correlation r=0.70 (p early detection as well as the treatment of both gynecomastia and the underlying medical problems, if any, that cause gynecomastia.

  8. Low dose radiation prevents doxorubicin-induced cardiotoxicity.

    Science.gov (United States)

    Jiang, Xin; Hong, Yaqiong; Zhao, Di; Meng, Xinxin; Zhao, Lijing; Du, Yanwei; Wang, Zan; Zheng, Yan; Cai, Lu; Jiang, Hongyu

    2018-01-02

    This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling.

  9. Risk at Low Doses: Scientific knowledge, uncertainties and management

    International Nuclear Information System (INIS)

    Giusssani, A.; Ballarini, F.; Ottolenghi, A.

    2002-01-01

    Most of the applications of ionizing radiation in the medical field, for the exposed workers as well as the majority of patients undergoing diagnostic examinations, can be seen as low situations. Epidemiological information is however available for dose and dose rates higher than the values typical of most medical situation. Main source of information is the Life Span Study (LSS) of Japanese. A-bomb survivors, supplemented by studies of selected groups of exposed workers (uranium miners, radium painters) or radiotherapy patients with a detailed follow-up history. All of these group studies, however, suffer from one or more of the following limitations: - lack of adequate dosimetry - lack of a reliable control group for the necessary comparison - influence of concomitant factors (not always easy to find out) - influence of social conditions. In addition exposed study populations are different than the population of patients for which the risk estimates are needed in the medical situation. Recent studies aimed to evaluate the available data on the cohorts of the inhabitants of the Techa river settlements as well as of the workers of the Mayak nuclear facilities may provide in the future useful information on large populations chronically exposed to relatively low doses. (Author)

  10. International Conference on Low Doses of Ionising Radiation

    International Nuclear Information System (INIS)

    McEwan, A.C.

    1998-01-01

    Is there a threshold? and is a little radiation good for you? were two questions raised at the International Conference on Low Doses of Ionising Radiation : Biological Effects and Regulatory Control, jointly organised by the IAEA and WHO, and convened in Seville, Spain, over 17-21 November 1997. The answer to both these questions appears to be 'Maybe', but the answer has no present implications for radiation protection practice and regulation. The conference which had over 500 participants from 65 countries, was organised around ten fora which explored basic molecular mechanisms of radiation effects, through to radiation protection principles and implementation in practices and interventions. Each forum was introduced by an overview presentation by an invited keynote speaker. Brief presentations of a few of the proffered papers followed, and then open discussion. There was opportunity for all proffered papers to be presented as posters. The fora, which occupied 3 full days, were preceded by reports on biological effects of radiation from international orgnaisations, and on related international conferences held in the recent past. The fora were followed by round table presentations of regulatory control and scientiFic research, and a summary session drawing together conclusions on the topic areas of the conference. (author)

  11. Bayesian approach in MN low dose of radiation counting

    International Nuclear Information System (INIS)

    Serna Berna, A.; Alcaraz, M.; Acevedo, C.; Navarro, J. L.; Alcanzar, M. D.; Canteras, M.

    2006-01-01

    The Micronucleus assay in lymphocytes is a well established technique for the assessment of genetic damage induced by ionizing radiation. Due to the presence of a natural background of MN the net MN is obtained by subtracting this value to the gross value. When very low doses of radiation are given the induced MN is close even lower than the predetermined background value. Furthermore, the damage distribution induced by the radiation follows a Poisson probability distribution. These two facts pose a difficult task to obtain the net counting rate in the exposed situations. It is possible to overcome this problem using a bayesian approach, in which the selection of a priori distributions for the background and net counting rate plays an important role. In the present work we make a detailed analysed using bayesian theory to infer the net counting rate in two different situations: a) when the background is known for an individual sample, using exact value value for the background and Jeffreys prior for the net counting rate, and b) when the background is not known and we make use of a population background distribution as background prior function and constant prior for the net counting rate. (Author)

  12. Dynamic low dose I-123-iodophenylpentadecanoic acid metabolic cardiac imaging

    International Nuclear Information System (INIS)

    Murray, G.L.; Magill, H.L.; Schad, N.C.

    1993-01-01

    Recognition of stunned and hibernating myocardium is essential in this era of cardiac revascularization. Positron emission tomography (PET) accurately identifies viability but is costly and unavailable to most patients. Dynamic low dose I-123-iodophenylpentadecanoic acid (IPPA) metabolic cardiac imaging is a potentially cost-effective alternative to PET. Using transmural myocardial biopsies obtained during coronary bypass surgery as the viability gold standard, resting IPPA imaging agreed with 39/43 (91%) biopsies, with a sensitivity for viability of 33/36(92%) and a specificity of 6/7 (86%) in patients with severe ischemic cardiomyopathy. Eighty percent of IPPA viable, infarcted segments improved wall motion postoperatively. Furthermore, when compared to reinjection thallium (SPECT-Tl) scans after myocardial infarction, there was IPPA-Tl concordance in 27/35 (77%)(Kappa=0.536, p=0.0003). Similar to PET, IPPA demonstrated more viability than SPECT-Tl, 26/35 (74%) vs. 18/35 (51%)(p=0.047). Finally, when compared to transvenous endomyocardial biopsy for detecting rejection following cardiac transplantation, IPPA sensitivity for ≥Grade II rejection was 100%, and IPPA screening assessment for the necessity of biopsy could result in a 31% cost-savings. Therefore, IPPA metabolic cardiac imaging is a safe, inexpensive technique with a promising future. (author)

  13. Low-dose caffeine physical dependence in humans.

    Science.gov (United States)

    Griffiths, R R; Evans, S M; Heishman, S J; Preston, K L; Sannerud, C A; Wolf, B; Woodson, P P

    1990-12-01

    This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized.

  14. Thermal stability of low dose Ga+ ion irradiated spin valves

    International Nuclear Information System (INIS)

    Qi Xianjin; Wang Yingang; Zhou Guanghong; Li Ziquan

    2009-01-01

    The thermal stability of low dose Ga + ion irradiated spin valves has been investigated and compared with that of the as-prepared ones. The dependences of exchange field, measured using vibrating sample magnetometer at room temperature, on magnetic field sweep rate and time spent at negative saturation of the pinned ferromagnetic layer, and training effect were explored. The training effect is observed on both the irradiated spin valves and the as-prepared ones. The magnetic field sweep rate dependence of the exchange bias field of the irradiated spin valves is nearly the same as that of the as-prepared ones. For the as-prepared structure thermal activation has been observed, which showed that holding the irradiated structure at negative saturation of the pinned ferromagnetic layer for up to 28 hours results in no change in the exchange field. The results indicate that the thermal stability of the ion irradiated spin valves is the same as or even better than the as-prepared ones.

  15. Biological effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Gonzalez, A.J.

    1994-01-01

    Few weeks ago, when the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) submitted to the U.N. General Assembly the UNSCEAR 1994 report, the international community had at its disposal a broad view of the biological effects of low doses of ionizing radiation. The 1994 report (272 pages) specifically addressed the epidemiological studies of radiation carcinogenesis and the adaptive responses to radiation in cells and organisms. The report was aimed to supplement the UNSCEAR 1993 report to the U.N. General Assembly- an extensive document of 928 pages-which addressed the global levels of radiation exposing the world population, as well as some issues on the effects of ionizing radiation, including: mechanisms of radiation oncogenesis due to radiation exposure, influence of the level of dose and dose rate on stochastic effects of radiation, hereditary effects of radiation effects on the developing human brain, and the late deterministic effects in children. Those two UNSCEAR reports taken together provide an impressive overview of current knowledge on the biological effects of ionizing radiation. This article summarizes the essential issues of both reports, although it cannot cover all available information. (Author)

  16. Health Effects of Exposure to Low Dose of Radiation

    International Nuclear Information System (INIS)

    Alatas, Zubaidah

    2003-01-01

    Human beings are exposed to natural radiation from external sources include radionuclides in the earth and cosmic radiation, and by internal radiation from radionuclides, mainly uranium and thorium series, incorporated into the body. Living systems have adapted to the natural levels of radiation and radioactivity. But some industrial practices involving natural resources enhance these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Biological effects of ionizing radiation are the outcomes of physical and chemical processes that occur immediately after the exposure, then followed by biological process in the body. These processes will involve successive changes in the molecular, cellular, tissue and whole organism levels. Any dose of radiation, no matter how small, may produce health effects since even a single ionizing event can result in DNA damage. The damage to DNA in the nucleus is considered to be the main initiating event by which radiation causes damage to cells that results in the development of cancer and hereditary disease. It has also been indicated that cytogenetic damage can occur in cells that receive no direct radiation exposure, known as bystander effects. This paper reviews health risks of low dose radiation exposure to human body causing stochastic effects, i.e. cancer induction in somatic cells and hereditary disease in genetic cells. (author)

  17. Low dose CT perfusion in acute ischemic stroke

    International Nuclear Information System (INIS)

    Murphy, Amanda; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I.; So, Aaron; Lee, Ting-Yim

    2014-01-01

    The purpose of this investigation is to determine if CT perfusion (CTP) measurements at low doses (LD = 20 or 50 mAs) are similar to those obtained at regular doses (RD = 100 mAs), with and without the addition of adaptive statistical iterative reconstruction (ASIR). A single-center, prospective study was performed in patients with acute ischemic stroke (n = 37; 54 % male; age = 74 ± 15 years). Two CTP scans were performed on each subject: one at 100 mAs (RD) and one at either 50 or 20 mAs (LD). CTP parameters were compared between the RD and LD scans in regions of ischemia, infarction, and normal tissue. Differences were determined using a within-subjects ANOVA (p 0.05). CTP-derived CBF and CBV are not different at 50 mAs compared to 100 mAs, even without the addition of ASIR. Current CTP protocols can be modified to reduce the effective dose by 50 % without altering CTP measurements. (orig.)

  18. Low dose CT perfusion in acute ischemic stroke.

    Science.gov (United States)

    Murphy, Amanda; So, Aaron; Lee, Ting-Yim; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I

    2014-12-01

    The purpose of this investigation is to determine if CT perfusion (CTP) measurements at low doses (LD = 20 or 50 mAs) are similar to those obtained at regular doses (RD = 100 mAs), with and without the addition of adaptive statistical iterative reconstruction (ASIR). A single-center, prospective study was performed in patients with acute ischemic stroke (n = 37; 54% male; age = 74 ± 15 years). Two CTP scans were performed on each subject: one at 100 mAs (RD) and one at either 50 or 20 mAs (LD). CTP parameters were compared between the RD and LD scans in regions of ischemia, infarction, and normal tissue. Differences were determined using a within-subjects ANOVA (p test post hoc analysis (p 50 mAs, there was no significant difference between cerebral blood flow (CBF), cerebral blood volume (CBV), or time to maximum enhancement (Tmax) values for the RD and LD scans in the ischemic, infarcted, or normal contralateral regions (p LD scans for all parameters in the ischemic and normal tissue regions (p > 0.05). CTP-derived CBF and CBV are not different at 50 mAs compared to 100 mAs, even without the addition of ASIR. Current CTP protocols can be modified to reduce the effective dose by 50 % without altering CTP measurements.

  19. Low dose radiation damage effects in silicon strip detectors

    International Nuclear Information System (INIS)

    Wiącek, P.; Dąbrowski, W.

    2016-01-01

    The radiation damage effects in silicon segmented detectors caused by X-rays have become recently an important research topic driven mainly by development of new detectors for applications at the European X-ray Free Electron Laser (E-XFEL). However, radiation damage in silicon strip is observed not only after extreme doses up to 1 GGy expected at E-XFEL, but also at doses in the range of tens of Gy, to which the detectors in laboratory instruments like X-ray diffractometers or X-ray spectrometers can be exposed. In this paper we report on investigation of radiation damage effects in a custom developed silicon strip detector used in laboratory diffractometers equipped with X-ray tubes. Our results show that significant degradation of detector performance occurs at low doses, well below 200 Gy, which can be reached during normal operation of laboratory instruments. Degradation of the detector energy resolution can be explained by increasing leakage current and increasing interstrip capacitance of the sensor. Another observed effect caused by accumulation of charge trapped in the surface oxide layer is change of charge division between adjacent strips. In addition, we have observed unexpected anomalies in the annealing process.

  20. Low dose radiation damage effects in silicon strip detectors

    Science.gov (United States)

    Wiącek, P.; Dąbrowski, W.

    2016-11-01

    The radiation damage effects in silicon segmented detectors caused by X-rays have become recently an important research topic driven mainly by development of new detectors for applications at the European X-ray Free Electron Laser (E-XFEL). However, radiation damage in silicon strip is observed not only after extreme doses up to 1 GGy expected at E-XFEL, but also at doses in the range of tens of Gy, to which the detectors in laboratory instruments like X-ray diffractometers or X-ray spectrometers can be exposed. In this paper we report on investigation of radiation damage effects in a custom developed silicon strip detector used in laboratory diffractometers equipped with X-ray tubes. Our results show that significant degradation of detector performance occurs at low doses, well below 200 Gy, which can be reached during normal operation of laboratory instruments. Degradation of the detector energy resolution can be explained by increasing leakage current and increasing interstrip capacitance of the sensor. Another observed effect caused by accumulation of charge trapped in the surface oxide layer is change of charge division between adjacent strips. In addition, we have observed unexpected anomalies in the annealing process.

  1. A nanovehicle developed for treating deep-seated bacteria using low-dose X-ray.

    Science.gov (United States)

    Pan, Chien-Lin; Chen, Ming-Hong; Tung, Fu-I; Liu, Tse-Ying

    2017-01-01

    Many non-antibiotic strategies, such as photocatalysis and photodynamic therapy, have been proposed to inhibit and/or kill bacteria. However, these approaches still have drawbacks such as insufficient bacterial specificity and the limited penetration depth of ultraviolet and near-infrared light. To overcome these limitations, we developed a bacteria-specific anti-bacterial technique via using low-dose X-ray. Graphene oxide quantum dots (GQDs, a multifunctional vehicle) conjugated with vancomycin (Van, a bacteria-targeting ligand) were assembled with Protoporphyrin IX (PpIX, a photo/radiation sensitizer) to yield a novel Van-GQDs/PpIX complex that specifically attached to Escherichia coli and efficiently generated intracellular reactive oxygen species following X-ray activation. Delivery using GQDs increased the PpIX/Van ratio in the target bacterial cell, damaged bacterial cell wall, and enhanced X-ray-induced PpIX activation. Hence, this approach allowed for the use of a low-dose X-ray to efficiently activate the Van-GQDs/PpIX complex to exert its bactericidal effects on Escherichia coli without damaging normal cells. Furthermore, the E. coli did not develop resistance to the proposed approach for at least 7 rounds of repeated administration during one week. Thus, this proposed vehicle exhibiting bacteria-specific X-ray-triggered toxicity is a promising alternative to antibiotics for treating serious bacterial infections occurring in deep-seated tissues/organs (e.g., osteomyelitis and peritonitis). Administration of antibiotics is the most common treatment modality for bacterial infections. However, in some cases, patient attributes such as age, health, tolerance to antibiotics do not allow for the use of high-dose antibiotics. In addition, some bacteria develop resistance to antibiotics because of improper and long-term use of these agents. Therefore, non-antibiotic strategies to treat deeply situated bacterial infections, such as osteomyelitis, are urgently

  2. Rapid Emergence of Resistance to Linezolid during Linezolid Therapy of an Enterococcus faecium Infection▿

    OpenAIRE

    Seedat, Jamela; Zick, Günther; Klare, Ingo; Konstabel, Carola; Weiler, Norbert; Sahly, Hany

    2006-01-01

    We report the emergence of linezolid resistance (MICs of 16 to 32 mg/liter) in clonally related vancomycin-susceptible and -resistant Enterococcus faecium isolates from an intensive care unit patient after 12 days of linezolid therapy. Only linezolid-susceptible isolates of the same clone were detected at 28 days after termination of linezolid therapy.

  3. Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats

    Directory of Open Access Journals (Sweden)

    Barhoum Rima

    2011-07-01

    Full Text Available Abstract Background GH and IGFs serum levels decline with age. Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver in aging rats. Using the same experimental model, the aim of this work was to study whether the exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in aging rats. Methods Three experimental groups were included in this study: young healthy controls (yCO, 17 weeks old; untreated old rats (O, 103 weeks old; and aging rats treated with IGF-II (O+IGF-II, 2 μg * 100 g body weight-1 * day-1 for 30 days. Analytical parameters were determined in serum by routine laboratory methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel, Switzerland. Serum levels of hormones (testosterone, IGF-I and insulin were assessed by RIA. Serum Total Antioxidant Status was evaluated using a colorimetric assay. Mitochondrial membrane potential was evaluated using rhodamine 123 dye (adding different substrates to determine the different states. ATP synthesis in isolated mitochondria was determined by an enzymatic method. Results Compared with young controls, untreated old rats showed a reduction of IGF-I and testosterone levels with a decrease of serum total antioxidant status (TAS. IGF-II therapy improved serum antioxidant capability without modifying testosterone and IGF-I circulating concentrations. In addition, IGF-II treatment reduced oxidative damage in brain and liver, improving antioxidant enzyme activities and mitochondrial function. IGF-II was also able to reduce cholesterol and triglycerides levels increasing free fatty acids concentrations. Conclusions We demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and

  4. Cystic Fibrosis and Its Management Through Established and Emerging Therapies.

    Science.gov (United States)

    Spielberg, David R; Clancy, John P

    2016-08-31

    Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disorder in the Caucasian population and occurs in many other ethnicities worldwide. The daily treatment burden is substantial for CF patients even when they are well, with numerous pharmacologic and physical therapies targeting lung disease requiring the greatest time commitment. CF treatments continue to advance with greater understanding of factors influencing long-term morbidity and mortality. In recent years, in-depth understanding of genetic and protein structure-function relationships has led to the introduction of targeted therapies for patients with specific CF genotypes. With these advances, CF has become a model of personalized or precision medicine. The near future will see greater access to targeted therapies for most patients carrying common mutations, which will mandate individualized bench-to-bedside methodologies for those with rare genotypes.

  5. What is Financial Therapy? Discovering Mechanisms and Aspects of an Emerging Field

    OpenAIRE

    Kristy L. Archuleta; Emily A. Burr; Anita K. Dale; Anthony Canale; Dan Danford; Erika Rasure; Jeff Nelson; Kelley Williams; Kurt Schindler; Brett Coffman; Ed Horwitz

    2012-01-01

    Very little research currently exists specifically on the topic of financial therapy. In this emerging field, it is important to lay the groundwork for future practice and study. The purpose of this study was to answer the question, “What are the mechanisms and aspects of financial therapy?” Using qualitative methods, eighteen members of the Financial Therapy Association were interviewed by members of the research team. The participants included six financial professi...

  6. Nucleic acid aptamers: an emerging frontier in cancer therapy.

    Science.gov (United States)

    Zhu, Guizhi; Ye, Mao; Donovan, Michael J; Song, Erqun; Zhao, Zilong; Tan, Weihong

    2012-11-04

    The last two decades have witnessed the development and application of nucleic acid aptamers in a variety of fields, including target analysis, disease therapy, and molecular and cellular engineering. The efficient and widely applicable aptamer selection, reproducible chemical synthesis and modification, generally impressive target binding selectivity and affinity, relatively rapid tissue penetration, low immunogenicity, and rapid systemic clearance make aptamers ideal recognition elements for use as therapeutics or for in vivo delivery of therapeutics. In this feature article, we discuss the development and biomedical application of nucleic acid aptamers, with emphasis on cancer cell aptamer isolation, targeted cancer therapy, oncology biomarker identification and drug discovery.

  7. Emerging Approaches to Counseling Intervention: Dialectical Behavior Therapy

    Science.gov (United States)

    Neacsiu, Andrada D.; Ward-Ciesielski, Erin F.; Linehan, Marsha M.

    2012-01-01

    Dialectical Behavior Therapy (DBT) is a comprehensive, multimodal cognitive behavioral treatment originally developed for individuals who met criteria for borderline personality disorder (BPD) who displayed suicidal tendencies. DBT is based on behavioral theory but also includes principles of acceptance, mindfulness, and validation. Since its…

  8. Emerging Technologies in Autism Diagnosis, Therapy, Treatment, and Teaching

    Science.gov (United States)

    Nelson, Angela C.

    2014-01-01

    Autism Spectrum Disorder is the fastest growing developmental disability today. Autism is a syndrome with a diverse set of symptoms--rarely consistent across diagnosed individuals, and requiring a combination of therapies, educational approaches, and treatments. There is no known cure for autism. Instead treatment is left to educators and…

  9. Effect of low-dose irradiation on pregnant mouse haemopoiesis

    International Nuclear Information System (INIS)

    Weinberg, S.R.; McCarthy, E.G.; MacVittie, T.J.; Baum, S.J.

    1981-01-01

    The effects of low-dose gamma radiation to haemopoietic progenitor cell compartments of the marrow and spleen of virgin female mice and pregnant mice were studied. Microplasma clot cultures were used to assess burst-forming uniterythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) activity, and double-layer agar cultures were established to evaluate granulocyte-macrophage colony-forming cell (GM-CFC) and macrophage colony-forming cell (M-CFC). The apparent shift in maternal erythropoiesis from the bone marrow to the enlarged spleen was reflected by an increase in CFU-E and BFU-E per spleen and a concomitant decrease in CFU-E and BFU-E per femur. Whereas maternal GM-CFC values per femur increased 36%, maternal GM-CFC per spleen increased by 172% compared to virgin values. Total-body irradiation to the day-10.5 pregnant mouse caused a further suppression of day-14.5 medullary erythropoiesis (i.e. decreased CFU-E values) compared to the virgin female mouse. An ability of the maternal spleen to support further compensatory erythropoiesis following increasing doses of radiation was demonstrated. Four days after 1.0 Gy exposure, maternal values for GM-CFC per femur or spleen decreased to nonirradiated virgin mice values. M-CFC per maternal femur decreased to nonirradiated virgin mice values. M-CFC per maternal femur decreased following 1.5 Gy, but M-CFC per spleen appeared to be unaffected with doses from 0.5 to 2.0 Gy. (author)

  10. Low dose TBT exposure decreases amphipod immunocompetence and reproductive fitness.

    Science.gov (United States)

    Jacobson, Therese; Sundelin, Brita; Yang, Gongda; Ford, Alex T

    2011-01-17

    The antifouling agent tributyltin (TBT) is a highly toxic pollutant present in many aquatic ecosystems. Despite of regulations on the usage of TBT, it remains in high concentrations in sediments both in harbors and in off-shore sites. The toxicity of TBT in mollusks is well documented. However, adverse effects in other aquatic organisms, such as crustaceans, are less well known. This study is an effort to assess the effects of environmentally realistic concentrations of TBT on an ecologically important species in Swedish fresh and brackish water ecosystems, the benthic amphipod Monoporeia affinis. Field collected animals were exposed during gonad maturation to TBT (70 and 170 ng/g sediment d wt) for five weeks in static microcosms with natural sediment. Exposure concentrations were chosen to reflect effects at concentrations found in Swedish coastal sediment, but below expected effects on survival. TBT exposure resulted in a statistically significant adverse effect on oocyte viability and a doubling of the prevalence of microsporidian parasites in females, from 17% in the control to 34% in the 170 ng TBT/g sediment d wt exposure. No effects on survival were observed. Borderline significant effects were observed on male sexual maturation in the 70 ng TBT/g d wt exposure and on ecdysteroid levels in the 170 ng/g sediment d wt exposure. Both reproduction and parasite infection effects are of ecological importance since they have the potential to affect population viability in the field. This study gives further evidence to the connection between low dose contaminant exposure and increases in microsporidian parasite infection. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Relationship to carcinogenesis of repetitive low-dose radiation exposure

    International Nuclear Information System (INIS)

    Ootsuyama, Akira

    2016-01-01

    We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose. (author)

  12. Pb low doses induced genotoxicity in Lactuca sativa plants.

    Science.gov (United States)

    Silva, S; Silva, P; Oliveira, H; Gaivão, I; Matos, M; Pinto-Carnide, O; Santos, C

    2017-03-01

    Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L -1 . In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO 3 ) 2 up to 20 mg L -1 . The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used. However, for doses higher than 5 mg L -1 significant DNA damage was detected: Comet assay detected DNA fragmentation at ≥ 5 mg L -1 and presence of micronuclei (MN) were detected for 20 mg L -1 . Also, cell cycle impairment was observed for doses as low as 0.05 mg L -1 and 0.5 mg L -1 (mostly G 2 arrest). Our data show that for the low doses of Pb used, the OECD endpoints were not able to detect toxicity, while more sensitive endpoints (related with DNA damage and mitotic/interphase disorders) identified genotoxic and cytostatic effects. Furthermore, the nature of the genotoxic effect was dependent on the concentration. Finally, we recommend that MN test and the comet assay should be included as sensitive endpoints in (eco)toxicological assays. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Evaluation of a low-dose neonatal chest radiographic system

    International Nuclear Information System (INIS)

    Burton, E.M.; Kirks, D.R.; Strife, J.L.; Henry, G.C.; Kereiakes, J.G.

    1988-01-01

    A new low-dose chest radiographic system for use in the neonatal nursery was evaluated. This test system, composed of a Du Pont Kevlar fiber-front cassette, Quanta fast-detail screen, Cronex 4L film (wide latitude), and additional yttrium filtration (0.1 mm), reduced the radiation dose in neonatal chest radiography by 69% (0.9 vs 2.9 mrad [0.009 vs 0.029 mGy]) as compared with a conventional system without added yttrium filtration; the thyroid dose was reduced by 76% (0.9 vs 3.7 mrad [0.009 vs 0.037 mGy]). The cumulative dose reduction was achieved through a combination of factors, including (1) beam hardening by the added yttrium filter, (2) increased X-ray transmission through the Kevlar cassette, and (3) a fast film-screen combination. Scatter radiation at distances of 1 and 6 ft. (0.3 and 1.8 m) was negligible for both systems. Image sharpness was compared for the conventional system with and without added yttrium filtration and for the Kevlar system with yttrium. Although sharpness of bony detail was unchanged by adding yttrium filtration to the conventional system, a decrease in sharpness was noted with the Kevlar system. Because image sharpness was affected in the test system, we are not using the Kevlar-Cronex 4L system for mobile chest radiography in the neonatal intensive care unit, despite dose reductions. However, further study is recommended to determine if there is a slower film-screen combination with yttrium filtration that will not degrade image sharpness

  14. A new study on the effects of low doses

    International Nuclear Information System (INIS)

    Dousset, M.; Jammet, H.

    1986-01-01

    A study conducted by prof. Rose has investigated mortality among 39540 employees of the UKAEA, from 1946 to 1978. The three main points are: 1. General mortality and mortality from malignant diseases are lower than in the population of England and Wales (74 and 79 per cent respectively), thus showing no major difference between workers monitored for exposure to radiation and other workers. 2. For monitored workers, the only death cause for which there is a statistically significant correlation with radiation exposure is prostate cancer; there are many cases especially in workers with doses exceeding 0.05 Sv (5 rem) and monitored for tritium. Such a correlation has never been found in any other epidemiologic survey of workers exposed to low-level doses, Hanford (USA) workers especially; conversely, mortality from either multiple myeloma or pancreas cancer is not found here. These facts plead for a cautious interpretation of the results as a whole. 3. A linear representation of the variations of leukemia and cancer mortality vs exposure results in lines, the slopes of which are 3 times higher than those of the lines adopted by ICRP; however, the 95% confidence intervals (-2.7 + 12.4 and -22 + 52.5) are such that the results are compatible with a null effect (slope 0) and even with a benefic effect (negative slope). They are therefore compatible with ICRP estimations. A recent attempt to evaluate the two main investigations on low-dose occupational exposures (UKAEA and Hanford) suggests a dose-response relationship very near that of ICRP [fr

  15. Lung cancer risk at low doses of alpha particles

    International Nuclear Information System (INIS)

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

    1986-01-01

    A survey of inhabitant exposures arising from the inhalation of 222 Rn and 220 Rn progeny, and lung cancer mortality has been carried out in two adjacent areas in Guangdong Province, People's Republic of China, designated as the high background and the control area. Annual exposure rates are 0.38 working level months (WLM) per year in the high background, and 0.16 WLM/yr in the control area. In 14 yr of continuous study, from 1970 to 1983, age-adjusted mortality rates were found to be 2.7 per 10(5) living persons of all ages in the high background area, and 2.9 per 10(5) living persons in the control area. From this data, we conclude that we are unable to determine excess lung cancers over the normal fluctuations below a cumulative exposure of 15 WLM. This conclusion is supported by lung cancer mortality data from Austrian and Finnish high-background areas. A theoretical analysis of epidemiological data on human lung cancer incidence from inhaled 2 ]2'' 2 Rn and 220 Rn progeny, which takes into account cell killing as competitive with malignant transformation, leads to the evaluation of a risk factor which is either a linear-exponential or a quadratic-exponential function of the alpha-particle dose. Animal lung cancer data and theoretical considerations can be supplied to support either hypothesis. Thus we conclude that at our current stage of knowledge both the linear-exponential and the quadratic-exponential extrapolation to low doses seem to be equally acceptable for Rn-induced lung cancer risk, possibly suggesting a linear-quadratic transformation function with an exponential cell-killing term, or the influence of risk-modifying factors such as repair or proliferation stimuli

  16. Low dose CT perfusion in acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Amanda; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I. [Sunnybrook Health Sciences Centre, Toronto, ON (Canada); So, Aaron; Lee, Ting-Yim [Robarts Research Institute, London, Ontario (Canada)

    2014-12-15

    The purpose of this investigation is to determine if CT perfusion (CTP) measurements at low doses (LD = 20 or 50 mAs) are similar to those obtained at regular doses (RD = 100 mAs), with and without the addition of adaptive statistical iterative reconstruction (ASIR). A single-center, prospective study was performed in patients with acute ischemic stroke (n = 37; 54 % male; age = 74 ± 15 years). Two CTP scans were performed on each subject: one at 100 mAs (RD) and one at either 50 or 20 mAs (LD). CTP parameters were compared between the RD and LD scans in regions of ischemia, infarction, and normal tissue. Differences were determined using a within-subjects ANOVA (p < 0.05) followed by a paired t test post hoc analysis (p < 0.01). At 50 mAs, there was no significant difference between cerebral blood flow (CBF), cerebral blood volume (CBV), or time to maximum enhancement (Tmax) values for the RD and LD scans in the ischemic, infarcted, or normal contralateral regions (p < 0.05). At 20 mAs, there were significant differences between the RD and LD scans for all parameters in the ischemic and normal tissue regions (p > 0.05). CTP-derived CBF and CBV are not different at 50 mAs compared to 100 mAs, even without the addition of ASIR. Current CTP protocols can be modified to reduce the effective dose by 50 % without altering CTP measurements. (orig.)

  17. What is Financial Therapy? Discovering Mechanisms and Aspects of an Emerging Field

    Directory of Open Access Journals (Sweden)

    Kristy L. Archuleta

    2012-12-01

    Full Text Available

    Very little research currently exists specifically on the topic of financial therapy. In this emerging field, it is important to lay the groundwork for future practice and study. The purpose of this study was to answer the question, “What are the mechanisms and aspects of financial therapy?” Using qualitative methods, eighteen members of the Financial Therapy Association were interviewed by members of the research team. The participants included six financial professionals, six mental health professions, and six researchers/educators all engaged in financial therapy. Six categories emerged from the analysis of data, including: (a integration, (b complexity, (c help seeker issues, (d helper issues, (e process, and (f research. The analysis resulted in a conceptual framework and ten theoretical assumptions of financial therapy.

  18. Effectiveness of low-dose midazolam plus ketamine in the ...

    African Journals Online (AJOL)

    2012-11-01

    Nov 1, 2012 ... to mild physical stimulation; and 5 = eyes closed, but unarousable to mild ... 3 and above. They were given pethidine as rescue therapy, according to protocol. ..... function of geriatric patients under spinal anesthesia. Korean J.

  19. Emerging options in growth hormone therapy: an update

    Directory of Open Access Journals (Sweden)

    Kemp SF

    2011-08-01

    Full Text Available Stephen F Kemp, J Paul FrindikUniversity of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USAAbstract: Growth hormone (GH was first used to treat a patient in 1958. For the next 25 years it was available only from cadaver sources, which was of concern because of safety considerations and short supply. In 1985, GH produced by recombinant DNA techniques became available, expanding its possible uses. Since that time there have been three indications approved by the US Food and Drug Administration (FDA for GH-deficiency states and nine indications approved for non-GH-deficiency states. In 2003 the FDA approved GH for use in idiopathic short stature (ISS, which may indirectly cover other diagnoses that have short stature as a feature. However, coverage for GH therapy is usually more reliably obtainable for a specific indication, rather than the ISS indication. Possible future uses for GH therapy could include the treatment of syndromes such as Russell–Silver syndrome or chondrodystrophy. Other non-short-stature indications could include wound healing and burns. Other uses that have been poorly studied include aging and physical performance, in spite of the interest already shown by elite athletes in using GH. The safety profile of GH developed over the past 25 years has shown it to be a very safe hormone with few adverse events associated with it. The challenge for the future is to follow these patients into adulthood to determine whether GH therapy poses any long-term risks.Keywords: growth hormone, somatotropin, anabolic, short stature

  20. Efficacy and safety of low-dose topical tacrolimus in vernal keratoconjunctivitis.

    Science.gov (United States)

    Shoughy, Samir S; Jaroudi, Mahmoud O; Tabbara, Khalid F

    2016-01-01

    The objective of this study was to evaluate the efficacy and safety of topical low-dose tacrolimus (0.01%) solution in patients with vernal keratoconjunctivitis (VKC). A total of 62 consecutive patients with VKC refractory to conventional treatment were included retrospectively. Tacrolimus 0.01% ophthalmic solution was administered to patients twice daily after discontinuation of all previous topical medications. The duration of treatment ranged from 1 month to 29 months. The clinical symptoms of itching, redness, foreign body sensation, and discharge and the clinical signs of conjunctival hyperemia, conjunctival papillary hypertrophy, limbal infiltration, Trantas dots, and superficial punctate keratopathy were graded as 0 (normal), 1+ (mild), 2+ (moderate), or 3+ (severe). Assessment was carried out before initiation of therapy and on the last visit after treatment. There were 62 patients with VKC comprising 49 male and 13 female patients. The median age was 12 years (range: 5-47 years). The mean visual acuity improved from 20/30 to 20/25 following treatment. There was statistically significant improvement in symptoms of itching (P<0.001), redness (P<0.001), foreign body sensation (P<0.001), and discharge (P<0.001). Statistically significant improvement was also observed in clinical signs of conjunctival hyperemia (P<0.001), limbal infiltration (P<0.001), Trantas dots (P<0.001), superficial punctate keratopathy (P<0.001), and conjunctival papillary hypertrophy (P<0.001). The solution form of tacrolimus was well tolerated. None of the patients developed elevation of intraocular pressure, cataract, or infectious keratitis. Low-dose topical tacrolimus 0.01% solution is effective and safe in the management of patients with refractory VKC.

  1. Effect of low dose radiation on expression of p16 gene in chronic myelogenous leukemia cells

    International Nuclear Information System (INIS)

    Zhang Longzhen; Ding Xin; Li Xiangyang; Cen Jiannong; Shen Hongjie; Chen Zixing

    2010-01-01

    Objective: To investigate the effect of low dose radiation on the expression on p16 gene in chronic myelogenous leukemia. Methods: Leukemic stem cells (LSCs) which expressed CD34 +, CD38 - and CD123 + were isolated from bone marrow cells obtained from twenty patients newly-diagnosedas chronic myeloid leukemia with EasySep TM magnet beads. Hematopoietic stem cells (HSCs) which expressed CD34 + and CD38 - were isolated from human cord blood cells obtained from twenty full-term deliveries with EasySep TM magnet beads as control. HSCs vs LSCs samples were further divided into three dose groups, including 0, 12.5 and 50 cGy, respectively. RT-PCR and real-time quantitative reverse transcription-polymerase chain reaction methods were used to detect mRNA expression of p16 gene in HSCs and LSCs after irradiation. Cells were harvested at different time for detection of cell cycle and apoptosis by flow cytometer. Results: p16 mRNA level in CML-LSCs was increased slightly at 12.5 cGy, and significantly increased at 50 cGy (Z=-3.39, P 0 /G 1 stagewas increased 48 h after 12.5 cGy irradiation, and 72 h post-irradiation with 50 cGy. The apoptosis rate of CML-LSCs was gradually raised after LDR, especially at 72 h post-irradiation of 50 cGy [(17.75±11.760% vs (6.13±4.71)%, Z=-2.37, P<0.01]. Conclusions: p16 gene transcription could be up-regulated by low dose radiation, which might provide a theoretical evidence for CML therapy and LDR in leukemic clinical application. (authors)

  2. Pharmacological radionuclide ventriculography for detection of myocardial contractile reserve in patients after myocardial infarction: head-to-head comparison of low dose dobutamine and low dose dypiridamole

    International Nuclear Information System (INIS)

    Petrasinovic, Z.; Ostojic, M.; Beleslin, B.; Stojkovic, S.; Nedeljkovic, M.; Stankovic, G.; Dikic, A.; Pavlovic, S.; Sobic, D.

    2002-01-01

    Background. Low dose pharmacological stress echocardiography with either dobutamine or dipyridamole infusion has been proposed for recognition of myocardial viability. However, dependence on adequate acoustic window, observer experience, and the mild degree of wall motion changes make the viability assessment by stress echocardiography especially bothersome. The objective of the study was to evaluate the ability of low dose dobutamine and low dose dipyridamole radionuclide ventriculography to detect contractile reserve in patients after myocardial infarction and functional recovery after coronary angioplasty. Methods. The study group consisted of 20 consecutive patients (52±10 years, 17 male) with previous myocardial infarction and resting regional dyssynergy, in whom diagnostic cardiac catheterization revealed significant one-vessel coronary artery stenosis suitable for angioplasty. Each patient underwent equilibrium 99m-Tc radionuclide ventriculography which was performed at rest and during low dose dipyridamole (0.28 mg/kg over 2 minutes) and low dose dobutamine infusion (up to 10 mcg/kg/min). Left ventricular global and regional ejection fractions were determined. Increase of regional ejection fraction for >5% (inferoapical and posterolateral regions) or >10% (anteroseptal regions) during low dose dobutamine and dipyridamole in infarcted regions, as well as in the follow up period, was considered as index of contractile reserve. After 8 weeks of successful angioplasty, resting radionuclide ventriculography was repeated in all patients in order to identify functional recovery of the infarct zone. Results. Out of the 180 analyzed segments (20x9), 90 regional ejection fractions have shown depressed contractility. The mean of the regional ejection fractions showing depressed contractility increased from the resting value of 34±12% to 42±14% in the follow-up period (p=0.06). Of the 90 with baseline dyssynergy, 46 were responders during low-dose dobutamine (51

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-15

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

  4. Experience with the low-dose in Bangladesh.

    Science.gov (United States)

    1982-03-01

    Condom sales (brand name Raja) have grown dramatically in Bangladesh and presently, sales account for over 50% of condoms distributed and represent more than 500,000 couple-years of protection (CYP). By contrast, sales of Maya, Noriday's brand name, accounts for only 8.5% of the total oral contraceptive (OC) distribution in Bangladesh and accounts for less than 50,000 CYP. According to the Director of the Bangladesh Social Marketing Program, poor performance of Maya is attributable to marketing factors. The mass media program was ineffectual in motivating new acceptors but it did make Maya a "household word" and it is now almost synonymous with the pill. Despite the nonuse, the number of potential OC users is high and therefore the CSM Project management decided that a new product with a distinct name, a new price, and a new marketing strategy was necessary. Norminest, a low-dose 0.35 mg ethinyl estradiol became available through AID and it was seen as a real alternative to those hormonal contraceptive products already available. The name selected was Ovacon and its packaging (which included goldleaf to signify high quality) was quite different than what came before. The price was set at 4.00 taka/cycle ($.21 in U.S.) which was higher than the Maya but lower than other commercially available OCs. Distribution of this new product was to center around physicians and other medical professionals in urban areas and promotion was to be limited to professional publications. This strategy had 2 objectives: establish personal contact with users and overcome the common practice of blaming the health of clients for the complaints heard. Ovacon was launched in June 1980 and now it is being detailed to rural practitioners. It is still not available in high traffic shops or through panwallahs. While sales have grown to 20-25,000 cycles/month, they are still about 1/2 of Maya sales. Together, these 2 methods represent 50,000 CYP. What was not anticipated was the magnitude of

  5. Spectroscopic characterization of low dose rate brachytherapy sources

    Science.gov (United States)

    Beach, Stephen M.

    The low dose rate (LDR) brachytherapy seeds employed in permanent radioactive-source implant treatments usually use one of two radionuclides, 125I or 103Pd. The theoretically expected source spectroscopic output from these sources can be obtained via Monte Carlo calculation based upon seed dimensions and materials as well as the bare-source photon emissions for that specific radionuclide. However the discrepancies resulting from inconsistent manufacturing of sources in comparison to each other within model groups and simplified Monte Carlo calculational geometries ultimately result in undesirably large uncertainties in the Monte Carlo calculated values. This dissertation describes experimentally attained spectroscopic outputs of the clinically used brachytherapy sources in air and in liquid water. Such knowledge can then be applied to characterize these sources by a more fundamental and metro logically-pure classification, that of energy-based dosimetry. The spectroscopic results contained within this dissertation can be utilized in the verification and benchmarking of Monte Carlo calculational models of these brachytherapy sources. This body of work was undertaken to establish a usable spectroscopy system and analysis methods for the meaningful study of LDR brachytherapy seeds. The development of a correction algorithm and the analysis of the resultant spectroscopic measurements are presented. The characterization of the spectrometer and the subsequent deconvolution of the measured spectrum to obtain the true spectrum free of any perturbations caused by the spectrometer itself is an important contribution of this work. The approach of spectroscopic deconvolution that was applied in this work is derived in detail and it is applied to the physical measurements. In addition, the spectroscopically based analogs to the LDR dosimetry parameters that are currently employed are detailed, as well as the development of the theory and measurement methods to arrive at these

  6. Lyssavirus infection: 'low dose, multiple exposure' in the mouse model.

    Science.gov (United States)

    Banyard, Ashley C; Healy, Derek M; Brookes, Sharon M; Voller, Katja; Hicks, Daniel J; Núñez, Alejandro; Fooks, Anthony R

    2014-03-06

    The European bat lyssaviruses (EBLV-1 and EBLV-2) are zoonotic pathogens present within bat populations across Europe. The maintenance and transmission of lyssaviruses within bat colonies is poorly understood. Cases of repeated isolation of lyssaviruses from bat roosts have raised questions regarding the maintenance and intraspecies transmissibility of these viruses within colonies. Furthermore, the significance of seropositive bats in colonies remains unclear. Due to the protected nature of European bat species, and hence restrictions to working with the natural host for lyssaviruses, this study analysed the outcome following repeat inoculation of low doses of lyssaviruses in a murine model. A standardized dose of virus, EBLV-1, EBLV-2 or a 'street strain' of rabies (RABV), was administered via a peripheral route to attempt to mimic what is hypothesized as natural infection. Each mouse (n=10/virus/group/dilution) received four inoculations, two doses in each footpad over a period of four months, alternating footpad with each inoculation. Mice were tail bled between inoculations to evaluate antibody responses to infection. Mice succumbed to infection after each inoculation with 26.6% of mice developing clinical disease following the initial exposure across all dilutions (RABV, 32.5% (n=13/40); EBLV-1, 35% (n=13/40); EBLV-2, 12.5% (n=5/40)). Interestingly, the lowest dose caused clinical disease in some mice upon first exposure ((RABV, 20% (n=2/10) after first inoculation; RABV, 12.5% (n=1/8) after second inoculation; EBLV-2, 10% (n=1/10) after primary inoculation). Furthermore, five mice developed clinical disease following the second exposure to live virus (RABV, n=1; EBLV-1, n=1; EBLV-2, n=3) although histopathological examination indicated that the primary inoculation was the most probably cause of death due to levels of inflammation and virus antigen distribution observed. All the remaining mice (RABV, n=26; EBLV-1, n=26; EBLV-2, n=29) survived the tertiary and

  7. Second International MELODI Workshop on Low Dose Risk Research - Slides of the presentations

    International Nuclear Information System (INIS)

    Repussard, J.; Weiss, W.; Quintana Trias, O.; Rosario Perez, M. del; Andersen, M.; Rudiger Trott, K.; Ottolenghi, A.; Smyth, V.; Graw, J.; Little, M.P.; Yonai, S.; Barcellos-Hoff, M.H.; Bouffler, S.; Chevillard, S.; Jeggo, P.; Sabatier, L.; Baatout, S.; Niwa, O.; Oesch, F.; Atkinson, M.; Averbeck, D.; Lloyd, D.; O'Neill, P.

    2011-01-01

    The MELODI (Multidisciplinary European Low Dose Initiative) mission is to impulse low dose risk research in Europe through a strategic research agenda (SRA) and road-map of priorities. The last presentation is dedicated to the SRA and its preference research programs. The other presentations deal principally with the low-dose exposure in medical uses of ionizing radiations, radiosensitivity, radiation-induced cataracts, or epidemiology and radiobiology of cardiovascular disease. This document is composed of the slides of the presentations

  8. The Potential Neurotoxic Effects of Low-Dose Sarin Exposure in a Guinea Pig Model

    Science.gov (United States)

    2002-01-01

    1 THE POTENTIAL NEUROTOXIC EFFECTS OF LOW-DOSE SARIN EXPOSURE IN A GUINEA PIG MODEL Melinda R. Roberson, PhD, Michelle B. Schmidt...Proving Ground, MD 21010 USA ABSTRACT This study is assessing the effects in guinea pigs of repeated low-dose exposure to the nerve...COVERED - 4. TITLE AND SUBTITLE The Potential Neurotoxic Effects Of Low-Dose Sarin Exposure In A Guinea Pig Model 5a. CONTRACT NUMBER 5b

  9. 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.

  10. Primary stenting as emergency therapy in acute basilar artery occlusion

    International Nuclear Information System (INIS)

    Spreer, Joachim; Arnold, Sebastian; Klisch, Joachim; Schumacher, Martin; Els, Thomas; Hetzel, Andreas; Huppertz, Hans-Juergen; Oehm, Eckhardt

    2002-01-01

    In three patients with acute occlusion of the basilar artery intra-arterial fibrinolysis resulted in only partial recanalization and revealed severe stenosis as the underlying cause. Application of micro-stents without previous dilatation resulted in vessel re-opening. Two patients had an excellent clinical outcome. One patient died 10 days after the stroke due to brainstem infarction. Emergency primary stent application may improve the outcome in acute basilar artery occlusion, if intra-arterial thrombolysis fails to re-establish a sufficient flow. (orig.)

  11. 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.

  12. Current and emerging therapies for the treatment of myasthenia gravis

    Directory of Open Access Journals (Sweden)

    Renato Mantegazza

    2011-03-01

    Full Text Available Renato Mantegazza, Silvia Bonanno, Giorgia Camera, Carlo AntozziDepartment of Neuromuscular Diseases and Neuroimmunology, Fondazione Istituto Neurologico Carlo Besta, Milan, ItalyAbstract: Myasthenia gravis (MG is an autoimmmune disease in which autoantibodies to different antigens of the neuromuscular junction cause the typical weakness and fatigability. Treatment includes anticholinesterase drugs, immunosuppression, immunomodulation, and thymectomy. The autoimmune response is maintained under control by corticosteroids frequently associated with immunosuppressive drugs, with improvement in the majority of patients. In case of acute exacerbations with bulbar symptoms or repeated relapses, modulation of autoantibody activity by plasmapheresis or intravenous immunoglobulins provides rapid improvement. Recently, techniques removing only circulating immunoglobulins have been developed for the chronic management of treatment-resistant patients. The rationale for thymectomy relies on the central role of the thymus. Despite the lack of controlled studies, thymectomy is recommended as an option to improve the clinical outcome or promote complete remission. New videothoracoscopic techniques have been developed to offer the maximal surgical approach with the minimal invasiveness and hence patient tolerability. The use of biological drugs such as anti-CD20 antibodies is still limited but promising. Studies performed in the animal model of MG demonstrated that several more selective or antigen-specific approaches, ranging from mucosal tolerization to inhibition of complement activity or cellular therapy, might be feasible. Investigation of the transfer of these therapeutic approaches to the human disease will be the challenge for the future.Keywords: myasthenia gravis, therapy, immunosuppression, thymectomy, plasmapheresis

  13. Randomized study on hydroxyurea alone versus hydroxyurea combined with low-dose interferon-alpha 2b for chronic myeloid leukemia

    NARCIS (Netherlands)

    Kluin-Nelemans, JC; Delannoy, A; Louwagie, A; Le Cessie, S; Hermans, J; van der Burgh, JF; Hagemeijer, AM; Van den Berghe, H

    1998-01-01

    Interferon-alpha (IFN-alpha) is considered the standard therapy for chronic myeloid leukemia (CML) patients not suitable for allogeneic stem cell transplantation. From 1987 through 1992, 195 patients in the Benelux with recent untreated CML were randomized between low-dose IFN-alpha 2b (3 MIU, 5

  14. Influence of low dose ionizing radiation on amplification and antitumor activity of LAK/TIL cells

    International Nuclear Information System (INIS)

    Liu Wei; Hou Dianjun; Qiao Jianwei; Shang Ximei; Li Jieqing

    2000-01-01

    Objective: To study the influence of low dose ionization on amplification and antitumor activity of LAK/TIL cells. Methods: TIL cells isolated from Lewis lung cancer tissues and LAK cells from spleen of tumor-bearing mouse were irradiated with different low doses of X-rays and were cultured after irradiation. Results: Low dose ionizing radiation improved the amplification volume of LAK/TIL cells, decreased the cell death ratio in amplification process, and increased the toxicity of LAK/TIL cells, Conclusions: Low dose ionizing radiation can result in amplification of biologically activated lymphocytes, and decreases the death ratio of the cells in amplification process

  15. Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options

    Directory of Open Access Journals (Sweden)

    Milic S

    2015-08-01

    Full Text Available Sandra Milic,1 Ivana Mikolasevic,1,2 Irena Krznaric-Zrnic,1 Marija Stanic,3 Goran Poropat,1 Davor Stimac,1 Vera Vlahovic-Palcevski,4 Lidija Orlic2 1Department of Gastroenterology, UHC Rijeka, Rijeka, Croatia; 2Department of Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, Rijeka, Croatia; 3Department of Hematology, UHC Rijeka, Rijeka, Croatia; 4Department for Clinical Pharmacology, University of Rijeka Medical School, UHC Rijeka, Rijeka, Croatia Abstract: Diet and lifestyle changes have led to worldwide increases in the prevalences of obesity and metabolic syndrome, resulting in substantially greater incidence of nonalcoholic fatty liver disease (NAFLD. NAFLD is considered a hepatic manifestation of metabolic syndrome and is related to diabetes, insulin resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic steatohepatitis (NASH is an entity that describes liver inflammation due to NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a clinical burden that is not only confined to liver-related morbidity and mortality, but that also affects several extra-hepatic organs and regulatory pathways. Thus, NAFLD is considered an important public health issue, but there is currently no effective therapy for all NAFLD patients in the general population. Studies seeking optimal therapy for NAFLD and NASH have not yet led to development of a universal protocol for treating this growing problem. Several pharmacological agents have been studied in an effort to improve insulin resistance and the proinflammatory mediators that may be responsible for NASH progression. Cardiovascular risk factors are highly prevalent among NASH patients, and the backbone of treatment regimens for these patients still comprises general lifestyle interventions, including dietary changes and increased physical activity. Vitamin E and thiazolidinedione derivatives are currently the most evidence-based therapeutic options, but only

  16. Pregnancy course in patients with intrahepatic cholestasis of pregnancy treated with very low doses of ursodeoxycholic acid.

    Science.gov (United States)

    Grymowicz, Monika; Czajkowski, Krzysztof; Smolarczyk, Roman

    2016-01-01

    Ursodeoxycholic acid (UDCA) has been proposed as the optimal pharmacological treatment for intrahepatic cholestasis of pregnancy (ICP). The lowest effective dosage of UDCA in women with ICP has not been established. The objective is to determine the risk of adverse pregnancy outcomes resulting from ICP and to measure changes in liver function parameters and pruritus severity in ICP patients treated with low doses of UDCA. ICP was diagnosed in 203 patients on the basis of pruritus and elevated liver biochemical parameters. Patients with total bile acids (TBA) ≥ 10 μmol/l (n = 157) received UDCA (300-450 mg/day; 4-6 mg/kg/day) until delivery. Maternal and fetal outcomes of women with ICP were compared with 100 patients without cholestasis. Patients with ICP were hospitalized for treatment and fetal surveillance. There was no correlation between fetal and neonatal complication rates in ICP patients and biochemical markers of cholestasis. Significant declines in serum TBA (p = 0.003), bilirubin concentration (p = 0.026) and aminotransferase activity (p < 0.001) were observed during treatment with low doses of UDCA. Moreover, severity of pruritus was ameliorated during the 2 weeks of therapy (p = 0.037). A total of 17 patients (10.9%) did not respond to treatment. UDCA at low doses improved biochemical markers and clinical symptoms in almost 90% of ICP patients.

  17. New and emerging therapies for the treatment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Michael G Feely

    2010-07-01

    Full Text Available Michael G FeelyDivision of Rheumatology and Immunology, Department of Internal Medicine, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, USAAbstract: The introduction of tumor necrosis factor (TNF inhibitors in the late 1990s ­significantly changed the therapeutic approach for rheumatoid arthritis (RA. With the approval of subsequent TNF inhibitors as well as other biologic agents effective in the management of RA, the treatment paradigm has become increasingly complex. This review examines the current literature regarding the efficacy and toxicity of these and other new anti-rheumatic therapies and discusses effective therapeutic strategies for their use.Keywords: biologics, tumor necrosis factor inhibitors, DMARDs, infliximab, etancercept, adalimumab, golimumab, certolizumab, abatacept, rituximab, tocilizumab

  18. The nucleolus: an emerging target for cancer therapy.

    Science.gov (United States)

    Hein, Nadine; Hannan, Katherine M; George, Amee J; Sanij, Elaine; Hannan, Ross D

    2013-11-01

    For over 100 years, pathologists have utilised an increase in size and number of nucleoli, the subnuclear site of ribosome synthesis, as a marker of aggressive tumours. Despite this, the contribution of the nucleolus and ribosomal RNA synthesis to cancer has been largely overlooked. This concept has recently changed with the demonstration that the nucleolus indirectly controls numerous other cellular functions, in particular, the cellular activity of the critical tumour suppressor protein, p53. Moreover, selective inhibition of ribosomal gene transcription in the nucleolus has been shown to be an effective therapeutic strategy to promote cancer-specific activation of p53. This article reviews the largely untapped potential of the nucleolus and ribosomal gene transcription as exciting new targets for cancer therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. 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

  20. Human papillomavirus E6 and E7 oncoproteins alter cell cycle progression but not radiosensitivity of carcinoma cells treated with low-dose-rate radiation

    International Nuclear Information System (INIS)

    DeWeese, Theodore L.; Walsh, Jonathan C.; Dillehay, Larry E.; Kessis, Theodore D.; Hedrick, Lora; Cho, Kathleen R.; Nelson, William G.

    1997-01-01

    Purpose: Low-dose-rate radiation therapy has been widely used in the treatment of urogenital malignancies. When continuously exposed to low-dose-rate ionizing radiation, target cancer cells typically exhibit abnormalities in replicative cell-cycle progression. Cancer cells that arrest in the G2 phase of the cell cycle when irradiated may become exquisitely sensitive to killing by further low-dose-rate radiation treatment. Oncogenic human papillomaviruses (HPVs), which play a major role in the pathogenesis of uterine cervix cancers and other urogenital cancers, encode E6 and E7 transforming proteins known to abrogate a p53-dependent G1 cell-cycle checkpoint activated by conventional acute-dose radiation exposure. This study examined whether expression of HPV E6 and E7 oncoproteins by cancer cells alters the cell-cycle redistribution patterns accompanying low-dose-rate radiation treatment, and whether such alterations in cell-cycle redistribution affect cancer cell killing. Methods and Materials: RKO carcinoma cells, which contain wild-type P53 alleles, and RKO cell sublines genetically engineered to express HPV E6 and E7 oncoproteins, were treated with low-dose-rate (0.25-Gy/h) radiation and then assessed for p53 and p21WAF1/CIP1 polypeptide induction by immunoblot analysis, for cell-cycle redistribution by flow cytometry, and for cytotoxicity by clonogenic survival assay. Results: Low-dose-rate radiation of RKO carcinoma cells triggered p53 polypeptide elevations, p21WAF1/CIP1 induction, and arrest in the G1 and G2 phases of the cell cycle. In contrast, RKO cells expressing E6 and E7 transforming proteins from high-risk oncogenic HPVs (HPV 16) arrested in G2, but failed to arrest in G1, when treated with low-dose-rate ionizing radiation. Abrogation of the G1 cell-cycle checkpoint activated by low-dose-rate radiation exposure appeared to be a characteristic feature of transforming proteins from high-risk oncogenic HPVs: RKO cells expressing E6 from a low

  1. Low dose of caffeine enhances the efficacy of antidepressants in major depressive disorder and the underlying neural substrates.

    Science.gov (United States)

    Liu, Qing-Shan; Deng, Ran; Fan, Yuyan; Li, Keqin; Meng, Fangang; Li, Xueli; Liu, Rui

    2017-08-01

    Caffeine is one of the most frequently used psychoactive substances ingested mainly via beverage or food products. Major depressive disorder is a serious and devastating psychiatric disorder. Emerging evidence indicates that caffeine enhances the antidepressant-like activity of common antidepressant drugs in rodents. However, whether joint administration of low dose of caffeine enhances the antidepressant actions in depressed patients remains unclear. A total of 95 male inpatients were assigned to three groups and were asked to take either caffeine (60, 120 mg) or placebo (soymilk powder) daily for 4 wk on the basis of their current antidepressant medications. Results showed that chronic supplementation with low dose of caffeine (60 mg) produced rapid antidepressant action by reduction of depressive scores. Furthermore, low dose of caffeine improved cognitive performance in depressed patients. However, caffeine did not affect sleep as measured by overnight polysomnography. Moreover, chronic caffeine consumption elicited inhibition of hypothalamic-pituitary-adrenal axis activation by normalization of salivary cortisol induced by Trier social stress test. These findings indicated the potential benefits of further implications of supplementary administration of caffeine to reverse the development of depression and enhance the outcome of antidepressants treatment in major depressive disorder. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Emergency Victim Care. A Training Manual for Emergency Medical Technicians. Module 5. CPR, Oxygen Therapy. Revised.

    Science.gov (United States)

    Ohio State Dept. of Education, Columbus. Div. of Vocational Education.

    This student manual, the fifth in a set of 14 modules, is designed to train emergency medical technicians (EMTs) in Ohio. The module contains two sections covering the following course content; cardiopulmonary resuscitation (CPR) (including artificial ventilation, foreign body obstructions, adjunctive equipment and special techniques, artificial…

  3. The results of randomized controlled trial of low-dose radiation for wet-type age-related macular degeneration on a 1 year term basis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-06-01

    Evaluation of low dose radiation therapy to the wet-type age-related macular degeneration (AMD) located at the fovea centralis. Patients were irradiated with 10 fractions of 2 Gy external beam or just observed. Between the treated (39) and untreated (31) cases, there was no significant difference in gender, age, initial visual acuity, or size of the neovascular membrane. With the follow-up of 12 months, the visual acuity was significantly well preserved and the size of the neovascular membrane was decreased. These results indicate that low dose irradiation is effective for the wet-type AMD of the stage we treated in the present study. (author)

  4. 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

  5. Low dose coronary CT angiography with 256-slice helical CT

    International Nuclear Information System (INIS)

    Zhang Xiaodong; Tang Binghang; Li Fangyun

    2011-01-01

    of 573) in B, 96.1% (548 of 570) in C, and 85.7% (505/589) in D, with no significant difference for A vs C (Z= -1.351, P>0.05) and with significant differences for B vs D (Z=-2.236, P<0.05). Linear correlation analysis indicated a significant degradation of image quality with the increase of heart rate using SAS mode (Spearman correlation, r=0.577, P<0.01). ROC analysis established an upper HR threshold of 78 bpm for obtaining diagnostic image quality using SAS mode (AUC = 0.827, P<0.05). The average radiation dose in group A [(2.6±0.5) mSv] reduced 75% comparing with that in group C [(10.6±2.3) mSv], and the average radiation dose in group B [(4.0±0.7) mSv] reduced 69% comparing with that in group D [(13.0±1.4) mSv]. Conclusion: Using SAS mode to perform low-dose CCTA with 256-slice helical CT could keep the image quality and reduce radiation dose significantly. Our preliminary experience suggests a good promise of this technique which could be applied to a wider group of patients such as with higher heart rates. (authors)

  6. The effects of repeated low-dose sarin exposure

    International Nuclear Information System (INIS)

    Shih, T.-M.; Hulet, S.W.; McDonough, J.H.

    2006-01-01

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD 5 dose of sarin (42 μg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD 5 of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD 5 of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD 5 sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD 5 sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD 5 sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD 5 sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD 5 doses of sarin failed to

  7. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders.

    Science.gov (United States)

    Patten, Denise K; Schultz, Bob G; Berlau, Daniel J

    2018-03-01

    Chronic inflammatory diseases are complex to treat and have an impact on a large number of patients. Due to the difficulty of treating these diseases and the great impact on quality of life, patients often seek off-label, complimentary, or alternative medicines to gain relief from symptoms. Low-dose naltrexone has been used off-label for treatment of pain and inflammation in multiple sclerosis, Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid receptor antagonist indicated by the U.S. Food and Drug Administration for opioid and alcohol dependence. It is hypothesized that lower than standard doses of naltrexone inhibit cellular proliferation of T and B cells and block Toll-like receptor 4, resulting in an analgesic and antiinflammatory effect. It is the purpose of this review to examine the evidence of the safety, tolerability, and efficacy of low-dose naltrexone for use in chronic pain and inflammatory conditions. Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn's disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited. However, further randomized controlled trials are needed to determine the efficacy of low-dose naltrexone due to insufficient evidence supporting its use in these disease states. This review provides practitioners with the extent of low-dose naltrexone evidence so that they can be cognizant of situations where it may not be the most appropriate therapy. © 2018 Pharmacotherapy Publications, Inc.

  8. Low-dose Norfloxacin-treated leptospires induce less IL-1β release in J774A.1 cells following discrepant leptospiral gene expression.

    Science.gov (United States)

    Cao, Yongguo; Xie, Xufeng; Zhang, Wenlong; Wu, Dianjun; Tu, Changchun

    2018-06-01

    Currently, accumulating evidence is challenging subtherapeutic therapy. Low-dose Norfloxacin (Nor) has been reported to suppress the immune response and worsen leptospirosis. In this study, we investigated the influence of low-dose Nor (0.03 μg/ml, 0.06 μg/ml, 0.125 μg/ml) on leptospiral gene expression and analyzed the immunomodulatory effects of low-dose Nor-treated leptospires in J774A.1 cells. To study the expression profiles of low-dose Nor-treated leptospires, we chose LipL71/LipL21 as reference genes determined by the geNorm applet in this experiment. The results showed that low-dose Nor up-regulated the expression of FlaB and inhibited the expression of 16S rRNA, LipL32, LipL41, Loa22, KdpA, and KdpB compared with the untreated leptospires. These results indicated that low-dose Nor could regulate leptospiral gene expression. Using RT-PCR, the gene expression of IL-1β and TNF-α in J774A.1 cells was detected. Nor-treated leptospires induced higher expression levels of both IL-1β and TNF-α. However, when analyzed by ELISA, the release of mature IL-1β was reduced compared with that observed in cells induced with no Nor-treated leptospires, although the TNF-α protein level showed no significant change. Our study indicated that the gene expression of leptospires could be modulated by low-dose Nor, which induced less IL-1β release in J774A.1 cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Evaluation of low doses of gamma irradiation in the formation of mineralization nodules in osteoblasts culture

    Energy Technology Data Exchange (ETDEWEB)

    Targino, Bárbara; Pinto, Thais Lazarine; Silva, Evily Fernandes; Somessari, E.S.R.; Bellini, Maria Helena; Affonso, Regina [Instituto De Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    Full text: Introduction: Osteoblasts are specialized fibroblasts that secrete and mineralize the bone matrix. The mineralized extracellular matrix is mainly composed of type I collagen, osteocalcin, and the inorganic mineral hydroxylapatite1. The use of radiation as therapy in some cancers causes great bone loss. However, low dose radiation may have the opposite effect. Low dose X-irradiation on osteoblastic culture had effects on proliferation and differentiation with increase of mineralization nodules2. However, there is little information on the potential therapeutic efficacy of low-dose gamma-irradiation in the formation of mineralization nodules. Objective: To evaluate the effects of irradiation with 60Co γ-rays in low doses in the formation of mineralization nodules in culture of osteoblasts. Methods: MC3T3-E1 cells were bought by the Banco de Células do Rio de Janeiro, Brazil (MC3T3-E1 Subclone 14). The cells were cultured in α-MEM medium consisting of 10% FBS and without β-glycerophosphate and L-ascorbic acid (GIBCO, Custom Product, Catalog No. A1049001) (Zhao Y, Guan H, Liu S et al. Biol. Pharm. Bull. 2005, 28(8):1371-1376). Plating efficiency assays: cells were plated at a density of 100 cell/plate into 60 mm Petri dishes. After 14 days the places were stained with violet crystal and the colonies were counted. -glycerophosphate and 50 mg/ml ascorbic acid, and analyzed on days 7, 14 and 21. Osteoblast culture irradiation assay: cells were plated at a density of 1 x 105 cells/plate on 60 mm dishes and the next day were irradiated by 60Co source with 0 (as the control), 0.5, 1.0, 1.5 and 2.0 Gy using the GammaCell 220 - Irradiation Unit of Canadian-Atomic Energy Commission Ltd. (CTR-IPEN). On day 21 of culture, undifferentiated (without ascorbic acid and β-glycerophosphate), differentiating cells (0 Gy) and irradiated cells at different doses, the medium was removed, cells were washed with phosphate buffer saline, fixed with 70% ethyl alcohol and

  10. Evaluation of low doses of gamma irradiation in the formation of mineralization nodules in osteoblasts culture

    International Nuclear Information System (INIS)

    Targino, Bárbara; Pinto, Thais Lazarine; Silva, Evily Fernandes; Somessari, E.S.R.; Bellini, Maria Helena; Affonso, Regina

    2017-01-01

    Full text: Introduction: Osteoblasts are specialized fibroblasts that secrete and mineralize the bone matrix. The mineralized extracellular matrix is mainly composed of type I collagen, osteocalcin, and the inorganic mineral hydroxylapatite1. The use of radiation as therapy in some cancers causes great bone loss. However, low dose radiation may have the opposite effect. Low dose X-irradiation on osteoblastic culture had effects on proliferation and differentiation with increase of mineralization nodules2. However, there is little information on the potential therapeutic efficacy of low-dose gamma-irradiation in the formation of mineralization nodules. Objective: To evaluate the effects of irradiation with 60Co γ-rays in low doses in the formation of mineralization nodules in culture of osteoblasts. Methods: MC3T3-E1 cells were bought by the Banco de Células do Rio de Janeiro, Brazil (MC3T3-E1 Subclone 14). The cells were cultured in α-MEM medium consisting of 10% FBS and without β-glycerophosphate and L-ascorbic acid (GIBCO, Custom Product, Catalog No. A1049001) (Zhao Y, Guan H, Liu S et al. Biol. Pharm. Bull. 2005, 28(8):1371-1376). Plating efficiency assays: cells were plated at a density of 100 cell/plate into 60 mm Petri dishes. After 14 days the places were stained with violet crystal and the colonies were counted. -glycerophosphate and 50 mg/ml ascorbic acid, and analyzed on days 7, 14 and 21. Osteoblast culture irradiation assay: cells were plated at a density of 1 x 105 cells/plate on 60 mm dishes and the next day were irradiated by 60Co source with 0 (as the control), 0.5, 1.0, 1.5 and 2.0 Gy using the GammaCell 220 - Irradiation Unit of Canadian-Atomic Energy Commission Ltd. (CTR-IPEN). On day 21 of culture, undifferentiated (without ascorbic acid and β-glycerophosphate), differentiating cells (0 Gy) and irradiated cells at different doses, the medium was removed, cells were washed with phosphate buffer saline, fixed with 70% ethyl alcohol and

  11. Emerging targeted therapies for plaque psoriasis – impact of ixekizumab

    Directory of Open Access Journals (Sweden)

    Kazemi T

    2017-04-01

    Full Text Available Tiana Kazemi,1 Benjamin Farahnik,2 John Koo,3 Kourosh Beroukhim1 1University of California – Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 2University of Vermont College of Medicine, Burlington, VT, 3University of California – San Francisco, Department of Dermatology, Psoriasis and Skin Treatment Center, San Francisco, CA, USA Background: Recent studies into the pathogenesis of psoriasis have identified the importance of interleukin 17 (IL-17 in disease activity and have thus provided a new target for biologic therapy. Ixekizumab, the most recent US Food and Drug Administration (FDA-approved anti-IL-17 biologic agent, appears to be a promising medication for patients suffering from moderate-to-severe plaque psoriasis. Methods: We reviewed the results of phase III trials for ixekizumab in order to assess the efficacy, safety, and impact on quality of life of this agent in the treatment of plaque psoriasis. Additionally, we compared these results to phase II and phase III trials for other biologic psoriasis medications including the anti-IL-23 agents tildrakizumab and guselkumab, the combined anti-IL-12 and anti-IL-23 agent ustekinumab, and the anti-IL-17 agents brodalumab and secukinumab. Results: Pooled results from individual studies demonstrate that among the most efficacious dosing regimens of these anti-interleukin therapies, ixekizumab achieves higher Psoriasis Area and Severity Index 75 rates and similar or higher static Physician Global Assessment 0-1 rates than the other anti-IL-17 and anti-IL-23 agents. The safety profile of ixekizumab is similar to these agents, with nasopharyngitis, upper respiratory infection, headache, arthralgia, and injection-site erythema as the most commonly reported adverse events. Conclusion: Ixekizumab is a highly efficacious, newly FDA-approved treatment for moderate-to-severe plaque psoriasis that demonstrates a robust clinical response, significant improvement in patient quality of

  12. Emerging surgical therapy in the treatment of glaucoma.

    Science.gov (United States)

    Nardi, Marco; Casini, Giamberto; Guidi, Gianluca; Figus, Michele

    2015-01-01

    There is general consensus that surgery gives a better intraocular pressure (IOP) control than medical therapy, but surgery may be affected by complications and failures, and for this reason nowadays, it is reserved to advanced or clearly progressive glaucoma. In recent years, there have been a lot of efforts to enhance safety and efficacy of conventional surgery as to find new techniques more safer and more effective. Actually, this is a field in rapid evolution, and we have a great number of innovative procedures, often working on complete different basis. These procedures are classified according to their mechanism of action and the type of surgical approach, in order to clearly understand of what we are speaking about. From a general point of view, surgical procedures may be divided in procedures that increase outflow and procedures that reduce aqueous production: most of these procedures can be performed with an ab externo or an ab interno approach. The ab interno approach has great advantages and enormous potential of development; probably, its diffusion will be facilitated by the development of new devices for angle visualization. Nevertheless, it is important to remember that actually none of the new procedures has been validated in large controlled clinical trials and none of the new procedures is indicated when IOP target is very low. © 2015 Elsevier B.V. All rights reserved.

  13. Current and emerging therapies for the treatment of myasthenia gravis

    Science.gov (United States)

    Mantegazza, Renato; Bonanno, Silvia; Camera, Giorgia; Antozzi, Carlo

    2011-01-01

    Myasthenia gravis (MG) is an autoimmmune disease in which autoantibodies to different antigens of the neuromuscular junction cause the typical weakness and fatigability. Treatment includes anticholinesterase drugs, immunosuppression, immunomodulation, and thymectomy. The autoimmune response is maintained under control by corticosteroids frequently associated with immunosuppressive drugs, with improvement in the majority of patients. In case of acute exacerbations with bulbar symptoms or repeated relapses, modulation of autoantibody activity by plasmapheresis or intravenous immunoglobulins provides rapid improvement. Recently, techniques removing only circulating immunoglobulins have been developed for the chronic management of treatment-resistant patients. The rationale for thymectomy relies on the central role of the thymus. Despite the lack of controlled studies, thymectomy is recommended as an option to improve the clinical outcome or promote complete remission. New videothoracoscopic techniques have been developed to offer the maximal surgical approach with the minimal invasiveness and hence patient tolerability. The use of biological drugs such as anti-CD20 antibodies is still limited but promising. Studies performed in the animal model of MG demonstrated that several more selective or antigen-specific approaches, ranging from mucosal tolerization to inhibition of complement activity or cellular therapy, might be feasible. Investigation of the transfer of these therapeutic approaches to the human disease will be the challenge for the future. PMID:21552317

  14. 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.

  15. The biological effects of low doses of radiation: medical, biological and ecological aspects

    International Nuclear Information System (INIS)

    Gun-Aajav, T.; Ajnai, L.; Manlaijav, G.

    2007-01-01

    Full text: The results of recent studies show that low doses of radiation make many different structural and functional changes in a cell and these changes are preserved for a long time. This phenomenon is called as effects of low doses of radiation in biophysics, radiation biology and radiation medicine. The structural and functional changes depend on doses and this dependence has non-linear and bimodal behaviour. More detail, the radiation effect goes up and reaches its maximum (Low doses maximum) in low doses region, then it goes down and takes its stationary means (there is a negative effect in a few cases). With increases in doses and with further increases it goes up. It is established that low dose's maximum depends on physiological state of a biological object, radiation quality and dose rate. During the experiments another special date was established. This specialty is that many different physical and chemical factors are mutually connected and have synergetic behaviour. At present, researches are concentrating their attention on the following three directions: 1. Direct and indirect interaction of radiation's low doses: 2. Interpretation of its molecular mechanism, regulation of the positive effects and elaboration of ways o removing negative effects: 3. Application of the objective research results into practice. In conclusion the authors mention the current concepts on interpretation of low doses effect mechanism, forward their own views and emphasize the importance of considering low doses effects in researches of environmental radiation pollution, radiation medicine and radiation protection. (author)

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

    International Nuclear Information System (INIS)

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

    1997-02-01

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

  17. Emergency surgery due to complications during molecular targeted therapy in advanced gastrointestinal stromal tumors (GIST)

    International Nuclear Information System (INIS)

    Rutkowski, P.; Nowecki, Z. I.; Dziewirski, W.; Ruka, W.; Siedlecki, J. A.; Grzesiakowska, U.

    2010-01-01

    Aim. The aim of the study was to assess the frequency and results of disease/treatment-related emergency operations during molecular targeted therapy of advanced gastrointestinal stromal tumors (GISTs). Methods. We analyzed emergency operations in patients with metastatic/inoperable GISTs treated with 1 st -line imatinib - IM (group I: 232 patients; median follow-up time 31 months) and 2 nd -line sunitinib - SU (group II: 43 patients; median follow-up 13 months; 35 patients in trial A6181036) enrolled into the Polish Clinical GIST Registry. Results. In group I 3 patients (1.3%) underwent emergency surgery due to disease/treatment related complications: one due to bleeding from a ruptured liver tumor (1 month after IM onset) and two due to bowel perforation on the tumor with subsequent intraperitoneal abscess (both 2 months after IM onset). IM was restarted 5-8 days after surgery and no complications in wound healing were observed. In group II 4 patients (9.5%) underwent emergency operations due to disease/treatment related complications: three due to bowel perforations on the tumor (2 days, 20 days and 10 months after SU onset; 1 subsequent death) and one due to intraperitoneal bleeding from ruptured, necrotic tumor (3.5 months after SU start). SU was restarted 12-18 days after surgery and no complications in wound healing were observed. Conclusions. Emergency operations associated with disease or therapy during imatinib treatment of advanced GISTs are rare. The frequency of emergency operations during sunitinib therapy is considered to be higher than during first line therapy with imatinib which may be associated with more advanced and more resistant disease or to the direct mechanism of sunitinib action, i.e. combining cytotoxic and antiangiogenic activity and thus leading to dramatic tumor response. Molecular targeted therapy in GISTs should always be conducted in cooperation with an experienced surgeon. (authors)

  18. Utilization of Emergency Medical Service Increases Chance of Thrombolytic Therapy in Patients with Acute Ischemic Stroke

    Science.gov (United States)

    Hsieh, Ming-Ju; Tang, Sung-Chun; Chiang, Wen-Chu; Huang, Kuang-Yu; Chang, Anna Marie; Ko, Patrick Chow-In; Tsai, Li-Kai; Jeng, Jiann-Shing; Ma, Matthew Huei-Ming

    2014-01-01

    Objective To determine whether utilization of emergency medical service (EMS) can expedite and improve the rate of thrombolytic therapy administration in acute ischemic stroke patients. Methods This is a prospective observational study of consecutive patients presenting to the emergency department (ED) with an ischemic stroke within 72 hours of symptom onset. Variables associated with early ED arrival (within 3 hours of stroke onset), and administration of thrombolytic therapy were analyzed. We also evaluated the factors related to onset-to-needle time in patients receiving thrombolytic therapy. Results From January 1, 2010 to July 31, 2011, there were 1081 patients (62.3% men, age 69.6 ± 13 years) included in this study. Among them, 289 (26.7%) arrived in the ED within 3 hours, and 88 (8.1%) received intravenous thrombolytic therapy. Patients who arrived to the ED by EMS (n=279, 25.8 %) were independently associated with earlier ED arrival (adjusted odds ratio [OR] = 3.68, 95% confidence interval [CI] = 2.54 to 5.33), and higher chance of receiving thrombolytic therapy (adjusted OR = 3.89, 95% CI= 1.86 to 8.17). Furthermore, utilization of EMS decreased onset-to-needle time by 26 minutes in patients receiving thrombolytic therapy. Conclusion Utilization of EMS can help acute ischemic stroke patients in early presentation to ED, facilitate thrombolytic therapy, and reduce the onset to needle time. PMID:24296308

  19. Low-dose radiation induces drosophila innate immunity through toll pathway activation

    International Nuclear Information System (INIS)

    Seong, Ki Moon; Kim, Cha Soon; Lee, Byung-Sub; Nam, Seon Young; Yang, Kwang Hee; Kim, Ji-Young; Jin, Young-Woo; Park, Joong-Jean; Min, Kyung-Jin

    2012-01-01

    Numerous studies report that exposing certain organisms to low-dose radiation induces beneficial effects on lifespan, tumorigenesis, and immunity. By analyzing survival after bacterial infection and antimicrobial peptide gene expression in irradiated flies, we demonstrate that low-dose irradiation of Drosophila enhances innate immunity. Low-dose irradiation of flies significantly increased resistance against gram-positive and gram-negative bacterial infections, as well as expression of several antimicrobial peptide genes. Additionally, low-dose irradiation also resulted in a specific increase in expression of key proteins of the Toll signaling pathway and phosphorylated forms of p38 and N-terminal kinase (JNK). These results indicate that innate immunity is activated after low-dose irradiation through Toll signaling pathway in Drosophila. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-15

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

  1. 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...

  2. Diagnosis and interventional neuroradiology in cranial emergencies. Neuroradiologische Notfalldiagnostik und -therapie kranieller Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Wakhloo, A.K.; Schumacher, M. (Freiburg Univ. (Germany, F.R.). Sektion Neuroradiologie)

    1991-01-01

    The most efficient diagnostic procedures are described for cases of intracranial mass, cerebral sinus and venous thrombosis, thrombosis of vertebral and basilar arteries, subarachnoid hemorrhage, carotid-cavernous fistulas, intractable epistaxis, Wernicke's encephalopathy and inflammatory cranial diseases. The importance of CT, MRI and angiography is discussed for these cranial emergencies. The different forms of interventional therapy possible are specified. (orig.).

  3. 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.

  4. Low dose radiation induced protein and its experimental and ophthalmic clinical research

    International Nuclear Information System (INIS)

    Shen Wei; Su Liaoyuan; Liu Fenju; Ding Jie; Li Longbiao; Pan Chengsi

    2001-01-01

    The protective effects of low dose radiation (LDR) induced protein on cellular impairments caused by some harmful chemical and physical factors were studied. Male Kunming mice were irradiated with LDR, then the spleen cells of the mice were broken with ultrasonic energy and then ultracentrifugalized. The supernatant solution contained with LDR induced protein. The newly emerging protein was detected by gel filtration and its molecular weight was determined by gel electrophoresis. The content of newly emerging protein (LDR induced protein) was determined by Lowry's method. The method of isotope incorporation was used to observe the biological activity and its influence factors, the protective effects of LDR induced protein on the cells impaired by irradiating with ultraviolet (UV), high doses of 60 Co γ-rays and exposed to heat respectively, and the stimulative effects of LDR induced protein on human peripheral blood lymphocytes. Newly emerging protein has been observed in the experiment. The molecular weight of the protein is in the region 76.9 KD+- - 110.0 KD+-, the yield of the protein was 613.33 +- 213.42 μg per 3 x 10 7 spleen cells. DPM values (isotope were incorporated) of normal and injured mice spleen cells increased significantly after stimulating with the solution contained LDR induced protein. It is concluded that LDR induced protein could be obtained from mice spleen cells exposed to 5 - 15 cGy radiation for 2 - 16 h. The protein had biological activity and was able to stimulate the transformation of the spleen cells in vitro. It had obvious protective effects on some impaired cells caused by high dose radiation, UV radiation, heat and so on. It also had stimulative effects on the transformation of peripheral blood T and B lymphocytes of healthy individual and patients with eye diseases. It indicates that LDR induced protein increased immune function of human

  5. Apoptosis of bone marrow leukemia cells in mice after low dose radiation at different time

    International Nuclear Information System (INIS)

    Li Guangyu; Yu Mingming; Li Xianjun; Liu Zhixiang

    2007-01-01

    Objective: To investigate the apoptosis of bone marrow leukemia cell in mice after low dose radiation (LDR) at different time and the experimental basis for LDR auxiliary therapy on leukemia. Methods: WEHI-3 cells were injected into BALB/c mice through tail veins to make an experimental mice model of myelornonocytic leukemia. 60 leukemia mice models were divided half-and half. 30 mice models in experimental group were irradiated with LDR of 75mGy at the same time while the others 30 in the control group were not. 6 mice models with LDR and 6 mice models without LDR would be killed at the time the 1st day, the 2nd day, the 3rd day, the 5th day- and the l0th day after LDR in order to extract bone marrow samples. The apoptosis percentage of leukemia cells in bone marrow was examined. Results: The apoptosis percentage of leukemia cells in experimental group was increasing after LDR and went to top on the 2nd day and the 3rd day. The apoptosis percentage of leukemia cells was remarkably different between experimental and control group, all P<0.05. Conclusion: LDR could significantly increase the apoptosis percentage of bone marrow leukemia cells in mice. Its mechanism is remarkably different in kill and wound of big dose radiation to tumour cells. It is probably related to of the increase immune exciting response as to promote some cytokine secretion, in leukemia mice. (authors)

  6. Langerhans Cell Histiocytosis of the Cranial Base: Is Low-Dose Radiotherapy Effective?

    Directory of Open Access Journals (Sweden)

    Andreas Meyer

    2012-01-01

    Full Text Available Introduction. Langerhans cell histiocytosis (LCH is a rare disease of unknown etiology with different clinical features. A standardised treatment has not been established so far. Case Report. We report a case of a 28-year-old patient who initially presented with hypesthesia of the fifth cranial nerve and pain of the left ear. Diagnosis showed a tumour localised in the cranial base with a maximum diameter of 4.1 cm. The diagnosis of LCH was confirmed histologically by biopsy. Diagnostic workup verified the cranial lesion as the sole manifestation of LCH. A total dose of 9 Gy (single dose 1.8 Gy was delivered. The symptoms dissolved completely within 6 months after radiation; repeated CT and MRI scans revealed a reduction in size of the lesion and a remineralisation of the bone. After a followup of 13 years the patient remains free of symptoms without relapse or any side effects from therapy. Discussion. Due to the indolent course of the disease with a high rate of spontaneous remissions the choice of treatment strongly depends on the individual clinical situation. In the presented case low-dose radiotherapy was sufficient to obtain long-term local control in a region with critical structures and tissues.

  7. 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.

  8. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. 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.

  11. Monte Carlo investigation of the low-dose envelope from scanned proton pencil beams

    International Nuclear Information System (INIS)

    Sawakuchi, Gabriel O; Titt, Uwe; Mirkovic, Dragan; Ciangaru, George; Zhu, X Ronald; Sahoo, Narayan; Gillin, Michael T; Mohan, Radhe

    2010-01-01

    Scanned proton pencil beams carry a low-dose envelope that extends several centimeters from the individual beam's central axis. Thus, the total delivered dose depends on the size of the target volume and the corresponding number and intensity of beams necessary to cover the target volume uniformly. This dependence must be considered in dose calculation algorithms used by treatment planning systems. In this work, we investigated the sources of particles contributing to the low-dose envelope using the Monte Carlo technique. We used a validated model of our institution's scanning beam line to determine the contributions to the low-dose envelope from secondary particles created in a water phantom and particles scattered in beam line components. Our results suggested that, for high-energy beams, secondary particles produced by nuclear interactions in the water phantom are the major contributors to the low-dose envelope. For low-energy beams, the low-dose envelope is dominated by particles undergoing multiple Coulomb scattering in the beam line components and water phantom. Clearly, in the latter situation, the low-dose envelope depends directly on beam line design features. Finally, we investigated the dosimetric consequences of the low-dose envelope. Our results showed that if not modeled properly the low-dose envelope may cause clinically relevant dose disturbance in the target volume. This work suggested that this low-dose envelope is beam line specific for low-energy beams, should be thoroughly experimentally characterized and validated during commissioning