The effect of low-dose total body irradiation on tumor control

International Nuclear Information System (INIS)

Sakamoto, Kiyohiko; Miyamoto, Miyako; Watabe, Nobuyuki.

1987-01-01

Total body irradiation (TBI) is considered to bring about an immunosuppressive effect on an organism, on the basis of data obtained from sublethal doses of TBI. However, there are no data on how low-dose TBI affects an organism. Over the last five years, we have been studying the effects of low-dose TBI on normal or tumor-bearing mice and the immunological background of these effects. In experimental studies, an increase in the TD50 value (the number of cells required for a tumor incidence of 50 %) in mice exposed to 10 rad was recognized and showed a remarkable increase at 6 hours to 15 hours after irradiation. TBI of 10 rad also showed an enhancement effect on tumor cell killing when given 12 hours before local tumor irradiation. In order to clarify the mechanism of this kind of effect, some immunological studies were performed using several immunological procedures, and the results suggested that 10 rad of TBI caused increasing tumor immunity in irradiated mice. Clinical trials in some patients with advanced tumors are now being undertaken on the basis of these experimental data, and the effect of TBI on tumor control appears promising, although it is too early to draw conclusions. (author)

Risk management in radiotherapy: analysis for total body irradiation

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Banguero, Y., E-mail: ybanguero@cin.edu.uy [Universidad de la República, Montevideo (Uruguay); Píriz, G.; Guerrero, L.; Cardozo, L.; Quarneti, A. [Centro Hospital Pereira Rossell, Montevideo (Uruguay); Nader, A. [Autoridad Reguladora Nacional de Radioprotección, Montevideo (Uruguay)

2017-07-01

Introduction: Management of risk in any technique that is using radiation energy is very important to prevent incidents and accidents. Pretending evaluate the risk in the all process of Total Body Irradiation (TBI), this work present a risk matrix with different possible events than could occur. Methods: SEVRRA-R platform that run in windows is using to build a risk matrix separating the process of TBI in commissioning, prescription, planning and delivering dose. Any stage has a procedure with different errors associated. We build a matrix using all this information to evaluate the kind of risk we have in the technique. Results: It was obtained a template that describes in general the process of TBI with principles events, barriers and consequences. Conclusion: Analyzing the risk in any stage of the process in Total Body irradiation is a useful tool to understand the key points to work in safety for this technique. (author)

Radiobiological speculations on therapeutic total body irradiation

International Nuclear Information System (INIS)

Vriesendorp, H.M.

1990-01-01

Unexpected total body irradiation (TBI) of human beings, involved in nuclear warfare or in accidents in nuclear reactors can be lethal. In the 1950s, bone marrow transplantation was discovered as a potentially life saving procedure after TBI in the dose range of 5.0 to 12.0 Gy. Since that time, deliberate or therapeutic TBI has been used to condition patients with a lethal bone marrow disorder for bone marrow replacement. The therapeutic ratio of TBI followed by bone marrow transplantation is small. Many potentially lethal complications can occur, such as acute TBI side effects, late TBI side effects or immunological complications of bone marrow transplantation such as graft versus host disease or graft rejection. The benefits of TBI and bone marrow transplantation are that they offer a chance for cure of previously lethal bone marrow disorders. The optimal parameters for TBI remain to be defined. The review discusses the current clinical and experimental animal data, as they relate to the future definition of less toxic TBI procedures with a better therapeutic ratio. Different TBI procedures are required for patients with malignant vs. non-malignant disorders or for patients with histoincompatible vs. histocompatible bone marrow donors.77 references

Computer-based anthropometrical system for total body irradiation.

Science.gov (United States)

Sánchez-Nieto, B; Sánchez-Doblado, F; Terrón, J A; Arráns, R; Errazquin, L

1997-05-01

For total body irradiation (TBI) dose calculation requirements, anatomical information about the whole body is needed. Despite the fact that video image grabbing techniques are used by some treatment planning systems for standard radiotherapy, there are no such systems designed to generate anatomical parameters for TBI planning. The paper describes an anthropometrical computerised system based on video image grabbing which was purpose-built to provide anatomical data for a PC-based TBI planning system. Using software, the system controls the acquisition and digitalisation of the images (external images of the patient in treatment position) and the measurement procedure itself (on the external images or the digital CT information). An ASCII file, readable by the TBI planning system, is generated to store the required parameters of the dose calculation points, i.e. depth, backscatter tissue thickness, thickness of inhomogeneity, off-axis distance (OAD) and source to skin distance (SSD).

ACPSEM ROSG TBI working group recommendations for quality assurance in total body irradiation

International Nuclear Information System (INIS)

Nelligan, Raelene; Bailey, Michael; Tran, Thu; Baldwin, Zoe

2015-01-01

The Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) radiation oncology specialty group (ROSG) formed a series of working groups in 2011 to develop recommendations for guidance of radiation oncology medical physics practice within the Australasian setting. These recommendations are intended to provide guidance for safe work practices and a suitable level of quality control without detailed work instructions. It is the responsibility of the medical physicist to ensure that locally available equipment and procedures are sufficiently sensitive to establish compliance to these recommendations. The recommendations are endorsed by the ROSG, and have been subject to independent expert reviews. For the Australian audience, these recommendations should be read in conjunction with the tripartite radiation oncology practice standards [1, 2]. This publication presents the recommendations of the ACPSEM total body irradiation working group (TBIWG) and has been developed in alignment with other international associations. However, these recommendations should be read in conjunction with relevant national, state or territory legislation and local requirements, which take precedence over the ACPSEM recommendations. It is hoped that the users of this and other ACPSEM recommendations will contribute to the development of future versions through the ROSG of the ACPSEM. This document serves as a guideline for calibration and quality assurance of equipment used for TBI in Australasia.

SU-C-213-04: Application of Depth Sensing and 3D-Printing Technique for Total Body Irradiation (TBI) Patient Measurement and Treatment Planning

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Lee, M; Suh, T [Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Han, B; Xing, L [Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA (United States); Jenkins, C [Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA (United States); Department of Mechanical Engineering, Stanford University, Palo Alto, CA (United States)

2015-06-15

Purpose: To develop and validate an innovative method of using depth sensing cameras and 3D printing techniques for Total Body Irradiation (TBI) treatment planning and compensator fabrication. Methods: A tablet with motion tracking cameras and integrated depth sensing was used to scan a RANDOTM phantom arranged in a TBI treatment booth to detect and store the 3D surface in a point cloud (PC) format. The accuracy of the detected surface was evaluated by comparison to extracted measurements from CT scan images. The thickness, source to surface distance and off-axis distance of the phantom at different body section was measured for TBI treatment planning. A 2D map containing a detailed compensator design was calculated to achieve uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors (OSLDs). Results: The whole scan of the anthropomorphic phantom took approximately 30 seconds. The mean error for thickness measurements at each section of phantom compare to CT was 0.44 ± 0.268 cm. These errors resulted in approximately 2% dose error calculation and 0.4 mm tungsten thickness deviation for the compensator design. The accuracy of 3D compensator printing was within 0.2 mm. In vivo measurements for an end-to-end test showed the overall dose difference was within 3%. Conclusion: Motion cameras and depth sensing techniques proved to be an accurate and efficient tool for TBI patient measurement and treatment planning. 3D printing technique improved the efficiency and accuracy of the compensator production and ensured a more accurate treatment delivery.

SU-C-213-04: Application of Depth Sensing and 3D-Printing Technique for Total Body Irradiation (TBI) Patient Measurement and Treatment Planning

International Nuclear Information System (INIS)

Lee, M; Suh, T; Han, B; Xing, L; Jenkins, C

2015-01-01

Purpose: To develop and validate an innovative method of using depth sensing cameras and 3D printing techniques for Total Body Irradiation (TBI) treatment planning and compensator fabrication. Methods: A tablet with motion tracking cameras and integrated depth sensing was used to scan a RANDOTM phantom arranged in a TBI treatment booth to detect and store the 3D surface in a point cloud (PC) format. The accuracy of the detected surface was evaluated by comparison to extracted measurements from CT scan images. The thickness, source to surface distance and off-axis distance of the phantom at different body section was measured for TBI treatment planning. A 2D map containing a detailed compensator design was calculated to achieve uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors (OSLDs). Results: The whole scan of the anthropomorphic phantom took approximately 30 seconds. The mean error for thickness measurements at each section of phantom compare to CT was 0.44 ± 0.268 cm. These errors resulted in approximately 2% dose error calculation and 0.4 mm tungsten thickness deviation for the compensator design. The accuracy of 3D compensator printing was within 0.2 mm. In vivo measurements for an end-to-end test showed the overall dose difference was within 3%. Conclusion: Motion cameras and depth sensing techniques proved to be an accurate and efficient tool for TBI patient measurement and treatment planning. 3D printing technique improved the efficiency and accuracy of the compensator production and ensured a more accurate treatment delivery

Factors modifying the toxicity of total body irradiation (TBI) with bone marrow transplant

International Nuclear Information System (INIS)

Fish, B.L.; Moulder, J.E.

1987-01-01

In defined-flora, barrier-maintained rats, radiation nephritis is the principle late toxicity seen after single dose, high dose rate TBI with bone marrow transplant. Shielding the kidneys eliminates this late toxicity. If rats are exposed to a conventional microbiological environment during and after TBI and bone marrow transplant, the principle late toxicity is pneumonitis. Low dose rate TBI gives similar renal toxicity but at doses twice as large. Clinically, TBI and bone marrow transplant is preceded by intensive drug treatment, typically with cyclophosphamide (Cytoxan) and cytosine arabinoside (ara-C). Pretreatment with a standard cytoxan/ara-C regimen, has no effect on the gastrointestinal toxicity of TBI, but results in a decrease in marrow toxicity. Late renal toxicity still occurs when bone marrow transplants are given, but it is to early to determine whether drug treatment has affected late renal tolerance. Experiments are also underway to determine the effects of fractionated TBI (3, 6 and 9 fractions in 60 hours) on acute tolerance and on late tolerance after bone marrow transplantation

Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Lapidot, T.; Singer, T.S.; Salomon, O.; Terenzi, A.; Schwartz, E.; Reisner, Y.

1988-01-01

Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection

Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

Science.gov (United States)

Lenarczyk, Marek; Su, Jidong; Haworth, Steven T; Komorowski, Richard; Fish, Brian L; Migrino, Raymond Q; Harmann, Leanne; Hopewell, John W; Kronenberg, Amy; Patel, Shailendra; Moulder, John E; Baker, John E

2015-06-01

The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

The role of total body irradiation in preparation for bone marrow transplantation in acute leukaemia. A review

International Nuclear Information System (INIS)

Zwaan, F.E.

1979-01-01

From extrapolation obtained from animal studies and radiation accidents, it is assumed that for man the LD 50 (30) will be between 300-500 rads total body irradiation (TBI) and the LD 100 at least 600 rads TBI. A dose of 1000 rads TBI is generally used in man for conditioning for bone marrow transplantation. In acute leukemia, total body irradiation is usually associated with cytoreductive chemotherapy. In Seattle 110 patients underwent bone marrow transplantation for acute leukemia in relapse. 15 patients became long term survivors. The main cause of failure were GVH, interstitial pneumonitis and leukemic relapse. New attempts are being made to improve the results: (1) better cytoreductive therapy preceding transplantation, (2) bone marrow transplantation during remission of the disease, (3) prevention of interstitial pneumonitis by modifications of the TBI technique

Anti-tumor effect of total body irradiation of low doses on WHT/Ht mice

International Nuclear Information System (INIS)

Miyamoto, Miyako; Sakamoto, Kiyohiko

1987-01-01

The effect of low dose (0.05 - 1.0 Gy) of total body irradiation (TBI) on non-tumor bearing and tumor bearing mice were investigated. Mice received TBI of 0.1 Gy during 6 - 12 hours before tumor cell inoculation demonstrated to need larger number of tumor cells (approximately 2.5 times) for 50 per cent tumor incidence, compared to recipient mice not to receive TBI. On the other hand, in tumor bearing mice given 0.1 Gy of TBI only tumor cell killing effect was not detected, however enhancement of tumor cell killing effect and prolonged growth delay were observed when tumor bearing mice were treated with 0.1 Gy of TBI in combined with local irradiation on tumors, especially cell killing effect was remarkable in dose range over 6 Gy of local exposure. The mechanism of the effect of 0.1 Gy TBI is considered to be host mediated reactions from the other our experimental results. (author)

Radiobiological considerations in the treatment of neuroblastoma by total body irradiation

International Nuclear Information System (INIS)

Wheldon, T.E.; O'Donoghue, J.; Gregor, A.; Livingstone, A.; Wilson, L.; West of Scotland Health Boards, Glasgow

1986-01-01

Neuroblastoma is a radiosensitive neoplasm for which total body irradiation (TBI) is presently under clinical consideration. Collated data on the radiobiology of human neuroblastoma cells in vitro indicates moderate cellular radiosensitivity and low capacity for accumulation of sublethal damage. Mathematical studies incorporating these parameters suggest that low dose fractionated TBI is unlikely to achieve significant levels of tumour cell kill. When high dose TBI is used in conjuction with bone marrow rescue a tumour 'log cell kill' of 4-5 should be achievable. This effect would be additional to that acheived by chemotherapy. Fractionated TBI with bone marrow rescue may be curative for some patients in clinical remission who are presently destined to relapse. (Auth.)

Total lymphoid irradiation and total body irradiation for allogeneic bone marrow transplantation in aplastic anemia

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Kurisu, Koichi; Hishikawa, Yoshio; Taniguchi, Midori; Kamikonya, Norihiko; Miura, Takashi; Kanamaru, Akihisa; Kakishita, Eizo; Kai, Shunro; Hara, Hiroshi (Hyogo Coll. of Medicine, Nishinomiya (Japan))

Between April 1980 and June 1989, 15 patients with severe aplastic anemia (SAA) were treated at Hyogo College of Medicine with bone marrow transplantation (BMT) after preparation consisting of cyclophosphamide (CY) and total lymphoid irradiation (TLI) or total body irradiation (TBI) for the purpose of reducing the incidence of graft rejection. All patients had initial evidence of engraftment after the first transplantation except for one patient who died of heart failure due to CY on the third day after transplantation and could not be evaluated for engraftment. Rejection later occurred in four of these 14 patients, who then underwent successful regrafting. One of these four patients, who was conditioned with CY alone at the first grafting, underwent successful regrafting after a conditioning regimen of CY and TBI. In the other three patients, irradiation was performed twice as the conditioning regimen. Thus, 14 of 15 patients underwent successful BMT and are alive with restored hematopoietic function. From the above results, the combination of TLI or TBI and CY was considered to be very useful as a conditioning regimen for BMT in patients with SAA. (author).

Patterns of patient specific dosimetry in total body irradiation

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Akino, Yuichi [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 (United States); Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871 (Japan); McMullen, Kevin P.; Das, Indra J. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 (United States)

2013-04-15

Purpose: Total body irradiation (TBI) has been used for bone marrow transplant for hematologic and immune deficiency conditions. The goal of TBI is to deliver a homogeneous dose to the entire body, with a generally accepted range of dose uniformity being within {+-}10% of the prescribed dose. The moving table technique for TBI could make dose uniform in whole body by adjusting couch speed. However, it is difficult to accurately estimate the actual dose by calculation and hence in vivo dosimetry (IVD) is routinely performed. Here, the authors present patterns of patient-specific IVD in 161 TBI patients treated at our institution. Methods: Cobalt-60 teletherapy unit (Model C9 Cobalt-60 teletherapy unit, Picker X-ray Corporation) with customized moving bed (SITI Industrial Products, Inc., Fishers, IN) were used for TBI treatment. During treatment, OneDose{sup TM} (Sicel Technology, NC) Metal Oxide-silicon Semiconductor Field Effect Transistor detectors were placed at patient body surface; both entrance and exit side of the beam at patient head, neck, mediastinum, umbilicus, and knee to estimate midplane dose. When large differences (>10%) between the prescribed and measured dose were observed, dose delivery was corrected for subsequent fractions by the adjustment of couch speed and/or bolus placement. Under IRB exempt status, the authors retrospectively analyzed the treatment records of 161 patients who received TBI treatment between 2006 and 2011. Results: Across the entire cohort, the median {+-} SD (range) percent variance between calculated and measured dose for head, neck, mediastinum, umbilicus, and knee was -2.3 {+-} 10.2% (-66.2 to +35.3), 1.1 {+-} 11.5% (-62.2 to +40.3), -1.9 {+-} 9.5% (-66.4 to +46.6), -1.1 {+-} 7.2% (-35.2 to +42.9), and 3.4 {+-} 12.2% (-47.9 to +108.5), respectively. More than half of treatments were within {+-}10% of the prescribed dose for all anatomical regions. For 80% of treatments (10%-90%), dose at the umbilicus was within {+-}10

Total body irradiation with a compensator fabricated using a 3D optical scanner and a 3D printer.

Science.gov (United States)

Park, So-Yeon; Kim, Jung-In; Joo, Yoon Ha; Lee, Jung Chan; Park, Jong Min

2017-05-07

We propose bilateral total body irradiation (TBI) utilizing a 3D printer and a 3D optical scanner. We acquired surface information of an anthropomorphic phantom with the 3D scanner and fabricated the 3D compensator with the 3D printer, which could continuously compensate for the lateral missing tissue of an entire body from the beam's eye view. To test the system's performance, we measured doses with optically stimulated luminescent dosimeters (OSLDs) as well as EBT3 films with the anthropomorphic phantom during TBI without a compensator, conventional bilateral TBI, and TBI with the 3D compensator (3D TBI). The 3D TBI showed the most uniform dose delivery to the phantom. From the OSLD measurements of the 3D TBI, the deviations between the measured doses and the prescription dose ranged from  -6.7% to 2.4% inside the phantom and from  -2.3% to 0.6% on the phantom's surface. From the EBT3 film measurements, the prescription dose could be delivered to the entire body of the phantom within  ±10% accuracy, except for the chest region, where tissue heterogeneity is extreme. The 3D TBI doses were much more uniform than those of the other irradiation techniques, especially in the anterior-to-posterior direction. The 3D TBI was advantageous, owing to its uniform dose delivery as well as its efficient treatment procedure.

Feasibility study of helical tomotherapy for total body or total marrow irradiation

International Nuclear Information System (INIS)

Hui, Susanta K.; Kapatoes, Jeff; Fowler, Jack; Henderson, Douglas; Olivera, Gustavo; Manon, Rafael R.; Gerbi, Bruce; Mackie, T. R.; Welsh, James S.

2005-01-01

Total body radiation (TBI) has been used for many years as a preconditioning agent before bone marrow transplantation. Many side effects still plague its use. We investigated the planning and delivery of total body irradiation (TBI) and selective total marrow irradiation (TMI) and a reduced radiation dose to sensitive structures using image-guided helical tomotherapy. To assess the feasibility of using helical tomotherapy (A) we studied variations in pitch, field width, and modulation factor on total body and total marrow helical tomotherapy treatments. We varied these parameters to provide a uniform dose along with a treatment times similar to conventional TBI (15-30 min). (B) We also investigated limited (head, chest, and pelvis) megavoltage CT (MVCT) scanning for the dimensional pretreatment setup verification rather than total body MVCT scanning to shorten the overall treatment time per treatment fraction. (C) We placed thermoluminescent detectors (TLDs) inside a Rando phantom to measure the dose at seven anatomical sites, including the lungs. A simulated TBI treatment showed homogeneous dose coverage (±10%) to the whole body. Doses to the sensitive organs were reduced by 35%-70% of the target dose. TLD measurements on Rando showed an accurate dose delivery (±7%) to the target and critical organs. In the TMI study, the dose was delivered conformally to the bone marrow only. The TBI and TMI treatment delivery time was reduced (by 50%) by increasing the field width from 2.5 to 5.0 cm in the inferior-superior direction. A limited MVCT reduced the target localization time 60% compared to whole body MVCT. MVCT image-guided helical tomotherapy offers a novel method to deliver a precise, homogeneous radiation dose to the whole body target while reducing the dose significantly to all critical organs. A judicious selection of pitch, modulation factor, and field size is required to produce a homogeneous dose distribution along with an acceptable treatment time. In

Indication of total body irradiation in adult allogeneic bone marrow transplantation

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Kasai, Masaharu (Sapporo Hokuyu Hospital (Japan). Artificial Organ and Transplantation Hospital)

1992-10-01

Indication of total body irradiation (TBI) in adult allogeneic bone marrow transplantation was discussed in comparison with non-TBI method of busulfan and cyclophosphamide (BU+CY). Each method has unique advantages and disadvantages. Concerning adverse effects of interstitial pneumonia, liver dysfunction and so on, there are no significant differences in both methods. TBI method should be preferably indicated for lymphatic leukemias and leukemias involving central nervous systems. It is important to clarify what kinds of combination regimen depending on the type and the stage of disease are most suitable for the longer survival of patients with leukemia or aplastic anemia by multicentric randomized study. (author).

An Acute Transverse Myelitis Attack after Total Body Irradiation: A Rare Case

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Muzaffer Keklik

2013-01-01

Full Text Available Total body irradiation (TBI combined with chemotherapy is widely used as a pretreatment regimen of bone marrow transplantation (BMT in hematologic disorders. Late complications related to TBI as part of the conditioning regimen for hematopoietic stem cell transplantation have been revealed. Acute transverse myelitis (ATM is a neurological syndrome characterized by disorder of motor, sensorial, and autonomic nerves, and tracts at medulla spinalis, which is resulted from involvement of spinal cord. In this paper, we presented an ATM attack developed after TBI in a patient with acute lymphoblastic leukemia (ALL as it is a rarely seen case.

Total body irradiation for myasthenia gravis with thymoma: case report

International Nuclear Information System (INIS)

Kang, Ki Mun; Choi, Ihl Bohng; Kim, In Ah

1999-01-01

Myasthenia Gravis (MG) is relatively rare occuring as one of important autoimmune disease to affect neuromuscular junction. This study was clinically to evaluate total body irradiation (TBI) against two patients including 33-year and 39-year females for chronic MG with thymoma who hospitalized in the St. Mary's Hospital, Catholic University since 1994 as well as who showed no response by thymectomy, immunotherapy and hormonal therapy. TBI designed by the dose of 150-180 cGy consisting of 10 cGy per fraction, three times a week, for 5-6 weeks using linear accelerator of 6 MV. During the treatment of TBI, they did complain acute side effect such as vomiting and also appear improved physical condition from 4-6 weeks after TBI. Through the follow-up period of 18 or 42 months after TBI, they did not have any symptomatic recurrence. Consequently, the results suggest that TBI can be used as an alternative tool for the patients concurrently for MG with thymoma who had been refractory to various conventional therapies like thymectomy, immunotherapy and hormonal therapy

Total body irradiation for myasthenia gravis with thymoma: case report

Energy Technology Data Exchange (ETDEWEB)

Kang, Ki Mun; Choi, Ihl Bohng; Kim, In Ah [College of Medicine, Catholic Univ., Seoul (Korea, Republic of)

1999-06-01

Myasthenia Gravis (MG) is relatively rare occuring as one of important autoimmune disease to affect neuromuscular junction. This study was clinically to evaluate total body irradiation (TBI) against two patients including 33-year and 39-year females for chronic MG with thymoma who hospitalized in the St. Mary's Hospital, Catholic University since 1994 as well as who showed no response by thymectomy, immunotherapy and hormonal therapy. TBI designed by the dose of 150-180 cGy consisting of 10 cGy per fraction, three times a week, for 5-6 weeks using linear accelerator of 6 MV. During the treatment of TBI, they did complain acute side effect such as vomiting and also appear improved physical condition from 4-6 weeks after TBI. Through the follow-up period of 18 or 42 months after TBI, they did not have any symptomatic recurrence. Consequently, the results suggest that TBI can be used as an alternative tool for the patients concurrently for MG with thymoma who had been refractory to various conventional therapies like thymectomy, immunotherapy and hormonal therapy.

Renal toxicity in children undergoing total body irradiation for bone marrow transplant

International Nuclear Information System (INIS)

Esiashvili, Natia; Chiang, K.-Y.; Hasselle, Michael D.; Bryant, Cynthia; Riffenburgh, Robert H.; Paulino, Arnold C.

2009-01-01

Purpose: Contribution of total body irradiation (TBI) to renal toxicity in children undergoing the bone marrow transplant (BMT) remains controversial. We report our institutional retrospective study that evaluates the frequency of acute and chronic renal dysfunction in children after using total body irradiation (TBI) conditioning regimens. Materials and methods: Between 1995 and 2003, 60 children with hematological malignancies underwent TBI as part of a conditioning regimen before allogeneic BMT. Patients received 4-14 Gy at 1.75-2 Gy/fraction in six-eight fractions. Lung shielding was used in all patients to limit lung dose to less than 10 Gy; renal shielding was not utilized. All patients had baseline renal function assessment and renal dysfunction post-BM was mainly evaluated on the basis of persistent serum creatinine elevation at acute (0-90 days) and chronic (>90 days) intervals after completion of BMT. Results: Acute renal dysfunction (ARD) was documented in 27 patients (45%); the majority had concurrent diagnosis of veno-occlusive disease (VOD) or graft-versus-host disease (GVHD) and other potential causes (sepsis, antibiotic). The risk for delayed renal dysfunction (DRD) at 1 year approached 25% for surviving patients. The ARD was strongly linked with the risk of the DRD. There was no statistically significant relationship between ARD, DRD and underlying diagnosis, GVHD, VOD or TBI doses with both univariate and multivariate analyses. The younger age (<5 years) had significantly increased risk for the development of ARD (p = 0.011). Conclusion: Our analysis validates high incidence of renal dysfunction in the pediatric BMT population. In contrast to other reports we did not find total body irradiation dose to be a risk factor for renal dysfunction. Future prospective studies are needed to assess risk factors and interventions for this serious toxicity in children following allogeneic BM

Effects of Zinc Compound on Body Weight and Recovery of Bone Marrow in Mice Treated with Total Body Irradiation

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Ming-Yii Huang

2007-09-01

Full Text Available This study aimed to investigate if zinc compound would have effects on body weight loss and bone marrow suppression induced by total body irradiation (TBI. ICR mice were divided randomly into two groups and treated with test or control compounds. The test compound contained zinc (amino acid chelated with bovine prostate extract, and the control was reverse osmosis pure water (RO water. One week after receiving the treatment, mice were unirradiated, or irradiated with 6 or 3 Gy by 6MV photon beams to the total body. Body weight changes were examined at regular intervals. Three and 5 weeks after the radiation, animals were sacrificed to examine the histologic changes in the bone marrow. Lower body weight in the period of 1-5 weeks after radiation and poor survival rate were found after the 6 Gy TBI, as compared with the 3 Gy groups. The median survival time after 6 Gy and 3 Gy TBI for mice given the test compound were 26 and 76 days, respectively, and the corresponding figures were 14 and 70 days, respectively, for mice given the control compound (p < 0.00001. With zinc supplement, the mean body weight in mice which received the same dose of radiation was 7-8 g heavier than in the water-supplement groups during the second and third weeks (p < 0.05. Hence, there was no statistically significant difference in survival rate between zinc and water supplement in mice given the same dose of irradiation. Histopathologically there was less recovery of bone marrow cells in the 6Gy groups compared with the 3Gy groups. In the 3 Gy water-supplement group, the nucleated cells and megakaryocytes were recovered in the fifth week when recovery was still not seen in the 6Gy group. With zinc supplement, these cells were recovered in the third week. In this study, we found that zinc is beneficial to body weight in mice treated with TBI. Histologic examination of bone marrow showed better recovery of bone marrow cells in groups of mice fed with zinc. This study

The carcinogenic risk of high dose total body irradiation in non-human primates

International Nuclear Information System (INIS)

Broerse, J.J.; Bartstra, R.W.; Bekkum, D.W. van; Hage, M.H. van der; Zurcher, C.; Zwieten, M.J. van; Hollander, C.F.

2000-01-01

High dose total body irradiation (TBI) in combination with chemotherapy, followed by rescue with bone marrow transplantation (BMT), is increasingly used for the treatment of haematological malignancies. With the increasing success of this treatment and its current introduction for treating refractory autoimmune diseases the risk of radiation carcinogenesis is of growing concern. Studies on turnout induction in non-human primates are of relevance in this context since the response of this species to radiation does not differ much from that in man. Since the early sixties, studies have been performed on acute effects in Rhesus monkeys and the protective action of bone marrow transplantation after irradiation with X-rays (average total body dose 6.8 Gy) and fission neutrons (average dose 3.4 Gy). Of those monkeys, which were irradiated and reconstituted with autologous bone marrow, 20 animals in the X-irradiated group and nine animals in the neutron group survived more than 3 years. A group of 21 non-irradiated Rhesus monkeys of a comparable age distribution served as controls. All animals were regularly screened for the occurrence of neoplasms. Complete necropsies were performed after natural death or euthanasia. At post-irradiation intervals of 4-21 years an appreciable number of tumours was observed. In the neutron irradiated group eight out of nine animals died with one or more malignant tumours. In the X-irradiated group this fraction was 10 out of 20. The tumours in the control group, in seven out of the 21 animals, appeared at much older a-e compared with those in the irradiated cohorts. The histogenesis of the tumours was diverse with a preponderance of renal carcinoma, sarcomas among which osteosarcormas, and malignant glomus tumours in the irradiated groups. When corrected for competing risks, the carcinogenic risk of TBI in the Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a

Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice.

Science.gov (United States)

Chang, Jianhui; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-12-01

Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated. We exposed male C57BL/6 mice to 0.5 and 1.0 Gy proton total body irradiation (proton-TBI, 150 MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure. 1.0 Gy proton-TBI significantly reduced the numbers of peripheral blood cells compared to 0.5 Gy proton-TBI and unirradiated animals, while the numbers of peripheral blood cell counts were comparable between 0.5 Gy proton-TBI and unirradiated mice. The frequencies and numbers of LSK cells and CMPs in BM of 0.5 and 1.0 Gy irradiated mice were decreased in comparison to those of normal controls. LSK cells and CMPs and their progeny exhibited a radiation-induced impairment in clonogenic function. Exposure to 1.0 Gy increased cellular apoptosis but not the production of reactive oxygen species (ROS) in CMPs two weeks after irradiation. LSK cells from irradiated mice exhibited an increase in ROS production and apoptosis. Exposure to proton-TBI can induce acute damage to BM progenitors and LSK cells.

In vivo dosimetry with silicon diodes in total body irradiation

International Nuclear Information System (INIS)

Oliveira, F.F.; Amaral, L.L.; Costa, A.M.; Netto, T.G.

2014-01-01

The aim of this work is the characterization and application of silicon diode detectors for in vivo dosimetry in total body irradiation (TBI) treatments. It was evaluated the diode response with temperature, dose rate, gantry angulations and field size. A maximum response variation of 2.2% was obtained for temperature dependence. The response variation for dose rate and angular was within 1.2%. For field size dependence, the detector response increased with field until reach a saturation region, where no more primary radiation beam contributes for dose. The calibration was performed in a TBI setup. Different lateral thicknesses from one patient were simulated and then the calibration factors were determined by means of maximum depth dose readings. Subsequent to calibration, in vivo dosimetry measurements were performed. The response difference between diode readings and the prescribed dose for all treatments was below 4%. This difference is in agreement as recommended by the International Commission on Radiation Units and Measurements (ICRU), which is ±5%. The present work to test the applicability of a silicon diode dosimetry system for performing in vivo dose measurements in TBI techniques presented good results. These measurements demonstrated the value of diode dosimetry as a treatment verification method and its applicability as a part of a quality assurance program in TBI treatments. - Highlights: ► Characterization of a silicon diode dosimetry system. ► Application of the diodes for in vivo dosimetry in total body irradiation treatments. ► Implementation of in vivo dosimetry as a part of a quality assurance program in radiotherapy

Comparison of total body irradiation-based or non-total body irradiation-based conditioning regimens for allogeneic stem cell transplantation in pediatric leukemia patients

Directory of Open Access Journals (Sweden)

Sang Jeong Kim

2010-04-01

Full Text Available Purpose : This study aims to compare the outcome of total body irradiation (TBI- or non-TBI-containing conditioning regimens for leukemia in children. Methods : We retrospectively evaluated 77 children conditioned with TBI (n=40 or non-TBI (n=37 regimens, transplanted at Chonnam National University Hospital between January 1996 and December 2007. The type of transplantation, disease status at the time of transplant, conditioning regimen, engraftment kinetics, development of graft-versus-host disease (GVHD, complications, cause of deaths, overall survival (OS, and event-free survival (EFS were compared between the 2 groups. Results : Among 34 patients with acute lymphoblastic leukemia (ALL, 28 (82.4% were in the TBI group, while 72.7% (24/33 of patients with myeloid leukemia were in the non-TBI group. Although the 5-year EFS of the 2 groups was similar for all patients (62% vs 63%, the TBI group showed a better 5-year EFS than the non-TBI group when only ALL patients were analyzed (65% vs 17%; P =0.005. In acute myelogenous leukemia patients, the non-TBI group had better survival tendency (73% vs 38%; P=0.089. The incidence of GVHD, engraftment, survival, cause of death, and late complications was not different between the 2 groups. Conclusion : The TBI and non-TBI groups showed comparable results, but the TBI group showed a significantly higher 5-year EFS than the non-TBI group in ALL patients. Further prospective, randomized controlled studies involving larger number of patients are needed to assess the late-onset complications and to compare the socioeconomic quality of life.

Treatment verification and in vivo dosimetry for total body irradiation using thermoluminescent and semiconductor detectors

International Nuclear Information System (INIS)

Oliveira, F.F.; Amaral, L.L.; Costa, A.M.; Netto, T.G.

2014-01-01

The objective of this work is the characterization of thermoluminescent and semiconductor detectors and their applications in treatment verification and in vivo dosimetry for total body irradiation (TBI) technique. Dose measurements of TBI treatment simulation performed with thermoluminescent detectors inserted in the holes of a “Rando anthropomorphic phantom” showed agreement with the prescribed dose. For regions of the upper and lower chest where thermoluminescent detectors received higher doses it was recommended the use of compensating dose in clinic. The results of in vivo entrance dose measurements for three patients are presented. The maximum percentual deviation between the measurements and the prescribed dose was 3.6%, which is consistent with the action level recommended by the International Commission on Radiation Units and Measurements (ICRU), i.e., ±5%. The present work to test the applicability of a thermoluminescent dosimetric system and of a semiconductor dosimetric system for performing treatment verification and in vivo dose measurements in TBI techniques demonstrated the value of these methods and the applicability as a part of a quality assurance program in TBI treatments. - Highlights: • Characterization of a semiconductor dosimetric system. • Characterization of a thermoluminescent dosimetric system. • Application of the TLDs for treatment verification in total body irradiation treatments. • Application of semiconductor detectors for in vivo dosimetry in total body irradiation treatments. • Implementation of in vivo dosimetry as a part of a quality assurance program in radiotherapy

Endocrine dysfunction after total body irradiation and bone marrow transplantation

International Nuclear Information System (INIS)

Feyer, P.; Titlbach, O.; Hoffmann, F.A.; Kubel, M.; Helbig, W.; Leipzig Univ.

1989-01-01

Data regarding changes of endocrine parameters after total body irradiation (TBI) and bone marrow transplantation (BMT) are described. Endocrine glands are usually resistant to irradiation under morphological aspects. But new methods of determination and sensitive tests were developed in the last few years. Now it is possible to detect already small functional changes. Endocrine studies in the course of the disease were followed serially in 16 patients with TBI and BMT. Pretransplant conditioning consisted of single-dose irradiation combined with a high-dose, short-term chemotherapy. Reactions of the endocrine system showed a defined temporary order. Changes of ACTH and cortisol were in the beginning. The pituitary-adrenal cortex system responds in a different way. The pituitary-thyroid system develops a short-term 'low-T 3 -syndrome' reflecting the extreme stress of the organism. At the same time we obtained an increase of thyroxine. Testosterone and luteotropic hormone, the sexual steroids showed levels representing a primary gonadal insufficiency. The studies in the posttransplant period yielded a return to the normal range at most of the hormonal levels with the exception of the sexual steroids. Sterility is one of the late effects of TBI. A tendency towards hypothyroidism could be noticed in some cases being only subclinical forms. Reasons and possible therapy are discussed. (author)

TBI parameters and relapse of acute leukemia

International Nuclear Information System (INIS)

Sugawara, Tadashi; Inoue, Toshihiko; Mori, Tomoyuki.

1994-01-01

The purpose of this study, which involved 240 acute leukemia patients (ALL: 115, ANL: 125) who received an allogeneic bone marrow transplantation (BMT) with preconditioning by total body irradiation (TBI) and chemotherapy, was to examine retrospectively the TBI factors that may have influenced a leukemic relapse. The patients were divided into two groups: 124 patients who had received their BMT within a diagnosis-transplantation period of 9 months or less (DTP9 group), and 116 patients who had received their BMT within a diagnosis-transplantation period of 10 months or more (DTP10 group). It was concluded that: (1) the higher the TBI dose, the fewer the relapse rates in DTP9 group; (2) the longer the TBI period, the greater the increase in the relapse rate in DTP10 group. It was thus speculated that an effective TBI regimen for acute leukemia patients may vary depending on the length of time that has elapsed from the diagnosis of leukemia to the BMT. (author)

Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

International Nuclear Information System (INIS)

Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo

1996-01-01

We previously demonstrated that a nonmyeloablative preparative regimen can induce mixed chimerism and renal allograft tolerance between MHC-disparate non-human primates. The basic regimen includes anti-thymocyte globulin (ATG), total body irradiation (TBI, 300 cGy), thymic irradiation (TI, 700 cGy), splenectomy, donor bone marrow (DBM) infusion, and posttransplant cyclosporine therapy (CYA, discontinued after 4 weeks). To evaluate the importance and to minimize the toxicity of irradiation, kidney allografts were transplanted with various manipulations of the irradiation protocol. Monkeys treated with the basic protocol without TBI and TI did not develop chimerism or long-term allograft survival. In monkeys treated with the full protocol, all six monkeys treated with two fractionated dose of 150 cGy developed chimerism and five monkeys appeared tolerant. In contrast, only two of the four monkeys treated with fractionated doses of 125 cGy developed chimerism and only one monkey survived long term. The degree of lymphocyte depletion in all recipients was proportional to the TBI dose. The fractionated TBI regimen of 150 cGy appears to be the most consistently effective regimen for establishing donor bone marrow cell engraftment and allograft tolerance. (author)

Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

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Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)

1996-12-01

We previously demonstrated that a nonmyeloablative preparative regimen can induce mixed chimerism and renal allograft tolerance between MHC-disparate non-human primates. The basic regimen includes anti-thymocyte globulin (ATG), total body irradiation (TBI, 300 cGy), thymic irradiation (TI, 700 cGy), splenectomy, donor bone marrow (DBM) infusion, and posttransplant cyclosporine therapy (CYA, discontinued after 4 weeks). To evaluate the importance and to minimize the toxicity of irradiation, kidney allografts were transplanted with various manipulations of the irradiation protocol. Monkeys treated with the basic protocol without TBI and TI did not develop chimerism or long-term allograft survival. In monkeys treated with the full protocol, all six monkeys treated with two fractionated dose of 150 cGy developed chimerism and five monkeys appeared tolerant. In contrast, only two of the four monkeys treated with fractionated doses of 125 cGy developed chimerism and only one monkey survived long term. The degree of lymphocyte depletion in all recipients was proportional to the TBI dose. The fractionated TBI regimen of 150 cGy appears to be the most consistently effective regimen for establishing donor bone marrow cell engraftment and allograft tolerance. (author)

Total-body irradiation and bone-marrow transplantation - first observations on clinical tolerance

International Nuclear Information System (INIS)

Gocheva, L.; Sergieva, K.; Koleva, I.; Mlachkova, D.; Michailov, G.; Avramova, B.

2004-01-01

About 50 000 bone-marrow transplantations (BMT) are performed annually at the present stage in numerous clinical centers all over the world. The Bulgarian experience in total-body irradiation (TBI) with following BMT is rather scarce. The routine TBI procedures in the oncological practice in the country date back just to 2001. The aim of the present publication is to describe the Bulgarian experience and the first impressions from the clinical tolerance of the total-body irradiation (TBI) with subsequent allogeneic peripheral stem cell transplantation (PSCT). Patient characteristics are presented in detail, including their distribution with respect to sex, age, primary diagnose, recurrence number till BMT, patient status during BMT performance (clinical hematological remission or relapse), as well as the basic parameters of the conditioning regime including TBI with subsequent allogeneic PSCT. The position of the patient and the applied radiotherapeutic equipment are described as well as the TBI schemes, respectively 5 fractions of 2 Gy per day for two patients and 3-day irradiation with 6 fractions (two fractions with a 6-hour interval between them) for the rest of the patients. The total dose (TD) of 10 Gy is realized for all patients. The clinical tolerance of 7 patients subjected to TBI and allogeneic PSCT is discussed. All patients were tolerable to the TBI treatment and had no serious problems. The radiotherapy was interrupted only in the case of the first two patients due to slight gastro-intestinal reactions. The first days of radiation were accompanied with a light degree of headache, nausea and vomiting, which were successfully overcome by granisetron. Diarrhea syndrome and mucositis to the II-III degree were developed subsequently without parotitis development. On the days 0 and +1 of the clinical protocol transplantation was realized of non- T-cell-depleted grafts (in 5 patients) and T-cell-depleted grafts (in 2 patients), which had no serious

Gastrointestinal decontamination of dogs treated with total body irradiation and bone marrow transplantation

NARCIS (Netherlands)

Vriesendorp, H.M.; Heidt, P.J.; Zurcher, C.

1981-01-01

Procedures for total and selective gastrointestinal decontamination of dogs are described. The selective procedure removed only Gram negative aerobic bacteria, yeast and fungi. Dogs receiving total decontamination were less susceptible to the GI syndrome following total body irradiation (TBI) than

TH-EF-BRB-06: Implementation of a Modulated-Arc Total Body Irradiation (TBI) Technique Using the RayStation Treatment Planning System

Energy Technology Data Exchange (ETDEWEB)

Phillips, J; Cheung, J; Held, M; Han, D; Morin, O [UCSF, San Francisco, CA (United States)

2016-06-15

Purpose: To develop a clinical workflow for delivering a modulated-arc total body irradiation (TBI) with RayStation scripting. This technique uses arc fields with the patient lying at floor level on a padded table and is validated through measurements taken on a custom-made TBI phantom. Methods: Treatment planning was performed for a retrospective cohort of eight patients with a diverse range of heights and body types. Each was replanned using an open-field dual arc method, with the patient in supine and prone positions on the floor of the vault. All plans were optimized using Raystation Planning 4.7.2.5 (RaySearch Laboratories, Stockholm, Sweden), with 200 cGy prescribed to the 95% of the body contour − 5mm. This results in an open-field beam that sweeps craniocaudally across the length of the patient. The technique is validated with measurements at 10 cm intervals in a custom-milled, 5 cm thick acrylic phantom. A centrally located CC13 ion chamber and a Mobile MOSFET (Best Medical Canada, Ottawa, ON) detector array were used to measure dose. Supine and prone arcs for each patient were consecutively delivered, and the aggregate dose at each point was compared to the planned dose calculated in the phantom. Results: The ion chamber measurements differed from the planned dose by an average of .5%, with a standard deviation of 2.1%. All measured data for the MOSFETS were within 10% of the corresponding planned dose except for two outlying points. The standard deviation of dose differences across the entire cohort was 4.0%. Most significant discrepancies occurred either in inhomogeneous regions with large gradients, or at inferior points where beam angle was steepest. Conclusion: We have confirmed that the planned dose is well matched to our measurements within 10% for this method of planning and delivery. We are currently incorporating this technique into our clinical workflow. This work is supported by RaySearch.

Role of total body irradiation as based on the comparison of preparation regimens for allogeneic bone marrow transplantation for acute leukemia in first complete remission

International Nuclear Information System (INIS)

Inoue, T.; Ikeda, H.; Yamazaki, H.; Tang, J.T.; Song, C.; Teshima, T.; Murayama, S.; Ohtani, M.; Shibata, H.; Masaoka, T.

1993-01-01

The role of total body irradiation (TBI) for allogeneic bone marrow transplantation (BMT) for acute leukemia in first complete remission was reevaluated in this study. From Japanese BMT Registry, data of 123 acute leukemia patients in first complete remission who underwent allogeneic bone marrow transplantation in 22 hospitals between 1988 and 1990 were available for the present comparative study of preparation regimens with or without total body irradiation. Two-year survivals were 77% and 51% in the TBI containing regimen group and in the non-TBI regimen group, respectively (p=0.0010). Corresponding two-year relapse rates were 16% and 37%, respectively (p=0.0197). Corresponding probabilities of developing interstitial pneumonitis were 21% and 24%, respectively (p=0.8127). The analysis of causes of death indicated that non-TBI regimen increased the incidence of septicemia and lethal organ failures, such as liver, heart, lung and other multiple sites. It was emphasized that an additional role of total body irradiation was to disperse the treatment-related toxicity in allogeneic bone marrow transplantation for acute leukemia. (orig.) [de

Effect of fractionated versus unfractionated total body irradiation on the growth of the BN acute myelocytic leukemia

International Nuclear Information System (INIS)

Hagenbeek, A.; Martens, A.C.M.

1981-01-01

The efficacy of various total body irradiation (TBI) regimens prior to bone marrow transplantation was evaluated in a rat model for acute myelocytic leukemia (Dq = 85.1 cGy gamma ; N = 3.7). Using high dose rate gamma-irradiation (115 cGy/min), fractionated TBI with large total daily doses (400 to 600 cGy), either given as acute doses or as split doses at 8 hr intervals, was most effective. Split doses (2 fractions per day) offered no additional advantage. At the most, a 4 log leukemic cell kill was induced. No lethal toxicity was observed. Nine-hundred cGy flash TBI had a similar anti-tumor effect, but with this regimen almost half of the rats died from radiation-induced toxicity (lungs and gastro-intestinal tract). The results are explained in terms of differences between normal and leukemic cells as regards (a) repair of sublethal damage; and (b) repopulation. Low dose rate continuous gamma-irradiation (0.26 cGy/min) with total doses ranging from 900 to 2000 cGy was also quite effective. Maximally a 4 log cell kill was obtained. With 2000 cGy, 50% of the rats died from the gastro-intestinal tract-syndrome. In addition to the major role played by chemotherapy, TBI is mainly of importance in sterilizing the various sanctuaries in the body which contain leukemic cells anatomically resistant to most cytostatic agents

Bone marrow transplantation in the patients with malignant tumor. Studies on supralethal total body irradiation

Energy Technology Data Exchange (ETDEWEB)

Tatsuno, Ikuro; Saito, Yasuo

1984-11-01

Based on evidence gained from ten patients of allogeneic bone marrow transplantation (BMT) and eight patients of autologous BMT, recent knowledge on literatures of BMT and total body irradiation (TBI) is summarized. Interstitial pneumonia after BMT has a strong correlation with TBI. Low dose-rate and fractionation of TBI are seemed to reduce the lung injury, thereby reducing the incidence of nonleukemia deaths. BMT is applied to not only acute leukemia, malignant lymphoma and solid tumors but also to chronic leukemia. It is emphasized that several of the important prognostic factors are within the control of the transplantation team.

A comparative study of total body irradiation as a method of inducing granulocyte depletion in mice

International Nuclear Information System (INIS)

Bogman, M.J.J.T.; Cornelissen, I.M.H.A.; Berden, J.H.M.; Jong, J. de; Koene, R.A.P.

1984-01-01

Since conventional methods of inducing depletion of polymorphonuclear granulocytes (PMNs) in mice, such as treatment with cytostatic drugs and anti-PMN sera, proved to be insufficient to induce a stable PMN depletion for several days, and were accompanied by considerable toxic side effects, we induced neutrophil depletion in mice by total body irradiation (TBI) in a single dose of 6.0 Gy (600 rads.) at a dose rate of 0.20 Gy/min. This treatment reduced the number of PMNs in the peripheral circulation to values below 150/μl from day 3-10 after irradiation. The number of lymphocytes fell simultaneously. Platelet counts remained above 60% of normal values during the first 7 days after irradiation. Complement levels were not significantly affected by TBI. The results show that TBI of 6.0 Gy induces pronounced and stable PMN depletion in mice for at least 7 days. Furthermore, under an aseptic regimen the mice can be kept in good condition and losses are less than 5%. (Auth.)

Study on the immunological suppressive mechanisms of the cyclophosphamide-administration and total body irradiation

International Nuclear Information System (INIS)

Wakizaka, Yoshitaka; Uchino, Junichi; Yang, Zi-Bo.

1994-01-01

High dose-cyclophosphamide (CP) administration and total body irradiation (TBI) are often used for bone marrow transplantation in order to eradicate the residual tumor cells and to induce the immunological tolerance in the recipients. But CP is difficult to use as an immunosuppressant because this drug has indefinite effects on host's immune status depending on the dose, i.e. augment the humoral antibody production in small dosage and inhibit the rejective reaction in large dosage. Thus we study on the immunological mechanisms of this drug and the TBI used often with CP for bone marrow transplantation in leukemic patients. 150 mg/kg of CP was administered via tail vein, and 3 Gy (300 rads) of X-ray was irradiated. CP could suppress the host's cellular immunity within 5 days after administration but TBI could within 3 days. Reversely, CP augmented the cellular immunity since 5 days after treatment. CP damaged the IL-2 production irreversibely, but IL-3 production was inhibited by CP for only a few days and recovered rapidly. These characters were thought to be a big help for the implantation and development of the multipotent stem cells in the recipient's body after transplantation. (author)

Total body irradiation in bone marrow transplantation

International Nuclear Information System (INIS)

Gluckman, E.; Devergie, A.; Boiron, M.; Bernard, Jean; Dutreix, A.; Dutreix, J.

1979-01-01

Total body irradiation was used in 22 patients as part of their conditioning regimen for bone marrow transplantation. Nine patients with acute leukemia received 1000 cGy TBI in addition with chemotherapy. None of them survived and the main cause of death was interstitial pneumonitis (50%). 4 patients received 1000 cGy with a lung shielding of 500 cGy. Two patients with acute leukemia died of leukemia and sepsis, two patients had aplastic anemia, one is surviving, the other died of severe GVHD and infectious complications. Nine patients with severe aplastic anemia strongly immunized by previous blood transfusions received 800 cGy TBI with a lung shielding of 400 cGy. No rejection was observed and 7 patients (63%) are currently alive. One patient died of interstitial pneumonitis probably related to CMV infection, one of subacute necrotizing hepatitis, two of severe acute GVHD. It is concluded from this study that TBI remains the best immunosuppressive conditioning regimen even in strongly immunized patients. It may be a contributing factor of the incidence and severity of interstitial pneumonitis. A reduction of the dose of the lung to 400-500 cGy seems to decrease the severity of this complication

Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation

International Nuclear Information System (INIS)

Li, Richard; Polishchuk, Alexei; DuBois, Steven; Hawkins, Randall; Lee, Stephanie W.; Bagatell, Rochelle; Shusterman, Suzanne; Hill-Kayser, Christine; Al-Sayegh, Hasan; Diller, Lisa; Haas-Kogan, Daphne A.; Matthay, Katherine K.; London, Wendy B.

2017-01-01

Purpose: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. Methods and Materials: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012. Anatomic sites of disease, defined by metaiodobenzylguanidine (MIBG) avidity, were compared at diagnosis and at first relapse. The Fisher exact test was performed to compare relapse in initially involved sites between patients treated with and without TBI. Results: Seventy-four patients with a median age at diagnosis of 3.5 years (range, 0.3-15.3 years) had relapse in 227 sites of MIBG-avid metastatic disease, with a median time to relapse of 1.8 years. Of the 227 sites of first relapse, 154 sites (68%) were involved at diagnosis. When we compared relapse patterns in patients treated with and without TBI, 12 of 23 patients (52%) treated with TBI had relapse in ≥1 previously MIBG-avid site of disease whereas 40 of 51 patients (78%) treated without TBI had relapse in ≥1 previously MIBG-avid site of disease (P=.03). Conclusions: Patients treated with systemic irradiation in the form of TBI were significantly less likely to have relapse in prior sites of disease. These findings support further investigation into the role of radiopharmaceutical therapies in curative multimodality therapy.

Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation

Energy Technology Data Exchange (ETDEWEB)

Li, Richard [Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Polishchuk, Alexei [School of Medicine, University of California San Francisco, San Francisco, California (United States); DuBois, Steven [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Hawkins, Randall [School of Medicine, University of California San Francisco, San Francisco, California (United States); Lee, Stephanie W. [Brigham and Women' s Hospital, Boston, Massachusetts (United States); Bagatell, Rochelle [Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Shusterman, Suzanne [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Hill-Kayser, Christine [Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Al-Sayegh, Hasan [Brigham and Women' s Hospital, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Diller, Lisa [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Haas-Kogan, Daphne A. [Harvard Medical School, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); Matthay, Katherine K. [School of Medicine, University of California San Francisco, San Francisco, California (United States); London, Wendy B. [Harvard Medical School, Boston, Massachusetts (United States); Dana-Farber/Boston Children' s Cancer and Blood Disorders Center, Boston, Massachusetts (United States); and others

2017-02-01

Purpose: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. Methods and Materials: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012. Anatomic sites of disease, defined by metaiodobenzylguanidine (MIBG) avidity, were compared at diagnosis and at first relapse. The Fisher exact test was performed to compare relapse in initially involved sites between patients treated with and without TBI. Results: Seventy-four patients with a median age at diagnosis of 3.5 years (range, 0.3-15.3 years) had relapse in 227 sites of MIBG-avid metastatic disease, with a median time to relapse of 1.8 years. Of the 227 sites of first relapse, 154 sites (68%) were involved at diagnosis. When we compared relapse patterns in patients treated with and without TBI, 12 of 23 patients (52%) treated with TBI had relapse in ≥1 previously MIBG-avid site of disease whereas 40 of 51 patients (78%) treated without TBI had relapse in ≥1 previously MIBG-avid site of disease (P=.03). Conclusions: Patients treated with systemic irradiation in the form of TBI were significantly less likely to have relapse in prior sites of disease. These findings support further investigation into the role of radiopharmaceutical therapies in curative multimodality therapy.

Modeling, planning and XiO R CMS validation of TBI treatment (extended SSD 400 cm); Modelacion, planificacion y validacion del XiO CMS para tratamientos TBI (SSD extendida de 400 cm)

Energy Technology Data Exchange (ETDEWEB)

Teijeiro, A.; Pereira, L.; Moral, F. del; Vazquez, J.; Lopez Medina, A.; Meal, A.; Andrade Alvarez, B.; Salgado Fernandez, M.; Munoz, V.

2011-07-01

The whole body irradiation (TBI) is a radiotherapy technique previously used a bone marrow transplant and for certain blood diseases, in which a patient is irradiated to extended distance (SSD from 350 to 400). The aim of the TBI is to kill tumor cells in the receiver and prevent rejection of transplanted bone marrow. The dose is prescribed at the midpoint of the abdomen around the navel wing. The most planners not permit the treatment of patients with a much higher SSD to 100 cm, also using the table TBI with spoiler to increase skin dose should be taken into account This requires measurements and checks ad hoc if you use a planner, because modeling is not optimized a priori for an SSD of 400 cm.

TNF, IL-1 and IL-6 in circulating blood after total-body and localized irradiation in rats

NARCIS (Netherlands)

Haveman, J.; Geerdink, A. G.; Rodermond, H. M.

1998-01-01

The levels of TNF, IL-1 and IL-6 in circulating blood of female WAG/Rij rats were assessed both after total-body irradiation (TBI) and localized irradiation of the right hind leg. The results show that enhanced levels of IL-1 in the circulation reflect a stress situation presumably resulting from

Total body irradiation therapy for thymectomized myasthenic patients and immunological evaluations

Energy Technology Data Exchange (ETDEWEB)

Yamanaka, Nobukazu; Tanaka, Masayuki; Kurihara, Teruyuki (Miyazaki Medical College (Japan))

1983-06-01

Three patients with intractable myasthenia gravis (MG) were treated with total body irradiation (TBI). All the three patients had been unstable after extended thymectomy and poorly responding to prednisolone therapy. Radiation therapy consisted of 10 doses of 10 rads/day given over five weeks. After the radiation therapy the three patients improved clinically, and an objective parameter, area of M-waves also improved. No significant side effects were noted. TBI therapy can be considered as a safe method to induce selective reduction of circulating lymphocytes. This was indeed achieved, as evidenced by a drop of the lymphocyte counts to the levels of 20-40 % of the pretreatment level. The effects were persistent over twelve weeks. Early radiosensitivity of B lymphocytes were recognized. The levels of T..gamma.. cells were low before TBI therapy, increasing gradually during TBI therapy and returned to normal range after twelve weeks. Serum anti-AChR antibody titers decreased in all the cases, but it was impossible to determine whether the decrement was due to the therapy or natural course after thymectomy. Two of our three cases had a significant percentage decrement of the titers after TBI therapy. We suggest that TBI therapy is a safe method of immunosupperssive treatment for the myasthenic patients after thymectomy.

Total body irradiation therapy for thymectomized myasthenic patients and immunological evaluations

International Nuclear Information System (INIS)

Yamanaka, Nobukazu; Tanaka, Masayuki; Kurihara, Teruyuki

1983-01-01

Three patients with intractable myasthenia gravis (MG) were treated with total body irradiation (TBI). All the three patients had been unstable after extended thymectomy and poorly responding to prednisolone therapy. Radiation therapy consisted of 10 doses of 10 rads/day given over five weeks. After the radiation therapy the three patients improved clinically, and an objective parameter, area of M-waves also improved. No significant side effects were noted. TBI therapy can be considered as a safe method to induce selective reduction of circulating lymphocytes. This was indeed achieved, as evidenced by a drop of the lymphocyte counts to the levels of 20-40 % of the pretreatment level. The effects were persistent over twelve weeks. Early radiosensitivity of B lymphocytes were recognized. The levels of Tγ cells were low before TBI therapy, increasing gradually during TBI therapy and returned to normal range after twelve weeks. Serum anti-AChR antibody titers decreased in all the cases, but it was impossible to determine whether the decrement was due to the therapy or natural course after thymectomy. Tow of our three cases had a significant percentage decrement of the titers after TBI therapy. We suggest that TBI therapy is a safe method of immunosupperssive treatment for the myasthenic patients after thymectomy. (author)

Neurobehavioral toxicity of total body irradiation: a follow-up in long-term survivors

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Peper, Martin; Steinvorth, Sarah; Schraube, Peter; Fruehauf, Stefan; Haas, Rainer; Kimmig, Bernhard N.; Lohr, Frank; Wenz, Frederik; Wannenmacher, Michael

2000-01-01

Purpose: Total body irradiation (TBI) in preparation for bone marrow transplantation (BMT) is a routine treatment of hematological malignancy. A retrospective and a prospective group study of long-term cerebral side effects was performed, with a special emphasis on neurobehavioral toxicity effects. Methods and Materials: Twenty disease-free patients treated with hyperfractionated TBI (14.4 Gy, 12 x 1.2 Gy, 4 days), 50 mg/kg cyclophosphamide, and autologous BMT (mean age 38 years, range 17-52 years; age at TBI 35 years, 16-50 years; follow-up time 32 months, 9-65 months) participated in a neuropsychological, neuroradiological, and neurological examination. Data were compared to 14 patients who were investigated prior to TBI. Eleven patients with renal insufficiencies matched for sex and age (38 years, 20-52 years) served as controls. In a longitudinal approach, neuropsychological follow-up data were assessed in 12 long-term survivors (45 years, 23-59 years; follow-up time 8.8 years, 7-10.8 years; time since diagnosis 10.1 years, 7.5-14.2 years). Results: No evidence of neurological deficits was found in post-TBI patients except one case of peripheral movement disorder of unknown origin. Some patients showed moderate brain atrophy. Neuropsychological assessment showed a subtle reduction of memory performance of about one standard deviation. Cognitive decline in individual patients appeared to be associated with pretreatment (brain irradiation, intrathecal methotrexate). Ten-years post disease onset, survivors without pretreatment showed behavioral improvement up to the premorbid level. Conclusion: The incidence of long-term neurobehavioral toxicity was very low for the present TBI/BMT regimen

In vivo dosimetry with semiconducting diodes for dose verification in total-body irradiation. A 10-year experience

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Ramm, U.; Licher, J.; Moog, J.; Scherf, C.; Kara, E.; Boettcher, H.D.; Roedel, C.; Mose, S.

2008-01-01

Background and purpose: for total-body irradiation (TBI) using the translation method, dose distribution cannot be computed with computer-assisted three-dimensional planning systems. Therefore, dose distribution has to be primarily estimated based on CT scans (beam-zone method) which is followed by in vivo measurements to ascertain a homogeneous dose delivery. The aim of this study was to clinically establish semiconductor probes as a simple and fast method to obtain an online verification of the dose at relevant points. Patients and methods: in 110 consecutively irradiated TBI patients (12.6 Gy, 2 x 1.8 Gy/day), six semiconductor probes were attached to the body surface at dose-relevant points (eye/head, neck, lung, navel). The mid-body point of the abdomen was defined as dose reference point. The speed of translation was optimized to definitively reach the prescribed dose in this point. Based on the entrance and exit doses, the mid-body doses at the other points were computed. The dose homogeneity in the entire target volume was determined comparing all measured data with the dose at the reference point. Results: after calibration of the semiconductor probes under treatment conditions the dose in selected points and the dose homogeneity in the target volume could be quantitatively specified. In the TBI patients, conformity of calculated and measured doses in the given points was achieved with small deviations of adequate accuracy. The data of 80% of the patients are within an uncertainty of ± 5%. Conclusion: during TBI using the translation method, dose distribution and dose homogeneity can be easily controlled in selected points by means of semiconductor probes. Semiconductor probes are recommended for further use in the physical evaluation of TBI. (orig.)

Cell biological effects of total body irradiation on growth and differentiation of acute myelogenous leukemia cells compared to normal bone marrow

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Greenberger, J S; Weichselbaum, R R; Botnick, L E; Sakakeeny, M; Moloney, W C

1979-01-01

Radiation therapy is used as total body treatment in preparation of the acute myelogenous leukemia (AML) patient for bone marrow transplantation. Many AML patients will have residual leukemia cells at the time of total body irradiation (TBI). In the present study, the effect of TBI on leukemic myeloid cells was compared to the effect on normal marrow granulocytic stem cells (CFUc) in vitro. Little difference from that of normal CFUc was found in the radiosensitivity of two mouse myeloid leukemia cell lines. The effect of TBI on growth of WEHI-3 or J774 cells in millipore diffusion chambers was stimulatory. These AML cell lines as well as others derived from Friend or Abelson virus infected in vitro long term mouse marrow cultures showed some morphologic differentiation by 7 days growth in diffusion chambers in irradiated heterologous rat hosts, but immature cells predominated by day 21. Thus, evidence in murine models of AML indicates that residual AML cells surviving chemotherapy will show no greater susceptibility to radiation killing compared to normal stem cells and will rapidly repopulate the irradiated host.

MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats

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Jianzhong Li

2016-05-01

Full Text Available Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.

Disturbances in dental development after total body irradiation in bone marrow transplant recipients

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Dahlloef, G.B.; Barr, M.; Bolme, P.; Modeer, T.; Loennqvist, B.R.; Ringden, O.; Heimdahl, A.

1988-01-01

The dental status of 16 children who had been treated with bone marrow transplantation (BMT) for serious bone marrow diseases was followed for up to 6 years. Several types of disturbances in dental development were observed in children who had been conditioned with total body irradiation (TBI) at 10 Gy before BMT. Thus, impaired root development that caused short V-shaped roots was found in all patients, a complete failure of root development and premature apical closure were found in five patients, enamel hypoplasia was observed in four patients, and microdontia was observed in three patients conditioned with TBI. Patients younger than 6 years of age at BMT exhibited the most severe and extensive dental aberrations. The TBI at 10 Gy appeared to be the major cause of the disturbances found

Therapeutic effect of bone marrow transplantation plue previous blood transfusion on rats with total body irradiation

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Yan Yongtang; Ran Xinze; Wei Shuqing

1988-01-01

Therapeutic effect of bone marrow transplantation (BMT) and blood transfusion on different groups of rats subjected to various doses of total body irradiation (TBI) was studied. In the control group, 80 rats that received TBI of 8,9,10,11 and 12 Gy died between 3∼14 days. In the second group, 67 rats that received the same doses of irradiation were treated with BMT. Except that 8 rats died from lung hemorrhages at 4∼6 days after TBI. 85% of these animals (500/59) showed hemopoietic engraftment. The survival rates of 8, 9, 10, 11 and 12 Gy subgroups at 90 days after BMT were 90%, 56%, 56%, 25% and 0% respectively. In the third group, 82 rats receive TBI and blood transfusion prior to BMT. Except that 8 rats subjected to 11∼12 Gy irradiation died from lung hemorrhage at 4∼6 days after BMT, 97% of these animals (72/74) showed hemopoietic engraftment. The 90-day survival rates of 8, 9, 10, 11 and 12 Gy subgroups were 93%, 80%, 80%, 60% and 6% respectively. The 90-day survival rate of 50 rats subjected to 9∼11 Gy TBI and treated with blood transfusion and BMT, was 72%, while that 47 rats treated simply with BMT was only 42%. These results showed clearly that previous blood transfusion could increase the rate of hemopoietic engraftment, reduce the incidence if rejection, and raise the survival rate

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

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Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

1981-01-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors

Dose rate and dose fractionation studies in total body irradiation of dogs

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Kolb, H.J.; Netzel, B.; Schaffer, E.; Kolb, H.

1979-01-01

Total body irradiation (TBI) with 800-900 rads and allogeneic bone marrow transplantation according to the regimen designated by the Seattle group has induced remissions in patients with otherwise refractory acute leukemias. Relapse of leukemia after bone marrow transplantation remains the major problem, when the Seattle set up of two opposing 60 Co-sources and a low dose rate is used in TBI. Studies in dogs with TBI at various dose rates confirmed observations in mice that gastrointestinal toxicity is unlike toxicity against hemopoietic stem cells and possibly also leukemic stem cells depending on the dose rate. However, following very high single doses (2400 R) and marrow infusion acute gastrointestinal toxicity was not prevented by the lowest dose rate studied (0.5 R/min). Fractionated TBI with fractions of 600 R in addition to 1200 R (1000 rads) permitted the application of total doses up to 300 R followed by marrow infusion without irreversible toxicity. 26 dogs given 2400-3000 R have been observed for presently up to 2 years with regard to delayed radiation toxicity. This toxicity was mild in dogs given single doses at a low dose rate or fractionated TBI. Fractionated TBI is presently evaluated with allogeneic transplants in the dog before being applied to leukemic patients

A prospective study of the early clinical symptoms following a 2 Gy therapeutic whole-body irradiation

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Fizazi, K.; Chaillet, M.P.; Fourquet, A.; Jammet, P.; Cosset, J.M.

1995-01-01

Early human tolerance following total body irradiation (TBI) according to the dose received is still poorly known. Thirteen selected patients were prospectively evaluated for clinical side effects during the first 10 hours following a 2 Gy TBI prior to bone marrow transplantation. All of them but one were treated for haematological malignancies and were in clinical remission at the date of TBI. There were 10 males and 3 females, with a median age of 43 y (range 16*61) and a good performance status (WHO 0-1). They received granisetron (3 mg) injected intravenously 1 h before the time of TBI in order to prevent nausea and vomiting. The main symptoms consisted in drowsiness (69%), headache (62%), xerostomia (62%), nausea and vomiting (46%), anorexia (38%), parotid gland pain (23%) and abdominal pain (8%). Their intensity was always moderate, except for 2 patients who experimented severe vomiting. The incidence rate and the time-course of the symptoms of the prodromal phase may proved to be helpful for early clinical evaluation and triage of victims of an accidental irradiation. In particular, absence of fever at the 6 th h after TBI supports the assumption of an estimated exposure dose below 2 Gy. (authors). 23 refs., 2 tabs

CT analysis of lung density changes in patients undergoing total body irradiation prior to bone marrow transplantation

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Lee, J.Y.; Shank, B.; Bonfiglio, P.; Reid, A.

1984-01-01

Sequential changes in lung density measured by CT are potentially sensitive and convenient monitors of lung abnormalities following total body irradiation (TBI). Methods have been developed to compare pre- and post-TBI CT of lung. The average local features of a cross-sectional lung slice are extracted from three peripheral regions of interest in the anterior, posterior, and lateral portions of the CT image. Also, density profiles across a specific region may be obtained. These may be compared first for verification of patient position and breathing status and then for changes between pre- and post-TBI. These may also be compared with radiation dose profiles through the lung. A preliminary study on 21 leukemia patients undergoing total body irradiation indicates the following: (a) Density gradients of patients' lungs in the antero-posterior direction show a marked heterogeneity before and after transplantation compared with normal lungs. The patients with departures from normal density gradients pre-TBI correlate with later pulmonary complications. (b) Measurements of average peripheral lung densities have demonstrated that the average lung density in the younger age group is substantially higher: pre-TBI, the average CT number (1,000 scale) is -638 +/- 39 Hounsfield unit (HU) for 0-10 years old and -739 +/- 53 HU for 21-40 years old. (c) Density profiles showed no post-TBI regional changes in lung density corresponding to the dose profile across the lung, so no differentiation of a radiation-specific effect has yet been possible. Computed tomographic density profiles in the antero-posterior direction are successfully used to verify positioning of the CT slice and the breathing level of the lung

Dosimetry and verification of 60Co total body irradiation with human phantom and semiconductor diodes

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Allahverdi Mahmoud

2007-01-01

Full Text Available Total Body Irradiation (TBI is a form of radiotherapy used for patients prior to bone marrow or stem cell transplant to destroy any undetectable cancer cells. The dosimetry characteristics of a 60 Co unit for TBI were studied and a simple method for the calculation of the prescribed dose for TBI is presented. Dose homogeneity was verified in a human phantom. Dose measurements were made in water phantom (30 x 30 x 30 cm 3 , using farmer ionization chamber (0.6 cc, TM30010, PTW and a parallel plate ionization chamber (TM23343, PTW. Point dose measurements for AP/PA irradiation were measured in a human phantom using silicon diodes (T60010L, PTW. The lung dose was measured with an ionization chamber (0.3 cc, TM31013. The validity of the proposed algorithm was checked at TBI distance using the human phantom. The accuracy of the proposed algorithm was within 3.5%. The dose delivered to the mid-lobe of the lung was 14.14 Gy and it has been reduced to 8.16 Gy by applying the proper shield. Dose homogeneity was within ±7% for all measured points. The results indicate that a good agreement between the total prescribed and calculated midplane doses can be achieved using this method. Therefore, it could be possible to use calculated data for TBI treatments.

Renal toxicity after total body irradiation

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Borg, Martin; Hughes, Timothy; Horvath, Noemi; Rice, Michael; Thomas, Anthony C.

2002-01-01

Purpose: To evaluate the incidence of renal dysfunction after total body irradiation (TBI). Methods and Materials: Between 1990 and 1997, 64 patients (median age 50 years) received TBI as part of the conditioning regimen before bone marrow transplantation (BMT). Five patients with abnormal renal function at the beginning of treatment or with incomplete data were excluded. All patients received a total of 12 Gy (6 fractions twice daily for 3 consecutive days) prescribed to the peak lung dose (corrected for lung transmission) at a dose rate of 7.5 cGy/min. Renal shielding was not used. Renal dysfunction was assessed on the basis of the serum creatinine levels measured at the start and end of TBI and at 6, 12, 18, and 24 months after completion of BMT. Cox proportional hazard analysis was used to evaluate the various factors known to affect renal function. Results: Only 4 patients had elevated serum creatinine levels at 12 months and subsequently only 2 of the 33 surviving patients had persistent elevated renal serum creatinine levels 24 months after BMT. A fifth patient developed proteinuria and mildly elevated serum creatinine levels at 2.5 years. In 2 patients, the elevation coincided with disease relapse and normalized once remission was achieved. In the third patient, the elevation in serum creatinine levels coincided with relapse of multiple myeloma and the presence of Bence-Jones proteinuria. The fourth patient was the only patient who developed chronic renal failure secondary to radiation nephritis at 2 years. The etiology of the fifth patient's rise in creatinine was unknown, but may have been secondary to radiation nephritis. On univariate analysis, but not on multivariate analysis, a significant correlation was found between TBI-related renal dysfunction and hypertension before and after BMT. Conclusion: A dose of 12 Gy at 2 Gy/fraction resulted in only 1 case of radiation nephritis in the 59 patients studied 24 months after the completion of TBI and BMT

The biological effects of high dose total body irradiation in beagle dogs

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Luo Qingliang; Liu Xiaolan; Hao Jing; Xiong Guolin; Dong Bo; Zhao Zhenhu; Xia Zhengbiao; Qiu Liling; Mao Bingzhi

2002-01-01

Objective: To evaluate the biological effects of Beagle dogs irradiated by γ-rays at different doses. Methods: All Beagle dogs were divided into six groups and were subjected respectively to total-body irradiation (TBI) with a single dose of 6.5, 5.5, 5.0, 4.5, 3, 5 and 2.5 Gy γ-rays delivered by 60 Co sources at 7.224 x 10 -2 C/kg per minute. The general condition, blood cell counts and bone marrow cell CFC assays were observed. Results: Vomiting occurred at 0.5 to 2 hours after TBI in all groups. In 6.5 Gy group 3/5 dogs had blood-watery stool and 1/5 in 5.5 Gy group had watery stool. Diarrhea occurred in all other animals. Only one dog in 2.5 Gy group survived, all of others died. in order of decreasing irradiation dosage, the average survival time was 5.0, 8.0, 9.3, 9.5, 10.5 and 14.1 days, respectively. Conclusions: According to the clinical symptoms, leukocyte count and survival time of the dogs, the irradiation dose which will induce very severe hematopoietic radiation syndrome in Beagle dogs is 4.5 to 5.0 Gy

Radiobiological basis of total body irradiation with different dose rate and fractionation: repair capacity of hemopoietic cells

International Nuclear Information System (INIS)

Song, C.W.; Kim, T.H.; Khan, F.M.; Kersey, J.H.; Levitt, S.H.

1981-01-01

Total body irradiation (TBI) followed by bone marrow transplantation is being used in the treatment of malignant or non-malignant hemopoietic disorders. It has been believed that the ability of hemopoietic cells to repair sublethal radiation damage is negligible. Therefore, several schools of investigators suggested that TBI in a single exposure at extremely low dose rate (5 rad/min) over several hours, or in several fractions in 2-3 days, should yield a higher therapeutic gain, as compared with a single exposure at a high dose rate (26 rad/min). We reviewed the existing data in the literature, in particular, the response of hemopoietic cells to fractionated doses of irradiation and found that the repair capacity of both malignant and non-malignant hemopoietic cells might be greater than has been thought. It is concluded that we should not underestimate the ability of hemopoietic cells to repair sublethal radiation damage in using TBI

Single center experience with total body irradiation and melphalan (TBI-MEL) myeloablative conditioning regimen for allogeneic stem cell transplantation (SCT) in patients with refractory hematologic malignancies.

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Bhatnagar, Bhavana; Rapoport, Aaron P; Fang, Hong-Bin; Ilyas, Can; Marangoz, Deniz; Akbulut, Vinil; Ruehle, Kathleen; Badros, Ashraf; Yanovich, Saul; Akpek, Görgün

2014-04-01

We retrospectively evaluated the tolerability and efficacy of fractionated total body irradiation (TBI) (1,200 cGy) and melphalan (MEL) (100-110 mg/m(2)) myeloablative conditioning in 48 patients with nonremission AML (n = 14), ALL (n = 10), NHL (n = 18), and other refractory hematologic malignancies (n = 6) who received allogeneic stem cell transplantation (SCT) between 2002 and 2011. Median age was 48 years (22 to 68); 14 out of 26 leukemia patients (54 %) had circulating blasts at transplant, 20 (50 %) evaluable patients had poor-risk cytogenetics, 12 (25 %) had prior SCT, and 10 (21 %) received stem cells from a mismatch donor. All patients received tacrolimus with or without methotrexate for GVHD prophylaxis. At the time of analysis, 13 patients (27 %) were alive and disease free. Engraftment was complete in all patients. The median time to ANC recovery (>500) was 12 days (range, 6-28). The most common grade III and IV toxicities were mucositis and infections. Eighteen patients (43 %) developed grade II-IV acute GVHD, and eight (26 %) had extensive chronic GVHD. Of 44 evaluable patients for response, 28 (64 %) achieved a complete remission (CR), and seven (15 %) had a partial remission after the transplant. With a median follow-up of 30 months (4 to 124 months) for surviving patients, the cumulative incidence of relapse was 45 % at 1 year, and the probability of overall survival (OS) at 5 years was 22.5 %. Multivariate analysis showed that platelet count (500 IU/L) at SCT were associated with relapse. Age less than 53 years and CR after SCT were associated with better OS. Our data suggest that TBI-MEL can result in CR in two thirds, durable remission in one third, and 5-year survival in about one quarter of patients with nonremission hematologic malignancies. Further studies with TBI-MEL in standard risk transplant patients are warranted.

Incidence of interstitial pneumonia after hyperfractionated total body irradiation before autologous bone marrow/stem cell transplantation

International Nuclear Information System (INIS)

Lohr, F.; Schraube, P.; Wenz, F.; Flentje, M.; Kalle, K. von; Haas, R.; Hunstein, W.; Wannenmacher, M.

1995-01-01

Purpose/Objectives Interstitial pneumonia (IP) is a severe complication after allogenic bone marrow transplantation (BMT) with incidence rates between 10 % and 40 % in different series. It is a polyetiologic disease that occurs depending on age, graft vs. host disease (GvHD), CMV-status, total body irradiation (TBI) and immunosuppressive therapy after BMT. The effects of fractionation and dose rate are not entirely clear. This study evaluates the incidence of lethal IP after hyperfractionated TBI for autologous BMT or stem cell transplantation. Materials and Methods Between 1982 and 1992, 182 patients (60 % male, 40 % female) were treated with hyperfractionated total body irradiation (TBI) before autologous bone marrow transplantation. Main indications were leukemias and lymphomas (53 % AML, 21 % ALL, 22 % NHL, 4 % others) Median age was 30 ys (15 - 55 ys). A total dose of 14.4 Gy was applied using lung blocks (12 fractions of 1.2 Gy in 4 days, dose rate 7-18 cGy/min, lung dose 9 - 9.5 Gy). TBI was followed by cyclophosphamide (200 mg/kg). 72 % were treated with bone marrow transplantation, 28 % were treated with stem cell transplantation. Interstitial pneumonia was diagnosed clinically, radiologically and by autopsy. Results 4 patients died most likely of interstitial pneumonia. For another 12 patients interstitial pneumonia was not the most likely cause of death but could not be excluded. Thus, the incidence of lethal IP was at least 2.2 % but certainly below 8.8 %. Conclusion Lethal interstitial pneumonia is a rare complication after total body irradiation before autologous bone marrow transplantation in this large, homogeously treated series. In the autologous setting, total doses of 14.4 Gy can be applied with a low risk for developing interstitial pneumonia if hyperfractionation and lung blocks are used. This falls in line with data from series with identical twins or t-cell depleted marrow and smaller, less homogeneous autologous transplant studies. Thus

SU-E-T-522: Investigation of Underdosage of Total Body Irradiation with Bilateral Irradiation Scheme

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Lin, T; Eldib, A; Hossain, M; Price, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

2015-06-15

Purpose: Patient in-vivo measurements report lower readings than those predicted from TMR-based treatment planning on TBI patient knees and ankles where rice was placed to fill the gap between patient’s legs. This study is to understand and correct the under dosage of Total Body Irradiation(TBI) with rice tissue equivalent bolus placement at TBI treatment patient setup. Methods: Bilateral TBI scheme was investigated with rice bags bolus placing between patient’s two legs acting as missing tissue. In-house TMR based treatment planning system was commissioned with measurements under TBI condition at 10MV, i.e. source-to-reference distance 383.4cm with 40×40cm field size with 1cm thickness Lucite. Predictions of patient specific dose points are reported at different sites with 200cGy prescription at patient umbilicus point. Solid water and rice bag phantoms are used at TBI conditions for the attenuation factor verification and CT scanned to verify the CT number and electron density. Results: We found that the rice bag bolus overall density is 11% lower than the water; however, the attenuation factor of rice bags could become 15% lower than that of water at TBI condition. This overestimate of rice bag electron density could cause the lack of lateral scatter and the lack of backscatter. This could Result in an overestimate of dose at in-vivo dosimeter measurement points with TMR-based treatment planning systems. Observations of patient specific optically stimulated luminescent dosimeters(OSLDs) were used to confirm this overestimation. Measurements of setups with increasing the rice bag filled patient leg separation were performed to demonstrate eliminating the overdose issue. Conclusion: Rice bolus has a lower electron density than water does(11%) but results in 15% lower in attenuation factor at TBI condition. This effect was observed in patient delivery with OSLD measurements and can be corrected by increasing the filling rice bolus thickness with 15% longer of

SU-E-T-522: Investigation of Underdosage of Total Body Irradiation with Bilateral Irradiation Scheme

International Nuclear Information System (INIS)

Lin, T; Eldib, A; Hossain, M; Price, R; Ma, C

2015-01-01

Purpose: Patient in-vivo measurements report lower readings than those predicted from TMR-based treatment planning on TBI patient knees and ankles where rice was placed to fill the gap between patient’s legs. This study is to understand and correct the under dosage of Total Body Irradiation(TBI) with rice tissue equivalent bolus placement at TBI treatment patient setup. Methods: Bilateral TBI scheme was investigated with rice bags bolus placing between patient’s two legs acting as missing tissue. In-house TMR based treatment planning system was commissioned with measurements under TBI condition at 10MV, i.e. source-to-reference distance 383.4cm with 40×40cm field size with 1cm thickness Lucite. Predictions of patient specific dose points are reported at different sites with 200cGy prescription at patient umbilicus point. Solid water and rice bag phantoms are used at TBI conditions for the attenuation factor verification and CT scanned to verify the CT number and electron density. Results: We found that the rice bag bolus overall density is 11% lower than the water; however, the attenuation factor of rice bags could become 15% lower than that of water at TBI condition. This overestimate of rice bag electron density could cause the lack of lateral scatter and the lack of backscatter. This could Result in an overestimate of dose at in-vivo dosimeter measurement points with TMR-based treatment planning systems. Observations of patient specific optically stimulated luminescent dosimeters(OSLDs) were used to confirm this overestimation. Measurements of setups with increasing the rice bag filled patient leg separation were performed to demonstrate eliminating the overdose issue. Conclusion: Rice bolus has a lower electron density than water does(11%) but results in 15% lower in attenuation factor at TBI condition. This effect was observed in patient delivery with OSLD measurements and can be corrected by increasing the filling rice bolus thickness with 15% longer of

Total body irradiation in bone marrow transplantation: the influence of fractionation and delay of marrow infusion

International Nuclear Information System (INIS)

Lichter, A.S.; Tracy, D.; Lam, W.C.; Order, S.E.

1980-01-01

Bone marrow transplantation (BMT) after total body irradiation (TBI) and cyclophosphamide is being employed increasingly in the therapy of end stage leukemia. Interstitial pneumonitis (IP) represents a major acute toxicity after allogeneic transplantation. A more rapid reconstitution of lymphoid organs and bone marrow post transplant may result in increased immune competence and hence fewer opportunistic pulmonary infections and IP. By delaying the infusion of marrow to 72 hr after TBI (1250 rad at 7.5 rad/min) instead of the customary 24 hr, we can demonstrate an increase in initial repopulation of thymus, spleen and bone marrow, with syngeneic transplants in Lewis rats. Interstitial pneumonitis may also be caused, in part, by the pulmonary toxicity of large single exposures of TBI. Clinical and laboratory data suggest that fractionated TBI may be less toxic to the lung. When fractionated TBI (625 rad x 2, 7.5 rad/min) is compared to single dose TBI (1250 rad, 7.5 rad/min), and increased initial repopulation of lymphoid organs is observed when fractionated therapy is employed. Delay in marrow infusion and fractionation of TBI exposure may have clinical advantages in patients who receive BMT

Effect of radiation dose rate and cyclophosphamide on pulmonary toxicity after total body irradiation in a mouse model

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Safwat, Akmal; Nielsen, Ole S.; El-Badawy, Samy; Overgaard, Jens

1996-01-01

Purpose: Interstitial pneumonitis (IP) is still a major complication after total body irradiation (TBI) and bone marrow transplantation (BMT). It is difficult to determine the exact role of radiation in this multifactorial complication, especially because most of the experimental work on lung damage was done using localized lung irradiation and not TBI. We have thus tested the effect of radiation dose rate and combining cyclophosphamide (CTX) with single fraction TBI on lung damage in a mouse model for BMT. Methods and Materials: TBI was given as a single fraction at a high dose rate (HDR, 0.71 Gy/min) or a low dose rate (LDR, 0.08 Gy/min). CTX (250 mg/kg) was given 24 h before TBI. Bone marrow transplantation (BMT) was performed 4-6 h after the last treatment. Lung damage was assessed using ventilation rate (VR) and lethality between 28 and 180 days (LD (50(28))-180 ). Results: The LD 50 for lung damage, ± standard error (SE), increased from 12.0 (± 0.2) Gy using single fraction HDR to 15.8 (± 0.6) Gy using LDR. Adding CTX shifted the dose-response curves towards lower doses. The LD 50 values for the combined treatment were 5.3 (± 0.2) and 3.5 (± 0.2) Gy for HDR and LDR, respectively. This indicates that the combined effect of CTX and LDR was more toxic than that of combined CTX and HDR. Lung damage evaluated by VR demonstrated two waves of VR increase. The first wave of VR increase occurred after 6 weeks using TBI only and after 3 weeks in the combined CTX-TBI treatment, irrespective of total dose or dose rate. The second wave of VR elevation resembled the IP that follows localized thoracic irradiation in its time of occurrence. Conclusions: Lung damage following TBI could be spared using LDR. However, CTX markedly enhances TBI-induced lung damage. The combination of CTX and LDR is more toxic to the lungs than combining CTX and HDR

The dosimetry of cobalt-60 γ-ray total body irradiation before bone marrow transplantation

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Dong Fan; Zhang Guiru

1989-11-01

The dosimetric considerations of using conventional cobalt-60 unit total body irradiation (TBI) are presented. By extending the source-to-midplane distance (SMD) to 346 cm, a 92 x 98 cm 2 rectangular field with diagonal dimension 134 cm was obtained. The results from the phantom measurements showed: (1) the effective field corresponding to an average-size patient is 25 x 25 cm 2 , and a method for estimating the effective field of human body is given; (2) the midplane doses are consistently higher than those of surfaces, but the dose ratio of midplane to surface decreases as the body thickness increases, and a significant negative correlation is existed between the dose ratio and thickness, thus a linear regression line is fitted; (3) the anterior-posterior (AP) or AP + bilateral irradiation will yield a more uniform dose distribution in the whole body than the bilateral irradiation; (4) the dose uniformity can apparently be improved by the tissue compensation, for which the technique is described

Induction of systemic bone changes by preconditioning total body irradiation for bone marrow transplantation

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Miyazaki, Osamu; Okamoto, Reiko; Masaki, Hidekazu; Nishimura, Gen; Kumagai, Masaaki; Shioda, Yoko; Nozawa, Kumiko; Kitoh, Hiroshi

2009-01-01

Preconditioning total body irradiation (TBI) prior to bone marrow transplantation (BMT) has been believed to be a safe procedure that does not cause late morbidity; yet, a recent report raises the suspicion that TBI-induced chondroosseous abnormalities do occur. To evaluate the radiological manifestations of TBI-induced skeletal alterations and their orthopaedic morbidity. Subjects included 11 children with TBI-induced skeletal changes, including 9 in our hospital and 2 in other hospitals. The former were selected from 53 children who had undergone TBI with BMT. Radiographic examinations (n=11), MRI (n=3), CT (n=2), and medical records in the 11 children were retrospectively reviewed. The skeletal alterations included abnormal epiphyseal ossification and metaphyseal fraying (8/11), longitudinal metaphyseal striations (8/11), irregular metaphyseal sclerosis (6/11), osteochondromas (4/11), slipped capital femoral epiphysis (2/10), genu valgum (3/10), and platyspondyly (2/3). MRI demonstrated immature primary spongiosa in the metaphysis. Of the 11 children, 9 had clinical symptoms. TBI can induce polyostotic and/or generalized bone changes, mainly affecting the epiphyseal/metaphyseal regions and occasionally the spine. The epi-/metaphyseal abnormalities represent impaired chondrogenesis in the epiphysis and growth plate and abnormal remodelling in the metaphysis. Generalized spine changes may lead to misdiagnosis of a skeletal dysplasia. (orig.)

The evaluation of a modified technique of Total Body Irradiation in respect of treatment results and toxicity

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Skowronska-Gardas, A.; Dabrowski, R.; Pedziwiatr, K.

2006-01-01

Total body irradiation (TBI) is a well established part of the conditioning regimen prior to bone marrow transplantation (BMT). Numerous different techniques are used and every center elaborates own solutions. The aim of our study to present the method of TBI developed in our department, and to discuss the results of treatment with respect of early and late toxicity. Between 11.2000 and 08.2004, 23 patients were with fractionated TBI at the Department of Radiotherapy of the M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw (MSCMCC). Conditioning chemotherapy and BMT were performed in different hematological departments. All patients were irradiated with a total midline dose of 12 Gy in 6 fractions over 3 consecutive days. Doses to the lung did not exceed 11 Gy. The TBI method used in our department was evaluated over a few years. The following modifications have been introduced to the previously applied technique: change of photon energy 6 MV to 15 MV; increase of lung dose from 9 Gy to 11 Gy; the use of an individual bolus as a lung compensator in lateral fields; more frequent boost irradiation of the mediastinum and legs with small fields; calculations of Monitor Units based on dosimetric data. Boost irradiation of chest wall with electrons been abandoned. Median follow up was 12 months. Up till now, 17/23 patients are alive, of these 16 with no relapse. Immediate toxicity was low. Early complications were observed during the first 6 months after BMT in 11 patients. In the case of 4 patients these complications were fatal. Late complications were observed in 10 patients, including chronic GVHD and hormone disturbance. Only one patient had developed the first symptoms of cataract. In one case Lhermitte's syndrome was observed. One patient died due to liver insufficiency. The results of treatment and the complications rates in patients treated with TBI at our department are consistent with those published in literature. We conclude that

Biologically effective dose in total-body irradiation and hematopoietic stem cell transplantation

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Kal, H.B.; Kempen-Harteveld, M.L. van; Heijenbrok-Kal, M.H.; Struikmans, H.

2006-01-01

Background and Purpose: Total-body irradiation (TBI) is an important part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. The results after treatment with various TBI regimes were compared, and dose-effect relationships for the endpoints relapse incidence, disease-free survival, treatment-related mortality, and overall survival were derived. The aim was to define requirements for an optimal treatment schedule with respect to leukemic cell kill and late normal-tissue morbidity. Material and Methods: A literature search was performed. Three randomized studies, four studies comparing results of two or three TBI regimens, and nine reports with results of one specific TBI regimen were identified. Biologically effective doses (BEDs) were calculated. The results of the randomized studies and the studies comparing results of two or three TBI regimens were pooled, and the pooled relative risk (RR) was calculated for the treatments with high BED values versus treatments with a low BED. BED-effect relationships were obtained. Results: RRs for the high BED treatments were significantly lower for relapse incidence, not significantly different for disease-free survival and treatment-related mortality, and significantly higher for overall survival. BED-effect relationships indicate a decrease in relapse incidence and treatment-related mortality and an increase in disease-free and overall survival with higher BED values. Conclusion: 'More dose is better', provided that a TBI setting is used limiting the BEDs of lungs, kidneys, and eye lenses. (orig.)

Prospective neurodevelopmental studies of two children treated with total body irradiation and bone marrow transplantation for acute leukemia in infancy

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Kaleita, T.; Tesler, A.; Feig, S.A.

1987-01-01

Five-year neurodevelopmental studies of two infants with acute leukemia are presented. Both patients underwent bone marrow transplantation (BMT) after conditioning with cyclophosphamide and total body irradiation (TBI). Neither patient was treated with intrathecal chemotherapy. Their outcome is remarkable for normal development of intelligence, language, perception, and motor coordination. These results suggest that TBI and BMT should be considered in future therapeutic studies of infants with acute leukemia, who are at great risk for failure of conventional therapy

Treatment of neuroblastoma. Role of total Body Irradiation

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Dini, G; Perin, G P; Franzone, P; Corvo, R; Scarpati, D

1986-01-01

Advanced neuroblastoma, scarcely responsive to conventional therapies, can take advantage of high dose chemio-radiotherapic treatment followed by bone marrow transplant. Nineteen young patients underwent an ablative chemotherapy with high dose Vincristine and Melphalan plus Total Body Irradiation in Genoa, Italy; all of them underwent autologus bone marrow transplantation. Fourteen children were in complete remission (CR), 5 had residual disease. Thirteen are alive after a median of 7 months following transplant; 9 are in CR; 4 have disease; 1 died for toxicity; 5 for relapse. The results seem to suggest that ablative therapy should be given to patients in CR. Toxicity was not remarkable mainly as far as TBI is concerned.

Transition pattern and mechanism of B-lymphocyte precursors in regenerated mouse bone marrow after subtotal body irradiation.

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Deping Han

Full Text Available Little is known about the effects of ionizing radiation on the transition and the related signal transduction of progenitor B cells in the bone marrow. Thus, using an NIH Swiss mouse model, we explored the impact of ionizing radiation on the early stage of B-cell development via an examination of the transition of CLP to pro-B to pre-B cells within bone marrow as a function of radiation doses and times. Our results showed that while the total number of bone marrow lymphoid cells at different stages were greatly reduced by subtotal body irradiation (sub-TBI, the surviving cells continued to transition from common lymphoid progenitors to pro-B and then to pre-B in a reproducible temporal pattern. The rearrangement of the immunoglobulin heavy chain increased significantly 1-2 weeks after irradiation, but no change occurred after 3-4 weeks. The rearrangement of the immunoglobulin light chain decreased significantly 1-2 weeks after sub-TBI but increased dramatically after 3-4 weeks. In addition, several key transcription factors and signaling pathways were involved in B-precursor transitions after sub-TBI. The data indicate that week 2 after irradiation is a critical time for the transition from pro-B cells to pre-B cells, reflecting that the functional processes for different B-cell stages are well preserved even after high-dose irradiation.

Hyperfractionated total body irradiation for T-depleted HLA identical bone marrow transplants

International Nuclear Information System (INIS)

Latini, P.; Checcaglini, F.; Maranzano, E.; Aristei, C.; Panizza, B.M.; Gobbi, G.; Raymondi, C.; Aversa, F.; Martelli, M.F.

1988-01-01

Twenty patients suffering from malignant hemopathies (mean age 31.7 years) were given hyperfractionated total body irradiation (TBI) as conditioning for T-depleted HLA identical allogeneic bone marrow transplantation. At an average of 12 months (range of 4.5-22 months) follow-up there were two cases of early death and two cases (11%) of rejection. There were no cases of acute or chronic graft versus host disease nor cases of interstitial pneumonitis. The average time for durable engraftment was 22 days. Disease-free survival at 12 months was 65%. To improve the results and further reduce the percent of rejection, the authors propose intensifying the immunosuppressive conditioning by increasing the cyclophosphamide dose and that of TBI so that a total dose of 1560 cGy is reached. 35 refs.; 1 figure

Total body irradiation in the bone marrow transplantation in leukemia:an experience

International Nuclear Information System (INIS)

Zapatero, A.; Martin de Vidales, C.; Pinar, B.; Marin, A.; Cerezo, L.; Dominguez, P.; Perez, A.

1996-01-01

The purpose of this report was to evaluate long-term survival and morbidity of fractioned total body irradiation (TBI) prior to allogeneicbone marrow transplantation (BMT) for leukemia. From June 1985 to May 1992, 94 patients with acute leukemia and chronic myelogenous leukemia (CML), were treated with high dose cyclophosphamide(CY) and fractionated TBI to a total dose of 12 Gy in six fractions prior to allogeneic BMT. The Kaplan-Meier 5-year overall survival and disease-free survival were 53% +-6 and 48%+- respectively for patients with standard risk disease (first remission of acute leukemia and first chronic phase of CML), and 24%+-7 and 21%+-6 for patients with more advanced disease (p=3D0.01). The incidence of interstitial pneumonitis (IP), venoocclusive disease of the liver (VOD) and grade=3D>II acute graft-versus-host disease (GVHD) were respectively 15%, 29% and 51%. Fractionated TBI combined with high dose CY before allogeneic BMT for leukemia is an effective treatment in prolonging relapse-free survival witha low incidence of lung toxicity. (Author) 13 refs

The modifying effect of ibuprofen on total body irradiation-induced elevation of oxidative reactions in male hamsters

International Nuclear Information System (INIS)

Dokmeci, D.; Akpolat, M.; Aydogdu, N.; Uzal, C.; Turan, N.F.

2004-01-01

Radiation therapy plays an important role in curative and palliative treatments of malignant diseases. Because of the lipid component in the membrane, lipid peroxidation has been reported to be particularly susceptible to radiation damage. However, lipid peroxidation is reversed by cellular defense mechanisms, and the use of various antioxidants involved in these mechanisms have recently been suggested to be beneficial. It is known that ibuprofen has antioxidative and/or free radical scavenging activities. Our purpose is to examine the antioxidant capacity of ibuprofen in hamsters undergoing total body irradiation (TBI). Ibuprofen was given by gavage at dose of 10 mg/kg for 15 consecutive days. After this period, animals were exposed to TBI 60 Co gamma irradiation with a single dose of 8 Gy. After 24 h radiation exposure, the hamsters were killed and samples were taken from blood. Plasma thiobarbituric acid reactive substances (TBARS) increased significantly after radiation exposure, and ibuprofen diminished the amounts of TBARS. Significant protection of the radiation-induced changes in the activities of superoxide dismutase (SOD) and catalase was also recorded in the blood of ibuprofen-treated and -irradiated hamsters. These results suggest that ibuprofen with its antioxidant capacity could play a modulatory role against cellular damage effected by free radicals induced by TBI. (author)

Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.

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Amory Koch

Full Text Available Acute radiation sickness (ARS following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS developed at the Veterinary Sciences Department (VSD of the Armed Forces Radiobiology Research Institute (AFRRI to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male TBI model (6-14 Gy, 60Co γ-rays at 0.6 Gy min-1, which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated, 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors. In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2-4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies.

Total-body irradiation - role and indications. Results from the German Registry for Stem Cell Transplantation (DRST)

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Heinzelmann, F.; Bamberg, M.; Belka, C.; Ottinger, H.; Mueller, C.H.; Allgaier, S.; Faul, C.

2006-01-01

Background and purpose: total-body irradiation (TBI) is a key part of the conditioning regimen before hematopoietic stem cell transplantation (HSCT). The exact role of TBI as part of the conditioning regimen is largely unclear. In order to determine the relevance of TBI, the status of TBI utilization was analyzed on the basis of a nationwide registry. Material and methods: 14,371 patients (1998-2002) documented in the German Stem Cell Transplantation Registry (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic transplantation, underlying disorder, type of donor, stem cell source, and size of the treatment center. Results: for autologous HSCT ∝10% of the patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL, ∝80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL, ∝35%, 330/929) being the most important disorders. In the allogeneic setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The type of donor, stem cell source and center size did not strongly influence the use of TBI. Conclusion: TBI has only a limited role for the conditioning prior to autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes over the observation time. The use of TBI is generally accepted for ALL, whereas approximately half of the patients with CML or AML received TBI. Although a considerably large database was analyzed, no clear determinants for the use of TBI could be distinguished. (orig.)

Total-body irradiation - role and indications. Results from the German Registry for Stem Cell Transplantation (DRST)

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Heinzelmann, F.; Bamberg, M.; Belka, C. [Dept. of Radiation Oncology, Univ. of Tuebingen (Germany); Ottinger, H. [German Registry for Stem Cell Transplantation (DRST) Secretary, Univ. of Essen (Germany); Mueller, C.H.; Allgaier, S. [DRST Datacenter, DRK Bloodbank Center Ulm (Germany); Faul, C. [Dept. of Internal Medicine II, Univ. of Tuebingen (Germany)

2006-04-15

Background and purpose: total-body irradiation (TBI) is a key part of the conditioning regimen before hematopoietic stem cell transplantation (HSCT). The exact role of TBI as part of the conditioning regimen is largely unclear. In order to determine the relevance of TBI, the status of TBI utilization was analyzed on the basis of a nationwide registry. Material and methods: 14,371 patients (1998-2002) documented in the German Stem Cell Transplantation Registry (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic transplantation, underlying disorder, type of donor, stem cell source, and size of the treatment center. Results: for autologous HSCT {proportional_to}10% of the patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL, {proportional_to}80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL, {proportional_to}35%, 330/929) being the most important disorders. In the allogeneic setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The type of donor, stem cell source and center size did not strongly influence the use of TBI. Conclusion: TBI has only a limited role for the conditioning prior to autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes over the observation time. The use of TBI is generally accepted for ALL, whereas approximately half of the patients with CML or AML received TBI. Although a considerably large database was analyzed, no clear determinants for the use of TBI could be distinguished. (orig.)

A prospective study of the early clinical symptoms following a 2 Gy therapeutic whole-body irradiation; Etude prospective de la symptomatologie clinique precoce apres irradiation corporelle totale therapeutique de 2 Gy

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Fizazi, K.; Chaillet, M.P.; Fourquet, A.; Jammet, P.; Cosset, J.M. [Institut Curie, 75 - Paris (France)

1995-10-01

Early human tolerance following total body irradiation (TBI) according to the dose received is still poorly known. Thirteen selected patients were prospectively evaluated for clinical side effects during the first 10 hours following a 2 Gy TBI prior to bone marrow transplantation. All of them but one were treated for haematological malignancies and were in clinical remission at the date of TBI. There were 10 males and 3 females, with a median age of 43 y (range 16*61) and a good performance status (WHO 0-1). They received granisetron (3 mg) injected intravenously 1 h before the time of TBI in order to prevent nausea and vomiting. The main symptoms consisted in drowsiness (69%), headache (62%), xerostomia (62%), nausea and vomiting (46%), anorexia (38%), parotid gland pain (23%) and abdominal pain (8%). Their intensity was always moderate, except for 2 patients who experimented severe vomiting. The incidence rate and the time-course of the symptoms of the prodromal phase may proved to be helpful for early clinical evaluation and triage of victims of an accidental irradiation. In particular, absence of fever at the 6{sup th} h after TBI supports the assumption of an estimated exposure dose below 2 Gy. (authors). 23 refs., 2 tabs.

Efficacy of granisetron in the prevention of GIT problems in patients undergoing total body irradiation

International Nuclear Information System (INIS)

Feuvret, L.; Jammet, P.; Campana, F.; Cosset, J.M.; Fourquet, A.

1994-01-01

From december 1991 to september 1992, 20 patients due to receive total body irradiation (TBI) prior to allogeneic or autologous bone marrow transplantation were given granisetron (Kytril) in order to prevent intestinal (nausea and vomiting) early intolerance, TBI regimen was delivered on a fractional basis of six fractions, over 3 days. Twelve grays were delivered with a lung protection decreasing the pulmonary dose to 9 Gy Granisetron (3 mg) was administered by a 5-min intravenous infusion, 1 h before TBI. Up to two further infusions were given if nausea or vomiting occurred. The pretreatment perfusion was sufficient to prevent nausea and vomiting in 10/20 patients, one additional post-treatment perfusion was necessary in 7/20 patients, and two in 1/20 patients. In 2/20 cases, nausea and vomiting persisted in spite of three perfusions. Excellent or good efficacy was noted in 15/20 patients and a minor (or no) efficacy in five. Granisetron appears to be superior to the conventional anti emetic schemes to prevent nausea and vomiting in patients receiving TBI for bone marrow transplantation. 15 Refs

'Mini' total body irradiation and allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Gocheva, L.; Sergieva, K.; Koleva, I.; Avramova, V.; Vassileva, V.; Georgieva, S.; Sultanov, B.

2006-01-01

Full text: The total body irradiation (TBI) combined with intensive chemotherapy plays an important role in the preparation of patients for bone marrow transplantation (BMT). The first autologous BMT in Bulgaria was performed in 1997 in the Specialized Pediatric Hospital for Active Treatment (SPHAT) of oncohematological diseases. The first TBI, followed by allogeneic BMT, was carried out in 2002 in the 'Queen Giovanna' University Hospital, after which its routine application as a basic form of large field radiotherapy and a main stage of the conditioning regimen for BMT was started. Fourteen allogeneic BMTs including TBI as a basic conditioning regimen have been performed till May 2006. The objective of the present report is to present the first clinical observations in the Bulgarian oncological practice on 'mini' TBI followed by allogeneic blood stem cell transplantation. During the period October 2005 - May 2006, 'mini' TBI followed by allogeneic BMT was carried out for two patients of the age 43 and 50 years. The diagnosis of both patients was acute non-lymphoblastic leukemia, in the remission stage, after one relapse, respectively. Intensive preceding chemotherapy was applied for both patients. A conditioning regimen was applied including the fludarabine purine analogue (3 x 30 mg/m 2 ) and 200 cGy TBI. It was followed by transplantation of allogeneic cell concentrate containing 2.5 x10 6 /kg CD34+ and 4.0 x10 6 /kg CD34+ blood stem cells of partially compatible family donors (a sister and a son), which were tolerable for the patients without complications. Cyclosporine and mycophelonate mofetile were applied as post-transplantation treatment. Active antibiotic, antiviral, symptomatic and substituting therapy, as well as GvHD prophylaxis was applied for both patients. Good clinical tolerance was recorded for the applied low dose conditioning regimen. The patients were discharged within 30 days in good general condition and stable draft action, with

Biochemical and hematological indicators in model of total body irradiation

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Dubner, D; Gisone, P.; Perez, M.R.; Barboza, M.; Luchetta, P.; Longoni, H.; Sorrentino, M.; Robison, A.

1998-01-01

With the purpose of evaluating the applicability of several biological indicators in accidental overexposures a study was carried out in 20 patients undergoing therapeutical total body irradiation (TBI). The following parameters were evaluated: a) Oxidative stress indicators: erythrocyte superoxide dismutase (SOD) and catalase activity (CAT), lipo peroxyde levels (TBARS) and total plasma antioxidant activity (TAA). b) Haematological indicators: reticulocyte maturity index (RMI) and charges in lymphocyte subpopulations. Non significant changes in SOD and CAT activity were observed. Significant higher TBARS levels were found in patients with unfavorable post-BTM course without any significant correlation with TAA. RMI decreased early and dropped to zero in most of the patients and rose several days prior to reticulocyte, neutrophils and platelets counts. A significant decrease in absolute counts of all lymphocyte subpopulations was observed during TBI, particularly for B lymphocytes. A subpopulation of natural killer (NK) cells (CD16+/ CD 56 +) showed a relative higher radioresistance. Cytotoxic activity was significantly decreased after TBI. These data suggest that TBARS could provide an useful evolutive indicator in accidental over exposure d patients and RMI is an early indicator of bone marrow recovery after radioinduced aplasia. The implications of the different radiosensitivities within the NK subsets remains unanswered. (author) [es

Cobalt-60 total body irradiation dosimetry at 220 cm source-axis distance

International Nuclear Information System (INIS)

Glasgow, G.P.; Mill, W.B.

1980-01-01

Adults with acute leukemia are treated with cyclophosphamide and total body irradiation (TBI) followed by autologous marrow transplants. For TBI, patients seated in a stand angled 45 0 above the floor are treated for about 2 hours at 220 cm source-axis distance (SAD) with sequential right and left lateral 87 cm x 87 cm fields to a 900 rad mid-pelvic dose at about 8 rad/min using a 5000 Ci cobalt unit. Maximum (lateral) to minimum (mid-plane) dose ratios are: hips--1.15, shoulders--1.30, and head--1.05, which is shielded by a compensator filter. Organ doses are small intestine, liver and kidneys--1100 rad, lung--1100 to 1200 rad, and heart--1300 rad. Verification dosimetry reveals the prescribed dose is delivered to within +-5%. Details of the dosimetry of this treatment are presented

Modeling, planning and XiO R CMS validation of TBI treatment (extended SSD 400 cm)

International Nuclear Information System (INIS)

Teijeiro, A.; Pereira, L.; Moral, F. del; Vazquez, J.; Lopez Medina, A.; Meal, A.; Andrade Alvarez, B.; Salgado Fernandez, M.; Munoz, V.

2011-01-01

The whole body irradiation (TBI) is a radiotherapy technique previously used a bone marrow transplant and for certain blood diseases, in which a patient is irradiated to extended distance (SSD from 350 to 400). The aim of the TBI is to kill tumor cells in the receiver and prevent rejection of transplanted bone marrow. The dose is prescribed at the midpoint of the abdomen around the navel wing. The most planners not permit the treatment of patients with a much higher SSD to 100 cm, also using the table LUT with spoiler to increase skin dose should be taken into account This requires measurements and checks ad hoc if you use a planner, because modeling is not optimized a priori for an SSD of 400 cm.

28Si total body irradiation injures bone marrow hematopoietic stem cells via induction of cellular apoptosis

Science.gov (United States)

Chang, Jianhui; Feng, Wei; Wang, Yingying; Allen, Antiño R.; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-05-01

Long-term space mission exposes astronauts to a radiation environment with potential health hazards. High-energy charged particles (HZE), including 28Si nuclei in space, have deleterious effects on cells due to their characteristics with high linear energy transfer and dense ionization. The influence of 28Si ions contributes more than 10% to the radiation dose equivalent in the space environment. Understanding the biological effects of 28Si irradiation is important to assess the potential health hazards of long-term space missions. The hematopoietic system is highly sensitive to radiation injury and bone marrow (BM) suppression is the primary life-threatening injuries after exposure to a moderate dose of radiation. Therefore, in the present study we investigated the acute effects of low doses of 28Si irradiation on the hematopoietic system in a mouse model. Specifically, 6-month-old C57BL/6 J mice were exposed to 0.3, 0.6 and 0.9 Gy 28Si (600 MeV) total body irradiation (TBI). The effects of 28Si TBI on BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were examined four weeks after the exposure. The results showed that exposure to 28Si TBI dramatically reduced the frequencies and numbers of HSCs in irradiated mice, compared to non-irradiated controls, in a radiation dose-dependent manner. In contrast, no significant changes were observed in BM HPCs regardless of radiation doses. Furthermore, irradiated HSCs exhibited a significant impairment in clonogenic ability. These acute effects of 28Si irradiation on HSCs may be attributable to radiation-induced apoptosis of HSCs, because HSCs, but not HPCs, from irradiated mice exhibited a significant increase in apoptosis in a radiation dose-dependent manner. However, exposure to low doses of 28Si did not result in an increased production of reactive oxygen species and DNA damage in HSCs and HPCs. These findings indicate that exposure to 28Si irradiation leads to acute HSC damage.

Fiber-coupled Al₂O₃:C radioluminescence dosimetry for total body irradiations

DEFF Research Database (Denmark)

Buranurak, Siritorn; Andersen, Claus E.

2016-01-01

in the context of Total Body Irradiations (TBIs) where patients are treated with large fields of 6 or 18 MV photons at an extended source-to-surface distance (SSD). The study shows that Al2O3:C dosimetry using the saturated-RL protocol may be suitable for real-time in vivo dosimetry during TBI treatments from...... the perspective of the good agreement with alanine dosimetry and other critical phantom tests, including the ability to cope with the large stem signal experienced during TBI treatments at extended SSD. In contrast, the chromatic stem removal technique often used for organic plastic scintillators did not work...

In vivo dosimetry for total body irradiation: five‐year results and technique comparison

Science.gov (United States)

Warry, Alison J.; Eaton, David J.; Collis, Christopher H.; Rosenberg, Ivan

2014-01-01

The aim of this work is to establish if the new CT‐based total body irradiation (TBI) planning techniques used at University College London Hospital (UCLH) and Royal Free Hospital (RFH) are comparable to the previous technique at the Middlesex Hospital (MXH) by analyzing predicted and measured diode results. TBI aims to deliver a homogeneous dose to the entire body, typically using extended SSD fields with beam modulation to limit doses to organs at risk. In vivo dosimetry is used to verify the accuracy of delivered doses. In 2005, when the Middlesex Hospital was decommissioned and merged with UCLH, both UCLH and the RFH introduced updated CT‐planned TBI techniques, based on the old MXH technique. More CT slices and in vivo measurement points were used by both; UCLH introduced a beam modulation technique using MLC segments, while RFH updated to a combination of lead compensators and bolus. Semiconductor diodes were used to measure entrance and exit doses in several anatomical locations along the entire body. Diode results from both centers for over five years of treatments were analyzed and compared to the previous MXH technique for accuracy and precision of delivered doses. The most stable location was the field center with standard deviations of 4.1% (MXH), 3.7% (UCLH), and 1.7% (RFH). The least stable position was the ankles. Mean variation with fraction number was within 1.5% for all three techniques. In vivo dosimetry can be used to verify complex modulated CT‐planned TBI, and demonstrate improvements and limitations in techniques. The results show that the new UCLH technique is no worse than the previous MXH one and comparable to the current RFH technique. PACS numbers: 87.55.Qr, 87.56.N‐ PMID:25207423

Immunosuppression prior to marrow transplantation for sensitized aplastic anemia patients: comparison of TLI with TBI

International Nuclear Information System (INIS)

Shank, B.; Brochstein, J.A.; Castro-Malaspina, H.; Yahalom, J.; Bonfiglio, P.; O'Reilly, R.J.

1988-01-01

From May 1980 through July 1986, 26 patients with severe aplastic anemia, sensitized with multiple transfusions of blood products, were treated on either of two immunosuppressive regimens in preparation for bone marrow transplantation from a matched donor. There were 10 patients treated with total body irradiation (TBI), 200 cGy/fraction X 4 daily fractions (800 cGy total dose), followed by cyclophosphamide, 60 mg/kg/d X 2 d. An additional 16 patients were treated with total lymphoid irradiation (TLI) [or, if they were infants, a modified TLI or thoracoabdominal irradiation (TAI)], 100 cGy/fraction, 3 fractions/d X 2 d (600 cGy total dose), followed by cyclophosphamide, 40 mg/kg/d X 4 d. The extent of immunosuppression was similar in both groups as measured by peripheral blood lymphocyte depression at the completion of the course of irradiation (5% of initial concentration for TBI and 24% for TLI), neutrophil engraftment (10/10 for TBI and 15/16 for TLI), and time to neutrophil engraftment (median of 22 d for TBI and 17 d for TLI). Marrow and peripheral blood cytogenetic analysis for assessment of percent donor cells was also compared in those patients in whom it was available. 2/2 patients studied with TBI had 100% donor cells, whereas 6/11 with TLI had 100% donor cells. Of the five who did not, three were stable mixed chimeras with greater than or equal to 70% donor cells, one became a mixed chimera with about 50% donor cells, but became aplastic again after Cyclosporine A cessation 5 mo post-transplant, and the fifth reverted to all host cells by d. 18 post-transplant. Overall actuarial survival at 2 years was 56% in the TLI group compared with 30% in the TBI group although this was not statistically significant. No survival decrement has been seen after 2 years in either group

Behavioural consequences of an 8 Gy total body irradiation in mice: Regulation by interleukin-4

International Nuclear Information System (INIS)

Van der Meeren, A.; Lebaron-Jacobs, L.

2001-01-01

The effects of an 8 Gy γ total body irradiation (TBI) on exploration and locomotion activities as well as temperature were studied in C57BL6/J mice. Survival, body weight, and blood cell counts were also assessed in irradiated mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment on improvement in exploration activity was evaluated. The study was carried out from 3 h to 30 days following exposure. Our results showed a biphasic response to irradiation concerning the exploration activity of mice. Irradiated mice had reduced activity as early as 3 h after exposure, with recovery of activity within 24 h. The exploration activity again decreased 4 days after irradiation and the recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in mice in both phases. The locomotion activity was studied using a telemetry apparatus. A similar pattern to that of the exploration data was observed, with a minimal activity observed between days 13 and 17. A radiation-induced hypothermia was also noticed over the same time period. (author)

Behavioural consequences of an 8 Gy total body irradiation in mice: Regulation by interleukin-4

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Van der Meeren, A.; Lebaron-Jacobs, L. [Inst. de Protection et de Surete Nucleaire, Dept. de Protection de la sante de l' Homme et de Dosimetrie, Section Autonome de Radiobiologie Appliquee a la Medecine, IPSN, Fontenay-aux-Roses (France)

2001-02-01

The effects of an 8 Gy {gamma} total body irradiation (TBI) on exploration and locomotion activities as well as temperature were studied in C57BL6/J mice. Survival, body weight, and blood cell counts were also assessed in irradiated mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment on improvement in exploration activity was evaluated. The study was carried out from 3 h to 30 days following exposure. Our results showed a biphasic response to irradiation concerning the exploration activity of mice. Irradiated mice had reduced activity as early as 3 h after exposure, with recovery of activity within 24 h. The exploration activity again decreased 4 days after irradiation and the recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in mice in both phases. The locomotion activity was studied using a telemetry apparatus. A similar pattern to that of the exploration data was observed, with a minimal activity observed between days 13 and 17. A radiation-induced hypothermia was also noticed over the same time period. (author)

Central axis dose verification in patients treated with total body irradiation of photons using a Computed Radiography system

International Nuclear Information System (INIS)

Rubio Rivero, A.; Caballero Pinelo, R.; Gonzalez Perez, Y.

2015-01-01

To propose and evaluate a method for the central axis dose verification in patients treated with total body irradiation (TBI) of photons using images obtained through a Computed Radiography (CR) system. It was used the Computed Radiography (Fuji) portal imaging cassette readings and correlate with measured of absorbed dose in water using 10 x 10 irradiation fields with ionization chamber in the 60 Co equipment. The analytical and graphic expression is obtained through software 'Origin8', the TBI patient portal verification images were processed using software ImageJ, to obtain the patient dose. To validate the results, the absorbed dose in RW3 models was measured with ionization chamber with different thickness, simulating TBI real conditions. Finally it was performed a retrospective study over the last 4 years obtaining the patients absorbed dose based on the reading in the image and comparing with the planned dose. The analytical equation obtained permits estimate the absorbed dose using image pixel value and the dose measured with ionization chamber and correlated with patient clinical records. Those results are compared with reported evidence obtaining a difference less than 02%, the 3 methods were compared and the results are within 10%. (Author)

Paraphyseal changes on bone-age studies predict risk of delayed radiation-associated skeletal complications following total body irradiation

International Nuclear Information System (INIS)

Kitazono Hammell, Mary T.; Edgar, J.C.; Jaramillo, Diego; Bunin, Nancy

2013-01-01

Children undergoing total body irradiation (TBI) often develop delayed skeletal complications. Bone-age studies in these children often reveal subtle paraphyseal changes including physeal widening, metaphyseal irregularity and paraphyseal exostoses. To investigate whether paraphyseal changes on a bone-age study following TBI indicate a predisposition toward developing other radiation-associated skeletal complications. We retrospectively reviewed medical records and bone-age studies of 77 children receiving TBI at our institution between 1995 and 2008 who had at least 2 years of clinical follow-up and one bone-age study after TBI. We graded bone-age studies according to the severity of paraphyseal changes. All documented skeletal complications following TBI were tabulated. Kendall's tau-b was used to examine associations between degree of paraphyseal change and development of a skeletal complication. Kendall's tau analyses showed that physeal widening and metaphyseal irregularity/sclerosis (tau = 0.87, P < 0.001) and paraphyseal exostoses (tau = 0.68, P < 0.001) seen on bone-age studies were significantly positively associated with the development of delayed skeletal complications following TBI. Thirty percent of children with no or mild paraphyseal changes developed a delayed skeletal complication, compared with 58% of children with moderate paraphyseal changes and 90% of children with severe paraphyseal changes. Paraphyseal changes identified on a bone-age study correlate positively with the development of delayed skeletal complications elsewhere in the skeleton following TBI. (orig.)

Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia

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Chung, Su Mi; Choi, Ihl Bohng; Kang, Ki Mun; Kim, In Ah; Shinn, Kyung Sub; Kim, Choon Choo; Kim, Dong Jip [Catholic University College of Medicine, Seoul (Korea, Republic of)

1994-06-15

Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6 fractions/3 days (6 patients) or 1320 cGy/8 fractions/4 days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase.

Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia

International Nuclear Information System (INIS)

Chung, Su Mi; Choi, Ihl Bohng; Kang, Ki Mun; Kim, In Ah; Shinn, Kyung Sub; Kim, Choon Choo; Kim, Dong Jip

1994-01-01

Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6 fractions/3 days (6 patients) or 1320 cGy/8 fractions/4 days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase

Factors associated with pulmonary toxicity after myeloablative conditioning using fractionated total body irradiation

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Byun, Hwa Kyung; Yoon, Hong In; Cho, Jae Ho [Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); and others

2017-09-15

Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.

Factors associated with pulmonary toxicity after myeloablative conditioning using fractionated total body irradiation

International Nuclear Information System (INIS)

Byun, Hwa Kyung; Yoon, Hong In; Cho, Jae Ho

2017-01-01

Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI

Total body irradiation in intensive treatment necessitating bone marrow graft, of malignant hematological diseases

International Nuclear Information System (INIS)

Regnier, R.; Van Houtte, P.; Piron, A.; Debusscher, L.; Strijckmans, P.

1990-01-01

From 1980 to 1988, 65 consecutive patients were treated with a program of intensive chemotherapy and total body irradiation (TBI) for malignant hematological diseases at the Institut Jules-Bordet. Results were analyzed according to different prognostic factors as well as to the radiation technique; 3 different schedules were used: 3 fractions of 2.66 Gy given in one day at 3-h intervals, 6 daily fractions of 2 Gy in 6 days and 7 fractions of 2.25 Gy in 8 days. The second radiation schedule appears to give the best results as relapses were higher with the 1-day program and there was an increase in later effects and early deaths with 7 fractions of 2.25 Gy. Nevertheless, the results indicate that after administration of 5 or 6 times 2 Gy TBI, there might be possible benefit in treating certain parts of the body by radiation, those in particular that could be sanctuary sites for malignant cells from chemotherapy. The authors propose a simple and easy way of uniformizing the radiation schedule to carry out a multicentric trial [fr

Total body irradiation and autologus bone marrow transplantation in acute leukemias and non Hodgkin-lymphomas

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Corvo, R; Franzone, P; Scarpati, D; Congiu, M; Carella, A

1986-01-01

From january 1984 to may 1986, 31 patients, 15 ANLL, 8 ALL (in remission status) and 8 NHL (6 in remission, 2 in relapse) have been treated with chemo-radiotherapy (cyclophosphamide 60 mg/kg x 2 days + total body irradiation (TBI): 10 Gy/3 fr./3 days with 4 Gy boost testicular dose in ALL) and autologous bone marrow transplantation (BMT). Seventeen patients are alive, 16 in remission: 9 (60%) ANLL, 2 (25%) ALL, 5 (62%) NHL (median 8+ months, follow up 1+ /29+); 2 patients presented interstitial pneumonitis (6.45%). In this series, very good results have been achieved in ANLL, where no relapse was noted, encouraging achievements in NHL, with 4/8 relapse. Advantages and disadvanteges of autologus relative to allogenic BMT, and of conditioning regimen with or without TBI are discussed.

Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation

International Nuclear Information System (INIS)

Vriesendorp, H.M.; Halliwell, R.E.; Johnson, P.M.; Fey, T.A.; McDonough, C.M.

1985-01-01

The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated

Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

International Nuclear Information System (INIS)

Hiniker, Susan M.; Agarwal, Rajni; Modlin, Leslie A.; Gray, Christine C.; Harris, Jeremy P.; Million, Lynn; Kiamanesh, Eileen F.; Donaldson, Sarah S.

2014-01-01

Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy

Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

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Hiniker, Susan M. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Agarwal, Rajni [Section of Stem Cell Transplantation, Department of Pediatrics, Stanford University, Stanford, California (United States); Modlin, Leslie A. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gray, Christine C. [Division of Child and Adolescent Psychiatry, Department of Psychiatry, Stanford University, Stanford, California (United States); Harris, Jeremy P.; Million, Lynn [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Kiamanesh, Eileen F. [Cancer Clinical Trials Office, Stanford Cancer Institute, Stanford University, Stanford, California (United States); Donaldson, Sarah S., E-mail: sarah2@stanford.edu [Department of Radiation Oncology, Stanford University, Stanford, California (United States)

2014-05-01

Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy

Repair capacity of mouse lung after total body irradiation alone or combined with cyclophosphamide

International Nuclear Information System (INIS)

Safwat, Akmal; Bentzen, Soeren M.; Nielsen, Ole S.; Mahmoud, Hossam K.; Overgaard, Jens

1996-01-01

Purpose. Cyclophosphamide (CTX) combined with fractionated total body irradiation (TBI) is frequently used in the conditioning of patients prior to bone marrow transplantation (BMT). This study was performed to investigate the effect of CTX on the repair capacity of lung tissue after TBI in a mouse model for BMT. Materials and methods. TBI was given as a single fraction, 3 fractions in 3 days (Fx 3) or 9 fractions in 3 days (Fx 9) either alone or 24 h after a single dose of CTX. The single fraction TBI was given at either high dose rate (HDR) of 0.71 Gy/min or low dose rate (LDR) of 0.08 Gy/min. All mice were transplanted 4-6 h after the last TBI fraction. Lung damage was assessed using ventilation rate (VR) and lethality between 28 and 180 days. The repair capacity of lung tissue was estimated using the direct analysis method with the probability of reaching the end point described by a logistic formulation of the linear quadratic model. Results. The VR data confirmed the high repair capacity of lung tissue with an α/β ratio of 4.4 Gy though with a wide 95% confidence interval (CI = 0.03-10.5). Giving CTX before fractionated TBI marked reduced the doses needed to cause response in 50% of the animals. The sparing effect of using fractionated TBI was still evident in the combined CTX-TBI schedules. The estimated α/β ratio was 1.6 Gy (CI = 0.01-4.7) which is within the range of values reported after thoracic radiation only. On the other hand, the sparing effect seen in going from single fraction HDR to LDR was completely abolished when CTX was given 24 h before TBI. The same pattern was repeated when lethality between 28-180 days was used. Yet, the use of lethality to estimate lung damage in a TBI model, markedly underestimated the repair capacity. Conclusions. These results confirm the high repair capacity of lung tissue after TBI and emphasize the value of using a specific end point in testing lung damage after TBI. It also shows that there can be a negative

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

International Nuclear Information System (INIS)

Schultheiss, Timothy E.; Wong, Jeffrey; Liu, An; Olivera, Gustavo; Somlo, George

2007-01-01

Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribs and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk

Backscatter Correction Algorithm for TBI Treatment Conditions

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Sanchez-Nieto, B.; Sanchez-Doblado, F.; Arrans, R.; Terron, J.A. [Dpto. Fisiología Médica y Biofísica, Universidad de Sevilla, Avda. Sánchez Pizjuán, 4. E-41009, Sevilla (Spain); Errazquin, L. [Servicio Oncología Radioterápica, Hospital Univ.V. Macarena. Dr. Fedriani, s/n. E-41009, Sevilla (Spain)

2015-01-15

The accuracy requirements in target dose delivery is, according to ICRU, ±5%. This is so not only in standard radiotherapy but also in total body irradiation (TBI). Physical dosimetry plays an important role in achieving this recommended level. The semi-infinite phantoms, customarily used for dosimetry purposes, give scatter conditions different to those of the finite thickness of the patient. So dose calculated in patient’s points close to beam exit surface may be overestimated. It is then necessary to quantify the backscatter factor in order to decrease the uncertainty in this dose calculation. The backward scatter has been well studied at standard distances. The present work intends to evaluate the backscatter phenomenon under our particular TBI treatment conditions. As a consequence of this study, a semi-empirical expression has been derived to calculate (within 0.3% uncertainty) the backscatter factor. This factor depends lineally on the depth and exponentially on the underlying tissue. Differences found in the qualitative behavior with respect to standard distances are due to scatter in the bunker wall close to the measurement point.

Efficacy of granisetron in the prevention of GIT problems in patients undergoing total body irradiation. Interet du granisetron dans la prevention des troubles digestifs lors des irradiations corporelles totales

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Feuvret, L.; Jammet, P.; Campana, F.; Cosset, J.M.; Fourquet, A. (Institut Curie, 75 - Paris (France))

1994-01-01

From december 1991 to september 1992, 20 patients due to receive total body irradiation (TBI) prior to allogeneic or autologous bone marrow transplantation were given granisetron (Kytril) in order to prevent intestinal (nausea and vomiting) early intolerance, TBI regimen was delivered on a fractional basis of six fractions, over 3 days. Twelve grays were delivered with a lung protection decreasing the pulmonary dose to 9 Gy Granisetron (3 mg) was administered by a 5-min intravenous infusion, 1 h before TBI. Up to two further infusions were given if nausea or vomiting occurred. The pretreatment perfusion was sufficient to prevent nausea and vomiting in 10/20 patients, one additional post-treatment perfusion was necessary in 7/20 patients, and two in 1/20 patients. In 2/20 cases, nausea and vomiting persisted in spite of three perfusions. Excellent or good efficacy was noted in 15/20 patients and a minor (or no) efficacy in five. Granisetron appears to be superior to the conventional anti emetic schemes to prevent nausea and vomiting in patients receiving TBI for bone marrow transplantation. 15 Refs.

Current status of total body irradiation in conditioning regimen for childhood acute lymphoblastic leukemia. Survey in the Japan Association of Childhood Leukemia Study (JACLS) Group

International Nuclear Information System (INIS)

Suzuki, Nobuhiro; Hara, Jun-ichi; Chayama, Kohsuke; Akiyama, Yuichi; Nakahata, Tatsutoshi

2005-01-01

We surveyed methods of total body irradiation (TB I) in conditioning regimens of stem cell transplantation (SCT) for children with acute lymphoblastic leukemia (ALL) at participating institutions of the Japan Association of Childhood Leukemia Study (JACLS) ALL-97 protocol. We obtained information about TBI from 25 institutions. Total dose of 12 Gy fractionated by four to six in two to three days for TBI was conducted in 22 of 25 institutions. High-risk patients, such as patients with Philadelphia positive ALL, received over 12 Gy in five institutions. Beam direction and patient's positioning were horizontal and lateral respectively in 15 institutions. Shielding of lung and/or eyes and boost irradiation to central nervous system and/or testis were done in 24 and 11 institutions respectively, but in various ways. We have to keep in mind that a great variety of TBI have been undergone in each institution when we intend to interpret multi-institutional trials of treatment including SCT for patients with ALL. (author)

An experimental model of acute encephalopathy after total body irradiation in the rat: effect of liposome-entrapped Cu/Zn superoxide dismutase

International Nuclear Information System (INIS)

Lamproglou, Ioannis; Magdelenat, Henri; Boisserie, Gilbert; Baillet, Francois; Mayo, Willy; Fessi, Hatem; Puisieux, Francis; Perderau, Bernard; Colas-Linhart, Nicole; Delattre, Jean-Yves

1998-01-01

Purpose: To develop an experimental model of acute encephalopathy following total body irradiation in rats and to define the therapeutic effect of liposome-entrapped Cu/Zn superoxide dismutase. Methods and Materials: A total of 120 4-month-old rats received 4.5 Gy total body irradiation (TBI) while 120 rats received sham irradiation. A behavioral study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed 5 hours before irradiation and repeated the following days. Subcutaneous treatment was started 1 hour after irradiation and repeated daily for 2 weeks. In both the irradiated and sham group, three subgroups were defined according to the treatment received: liposome-entrapped Cu/Zn superoxide dismutase (0.5 mg/kg), liposomes only, normal saline. Results: This work comprised two consecutive studies. In study A (90 rats) the one-way avoidance test was administered daily from day 0 to day 4 with a recall session at day 14. In study B (validation phase in 150 rats) the behavioral test was performed only from day 0 to day 6. Before irradiation, all rats showed a similar behavioral response. Study A (6 groups of 15 rats): Following TBI, irradiated rats treated with liposomes only or saline demonstrated a significant delay in learning the one-way avoidance test in comparison with sham-irradiated rats (0.05 < p <0.001 depending upon the day of evaluation and the subgroup type). In contrast, irradiated rats treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from sham-irradiated rats. Study B (6 groups of 25 rats): The results were the same as those in study A, demonstrating a significant delay in the learning of the test in the liposome and saline-treated irradiated rats in comparison with sham-irradiated rats (0.02 < p < 0.001). The irradiated rats, treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from the sham-irradiated controls. Conclusion: This study indicates that a relatively

The effects of single dose TBI on hepatic and renal function in non-human primates and patients

International Nuclear Information System (INIS)

Broerse, J.J.; Bakker, B.; Davelaar, J.; Leer, J.W.H.; Niemer-Tucker, M.M.B.; Noordijk, E.M.

1996-01-01

Total body irradiation (TBI) and bone marrow transplantation (BMT) are common procedures in the treatment of severe combined immune deficiency syndromes, leukemia, non-Hodgkin lymphoma and other hematological disorders. Improved results following TBI and BMT have increased the number of patients in long term follow up. Late detrimental effects of TBI have been investigated in non-human primates and patients with emphasis on vital organs like liver and kidney. The response of monkeys to radiation is not significantly different from that in man. Long term effects of TBI could be studied by keeping 84 monkeys of different ages under continuous observation for a period up to 25 years. Effects on hepatic and renal function were demonstrated using serological and histological parameters. The values of the liver function parameters such as alkaline phosphatase and gamma glutamyl transferase in the irradiated group are significantly increased after TBI. Also the parameters of kidney dysfunction, e.g., Ht and urea show a significant change in the irradiated old aged cohort with respect to the controls. Between 1967 and 1993, 336 bone marrow transplantations were performed at the University Hospital Leiden. The present Study was restricted to those patients who survived at least 18 months after transplantation. This retrospective analysis consequently amounts to 120 patients. The monkey data indicated subclinical organ damage for postirradiation intervals exceeding 15 years. However, up to the present time, the human data do not support these findings since the follow up time is still restricted to a median survival of 4,5 years. Detrimental effects in liver and kidney function at a later stage can not be excluded yet, and careful examinations of the patients remain indicated

Fiber-coupled Al_2O_3:C radioluminescence dosimetry for total body irradiations

International Nuclear Information System (INIS)

Buranurak, S.; Andersen, C.E.

2016-01-01

In vivo dosimetry can be important and relevant in radiotherapy, especially when commissioning new treatment techniques at hospitals. This study investigates the potential use of fiber-coupled radioluminescence (RL) dosimetry based on Al_2O_3:C or organic plastic scintillators for this purpose in the context of Total Body Irradiations (TBIs) where patients are treated with large fields of 6 or 18 MV photons at an extended source-to-surface distance (SSD). The study shows that Al_2O_3:C dosimetry using the saturated-RL protocol may be suitable for real-time in vivo dosimetry during TBI treatments from the perspective of the good agreement with alanine dosimetry and other critical phantom tests, including the ability to cope with the large stem signal experienced during TBI treatments at extended SSD. In contrast, the chromatic stem removal technique often used for organic plastic scintillators did not work well in large fields with the tested calibration procedure and instrumentation. An apparent dose-rate effect discussed in a previous study of the RL properties of Al_2O_3:C (Andersen et al., 2011) was found to have resulted from an overlooked dead time problem in the counting system, and this potential caveat can therefore be removed from the list of potential problems associated with fiber-coupled Al_2O_3:C dosimetry using the saturated-RL protocol. This further has implications for TBI dosimetry using the RL Al_2O_3:C system due to large dose-rate differences between calibrations at the iso-center and in vivo measurements at extended source-to-surface distances. - Highlights: • Fiber-coupled dosimetry can be used for measurements during total body irradiations. • An apparent dose-effect associated with radioluminescence from Al2O3:C was resolved. • The gated-counting stem removal procedure worked well for Al2O3:C in pulsed accelerator beams. • The chromatic stem removal procedure did not work well with the tested instrumentation and organic plastic

The Basel experience with total body irradiation for conditioning patients with acute leukemia for allogenic bone marrow transplantation

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Speck, B.; Cornu, P.; Nissen, C.; Gratwohl, A.; Sartorius, J.

1979-01-01

We are reporting our experience with 13 patients suffering from end stage acute leukemia that were prepared for allogeneic bone marrow transplantation by combined chemotherapy followed by high dose cyclophosphamide (Cy) and total body irradiation (TBI). Only one patient became a long term survivor. Of the evaluable 12 patients, 6 died of interstitial pneumonia, 4 of GvH and 1 of recurrent leukemia. We conclude that adding combined chemotherapy to the standard conditioning program with Cy and TBI probably increases the risk of developing fatal interstitial pneumonia without eliminating the risk of recurrent leukemia. We suggest that allogenic marrow grafts should be performed earlier in the course of refractory acute leukemias, because in patients with end stage disease its chances of being curative are small

p38 MAPK Inhibitor Insufficiently Attenuates HSC Senescence Administered Long-Term after 6 Gy Total Body Irradiation in Mice

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Lu Lu

2016-06-01

Full Text Available Senescent hematopoietic stem cells (HSCs accumulate with age and exposure to stress, such as total-body irradiation (TBI, which may cause long-term myelosuppression in the clinic. However, the methods available for long-term myelosuppression remain limited. Previous studies have demonstrated that sustained p38 mitogen-activated protein kinases (p38 MAPK activation in HSCs following exposure to TBI in mice and the administration of its inhibitor twenty-four hours after TBI may partially prevent long-term myelosuppression. However, long-term myelosuppression is latent and identified long after the administration of radiation. In this study, we investigated the effects of SB203580 (a small molecule inhibitor of p38 MAPK on long-term myelosuppression induced by TBI. Mice with hematopoietic injury were injected intraperitoneally with SB203580 every other day five times beginning 70 days after 6 Gy of 137Cs γ ray TBI. Our results at 80 days demonstrated that SB203580 did not significantly improve the TBI-induced long-term reduction of peripheral blood cell and bone marrow nucleated cell (BMNC counts, or defects in hematopoietic progenitor cells (HPCs and HSC clonogenic function. SB203580 reduced reactive oxygen species (ROS production and p-p38 expression; however, SB203580 had no effect on p16 expression in the HSCs of mice. In conclusion, these findings suggest that treatment with SB203580 70 days after TBI in mice inhibits the ROS-p38 oxidative stress pathway; however, it has no therapeutic effect on long-term myelosuppression induced by TBI.

Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

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Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

2011-01-01

Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

Dose-escalated total body irradiation and autologous stem cell transplantation for refractory hematologic malignancy

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McAfee, Steven L.; Powell, Simon N.; Colby, Christine; Spitzer, Thomas R.

2002-01-01

Purpose: To evaluate the feasibility of dose escalation of total body irradiation (TBI) above the previously reported maximally tolerated dose, we have undertaken a Phase I-II trial of dose-escalated TBI with autologous peripheral blood stem cell transplantation (PBSCT) for chemotherapy-refractory lymphoma. Methods and Materials: Nine lymphoma patients with primary refractory disease (PRD) or in resistant relapse (RR) received dose-escalated TBI and PBSCT. The three dose levels of fractionated TBI (200 cGy twice daily) were 1,600 cGy, 1,800 cGy, and 2,000 cGy. Lung blocks were used to reduce the TBI transmission dose by 50%, and the chest wall dose was supplemented to the prescribed dose using electrons. Shielding of the kidneys was performed to keep the maximal renal dose at 1,600 cGy. Three patients, two with non-Hodgkin's lymphoma (NHL) in RR and one with PRD Hodgkin's disease, received 1,600 cGy + PBSCT, three patients (two NHL in RR, one PRD) received 1,800 cGy + PBSCT, and three patients with NHL (two in RR, one PRD) received 2,000 cGy + PBSCT. Results: Toxicities associated with this high-dose TBI regimen included reversible hepatic veno-occlusive disease in 1 patient, Grade 2 mucositis requiring narcotic analgesics in 8 patients, and neurologic toxicities consisting of a symmetrical sensory neuropathy (n=4) and Lhermitte's syndrome (n=1). Interstitial pneumonitis developed in 1 patient who received 1,800 cGy after receiving recombinant α-interferon (with exacerbation after rechallenge with interferon). Six (66%) patients achieved a response. Four (44%) patients achieved complete responses, three of which were of a duration greater than 1 year, and 2 (22%) patients achieved a partial response. One patient remains disease-free more than 5 years posttransplant. Corticosteroid-induced gastritis and postoperative infection resulted in the death of 1 patient in complete response, 429 days posttransplant. Conclusion: TBI in a dose range 1,600-2,000 cGy as

A study on dose attenuation in bone density when TBI using diode detector and TLD

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Im, Hyun Sil; Lee, Jung Jin; Jang, Ahn Ki; KIm, Wan Sun

2003-01-01

Uniform dose distribution of the whole body is essential factor for the total body irradiation(TBI). In order to achieved this goal, we used to compensation filter to compensate body contour irregularity and thickness differences. But we can not compensate components of body, namely lung or bone. The purpose of this study is evaluation of dose attenuation in bone tissue when TBI using diode detectors and TLD system. The object of this study were 5 patients who undergo TBI at our hospital. Dosimetry system were diode detectors and TLD system. Treatment method was bilateral and delivered 10 MV X-ray from linear accelerator. Measurement points were head, neck, pelvis, knees and ankles. TLD used two patients and diode detectors used three patients. Results are as followed. All measured dose value were normalized skin dose. TLD dosimetry : Measured skin dose of head, neck, pelvis, knees and ankles were 92.78±3.3, 104.34±2.3, 98.03±1.4, 99.9±2.53, 98.17±0.56 respectably. Measured mid-depth dose of pelvis, knees and ankles were 86±1.82, 93.24±2.53, 91.50±2.84 respectably. There were 6.67%-11.65% dose attenuation at mid-depth in pelvis, knees and ankles. Diode detector : Measured skin dose of head, neck, pelvis, knees and ankles were 95.23±1.18, 98.33±0.6, 93.5±1.5, 87.3±1.5, 86.90±1.16 respectably. There were 4.53%-12.6% dose attenuation at mid-depth in pelvis, knees and ankles. We concluded that dose measurement with TLD or diode detector was inevitable when TBI treatment. Considered dose attenuation in bone tissue, We must have adequately deduction of compensator thickness that body portion involved bone tissue.

Clinical evaluation of bone marrow transplantation using total body irradiation and induction chemotherapy. Treatment results during twelve years at our hospital and some problems on the therapy

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Kawamura, Toshiki; Koga, Sukehiko; Kikukawa, Kaoru; Okamoto, Masataka; Miyazaki, Hitoshi; Kojima, Hiroshi; Esaki, Kohji

2000-01-01

We performed sixty patients with hematological malignancies the total body irradiation prior to bone marrow transplantation (TBI-BMT) from 1988 to 2000. We delivered our each patient hyperfractionated TBI consisting of 2 fractions of 3 Gy per day for 2 consecutive days following induction chemotherapy. It proved that TBI-BMT was a valuable treatment method for hematological malignancies which have poor prognosis. About the cumulative survival rate, patients of first remission were better outcome than patients beyond second remission. However, the therapy remained some problems which were the prophylaxis of GVHD for HLA-matched unrelated recipients. And we have to consider a new maintenance procedure to prevent relapse from transplanted donor cell. (author)

Cataract after total body irradiation and bone marrow transplantation degree of visual impairment

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Kempen-Harteveld, M. Loes van; Struikmans, Henk; Kal, Henk B.; Tweel, Ingeborg van der; Mourits, Maarten P.; Verdonck, Leo F.; Schipper, Jan; Battermann, Jan J.

2002-01-01

Purpose: To assess the degree of visual impairment as a result of cataract formation after total body irradiation (TBI) for bone marrow transplantation. Methods and Materials: The data from 93 patients who received TBI in 1 or 2 fractions as a part of their conditioning regimen for bone marrow transplantation were analyzed with respect to the degree of visual impairment as a result of cataract formation. The probability to develop severe visual impairment (SVI) was determined for all patients, and the degree of visual impairment was assessed for 56 patients with stabilized cataract, using three categories: no, mild, or severe. Results: For all 93 patients, the probability of developing a cataract causing SVI was 0.44. For allogeneic patients, it was 0.33 without and 0.71 with steroid treatment (p<0.001). All SVI-free probability curves reached a plateau distinct from the cataract-free curves. Apparently, cataracts developing late in the follow-up period rarely cause SVI. Of the patients with stabilized cataract, 32% had no visual impairment, 16% had mild, and 52% severe impairment. No or mild visual impairment was present in 61% of all patients with stable cataract and no steroid treatment compared with only 13% of the patients treated with steroids (p=0.035). Conclusion: SVI occurs in only some of the patients (52%) with stable cataract after TBI for bone marrow transplantation in 1 or 2 fractions. Steroid treatment markedly increases the probability of developing visual problems as result of a cataract after TBI

Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.

Science.gov (United States)

Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O'Connor, Mark J; Yu, Jian; Beumer, Jan H; Bakkenist, Christopher J

2017-02-01

We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21 CIP/WAF1 )-/- mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21 CIP/WAF1 )-/- mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21 CIP/WAF1 )-/-, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21 CIP/WAF1 )-/- mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI.

Enhancement of distribution of dermal multipotent stem cells to bone marrow in rats of total body irradiation by platelet-derived growth factor-AA treatment

International Nuclear Information System (INIS)

Zong Zhaowen; Ren Yongchuan; Shen Yue; Chen Yonghua; Ran Xinze; Shi Chunmeng; Cheng Tianmin

2011-01-01

Objective: To observe whether dermal multipotent stem cells (dMSCs) treated with platelet-derived growth factor-AA (PDGF-AA) could distribute more frequently to the bone marrow in rats of total body irradiation (TBI). Methods: Male dMSCs were isolated and 10 μg/L PDGF-AA was added to the culture medium and further cultured for 2 h. Then the expression of tenascin-C were examined by Western blot, and the migration ability of dMSCs was assessed in transwell chamber. The pre-treated dMSCs were transplanted by tail vein injection into female rats administered with total body irradiation, and 2 weeks after transplantation, real-time PCR was employed to measure the amount of dMSCs in bone marrow. Non-treated dMSCs served as control.Results PDGF-AA treatment increased the expression of tenascin-C in dMSCs, made (1.79 ± 0.13) × 10 5 cells migrate to the lower chamber under the effect of bone marrow extract, and distributed to bone marrow in TBI rats, significantly more than (1.24 ± 0.09) ×10 5 in non-treated dMSCs (t=8.833, P<0.01). Conclusions: PDGF-AA treatment could enhance the migration ability of dMSCs and increase the amount of dMSCs in bone marrow of TBI rats after transplantation. (authors)

SU-E-T-540: Volumetric Modulated Total Body Irradiation Using a Rotational Lazy Susan-Like Immobilization System

International Nuclear Information System (INIS)

Gu, X; Hrycushko, B; Lee, H; Lamphier, R; Jiang, S; Abdulrahman, R; Timmerman, R

2014-01-01

Purpose: Traditional extended SSD total body irradiation (TBI) techniques can be problematic in terms of patient comfort and/or dose uniformity. This work aims to develop a comfortable TBI technique that achieves a uniform dose distribution to the total body while reducing the dose to organs at risk for complications. Methods: To maximize patient comfort, a lazy Susan-like couch top immobilization system which rotates about a pivot point was developed. During CT simulation, a patient is immobilized by a Vac-Lok bag within the body frame. The patient is scanned head-first and then feet-first following 180° rotation of the frame. The two scans are imported into the Pinnacle treatment planning system and concatenated to give a full-body CT dataset. Treatment planning matches multiple isocenter volumetric modulated arc (VMAT) fields of the upper body and multiple isocenter parallel-opposed fields of the lower body. VMAT fields of the torso are optimized to satisfy lung dose constraints while achieving a therapeutic dose to the torso. The multiple isocenter VMAT fields are delivered with an indexed couch, followed by body frame rotation about the pivot point to treat the lower body isocenters. The treatment workflow was simulated with a Rando phantom, and the plan was mapped to a solid water slab phantom for point- and film-dose measurements at multiple locations. Results: The treatment plan of 12Gy over 8 fractions achieved 80.2% coverage of the total body volume within ±10% of the prescription dose. The mean lung dose was 8.1 Gy. All ion chamber measurements were within ±1.7% compared to the calculated point doses. All relative film dosimetry showed at least a 98.0% gamma passing rate using a 3mm/3% passing criteria. Conclusion: The proposed patient comfort-oriented TBI technique provides for a uniform dose distribution within the total body while reducing the dose to the lungs

Morphological study of the effect of cyclophosphamide, dimethylmyleran and whole-body irradiation for the conditioning of dogs to bone marrow transplantation

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Bayer, L.

1980-01-01

Dogs were treated with either cyclophosphamide (CY) or dimethylmyleran (DMM), both cytostatics or with total body irradiation (TBI) in order to find out which agents are most suitable for conditioning for bone marrow (BM) transplantation. The histomorphological changes in various organs (lung, bone marrow, lymphatic tissues, digestive tract, liver, kidney, bladder, heart and gonads) after treatment with different doses are described. (orig./MG) [de

Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology

International Nuclear Information System (INIS)

Flandin, Isabelle; Hartmann, Olivier; Michon, Jean; Pinkerton, Ross; Coze, Carole; Stephan, Jean Louis; Fourquet, Bernard; Valteau-Couanet, Dominique; Bergeron, Christophe; Philip, Thierry; Carrie, Christian

2006-01-01

Purpose: To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma. Patients and Methods: We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n 30) received conditioning without TBI (1985-1992). Analysis 12 years later focused on growth, weight and corpulence (body mass index) delay; hormonal deficiencies; liver, kidney, heart, ear, eye, and dental sequelae; school performance; and the incidence of secondary tumors. Results: Impact of TBI was most marked in relation to growth and weight delay, although the mean delay was not severe, probably because of treatment with growth hormones. Other consequences of TBI were thyroid insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss and dental agenesis were more prominent in the group treated with CT alone. No differences were observed in school performance. Conclusion: The most frequent side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but more worrying is the risk of secondary tumors. Because of the young mean age of patients and the toxicity of TBI regimens without any survival advantage, regimens without TBI are preferable in the management of Stage IV neuroblastoma

Effects of total body irradiation-based conditioning allogenic sem cell transplantation for pediatric acute leukemia: A single-institution study

International Nuclear Information System (INIS)

Park, Jong Moo; Choi, Eun Kyung; Kim, Jong Hoon

2014-01-01

To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

Effects of total body irradiation-based conditioning allogenic sem cell transplantation for pediatric acute leukemia: A single-institution study

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Park, Jong Moo; Choi, Eun Kyung; Kim, Jong Hoon [Dept.of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); and others

2014-09-15

To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (Interleukin Beta, Interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans

International Nuclear Information System (INIS)

Girinsky, T.A.; Pallardy, M.; Comoy, E.; Benassi, T.; Roger, R.; Ganem, G.; Socie, G.; Cossett, J.M.; Magdelenat, H.

1994-01-01

Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamopituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is a common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cyctokines induced by ionizing radiation remain to be determined. 25 refs., 1 fig

Dose rate-dependent marrow toxicity of TBI in dogs and marrow sparing effect at high dose rate by dose fractionation.

Science.gov (United States)

Storb, R; Raff, R F; Graham, T; Appelbaum, F R; Deeg, H J; Schuening, F G; Sale, G; Seidel, K

1999-01-01

We evaluated the marrow toxicity of 200 and 300 cGy total-body irradiation (TBI) delivered at 10 and 60 cGy/min, respectively, in dogs not rescued by marrow transplant. Additionally, we compared toxicities after 300 cGy fractionated TBI (100 cGy fractions) to that after single-dose TBI at 10 and 60 cGy/min. Marrow toxicities were assessed on the basis of peripheral blood cell count changes and mortality from radiation-induced pancytopenia. TBI doses studied were just below the dose at which all dogs die despite optimal support. Specifically, 18 dogs were given single doses of 200 cGy TBI, delivered at either 10 (n=13) or 60 (n=5) cGy/min. Thirty-one dogs received 300 cGy TBI at 10 cGy/min, delivered as either single doses (n=21) or three fractions of 100 cGy each (n=10). Seventeen dogs were given 300 cGy TBI at 60 cGy/min, administered either as single doses (n=5) or three fractions of 100 cGy each (n=10). Within the limitations of the experimental design, three conclusions were drawn: 1) with 200 and 300 cGy single-dose TBI, an increase of dose rate from 10 to 60 cGy/min, respectively, caused significant increases in marrow toxicity; 2) at 60 cGy/min, dose fractionation resulted in a significant decrease in marrow toxicities, whereas such a protective effect was not seen at 10 cGy/min; and 3) with fractionated TBI, no significant differences in marrow toxicity were seen between dogs irradiated at 60 and 10 cGy/min. The reduced effectiveness of TBI when a dose of 300 cGy was divided into three fractions of 100 cGy or when dose rate was reduced from 60 cGy/min to 10 cGy/min was consistent with models of radiation toxicity that allow for repair of sublethal injury in DNA.

Growth impairment after TBI of leukemia survivors children: a model- based investigation.

Science.gov (United States)

Galletto, Chiara; Gliozzi, Antonio; Nucera, Daniele; Bertorello, Nicoletta; Biasin, Eleonora; Corrias, Andrea; Chiabotto, Patrizia; Fagioli, Franca; Guiot, Caterina

2014-10-13

Children receiving Total Body Irradiation (TBI) in preparation for Hematopoietic Stem Cell Transplantation (HSCT) are at risk for Growth Hormone Deficiency (GHD), which sometimes severely compromises their Final Height (FH). To better represent the impact of such therapies on growth we apply a mathematical model, which accounts both for the gompertzian-like growth trend and the hormone-related 'spurts', and evaluate how the parameter values estimated on the children undergoing TBI differ from those of the matched normal population. 25 patients long-term childhood lymphoblastic and myeloid acute leukaemia survivors followed at Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital (Turin, Italy) were retrospectively analysed for assessing the influence of TBI on their longitudinal growth and for validating a new method to estimate the GH therapy effects. Six were treated with GH therapy after a GHD diagnosis. We show that when TBI was performed before puberty overall growth and pubertal duration were significantly impaired, but such growth limitations were completely reverted in the small sample (6 over 25) of children who underwent GH replacement therapies. Since in principle the model could account for any additional growth 'spurt' induced by therapy, it may become a useful 'simulation' tool for paediatricians for comparing the predicted therapy effectiveness depending on its timing and dosage.

Mitigating the Effects of Xuebijing Injection on Hematopoietic Cell Injury Induced by Total Body Irradiation with γ rays by Decreasing Reactive Oxygen Species Levels

Directory of Open Access Journals (Sweden)

Deguan Li

2014-06-01

Full Text Available Hematopoietic injury is the most common side effect of radiotherapy. However, the methods available for the mitigating of radiation injury remain limited. Xuebijing injection (XBJ is a traditional Chinese medicine used to treat sepsis in the clinic. In this study, we investigated the effects of XBJ on the survival rate in mice with hematopoietic injury induced by γ ray ionizing radiation (IR. Mice were intraperitoneally injected with XBJ daily for seven days after total body irradiation (TBI. Our results showed that XBJ (0.4 mL/kg significantly increased 30-day survival rates in mice exposed to 7.5 Gy TBI. This effect may be attributable to improved preservation of white blood cells (WBCs and hematopoietic cells, given that bone marrow (BM cells from XBJ-treated mice produced more granulocyte-macrophage colony forming units (CFU-GM than that in the 2 Gy/TBI group. XBJ also decreased the levels of reactive oxygen species (ROS by increasing glutathione (GSH and superoxide dismutase (SOD levels in serum and attenuated the increased BM cell apoptosis caused by 2 Gy/TBI. In conclusion, these findings suggest that XBJ enhances the survival rate of irradiated mice and attenuates the effects of radiation on hematopoietic injury by decreasing ROS production in BM cells, indicating that XBJ may be a promising therapeutic candidate for reducing hematopoietic radiation injury.

Extreme heterogeneity of myeloablative total body irradiation techniques in clinical practice: a survey of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Science.gov (United States)

Giebel, Sebastian; Miszczyk, Leszek; Slosarek, Krzysztof; Moukhtari, Leila; Ciceri, Fabio; Esteve, Jordi; Gorin, Norbert-Claude; Labopin, Myriam; Nagler, Arnon; Schmid, Christoph; Mohty, Mohamad

2014-09-01

Total body irradiation (TBI) is widely used for conditioning before hematopoietic cell transplantation. Its efficacy and toxicity may depend on many methodological aspects. The goal of the current study was to explore current clinical practice in this field. A questionnaire was sent to all centers collaborating in the European Group for Blood and Marrow Transplantation and included 19 questions regarding various aspects of TBI. A total of 56 centers from 23 countries responded. All centers differed with regard to at least 1 answer. The total maximum dose of TBI used for myeloablative transplantation ranged from 8 grays (Gy) to 14.4 Gy, whereas the dose per fraction was 1.65 Gy to 8 Gy. A total of 16 dose/fractionation modalities were identified. The dose rate ranged from 2.25 centigrays to 37.5 centigrays per minute. The treatment unit was linear accelerator (LINAC) (91%) or cobalt unit (9%). Beams (photons) used for LINAC were reported to range from 6 to 25 megavolts. The most frequent technique used for irradiation was "patient in 1 field," in which 2 fields and 2 patient positions per fraction are used (64%). In 41% of centers, patients were immobilized during TBI. Approximately 93% of centers used in vivo dosimetry with accepted discrepancies between the planned and measured doses of 1.5% to 10%. In 84% of centers, the lungs were shielded during irradiation. The maximum accepted dose for the lungs was 6 Gy to 14.4 Gy. TBI is an extremely heterogeneous treatment modality. The findings of the current study should warrant caution in the interpretation of clinical studies involving TBI. Further investigation is needed to evaluate how methodological differences influence outcome. Efforts to standardize the method should be considered. © 2014 American Cancer Society.

One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation

International Nuclear Information System (INIS)

Thomas, E.D.; Buckner, C.D.; Banaji, M.

1977-01-01

One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3 to 17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted rejected and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1--4 1 / 2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA-matched sibling marrow donor

The indication and the point at issue in total body irradiation (TBI)

International Nuclear Information System (INIS)

Kikuchi, Yuzo; Nishino, Shigeo.

1992-01-01

The role of radiation in the cause of interstitial pneumonitis (IP) was analysed here. Also optimal dose fractionation was discussed about total absorbed lung dose, dose rate and fractionation in spect of IP. After all optimal time schedule was recommended 3, 4 and 6 fraction of ≤ 4 Gy of fraction size using conventional and hyperfractionated irradiation. In the end the present condition and the point at issue in the irradiation of blood for prevention GVHD were discussed. (author)

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 10: Results from Canada Wide Survey on Total Body Irradiation Practice

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Studinski, Ryan; Fraser, Danielle; Samant, Rajiv; MacPherson, Miller [The Ottawa Hospital Cancer Centre, The Ottawa Hospital Cancer Centre, The Ottawa Hospital Cancer Centre, The Ottawa Hospital Cancer Centre (Canada)

2016-08-15

Purpose: Total Body Irradiation (TBI) is delivered to a relatively small number of patients with a variety of techniques; it has been a challenge to develop consensus studies for best practice. This survey was created to assess the current state of TBI in Canada. Methods: The survey was created with questions focusing on the radiation prescription, delivery technique and resources involved. The survey was circulated electronically to the heads of every clinical medical physics department in Canada. Responses were gathered and collated, and centres that were known to deliver TBI were urged to respond. Results: Responses from 20 centres were received, including 12 from centres that perform TBI. Although a variety of TBI dose prescriptions were reported, 12 Gy in 6 fractions was used in 11 centres while 5 centres use unique prescriptions. For dose rate, a range of 9 to 51 cGy/min was reported. Most centres use an extended SSD technique, with the patient standing or lying down against a wall. The rest use either a “sweeping” technique or a more complicated multi-field technique. All centres but one indicated that they shield the lungs, and only a minority shield other organs. The survey also showed that considerable resources are used for TBI including extra staffing, extended planning and treatment times and the use of locally developed hardware or software. Conclusions: This survey highlights that both similarities and important discrepancies exist between TBI techniques across the country, and is an opportunity to prompt more collaboration between centres.

Design and characteristics of a 4 MV total body irradiator

International Nuclear Information System (INIS)

Lutz, W.R.; Chin, L.M.

1988-01-01

A facility for total body X-ray irradiation (TBI) has been built using two 4 MV linear accelerators, one mounted under the ceiling, the other in a floor-pit. The distance between the two sources is 410 cm to produce a field size of 200 cm x 75 cm in the midplane. This field covers the patient, lying supine on a stretcher halfway between the sources. Components from commercially available accelerators were used. Special beam hardening and flattening filters were built to achieve acceptable dose profiles in the large field. The primary collimator was modified to produce a 235 cm x 92 cm field at 205 cm from the source, while movable focused collimators were designed to define fields up to 220 cm x 80 cm. Because of the wide beams, large rectangular parallel-plate ionization chambers were built to serve as beam monitors. The dose rate at 205 cm distance from the sources can be set between 5 and 80 cGy/min, each machine contributing half. The dosimetric characteristics are practically the same for both units. The per cent depth dose for the TBI beams is 76% at a source-surface distance of 195 cm. The half value layer decreases by 12% from the centre to near the edge of the beam. Owing to the large field size, the surface dose for the TBI beams is about 80% of the dose at 1 cm depth. The dose delivery has been verified to be within 2% of the calculated value at the reference point in a homogeneous water humanoid phantom. Measurements indicate that lung doses can be predicted by the ratio-of-TMR (tissue-to-maximum ratio) method with acceptable accuracy. Lead sheets are used as attenuators to prevent excessive lung doses. (author). 7 refs, 7 figs

Autologous stem cell transplantation following high-dose whole-body irradiation of dogs - influence of cell number and fractionation regimes

International Nuclear Information System (INIS)

Bodenberger, U.

1981-01-01

The acute radiation syndrome after a single dose of 1600 R (approx. 12-14 Gy in body midline) and after fractionated irradiation with 2400 R (approx. 18-20 Gy) was studied with regard to fractionation time and to the number of bone marrow cells infused. The acute radiation syndrome consisted of damage to the alimentary tract and of damage to the hemopoietic system. Damage of hemopoiesis was reversible in dogs which had been given a sufficient amount of hemopoietic cells. Furthermore changes in skin and in the mucous membranes occurred. Hemopoietic recovery following infusion of various amounts of bone marrow was investigated in dogs which were irradiated with 2400 R within 7 days. Repopulation of bone marrow as well as rise of leukocyte and platelet counts in the peripheral blood was taken as evidence of complete hemopoietic reconstitution. The results indicate that the acute radiation syndrom following 2400 R TBI and autologous BMT can be controlled by fractionation of this dose within 5 or 7 days. The acute gastrointestinal syndrome is aggravated by infusion of a lesser amount of hemopoietic cells. However, TBI with 2400 R does not require greater numbers of hemopoietic cells for restoration of hemopoiesis. Thus, the hemopoiesis supporting tissue can not be damage by this radiation dose to an essential degree. Longterm observations have not revealed serious late defects which could represent a contraindication to the treatment of malignent diseases with 2400 R of TBI. (orig./MG) [de

Serum immunoglobulin levels in humans exposed to therapeutic total-body gamma irradiation

International Nuclear Information System (INIS)

Chaskes, S.; Kingdon, G.C.; Balish, E.

1975-01-01

Reduced serum immunoglobulin (IgA, IgG, IgM) levels developed in the majority of 27 patients with hematologic disorders after treatment with 100 to 350 R total-body gamma-ray exposures at a dose rate of either 1.5 R/min to 1.5 R/hr. A reduction in IgA of 20 percent or more was found in 66 percent of the cases, while 56 percent showed an IgM decrease, and 49 percent an IgG decrease of 20 percent. The severity of immunoglobulin depression was influenced by the total radiation dose and the patient's primary disease. The occurrence of IgG and IgM depression was greater when the radiation was given at 1.5 R/hr than when the dose rate was 1.5 R/min. Substantial but incomplete recovery toward preirradiation immunoglobulin levels was found for most patients by 7 wk after total-body irradiation (TBI). (U.S.)

Lung damage following bone marrow transplantation after hyperfractionated total body irradiation

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Latini, Paolo; Aristei, Cynthia; Checcaglini, Franco; Maranzano, Ernesto; Panizza, B.M.; Perrucci, Elisabetta (University and Hospital, Policlinico, Perugia (Italy). Radiation Oncology Service); Aversa, Franco; Martelli, M.F. (University and Hospital, Policlinico, Perugia (Italy). Department of Haematology); Raymondi, Carlo (University and Hospital, Policlinico, Perugia (Italy). Radiation Physics Service)

1991-10-01

From July 1985 to December 1989, 72 evaluable patients aged 6-51 (median age 27) suffering from hematological malignancies received allo-geneic bone marrow transplant (BMT) depleted of T-lymphocytes to reduce risks of graft-versus-host-disease (GvHD); 57 were matched and 15 mis-matched. Three different conditioning regiments were used in an effort to enhance cytoreduction without increase extramedullary toxicity. Mis-matched patients were treated with more immunosuppressive regimens. Total body irradiation (TBI) was given in 3 doses/day, 5 h apart over 4 days for a total of 12 fractions. The dose to the lungs was 14.4, 15.6 and 9 Gy according to the conditioning regimen. The incidence of inter-stitial pneumonia (IP) was 12.3 percent in matched and 46.7 in mis-matched patients. The results seem to indicate that lung toxicity is correlated with the intensity of the conditioning regimen, the stage of disease and, in mismatched patients, with the degree of human leucocyte antigen (HLA) disparity and the poor post-BMT reconstitution, rather than the radiotherapy dose delivered to the lungs. On the contrary, the hyperfractionated scheme adopted, the absence of GvHD and, perhaps, the post-TBI administration of cyclophosphamide all seem to have contributed to the low incidence of IP in the matched patients. (author). 30 refs.; 5 figs.; 1 tab.

Lung damage following bone marrow transplantation after hyperfractionated total body irradiation

International Nuclear Information System (INIS)

Latini, Paolo; Aristei, Cynthia; Checcaglini, Franco; Maranzano, Ernesto; Panizza, B.M.; Perrucci, Elisabetta; Aversa, Franco; Martelli, M.F.; Raymondi, Carlo

1991-01-01

From July 1985 to December 1989, 72 evaluable patients aged 6-51 (median age 27) suffering from hematological malignancies received allo-geneic bone marrow transplant (BMT) depleted of T-lymphocytes to reduce risks of graft-versus-host-disease (GvHD); 57 were matched and 15 mis-matched. Three different conditioning regiments were used in an effort to enhance cytoreduction without increase extramedullary toxicity. Mis-matched patients were treated with more immunosuppressive regimens. Total body irradiation (TBI) was given in 3 doses/day, 5 h apart over 4 days for a total of 12 fractions. The dose to the lungs was 14.4, 15.6 and 9 Gy according to the conditioning regimen. The incidence of inter-stitial pneumonia (IP) was 12.3 percent in matched and 46.7 in mis-matched patients. The results seem to indicate that lung toxicity is correlated with the intensity of the conditioning regimen, the stage of disease and, in mismatched patients, with the degree of human leucocyte antigen (HLA) disparity and the poor post-BMT reconstitution, rather than the radiotherapy dose delivered to the lungs. On the contrary, the hyperfractionated scheme adopted, the absence of GvHD and, perhaps, the post-TBI administration of cyclophosphamide all seem to have contributed to the low incidence of IP in the matched patients. (author). 30 refs.; 5 figs.; 1 tab

The effects of gut commensal bacteria depletion on mice exposed to acute lethal irradiation

International Nuclear Information System (INIS)

Hou Bing; Xu Zhiwei; Zhang Chenggang

2007-01-01

The prevention and management of bacterial infection are the mainstays of therapies for irradiation victims. However, worries about adverse effects arise from gut commensal flora depletion owing to the broad-spectrum antibiotics treatment. In the present study, we investigated the effects of gut bacteria depletion on the mice receiving total-body irradiation (TBI) at a single dose of 12 Gy. One group of mice was merely exposed to TBI but was free of antibiotic treatment throughout the experiment, while the other two groups of mice were additionally given broad-spectrum antibiotics, either from 2 weeks before or immediately after irradiation. The survival time of each animal in each group was recorded for analysis. Results showed that the mean survival time of mice was longest in the group without antibiotic treatment and shortest in the group treated with broad-spectrum antibiotics from 2 weeks before TBI. In conclusion, our data suggested that depletion of gut commensal bacteria with broad-spectrum antibiotics seemed deleterious for mammals receiving lethal TBI. (author)

Differential effect of L3T4+ cells on recovery from total-body irradiation

International Nuclear Information System (INIS)

Pantel, K.; Nakeff, A.

1990-01-01

We have examined the importance of L3T4+ (murine equivalent to CD4+) cells for hematopoietic regulation in vivo in unperturbed mice and mice recovering from total-body irradiation (TBI) using a cytotoxic monoclonal antibody (MoAb) raised with the GK 1.5 hybridoma. Ablating L3T4+ cells in normal (unperturbed) B6D2F1 mice substantially decreased the S-phase fraction (determined by in vivo hydroxyurea suicide) of erythroid progenitor cells (erythroid colony-forming units, CFU-E) as compared to the pretreatment level (10% +/- 14.1% [day 3 following depletion] vs 79.8% +/- 15.9%, respectively) with a corresponding decrease in the marrow content of CFU-E at this time to approximately 1% of the pretreatment value. Although the S-phase fraction of CFU-GM was decreased to 2.2% +/- 3.1% 3 days after L3T4+ cell ablation from the 21.3% +/- 8.3% pretreatment value, CFU-GM cellularity showed little change over the 3 days following anti-L3T4 treatment. Anti-L3T4 MoAb treatment had little or no effect on either the S-phase fraction or the marrow content of hematopoietic stem cells (spleen colony-forming units, CFU-S) committed to myeloerythroid differentiation. Ablating L3T4+ cells prior to a single dose of 2 Gy TBI resulted in significantly reduced marrow contents of CFU-S on day 3 and granulocyte-macrophage colony-forming units (CFU-GM) on day 6 following TBI, with little or no effect on the corresponding recovery of CFU-E. The present findings provide the first in vivo evidence that L3T4+ cells are involved in: (1) maintaining the proliferative activity of CFU-E and CFU-GM in unperturbed mice and (2) supporting the restoration of CFU-S and CFU-GM following TBI-induced myelosuppression

In pediatric leukemia, dose evaluation according to the type of compensators in total body irradiation

Energy Technology Data Exchange (ETDEWEB)

Lee, Dong Yeon [Dongnam Inst. of Radiological and Medical science, Busan (Korea, Republic of); Kim, Chang Soo; Kim, Jung Hoon [Dept. of Radiological Science, College of Health Science, Catholic University of Busan, Busan (Korea, Republic of)

2015-04-15

Total body irradiation (TBI) and chemotherapy are the pre-treatment method of a stem cell transplantations of the childhood leukemia. in this study, we evaluate the Quantitative human body dose prior to the treatment. The MCNPX simulation program evaluated by changing the material of the tissue compensators with imitation material of pediatric exposure in a virtual space. As a result, first, the average skin dose with the material of the tissue compensators of Plexiglass tissue compensators is 74.60 mGy/min, Al is 73.96 mGy/min, Cu is 72.26 mGy/min and Pb 67.90 mGy/min respectively. Second, regardless of the tissue compensators material that organ dose were thyroid, gentile, digestive system, brain, lungs, kidneys higher in order. Finally, the ideal distance between body compensator and the patient were 50 cm aparting each other. In conclusion, tissue compensators Al, Cu, Pb are able to replace of the currently used in Plexiglass materials.

Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice

International Nuclear Information System (INIS)

Wang, Bing; Tanaka, Kaoru; Ji, Bin

2014-01-01

The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with 11 C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice. (author)

Results of Hematopoietic Stem Cell Transplantation After Treatment With Different High-Dose Total-Body Irradiation Regimens in Five Dutch Centers

International Nuclear Information System (INIS)

Loes van Kempen-Harteveld, M.; Brand, Ronald; Kal, Henk B.; Verdonck, Leo F.; Hofman, Pieter; Schattenberg, Anton V.; Maazen, Richard W. van der; Cornelissen, Jan J.; Eijkenboom, Wil M.H.; Lelie, Johannes P. van der; Oldenburger, Foppe; Barge, Renee M.; Biezen, Anja van; Vossen, Jaak M.J.J.; Noordijk, Evert M.; Struikmans, Henk

2008-01-01

Purpose: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. Methods and Materials: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia and non-Hodgkin's lymphoma. The TBI regimens were normalized by using the biological effective dose (BED) concept. The BED values were divided into three dose groups. Study end points were relapse incidence (RI), non-relapse mortality (NRM), relapse-free survival (RFS), and overall survival (OS). Multivariate analysis was performed, stratified by disease. Results: In the highest TBI dose group, RI was significantly lower and NRM was higher vs. the lower dose groups. However, a significant influence on RFS and OS was not found. Relapses in the eye region were found only after shielding to very low doses. Age was of significant influence on OS, RFS, and NRM in favor of younger patients. The NRM of patients older than 40 years significantly increased, and OS decreased. There was no influence of age on RI. Men had better OS and RFS and lower NRM. Type of transplantation significantly influenced RI and NRM for patients with acute leukemia and non-Hodgkin's lymphoma. There was no influence on RFS and OS. Conclusions: Both RI and NRM were significantly influenced by the size of the BED of single-dose or two-fraction TBI regimens; OS and RFS were not. Age was of highly significant influence on NRM, but there was no influence of age on RI. Hyperfractionated TBI with a high BED might be useful, assuming NRM can be reduced

The effect of total body irradiation dose and chronic graft-versus-host disease on leukaemic relapse after allogeneic bone marrow transplantation

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Frassoni, F; Bacigalupo, A [Ospedale San Martino (Italy). Centro Trapianti Midollo Osseo; Scarpati, D [Univ. di Genova (Italy). Ist. di Radiologia; and others

1989-10-01

One-hundred and five patients undergoing allo-geneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) (n=61) and chronic myeloid leukaemia (n=44) were analysed for risk factors associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 330 cGy on each of the three days prior to transplantation. A multivariate Cox analysis indicated that a lower TBI dose (less than 990 cGy) was the most significant factor associated with relapse and the second most important factor associated with recurrence of leukaemia was the absence of chronic graft-versus-host-disease (cGvHD). Actuarial relapse incidence was 62%, 28% and 18% for patients with no, limited or extensive chronic GvHD respectively. However, chronic GvHD had no significant impact on survival. Combined stratification for TBI dose and cGvHD showed that the dose effect of TBI on relapse was evident both in patients with and without cGvHD. Chronic GvHD influenced the risk of relapse only in patients receiving less than 990 cGy. These results suggest that a higher dose of TBI, within this schedule, produced long-term disease-free survival in the majority of AMLs and CMLs. Minor radiobiological side effects were experienced, but a small reduction of the dose may significantly increase the risk of relapse. (author).

The effect of total body irradiation dose and chronic graft-versus-host disease on leukaemic relapse after allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Frassoni, F.; Bacigalupo, A.; Scarpati, D.

1989-01-01

One-hundred and five patients undergoing allo-geneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) (n=61) and chronic myeloid leukaemia (n=44) were analysed for risk factors associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 330 cGy on each of the three days prior to transplantation. A multivariate Cox analysis indicated that a lower TBI dose (less than 990 cGy) was the most significant factor associated with relapse and the second most important factor associated with recurrence of leukaemia was the absence of chronic graft-versus-host-disease (cGvHD). Actuarial relapse incidence was 62%, 28% and 18% for patients with no, limited or extensive chronic GvHD respectively. However, chronic GvHD had no significant impact on survival. Combined stratification for TBI dose and cGvHD showed that the dose effect of TBI on relapse was evident both in patients with and without cGvHD. Chronic GvHD influenced the risk of relapse only in patients receiving less than 990 cGy. These results suggest that a higher dose of TBI, within this schedule, produced long-term disease-free survival in the majority of AMLs and CMLs. Minor radiobiological side effects were experienced, but a small reduction of the dose may significantly increase the risk of relapse. (author)

In vivo dosimetry study of semi-conductors EPD-20 in total body irradiation technique; Etude de la dosimetrie in vivo par semi-conducteurs EPD-20 dans les conditions de l'irradiation corporelle totale

Energy Technology Data Exchange (ETDEWEB)

Besbes, M.; Kochbati, L.; Ben Abdennabi, A.; Abdessaied, S.; Salem, L.; Frikha, H.; Nasr Ben Ammar, C.; Hentati, D.; Gargouri, W.; Messai, T.; Benna, F.; Maalej, M. [Institut Salah-Azaiz, Service de radiotherapie oncologique, Tunis (Tunisia); Mahjoubi, H. [Institut superieur des technologies medicales de Tunis, Dept. de biophysique, Tunis (Tunisia); Farhat, L. [CHU Habib-Bourguiba, Service de radiotherapie oncologique, Sfax (Tunisia)

2010-01-15

Purpose: The objective of this work was the study of in vivo dosimetry performed in a series of 54 patients receiving total body irradiation (T.B.I.) at the Salah-Azaiz Institute of Tunis since 2004. In vivo dosimetry measurements were compared to analytically calculated doses from monitor units delivered. Patients and method: The irradiation was conducted by a linear accelerator (Clinac 1800, Varian, Palo Alto, USA) using nominal X-rays energies of 6 MV and 18 MV, depending on the thickness of the patient at the abdomen. The dose was measured by semi-conductors p-type E.P.D.-20. These diodes were calibrated in advance with an ionization chamber 'P.T.W. Farmer' type of 0.6 cm{sup 3} and were placed on the surface of plexiglas phantom in the same T.B.I. conditions. A study of dosimetric characteristics of semi-conductors E.P.D.-20 was carried out as a function of beam direction and temperature. Afterwards, we conducted a comparative analysis of doses measured using these detectors during irradiation to those calculated retrospectively from monitor units delivered to each patient conditioned by T.B.I.. Results: Experience showed that semi-conductors are sensitive to the angle of beam radiation (0-90 degrees) and the temperature (22-40 Celsius degrees). The maximum variation is respectively 5 and 7%, but in our irradiation conditions these correction factors are less than 1%. The analysis of the results of the in vivo dosimetry had shown that the ratio of the average measured doses and analytically calculated doses at the abdomen, mediastinum, right lung and head are 1.005, 1.007, 1.0135 and 1.008 with a standard deviation 'type A' respectively of 3.04, 2.37, 7.09 et 4.15%. Conclusion: In vivo dosimetry by semi-conductors is in perfect agreement with dosimetry by calculation. However, in vivo dosimetry using semiconductors is the only technique that can reflect the dose actually received instantly by the patient during T.B.I. given the many factors

Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

International Nuclear Information System (INIS)

Fermand, J.P.; Levy, Y.; Gerota, J.; Benbunan, M.; Cosset, J.M.; Castaigne, S.; Seligmann, M.; Brouet, J.C.

1989-01-01

Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma

TU-CD-304-04: Scanning Field Total Body Irradiation Using Dynamic Arc with Variable Dose Rate and Gantry Speed

Energy Technology Data Exchange (ETDEWEB)

Yi, B; Xu, H; Mutaf, Y; Prado, K [Univ. of Maryland School Of Medicine, Baltimore, MD (United States)

2015-06-15

Purpose: Enable a scanning field total body irradiation (TBI) technique, using dynamic arcs, which is biologically equivalent to a moving couch TBI. Methods: Patient is treated slightly above the floor and the treatment field scans across the patient by a moving gantry. MLC positions change during gantry motion to keep same field opening at the level of the treatment plane (170 cm). This is done to mimic the same geometry as the moving couch TBI technique which has been used in our institution for over 10 years. The dose rate and the gantry speed are determined considering a constant speed of the moving field, variations in SSD and slanted depths resulting from oblique gantry angles. An Eclipse (Varian) planning system is commissioned to accommodate the extended SSD. The dosimetric foundations of the technique have been thoroughly investigated using phantom measurements. Results: Dose uniformity better than 2% across 180 cm length at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Treatment range can be extended by increasing gantry range. No device such as a gravity-oriented compensator is needed to achieve a uniform dose. It is feasible to modify the dose distribution by adjusting the dose rate at each gantry angle to compensate for body thickness differences. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 100 MU/min. Conclusion: This novel yet transportable moving field technique enables TBI treatment in a small treatment room with less program development preparation than other techniques. Treatment length can be extended per need, and. MLC-based thickness compensation and partial lung blocking are also possible.

The influence of x-ray energy on lung dose uniformity in total-body irradiation

International Nuclear Information System (INIS)

Ekstrand, Kenneth; Greven, Kathryn; Wu Qingrong

1997-01-01

Purpose: In this study we examine the influence of x-ray energy on the uniformity of the dose within the lung in total-body irradiation treatments in which partial transmission blocks are used to control the lung dose. Methods and Materials: A solid water phantom with a cork insert to simulate a lung was irradiated by x-rays with energies of either 6, 10, or 18 MV. The source to phantom distance was 3.9 meters. The cork insert was either 10 cm wide or 6 cm wide. Partial transmission blocks with transmission factors of 50% were placed anterior to the cork insert. The blocks were either 8 or 4 cm in width. Kodak XV-2 film was placed in the midline of the phantom to record the dose. Midplane dose profiles were measured with a densitometer. Results: For the 10 cm wide cork insert the uniformity of the dose over 80% of the block width varied from 6.6% for the 6 MV x-rays to 12.2% for the 18 MV x-rays. For the 6 cm wide cork insert the uniformity was comparable for all three x-ray energies, but for 18 MV the central dose increased by 9.4% compared to the 10 cm wide insert. Conclusion: Many factors must be considered in optimizing the dose for total-body irradiation. This study suggests that for AP/PA techniques lung dose uniformity is superior with 6 MV irradiation. The blanket recommendation that the highest x-ray energy be used in TBI is not valid for all situations

Total body irradiation: current indications; L`irradiation corporelle totale: les indications actuelles

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Giraud, P.; Danhier, S.; Dubray, B.; Cosset, J.M. [Institut Curie, 75 - Paris (France)

1998-05-01

The choice of dose and fractionation for total body irradiation is made difficult by the large number of considerations to be taken into account. The outcome of bone marrow transplantation after total body irradiation can be understood in terms of tumor cell killing, engraftment, and normal tissue damage, each of these endpoints being influenced by irradiation-, disease-, transplant-, and patient- related factors. Interpretation of clinical data is further hampered by the overwhelming influence of logistic constraints, the small numbers of randomized studies, and the concomitant variations in total dose and fraction size or dose rate. So far, three cautious conclusions can be drawn in order to tentatively adapt the total body irradiation schedule to clinically-relevant situations. Firstly, the organs at risk for normal tissue damage (lung, liver, lens, kidney) are protected by delivering small doses per fraction at low dose rate. This suggests that, when toxicity is at stake (e.g. in children), fractionated irradiation should be preferred, provided that inter-fraction intervals are long enough. Secondly, fractionated irradiation should be avoided in case of T-cell depleted transplant, given the high risk of graft rejection in this setting. An alternative would be to increase total (or fractional) dose of fractionated total body irradiation, but this approach is likely to induce more normal tissue toxicity. Thirdly, clinical data have shown higher relapse rates in chronic myeloid leukemia after fractionated or low dose rate total body irradiation, suggesting that fractionated irradiation should not be recommended, unless total (or fractional) dose is increased. Total body irradiation-containing regimens, primarily cyclophosphamide / total body irradiation, are either equivalent to or better than the chemotherapy-only regimens, primarily busulfan / cyclophosphamide. Busulfan / cyclophosphamide certainly represents a reasonable alternative, especially in patients who

Effect of Black Grape Juice against Heart Damage from Acute Gamma TBI in Rats

Directory of Open Access Journals (Sweden)

Edson Ramos de Andrade

2013-09-01

Full Text Available The aim of this study was to evaluate the potential positive effect of black grape juice (BGJ on lipid peroxidation considering Total Body Irradiation (TBI in Wistar rats. As a potential feasible means of evaluation in situ, blood serum lactate dehydrogenase (LDH levels were evaluated as a marker for heart damage from acute radiation syndrome (ARS. Twenty rats were divided into four groups, two of them being irradiated by gamma-rays from a Co-60 source. Animals were treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4 days after 6 Gy whole body gamma-irradiation, when they were euthanasiated. LDH on serum and lipid peroxidation on heart tissue were evaluated. High concentration of metabolites from lipid peroxidation in heart, and high LDH level on serum were found only in gamma-irradiated group given placebo, mainly at the first 24 h after radiation. Phytochemical analysis of BGJ was performed by determining total phenolics, flavonoids, and tannins followed by a high-performance liquid chromatography (HPLC/DAD analysis, which showed resveratrol as the major constituent. Results suggest that BGJ is a good protective candidate compound against heart damage from ARS and its effects suggest its use as a radiomodifier.

Secondary radiation dose during high-energy total body irradiation

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Janiszewska, M.; Raczkowski, M. [Lower Silesian Oncology Center, Medical Physics Department, Wroclaw (Poland); Polaczek-Grelik, K. [University of Silesia, Medical Physics Department, Katowice (Poland); Szafron, B.; Konefal, A.; Zipper, W. [University of Silesia, Department of Nuclear Physics and Its Applications, Katowice (Poland)

2014-05-15

The goal of this work was to assess the additional dose from secondary neutrons and γ-rays generated during total body irradiation (TBI) using a medical linac X-ray beam. Nuclear reactions that occur in the accelerator construction during emission of high-energy beams in teleradiotherapy are the source of secondary radiation. Induced activity is dependent on the half-lives of the generated radionuclides, whereas neutron flux accompanies the treatment process only. The TBI procedure using a 18 MV beam (Clinac 2100) was considered. Lateral and anterior-posterior/posterior-anterior fractions were investigated during delivery of 2 Gy of therapeutic dose. Neutron and photon flux densities were measured using neutron activation analysis (NAA) and semiconductor spectrometry. The secondary dose was estimated applying the fluence-to-dose conversion coefficients. The main contribution to the secondary dose is associated with fast neutrons. The main sources of γ-radiation are the following: {sup 56}Mn in the stainless steel and {sup 187}W of the collimation system as well as positron emitters, activated via (n,γ) and (γ,n) processes, respectively. In addition to 12 Gy of therapeutic dose, the patient could receive 57.43 mSv in the studied conditions, including 4.63 μSv from activated radionuclides. Neutron dose is mainly influenced by the time of beam emission. However, it is moderated by long source-surface distances (SSD) and application of plexiglass plates covering the patient body during treatment. Secondary radiation gives the whole body a dose, which should be taken into consideration especially when one fraction of irradiation does not cover the whole body at once. (orig.) [German] Die zusaetzliche Dosis durch sekundaere Neutronen- und γ-Strahlung waehrend der Ganzkoerperbestrahlung mit Roentgenstrahlung aus medizinischen Linearbeschleunigern wurde abgeschaetzt. Bei der Emission hochenergetischer Strahlen zur Teletherapie finden hauptsaechlich im Beschleuniger

TBI-ROC Part Nine: Diagnosing TBI and Psychiatric Disorders

Science.gov (United States)

Elias, Eileen; Weider, Katie; Mustafa, Ruman

2011-01-01

This article is the ninth of a multi-part series on traumatic brain injury (TBI). It focuses on the process of diagnosing TBI and psychiatric disorders. Diagnosing traumatic brain injury can be challenging. It can be difficult differentiating TBI and psychiatric symptoms, as both have similar symptoms (e.g., memory problems, emotional outbursts,…

Cataract incidence after total-body irradiation

International Nuclear Information System (INIS)

Zierhut, D.; Lohr, F.; Schraube, P.; Huber, P.; Haas, R.; Hunstein, W.; Wannenmacher, M.

1997-01-01

Purpose: Aim of this retrospective study was to evaluate cataract incidence in a homogeneous group of patients after total-body irradiation followed by autologous bone marrow transplantation or peripheral blood stem cell transplantation. Method and Materials: Between 11/1982 and 6/1994 in total 260 patients received in our hospital total-body irradiation for treatment of haematological malignancy. In 1996-96 patients out of these 260 patients were still alive. 85 from these still living patients (52 men, 33 women) answered evaluable on a questionnaire and could be examined ophthalmologically. Median age of these patients was 38,5 years (15 - 59 years) at time of total-body irradiation. Radiotherapy was applied as hyperfractionated total-body irradiation with a median dose of 14,4 Gy in 12 fractions over 4 days. Minimum time between fractions was 4 hours, photons with a energy of 23 MeV were used, and the dose rate was 7 - 18 cGy/min. Results: Median follow-up is now 5,8 years (1,7 - 13 years). Cataract occurred in (28(85)) patients after a median time of 47 months (1 - 104 months). In 6 out of these 28 patients who developed a cataract, surgery of the cataract was performed. Whole-brain irradiation prior to total-body irradiation was more often in the group of patients developing a cataract (14,3%) vs. 10,7% in the group of patients without cataract. Conclusion: Cataract is a common side effect of total-body irradiation. Cataract incidence found in our patients is comparable to results of other centres using a fractionated regimen for total-body irradiation. The hyperfractionated regimen used in our hospital does obviously not result in a even lower cataract incidence. In contrast to acute and late toxicity in other organ/organsystems, hyperfractionation of total-body irradiation does not further reduce toxicity for the eye-lens. Dose rate may have more influence on cataract incidence

Radiological protection in a patient during a total body irradiation procedure; Proteccion radiologica en un paciente durante un procedimiento de TBI (irradiacion de cuerpo entero)

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Hernandez O, J. O.; Hinojosa G, J.; Gomez M, E.; Balam de la Vega, J. A. [The American British Cowdray Medical Center, I. A. P., Sur 128 No. 143, Col. Americas, 01120 Mexico D. F. (Mexico); Deheza V, J. C., E-mail: johernandezo@abchospital.co [IPN, Escuela Superior de Fisica y Matematicas, Av. Luis Enrique Erro s/n, Edificio No. 9, Unidad Profesional Adolfo Lopez Mateos, Col. Lindavista, 07738 Mexico D. F. (Mexico)

2010-09-15

A technique used in the Service of Radiotherapy of the Cancer Center of the American British Cowdray Medical Center (ABC) for the bone marrow transplantation, is the total body irradiation. It is known that the dose calculation, for this irradiation type, is old, since the dosimetric calculation is carried out by hand and they exist infinity of techniques for the patients irradiation and different forms of protecting organs of risk, as well as a great uncertainty in the given dose. In the Cancer Center of the ABC Medical Center, was carried out an irradiation procedure to total body with the following methodology: Computerized tomography of the patient total body (two vacuum mattresses in the following positions: dorsal and lateral decubitus), where is combined the two treatment techniques anterior-posterior and bilateral, skin delineate and reference volumes, dose calculation with the planning system Xi O of CMS, dose determination using an ionization chamber and a lung phantom IMRT Thorax Phantom of the mark CIRS and dosimetry in vivo. In this work is presented the used treatment technique, the results, statistics and the actualization of the patient clinical state. (Author)

SU-E-T-485: In Vivo Dosimetry with EBT3 Radiochromic Films for TBI Treatments

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Lozares, S; Gracia, M; Olasolo, J; Gallardo, N; Fuentemilla, N; Pellejero, S; Miquelez, S; Maneru, F; Martin, M; Bragado, L; Rubio, A [Complejo Hospitalario de Navarra, Pamplona, Navarra (Spain)

2015-06-15

Purpose: Total body irradiation (TBI) is a technique that requires special equipment to control “in vivo” the dose to the patient because it is a complex technique performed in extraordinary conditions. There are several devices to perform this task (diodes, TLDs, ionization chambers, MOSFET). In this paper we study the possibility of performing these measurements with radiochromic films EBT3 properly calibrated. This method has been compared to the PTW diodes system for TBI. Methods: Once made the TC to the patients, we measured different thicknesses of the relevant areas of the body (head, neck, chest with or without arms, umbilicus area, knees and ankles); for each of these thicknesses we measured dose rate (cGy / UM) in RW3 phantom, in TBI conditions, with ionization chamber in the center; in turn, the input diode and the output of each configuration is placed to assign dose to each set of diodes. Movie calibration is performed according to manufacturer’s recommendations but TBI conditions. The dose at the center of each thickness compared to a linear interpolation of the dose at the entrance and exit, resulting in an adequate approximation. Finally in each session for each patient put a piece of film (2×2 cm2) at the entrance and another at the exit in each area, obtaining these readings and interpolating the estimated center dose, as with the diodes. Results: These results show a greater homogeneity in the distribution for use with film and validate the use of the same for this task and, if necessary, to avoid purchasing diode group if they have not. Conclusion: By using radiochromic films for this technique gives us a proper calculation of the dose received by the patient in the absence of other methods, or gives us a second additional track that already used normally.

SU-E-T-485: In Vivo Dosimetry with EBT3 Radiochromic Films for TBI Treatments

International Nuclear Information System (INIS)

Lozares, S; Gracia, M; Olasolo, J; Gallardo, N; Fuentemilla, N; Pellejero, S; Miquelez, S; Maneru, F; Martin, M; Bragado, L; Rubio, A

2015-01-01

Purpose: Total body irradiation (TBI) is a technique that requires special equipment to control “in vivo” the dose to the patient because it is a complex technique performed in extraordinary conditions. There are several devices to perform this task (diodes, TLDs, ionization chambers, MOSFET). In this paper we study the possibility of performing these measurements with radiochromic films EBT3 properly calibrated. This method has been compared to the PTW diodes system for TBI. Methods: Once made the TC to the patients, we measured different thicknesses of the relevant areas of the body (head, neck, chest with or without arms, umbilicus area, knees and ankles); for each of these thicknesses we measured dose rate (cGy / UM) in RW3 phantom, in TBI conditions, with ionization chamber in the center; in turn, the input diode and the output of each configuration is placed to assign dose to each set of diodes. Movie calibration is performed according to manufacturer’s recommendations but TBI conditions. The dose at the center of each thickness compared to a linear interpolation of the dose at the entrance and exit, resulting in an adequate approximation. Finally in each session for each patient put a piece of film (2×2 cm2) at the entrance and another at the exit in each area, obtaining these readings and interpolating the estimated center dose, as with the diodes. Results: These results show a greater homogeneity in the distribution for use with film and validate the use of the same for this task and, if necessary, to avoid purchasing diode group if they have not. Conclusion: By using radiochromic films for this technique gives us a proper calculation of the dose received by the patient in the absence of other methods, or gives us a second additional track that already used normally

CONTRASTING DOSE-RATE EFFECTS OF GAMMA-IRRADIATION ON RAT SALIVARY-GLAND FUNCTION

NARCIS (Netherlands)

VISSINK, A; DOWN, JD; KONINGS, AWT

The aim of this study was to investigate the effects of Co-60 irradiation delivered at high (HDR) and low (LDR) dose-rates on rat salivary gland function. Total-body irradiation (TBI; total doses 7.5, 10 and 12.5 Gy) was applied from a Co-60 source at dose-rates of 1 cGy/min (LDR) and 40 cGy/min

SU-E-T-92: Achieving Desirable Lung Doses in Total Body Irradiation Based On in Vivo Dosimetry and Custom Tissue Compensation

International Nuclear Information System (INIS)

Cui, G; Shiu, A; Zhou, S; Cui, J; Ballas, L

2015-01-01

Purpose: To achieve desirable lung doses in total body irradiation (TBI) based on in vivo dosimetry and custom tissue compensation. Methods: The 15 MV photon beam of a Varian TrueBeam STx linac was used for TBI. Patients were positioned in the lateral decubitus position for AP/PA treatment delivery. Dose was calculated using the midpoint of the separation distance across the patient’s umbilicus. Patients received 200 cGy twice daily for 3 days. The dose rate at the patient’s midplane was approximately 10 cGy/min. Cerrobend blocks with a 5-HVL thickness were used for the primary lung shielding. A custom styrofoam holder for rice-flour filled bags was created based on the lung block cutouts. This was used to provide further lung shielding based on in vivo dose measurements. Lucite plates and rice-flour bags were placed in the head, neck, chest, and lower extremity regions during the treatment to compensate for the beam off-axis output variations. Two patients were included in the study. Patients 1 and 2 received a craniospinal treatment (1080 cGy) and a mediastinum treatment (2520 cGy), respectively, before the TBI. During the TBI nanoDot dosimeters were placed on the patient skin in the forehead, neck, umbilicus, and lung regions for dose monitoring. The doses were readout immediately after the treatment. Based on the readings, fine tuning of the thickness of the rice-flour filled bags was exploited to achieve the desirable lung doses. Results: For both patients the mean lung doses, which took into consideration all treatments, were controlled within 900 +/−10% cGy, as desired. Doses to the forehead, neck, and umbilicus were achieved within +/−10% of the prescribed dose (1200 cGy). Conclusion: A reliable and robust method was developed to achieve desirable lung doses and uniform body dose in TBI based on in vivo dosimetry and custom tissue compensator

SU-E-T-92: Achieving Desirable Lung Doses in Total Body Irradiation Based On in Vivo Dosimetry and Custom Tissue Compensation

Energy Technology Data Exchange (ETDEWEB)

Cui, G; Shiu, A; Zhou, S; Cui, J; Ballas, L [Univ Southern California, Los Angeles, CA (United States)

2015-06-15

Purpose: To achieve desirable lung doses in total body irradiation (TBI) based on in vivo dosimetry and custom tissue compensation. Methods: The 15 MV photon beam of a Varian TrueBeam STx linac was used for TBI. Patients were positioned in the lateral decubitus position for AP/PA treatment delivery. Dose was calculated using the midpoint of the separation distance across the patient’s umbilicus. Patients received 200 cGy twice daily for 3 days. The dose rate at the patient’s midplane was approximately 10 cGy/min. Cerrobend blocks with a 5-HVL thickness were used for the primary lung shielding. A custom styrofoam holder for rice-flour filled bags was created based on the lung block cutouts. This was used to provide further lung shielding based on in vivo dose measurements. Lucite plates and rice-flour bags were placed in the head, neck, chest, and lower extremity regions during the treatment to compensate for the beam off-axis output variations. Two patients were included in the study. Patients 1 and 2 received a craniospinal treatment (1080 cGy) and a mediastinum treatment (2520 cGy), respectively, before the TBI. During the TBI nanoDot dosimeters were placed on the patient skin in the forehead, neck, umbilicus, and lung regions for dose monitoring. The doses were readout immediately after the treatment. Based on the readings, fine tuning of the thickness of the rice-flour filled bags was exploited to achieve the desirable lung doses. Results: For both patients the mean lung doses, which took into consideration all treatments, were controlled within 900 +/−10% cGy, as desired. Doses to the forehead, neck, and umbilicus were achieved within +/−10% of the prescribed dose (1200 cGy). Conclusion: A reliable and robust method was developed to achieve desirable lung doses and uniform body dose in TBI based on in vivo dosimetry and custom tissue compensator.

Low Dose Total Body Irradiation Combined With Recombinant CD19-Ligand × Soluble TRAIL Fusion Protein is Highly Effective Against Radiation-resistant B-precursor Acute Lymphoblastic Leukemia in Mice

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Fatih M. Uckun

2015-04-01

Full Text Available In high-risk remission B-precursor acute lymphoblastic leukemia (BPL patients, relapse rates have remained high post-hematopoietic stem cell transplantation (HSCT even after the use of very intensive total body irradiation (TBI-based conditioning regimens, especially in patients with a high “minimal residual disease” (MRD burden. New agents capable of killing radiation-resistant BPL cells and selectively augmenting their radiation sensitivity are therefore urgently needed. We report preclinical proof-of-principle that the potency of radiation therapy against BPL can be augmented by combining radiation with recombinant human CD19-Ligand × soluble TRAIL (“CD19L–sTRAIL” fusion protein. CD19L–sTRAIL consistently killed radiation-resistant primary leukemia cells from BPL patients as well as BPL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. Low dose total body irradiation (TBI combined with CD19L–sTRAIL was highly effective against (1 xenografted CD19+ radiochemotherapy-resistant human BPL in NOD/SCID (NS mice challenged with an otherwise invariably fatal dose of xenograft cells derived from relapsed BPL patients as well as (2 radiation-resistant advanced stage CD19+ murine BPL with lymphomatous features in CD22ΔE12xBCR-ABL double transgenic mice. We hypothesize that the incorporation of CD19L–sTRAIL into the pre-transplant TBI regimens of patients with very high-risk BPL will improve their survival outcome after HSCT.

Response of irradiated diet fed rats to whole body X irradiation

International Nuclear Information System (INIS)

Hasan, S.S.; Kushwaha, A.K.S.

1985-01-01

The response to whole body X irradiation has been studied in the brain of rats fed both on a normal diet (consisting of equal parts of wheat and gram flour) and on a low protein irradiated diet (consisting of a part of normal diet and three parts of wheat). The activity of enzymes related to the glucose metabolism (glucose 6-phosphate dehydrogenase and fructose diphosphate aldolase) is reduced, while that of peroxidant enzymes (catalase and lipid peroxidase) increased in the brain of rats that received a diet poor in proteins and irradiated diets (normal or hypoproteic). DNA and RNA levels and protein content show a significant reduction in the brain of rats with hypoproteic and irradiated diets. The total body irradiation causes serious alterations in the brain in animals with a hypoproteic malnutritions due both to a low protein and an irradiated diet. The brain of rats fed on a low protein and irradiated diet exhibits after whole body irradiation damages more severe than those in rats fed on a normal irradiated diet

Diagnosis of partial body radiation exposure in mice using peripheral blood gene expression profiles.

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Sarah K Meadows

2010-07-01

Full Text Available In the event of a terrorist-mediated attack in the United States using radiological or improvised nuclear weapons, it is expected that hundreds of thousands of people could be exposed to life-threatening levels of ionizing radiation. We have recently shown that genome-wide expression analysis of the peripheral blood (PB can generate gene expression profiles that can predict radiation exposure and distinguish the dose level of exposure following total body irradiation (TBI. However, in the event a radiation-mass casualty scenario, many victims will have heterogeneous exposure due to partial shielding and it is unknown whether PB gene expression profiles would be useful in predicting the status of partially irradiated individuals. Here, we identified gene expression profiles in the PB that were characteristic of anterior hemibody-, posterior hemibody- and single limb-irradiation at 0.5 Gy, 2 Gy and 10 Gy in C57Bl6 mice. These PB signatures predicted the radiation status of partially irradiated mice with a high level of accuracy (range 79-100% compared to non-irradiated mice. Interestingly, PB signatures of partial body irradiation were poorly predictive of radiation status by site of injury (range 16-43%, suggesting that the PB molecular response to partial body irradiation was anatomic site specific. Importantly, PB gene signatures generated from TBI-treated mice failed completely to predict the radiation status of partially irradiated animals or non-irradiated controls. These data demonstrate that partial body irradiation, even to a single limb, generates a characteristic PB signature of radiation injury and thus may necessitate the use of multiple signatures, both partial body and total body, to accurately assess the status of an individual exposed to radiation.

Leveraging Game Consoles for the Delivery of TBI Rehabilitation

Science.gov (United States)

Super, Taryn; Mastaglio, Thomas; Shen, Yuzhong; Walker, Robert

2011-01-01

Military personnel are at a greater risk for traumatic brain injury (TBI) than the civilian population. In addition, the increase in exposure to explosives, i.e. , improvised explosive devices, in the Afghanistan and Iraq wars, along with more effective body armor, has resulted in far more surviving casualties suffering from TBI than in previous wars. This effort presents the results of a feasibility study and early prototype of a brain injury rehabilitation delivery system (BIRDS). BIRDS is designed to provide medical personnel treating TBI with a capability to prescribe game activities for patients to execute using a commercially available game console, either in a clinical setting or in their homes. These therapeutic activities will contribute to recovery or remediation of the patients' cognitive dysfunctions. Solutions such as this that provide new applications for existing platforms have significant potential to address the growing incidence of TBI today.

Toxicities of total-body irradiation for pediatric bone marrow transplantation

International Nuclear Information System (INIS)

Chou, Rachel H.; Wong, Garrett B.; Kramer, Joel H.; Wara, Diane W.; Matthay, Katherine K.; Crittenden, Mary R.; Swift, Patrick S.; Cowan, Morton J.; Wara, William M.

1996-01-01

Purpose: To determine the acute and late effects, including cognitive function, of total body irradiation (TBI) and chemotherapy for bone marrow transplant (BMT) in children with immunodeficiency or hematologic disorders. Methods and Materials: At UCSF, 15 children with immunodeficiency disorders and 58 children with leukemia received chemoradiotherapy between July 1982 and November 1993 and were evaluated for toxicity. Patients with severe combined immunodeficiency disorder (SCID) received 7 Gy TBI while leukemia patients received 12 Gy TBI. Results: Eight immunodeficient patients (53%) are alive at 4 months to 11 years posttransplant. Acute toxicity was limited and treatment well tolerated. Most patients developed mild nausea and vomiting, skin rash, or erythema. Transient fever/chills, oral mucositis, and alopecia were noted in approximately 50% of patients. Seventy-three percent of patients demonstrated acute liver dysfunction, but only four (27%) developed veno-occlusive disease. All children had decreased growth velocity but normal growth hormone levels. Other endocrinologic evaluations including adrenocorticotropic hormone (ACTH), cortisol, and thyroid hormones were normal. Only one evaluable girl had delayed puberty with late onset of secondary sexual characteristics. Neuropsychological testing demonstrated an intelligence quotient (IQ) reduction between the baseline and 1 year post-BMT, with some recovery at 3 years. Only one patient developed a clinically significant cataract. Thirteen percent of patients had chronic interstitial lung disease. Four children developed exostosis. Only 1 of the 15 children developed a second malignancy (acute myelogenous leukemia) at age 5, 51 months posttransplant for SCID. For patients with leukemia, similar toxicities were observed. Twenty-nine percent disease-free survival was noted with a mean follow-up of 4.7 years. Twenty-two percent had chronic interstitial lung disease and two patients were diagnosed with cataracts

Comparison of Cyclophosphamide Combined with Total Body Irradiation, Oral Busulfan, or Intravenous Busulfan for Allogeneic Hematopoietic Cell Transplantation in Adults with Acute Lymphoblastic Leukemia.

Science.gov (United States)

Mitsuhashi, Kenjiro; Kako, Shinichi; Shigematsu, Akio; Atsuta, Yoshiko; Doki, Noriko; Fukuda, Takahiro; Kanamori, Heiwa; Onizuka, Makoto; Takahashi, Satoshi; Ozawa, Yukiyasu; Kurokawa, Mineo; Inoue, Yoshiko; Nagamura-Inoue, Tokiko; Morishima, Yasuo; Mizuta, Shuichi; Tanaka, Junji

2016-12-01

We conducted a retrospective analysis to compare outcomes in adult patients with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic cell transplantation (allo-HCT) with conditioning regimens containing cyclophosphamide (CY) in combination with total body irradiation (TBI), oral busulfan (p.o. BU), or intravenous busulfan (i.v. BU). We used data for January 2000 to December 2012 from the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation. We identified 2130 patients treated with TBI/CY (n = 2028), p.o. BU/CY (n = 60), or i.v. BU/CY (n = 42). Two-year overall survival (OS) and 2-year relapse-free survival rates were 69.0% and 62.1%, respectively, in the TBI/CY group, 55.9% and 54.2% in the p.o. BU/CY group, and 71.0% and 46.8% in the i.v. BU/CY group. In multivariate analysis, compared with TBI/CY, p.o. BU/CY, but not i.v. BU/CY, was associated with lower OS (hazard ratio [HR], 1.46; P = .047) and a higher incidence of sinusoidal obstruction syndrome (HR, 3.36; P = .030). No between-group differences were seen in the incidence of nonrelapse mortality, relapse, acute graft-versus-host disease (GVHD), or chronic GVHD. We suggest that i.v. BU/CY might be a possible alternative allo-HCT conditioning regimen for adults with ALL who are not suitable for TBI. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Marrow transplantation for leukemia following fractionated total body irradiation. A comparative trial of methotrexate and cyclosporine

International Nuclear Information System (INIS)

Irle, C.; Deeg, H.J.; Buckner, C.D.; Swedish Hospital Medical Center, Seattle, WA; Veterans Administration Hospital, Seattle, WA; Washington Univ., Seattle

1985-01-01

Fifty-six patients, 30-47 yr of age, with leukemia in relapse received allogeneic marrow transplants from HLA-identical siblings. All patients were treated with cyclophosphamide (120 mg/kg) and 7 daily fractions of 2.25 Gy of total body irradiation (TBI) for seven consecutive days. Nine patients (16%) are currently alive, free of disease, 324-845 days from transplantation. Actuarial relapse and survival rates at 2 yr were 56% and 9.5% respectively. These data were not remarkably different from those in previous studies using 10 Gy of TBI administered as a single dose. Thirty patients were randomized to receive methotrexate (MTX) and 26 to receive cyclosporine (CSP) as postgrafting prophylaxis for acute graft-versus-host disease (GVHD). Probability of developing significant acute GVHD by day 100 post-transplant was 71% for patients in the MTX group and 45% for patients in the CSP group (p<0.05). Probability of relapse was 37% for patients in the MTX group and 70% for patients in the CSP group (p<0.05). Transplant-related deaths were more frequent in the MTX group and leukemic deaths more frequent in the CSP group although this may have been related to an uneven distribution of high-risk patients. Long term disease-free survival was comparable. (author)

Factors Influencing Pulmonary Toxicity in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation-Based Myeloablative Conditioning

Energy Technology Data Exchange (ETDEWEB)

Abugideiri, Mustafa, E-mail: Mabugid@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Nanda, Ronica H. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Butker, Charlotte [Emory University, Atlanta, Georgia (United States); Zhang, Chao [Department of Biostatistics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Kim, Sungjin [Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California (United States); Chiang, Kuang-Yueh [Aflac Cancer Center and Blood Disorders Center, Children' s Healthcare of Atlanta, and Pediatric Hematology, Oncology, Bone Marrow Transplant, Emory University, Atlanta, Georgia (United States); Butker, Elizabeth; Khan, Mohammad K. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Haight, Ann E. [Aflac Cancer Center and Blood Disorders Center, Children' s Healthcare of Atlanta, and Pediatric Hematology, Oncology, Bone Marrow Transplant, Emory University, Atlanta, Georgia (United States); Chen, Zhengjia [Department of Biostatistics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Esiashvili, Natia [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

2016-02-01

Purpose: This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT). Methods and Materials: The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified using clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period. Results: PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS. Conclusions: A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly

A method for total body irradiation

International Nuclear Information System (INIS)

Yasukochi, Hiroshi; Higashi, Shizuka; Okuhata, Yoshitaka; Lee, Keiichi; Ishioka, Kuniaki; Murakami, Koji; Nagai, Jun; Kuniyasu, Yoshio

1988-01-01

In these two years, we have treated four infant patients of acute leukemia by Cobalt-60 total body irradiation and bone marrow transplantation. During total body irradiation, thermoluminescence dosimeters were attached to the skin of patients. For four patients, nine dosimetries were performed. Reliability of this method was examined by phantom experiment. Every irradiation for the patient per fraction was 2.4 Gy, that is, 60 cGy for each four positions, right decubitus A-P and PA directions and left decubitus A-P and PA directions under aseptic circumstances. Radiation dose was uniform by this technique for each patient, and average determined dose for surface of the patients was between 87 % and 106 % compared with the air dose of the center of aseptic space (wagon). As the result, we suggest that this method is suitable for the total body irradiation of acute leukemia of infant. (author)

The Total Body Irradiation Schedule Affects Acute Leukemia Relapse After Matched T Cell–Depleted Hematopoietic Stem Cell Transplantation

International Nuclear Information System (INIS)

Aristei, Cynthia; Carotti, Alessandra; Palazzari, Elisa; Amico, Lucia; Ruggeri, Loredana; Perrucci, Elisabetta; Falcinelli, Lorenzo; Lancellotta, Valentina; Palumbo, Isabella; Falzetti, Franca; Aversa, Franco; Merluzzi, Mara; Velardi, Andrea; Martelli, Massimo Fabrizio

2016-01-01

Purpose: We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell–depleted allogeneic hematopoietic stem cell transplantation from HLA identical siblings. Methods and Materials: The study recruited 55 patients (median age, 48 years; age range, 20-66 years; 30 men and 25 women; 34 with acute myeloid leukemia and 21 with acute lymphoid leukemia). Hyperfractionated TBI (HTBI) (1.2 Gy thrice daily for 4 days [for a total dose of 14.4 Gy] from day −12 to day −9) was administered to 29 patients. Single-dose TBI (STBI) (8 Gy, at a median dose rate of 10.7 cGy/min on day −9) was given to 26 patients. Results: All patients achieved primary, sustained engraftment with full donor-type chimerism. At 10 years, the overall cumulative incidence of transplant-related mortality was 11% (SE, ±0.1%). It was 7% (SE, ±0.2%) after HTBI and 15% (SE, ±0.5%) after STBI (P=.3). The overall cumulative incidence of relapse was 33% (SE, ±0.5). It was 13% (SE, ±0.5%) after HTBI and 46% (SE, ±1%) after STBI (P=.02). The overall probability of disease-free survival (DFS) was 59% (SE, ±7%). It was 67% (SE, ±0.84%) after HTBI and 37% (SE, ±1.4%) after STBI (P=.01). Multivariate analyses showed the TBI schedule was the only risk factor that significantly affected relapse and DFS (P=.01 and P=.03, respectively). Conclusions: In patients with acute leukemia, HTBI is more efficacious than STBI in eradicating minimal residual disease after HLA-matched T cell–depleted hematopoietic stem cell transplantation, thus affecting DFS.

The Total Body Irradiation Schedule Affects Acute Leukemia Relapse After Matched T Cell–Depleted Hematopoietic Stem Cell Transplantation

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Aristei, Cynthia, E-mail: cynthia.aristei@unipg.it [Radiation Oncology Section, Department of Surgery and Biomedical Sciences, University of Perugia and Perugia General Hospital, Perugia (Italy); Carotti, Alessandra [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy); Palazzari, Elisa [Radiation Oncology Section, University of Perugia, Perugia (Italy); Amico, Lucia; Ruggeri, Loredana [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy); Perrucci, Elisabetta; Falcinelli, Lorenzo [Radiation Oncology Division, Perugia General Hospital, Perugia (Italy); Lancellotta, Valentina [Radiation Oncology Section, University of Perugia, Perugia (Italy); Palumbo, Isabella [Radiation Oncology Section, Department of Surgery and Biomedical Sciences, University of Perugia and Perugia General Hospital, Perugia (Italy); Falzetti, Franca [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy); Aversa, Franco [Hematology and Bone Marrow Transplant Unit, Department of Clinical and Experimental Medicine, Parma General Hospital and University, Parma (Italy); Merluzzi, Mara; Velardi, Andrea; Martelli, Massimo Fabrizio [Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, Perugia General Hospital and University, Perugia (Italy)

2016-11-15

Purpose: We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell–depleted allogeneic hematopoietic stem cell transplantation from HLA identical siblings. Methods and Materials: The study recruited 55 patients (median age, 48 years; age range, 20-66 years; 30 men and 25 women; 34 with acute myeloid leukemia and 21 with acute lymphoid leukemia). Hyperfractionated TBI (HTBI) (1.2 Gy thrice daily for 4 days [for a total dose of 14.4 Gy] from day −12 to day −9) was administered to 29 patients. Single-dose TBI (STBI) (8 Gy, at a median dose rate of 10.7 cGy/min on day −9) was given to 26 patients. Results: All patients achieved primary, sustained engraftment with full donor-type chimerism. At 10 years, the overall cumulative incidence of transplant-related mortality was 11% (SE, ±0.1%). It was 7% (SE, ±0.2%) after HTBI and 15% (SE, ±0.5%) after STBI (P=.3). The overall cumulative incidence of relapse was 33% (SE, ±0.5). It was 13% (SE, ±0.5%) after HTBI and 46% (SE, ±1%) after STBI (P=.02). The overall probability of disease-free survival (DFS) was 59% (SE, ±7%). It was 67% (SE, ±0.84%) after HTBI and 37% (SE, ±1.4%) after STBI (P=.01). Multivariate analyses showed the TBI schedule was the only risk factor that significantly affected relapse and DFS (P=.01 and P=.03, respectively). Conclusions: In patients with acute leukemia, HTBI is more efficacious than STBI in eradicating minimal residual disease after HLA-matched T cell–depleted hematopoietic stem cell transplantation, thus affecting DFS.

The effects of dose rate in total body irradiation of dogs

International Nuclear Information System (INIS)

Kolb, H.J.; Bodenberger, U.; Holler, E.; Thierfelder, S.; Eckstein, R.

1986-01-01

In summary the studies in dogs show that the dose rate or exposure time has a great impact on survival of acute radiation syndromes. In contrast the inactivation of colony forming hemopoietic precursors is less influenced by the dose rate. The potential of hemopoietic recovery is determined by the survival of hemopoietic precursor cells. Therefore in patients with a suspected whole body exposure of more than 1.50 Gy, bacterial and fungal decontamination and reverse isolation in a sterile environment has to be started immediately. Human patients treated with about 10 Gy of TBI frequently developed nausea, elevated temperatures and swelling of the parotic glands at the first and second day. The extent of these changes varies from patient to patient. The temperature is rarely elevated above 38.5 0 C. The swelling of parotics and the nausea subside within 48 hours. The presence of such systemic symptoms may suggest the exposure to a lethal dose of radiation. The disappearance of immature red cells, i.e. reticulocytes, and bandforms of granulocytes within the first 5 days supports this suggestion. HLA typing of the victim and his family should be performed as soon as possible after the accident. An HLA-identical sibling would be a suitable bone marrow donor. Unlike therapeutic TBI accidental exposures bring about uncertainties in the calculation of dose, dose distribution and dose rate. Early after irradiation biological changes are extremely variable. Both biological and physical data have to be considered, when microbiological decontamination, reverse isolation and transplantation of bone marrow are to be decided upon. Obviously these intensive therapeutic efforts are limited to a small number of victims. (orig.)

TU-F-CAMPUS-T-01: Dose and Energy Spectra From Neutron Induced Radioactivity in Medical Linear Accelerators Following High Energy Total Body Irradiation

International Nuclear Information System (INIS)

Keehan, S; Taylor, M; Franich, R; Smith, R; Dunn, L; Kron, T

2015-01-01

Purpose: To assess the risk posed by neutron induced activation of components in medical linear accelerators (linacs) following the delivery of high monitor unit 18 MV photon beams such as used in TBI. Methods: Gamma spectroscopy was used to identify radioisotopes produced in components of a Varian 21EX and an Elekta Synergy following delivery of photon beams. Dose and risk estimates for TBI were assessed using dose deliveries from an actual patient treatment. A 1 litre spherical ion chamber (PTW, Germany) has been used to measure the dose at the beam exit window and at the total body irradiation (TBI) treatment couch following large and small field beams with long beam-on times. Measurements were also made outside of the closed jaws to quantify the benefit of the attenuation provided by the jaws. Results: The radioisotopes produced in the linac head have been identified as 187 W, 56 Mn, 24 Na and 28 Al, which have half-lives from between 2.3 min to 24 hours. The dose at the beam exit window following an 18 MV 2197 MU TBI beam delivery was 12.6 µSv in ten minutes. The dose rate at the TBI treatment couch 4.8 m away is a factor of ten lower. For a typical TBI delivered in six fractions each consisting of four beams and an annual patient load of 24, the annual dose estimate for a staff member at the treatment couch for ten minutes is 750 µSv. This can be further reduced by a factor of about twelve if the jaws are closed before entering the room, resulting in a dose estimate of 65 µSv. Conclusion: The dose resulting from the activation products for a representative TBI workload at our clinic of 24 patients per year is 750 µSv, which can be further reduced to 65 µSv by closing the jaws

Hyperfractionated total body irradiation for bone marrow transplantation. Results in seventy leukemia patients with allogeneic transplants

International Nuclear Information System (INIS)

Shank, B.; Chu, F.C.H.; Dinsmore, R.

1983-01-01

From May, 1979 to March, 1981, 76 leukemia patients were prepared for bone marrow transplantation (BMT) with a new hyperfractionated total body irradiation (TBI) regimen (1320 cGy in 11 fractions, 3x/day), followed by cyclophosphamide, 60 mg/kg, for two days. Partial lung shielding was done on each treatment, with supplemental electron beam treatments of the chest wall to compensate, and of the testes, a sanctuary site. This regimen was initiated to potentially reduce fatal interstitial pneumonitis as well as decrease leukemic relapse. Overall actuarial survival at 1 year for acute non-lymphocytic leukemia (ANLL) patients is 63%, while relapse-free survival at 1 year is 53%. On the other hand, for acute lymphocytic leukemia (ALL) patients, there is no significant difference between relapse or remission patients with regard to overall survival or relapse-free survival, when relapse is defined as > 5% blasts in the marrow at the time of cytoreduction. Overall actuarial survival at 1 year for ALL is 61% and relapse-free survival is 45% at 1 year. Fatal interstitial pneumonitis has dropped to 18% compared with 50% in our previous single-dose TBI regimen (1000 cGy), in which the same doses of cyclophosphamide were given prior to TBI. In conclusion, not only has fatal interstitial pneumonitis been reduced by hyperfractionation and partial lung blocking, but there may be a survival advantage in ALL patients in relapse, who have a survival equal to that of remission patients. This may indicate a greater cell kill with the higher dose (1320 cGy) attained with this regimen, in these patients with a higher leukemic cell burden

Total body irradiation in the bone marrow transplantation in leukemia: an experience; Irradiacion corporal total fraccionada en el transplante de medula osea ologenica en leucemias: experiencia de un centro

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Zapatero, A; Martin de Vidales, C; Pinar, B; Marin, A; Cerezo, L; Dominguez, P; Perez, A [Servicio de Oncologia Radidoterapica Hospital Universitario de la Princesa, Madrid (Spain)

1996-06-01

The purpose of this report was to evaluate long-term survival and morbidity of fractioned total body irradiation (TBI) prior to allogeneic bone marrow transplantation (BMT) for leukemia. From June 1985 to May 1992, 94 patients with acute leukemia and chronic myelogenous leukemia (CML), were treated with high dose cyclophosphamide (CY) and fractionated TBI to a total dose of 12 Gy in six fractions prior to allogeneic BMT. The Kaplan-Meier 5-year overall survival and disease-free survival were 53% +-6 and 48%+- respectively for patients with standard risk disease (first remission of acute leukemia and first chronic phase of CML), and 24%+-7 and 21%+-6 for patients with more advanced disease (p=0.01). The incidence of interstitial pneumonitis (IP), venoocclusive disease of the liver (VOD) and grade=>II acute graft-versus-host disease (GVHD) were respectively 15%, 29% and 51%. Fractionated TBI combined with high dose CY before allogeneic BMT for leukemia is an effective treatment in prolonging relapse-free survival with a low incidence of lung toxicity. (Author) 13 refs.

Therapeutic efficiency of synthokine SC-55494, a human IL-3 receptor agonist, in a nonhuman primate model of HIGH dose, sublethal, radiation-induced marrow aplasia; Efficacite therapeutique d`un variant d`interleukine-3 chez des macaques irradies

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Herodin, F.; Farese, A.; Grab, L.; McKearn, J.P.; Mestries, J.C.; McVittie, T.J.

1994-12-31

The synthetic cytokine (Synthokine) SC-55494 is a high affinity IL-3 receptor ligand. The therapeutic administration of Synthokine to total body irradiated (TBI) monkeys (7 Gy gamma) from day 1 post TBI for 23 days, significantly enhanced platelet recovery and modulated aneutrophil nadir. (author). 6 refs.

Low dose-rate irradiation in the treatment of acute myelogenous leukaemia in first remission

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Cattell, P A; Unwin, S F [Royal Marsden Hospital, Sutton (UK)

1981-04-01

Thirty-six patients with acute myelogenous leukaemia (AML) in first remission received sibling bone marrow transplants following cyclophosphamide and a single dose of 1000 rad total body irradiation (TBI). The preparation programme for a patient undergoing a bone marrow transplant is described. The aim of the cyclophosphamide and TBI is to eradicate all active bone marrow present in the patient and to reduce the immune response of the patient to the graft, thus preventing rejection. The cobalt unit and treatment box used for the TBI is described together with details of the planning for TBI including test doses on the patient. The procedure on the day of the 8 hour TBI treatment is then given. The likely reactions following the TBI and the graft are described. Of these transplanted patients, 64% remain alive, well and disease-free, nine of them for more than one year and one surviving more than three years. These results are a significant improvement on the results of AML treated with chemotherapy and immunotherapy.

Radiobiological considerations in magna-field irradiation

International Nuclear Information System (INIS)

Evans, R.G.

1983-01-01

Radiobiological considerations are described for total body irradiation (TBI) as given to patients undergoing bone marrow transplantation (BMT). Although much progress has been made in the use of BMT for refractory leukemias, many patients still die from interstitial pneumonia and relapse. Fractionated TBI has been introduced in order to improve leukemic cell kill, while increasing the degree of normal tissue tolerance. Traditionally, bone marrow stem cells, leukemic cells and immunocytes have been considered as having a limited ability to repair radiation damage while cells of lung tissue and intestinal epithelial cells have a greater capacity. During fractionated radiation therapy or continuous low-dose rate exposure, repair of sublethal damage between fractions allows greater recovery in the cells of lung tissue to those in the bone marrow. Clinically, the potential benefit of six fractions over one fraction or low dose-rate TBI has yet to be proved, although there is suggestive evidence for a reduced incidence of interstitial pneumonitis. However, other extraneous factors such as doses to the lung, differences in conditioning regimens, effect of increased delay in BMT for patients receiving fractionated TBI, and the unmeasurable differences between institutions make definite conclusions impossible. Despite this, a consensus for dose fractionation has developed and most centers are moving away from the use of large single dose TBI

Total body irradiation prior to bone marrow transplantation: efficacy and safety of granisetron in the prophylaxis and control of radiation-induced emesis

International Nuclear Information System (INIS)

Belkacemi, Yazid; Ozsahin, Mahmut; Pene, Francoise; Rio, Bernard; Sutton, Laurent; Laporte, Jean-Philippe; Touboul, Emmanuel; Gorin, Norbert-Claude; Laugier, Alain

1996-01-01

Purpose: Radiation-induced emisis is one of the most disturbing side effects of total body irradiation (TBI). To evaluate the efficacy and to determine the best schedule of granisetron (a selective 5-hydroxytryptamine 3 serotonin receptor antagonist) administration in the prevention of radiation-induced nausea and vomiting, we conducted a trial involving patients receiving single-dose TBI before bone marrow transplantation (BMT). Methods and Materials: Thirty-six patients with non-Hodgkin's lymphoma (n 12), multiple myeloma (n = 8), acute lymphoblastic leukemia (n = 7), acute nonlymphoblastic leukemia (n = 6), and chronic myeloid leukemia (n = 3) referred to our department between March 1992 and February 1994 were enrolled in this study to assess the efficacy of granisetron during single-dose TBI before autologous BMT (n = 26), allogeneic BMT (n = 8), or syngeneic BMT (n 2). The male-to-female ratio was 22:14 (1.57), and the mean age was 41 ± 11 years (range 16-58). Before TBI, conditioning chemotherapy consisted of cyclophosphamide (CY) alone (60 mg/kg per day on 2 successive days) in 24 patients, CY combined with other drugs in 6, and combinations without CY in 6. All patients received single-dose TBI (10 Gy administered to the midplane at L4, and 8 Gy to the lungs). The mean instantaneous and average dose rates were 0.039 ± 0.012 Gy/min (range 0.031-0.058), and 0.025-0.006 Gy/min (range 2.08-3.96), respectively. Granisetron was administered 30-45 min before TBI according to two different modalities: a total dose of 3 mg as a 5-min intravenous (i.v.) infusion (Treatment A, n = 15; 42%) or the same treatment plus 3 mg of granisetron as a 24-h continuous i.v. infusion (total dose: 6 mg, Treatment B, n = 21; 58%). Depending on the BMT teams, hyper diuresis was continued (n = 19, 53%) or suspended (n = 17, 47%) during TBI. Nausea and vomiting were assessed during the TBI session and the following 12 h, and were scored as follows: S1 = no nausea or vomiting; S2

Cytogenetic studies on recipients of allogeneic bone marrow transplants after fractionated total body irradiation

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Schmitz, N; Goedde-Salz, E; Loeffler, H [Christian-Albrechts-Univ., Kiel (Germany, F.R.)

1985-06-01

Cytogenetic findings from the bone marrow (BM) and the peripheral blood (PB) of nine consecutive patients after allogeneic bone marrow transplantation (BMT) for acute or chronic myelogenous leukaemia are reported. After a conditioning regimen consisting of cyclophosphamide and fractionated total body irradiation (TBI) given in five or six fractions of 2 Gy, persistence of host cells was detected in four out of seven cases with permanent engraftment. While one of these patients relapsed 4 months after host cells had been found in BM and PB, the other patients stayed relapse-free 124, 257 and 347 d after grafting. Before transplantation, the leukaemic cells in all three cases carried unique cytogenetic abnormalities giving the opportunity to distinguish the leukaemic population from chromosomally non-aberrant cells thought to represent residual normal host cells. As the persisting host cells after BMT lacked any cytogenetic abnormalities, it is suggested that they were members of residual normal clones not involved in the leukaemic process.

Cytogenetic studies on recipients of allogeneic bone marrow transplants after fractionated total body irradiation

International Nuclear Information System (INIS)

Schmitz, N.; Goedde-Salz, E.; Loeffler, H.

1985-01-01

Cytogenetic findings from the bone marrow (BM) and the peripheral blood (PB) of nine consecutive patients after allogeneic bone marrow transplantation (BMT) for acute or chronic myelogenous leukaemia are reported. After a conditioning regimen consisting of cyclophosphamide and fractionated total body irradiation (TBI) given in five or six fractions of 2 Gy, persistence of host cells was detected in four out of seven cases with permanent engraftment. While one of these patients relapsed 4 months after host cells had been found in BM and PB, the other patients stayed relapse-free 124, 257 and 347 d after grafting. Before transplantation, the leukaemic cells in all three cases carried unique cytogenetic abnormalities giving the opportunity to distinguish the leukaemic population from chromosomally non-aberrant cells thought to represent residual normal host cells. As the persisting host cells after BMT lacked any cytogenetic abnormalities, it is suggested that they were members of residual normal clones not involved in the leukaemic process. (author)

Calibration of semiconductors diodes for in vivo dosimetry in total body irradiation treatments; Calibracao de diodos semicondutores para dosimetria in vivo em tratamentos de irradiacao de corpo inteiro

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Fernanda F.; Costa, Alessandro M.; Ghilardi Netto, Thomaz, E-mail: ferretti.oliveira@gmail.com [Universidade de Sao Paulo (FFCLRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Ciencias e Letras. Departamento de Fisica; Amaral, Leonardo L. [Universidade de Sao Paulo (HCFMRP/USP), Ribeirao Preto, SP (Brazil). Hospital das Clinicas. Servico de Radioterapia

2012-08-15

This paper presents the results of in vivo dosimetry with p-type semiconductors diodes, EDP-15 (Scanditronix Wellhoefer) of two patients who underwent total body irradiation treatments, at Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto University of Sao Paulo (HCFMRP-USP). The diodes were well calibrated and the calibration factors were determined with the aid of a reference ionization chamber (FC065, IBA dosimetry, sensitive volume of 0.65 cm{sup 3}).The calibration was performed in a Total Body Irradiation (TBI) setup, using solid water phantoms. Different lateral thicknesses from one patient were simulated and then the calibration factors were determined by means of maximum depth dose readings (half of the lateral thickness). The response difference between diode readings and the prescribed dose for both treatments was below 4%. This difference is in agreement as recommended by International Commission on Radiation Units (ICRU), which is {+-}5%. (author)

Hyperfractionated high-dose total body irradiation in bone marrow transplantation for Ph{sup 1}-positive acute lymphoblastic leukemia

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Kikuchi, Akira; Ebihara, Yasuhiro; Mitsui, Tetsuo [Tokyo Univ. (Japan). Hospital of the Institute of Medical Science] [and others

1998-12-01

In two cases of Philadelphia-positive childhood acute lymphoblastic leukemia (Ph{sup 1} ALL), we performed allogeneic bone marrow transplantation (AlloBMT) with preconditioning regimen, including hyperfractionated high-dose total body irradiation (TBI) (13.5 Gy, in 9 fractions). Their disease statuses at BMT were hematological relapse in case 1 and molecular relapse in case 2. Bone marrow donors were unrelated in case 1, and HLA was a partially mismatched mother in case 2. Regimen-related toxicity was tolerable in both cases. Hematological recovery was rapid, and engraftment was obtained on day 14 in case 1 and on day 12 in case 2. BCR/ABL message in bone marrow disappeared on day 89 in case 1 and on day 19 in case 2 and throughout their subsequent clinical courses. Although short-term MTX and Cy-A continuous infusion were used for GVHD prophylaxis, grade IV GVHD was observed in case 1 and grade III in case 2. Both cases experienced hemorrhagic cystitis because of adenovirus type 11 infection. Although case 1 died of interstitial pneumonitis on day 442, case 2 has been free of disease through day 231. AlloBMT for Ph{sup 1} ALL with preconditioning regimen including hyperfractionated high-dose TBI is considered to be worth further investigation. (author)

Natural β-carotene and whole body irradiation in rats

International Nuclear Information System (INIS)

Ben-Amotz, A.; Rachmilevich, B.; Greenberg, S.; Sela, M.; Weshler, Z.

1996-01-01

β-Carotene and other carotenoids are reported to be potent free radical quenchers, singlet oxygen scavengers, and lipid antioxidants. Whole-body irradiation is known to cause an immunosuppression effect in mammals through the possible initiation and production of reactive oxygen species. We decided to test the possible antioxidative effect against whole-body irradiation of a natural β-carotene, composed of equal amounts of the all-trans and 9-cis isomers, obtained from the unicellular alga Dunaliella bardawil. Rats were fed on ground commercial food enriched with natural β-carotene (50 mg/kg diet). On completion of 1 week with β-carotene, the rats were exposed to a single dose of 4 Gy whole-body irradiation, after which their livers and blood were removed for β-carotene and retinol analysis in comparison with control livers of animals irradiated or not, or supplemented with β-carotene after irradiation. A normal increase in body weight with no ill effects was noted in the groups of rats whose diet was supplemented by β-carotene before and after irradiation, compared with the reduction in the specific growth rate in the group of rats irradiated without β-carotene. Liver β-carotene and retinol decreased significantly after irradiation compared with the rats which were not irradiated. This decrease was not shown in rats fed β-carotene prior to irradiation, and the effect of irradiation was partially cured by supplementation with β-carotene after irradiation. High-pressure liquid chromatography (HPLC) analysis of the irradiated animals showed a selective decline in 9-cis β-carotene and in retinol over all-trans β-carotene and retinyl esters. These results suggest that 9-cis β-carotene and retinol protect in vivo against the cellular damage by free radicals induced after whole-body irradiation. (orig.). With 1 fig., 2 tabs

Time- and radiation-dose dependent changes in the plasma proteome after total body irradiation of non-human primates: Implications for biomarker selection.

Directory of Open Access Journals (Sweden)

Stephanie D Byrum

Full Text Available Acute radiation syndrome (ARS is a complex multi-organ disease resulting from total body exposure to high doses of radiation. Individuals can be exposed to total body irradiation (TBI in a number of ways, including terrorist radiological weapons or nuclear accidents. In order to determine whether an individual has been exposed to high doses of radiation and needs countermeasure treatment, robust biomarkers are needed to estimate radiation exposure from biospecimens such as blood or urine. In order to identity such candidate biomarkers of radiation exposure, high-resolution proteomics was used to analyze plasma from non-human primates following whole body irradiation (Co-60 at 6.7 Gy and 7.4 Gy with a twelve day observation period. A total of 663 proteins were evaluated from the plasma proteome analysis. A panel of plasma proteins with characteristic time- and dose-dependent changes was identified. In addition to the plasma proteomics study reported here, we recently identified candidate biomarkers using urine from these same non-human primates. From the proteomic analysis of both plasma and urine, we identified ten overlapping proteins that significantly differentiate both time and dose variables. These shared plasma and urine proteins represent optimal candidate biomarkers of radiation exposure.

Stem cell factor enhances the survival of murine intestinal stem cells after photon irradiation

International Nuclear Information System (INIS)

Leigh, B.R.; Khan, W.; Hancock, S.L.

1995-01-01

Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 μ/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 ± 0.7 per duodenal cross section for controls to 30.0 ± 1.7 after treatment with SCF (P=0.03). The TBI dose producing 50% mortality of 6 days (LD 50/6 ) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine. 29 refs., 4 figs

Comparison of therapeutic effects between pulsed and continuous wave 810-nm wavelength laser irradiation for traumatic brain injury in mice.

Directory of Open Access Journals (Sweden)

Takahiro Ando

Full Text Available Transcranial low-level laser therapy (LLLT using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI. In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI.TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm(2 for 12-minutes giving a fluence of 36-J/cm(2. Neurological severity score (NSS and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain tissue was determined immediately after laser irradiation. We examined the role of LLLT on the psychological state of the mice at 1 day and 4 weeks after TBI using tail suspension test and forced swim test.The 810-nm laser pulsed at 10-Hz was the most effective judged by improvement in NSS and body weight although the other laser regimens were also effective. The brain lesion volume of mice treated with 10-Hz pulsed-laser irradiation was significantly lower than control group at 15-days and 4-weeks post-TBI. Moreover, we found an antidepressant effect of LLLT at 4-weeks as shown by forced swim and tail suspension tests.The therapeutic effect of LLLT for TBI with an 810-nm laser was more effective at 10-Hz pulse frequency than at CW and 100-Hz. This finding may provide a new insight into biological mechanisms of LLLT.

Myeloproliferative disorders in patients with rheumatoid arthritis treated with total body irradiation

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Urowitz, M.B.; Rider, W.D.

1985-01-01

Four patients with refractory rheumatoid arthritis were treated with total body irradiation administered in two sittings, 300 to 400 rads to each half of the body. All four patients had taken antimetabolites prior to receiving total body irradiation, and two continued to use them after total body irradiation. Two patients had taken alkylating agents before, and one had used them after total body irradiation. All patients showed clinical improvement. However, in two patients myeloproliferative disorders developed: a myelodysplastic preleukemia at 40 months after total body irradiation in one and acute myelogenous leukemia at 25 months in the other. Total body irradiation differs from total nodal irradiation in the total dose of irradiation (300 to 400 rads versus 2,000 to 3,000), and in the duration of the therapy (two sittings versus treatment over several weeks to months). Furthermore, the patients in the total body irradiation study frequently used cytotoxic drugs before and/or after irradiation, whereas in one total nodal irradiation study, azathioprine (2 mg/kg per day or less) was permitted, but no other cytotoxic agents were allowed. Rheumatologists may therefore face a binding decision when deciding to treat a patient with rheumatoid arthritis with either a cytotoxic drug or irradiation

[Blood amylase: a biological marker in irradiation accidents? Preliminary results obtained at the Gustave-Roussy Institut (GRI) and a literature review].

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Hennequin, C; Cosset, J M; Cailleux, P E; Girinsky, T; Ganem, G; Hubert, D; Comoy, E; Dutreix, J

1989-01-01

The retrospective evaluation of the dose after an irradiation accident is of paramount importance; it allows an adequate selection of patients and the most appropriate treatment can then be proposed. Classical physical dosimetry often lacks precision for dose assessment in such accidents. Cytogenetics, usually more reliable, is not 100% accurate and cannot be used in some particular instances. At the Institut Gustave-Roussy, we studied amylasemia in 15 patients who received a total body irradiation (TBI) for bone marrow grafting, at various dose levels (10, 2 and 1.35 Gy). Hyperamylasemia was found to be constant and dose-dependent. Ten additional patients given a localized irradiation of 2 Gy in the Waldeyer ring had a similar rise in amylasemia as did TBI patients who had received the same dose. In contrast, 13 patients given a pancreatic irradiation (as part of a localized abdominal irradiation) did not show any increase in amylasemia. This study seems to confirm reported data, which suggested that post-TBI hyperamylasemia is almost only related to salivary gland irradiation. Amylasemia could possibly be used as a "biological dosimeter"; however, the dose-effect relationship should be more precisely defined, as well as individual variations. Moreover, the definition of a "threshold-dose" below which hyperamylasemia can never be detected, would be of interest for radioprotection.

Allogeneic marrow transplantation following cyclophosphamide and escalating doses of hyperfractionated total body irradiation in patients with advanced lymphoid malignancies: a phase I/II trial

International Nuclear Information System (INIS)

Demirer, Taner; Petersen, Finn B.; Appelbaum, Frederick R.; Barnett, Todd A.; Sanders, Jean; Deeg, H. Joachim; Storb, Rainer; Doney, Kristine; Bensinger, William I.; Shannon-Dorcy, Kathleen; Buckner, C. Dean

1995-01-01

Purpose: To define the maximum tolerated dose (MTD) of unshielded total body irradiation (TBI) delivered from dual 60 C sources at an exposure rate of 0.08 Gy/min and given in thrice daily fractions of 1.2 Gy in patients with advanced lymphoid malignancies. Methods and Materials: Forty-four patients with a median age of 28 (range 6-48) years were entered into a Phase I/II study. All patients received cyclophosphamide (CY), 120 mg/kg administered over 2 days before TBI. Marrow from human leukocyte antigen (HLA) identical siblings was infused following the last dose of TBI. An escalation-deescalation schema designed to not exceed an incidence of 25% of Grade 3-4 regimen-related toxicities (RRTs) was used. The first dose level tested was 13.2 Gy followed by 14.4 Gy. Results: None of the four patients at the dose level of 13.2 Gy developed Grade 3-4 RRT. Two of the first eight patients receiving 14.4 Gy developed Grade 3-4 RRT, establishing this as the MTD. An additional 32 patients were evaluated at the 14.4 Gy level to confirm these initial observations. Of 40 patients receiving 14.4 Gy, 13 (32.5%) developed Grade 3-4 RRTs; 46% in adults and 12% in children. The primary dose limiting toxicity was Grade 3-4 hepatic toxicity, which occurred in 12.5% of patients. Noninfectious Grade 3-4 interstitial pneumonia syndrome occurred in 5% of patients. The actuarial probabilities of event-free survival, relapse, and nonrelapse mortality at 2 years were 0.10, 0.81, and 0.47, respectively, for patients who received 14.4 Gy of TBI. Conclusions: The outcome for patients receiving 14.4 Gy of TBI was not different from previous studies of other CY and TBI regimens in patients with advanced lymphoid malignancies. These data showed that the incidence of Grade 3-4 RRTs in adults was greater than the 25% maximum set as the goal of this study, suggesting that 13.2 Gy is a more appropriate dose of TBI for adults, while 14.4 Gy is an appropriate dose for children

SU-F-T-327: Total Body Irradiation In-Vivo Dose Measurements Using Optically Stimulated Luminescence (OSL) NanoDots and Farmer Type Ion Chamber

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Kaur, H; Kumar, S; Sarkar, B; Ganesh, T; Giri, U; Jassal, K; Rathinamuthu, S; Gulia, G; Gopal, V; Mohanti, B; Munshi, A

2016-01-01

Purpose: This study was performed to analyze the agreement between optically stimulated luminescence (OSL) nanoDots measured doses and 0.6 cc Farmer type ionization chamber measured doses during total body irradiation (TBI). Methods: In-vivo dose measurements using OSL nanoDots and Farmer chamber were done in a total of twelve patients who received TBI at our center by bilateral parallel-opposed beams technique. In this technique, the patient is kept inside the TBI box which is filled with rice bags and irradiated using two bilateral parallel opposed beams of 40×40 cm"2 size with 45° collimator rotation at an SSD of 333.5 cm in an Elekta Synergy linear accelerator. All patients received a dose of 2 Gy in single fraction as conditioning regimen. The beams were equally weighted at the midplane of the box. The nanoDots were placed over forehead, right and left neck, right and left lung, umbilicus, right and left abdomen, medial part of thigh, knee and toe. A 0.6 cc Farmer chamber was placed in between the thighs of the patient. Measured doses are reported along with the statistical comparisons using paired sample t-test. Results: For the above sites the mean doses were 212.2±21.1, 218.2±7.6, 218.7±9.3, 215.6±9.5, 217.5±11.5, 214.5±7.7, 218.3±6.8, 221.5±15, 229.1±11.0, 220.5±7.7 and 223.3±5.1 cGy respectively. For all OSL measurements the mean dose was 218.6±11.8 cGy. Farmer chamber measurements yielded a mean dose of 208.8±15.6 cGy. Statistical analysis revealed that there was no significant difference between OSL measured doses in forehead, right and left neck, right and left lung, umbilicus, right and left abdomen and toe and Farmer chamber measured doses (0.72≤p≤0.06). However the mean OSL doses at thigh and knee were statistically different (p<0.05) from the Farmer chamber measurements. Conclusion: OSL measurements were found to be in agreement with Farmer type ionization chamber measurements in in-vivo dosimetry of TBI.

Low-dose total body irradiation and G-CSF without hematopoietic stem cell support in the treatment of relapsed or refractory acute myelogenous leukemia (AML), or AML in second or subsequent remission

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Shulman, Lawrence N.; Tarbell, Nancy J.; Storen, Elizabeth; Marcus, Karen; Mauch, Peter M.

1998-01-01

Purpose: Patients with relapsed acute myelogenous leukemia (AML), who are not eligible for bone marrow transplantation, have a poor prognosis when treated with chemotherapy alone. Total body irradiation (TBI) is an effective modality against AML when used in doses of 1000-1400 cGy with hematopoietic stem cell support. We undertook a phase I study of TBI with granulocyte-colony-stimulating factor (G-CSF) support, without stem cell support in patients with AML either in relapse or second or subsequent remission. Methods and Materials: Patients with relapsed AML, or AML in second or subsequent remission were treated in a phase I study of TBI followed by G-CSF. The first dose level was 200 cGy. After the initial cohort of patients it was clear that patients with overt leukemia did not benefit from this treatment, and subsequent patients were required to be in remission at the time of TBI. Results: Eleven patients were treated, 4 in overt relapse, and 7 in remission. 200 cGy was used in all, and dose escalation was not possible due to prolonged thrombocytopenia in all patients but one. Neutrophil recovery was adequate in those patients who remained in remission after TBI. Patients with overt leukemia had transient reduction in blast counts, but rapid recurrence of their leukemia. Patients treated in remission had short remissions, with the exception of one patient who is in remission 32 months after treatment. Conclusion: There is some antileukemic effect of TBI even at 200 cGy, though this dose appears to be too low to help a significant number of patients. If TBI is to be escalated without stem cell support, then a thrombopoietic agent will need to be used

Abrogation of bone marrow allograft resistance in mice by increased total body irradiation correlates with eradication of host clonable T cells and alloreactive cytotoxic precursors

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Schwartz, E.; Lapidot, T.; Gozes, D.; Singer, T.S.; Reisner, Y.

1987-01-01

Host-vs-graft activity presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, conditioned exactly like leukemia patients, it was shown that residual host clonable T cells, as well as alloreactive cytotoxic precursors, were present in peripheral blood and spleen after completion of cytoreduction. We have now extended this study in a mouse model for allogeneic bone marrow transplantation. C 3 H/HeJ mice were treated by 9 Gy total body irradiation (TBI), and 24 hr later their spleen cells were cultured in the presence of T cell growth factor and phytohemagglutinin according to the limit dilution procedure. After 7 days of culture the average frequency of clonable cells was 2.5 X 10(-3) compared with 37 X 10(-3) in the spleens of normal mice. The T cell derivation of the growing cells was ascertained by complement-mediated cytotoxicity with anti-Thy-1 as well as with anti-Lyt-2 and anti-Ly-3T4. In parallel, we found that the initial engraftment rate of bone marrow allograft in mice given 9 Gy TBI was lower than that found in recipients of syngeneic marrow. The initial engraftment rate was measured by the number of colony-forming units in the spleen and by splenic uptake of 125 IUdR. A slight increase in TBI from 9 Gy to 11 Gy markedly reduced the difference in the number of spleen colony-forming units or the IUdR uptake between recipients of allogeneic and syngeneic bone marrow. This increase in TBI also coincided with eradication of detectable clonable T cells. Moreover, in mice transplanted with T cell-depleted bone marrow after 9 Gy TBI, we also demonstrate that cytotoxicity against donor-type target cells is present in the spleen 10 to 14 days posttransplantation, whereas in mice treated by 11 Gy TBI such alloreactivity could not be detected

Benefits of online in vivo dosimetry for single-fraction total body irradiation

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Eaton, David J., E-mail: davideaton@nhs.net [Department of Radiotherapy, Royal Free Hospital, London (United Kingdom); Warry, Alison J. [Department of Radiotherapy Physics, University College London Hospital, London (United Kingdom); Trimble, Rachel E.; Vilarino-Varela, Maria J.; Collis, Christopher H. [Department of Radiotherapy, Royal Free Hospital, London (United Kingdom)

2014-01-01

Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources.

Benefits of online in vivo dosimetry for single-fraction total body irradiation

International Nuclear Information System (INIS)

Eaton, David J.; Warry, Alison J.; Trimble, Rachel E.; Vilarino-Varela, Maria J.; Collis, Christopher H.

2014-01-01

Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources

Long-term results of total body irradiation in adults with acute lymphoblastic leukemia

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Marnitz, Simone; Zich, Alexander; Budach, Volker; Jahn, Ulrich; Neumann, Oliver [Charite University Medicine, Department of Radiation Oncology, Berlin (Germany); Martus, Peter [University Tuebingen, Institute of Clinical Epidemiology and Applied Biostatistics, Tuebingen (Germany); Arnold, Renate [Charite University Medicine, Campus CVK, Department of Hematology and Oncology, Bone Marrow Transplant Unit, Berlin (Germany)

2014-05-15

The aim of this chart review of adult patients treated for acute lymphoblastic leukemia (ALL) with total body irradiation (TBI) was to evaluate early and late toxicity and long-term outcome. A total of 110 adult patients (34 ± 12 years) with ALL underwent TBI (6 fractions of 2 Gy for a total of 12 Gy) as a part of the treatment regimen before transplantation. Treatment-related toxicity, mortality, and hematologic outcome are reported. Mean follow-up was 70 months. The 2- and 5-year leukemia-free survival rates were 78 and 72 %, respectively. In all, 29 % (32/110) patients suffered from medullary recurrence after a median time of 7 months. Gender was the only statistically significant prognostic factor in terms of overall survival in favor of female patients. Treatment-related mortality and overall survival after 2 and 5 years were 16 and 22 %, and 60 and 52.7 %, respectively. The most frequent late reaction wascGVHD of the skin (n = 33, 30 %). In addition, 15.5 % (17/110 patients) suffered pulmonary symptoms, and 6 patients developed lung fibrosis. Eyes were frequently affected by the radiation (31/110 = 28 %); 12 of 110 patients (11 %) presented with symptoms from osteoporosis, 5 of 110 patients (4.5 %) developed hypothyreosis and 2 patients diabetes mellitus. Of the male patients, 11 % reported erectile dysfunction or loss of libido, while 2 of 36 women reported menopausal syndrome at the mean time of 28 months after treatment with requirement for substitution. No women became pregnant after treatment. No acute or late cardiac toxicities were documented in our patients. No secondary malignancies were documented. Although hematologic outcome was in the upper range of that reported in the literature, treatment-related mortality (TRM) and medullary recurrences remain a challenge. Sophisticated radiation techniques allow for decreasing toxicity to certain organs and/or dose escalation to the bone marrow in highly selected patients in order to improve therapeutic

Traumatic Brain Injury (TBI) in Kids

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... Information Share Facebook Twitter Pinterest Email Print Traumatic Brain Injury (TBI): Condition Information What is TBI? TBI ... external force that affects the functioning of the brain. It can be caused by a bump or ...

Implantation of total body irradiation in radiotherapy

International Nuclear Information System (INIS)

Habitzreuter, Angela Beatriz

2010-01-01

Before implementing a treatment technique, the characteristics of the beam under irradiation conditions must be well acknowledged and studied. Each one of the parameters used to calculate the dose has to be measured and validated before its utilization in clinical practice. This is particularly necessary when dealing with special techniques. In this work, all necessary parameters and measurements are described for the total body irradiation implementation in facilities designed for conventional treatments that make use of unconventional geometries to generate desired enlarged field sizes. Furthermore, this work presents commissioning data of this modality at Hospital das Clinicas of Sao Paulo using comparison of three detectors types for measurements of entrance dose during total body irradiation treatment. (author)

Half-body irradiation-experience of size cases

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Andrade Carvalho, H. de; Aguilar, P.B.; Nadalin, W.; Weissberger, Y.; Scaff, L.A.M.; Lins, J.R.B.

1990-01-01

From 1983 to 1989, six patients with disseminated neoplastic disease non-responsive to conventional therapy were treated with palliative antialgic means. Three patients with breast cancer, two with prostate and one with Ewing's sarcoma received a total of eight treatments. The irradiation was first administered to the half-body presenting worst symptomatology. Total single dose of 800 cGy was delivered to the lower half-body and 600 cGy to the upper half-body. Pain relief was observed 24 to 48 hours after the irradiation in all patients. The haematological tolerance was good and deaths of these patients were not related to complications due to the radiation therapy. (author)

Necrostatin-1 rescues mice from lethal irradiation.

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Huang, Zhentai; Epperly, Michael; Watkins, Simon C; Greenberger, Joel S; Kagan, Valerian E; Bayır, Hülya

2016-04-01

There is an emerging need in new medical products that can mitigate and/or treat the short- and long-term consequences of radiation exposure after a radiological or nuclear terroristic event. The direct effects of ionizing radiation are realized primarily via apoptotic death pathways in rapidly proliferating cells within the initial 1-2days after the exposure. However later in the course of the radiation disease necrotic cell death may ensue via direct and indirect pathways from increased generation of pro-inflammatory cytokines. Here we evaluated radiomitigative potential of necrostatin-1 after total body irradiation (TBI) and the contribution of necroptosis to cell death induced by radiation. Circulating TNFα levels were increased starting on d1 after TBI and associated with increased plasmalemma permeability in ileum of irradiated mice. Necrostatin-1 given iv. 48h after 9.5Gy TBI attenuated radiation-induced receptor interacting protein kinase 3 (RIPK3) serine phosphorylation in ileum and improved survival vs. vehicle. Utilizing apoptosis resistant cytochrome c(-/-) cells, we showed that radiation can induce necroptosis, which is attenuated by RNAi knock down of RIPK1 and RIPK3 or by treatment with necrostatin-1 or -1s whereas 1-methyl-L-tryptophan, an indoleamine-2,3-dioxygenase inhibitor, did not exhibit radiomitigative effect. This suggests that the beneficial effect of necrostatin-1 is likely through inhibition of RIPK1-mediated necroptotic pathway. Overall, our data indicate that necroptosis, a form of programmed necrosis, may play a significant role in cell death contributing to radiation disease and mortality. This study provides a proof of principle that necrostatin-1 and perhaps other RIPK1 inhibitors are promising therapeutic agents for radiomitigation after TBI. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute tolerance of hyperfractionated accelerated total body irradiation

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Latz, D.; Schraube, P.; Wannenmacher, M.

1996-01-01

Background: Acute side effects of total body irradiation lead to intense molestations of the patients. Therefore, it is desirable to take measures to reduce these side effects. In a retrospective study the frequency on acute side effects of a hyperfractionated accelerated total body irradiation was assessed and compared to frequencies of other exposure schedules published in the literature. Additionally the influence of ondansetron on the frequency of nausea and vormiting was investigated. Patients and Method: From 1989 to 1992, 76 patients (47 male, 29 female; median age 38 years) underwent total body irradiation before autologeous bone marrow transplantation. They received 3 daily doses of 1.20 Gy each every 4 h on 4 successive days to a total dose of 14,40 Gy. Thirty-nine patients received 3x8 mg (daily, intravenous or per os) ondansetron during the whole course of irradiation. Results: The most relevant side effects were nausea and vomiting. Patients, who did not receive ondansetron (n=37) showed a nausea and emesis rate of 73%. With ondansetron (n=39) nausea and emesis were reduced to 38%. Also the grade of severity of these side effects was reduced. Conclusions: Ondansetron proved to be an effective medicament for relieving nausea and vormiting during total body irradiation. The results obtained are in concordance with those published in the literature. (orig.) [de

Whole-body irradiation in case of malignant lymphomas of low malignancy

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Labedzki, L; Schmidt, R E; Hartlapp, J H; Illiger, H J; Frommhold, H; Boldt, I

1982-04-01

27 consecutive patients with malignant lymphomas were submittet to whole-body irradiations with doses of 0.5 to 3 Gy. Among these patients ten had been treated before. There were two complete and 16 partial remissions. The condition of five patients could not be considerably improved. Four patients showed a tumor progression during the time of bone marrow depression. The remission period was 11.5 (3 to 22 +) months. The hematologic side effects were considerable; in ten cases, the whole-body irradiation could not be continued because of a thrombocytopenia or an aplastic syndrome. A remarkable fact was the appearance of symptoms similar to that of lupus erythematodes in two patients. An inefficacy of whole-body irradiation did not exclude a response to subsequent chemotherapy. Our own experiences allow to make the following conclusion: in most of all patients with malignant lymphomas of low malignancy a measurable tumor reduction is achieved by whole-body irradiation. Because of the hematologic side effects a whole-body irradiation should be applied only in cases of malignant lymphomas of low malignancy the slow growth of which is proved by observation and which have not been treated before. The thrombocyte numbers should be above 100 000/..mu..l before therapy. Otherwise, the whole-body irradiation has to be stopped before the intended effective dose is reached because of an inevitably developing thrombocytopenia. A whole-body irradiation in case of a malignant lymphoma of low grade malignancy necessitates strict follow-up examinations conducted at regular intervals for a period of at least six weeks after the irradiation. The whole-body irradiation should never be applied as ultima ratio.

Late complications following total-body irradiation and bone marrow rescue in mice: predominance of glomerular nephropathy and hemolytic anemia

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Down, J.D.; Berman, A.J.; Mauch, P.; Warhol, M.

1990-01-01

Late mortality and pathology were assessed in various mouse strains following total-body irradiation (TBI) and bone marrow transplantation. Long-term survival data revealed both radiation dose- and strain-dependent onset of mortality between 1 and 2 years post-treatment. Renal damage appeared to have contributed to the late mortality in most treatment groups as shown by glomerular lesions, elevated blood urea nitrogen and an accompanying fall in hematocrit. Hemolysis was deduced to be the major cause of anemia, as concluded from results of 51 Cr-labeled erythrocyte survival. No decrease in erythropoiesis was evident as seen from spleen and bone marrow 59 Fe uptake. These findings are together consistent with the manifestation of a hemolytic uremic syndrome (HUS) with kidney glomeruli representing the principal sites of injury responsible for both renal dysfunction and microangiopathic hemolysis. (author)

Late complications following total-body irradiation and bone marrow rescue in mice: predominance of glomerular nephropathy and hemolytic anemia

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Down, J.D.; Berman, A.J.; Mauch, P. (Harvard Medical School, Boston, MA (USA)); Warhol, M. (Pennsylvania Hospital, Philadelphia, PA (USA). Dept. of Pathology); Yeap, B. (Dana Farber Cancer Inst., Boston, MA (USA))

1990-03-01

Late mortality and pathology were assessed in various mouse strains following total-body irradiation (TBI) and bone marrow transplantation. Long-term survival data revealed both radiation dose- and strain-dependent onset of mortality between 1 and 2 years post-treatment. Renal damage appeared to have contributed to the late mortality in most treatment groups as shown by glomerular lesions, elevated blood urea nitrogen and an accompanying fall in hematocrit. Hemolysis was deduced to be the major cause of anemia, as concluded from results of {sup 51}Cr-labeled erythrocyte survival. No decrease in erythropoiesis was evident as seen from spleen and bone marrow {sup 59}Fe uptake. These findings are together consistent with the manifestation of a hemolytic uremic syndrome (HUS) with kidney glomeruli representing the principal sites of injury responsible for both renal dysfunction and microangiopathic hemolysis. (author).

Cataract-free interval and severity of cataract after total body irradiation and bone marrow transplantation: influence of treatment parameters

International Nuclear Information System (INIS)

Kempen-Harteveld, M. Loes van; Struikmans, Henk; Kal, Henk B.; Tweel, Ingeborg van der; Mourits, Maarten; Verdonck, Leo F.; Schipper, Jan; Battermann, Jan J.

2000-01-01

Purpose: To determine prospectively the cataract-free interval (latency time) after total body irradiation (TBI) and bone marrow transplantation (BMT) and to assess accurately the final severity of the cataract. Methods and Materials: Ninety-three of the patients who received TBI as a part of their conditioning regimen for BMT between 1982 and 1995 were followed with respect to cataract formation. Included were only patients who had a follow-up period of at least 23 months. TBI was applied in one fraction of 8 Gy or two fractions of 5 or 6 Gy. Cataract-free period was assessed and in 56 patients, who could be followed until stabilization of the cataract had occurred, final severity of the cataract was determined using a classification system. With respect to final severity, two groups were analyzed: subclinical low-grade cataract and high-grade cataract. Cataract-free period and final severity were determined with respect to type of transplantation, TBI dose, and posttransplant variables such as graft versus host disease (GVHD) and steroid treatment. Results: Cataract incidence of the analyzed patients was 89%. Median time to develop a cataract was 58 months for autologous transplanted patients. For allogeneic transplanted patients treated or not treated with steroids, median times were 33 and 46 months, respectively. Final severity was not significantly different for autologous or allogeneic patients. In allogeneic patients, however, final severity was significantly different for patients who had or had not been treated with steroids for GVHD: 93% versus 35% high-grade cataract, respectively. Final severity was also different for patients receiving 1 x 8 or 2 x 5 Gy TBI, from patients receiving 2 x 6 Gy as conditioning therapy: 33% versus 79% high-grade cataract, respectively. The group of patients receiving 2 x 6 Gy comprised, however, more patients with steroid treatment for GVHD. So the high percentage of high-grade cataract in the 2 x 6 Gy group might also

Effects of whole-body and partial-body x irradiation upon epidermal mitotic activity during wound healing in mouse skin

International Nuclear Information System (INIS)

Kobayashi, K.

1977-01-01

Mitotic activity of normal (unwounded) and wounded skin was measured in the control (nonirradiated) and whole-body or partial-body x-irradiated mouse. Higher mitotic activity in the anterior than in the posterior region of the body was found in both the normal and the wounded skin of the control mouse. Whole-body irradiation (500 R) depressed completely the mitotic activity of normal skin 2 to 4 days after irradiation. In spite of this depression in mitotic activity, a surgical incision made 1 to 3 days after irradiation could induce a burst of proliferation after an inhibition of an initial mitosis increase. When the animals were partially irradiated with 500 R 3 days before wounding, it was shown that mitosis at 24 hr after wounding was inhibited markedly by the local effect of irradiation and that mitosis also could be inhibited diversely by the abscopal effect of irradiation. Because of a close similarity of sequential mitotic patterns between whole-body-irradiated and flapped-skin-only-irradiated groups (direct irradiation), the effect of irradiation upon mitosis was considered to be primarily local. Some discussions were made concerning the possible reasons which made a difference in mitotic patterns between the head-only-irradiated group, the irradiated group including the head and other parts of the body except for the skin flap

Sixteen adult patients with acute leukemia treated by chemotherapy, total body irradiation and allogeneic marrow transplantation

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Kodera, Yoshihisa; Morishima, Yasuo; Morishita, Yoshihisa [Nagoya Univ. (Japan). Faculty of Medicine

1984-12-01

Since 1976, 16 adult patients with acute leukemia have been treated by chemotherapy, total body irradiation (TBI) and allogeneic bone marrow transplantation (BMT) in the medical school hospital and the satellite hospitals of Nagoya University. The first group of 10 patients were given marrow grafts at the time of leukemic relapse and the second group of six patients were given the grafts in the period of remission of their disease. For the first group (ALL/ANLL 2:8, age (median) 33, M/F 8:2), HLA-identical donor cells (25 x 10/sup 7//kg(median)) were infused after the patients were conditioned with NSC D 245382 (ACNU) or daunorubicin, cyclophosphamide (CY) and a single shot of 1000 rad of TBI. For the second group (ALL/ANLL 4:2, age (median) 20, M/F 5:1), HLA-identical donor cells (22 x 10/sup 7//kg(median)) were infused after the patients were conditioned with CY and fractionated (250 rad x 4) TBI. All the patients were isolated in a laminar air flow room (LAF) after gut and skin decontamination. Engraftment of donor cells was confirmed in 15 out of the 16 patients. Febrile periods in LAF and the days required for platelet transfusion were prolonged in the first group. All the patients in the first group died within 12-214 days after BMT because of interstitial pneumonitis (7 patients) or bacterial infection (3 patients). On the other hand, five out of six patients in the second group are alive 84-540 days after BMT. For the surviving patients, the complications of chronic graft versus host disease, viral infections, tuberculosis, hepatitis, hemorrhagic cystitis and recurrence of leukemia are now the problems. It can be stated that the patient's clinical condition at the time of BMT is one of the most essential factors for the success of BMT although the effects of other variables, such as a change in the conditioning regimens or the supportive care, must also be carefully analyzed.

Short- and long-term follow-up of thyroid dysfunction after allogeneic bone marrow transplantation without the use of preparative total body irradiation.

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Toubert, M E; Socié, G; Gluckman, E; Aractingi, S; Espérou, H; Devergie, A; Ribaud, P; Parquet, N; Schlageter, M H; Beressi, J P; Rain, J D; Vexiau, P

1997-08-01

We studied the incidence and potential prognostic value of thyroid abnormalities after allogeneic bone marrow transplantation (BMT) without total body irradiation (TBI) conditioning. 77 consecutive patients who received a chemotherapy-alone-based conditioning regimen pretransplant were included. Free serum thyroxine (FT4), free serum triiodothyronine (FT3) and serum thyrotropin (TSH) levels were assayed before and 3 and 14 months after BMT. Patients were classified in three categories: normal thyroid profile if FT3 and FT4 were within the normal range and TSH was normal or low, peripheral thyroid insufficiency (PTI) if TSH was >4 mIU/l, or an 'euthyroid sick syndrome' (ETS) if FT3 and/or FT4 were low and TSH was normal or low. The incidence of thyroid dysfunction at 3 months was 57%, and 29% at 14 months. This was mostly due to the occurrence of ETS which was more frequent at 3 months (48%, 29/61) than at 14 months (19%, 9/48). Furthermore, at 3 months, survival was significantly lower in the ETS group (34.5%) than in the euthyroid group (96.2%), or in the PTI group (83.3%) (P < 0.0001). PTI was observed even in the absence of TBI in 11 patients (14%) and was equally distributed at 3 months (n = 6) and 14 months (n = 5). In conclusion, thyroid dysfunction is not a rare complication even without pretransplant TBI conditioning regimen. Hypothyroidism prevalence was 10%, and ETS, which was more frequently observed, displayed a dismal predictive value at 3 months.

Fractionated or single-dose total body irradiation in 171 acute myeloblastic leukemias in first complete remission: is there a best choice?

International Nuclear Information System (INIS)

Resbeut, Michel; Cowen, Didier; Blaise, Didier; Gluckman, Eliane; Cosset, Jean-Marc; Rio, Bernard; Pene, Francoise; Milpied, Nicolas; Cuillere, Jean-Claude; Reiffers, Josy; Richaud, Pierre

1995-01-01

Purpose: To evaluate the importance of fractionating total body irradiation (TBI) in patients receiving an allogenic bone marrow transplant (BMT) for an acute myeloblastic leukemia (AML) in first complete remission (CR1). Methods and Materials: Between 1983 and 1990, 171 consecutive patients received either single dose TBI (STBI) (n = 65) or fractionated TBI (FTBI) (n = 106) after being conditioned with cyclophosphamide and before receiving a non-T-depleted Human Leucocyte Antigen (HLA)-identical marrow. Both groups were comparable except for date of BMT and diagnosis-to-BMT interval (D-BMT). Results: After 63 months median follow-up, transplant-related mortality (TRM), probability of relapse, and 5-year disease-free survival (DFS) were 0.38 and 0.27 (p = 0.04), 0.29 and 0.26 (p = 0.22), 0.43 and 0.56 (p = 0.06), respectively, for STBI and FTBI. The supposed influence of the schedule of TBI disappeared in the multivariate analysis: TRM was enhanced by severe acute graft vs. host disease (p = 0.0002), early years of transplant (before January 1, 1987) (p = 0.0003), and longer D-BMT intervals (p = 0.038). Relapse was linked to early years of transplant (p < 0.00001), and the absence of chronic GVHD (p = 0.007). Longer DFSs were observed for later years of transplant (after January 1, 1987 and later) (p = 0.001), milder acute GVHD (p = 0.005), and shorter D-BMT intervals (p = 0.045). Important improvements of the results were made during the 7-year observation period: TRM, probability of relapse, and DFS were, respectively, 0.36, 0.28, and 0.46 for patients transplanted before January 1, 1987 vs. 0.21, 0.15, and 0.67 after that date. Conclusion: Our data strongly suggest that allogenic BMT is the best postremission treatment for AML in CR1, and the results are better when BMT shortly follows the achievement of remission. The schedule of TBI was of little importance compared with the improvements made in the management of patients undergoing BMT during the 1980s, and

The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

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Moroni, Maria, E-mail: maria.moroni@usuhs.edu [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Ngudiankama, Barbara F. [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (United States); Christensen, Christine [Division of Comparative Pathology, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Olsen, Cara H. [Biostatistics Consulting Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Owens, Rossitsa [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Lombardini, Eric D. [Veterinary Medicine Department, Armed Forces Research Institute of Medical Sciences, Bangkok (Thailand); Holt, Rebecca K. [Veterinary Science Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Whitnall, Mark H. [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States)

2013-08-01

Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes.

The Gottingen minipig is a model of the hematopoietic acute radiation syndrome: G-colony stimulating factor stimulates hematopoiesis and enhances survival from lethal total-body γ-irradiation.

Science.gov (United States)

Moroni, Maria; Ngudiankama, Barbara F; Christensen, Christine; Olsen, Cara H; Owens, Rossitsa; Lombardini, Eric D; Holt, Rebecca K; Whitnall, Mark H

2013-08-01

We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes. Published by Elsevier Inc.

The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

International Nuclear Information System (INIS)

Moroni, Maria; Ngudiankama, Barbara F.; Christensen, Christine; Olsen, Cara H.; Owens, Rossitsa; Lombardini, Eric D.; Holt, Rebecca K.; Whitnall, Mark H.

2013-01-01

Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes

Q{sub {gamma}-H2AX}, an analysis method for partial-body radiation exposure using {gamma}-H2AX in non-human primate lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Redon, Christophe E., E-mail: redonc@mail.nih.gov [NIH, NCI, CCR, Laboratory of Molecular Pharmacology, Bethesda, MD 20892 (United States); Nakamura, Asako J.; Gouliaeva, Ksenia [NIH, NCI, CCR, Laboratory of Molecular Pharmacology, Bethesda, MD 20892 (United States); Rahman, Arifur; Blakely, William F. [Armed Forces Radiobiology Research Institute, Uniformed Services University, Bethesda, MD 20889-5603 (United States); Bonner, William M. [NIH, NCI, CCR, Laboratory of Molecular Pharmacology, Bethesda, MD 20892 (United States)

2011-09-15

We previously used the {gamma}-H2AX assay as a biodosimeter for total-body irradiation (TBI) exposure ({gamma}-rays) in a rhesus macaque (Macaca mulatta) model. Utilizing peripheral blood lymphocytes and plucked hairs, we obtained statistically significant {gamma}-H2AX responses days after total-body exposure to 1-8.5 Gy ({sup 60}Co {gamma}-rays at 55 cGy min{sup -1}). Here, we introduce a partial-body exposure analysis method, Q{sub {gamma}-H2AX}, which is based on the number of {gamma}-H2AX foci per damaged cells as evident by having one or more {gamma}-H2AX foci per cell. Results from the rhesus monkey - TBI study were used to establish Q{sub {gamma}-H2AX} dose-response calibration curves to assess acute partial-body exposures. {gamma}-H2AX foci were detected in plucked hairs for several days after in vivo irradiation demonstrating this assay's utility for dose assessment in various body regions. The quantitation of {gamma}-H2AX may provide a robust biodosimeter for analyzing partial-body exposures to ionizing radiation in humans.

Effects of categorization training in patients with TBI during postacute rehabilitation: preliminary findings.

Science.gov (United States)

Constantinidou, Fofi; Thomas, Robin D; Scharp, Victoria L; Laske, Kate M; Hammerly, Mark D; Guitonde, Suchita

2005-01-01

Previous research suggests that traumatic brain injury (TBI) interferes with the ability to extract and use attributes to describe objects. This study explored the effects of a systematic Categorization Program (CP) in participants with TBI and noninjured controls. Ten persons with moderate to severe TBI who received comprehensive postacute rehabilitation services and 13 matched noninjured controls participated in the study. All participants received CP training for 3 to 5 hours per week for 10 to 12 weeks that consisted of 8 levels and targeted concept formation, object categorization, and decision-making abilities. The Mayo-Portland Adaptability Inventory-3 (MPAI-3) and the Community Integration Questionnaire (CIQ). Two Categorization Tests (administered pretraining and posttraining) and 3 Probe Tasks (administered at specified intervals during training) assessed skills relating to categorization. Both groups showed significant improvement in categorization performance after the CP training on the 2 Categorization Tests related to the CP. They also were able to generalize and apply categorization and sorting skills in new situations (as measured by the Probe Tasks). Participants with TBI had improved functional outcome performance measured by the MPAI-3 and the CIQ. The systematic and hierarchical structure of the CP is beneficial to participants with TBI during postacute rehabilitation. This study contributes to the growing body of evidence supporting cognitive rehabilitation after moderate to severe TBI.

Defining the Pathophysiological Role of Tau in Experimental TBI

Science.gov (United States)

2017-10-01

neurodegenerative disorder ; and (iii) novel biomarkers for neurodegeneration are non-invasive blood measures of brain dysfunction valuable for the...dissociated from microtubules, aggregated, and mislocalized within cell bodies and proximal dendrites instead of axonal processes, abnormalities that... disorder , and TBI induced by inertial forces, concussive blows, or blast will sometimes lead to chronic, progressive brain atrophy and cognitive

SU-F-T-327: Total Body Irradiation In-Vivo Dose Measurements Using Optically Stimulated Luminescence (OSL) NanoDots and Farmer Type Ion Chamber

Energy Technology Data Exchange (ETDEWEB)

Kaur, H; Kumar, S; Sarkar, B; Ganesh, T; Giri, U; Jassal, K; Rathinamuthu, S; Gulia, G; Gopal, V; Mohanti, B; Munshi, A [Fortis Memorial Research Institute, Gurgaon, Haryana (India)

2016-06-15

Purpose: This study was performed to analyze the agreement between optically stimulated luminescence (OSL) nanoDots measured doses and 0.6 cc Farmer type ionization chamber measured doses during total body irradiation (TBI). Methods: In-vivo dose measurements using OSL nanoDots and Farmer chamber were done in a total of twelve patients who received TBI at our center by bilateral parallel-opposed beams technique. In this technique, the patient is kept inside the TBI box which is filled with rice bags and irradiated using two bilateral parallel opposed beams of 40×40 cm{sup 2} size with 45° collimator rotation at an SSD of 333.5 cm in an Elekta Synergy linear accelerator. All patients received a dose of 2 Gy in single fraction as conditioning regimen. The beams were equally weighted at the midplane of the box. The nanoDots were placed over forehead, right and left neck, right and left lung, umbilicus, right and left abdomen, medial part of thigh, knee and toe. A 0.6 cc Farmer chamber was placed in between the thighs of the patient. Measured doses are reported along with the statistical comparisons using paired sample t-test. Results: For the above sites the mean doses were 212.2±21.1, 218.2±7.6, 218.7±9.3, 215.6±9.5, 217.5±11.5, 214.5±7.7, 218.3±6.8, 221.5±15, 229.1±11.0, 220.5±7.7 and 223.3±5.1 cGy respectively. For all OSL measurements the mean dose was 218.6±11.8 cGy. Farmer chamber measurements yielded a mean dose of 208.8±15.6 cGy. Statistical analysis revealed that there was no significant difference between OSL measured doses in forehead, right and left neck, right and left lung, umbilicus, right and left abdomen and toe and Farmer chamber measured doses (0.72≤p≤0.06). However the mean OSL doses at thigh and knee were statistically different (p<0.05) from the Farmer chamber measurements. Conclusion: OSL measurements were found to be in agreement with Farmer type ionization chamber measurements in in-vivo dosimetry of TBI.

Traumatic Brain Injury (TBI) Data and Statistics

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... TBI Online Concussion Training Press Room Guide to Writing about TBI in News and Social Media Living with TBI HEADS UP to Brain Injury Awareness Get Email Updates To receive email updates about this topic, ...

On the effect of small radiation doses: Desoxyribonucleic acid (DNA) synthesis and DNA repair of thymus, spleen, and bone marrow cells in the rat after fractionated total body X-ray irradiation. Zur Wirkung kleiner Strahlendosen: Desoxyribonukleinsaeure-(DNA-)Synthese und DNA-Reparatur von Thymus-, Milz- und Knochenmarkszellen der Ratte nach fraktionierter Ganzkoerperroentgenbestrahlung

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Tempel, K.; Ehling, G. (Muenchen Univ. (Germany, F.R.). Inst. fuer Pharmakologie, Toxikologie und Pharmazie)

1989-09-01

After three to seven days following to fractionated total body X-ray irradiation (TBI) (four expositions with doses of 0.3 to 5.0 cGy per fraction at intervals of 24 hours), a maximum 50 percent stimulation of the semiconservative DNA synthesis (SDS) of spleen cells was measured in vitro. This was not dependent of the fact if an acute high-dose (400 and/or 800 cGy) unique irradiation was applied after the fractionated TBI at the moment of stimulation. A significant increase of {sup 3}H-thymidine incorporation into the DNA of bone marrow and thymus cells was only found when doses of 1.25 cGy per fraction had been used. After fractionated TBI with doses of {ge}5 cGy per fraction, an increase of DNA synthesis resistant to hydroxyurea ('unprogrammed' DNA synthesis, UDS) was demonstrated in spleen cells. The UV-simulated UDS decreased proportionately. The sedimentation of thymus, spleen, and bone marrow nucleoids in a neutral saccharose gradient gave no evidence of an increased DNA repair capacity after fractionated TBI. Whereas the SDS stimulation by fractionated TBI with small doses can be explained by a modified proliferation behavior of exposed cells, the UDS behavior of spleen cells after considerably higher radiation doses suggests regenerative processes correlated with an increased number of cells resistant to hydroxyurea and cells presenting an UV repair deficiency. These findings can be considered to be a further proof of the assumed immune-stimulating effect of small radiation doses. (orig.).

A new Bayesian model applied to cytogenetic partial body irradiation estimation

International Nuclear Information System (INIS)

Higueras, Manuel; Puig, Pedro; Ainsbury, Elizabeth A.; Vinnikov, Volodymyr A.; Rothkamm, Kai

2016-01-01

A new zero-inflated Poisson model is introduced for the estimation of partial body irradiation dose and fraction of body irradiated. The Bayes factors are introduced as tools to help determine whether a data set of chromosomal aberrations obtained from a blood sample reflects partial or whole body irradiation. Two examples of simulated cytogenetic radiation exposure data are presented to demonstrate the usefulness of this methodology in cytogenetic biological dosimetry. (authors)

Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

Energy Technology Data Exchange (ETDEWEB)

James, N D; Apperley, J F; Kam, K C; Mackinnon, S; Goldman, J M; Goolden, A W.G.; Sikora, K [Royal Postgraduate Medical School, London (UK)

1989-03-01

Between August 1985 and October 1987 35 patients with chronic myeloid leukaemia (CML) were treated by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n=31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n=35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. TLI did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. It is concluded that addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This is not associated with significantly increased toxicity. (author).

Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

International Nuclear Information System (INIS)

James, N.D.; Apperley, J.F.; Kam, K.C.; Mackinnon, S.; Goldman, J.M.; Goolden, A.W.G.; Sikora, K.

1989-01-01

Between August 1985 and October 1987 35 patients with chronic myeloid leukaemia (CML) were treated by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n=31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n=35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. TLI did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. It is concluded that addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This is not associated with significantly increased toxicity. (author)

Quality control of dosimetry in total body irradiation

International Nuclear Information System (INIS)

Kallinger, W.

1986-11-01

An on-line dose measurement system for the quality control of the treatment of leukemia by means of total body irradiation with Co-60 gamma radiation is introduced. An ionization chamber and 5 diodes arranged on the surface of the patient incorporated with a microprocessor provides useful information and data necessary for the treatment. Following the concerted treatment procedure employing this system, the treatment of leukemia by means of total body irradiation is expected to be improved

Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

Science.gov (United States)

Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

2016-08-01

Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement.

Science.gov (United States)

Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L; Creasey, Graham H; Manley, Geoffrey T; Ferguson, Adam R; Bresnahan, Jacqueline C; Beattie, Michael S

2013-10-01

A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral

Total body irradiation: what schedule(s). Les irradiations corporelles totales: quel(s) schema(s)

Energy Technology Data Exchange (ETDEWEB)

Cosset, J M [Institut Curie, 75 - Paris (France)

1993-01-01

In this article, the author explains why a whole-body irradiation is still an essential step before a bone marrow graft. He presents irradiation protocols for acute myeloid leukemia and chronic myeloid leukemia. 14 refs.

Comparative studies in the cellular immunostimulation by whole body irradiation

International Nuclear Information System (INIS)

Dietz, R.; Schwarze, G.

1992-01-01

The effect of the cellular immune response by total body irradiation was investigated. The transplant survival (skin grafts) was determined as immune parameter. Donors were colony bred Wistar rats and recipients were colony bred Sprague Dawley rats. The investigations were carried out with irradiated rats and with rats irradiated after thymectomy and/or adrenalectomy as well as with animals without irradiation. A single total-body irradiation (1 and 2 Gy) was administered. The skin graft survival in irradiated rats was significant shorter (radiogenic immunostimulation) than in unirradiated rats; there were no significant differences between the operated (thymectomy and/or adrenalectomy) and not operated animals. Including precedent examinations this radiogenic immunostimulation is caused by relativly selective inactivation of T-suppressor cells. (orig.) [de

C-reactive protein and serum amyloid A as early-phase and prognostic indicators of acute radiation exposure in nonhuman primate total-body irradiation model

Energy Technology Data Exchange (ETDEWEB)

Ossetrova, N.I., E-mail: ossetrova@afrri.usuhs.mil [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bldg. 42, Bethesda, MD 20889-5603 (United States); Sandgren, D.J.; Blakely, W.F. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bldg. 42, Bethesda, MD 20889-5603 (United States)

2011-09-15

Terrorist radiological attacks or nuclear accidents could expose large numbers of people to ionizing radiation. In mass-casualty radiological incidents early medical-management requires triage tools for first-responders to quantitatively identify individuals exposed to life-threatening radiation doses and for early initiation (i.e., within one day after radiation exposure) of cytokine therapy for treatment of bone marrow acute radiation syndrome. Herein, we present results from 30 rhesus macaques total-body irradiated (TBI) to a broad dose range of 1-8.5 Gy with {sup 60}Co {gamma}-rays (0.55 Gy min{sup -1}) and demonstrate dose- and time-dependent changes in blood of C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) measured by enzyme linked immunosorbent assay (ELISA). CRP and SAA dose-response results are consistent with {approx}1 Gy and {approx}0.2 Gy thresholds for photon-exposure at 24 h after TBI, respectively. Highly significant elevations of CRP and SAA (p = 0.00017 and p = 0.0024, respectively) were found in animal plasma at 6 h after all TBI doses suggesting their potential use as early-phase biodosimeters. Results also show that the dynamics and content of CRP and SAA levels reflect the course and severity of the acute radiation sickness (ARS) and may function as prognostic indicators of ARS outcome. These results demonstrate proof-of-concept that these radiation-responsive proteins show promise as a complementary approach to conventional biodosimetry for early assessment of radiation exposures and may also contribute as diagnostic indices in the medical management of radiation accidents.

Effect of whole body irradiation on different tissues

International Nuclear Information System (INIS)

Casati, V.; Nardino, A.; Tomassi, I.; Becciolini, A.; Rizzi, M.; Martelli, T.

1979-01-01

The uptake and elimination of 14 C leucine were analysed in controls and in rats irradiated 2 h before injection with 8 Gy whole-body irradiation. Plasma, small intestine, kidney and skin were assayed after homogenization for TCA soluble and insoluble activity curves. In highly differentiated tissues with poor proliferative activity and low protein turnover, the uptake and elimination of the tracer did not appear to be affected by irradiation. In the small intestine differences between control and irradiated animals seemed significant. (Auth.)

Growth in children following irradiation for bone marrow transplantation

International Nuclear Information System (INIS)

Bushhouse, S.; Ramsay, N.K.; Pescovitz, O.H.; Kim, T.; Robison, L.L.

1989-01-01

Longitudinal height data from 46 pediatric bone marrow transplant (BMT) patients, including 18 with aplastic anemia (AA), 19 with acute nonlymphoblastic leukemia (ANLL), and 9 with acute lymphoblastic leukemia (ALL), were analyzed to assess growth posttransplantation. Patients were prepared for BMT with high-dose cyclophosphamide followed by 7.5 Gy single-dose irradiation; AA patients received total lymphoid irradiation (TLI), and leukemia patients received total body irradiation (TBI). AA patients demonstrated reduced height posttransplant as reflected in a negative mean standard deviation score. The observed reduction was statistically significant only at 3 years following transplant. In contrast, leukemia patients showed a significant loss in relative height that was first visible at 1 year post-BMT and continued until at least 4 years post-BMT. Mean growth velocities in the leukemia patients were significantly below median for the 3 years following transplant. With a median follow-up of 4 years, antithymocyte globulin plus steroids in combination with methotrexate as graft vs. host prophylaxis was associated with less severe growth suppression than methotrexate alone, while there were no significant associations between growth during the first 2 years following transplant and prepubertal status at transplant (as defined by age), graft vs. host disease, thyroid or gonadal function, or previous therapies received by the leukemia patients. Children undergoing marrow transplantation, particularly those receiving TBI, are at significant risk of subsequent growth suppression

Validating Multidimensional Outcome Assessment Using the TBI Common Data Elements: An Analysis of the TRACK-TBI Pilot Sample.

Science.gov (United States)

Nelson, Lindsay D; Ranson, Jana; Ferguson, Adam R; Giacino, Joseph; Okonkwo, David O; Valadka, Alex; Manley, Geoffrey; McCrea, Michael

2017-06-08

The Glasgow Outcome Scale-Extended (GOSE) is often the primary outcome measure in clinical trials for traumatic brain injury (TBI). Although the GOSE's capture of global function outcome has several strengths, concerns have been raised about its limited ability to identify mild disability and failure to capture the full scope of problems patients exhibit after TBI. This analysis examined the convergence of disability ratings across a multidimensional set of outcome domains in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot study. The study collected measures recommended by the TBI Common Data Elements (CDE) Workgroup. Patients presenting to 3 emergency departments with a TBI of any severity enrolled in TRACK-TBI prospectively after injury; outcome measures were collected at 3 and six months postinjury. Analyses examined frequency of impairment and overlap between impairment status across the CDE outcome domains of Global Level of Functioning (GOSE), Neuropsychological (cognitive) Impairment, Psychological Status, TBI Symptoms, and Quality of Life. GOSE score correlated in the expected direction with other outcomes (M Spearman's rho = .21 and .49 with neurocognitive and self-report outcomes, respectively). The subsample in the Upper Good Recovery (GOSE 8) category appeared quite healthy across most other outcomes, although 19.0% had impaired executive functioning (Trail Making Test Part B). A significant minority of participants in the Lower Good Recovery subgroup (GOSE 7) met criteria for impairment across numerous other outcome measures. The findings highlight the multidimensional nature of TBI recovery and the limitations of applying only a single outcome measure.

Thiotepa-based versus total body irradiation-based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Science.gov (United States)

Eder, Sandra; Labopin, Myriam; Arcese, William; Or, Reuven; Majolino, Ignazio; Bacigalupo, Andrea; de Rosa, Gennaro; Volin, Liisa; Beelen, Dietrich; Veelken, Hendrik; Schaap, Nicolaas P M; Kuball, Jurgen; Cornelissen, Jan; Nagler, Arnon; Mohty, Mohamad

2016-01-01

Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Physical aspects of total-body irradiation at the Middlesex Hospital (UCL group of hospitals), London 1988 - 1993: II. In vivo planning and dosimetry

Science.gov (United States)

Planskoy, B.; Tapper, P. D.; Bedford, A. M.; Davis, F. M.

1996-11-01

Part II of this paper gives the results of applying the TBI methods described in part I, to in vivo patient planning and dosimetry. Patients are planned on nine CT based body slices, five of which pass through the lungs. Planned doses are verified with ten silicon diodes applied bi-laterally to five body sites, at each treatment. LiF TLDs are applied to seven other body sites at the first treatment only. For 84 patients and at least 1016 measurements per body site with the diodes, the mean measured total doses agreed with planned doses within at most 2% except at lung levels, where the mean measured dose was 3% too low. Standard deviations of the measurements about the mean were between 2.4 and 3.1%. For the LiF TLDs, the mean measured doses for all seven body sites were within of planned doses. A separate assessment of measured entrance and transmitted doses showed that the former agreed well with planned doses, but that the latter tended to be low, especially over the lungs, and that they had a wider dispersion. Possible reasons for this are discussed. These results show measurement uncertainties similar to those for non-TBI treatments of Nilsson et al, Leunens et al and Essers et al. An analysis of the treatment plans showed a mean dose inhomogeneity in the body (75 patients, nine slices) of (1 s.d.) and in the lungs (40 patients, five slices) of (1 s.d.). The conclusions are that, overall, the methods are reasonably satisfactory but that, with an extra effort, even closer agreement between measured and planned doses and a further limited reduction in the body dose inhomogeneity could be obtained. However, if it were thought desirable to make a substantial reduction in the dose inhomogeneity in the body and lungs, this could only be achieved with the available equipment by changing from lateral to anterior - posterior irradiation and any potential advantages of this change would have to be balanced against a likely deterioration in patient comfort and an

Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation.

Science.gov (United States)

Wong, Jeffrey Y C; Rosenthal, Joseph; Liu, An; Schultheiss, Timothy; Forman, Stephen; Somlo, George

2009-01-01

Total-body irradiation (TBI) has an important role in patients undergoing hematopoietic cell transplantation (HCT), but is associated with significant toxicities. Targeted TBI using helical tomotherapy results in reduced doses to normal organs, which predicts for reduced toxicities compared with standard TBI. Thirteen patients with multiple myeloma were treated in an autologous tandem transplantation Phase I trial with high-dose melphalan, followed 6 weeks later by total-marrow irradiation (TMI) to skeletal bone. Dose levels were 10, 12, 14, and 16 Gy at 2 Gy daily/twice daily. In a separate allogeneic HCT trial, 8 patients (5 with acute myelogenous leukemia, 1 with acute lymphoblastic leukemia, 1 with non-Hodgkin's lymphoma, and 1 with multiple myeloma) were treated with TMI plus total lymphoid irradiation plus splenic radiotherapy to 12 Gy (1.5 Gy twice daily) combined with fludarabine/melphalan. For the 13 patients in the tandem autologous HCT trial, median age was 54 years (range, 42-66 years). Median organ doses were 15-65% that of the gross target volume dose. Primarily Grades 1-2 acute toxicities were observed. Six patients reported no vomiting; 9 patients, no mucositis; 6 patients, no fatigue; and 8 patients, no diarrhea. For the 8 patients in the allogeneic HCT trial, median age was 52 years (range, 24-61 years). Grades 2-3 nausea, vomiting, mucositis, and diarrhea were observed. In both trials, no Grade 4 nonhematologic toxicity was observed, and all patients underwent successful engraftment. This study shows that TMI using helical tomotherapy is clinically feasible. The reduced acute toxicities observed compare favorably with those seen with standard TBI. Initial results are encouraging and warrant further evaluation as a method to dose escalate with acceptable toxicity or to offer TBI-containing regimens to patients unable to tolerate standard approaches.

Image-Guided Total-Marrow Irradiation Using Helical Tomotherapy in Patients With Multiple Myeloma and Acute Leukemia Undergoing Hematopoietic Cell Transplantation

International Nuclear Information System (INIS)

Wong, Jeffrey Y.C.; Rosenthal, Joseph; Liu An; Schultheiss, Timothy; Forman, Stephen; Somlo, George

2009-01-01

Purpose: Total-body irradiation (TBI) has an important role in patients undergoing hematopoietic cell transplantation (HCT), but is associated with significant toxicities. Targeted TBI using helical tomotherapy results in reduced doses to normal organs, which predicts for reduced toxicities compared with standard TBI. Methods and Materials: Thirteen patients with multiple myeloma were treated in an autologous tandem transplantation Phase I trial with high-dose melphalan, followed 6 weeks later by total-marrow irradiation (TMI) to skeletal bone. Dose levels were 10, 12, 14, and 16 Gy at 2 Gy daily/twice daily. In a separate allogeneic HCT trial, 8 patients (5 with acute myelogenous leukemia, 1 with acute lymphoblastic leukemia, 1 with non-Hodgkin's lymphoma, and 1 with multiple myeloma) were treated with TMI plus total lymphoid irradiation plus splenic radiotherapy to 12 Gy (1.5 Gy twice daily) combined with fludarabine/melphalan. Results: For the 13 patients in the tandem autologous HCT trial, median age was 54 years (range, 42-66 years). Median organ doses were 15-65% that of the gross target volume dose. Primarily Grades 1-2 acute toxicities were observed. Six patients reported no vomiting; 9 patients, no mucositis; 6 patients, no fatigue; and 8 patients, no diarrhea. For the 8 patients in the allogeneic HCT trial, median age was 52 years (range, 24-61 years). Grades 2-3 nausea, vomiting, mucositis, and diarrhea were observed. In both trials, no Grade 4 nonhematologic toxicity was observed, and all patients underwent successful engraftment. Conclusions: This study shows that TMI using helical tomotherapy is clinically feasible. The reduced acute toxicities observed compare favorably with those seen with standard TBI. Initial results are encouraging and warrant further evaluation as a method to dose escalate with acceptable toxicity or to offer TBI-containing regimens to patients unable to tolerate standard approaches

Mild TBI Diagnosis and Management Strategies

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Department of Veterans Affairs — The Mild Traumatic Brain Injury (TBI) Diagnosis and Management Strategies will assist in the study of TBI issues, such as the Influence of Concussion on Persistent...

Relative effect of radiation dose rate on hemopoietic and nonhemopoietic lethality of total-body irradiation

International Nuclear Information System (INIS)

Peters, L.J.; McNeill, J.; Karolis, C.; Thames, H.D. Jr.; Travis, E.L.

1986-01-01

Experiments were undertaken to determine the influence of dose rate on the toxicity of total-body irrdiation (TBI) with and without syngeneic bone-marrow rescue in mice. The results showed a much greater dose-rate dependence for death from nonhemopoietic toxicity than from bone-marrow ablation, with the ratio of LD 50 's increasing from 1.73 at 25 cGy/min to 2.80 at 1 cGy/min. At the higher dose rates, dose-limiting nonhemopoietic toxicity resulted from late organ injury, affecting the lungs, kidneys, and liver. At 1 cGy/min the major dose-limiting nonhemopoietic toxicity was acute gastrointestinal injury. The implications of these results in the context of TBI in preparation for bone-marrow transplantation are discussed. 15 refs., 4 figs

Total body irradiation with an arc and a gravity-oriented compensator

International Nuclear Information System (INIS)

Chui, C.-S.; Fontenla, Doracy P.; Mullokandov, Edward; Kapulsky, Alex; Lo, Y.-C.; Lo, C.-J.

1997-01-01

Purpose: To deliver uniform dose distributions for total-body irradiation (TBI) with an arc field and a gravity-oriented compensator. This technique allows the patient to be treated lying on the floor in a small treatment room. Methods and Materials: Through the sweeping motion of the gantry, a continuous arc field can deliver a large field to a patient lying on the floor. The dose profile, however, would not be uniform if no compensator were used, due to the effects of inverse square variation of beam intensity with distance as well as the slanted depth in patient. To solve this problem, a gravity-oriented compensator made of cerrobend alloy was designed. This compensator has a cross-section of an inverted isosceles triangle, with the apex always pointing downward, due to gravity. By properly selecting the thickness of the compensator, the width of the base, and the distance between the pivots to the base, the difference in the path length through the compensator can be made just right to compensate the effects of inverse-square and slanted depth, thus producing a uniform dose profile. Results: Arc fields with a gravity-oriented compensator were used for 6, 10, 15, and 18 MV photon beams. The arc field can cover a patient with a height up to 180 cm. The field width was chosen from 32 to 40 cm at the machine isocenter. The optimal thickness of the compensator was found to be 2.5 cm, and its base was 25 cm wide. The distance from the pivot points to the flat surface of the compensator proximal to the beam ranges from 13 to 14 cm for different beam energies. The dose uniformity at a depth of 10 cm is within ±5% for all beam energies used in this study. Conclusion: Highly uniform dose profiles for TBI treatments can be delivered with an arc and a gravity-oriented compensator. The proposed technique is simple and versatile. A single compensator can be used for all energies, because the amount of compensation can be adjusted by changing the distance to the pivot and

Renal Shielding and Dosimetry for Patients With Severe Systemic Sclerosis Receiving Immunoablation With Total Body Irradiation in the Scleroderma: Cyclophosphamide or Transplantation Trial

International Nuclear Information System (INIS)

Craciunescu, Oana I.; Steffey, Beverly A.; Kelsey, Chris R.; Larrier, Nicole A.; Paarz-Largay, Cathy J.; Prosnitz, Robert G.; Chao, Nelson; Chute, John; Gasparetto, Cristina; Horwitz, Mitchell; Long, Gwynn; Rizzieri, David; Sullivan, Keith M.

2011-01-01

Purpose: To describe renal shielding techniques and dosimetry in delivering total body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled in a hematopoietic stem cell transplant protocol. Methods and Materials: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) protocol uses a lymphoablative preparative regimen including 800 cGy TBI delivered in two 200-cGy fractions twice a day before CD34 + selected autologous hematopoietic stem cell transplantation. Lung and kidney doses are limited to 200 cGy to protect organs damaged by SSc. Kidney block proximity to the spinal cord was investigated, and guidelines were developed for acceptable lumbar area TBI dosing. Information about kidney size and the organ shifts from supine to standing positions were recorded using diagnostic ultrasound (US). Minimum distance between the kidney blocks (dkB) and the lumbar spine region dose was recorded, and in vivo dosimetry was performed at several locations to determine the radiation doses delivered. Results: Eleven patients were treated at our center with an anteroposterior (AP)/posteroanterior (PA) TBI technique. A 10% to 20% dose inhomogeneity in the lumbar spine region was achieved with a minimum kidney block separation of 4 to 5 cm. The average lumbar spine dose was 179.6 ± 18.1 cGy, with an average dkB of 5.0 ± 1.0 cm. Kidney block shield design was accomplished using a combination of US and noncontrast computerized tomography (CT) or CT imaging alone. The renal US revealed a wide range of kidney displacement from upright to supine positions. Overall, the average in vivo dose for the kidney prescription point was 193.4 ± 5.1 cGy. Conclusions: The dose to the kidneys can be attenuated while maintaining a 10% to 20% dose inhomogeneity in the lumbar spine area. Kidneys were localized more accurately using both US and CT imaging. With this technique, renal function has been preserved, and the study continues to enroll patients.

External-beam boost prior to total-body irradiation in relapsed NHL transplant patients

Energy Technology Data Exchange (ETDEWEB)

Monson, Jedidiah M; Neuberg, Donna; Freedman, Arnold S; Tarbell, Nancy J; Nadler, Lee M; Mauch, Peter

1995-07-01

PURPOSE: To determine the impact of an external beam boost (EBB) on the outcome, relapse pattern and normal tissue toxicities of patients undergoing total-body irradiation (TBI) prior to bone marrow transplantation (BMT) for relapsed NHL. MATERIALS AND METHODS: Between 1982 and 1994, 299 patients at our institution underwent BMT for relapsed NHL. Patients underwent induction chemotherapy (CT) followed by conditioning with cyclophosphamide and 12 Gy TBI delivered in 6 fractions over 3 days. A total of 77 patients had persistent gross disease, defined as 2 cm or greater, after induction CT and received an EBB prior to BMT (EBB cohort). The median EBB dose was 28.8 Gy (range, 5-63), the median field size was 13 cm{sup 2} (range, 5-29.4) and the median time from EBB to BMT was 3 weeks (range, 1-20). A total of 222 patients were free of measurable disease or had disease measuring <2cm after CT and did not receive EBB (no-EBB cohort). To assess normal tissue toxicity, patients' simulation films and/or treatment records were reviewed for all 77 patients treated with local EBB and estimates were made of the percentage lung, heart and kidney in the radiation field. RESULTS: A total of 79 of 222 patients (36%) in the no-EBB cohort have relapsed; 33 of 77 patients (43%) in the EBB cohort have relapsed (p=0.28, by Fisher exact test). Median time to relapse after BMT was 54 months for the no-EBB cohort and 38 months for the EBB cohort (p=0.26, by log-rank test). The 3-year actuarial freedom from relapse (deaths in remission censored) was 59% for the no-EBB cohort (90% CI: 52-66%) and 51% for the EBB cohort (90% CI: 40-62%). Data on site of relapse was available for 101 of the 112 relapses (75 no-EBB, 26 EBB). For the no-EBB cohort 33 of 75 relapses (44%) were in sites of prior nodal disease only. For the EBB cohort, 12 of 26 relapses (46%) were in sites of prior nodal disease only, of these, only 6 (23%) were within the EBB treatment field. A total of 26 patients had thoracic

Statistical analysis of dose heterogeneity in circulating blood: Implications for sequential methods of total body irradiation

International Nuclear Information System (INIS)

Molloy, Janelle A.

2010-01-01

Purpose: Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these ''sequential'' techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Methods: Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designs that incorporate deliberate organ sparing. Results: The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than ±10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times

Statistical analysis of dose heterogeneity in circulating blood: implications for sequential methods of total body irradiation.

Science.gov (United States)

Molloy, Janelle A

2010-11-01

Improvements in delivery techniques for total body irradiation (TBI) using Tomotherapy and intensity modulated radiation therapy have been proven feasible. Despite the promise of improved dose conformality, the application of these "sequential" techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the craniocaudal dimension. The average perfusion period for human circulation was estimated to be approximately 78 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates, and fractionation schemes. The model was then refined to account for random dispersion superimposed onto the underlying periodic blood flow. Finally, a fully stochastic model was developed using binomial and trinomial probability distributions. These models allowed for the analysis of nonlinear sequential treatment modalities and treatment designs that incorporate deliberate organ sparing. The dose received by individual blood voxels exhibited asymmetric behavior that depended on the coherence among the blood velocity, circulation phase, and the spatiotemporal characteristics of the irradiation beam. Heterogeneity increased with the perfusion period and decreased with the treatment time. Notwithstanding, heterogeneity was less than +/- 10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods, and short treatment times. However, the EUD was

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

International Nuclear Information System (INIS)

Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M.

1993-01-01

The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing 60 Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs

Long-term results of total body irradiation in adults with acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Marnitz, Simone; Zich, Alexander; Budach, Volker; Jahn, Ulrich; Neumann, Oliver; Martus, Peter; Arnold, Renate

2014-01-01

The aim of this chart review of adult patients treated for acute lymphoblastic leukemia (ALL) with total body irradiation (TBI) was to evaluate early and late toxicity and long-term outcome. A total of 110 adult patients (34 ± 12 years) with ALL underwent TBI (6 fractions of 2 Gy for a total of 12 Gy) as a part of the treatment regimen before transplantation. Treatment-related toxicity, mortality, and hematologic outcome are reported. Mean follow-up was 70 months. The 2- and 5-year leukemia-free survival rates were 78 and 72 %, respectively. In all, 29 % (32/110) patients suffered from medullary recurrence after a median time of 7 months. Gender was the only statistically significant prognostic factor in terms of overall survival in favor of female patients. Treatment-related mortality and overall survival after 2 and 5 years were 16 and 22 %, and 60 and 52.7 %, respectively. The most frequent late reaction wascGVHD of the skin (n = 33, 30 %). In addition, 15.5 % (17/110 patients) suffered pulmonary symptoms, and 6 patients developed lung fibrosis. Eyes were frequently affected by the radiation (31/110 = 28 %); 12 of 110 patients (11 %) presented with symptoms from osteoporosis, 5 of 110 patients (4.5 %) developed hypothyreosis and 2 patients diabetes mellitus. Of the male patients, 11 % reported erectile dysfunction or loss of libido, while 2 of 36 women reported menopausal syndrome at the mean time of 28 months after treatment with requirement for substitution. No women became pregnant after treatment. No acute or late cardiac toxicities were documented in our patients. No secondary malignancies were documented. Although hematologic outcome was in the upper range of that reported in the literature, treatment-related mortality (TRM) and medullary recurrences remain a challenge. Sophisticated radiation techniques allow for decreasing toxicity to certain organs and/or dose escalation to the bone marrow in highly selected patients in order to improve therapeutic

Whole-body irradiation technique: physical aspects

International Nuclear Information System (INIS)

Venencia, D.; Bustos, S.; Zunino, S.

1998-01-01

The objective of this work has been to implement a Total body irradiation technique that fulfill the following conditions: simplicity, repeatability, fast and comfortable positioning for the patient, homogeneity of the dose between 10-15 %, short times of treatments and In vivo dosimetric verifications. (Author)

Half body irradiation of malignant diseases in childhood

International Nuclear Information System (INIS)

Gocheva, L.

2000-01-01

The possibilities of modern medicine make the prognosis of children with malignant diseases more optimistic, compared to adult patients. At the present stage the favourable outcome of pediatric oncological diseases varies within the limits of 50 - 80 %. Despite the good treatment results after optimal complex treatment, the rest of the ill children represent a serious therapeutical problem. The achieved good local tumor control after performed radiotherapy represents a potential for its application as a systemic therapy in patients with advanced or resistant to chemotherapy tumours. The radiobiological bases of the half body irradiation as a systemic therapy in pediatric oncology and as one of the main forms of large field irradiation are considered. The important clinical investigations have been discussed. Half body irradiation can be considered as a valuable alternative of chemotherapy and as a complementary systemic treatment in the case of advanced malignant diseases in children's age. (author)

SU-E-T-357: Electronic Compensation Technique to Deliver Total Body Dose

Energy Technology Data Exchange (ETDEWEB)

Lakeman, T [State University of New York at Buffalo, Buffalo, NY (United States); Wang, I; Podgorsak, M [State University of New York at Buffalo, Buffalo, NY (United States); Roswell Park Cancer Institute, Buffalo, NY (United States)

2015-06-15

Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient’s immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has conventionally been used to compensate for the varying thickness through the entire body in large-field TBI. The goal of this study is to pursue utilizing the modern electronic compensation technique to more accurately and efficiently deliver dose to patients in need of TBI. Methods: Treatment plans utilizing electronic compensation to deliver a total body dose were created retrospectively for patients for whom CT data had been previously acquired. Each treatment plan includes two, specifically weighted, pair of opposed fields. One pair of open, large fields (collimator=45°), to encompass the patient’s entire anatomy, and one pair of smaller fields (collimator=0°) focused only on the thicker midsection of the patient. The optimal fluence for each one of the smaller fields was calculated at a patient specific penetration depth. Irregular surface compensators provide a more uniform dose distribution within the smaller opposed fields. Results: Dose-volume histograms (DVH) were calculated for the evaluating the electronic compensation technique. In one case, the maximum body doses calculated from the DVH were reduced from the non-compensated 195.8% to 165.3% in the electronically compensated plans, indicating a more uniform dose with the region of electronic compensation. The mean body doses calculated from the DVH were also reduced from the non-compensated 120.6% to 112.7% in the electronically compensated plans, indicating a more accurate delivery of the prescription dose. All calculated monitor units were well within clinically acceptable limits. Conclusion: Electronic compensation technique for TBI will not substantially increase the beam on time while it can significantly reduce the compensator

Enhanced Cognitive Rehabilitation to Treat Comorbid TBI and PTSD

Science.gov (United States)

2015-10-01

injury (TBI) and posttraumatic stress disorder ( PTSD ) benefit fully from interventions for both conditions. PTSD and TBI occur together frequently in...veterans with comorbid traumatic brain injury and posttraumatic stress disorder : study protocol for a randomized controlled trial. CONCLUSION: In...moderate TBI (mTBI) and PTSD . Emotional symptoms are likely a main cause of the persistence of post -concussive symptoms while thinking problems

Total body irradiation as a form of preparation for bone marrow transplantation

International Nuclear Information System (INIS)

Inoue, Toshihiko

1987-01-01

The history of total body irradiation and bone marrow transplantation is surprisingly old. Following the success of Thomas et al. in the 1970s, bone marrow transplantation appeared to be the sole curative treatment modality for high-risk leukemia. A supralethal dose of total body irradiation was widely accepted as a form of preparation for bone marrow transplantation. In this paper, I described the present status of bone marrow transplantation for leukemia patients in Japan based on the IVth national survey. Since interstitial pneumonitis was one of the most life threatening complications after bone marrow transplantation, I mentioned the dose, dose-rate and fraction of total body irradiation in more detail. In addition, I dealt with some problems of the total body irradiation, such as dose prescription, compensating contour as well as inhomogeneity, and shielding for the highrisk organs. (author) 82 refs

Morphological studies on the healing process of tooth extraction wounds in whole body irradiated rats

International Nuclear Information System (INIS)

Hosokawa, Yoichiro

1991-01-01

The present studies were performed to investigate the healing process of the tooth extraction wound in whole body irradiated rats and to clarify the effect of irradiation on bone metabolism. One hundred and seven Wistar rats of about 100 g body weight were used and divided into 3 groups. Whole body irradiated rats were given single exposure with a dose of 8 Gy. The region of the left upper molars of local irradiated rats as controls, was exposed to 8 Gy. On the 7th day after irradiation, the left upper first molar of each rat was extracted. The rats were sacrificed at intervals of 1 to 14 days after extraction. Non-irradiated rats were sacrificed at the same intervals after extraction. The maxillary bone including the extraction wound was evaluated, histologically, histometrically and ultrastructurally. From the histological and histometrical findings, the difference of the healing process between non-irradiated rats and locally irradiated rats is not significant. In whole body irradiated rats, the healing process especially in the socket was disturbed. The osteoblastic new bone formation following production of granulation tissue was interfered with. Ultrastructurally, the cytoplasmic organellae were poorly developed in the osteoblast and osteoid formation was reduced in the socket. But periosteal new bone formation was the same as that of the locally irradiated rats. In whole body irradiated rats, the osteoclasts in the interradicular alveolar bone were decreased and have smaller nuclei, compared with non-irradiated and locally irradiated rats. Histometrically, the amount of bone loss was decreased in whole body irradiated rats. Ultrastructurally, the cyoplasmic organellae and ruffled border were poorly developed in the osteoclasts of whole body irradiated rats. The findings suggested that irradiation induced cytological changes not only in osteoblasts but in osteoclasts and these changes resulted in the delayed healing of extraction wound. (author) 106 refs

Morphological studies on the healing process of tooth extraction wounds in whole body irradiated rats

Energy Technology Data Exchange (ETDEWEB)

Hosokawa, Yoichiro (Hokkaido Univ., Sapporo (Japan). School of Dentistry)

1991-06-01

The present studies were performed to investigate the healing process of the tooth extraction wound in whole body irradiated rats and to clarify the effect of irradiation on bone metabolism. One hundred and seven Wistar rats of about 100 g body weight were used and divided into 3 groups. Whole body irradiated rats were given single exposure with a dose of 8 Gy. The region of the left upper molars of local irradiated rats as controls, was exposed to 8 Gy. On the 7th day after irradiation, the left upper first molar of each rat was extracted. The rats were sacrificed at intervals of 1 to 14 days after extraction. Non-irradiated rats were sacrificed at the same intervals after extraction. The maxillary bone including the extraction wound was evaluated, histologically, histometrically and ultrastructurally. From the histological and histometrical findings, the difference of the healing process between non-irradiated rats and locally irradiated rats is not significant. In whole body irradiated rats, the healing process especially in the socket was disturbed. The osteoblastic new bone formation following production of granulation tissue was interfered with. Ultrastructurally, the cytoplasmic organellae were poorly developed in the osteoblast and osteoid formation was reduced in the socket. But periosteal new bone formation was the same as that of the locally irradiated rats. In whole body irradiated rats, the osteoclasts in the interradicular alveolar bone were decreased and have smaller nuclei, compared with non-irradiated and locally irradiated rats. Histometrically, the amount of bone loss was decreased in whole body irradiated rats. Ultrastructurally, the cyoplasmic organellae and ruffled border were poorly developed in the osteoclasts of whole body irradiated rats. The findings suggested that irradiation induced cytological changes not only in osteoblasts but in osteoclasts and these changes resulted in the delayed healing of extraction wound. (author) 106 refs.

Neutrophils in traumatic brain injury (TBI): friend or foe?

Science.gov (United States)

Liu, Yang-Wuyue; Li, Song; Dai, Shuang-Shuang

2018-05-17

Our knowledge of the pathophysiology about traumatic brain injury (TBI) is still limited. Neutrophils, as the most abundant leukocytes in circulation and the first-line transmigrated immune cells at the sites of injury, are highly involved in the initiation, development, and recovery of TBI. Nonetheless, our understanding about neutrophils in TBI is obsolete, and mounting evidences from recent studies have challenged the conventional views. This review summarizes what is known about the relationships between neutrophils and pathophysiology of TBI. In addition, discussions are made on the complex roles as well as the controversial views of neutrophils in TBI.

Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1{alpha}

Energy Technology Data Exchange (ETDEWEB)

Perlstein, R.S.; Mehta, N.R.; Neta, R.; Whitnall, M.H. [Armed Forces Radiobiology Research Institute, Bethesda, MD (United States); Mougey, E.H. [Walter Reed Army Institute of Research, Washington, DC (United States)

1995-03-01

Recombinant human interleukin-1{alpha} (rhIL-1{alpha}) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1{alpha} in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1{alpha} administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1{alpha}-induced increase in ACTH levels at the doses used. In fact, the rhIL-1{alpha}-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus. 36 refs., 3 figs.

Total body irradiation in a patient with fragile X syndrome for acute lymphoblastic leukemia in preparation for stem cell transplantation: A case report and literature review.

Science.gov (United States)

Collins, D T; Mannina, E M; Mendonca, M

2015-10-01

Fragile X syndrome (FXS) is a congenital disorder caused by expansion of CGG trinucleotide repeat at the 5' end of the fragile X mental retardation gene 1 (FMR1) on the X chromosome that leads to chromosomal instability and diminished serum levels of fragile X mental retardation protein (FMRP). Afflicted individuals often have elongated features, marfanoid habitus, macroorchidism and intellectual impairment. Evolving literature suggests the condition may actually protect from malignancy while chromosomal instability would presumably elevate the risk. Increased sensitivity to ionizing radiation should also be predicted by unstable sites within the DNA. Interestingly, in this report, we detail a patient with FXS diagnosed with acute lymphoblastic leukemia treated with induction followed by subsequent cycles of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) with a complete response who then was recommended to undergo peripheral stem cell transplantation. The patient underwent total body irradiation (TBI) as a component of his conditioning regimen and despite the concern of his clinicians, developed minimal acute toxicity and successful engraftment. The pertinent literature regarding irradiation of patients with FXS is also reviewed. © 2015 Wiley Periodicals, Inc.

Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.

Science.gov (United States)

Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

2015-09-01

In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. © 2015 British Society for Immunology.

Hematopoietic stem cell migration and proliferation after Partial body irradiation

International Nuclear Information System (INIS)

Murata, Takashi; Utsumi, Makoto; Hotta, Tomomitsu; Yamada, Hideo

1983-01-01

Stem cell migration in hematopoietic recovery after partial body irradiation was investigated with special emphasis on the comparative roles of the bone marrow and the spleen. The number of CFU-S in circulation declined rapidly and reached zero within a day after irradiation, thereafter it increased gradually. This finding suggests the presence of two different phases of stem cell migration. One is a rapid migrating phase in which stem cells are released rapidly within a day after irradiation, and the other is a slow migrating phase. The result of split doses of local body irradiation experiments implicated a role for the spleen distinct from that of the bone marrow in the preferential distribution of stem cells early after irradiation. The cell kinetic study showed that the proliferation of CFU-S occurred actively in irradiated bone marrow and the spleens as compared to that in unirradiated control. But on Day 7 and on Day 10 after irradiation, the proliferation of CFU-S in shielded bone marrow did not occur as actively as those in irradiated areas. The results of our present studies suggest that the spleen is not only the storage pools of migrating stem cells but also the main site of active proliferation of CFU-S in the early period of hematopoietic regeneration. (author)

Response of stem cell system to whole body and partial body irradiation

International Nuclear Information System (INIS)

Gidali, J.

1975-01-01

The pluripotent stem cell system, though being distributed in the body, reacts homogeneously to irradiation. This homogeneity is controlled by short-range (local) and long-range (humoral) regulations acting primarily on pluripotent and committed stem cells. Migration of stem cells from unirradiated to irradiated areas may play a role in the regeneration processes even if local regeneration may also occur. Migration induction as well as proliferation induction in the shielded area do not seem to be specific radiation-induced reactions. Both may be influenced either by some physiological regulators released after irradiation in a higher quantity or by some non-specific triggering agents. Both repeated and continuous irradiation induce the establishment of a new steady state. In the steady state after repeated sublethal irradiations, the CFU count stays at a suboptimal level either as a consequence of an increased differentiation or of some undefined damage in milieu control. In the new steady state during continuous irradiation, the number of mature elements in blood is close to the normal while CFU population is reduced to less than 2 percent of its original level

Osteochondroma after total body irradiation in bone marrow transplant recipients. Report of two cases

International Nuclear Information System (INIS)

Maeda, Go; Yokoyama, Ryohei; Ohtomo, Katsuyuki; Takayama, Jun; Beppu, Yasuo; Fukuma, Hisatoshi; Ohira, Mutsuro

1996-01-01

We present two cases of osteochondroma after total body irradiation in bone marrow recipients, the first in a 6-year-old boy with juvenile chronic myelogenous leukemia and the second in a 13-year-old boy with acute myelogenous leukemia. The patients developed multiple osteochondromas three years and seven years, respectively, after 12 Gy of total body irradiation. Neither had a family history of hereditary multiple osteochondromatosis. A review of the English literature revealed only one report describing five cases of osteochondroma after 12 Gy of total body irradiation in bone marrow transplant recipients. Osteochondroma should be considered as an additional adverse effect of total body irradiation. (author)

Development, fundamentals and objective of half-body irradiation as a method of systematic tumor therapy

International Nuclear Information System (INIS)

Eichhorn, H.J.

1988-01-01

A review is given on (1) the development of systemic radiotherapy - total body irradiation as well as sequential half-body irradiation in cases of palliative and curative treatment, resp., (2) radiobiological fundamentals of action and limits of the method, (3) clinical results of upper and lower half-body irradiation, resp., as palliative treatment of solid tumors, (4) studies of the prevention of radiation pneumonitis without decreasing radiation dose and (5) proposals for modification, improvement and combination of upper and lower half-body irradiation with other procedures such as hyperthermia and chemotherapy. 48 refs

Altered Mitochondrial Dynamics and TBI Pathophysiology

Directory of Open Access Journals (Sweden)

Tara Diane Fischer

2016-03-01

Full Text Available Mitochondrial function is intimately linked to cellular survival, growth, and death. Mitochondria not only generate ATP from oxidative phosphorylation, but also mediate intracellular calcium buffering, generation of reactive oxygen species (ROS, and apoptosis. Electron leakage from the electron transport chain, especially from damaged or depolarized mitochondria, can generate excess free radicals that damage cellular proteins, DNA, and lipids. Furthermore, mitochondrial damage releases pro-apoptotic factors to initiate cell death. Previous studies have reported that traumatic brain injury (TBI reduces mitochondrial respiration, enhances production of ROS, and triggers apoptotic cell death, suggesting a prominent role of mitochondria in TBI pathophysiology. Mitochondria maintain cellular energy homeostasis and health via balanced processes of fusion and fission, continuously dividing and fusing to form an interconnected network throughout the cell. An imbalance of these processes, particularly an excess of fission, can be detrimental to mitochondrial function, causing decreased respiration, ROS production, and apoptosis. Mitochondrial fission is regulated by the cytosolic GTPase, dynamin-related protein 1 (Drp1, which translocates to the mitochondrial outer membrane to initiate fission. Aberrant Drp1 activity has been linked to excessive mitochondrial fission and neurodegeneration. Measurement of Drp1 levels in purified hippocampal mitochondria showed an increase in TBI animals as compared to sham controls. Analysis of cryo-electron micrographs of these mitochondria also showed that TBI caused an initial increase in the length of hippocampal mitochondria at 24 hours post-injury, followed by a significant decrease in length at 72 hours. Post-TBI administration of Mdivi-1, a pharmacological inhibitor of Drp1, prevented this decrease in mitochondria length. Mdivi-1 treatment also reduced the loss of newborn neurons in the hippocampus and improved

Whole-body γ-irradiation decelerates rat hepatocyte polyploidization.

Science.gov (United States)

Ikhtiar, Adnan M

2015-07-01

To characterize hepatocyte polyploidization induced by intermediate dose of γ-ray. Male Wistar strain rats were whole-body irradiated (WBI) with 2 Gy of γ-ray at the age of 1 month, and 5-6 rats were sacrificed monthly at 0-25 months after irradiation. The nuclear DNA content of individual hepatocytes was measured by flow cytometry, then hepatocytes were classified into various ploidy classes. Survival percentage, after exposure up to the end of the study, did not indicate any differences between the irradiated groups and controls. The degree of polyploidization in hepatocytes of irradiated rats, was significantly lower than that for the control after 1 month of exposure, and it continued to be lower after up to 8 months. Thereafter, the degree of polyploidization in the irradiated group slowly returned to the control level when the irradiated rats reached the age of 10 months. Intermediate dose of ionizing radiation, in contrast to high doses, decelerate hepatocyte polyploidization, which may coincides with the hypothesis of the beneficial effects of low doses of ionizing radiation.

Caffeine protects mice against whole-body lethal dose of {gamma}-irradiation

Energy Technology Data Exchange (ETDEWEB)

George, K.C.; Hebbar, S.A.; Kale, S.P.; Kesavan, P.C. [Biosciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

1999-06-01

Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of {gamma}-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the toxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice. (author)

Treatment of TBI with Hormonal and Pharmacological Support, Preclinical Validation Using Diffuse and Mechanical TBI Animal Models

Science.gov (United States)

2016-05-01

Award Number: PT075653 (grant) W81XWH-08-2-0153 (contract) TITLE: Treatment of TBI with Hormonal and Pharmacological Support, Preclinical...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-08-2-0153 Treatment of TBI with Hormonal and Pharmacological Support, Preclinical Validation Using...rats. Our in vivo tests also included MRI imaging, focusing on edema resolution and reduction of diffuse axonal damage (fractional anisotropy

Autobiographical memory and structural brain changes in chronic phase TBI.

Science.gov (United States)

Esopenko, Carrie; Levine, Brian

2017-04-01

Traumatic brain injury (TBI) is associated with a range of neuropsychological deficits, including attention, memory, and executive functioning attributable to diffuse axonal injury (DAI) with accompanying focal frontal and temporal damage. Although the memory deficit of TBI has been well characterized with laboratory tests, comparatively little research has examined retrograde autobiographical memory (AM) at the chronic phase of TBI, with no prior studies of unselected patients drawn directly from hospital admissions for trauma. Moreover, little is known about the effects of TBI on canonical episodic and non-episodic (e.g., semantic) AM processes. In the present study, we assessed the effects of chronic-phase TBI on AM in patients with focal and DAI spanning the range of TBI severity. Patients and socioeconomic- and age-matched controls were administered the Autobiographical Interview (AI) (Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002) a widely used method for dissociating episodic and semantic elements of AM, along with tests of neuropsychological and functional outcome. Measures of episodic and non-episodic AM were compared with regional brain volumes derived from high-resolution structural magnetic resonance imaging (MRI). Severe TBI (but not mild or moderate TBI) was associated with reduced recall of episodic autobiographical details and increased recall of non-episodic details relative to healthy comparison participants. There were no significant associations between AM performance and neuropsychological or functional outcome measures. Within the full TBI sample, autobiographical episodic memory was associated with reduced volume distributed across temporal, parietal, and prefrontal regions considered to be part of the brain's AM network. These results suggest that TBI-related distributed volume loss affects episodic autobiographical recollection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prospective randomized comparison of single-dose versus hyperfractionated total-body irradiation in patients with hematologic malignancies

International Nuclear Information System (INIS)

Girinsky, T.; Benhamou, E.; Bourhis, J.H.; Dhermain, F.; Guillot-Valls, D.; Ganansia, V.; Luboinski, M.; Perez, A.; Cosset, J.M.; Socie, G.; Baume, D.; Bouaouina, N.; Briot, E.; Baudre, A.; Bridier, A.; Pico, J.L.

2001-01-01

The efficiency of the two irradiation modes are similar, but the hyperfractionated irradiation seems superior in term of global and specific survival. The incidence rates of pneumopathies are not different between the two groups but the incidence rate of the liver vein-occlusive illness is superior in the group treated by non fractionated whole body irradiation. The cost of the hyperfractionated whole body irradiation is superior to this one of the non fractionated whole body irradiation around a thousand dollars. (N.C.)

Blood and bone marrow response following total body irradiation in patients with lymphosarcomas

International Nuclear Information System (INIS)

Qasim, M.M.

1977-01-01

Marrow depression and associated peripheral blood changes following fractionated T.B.I. are considerable and appear alarming. However, provided the marrow reserve is good and is not compromised by previous chemotherapy and radiation therapy, recovery occurred in all cases and appeared to be complete. Bone marrow of 3 patients with previous T.B.I. did not show recovery after the second course of T.B.I. Extreme caution is indicated when such a therapy is repeated, as this may lead to progressive marrow hypoplasia. Fractionated low dose T.B.I. could be utilized as a useful therapeutic modality in the management of disseminated lymphosarcoma provided the marrow reserve is good. (author)

Neonatal irradiation nephropathy in the growing dog. I. Renal morphological and functional adaptations following neonatal, sublethal, whole-body irradiation

International Nuclear Information System (INIS)

Wilke, W.L.; Phemister, R.D.; Jaenke, R.S.

1979-01-01

Sixty beagles were used to study the effects of exposure to 330 R 60 Co γ radiation (bilateral, whole-body) at 2 days of age on renal functional and morphological development in the growing dog. A significant deficit in grams kidney per kilogram body weight was found in irradiated dogs at 50 days of age (P < 0.05), but not at 125 or 200 days of age. Glomerular filtration rate (GFR) per kilogram body weight and GFR per gram kidney were not significantly different between irradiated and nonirradiated dogs at 50, 125, or 200 days of age, but blood urea nitrogen (BUN) was significantly elevated in irradiated dogs throughout this period (P < 0.05). The fractional distribution of intracortical renal blood flow, as determined by radiolabeled microspheres, to the outermost cortex was found to be reduced in irradiated animals at all ages evaluated (P < 0.05). The fractional blood flow to the outermost renal cortex was negatively correlated with BUN in both irradiated (P < 0.05) and nonirradiated (P < 0.05) animals. Based on prior demonstrations of reductions in nephron numbers following similar irradiation, these data indicate increases in mean single nephron GFR and nephronal hypertrophy in the kidneys of the neonatally irradiated dog. The renal functional and morphological adaptations are sufficient to maintain adequate renal function in growing, neonatally irradiated dogs. The BUN elevations in irradiated dogs are believed to be related to changes in intracortical renal blood flow, rather than indicating renal insufficiency. The possible importance of the functional and morphological adaptations to the subsequent development of chronic renal failure in neonatally irradiated animals is discussed

Role of metabolomics in TBI research

Science.gov (United States)

Wolahan, Stephanie M.; Hirt, Daniel; Braas, Daniel; Glenn, Thomas C.

2016-01-01

Synopsis Metabolomics is an important member of the omics community in that it defines which small molecules may be responsible for disease states. This article reviews the essential principles of metabolomics from specimen preparation, chemical analysis, and advanced statistical methods. Metabolomics in TBI has so far been underutilized. Future metabolomics based studies focused on the diagnoses, prognoses, and treatment effects, need to be conducted across all types of TBI. PMID:27637396

Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

Energy Technology Data Exchange (ETDEWEB)

Yoshihara, Takao; Fujii, Noriko [Matsushita Memorial Hospital, Moriguchi, Osaka (Japan); Naya, Mayumi [and others

1999-02-01

We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m{sup 2} x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin`s lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

International Nuclear Information System (INIS)

Yoshihara, Takao; Fujii, Noriko; Naya, Mayumi

1999-01-01

We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m 2 x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin's lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

Myelopoiesis in whole-body-irradiated beagles

International Nuclear Information System (INIS)

Stevenson, A.F.G.

1985-01-01

The influence of dose-rate (DR) (either 5.2 or 52 cGy/min.) on the regeneration of bone marrow (BM) myelopoietic progenitor cells was studied in beagles after exposure to whole-body-irradiation (235, 375 and 1500 cGy + autologous BM-transplantation). Myelopoietic progenitor cells were assayed as colony-forming units in agar cultures (GM-CFU), in correlation with the colony-stimulation activity (CSA) in serum. At 235 cGy, the influence of DR on the recovery of GM-CFU was insignificant. However, at 375 cGy, the recovery was critically dependent on the DR. Depletion of GM-CFU numbers elevated CSA levels above pre-irradiation values. The DR determines the regenerative ability when the dose itself is critical to survival of the least number of hematopoietic stem cells (HSC) necessary for restitution. (author)

Radiological protection in a patient during a total body irradiation procedure

International Nuclear Information System (INIS)

Hernandez O, J. O.; Hinojosa G, J.; Gomez M, E.; Balam de la Vega, J. A.; Deheza V, J. C.

2010-09-01

A technique used in the Service of Radiotherapy of the Cancer Center of the American British Cowdray Medical Center (ABC) for the bone marrow transplantation, is the total body irradiation. It is known that the dose calculation, for this irradiation type, is old, since the dosimetric calculation is carried out by hand and they exist infinity of techniques for the patients irradiation and different forms of protecting organs of risk, as well as a great uncertainty in the given dose. In the Cancer Center of the ABC Medical Center, was carried out an irradiation procedure to total body with the following methodology: Computerized tomography of the patient total body (two vacuum mattresses in the following positions: dorsal and lateral decubitus), where is combined the two treatment techniques anterior-posterior and bilateral, skin delineate and reference volumes, dose calculation with the planning system Xi O of CMS, dose determination using an ionization chamber and a lung phantom IMRT Thorax Phantom of the mark CIRS and dosimetry in vivo. In this work is presented the used treatment technique, the results, statistics and the actualization of the patient clinical state. (Author)

Responses to selection for body weight in descendants of x-irradiated rats

International Nuclear Information System (INIS)

Gianola, D.; Chapman, A.B.; Rutledge, J.J.

1979-01-01

Th effectiveness of selection for high and low body weight at six weeks of age was studied in descendants of x-irradiated (R) and nonirradiated (C) inbred rats. There were two replicates of each of the direction of selection--irradiation treatments. In C lines, there were no consistent responses to selection, probably due to a low level of genetic variability. In R rats, selection was effective only for decreased body weight. The results of this experiment do not suggest the use of irradiation combined with selection as a means of enhancing responses to selection in animals

The pupal body temperature and inner space temperature of cocoon under microwave irradiation

International Nuclear Information System (INIS)

Kagawa, T.

1996-01-01

The temperature of pupal surface,body and inner space of cocoon on cocoon drying of microwave irradiation was investigated to make clear the effect of temperature with pupa and cocoon shell. After pupal surface temperature and body temperature were risen rapidly in early irradiation and slowly thereafter, these were done fast again. Then these rising degrees fell. The variation of inner space temperature consists three terms: as the first stage of rapidly rising on early irradiation, the second stage of slowly doing and the third stage of fast doing again in temperature. In the first stage and the second stage, the higher the temperature of sending air during irradiation was, the shorter the term was and the higher the reached temperature was. The surface, pupal body and inner space have reached higher temperature than the sending air before cocoon drying was over

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-06-01

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

Legacy Clinical Data from the Mission Connect Mild TBI Translational Research Consortium

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-2-0026 TITLE: Legacy Clinical Data from the Mission Connect Mild TBI Translational Research Consortium PRINCIPAL...2017 4. TITLE AND SUBTITLE Legacy Clinical Data from the Mission Connect Mild TBI Translational Research 5a. CONTRACT NUMBER Consortium 5b. GRANT...mTBI) Translational Research Consortium was to improve the diagnosis and treatment of mTBI. We enrolled a total of 88 mTBI patients and 73 orthopedic

TBI Assessment of Readiness Using a Gait Evaluation Test (TARGET): Development of a Portable mTBI Screening Device

Science.gov (United States)

2016-05-01

determine the validity and reliability of an Android device-based mTBI (mild traumatic brain injury) screening test app for assessing motor function. The...individuals and those with clinically confirmed mTBI in both a civilian and military population. 15. SUBJECT TERMS- 16. SECURITY CLASSIFICATION OF: 17...8 5. Changes/ Problems 9 6. Products 11 7. Participants & Other Collaborating Organizations 14 8. Special Reporting Requirements 16 9. Appendices

The effect of total-body γ-irradiation on pigeons

International Nuclear Information System (INIS)

Gadhia, P.K.; Shah, V.C.; Desai, R.

1979-01-01

A study of the effects of total-body 60 Coγ radiation (200 to 2000 rad) on the common pigeon (Columba livia) has indicated a LD 50/30 of 950 +- 50 rad. There were no deaths before 6 days and the peak frequency in average deaths occurred 9 days after irradiation. Most of the birds showed small changes in activity or behaviour in the first five days. A histopathological study was made of femoral bone marrow from irradiated (1000 rad) pigeons sacrificed 1 to 18 days post-irradiation. Slight aplasia was observed on the first day after irradiation, moderately marked on the third day and extensive on the fourth and fifth days. At the end of the second week regeneration was observed as the primitive lymphocyte-like cells were differentiating into granulocytes and erythrocytes. (UK)

Fractionated homogenous total-body irradiation prior to bone marrow transplantation

Energy Technology Data Exchange (ETDEWEB)

Duehmke, E; Brix, F; Hebbinghaus, D; Jensen, M; Wendhausen, H; Schmitz, N

1985-03-01

At the University of Kiel, myeloid and acute lymphatic leukemia is treated since 1983 by total-body irradiation applied prior to bone marrow transplantation. Dose deviations in the midplane caused by the irregular surface and tissue inhomogeneities of the patient are reduced down to +-3.5% compared to the central ray, with the help of CT-based individual compensators. This method prevents above all an excessive dose to the lungs. The radiobiologic advantages of fractionated irradiation have been employed for all patients treated hitherto (n = 9). At present, a total body dose of 12 Gy in six fractions is applied within three days. There were no undesired acute radiogenic reactions except a mild acute mucositis found in all patients. Chronic side effects, especially in the lungs, were not demonstrated, too. However, the average follow-up time of 149 days has been rather short. One patient died from relapse of leukemia after a total dose of 10 Gy, another patient died because the transplanted bone marrow was rejected, and a third died from catheter sepsis. Six out of nine patients are in complete remission with a maximum index of Karnofsky. The limited experiences gained hitherto show that the homogeneous accelerated-fractionated total-body irradiation offers essential advantages compared to non-compensated single dose irradiation with respect to the prevention of undesired radiogenic effects in sound tissues and that its therapeutic efficacy is at least the same.

SU-F-T-406: Verification of Total Body Irradiation Commissioned MU Lookup Table Accuracy Using Treatment Planning System for Wide Range of Patient Sizes

Energy Technology Data Exchange (ETDEWEB)

Lewis, D; Chi, P; Tailor, R; Aristophanous, M; Tung, S [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: To verify the accuracy of total body irradiation (TBI) measurement commissioning data using the treatment planning system (TPS) for a wide range of patient separations. Methods: Our institution conducts TBI treatments with an 18MV photon beam at 380cm extended SSD using an AP/PA technique. Currently, the monitor units (MU) per field for patient treatments are determined using a lookup table generated from TMR measurements in a water phantom (75 × 41 × 30.5 cm3). The dose prescribed to an umbilicus midline point at spine level is determined based on patient separation, dose/ field and dose rate/MU. One-dimensional heterogeneous dose calculations from Pinnacle TPS were validated with thermoluminescent dosimeters (TLD) placed in an average adult anthropomorphic phantom and also in-vivo on four patients with large separations. Subsequently, twelve patients with various separations (17–47cm) were retrospectively analyzed. Computed tomography (CT) scans were acquired in the left and right decubitus positions from vertex to knee. A treatment plan for each patient was generated. The ratio of the lookup table MU to the heterogeneous TPS MU was compared. Results: TLD Measurements in the anthropomorphic phantom and large TBI patients agreed with Pinnacle calculated dose within 2.8% and 2%, respectively. The heterogeneous calculation compared to the lookup table agreed within 8.1% (ratio range: 1.014–1.081). A trend of reduced accuracy was observed when patient separation increases. Conclusion: The TPS dose calculation accuracy was confirmed by TLD measurements, showing that Pinnacle can model the extended SSD dose without commissioning a special beam model for the extended SSD geometry. The difference between the lookup table and TPS calculation potentially comes from lack of scatter during commissioning when compared to extreme patient sizes. The observed trend suggests the need for development of a correction factor between the lookup table and TPS dose

Caffeine-induced hematological changes after whole-body irradiation in rat

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin Kyu [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Kim, Ji Hyang; Yoon Yong Dal [Hanyang University, Seoul (Korea, Republic of)

2004-07-01

Recent research indicated dietary antioxidants were useful radioprotectors to protect organisms against radiation-induced tissue lethality and other deleterious effects. Radioprotective effects of vitamin C have been demonstrated in certain cells and animals, which would result from scavenging free radicals. Moreover, the previous studies indicated that caffeine had been shown to potently act the radioprotector in irradiated mice. However it is not clear exactly about effects of caffeine treatments chronically after irradiation. So the present studies were designed to identify the hematological effect of caffeine treatments chronically one month after whole-body gamma irradiation.

Long-term effect of whole-body X-irradiation on cell-mediated immune reaction in mice

International Nuclear Information System (INIS)

Norimura, Toshiyuki; Tsuchiya, Takehiko

1989-01-01

Age-related change in immunological activity was examined at 10 to 91 weeks following whole-body irradiation by determining the specific anti-tumor cell-mediated immunity in host mice induced and/or enhanced by local irradiation to transplanted tumor. Median survival time of the non-irradiated C3H/He female mice was 98.6 weeks while the median life-span of the mice exposed to two and four Gy of 250 kVp X-rays at the age of 10-12 weeks was shortened by 14.9 and 23.4 weeks, respectively. The rate of tumor reduction within two weeks after local irradiation to tumor and the growth inhibitory activitiy of spleen cells from tumor irradiated mice were reduced in a dose-dependent manner when assessed 10 weeks after whole-body irradiation, but recovered to the near-complete level of the non-irradiated controls within a few months, then gradually decreased with normal aging. These results suggest that the age-dependent decline of this immunological activity apears earlier in the irradiated mice as a result of whole-body X-irradiation at a young age, suggesting accelerated aging of the immune system. (author)

TBI Endpoints Development

Science.gov (United States)

2015-10-01

therapy , and early mild physical activity, which result in fewer symptoms, lower mean severity of symptoms, less social disability, and fewer days off work...developing more precise TBI diagnostic tools, clinical endpoints, and effective therapies . We designed and executed an interactive program that combined...surgery, neuropsychology, neuroradiology, psychiatry, neurology, sports medicine, pediatrics, geriatrics , health economics, biostatistics, and informatics

Appearance of thymic nurse cells after gamma irradiation

International Nuclear Information System (INIS)

Mulder, A.H.; Bekkum, D.W. van

1983-01-01

Since prothymocytes home from the bone marrow to the thymus, it was tested in the mouse whether prothymocytes could be recaptured from thymic nurse cells (TNC). Bone marrow cells were labelled with the red fluorescing anthracycline daunomycin and varying numbers (up to 25 x 10 6 nucleated bone marrow cells) were injected into lethally irradiated recipients. At several time intervals after transplantation (up to 24 hours), thymuses were removed and the TNCs were isolated. No specific red fluorescence was found within the TNCs. These experiments were repeated with supravital compounds at concentrations which have been shown not to affect viability, homing pattern and function. Again, no specific fluoresence was found in the TNC after transplantation of labelled bone marrow into irradiated mice. The relationship between the dose of total body gamma irradiation and the time after irradiation was investigated. Maximal numbers of TNCs were found at 6 hours after irradiation with 4 Gy. Eight to 12 hours after irradiation, the number of TNCs isolated decreased and had returned to preirradiation levels at 24 hours. The relation between TBI dose and the number of TNCs per thymus is shown. The number determined at 3 hours increased with the dose to reach a maximum at 4 Gy. The authors later studied the morphology of the TNCs isolated at 4 to 6 hours after irradiation. On electron microscopic examination, signs of degeneration and death of the enclosed thymocytes was detected. (Auth.)

Blood coagulation and fibrinolysis of the whole-body irradiated rabbits

International Nuclear Information System (INIS)

Hishikawa-Itoh, Youko; Ayakawa, Yoshio; Miyata, Nobuki

1984-01-01

To study the effects of irradiation on blood coagulation and fibrinolysis, rabbits were irradiated with 60 Co γ-rays (whole-body: 0, 100, 400, 800, 1200 rads). Clotting time, activity of plasmin and plasminogen, and fibrinogen contents of irradiated rabbit plasma were measured at 4 days before, immediately after, and at 1, 3, 7, 10, and 14 days after irradiation. Both clotting times obtained by addition of (kaolin+phospholipid) which expressed effects on the total intrinsic coagulation system, and by addition of (Ca 2+ ) which expressed effects on the total extrinsic coagulation system, were prolonged with small dose irradiation (100 rads) immediately and 3 days after irradiation. However, with high dose irradiation (400-1200 rads), these clotting times were prolonged 1 day after irradiation. The times of manifestation of irradiation effects on clotting time were different in small and high dose irradiation. Plasmin activity was decreased immediately, 1 day after and recovered 3 days after irradiation. Plasminogen activity was markedly increased in 800 and 1200 rads irradiated groups from 3 days after irradiation. Conversion of plasminogen into plasmin was impaired by irradiation. Fibrinogen contents increased rapidly in all irradiated rabbits except for 100 rads from 1 day after irradiation. These results revealed decreased coagulation and fibrinolysis activities in rabbit blood, irradiation injury of both coagulation and fibrinolysis activation systems, and accumulation of the precursors of fibrin and plasmin (i.e., fibrinogen and plasminogen). (author)

EYE-TRAC: monitoring attention and utility for mTBI

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Maruta, Jun; Tong, Jianliang; Lee, Stephanie W.; Iqbal, Zarah; Schonberger, Alison; Ghajar, Jamshid

2012-06-01

Attention is a core function in cognition and also the most prevalent cognitive deficit in mild traumatic brain injury (mTBI). Predictive timing is an essential element of attention functioning because sensory processing and execution of goal-oriented behavior are facilitated by temporally accurate prediction. It is hypothesized that impaired synchronization between prediction and external events accounts for the attention deficit in mTBI. Other cognitive and somatic or affective symptoms associated with mTBI may be explained as secondary consequences of impaired predictive timing. Eye-Tracking Rapid Attention Computation (EYE-TRAC) is the quantification of predictive timing with indices of dynamic visuo-motor synchronization (DVS) between the gaze and the target during continuous predictive visual tracking. Such quantification allows for cognitive performance monitoring in comparison to the overall population as well as within individuals over time. We report preliminary results of normative data and data collected from subjects with a history of mTBI within 2 weeks of injury and post-concussive symptoms at the time of recruitment. A substantial proportion of mTBI subjects demonstrated DVS scores worse than 95% of normal subjects. In addition, longitudinal monitoring of acute mTBI subjects showed that initially abnormal DVS scores were followed by improvement toward the normal range. In summary, EYE-TRAC provides fast and objective indices of DVS that allow comparison of attention performance to a normative standard and monitoring of within-individual changes.

First application of hemi-body electron beam irradiation for Kaposi sarcoma at the lower extremities.

Science.gov (United States)

Platoni, Kalliopi; Diamantopoulos, Stefanos; Dilvoi, Maria; Delinikolas, Panagiotis; Kypraiou, Efrosyni; Efstathopoulos, Efstathios; Kouloulias, Vassilis

2018-01-01

Kaposi's sarcoma (KS) is a systemic neoplastic disease that can present cutaneous symptoms and is usually treated with a systematic approach due to its extent. Due to its radiosensitivity, radiotherapy is considered one of its main treatments, for palliation and local control of the skin and mucosal lesions. The aim of this paper was to report the first case of KS treated by hemi-body electron irradiation protocol in Greece. A fractionated 40 Gy hemi-body electron irradiation was prescribed to a 60-year-old male patient with KS at his legs. Dose uniformity was verified on a daily basis by thermoluminescence dosimetry (TLD). The treatment resulted to complete clinical response. Limited irradiation-derived side effects appeared. This is the first case ever to be treated with hemi-body electron irradiation protocol in Greece. To the best of our knowledge, this is also the first time that a single field hemi-body electron beam irradiation at a total skin electron beam (TSEB)-like configuration is reported to be used for KS.

Mission Connect Mild TBI Translational Research Consortium

Science.gov (United States)

2010-08-31

using magneto - Investigators A. Papanicolaou, PhD – PI J. Breier, PhD E. Castillo, PhD T. Kent, MD Project Summary Introduction: The aim of this...secondary insults such as hemorrhagic hypotension. Antioxidant therapies have had limited success in treating mTBI. We identified carbon nanomaterials... therapies for TBI using nanomaterials that are capable of addressing, for the first time, key components of the “neurovascular unit”. If the PEG-HCCs

Nuclear scintigraphic assessment of intestinal dysfunction after combined treatment with 9-amino-20(S)-camptothecin (9-AC) and irradiation

International Nuclear Information System (INIS)

Kirichenko, Alexander V.; Mason, Kathryn; Straume, Martin; Teates, Charles D.; Rich, Tyvin A.

2000-01-01

Purpose: The camptothecins (CPTs) are potent radiosensitizers of malignant tumors in vivo. The extent of normal tissue damage after combined CPT and radiation treatment is unknown. In this article, a jejunal absorption assay with 99m Tc- pertechnetate (Na[ 99m TcO 4 ]) was used to assess C3H/Kam mice given total body irradiation (TBI) of 4 Gy, 6 Gy, and 8 Gy, 2 mg/kg single intramuscular injection of 9-AC or a combination of 2 mg/kg 9-AC + 4 Gy TBI. We also correlated the absorption data with morphologic changes in the jejunal mucosa. Materials and Methods: ( 99m TcO 4 ) - absorption from the intestinal lumen into the circulation was studied with dynamic γ-scintigraphy combined with a multichannel analyzer to record the radiometry data in a time-dependent fashion. Jejunal cross sections were scored for the number of cells per villus and the percentage of apoptotic and mitotic cells in the crypt compartment. The jejunal microcolony assay was used to quantify jejunal crypt survival. Results: A dose-dependent decrease in the absorption function was observed 3.5 days following TBI. The mean absorption rate was reduced to 89 ± 16% of control in response to a sublethal 4 Gy TBI and dropped to 47.5 (9.8% in response to 8 Gy TBI. The mean rate of intestinal absorption was delayed by single sublethal 2 mg/kg 9-AC injection to 62 (11% in comparison with control values. The combination of a single 4 Gy TBI with a 9-AC treatment decreased the ( 99m TcO 4 ) - jejunal absorption in an additive fashion producing absorption lifetime values more than twofold longer than controls. The decrease in ( 99m TcO 4 ) - absorption at 3.5 days after irradiation, 9-AC treatment or the combination of the two agents correlates with the number of cells per villus and the percentage of apoptotic cells in the crypt compartment. Conclusion: Dynamic enteroscintigraphy with 99m Tc-pertechnetate is a sensitive functional assay for rapid evaluation of radiation and chemotherapy induced intestinal

Targeting Epigenetic Mechanisms in Pain due to Trauma and TBI

Science.gov (United States)

2017-10-01

disability after trauma, particularly in the setting of TBI. This objective is closely in alignment with the pain management focus area of the CRMRP... management of acute and chronic pain under the care of a clinician in non-deployed settings (specifically in patients with TBI), and 3) research...distant from the head after TBI. This constitutes a fundamental contribution to the discipline. What was the impact on other disciplines? The field

Aspects of radioprotection in whole body irradiation treatments (TBI)

International Nuclear Information System (INIS)

Pinella, Yuliana M. Ayala; Chavez, Cesar Picon

2013-01-01

Radiation protection occupationally exposed personnel and the public is considered in this study. It was done the experimental determination of the exposure rates at critical points in the area of radiotherapy and it was evaluated the staff dosimetry

2nd Tuebingen radiotherapy symposium: Whole body, large field and whole skin irradiation. Introduction

International Nuclear Information System (INIS)

Huebener, K.H.; Frommhold, W.

1987-01-01

The symposium which took place on the 11th and 12th April 1986 set itself the task of discussing three different groups of radiotherapy topics. The chief issue was whole-body irradiation prior to bone marrow transplants, in which all the therapy centres in West Germany, Austria, East Germany and German-speaking Switzerland made clinical and radiophysical contributions. The second part of the Symposium consisted mainly of talks and discussions on large-field irradiation, more precisely half-body and sequential partial body irradiation. This topic was chosen because this type of therapy is scarcely practised at all, particularly in West Germany, whereas in the United States, East Germany, Switzerland and a number of other countries it has long since become one of the established methods. The last talk at the Symposium explained clinical and radiophysical aspects of whole-skin irradiation. Here too, one was impressed by the wide diversity of the equipment and methods of irradiation used which, nevertheless, all demonstrated satisfactory practical solutions in their common aim of distributing the dose as homogeneously as possible. (orig./MG) [de

Effects of local and whole body irradiation on appearance of osteoclasts during wound healing of tooth extraction sockets in rats

International Nuclear Information System (INIS)

Hosokawa, Yoichiro; Sakakura, Yasunori; Tanaka, Likinobu; Okumura, Kazuhiko; Yajima, Toshihiko; Kaneko, Masayuki

2007-01-01

We examined effects of local and whole body irradiation before tooth extraction on appearance and differentiation of osteoclasts in the alveolar bone of rat maxillary first molars. Wistar rats weighting 100 g were divided into three groups: non-irradiation group, local irradiation group, and whole body irradiation group. In the local irradiation group, a field made with lead blocks was placed over the maxillary left first molar tooth. In the whole body irradiation group, the animals were irradiated in cages. Both groups were irradiated at 8 Gy. The number of osteoclasts around the interradicular alveolar bone showed chronological changes common to non-irradiated and irradiated animals. Several osteoclasts appeared one day after tooth extraction, and the maximal peak was observed 3 days after extraction. Local irradiation had no difference from non-irradiated controls. In animals receiving whole body irradiation, tooth extraction one day after irradiation caused smaller number of osteoclasts than that 7 day after irradiation during the experimental period. Whole body-irradiated rats had small osteoclasts with only a few nuclei and narrow resorption lacunae, indicating deficiency of radioresistant osteoclast precursor cells. Injection of intact bone marrow cells to whole body-irradiated animals immediately after tooth extraction recovered to some content the number of osteoclasts. These findings suggest that bone resorption in the wound healing of alveolar socket requires radioresistant, postmitotic osteoclast precursor cells from hematopoietic organs, but not from local sources around the alveolar socket, at the initial phase of wound healing. (author)

Effects of local and whole body irradiation on appearance of osteoclasts during wound healing of tooth extraction sockets in rats.

Science.gov (United States)

Hosokawa, Yoichiro; Sakakura, Yasunori; Tanaka, Likinobu; Okumura, Kazuhiko; Yajima, Toshihiko; Kaneko, Masayuki

2007-07-01

We examined effects of local and whole body irradiation before tooth extraction on appearance and differentiation of osteoclasts in the alveolar bone of rat maxillary first molars. Wistar rats weighting 100 g were divided into three groups: non-irradiation group, local irradiation group, and whole body irradiation group. In the local irradiation group, a field made with lead blocks was placed over the maxillary left first molar tooth. In the whole body irradiation group, the animals were irradiated in cages. Both groups were irradiated at 8 Gy. The number of osteoclasts around the interradicular alveolar bone showed chronological changes common to non-irradiated and irradiated animals. Several osteoclasts appeared one day after tooth extraction, and the maximal peak was observed 3 days after extraction. Local irradiation had no difference from non-irradiated controls. In animals receiving whole body irradiation, tooth extraction one day after irradiation caused smaller number of osteoclasts than that 7 day after irradiation during the experimental period. Whole body-irradiated rats had small osteoclasts with only a few nuclei and narrow resorption lacunae, indicating deficiency of radioresistant osteoclast precursor cells. Injection of intact bone marrow cells to whole body-irradiated animals immediately after tooth extraction recovered to some content the number of osteoclasts. These findings suggest that bone resorption in the wound healing of alveolar socket requires radioresistant, postmitotic osteoclast precursor cells from hematopoietic organs, but not from local sources around the alveolar socket, at the initial phase of wound healing.

Body composition changes following the supplementation of different food additives to irradiated animals

International Nuclear Information System (INIS)

Fahmy, M.O.

1980-01-01

This study was conducted to examine the hypothesis that deposition of fat and / or protein in animal's body before irradiation or using radio - protector material such as soyabean oil may reduce the hazard effects of radiation on life span, body weight and body compartments. Therefore, 286 mice ( 144 males and 142 females) after chemical maturity were used in this study. The animals were divided to 4 major groups. The first group was fed on chow diet, the second group was fed on radioprotector diet ( basel diet), the third group was fed on high energy diet and the forth group fed on high protein diet, for 7 weeks before the exposure to gamma-rays. At the exposure day each nutritional group was divided to 3 exposure treatments ( non-irradiated, 800 and 1200 rads). The previous hypothesis was studied for 42 days after irradiation

Traumatic Brain Injury Registry (TBI)

Data.gov (United States)

Department of Veterans Affairs — As the number of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Traumatic Brain Injury (TBI) patients has grown, so has the need to track and monitor...

The effect of whole body irradiation on the action of strong analgesics of mice

International Nuclear Information System (INIS)

Cvetkovicj, M.; Milovanovicj, A.; Tanasijevicj, D.

1987-01-01

The effect of whole body irradiation of male mice with single doses of 3 and 7 Gy ( 60 Co source) on analgesic action of three morphine-like drugs was studied. Over the first 6 days after irradiation, the analgesic effect of alfentanil and fentanyl was significantly less pronounced in irradiated animals than in control ones. During the subsequent period of 24 days till the end of experiment, the analgesic effect in irradiated animals gradually increased reaching and exceeding the control values. On the contrary, the analgesic effect of butorphanole was less pronounced in irradiated animals than in control ones, although the difference was not significantly. The difference between butorphanole and other two drugs are probably due to chemical structure and the metabolic fate in the body. (author) 8 refs.; 2 figs

Whole-body X-irradiation of mice accelerates polyploidization of hepatocytes

International Nuclear Information System (INIS)

Shima, A.; Egami, N.

1985-01-01

Male C57BL/6 mice were whole-body irradiated with 4.75 gy of X-rays at the age of 2 months and killed at 2, 6, 12 and 19 months after irradiation. The percentage survival began to decline earlier and faster in the irradiated group than the controls up to 19 months after exposure when the study was terminated. The nuclear DNA content of individual hepatocytes was measured by a Feulgen-DNA microfluorometric method, and hepatocytes were classified into various ploidy classes. In the irradiated mice, the degree of polyploidization was significantly higher than the controls by 2 months after exposure and steadily increased up to 6 months after exposure. Thereafter, however, a slow return to the control level was found up to 19 months after irradiation. These results appear to support a hypothesis that radiation accelerates the ageing process as judged from hepatocyte polyploidization. (author)

Total body irradiation for children with malignancies

Energy Technology Data Exchange (ETDEWEB)

Sanuki, Eiichi; Maeno, Toshio; Kamata, Rikisaburo; Tanaka, Yoshiaki; Mugishima, Hideo [Nihon Univ., Tokyo (Japan). School of Medicine

1995-12-01

Total body irradiation combined with high dose chemotherapy has been performed just before bone marrow transplantation in 35 children with advanced malignancies, with the object of achieving successful transplantation and improving the prognosis. Simulation was performed as follows: back scatter, flatness, dose accumulation using randophantom and dose distribution using a thermo-luminescence dosimeter and linac-graphy. The standard error of dose distribution was within 10%. In neuroblastoma, of which there were 14 cases in stage IV and one case in stage III, the 5-year survival rate was 55%. In leukemia, of which all cases were in the high-risk group (7 cases of acute lymphoblastic leukemia and 2 of acute myeloblastic leukemia) the 5-year survival rate was 55%. The 5 cases having first remission survived disease-free while the 4 cases having non-first remission died. In malignant lymphoma (6 cases in stage IV and one case in stage III, with bulky mass) the 5-year survival rate was 67%. Four cases with other diagnoses (severe aplastic anemia, and others) all survived. As yet no side effects resulting from total body irradiation have been recognized in our cases, but a longer follow-up period is necessary to observe possible late side effects. (author).

Caregiver functioning following early childhood TBI: do moms and dads respond differently?

Science.gov (United States)

Wade, Shari L; Walz, Nicolay C; Cassedy, Amy; Taylor, H Gerry; Stancin, Terry; Yeates, Keith Owen

2010-01-01

Research suggests that pediatric TBI results in injury-related stress and burden and psychological distress for parents. However, existing studies have focused almost exclusively on mothers, so that we know relatively little about the impact of childhood TBI on fathers. The aims were to prospectively examine differences in maternal and paternal response to early childhood TBI over time relative to a comparison cohort of mothers and fathers of children with orthopedic injuries (OI). The concurrent cohort/prospective research design involved repeated assessments of children aged 3-6 years with TBI or OI requiring hospitalization and their families. Shortly after injury and at 6, 12, and 18 months post injury, parents of 48 children with TBI (11 severe and 37 moderate) and 89 with OI completed standardized assessments of injury-related stress and burden, parental distress, and coping strategies. Mixed models analyses and Generalized Estimating Equations examined differences in maternal versus paternal burden, distress, and coping over time. The analyses included interactions of parent sex with group (severe TBI, moderate TBI, OI) and time since injury, to examine the moderating effects of injury severity on parental response to injury over time. Fathers were more likely than mothers to use denial to cope following moderate and severe TBI, but not OI. Conversely, mothers were more likely to prefer acceptance and emotion-focused strategies than fathers regardless of the type of injury. The use of active coping strategies varied as a function of injury type, parent sex, and time since injury. Fathers reported greater injury-related stress and distress than mothers over time, with pronounced differences in the severe TBI and OI groups. Mothers and fathers appear to respond differently following TBI. The different types of responses may serve to exacerbate emerging family dysfunction.

Melatonin, a potential effective protector in whole body γ-irradiated rats

International Nuclear Information System (INIS)

Tawfik, S.S; El-Nashar, D.E; Ahmed, M.M; Hanafy, Z.E

2010-01-01

Melatonin (N-acetyl-5-methoxytryptamine), the chief hormone of pineal gland, is widely distributed in animal kingdom. It is claimed for its antioxidant and free radical properties. The present study aimed to examine the radio protective potentiality and efficacy of melatonin against damages induced in whole body γ-irradiated rats. Animals received melatonin (10 mg/ kg body wt/ day) for 10 successive days pre-exposure to 3 Gy of γ-radiation (acute dose). Rats sacrificed at 10 and 20 days post the irradiation time. The results revealed that the prolonged administration of melatonin has ameliorated the radiation- induced depletion in brain, testis and serum glutathione (GSH) level and a decrease in serum glutathione peroxidase (GPX) activity when compared with their matched values in irradiated rats. In addition, remarkable decreases in the concentration of lipid peroxidation (LPO) product; malondialdhyde (MDA) was observed in brain, testis and serum of rats received melatonin pre-radiation exposure. As well as, significant decreases in disulphide glutathione (GSSG) were observed in serum.Histopathological examination of brain and testis showed that administration of melatonin pre-irradiation according to the present regimen has attenuated radiation induced tissue damages and improved tissue architecture. Cytogenetically, the chromosomal aberration (CA) assay in bone marrow pointed out a significant difference between rats received melatonin pre-irradiation and γ-irradiated rats in most CA types. Accordingly, it could be postulated the tissue diversity and cytogenetic impact of the administrated melatonin against acute ion syndrome in rat model.

Prediction of midline dose from entrance ad exit dose using OSLD measurements for total irradiation

Energy Technology Data Exchange (ETDEWEB)

Choi, Chang Heon; Park, Jong Min; Park, So Yeon; Chun, Min Soo; Han, Ji Hye; Cho, Jin Dong; Kim, Jung In [Dept. of Radiation Oncology, Seoul National University Hospital, Seoul (Korea, Republic of)

2017-06-15

This study aims to predict the midline dose based on the entrance and exit doses from optically stimulated luminescence detector (OSLD) measurements for total body irradiation (TBI). For TBI treatment, beam data sets were measured for 6 MV and 15 MV beams. To evaluate the tissue lateral effect of various thicknesses, the midline dose and peak dose were measured using a solid water phantom (SWP) and ion chamber. The entrance and exit doses were measured using OSLDs. OSLDs were attached onto the central beam axis at the entrance and exit surfaces of the phantom. The predicted midline dose was evaluated as the sum of the entrance and exit doses by OSLD measurement. The ratio of the entrance dose to the exit dose was evaluated at various thicknesses. The ratio of the peak dose to the midline dose was 1.12 for a 30 cm thick SWP at both energies. When the patient thickness is greater than 30 cm, the 15 MV should be used to ensure dose homogeneity. The ratio of the entrance dose to the exit dose was less than 1.0 for thicknesses of less than 30 cm and 40 cm at 6 MV and 15 MV, respectively. Therefore, the predicted midline dose can be underestimated for thinner body. At 15 MV, the ratios were approximately 1.06 for a thickness of 50 cm. In cases where adult patients are treated with the 15 MV photon beam, it is possible for the predicted midline dose to be overestimated for parts of the body with a thickness of 50 cm or greater. The predicted midline dose and OSLD-measured midline dose depend on the phantom thickness. For in-vivo dosimetry of TBI, the measurement dose should be corrected in order to accurately predict the midline dose.

Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction; Etude de la capacite plastique des Cellules Souches Mesenchymateuses humaines (CSM) apres irradiation du tissu receveur: approche therapeutique de l'atteinte multiorgane radio-induite

Energy Technology Data Exchange (ETDEWEB)

Francois, S

2006-01-15

The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

Inhibitory mechanism of low-dose, whole-body irradiation with gamma-rays against tumor metastasis

International Nuclear Information System (INIS)

Yasuhiro Ohsima; Mitsutoshi Tukimoto; Shuji Kojima

2007-01-01

Complete text of publication follows. A lot of beneficial effects of low-dose irradiation are well known. Of them, an inhibitory effect of the radiation on lung metastasis is reported so far. It has been reported that low-dose whole-body irradiation with gamma rays enhanced cytotoxic immune response as one of the mechanisms. In our laboratory, it has been confirmed an enhancement of natural killer activity in mice irradiated with whole-body 0.5Gy gamma-rays. Metastasis is accomplished by multistep process, involving basement membrane destruction, local invasion, intravasation, survival in the bloodstream, extravasation into distant organs, and proliferation at the target site. Besides, a lot of growth factors and proteases are involved in these steps. As to mechanism of inhibition of tumor metastasis induced by low-dose whole-body irradiation, studies from the standpoint of tumor invasion have not been reported. Here, inhibitory effect of 0.5Gy whole-body gamma-ray irradiation on tumor metastasis and its mechanism were examined in pulmonary metastasis model mice injected with B16 melanoma cells. Consequently, 0.5Gy whole-body gamma ray irradiation significantly suppressed colony formation in the lungs. Expression of matrix metalloproteinase- 2 (MMP- 2), a proteinase related to metastasis, in lung tissues was suppressed by the radiation. Alteration of tissue inhibitor of matrix metalloproteinase (TIMP) after the gamma-ray irradiation was examined. Expression of TIMP-1 and TIMP-2 mRNA in the lungs were significantly increased. In order to clarify the inhibitory effect obtained in the in vivo metastatic lung cancer model mice, we studied effects of gamma-rays on cell proliferation, alterations of mRNA and proteins related to tumor metastasis in cultured B16 melanoma cells. Proliferation of B16 melanoma cells was decreased in a dose-dependent manner. MMP-2 mRNA expression was not altered in any doses of gamma-rays. Thought expression of the protein was slightly

Indicators of complicated mild TBI predict MMPI-2 scores after 23 years.

Science.gov (United States)

Hessen, Erik; Nestvold, Knut

2009-03-01

Research suggests that post-concussive syndrome may become persistent after mild traumatic brain injury (mTBI). The aim of this study was to investigate determinants of subjective complaints, characteristic for post-concussive syndrome, 23 years after mTBI. The study was a follow-up after a prospective head injury study at a general hospital in Norway. Ninety-seven patients were assessed with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) 23 years after sustaining primarily mTBI. A good overall outcome was found with scores close to the normative mean, average length of education and normal employment rate. However, the patients that sustained complicated mTBI showed somewhat more pathological scores, well-matched with mild post-concussive syndrome. The most important predictors of poor outcome were a combination of post-traumatic amnesia >30 minutes and EEG pathology within 24 hours after TBI. No influence of pre- and post-injury risk factors on current MMPI-2 profiles was found. The results are in line with previous research findings and support the notion of potentially differential impact of uncomplicated vs. complicated mTBI. The findings suggest that complicated mTBI may cause subtle chronic symptoms typical of post-concussive syndrome.

Hematological changes after single large dose half-body irradiation

International Nuclear Information System (INIS)

Herrmann, T.; Friedrich, S.; Jochem, I.; Eberhardt, H.J.; Koch, R.; Knorr, A.

1981-01-01

The determination of different peripheral blood parameters aimed at the study of side effects on the hematological cellular system following a 5 - 8 Gy single large dose half-body irradiation in 20 patients. Compared to the initial values the leukocytes between the 6. and 14., the thrombocytes between the 14. and 21. postirradiation day as well as the lymphocytes between 3 hours and 4 weeks postirradiation were significantly decreased without exhibiting complications such as hemorrhages or infections. The hemoglobin, hematocrit and reticulocyte values revealed but a slight decrease normalized within a 28 days postirradiation period. Transfusions were necessary when a tumor-caused anemia was present prior to irradiation. Changes in serum activity of aminotransferases and lactate dehydrogenase occured during the first hours after irradiation and were due to enzyme release from destroyed tumor cells

Therapeutic efficiency of synthokine SC-55494, a human IL-3 receptor agonist, in a nonhuman primate model of HIGH dose, sublethal, radiation-induced marrow aplasia

International Nuclear Information System (INIS)

Herodin, F.; Farese, A.; Grab, L.; McKearn, J.P.; Mestries, J.C.; McVittie, T.J.

1994-01-01

The synthetic cytokine (Synthokine) SC-55494 is a high affinity IL-3 receptor ligand. The therapeutic administration of Synthokine to total body irradiated (TBI) monkeys (7 Gy gamma) from day 1 post TBI for 23 days, significantly enhanced platelet recovery and modulated aneutrophil nadir. (author)

Combined modality therapy of diffuse histology non-Hodgkin's lymphoma with cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) and total body irradiation

International Nuclear Information System (INIS)

Weick, J.K.; Antunez, A.; Kraus, T.A.; Fabian, C.J.; Dixon, D.

1983-01-01

The combination of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) alternating with total body irradiation (TBI) has been shown earlier to be effective therapy in patients with malignant lymphoma who have received prior chemotherapy and/or radiation therapy. A limited institutional pilot study was therefore done by the Southwest Oncology Group between October 1977, and November 1978 to test the benefit of this program in previously untreated persons with Stages 3 and 4 diffuse histology non-Hodgkin's lymphoma. Eleven evaluable patients with the following histologies were treated: 7 poorly differentiated, 2 with histiocytic, 1 with mixed lymphoma and 1 with well-differentiated morphology. Responses were seen in 8/11 patients (6 CR and 2 PR); 5 persons are currently alive and 6 are dead. The median duration of remission is 15 months and the median survival for all patients is 48 months. The therapy was well tolerated with a mean nadir leukocyte count of 3020 x 10 9 /μl (range 1.2 to 5.5) and a mean nadir platelet count of 188 x 10 9 /μl (range 016 to 270). As delivered, this program is capable of producing durable remissions and needs to be verified in a larger series of patients

Acute effects of whole body gamma irradiation on exocrine pancreatic secretion in the pig

International Nuclear Information System (INIS)

Monti, P.; Scanff, P.; Joubert, C.; Vergnet, M.; Grison, S.; Griffiths, N.

2004-01-01

Reports on radiation damage to the pancreas deal essentially with long-term morphological changes with few data on pancreatic exocrine function. The aim of this work was to study the acute effects of whole body irradiation on volume and enzyme activities in the pancreatic juice. A whole body gamma irradiation (6 Gy) was investigated in pigs with continuous sampling of pancreatic juice before and after exposure via an indwelling catheter in the pancreatic duct. For each sample collected, total protein concentration and enzyme activities of trypsin, chymotrypsin, elastase, lipase and amylase were determined. Pancreatic juice volume was monitored during all periods of collection. The volume of pancreatic juice secreted daily decreased one day after irradiation and remained lower than the control values over the experimental period. Total proteins secreted in the pancreatic juice and total activities of pancreatic enzymes were reduced similarly. On the other hand, only specific activities of elastase and lipase were affected by irradiation. Whole body gamma irradiation resulted in a rapid and marked decrease of exocrine pancreatic secretion, in terms of volume as well as secreted enzymes. This may contribute in part to the intestinal manifestations of the acute and/or late radiation syndrome. (author)

Study of human mesenchymal stem cells plasticity into radiation injured tissues in a N.O.D./S.C.I.D. mouse model: therapeutic approach of the multiple organ dysfunction; Etude de la capacite plastique des Cellules Souches Mesenchymateuses humaines (CSM) apres irradiation du tissu receveur: approche therapeutique de l'atteinte multiorgane radio-induite

Energy Technology Data Exchange (ETDEWEB)

Francois, S

2006-01-15

The therapeutic potential of bone marrow-derived human mesenchymal stem cells (h.M.S.C.) has recently been brought into the spotlight of many fields of research. One possible application of the approach is the repair of injured tissues arising from side effects of radiation treatments and accidents. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both questions using h.M.S.C. cultured and then infused to Non Obese Diabetes/Severe Combined Immunodeficiency (N.O.D./S.C.I.D.) mice submitted to total body irradiation. Further, we tested the impact of additional local irradiation superimposed to total body irradiation (T.B.I.), as a model of accidental irradiation. Our results showed that the h.M.S.C. used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, h.M.S.C. not only migrate in bone marrow but also into other tissues. Total body irradiation increased h.M.S.C. implantation in bone marrow and muscle and further led to engraftment in brain, heart, and liver. Local irradiation, in addition to T.B.I., increased both specific homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. M.S.C. may participate to restoration of intestinal homeostasis 3 days post abdominal irradiation. This study suggests that using the potential of h.M.S.C. to home to various organs in response to tissue injuries could be a promising strategy to repair the radiation induced damages. (author)

Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage.

Science.gov (United States)

Shirazi, Alireza; Mihandoost, Ehsan; Ghobadi, Ghazale; Mohseni, Mehran; Ghazi-Khansari, Mahmoud

2013-01-01

Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system.The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study,thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin (30 mg/kg on the first day and 30 mg/kg on the following days), group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal (IP) injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde (MDA) and glutathione (GSH). Each data point represents mean ± standard error on the mean (SEM) of at least eight animals per group. A one-way analysis of variance (ANOVA) was performed to compare different groups, followed by Tukey's multiple comparison tests (p<0.05). The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin (30 mg/kg) were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation.

Automated Comprehensive Evaluation of mTBI Visual Dysfunction

Science.gov (United States)

2017-04-01

of the NODe . Subtask 1: Statistical analysis of NODe data from controls and mTBI patients: COMPLETED Data Processing : Automated data analyses are...order visual processing dysfunctions on a large population of Warfighters with acute mTBI as compared to healthy age-matched controls . This study also... controls ) military personnel will be recruited from the patient population at Womack Army Medical Center (WAMC). The central hypothesis is that a NODe test

Sleep Disturbances, TBI and PTSD: Implications for Treatment and Recovery

Science.gov (United States)

Gilbert, Karina Stavitsky; Kark, Sarah M.; Gehrman, Philip; Bogdanova, Yelena

2015-01-01

Post-Traumatic Stress Disorder (PTSD), traumatic brain injury (TBI), and sleep problems significantly affect recovery and functional status in military personnel and Veterans returning from combat. Despite recent attention, sleep is understudied in the Veteran population. Few treatments and rehabilitation protocols target sleep, although poor sleep remains at clinical levels and continues to adversely impact functioning even after the resolution of PTSD or mild TBI symptoms. Recent developments in non-pharmacologic sleep treatments have proven efficacious as stand-alone interventions and have potential to improve treatment outcomes by augmenting traditional behavioral and cognitive therapies. This review discusses the extensive scope of work in the area of sleep as it relates to TBI and PTSD, including pathophysiology and neurobiology of sleep; existing and emerging treatment options; as well as methodological issues in sleep measurements for TBI and PTSD. Understanding sleep problems and their role in the development and maintenance of PTSD and TBI symptoms may lead to improvement in overall treatment outcomes while offering a non-stigmatizing entry in mental health services and make current treatments more comprehensive by helping to address a broader spectrum of difficulties. PMID:26164549

Hypodontia in the beagle after perinatal whole-body 60Co gamma irradiation

International Nuclear Information System (INIS)

Lee, A.C.; Angleton, G.M.; Benjamin, S.A.

1989-01-01

As part of a long-term study to evaluate health effects of pre- and postnatal irradiation, dental development was examined. Beagles were irradiated in utero at 8, 28, or 55 days postcoitus or postnatally at 2, 70, or 365 days postpartum. Whole-body 60 Co gamma radiation doses ranged from 0 to 3.8 Gy. There was an age-dependent dose-related increase in premolar hypodontia for animals irradiated at 55 days postcoitus or 2 days postpartum with doses of 0.83 Gy or higher and for those irradiated at 28 days postcoitus with 1.2 Gy or higher

Sexual Functioning, Desire, and Satisfaction in Women with TBI and Healthy Controls

Directory of Open Access Journals (Sweden)

Jenna Strizzi

2015-01-01

Full Text Available Traumatic brain injury (TBI can substantially alter many areas of a person’s life and there has been little research published regarding sexual functioning in women with TBI. Methods. A total of 58 women (29 with TBI and 29 healthy controls from Neiva, Colombia, participated. There were no statistically significant differences between groups in sociodemographic characteristics. All 58 women completed the Sexual Quality of Life Questionnaire (SQoL, Female Sexual Functioning Index (FSFI, Sexual Desire Inventory (SDI, and the Sexual Satisfaction Index (ISS. Results. Women with TBI scored statistically significantly lower on the SQoL (p<0.001, FSFI subscales of desire (p<0.05, arousal (p<0.05, lubrication (p<0.05, orgasm (p<0.05, and satisfaction (p<0.05, and the ISS (p<0.001 than healthy controls. Multiple linear regressions revealed that age was negatively associated with some sexuality measures, while months since the TBI incident were positively associated with these variables. Conclusion. These results disclose that women with TBI do not fare as well as controls in these measures of sexual functioning and were less sexually satisfied. Future research is required to further understand the impact of TBI on sexual function and satisfaction to inform for rehabilitation programs.

Effects of whole body UV-irradiation on oxygen delivery from the erythrocyte

International Nuclear Information System (INIS)

Humpeler, E.; Mairbaeurl, H.; Hoenigsmann, H.

1982-01-01

In 16 healthy caucasian volunteers (mean age: 22.2 years) the influence of whole body UV-irradiation on the oxygen transport properties of erythrocytes was investigated. Four hours after irradiation with UV (using the minimal erythema dose, MED) no variation of haemoglobin concentration, hematocrit, mean corpuscular haemoglobin concentration, pH or standard bicarbonate could be found, whereas inorganic plasma phosphate (Psub(i)), calcium, the intraerythrocytic 2,3-diphosphoglycerate (2,3-DPG), the activity of erythrocytic phosphofructokinase (PFK) and pyruvatekinase (PK) increased significantly. The half saturation tension of oxygen (P 50 -value) tended to increase. The increase of Psub(i) causes - via a stimulation of the glycolytic pathway - an increase in 2,3-DPG concentration and thus results in a shift of the oxygen dissociation curve. It is therefore possible to enhance tissue oxygenation by whole body UV-irradiation. (orig.)

Effect of whole-body X-irradiation on lysosomal enzymes

Energy Technology Data Exchange (ETDEWEB)

D' souza, D W; Vakil, U K; Srinivasan, A [Bhabha Atomic Research Centre, Bombay (India). Biochemistry and Food Technology Div.

1974-06-01

Effects of whole-body x irradiation with sublethal dose (400 rad) on three intestinal lysosomal enzymes, namely, arylsulphatase, cathepsin and acid phosphatases, have been studied. They are almost equally distributed throughout the entire small intestine region. X irradiation adversely affects the integrity of lysosomal membranes. ''Free'' and ''total'' lysosomal enzyme activities exhibit maxima on 6th day. These activities return to normal level on 14th day when there is rapid generation of villi, indicating that lysosomal activities correlate with the progression of injury and of repair mechanism after sublethal dose of x irradiation. The increase in total lysosomal activity may be due to its decreased breakdown, since the rate of protein synthesis in intestinal mucosa is reduced. This is evidenced by reduced incorporation of orally fed /sup 14/C leucine into acid insoluble proteins. (auth)

Head injuries (TBI) to adults and children in motor vehicle crashes.

Science.gov (United States)

Viano, David C; Parenteau, Chantal S; Xu, Likang; Faul, Mark

2017-08-18

This is a descriptive study. It determined the annual, national incidence of head injuries (traumatic brain injury, TBI) to adults and children in motor vehicle crashes. It evaluated NASS-CDS for exposure and incidence of various head injuries in towaway crashes. It evaluated 3 health databases for emergency department (ED) visits, hospitalizations, and deaths due to TBI in motor vehicle occupants. Four databases were evaluated using 1997-2010 data on adult (15+ years old) and child (0-14 years old) occupants in motor vehicle crashes: (1) NASS-CDS estimated the annual incidence of various head injuries and outcomes in towaway crashes, (2) National Hospital Ambulatory Medical Care Survey (NHAMCS)-estimated ED visits for TBI, (3) National Hospital Discharge Survey (NHDS) estimated hospitalizations for TBI, and (4) National Vital Statistics System (NVSS) estimated TBI deaths. The 4 databases provide annual national totals for TBI related injury and death in motor vehicle crashes based on differing definitions with TBI coded by the Abbreviated Injury Scale (AIS) in NASS-CDS and by International Classification of Diseases (ICD) in the health data. Adults: NASS-CDS had 16,980 ± 2,411 (risk = 0.43 ± 0.06%) with severe head injury (AIS 4+) out of 3,930,543 exposed adults in towaway crashes annually. There were 49,881 ± 9,729 (risk = 1.27 ± 0.25%) hospitalized with AIS 2+ head injury, without death. There were 6,753 ± 882 (risk = 0.17 ± 0.02%) fatalities with a head injury cause. The public health data had 89,331 ± 6,870 ED visits, 33,598 ± 1,052 hospitalizations, and 6,682 ± 22 deaths with TBI. NASS-CDS estimated 48% more hospitalized with AIS 2+ head injury without death than NHDS occupants hospitalized with TBI. NASS-CDS estimated 29% more deaths with AIS 3+ head injury than NVSS occupant TBI deaths but only 1% more deaths with a head injury cause. Children: NASS-CDS had 1,453 ± 318 (risk = 0.32 ± 0.07%) with severe head injury (AIS 4+) out of 454,973 exposed

Half-body irradiation in the treatment of metastatic prostatic carcinoma

International Nuclear Information System (INIS)

Rowland, C.G.; Bullimore, J.A.; Smith, P.J.B.; Roberts, J.B.M.

1981-01-01

High dose radiation therapy given as a single fraction to the upper and lower halves of the body gives effective palliation for metastatic solid tumours. This treatment modality appears to be particularly effective in tumours which may have a slow doubling time such as carcinoma of the prostate. Fifty-two patients with metastatic carcinoma of the prostate involving the skeletal system have received half-body irradiation (8 MeV X-rays at a dose rate of about 100 cGy/min). All had prior treatment with additive hormones or orchiectomy and the majority had received localised irradiation and/or chemotherapy. Significant immediate pain relief was achieved in 42 out of 52 patients (80%). This pain relief was maintained until death in 29 out of 43 patients (67%). Pain relief in responders appears to occur within 24 to 48 h of treatment. (author)

The role of low-dose total body irradiation in treatment of non-Hodgkin's lymphoma: a new look at an old method

International Nuclear Information System (INIS)

Safwat, A.

2000-01-01

The use of low-dose total body irradiation (LTBI) in treatment of lymphomatous malignancies dates back to the 1920s. The usual practice was to give very low individual TBI fraction sizes (0. 1-0.25 Gy) several times a week to a total dose of 1.5-2 Gy. Despite this very low total dose, LTBI could induce long term remissions and was always as effective as the chemotherapy to which it was compared. In modem radiotherapy, LTBI is still a valid option in treatment of chronic lymphocytic leukaemia (CLL) and the advanced stages of indolent low-grade non-Hodgkin's lymphoma (NHL). Its use in the early stages of low-grade NHL is under investigation in a large multi-institutional trial. The efficacy of LTBI is believed to stem from three mechanisms, namely; immune-enhancement, induction of apoptosis, and the intrinsic hypersensitivity to low-radiation doses demonstrated in many cell lines and tumour systems. Thus, LTBI seems to provide 'alternative' mechanisms of action against cancer cells. This should encourage researchers to explore strategies that integrate LTBI in new and innovative experimental treatment protocols that explore the possible synergism between LTBI and chemotherapy, biological response modifiers and/or immunotherapy. The increased incidence of secondary leukaemia that occurs when LTBI is combined with alkylating agents and/or total lymphoid irradiation should be kept in mind when designing such protocols as it may limit the use of LTBI in highly curable diseases and young patients in whom long survival is expected. (author)

Uptake of carbon monoxide by C3H mice following X irradiation of lung only or total-body irradiation with 60Co

International Nuclear Information System (INIS)

Rappaport, D.S.; Niewoehner, D.E.; Kim, T.H.; Song, C.W.; Levitt, S.H.

1983-01-01

Carbon monoxide uptake (V/sub co/) and ventilation rate (VR) of C3H mice were determined at 14 weeks following either X irradiation of lungs only or total-body irradiation with 60 Co at different dose rates. Following localized X irradiation of lung at 97 /sub c/Gy/min there was a reduction in V/sub co/, which was inversely related to radiation dose, with a small reduction below control levels being detected at 7 Gy, the lowest dose tested. An increase in VR could be detected only at doses of 11 Gy, or more. Another group of animals received 11.5 Gy total-body irradiation at either 26.2 or 4.85 /sub c/Gy/min fllowed by transplantation with syngeneic bone marrow. Following total-body irradiation, V/sub co/ was significantly reduced by about 37% at the higher dose rate and 23% at the lower dose rate. In contrast, a trend toward elevated VR was detected only at the higher dose rate.The results indicate that V/sub co/ is a sensitive indicator of radiation-induced lung injury and that under the experimental conditions used V/sub co/ is a more sensitive indicator of radiation-induced lung injury in C3H mice than VR

Development of fibrosis in dogs as a late consequence of whole-body X-irradiation

International Nuclear Information System (INIS)

Calvo, W.; Fliedner, T.M.; Steinbach, I.; Alcober, V.; Nothdurft, W.; Fache, I.

1978-01-01

Dogs wre whole-body irradiated with a single mid-line dose of 1200 R at 300 kV. This high dose will kill non-treated animals within a few days. To save these animals, leukocytes were previously collected during a four-hour leukapheresis using a continuous-flow centrifuge and were stored under liquid nitrogen. Shortly after the whole-body irradiation each dog received its own cryopreserved cells thawed immediately beforehand. The dogs received between 0.32x10 9 and 1.63x10 9 mononuclear blood cells per kilogram of body weight. The number of colony-forming cells contained in the transfusate ranged between 0.19x10 5 and 1.38x10 5 per kilogram of body weight. This blood stem transfusion, together with general supportive therapy, enabled the dogs to overcome the acute radiation syndrome and to recover. The dogs were subsequently sacrificed in two groups after observation for about 260 days or 700-898 days respectively. Pathological findings are described. A particular situation existed in the marrow, whre non-irradiated stem cells had colonized bone cavities containing irradiated stroma. Progressive fibrosis developed in the endosteal areas of the bone cavities in most of the animals. (author)

Acid-base status after whole-body irradiation in dairy cows

International Nuclear Information System (INIS)

Schaefer, M.; Koch, F.; Dyrba, W.; Kirbach, M.

1989-01-01

Whole-body irradiation using 9 MeV X-rays of a linear accelerator of 10 clinically healthy lactating cows aged between 3.5 and 8 years produced an acute radiation syndrome in the LD 100/30 range. Blood analysis 1 day after irradiation showed a compensated metabolic acidosis with a low renal net acid-base excretion and hyerphosphaturia. Later the acid-base status indicated a differently marked metabolic alkalosis. In the main reaction period acidotic disturbances occurred, which partially were camouflaged by respiratory alkalosis. (author)

Influence of whole-body irradiation on calcium and phosphate homeostasis in the rat

International Nuclear Information System (INIS)

Pento, J.T.; Kenny, A.D.

1975-01-01

Previous irradiation studies have revealed marked alterations in calcium metabolism. Moreover, the maintenance of calcium homeostasis with parathyroid hormone or calcium salts has been reported to reduce radiation lethality. Therefore, the present study was designed to evaluate the influence of irradiation on calcium homeostasis in the rat. Nine hundred rad of whole-body irradiation produced a significant depression of both plasma calcium and phosphate at 4 days postirradiation. This effect of irradiation was observed to be dose-dependent over a range of 600 to 1200 rad, and possibly related to irradiation-induced anorexia. The physiological significance of these observations is discussed

Technical problems of TBI in case of the moving couch method

Energy Technology Data Exchange (ETDEWEB)

Tsuda, Masayuki (Tokai Univ., Isehara, Kanagawa (Japan). Hospital)

1991-12-01

In Tokai University Hospital ever since 1982, TBI for bone marrow transplantation has been performed by the moving couch method. In this method, the patient is irradiated from the opposite direction of A-P and P-A in a comfortable supine position as is. This technique has been well studied and greatly improved. For example, the moving speed of the couch is automatically varied depending on the dose rate deviation of the electron linear accelerator, function having variable speed with the dose rate (VSDR). Another function in variable speed with division (VSDV). In addition it has a self-recording function for the actual condition for the dose and couch movement. In such small areas as the eyes and gonad, the shielding effect cannot be effectively used. For the lungs, but it is able to shield and compensate to a sufficient extent. It applied to actual treatment resulting from data obtained from the measurements using a phantom. During the irradiation we must check the reproducibility of the systems which are dose rate, couch position, and so on. This is one reasonable concept of the dose monitor. (author).

Impairment in extinction of contextual and cued, fear following post-training whole body irradiation

Directory of Open Access Journals (Sweden)

Reid HJ Olsen

2014-07-01

Full Text Available Because of the use of radiation in cancer therapy, the risk of nuclear contamination from power plants, military conflicts, and terrorism, there is a compelling scientific and public health interest in the effects of environmental radiation exposure on brain function, in particular hippocampal function and learning and memory. Previous studies have emphasized changes in learning and memory following radiation exposure. These approaches have ignored the question of how radiation exposure might impact recently acquired memories, which might be acquired under traumatic circumstances (cancer treatment, nuclear disaster, etc.. To address the question of how radiation exposure might affect the processing and recall of recently acquired memories, we employed a fear-conditioning paradigm wherein animals were trained, and subsequently irradiated (whole-body X-ray irradiation 24 hours later. Animals were given two weeks to recover, and were tested for retention and extinction of hippocampus-dependent contextual fear conditioning. Exposure to irradiation following training was associated with reduced daily increases in body weights over the 22 days of the study and resulted in greater freezing levels and aberrant extinction 2 weeks later. This was also observed when the intensity of the training protocol was increased. Cued freezing levels and measures of anxiety 2 weeks after training were also higher in irradiated than sham-irradiated mice. In contrast to contextual freezing levels, cued freezing levels were even higher in irradiated mice receiving 5 shocks during training than sham-irradiated mice receiving 10 shocks during training. In addition, the effects of radiation on extinction of contextual fear were more profound than those on the extinction of cued fear. Thus, whole body irradiation elevates contextual and cued fear memory recall.

Impact of anemia prevention by recombinant human erythropoietin on the sensitivity of xenografted glioblastomas to fractionated irradiation

International Nuclear Information System (INIS)

Stueben, G.; Poettgen, C.; Knuehmann, K.; Sack, H.; Stuschke, M.; Thews, O.; Vaupel, P.

2003-01-01

Background: Pronounced oxygen deficiency in tumors which might be caused by a diminished oxygen transport capacity of the blood (e.g., in anemia) reduces the efficacy of ionizing radiation. The aim of this study was to analyze whether anemia prevention by recombinant human erythropoietin (rHuEPO) affects the radiosensitivity of human glioblastoma xenografts during fractionated irradiation. Material and Methods: Anemia was induced by total body irradiation (TBI, 2 x 4 Gy) of mice prior to tumor implantation into the subcutis of the hind leg. In one experimental group, the development of anemia was prevented by rHuEPO (750 U/kg s.c.) given three times weekly starting 10 days prior to TBI. 13 days after tumor implantation (tumor volume approx. 40 mm 3 ), fractionated irradiation (4 x 7 Gy, one daily fraction) of the glioblastomas was performed resulting in a growth delay with subsequent regrowth of the tumors. Results: Compared to nonanemic control animals (hemoglobin concentration cHb = 14.7 g/dl), the growth delay in anemic mice (cHb = 9.9 g/dl) was significantly shorter (49 ± 5 days vs. 79 ± 4 days to reach four times the initial tumor volume) upon fractionated radiation. The prevention of anemia by rHuEPO treatment (cHb = 13.3 g/dl) resulted in a significantly prolonged growth delay (61 ± 5 days) compared to the anemia group, even though the growth inhibition found in control animals was not completely achieved. Conclusions: These data indicate that moderate anemia significantly reduces the efficacy of radiotherapy. Prevention of anemia with rHuEPO partially restores the radiosensitivity of xenografted glioblastomas to fractionated irradiation. (orig.)

Influence of whole-body gamma irradiation upon arachidonic acid metabolism in rat platelets

International Nuclear Information System (INIS)

Lognonne, J.L.; Ducousso, R.; Rocquet, G.; Kergonou, J.F.

1985-01-01

The effects of whole-body gamma irradiation (8.4 Gy) were studied on arachidonic acid (AA) metabolism in rat's blood platelets, from day D + 1 to day D + 10 after irradiation. AA conversion into thromboxane B 2 (TxB 2 ) increased at D + 1 and then gradually decreased to very low values from D + 7 to D + 10. This decrease in the conversion of exogenous AA into TxB 2 was due to a lower AA incorporation into platelets and not to a decrease of cyclooxygenase and thromboxane-synthetase activities. AA incorporation into membrane phospholipids of blood platelets was much more decreased than AA incorporation into whole platelets; moreover, the lipid composition of the platelet membranes was markedly modified after irradiation, which must have resulted in structural and functional changes in these membranes; from these effects of whole-body gamma irradiation on platelets, the latter's membranes appeared as a major site of in vivo radiation damage in these cells

Effects of whole-body irradiation on neonatally thymectomized mice. Incidence of benign and malignant tumors

International Nuclear Information System (INIS)

Anderson, R.E.; Howarth, J.L.; Troup, G.M.

1978-01-01

The individual and combined effects of neonatal thymectomy and whole-body irradiation on the prevalence of benign and malignant tumors in germ-free female mice of the Charles Rivers line were studied to determine if a portion of the tumorigenic effects of irradiation can be attributed to injury of the thymic-dependent component of the immune response. Neonatal thymectomy increased (a) the incidence of benign and malignant tumors and (b) the prevalence of multiple primary neoplasms in an individual mouse. Whole-body exposure to 700 rad at 6 weeks of age further increased the incidence of tumors, but the relative magnitude of this increase was less pronounced than in sham-operated controls. Thus, the cumulative effects of thymectomy plus irradiation are less pronounced than the sum of the individual effects. One of several possible explanations for this observation is that a portion of the carcinogenic effects of whole-body irradiation is mediated by suppression of the thymic-dependent component of the immune response

Dose calculation method with 60-cobalt gamma rays in total body irradiation

International Nuclear Information System (INIS)

Scaff, Luiz Alberto Malaguti

2001-01-01

Physical factors associated to total body irradiation using 60 Co gamma rays beams, were studied in order to develop a calculation method of the dose distribution that could be reproduced in any radiotherapy center with good precision. The method is based on considering total body irradiation as a large and irregular field with heterogeneities. To calculate doses, or doses rates, of each area of interest (head, thorax, thigh, etc.), scattered radiation is determined. It was observed that if dismagnified fields were considered to calculate the scattered radiation, the resulting values could be applied on a projection to the real size to obtain the values for dose rate calculations. In a parallel work it was determined the variation of the dose rate in the air, for the distance of treatment, and for points out of the central axis. This confirm that the use of the inverse square law is not valid. An attenuation curve for a broad beam was also determined in order to allow the use of absorbers. In this work all the adapted formulas for dose rate calculations in several areas of the body are described, as well time/dose templates sheets for total body irradiation. The in vivo dosimetry, proved that either experimental or calculated dose rate values (achieved by the proposed method), did not have significant discrepancies. (author)

Busulfan, cyclophosphamide and fractionated total body irradiation as a conditioning regimen for allogeneic bone marrow transplantation in patients with non-lymphocytic hematopoietic malignancies

International Nuclear Information System (INIS)

Watanabe, Hiroshi

1996-01-01

Allogeneic bone marrow transplantation (BMT) with the conditioning regimen of 8 mg/kg of busulfan (BUS), 120 mg/kg of cyclophosphamide (CPM) and 10 Gy of total body irradiation (TBI) was evaluated in the patients with non-lymphocytic hematopoietic malignancies. The disease distribution of the 22 patients was as follows; 14 in the standard risk group (SRG), 8 in the high risk group (HRG). SRG included the patients with acute myeloid leukemia (AML) in the first complete remission, chronic myelogenous leukemia (CML) in chronic phase and myelodysplastic syndrome with refractory anemia, while HRG included the patients with refractory AML and CML in blastic phase. The median age of patients was 33 years old (y.o.), and the median observation period was 34.5 months No relapse occurred, but 8 patients (36%) died of various complications. Ail the patients who died of interstitial pneumonitis (4 cases) were 40 y.o. and more. Acute graft-versus-host disease (GvHD) and chronic GvHD were clinically controllable. The probability of disease-free survival rate at 5 years (5y-DFS) was 50.0% in overall patients. The 5y-DFS was 57.1% in HRG (7 cases), while 54.3% in SRG (13 cases) donated from the HLA identical siblings (20 cases). In these 13 patients in SRG, the 5y-DFS was 100% in patients under 40 y.o. (6 cases), while the probability of disease-free survival rate at 3 years was 68.6% and the 5y-DFS was 0% in patients over 40 y.o. (7 cases). Our data indicate that the conditioning regimen combining BUS, CPM and TBI for allogeneic BMT is promising for the treatment of the patients of HRG and the patients under 40 y.o. in SRG. (author)

Busulfan, cyclophosphamide and fractionated total body irradiation as a conditioning regimen for allogeneic bone marrow transplantation in patients with non-lymphocytic hematopoietic malignancies

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Hiroshi [Jikei Univ., Tokyo (Japan). School of Medicine

1996-11-01

Allogeneic bone marrow transplantation (BMT) with the conditioning regimen of 8 mg/kg of busulfan (BUS), 120 mg/kg of cyclophosphamide (CPM) and 10 Gy of total body irradiation (TBI) was evaluated in the patients with non-lymphocytic hematopoietic malignancies. The disease distribution of the 22 patients was as follows; 14 in the standard risk group (SRG), 8 in the high risk group (HRG). SRG included the patients with acute myeloid leukemia (AML) in the first complete remission, chronic myelogenous leukemia (CML) in chronic phase and myelodysplastic syndrome with refractory anemia, while HRG included the patients with refractory AML and CML in blastic phase. The median age of patients was 33 years old (y.o.), and the median observation period was 34.5 months No relapse occurred, but 8 patients (36%) died of various complications. Ail the patients who died of interstitial pneumonitis (4 cases) were 40 y.o. and more. Acute graft-versus-host disease (GvHD) and chronic GvHD were clinically controllable. The probability of disease-free survival rate at 5 years (5y-DFS) was 50.0% in overall patients. The 5y-DFS was 57.1% in HRG (7 cases), while 54.3% in SRG (13 cases) donated from the HLA identical siblings (20 cases). In these 13 patients in SRG, the 5y-DFS was 100% in patients under 40 y.o. (6 cases), while the probability of disease-free survival rate at 3 years was 68.6% and the 5y-DFS was 0% in patients over 40 y.o. (7 cases). Our data indicate that the conditioning regimen combining BUS, CPM and TBI for allogeneic BMT is promising for the treatment of the patients of HRG and the patients under 40 y.o. in SRG. (author)

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism.

Science.gov (United States)

Pierce, Janet D; Gupte, Raeesa; Thimmesch, Amanda; Shen, Qiuhua; Hiebert, John B; Brooks, William M; Clancy, Richard L; Diaz, Francisco J; Harris, Janna L

2018-06-01

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI. © 2018 Wiley Periodicals, Inc.

Effect of bifidobacteria implantation on the survival time of whole-body irradiated mice

International Nuclear Information System (INIS)

Yokokura, Teruo; Onoue, Masaharu; Mutai, Masahiko

1980-01-01

Letahl dose (2 KR) of gamma-ray was irradiated on the whole bodies of mice. Survival time after irradiation was significantly longer in mice with administration of both Bifidobacterium breve YIT 4008 and transgalactosyl oligosaccharide than in mice with administration of either of the two or nothing. (Tsunoda, M.)

Effects of ancestral x irradiation followed by random mating on body weight of rats

International Nuclear Information System (INIS)

Gianola, D.; Chapman, A.B.; Rutledge, J.J.

1977-01-01

Effects of nine generations of 450R per generation of ancestral spermatogonial x irradiation of inbred rats on body weight were examined. After six generations of random mating (avoiding inbreeding) following the termination of irradiation, descendants of irradiated males (R) were significantly lighter than their controls (C) at 3 and 6 weeks, but not at 10 weeks of age. However, differences in growth between R and C populations were small. Among-litter and within-litter variance estimates were generally larger in the R lines than in the C lines, suggesting that selection responses would be greater in R than in C lines. In conjunction with previous evidence--obtained during the irradiation phase of the experiment--this suggested that more rapid response to selection for 6-week body weight, in particular, might accrue in the R lines

Report of experience with large dose single upper and lower half-body irradiation. 3. Hematological and serological findings

Energy Technology Data Exchange (ETDEWEB)

Dalluege, K H; Eichhorn, H J; Grunau, H [Akademie der Wissenschaften der DDR, Berlin. Zentralinstitut fuer Krebsforschung

1981-08-01

The reaction of hematological and serological parameters in 47 patients having received a large dose single irradiation of the upper and the parvicellular bronchial carcinoma, resp., of the upper and of the lower half of the body with 8.4 Gy for the mid-line is reported. Different positions of the patients during irradiation and different fractionations were compared. Subdivision of the half-body irradiation dose, anteroposterior direction of irradiation and partial sparing of the extremities during treatment proved to be the most careful method for the leukopoietic system because the leukocytes reached their initial values 6 weeks and the lymphocytes 2 months after irradiation. Serum aldolase is a suitable parameter for tumor response and for the demonstration of eventually not yet known metastases in the irradiated half of the body with an increase of the values above 8 IU per liter after irradiation. Creatine kinase is an indicator of the radiation response of the muscles.

Optimum combination of targeted 131I and total body irradiation for treatment of disseminated cancer

International Nuclear Information System (INIS)

Amin, Amin E.; Wheldon, Tom E.; O'Donoghue, Joseph A.; Gaze, Mark N.; Barrett, Ann

1995-01-01

Purpose: Radiobiological modeling was used to explore optimum combination strategies for treatment of disseminated malignancies of differing radiosensitivity and differing patterns of metastatic spread. The purpose of the study was to derive robust conclusions about the design of combination strategies that incorporate a targeting component. Preliminary clinical experience of a neuroblastoma treatment strategy, which is based upon general principles obtained from modelling, is briefly described. Methods and Materials: The radiobiological analysis was based on an extended (dose-rate dependent) formulation of the linear quadratic model. Radiation dose and dose rate for targeted irradiation of tumors of differing size was in part based on microdosimetric considerations. The analysis was applied to several tumor types with postulated differences in the pattern of metastatic spread, represented by the steepness of the slope of the relationship between numbers of tumors present and tumor diameter. The clinical pilot study entailed the treatment of five children with advanced neuroblastoma using a combination of 131 I metaiodobenzylguanidine (mIBG) and total body irradiation followed by bone marrow rescue. Results: The theoretical analysis shows that both intrinsic radiosensitivity and pattern of metastatic spread can influence the composition of the ideal optimum combination strategy. High intrinsic radiosensitivity generally favors a high proportion of targeting component in the combination treatment, while a strong tendency to micrometastatic spread favors a major contribution by total body irradiation. The neuroblastoma patients were treated using a combination regimen with an initially low targeting component (2 Gy whole body dose from targeting component plus 12 Gy from total body irradiation). The treatment was tolerable and resulted in remissions in excess of 9 months in each of these advanced neuroblastoma patients. Conclusions: Radiobiological analysis, which

A Study on the Effectiveness of the Manufacture of Compensator and Setup Position for Total Body Irradiation Using Computed Tomography-simulator's Images

International Nuclear Information System (INIS)

Lee, Woo Suk; Kim, Dae Sup; Park, Seong Ho; Yun, In Ha; Back, Geum Mun; Kim, Jeong Man

2005-01-01

We should use a computed tomography-simulator for the body measure and compensator manufacture process was practiced with TBI's positioning in process and to estimate the availability. Patient took position that lied down. and got picture through computed tomography-simulator. This picture transmitted to Somavision and measured about body measure point on the picture. Measurement was done with skin, and used the image to use measure the image about lungs. We decided thickness of compensator through value that was measured by the image. Also, We decided and confirmed position of compensator through image. Finally, We measured dosage with TLD in the treatment department. About thickness at body measure point. we could find difference of 1-2 cm relationship general measure and image measure. General measure and image measure of body length was seen difference of 3-4 cm. Also, we could paint first drawing of compensator through the image. The value of dose measurement used TLD on head, neck, axilla, chest(lungs inclusion), knee region were measured by 92-98% and abdomen, pelvis, inquinal region, feet region were measured by 102-109%. It was useful for TBI's positioning to use an image of computed tomography-simulator in the process. There was not that is difference of body thickness measure point, but measure about length was achieved definitely. Like this, manufacture of various compensator that consider body density if use image is available. Positioning of compensator could be done exactly, and produce easily without shape of compensator is courted Positioning in the treatment department could shortened overall 15 minute time. and reduce compensator manufacture time about 15 minutes.

Delivery of mental health treatment to combat veterans with psychiatric diagnoses and TBI histories.

Directory of Open Access Journals (Sweden)

Shannon R Miles

Full Text Available Traumatic brain injury (TBI and mental health (MH disorders are prevalent in combat veterans returning from Afghanistan and/or Iraq (hereafter referred to as returning veterans. Accurate estimates of service utilization for veterans with and without TBI exposure (referred to as TBI history are imperative in order to provide high quality healthcare to returning veterans. We examined associations between TBI history and MH service utilization in a subsample of returning veterans who were newly diagnosed with posttraumatic stress disorder (PTSD, depression, and/or anxiety in the 2010 fiscal year (N = 55,458. Data were extracted from the Veterans Health Administration (VHA National Patient Care Database. Veterans with MH diagnoses and TBI histories attended significantly more psychotherapy visits, (M = 8.32 visits, SD = 17.15 and were more likely to attend at least 8 psychotherapy visits, (15.7% than veterans with MH diagnoses but no TBI history (M = 6.48 visits, SD = 12.12; 10.1% attended at least 8 sessions. PTSD and TBI history, but not depression or anxiety, were associated with a greater number of psychotherapy visits when controlling for demographic and clinical variables. PTSD, anxiety, depression, and TBI history were associated with number of psychotropic medication-management visits. TBI history was related to greater MH service utilization, independent of MH diagnoses. Future research should examine what MH services are being utilized and if these services are helping veterans recover from their disorders.

Continuous gamma irradiation influence on food intake, body weight, and weight of some rat organs

Energy Technology Data Exchange (ETDEWEB)

Malatova, Z [Institute of Neurobiology SAV, Kosice (Czechoslovakia); Sedlakova, A; Ahlers, I; Praslicka, M [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Prirodovedecka Fakulta

1977-01-01

Food intake, body weight and weight of some organs were studied in male Wistar rats within 25 days of continuous gamma irradiation at a dose rate of 15.48 x 10/sup -3/ C/kg (6O R) per day in an experimental gamma field. A decrease in food intake and body weight and a decrease in thymus and spleen weights were found during the first week in irradiated rats. The thymus and spleen involutions did not progress within the second week. From the beginning of the third week till the end of the experiment the irradiated animals increased their weight and the food intake was even higher during the last week of irradiation in comparison with controls. The spleen and thymus involutions stopped but the weight remained at the lower level. The relative weight of the adrenal glands in irradiated animals only increased at the end of the period.

Electropalatographic (EPG) assessment of tongue-to-palate contacts in dysarthric speakers following TBI.

Science.gov (United States)

Kuruvilla, Mili S; Murdoch, Bruce E; Goozee, Justine V

2008-09-01

The aim of the investigation was to compare EPG-derived spatial and timing measures between a group of 11 dysarthric individuals post-severe TBI and 10 age- and sex-matched neurologically non-impaired individuals. Participants of the TBI group were diagnosed with dysarthria ranging from mild-to-moderate-severe dysarthria. Each participant from the TBI and comparison group was fitted with a custom-made artificial acrylic palate that recorded lingual palatal contact during target consonant production in sentence- and syllable-repetition tasks at a habitual rate and loudness level. Analysis of temporal parameters between the comparison and TBI groups revealed prolonged durations of the various phases of consonant production, which were attributed to articulatory slowness, impaired speech motor control, impaired accuracy, and impaired coordination of articulatory movements in the dysarthric speakers post-TBI. For the spatial measurements, quantitative analysis, as well as visual inspection of the tongue-to-palate contact diagrams, indicated spatial aberrations in dysarthric speech post-TBI. Both the spatial and temporal aberrations may have at least partially caused the perceptual judgement of articulatory impairments in the dysarthric speakers.

Effect of BCNU combined with total body irradiation or cyclophosphamide on survival of dogs after autologous marrow grafts

International Nuclear Information System (INIS)

Paterson, A.H.G.; English, D.

1979-01-01

Dogs were treated with either: (1) 750 rad total body irradiation; (2) BCNU 2 or 4 mg/kg IV 48 hours prior to 750 rad total body irradiation; or (3) BCNU 4 mg/kg IV plus cyclophosphamide 30 mg/kg IV. Results showed that of 11 dogs who received 750 rad total body irradiation and did not receive cryopreserved autologous bone marrow cells, none survived, compared to an 88% survival (31 of 35 dogs) after 750 rad total body irradiation if the dogs received stored autologous bone marrow cells. However, when the dogs were treated with BCNU 2 or 4 mg/kg prior to 750 rad total body irradiation the survival rate, despite infusion of autologous bone marrow cells, dropped to 25% (3 of 12 dogs) for BCNU 2 mg/kg, and 17% (2 of 12 dogs) for BCNU 4 mg/kg. This effect did not seem to be due to direct serum inhibition of hemopoietic cell proliferation since serum obtained at various intervals after BCNU administrations failed to inhibit CFU growth in vitro. The dogs died from hemorrhage and infection; at autopsy there was hemorrhagic pneumonitis and intestinal ulcerations with petechial hemorrhages, suggesting that the combination of BCNU and total body irradiation may have synergistic toxicity on the canine gastro-intestinal tract. When BCNU was combined with cyclophosphamide, reversal of marrow toxicity occurred in 54% (6 of 11 dogs) with stored autologous bone marrow cells compared to no survival (0 of 8 dogs) with stored autologous bone marrow cells. Thus while autologous bone marrow grafts are useful for reversal of marrow toxicity due to many therapeutic protocols, such grafts alone may not provide protection against toxicity due to the combination of high dosage BCNU and total body irradiation

Modulator Effect of Turmeric on Oxidative Damage in Whole Body Gamma Irradiated rats

International Nuclear Information System (INIS)

Amin, H.H.; Abdou, M.I.

2012-01-01

Because of its penetrating power and its ability to travel great distances, gamma rays are considered the primary hazard to the population during most radiological emergencies. So, there is a need to develop medical countermeasures to protect the first responders and remediation workers from biomedical effect of ionizing radiation. Turmeric has been reported to have many beneficial health effects, including a strong anti-oxidant effect, anti-inflammatory and anti-microbial properties. In the present study, turmeric was investigated as a therapeutic agent against hazards induced by ionizing radiation on kidney, liver, urinary and serum calcium levels and blood counts. A daily dose of 0.5 g/kg body weight was used in whole body gamma irradiated female rats with 3 Gy. Radiation effects were followed up for four weeks post irradiation. The results revealed that the administration of turmeric post-irradiation resulted in a significant inhibition in the frequency of radiation induced oxidative damage. It could be concluded that definite turmeric dose exerts a vital modulator role against gamma irradiation hazard

Radioprotection of liver lipids of whole-body gamma-irradiated female rats by cystamine

International Nuclear Information System (INIS)

Ramanathan, R.; Misra, U.K.

1976-01-01

The effect of administration of cystamine (5 mg/100 g body weight) before 1,200 R whole-body gamma irradiation has been studied on irradiation-induced changes in liver and its subcellular fractions'lipids of fasted female rats. Cystamine prevented the irradiation-induced increase in liver triglycerides and liver mitochondrial total phospholipids, but it decreased microsomal total phospholipids and proteins. Cystamine prevented the radiation-induced increased 32 P-radioactivity (counts/min/μmole phospholipid phosphorus) of microsomal phosphatidyl choline. Cystamine prevented the radiation-induced increased uptake of NaH 2 32 PO 4 (counts/min/g liver) in liver microsomal phosphatidyl ethanolamine and supernatant phosphatidyl choline; but in microsomal phosphatidyl choline, cystamine did not do so, but on the other hand it itself increased the uptake in control rats. Cystamine did not prevent the irradiation-induced decreased incorporation of (U- 14 C)glucose into liver triglycerides, total phospholipids and phosphatidyl choline. Cystamine itself decreased the incorporation of (U- 14 C)glucose into liver triglycerides and phosphoglycerides of control rats. (orig.) [de

Role of Sertraline in insomnia associated with post traumatic brain injury (TBI depression

Directory of Open Access Journals (Sweden)

Ansari Ahmed

2016-09-01

Full Text Available Traumatic brain injury (TBI is a major cause of disability (1, 2. Sleep disturbances, such as insomnia, are very common following traumatic brain injury and have been reported in frequencies from 40% (3 to as high as 84% (4. Sleep disruption can be related to the TBI itself but may also be secondary to neuropsychiatric (e.g., depression or neuromuscular (e.g., pain conditions associated with TBI or to the pharmacological management of the injury and its consequences. Post-TBI insomnia has been associated with numerous negative outcomes including daytime fatigue, tiredness, difficulty functioning: impaired performance at work, memory problems, mood problems, greater functional disability, reduced participation in activities of daily living, less social and recreational activity, less employment potential, increased caregiver burden, greater sexual dysfunction, and also lower ratings of health, poor subjective wellbeing. These negative consequences can hamper the person’s reintegration into the community, adjustment after injury, and overall QOL. (5 The connection between depression and insomnia has not been investigated within the post TBI population to a great extent. For the general population, clinically significant insomnia is often associated with the presence of an emotional disorder (6. Fichtenberg et al. (2002 (7, in his study established that the strongest relationship with the diagnosis of insomnia belonged to depression. Given the high prevalence of depression during the first 2 years following TBI (8, a link between depression and insomnia among TBI patients makes innate sense. The present study aims at assessing role of sertralline in post TBI insomnia associated with depression.

The influence of whole body 60Co-irradiation on distribution of 67Ga in tumor-bearing mice

International Nuclear Information System (INIS)

Wakao, Hiromi; Shimura, Akira; Higashi, Tomomitsu

1981-01-01

Since the initial findings that 67 Ga has a preferential affinity for soft tissue tumors, in humans numerous suggestions have been advanced for the basic mechanism involved. The effects produced by whole-body X-irradiation on the excretion and tissue distribution of 67 Ga have been reported by Swartzendruber and others. Bradley and coworkers have shown that these irradiation effects were associated with an increase in serum iron. The present investigation was undertaken in order to study the relationships between the change in the serum iron concentration and 67 Ga accumulation in the tumor and soft tissues in mice bearing Ehrlich's ascites tumor. The following results were obtained. (1) The serum iron concentration was significantly decreased between 3 and 6 hours after 10 Gy (1,000 rad) dose of whole-body 60 Co-irradiation. Subsequently, the serum iron levels were slowly elevated. (2) The uptake of 67 Ga in the tumor and soft tissues was increased if the serum iron concentration was decreased by whole-body 60 Co-irradiation during the early phase. On the contrary, if the serum iron concentration was high, the uptake of 67 Ga in the tumor was decreased. (3) The excretion of 67 Ga from the body was delayed if the serum iron concentration was decreased by whole-body 60 Co-irradiation. However, if the serum iron concentration was high, the excretion of 67 Ga from the body significantly increased. (author)

Role of sequential hemi-body irradiation in multiple myeloma: preliminary observations

International Nuclear Information System (INIS)

Kumar, H.S.; Chaudhary, R.K.; Kumar, Vanita

1993-01-01

Ten patients with multiple myeloma presenting in a highly painful condition were included in the study. They were treated by sequential hemi-body irradiation. A dose of 600 cGy was delivered to the upper hemi-body and 800 c Gy to the lower hemi-body. All patients has appreciable relief from pain. The maximum effect was achieved within 24 to 48 hours of treatment. 9 out of the 10 patients has an improvement in the performance status. All these patients were later subjected to combination chemotherapy. (author). 9 refs., 3 tabs

Changes in Serum Zinc, Copper and Ceruloplasmin Levels of Whole Body Gamma Irradiated Rats

International Nuclear Information System (INIS)

Abdou, M.I.; Shaban, H.A.; El Gohary, M.I.

2011-01-01

Rats are whole body irradiated with different Gamma radiation doses. Zinc and Copper, two important trace elements in the biological processes and Ceruloplasmin, a protein which carries more than 95% of serum Cu and has important roles in many vital processes are followed up in the irradiated rat sera. This work aimed to determine the changes in the serum levels of the three parameters (Zinc, Copper and Ceruloplasmin) through eight weeks follow up period (1st, 2nd, 3rd, 4th, 6th, and 8th week) post whole body gamma irradiation with three sub-lethal doses (2, 3.5 and 5 Gy) of rats. All the experimental animals did not receive any medical treatment. Zinc and Copper were measured using discrete nebulization flame atomic absorption spectrometry. Ceruloplasmin was measured using a colorimetric method. The statistical analyses of the results show that the Zinc levels of the irradiated groups decreased significantly post irradiation and then were recovered at the 6th week post irradiation. The Copper levels of the irradiated groups increased significantly and then were recovered at 6th week post irradiation. The levels of Ceruloplasmin in the same groups increased significantly throughout the whole follow up period. The conclusion is that, Zinc, Copper and Ceruloplasmin levels changed significantly in the irradiated groups compared to the control group with a maximum effect noted in the groups irradiated with the higher doses and that the lower dose irradiated groups recover earlier than the higher ones. Also the correlation between Copper and Zinc is reversible at different doses and that between Copper and Ceruloplasmin is direct

Effect of Hippophae leaves on neurotransmitters and hematological parameters in whole body irradiated rats

International Nuclear Information System (INIS)

Gupta, Vanita; Prasad, Jagdish; Madhu Bala

2012-01-01

Till date no approved radio-protective agent is available world over. WR-2721 had severe side effects and was behaviourally toxic even at sub-lethal doses of ionizing radiation. Seabuckthorn (Hippophae rhamnoides L.) is known for its nutraceutical and therapeutic values. Our studies demonstrated that treatment with leaves of H. rhamnoides rendered > 90% whole body radioprotection in 60 Co-g-irradiated (10 Gy) mice population in comparison to 100% death in non-Hippophae treated irradiated (10 Gy) mice population. Our studies also demonstrated that treatment with leaves of H. rhamnoides prevented conditioned taste aversion (CTA) in irradiated (2 Gy) Sprague-Dawley rats. The present study was planned to evaluate the effects of aqueous extract of Hippophae leaves on changes in levels of neurotransmitters ((acetylcholine esterase (AChE) and dopamine (DA)) in plasma and brain, haematological parameters in blood/plasma; and brain histology in Sprague-Dawley rats showing CTA after 60 Co-g-irradiation (2 Gy). The results showed that whole body 60 Co-g-irradiation (2 Gy) (i) increased the levels of Ach, Eepinephrine (E) and norepinephrine (NE); oxidative stress (MDA and NO), and (ii) decreased the levels of DA; WBC counts and RBC counts and antioxidants (GSH), in comparison to untreated control. Treatment with 12 mg/kg b.w. drug concentration, prior to irradiation significantly (p<0.05) (i) decreased the levels of AChE, E and NE, and MDA and NO levels in plasma and brain, and (ii) increased the WBC counts; RBC counts and levels of antioxidants (GSH), in comparison to radiation control group. Histological changes in brain were also recorded. The results demonstrated that Hippophae leaves extract had neuro-protective and reduced oxidative stress in brain of whole body irradiated mice and could be, thereby contributing to behavioural protection. (author)

DNA damage focus analysis in blood samples of minipigs reveals acute partial body irradiation.

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Andreas Lamkowski

Full Text Available Radiation accidents frequently involve acute high dose partial body irradiation leading to victims with radiation sickness and cutaneous radiation syndrome that implements radiation-induced cell death. Cells that are not lethally hit seek to repair ionizing radiation (IR induced damage, albeit at the expense of an increased risk of mutation and tumor formation due to misrepair of IR-induced DNA double strand breaks (DSBs. The response to DNA damage includes phosphorylation of histone H2AX in the vicinity of DSBs, creating foci in the nucleus whose enumeration can serve as a radiation biodosimeter. Here, we investigated γH2AX and DNA repair foci in peripheral blood lymphocytes of Göttingen minipigs that experienced acute partial body irradiation (PBI with 49 Gy (± 6% Co-60 γ-rays of the upper lumbar region. Blood samples taken 4, 24 and 168 hours post PBI were subjected to γ-H2AX, 53BP1 and MRE11 focus enumeration. Peripheral blood lymphocytes (PBL of 49 Gy partial body irradiated minipigs were found to display 1-8 DNA damage foci/cell. These PBL values significantly deceed the high foci numbers observed in keratinocyte nuclei of the directly γ-irradiated minipig skin regions, indicating a limited resident time of PBL in the exposed tissue volume. Nonetheless, PBL samples obtained 4 h post IR in average contained 2.2% of cells displaying a pan-γH2AX signal, suggesting that these received a higher IR dose. Moreover, dispersion analysis indicated partial body irradiation for all 13 minipigs at 4 h post IR. While dose reconstruction using γH2AX DNA repair foci in lymphocytes after in vivo PBI represents a challenge, the DNA damage focus assay may serve as a rapid, first line indicator of radiation exposure. The occurrence of PBLs with pan-γH2AX staining and of cells with relatively high foci numbers that skew a Poisson distribution may be taken as indicator of acute high dose partial body irradiation, particularly when samples are available

When Injury Clouds Understanding of Others: Theory of Mind after Mild TBI in Preschool Children.

Science.gov (United States)

Bellerose, Jenny; Bernier, Annie; Beaudoin, Cindy; Gravel, Jocelyn; Beauchamp, Miriam H

2015-08-01

There is evidence to suggest that social skills, such as the ability to understand the perspective of others (theory of mind), may be affected by childhood traumatic brain injuries; however, studies to date have only considered moderate and severe traumatic brain injury (TBI). This study aimed to assess theory of mind after early, mild TBI (mTBI). Fifty-one children who sustained mTBI between 18 and 60 months were evaluated 6 months post-injury on emotion and desires reasoning and false-belief understanding tasks. Their results were compared to that of 50 typically developing children. The two groups did not differ on baseline characteristics, except for pre- and post-injury externalizing behavior. The mTBI group obtained poorer scores relative to controls on both the emotion and desires task and the false-belief understanding task, even after controlling for pre-injury externalizing behavior. No correlations were found between TBI injury characteristics and theory of mind. This is the first evidence that mTBI in preschool children is associated with theory of mind difficulties. Reduced perspective taking abilities could be linked with the social impairments that have been shown to arise following TBI.

Individual neuropsychological support and group sessions for relatives to TBI patients

DEFF Research Database (Denmark)

Siert, Lars

TITLE: Individual neuropsychological support and group sessions for relatives to TBI patients. OBJECTIVE: To describe how the neuropsychologist work with early and ongoing individual support and group sessions for relatives to adult TBI patients in the acute and sub acute phase and after discharge...

Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

Science.gov (United States)

Greco, Tiffany; Hovda, David A; Prins, Mayumi L

2015-02-01

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

Effect of whole body irradiation on O2- production in polymorphonuclear leukocyte of guinea pig

International Nuclear Information System (INIS)

Niiya, Harutaka

1987-01-01

The capacity of superoxide anion production of polymorphonuclear leukocytes (PMNL) has been determined after whole body irradiation. A diminished capacity of superoxide anion production in the presence of opsonized zymosan was found in PMNL taken from guinea pigs irradiated in vivo with 5, 10, and 20 Gy. However, no such diminution was found after a dose of 2 Gy. On the other hand, levels of superoxide anion production stimulated by myristate, N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP), and Concanavalin A remained unchanged compared to the control. PMNL irradiated in vitro with 20 Gy had a capacity of superoxide anion production similar to that of the control samples in the presence of either opsonized zymosan or FMLP and myristate. These results suggest that the capacity of superoxide anion production stimulated by zymosan is damaged by whole body irradiation. (author)

Sorption of carbohydrates following the whole-body irradiation and irradiation of the abdominal cavity (Experimental investigation)

International Nuclear Information System (INIS)

Neumeister, K.; Koch, F.; Mehlgorn, G.; Panndorf, H.; Iohannsen, U.

1974-01-01

Experiments were conducted to determine the effect of fractionated irradiation of the abdominal cavity and the whole body on carbohydrate absorption. It was found that enhanced D-xylose absorption is a function of dose. The relationship between impairment of absorption and the severity of clinical, pathomorphological and roentgenological changes was noted. (V.A.P.)

Towards systemic sustainable performance of TBI care systems: emergency leadership frontiers.

Science.gov (United States)

Caro, Denis H J

2010-11-10

Traumatic brain injuries (TBIs) continue as a twenty-first century subterranean and almost invisible scourge internationally. TBI care systems provide a safety net for survival, recovery, and reintegration into social communities from this scourge, particularly in Canada, the European Union, and the USA. This paper examines the underlying issues of systemic performance and sustainability of TBI care systems, in the light of decreasing care resources and increasing demands for services. This paper reviews the extant literature on TBI care systems, systems reengineering, and emergency leadership literature. This paper presents a seven care layer paradigm, which forms the essence of systemic performance in the care of patients with TBIs. It also identifies five key strategic drivers that hold promise for the future systemic sustainability of TBI care systems. Transformational leadership and engagement from the international emergency medical community is the key to generating positive change. The sustainability/performance care framework is relevant and pertinent for consideration internationally and in the context of other emergency medical populations.

Comparative studies in the cellular immunostimulation by whole body irradiation. Vergleichende Untersuchungen ueber die zellulaere Immunstimulation durch Ganzkoerperbestrahlung

Energy Technology Data Exchange (ETDEWEB)

Dietz, R.; Schwarze, G. (Service de Radiologie, Centre Hospitalier de Luxembourg (Luxembourg) Medizinische Universitaetsklinik I, Homburg/Saar (Germany))

1992-04-01

The effect of the cellular immune response by total body irradiation was investigated. The transplant survival (skin grafts) was determined as immune parameter. Donors were colony bred Wistar rats and recipients were colony bred Sprague Dawley rats. The investigations were carried out with irradiated rats and with rats irradiated after thymectomy and/or adrenalectomy as well as with animals without irradiation. A single total-body irradiation (1 and 2 Gy) was administered. The skin graft survival in irradiated rats was significant shorter (radiogenic immunostimulation) than in unirradiated rats; there were no significant differences between the operated (thymectomy and/or adrenalectomy) and not operated animals. Including precedent examinations this radiogenic immunostimulation is caused by relativly selective inactivation of T-suppressor cells. (orig.).

Rates of TBI-related Deaths by Age Group - United States, 2001 - 2010

Data.gov (United States)

U.S. Department of Health & Human Services — Changes in the rates of TBI-related deaths vary depending on age. For persons 44 years of age and younger, TBI-related deaths decreased between the periods of...

The effect of whole body or total-head x irradiation of the metallophilic cells in the mice spleen

International Nuclear Information System (INIS)

Sasaki, Osamu; Matsueda, Yasutoshi; Mizuguchi, Hiroshi; Moriguchi, Kenzo; Ogata, Kunitoshi; Sugie, Tsuneto

1984-01-01

The purpose of this paper is to clarify morphological changes of the reticuloendothelial cells in the spleen following X-irradiation by Katsura's silver impregnation method. The animals used in this experiment were ddN female mice weighing 20 to 25g. The mice were given X-irradiation to the total-head (1,500R) or whole body (300R). The metallophilic cells in the spleen of control mice were of the small foamy type in the follicle, the large stellate type in the marginal metallophils, the small branching type in the marginal zone and the small foamy or round type in the red pulp, respectively. The metallophilic cells decreased immediately after whole body irradiation and the number of cells returned to normal in from 10 to 14 days. On the other hand, the number of the metallophilic cells in the follicle and the perifollicular region increased immediately after total-head X-irradiation. This state continued for several days. In the marginal zone and red pulp, the number of amoebian type cells appeared from 24 hours after irradiation and the number of cells in total-head irradiation group were more clearly distinguishable than in the whole body irradiated group. (author)

Evaluating the impact of treatment for sleep/wake disorders on recovery of cognition and communication in adults with chronic TBI.

Science.gov (United States)

Wiseman-Hakes, Catherine; Murray, Brian; Moineddin, Rahim; Rochon, Elizabeth; Cullen, Nora; Gargaro, Judith; Colantonio, Angela

2013-01-01

To longitudinally examine objective and self-reported outcomes for recovery of cognition, communication, mood and participation in adults with traumatic brain injury (TBI) and co-morbid post-traumatic sleep/wake disorders. Prospective, longitudinal, single blind outcome study. Community-based. Ten adults with moderate-severe TBI and two adults with mild TBI and persistent symptoms aged 18-58 years. Six males and six females, who were 1-22 years post-injury and presented with self-reported sleep/wake disturbances with onset post-injury. Individualized treatments for sleep/wake disorders that included sleep hygiene recommendations, pharmacological interventions and/or treatments for sleep apnea with follow-up. Insomnia Severity Index, Beck Depression and Anxiety Inventories, Latrobe Communication Questionnaire, Speed and Capacity of Language Processing, Test of Everyday Attention, Repeatable Battery for the Assessment of Neuropsychological Status, Daily Cognitive-Communication and Sleep Profile. Group analysis revealed positive trends in change for each measure and across sub-tests of all measures. Statistically significant changes were noted in insomnia severity, p = 0.0003; depression severity, p = 0.03; language, p = 0.01; speed of language processing, p = 0.007. These results add to a small but growing body of evidence that sleep/wake disorders associated with TBI exacerbate trauma-related cognitive, communication and mood impairments. Treatment for sleep/wake disorders may optimize recovery and outcomes.

Effects of local and whole body irradiation on the appearance of osteoblasts during wound healing in tooth extraction sockets in rats.

Science.gov (United States)

Hosokawa, Yoichiro; Sakakura, Yasunori; Irie, Kazuharu; Kudo, Kohsei; Kashiwakura, Ikuo

2010-01-01

Irradiation before tooth extraction delays wound healing in the alveolar socket. This study examined the influences of local and whole body irradiation before tooth extraction on appearance of osteoblasts in the alveolar bone of rat maxillary first molars because bone formation is observed at the initial phase of wound healing. Several osteoblasts were generated 3 days after tooth extraction, and the number of cells increased day by day. Morphological studies showed there were little differences between local irradiation and non-irradiated controls. In contrast, the extraction wound in the whole body irradiation group showed delayed healing, and there was poor granulation tissue and very few osteoblasts at the bottom of the socket. An ultrastructural study showed that the osteoblasts in the extraction socket of whole body irradiation rats were smaller, and had poorly developed organelles. Injection of bone marrow cells to whole body-irradiated animals immediately after tooth extraction partially restored the number of osteoblasts. New periosteal bone formations outside of sockets showed little delay in the whole body irradiation group. These findings suggest that bone formation in the wound healing of extraction socket requires bone marrow cells from hematopoietic organs such as the bone marrow as well as local sources around the alveolar socket, during the initial phase of wound healing.

Effects of local and whole body irradiation on the appearance of osteoblasts during wound healing in tooth extraction sockets in rats

International Nuclear Information System (INIS)

Hosokawa, Yoichiro; Kudo, Kohsei; Kashiwakura, Ikuo; Sakakura, Yasunori; Irie, Kazuharu

2010-01-01

Irradiation before tooth extraction delays wound healing in the alveolar socket. This study examined the influences of local and whole body irradiation before tooth extraction on appearance of osteoblasts in the alveolar bone of rat maxillary first molars because bone formation is observed at the initial phase of wound healing. Several osteoblasts were generated 3 days after tooth extraction, and the number of cells increased day by day. Morphological studies showed there were little differences between local irradiation and non-irradiated controls. In contrast, the extraction wound in the whole body irradiation group showed delayed healing, and there was poor granulation tissue and very few osteoblasts at the bottom of the socket. An ultrastructural study showed that the osteoblasts in the extraction socket of whole body irradiation rats were smaller, and had poorly developed organelles. Injection of bone marrow cells to whole body-irradiated animals immediately after tooth extraction partially restored the number of osteoblasts. New periosteal bone formations outside of sockets showed little delay in the whole body irradiation group. These findings suggest that bone formation in the wound healing of extraction socket requires bone marrow cells from hematopoietic organs such as the bone marrow as well as local sources around the alveolar socket, during the initial phase of wound healing. (author)

Preventing Older Adult Falls and TBI

Centers for Disease Control (CDC) Podcasts

2008-03-05

This podcast provides tips on how older adults can prevent falls and related injuries, such as traumatic brain injuries (TBI).  Created: 3/5/2008 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 3/7/2008.

Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

Science.gov (United States)

Prodam, F; Gasco, V; Caputo, M; Zavattaro, M; Pagano, L; Marzullo, P; Belcastro, S; Busti, A; Perino, C; Grottoli, S; Ghigo, E; Aimaretti, G

2013-08-01

Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (phypopituitaric patients. In particular, triglycerides (phypopituitaric TBI patients. We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hepatotoxicity after liver irradiation in children and adolescents. Results from the RiSK

Energy Technology Data Exchange (ETDEWEB)

Roesler, Pascal; Christiansen, Hans [Medical School Hannover, Department of Radiotherapy and Special Oncology, Hannover (Germany); Kortmann, Rolf-Dieter [University of Leipzig, Department of Radiotherapy, Leipzig (Germany); Martini, Carmen [University Hospital of Freiburg, Department of Radiotherapy, Freiburg im Breisgau (Germany); Matuschek, Christiane [Heinrich-Heine University of Duesseldorf, Department of Radiotherapy, Medical Faculty, Duesseldorf (Germany); Meyer, Frank [Hospital Augsburg, Department of Radiotherapy, Augsburg (Germany); Ruebe, Christian [University Hospital of Homburg/Saar, Department of Radiotherapy, Homburg/Saar (Germany); Langer, Thorsten [University Hospital of Schleswig-Holstein, Department of Pediatrics, Pediatric Oncology, Campus Luebeck (Germany); Koch, Raphael [University of Muenster, Institute of Biostatistics and Clinical Research, Muenster (Germany); Eich, Hans Theodor; Willich, Normann [University Hospital of Muenster, Department of Radiotherapy, Muenster (Germany); Steinmann, Diana [Medical School Hannover, Department of Radiotherapy and Special Oncology, Hannover (Germany); University Hospital of Muenster, Department of Radiotherapy, Muenster (Germany)

2015-05-01

The aim of this study was to evaluate acute and late radiotherapy-associated hepatotoxicity in consideration of dose-volume effects and liver function in childhood and adolescence. Since 2001, irradiated children and adolescents in Germany have been prospectively documented in the ''Register of Treatment-Associated Late Effects After Radiotherapy of Malignant Diseases in Childhood and Adolescence (RiSK)'' using standardized forms. Toxicity was graded according to the Radiation Therapy Oncology Group (RTOG) criteria. Until April 2012, 1,392 children and adolescents from 62 radiotherapy centers were recruited. In all, 216 patients underwent irradiation of the liver (median age 9 years, range 1-18 years, 70 patients with total-body irradiation, TBI). For 75 % of patients without TBI, information on acute toxicity of the liver was available: 24 patients had acute toxicity of grade 1-4 (grade 1, 2, and 4, in 20, 3, and 1 patient, respectively), including five patients receiving simultaneous hepatotoxic chemotherapy. Information on late toxicity was documented in 465 forms from 216 patients, with a median follow-up of 2 years. A maximum grade of toxicity of ≥ 0 occurred in 18 patients over time (with grade 1, 2, and 3 toxicity occurring in 15, 2, and 1 patient, respectively), including three patients (17 %) with TBI. One of them received simultaneous hepatotoxic chemotherapy. In multivariable analysis, volume-dose correlations showed no statistically noticeable effect on acute or chronic toxicity. Only low hepatotoxicity developed in children after irradiation of various abdominal and thoracic tumors. Due to the low radiation doses to the liver (median liver dose = 5 Gy) and the low toxicities that were consecutively observed, dose-volume curves for liver toxicity could not be established. These findings reflect the cautious attitude of radiation oncologists in terms of attributable liver doses in the treatment of the investigated tumor entities. It

Late adverse effects of whole cranial irradiation in childhood hematological disorders

Energy Technology Data Exchange (ETDEWEB)

Someya, Masanori; Nakata, Kensei; Nagakura, Hisayasu; Oouchi, Atsushi; Sakata, Kohichi; Hareyama, Masato [Sapporo Medical Coll. (Japan)

2003-03-01

The purpose of this study was to examine the late adverse effects of childhood hematological disorders treated with chemotherapy and radiotherapy including whole cranial irradiation at Sapporo Medical University Hospital. Twenty-eight patients were treated with chemotherapy and 18-24 Gy of prophylactic cranial irradiation (PCI) for acute lymphoblastic leukemia (ALL), and 14 patients were treated with 3-12.8 Gy of total body irradiation (TBI) and bone marrow transplantation (BMT) for ALL, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), myelodysplastic syndrome (MDS), malignant lymphoma, and aplastic anemia (AA). Age at diagnosis ranged from 2 to 15 years old, and 28 were males and 14 were females. All patients were disease-free more than 2 years after diagnosis. Of 42 patients, 4 patients had decreased height (less than -2 S.D.), 3 patients required hormone replacement therapy, 2 patients had mental retardation, 3 patients had leukoencephalopathy, and 1 patient had a second malignancy. Except for the cases of decreased height, 3 of 7 late adverse effects were occurred in patients who had relapse of disease, and the risk of the adverse effects seemed to be higher for those patients whose doses of PCI were 22 Gy or more, or who received an additional craniospinal irradiation due to relapse of disease, and 18 Gy of PCI did not increase the risk of adverse effects. (author)

Neural Markers and Rehabilitation of Executive Functioning in Veterans with TBI and PTSD

Science.gov (United States)

2016-10-01

1 Award Number: W81XWH-11-1-0796 TITLE: Neural Markers and Rehabilitation of Executive Functioning in Veterans with TBI and PTSD PRINCIPAL...30Sept2015 - 29Sept2016 4. TITLE AND SUBTITLE: Neural Markers and Rehabilitation of Executive Functioning in Veterans with TBI and PTSD 5a. CONTRACT... met criteria for TBI during military service, 48.8% of whom reported multiple head injuries. The most common mechanisms of injury included blast

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

International Nuclear Information System (INIS)

Ina, Yasuhiro; Sakai, Kazuo

2003-01-01

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

An audit of traumatic brain injury (TBI) in a busy developing-world ...

African Journals Online (AJOL)

Committee in Neurotraumatology.[7] Four years later, at the ... the resources necessary to manage severe TBI according to interna- ... An audit of traumatic brain injury (TBI) in a busy .... The danger with this approach is that it risks becoming a.

Rrol of Zinc Cystenine in the Regulation of Metallothionnein Induction in whole body gamma irradiation rats

International Nuclear Information System (INIS)

Azab, Kh. Sh.; Zaharn, A.M.; Noaman, E.

2004-01-01

The antioxidant competence of metallothionein (MT) in cellular injury lunched by free radicals released in view of ionizing radiation has been proposed. The present work was conducted to elucidate the role of Zinc cysteine in the regulation of metallothionein induction in whole body gamma irradiated rats. cysteine was delivered to rats via intraperitoneal (i.p) injection at a concentration of 25-mg/kg body weight/day for two successive 2 days. The second injection was 30- min. pre irradiation. Whole body γ- irradiation at dose level 6.5 Gy induced significant increase in the levels of metallothionein in all investigated tissues (serum, liver and kidney) accompanied with significant increase in the levels of Zn in the liver. Cu concentrations increased in serum and kidney and decreased significantly in liver tissues. Data of lipid peroxidation demonstrated significant increase in TBARS as compared with control valuws in serum, liver and kidney. Iron was decreased significantly in serum and liver but a significant increase was recorded in kidney at 7 days after irradiation. Ca increased significantly in the liver only as compared with control rats. In addition, K concentration increased significantly in serum, liver and kidney while, P increased in serum and liver when compared with control values. The administration of zinc cysteine pre-irradiation induces significant increases in liver metallothionin from irradiated rat's value. It is only serum show significant decrease in level of MT from the irradiated rat's value on the 1st day post irradiation. However, the changes observed in the levels of Zn, Cu, Iron and Ca, K and P are less manifested when compared with values of irradiated animals. The reduction in the levels of TBARS was obvious comparing with irradiated rat's data. The amelioration occurred in the levels of Zn, Cu, Fe, Ca, P and K when, zinc cysteine administrated before irradiation postulate the positive role zinc cysteine in the adjustment of

Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation

International Nuclear Information System (INIS)

Sanders, J.E.; Buckner, C.D.; Leonard, J.M.; Sullivan, K.M.; Witherspoon, R.P.; Deeg, H.J.; Storb, R.; Thomas, E.D.

1983-01-01

One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30 had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients