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Sample records for irradiated primary brain

  1. Mitochondrial activity assessed by cytofluorescence after in-vitro-irradiation of primary rat brain cultures

    International Nuclear Information System (INIS)

    Cervos-Navarro, J.; Hamdorf, G.

    1993-01-01

    Mitochondria play a key role in cell homeostasis and are the first cell organells affected by ionizing irradiation, as it was proved by previous electron microscopic investigations. In order to observe functional parameters of mitochondria after low-dose irradiation, primary rat brain cultures (prepared from 15-day-old rat fetuses) were irradiated from a 60 Co-source with 0.5 and 1 Gy at the age of 2 or 7 days in vitro (div). Cytofluorescence measurement was made by a Cytofluor trademark2350 using Rhodamine 123. This fluorescent dye is positively charged and accumulates specifically in the mitochondria of living cells without cytotoxic effect. Since its retention depends on the negative membrane potential as well as the proton gradient that exists across the inner mitochondrial membrane, Rhodamine 123 accumulation reflects the status of mitochondrial activity as a whole. After irradiation with 0.5 and 1 Gy on day 2 in culture there was a decrease in Rhodamine uptake in the irradiated cultures during the first week after the irradiation insult which reached minimum values after 3 days. Rhodamine uptake increased during the following period and finally reached the values of the control cultures. In the second experiment with irradiated cultures on day 7 and the same doses of 0.5 and 1 Gy the accumulation of Rhodamine decreased only initially then increased tremendously. After both doses values of Rhodamine-accumulation were higher than the control level. The results demonstrated that irradiation caused a change in mitochondrial activity depending on the time of irradiation. The dramatic increase over the control levels after irradiation on day 7 in vitro is attributed to the fact that at this time synapses have already developed. Deficiency of mitochondrial activity as well as hyperactivity and the consequent change in energy production may lead to changes in neuronal metabolism including an increase in production of free radicals

  2. Disruption of the blood-brain barrier as the primary effect of CNS irradiation.

    Science.gov (United States)

    Rubin, P; Gash, D M; Hansen, J T; Nelson, D F; Williams, J P

    1994-04-01

    The blood-brain barrier (BBB) is believed to be unique in organ microcirculation due to the 'tight junctions' which exist between endothelial cells and, some argue, the additional functional components represented by the perivascular boundary of neuroglial cells; these selectively exclude proteins and drugs from the brain parenchyma. This study was designed to examine the effects of irradiation on the BBB and determine the impact of the altered pathophysiology on the production of central nervous system (CNS) late effects such as demyelination, gliosis and necrosis. Rats, irradiated at 60 Gy, were serially sacrificed at 2, 6, 12 and 24 weeks. Magnetic resonance image analysis (MRI) was obtained prior to sacrifice with selected animals from each group. The remaining animals underwent horse-radish peroxidase (HRP) perfusion at the time of sacrifice. The serial studies showed a detectable disruption of the BBB at 2 weeks post-irradiation and this was manifested as discrete leakage; late injury seen at 24 weeks indicated diffuse vasculature leakage, severe loss of the capillary network, cortical atrophy and white matter necrosis. Reversal or repair of radiation injury was seen between 6 and 12 weeks, indicating a bimodal peak in events. Blood-brain barrier disruption is an early, readily recognizable pathophysiological event occurring after radiation injury, is detectable in vivo/in vitro by MRI and HRP studies, and appears to precede white matter necrosis. Dose response studies over a wide range of doses, utilizing both external and interstitial irradiation, are in progress along with correlative histopathologic and ultrastructural studies.

  3. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  4. Soft-tissue reactions following irradiation of primary brain and pituitary tumors

    International Nuclear Information System (INIS)

    Baglan, R.J.; Marks, J.E.

    1981-01-01

    One hundred and ninety-nine patients who received radiation therapy for a primary brain or pituitary tumor were studied for radiation-induced soft-tissue reactions of the cranium, scalp, ears and jaw. The frequency of these reactions was studied as a function of: the radiation dose 5 mm below the skin surface, dose distribution, field size and fraction size. Forty percent of patients had complete and permanent epilation, while 21% had some other soft-tissue complication, including: scalp swelling-6%, external otitis-6%, otitis media-5%, ear swelling-4%, etc. The frequency of soft-tissue reactions correlates directly with the radiation dose at 5 mm below the skin surface. Patients treated with small portals ( 2 ) had few soft-tissue reactions. The dose to superficial tissues, and hence the frequency of soft-tissue reactions can be reduced by: (1) using high-energy megavoltage beams; (2) using equal loading of beams; and (3) possibly avoiding the use of electron beams

  5. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  6. Therapeutic irradiation and brain injury

    International Nuclear Information System (INIS)

    Sheline, G.E.; Wara, W.M.; Smith, V.

    1980-01-01

    This is a review and reanalysis of the literature on adverse effects of therapeutic irradiation on the brain. Reactions have been grouped and considered according to time of appearance. The emphasis of the analysis is on delayed reactions, especially those that occur from a few months to several years after irradiation. All dose specifications were converted into equivalent megavoltage rads. The data were analyzed in terms of total dose, overall treatment time and number of treatment fractions. Also discussed were acute radiation reactions, early delayed radiation reactions, somnolence and leukoencephalopathy post-irradiation/chemotherapy and combined effects of radiation and chemotherapy

  7. Re-irradiation for metastatic brain tumors with whole-brain radiotherapy

    International Nuclear Information System (INIS)

    Akiba, Takeshi; Kunieda, Etsuo; Kogawa, Asuka; Komatsu, Tetsuya; Tamai, Yoshifumi; Ohizumi, Yukio

    2012-01-01

    The objective of this study was to determine whether second whole-brain irradiation is beneficial for patients previously treated with whole-brain irradiation. A retrospective analysis was done for 31 patients with brain metastases who had undergone re-irradiation. Initial whole-brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole-brain re-irradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). Three patients underwent a third whole-brain irradiation. The median interval between the initial irradiation and re-irradiation was 10 months (range: 2-69 months). The median survival time after re-irradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after re-irradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed Grade 1 acute reactions. On magnetic resonance imaging, brain atrophy was observed in 36% of these patients after the initial irradiation and 74% after re-irradiation. Grade ≥2 encephalopathy or cognitive disturbance was observed in 10 patients (32%) after re-irradiation. Based on univariate analysis, significant factors related to survival after re-irradiation were the location of the primary cancer (P=0.003) and the Karnofsky performance status at the time of re-irradiation (P=0.008). A Karnofsky performance status ≥70 was significant based on multivariate analysis (P=0.050). Whole-brain re-irradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. However, their remaining survival time was limited and the incidence of cognitive disturbance was rather high. (author)

  8. Relapsing pattern of brain metastasis after brain irradiation in small cell lung cancer

    International Nuclear Information System (INIS)

    Murakami, Masao; Kuroda, Yasumasa; Okamoto, Yoshiaki; Kono, Koichi; Yoden, Eisaku; Mori, Takeki

    1997-01-01

    Many reports concerning radiation therapy for brain metastasis have been published, and which of the various methods urged by these reports provide optional control is still controversial. According to developing diagnosis of metastasis in CNS, therapeutic problems should be referred. We reviewed 67 patients with small cell lung cancer and brain metastasis who underwent brain irradiation (Ave. 47 Gy/5W), and all 15 patients with brain relapse after the irradiation. Relapsing patterns in this clinical setting were divided into local regrowth in the same lesions and re-metastasis (reseeding) in other regions, by reviewing follow up CT and MRI studies. Total survival among 15 patients with brain relapse and 52 without relapse was longer in the former cases than the later: 1-, and 2-year survival (47/19%, 13/8%) and MST (10.8/5.7 months), from the initial brain irradiation. The concerned significant factors limited in younger age, low value of LDH and improvement of NF. Of the 15 patients with brain relapse, 4 developed local regrowth and 11 did re-metastasis. The period of remission since brain irradiation were 172±94.4 and 393±281 days, respectively. Lower number of brain metastasis and lower value of LDH were shown in re-metastasis patients. At the time of brain relapse, 11 patients had recurrence of carcinomatous meningitis. 4 patients were treated with whole brain re-irradiation. All patients died of cancer, including 12 of relapsing CNS diseases and 3 of primary lesion and hepatic metastasis. Leukoencephalopathy developed in 2 patients. Survival since the brain relapse was 2 to 238 days without significant difference in cases of local regrowth and re-metastasis. According to our data on relapsing pattern of brain metastasis after conventional fractionated brain irradiation with an objective dose of 50 Gy, 75% of brain relapse were re-metastasis, we appreciate this irradiation for initial brain metastasis if limited to the brain. (author)

  9. Histopathological studies on the irradiated brain tumors

    International Nuclear Information System (INIS)

    Narita, Tadao

    1980-01-01

    Of 43 cases of irradiated brain tumor, histological findings showed extensive necrosis or disappearance of the neoplasm, considered to be attributable to radiation treatment, in 30 (70%). Extensive necrosis of the tumor in areas exposed to radiation was found in 16 treated cases (37.2%). The histopathology of massive necrosis was that of simple coagulative necrosis, sometimes with marked vascular alterations and extravasation of fibrinoid material into the necrotic tissue. Necrosis was almost always incomplete, and foci of residual tumors were found at the periphery of the tumors. The terminal picture in cases of massive necrosis was often that of widespread intra- and extracranial metastasis. Almost complete disappearance of the tumor was observed in some cases with subsequent diffuse degenerative changes in the brain parenchyma exposed to radiation. In 5 cases of irradiated tumors, autopsy findings suggested that the growth of the primary tumor might have been restricted. And in 5 cases tumor cytology revealed the marked presence of a large number of multinucleated, bizarre giant cells with evidence of degeneration in both the cytoplasm and the nucleus. Multifocal necrosis of the brain, with axonal swelling and sponginess of the tissue, was observed in two patients following combined radiation and antineoplastic chemotherapy. Diffuse loss and degeneration of nerve cells of the cerebral cortex in pseudo-laminar fashion was observed in 7 patients with or without bilateral necrosis of the globus pallidus. Histological findings revealed typical anoxic encephalopathy. (J.P.N.)

  10. Histopathological studies on the irradiated brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Narita, T [Gunma Univ., Maebashi (Japan).School of Medicine

    1980-01-01

    Of 43 cases of irradiated brain tumor, histological findings showed extensive necrosis or disappearance of the neoplasm, considered to be attributable to radiation treatment, in 30 (70%). Extensive necrosis of the tumor in areas exposed to radiation was found in 16 treated cases (37.2%). The histopathology of massive necrosis was that of simple coagulative necrosis, sometimes with marked vascular alterations and extravasation of fibrinoid material into the necrotic tissue. Necrosis was almost always incomplete, and foci of residual tumors were found at the periphery of the tumors. The terminal picture in cases of massive necrosis was often that of widespread intra- and extracranial metastasis. Almost complete disappearance of the tumor was observed in some cases with subsequent diffuse degenerative changes in the brain parenchyma exposed to radiation. In 5 cases of irradiated tumors, autopsy findings suggested that the growth of the primary tumor might have been restricted. And in 5 cases tumor cytology revealed the marked presence of a large number of multinucleated, bizarre giant cells with evidence of degeneration in both the cytoplasm and the nucleus. Multifocal necrosis of the brain, with axonal swelling and sponginess of the tissue, was observed in two patients following combined radiation and antineoplastic chemotherapy. Diffuse loss and degeneration of nerve cells of the cerebral cortex in pseudo-laminar fashion was observed in 7 patients with or without bilateral necrosis of the globus pallidus. Histological findings revealed typical anoxic encephalopathy.

  11. Traumatic primary brain stem haemorrhage

    International Nuclear Information System (INIS)

    Andrioli, G.C.; Zuccarello, M.; Trincia, G.; Fiore, D.L.; De Caro, R.

    1983-01-01

    We report 36 cases of post-traumatic 'primary brain stem haemorrhage' visualized by the CT scan and confirmed at autopsy. Clinical experience shows that many technical factors influence the inability to visualize brain stem haemorrhages. Experimental injection of fresh blood into the pons and midbrain of cadavers shows that lesions as small as 0.25 ml in volume may be visualized. The volume and the anatomical configuration of traumatic lesions of the brain stem extended over a rostro-caudal direction, and their proximity to bony structures at the base of the skull are obstacles to the visualization of brain stem haemorrhages. (Author)

  12. Brain fibronectin expression in prenatally irradiated mice

    International Nuclear Information System (INIS)

    Meznarich, H.K.; McCoy, L.S.; Bale, T.L.; Stiegler, G.L.; Sikov, M.R.

    1993-01-01

    Activation of gene transcription by radiation has been recently demonstrated in vivo. However, little is known on the specificity of these alterations on gene transcription. Prenatal irradiation is a known teratogen that affects the developing mammalian central nervous system (CNS). Altered neuronal migration has been suggested as a mechanism for abnormal development of prenatally irradiated brains. Fibronectin (FN), an extracellular glycoprotein, is essential for neural crest cell migration and neural cell growth. In addition, elevated levels of FN have been found in the extracellular matrix of irradiated lung. To test whether brain FN is affected by radiation, either FN level in insoluble matrix fraction or expression of FN mRNA was examined pre- and postnatally after irradiation. Mice (CD1), at 13 d of gestation (DG), served either as controls or were irradiated with 14 DG, 17 DG, or 5,6, or 14 d postnatal. Brain and liver were collected from offspring and analyzed for either total FN protein levels or relative mRNAs for FN and tubulin. Results of prenatal irradiation on reduction of postnatal brain weight relative to whole are comparable to that reported by others. Insoluble matrix fraction (IMF) per gram of brain, liver, lung, and heart weight was not significantly different either between control and irradiated groups or between postnatal stages, suggesting that radiation did not affect the IMF. However, total amounts of FN in brain IMF at 17 DG were significantly different (p < .02) between normal (1.66 ± 0.80 μg) and irradiated brains (0.58 ± 0.22 μg). FN mRNA was detectable at 13, 14, and 17 DG, but was not detectable at 6 and 14 d postnatal, indicating that FN mRNA is developmentally regulated. 41 refs., 4 figs., 3 tabs

  13. Acute effects of irradiation on cognition: changes in attention on a computerized continuous performance test during radiotherapy in pediatric patients with localized primary brain tumors

    International Nuclear Information System (INIS)

    Merchant, Thomas E.; Kiehna, Erin N.; Miles, Mark A.; Zhu Junhong; Xiong Xiaoping; Mulhern, Raymond K.

    2002-01-01

    Purpose: To assess sustained attention, impulsivity, and reaction time during radiotherapy (RT) for pediatric patients with localized primary brain tumors. Methods and Materials: Thirty-nine patients (median age 12.3 years, range 5.9-22.9) with primary brain tumors were evaluated prospectively using the computerized Conners' continuous performance test (CPT) before and during conformal RT (CRT). The data were modeled to assess the longitudinal changes in the CPT scores and the effects of clinical variables on these changes during the first 50 days after the initiation of CRT. Results: The CPT scores exhibited an increasing trend for errors of omission (inattentiveness), decreasing trend for errors of commission (impulsivity), and slower reaction times. However, none of the changes were statistically significant. The overall index, which is an algorithm-based weighted sum of the CPT scores, remained within the range of normal throughout treatment. Older patients (age >12 years) were more attentive (p<0.0005), less impulsive (p<0.07), and had faster reaction times (p<0.001) at baseline than the younger patients. The reaction time was significantly reduced during treatment for the older patients and lengthened significantly for the younger patients (p<0.04). Patients with a shunted hydrocephalus (p<0.02), seizure history (p<0.0006), and residual tumor (p<0.02) were significantly more impulsive. Nonshunted patients (p<0.0001), those with more extensive resection (p<0.0001), and patients with ependymoma (p<0.006) had slower initial reaction times. Conclusion: Children with brain tumors have problems with sustained attention and reaction time resulting from the tumor and therapeutic interventions before RT. The reaction time slowed during treatment for patients <12 years old. RT, as administered in the trial from which these data were derived, has limited acute effects on changes in the CPT scores measuring attention, impulsiveness, and reaction time

  14. Hypothalamic dysfunction following whole-brain irradiation

    International Nuclear Information System (INIS)

    Mechanick, J.I.; Hochberg, F.H.; LaRocque, A.

    1986-01-01

    The authors describe 15 cases with evidence of hypothalamic dysfunction 2 to 9 years following megavoltage whole-brain x-irradiation for primary glial neoplasm. The patients received 4000 to 5000 rads in 180- to 200-rad fractions. Dysfunction occurred in the absence of computerized tomography-delineated radiation necrosis or hypothalamic invasion by tumor, and antedated the onset of dementia. Fourteen patients displayed symptoms reflecting disturbances of personality, libido, thirst, appetite, or sleep. Hyperprolactinemia (with prolactin levels up to 70 ng/ml) was present in all of the nine patients so tested. Of seven patients tested with thyrotropin-releasing hormone, one demonstrated an abnormal pituitary gland response consistent with a hypothalamic disorder. Seven patients developed cognitive abnormalities. Computerized tomography scans performed a median of 4 years after tumor diagnosis revealed no hypothalamic tumor or diminished density of the hypothalamus. Cortical atrophy was present in 50% of cases and third ventricular dilatation in 58%. Hypothalamic dysfunction, heralded by endocrine, behavioral, and cognitive impairment, represents a common, subtle form of radiation damage

  15. Significance of primary irradiation creep in graphite

    CSIR Research Space (South Africa)

    Erasmus, C

    2013-05-01

    Full Text Available Traditionally primary irradiation creep is introduced into graphite analysis by applying the appropriate amount of creep strain to the model at the initial time-step. This is valid for graphite components that are subjected to high fast neutron flux...

  16. Irradiation of meningioma: a prototype circumscribed tumor for planning high-dose irradiation of the brain

    International Nuclear Information System (INIS)

    Friedman, M.

    1977-01-01

    The purpose of this report is to provide specific data concerning the radiation dose required to destroy meningioma, and to demonstrate that radiation doses much greater than the alleged tolerance dose, can be administered to the brain in some patients. Most meninglomas are not responsive to irradiation, but, some surgically incurable lesions benefit from irradiation with radically high doses to small volumes of tissue. The arrest of 7 of 12 consecutive meningiomas in adults for periods of 2 to 17 years following maximum tumor doses up to 8800 R in 40 days is reported in this paper. All patients, when irradiated, had active tumor in the form of inoperable primary tumor, recurrence, or known postoperative residual tumor. Three of the successful results were achieved with orthovoltage radiation. The incidence of brain damage may be acceptable to the patient when it is related to arrest of tumor growth but he must be forewarned of possible brain damage. The factors influencing the radioresponsiveness of meningioma are: the required tumor lethal dose, histology and vascularity of the tumor, anatomical site in the brain, treatment technique for each tumor site, small size of the treated volume, growth rate of the tumor, displacement of normal brain tissue by tumor, inherent individual variations of tumor and normal tissues, quality of the radiation, and tolerance of normal brain tissues. The role of these factors is discussed in the light of modern radiobiological concepts

  17. Late vascular effects in irradiated mice brain

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Maki, Yutaka; Phillips, T.L.

    1982-01-01

    The whole brains of mice were irradiated with 250 kVp X-ray at 120 rad min -1 (1.6 mm Cu HVL, TSD 50 cm) and a histological study was done. The dose range of X-irradiation was from 1300 to 2500 rads. i.e., 1300, 1500, 1750, 2000, and 2500 rads. In the microscopic examination, the mice were killed at the regular postirradiation intervals of between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. A histological examination was performed by a morphometric estimation of vascular lesion in which the degree of the damage to the arterial system was scored through whole serial brain sections. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectatic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large artery were observed. Incidence of the fibrinoid necrosis increased dose dependently between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 - 87 weeks and can be used to quantify the vessel injury and a fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis. (author)

  18. Stereotactic irradiation for metastatic brain tumor

    International Nuclear Information System (INIS)

    Nomura, Ryutaro

    2017-01-01

    First, this paper reviewed the latest findings of stereotactic irradiation (STI) for metastatic brain tumors. Then, it described the results of randomized controlled trials for single or a few (2-4) metastasis in the following comparison tests: (1) comparison between whole brain radiotherapy (WBRT) alone group and (WBRT + STI) group, (2) comparison between STI alone group and (STI + WBRT) group, (3) comparison between STI alone group and (tumorectomy + WBRT) group, (4) comparison between (STI + WBRT) group and (tumorectomy + WBRT) group, and (5) between (tumorectomy + WBRT) group and (tumorectomy + STI) group. Among these, STI alone without WBRT has obtained a certain consensus. Against multiple metastatic brain tumors of 5 or more, when considering cognitive impairment and QOL loss by adding WBRT, it is general consensus that STI alone may be sufficient. At the authors' institution, cyber knife (CK) was introduced in 2008 and nearly 300 stereotactic radiotherapy for metastatic brain tumors have been performed annually. By adopting a robot arm and development of a lesion tracking system, the positional correction against the deviation of the bone margin of the skull is guaranteed in real time to ensure accuracy during irradiation, and hypofractionated stereotactic irradiation becomes easier. (A.O.)

  19. Elective brain irradiation in patients with small-cell carcinoma of the lung: preliminary report

    International Nuclear Information System (INIS)

    Katsenis, A.T.; Karpasitis, N.; Giannakakis, D.; Maragoudakis, N.; Kiparissiadis, P.

    1982-01-01

    The brain is a common site of metastases in small-cell carcinoma of the lung. Prophylactic brain irradiation with doses of 4000-4500 rads in 3-4 weeks appears to decrease the occurrence of brain metastases although it does not prevent this completely. In a group of patients with small-cell carcinoma of the lung and without evidence of brain metastases, the authors review the site and extent of the primary, the methods of treatment, the techniques of brain irradiation, and the relapses rate in relation to the status of the primary and the rate of brain metastases in another group without prophylactic brain irradiation. They further attempt to investigate combined modalities of treatment which would prolong life and prevent neurological complications in the small number of long survivors with small-cell carcinoma of the lung. (Auth.)

  20. 3-62 Protective Effects of Hydroxysaffor Yellow A on Brain Injury in Mice Irradiated by 300 MeV/u 12C6+ Ions

    Institute of Scientific and Technical Information of China (English)

    Gan; Lu[1; Zhang; Hong[1

    2015-01-01

    Radiotherapy is a common treatment modality for head and neck cancers, nasopharyngeal cancers, primary brain tumors and brain metastases. A large number of patients in the world with primary or metastatic brain tumors will require large volume or whole brain irradiation every year. However, therapeutic irradiation not only kills tumor cells, but also injures normal brain tissue, which is commonly associated with significant functional morbidity and decreased quality of life in patients treated with brain radiotherapy[1].

  1. Ten years summary: FDG-PET on irradiated brain tumour

    International Nuclear Information System (INIS)

    Wang Shuxia; Boethius, J.

    2004-01-01

    Purpose: To retrospectively evaluate FDG-PET in differentiation of post-radiotherapy status: recurrence, radiation necrosis, malignant regression of low grade primary brain tumour, and to evaluate PET in terms of survival prediction. Material and methods: 117 irradiated patients (156 PET) were consecutively included. PET results were judged by a set of rigid follow-up standards. Brain metastases from lung carcinoma were further studied. Survival time was analysed with Kaplan-Meier method. Results: There were 61 true-positive, 2 false-positive, 15 false-negative, 51 true-negative PET; leaving 5 positive and 22 negative PET results indeterminate. PET positive predictive value was 96% in all and 100% in brain metastasis from lung carcinoma. PET negative predictive value was 55.6% among surgically selected cases. Survival time was significantly longer in patient's with negative PET, both brain metastasis and primary brain tumour. Conclusions: FDG-PET was a good method to pick up tumour recurrence from radiation necrosis, especially metastasis from lung carcinoma. FDG uptake could be used as a non-invasive parameter to predict patient's prognosis. (authors)

  2. Damage and repair of irradiated mammalian brain

    International Nuclear Information System (INIS)

    Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K.

    1989-07-01

    We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as ''vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs

  3. Damage and repair of irradiated mammalian brain

    Energy Technology Data Exchange (ETDEWEB)

    Frankel, K.; Lo, E.; Phillips, M.; Fabrikant, J.; Brennan, K.; Valk, P.; Poljak, A.; Delapaz, R.; Woodruff, K. (Lawrence Berkeley Lab., CA (USA); Stanford Univ., CA (USA). Medical Center; Brookside Hospital, San Pablo, CA (USA))

    1989-07-01

    We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress to serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs.

  4. Stereotaxic external irradiation for brain tumors

    International Nuclear Information System (INIS)

    Kim, Y.H.; Fayos, J.V.; Houdek, P.V.; Landy, H.; Van Buren, J.

    1987-01-01

    A system has been developed to deliver precision radiation therapy to a limited volume of brain tissue. A CT-compatible nonmetallic headband, or ''halo,'' is secured to the skull with screw pins. A metal frame attached to the CT couch and the patient's head is secured to the couch by temporarily affixing the halo to the frame. A CT scan is obtained to determine the x,y,z coordinates of the brain lesion. The same halo, frame, and coordinates are used in daily treatment with 10-MVX accelerator and a coplanar arc rotation technique. Field size is determined to cover the target volume with the 90% isodose line. Verification films are obtained twice a week. On completion of treatment, the halo is removed. From December 1982 to January 1986, 14 patients were treated with this system. Six had pituitary tumors, two had craniopharyngiomas, and six had astrocytomas. The dose delivered ranged from 3,600 rad in 12 fractions to 6,250 rad in 25 fractions at a rate of one fraction per day, 5 days a week. Judging from the verification films, daily administration of intended radiation was extremely good. Superficial infection of the screw-pin sites healed without sequelae. All patients were alive at the last follow-up. This system is relatively simple yet able to deliver precision irradiation without any remarkable complications

  5. Primary brain tumours, meningiomas and brain metastases in pregnancy

    DEFF Research Database (Denmark)

    Verheecke, Magali; Halaska, Michael J; Lok, Christianne A

    2014-01-01

    to obtain better insight into outcome and possibilities of treatment in pregnancy. METHODS: We collected all intracranial tumours (primary brain tumour, cerebral metastasis, or meningioma) diagnosed during pregnancy, registered prospectively and retrospectively by international collaboration since 1973......, respectively. Eight patients (30%) underwent brain surgery, seven patients (26%) had radiotherapy and in three patients (11%) chemotherapy was administered during gestation. Two patients died during pregnancy and four pregnancies were terminated. In 16 (59%) patients elective caesarean section was performed...... were reassuring. CONCLUSION: Adherence to standard protocol for the treatment of brain tumours during pregnancy appears to allow a term delivery and a higher probability of a vaginal delivery....

  6. Stereotactic irradiation without whole-brain irradiation for single brain metastasis

    International Nuclear Information System (INIS)

    Shirato, Hiroki; Takamura, Akio; Tomita, Masayoshi; Suzuki, Keishiro; Nishioka, Takashi; Isu, Toyohiko; Kato, Tsutomu; Sawamura, Yutaka; Miyamachi, Keikichi; Abe, Hiroshi; Miyasaka, Kazuo

    1997-01-01

    Purpose: The effectiveness of stereotactic irradiation (STI) alone without whole-brain irradiation (WBI) for a single metastatic brain tumor was analyzed retrospectively. Methods and Materials: Forty-four patients with this condition were treated using radiosurgery (RS) alone or fractionated stereotactic radiotherapy (FSR) without WBI. Results: The initial response rate was 92% and the overall local control rate was 84% (37 of 44 patients). A total of 39% (18 of 44) of patients experienced intracranial relapse outside the initial target area. Forty-eight percent (21 of 44) of patients required salvage treatment for intracranial relapse. All 7 patients who received WBI as salvage treatment required no further salvage treatment, but 5 of the 14 patients who received salvage STI without WBI required three to four treatments for brain metastasis. Late radiation damage was not seen with initial treatment but was observed with retreatment. The overall median survival time was 261 days, with a standard error of 64 days. Actuarial survival at 12 and 24 months was 34% and 9%, respectively. The actuarial survival rate was significantly affected by the existence of active extracranial disease (p = 0.041). Conclusion: The high response rate and short treatment period of STI alone are advantageous in the treatment of single brain metastasis in patients with active extracranial disease with WBI reserved for relapse. Because of the low complication rate, STI alone may be also useful in patients with good prognosis, without extracranial disease

  7. Brain anomalies induced by gamma irradiation in prenatal period

    International Nuclear Information System (INIS)

    Schmidt, S.L.

    1992-01-01

    Gamma irradiation has been utilized in order to produce cortical and callosal abnormalities. We have also checked for the presence of the aberrant longitudinal bundle in the brains of mice born acallosal due to prenatal irradiation is also checked. Pregnant mice were exposed to gamma irradiation from a 6 0 Co source at 16, 17 and 19 days of gestational age (E 16, E 17 and E 19) with total doses of 2 Gy and 3 Gy. At 60 days postnatal the offspring of irradiated animals were intra cardiac perfused, the brains were removed from the cranio and cut into coronal or para sagittal sections. (author)

  8. Computerized tomographic evaluation of primary brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jin Ok; Lee, Jong Soon; Jeon, Doo Sung; Kim, Hong Soo; Rhee, Hak Song [Presbyterian Mediacal center, Cheonju (Korea, Republic of); Kim, Jong Deok [Inje Medical College, Paik Hospital, Pusan (Korea, Republic of)

    1985-10-15

    In a study of primary brain tumors 104 cases having satisfactory clinical, operative and histological proofs were analyzed by computerized tomography at Presbyterian Medical Center from May, 1982 to April 1985. The results were as follows: 1. The male to female ratio of primary brain tumor was 54 : 46. 2. The 2nd decade group (26%) was the most prevalent age group, followed by the 5th decade (16.3%), 1st decade (14.4%) , 3rd decade (12.5%), 4th decade (11.5%), 6th decade (10.6%), 7th decade (8.7%) in that order. 3. The incidence of primary brain tumors was found to be: glioma 64 cases (61.6%) among the GM, the most frequent 17 cases (16.3%), followed by meningioma 12 cases (11.5%), pituitary adenoma 10 cases (9.6%), craniopharyngioma 6 cases (5.8%), pinealoma and germinoma 3 cases (2.9%) respectively, and dermoid cyst 2 cases (1.9%) in that order. 4. The location of the primary brain tumors were as follows: cb. hemisphere (49%) of these 24.5% in parietal region, 11.9% in temporal region, 9.7% in frontal region, 3.0% in occipital region: juxtasella area (16.3%), cerebellar hemisphere (8.7%), parapineal and intraventricle (7.7%) respectively, cerebello-pontine angle area (5.8%), vermis and 4th ventricular region (4.8%). 5. There were no remarkable differences in the findings of pre- and post-contrast CT scanning of primary brain tumors computed with others.

  9. Primary brain lymphoma presenting as Parkinson's disease

    International Nuclear Information System (INIS)

    Sanchez-Guerra, M.; Leno, C.; Berciano, J.; Cerezal, L.; Diez, C.; Figols, J.

    2001-01-01

    Neoplasm is an uncommon cause of a parkinsonian syndrome. We report a woman with primary brain B-cell lymphoma presenting as Parkinson's disease. After 1 year of the illness, CT and MRI showed lesions without mass effect in the basal ganglia and corpus callosum. The patient did not respond to levodopa and right cerebellar and brain-stem signs appeared, which prompted further neuroimaging, showing an increase in size of the lesions and a right cerebellar and pontine mass. Stereotactic biopsy of the basal ganglia showed high-grade B-cell lymphoma. Despite the basal ganglia frequently being involved in lymphoma of the brain, presentation with typical or atypical parkinsonism is exceptional. (orig.)

  10. Somatic radiation risk in case of irradiation of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Nocken, U.; Ewen, K.; Makoski, H.B.

    1983-09-01

    The somatic dose index for irradiation of the brain was determined for the 10 MeV bremsstrahlung of a linear electron-accelerator. A small volume rotation technique and the irradiation of the total neurocranium were chosen as extreme conditions for the radiation exposure of the skull. On the basis of a target volume dose of 50 Gy for the total irradiation series, the somatic dose index of the small volume technique is within the scope of coronarography. In case of irradiation of the total neurocranium, however, the somatic dose index largely exceeds the maximum values of X-ray diagnosis.

  11. Effect of brain prenatal irradiations (review)

    International Nuclear Information System (INIS)

    Nyagu, A.I.; Loganovskij, K.N.; Loganovskaya, T.K.

    1998-01-01

    Tendency of intellectual deficiency and emotion disturbance among children which were irradiated in womb was found. Study of the risk of endogenic psychic disorder development and, first of all, schizophrenia in pre-natally irradiated children, as a result of Chernobyl catastrophe, is of special interest. 256 refs., 1 tab

  12. Regulation of prostaglandin E2 synthesis after brain irradiation

    International Nuclear Information System (INIS)

    Moore, Amy H.; Olschowka, John A.; Williams, Jacqueline P.; Okunieff, Paul; O'Banion, M. Kerry

    2005-01-01

    Purpose: A local tissue reaction, termed neuroinflammation, occurs after irradiation of brain tissue. Previous work suggested that cyclooxygenase (COX)-2 activity was important for changes in gene expression associated with neuroinflammation as well as increased prostaglandin E 2 (PGE 2 ) levels seen after radiation treatment. Methods and materials: To begin to determine the contributions of other enzymes involved in PGE 2 production, we examined protein levels of COX-1 and COX-2 as well as 2 PGE synthases (membrane and cytosolic PGES) 4 h after 35 Gy single dose irradiation to the brains of C3HeN mice. We also evaluated the effects of specific COX inhibitors on PGE 2 production and PGES expression. Results: As expected, COX-2 expression increased after radiation exposure. Brain irradiation also increased tissue protein levels for both PGES isoforms. Specific COX-2 inhibition with NS398 lowered brain PGE 2 levels by about 60%. Surprisingly, COX-1 inhibition with SC560 completely prevented the elevation of PGE 2 seen after irradiation. Interestingly, NS398 reduced the membrane-associated PGES isoform, whereas SC560 treatment lowered cytosolic isoform levels below those seen in unirradiated controls. Conclusions: Taken together, these data indicate that both cyclooxygenases contribute to PGE 2 production in irradiated brain and reveal dependence of PGES isoforms expression on specific cyclooxygenase activities

  13. Treatment for delayed brain injury after pituitary irradiation

    International Nuclear Information System (INIS)

    Fujii, Takashi; Misumi, Shuzoh; Shibasaki, Takashi; Tamura, Masaru; Kunimine, Hideo; Hayakawa, Kazushige; Niibe, Hideo; Miyazaki, Mizuho; Miyagi, Osamu.

    1988-01-01

    Treatment for delayed brain injury after pituitary irradiation is discussed. Six cases with delayed brain injury were treated with a combination of dexamethasone or betamethasone, with heparin, glycerol, dextran 40 and some vasodilators. Two cases with temporal lobe syndrome were treated in the early stages of brain injury for a period of over 12 months were almost completely cured, another two cases with chiasma syndrome were treated in the relatively late stages, showed a partial improvement. One case which was irradiated 120 GY during 13 years did not improve. The final case treated with steroids for a short period also resulted in failure and the patient underwent an operation for the removal of the necrotic mass three years after the radiotherapy. Steroid therapy started in the early stages of brain injury after irradiation for over the 12 months is thought to be effective. Heparin therapy was also effective in one out of three cases, but in one of the cases subarachnoid hemorrhage from a traumatic aneurysm occurred during the therapy. In an acute phase, showing edematous change of the injured brain, the administration of glycerol is also thought to be useful. But the effectiveness of the other medicines containing some vasodilators was obscure or doubtful. We propose the following : (1) A meticulous observation is essential for the patients who received high doses of irradiation to diagnose brain injury in the early reversible stage. (2) Steroids should be given immediately in this reversible stage of brain injury before the irreversible ''necrosis'' occurs. (3) Steroids should be maintained for a long period over 12 months. (4) Heparin therapy is also thought to be effective, but careful precautions to avoid hemorrhagic complications before the therapy should be scheduled. This recommended plan may also be used for the treatment of brain injuries after cranial irradiation for other intracranial tumors. (author)

  14. Characteristic effects of heavy ion irradiation on the rat brain

    International Nuclear Information System (INIS)

    Sun, X.Z.; Takahashi, S.; Kubota, Y.; Yoshida, S.; Takeda, H.; Zhang, R.; Fukui, Y.

    2005-01-01

    Heavy ion irradiation has the feature to administer a large radiation dose in the vicinity of the endpoint in the beam range, and its irradiation system and biophysical characteristics are different from ordinary irradiation instruments like X- or gamma-rays. Using this special feature, heavy ion irradiation has been applied for cancer treatment. The safety and efficacy of heavy ion irradiator have been demonstrated to a great extent. For instance, brain tumors treated by heavy-ion beams became smaller or disappearance. However, fundamental research related to such clinical phenotypes and their underlying mechanisms are little known. In order to clarify characteristic effects of heavy ion irradiation on the brain, we developed an experimental system for irradiating a restricted region of the rat brain using heavy ion beams. The characteristics of the heavy ion beams, histological, behavioral and elemental changes were studied in the rat following heavy ion irradiation. Adult male Sprague-Dawley rats, aged 12 weeks and weighing 260-340 g (Shizuoka Laboratory Animal Center, Hamamatsu, Japan) were used. Rats were deeply anesthetized 10-15 minutes before irradiation with ketamine (40 mg/kg) and xylazine (10 mg/kg), immobilized in a specifically designed jig, and irradiated with 290 MeV/nucleon charged carbon beams in a dorsal-to ventral direction, The left cerebral hemispheres of the brain were irradiated at doses of 100 Gy charged carbon particles. The depth-dose distribution of the heavy ion beams was modified to make a spread-out bragg peak of 5 mm wide with a range modulator. The characteristics of the heavy-ion beams (field and depth of the heavy-ion beams) were examined by a measuring paraffin section of rat brain at different thickness. That extensive necrosis was observed between 2.5 mm and 7.5 mm depth from the surface of the rat head, suggesting a relatively high dose and uniform dose was delivered among designed depths and the spread-out bragg peak used here

  15. Imaging biomarkers in primary brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)

    2015-04-01

    We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

  16. Primary brain tumor presenting as intracranial hemorrhage

    International Nuclear Information System (INIS)

    Tsunoda, Shigeru; Sakaki, Toshisuke; Miyamoto, Seiji; Kyoi, Kikuo; Utsumi, Shozaburo; Kamada, Kitaro; Inui, Shoji; Masuda, Akio.

    1989-01-01

    Ten cases of primary brain tumor presenting as intracranial hemorrhage were studied in terms of the radiological and histological findings. The cases having hemorrhage in the tumor, as established through CT or histologically, were excluded if their onsets were not sudden due to intracranial hemorrhages. The results obtained may be summarized as follows: 1) From an anatomical point of view, cerebral subcortical hemorrhages account for 80%; hemorrhages in the cerebellopontine angle, 10%, and hemorrhages in the basal ganglia, 10%. 2) Plain CT findings showed perifocal low-density areas within 24 hours after onset in all 10 cases. 3) Enhanced CT findings showed enhanced areas in 4 or 6 cases. 4) Angiographic findings revealed abnormalities besides the mass effect in 5 of the 10 cases. 4) Angiographic findings revealed abnormalities besides the mass effect in 5 of the 10 cases. 5) From a histological point of view, glioblastomas account for 30%; malignant astrocytomas, 20%; astrocytomas, 20%; malignant ependymomas, 10%; hemangioblastoma, 10%, and transitional meningiomas, 10%. In conclusion, a perifocal low-density area on CT within 24 hours after onset is the most meaningful indication of intracranial hemorrhage originating from a brain tumor. A histological 'perinuclear halo' in an astrocytoma as an artifact due to hemorrhage may often be misleading in diagnosing mixed oligo-astrocytomas. (author)

  17. Histological studies in developing brain after 0.5 Gy neutron irradiation in utero

    International Nuclear Information System (INIS)

    Antal, S.; Fueloep, Z.

    1986-01-01

    Pregnant mice were irradiated with 0.5 Gy neutrons on day 13, 15 or 18 of gestation. There was no significant difference in number of living young born per litter between in neutron irradiated mice and controls. Mortality of irradiated offspings increased in the first 3 days after birth. The brain weight of 21-day old animals after neutron irradiation averaged only 55, 56 and 69% of controls, resp. At six hours after irradiation morphological analysis showed nuclear pyknosis in the central nervous system. On day 13 the telencephalon was severely affected. The 30% cells were pyknotic in the wall of the cerebral hemisphere and 20% of cells in corpus striatum. In the metencephalon marked pyknosis was established in the tectal lamina of mesencephalon (16%) and in the cerebellar anlage (21%). The olfactory plate (24%), the ventricular zone of cerebral hemisphere (30%) and colliculus ganglionaris were damaged mostly (40%) after radiation on day 15 of gestation. The tectum of the mesencephali and in metencephalon the external granular layer of cerebellum and area of the rhombic lip were affected by irradiation (17-20%). The telencephalon found pyknotic but to a less extent in group irradiated on day 18 than it was on day 15. In the olfactory bulb 10% of pyknotic cells were seen and 16% of primary cortex of cerebral hemisphere more over 30% of nucleus caudatus/putamen were affected. In metencephalon 19% of external granular layer of cerebellum and 13% of trigonum cerebelli were pyknotic. In general, lesions of irradiation were rather mild in diencephalon and myelencephalon at all examined ages. Histological examinations support that defined parts of brain are damaged after neutron irradiation in utero and it may lead to the described physiological 18-20 and biochemical consequences 20,23 . (orig.)

  18. Intensity-Modulated Radiation Therapy for Primary Brain Tumors

    Institute of Scientific and Technical Information of China (English)

    Zhong-min Wang

    2004-01-01

    Radiation therapy has been used to treat primary brain tumors as standard primary and/or adjunctive therapies for decades. It is difficult for conventional radiotherapy to deliver a lethal dose of radiation to the tumors while sparing surrounding normal brain due to complicated structures and multifunction in human brain. With the understanding of radiation physics and computer technology, a number of novel and more precise radiotherapies have been developed in recent years. Intensity modulated radiotherapy (IMRT) is one of these strategies. The use of IMRT in the treatment of primary brain tumors is being increasing nowadays. It shows great promise for some of primary brain tumors and also presents some problems, This review highlights current IMRT in the treatment of mainly primary brain tumors.

  19. Fetal antigen 2 in primary and secondary brain tumors

    DEFF Research Database (Denmark)

    Rasmussen, H Boje; Teisner, B; Schrøder, H D

    1991-01-01

    Immunohistochemical deposition and distribution of fetal antigen 2 (FA2) was examined in normal brain tissue and in primary and metastatic tumors of the brain. In normal brain tissue FA2 was exclusively found linearly around the vessels, along pia and in arachnoidea. A similar localization was seen...

  20. Crystals in brain and meninges in primary hyperoxaluria and oxalosis.

    Science.gov (United States)

    Haqqani, M T

    1977-01-01

    A case of primary hyperoxaluria and oxalosis with chronic renal failure, crystalline myocarditis, and disseminated calcium oxalate crystal deposition in various tissues including the brain and meninges is described. Deposition of crystals in brain and meninges is exceptionally rare in primary oxalosis. Images PMID:838867

  1. Early radiation changes of normal dog brain following internal and external brain irradiation: A preliminary report

    International Nuclear Information System (INIS)

    Chin, H.; Maruyama, Y.; Markesbery, W.; Goldstein, S.; Wang, P.; Tibbs, P.; Young, B.; Feola, J.; Beach, L.

    1984-01-01

    To examine radiation-induced changes in the normal brain, internal or external radiation was given to normal dog brain. Seven medium-sized dogs were used in this study. Two dogs were controls and an ice-pick (plastic implant applicator) was placed in the right frontal lobe for about 5 hours but no irradiation. Two dogs underwent Cs-137 brain implantation for 4 and 5 hours, respectively using an ice-pick technique. Two dogs were given internal neutron irradiation using the same technique of intracerebral ice-pick brachytherapy. One dog received an external photon irradiation using 6-Mev Linear Accelerator. Postmortem microscopic examination was made to study the early cerebral changes to irradiation in three dogs: one control with no irradiation; one received intracerebral Cesium implantation; and one external photon irradiation. Vascular change was the most prominent microscopic finding. There were hemorrhage, endothelial proliferation and fibrinoid changes of small vessel wall. Most of the changes were localized in the white matter and the cortex remained intact. Details (CT, NMR and histological studies) are discussed

  2. Neurosarcoidosis associated with hypersomnolence treated with corticosteroids and brain irradiation

    International Nuclear Information System (INIS)

    Rubinstein, I.; Gray, T.A.; Moldofsky, H.; Hoffstein, V.

    1988-01-01

    Narcoleptic features developed in a young man with CNS sarcoidosis. This was associated with a structural lesion in the hypothalamus as demonstrated on CT scans of the head. The diagnosis of narcolepsy was established by compatible clinical history and the Multiple Sleep Latency Test. Treatment with high-dose corticosteroids was ineffective, but when the low-dose, whole-brain irradiation was added, complete resolution of the narcoleptic features ensued

  3. Gamma knife radiosurgery for ten or more brain metastases. Analysis of the whole brain irradiation doses

    International Nuclear Information System (INIS)

    Nakaya, Kotaro; Hori, Tomokatsu; Izawa, Masahiro; Yamamoto, Masaaki

    2002-01-01

    Gamma knife (GK) radiosurgery has recently been recognized as the most powerful treatment modality in managing patients with brain metastasis, be they radioresistant or not, solitary or multiple. Very recently, this treatment has been employed in patients with numerous brain metastases, even those with 10 or more lesions. However, cumulative irradiation doses to the whole brain, with such treatment, remain unknown. Since the Gamma Plan ver. 5.10 (ver. 5.30 is presently available, Leksell Gamma Plan) became available in November, 1998, 105 GK procedures have been performed at our two facilities, Tokyo Women's Medical University and Katsuta Hospital Mito Gamma House. The median lesion number was 17, ranging 10-43, and the median cumulative volume of all tumors was 8.72 cm 3 , ranging 0.41-81.41 cm 3 . The selected doses at the lesion periphery ranged 12-25 Gy, the median being 20 Gy. Based on these treatment protocols, the cumulative irradiation dose was computed. The median cumulative irradiation dose to the whole brain was 4.83, ranging 2.16-8.51 Gy: the median integrated dose to the whole brain was 6.2 J, ranging 2.16-11.9 J. The median brain volumes receiving ≥2, ≥5, ≥10, ≥15 and ≥20 Gy were 1105 (range: 410-1501), 309 (46-1247), 64 (13-282), 24 (2-77), and 8 (0-40) cm 3 , respectively. The cumulative whole brain irradiation doses for patients with numerous radiosurgical targets were considered not to exceed the threshold level of normal brain necrosis. (author)

  4. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    NARCIS (Netherlands)

    Meyners, T.; Heisterkamp, C.; Kueter, J.D.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.; Rades, D.

    2010-01-01

    Background: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from

  5. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    NARCIS (Netherlands)

    Meyners, Thekla; Heisterkamp, Christine; Kueter, Jan-Dirk; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.; Rades, Dirk

    2010-01-01

    This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the

  6. Effects of preoperative irradiation on primary tracheal anastomosis

    International Nuclear Information System (INIS)

    Tsubota, N.; Simpson, W.J.; Van Nostrand, A.W.P.; Pearson, F.G.

    1975-01-01

    Preoperative radiotherapy was used in the management of selected patients with cancer of the lung or trachea who might subsequently require segmental resection of bronchus or trachea and reconstruction by primary anastomosis. This study was designed to determine the effects of varying dosages of preoperative irradiation on anastomotic healing. Two rings were resected from the cervical trachea of 20 dogs following irradiation with varying doses of cesium. There were no important adverse effects on healing of the trachea or adjacent organs in dogs receiving up to 3,500 rads. All dogs receiving a higher dose than this developed some anastomotic stenosis, which was severe in 6 of 8 animals. Similar adverse effects were observed in 2 patients managed by preoperative radiotherapy (4,000 rads in three weeks) and tracheal resection with primary anastomosis

  7. Effects of preoperative irradiation on primary tracheal anastomosis

    Energy Technology Data Exchange (ETDEWEB)

    Tsubota, N.; Simpson, W.J.; Van Nostrand, A.W.P.; Pearson, F.G.

    1975-08-01

    Preoperative radiotherapy was used in the management of selected patients with cancer of the lung or trachea who might subsequently require segmental resection of bronchus or trachea and reconstruction by primary anastomosis. This study was designed to determine the effects of varying dosages of preoperative irradiation on anastomotic healing. Two rings were resected from the cervical trachea of 20 dogs following irradiation with varying doses of cesium. There were no important adverse effects on healing of the trachea or adjacent organs in dogs receiving up to 3,500 rads. All dogs receiving a higher dose than this developed some anastomotic stenosis, which was severe in 6 of 8 animals. Similar adverse effects were observed in 2 patients managed by preoperative radiotherapy (4,000 rads in three weeks) and tracheal resection with primary anastomosis.

  8. Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial.

    Science.gov (United States)

    Rapp, Stephen R; Case, L Doug; Peiffer, Ann; Naughton, Michelle M; Chan, Michael D; Stieber, Volker W; Moore, Dennis F; Falchuk, Steven C; Piephoff, James V; Edenfield, William J; Giguere, Jeffrey K; Loghin, Monica E; Shaw, Edward G

    2015-05-20

    Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment. Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments. © 2015 by American Society of Clinical Oncology.

  9. Late effects of whole brain irradiation within the therapeutic range

    International Nuclear Information System (INIS)

    Caveness, W.F.; Carsten, A.L.

    1978-01-01

    Whole brain exposure with supervoltage irradiation was carried out on three sets of Macaca mulatta. Two sets of 12 monkeys each, at puberty, received single and fractionated exposures respectively. One set of 21 monkeys in adulthood received a fractionated exposure. Exposure to 1000 rads in a single dose, at puberty, caused no late effects. Exposure to 1500 rads caused small areas of necrosis in the forebrain white matter at 26 weeks, but a much more extensive involvementat and beyond 52 weeks that included confluent areas of necrosis in gray and white matter. Brain loss resulted in ventricular dilatation. Gliomas appeared in two out of three monkeys at or beyond 52 weeks. Exposure to 2000 rads caused such a wide scatter of focal areas of necrosis, including those in the brain stem, that survival beyond 20-26 weeks was not possible. All showed enlarged ventricular systems. Whole brain exposure, 200 rads a day, five days a week, for a course of 4000 rads, at puberty, resulted in no delayed effects. An exposure to 6000 rads, in a six weeks course, caused small, less than 1 mm, widely scattered necrotic lesions with a predilection for the forebrain white matter but not excluding the central gray matter and brain stem, at 26 weeks. At 52 weeks, there was considerable mineralization of the lesions and widespread telangiectasia. In the developing lesions, multiple minute breaks in the blood brain barrier caused diffuse brain swelling, reflected by papilloedema. Whole brain exposure to 6000 rads in a six weeks course, in the adult, produced less effects than the same dose at puberty. The onset of the scattered necrotic lesions was later than expected, appearing in one out of three animals at 33 weeks, two out of three animals at 52 weeks, and two out of three at 104 weeks. The lesions at 104 weeks were predominantly mineralized, but were accompanied by a greater extent of telangiectasia than seen in the pubescent monkeys

  10. Impact of drug permeability of blood-brain barrier after whole brain conventional fractionation irradiation

    International Nuclear Information System (INIS)

    Zhang Longzhen; Cao Yuandong; Chen Yong; Yu Changzhou; Zhuang Ming

    2006-01-01

    Objective: To explore the effect of drug permeability in rat blood-brain barrier(BBB) after different doses of whole brain conventional fractionation irradiation in rats and provide the experimental basis for the optimum time of clinical chemotherapy. Methods: According to different irradiation doses, 100 adult Sprague-Dowley rats were divided randomly into 5 groups: the normal control group(0 Gy); 10 Gy; 20 Gy; 30 Gy; and 40 Gy group. All rats were exposed to conventional fractionation(2 Gy/d, 5 d/w) with 60 Co γ-ray. MTX(25 mg/kg) was injected through the tail mainline 16 hours after whole brain irradiation. Cerebrospinal fluid(CSF) and blood were collected 2 hours later. Those samples were used to assay MTX concentration using RP-HPLC. Results: MTX mean concentrations in CSF was 0.07, 0.08, 0.12, 0.24, 0.23 mg/L in the control, 10 Gy, 20 Gy, 30 Gy, 40 Gy groups, respectively. All the data was analyzed with rank test of transform. MTX concentration of CSF was significantly different except the control and 10 Gy, 30 Gy and 40 Gy group. MTX concentration of blood was not significantly different in all groups (P>0.05). Conclusions: Irradiation can directly damage the function of BBB. BBB would be opened gradually following the increase of irradiation dose. It could be considered as the optimum time of chemotherapy when the whole brain irradiation ranges from 20 Gy to 30 Gy. (authors)

  11. The spreading of focal brain edema induced by ultraviolet irradiation

    International Nuclear Information System (INIS)

    Ferszt, R.; Neu, S.; Cervos-Navarro, J.; Sperner, J.

    1978-01-01

    Focal brain edema limited to one cerebral hemisphere was produced by ultraviolet irradiation of the exposed cortex. Tissue water content was determined by the gravimetric method which allows microsampling. Therefore, the spread of edema around the small necrotic area be mapped more precisely than by determination of dry weight which calls for larger samples. As early as 30 min after irradiation, hyperemia and swelling of the brain are observed under the operating microscope. This correlates with venous stasis, hyperemia, and broadened perivascular spaces around venules and large capillaries accompanied by a marked rise in the specific weigth of the tissue. After 4h an edema front can be observed spreading from the perinerotic zone in which there is a marked rise in endothelial cell vesicular activity. Edema reaches maximum levels in the deep white matter at 48h post irradiation with normalisation of the tissue water content after 96h. The velocity at which the edema front spreads from the cortex to the periventricular area lies in the range of 0.25mm/h. Edema reabsorption coincides with signs of retrograde micropinocytosis in endothelial cells. (orig./AJ) [de

  12. Spreading of focal brain edema induced by ultraviolet irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ferszt, R; Neu, S; Cervos-Navarro, J; Sperner, J [Freie Univ. Berlin (Germany, F.R.). Inst. fuer Neuropathologie

    1978-01-01

    Focal brain edema limited to one cerebral hemisphere was produced by ultraviolet irradiation of the exposed cortex. Tissue water content was determined by the gravimetric method which allows microsampling. Therefore, the spread of edema around the small necrotic area be mapped more precisely than by determination of dry weight which calls for larger samples. As early as 30 min after irradiation, hyperemia and swelling of the brain are observed under the operating microscope. This correlates with venous stasis, hyperemia, and broadened perivascular spaces around venules and large capillaries accompanied by a marked rise in the specific weigth of the tissue. After 4h an edema front can be observed spreading from the perinerotic zone in which there is a marked rise in endothelial cell vesicular activity. Edema reaches maximum levels in the deep white matter at 48h post irradiation with normalisation of the tissue water content after 96h. The velocity at which the edema front spreads from the cortex to the periventricular area lies in the range of 0.25mm/h. Edema reabsorption coincides with signs of retrograde micropinocytosis in endothelial cells.

  13. Post-irradiation brain-necrosis resulting in apoplexia and death after 33 years of irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Froehlich, A [Foevarosi Laszlo Korhaz, Budapest (Hungary). Korbonctani es Korszoevettani Oszt.

    1980-04-01

    A case of post-irradiation brain-necrosis resulting in apoplexia of the cerebellum after 33 years of irradiation (19984 r.) of a presumptive cerebellar tumour is reported. The pathohistologic study revealed symptoms of the ''late'' damage and the vascular changes appeared to be the most prominent. The thickening of the vessel walls, hyperplasia of collagen fibres and deposition of calcium in the media, were the most characteristic lesions revealed. In some of the small vessels isolated calcification of the media was observed. It seems most probable that in the development of apoplexia vascular alterations could play an important role. In the available literature no report has been found on a similarly long interval elapsing between the irradiation and death.

  14. Post-irradiation brain-necrosis resulting in apoplexia and death after 33 years of irradiation

    International Nuclear Information System (INIS)

    Froehlich, A.

    1980-01-01

    A case of post-irradiation brain-necrosis resulting in apoplexia of the cerebellum after 33 years of irradiation (19984 r.) of a presumptive cerebellar tumour is reported. The pathohistologic study revealed symptoms of the ''late'' damage and the vascular changes appeared to be the most prominent. The thickening of the vessel walls, hyperplasia of collagen fibres and deposition of calcium in the media, were the most characteristic lesions revealed. In some of the small vessels isolated calcification of the media was observed. It seems most probable that in the development of apoplexia vascular alterations could play an important role. In the available literature no report has been found on a similarly long interval elapsing between the irradiation and death. (author)

  15. Late effects of whole brain irradiation within the therapeutic range

    International Nuclear Information System (INIS)

    Caveness, W.F.; Carsten, A.L.

    1978-01-01

    Whole brain exposure with supervoltage x irradiation was carried out in three sets of Macaca mulatta. Two sets of 12 monkeys each, at puberty, received single and fractionated exposures, respectively. One set of 21 monkeys in adulthood received a fractionated exposure. Exposure to 1000 rads in a single dose, at puberty, caused no late effects. Exposure to 1500 rads caused small areas of necrosis in the forebrain white matter at 26 weeks, but a much more extensive involvement at and beyond 52 weeks that included confluent areas of necrosis in gray and white matter. Brain loss resulted in ventricular dilatation. Gliomas appeared in two out of three monkeys at or beyond 52 weeks. Exposure to 2000 rads caused such a wide scatter of focal areas of necrosis, including those in the brain stem, that survival beyond 20 to 26 weeks was not possible. All showed enlarged ventricular systems. Whole brain exposure, 200 rads a day, five days a week, for a course of 4000 rads, at puberty, resulted in no delayed effects. Whole brain exposure to 6000 rads in a six weeks course, in the adult, produced less effects than the same dose at puberty. The onset of the scattered necrotic lesions was later than expected, appearing in one out of three animals at 33 weeks, two out of three animals at 52 weeks, and two out of three at 104 weeks. The lesions at 104 weeks were predominantly mineralized, but were accompanied by a greater extent of telangiectasia than seen in the pubescent monkeys

  16. The early effects in the brain after irradiation with carbon ions using mice

    International Nuclear Information System (INIS)

    Takai, Nobuhiko; Nakamura, Saori; Ohba, Yoshihito; Uzawa, Akiko; Furusawa, Yoshiya; Koike, Sachiko; Matsumoto, Yoshitaka; Hirayama, Ryoichi

    2011-01-01

    This study investigated both early and late effects in the brain after irradiation with carbon ions using mice. The irradiation dose was set at level known to produce vascular change followed by necrosis, which appeared the late period after irradiation with 30 Gy. The whole of brain was irradiated, excluding eyes and brain stem. The mice irradiated with single dose of 30 Gy showed deficit in short-term working memory assessed at 36 hr after irradiation, whereas mice receiving carbon irradiation showed no deficit in long-term reference memory. At 16 weeks after irradiation, the irradiated mice showed marked learning impairment compared with age-matched controls and the irradiated mice showed substantial impairment of working memory. Histopathological observation revealed no abnormal finding in the irradiated brain at 36 hr after irradiation, although irradiated mice showed marked neuronal degeneration at the hippocampus within CA1 to CA3 layers at 16 weeks after irradiation. In the irradiated group, neuronal cells in the hippocampal CA1-3 areas were reduced by 30-49%. These results suggest that although irradiation-induced hippocampal degeneration is associated with learning disability, cognitive deficits may also be detected on the early stage, not associated with hippocampal degeneration. (author)

  17. Tolerance of the brain and spinal cord to conventional irradiation

    International Nuclear Information System (INIS)

    Leibel, S.A.; Sheline, G.E.

    1991-01-01

    In this paper, the authors discuss the clinical features and time-dose relations associated with radiation injury of the brain and spinal cord. Limits of radiation tolerance have not been well defined. In general, the literature on central nervous system (CNS) injury is anecdotal and incomplete. Relevant information such as total dose at the site of injury, size and number of treatment fractions, overall treatment time, radiation field arrangement, and volume treated is often omitted. Therefore, it is difficult to formulate firm conclusions regarding the risk of radiation injury and its association with any given set of therapeutic approaches and patient characteristics. The material presented in this chapter is based on conventional photon and gamma irradiation, and does not apply to large single dose fractions used in stereotaxic small-field external irradiation (radiosurgery) or to other forms of ionizing radiation such as neutrons or heavy particles

  18. [Alterations of glial fibrillary acidic protein in rat brain after gamma knife irradiation].

    Science.gov (United States)

    Ma, Z M; Jiang, B; Ma, J R

    2001-08-28

    To study glial fibrillary acidic protein (GFAP) immunoreactivity in different time and water content of the rat brain treated with gamma knife radiotherapy and to understand the alteration course of the brain lesion after a single high dose radiosurgical treatment. In the brains of the normal rats were irradiated by gamma knife with 160 Gy-high dose. The irradiated rats were then killed on the 1st day, 7th day, 14th day, and 28th day after radiotherapy, respectively. The positive cells of GFAP in brain tissue were detected by immunostaining; the water content of the brain tissue was measured by microgravimetry. The histological study of the irradiated brain tissue was performed with H.E. and examined under light microscope. The numbers of GFAP-positive astrocytes began to increase on the 1st day after gamma knife irradiation. It was enlarged markedly in the number and size of GFAP-stained astrocytes over the irradiated areas. Up to the 28th day, circumscribed necrosis foci (4 mm in diameter) was seen in the central area of the target. In the brain tissue around the necrosis, GFAP-positive astrocytes significantly increased (P gravity in the irradiated brain tissue the 14th and 28th day after irradiation. The results suggest that GFAP can be used as a marker for the radiation-induced brain injury. The brain edema and disruption of brain-blood barrier can be occurred during the acute stage after irradiation.

  19. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Science.gov (United States)

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  20. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Directory of Open Access Journals (Sweden)

    Kun Hua

    Full Text Available Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like

  1. Minocycline ameliorates cognitive impairment induced by whole-brain irradiation: an animal study

    International Nuclear Information System (INIS)

    Zhang, Liyuan; Li, Kun; Sun, Rui; Zhang, Yuan; Ji, JianFeng; Huang, Peigeng; Yang, Hongying; Tian, Ye

    2014-01-01

    It has been long recognized that cranial irradiation used for the treatment of primary and metastatic brain tumor often causes neurological side-effects such as intellectual impairment, memory loss and dementia, especially in children patients. Our previous study has demonstrated that whole-brain irradiation (WBI) can cause cognitive decline in rats. Minocycline is an antibiotic that has shown neuroprotective properties in a variety of experimental models of neurological diseases. However, whether minocycline can ameliorate cognitive impairment induced by ionizing radiation (IR) has not been tested. Thus this study aimed to demonstrate the potential implication of minocycline in the treatment of WBI-induced cognitive deficits by using a rat model. Sprague Dawley rats were cranial irradiated with electron beams delivered by a linear accelerator with a single dose of 20 Gy. Minocycline was administered via oral gavages directly into the stomach before and after irradiation. The open field test was used to assess the anxiety level of rats. The Morris water maze (MWM) was used to assess the spatial learning and memory of rats. The level of apoptosis in hippocampal neurons was measured using immunohistochemistry for caspase-3 and relative markers for mature neurons (NeuN) or for newborn neurons (Doublecortin (DCX)). Neurogenesis was determined by BrdU incorporation method. Neither WBI nor minocycline affected the locomotor activity and anxiety level of rats. However, compared with the sham-irradiated controls, WBI caused a significant loss of learning and memory manifest as longer latency to reach the hidden platform in the MWM task. Minocycline intervention significantly improved the memory retention of irradiated rats. Although minocycline did not rescue neurogenesis deficit caused by WBI 2 months post-IR, it did significantly decreased WBI-induced apoptosis in the DCX positive neurons, thereby resulting in less newborn neuron depletion 12 h after irradiation

  2. Modulation of the brain acetylcholinesterase activity after gamma irradiation or cytokine administration

    International Nuclear Information System (INIS)

    Clarencon, D.; Multon, E.; Galonnier, M.; Fournier, C.; Fatome, M.; Gourmelon, P.

    1997-01-01

    The central nervous system exhibits a functional radiosensitivity, with different abnormalities in the neuronal transmission. In particular we observed a decrease in AChE activity in the rat brain after a whole body gamma exposure. This could not be explained by a direct effect on the protein: the AChE is particularly radioresistant, since several hundred of grays are necessary to modify the in vitro enzymatic activity. Radiations have no effect on primary neuronal culture, and the in vivo radiogenic decrease in brain AChE activity could imply more complex mechanisms than nervous transmissions alone, involving the participation of several intercellular communication systems. The second part of our experimental results showed that both peripheral or central administration of IL-6 can reproduce the decrease in the brain AChE activity observed after an irradiation. The role of inflammatory mediators in the acute radiation syndrome is now well documented. The way these cellular mediators could activate the CNS remains unclear. An induction of messengers of IL-1 and TNF in different brain areas has been recently demonstrated. However, it could be mentioned that, by using primary neuronal cultures, neither the membranes-bound nor the release enzyme activities were modified by incubation with IL-6. On the other hand, when the primary neurons were plated with a subculture of glial cells, the release of enzyme was greatly reduced during a few hours after incubation with IL-6, but the membrane-bound enzyme, which represent more than 90% of the total activity, was not modified. Hence, the mechanisms by which cytokines act on the CNS seem to be more complex, with the participation of glial cells. We suggest that the peripheral early inflammatory response which occurs after irradiation might participate in the nervous damage. (N.C.)

  3. Primary brain lymphoma in a patient after renal transplantation

    International Nuclear Information System (INIS)

    Arteaga, Carlos; Duarte, Monica; Bayona, Hernan

    2009-01-01

    The incidence of primary central nervous system lymphoma (PCNSL) has increased during the past 40 years. This has been associated with immunodeficiency, mainly in patients infected with the human immunodeficiency virus (HIV) and in transplant patients. Tumor genesis is related with the Epstein-Barr virus (EBV). The most frequent PCNSL immuno phenotype is B-cell lymphoma. Clinical manifestations depend on tumor localization, and are usually behavior dysfunctions and intracranial hypertension syndrome. Differential diagnosis must take into consideration infectious processes, stroke, primary brain tumors, and metastases. The diagnosis of PCNSL requires brain MRI and brain biopsy. It is important to assess HIV infection when diagnosing PCNSL. This review reports a case of primary brain lymphoma in a patient who underwent renal transplantation due to polycystic kidney disease 8 years before.

  4. The blood-brain barrier in vitro using primary culture

    DEFF Research Database (Denmark)

    Larsen, Annette Burkhart

    The brain is protected from the entry of unwanted substances by means of the blood-brain barrier (BBB) formed by the brain microvasculature. This BBB is composed of non-fenestrated brain capillary endothelial cells (BCECs) with their intermingling tight junctions. The presence of the BBB is a huge...... obstacle for the treatment of central nervous system (CNS) diseases, as many potentially CNS active drugs are unable to reach their site of action within the brain. In vitro BBB models are, therefore, being developed to investigate the BBB permeability of a drug early in its development. The first part...... of the thesis involves the establishment and characterization of an in vitro BBB models based on primary cells isolated from the rat brain. Co-culture and triple culture models with astrocytes and pericytes were found to be the superior to mono cultured BCECs with respect to many important BBB characteristics...

  5. Global cerebral blood flow changes measured by brain perfusion SPECT immediately after whole brain irradiation

    International Nuclear Information System (INIS)

    Ohtawa, Nobuyuki; Machida, Kikuo; Honda, Norinari; Hosono, Makoto; Takahashi, Takeo

    2003-01-01

    Whole brain irradiation (WBI) is still a major treatment option for patients with metastatic brain tumor despite recent advances in chemotherapy and newer techniques of radiation therapy. Cerebral blood flow (CBF) of changes induced by whole brain radiation is not fully investigated, and the aim of the study was to measure CBF changes non-invasively with brain perfusion SPECT to correlate with treatment effect or prognosis. Total of 106 patients underwent WBI during April 1998 to March 2002. Both brain MRI and brain perfusion SPECT could be performed before (less than 1 week before or less than 10 Gy of WBI) and immediately after (between 1 week before and 2 weeks after the completion of WBI) the therapy in 17 of these patients. They, 10 men and 7 women, all had metastatic brain tumor with age range of 45 to 87 (mean of 61.4) years. Tc-99m brain perfusion agent (HMPAO in 4, ECD in 13) was rapidly administered in a 740-MBq dose to measure global and regional CBF according to Matsuda's method, which based on both Patlak plot and Lassens' linearity correction. Brain MRI was used to measure therapeutic response according to World Health Organization (WHO) classification as complete remission (CR), partial response (PR), no change (NC), and progressive disease (PD). Survival period was measured from the completion of WBI. Mean global CBF was 40.6 and 41.5 ml/100 g/min before and immediately after the WBI, respectively. Four patients increased (greater than 10%) their global mean CBF, 10 unchanged (less than 10% increase or decrease), and 3 decreased after the WBI. The WBI achieved CR in none, PR in 8, NC in 6, and PD in 3 on brain MRI. Change in global mean CBF (mean±SD) was significantly larger in PR (4.3±2.0 ml/100 g/min, p=0.002) and in NC (-0.1±4.5) than in PD (-3.9±6.4, P=0.002, P=0.016, respectively). Survival was not significantly (p>0.05) different among the patients with CR (20 weeks), NC (48 weeks), and PD (21 weeks). Change in global CBF and survival was

  6. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Hee [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Warrington, Junie P.; Sonntag, William E. [Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Lee, Yong Woo, E-mail: ywlee@vt.edu [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States)

    2012-04-01

    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  7. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    International Nuclear Information System (INIS)

    Lee, Won Hee; Warrington, Junie P.; Sonntag, William E.; Lee, Yong Woo

    2012-01-01

    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy γ-rays or a fractionated dose of 40 Gy γ-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  8. Prognostic factors derived from recursive partition analysis (RPA) of radiation therapy oncology group (RTOG) brain metastases trials applied to surgically resected and irradiated brain metastatic cases

    International Nuclear Information System (INIS)

    Agboola, Olusegun; Benoit, Brien; Cross, Peter; Silva, Vasco da; Esche, Bernd; Lesiuk, Howard; Gonsalves, Carol

    1998-01-01

    Purpose: (a) To identify the prognostic factors that determine survival after surgical resection and irradiation of tumors metastatic to brain. (b) To determine if the prognostic factors used in the recursive partition analysis (RPA) of brain metastases cases from Radiation Therapy Oncology Group (RTOG) studies into three distinct survival classes is applicable to surgically resected and irradiated patients. Method: The medical records of 125 patients who had surgical resection and radiotherapy for brain metastases from 1985 to 1997 were reviewed. The patients' disease and treatment related factors were analyzed to identify factors that independently determine survival after diagnosis of brain metastasis. The patients were also grouped into three classes using the RPA-derived prognostic parameters which are: age, performance status, state of the primary disease, and presence or absence of extracranial metastases. Class 1: patients ≤ 65 years of age, Karnofsky performance status (KPS) of ≥70, with controlled primary disease and no extracranial metastases; Class 3: patients with KPS < 70. Patients who do not qualify for Class 1 or 3 are grouped as Class 2. The survival of these patients was determined from the time of diagnosis of brain metastases to the time of death. Results: The median survival of the entire group was 9.5 months. The three classes of patients as grouped had median survivals of 14.8, 9.9, and 6.0 months respectively (p = 0.0002). Age of < 65 years, KPS of ≥ 70, controlled primary disease, absence of extracranial metastases, complete surgical resection of the brain lesion(s) were found to be independent prognostic factors for survival; the total dose of radiation was not. Conclusion: Based on the results of this study, the patients and disease characteristics have significant impact on the survival of patients with brain metastases treated with a combination of surgical resection and radiotherapy. These parameters could be used in selecting

  9. Primary lymphoma of brain: results of management of a modern cohort with radiation therapy

    International Nuclear Information System (INIS)

    Laperriere, Normand J.; Cerezo, Laura; Milosevic, Michael F.; Wong, C. Shun; Patterson, Bruce; Panzarella, Tony

    1997-01-01

    Purpose: To assess the outcome and prognostic factors for patients with primary lymphoma of brain managed with radiation therapy between 1979 and 1988. Methods and materials: A retrospective review was undertaken of 49 patients referred to Princess Margaret Hospital. There were 25 males and 24 females. Median age was 60 years, with a range of 17-80 years. Tumors were located supratentorially in 35, infratentorially in 10, and both in 4 patients. Single masses were demonstrated on CT brain in 36, and multiple lesions in 13 patients. Cranial irradiation was given in 48, and 11 patients received chemotherapy. All patients in this series were immunocompetent. Results: Over a follow-up range of 3-11 years of surviving patients, with a median of 6 years, (40(49)) patients have died. Overall median survival was 1.4 years (17 months) and 5-year actuarial survival was 26%. Statistical analysis revealed the following significant factors: Karnofsky performance status (KPS), age, and distribution pattern of disease on presenting CT brain. Five-year actuarial survival for patients with a KPS > 60 or 60, 5-year actuarial survival was 42% and 9%, respectively (P = 0.03); for patients with solitary or multiple lesions, 5-year actuarial survival was 30% and 15%, respectively (P = 0.04). Conclusions: We conclude that Karnofsky performance status, age, and distribution pattern on pretreatment CT of brain are significant prognostic factors in primary lymphoma of brain, and that new approaches need to be developed for these patients

  10. Similarity between the effects of carbon-ion irradiation and X-irradiation on the development of rat brain

    International Nuclear Information System (INIS)

    Inouye, Minoru; Hayasaka, Shizu; Murata, Yoshiharu; Takahashi, Sentaro; Kubota, Yoshihisa

    2000-01-01

    The effects of carbon-ion irradiation and X-irradiation on the development of rat brain were compared. Twenty pregnant rats were injected with bromodeoxyuridine (BrdU) at 9 pm on day 18 pregnancy and divided into five groups. Three hours after injection (day 19.0) one group was exposed to 290 MeV/u carbon-ion radiation by a single dose of 1.5 Gy. Other groups were exposed to X-radiation by 1.5, 2.0 or 2.5 Gy, or sham-treated, respectively. Fetuses were removed from one dam in each group 8 h after exposure and examined histologically. Extensive cell death was observed in the brain mantle from the irradiated groups. The cell death after 1.5 Gy carbon-ion irradiation was remarkably more extensive than that after 1.5 Gy X-irradiation, but comparable to that after 2.0 Gy or 2.5 Gy X-irradiation. The remaining rats were allowed to give birth and the offspring were sacrificed at 6 weeks of age. All of the irradiated offspring manifested microcephaly. The size of the brain mantle exposed to 1.5 Gy carbon-ion radiation was significantly smaller than that exposed to 1.5 Gy X-radiation and larger than that exposed to 2.5 Gy X-radiation. A histological examination of the cerebral cortex revealed that cortical layers II-IV were malformed. The defect by 1.5 Gy carbon-ion irradiation was more severe than that by the same dose of X-irradiation. Although the BrdU-incorporated neurons were greatly reduced in number in all irradiated groups, these cells reached the superficial area of the cortex. These findings indicated that the effects of both carbon-ion irradiation and X-irradiation on the development of rat brain are similar in character, and the effect of 1.5 Gy carbon-ion irradiation compares to that of 2.0-2.5 Gy X-irradiation. (author)

  11. The role of CT simulation in whole-brain irradiation

    International Nuclear Information System (INIS)

    Gripp, Stephan; Doeker, Rolf; Glag, Michael; Vogelsang, Petra; Bannach, Burckhardt; Doll, Thorsten; Muskalla, Klaus; Schmitt, Gerd

    1999-01-01

    Purpose: Evidence is growing that incorrect field-shaping is a major cause of treatment failure in whole-brain irradiation (WBI). To evaluate the potential benefits of CT simulation in WBI we compared field-shaping based on 3D CT simulation to conventional 2D simulation. Methods: CT head scans were obtained from 20 patients. Conventional 2D planning was imitated by drawing the block contours on digitally reconstructed radiographs (DRR) by four radiotherapists. Critical parts of the target and the eye lenses were subsequently marked and planning was repeated using 3D information ('3D planning'). The results of both methods were compared by evaluation of the minimal distance from the field edge according to each site. Results: In conventional planning using DRR, major geographic mismatches (< -3 mm) occurred in the subfrontal region and both eye lenses with 1% each location. Minor mismatches (-3 to 0 mm) predominantly occurred in the contralateral lens (21%), ipsilateral lens (10%), and subfrontal region (9%). Close margins (0-5 mm) were most frequently noted at the contralateral lens (49%), ipsilateral lens (35%), and the subfrontal region (28%). When 3D planning was used, mismatches were not found. However, close margins were inevitable at the ipsilateral lens (5%), subfrontal region (30%), and contralateral lens (70%). Conclusions: CT simulation in WBI is significantly superior to conventional simulation with respect to complete coverage of the target volume and protection of the eye lenses. The narrow passage between the ocular lenses and lamina cribrosa represents a serious limitation. These patients are safely identified with CT simulation and can be referred for modified irradiation techniques

  12. The influence of Listeria monocytogenes cells on the primary immunologic response in irradiated mice

    International Nuclear Information System (INIS)

    Borowski, J.; Jokoniuk, P.

    1977-01-01

    The influence of killed Listeria monocytogenes cells on the primary immunologic response in mice irradiated with 300 or 500 R was studied. The immunologic response of the mice to sheep red blood cells used as antigen was assessed at the cellular level (by counting PFC) and humoral level. Injection of killed Listeria monocytogenes cells before irradiation of the mice diminished the immunosuppressive effect of roentgen radiation. Injection of the cells after irradiation accelerated regeneration of immunologic reactivity in the irradiated mice. (author)

  13. Asymptomatic cystic changes in the brain of children after cranial irradiation: frequency, latency, and relationship to age

    International Nuclear Information System (INIS)

    Kitajima, Mika; Hirai, Toshinori; Maruyama, Natsuki; Yamura, Masayuki; Hayashida, Yoshiko; Baba, Yuji; Yamashita, Yasuyuki; Murakami, Ryuji; Korogi, Yukunori; Nakamura, Hideo; Kuratsu, Jun-ichi

    2007-01-01

    Although radiation therapy plays an important role in the management of children with brain tumors, radiation-induced brain damage sometimes occurs after radiation therapy. In some pediatric patients who had undergone cranial radiation therapy, we noticed cystic changes in the brain on follow-up MRI. The purpose of this study was to determine the frequency, latency, relationship with patient age, radiation dose, and serial change in the cystic changes in children after cranial irradiation. We retrospectively studied MRI in 33 children who had undergone cranial irradiation for their primary brain tumors. Postirradiation cystic change in the brain on follow-up MRI was defined as a well-demarcated, oval-shaped, CSF-like signal intensity area, and no contrast enhancement. Of the 33 patients, 6 (18.2%) had one or more cystic lesions. The latency of the cystic changes ranged from 1.5 to 7 years (mean 2.6 years). Cystic changes were found in the subcortical, periventricular and other deep white matter and the basal ganglia. The size of the lesions ranged from 1 to 10 mm at their first appearance; eight cystic lesions increased in size. None the cystic lesions reduced in size or resolved with time and none required intervention. All patients with cystic changes had received irradiation when they were 6 years of age or younger. The cystic changes occurred within the radiation field in patients treated with a radiation dose of 36 Gy or more. Asymptomatic brain parenchymal cystic changes appear to occur in children who have undergone cranial irradiation at 6 years of age or younger. (orig.)

  14. Brain imaging before primary lung cancer resection: a controversial topic.

    Science.gov (United States)

    Hudson, Zoe; Internullo, Eveline; Edey, Anthony; Laurence, Isabel; Bianchi, Davide; Addeo, Alfredo

    2017-01-01

    International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England Clin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources. Our aim was to determine local practice based on historic outcomes in this patient cohort. This retrospective study took place in a regional thoracic surgical centre in the United Kingdom. Pathology records for all patients who had undergone lung resection with curative intent during the time period January 2012-December 2014 were analysed in October 2015. Electronic pathology and radiology reports were accessed for each patient and data collected about their histological findings, TNM stage, resection margins, and the presence of brain metastases on either pre-operative or post-operative imaging. From the dates given on imaging, we calculated the number of days post-resection that the brain metastases were detected. 585 patients were identified who had undergone resection of their lung cancer. Of these, 471 had accessible electronic radiology records to assess for the radiological evidence of brain metastases. When their electronic records were evaluated, 25/471 (5.3%) patients had radiological evidence of brain metastasis. Of these, five patients had been diagnosed with a brain metastasis at initial presentation and had undergone primary resection of the brain metastasis followed by resection of the lung primary. One patient had been diagnosed with both a primary lung and a primary bowel adenocarcinoma; on review of the case, it was felt that the brain metastasis was more likely to have

  15. Cognitive dysfunction and histological findings in adult rats one year after whole brain irradiation

    International Nuclear Information System (INIS)

    Akiyama, Katsuhiko; Tanaka, Ryuichi; Sato, Mitsuya; Takeda, Norio

    2001-01-01

    Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis. (author)

  16. Treatment of brain metastases from primary lung cancer

    International Nuclear Information System (INIS)

    Ryan, Gail F.; Ball, David L.; Smith, Jennifer G.

    1995-01-01

    Purpose: A retrospective study of patients treated at the Peter MacCallum Cancer Institute for brain metastases from primary carcinoma of the lung is presented. Methods and Materials: The medical records of 416 patients with the diagnosis of primary carcinoma of the lung who presented with, or subsequently developed, brain metastases during the period January 1984 to December 1987 were reviewed. Information on a number of factors of potential prognostic significance (sex, age, histology, performance status and interval between diagnosis of the primary and brain metastases) was collected. Details of surgery, radiation and steroid usage were recorded, and any steroid side effects documented. Survival was calculated from the date of diagnosis of brain metastases. Stepwise regression based on Cox's proportional hazards model was used to determine significant prognostic factors affecting survival. Patients with and without steroid side effects were compared using Yate's corrected chi-square test. Results: The overall estimated median survival was only 3.3 months (95% confidence interval 2.9-3.7 months). Only two factors were found to be associated with a significantly improved survival--surgical intervention and good performance status. After taking these two factors into account, the dose of radiation used (< 30 Gy or ≥ 30 Gy) did not influence survival. There was a 3% incidence of gastric bleeding or perforation in patients taking steroids, with a 40% fatality rate. Predisposing factors to gastric side effects were a prior history of peptic ulcer and/or aspirin or nonsteroidal anti-inflammatory drug consumption. Conclusion: Radiation of brain metastases from primary lung cancer results in modest survival benefit. Radiation dose (< 30 Gy or ≥ 30 Gy) is not a significant determinant of survival. Other treatment modifications, such as concurrent radiation and chemotherapy, should be explored. Steroids should be used with caution as fatal side effects can occur

  17. Effect of Irradiation Maternal Diets on the Post-natal Development of Brain Rat Pups

    International Nuclear Information System (INIS)

    Hasan, S.S.

    2005-09-01

    Full text: Effect of Protein-calorie malnutrition was studied on the pups born to mothers receiving either irradiated normal diet (consisted equal parts of gram and wheat) or irradiation low protein diet (consisted one part of normal diet and three parts of heat). Level of DNA, RNA and protein content were found markedly reduced in the brain of irradiated low protein diet fed pups than in the pups fed on the irradiated normal diet. Glucose 6-phosphate dehydrogenase activity was found lower while catalase and lipid peroxidation activity were higher in the pups given irradiated low protein diet, compared whit the pups fed irradiated normal diet. On the whole both the irradiated low protein diet as well as irradiated normal diet fed pups showed higher index of biochemical changes than in the unirradiated low protein diet fed pups. Post-natal mortality was 60% in the pups given irradiated low protein diet, whereas the pups fed on the irradiated normal diet and unirradiated low protein diet did not show any death. The study given evidence that feeding of the irradiated low protein diet interferes more with the development of brain compared with the pups fed on irradiated normal diet

  18. Full scale IQ (FSIQ) changes in children treated with whole brain and partial brain irradiation. A review and analysis

    International Nuclear Information System (INIS)

    Fuss, M.; Poljanc, K.; Hug, E.B.; Loma Linda Univ. Medical Center, Loma Linda, CA

    2000-01-01

    The purpose of this analysis was to assess current knowledge, with focus on correlation with radiation dose, irradiated volume and age. Method: Full Scale IQ (FSIQ) data, representing 1,938 children, were derived from 36 publications and analyzed as to radiation dose, irradiated volume, and age. Results: FSIQ after whole brain irradiation showed a non-linear decline as dosage increased. The dose-effect relationship was age-related, with more pronounced FSIQ decline at younger age. FSIQ test results below the normal level ( 50 Gy. Conclusion: The collected data suggest that whole brain irradiation doses of 18 and 24 Gy have no major impact on intellectual outcome in children older than age 6, but may cause impairment in younger children. Doses >24 Gy comprise a substantial risk for FSIQ decline, even in older children. At equal dose levels, partial brain irradiation is less damaging than whole brain irradiation. The authors are well aware of limitations in the interpretation of data collected for the current review. (orig.) [de

  19. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

    Science.gov (United States)

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-26

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

  20. Impairments of learning and memory in the rats after brain irradiation

    International Nuclear Information System (INIS)

    Takai, Nobuhiko

    2002-01-01

    Clinical trials of hadrontherapy have been carried out world wide at several facilities including National Institute of Radiological Sciences (NIRS). Cerebral dysfunction is one of the major concerns associated with radiotherapy of brain tumors. However, little is known about the neurochemical basis of brain dysfunction induced by proton irradiation. We investigated and reported here the early consequences of brain damages caused by proton beam. The animals that had memorized the location of the standard position were locally irradiated to brain with either 70 MeV protons or 290 MeV carbon ions. At 24 hr after irradiation, impairment of the long-term memory was not observed in the irradiated rats compared to control. Irradiated animals, however, required substantially longer time finding out the standard position than control rats when the standard platform displaced to a position different from memorized position. This follows that a single doses of 30 Gy, either protons or carbon ions, impairs the working memory of animals. Function of muscarinic acetylcholine receptors was analyzed by an in vivo binding assay using radioligand quinuclidinyl benzilate (QNB). Irradiated rats were intravenously injected with 5.5 MBq of 3 H-QNB 24 hr after the irradiation, and decapitated 60 min after tracer injection. The autoradiographic studies showed an transitional increase of 3 H-QNB in vivo binding in the early phase after proton irradiation, even though no change in in-vitro 3 H-QNB binding was see in brain autoradiograms of irradiated rats. The cerebral blood flow and the histrogical features of brain were also changed at 3 months post-irradiation. These results indicate that the memory impairment caused by radiation is closely related to the early change of acetylcholine receptor in vivo. (author)

  1. Impairments of learning and memory in the rats after brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Takai, Nobuhiko [National Inst. of Radiological Sciences, Chiba (Japan)

    2002-06-01

    Clinical trials of hadrontherapy have been carried out world wide at several facilities including National Institute of Radiological Sciences (NIRS). Cerebral dysfunction is one of the major concerns associated with radiotherapy of brain tumors. However, little is known about the neurochemical basis of brain dysfunction induced by proton irradiation. We investigated and reported here the early consequences of brain damages caused by proton beam. The animals that had memorized the location of the standard position were locally irradiated to brain with either 70 MeV protons or 290 MeV carbon ions. At 24 hr after irradiation, impairment of the long-term memory was not observed in the irradiated rats compared to control. Irradiated animals, however, required substantially longer time finding out the standard position than control rats when the standard platform displaced to a position different from memorized position. This follows that a single doses of 30 Gy, either protons or carbon ions, impairs the working memory of animals. Function of muscarinic acetylcholine receptors was analyzed by an in vivo binding assay using radioligand quinuclidinyl benzilate (QNB). Irradiated rats were intravenously injected with 5.5 MBq of {sup 3}H-QNB 24 hr after the irradiation, and decapitated 60 min after tracer injection. The autoradiographic studies showed an transitional increase of {sup 3}H-QNB in vivo binding in the early phase after proton irradiation, even though no change in in-vitro {sup 3}H-QNB binding was see in brain autoradiograms of irradiated rats. The cerebral blood flow and the histrogical features of brain were also changed at 3 months post-irradiation. These results indicate that the memory impairment caused by radiation is closely related to the early change of acetylcholine receptor in vivo. (author)

  2. Whole brain irradiation in case of brain metastases in from 2005 to 2011 in the clinic for nuclear medicine of the university hospital Freiburg

    International Nuclear Information System (INIS)

    Hintz, Mandy

    2017-01-01

    Brain metastases are the largest group of brain tumors. Their occurrence influences the overall survival and the quality of life. The retrospective study deals with the overall survival, the local tumor control and the prognostic factors of patients treated with whole brain irradiation. The data were evaluated using multivariate analysis. Whole brain irradiation has shown to be an efficient therapy option for patients with brain metastases and has the possibility to improve the overall progress-free survival and the symptom control.

  3. MRI findings in primary brain lymphoma in immunocompetent patients

    Directory of Open Access Journals (Sweden)

    Saeed Nadhim Younis

    2017-08-01

    Full Text Available Background and objective: Primary brain lymphoma is an extranodal aggressive intracranial neoplasm of lymphocytic origin originating and confined to the brain parenchyma and meninges. It is rare in immune competent patients, but its incidence is increasing. This retrospective study was conducted to record the MRI features of primary brain lymphoma at the time of diagnosis in immunocompetent patients. Methods: Of the 450 patients diagnosed with the brain tumor during a period of five years from 2008 to 2013, the clinical features and MRI findings of 16 cases of pathologically proven to be non-Hodgkin’s lymphoma were studied. All the patients were tested negative for HIV and there was no history of immune suppression drugs or any other chronic illness. All the patients were examined with MRI observing the tumor location, multifocality, signal intensity in different sequences, enhancement patterns, peritumoral edema, the presence of hemorrhage and calcification. Results: Of the 16 patients, including the monofocal and multifocal cases, 30 lesions exhibited. The mean age at diagnosis was 53 years. Nine patients (56.25% found to have a multifocal disease. In more than 75% of lesions, MRI was hypo to iso signal on T1 and T2. Mild to moderate perilesional edema, strong contrast enhancement and restricted diffusion were seen in all cases. The hemorrhagic tumor was noticed in four lesions (13.3%. No calcification and no leptomeningeal lesions were noted. The MRI images in post steroid therapy were studied within one month of treatment. Tumour regression was noticed in 21/30 (70%, stable in 3/30 (10% and progressing in 6/30 (20%. Conclusion: MRI is a reliable imaging technique in the management of patients with primary brain lymphoma. Early accurate diagnosis is crucial to avoid the unnecessary operation and shift patients from extensive surgery to chemoradiotherapy.

  4. Investigations of primary blast-induced traumatic brain injury

    Science.gov (United States)

    Sawyer, T. W.; Josey, T.; Wang, Y.; Villanueva, M.; Ritzel, D. V.; Nelson, P.; Lee, J. J.

    2018-01-01

    The development of an advanced blast simulator (ABS) has enabled the reproducible generation of single-pulse shock waves that simulate free-field blast with high fidelity. Studies with rodents in the ABS demonstrated the necessity of head restraint during head-only exposures. When the head was not restrained, violent global head motion was induced by pressures that would not produce similar movement of a target the size and mass of a human head. This scaling artefact produced changes in brain function that were reminiscent of traumatic brain injury (TBI) due to impact-acceleration effects. Restraint of the rodent head eliminated these, but still produced subtle changes in brain biochemistry, showing that blast-induced pressure waves do cause brain deficits. Further experiments were carried out with rat brain cell aggregate cultures that enabled the conduct of studies without the gross movement encountered when using rodents. The suspension nature of this model was also exploited to minimize the boundary effects that complicate the interpretation of primary blast studies using surface cultures. Using this system, brain tissue was found not only to be sensitive to pressure changes, but also able to discriminate between the highly defined single-pulse shock waves produced by underwater blast and the complex pressure history exposures experienced by aggregates encased within a sphere and subjected to simulated air blast. The nature of blast-induced primary TBI requires a multidisciplinary research approach that addresses the fidelity of the blast insult, its accurate measurement and characterization, as well as the limitations of the biological models used.

  5. Histopathological investigation of radiation necrosis. Coagulation necrosis in the irradiated and non-irradiated brain tumors and in the normal brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, N [Niigata Univ. (Japan). Brain Research Inst.

    1977-01-01

    Eighty four irradiated tumors (including 59 gliomas) and the surrounding brain tissue were analyzed. In 'normal' brain tissue, typical coagulation necrosis attributable to irradiation was observed in the cerebral white matter, presenting a whitish-yellow color but no remarkable changes in volume. Histologically there was complete desintegration of myelin and axon. Vascular changes included hyalinous thickening, concentric cleavage, fibrinoid degeneration, adventitial fibrosis and edema of small arteries, fibrin thrombi or occlusion of arterioles and capillaries, and telangiectasia of small veins and venules. While other tumors showed hyalinous or fibrous scar tissue and decrease in volume, the gliomas maintained their original volume without residual tumor cells. Massive coagulation necrosis was occasionally found even in full volume, non-irradiated gliomas (controls), although the changes were fewer and not so varied as in typical radiation necrosis. With small dosages, it was difficult to judge whether the necrosis was caused by irradiation or occurred spontaneously. Coagulation necrosis in tumor tissue was found in 25 of 59 cases (42%) of irradiated gliomas, but in only 2 of 49 cases (4%) of the nonirradiated gliomas. In 49 cases no coagulation necrosis of the surrounding tissue was found. Although histopathological judgement is difficult, it is suggested that there is a significant correlation between coagulation necrosis and irradiation. Discussion of the relationship between coagulation necrosis and NSD (nominal standard dose) led to the conclusion that coagulation necrosis will not be caused by irradiation of less than 1400 rets in NSD.

  6. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Manley, N.B.; Fabrikant, J.I.; Alpen, E.L.

    1988-12-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. This study concerns the cell population and cell cycle kinetics of the subependymal layer in the mouse brain, and the effects of charged particle irradiations on this cell population. Quantitative high resolution autoradiography was used to study the kinetic parameters in this cell layer. This study should help in understanding the effects of these high-energy heavy ions on normal mammalian brain tissue. The response of the mammalian brain exposure to charged particle ionizing radiation may be extremely variable. It varies from minimal physiological changes to overt tissue necrosis depending on a number of factors such as: the administered dose, dose-rate, the volume of the irradiated tissue, and the biological end-point being examined.

  7. Effects of fast neutron irradiation on the development of the mouse brain

    International Nuclear Information System (INIS)

    Deguchi, Hisao

    1977-01-01

    Mice on the 4th to 11th day of pregnancy were irradiated with 14.1 MeV fast neutron at a dose of 100 rad and their fetuses were examined macroscopically and histologically on the 9th to the 19th day of gestation. Sixty-one cases out of 73 malformed fetuses (20.3%) were arbitrarily chosen and examined. Two cases of exencephaly were observed by irradiation on the 7th day of pregnancy, 2 cases of microcephaly by irradiation on the 9th day, 2 cases of hydrocephaly by irradiation on the 6th day and 3 cases of hydrocephaly by irradiation on the 11th day. Three cases of tumor were observed by irradiation on the 7th day of pregnancy and one case of tumor by irradiation on the 10th day. One case each of abnormal folding of the pallium was detected by irradiation on the 7th day and 10th day of pregnancy. After irradiation, penetration of blood vessels into the developing brain resembles to that of the control group. In some cases, invasion of fibroblast-like cells was observed. In cases with tumor formation, the tumors consisted of homogeneous ventricular cells without any sign of malignancy. Three to four days after irradiation on the 10th or 11th day of pregnancy, rosette formation was observed in the pallium which later disappeared. It appears that slight damages of brain tissue could be repaired without resulting in any external morphological abnormalities. (auth.)

  8. Aggregation patterns of fetal rat brain cells following exposure to X-irradiation

    International Nuclear Information System (INIS)

    Shoji, R.; Suzuki, K.; Lee, I.P.

    1980-01-01

    In our search for a simplified in vitro test system to assess the teratogenic effects of physical factors, we studied the effects of total maternal body X-irradiation on aggregation patterns of enzymatically isolated fetal rat brain cells and on ultrastructural aggregate changes. The fetal brain cells were derived from day 14 gestation fetuses of pregnant Sprague-Dawley (CD strain) rats exposed to X-irradiation (25 - 200 R) one hour prior to sacrifice. Notable changes in the cell aggregates following X-irradiation included a reduction in cell aggregate size and an increase in number. The frequency of cell aggregates was higher in the treated than in the control group, and the mean diameter of cell aggregates was inversely related to increasing X-irradiation doses. Transmission electron microscopy revealed in isolated cells features of degenerative process which were similar to those found in intact fetal brain lesions caused by maternal X-irradiation. Furthermore, scanning electron microscopy revealed that inhibition of cell aggregation following X-irradiation could probably be attributed to inhibition of membrane filopodia development and a consequent failure of cell aggregates to fuse into a greater cell aggregate mass. These results suggest that the membrane factors which influence cell aggregation may be a useful parameter to assess early effects of X-irradiation-induced brain deformity. Presently, the cell aggregation culture system is being further evaluated as a short term test system for environmental teratogens

  9. Histochemical changes of capillaries in rat brain cortex after irradiation with supralethal doses of gamma radiation

    International Nuclear Information System (INIS)

    Kamarad, V.; Dosoudilova, M.

    1987-01-01

    Changes were studied in the activities of alkaline phosphatase, ATP-splitting enzyme, thiaminepyrophosphatase, acetylcholinesterase, and of butyrylcholinesterase in the capillary sheet of the rat brain cortex of the laterobasal section of a parietal lobe following irradiation with 150 and 300 Gy. The animals were exposed to local irradiation of the head with gamma radiation using 60 Co at a dose rate of 6.9 Gy per min. The material was removed at the intervals of 30 and 60 mins after irradiation. All the studied enzymes, except the ATP-splitting enzyme, showed identical reaction to irradiation. At both intervals, the reaction after irradiation with 300 Gy was lower when compared to that after irradiation with 150 Gy. 30 mins after irradiation with 150 Gy an increased enzyme activity was shown followed by a marked decrease in the activity 60 mins after irradiation, compared with findings obtained from control animals. No similar time dependence was observed after irradiation with 300 Gy. The ATP-splitting enzyme showed a significant decrease in the activity 30 mins after irradiation with 150 Gy. On the other hand, 60 mins after irradiation with 150 Gy and at both time intervals after irradiation with 300 Gy, the activity was higher than that in control animals. (author). 6 figs., 14 refs

  10. Brain MRI findings in infants with primary congenital glaucoma

    International Nuclear Information System (INIS)

    Dai, A. Ibrahym; Saygili, O.

    2007-01-01

    Congenital glaucoma appears in the first months of life, eventually at birth. Isolated congenital glaucoma is characterized by minor malformations of the irido-corneal angle of the anterior chamber of the eye. Clinical manifestations include tearing, photophobia and enlargement of the globe appearing in the first months of life. Imaging technology such as optical coherence tomography and measurement of central corneal thickness may play an important role in the assessment of children with suspected or known glaucoma. However, no MRI findings of the CNS in patients with primary congenital glaucoma (PCG) were reported in the literature. The purpose of this study was to investigate MRI findings of the brain in infants with PCG. We reviewed the radiological and histopathological and clinical characteristics of infants with primary congenital glaucoma. The records of 17 patients with PCG were reviewed and the MRIs of the brain and associated manifestations were analyzed. Three patients with PCG had abnormal MRI findings suggesting agenesis of the corpus callosum. Two infants had delayed myelinization of the brain. Significant abnormal optic nerve excavation and increased corneal diameters in 2 patients with delayed myelinization may suggest that intraocular pressure can be more striking and more severe, revealing a close relationship with PCG and abnormal myelinization in white matter. Studies with more patients are needed to confirm these results. (author)

  11. CT findings of traumatic primary brain-stem injury

    International Nuclear Information System (INIS)

    Hosaka, Yasuaki; Hatashita, Shizuo; Bandou, Kuniaki; Ueki, Yasuyuki; Abe, Kouzou; Koga, Nobunori; Sugimura, Jun; Sakakibara, Tokiwa; Takagi, Suguru

    1984-01-01

    A series of 27 consecutive patients with traumatic primary brain stem injuries was studied. They were diagnosed by means of clinical signs, neurological examination, and computerized tomography (CT). The CT findings of the brain-stem lesions were classified into 4 types: Type H, spotty, high-density; Type H and L, high- and low-densities; Type L, low-density; Type I, isodensity. The Glasgow coma scale (GCS), neurological findings on admission, CT findings (findings in the brain stem, obliteration of perimesencephalic cistern (PMC), and other findings), and the Glasgow outcome scale (GOS) were examined. In the 9 cases of Type H, there was a correlation between the GCS and the GOS, and the spotty, high-density lesions were localized mainly in the dorsal and/or ventral midbrain parenchyma, but these lesions did not show focal signs and symptoms. Without an obliteration of the PMC, Type-H patients did not always have a bad outcome. In the 4 cases of Type H and L, the 2 cases of Type L, and the 12 cases of Type I, there was an obliteration of the PMC. All of the these cases had a bad outcome (1 case of moderate disability, 3 cases of severe disability, and 14 cases of death). The mechanism producing a spotty, high-density area was discussed. The weaker impact (than the other types) and individual anatomical differences weresupposed to make for a spotty, high-density are in the brain stem. (author)

  12. Accumulation of silver nanoparticles by cultured primary brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Luther, Eva M; Koehler, Yvonne; Dringen, Ralf [Center for Biomolecular Interactions Bremen, University of Bremen, PO Box 330440, D-28334 Bremen (Germany); Diendorf, Joerg; Epple, Matthias, E-mail: ralf.dringen@uni-bremen.de [Inorganic Chemistry and Center for Nanointegration Duisburg-Essen, University of Duisburg-Essen, Universitaetsstrasse 5-7, D-45117 Essen (Germany)

    2011-09-16

    Silver nanoparticles (AgNP) are components of various food industry products and are frequently used for medical equipment and materials. Although such particles enter the vertebrate brain, little is known on their biocompatibility for brain cells. To study the consequences of an AgNP exposure of brain cells we have treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated AgNP. The incubation of cultured astrocytes with micromolar concentrations of AgNP for up to 24 h resulted in a time- and concentration-dependent accumulation of silver, but did not compromise the cell viability nor lower the cellular glutathione content. In contrast, the incubation of astrocytes for 4 h with identical amounts of silver as AgNO{sub 3} already severely compromised the cell viability and completely deprived the cells of glutathione. The accumulation of AgNP by astrocytes was proportional to the concentration of AgNP applied and significantly lowered by about 30% in the presence of the endocytosis inhibitors chloroquine or amiloride. Incubation at 4 {sup 0}C reduced the accumulation of AgNP by 80% compared to the values obtained for cells that had been exposed to AgNP at 37 {sup 0}C. These data demonstrate that viable cultured brain astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent process that most likely involves endocytotic pathways.

  13. Protective effects of edaravone on the radiation response of oligodendrocyte in rats following whole brain irradiation

    International Nuclear Information System (INIS)

    Chen Yingzhu; Tian Ye; Bao Shiyao; Bao Huan; Zhan Zhilin

    2007-01-01

    Objective: To investigate the changes of the oligodendrocyte lineage cells in the cortex following whole brain irradiation and the effects of the neotype free radical scavenger, edaravone on radiation response of oligodendrocyte in rats. Methods: 120 male Sprague Dawley rats were randomly divided into sham- irradiation group, irradiation group and edaravone group. The model of whole-brain irradiation was established with exposure of the whole brain of the rats to 4 MeV X-rays with a single-dose of 10 Gy. The rats were injected intraperitoneally with edaravone at 0.3, 1.0 and 3.0 mg/kg. Tissue microarray of irradiation-induced brain injury in rats was constructed. The expression of A2BS, oligodendrocyte market 4(O4) and 2', 3'-cyclic nucleotide 3'- phosphodiesterase (CNPase) in the cortex was examined by tissue microarray technology and immunohistochemistry. The positive cells were counted. Results: Compared with the sham-irradiation group, the number of A2BS-positive cells increased and the number of O4, CNPase-positive cells decreased significantly at certain time in the irradiation group(P<0.05). Compared with irradiation group, A2BS-positive cells decreased significantly after edaravone treatment, while O4-positive cells and CNPase-positive cells increased significantly (P<0.05, or P<0.01). Conclusions: The number of oligodendrocyte precursor cells in the cortex of rats increased reactively following whole brain irradiation and changed with time. Edaravone played a protective role in oligodendrocyte ischemic reaction in a dose-dependent manner. (authors)

  14. Protective effects of edaravone on the radiation response of oligodendrocyte in rats following whole brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yingzhu, Chen; Ye, Tian; Shiyao, Bao; Huan, Bao; Zhilin, Zhan [The Second Affiliated Hospital of Suzhou Univ., Suzhou (China)

    2007-08-15

    Objective: To investigate the changes of the oligodendrocyte lineage cells in the cortex following whole brain irradiation and the effects of the neotype free radical scavenger, edaravone on radiation response of oligodendrocyte in rats. Methods: 120 male Sprague Dawley rats were randomly divided into sham- irradiation group, irradiation group and edaravone group. The model of whole-brain irradiation was established with exposure of the whole brain of the rats to 4 MeV X-rays with a single-dose of 10 Gy. The rats were injected intraperitoneally with edaravone at 0.3, 1.0 and 3.0 mg/kg. Tissue microarray of irradiation-induced brain injury in rats was constructed. The expression of A2BS, oligodendrocyte market 4(O4) and 2', 3'-cyclic nucleotide 3'- phosphodiesterase (CNPase) in the cortex was examined by tissue microarray technology and immunohistochemistry. The positive cells were counted. Results: Compared with the sham-irradiation group, the number of A2BS-positive cells increased and the number of O4, CNPase-positive cells decreased significantly at certain time in the irradiation group(P<0.05). Compared with irradiation group, A2BS-positive cells decreased significantly after edaravone treatment, while O4-positive cells and CNPase-positive cells increased significantly (P<0.05, or P<0.01). Conclusions: The number of oligodendrocyte precursor cells in the cortex of rats increased reactively following whole brain irradiation and changed with time. Edaravone played a protective role in oligodendrocyte ischemic reaction in a dose-dependent manner. (authors)

  15. Field in field technique in two-dimensional planning for whole brain irradiation; Tecnica field in field em planejamentos bidimensionais para irradiacao de cerebro total

    Energy Technology Data Exchange (ETDEWEB)

    Castro, A.L.S.; Campos, T.P.R., E-mail: radioterapia.andre@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Departamento de Engenharia Nuclear

    2016-11-01

    Radiotherapy is the most used clinical method used for brain metastases treatment, the most frequent secondary tumors provided by breast, lung and melanomas as primary origin. The protocols often use high daily doses and, depending on the irradiation technique there is high probability of complications in health tissues. In order to minimize adverse effects, it is important the dosimetric analysis of three-dimensional radiotherapy planning through tomographic images or, concerning to the 2D simulations, by the application of techniques that optimize dose distribution by increasing the homogeneity. The study aimed to compare the 2D and 3D conformal planning for total brain irradiation in a individual equivalent situation and evaluate the progress of these planning applying the field in field technique. The methodology consisted of simulating a two-dimensional planning, reproduce it on a set of tomographic images and compare it with the conformal plan for two fields and four fields (field in field). The results showed no significant difference between 2D and 3D planning for whole brain irradiation, and the field in field technique significantly improved the dose distribution in brain volume compared with two fields for the proposal situation. As conclusion, the two-dimensional plane for the four fields described was viable for whole brain irradiation in the treatment of brain metastases at the proposal situation. (author)

  16. Assessment of cognitive functions after prophylactic and therapeutic whole brain irradiation using neuropsychological testing

    International Nuclear Information System (INIS)

    Penitzka, S.; Wannenmacher, M.; Steinvorth, S.; MIT, Cambridge, MT; Sehlleier, S.; Universitaetsklinikum Wuerzburg; Fuss, M.; Texas Univ., San Antonio, TX; Wenz, F.; Universitaetsklinikum Mannheim

    2002-01-01

    Purpose: Aim of this study was the assessment of neuropsychological changes after whole brain irradiation. Patients and Method: 64 patients were tested before, and 29 after whole brain irradiation, including 28 patients with small cell lung cancer (SCLC) before prophylactic cranial irradiation (PCI) and 36 patients with cerebral metastases before therapeutic cranial irradiation (TCI), as well as 14 patients after PCI and 15 after TCI (Table 1). Intelligence, attention and memory were assessed applying a 90-minute test battery of standardized, neuropsychological tests (Table 3). Results: Patients with SCLC showed test results significantly below average before PCI (n=28, mean IQ=83, SD=17). Neither after PCI, nor after TCI the tested neuropsychological functions decreased significantly (Tables 4, 5). A comparison between SCLC-patients with and without cerebral metastases before whole brain irradiation showed better test-results in patients with cerebral metastases and fewer cycles of preceding chemotherapy (Table 7). Conclusion: Neuropsychological capacity in patients with SCLC was impaired even before PCI. Possible reason is the preceding chemotherapy. Whole brain irradiation did not induce a significant decline of cognitive functions in patients with PCI or TCI. A decline in a longer follow-up nevertheless seems possible. (orig.) [de

  17. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    International Nuclear Information System (INIS)

    Manley, N.B.

    1988-01-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. The decrease in the values of the labeling indices 1 week after charged particle irradiation was dose- and ion-dependent. Mitotic indices 1 week after 10 and 25 Gy helium and after 10 Gy neon were the same as those seen in the control mice. Analysis of cell kinetics 1 week after 10 Gy helium and 10 Gy neon irradiation suggests the presence of a progenitor subpopulation that is proliferating with a shorter cell cycle. Comparison of the responses to the different charged particle beams indicates that neon ions are more effective in producing direct cellular damage than the helium ions, but the surviving proliferating cells several divisions later continue to maintain active cell renewal. Based on the 1 week post-irradiation H 3 -TdR labeling indices, a rough estimate of the RBE for neon ions is at least 2.5 when compared to helium ions

  18. Splenic irradiation as primary therapy for prolymphocytic leukaemia

    International Nuclear Information System (INIS)

    Muncunill, J.; Villa, S.; Domingo, A.; Domenech, P.; Arnaiz, M.D.; Callis, M.

    1990-01-01

    A case report is presented of a 60 year old man whose prolympocytic leukemia responded to lymphocytapheresis (one procedure) and Splenic irradiation (1 Gy 3 times a week, total dose 10 Gy.) A fast and stable clinical and analytic response was obtained during 12 months. (UK)

  19. Rationale for the Use of Upfront Whole Brain Irradiation in Patients with Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Agnes V. Tallet

    2014-05-01

    Full Text Available Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

  20. Is primary care access to CT brain examinations effective?

    International Nuclear Information System (INIS)

    Benamore, R.E.; Wright, D.; Britton, I.

    2005-01-01

    AIM: Primary care access to CT head examinations could enable common neurological conditions to be managed within primary care. Outcome data from the first 8 years of a local service were used to identify effective referral criteria. METHODS: Primary care head CT results from 1 March 1995 to 31 October 2003 were categorized as normal, incidental or significant findings. Normal reports were cross-referenced for referral to secondary care. Case notes with incidental or significant CT findings were reviewed for secondary care attendance and outcome. RESULTS: Records of 1403/1645 CT head examinations (85%) were available for review. Of these 1403, 951 (67.8%) returned normal findings, 317 (22.6%) incidental findings and 135 (9.6%) significant findings. The commonest indication for referral was investigation of headaches (46.6%). Of the total 533 patients under 50 years of age, 13 (2.4%) yielded significant findings and all 13 showed other features in addition to headache. Of 314 cases presenting with focal neurology, 83 (26.4%) showed significant findings. 314 patients were referred from primary to secondary care. 189 had normal scans and 74 had findings described as incidental. 60% of secondary care referrals were for normal CT scans. In patients with focal neurology, 90 of 314 were referred, allowing 71% to be managed in primary care. Yield was also 0% for headaches, dizziness, visual disturbance or nausea and vomiting. CONCLUSION: Primary care access to CT brain examinations is effective for patients with focal neurology, neurological symptoms or a known malignancy, but not for patients aged less than 50 years, or with uncomplicated headaches, dizziness or diplopia

  1. Is primary care access to CT brain examinations effective?

    Energy Technology Data Exchange (ETDEWEB)

    Benamore, R.E. [Department of Radiology, Pilgrim Hospital, Boston (United Kingdom)]. E-mail: rachelbenamore@doctors.org.uk; Wright, D. [Department of Radiology, Pilgrim Hospital, Boston (United Kingdom); Britton, I. [Department of Radiology, Pilgrim Hospital, Boston (United Kingdom)

    2005-10-01

    AIM: Primary care access to CT head examinations could enable common neurological conditions to be managed within primary care. Outcome data from the first 8 years of a local service were used to identify effective referral criteria. METHODS: Primary care head CT results from 1 March 1995 to 31 October 2003 were categorized as normal, incidental or significant findings. Normal reports were cross-referenced for referral to secondary care. Case notes with incidental or significant CT findings were reviewed for secondary care attendance and outcome. RESULTS: Records of 1403/1645 CT head examinations (85%) were available for review. Of these 1403, 951 (67.8%) returned normal findings, 317 (22.6%) incidental findings and 135 (9.6%) significant findings. The commonest indication for referral was investigation of headaches (46.6%). Of the total 533 patients under 50 years of age, 13 (2.4%) yielded significant findings and all 13 showed other features in addition to headache. Of 314 cases presenting with focal neurology, 83 (26.4%) showed significant findings. 314 patients were referred from primary to secondary care. 189 had normal scans and 74 had findings described as incidental. 60% of secondary care referrals were for normal CT scans. In patients with focal neurology, 90 of 314 were referred, allowing 71% to be managed in primary care. Yield was also 0% for headaches, dizziness, visual disturbance or nausea and vomiting. CONCLUSION: Primary care access to CT brain examinations is effective for patients with focal neurology, neurological symptoms or a known malignancy, but not for patients aged less than 50 years, or with uncomplicated headaches, dizziness or diplopia.

  2. Gamma irradiation of the brain for prophylaxis of neuroleukemia in children

    International Nuclear Information System (INIS)

    Ankudinov, V.A.; Moiseenko, E.I.; Mayakova, S.A.; Sotnikov, V.M.

    1979-01-01

    Demonstrated is experience in treatment of 21 children with acute lymphoblast leukemia. The method of neuroleukemia prophylaxis was used, it included combined chemo- and rediation therapy. After remission and a quintuple endolumber administration of methotrexate to the patients irradiation of the brain on the gamma-therapeutic unit through the open fields was made. The scope of irradiation included the whole of the brain, retrobulbular space, the base of the skull. The lower border of the field was the level of the third cervical vertebra. Irradiation was made from 2 reciprocating side fields, a total seance dose-200-220 rad with daily treatment. The cumulative focal dose for the whole brain was brought to 2500 rad. The analysis of the results with follow-up periods up to 32 months did not reveal a single case of neuroleukemia development. The average life span was 32.8+-1.3 months

  3. 60Co γ-irradiation enhances expression of GAP-43 mRNA in rat brain

    International Nuclear Information System (INIS)

    Su Bingyin; Cai Wenqin; Zhang Chenggang

    2001-01-01

    Objective: To study the relationship between the expression of GAP-43 mRNA and nerve regeneration in rat brain after 60 Co γ-irradiation. Methods: Wistar rats were subjected to whole-body irradiation with 8 Gy 60 Co γ-rays. The expression of GAP-43 was detected by in situ hybridization histochemistry using Dig-cRNA probe. Results: It was found that the expression of GAP-43 mRNA increased in the cerebral cortex, caudate, putamen, globus pallidum, thalamus and hypothalamus one week after 8 Gy 60 Co γ-irradiation. The peak of GAP-43 mRNA expression was observed in the fourth week and then began to decrease but still remained at a higher than normal level. However, it decreased to a low level after 7 weeks. Conclusion: Enhanced expression of GAP-43 mRNA after 60 Co γ-irradiation in rat brain is associated with nerve regeneration and reconstruction of synapse

  4. Generation of primary cultures of bovine brain endothelial cells and setup of cocultures with rat astrocytes

    DEFF Research Database (Denmark)

    Helms, Hans C; Brodin, Birger

    2014-01-01

    -brain barrier. The present protocol describes the setup of an in vitro coculture model based on primary cultures of endothelial cells from bovine brain microvessels and primary cultures of rat astrocytes. The model displays a high electrical tightness and expresses blood-brain barrier marker proteins....

  5. Acquired immunodeficiency syndrome-related primary cerebral lymphoma: response to irradiation

    International Nuclear Information System (INIS)

    Khoo, V.S.; Wilson, P.C.; Sexton, M.J.; Liew, K.H.

    2000-01-01

    Acquired immunodeficiency syndrome-related primary cerebral lymphoma (AIDS-PCL) is uncommon. Fourteen cases of presumed AIDS-PCL between 1986 and 1995 were reviewed retrospectively in order to characterize the natural history, and the response to radiotherapy. The median age was 38 years (range 24-65). The median interval between seropositive diagnosis of HIV and AIDS-PCL was 28 months (range 5-113). The median duration of symptoms was 2 weeks (range 0.2-12). At presentation, the Eastern Cooperative Oncology Group performance status (PS) was PS1 (2/14 patients), PS2 (6/14) and PS3 (6/14). The symptoms and signs were non-specific and depended on the site and extent of cerebral involvement. There was no characteristic pattern of brain imaging in terms of size, number, location or pattern of contrast enhancement of the cerebral lesions. Nine patients received various fractionation-dose schedules (range 8-50 Gy). Complete and partial responses were seen in 2/9 and 3/9 cases, respectively. Clinical stabilization of neurological symptoms was noted in 3/9 cases and disease progression in 1/9. The median survival times (MST) from presentation for irradiated and non-irradiated patients were 9.3 and 2.1 weeks, respectively (range 0.9-43.1). Although patient selection introduced bias, there appears to be a modest improvement in MST for treated patients. The MST with radiotherapy alone remains poor, but radiotherapy may provide palliation. For some selected patients, a prolonged response is possible. Copyright (1999) Blackwell Science Pty Ltd

  6. The expression changes of inflammatory cytokines in the hippocampus following whole-brain irradiation in rats

    International Nuclear Information System (INIS)

    Yu De; Tian Ye; Ding Weijun; Zhu Yaqun; Liu Chunfeng

    2004-01-01

    To investigate the change pattern of some inflammatory cytokines in brain tissue at the acute phase after brain irradiated. The whole brain of SD rats was irradiated by the single dose of 2, 15 or 30 Gy of 4 MeV electron beam. The enzyme-linked immunosorbent assay (ELISA) was used for the measurement of IL-1 β, IL-6, and TNF-α content in hippocampus tissue of rats at 1h, 6h, 12h, 1d, 2 and 1 week post-irradiation. The mRNA of IL-1 β, IL-6, and TNF-α were detected by reverse-transcription polymerase chain reaction (RT-PCR) in the same experimental groups. It was analyzed about the influence of dosage and post-irradiation duration with the cytokines expression. Compared with both the normal control and the anesthetized with chloral hydrate but sham-irradiation groups, there were no difference about the three inflammatory cytokines expression in rats with 2 Gy irradiated. At 6h after irradiation with 15 Gy, 6 and 12h with 30 Gy groups, the content of IL-1β and TNF-α in hippocampus tissue were significantly increased, and were returned to normal level after 12 to 24h. The same change tendency of their mRNA relational level was observed in 15 and 30 Gy groups, but it happened earlier in 1h after exposure. Although the content of IL-6 in hippocampus kept stable in all the groups, its mRNA level raised obviously in 12h group. After 15-30 Gy whole-brain irradiation, the expression of some inflammatory cytokines increased abruptly in the hippocampus of SD rat within 1 day, but the interplay between inflammatory cytokines changes and the pathogenesis of radiation injury was incompletely understood at present. (authors)

  7. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    International Nuclear Information System (INIS)

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 ± 0.62 Gy and 6.29 ± 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 ± 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 ± 0.7 Gy and 32.7 ± 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 ± 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  8. Primary blast-induced traumatic brain injury: lessons from lithotripsy

    Science.gov (United States)

    Nakagawa, A.; Ohtani, K.; Armonda, R.; Tomita, H.; Sakuma, A.; Mugikura, S.; Takayama, K.; Kushimoto, S.; Tominaga, T.

    2017-11-01

    Traumatic injury caused by explosive or blast events is traditionally divided into four mechanisms: primary, secondary, tertiary, and quaternary blast injury. The mechanisms of blast-induced traumatic brain injury (bTBI) are biomechanically distinct and can be modeled in both in vivo and in vitro systems. The primary bTBI injury mechanism is associated with the response of brain tissue to the initial blast wave. Among the four mechanisms of bTBI, there is a remarkable lack of information regarding the mechanism of primary bTBI. On the other hand, 30 years of research on the medical application of shock waves (SWs) has given us insight into the mechanisms of tissue and cellular damage in bTBI, including both air-mediated and underwater SW sources. From a basic physics perspective, the typical blast wave consists of a lead SW followed by shock-accelerated flow. The resultant tissue injury includes several features observed in primary bTBI, such as hemorrhage, edema, pseudo-aneurysm formation, vasoconstriction, and induction of apoptosis. These are well-described pathological findings within the SW literature. Acoustic impedance mismatch, penetration of tissue by shock/bubble interaction, geometry of the skull, shear stress, tensile stress, and subsequent cavitation formation are all important factors in determining the extent of SW-induced tissue and cellular injury. In addition, neuropsychiatric aspects of blast events need to be taken into account, as evidenced by reports of comorbidity and of some similar symptoms between physical injury resulting in bTBI and the psychiatric sequelae of post-traumatic stress. Research into blast injury biophysics is important to elucidate specific pathophysiologic mechanisms of blast injury, which enable accurate differential diagnosis, as well as development of effective treatments. Herein we describe the requirements for an adequate experimental setup when investigating blast-induced tissue and cellular injury; review SW physics

  9. Prenatal irradiation and developmental disorders of the brain

    International Nuclear Information System (INIS)

    Kameyama, Yoshiro

    1987-01-01

    The radiation sensitivity of the brain of a growing fetus is higher than that of other organs and tissues. Of the various organs in the human body, the brain has the most complicated structure. The major features of developmental disorders of the brain, which are produced rather easily by external causes, are: (a) the sensitive period for developmental disorders is long, (b) undifferentiated nerve cells are sensitive to external causes and (c) such disorders leads to irreversible functional failures after birth. The malformation of the brain and its relations with the sensitivity are briefly described. Experiments with prenatal animals have shown that major developmental disorders of brain tissue include death of undifferentiated cells, lack of constituent neurons and disturbance in structure of the cortex, and that typical developmental abnormalities include dysgenetic hydrocephaly, microcephalia, etc. Teratological features of histogenetic disorders of the brain are then briefly outlined. Various experimental results on these and other disorders caused by radiations are presented and discussed. Data on fetuses exposed to radiations at Hiroshima and Nagasaki are also given and discussed. The last section of the report deals with risk evaluation. (Nogami, K.)

  10. Long-term evolution of cerebral hemodynamics after brain irradiation in the rat

    International Nuclear Information System (INIS)

    Keyeux, A.; Ochrymowicz-Bemelmans, D.

    1985-01-01

    Long-term evolution of radioisotope indices, evaluating respectively the cerebral blood flow (CBF), the cerebral blood volume (CBV) and the cephalic specific distribution space of iodoantipyrine (ΔIAP) of rat, was studied after brain irradiation at 20 Gy. Radioinduced hemodynamic alterations evidenced by this approach are biphasic and support the prominent role of circulation impairment in the genesis of delayed brain radionecrosis [fr

  11. Altered brain network measures in patients with primary writing tremor

    Energy Technology Data Exchange (ETDEWEB)

    Lenka, Abhishek; Jhunjhunwala, Ketan Ramakant [National Institute of Mental Health and Neurosciences, Department of Clinical Neurosciences, Bangalore, Karnataka (India); National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore, Karnataka (India); Panda, Rajanikant; Saini, Jitender; Bharath, Rose Dawn [National Institute of Mental Health and Neurosciences, Department of Neuroimaging and Interventional Radiology, Bangalore, Karnataka (India); Yadav, Ravi; Pal, Pramod Kumar [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore, Karnataka (India)

    2017-10-15

    Primary writing tremor (PWT) is a rare task-specific tremor, which occurs only while writing or while adopting the hand in the writing position. The basic pathophysiology of PWT has not been fully understood. The objective of this study is to explore the alterations in the resting state functional brain connectivity, if any, in patients with PWT using graph theory-based analysis. This prospective case-control study included 10 patients with PWT and 10 age and gender matched healthy controls. All subjects underwent MRI in a 3-Tesla scanner. Several parameters of small-world functional connectivity were compared between patients and healthy controls by using graph theory-based analysis. There were no significant differences in age, handedness (all right handed), gender distribution (all were males), and MMSE scores between the patients and controls. The mean age at presentation of tremor in the patient group was 51.7 ± 8.6 years, and the mean duration of tremor was 3.5 ± 1.9 years. Graph theory-based analysis revealed that patients with PWT had significantly lower clustering coefficient and higher path length compared to healthy controls suggesting alterations in small-world architecture of the brain. The clustering coefficients were lower in PWT patients in left and right medial cerebellum, right dorsolateral prefrontal cortex (DLPFC), and left posterior parietal cortex (PPC). Patients with PWT have significantly altered small-world brain connectivity in bilateral medial cerebellum, right DLPFC, and left PPC. Further studies with larger sample size are required to confirm our results. (orig.)

  12. Altered brain network measures in patients with primary writing tremor

    International Nuclear Information System (INIS)

    Lenka, Abhishek; Jhunjhunwala, Ketan Ramakant; Panda, Rajanikant; Saini, Jitender; Bharath, Rose Dawn; Yadav, Ravi; Pal, Pramod Kumar

    2017-01-01

    Primary writing tremor (PWT) is a rare task-specific tremor, which occurs only while writing or while adopting the hand in the writing position. The basic pathophysiology of PWT has not been fully understood. The objective of this study is to explore the alterations in the resting state functional brain connectivity, if any, in patients with PWT using graph theory-based analysis. This prospective case-control study included 10 patients with PWT and 10 age and gender matched healthy controls. All subjects underwent MRI in a 3-Tesla scanner. Several parameters of small-world functional connectivity were compared between patients and healthy controls by using graph theory-based analysis. There were no significant differences in age, handedness (all right handed), gender distribution (all were males), and MMSE scores between the patients and controls. The mean age at presentation of tremor in the patient group was 51.7 ± 8.6 years, and the mean duration of tremor was 3.5 ± 1.9 years. Graph theory-based analysis revealed that patients with PWT had significantly lower clustering coefficient and higher path length compared to healthy controls suggesting alterations in small-world architecture of the brain. The clustering coefficients were lower in PWT patients in left and right medial cerebellum, right dorsolateral prefrontal cortex (DLPFC), and left posterior parietal cortex (PPC). Patients with PWT have significantly altered small-world brain connectivity in bilateral medial cerebellum, right DLPFC, and left PPC. Further studies with larger sample size are required to confirm our results. (orig.)

  13. Altered brain network measures in patients with primary writing tremor.

    Science.gov (United States)

    Lenka, Abhishek; Jhunjhunwala, Ketan Ramakant; Panda, Rajanikant; Saini, Jitender; Bharath, Rose Dawn; Yadav, Ravi; Pal, Pramod Kumar

    2017-10-01

    Primary writing tremor (PWT) is a rare task-specific tremor, which occurs only while writing or while adopting the hand in the writing position. The basic pathophysiology of PWT has not been fully understood. The objective of this study is to explore the alterations in the resting state functional brain connectivity, if any, in patients with PWT using graph theory-based analysis. This prospective case-control study included 10 patients with PWT and 10 age and gender matched healthy controls. All subjects underwent MRI in a 3-Tesla scanner. Several parameters of small-world functional connectivity were compared between patients and healthy controls by using graph theory-based analysis. There were no significant differences in age, handedness (all right handed), gender distribution (all were males), and MMSE scores between the patients and controls. The mean age at presentation of tremor in the patient group was 51.7 ± 8.6 years, and the mean duration of tremor was 3.5 ± 1.9 years. Graph theory-based analysis revealed that patients with PWT had significantly lower clustering coefficient and higher path length compared to healthy controls suggesting alterations in small-world architecture of the brain. The clustering coefficients were lower in PWT patients in left and right medial cerebellum, right dorsolateral prefrontal cortex (DLPFC), and left posterior parietal cortex (PPC). Patients with PWT have significantly altered small-world brain connectivity in bilateral medial cerebellum, right DLPFC, and left PPC. Further studies with larger sample size are required to confirm our results.

  14. Whole body X-irradiation and impact of dietary factors on brain and testes of albino rats

    International Nuclear Information System (INIS)

    Hasan, S.S.; Chaturvedi, P.K.

    1988-01-01

    The study was undertaken to investigate the radioprotective effect of protein diet on the irradiated brain and testes. The study indicated that the less availability of protein in the diet caused a marked reduction in the protein and nucleic acid (DNA and RNA) contents of brain after irradiation. Further, the protein deficiency in diet brought about an increased deamination of protein in the brain of irradiated rats. It was noted that in response to irradiation the testes of protein deficient diet fed rats got adversely affected as compared to high protein diet fed animals. This paper gives evidence that feeding of protein enriched diet provides protection against ionizing radiation. (orig.) [de

  15. Transfection of brain capillary endothelial cells in primary culture with defined blood-brain barrier properties.

    Science.gov (United States)

    Burkhart, Annette; Thomsen, Louiza Bohn; Thomsen, Maj Schneider; Lichota, Jacek; Fazakas, Csilla; Krizbai, István; Moos, Torben

    2015-08-07

    Primary brain capillary endothelial cells (BCECs) are a promising tool to study the blood-brain barrier (BBB) in vitro, as they maintain many important characteristics of the BBB in vivo, especially when co-cultured with pericytes and/or astrocytes. A novel strategy for drug delivery to the brain is to transform BCECs into protein factories by genetic modifications leading to secretion of otherwise BBB impermeable proteins into the central nervous system. However, a huge challenge underlying this strategy is to enable transfection of non-mitotic BCECs, taking a non-viral approach. We therefore aimed to study transfection in primary, non-mitotic BCECs cultured with defined BBB properties without disrupting the cells' integrity. Primary cultures of BCECs, pericytes and astrocytes were generated from rat brains and used in three different in vitro BBB experimental arrangements, which were characterised based on a their expression of tight junction proteins and other BBB specific proteins, high trans-endothelial electrical resistance (TEER), and low passive permeability to radiolabeled mannitol. Recombinant gene expression and protein synthesis were examined in primary BCECs. The BCECs were transfected using a commercially available transfection agent Turbofect™ to express the red fluorescent protein HcRed1-C1. The BCECs were transfected at different time points to monitor transfection in relation to mitotic or non-mitotic cells, as indicated by fluorescence-activated cell sorting analysis after 5-and 6-carboxylfluorescein diacetate succinidyl ester incorporation. The cell cultures exhibited important BBB characteristics judged from their expression of BBB specific proteins, high TEER values, and low passive permeability. Among the three in vitro BBB models, co-culturing with BCECs and astrocytes was well suited for the transfection studies. Transfection was independent of cell division and with equal efficacy between the mitotic and non-mitotic BCECs. Importantly

  16. Electroencephalogram in relation to brain glycogen level in irradiated rats treated with vitamin E as a radioprotective compound

    International Nuclear Information System (INIS)

    Mahdy, A.M.

    1992-01-01

    Whole body gamma irradiation of untreated rats at the dose of 7 Gy induced severe abnormalities in the brain electrical activity, electroencephalogram (EEG), patterns of both frontal and occipital cortical areas. The visual analysis of the frontal EEG records showed a significant shift of frequencies towards faster and higher voltage activity along the experiment period (first , third, seventh and tenth days post irradiation). However, an opposite picture was prominent on the occipital EEG records after irradiation. On the other hand,the level of brain glycogen, which is considered as an important energy source for brain functions, significantly increased at all intervals of post irradiation. The treatment of rats with intraperitoneal injection of vitamin E pre-irradiation succeeded in diminishing the deleterious abnormalities in the EEG records in both frontal and occipital areas as well as the changes induced in the level of brain glycogen after whole body gamma irradiation.4 fig

  17. A model of chronic local irradiation in the brain

    International Nuclear Information System (INIS)

    Sataev, M.M.

    1981-01-01

    Radionecrosis of tissues was detected after implantation of 90 S- 90 Y sources (0.5-0.2 Gy/h) to the rabbit brain. A repair inflammatory reaction developed around the point of affection which resulted, at a dose of 0.5 Gy/h, in the formation of the connective tissue capsules or gliomesencymal cicatrices, or in the diffuse, hyperplasia of cell elements of neuroglia, membranes and vessels of the brain at doses of 1.4 to 2.0 Gy/h. This is the reason for the appearance of focal epitheliocellular granulomas [ru

  18. Results of irradiating brain tumours (1959-1969)

    Energy Technology Data Exchange (ETDEWEB)

    Zu Eulenburg, G

    1973-01-01

    The results of the radiation treatment of brain tumours were evaluated for 78 patients. The calculated average survival times, as well as the shape of survival curves show, as compared to numerous other authors, that there is no great deviation for any tumour group. The interpretation of the ratio of an amnesis to survival time shows that with fast growing brain tumours as with glioblastoma, the success of radiotherapy is very small. Radiotherapy was well successful in almost all cases of patients with a longer than average anamnesis.

  19. Histological and elemental changes in the rat brain after local irradiation with carbon ion beams

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Sentaro; Sun, Xue-Zhi; Kubota, Yoshihisa; Takai, Nobuhiko; Nojima, Kumie [National Inst. of Radiological Sciences, Chiba (Japan)

    2002-06-01

    The left cerebral hemispheres of adult Sprague-Dawley rat brains were irradiated at doses of 30, 50, or 100 Gy with charged carbon particles (290 MeV/nucleon; 5 mm spread-out Bragg peak). The spread-out Bragg peak used here successfully and satisfactorily retained its high-dose localization in the defined region. A histological examination showed that necrotic tissue damage, hemorrhage in the thalamus, and vasodilatations around the necrotic region were induced at 8 weeks after 100 Gy irradiation. The regions with tissue damage correlated well with those expected from the radiation-dose distribution, indicating an advantage of charged carbon particles for irradiating restricted brain regions. An X-ray fluorescent analysis demonstrated a decrease in the concentrations of K and P, and an increase in the concentrations of Cl, Fe, Zn in the damaged region at 8 weeks post-irradiation, though no significant changes were observed before 4 weeks of post-irradiation. This may indicate that even the very high radiation doses used here did not induce acute and immediate neuronal cell death, in contrast with ischemic brain injury where acute neuronal cell death occurred and the elemental concentrations changed within a day after the induction of ischemia. (author)

  20. Effect of 60Co-irradiation on normal and low protein diet fed rat brain

    International Nuclear Information System (INIS)

    Hasan, S.S.; Habibullah, M.

    1980-01-01

    The effect of whole-body irradiation (Co-60) on the brain tissue in Holtzmann strain adult male rats was studied. Two doses of irradiation (450 R,950 R) were tried on animals which were fed on normal as well as low protein diets over a period of 10 generations. In the normal rats, 450 R initially caused a lowered total protein. DNA and RNA content in the brain. After 7 days a tendency towards normalcy was observed. In the 950 R irradiated normal rats the diminution of protein content appeared irreversible. In malnourished 450 R irradiated rats, the protein content rose less steeply over the 7 days of observation. A higher dose of 950 R enhanced this effect on protein and also lowered the DNA content on day 5. The RNA content in the 950 R group with malnutrition showed a marked increase towards or beyond control perhaps as an expression of uncoupled feedback control. The paper gives evidence that protein deficiency may interfere with cellular regeneration in irradiated brain. (orig.) [de

  1. Effect of /sup 60/Co-irradiation on normal and low protein diet fed rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Hasan, S S [Garhwal Univ., Srinagar, Uttar Pradesh (India). Dept. of Zoology; Habibullah, M [Jawaharlal Nehru Univ., New Delhi (India). Neurobiology Lab.

    1980-06-01

    The effect of whole-body irradiation (Co-60) on the brain tissue in Holtzmann strain adult male rats was studied. Two doses of irradiation (450 R,950 R) were tried on animals which were fed on normal as well as low protein diets over a period of 10 generations. In the normal rats, 450 R initially caused a lowered total protein. DNA and RNA content in the brain. After 7 days a tendency towards normalcy was observed. In the 950 R irradiated normal rats the diminution of protein content appeared irreversible. In malnourished 450 R irradiated rats, the protein content rose less steeply over the 7 days of observation. A higher dose of 950 R enhanced this effect on protein and also lowered the DNA content on day 5. The RNA content in the 950 R group with malnutrition showed a marked increase towards or beyond control perhaps as an expression of uncoupled feedback control. The paper gives evidence that protein deficiency may interfere with cellular regeneration in irradiated brain.

  2. Effects of Microwave Irradiation on Embryonic Brain Tissue.

    Science.gov (United States)

    1979-03-01

    less than 1 hour) post partum in the experiment described in Section III, page 13. Table 2 The significance of the difference in weight of the irradiated...appeared normal. Two of the control and two of the exposed rats showed small depressions of the external surface of the hemisphere unilaterally with...some thinning of the underlying cortex. The depressions occurred, one just dorsal to the rhinal fissure and the other lateral to the longitudinal sulcus

  3. Mitochondrial monoaminoxidase activity and serotonin content in rat brain after whole-body γ-irradiation

    International Nuclear Information System (INIS)

    Savitskij, I.V.; Tsybul'skij, V.V.; Grivtsev, B.A.

    1985-01-01

    It is shown that γ-irradiation of albino rats with a dose of 30 Gy leads to pronounced phase changes in monoaminoxidase activity and serotonin content in rat brain at early times after whole-body exposure. These is a similar direction of changes in the activity of the enzyme and in the content of the substrate adequate to the latter

  4. Microtensile Bond Strength of Polyacid-modified Composite Resin to Irradiated Primary Molars.

    Science.gov (United States)

    Keles, Sultan; Yilmaz, Yucel; Sezen, Orhan

    2018-02-01

    This study evaluated the influence of various doses of radiotherapy on the microtensile bond strength (pTBS) of compomer resin to dentin and enamel in primary molars. Thirty-five intact primary molars were collected and divided into seven groups. Teeth were irradiated with doses from 10 to 60 Gy, except for the control group. Compomer restorations were performed, and enamel-compomer resin beams and dentin-compomer resin beams were tested at a crosshead speed of 1 mm/min. No statistically significant difference was found between the irradiated tooth enamel and the control group (F = 1.1468; p = 0.194). However, statistically significant differences were evident among the dentin groups (F = 11.050; p pTBS of compomer resin to primary tooth enamel, but appears to dose dependently decrease its bond strength to primary tooth dentin. Radiotherapy may affect the success rate of compomer fillings in primary teeth, especially in deeper cavities with exposed dentin.

  5. A non-invasive method for fractionated steriotactic irradiation of brain tumors with linear accelerator

    International Nuclear Information System (INIS)

    Hariz, M.I.; Laitinen, L.V.; Henriksson, R.; Saeterborg, N.-E.; Loefroth, P.-O.

    1990-01-01

    A new technique for fractionated stereotactic irradiation of intracranial lesions is described. The treatment is based on a versatile, non-invasive interface for stereotactic localization of the brain target imaged by computed tomography (CT), angiography or magnetic resonance tomography (MRT), and subsequent repetitive stereotactic irradiation of the target using a linear accelerator. The fractionation of the stereotactic irradiation was intended to meet the requirements of the basic principles of radiobiology. The radiophysical evaluation using phantoms, and the clinical results in a small number of patients, demonstrated a good reproducibilit between repeated positionings of the target in the isocenter of the accelerator, and a high degree of accuracy in the treatment of brain lesions. (authors). 28 refs.; 11 figs.; 1 tab

  6. Irradiation effects on the tumor and adjacent tissues of brain tumor-bearing mice

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Maki, Yutaka; Tsunemoto, Hiroshi; Koike, Sachiko; Furukawa, Shigeo.

    1979-01-01

    C 3 H mice aged 56 - 70 days, weighing 27 - 37 g were used throughout this experiment. A transplantable fibrosarcoma arising spontaneously from C 3 H mice was used. For experiment, 10 4 tumor cells suspended in 0.025 ml of saline solution were injected into the cerebral hemisphere by a 26 gauge needle with a micrometer syringe under nembutal anesthesia. Whole brain irradiation was performed at 7 days after injection of the tumor cells and the radiation doses were 2,000 and 20,000 rads, respectively. The feature of x-rays were 200 kVp, 20 mA, 0.5 mm Cu + 0.5 mm Al filtration and TSD 20 cm. The dose-rate was 340 - 360 R/min. The articles of this study were as follows: a) Determination of LD 50 values for the mice, tumor-bearing in the brain or non-tumor-bearing; and b) Observation of clinical features and gross autopsy findings of the mice following irradiation. The LD 50 values for 2,000 rad irradiation in the tumor-bearing or non-tumor-bearing mice were 10.9 and 11.4 days, respectively. LD 50 values of 3.7 days and 4.3 days were the results for the tumor-bearing and non-tumor-bearing mice irradiated by 20,000 rad, respectively. On the other hand, the LD 50 value for the control group, i.e. non-irradiated mice, was 6.7 days. At postmortem examinations, gastrointestinal bleeding was observed frequently in mice bearing tumor in the brain. Whole brain irradiation is effective to prolong the life of tumor-bearing mice. However, in some instances, deaths have occurred earlier in tumor-bearing mice compared to the control group. (author)

  7. Adverse effects of brain irradiation correlated with MR and CT imaging

    International Nuclear Information System (INIS)

    Constine, L.S.; Konski, A.; Ekholm, S.; McDonald, S.; Rubin, P.

    1988-01-01

    Forty-one patients treated for primary malignancies of the brain at the University of Rochester Cancer Center since 1970 were assessed for adverse effects of irradiation clinically, and by computerized tomography (CT) and magnetic resonance (MR) imaging. At diagnosis, patients ranged in age from 1-65 years (median 19 years) and the most common tumor (in 30) was astrocytoma. Radiation doses ranged from 45 to 81.3 Gy (median 56.8 Gy). White matter changes visible on MR were graded on a scale of 1-4, with grades 1-2 known to occur in some normal patients. Areas of increased signal intensity not associated with the tumor or surgery were visible in all patients (gr 1 = 37%, gr 2 = 32%, gr 3 = 17%, gr 4 = 15%) whereas only 35% had regions of abnormality (hypodensity) on CT. Sulci enlargement and ventricular abnormalities (asymmetry or dilatation) were present in approximately 50% of patients by each technique. Higher grade MR lesions were associated with radiation to large volumes and high doses. For the 36 patients treated with 1.5-2.0 Gy daily fractions, the mean radiation dose by grade was as follows: gr 1 = 55.1 Gy, gr 2 = 58.8 Gy, gr 3 = 60.0 Gy, gr 4 = 63.5 Gy. All 5 patients treated on a hyperfractionated schedule had gr 1-2 changes despite receiving greater than 70 Gy. Fifty percent of patients treated to the whole brain (+/- boost) had gr 3-4 changes, compared with 14% treated with local fields (peak dose regions similar in both groups). Among the children (less than or equal to 13 years), 20% had gr 3-4 changes compared with 56% of adults (excluding hyperfractionated patients). This finding may be due entirely or in part to the lower radiation doses used for children (mean 54.4 Gy vs. 63.7 Gy in adults). Clinical abnormalities attributable to irradiation included an impairment in mental functioning in 7 adults, and learning disabilities in 5 children

  8. The method of estimating the irradiated lung volume in primary breast irradiation

    International Nuclear Information System (INIS)

    Leite, Miguel Torres Teixeira; Marques, Iara Silva; Geraldo, Jony Marques

    1999-01-01

    Tangential breast fields irradiation usually includes some volume of lung and it is occasionally associated with pneumonitis. The estimation of the amount of lung irradiated can be determined measuring the central lung distance (CLD) by the port films, and it must be inferior to 2.5 cm. The purpose of this study was to determine through a linear regression analysis the relationship between CLD and the geometrical parameters of the treatment, and to develop an equation to predict this volume. The studied population consisted of 100 patients who received definitive radiation for clinical stage I and II breast cancer between January, 1996 and June, 1997. According to the contour of the breast and thorax was determined the angle of the tangential fields. In 71% of the patients the CLD measured by the portal films were superior to 2.5 cm, requiring a new beam arrangement. We develop a simple and convenient quantitative model to predict the irradiated lung volume based on portal films. We need further analysis in order to include variables and antomical variations. (author)

  9. Detection of tumor recurrence using technetium99m-tetrofosmin brain SPECT in patients with previously irradiated brain tumors

    International Nuclear Information System (INIS)

    Llamas A; Reyes A; Uribe, L F; Martinez T

    2004-01-01

    Objective: to assess the clinical utility of brain SPECT with Tc-99m Tetrofosmin to differentiate between tumor recurrence and radionecrosis in patients with primary brain tumors previously treated with external beam radiotherapy. Materials and methods: thirteen patients with clinical or radiological suspicion of tumor recurrence were studied with brain SPECT using 20-mCi of Tc-99m Tetrofosmin. Obtained images were interpreted by consensus between two experienced observers and subsequently classified as positive or negative for tumor viability. Results were compared to those of conventional diagnostic imaging techniques. Diagnostic test values and 95% confidence intervals were quantified. Results: SPECT results included 7 true-positives, 5 true-negatives and 1 false negative result. Conclusions: Tc-99m Tetrofosmin brain SPECT night be a useful alternative to diagnose recurrent brain tumors, especially with non-conclusive clinical and radiological findings

  10. Disrupted modular organization of primary sensory brain areas in schizophrenia

    Directory of Open Access Journals (Sweden)

    Cécile Bordier

    Full Text Available Abnormal brain resting-state functional connectivity has been consistently observed in patients affected by schizophrenia (SCZ using functional MRI and other neuroimaging techniques. Graph theoretical methods provide a framework to investigate these defective functional interactions and their effects on the organization of brain connectivity networks. A few studies have shown altered distribution of connectivity within and between functional modules in SCZ patients, an indication of imbalanced functional segregation ad integration. However, no major alterations of modular organization have been reported in patients, and unambiguous identification of the neural substrates affected remains elusive. Recently, it has been demonstrated that current modularity analysis methods suffer from a fundamental and severe resolution limit, as they fail to detect features that are smaller than a scale determined by the size of the entire connectivity network. This resolution limit is likely to have hampered the ability to resolve differences between patients and controls in previous studies. Here, we apply Surprise, a novel resolution limit-free approach, to study the modular organization of resting state functional connectivity networks in a large cohort of SCZ patients and in matched healthy controls. Leveraging these important methodological advances we find new evidence of substantial fragmentation and reorganization involving primary sensory, auditory and visual areas in SCZ patients. Conversely, frontal and prefrontal areas, typically associated with higher cognitive functions, appear to be largely unaffected, with changes selectively involving language and speech processing areas. Our findings support the hypothesis that cognitive dysfunction in SCZ may involve deficits occurring already at early stages of sensory processing. Keywords: Schizophrenia, Surprise, Asymptotical surprise, Functional connectivity, Community detection, Modularity, Graph theory

  11. Multiple brain metastases irradiation with Eleka Axesse stereotactic system

    Science.gov (United States)

    Filatov, P. V.; Polovnikov, E. S.; Orlov, K. Yu.; Krutko, A. V.; Kirilova, I. A.; Moskalev, A. V.; Filatova, E. V.; Zheravin, A. A.

    2017-09-01

    Brain metastases are one of the factors complicating the treatment of a malignant tumor. Radiation therapy, especially radiosurgery, plays an important role in the modern treatment practice. During 2011-2016, 32 patients (from 29 to 67 years old) with multiple brain metastases underwent the treatment with SRS or SRT in our center. The number of secondary lesions varied from 2 to 11. Eight patients underwent microsurgery resection. Seven patients had recurrence after whole brain radiotherapy. Thirty patient underwent single fraction SRS and two patients with large metastases (bigger than 3 cm) underwent fractionated SRT. The treatment was done with dedicated linear accelerator stereotactic system Elekta Axesse (Elekta AB, Stockholm, Sweden). Different stereotactic fixation devices were used, namely, Leksell G frame, non-invasive HeadFIX frame, and reinforced thermoplastic mask (IMRT perforation). All treatments included a volumetric modulated arc therapy (VMAT) technique and of Inage Guided Radiation Therapy (IGRT) technique. All lesions were treated from a single isocenter, which allowed reducing the treatment time and overall dose to the patient's body. All patients suffered the treatment satisfactorily. No adverse reactions or complications were met in any case during or right after the treatment. Different stereotactic fixation devices and modern treatment techniques allowed creating an optimal, safe and comfortable way for patient treatment. The treatment time was from 15 to 50 minutes. Patient position verification after or during the treatment demonstrated good accuracy for all fixation types and low level of intrafraction motion.

  12. Primary hypothyroidism in breast cancer patients with irradiated supraclavicular lymph nodes

    International Nuclear Information System (INIS)

    Bruning, P.; Bonfrer, J.; Jong-Bakker, M. de; Nooyen, W.; Burgers, M.

    1985-01-01

    Since the treatment of postmenopausal breast cancer patients with aminoglutethimide caused hypothyroidism with an unexpectedly high frequency previous treatment was suspected to contribute to hypofunction of the thyroid. Serum thyrotropin, triiodothyronine and free thyroxine index were compared between breast cancer patients who had undergone irradiation of regional lymph nodes and non-irradiated breast cancer patients, as well as patients having endometrial or colorectal carcinoma. Subclinical and clinical primary hypothyroidism was significantly more frequent in breast cancer patients who had previously received irradiation on supraclavicular lymph nodes comprising a minor part of the thyroid. Testing for the presence of autoantibodies against thyroid tissue components gave no evidence for radiation-induced autoimmune thyroiditis. Drugs suppressing thyroid hormone synthesis like aminoglutethimide may frequently cause myxedema in such irradiated women, especially at postmenopausal age. (author)

  13. Late vascular effects in irradiated mice brain. In relation to experimental radionecrosis

    Energy Technology Data Exchange (ETDEWEB)

    Yoshii, Y; Maki, Y [Tsukuba Univ., Sakura, Ibaraki (Japan); Phillips, T L

    1982-03-01

    The whole brains of mice were irradiated with 250 kVp X-ray at 120 rad min/sup -1/ (1.6 mm Cu HVL, TSD 50 cm) and a histological study was done. The dose range of X-irradiation was from 1300 to 2500 rads. i.e., 1300, 1500, 1750, 2000, and 2500 rads. In the microscopic examination, the mice were killed at the regular postirradiation intervals of between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. A histological examination was performed by a morphometric estimation of vascular lesion in which the degree of the damage to the arterial system was scored through whole serial brain sections. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectatic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large artery were observed. Incidence of the fibrinoid necrosis increased dose dependently between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 - 87 weeks and can be used to quantify the vessel injury and a fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis.

  14. Activity of respiratory system during laser irradiation of brain structures

    Science.gov (United States)

    Merkulova, N. A.; Sergeyeva, L. I.

    1984-06-01

    The performance of one of the principal links of the respiratory system, the respiratory center, was studied as a function of the exposure of the medulla oblongata and the sensomotor zone of the cerebral hemisphere cortex to low level laser irradiation in the red wavelength of the spectrum. Experiments were done on white rats under barbital anesthesia. Under such conditions a substantial effect was observed on the activity of the respiratory center. Laser light may display activating or inhibitory influences, in some cases the bilateral symmetry of the activity of the respiratory center is affected indicating deep changes in the integrative mechanism of the functioning of the right and left sides of the hemispheres. The laser beam effect depends on many factors: specific light properties, duration of the exposure, repetition of exposures, initial functional state of the CNS, etc.

  15. (18)F-Fluorodeoxyglucose PET/Computed Tomography for Primary Brain Tumors

    DEFF Research Database (Denmark)

    Antonsen Segtnan, Eivind; Hess, Søren; Grupe, Peter

    2015-01-01

    Structural imaging with computed tomography (CT) and MR imaging is the mainstay in primary diagnosis of primary brain tumors, but these modalities depend on morphologic appearance and an intact blood-brain barrier, and important aspects of tumor biology are not addressed. Such issues may...

  16. Fetal hypothalamic transplants into brain irradiated rats: Graft morphometry and host behavioral responses

    International Nuclear Information System (INIS)

    Pearlman, S.H.; Rubin, P.; White, H.C.; Wiegand, S.J.; Gash, D.M.

    1990-01-01

    This study was designed to test the hypothesis that neural implants can ameliorate or prevent some of the long-term changes associated with CNS irradiation. Using a rat model, the initial study focused on establishing motor, regulatory, and morphological changes associated with brain radiation treatments. Secondly, fetal hypothalamic tissue grafts were placed into the third ventricle of rats which had been previously irradiated. Adult male Long Evans rats received one of three radiation doses (15, 22.5, ampersand 30 Gy) or no radiation. Three days after irradiation, 7 animals in each dose group received an embryonic day 17 hypothalamic graft into the third ventricle while the remaining 8-9 animals in each group received injections of vehicle solution (sham). Few changes were observed in the 15 and 22.5 Gy animals, however rats in the 30 Gy treatment group showed stereotypic and ambulatory behavioral hyperactivity 32 weeks after irradiation. Regulatory changes in the high dose group included decreased growth rate and decreased urine osmolalities, but these measures were extremely variable among animals. Morphological results demonstrated that 30 Gy irradiated animals showed extensive necrosis primarily in the fimbria, which extended into the internal capsule, optic nerve, hippocampus, and thalamus. Hemorrhages were found in the hippocampus, thalamus, and fimbria. Defects in the blood-brain barrier also were evident by entry of intravascularly injected horseradish peroxidase into the parenchyma of the brain. Animals in the 30 Gy grafted group showed fewer behavioral changes and less brain damage than their sham grafted counterparts. Specifically, activity measures were comparable to normal levels, and a dilute urine was not found in the 30 Gy implanted rats. Morphological changes support these behavioral results since only two 30 Gy implanted rats showed necrosis

  17. Pencilbeam irradiation technique for whole brain radiotherapy: technical and biological challenges in a small animal model.

    Science.gov (United States)

    Schültke, Elisabeth; Trippel, Michael; Bräuer-Krisch, Elke; Renier, Michel; Bartzsch, Stefan; Requardt, Herwig; Döbrössy, Máté D; Nikkhah, Guido

    2013-01-01

    We have conducted the first in-vivo experiments in pencilbeam irradiation, a new synchrotron radiation technique based on the principle of microbeam irradiation, a concept of spatially fractionated high-dose irradiation. In an animal model of adult C57 BL/6J mice we have determined technical and physiological limitations with the present technical setup of the technique. Fifty-eight animals were distributed in eleven experimental groups, ten groups receiving whole brain radiotherapy with arrays of 50 µm wide beams. We have tested peak doses ranging between 172 Gy and 2,298 Gy at 3 mm depth. Animals in five groups received whole brain radiotherapy with a center-to-center (ctc) distance of 200 µm and a peak-to-valley ratio (PVDR) of ∼ 100, in the other five groups the ctc was 400 µm (PVDR ∼ 400). Motor and memory abilities were assessed during a six months observation period following irradiation. The lower dose limit, determined by the technical equipment, was at 172 Gy. The LD50 was about 1,164 Gy for a ctc of 200 µm and higher than 2,298 Gy for a ctc of 400 µm. Age-dependent loss in motor and memory performance was seen in all groups. Better overall performance (close to that of healthy controls) was seen in the groups irradiated with a ctc of 400 µm.

  18. Primary oxidation and reduction products in x-irradiated aspartic acid

    International Nuclear Information System (INIS)

    Adams, S.M.; Budzinski, E.E.; Box, H.C.

    1976-01-01

    The primary reduction products identified by ESR--ENDOR spectroscopy in single crystals of DL-aspartic acid hydrochloride irradiated at 4.2degreeK are anions formed by addition of an electron to the carbonyl oxygen atoms of the carboxylic acid groups. The main consequence of the oxidation process is to produce a hole centered mainly on atomic chlorine

  19. FDG-PET on Irradiated Brain Tumor: Ten Years' Summary

    International Nuclear Information System (INIS)

    Wang, S.X.; Boethius, J.; Ericson, K.

    2006-01-01

    Purpose: To evaluate FDG-PET in post-radiotherapy differentiation of tumor recurrence/malignant degeneration and radiation reaction, and to assess the role of PET in terms of survival. Material and Methods: 117 consecutive patients with a total of 156 FDG-PET examinations with positive but non-diagnostic MRI and/or CT were included. Final diagnosis was based on histopathology or correlated with radiologic and clinical follow-up. Brain metastases from lung carcinomas were further studied separately. Survival time was analysed using the Kaplan-Meier method. Results: There were 61 true-positive, 2 false-positive, 15 false-negative, and 51 true-negative PET examinations; 5 positive and 22 negative PET examinations were indeterminate. The positive predictive value of a PET examination was 96% in all and 100% in brain metastases from lung carcinoma. The negative predictive value based on the histopathologic results was 55.6%. Survival time was significantly longer in patients with negative PET. Conclusion: FDG-PET is a valuable tool in the detection of tumor recurrence, especially lung carcinoma metastasis. FDG uptake is a prognostic marker

  20. Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

    International Nuclear Information System (INIS)

    Constanzo, Julie; Paquette, Benoit; Charest, Gabriel; Masson-Côté, Laurence; Guillot, Mathieu

    2015-01-01

    Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brain were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife

  1. 1H-MR spectroscopy of the rat hippocampus after whole brain irradiation: an in vivo study

    International Nuclear Information System (INIS)

    Ding Weijun; Yang Haihua; Wang Xufeng; Hu Wei; Lei Hao; Li Chunxia; Fang Fang; Fang Zhouxi

    2008-01-01

    Objective: To study the relationships between dynamic changes of the hippocampus metabolites, cognitive impairment and ultrastructural changes of hippocampus in rats during the initial 4 weeks after 6 MV X-ray whole-brain irradiation. Methods: 65 rats were randomly divided into foul groups as sham control (n=5), 10 Gy, 20 Gy and 30 Gy groups (n=20). The learning and memory ability was measured with the Y maze test 4, 8 weeks, 2, 6 months after irradiation. 1 H-MRS was performed after 2 or 4 weeks' brain irradiation. The ultrastructural changes of the hippocampus were observed by electronic microscope. Results: The learning and memorizing ability of irradiation groups was significantly different from that of control group. Compared with control group, the NAA/Ct and Cho/Cr ratio in the left hippocampus in 10 Gy, 20 Gy and 30 Gy groups at 2 weeks and 4 weeks decreased significantly. Neuronal mitochondria edema, endothelial cells swelling and lamina dissociation in myelin sheath were demonstrated in various degrees by electromicroscope at 4 weeks following whole brain irradiation. Conclusions: 1 H-MRS can be used to non-invasively monitor the metabolic changes, both quantitatively and dynamically, of the irradiated rat brain, 1 H-MRS is superior to MRI in detecting early abnormality of the brain. The NAA/Cr and Cho/Cr ratio in irradiated hippocampus could reflect the severity of the brain injury to some extent. (authors)

  2. Scrotal Irradiation in Primary Testicular Lymphoma: Review of the Literature and In Silico Planning Comparative Study

    International Nuclear Information System (INIS)

    Brouwer, Charlotte L.; Wiesendanger, Esther M.; Hulst, Peter C. van der; Imhoff, Gustaaf W. van; Langendijk, Johannes A.; Beijert, Max

    2013-01-01

    We examined adjuvant irradiation of the scrotum in primary testicular lymphoma (PTL) by means of a literature review in MEDLINE, a telephone survey among Dutch institutes, and an in silico planning comparative study on scrotal irradiation in PTL. We did not find any uniform adjuvant irradiation technique assuring a safe planning target volume (PTV) coverage in published reports, and the definition of the clinical target volume is unclear. Histopathologic studies of PTL show a high invasion rate of the tunica albuginea, the epididymis, and the spermatic cord. In retrospective studies, a prescribed dose of at least 30 Gy involving the scrotum is associated with best survival. The majority of Dutch institutes irradiate the whole scrotum without using a planning computed tomography scan, with a single electron beam and a total dose of 30 Gy. The in silico planning comparative study showed that all evaluated approaches met a D 95% scrotal dose of at least 85% of the prescription dose, without exceeding the dose limits of critical organs. Photon irradiation with 2 oblique beams using wedges resulted in the best PTV coverage, with a mean value of 95% of the prescribed dose, with lowest maximum dose. Adjuvant photon or electron irradiation of the whole scrotum including the contralateral testicle with a minimum dose of 30 Gy is recommended in PTL. Computed tomography-based radiation therapy treatment planning with proper patient positioning and position verification guarantees optimal dose coverage.

  3. Right hemicolectomy and ileal resection with primary reanastomosis for irradiation injury of the terminal ileum

    International Nuclear Information System (INIS)

    Hoskins, W.J.; Burke, T.W.; Weiser, E.B.; Heller, P.B.; Grayson, J.; Park, R.C.

    1987-01-01

    Injury to the small intestine from pelvic irradiation increases in frequency when extended treatment fields are utilized and when radiation therapy follows a major abdominal operation. Recommended surgical correction of such injury has been intestinal bypass to avoid the excessive morbidity and mortality from anastamotic leaks associated with primary resection and anastomosis. Since 1980, eight patients with extensive ileal injury secondary to irradiation have been seen at the Naval Hospital Bethesda, Maryland. All patients had previously undergone an abdominal operation and three patients had irradiation utilizing extended fields. In all cases, right hemicolectomy and extended ileal resection were performed with primary anastamosis of the ileum to the ascending colon or the transverse colon. Operating time averaged 4 1/2 hr utilizing hand closure anastomoses and 2 1/2 hr with stapled anastomoses. All patients received postoperative hyperalimentation and six of eight patients received preoperative hyperalimentation. One operative death occurred in a patient with intestinal perforation who required multiple resections. The remaining seven patients experienced no serious complications and had rapid return of bowel function. Our experience indicates that wide ileal resection with right hemicolectomy and primary reanastomosis is an acceptable alternative to intestinal bypass for the treatment of severe irradiation injury, especially when performed with gastrointestinal stapling devices

  4. Right hemicolectomy and ileal resection with primary reanastomosis for irradiation injury of the terminal ileum

    Energy Technology Data Exchange (ETDEWEB)

    Hoskins, W.J.; Burke, T.W.; Weiser, E.B.; Heller, P.B.; Grayson, J.; Park, R.C.

    1987-02-01

    Injury to the small intestine from pelvic irradiation increases in frequency when extended treatment fields are utilized and when radiation therapy follows a major abdominal operation. Recommended surgical correction of such injury has been intestinal bypass to avoid the excessive morbidity and mortality from anastamotic leaks associated with primary resection and anastomosis. Since 1980, eight patients with extensive ileal injury secondary to irradiation have been seen at the Naval Hospital Bethesda, Maryland. All patients had previously undergone an abdominal operation and three patients had irradiation utilizing extended fields. In all cases, right hemicolectomy and extended ileal resection were performed with primary anastamosis of the ileum to the ascending colon or the transverse colon. Operating time averaged 4 1/2 hr utilizing hand closure anastomoses and 2 1/2 hr with stapled anastomoses. All patients received postoperative hyperalimentation and six of eight patients received preoperative hyperalimentation. One operative death occurred in a patient with intestinal perforation who required multiple resections. The remaining seven patients experienced no serious complications and had rapid return of bowel function. Our experience indicates that wide ileal resection with right hemicolectomy and primary reanastomosis is an acceptable alternative to intestinal bypass for the treatment of severe irradiation injury, especially when performed with gastrointestinal stapling devices.

  5. Superoxide radical formation, superoxide dismutase and glutathione reductase activity in the brain of irradiated rats

    International Nuclear Information System (INIS)

    Stanimirovic, D.; Ivanovic, L.; Simovic, M.; Cernak, I.; Savic, J.

    1989-01-01

    In the forebrain cortex, basal ganglia and hippocampus of irradiated rats (whole body, X-ray, 9 Gy), nitroblue-tetrazolium (NBT) reduction was measured as a probe of superoxide radical formation 1 hr, 6 hrs, 24 hrs and 72 hrs after irradiation. Increased superoxide radical formation was found in parallel with increase of superoxide dismutase (SOD) activity and marked decrease of glutathione reductase (GR) activity which is the most pronounced in basal ganglia. The results indicate that in the postradiation period disproportion among free radical production and capacity of brain antioxidative system occurs. This disbalance is more expressed in the brain regions known as selective vulnerable (basal ganglia, hippocampus). (author). 10 refs.; 2 tabs

  6. Effect of intracerebral administration of catecholamines and subsequent x-irradiation on brain metabolism

    International Nuclear Information System (INIS)

    Pikulev, A.T.; Khripchenko, I.P.; Kukulyanskaya, M.F.; Chernoguzov, V.M.; Lavrova, V.M.

    1987-01-01

    The effect of X-radiation in a relatively small dose on the content of glutamic acid and enzyme activity related to its exchange, as well as on certain links of carbohydrate - energy exchange in rat brain, was studied. It is shown that changes in the activity of hexokinase at the background of intercerebral administration of adrenaline prior to irradiation are related to the switching on of nonspecific regulation mechanisms. The detected single direction of changes in hexokinase activity, level of aminoacids and enzymes of reamination in subcellar fractions of brain in intact and irradiated rats both in case of intracerebral and intraperitoneal administration of catecholamines permits to consider that the realization of nonspecific component of ionizing radiation proceeds via changes in hormonal status of organism and changes in the functions of mediator systems

  7. Late vascular effects of whole brain X-irradiation in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Yoshii, Y [Tsukuba Univ., Sakma, Ibaraki (Japan). Inst. of Clinical Medicine; Phillips, T L [California Univ., San Francisco (USA). Dept. of Radiation Oncology

    1982-01-01

    The whole brains of mice were irradiated with 250kVp X-rays at 120 rads min/sup -1/ (1.6 mm Cu HVL, TSD 50 cm), and a histological study was carried out. The dose range of X-irradiation was from 1,300 to 2,500 rads, i.e., 1,300, 1,500, 1,750, 2,000, and 2,500 rads. Eighty-six mice were used for histological examination. For microscopic examination, the mice were killed at regular postirradiation intervals between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. The brains were removed immediately thereafter, fixed in Bouin's solution, and embedded in paraffin. A histological examination was performed by a morphometric estimation of vascular lesions, in which the degree of the damage to the arterial system was scored in whole serial brain section. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectactic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large arteries, were observed. Dose-dependent incidence of the fibrinoid necrosis increased between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 to 87 weeks, and can be used to quantify the vessel injury, and that fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis.

  8. Late vascular effects of whole brain X-irradiation in the mouse

    International Nuclear Information System (INIS)

    Yoshii, Y.; Phillips, T.L.

    1982-01-01

    The whole brains of mice were irradiated with 250kVp X-rays at 120 rads min -1 (1.6 mm Cu HVL, TSD 50 cm), and a histological study was carried out. The dose range of X-irradiation was from 1,300 to 2,500 rads, i.e., 1,300, 1,500, 1,750, 2,000, and 2,500 rads. Eighty-six mice were used for histological examination. For microscopic examination, the mice were killed at regular postirradiation intervals between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. The brains were removed immediately thereafter, fixed in Bouin's solution, and embedded in paraffin. A histological examination was performed by a morphometric estimation of vascular lesions, in which the degree of the damage to the arterial system was scored in whole serial brain section. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectactic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large arteries, were observed. Dose-dependent incidence of the fibrinoid necrosis increased between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 to 87 weeks, and can be used to quantify the vessel injury, and that fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis. (Author)

  9. Autoradiographic study of gamma-irradiated mouse spleen during primary immune response

    International Nuclear Information System (INIS)

    Gitsov, L.G.; Kyncheva, L.S.; Burneva, V.G.; Martinova, J.Sh.; Viklichka, S.

    1978-01-01

    Study on the kinetics of the cells in the mouse spleen during the primary immune response against thymusdependent antigen after sublethal irradiation was carried out. For this purpose the animals were immunized with sheep erythrocytes one day after their irradiation with 700 r gamma rays. On the 5th day after the immunization, tritium labelled thymidine was injected three times at two hourly intervals. Mice were killed two hours after the third injection for preparation of routine histological samples and autoradiographs. Immunized, but not irradiated mice were utilized as controls. Extensive zones of lymphocyte destruction were observed in the spleen of the irradiated mice - accumulation of picnotic lymphocyte nuclei, surrounded by reticulo-histocyte elements. The number of the labelled cells and the intensity of labelled are lower than that of the germinal centres in control animal. There is no marked cell destruction in the periarteriolar zone nor labelled cells, whereas in the controls there is a considerable number of labelled blast cells. In the red pulp of the irradiated animals islands of erythroblasts were found, whereas in the controls - parallely to the erythroblast islands, there are islands of proliferating lymphocytes and plasmocytes. The decrease of lymphocyte number in irradiated mice is connected with their destruction and with the altered lymphocytopoiesis in the red pulp. It is assumed that the observed preservation of the periarteriolar lymphatic sheaths in an expression of a higher radioresistance of the T-cells as compared to the B-cells in the white pulp. This study contributes for elucidation of the irradiation immunosuppressive effect. It points out also that the post-irradiation lymphopaenia is due not only to the cell death but also to the exclusion of part of the T-lymphocytes from the circulation and their selective deposition in the thymus-dependent zones of the peripheral lymphoid organs. (A.B.)

  10. Alternative causes of hypopituitarism: traumatic brain injury, cranial irradiation, and infections.

    Science.gov (United States)

    Pekic, Sandra; Popovic, Vera

    2014-01-01

    Hypopituitarism often remains unrecognized due to subtle clinical manifestations. Anterior pituitary hormone deficiencies may present as isolated or multiple and may be transient or permanent. Traumatic brain injury (TBI) is recognized as a risk factor for hypopituitarism, most frequently presenting with isolated growth hormone deficiency (GHD). Data analysis shows that about 15% of patients with TBI have some degree of hypopituitarism which if not recognized may be mistakenly ascribed to persistent neurologic injury and cognitive impairment. Identification of predictors for hypopituitarism after TBI is important, one of them being the severity of TBI. The mechanisms involve lesions in the hypothalamic-pituitary axis and inflammatory changes in the central nervous system (CNS). With time, hypopituitarism after TBI may progress or reverse. Cranial irradiation is another important risk factor for hypopituitarism. Deficiencies in anterior pituitary hormone secretion (partial or complete) occur following radiation damage to the hypothalamic-pituitary region, the severity and frequency of which correlate with the total radiation dose delivered to the region and the length of follow-up. These radiation-induced hormone deficiencies are irreversible and progressive. Despite numerous case reports, the incidence of hypothalamic-pituitary dysfunction following infectious diseases of the CNS has been underestimated. Hypopituitarism usually relates to the severity of the disease, type of causative agent (bacterial, TBC, fungal, or viral) and primary localization of the infection. Unrecognized hypopituitarism may be misdiagnosed as postencephalitic syndrome, while the presence of a sellar mass with suprasellar extension may be misdiagnosed as pituitary macroadenoma in a patient with pituitary abscess which is potentially a life-threatening disease. © 2014 Elsevier B.V. All rights reserved.

  11. The effect of steroids on experimental brain edema induced by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, M [Kobe Univ. (Japan). School of Medicine; Kakei, M

    1975-04-01

    In order to study the effect of steroids on brain edema, complicated by radiotherapy to brain tumors, an experiment was carried out in rats. Five thousand rads of cobalt-60 were irradiated to the head only of a rat, and 20 mg/kg of water-soluble prednine was given intraperitoneally. A single administration of the whole dose increased the amount of brain fluid to 79.35 +- 0.30 g/ 100 g wet wt.. This value was not significantly different from that of the rat which had received only the 5,000 rad irradiation. In a rat which received prednine in 6 divided doses at intervals of 4 hours, the fluid amount reached 78.33 +- 0.52 g/ 100 g wet wt. and was clearly lower than that of the rat which had been irradiated only, 79.51 +- 0.23 g/ 100 g wet wt. neither was the value significantly different from that of a normal rat which had not been exposed 78.72 +- 0.82 g/ 100 g wet wt.. Therefore, fractional administration of prednine was demonstrated to be effective.

  12. Biogenic amines, amino acids and regional blood flow in rat brain after prenatal irradiation

    International Nuclear Information System (INIS)

    Deroo, J.; Gerber, G.B.; Maes, J.

    1986-01-01

    Damage to nerve cells after prenatal irradiation could affect their later ability to function normally. The concentration of several biogenic amines and amino acids was therefore determined at different times after prenatal irradiation with 0.95 Gy on day 10, 12 or 15 of pregnancy. The offspring was sacrified 0.5, 1, 3 and 6 months after birth and the following structures were dissected: Cortex, hippocampus, striatum, thalamus, hypothalamus, cerebellum and medulla. Biogenic amines isolated by HPLC and detected electrochemically were: Dopamine, DOPA, DOPAC, epinephrine, norepinephrine, serotonin and hydroxyindolacetate. Amino acids converted to their dansyl derivatives and separated by HPLC were: Aspartate, glutamate, glutamine, gamma aminobutyrate and taurine. Many neurotransmitters were found increased in brain after prenatal irradiation, particularly on day 12 and 15 p.c. Marked changes were found for serotonin in several brain structures and for dopamin in striatum. An increase was also found in glutamate, glutamine and GABA. Studies on regional blood flow using injection of labelled 15 μ microspheres did not reveal significant alterations after prenatal irradiation. (orig.)

  13. Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy

    International Nuclear Information System (INIS)

    Shank, B.; Natale, R.B.; Hilaris, B.S.; Wittes, R.E.

    1981-01-01

    Survival of patients with small cell carcinoma of lung, treated on a new combined radiotherapy-chemotherapy protocol, compares favorably with other regimens in the literature and our own previous combined approaches. Radiation, given after induction chemotherapy, consisted of whole brain prophylaxis in all 44 evaluable patients. Patients with limited disease were also treated to the primary and mediastinum to a high dose (5000 rad equivalent) using multiple fields. The new chemotherapy regimen consisted of induction with cyclophosphamide, doxorubicin, and vincristine alternated with cis-platinum and VP-16 (an epipodophyllotoxin) for two cycles, followed by consolidation with low dose cyclophosphamide and vincristine concurrent with irradiation. Patients with limited disease who achieved less than complete response, and all patients with extensive disease were not continued on maintenance chemotherapy. Out of 24 evaluable patients with limited disease, there was 73% survival at 1 year by life-table analysis, measured from treatment initiation. After induction, 16/24 of these limited disease patients were CR (complete responders): 20/24 were CR at completion of their irradiation. Out of 20 evaluable patients with extensive disease, there was 59% survival at 1 year by life-table analysis. Only 4/44 (9%) brain parenchymal relapses occurred, one at 3 months and one at 6 months after local failure and two in patients who did not become CRs, implicating a possible re-seeding mechanism. Five patients had central nervous system relapses outside of brain parenchyma (spinal epidural and leptomeningeal); in three patients this was the initial site of failure. Significant complications included leukopenia (50%) and thrombocytopenia (24%) primarily during induction, and chronic pulmonary fibrosis (25%), possibly contributing to two deaths

  14. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Schild Steven E

    2010-10-01

    Full Text Available Abstract Background This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated. Methods Data from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA class. Results Survival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038, KPS ≥70 (p Conclusions Improved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.

  15. Yields of primary products from chloroethylenes in air under electron beam irradiation

    International Nuclear Information System (INIS)

    Hakoda, Teruyuki; Hashimoto, Shoji; Kojima, Takuji

    2003-01-01

    The quantitative analysis of toxic primary irradiation products was carried out for the development of the purification technology of chloroethylenes/air mixtures using an electron beam (EB). Degradation of chloroethylenes in humid air proceeded through the formation of primary products retaining a carbon-carbon (C-C) bond such as chloroacetyl chlorides and chloroacetyl aldehyde as well as that of primary products of COCl 2 and HCOCl through C-C bond cleavage. Chloroethylenes having one carbon bonded to two Cl atoms was decomposed into the primary products retaining a C-C bond prior to breaking a C-C bond. The number of Cl atoms of a chloroethylene molecule enhanced the formation ratio of primary products retaining a C-C bond. On the other hand, chloroethylene having two carbons bonded to one Cl atom was degraded thought the scission of a C-C bond predominantly C-C bond maintenance. (author)

  16. Directional and Spectral Irradiance in Ocean Models: Effects on Simulated Global Phytoplankton, Nutrients, and Primary Production

    Science.gov (United States)

    Gregg, Watson W.; Rousseaux, Cecile S.

    2016-01-01

    The importance of including directional and spectral light in simulations of ocean radiative transfer was investigated using a coupled biogeochemical-circulation-radiative model of the global oceans. The effort focused on phytoplankton abundances, nutrient concentrations and vertically-integrated net primary production. The importance was approached by sequentially removing directional (i.e., direct vs. diffuse) and spectral irradiance and comparing results of the above variables to a fully directionally and spectrally-resolved model. In each case the total irradiance was kept constant; it was only the pathways and spectral nature that were changed. Assuming all irradiance was diffuse had negligible effect on global ocean primary production. Global nitrate and total chlorophyll concentrations declined by about 20% each. The largest changes occurred in the tropics and sub-tropics rather than the high latitudes, where most of the irradiance is already diffuse. Disregarding spectral irradiance had effects that depended upon the choice of attenuation wavelength. The wavelength closest to the spectrally-resolved model, 500 nm, produced lower nitrate (19%) and chlorophyll (8%) and higher primary production (2%) than the spectral model. Phytoplankton relative abundances were very sensitive to the choice of non-spectral wavelength transmittance. The combined effects of neglecting both directional and spectral irradiance exacerbated the differences, despite using attenuation at 500 nm. Global nitrate decreased 33% and chlorophyll decreased 24%. Changes in phytoplankton community structure were considerable, representing a change from chlorophytes to cyanobacteria and coccolithophores. This suggested a shift in community function, from light-limitation to nutrient limitation: lower demands for nutrients from cyanobacteria and coccolithophores favored them over the more nutrient-demanding chlorophytes. Although diatoms have the highest nutrient demands in the model, their

  17. Measurement of radiation dose to the eye-lens with bilateral whole brain irradiation

    International Nuclear Information System (INIS)

    Kim, Ki Hwan; Park, Charn Il; Kang, Wee Saing; Choo, Dong Woon

    1985-01-01

    In 40 patients with metastatic brain tumor and acute lymphoblastic leukemia received whole brain irradiation, the dose delivered to the eye lens was measured using T.L.D. chips applied on the eyes as usual shield. The dose to the eye lens was expressed the relative dose to the mid brain dose. Radiotherapy was administrated using Co-60 teletherapy with bilateral whole brain irradiation. The results are as follows: 1. The dose to the right eye from its incipient field is 16.6% of tumor dose while the dose to the same eye from the opposite field is 41.2%. On left eye, 19.2% from incipient field while 39.2% from the opposite field. 2. Total received dose to right and left eyes is 28.9%, 29.8% of tumor dose respectively. 3. Comparing lens shield group with orbit shield group dose is 22.5%, 15.8% of tumor dose, respectively. 4. The dose delivered to the eye lens in ipsilateral side depends upon internal scattering, location of lead shield and penetrating dose of lead in itself. The dose in contralateral side depends upon divergency of radiation beam and patient's malposition. 5. The dose to the eye lens should be less than 10% of tumor dose with adequate shield, also not missing the chance of leptomeningeal recurrence because of overshielding.

  18. Whole brain radiotherapy for brain metastases: The technique of irradiation influences the dose to parotid glands

    International Nuclear Information System (INIS)

    Loos, G.; Paulon, R.; Verrelle, P.; Lapeyre, M.

    2012-01-01

    In the treatment of brain metastases, whole brain radiotherapy can be carried out according two distinct methods: one using multi-leaf collimator for field shaping and protection of organs at risk, and a second one is to make a rotation of the field to avoid the eyes. The aim of the study was to compare for 10 patients the dose distributions at organs at risk for each method. Patients received 30 Gy in 10 fractions. Except for parotid glands, the dose received by organs at risk and the planning target volume was the same with each method. For whole brain radiotherapy, excluding the cisterna cerebellomedullaris, the mean parotid dose was 9.63 Gy using the multi-leaf collimator versus 12.32 Gy using the field rotation (P = 0.04). For whole brain radiotherapy including the cisterna cerebellomedullaris, the mean parotid dose was 11.12 Gy using the multi-leaf collimator versus 20.06 Gy using field rotation (P < 0.001). Using the multi-leaf collimator seems recommended for whole brain radiotherapy, to reduce the dose to the parotids. (authors)

  19. SU-E-T-492: Implementing a Method for Brain Irradiation in Rats Utilizing a Commercially Available Radiosurgery Irradiator

    International Nuclear Information System (INIS)

    Cates, J; Drzymala, R

    2014-01-01

    Purpose: The purpose of the study was to implement a method for accurate rat brain irradiation using the Gamma Knife Perfexion unit. The system needed to be repeatable, efficient, and dosimetrically and spatially accurate. Methods: A platform (“rat holder”) was made such that it is attachable to the Leskell Gamma Knife G Frame. The rat holder utilizes two ear bars contacting bony anatomy and a front tooth bar to secure the rat. The rat holder fits inside of the Leskell localizer box, which utilizes fiducial markers to register with the GammaPlan planning system. This method allows for accurate, repeatable setup.A cylindrical phantom was made so that film can be placed axially in the phantom. We then acquired CT image sets of the rat holder and localizer box with both a rat and the phantom. Three treatment plans were created: a plan on the rat CT dataset, a phantom plan with the same prescription dose as the rat plan, and a phantom plan with the same delivery time as the rat plan. Results: Film analysis from the phantom showed that our setup is spatially accurate and repeatable. It is also dosimetrically accurate, with an difference between predicted and measured dose of 2.9%. Film analysis with prescription dose equal between rat and phantom plans showed a difference of 3.8%, showing that our phantom is a good representation of the rat for dosimetry purposes, allowing for +/- 3mm diameter variation. Film analysis with treatment time equal showed an error of 2.6%, which means we can deliver a prescription dose within 3% accuracy. Conclusion: Our method for irradiation of rat brain has been shown to be repeatable, efficient, and accurate, both dosimetrically and spatially. We can treat a large number of rats efficiently while delivering prescription doses within 3% at millimeter level accuracy

  20. A retrospective study of primary hyperparathyroidism after neck irradiation. Report of 14 cases

    International Nuclear Information System (INIS)

    Kanbe, Masako; Obara, Takao; Yamazaki, Kiyomi; Hirose, Kenzo; Okamoto, Takahiro; Yamashita, Tomoyuki; Ito, Yukio; Fujimoto, Yoshihide

    1997-01-01

    A retrospective review of 396 patients with primary hyperparathyroidism (pHPT) treated surgically revealed a past history of neck external irradiation in 14 patients (35%). The mean interval between radiation exposure and the diagnosis of pHPT was 41 years (range, 31-49 years). All of the patients were women who had been exposed to radiation more than 31 years before. There was a significant difference in the male:female ratio of affected patients (p<0.001). The parathyroid histology was adenoma in 13 patients and carcinoma in one. In ten patients, normal parathyroid gland biopsies were undertaken. Among normal parathyroid glands from two patients, there were nodular lesions. Thirteen (93%) of the 14 patients who had undergone neck irradiation had thyroid nodular disease. In contrast, only 98 (26%) of the 382 patients who had not undergone neck external irradiation had thyroid nodular disease, and the difference between the two groups was significant (p<0.001). Neck irradiation has been shown to increase the risk of parathyroid and thyroid nodular diseases. If neck exploration is necessary in a patient who has received neck irradiation, both the thyroid and parathyroid glands should be carefully evaluated before and during surgery. (author)

  1. Biorhythm theory and primary irradiation of inoperable cancer of the cervix

    International Nuclear Information System (INIS)

    Kucera, H.; Riss, P.; Weghaupt, K.

    1980-01-01

    Hundred patients with inoperable cancer of the cervix, who had been treated by primary irradiation, were reviewed with regard to biorhythm on the days of radium application. 5-year survival was lower in patients with unfavorable biorhythm; the differences, however, were not significant. It is concluded that the calculation of biorhythm for the day of radiotherapy has little or no influence on the results of therapy. (orig.) [de

  2. Effects of Irradiation on Brain Vasculature Using an In Situ Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Zawaski, Janice A. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Gaber, M. Waleed, E-mail: gaber@bcm.edu [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States); Sabek, Omaima M. [Department of Surgery, Methodist Hospital Research Institute, Houston, TX (United States); Wilson, Christy M. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Duntsch, Christopher D. [Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN (United States); Merchant, Thomas E. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Department of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2012-03-01

    Purpose: Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials: Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood-brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results: The presence of tumor alone increases permeability but has little effect on leukocyte-endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions: We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation.

  3. EFFECTS OF IRRADIATION ON BRAIN VASCULATURE USING AN IN SITU TUMOR MODEL

    Science.gov (United States)

    Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

    2013-01-01

    Purpose Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood–brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results The presence of tumor alone increases permeability but has little effect on leukocyte–endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation. PMID:22197233

  4. The PPARα Agonist Fenofibrate Preserves Hippocampal Neurogenesis and Inhibits Microglial Activation After Whole-Brain Irradiation

    International Nuclear Information System (INIS)

    Ramanan, Sriram; Kooshki, Mitra; Zhao Weiling; Hsu, F.-C.; Riddle, David R.; Robbins, Mike E.

    2009-01-01

    Purpose: Whole-brain irradiation (WBI) leads to cognitive impairment months to years after radiation. Numerous studies suggest that decreased hippocampal neurogenesis and microglial activation are involved in the pathogenesis of WBI-induced brain injury. The goal of this study was to investigate whether administration of the peroxisomal proliferator-activated receptor (PPAR) α agonist fenofibrate would prevent the detrimental effect of WBI on hippocampal neurogenesis. Methods and Materials: For this study, 129S1/SvImJ wild-type and PPARα knockout mice that were fed either regular or 0.2% wt/wt fenofibrate-containing chow received either sham irradiation or WBI (10-Gy single dose of 137 Cs γ-rays). Mice were injected intraperitoneally with bromodeoxyuridine to label the surviving cells at 1 month after WBI, and the newborn neurons were counted at 2 months after WBI by use of bromodeoxyuridine/neuronal nuclei double immunofluorescence. Proliferation in the subgranular zone and microglial activation were measured at 1 week and 2 months after WBI by use of Ki-67 and CD68 immunohistochemistry, respectively. Results: Whole-brain irradiation led to a significant decrease in the number of newborn hippocampal neurons 2 months after it was performed. Fenofibrate prevented this decrease by promoting the survival of newborn cells in the dentate gyrus. In addition, fenofibrate treatment was associated with decreased microglial activation in the dentate gyrus after WBI. The neuroprotective effects of fenofibrate were abolished in the knockout mice, indicating a PPARα-dependent mechanism or mechanisms. Conclusions: These data highlight a novel role for PPARα ligands in improving neurogenesis after WBI and offer the promise of improving the quality of life for brain cancer patients receiving radiotherapy.

  5. Chromatographic study of nucleosides and nucleotides of central nervous system. Identification and first results on changes after total gamma irradiation of brain

    International Nuclear Information System (INIS)

    Valle, C.; Marquer, C.; Pasquier, C.

    Changes of brain energetic state and of different levels after irradiation are studied. The results will be compared with the variations of brain electric activity due to irradiation. Using an ion exchange chromatographic method for separation and quantitative analysis of nucleotides, evaluation of adenylic nucleotides in brain rat have been chosen [fr

  6. Brain scintigraphy (SPECT) using 201thallium in patients with primary tumors of the brain

    International Nuclear Information System (INIS)

    Barzen, G.; Schubert, C.; Richter, W.; Calder, D.; Eichstaedt, H.; Felix, R.; Baerwald, M.

    1992-01-01

    We evaluated the role of thallium 201 Single-Photon-Emission-Computed-Tomography (SPECT) in diagnosis, differential diagnosis and follow-up of 33 patients with primary brain tumors. 27 of 33 lesions were detectable by Tl-201-SPECT because only two of eight low-grade (grade 1 and 2) astrocytomas showed Tl-201 accumulation up to a tumor to nontumor ratio of 2.6. High grade (grade 3 and 4) astrocytomas showed Tl-201 accumulation in the range of 2.2 up to 13.0 and were different from low-grade astrocytomas. Noninvasive grading of astrocytomas is therefore possible, whereas differential diagnosis of oligodendrogliomas and astrocytomas or meningeomas was not possible with Tl-201. In the follow-up of six patients, we could demonstrate, that tumor progression is correlated with increasing and tumor regression with decreasing Tl-201 accumulations. This functional changings proceed morphological findings in CT. But vanishing of Tl-201 accumulation during therapy does not mean vanishing of tumor as could be demonstrated by follow-up. (orig.) [de

  7. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export

    NARCIS (Netherlands)

    A. Legati (Andrea); D. Giovannini (Donatella); G. Nicolas (Gaël); U. López-Sánchez (Uriel); B. Quintáns (Beatriz); J.R. Oliveira (Joao); R.L. Sears (Renee L); E.M. Ramos (Eliana Marisa); E. Spiteri (Elizabeth); M.J. Sobrido (Maria); A. Carracedo (Angel); C. Castro-Fernández (Cristina); S. Cubizolle (Stéphanie); B.L. Fogel (Brent L); C. Goizet (Cyril); J.C. Jen (Joanna C); S. Kirdlarp (Suppachok); A.E. Lang (Anthony E); Z. Miedzybrodzka (Zosia); W. Mitarnun (Witoon); M. Paucar (Martin); H.L. Paulson (Henry); J. Pariente (Jérémie); A.-C. Richard (Anne-Claire); N.S. Salins (Naomi S); S.A. Simpson (Sheila A); P. Striano (Pasquale); P. Svenningsson (Per); F. Tison (François); V.K. Unni (Vivek K); O. Vanakker (Olivier); M.W. Wessels (Marja); S. Wetchaphanphesat (Suppachok); M. Yang (Michele); F. Boller (Francois); D. Campion (Dominique); D. Hannequin (Didier); M. Sitbon (Marc); H. Geschwind; J.-L. Battini (Jean-Luc); D. Coppola (Domenico)

    2015-01-01

    textabstractPrimary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions and has thus far been associated with SLC20A2, PDGFB or PDGFRB mutations. We identified in multiple families with PFBC mutations

  8. Effect of dietary poly unsaturated fatty acids on total brain lipid concentration and anxiety levels of electron beam irradiated mice

    International Nuclear Information System (INIS)

    Suchetha Kumari; Bekal, Mahesh

    2013-01-01

    The whole brain irradiation causes injury to the nervous system at various levels. Omega-3 poly unsaturated fatty acids are very much essential for the growth and development of nervous system. Dietary supplementation of these nutrients will promote the development of injured neuronal cells. Therefore this study was undertaken to establish the role of Omega-3 poly unsaturated fatty acids on total brain lipid concentration, lipid peroxidation and anxiety levels in the irradiated mice. The effect of Electron Beam Radiation (EBR) on total brain lipid concentration, lipid peroxidation and anxiety level were investigated in male Swiss albino mice. The study groups were subjected to a sub-lethal dose of EBR and also the flax seed extract and fish oil were given orally to the irradiated mice. Irradiated groups show significant elevation in anxiety levels when compared to control group, indicating the acute radiation effects on the central nervous system. But the oral supplementation of dietary PUFA source decrees the anxiety level in the irradiated group. The analysis of lipid peroxidation showed a significant level of changes when compared between control and radiation groups. Dietary PUFA supplementation showed a significant level of decrease in the lipid peroxidation in the irradiated groups. The observation of total lipids in brain shows decrease in concentration in the irradiated groups, the differences in the variables follow the similar patterns as of that the MDA levels. This study suggests that the dietary intake of PUFAs may help in prevention and recovery of the oxidative stress caused by radiation. (author)

  9. Whole brain irradiation in case of brain metastases in from 2005 to 2011 in the clinic for nuclear medicine of the university hospital Freiburg; Ganzhirnbestrahlung bei Hirnmetastasen von 2005 bis 2011 in der Klinik fuer Strahlenheilkunde des Universitaetsklinikums Freiburg

    Energy Technology Data Exchange (ETDEWEB)

    Hintz, Mandy

    2017-10-01

    Brain metastases are the largest group of brain tumors. Their occurrence influences the overall survival and the quality of life. The retrospective study deals with the overall survival, the local tumor control and the prognostic factors of patients treated with whole brain irradiation. The data were evaluated using multivariate analysis. Whole brain irradiation has shown to be an efficient therapy option for patients with brain metastases and has the possibility to improve the overall progress-free survival and the symptom control.

  10. A case of acute lymphoblastic leukemia with abnormal brain CT scan after cranial irradiation for central nervous system leukemia

    International Nuclear Information System (INIS)

    Sato, Junko; Abe, Takanori; Watanabe, Tsutomu

    1988-01-01

    A 21-year-old woman with acute lymphoblastic leukemia presented with central neurologic symptoms immediately after the second irradiation (20 Gy to the brain and 10 Gy to the spinal cord) for central nervous system (CNS)-leukemia 3 years and 2 months after the first cranial irradiation with 20 Gy. White matter was depicted as diffusely high density area on CT; histology revealed necrosis of leukemic cells. In the present patient with repeated recurrent CNS-leukemia, leukemic cells seemed to have been damaged simultaneously after irradiation because of parenchymal widespread involvement of leukemic cells, resulting in brain edema, an increased intracranial pressure and parenchymal disturbance. This finding may have an important implication for the risk of cranial irradiation in the case of widespread involvement of leukemic cells. Re-evaluation of cranial irradiation in such cases is suggested. (Namekawa, K.)

  11. PROFOUND AND SEXUALLY DIMORPHIC EFFECTS OF CLINICALLY-RELEVANT LOW DOSE SCATTER IRRADIATION ON THE BRAIN AND BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Anna eKovalchuk

    2016-06-01

    Full Text Available Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders. While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way.

  12. Brain damage in relation to irradiation and chemotherapy of central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Similae, S; Heikkinen, E; Blanco, G; Taskinen, P J; Kouvalainen, K; Lanning, M; Saukkonen, A -L [Oulu Univ. (Finland)

    1977-05-07

    Measurements have been made of the concentrations of 3',5'-mono-phosphate, protein and sugar, and of the activities of lactic dehydrogenase (LD), aspartate aminotransferase (AsAT), creatine kinase (CK), and acid phosphatase (AcPhos) in the cerebrospinal fluid (CSF) during /sup 60/Co CNS radiotherapy and chemotherapy in eight children with acute lymphoblastic leukaemia (A.L.L.). The CSF white-blood-cell count of the A.L.L. patients did not differ significantly from that of the controls, but protein content rose and sugar content fell during CNS irradiation and chemotherapy (intrathecal methotrexate). LD and AsAT activities were significantly higher during CNS treatment, and a similar tendency was seen for AcPhos and CK activities. The results provide clear biochemical signs of brain injury caused by prophylactic CNS irradiation and chemotherapy.

  13. Histochemical study of reaction of the nucleus supraopticus of rat brain to irradiation with 500 Gy

    International Nuclear Information System (INIS)

    Dosoudilova, M.; Kamarad, V.

    1987-01-01

    The activities were described of some enzymes in nucleus supraopticus of the rat brain at an early interval (5 min) after gamma irradiation with 500 Gy, at a dose rate of 6.9 Gy per minute. The study was performed using cryostat sections. The activities of the following enzymes were shown: alkaline phosphatase, acid phosphatase, ATP-splitting enzyme, thiaminepyrophosphatase, butyrylcholinesterase, acetylcholinesterase, glycero-3-phosphate-dehydrogenase, succinate dehydrogenase, acid nonspecific esterase, and beta glucuronidase. After irradiation, increased activities of acid phosphatase, thiaminepyrophosphatase, and acetylcholinesterase was observed in perikarya of magnocelullar neurons of the nucleus, whereas the activities of other enzymes were weak when compared to controls. A significant decrease in the activity of acidic nonspecific esterase was found. In contrast to the controls, blood capillaries showed increased activities of ATP-splitting enzyme, butyrylcholinesterase, thiaminepyrophosphatase. The activities of alkaline phosphatase and acid phosphatase were not changed. No activity of other enzymes was observed in that site. (author). 13 refs

  14. Brain sarcoma of meningeal origin after cranial irradiation in childhood acute lymphocytic leukemia. Case report

    International Nuclear Information System (INIS)

    Tiberin, P.; Maor, E.; Zaizov, R.; Cohen, I.J.; Hirsch, M.; Yosefovich, T.; Ronen, J.; Goldstein, J.

    1984-01-01

    The authors report their experience with an unusual case of intracerebral sarcoma of meningeal cell origin in an 8 1/2-year-old girl. This tumor occurred 6 1/2 years after cranial irradiation at relatively low dosage (2200 rads) had been delivered to the head in the course of a multimodality treatment for acute lymphocytic leukemia. The tumor recurred approximately 10 months after the first surgical intervention. Macroscopic total excision of the recurrent growth followed by whole-brain irradiation (4500 rads) failed to eradicate it completely and local recurrence prompted reoperation 18 months later. This complication of treatment in long-term childhood leukemia survivors is briefly discussed, as well as the pathology of meningeal sarcomas

  15. Evolution of growth hormone neurosecretory disturbance after cranial irradiation for childhood brain tumours: a prospective study

    International Nuclear Information System (INIS)

    Spoudeas, H.A.; Hindmarsh, P.C.; Brook, C.G.D.; Matthews, D.R.

    1996-01-01

    To determine the aetiopathology of post-irradiation growth hormone (GH) deficiency, we performed a mixed longitudinal analysis of 56 24 h serum GH concentration profiles and 45 paired insulin-induced hypoglycaemia tests (ITT) in 35 prepubertal children, aged 1.5-11.8 years, with brain tumours in the posterior foss (n = 25) or cerebral hemispheres (n 10). Assessments were made before (n = 16), 1 year (n = 25) and 2 to 5 years (n = 15) after a cranial irradiation (DXR) dose of at least 30 Gy. Fourier transforms, occupancy percentage, first-order derivatives (FOD) and mean concentrations were determined from the GH profiles taken after neurosurgery but before radiotherapy (n = 16) and in three treatment groups: Group 1: neurosurgery only without DXR 9n 9); Group 2: ≥ 30 Gy DXR only (n = 22); Group 3: ≥ 30 Gy DXR with additional chemotherapy (n = 9). Results were compared with those from 26 short normally growing (SN) children. (author)

  16. Novel technique for high-precision stereotactic irradiation of mouse brains

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, J.; Woelfelschneider, J.; Derer, A.; Fietkau, R.; Gaipl, U.S.; Bert, C.; Frey, B. [Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Department of Radiation Oncology, Universitaetsklinikum Erlangen, Erlangen (Germany); Stache, C.; Buslei, R.; Hoelsken, A. [Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Institute of Neuropathology, Universitaetsklinikum Erlangen, Erlangen (Germany); Schwarz, M.; Baeuerle, T. [Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Institute of Radiology, Preclinical Imaging Platform Erlangen (PIPE), Universitaetsklinikum Erlangen, Erlangen (Germany)

    2016-11-15

    Small animal irradiation systems were developed for preclinical evaluation of tumor therapy closely resembling the clinical situation. Mostly only clinical LINACs are available, so protocols for small animal partial body irradiation using a conventional clinical system are essential. This study defines a protocol for conformal brain tumor irradiations in mice. CT and MRI images were used to demarcate the target volume and organs at risk. Three 6 MV photon beams were planned for a total dose of 10 fractions of 1.8 Gy. The mouse position in a dedicated applicator was verified by an X-ray patient positioning system before each irradiation. Dosimetric verifications (using ionization chambers and films) were performed. Irradiation-induced DNA damage was analyzed to verify the treatment effects on the cellular level. The defined treatment protocol and the applied fractionation scheme were feasible. The in-house developed applicator was suitable for individual positioning at submillimeter accuracy of anesthetized mice during irradiation, altogether performed in less than 10 min. All mice tolerated the treatment well. Measured dose values perfectly matched the nominal values from treatment planning. Cellular response was restricted to the target volume. Clinical LINAC-based irradiations of mice offer the potential to treat orthotopic tumors conformably. Especially with respect to lateral penumbra, dedicated small animal irradiation systems exceed the clinical LINAC solution. (orig.) [German] Kleintierbestrahlungsanlagen wurden entwickelt um praeklinische Studien in der Tumortherapie unter moeglichst klinischen Bedingungen durchzufuehren. Da an den meisten Instituten nur klinische LINACs zur Verfuegung stehen, werden Standardprotokolle zur Kleintierbestrahlung benoetigt, die konventionelle Systeme nutzen. In dieser Studie wird ein solches Protokoll fuer tumorkonforme Hirnbestrahlung von Maeusen definiert. CT- und MRT-Bilder wurden aufgenommen, um Zielvolumen und

  17. Decreased weight, DNA, RNA and protein content of the brain after neutron irradiation of the 18-day mouse embryo

    International Nuclear Information System (INIS)

    Antal, S.; Fonagy, A.; Hidvegi, E.J.; Fueloep, Z.; Vogel, H.H. Jr.

    1984-01-01

    Pregnant mice were irradiated with 0.5 Gy fission neutrons on the eighteenth day of gestation. Average litter size at birth was unchanged but mortality increased 5-6 fold in the first 3 days. Irradiated mice were the same weight as control mice at birth but showed a progressively increasing weight deficiency up to at least 36 days compared to controls. Brain weight was 37, 45 and 25% less in 2-, 3- and 52-week old irradiated animals; the ratio of brain weight to body weight was 25, 27 and 13% less. The concentrations of DNA, RNA and protein (mg/g wet tissue) were the same in irradiated and control mice in brain and liver at all three ages. Total DNA, RNA and protein contents of whole brain after irradiation were 56-75% of control levels. No definite decrease was observed in liver. Histological study at 6 hours after irradiation showed nuclear pyknosis in the central nervous system from definite to very severe according to the part examined. It is concluded that damage to the central nervous system of the 18-day mouse foetus is mainly due to killing and/or inhibition of the differentiation of neuroblasts. (author)

  18. Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Robert J.; Jun, Brandon J. [Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California (United States); Advanced Imaging Laboratory, Department of Radiology, Children' s Hospital Los Angeles, Los Angeles, California (United States); Rudi Schulte Research Institute, Santa Barbara, California (United States); Cushman, Jesse D. [Department of Psychology, University of California, Los Angeles, Los Angeles, California (United States); Nguyen, Christine; Beighley, Adam H.; Blanchard, Johnny; Iwamoto, Kei; Schaue, Dorthe [Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California (United States); Harris, Neil G. [UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA Center for the Health Sciences, Los Angeles, California (United States); Jentsch, James D. [Department of Psychology, University of California, Los Angeles, Los Angeles, California (United States); Bluml, Stefan [Advanced Imaging Laboratory, Department of Radiology, Children' s Hospital Los Angeles, Los Angeles, California (United States); Rudi Schulte Research Institute, Santa Barbara, California (United States); McBride, William H., E-mail: wmcbride@mednet.ucla.edu [Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California (United States)

    2016-10-01

    Purpose: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. Methods and Materials: Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. Results: Fractional anisotropy in the splenium of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. Conclusions: The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic

  19. Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation

    International Nuclear Information System (INIS)

    Brown, Robert J.; Jun, Brandon J.; Cushman, Jesse D.; Nguyen, Christine; Beighley, Adam H.; Blanchard, Johnny; Iwamoto, Kei; Schaue, Dorthe; Harris, Neil G.; Jentsch, James D.; Bluml, Stefan; McBride, William H.

    2016-01-01

    Purpose: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. Methods and Materials: Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. Results: Fractional anisotropy in the splenium of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. Conclusions: The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic

  20. SU-F-T-668: Irradiating Mouse Brain with a Clinical Linear Accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Torres, C [N Rancilio Purdue University, West Lafayette, IN (United States)

    2016-06-15

    Purpose: To design and construct a “mouse jig” device that would allow for irradiation of the mouse brain with a clinical Varian 6 MeV Linear Accelerator. This device must serve as a head immobilizer, gaseous anesthesia delivery, and radiation bolus concurrently. Methods: The mouse jig was machined out of nylon given that it is inexpensive, easy to machine, and has similar electron density to water. A cylindrical opening with diameter of 16 mm and 40 mm depth was drilled into a nylon block sized 56×56×50 mm (width, length, depth). Additional slots were included in the block for ear bars and a tooth bar to serve as a three-point immobilization device as well as for anesthesia delivery and scavenging. For ease of access when loading the mouse into the holder, there is a removable piece at the top of the block that is 15 mm in depth. This serves a dual purpose, as with the proper extra shielding, the mouse jig could be used with lower linear energy transfer photons with this piece removed. A baseplate was then constructed with five square slots where the mouse jig can securely be inserted plus additional slots that would allow the baseplate to be mounted on a standard lock bar in the treatment couch. This maximizes the reproducibility of placement between imaging and treatment and between treatment sessions. Results: CT imaging and radiation treatment planning was performed that showed acceptable coverage and uniformity of radiation dose in the mouse brain while sparing the throat and eyes. Conclusion: We have designed and manufactured a device that fulfills our criteria allowing us to selectively irradiate the mouse brain with a clinical linear accelerator. This setup will be used for generating mouse models of radiation-induced brain injury.

  1. Electron beam irradiation process applied to primary and secondary recycled high density polyethylene

    Energy Technology Data Exchange (ETDEWEB)

    Cardoso, Jéssica R.; Moura, Eduardo de; Geraldo, Áurea B.C., E-mail: ageraldo@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    Plastic bags, packaging and furniture items are examples of plastic utilities always present in life. However, the end-of-life of plastics impacts the environment because of this ubiquity and also often their high degradation time. Recycling processes are important in this scenario because they offer many solutions to this problem. Basically, four ways are known for plastic recycling: primary recycling, which consists in re-extrusion of clean plastic scraps from a production plant; secondary recycling, that uses end-of-life products that generally are reduced in size by extrusion to obtain a more desirable shape for reprocessing (pellets and powder); tertiary recover which is related to thermo-chemical methods to produce fuels and petrochemical feedstock; and quaternary route, that is related to energy recovery and it is done in appropriate reactors. In this work, high density polyethylene (HDPE) was recovered to simulate empirically the primary and secondary recycling ways using materials which ranged from pristine to 20-fold re-extrused materials. The final 20-fold recycled thermoplastic was irradiated in an electron beam accelerator under a dose rate of 22.4 kGy/s and absorbed doses of 50 kGy and 100 kGy. The characterization of HDPE in distinct levels of recovering was performed by infrared spectroscopy (FTIR) and thermogravimetric degradation. In the HDPE recycling, degradation and crosslinking are consecutive processes; degradation is very noticeable in the 20-fold recycled product. Despite this, the 20-fold recycled product presents crosslinking after irradiation process and the post-irradiation product presents similarities in spectroscopic and thermal degradation characteristics of pristine, irradiated HDPE. These results are discussed. (author)

  2. Electron beam irradiation process applied to primary and secondary recycled high density polyethylene

    International Nuclear Information System (INIS)

    Cardoso, Jéssica R.; Moura, Eduardo de; Geraldo, Áurea B.C.

    2017-01-01

    Plastic bags, packaging and furniture items are examples of plastic utilities always present in life. However, the end-of-life of plastics impacts the environment because of this ubiquity and also often their high degradation time. Recycling processes are important in this scenario because they offer many solutions to this problem. Basically, four ways are known for plastic recycling: primary recycling, which consists in re-extrusion of clean plastic scraps from a production plant; secondary recycling, that uses end-of-life products that generally are reduced in size by extrusion to obtain a more desirable shape for reprocessing (pellets and powder); tertiary recover which is related to thermo-chemical methods to produce fuels and petrochemical feedstock; and quaternary route, that is related to energy recovery and it is done in appropriate reactors. In this work, high density polyethylene (HDPE) was recovered to simulate empirically the primary and secondary recycling ways using materials which ranged from pristine to 20-fold re-extrused materials. The final 20-fold recycled thermoplastic was irradiated in an electron beam accelerator under a dose rate of 22.4 kGy/s and absorbed doses of 50 kGy and 100 kGy. The characterization of HDPE in distinct levels of recovering was performed by infrared spectroscopy (FTIR) and thermogravimetric degradation. In the HDPE recycling, degradation and crosslinking are consecutive processes; degradation is very noticeable in the 20-fold recycled product. Despite this, the 20-fold recycled product presents crosslinking after irradiation process and the post-irradiation product presents similarities in spectroscopic and thermal degradation characteristics of pristine, irradiated HDPE. These results are discussed. (author)

  3. Ipsilateral Irradiation for Oral and Oropharyngeal Carcinoma Treated With Primary Surgery and Postoperative Radiotherapy

    International Nuclear Information System (INIS)

    Vergeer, Marije R.; Doornaert, Patricia; Jonkman, Anja; Kaanders, Johannes H.A.M.; Ende, Piet L.A. van den; Jong, Martin A. de; Leemans, C. Rene; Slotman, Ben J.; Langendijk, Johannes A.

    2010-01-01

    Purpose: The purpose was to evaluate the contralateral nodal control (CLNC) in postoperative patients with oral and oropharyngeal cancer treated with ipsilateral irradiation of the neck and primary site. Late radiation-induced morbidity was also evaluated. Methods and Materials: The study included 123 patients with well-lateralized squamous cell carcinomas treated with surgery and unilateral postoperative irradiation. Most patients had tumors of the gingiva (41%) or buccal mucosa (21%). The majority of patients underwent surgery of the ipsilateral neck (n = 102 [83%]). The N classification was N0 in 73 cases (59%), N1 or N2a in 23 (19%), and N2b in 27 cases (22%). Results: Contralateral metastases developed in 7 patients (6%). The 5-year actuarial CLNC was 92%. The number of lymph node metastases was the only significant prognostic factor with regard to CLNC. The 5-year CLNC was 99% in N0 cases, 88% in N1 or N2a cases, and 73% in N2b cases (p = 0.008). Borderline significance (p = 0.06) was found for extranodal spread. Successful salvage could be performed in 71% of patients with contralateral metastases. The prevalence of Grade 2 or higher xerostomia was 2.6% at 5 years. Conclusions: Selected patients with oral or oropharyngeal carcinoma treated with primary surgery and postoperative ipsilateral radiotherapy have a very high CLNC with a high probability of successful salvage in case of contralateral metastases. However, bilateral irradiation should be applied in case of multiple lymph node metastases in the ipsilateral neck, particularly in the presence of extranodal spread. The incidence of radiation-induced morbidity is considerably lower as observed after bilateral irradiation.

  4. Primary radiation damage characterization of α-iron under irradiation temperature for various PKA energies

    Science.gov (United States)

    Sahi, Qurat-ul-ain; Kim, Yong-Soo

    2018-04-01

    The understanding of radiation-induced microstructural defects in body-centered cubic (BCC) iron is of major interest to those using advanced steel under extreme conditions in nuclear reactors. In this study, molecular dynamics (MD) simulations were implemented to examine the primary radiation damage in BCC iron with displacement cascades of energy 1, 5, 10, 20, and 30 keV at temperatures ranging from 100 to 1000 K. Statistical analysis of eight MD simulations of collision cascades were carried out along each [110], [112], [111] and a high index [135] direction and the temperature dependence of the surviving number of point defects and the in-cascade clustering of vacancies and interstitials were studied. The peak time and the corresponding number of defects increase with increasing irradiation temperature and primary knock-on atom (PKA) energy. However, the final number of surviving point defects decreases with increasing lattice temperature. This is associated with the increase of thermal spike at high PKA energy and its long timespan at higher temperatures. Defect production efficiency (i.e., surviving MD defects, per Norgett-Robinson-Torrens displacements) also showed a continuous decrease with the increasing irradiation temperature and PKA energy. The number of interstitial clusters increases with both irradiation temperature and PKA energy. However, the increase in the number of vacancy clusters with PKA energy is minimal-to-constant and decreases as the irradiation temperature increases. Similarly, the probability and cluster size distribution for larger interstitials increase with temperature, whereas only smaller size vacancy clusters were observed at higher temperatures.

  5. Impaired cholesterol esterification in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) mouse mutant

    International Nuclear Information System (INIS)

    Patel, S.C.; Suresh, S.; Weintroub, H.; Brady, R.O.; Pentchev, P.G.

    1987-01-01

    Esterification of cholesterol was investigated in primary neuroglial cultures obtained from newborn lysosomal cholesterol storage disorder (LCSD) mouse mutants. An impairment in 3 H-oleic acid incorporation into cholesteryl esters was demonstrated in cultures of homozygous LCSD brain. Primary cultures derived from other phenotypically normal pups of the carrier breeders esterified cholesterol at normal levels or at levels which were intermediary between normal and deficient indicating a phenotypic expression of the LCSD heterozygote genotype. These observations on LCSD mutant brain cells indicate that the defect in cholesterol esterification is closely related to the primary genetic defect and is expressed in neuroglial cells in culture

  6. Re-irradiation of recurrent esophageal cancer after primary definitive radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Suk; Lee, Chang Geol; Kim, Kyung Hwan; Kim, Tae Hyung [Dept. of Radiation Oncology, Yonsei University Health System, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-12-15

    For recurrent esophageal cancer after primary definitive radiotherapy, no general treatment guidelines are available. We evaluated the toxicities and clinical outcomes of re-irradiation (re-RT) for recurrent esophageal cancer. We analyzed 10 patients with recurrent esophageal cancer treated with re-RT after primary definitive radiotherapy. The median time interval between primary radiotherapy and re-RT was 15.6 months (range, 4.8 to 36.4 months). The total dose of primary radiotherapy was a median of 50.4 Gy (range, 50.4 to 63.0 Gy). The total dose of re-RT was a median of 46.5 Gy (range, 44.0 to 50.4 Gy). The median follow-up period was 4.9 months (range, 2.6 to 11.4 months). The tumor response at 3 months after the end of re-RT was complete response (n = 2), partial response (n = 1), stable disease (n = 2), and progressive disease (n = 5). Grade 5 tracheoesophageal fistula developed in three patients. The time interval between primary radiotherapy and re-RT was less than 12 months in two of these three patients. Late toxicities included grade 1 dysphagia (n = 1). Re-RT of recurrent esophageal cancer after primary radiotherapy can cause severe toxicity.

  7. Re-irradiation of recurrent esophageal cancer after primary definitive radiotherapy

    International Nuclear Information System (INIS)

    Kim, Young Suk; Lee, Chang Geol; Kim, Kyung Hwan; Kim, Tae Hyung

    2012-01-01

    For recurrent esophageal cancer after primary definitive radiotherapy, no general treatment guidelines are available. We evaluated the toxicities and clinical outcomes of re-irradiation (re-RT) for recurrent esophageal cancer. We analyzed 10 patients with recurrent esophageal cancer treated with re-RT after primary definitive radiotherapy. The median time interval between primary radiotherapy and re-RT was 15.6 months (range, 4.8 to 36.4 months). The total dose of primary radiotherapy was a median of 50.4 Gy (range, 50.4 to 63.0 Gy). The total dose of re-RT was a median of 46.5 Gy (range, 44.0 to 50.4 Gy). The median follow-up period was 4.9 months (range, 2.6 to 11.4 months). The tumor response at 3 months after the end of re-RT was complete response (n = 2), partial response (n = 1), stable disease (n = 2), and progressive disease (n = 5). Grade 5 tracheoesophageal fistula developed in three patients. The time interval between primary radiotherapy and re-RT was less than 12 months in two of these three patients. Late toxicities included grade 1 dysphagia (n = 1). Re-RT of recurrent esophageal cancer after primary radiotherapy can cause severe toxicity.

  8. SU-E-T-457: Design and Characterization of An Economical 192Ir Hemi-Brain Small Animal Irradiator

    International Nuclear Information System (INIS)

    Grams, M; Wilson, Z; Sio, T; Beltran, C; Tryggestad, E; Gupta, S; Blackwell, C; McCollough, K; Sarkaria, J; Furutani, K

    2014-01-01

    Purpose: To describe the design and dosimetric characterization of a simple and economical small animal irradiator. Methods: A high dose rate 192Ir brachytherapy source from a commercially available afterloader was used with a 1.3 centimeter thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit is equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film. The penumbra from the small animal irradiator was compared under similar collimating conditions to the penumbra from 6 MV photons, 6 MeV electrons, and 20 MeV electrons from a linear accelerator as well as 300 kVp photons from an orthovoltage unit and Monte Carlo simulated 90 MeV protons. Results: The tungsten collimator provides a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator. Additionally, the penumbra was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. Conclusions: The small animal irradiator described here can be built for under $1,000 and used in conjunction with any commercial brachytherapy afterloader to provide a convenient and cost-effective option for small animal irradiation experiments. The unit offers high dose rate delivery and sharp penumbra, which is ideal for hemi-brain irradiation of mice. With slight modifications to the design, irradiation of sites other than the brain could be accomplished easily. Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring a sharp penumbra

  9. Energy spectra of primary knock-on atoms under neutron irradiation

    International Nuclear Information System (INIS)

    Gilbert, M.R.; Marian, J.; Sublet, J.-Ch.

    2015-01-01

    Materials subjected to neutron irradiation will suffer from a build-up of damage caused by the displacement cascades initiated by nuclear reactions. Previously, the main “measure” of this damage accumulation has been through the displacements per atom (dpa) index, which has known limitations. This paper describes a rigorous methodology to calculate the primary atomic recoil events (often called the primary knock-on atoms or PKAs) that lead to cascade damage events as a function of energy and recoiling species. A new processing code SPECTRA-PKA combines a neutron irradiation spectrum with nuclear recoil data obtained from the latest nuclear data libraries to produce PKA spectra for any material composition. Via examples of fusion relevant materials, it is shown that these PKA spectra can be complex, involving many different recoiling species, potentially differing in both proton and neutron number from the original target nuclei, including high energy recoils of light emitted particles such as α-particles and protons. The variations in PKA spectra as a function of time, neutron field, and material are explored. The application of PKA spectra to the quantification of radiation damage is exemplified using two approaches: the binary collision approximation and stochastic cluster dynamics, and the results from these different models are discussed and compared. - Highlights: • Recoil cross-section matrices under neutron irradiation are generated. • Primary knock-on atoms (PKA) spectra are calculated for fusion relevant materials. • Variation in PKA spectra due to changes in geometry are considered. • Inventory simulations to consider time-evolution in PKA spectra. • Damage quantification using damage functions from different approximations.

  10. Implantation of glioblastoma spheroids into organotypic brain slice cultures as a model for investigating effects of irradiation

    DEFF Research Database (Denmark)

    Petterson, Stine Asferg; Jakobsen, Ida Pind; Jensen, Stine Skov

    2016-01-01

    , models for studying the effects of radiotherapy in combination with novel strategies are lacking but important since radiotherapy is the most successful non-surgical treatment of brain tumors. The aim of this study was to establish a glioblastoma spheroid-organotypic rat brain slice culture model...... comprising both tumors, tumor-brain interface and brain tissue to provide a proof of concept that this model is useful for studying effects of radiotherapy. Organotypic brain slice cultures cultured for 1-2 days or 11-16 days corresponding to immature brain and mature brain respectively were irradiated...... with doses between 10 and 50 Gy. There was a high uptake of the cell death marker propidium iodide in the immature cultures. In addition, MAP2 expression decreased whereas GFAP expression increased in these cultures suggesting neuronal death and astrogliosis. We therefore proceeded with the mature cultures...

  11. Metastatic carcinoma in the cervical lymph nodes from an unknown primary site: results of bilateral neck plus mucosal irradiation vs. ipsilateral neck irradiation

    International Nuclear Information System (INIS)

    Reddy, Sarada P.; Marks, James E.

    1997-01-01

    Purpose: To compare the outcome for patients with squamous cell carcinoma of cervical lymph nodes metastatic from an unknown primary site who were irradiated to both sides of the neck and potential mucosal sites with opposed photon beams, and for those irradiated to the ipsilateral side of the neck alone with an electron beam. Methods and Materials: Fifty-two patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site were irradiated by two different methods. Thirty-six were irradiated with a bilateral technique (BT), i.e., to both sides of the neck, including the naso-oro-hypopharyngeal mucosa, and 16 were irradiated with an electron beam (EB) to the ipsilateral side of the neck alone. Twenty patients of the BT group and 11 of the EB group had cervical lymph node dissections, and the remaining 21 patients had lymph node biopsies, prior to radiotherapy. Results: Tumor control in the ipsilateral side of the neck did not differ for either radiation technique, but was significantly higher after lymph node dissection than after biopsy (90 vs. 48%; p = 0.0004). Control of subclinical metastases in the contralateral cervical lymph nodes was higher for patients irradiated with BT than for patients irradiated with EB (86 vs. 56%; p 0.03). The occult primary was later discovered in 8% of the patients in the BT group and 44% of the EB group (p = 0.0005). The disease-free survival rate at 5 years for patients who had lymph node dissection prior to irradiation was 61%, and was 37% for those who had biopsy (p = 0.05). Only 20% of patients who subsequently developed an occult primary were salvaged and survived for 5 years after salvage treatment. Conclusion: Bilateral neck and mucosal irradiation is superior to ipsilateral neck irradiation in preventing contralateral cervical lymph node metastases and the subsequent appearance of an occult primary cancer. Both techniques combined with cervical lymph node dissection were equally effective

  12. Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Hulshof, M C.C.M.; Sminia, P; Gonzalez, D G [Amsterdam Univ. (Netherlands). Dept. of Radiation Oncology; Stark, N M; Smeding, H M.M. [Amsterdam Univ. (Netherlands). Dept. of Neurology; Kleij, A van der [Amsterdam Univ. (Netherlands). Dept. of Surgery/Hyperbaric Oxygen

    2002-04-01

    Purpose: Analysis of the feasibility and effect of hyperbaric oxygen treatment (HBO) on cognitive functioning in patients with cognitive disorders after irradiation of the brain. Patients and Method: Seven patients with cognitive impairment after brain irradiation, with an interval of at least 1.5 years after treatment, were treated with 30 sessions of HBO in a phase I-II study. A comprehensive neuropsychological test battery was performed before treatment, at 3 and 6 months thereafter. Patients were randomized into an immediate treatment group and a delayed treatment group. The delayed group had a second neurospychological test at 3 months without treatment in that period and started HBO thereafter. Results: All eligible patients completed the HBO treatment and the extensive neuropsychological testing. One out of seven patients had a meaningful improvement in neuropsychological functioning. At 3 months there was a small, but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment. Six out of seven patients eventually showed improvement after HBO in one to nine (median 2.5) of the 31 tests, although without statistical significance. Conclusion: HBO treatment was feasible and resulted in a meaningful improvement of cognitive functioning in one out of seven patients. Overall there was a small but not significant improvement. (orig.)

  13. Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain

    International Nuclear Information System (INIS)

    Hulshof, M.C.C.M.; Sminia, P.; Gonzalez, D.G.; Stark, N.M.; Smeding, H.M.M.; Kleij, A. van der

    2002-01-01

    Purpose: Analysis of the feasibility and effect of hyperbaric oxygen treatment (HBO) on cognitive functioning in patients with cognitive disorders after irradiation of the brain. Patients and Method: Seven patients with cognitive impairment after brain irradiation, with an interval of at least 1.5 years after treatment, were treated with 30 sessions of HBO in a phase I-II study. A comprehensive neuropsychological test battery was performed before treatment, at 3 and 6 months thereafter. Patients were randomized into an immediate treatment group and a delayed treatment group. The delayed group had a second neurospychological test at 3 months without treatment in that period and started HBO thereafter. Results: All eligible patients completed the HBO treatment and the extensive neuropsychological testing. One out of seven patients had a meaningful improvement in neuropsychological functioning. At 3 months there was a small, but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment. Six out of seven patients eventually showed improvement after HBO in one to nine (median 2.5) of the 31 tests, although without statistical significance. Conclusion: HBO treatment was feasible and resulted in a meaningful improvement of cognitive functioning in one out of seven patients. Overall there was a small but not significant improvement. (orig.)

  14. Hippocampal Neuron Number Is Unchanged 1 Year After Fractionated Whole-Brain Irradiation at Middle Age

    International Nuclear Information System (INIS)

    Shi Lei; Molina, Doris P.; Robbins, Michael E.; Wheeler, Kenneth T.; Brunso-Bechtold, Judy K.

    2008-01-01

    Purpose: To determine whether hippocampal neurons are lost 12 months after middle-aged rats received a fractionated course of whole-brain irradiation (WBI) that is expected to be biologically equivalent to the regimens used clinically in the treatment of brain tumors. Methods and Materials: Twelve-month-old Fischer 344 X Brown Norway male rats were divided into WBI and control (CON) groups (n = 6 per group). Anesthetized WBI rats received 45 Gy of 137 Cs γ rays delivered as 9 5-Gy fractions twice per week for 4.5 weeks. Control rats were anesthetized but not irradiated. Twelve months after WBI completion, all rats were anesthetized and perfused with paraformaldehyde, and hippocampal sections were immunostained with the neuron-specific antibody NeuN. Using unbiased stereology, total neuron number and the volume of the neuronal and neuropil layers were determined in the dentate gyrus, CA3, and CA1 subregions of hippocampus. Results: No differences in tissue integrity or neuron distribution were observed between the WBI and CON groups. Moreover, quantitative analysis demonstrated that neither total neuron number nor the volume of neuronal or neuropil layers differed between the two groups for any subregion. Conclusions: Impairment on a hippocampal-dependent learning and memory test occurs 1 year after fractionated WBI at middle age. The same WBI regimen, however, does not lead to a loss of neurons or a reduction in the volume of hippocampus

  15. Structural alterations of the DNA in cerebellar neurons after whole-brain irradiation

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Winstein, R.E.; Kaufman, K.; Ritter, P.

    1981-01-01

    Male Sprague-Dawley rats weighing 260 to 280 g were whole-brain-irradiated with x-ray doses of 433, 867, 1083, 1300, 1516, and 1713 rad. Over the next 2.25 years rats were killed at various times, and the state of the DNA in their cerebellar neurons was examined by sedimentation through alkaline sucrose gradients in reorienting zonal rotors. The data were analyzed as the percentage of the sedimenting DNA with sedimentation coefficients greater than 300 S, an arbitrarily selected category of no defined molecular significance. The general pattern at all doses consisted first of a slow return to the unirradiated DNA state that was relatively dose dependent. This was followed by an increase in the amount of DNA sedimenting >300 S; both the extent and time course of this increase appeared to be dose dependent. Finally, the DNA degraded at a relatively dose independent rate. There was little change in the neuronal DNA from unirradiated rats during this study. The data suggest that increases in the amount of fast-sedimenting DNA observed 30 to 80 weeks after low to moderate doses of whole-brain irradiation represent a type of DNA damage rather than repair and that this damage ultimately results in degradation of the neuronal DNA and death of the rat

  16. The state of glutathion system of blood, brain and liver of white rats after chronic gamma-irradiation

    International Nuclear Information System (INIS)

    Petushok, N.Eh.; Lashak, L.K.; Trebukhina, R.V.

    1999-01-01

    The effects of 3-fold gamma-irradiation in total dose 0,75 Gy on the glutathion system in different periods after exposure (1 hour, 1 day, 1 and 4 weeks) in blood, brain and liver of white rats were studied. It was concluded that liver and brain have higher ability to maintain the stability of antioxidant system than blood has. After shot disturbances caused by irradiation in brain and liver the state of glutathion system of detoxication has normalized, while concentration of malonic dialdehyde was raised in all terms. The most pronounced changes of antioxidant system were registered in blood at early terms (1 hour) after irradiation that was manifested in increasing of reduced glutathion content, raising of glutathion reductase and catalase activity. In remote period the activity of this system in blood was exhausted

  17. The effect of high energy electron irradiation on blood-brain barrier permeability to haloperidol and stobadin in rats

    Energy Technology Data Exchange (ETDEWEB)

    Trnovec, T; Kallay, Z [Komenskeho Univ., Bratislava (Czechoslovakia). Inst. of Preventive and Clinical Medicine; Volenec, K [Karlova Univ., Hradec Kralove (Czechoslovakia). Lekarska Fakulta; Bezek, S; Durisova, M; Scasnar, V; Kubu, M [Slovenska Akademia Vied, Bratislava (Czechoslovakia). Ustav Experimentalnej Farmakologie; Svoboda, V [Medical Academy J.E. Purkyne, Hradec Kralove (Czechoslovakia)

    1991-10-01

    The heads of rats were irradiated by 4 MeV electrons in doses 90, 180, and 360 Gy. The observed times of deaths ranged 120-600, 60-420, and 150-370 min after 90, 180, and 360 Gy, respectively. A dose dependent decrease of the brain uptake index of haloperidol was observed 1 and 3 h post radiation. On the other hand an increased brain uptake index was found for stobadin after head irradiation with doses of 180 and 360 Gy. Regional cerebral blood flow, blood pressure, and heart rate were not significantly altered in the period following irradiation with 180 Gy. The observed changes in blood-brain barrier (BBB) permeability seem to be the result of the damaged function of morphological structures forming the BBB rather than altered regional blood flow. (orig.).

  18. Primary experimental studies on mid-infrared FEL irradiation on dental substances at BFEL

    CERN Document Server

    Biao, Z J; Gao Xue Ju; He Wei; Huang Yu Ying; Li Yong Gui; LiuNianQing; Wang Min Kai; Wu Gan; Yan Xue Pin; Zhang Guo Qing

    2001-01-01

    A free electron laser (FEL) with its characteristics of wide wavelength tunability, ultrashort pulse time structure, and high peak power density is predominantly superior to all other conventional lasers in applications. Several experimental studies on mid-infrared FEL irradiation on dental enamel and dentine were performed at the Beijing FEL. Experimental aims were to investigate changes in the hardness, ratios of P to Ca and Cs before and after irradiation on samples with a characteristic absorption wavelength of 9.66 mu m, in the colors of these sample surfaces after irradiation with different wavelengths around the peak wavelength. The time dependence of temperature of the dentine sample was measured with its ps pulse effects compared to that with a continuous CO sub 2 laser. FTIR absorption spectra in the range of 2.5-15.4 mu m for samples of these hard dental substances and pure hydroxyapatite were first examined to decide their chemical components and absorption maximums. Primary experimental results w...

  19. Bystander-induced apoptosis and premature differentiation in primary urothelial explants after charged particle microbeam irradiation

    International Nuclear Information System (INIS)

    Belyakov, O.V.; Folkard, M.; Mothersill, C.; Prise, K.M.; Michael, B.D.

    2002-01-01

    The ureter primary explant technique was developed to study bystander effects under in vivo like conditions where stem and differentiated cells are present. Irradiation was performed with a 3 He 2+ charged particle microbeam available at the Gray Cancer Institute, with high (∼2 μm) precision. Tissue sections from porcine ureters were pre-irradiated with the microbeam at a single location with 10 3 He 2+ particles (5 MeV; LET 70 keV.μm -1 ). After irradiation, the tissue section was incubated for 7 days, thus allowing the explant outgrowth to form. Total cellular damage (total fraction of micronucleated and apoptotic cells) was measured according to morphological criteria. Apoptosis was also assessed using a 3'-OH DNA end-labelling technique. Premature differentiation was estimated using antibodies to uroplakin III, a specific marker of terminal urothelial differentiation. Results of our experiments demonstrated a significant bystander-induced differentiation and a less significant increase in apoptotic and micronucleated cells. A hypothesis based on the protective nature of the bystander effect is proposed. (author)

  20. Induction and repair of strand breaks and 3'-hydroxy terminals in the DNA of mouse brain following gamma irradiation

    International Nuclear Information System (INIS)

    Yoshizawa, K.; Furuno, I.; Yada, T.; Matsudaira, H.

    1978-01-01

    DNA was isolated from mouse brain after in vivo γ-ray irradiation, treated with endonuclease S 1 from Aspergillus oryzae if necessary, and analysed further by alkaline and neutral sucrose gradient centrifugation. In parallel, its template activity was determined by DNA polymerase (EC 2.7.7.7, enzyme A of Klenow from Escherichia coli) assay as described previously. Similar experiments were performed with cultured mouse leukaemia cells (L5178Y) irradiated in vitro at 0 0 C. (Auth.)

  1. Mechanical Properties of Post Irradiation Primary Cooling Piping of Bandung Research Reactor

    International Nuclear Information System (INIS)

    Histori; Renaningsih S; Sri Nitiswati; Ari Triyadi

    2003-01-01

    Testing on primary coolant piping of research reactor Bandung have been done. Primary coolant piping were made from Al 6061-T6. The goal of this activity is to investigate the mechanical properties changes caused by aging process after 33 years in irradiated. Type of testing i.e visual examination, thickness measurement, tensile and hardness test were done. The test data shown that there was a deposit at the inside surface of pipe, thickness decreased about 0.2 mm, tensile strength is 293 MPa, yield strength is 262 MPa, while the hardness is about 83 HRE (mean value). The test data than compared with ASTM standard. As the conclusion tensile and yield strength of pipe still fulfill the ASTM requirements, except the hardness is unsignificantly less/decreased. (author)

  2. Alteration of UV primary fluorescence of vital tumor cells following irradiation with neutrons and gamma rays

    International Nuclear Information System (INIS)

    Merkle, K.

    1980-01-01

    The change of UV primary fluorescence intensity of vital unstained cells of Ehrlich ascites carcinoma after 60 Co-gamma and neutron irradiation was investigated. The mean neutron energy was 6.2 MeV. Fluorescence intensity was detected using impulse cytophotometry. The UV intensity of single cells was measured in the spectral range from 300-400 nm. An monotonous increase of dose-effect curves and a maximum at 3.5 Gy (neutrons) and 30 Gy (γ-rays) was obtained. The first relevant increase of fluorescence intensity was detected at 0.4 Gy (neutrons) and 0.75 Gy (γ-rays). Factors influencing the increase and decrease of primary fluorescence behavior of vital cells are discussed. (author)

  3. The formation of tigroid substance during postnatal maturation of the brain of mice after pre- and perinatal X-irradiation

    International Nuclear Information System (INIS)

    Konermann, G.; Schwald, I.

    1980-01-01

    Using Nissl stained slices of postnatal brain, tigroid formation in neurons of the cortex, thalamus, cerebellum, hippocampus, gyrus dentatus and nucleus mot. trigemini was examined in X-irradiated mice. Following exposure on days 13, 16, 18,5 or 22 post conception with doses ranging grom 0.5 Gy to 3.0 Gy tigroid formation was studied by means of a selective microphotometrical measurement technique. After irradiation, a fluctuating diminution in the tigroid density was observed in relation to the controls. It was dependent both on the dose and on the stage of development during exposure. In several brain regions fluctuating tigroid responses, being most pronounced during the critical periods of postnatal brain maturation, resulted in a longterm compensation of a deficit in the tigroid density after irradiation with 0.5 Gy. After the higher doses the density diminution was either not compensated or was progressive. The late tigroid responses decrease from irradiation on day 13 p.c. to irradiation day 22 p.c. Hence, this type of late maturation impairment was either extended through several cell generations or it was induced to a lesser degree in the early postmitotic neurons. Changes in the total RNA-content of the brain are concomitant with the third week after birth. The tigroid reactions were interpreted as a chain of interdependent processes of retardation and stabilization. Accordingly, to obtain a better understanding of long-term maturation defects, a comprehensive evaluation of the whole chain of events will be required. (orig.) [de

  4. Primary gonadal damage following treatment of brain tumors in childhood

    International Nuclear Information System (INIS)

    Ahmed, S.R.; Shalet, S.M.; Campbell, R.H.; Deakin, D.P.

    1983-01-01

    Gonadal function was studied in two groups of children previously treated for medulloblastoma with surgery followed by postoperative craniospinal irradiation. In group 1 but not in group 2, the children also received adjuvant chemotherapy for one to two years. All children in group 1 received a nitrosourea (BCNU or CCNU), plus vincristine in four and procarbazine in three patients. The nine children in group 1 showed clinical and biochemical evidence of gonadal damage with elevated serum FSH concentrations and, in the boys, small testes for their stage of pubertal development. In group 2 (n . 8), each child had completed pubertal development normally, the boys had adult sized testes and the girls regular menses. Gonadotropin values were normal in all eight children. We conclude that nitrosoureas were responsible for the gonadal damage in the children in group 1, with procarbazine also contributing to the damage in the three children who received this drug. In view of the limited proved value of adjuvant chemotherapy with nitrosoureas in the treatment of medulloblastoma, recognition of this serious complication of cytotoxic drug therapy may necessitate reassessing in which subgroups of children with medulloblastoma the benefits of adjuvant chemotherapy outweigh the complications

  5. A longitudinal analysis of regional brain volumes in macaques exposed to X-irradiation in early gestation.

    Directory of Open Access Journals (Sweden)

    Kristina Aldridge

    Full Text Available Early gestation represents a period of vulnerability to environmental insult that has been associated with adult psychiatric disease. However, little is known about how prenatal perturbation translates into adult brain dysfunction. Here, we use a longitudinal study design to examine the effects of disruption of early gestational neurogenesis on brain volume in the non-human primate.Five Rhesus macaques were exposed to x-irradiation in early gestation (E30-E41, and four control monkeys were sham-irradiated at comparable ages. Whole brain magnetic resonance imaging was performed at 6 months, 12 months, and 3 and 5 years of age. Volumes of whole cerebrum, cortical gray matter, caudate, putamen, and thalamus were estimated using semi-automated segmentation methods and high dimensional brain mapping. Volume reductions spanning all ages were observed in irradiated monkeys in the putamen (15-24%, p = 0.01 and in cortical gray matter (6-15%, p = 0.01. Upon covarying for whole cerebral volume, group differences were reduced to trend levels (putamen: p = 0.07; cortical gray matter: p = 0.08. No group-by-age effects were significant.Due to the small number of observations, the conclusions drawn from this study must be viewed as tentative. Early gestational irradiation may result in non-uniform reduction of gray matter, mainly affecting the putamen and cerebral cortex. This may be relevant to understanding how early prenatal environmental insult could lead to brain morphological differences in neurodevelopmental diseases.

  6. Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

    Science.gov (United States)

    Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

    2016-12-01

    The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, pbrain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Histological changes in the hypothalamus and ependyne in the third ventricle of the brain in sheep after irradiation

    International Nuclear Information System (INIS)

    Stanikova, A.; Pastorova, B.

    2008-01-01

    We focused on changes in the hypothalamic neuro-secretion, morphology of brain ventricle ependyma of sheep after irradiation and hormonal stimulation. We observed sheep in anoestrous. Synchronization was ensured with Agelin for 10 days. On day 5 after instilation of sponges, we started with irradiation lasting for 5 days (2.5 Gy) and on day 10 we stimulated the sheep with SG and FSH. The samples from hypothalamus intended for REM, were processed according to Murakami et al. (1977). Hormonal treatment in combination with irradiation produced qualitative changes, more marked in the ependyma than in the hypothalamus. (authors)

  8. Structural brain alterations in primary open angle glaucoma: a 3T MRI study

    OpenAIRE

    Jieqiong Wang; Ting Li; Bernhard A. Sabel; Zhiqiang Chen; Hongwei Wen; Jianhong Li; Xiaobin Xie; Diya Yang; Weiwei Chen; Ningli Wang; Junfang Xian; Huiguang He

    2016-01-01

    Glaucoma is not only an eye disease but is also associated with degeneration of brain structures. We now investigated the pattern of visual and non-visual brain structural changes in 25 primary open angle glaucoma (POAG) patients and 25 age-gender-matched normal controls using T1-weighted imaging. MRI images were subjected to volume-based analysis (VBA) and surface-based analysis (SBA) in the whole brain as well as ROI-based analysis of the lateral geniculate nucleus (LGN), visual cortex (V1/...

  9. Gamma-knife radiosurgery for metastatic brain tumors from primary lung cancer

    International Nuclear Information System (INIS)

    Uchiyama, Bine; Satoh, Ken; Saijo, Yasuo

    1998-01-01

    Forty patients with metastatic brain tumors from primary lung cancer underwent radiosurgery (γ-knife). We retrospectively compared their prior treatment history, number of metastatic foci, and performance status, to evaluate the effects of, and indications for, γ-knife therapy. After both the primary and the metastatic tumors were controlled, performance status could be used as an index in the choice of γ-knife therapy. Our results demonstrate that repeated γ-knife radiosurgeries prolonged survival time. Gamma-knife radiosurgery improves quality of life and prognosis of patients with metastatic brain tumors. (author)

  10. Malignant primary germ-cell tumor of the brain

    International Nuclear Information System (INIS)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh

    1983-01-01

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported.FThe first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe.FTotal removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule.FHistological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma.FPrimary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma.FIn this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy. (author)

  11. Primary pleuropulmonary synovial sarcoma with brain metastases in a paediatric patient: an unusual presentation.

    Science.gov (United States)

    Chirmade, Pushpak Chandrakant; Parikh, Sonia; Anand, Asha; Panchal, Harsha; Patel, Apurva; Shah, Sandip

    2017-01-01

    Primary lung neoplasms are rare in children. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumour. Synovial sarcoma (SS) accounts for approximately 1% of all childhood malignancies. In absolute terms, the SS of the lungs and pleura are extremely rare and pose a diagnostic difficulty. Soft tissue sarcomas usually have a high potential for metastases, however, metastasis to the brain is rare, even in widely disseminated disease, and it has been described only in 3 case reports previously. Primary pleuropulmonary SS with brain metastases is even rarer. Here we present a case of an 11-year-old boy who presented with respiratory complaints, viz. fever and cough for 20 days. Initial impression was lung abscess, however, on histopathological, immunohistochemical and molecular study, the disorder was diagnosed as synovial sarcoma. After a week from the first consult, the child developed neurological symptoms, viz., an episode of convulsion and gradually worsening power of the lower limb. Computed tomography scan and Magnetic Resonance Spectroscopy was suggestive of brain metastases. Given the rarity of primary lung neoplasms in children, clinical detection remains a challenge. Delayed diagnoses are common as respiratory symptoms may be attributed to inflammatory or infective processes. Primary pleuropulmonary synovial sarcoma is a rare tumour and it is not known to commonly metastasise to the brain. Though rare, primary pleuropulmonary SS should be considered an important differential among peadiatric primary lung neoplasms due to its potential for curability if detected early, and more aggressive metastatic pattern, e.g. brain metastases making early detection imperative.

  12. Primary and aggregate color centers in proton irradiated LiF crystals and thin films for luminescent solid state detectors

    International Nuclear Information System (INIS)

    Piccinini, M; Ambrosini, F; Ampollini, A; Bonfigli, F; Libera, S; Picardi, L; Ronsivalle, C; Vincenti, M A; Montereali, R M

    2015-01-01

    Proton beams of 3 MeV energy, produced by the injector of a linear accelerator for proton therapy, were used to irradiate at room temperature lithium fluoride crystals and polycrystalline thin films grown by thermal evaporation. The irradiation fluence range was 10 11 -10 15 protons/cm 2 . The proton irradiation induced the stable formation of primary and aggregate color centers. Their formation was investigated by optical absorption and photoluminescence spectroscopy. The F 2 and F 3 + photoluminescence intensities, carefully measured in LiF crystals and thin films, show linear behaviours up to different maximum values of the irradiation fluence, after which a quenching is observed, depending on the nature of the samples (crystals and films). The Principal Component Analysis, applied to the absorption spectra of colored crystals, allowed to clearly identify the formation of more complex aggregate defects in samples irradiated at highest fluences. (paper)

  13. Primary and aggregate color centers in proton irradiated LiF crystals and thin films for luminescent solid state detectors

    Science.gov (United States)

    Piccinini, M.; Ambrosini, F.; Ampollini, A.; Bonfigli, F.; Libera, S.; Picardi, L.; Ronsivalle, C.; Vincenti, M. A.; Montereali, R. M.

    2015-04-01

    Proton beams of 3 MeV energy, produced by the injector of a linear accelerator for proton therapy, were used to irradiate at room temperature lithium fluoride crystals and polycrystalline thin films grown by thermal evaporation. The irradiation fluence range was 1011-1015 protons/cm2. The proton irradiation induced the stable formation of primary and aggregate color centers. Their formation was investigated by optical absorption and photoluminescence spectroscopy. The F2 and F3+ photoluminescence intensities, carefully measured in LiF crystals and thin films, show linear behaviours up to different maximum values of the irradiation fluence, after which a quenching is observed, depending on the nature of the samples (crystals and films). The Principal Component Analysis, applied to the absorption spectra of colored crystals, allowed to clearly identify the formation of more complex aggregate defects in samples irradiated at highest fluences.

  14. Diagnostic challenges in primary brain stem glioblastoma multiform; a case report

    Directory of Open Access Journals (Sweden)

    Muhammad Taimur Malik, MD

    2017-12-01

    Full Text Available Brainstem gliomas are rare form of primary brain tumors in adult and represent <2% of gliomas. Glioblastomas (GBM are much less common in pediatric patients; adult GBM vary in presentation and response to therapy, and generally have a very poor prognosis. GBM is less common in the brainstem, comprising <2% gliomas and there is therefore limited data available to provide a standard of care. Here we present a case report of a patient who presented with aggressive primary pontine GBM.

  15. The effect of Ginkgo biloba extract on parkinsonisminduced biochemical changes in brain of irradiated rats

    International Nuclear Information System (INIS)

    Abd El-Aziz, E.R.

    2012-01-01

    Parkinson's disease (PD) is the second most common neuro degenerative disorder after Alzheimer's disease. In the present study, neuro modulatory effects of standardized ginkgo biloba extract (EGb 761) and low dose whole-body γ-irradiation in a reserpine model of rat Parkinsonism were investigated. Male Wistar rats were pretreated orally with EGb 761 (100 mg/kg BW/day for 3 weeks) or low dose whole-body γ-irradiation (0.25 Gy once a week for 6 weeks) and their combination (EGb 761 was received during the last three weeks of the irradiation period) and then subjected to intraperitoneal injection of reserpine (5 mg/kg BW dissolved in 1% acetic acid) 24h after last dose of EGb761or radiation. All rats were sacrificed 24h after reserpine injection. Depletion of striatal dopamine (DA) level, increased oxidative stress indicated via depletion of glutathione (GSH), increased malondialdehyde (MDA) and iron levels; decrease of dopamine metabolites metabolizing enzymes; indicated by decrease of glutathione-S transferase (GST) and NADPH-quinone oxidoreductase (NQO) activities; mitochondrial dysfunction; indicated by decline of complex I activity and adenosine triphosphate (ATP) level and increased apoptosis; indicated by the decrease of mitochondrial B cell lymphoma-2 protein (Bcl-2) level and as shown by transmission electron microscope (TEM) were observed in brain of reserpine-induced PD model group, along with behavioral study indicated by increased catalepsy score. Moreover, the level of GSH was correlated with the levels of both DA (r = 0.78) and MDA (r = -0.93). The level of Bcl-2 was correlated with the complex I activity (r = 0.94) and ATP level (r = 0.98). Results revealed that either EGb 761 or irradiation and their combination ameliorated most of the biochemical and behavioral changes induced by reserpine possibly via replenishment of normal glutathione levels. This study revealed that EGb 761, which is a widely used herbal medicine and low dose of whole-body γ-irradiation

  16. Cranial irradiation in patients with brain metastasis. A retrospective study of timing

    International Nuclear Information System (INIS)

    Ampil, F.L.; Burton, G.V.; Mills, G.M.

    1999-01-01

    A retrospective study was conducted to determine the importance of the interval between diagnosis of brain metastasis (BRM) and cranial irradiation (CI). The charts of 92 patients with a known diagnosis of cancer and suspected BRM as shown on radioimaging studies were reviewed retrospectively. The median interval between diagnosis and the onset of CI for BRM was five days; one group of 48 individuals received CI within an interval of five days, and another group of 44 patients after an interval of five days. Symptom palliation, objective responses to CI and survival were evaluated in both groups. Neither symptomatic and objective responses to treatment nor overall survival differed significantly between the patient groups. These observations suggest that while CI is beneficial to most patients with BRM, its timing after the diagnosis of BRM may not seriously affect patient outcome. (author)

  17. Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Ge, Xiao-hui; Liu, Miao-ling; Lin, Qiang; Ren, Xiao-cang; Liu, Yue-e; Chen, Xue-ji; Wang, Dong-ying; Wang, Yong-qiang; Cao, Bin; Li, Zhi-gang

    2013-01-01

    Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer. Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT). From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ 2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ 2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ 2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups. Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent

  18. Primary Damage Characteristics in Metals Under Irradiation in the Cores of Thermal and Fast Reactors

    International Nuclear Information System (INIS)

    Pechenkin, V.A.

    2012-01-01

    For an analysis and forecasting of radiation-induced phenomena in structural materials of WWERs, PWRs and BN reactors the fast neutron fluence is usually used (for structural materials of the reactor cores and internals the fluence of neutrons with energy > 0.1 MeV, for WWER and PWRs vessel steels the fluence of neutrons with energy > 0.5 MeV in Russia and East Europe, and with energy > 1.0 MeV in USA and France). Displacements per atom (dpa) seem to be a more appropriate correlation parameter, because it allows comparing the results of materials irradiation in different neutron energy spectra or with different types of particles (neutrons, ions, fast electrons). Energy spectra of primary knocked atoms (PKA) and 'effective' dpa, which are introduced to take into account the point defect recombination during the relaxation stage of a displacement cascade, can be still better representation of the effect of irradiation on material properties. In this work the results of calculating dose rates (dpa/s, NRT-model), PKA energy spectra and PKA mean energies in metals under irradiation in the cores of Russian reactors WWER-440, WWER-1000 (both power thermal reactors) and BN-600 (power fast reactor) and BR-10 (test fast reactor) are presented. In all the reactors Fe and Zr are considered, with addition of Ti and W in BN-600. 'Effective' dose rates in these metals are calculated. Limitations and uncertainties in the standard dpa formulation (the NRT-dpa) are discussed. IPPE activities in the fields related to the TM subject are considered

  19. Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

    Science.gov (United States)

    Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

    2017-07-01

    Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

  20. Bioelectric activity of childish brain in case of antenatal irradiation caused by Chernobyl accident

    International Nuclear Information System (INIS)

    Igumnov, S.A.; Drozdovich, V.V.; Shal'kevich, V.B.; Sekach, N.S.; Sivolobova, L.A.; Shal'kevich, L.V.; Chujko, Z.A.

    2002-01-01

    Formation of bioelectric activity of the brain was studied in two hundred and fifty children aged 6-7 and 10-12 yrs irradiated prenatally because of Chernobyl accident. The control group consisted of two hundred and fifty children the same age from 'clean' areas of Belarus. The examination included the visual and the computerized analyses of their EEGs as well as the psychiatric examination and the intellectual level assessment. Variants of the age norms and the synchronized borderline EEG were revealed in both groups of the children aged 6-7 yrs. A relevant decrease of the σ and Θ activities levels was registered in the children aged 10-12 yrs. In the both groups. The slow type of EEG in most cases was transformed into the age norm and the synchronized type of EEG. The bioelectric activity was not found to correlate with the dosimetric data. So, the changes of the bioelectric activity revealed showed a distinct age dependency and their frequency in the children exposed to antenatal irradiation did not differ significantly from that in the control group. (authors)

  1. Radiation damage to the normal monkey brain. Experimental study induced by interstitial irradiation

    International Nuclear Information System (INIS)

    Mishima, Nobuya; Tamiya, Takashi; Matsumoto, Kengo; Furuta, Tomohisa; Ohmoto, Takashi

    2003-01-01

    Radiation damage to normal brain tissue induced by interstitial irradiation with iridium-192 seeds was sequentially evaluated by computed tomography (CT), magnetic resonance imaging (MRI), and histological examination. This study was carried out in 14 mature Japanese monkeys. The experimental area received more than 200-260 Gy of irradiation developed coagulative necrosis. Infiltration of macrophages to the periphery of the necrotic area was seen. In addition, neovascularization, hyalinization of vascular walls, and gliosis were found in the periphery of the area invaded by the macrophages. All sites at which the vascular walls were found to have acute stage fibrinoid necrosis eventually developed coagulative necrosis. The focus of necrosis was detected by MRI starting 1 week after the end of radiation treatment, and the size of the necrotic area did not change for 6 months. The peripheral areas showed clear ring enhancement with contrast material. Edema surrounding the lesions was the most significant 1 week after radiation and was reduced to a minimum level 1 month later. However, the edema then expanded once again and was sustained for as long as 6 months. CT did not provide as clear of a presentation as MRI, but it did reveal similar findings for the most part, and depicted calcification in the necrotic area. This experimental model is considered useful for conducting basic research on brachytherapy, as well as for achieving a better understanding of delayed radiation necrosis. (author)

  2. Effect of whole body neutron irradiation on certain enzyme activities in different brain areas in mice

    International Nuclear Information System (INIS)

    Kotb, M.A.; Ashour, A.M.; El-Bassiouni, E.A.

    1994-01-01

    Male swiss albino mice were exposed to whole-body irradiation by fast neutrons of 14 MeV average energy. Two single doses of 0.08 sievert and 0.16 sievert were used, corresponding to fluences of 1.27 X 10 8 and 2.54 X 10 8 n/cm 2 respectively. Two enzymes were assessed in different layers of the cerebrum and cerebellum of mouse brain. Changes in the activities of acid phosphatase (ACP) and succinic dehydrogenase (SDH) were taken to measure alterations in lysosomal and mitochondrial functions respectively. The degrees of lysosomal affection in different layers of the cerebrum were not uniform, while changes in A activity were very prominent in certain layers (e.g. external pyramidal layer, polymorphous cells layer and white matter), they were practically absent in others (e.g. internal pyramidal layer). Stronger effect was noted in the tissue layers of the cerebellum. The activity of SDH decreased as result of fast neutron irradiation. The response was more apparent for this enzyme than for ACP. This indicates more liability for a decrease in energy metabolism with consequent effect on behavioural and physiological functions under central nervous system control. 4 figs., 4 tabs

  3. Benefit of brain prophylactic irradiation in patients suffering from a small-cell bronchial cancer: retrospective study on 289 cases

    International Nuclear Information System (INIS)

    Assouline, A.; Tai, P.; Jancewicz, M.; Joseph, K.; Krzisch, C.; Yu, E.

    2011-01-01

    The authors report a study which aimed at determining the benefit of a brain prophylactic irradiation for patients suffering from a localized small-cell bronchial cancer and in partial response to the local-regional treatment of their disease. A retrospective analysis has been performed on a set of 289 patients who had been treated by chemo-radiotherapy with or without brain prophylactic irradiation between 1981 and 2007. Data are discussed in terms of remission level, survival with respect to the level of response to the local-regional treatment. Depending on this response level the irradiation increases or not the probability of global survival, or the probability of specific survival. Short communication

  4. The Primary Origin of Dose Rate Effects on Microstructural Evolution of Austenitic Alloys During Neutron Irradiation

    International Nuclear Information System (INIS)

    Okita, Taira; Sato, Toshihiko; Sekimura, Naoto; Garner, Francis A.; Greenwood, Lawrence R.

    2002-01-01

    The effect of dose rate on neutron-induced microstructural evolution was experimentally estimated. Solution-annealed austenitic model alloys were irradiated at approximately 400 degrees C with fast neutrons at seven different dose rates that vary more than two orders difference in magnitude, and two different doses were achieved at each dose rate. Both cavity nucleation and growth were found to be enhanced at lower dose rate. The net vacancy flux is calculated from the growth rate of cavities that had already nucleated during the first cycle of irradiation and grown during the second cycle. The net vacancy flux was found to be proportional to (dpa/sec) exp (1/2) up to 28.8 dpa and 8.4 x 10 exp (-7) dpa/sec. This implies that mutual recombination dominates point defect annihilation, in this experiment even though point defect sinks such as cavities and dislocations were well developed. Thus, mutual recombination is thought to be the primary origin of the effect of dose rate on microstructural evolution

  5. Primary photoluminescence in as-neutron (electron) -irradiated n-type 6H-SiC

    International Nuclear Information System (INIS)

    Zhong, Z.Q.; Wu, D.X.; Gong, M.; Wang, O.; Shi, S.L.; Xu, S.J.; Chen, X.D.; Ling, C.C.; Fung, S.; Beling, C.D.; Brauer, G.; Anwand, W.; Skorupa, W.

    2006-01-01

    Low-temperature photoluminescence spectroscopy has revealed a series of features labeled S 1 , S 2 , S 3 in n-type 6H-SiC after neutron and electron irradiation. Thermal annealing studies showed that the defects S 1 , S 2 , S 3 disappeared at 500 deg. C. However, the well-known D 1 center was only detected for annealing temperatures over 700 deg. C. This experimental observation not only indicated that the defects S 1 , S 2 , S 3 were a set of primary defects and the D 1 center was a kind of secondary defect, but also showed that the D 1 center and the E 1 , E 2 observed using deep level transient spectroscopy might not be the same type of defects arising from the same physical origin

  6. UVA and UVB irradiation differentially regulate microRNA expression in human primary keratinocytes.

    Directory of Open Access Journals (Sweden)

    Anne Kraemer

    Full Text Available MicroRNA (miRNA-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2, which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis.

  7. UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

    Science.gov (United States)

    Kraemer, Anne; Chen, I-Peng; Henning, Stefan; Faust, Alexandra; Volkmer, Beate; Atkinson, Michael J.; Moertl, Simone; Greinert, Ruediger

    2013-01-01

    MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2), which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis. PMID:24391759

  8. Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism.

    Science.gov (United States)

    Riedl, Julia; Preusser, Matthias; Nazari, Pegah Mir Seyed; Posch, Florian; Panzer, Simon; Marosi, Christine; Birner, Peter; Thaler, Johannes; Brostjan, Christine; Lötsch, Daniela; Berger, Walter; Hainfellner, Johannes A; Pabinger, Ingrid; Ay, Cihan

    2017-03-30

    Venous thromboembolism (VTE) is common in patients with brain tumors, and underlying mechanisms are unclear. We hypothesized that podoplanin, a sialomucin-like glycoprotein, increases the risk of VTE in primary brain tumors via its ability to induce platelet aggregation. Immunohistochemical staining against podoplanin and intratumoral platelet aggregates was performed in brain tumor specimens of 213 patients (mostly high-grade gliomas [89%]) included in the Vienna Cancer and Thrombosis Study, a prospective observational cohort study of patients with newly diagnosed cancer or progressive disease aimed at identifying patients at risk of VTE. Platelet aggregation in response to primary human glioblastoma cells was investigated in vitro. During 2-year follow-up, 29 (13.6%) patients developed VTE. One-hundred fifty-one tumor specimens stained positive for podoplanin (33 high expression, 47 medium expression, 71 low expression). Patients with podoplanin-positive tumors had lower peripheral blood platelet counts ( P < .001) and higher D-dimer levels ( P < .001). Podoplanin staining intensity was associated with increasing levels of intravascular platelet aggregates in tumor specimens ( P < .001). High podoplanin expression was associated with an increased risk of VTE (hazard ratio for high vs no podoplanin expression: 5.71; 95% confidence interval, 1.52-21.26; P = 010), independent of age, sex, and tumor type. Podoplanin-positive primary glioblastoma cells induced aggregation of human platelets in vitro, which could be abrogated by an antipodoplanin antibody. In conclusion, high podoplanin expression in primary brain tumors induces platelet aggregation, correlates with hypercoagulability, and is associated with increased risk of VTE. Our data indicate novel insights into the pathogenesis of VTE in primary brain tumors. © 2017 by The American Society of Hematology.

  9. Palliation of AIDS-related primary lymphoma of the brain: observations from a multi-institutional database

    International Nuclear Information System (INIS)

    Corn, Benjamin W.; Donahue, Bernadine R.; Rosenstock, Jeffrey G.; Cooper, Jay S.; Yang, Xie; Brandon, Alfred H.; Hegde, Hradaya H.; Sherr, David L.; Fisher, Scot A.; Berson, Anthony; Han, Hoke; Wahab, Maye Abdel; Koprowski, Christopher D.; Ruffer, James E.; Curran, Walter J.

    1997-01-01

    Purpose: To catalogue the presenting symptoms of patients with AIDS who are presumed to have primary central nervous system lymphoma (PCNSL). To document the palliative efficacy of cranial irradiation (RT) relative to the endpoints of complete and overall response for the respective symptoms. Methods: An analysis of 163 patients with AIDS-related PCNSL who were evaluated at nine urban hospitals was performed. These patients were treated for PCNSL after the establishment of a tissue diagnosis or on a presumptive basis after failing empiric treatment for toxoplasmosis. All patients were treated between 1983 and 1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and steroids (>90% dexamethasone). Because multiple fractionation schemes were used, prescriptions were converted to biologically effective doses according to the formula, Gy 10 = Total Dose x (1 + fractional dose/α-β); using an α-β value of 10. Results: The overall palliative response rate for the entire group was 53%. In univariate analysis, trends were present associating complete response rates with higher performance status (KPS ≥ 70 vs. KPS ≤ 60 = 17% vs. 5%), female gender (women vs. men = 29% vs. 8%), and the delivery of higher biologically effective doses (BED) of RT (Gy 10 > 39 vs. ≤ 39 = 20% vs. 5%). In multivariate analysis of factors predicting complete response, both higher KPS and higher BED retained independent significance. A separate univariate analysis identified high performance status (KPS ≥ 70 vs. KPS ≤ 60 = 71% vs. 47%), and young age (≤ 35 vs. > 35 = 61% vs. 40%) as factors significantly correlating with the endpoint of the overall response. In multivariate analysis, high performance status and the delivery of higher biologically effective doses of irradiation correlated significantly with higher overall response rates. Conclusion: Most AIDS patients who develop symptoms from primary lymphoma of the brain can achieve some palliation from a management

  10. Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Miyoshi, Ko, E-mail: miyoshi@cc.okayama-u.ac.jp [Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558 (Japan); Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato [Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558 (Japan)

    2009-10-30

    The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li{sub 2}CO{sub 3} were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

  11. Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

    International Nuclear Information System (INIS)

    Miyoshi, Ko; Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato

    2009-01-01

    The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li 2 CO 3 were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

  12. Is there an increased risk of second primaries following prostate irradiation?

    International Nuclear Information System (INIS)

    Movsas, Benjamin; Hanlon, Alexandra L.; Pinover, Wayne; Hanks, Gerald E.

    1998-01-01

    Purpose: To assess the risk of developing a second primary cancer following prostate irradiation compared to the underlying risk in patients with prostate cancer. Methods and Materials: The baseline rate of secondary cancers following prostate cancer was obtained from a study of 18,135 patients from the Connecticut Tumor Registry, of whom only 12.5% received radiotherapy. These patients, with a mean age of 72 and a mean follow-up of 3.9 years, were compared to a cohort of 543 patients (median age 70) with similar follow-up (median 3.9 years), all of whom were treated with definitive radiotherapy at Fox Chase Cancer Center. The possible association between various covariates (age, dose, palpation stage, field size, Gleason score, pretreatment PSA) and the development of a secondary cancer was assessed. Results: 1,053 of 18,135 patients (5.8%) in the Connecticut Tumor Registry developed a second primary cancer compared with 31 of 543 (5.7%) patients treated with prostate radiation (p = 0.99). Although this risk increases gradually over time, it is not significantly different, at any time period, between the two groups of patients. Of the 31 secondary primaries in the irradiated group, 82% had a history of tobacco and/or alcohol use. Only melanomas were significantly increased compared to the expected rate in an age-matched population (p <0.001). Five of the 31 secondary cancers occurred within the radiation field (four bladder, one colon), four within 3 years and only one occurred 9 years after radiotherapy. No association was found between age (<70 vs. ≥70 and as a continuous variable), dose (<74 vs. ≥74 Gy), palpation stage (< T2C vs. ≥T2C), field size (prostate vs. pelvic), radiation technique (conventional vs. conformal), Gleason score (2-6 vs. 7-10), or pretreatment PSA (<15 vs. ≥15 and as a continuous variable) and the risk of developing a second primary. Although a lower radiation dose (as a continuous variable) correlated with an increased risk of

  13. Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of {sup 56}Fe Irradiation on the Brain

    Energy Technology Data Exchange (ETDEWEB)

    Haley, Gwendolen E. [Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR (United States); Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR (United States); Villasana, Laura; Dayger, Catherine; Davis, Matthew J. [Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR (United States); Raber, Jacob, E-mail: raberj@ohsu.edu [Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR (United States); Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR (United States); Department of Neurology, Oregon Health and Science University, Portland, OR (United States)

    2012-11-01

    Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles ({epsilon}2, {epsilon}3, and {epsilon}4) and, compared to apoE3, apoE4 increases the risk of developing Alzheimer disease and cognitive impairments following various environmental challenges. Exposure to irradiation, including that of {sup 56}Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after {sup 56}Fe irradiation. Changes in reactive oxygen species (ROS) can affect cognition and are induced by irradiation. Therefore, after cognitive testing, we assessed hippocampal ROS levels in ex vivo brain slices, using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of 3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD, and apoE were assessed using Western blotting analysis. Results: In the water maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4 mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels in apoE3 but not apoE2 or apoE4 mice. Conclusions: The short-term effects of {sup 56}Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.

  14. Apolipoprotein E Genotype-Dependent Paradoxical Short-Term Effects of 56Fe Irradiation on the Brain

    International Nuclear Information System (INIS)

    Haley, Gwendolen E.; Villasana, Laura; Dayger, Catherine; Davis, Matthew J.; Raber, Jacob

    2012-01-01

    Purpose: In humans, apolipoprotein E (apoE) is encoded by three major alleles (ε2, ε3, and ε4) and, compared to apoE3, apoE4 increases the risk of developing Alzheimer disease and cognitive impairments following various environmental challenges. Exposure to irradiation, including that of 56 Fe, during space missions poses a significant risk to the central nervous system, and apoE isoform might modulate this risk. Methods and Materials: We investigated whether apoE isoform modulates hippocampus-dependent cognitive performance starting 2 weeks after 56 Fe irradiation. Changes in reactive oxygen species (ROS) can affect cognition and are induced by irradiation. Therefore, after cognitive testing, we assessed hippocampal ROS levels in ex vivo brain slices, using the ROS-sensitive fluorescent probe, dihydroethidium (DHE). Brain levels of 3-nitrotyrosine (3-NT), CuZn superoxide dismutase (CuZnSOD), extracellular SOD, and apoE were assessed using Western blotting analysis. Results: In the water maze, spatial memory retention was impaired by irradiation in apoE2 and apoE4 mice but enhanced by irradiation in apoE3 mice. Irradiation reduced DHE-oxidation levels in the enclosed blade of the dentate gyrus and levels of 3-NT and CuZnSOD in apoE2 but not apoE3 or apoE4 mice. Finally, irradiation increased apoE levels in apoE3 but not apoE2 or apoE4 mice. Conclusions: The short-term effects of 56 Fe irradiation on hippocampal ROS levels and hippocampus-dependent spatial memory retention are apoE isoform-dependent.

  15. Hypotonic hyponatremia by primary polydipsia caused brain death in a 10-year-old boy

    Directory of Open Access Journals (Sweden)

    A Ra Ko

    2015-09-01

    Full Text Available Hypotonic hyponatremia by primary polydipsia can cause severe neurologic complications due to cerebral edema. A 10-year-and-4-month-old boy with a psychiatric history of intellectual disability and behavioral disorders who presented with chief complaints of seizure and mental change showed severe hypotonic hyponatremia with low urine osmolality (serum sodium, 101 mmol/L; serum osmolality, 215 mOsm/kg; urine osmolality, 108 mOsm/kg. The patient had been polydipsic for a few months prior, and this had been worse in the previous few days. A diagnosis of hypotonic hyponatremia caused by primary polydipsia was made. The patient was in a coma, and developed respiratory arrest and became brain death shortly after admission, despite the treatment. The initial brain magnetic resonance imaging showed severe brain swelling with tonsillar and uncal herniation, and the patient was declared as brain death. It has been reported that antidiuretic hormone suppression is inadequate in patients with chronic polydipsia, and that this inadequate suppression of antidiuretic hormone is aggravated in patients with acute psychosis. Therefore, hyponatremia by primary polydipsia, although it is rare, can cause serious and life-threatening neurologic complications.

  16. Aluminium and Gamma Irradiation Induced Oxidative Damage in Brain Tissue of Male Rats - Protective Role of Ferulic Acid

    International Nuclear Information System (INIS)

    Mansour, S.Z.; Hanafi, N.; Noaman, E.

    2011-01-01

    The current study was carried out to investigate the potential role of ferulic acid (FA) against Aluminium chloride (AlCl 3 ), γ- radiation either alone or combination induced oxidative stress in brain tissue of Wistar rats. The period of the experiment was eight weeks. Animals were administrated by aluminium chloride at a dose of 8.5 mg/kg/day and exposed to a single dose (4 Gy) of γ-radiation. FA was administered orally (50 mg/Kg body weight)/day. Histopathological observations and myeloid protein distribution were recorded in brain tissue. Induction of oxidative stress was recorded after all exposures. Brain tissue of AlCl 3 and γ- irradiation treatments either alone or combined revealed many altered changes and myeloid protein distribution. Also a decrease in serotonin concentration was recorded. An increase in Malonaldialdahyde (MDA) and acetylcholinesterase activity and percentage of saturated fatty acids in plasma and brain tissue was recorded. Reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) in blood and brain showed a significant decrease. Treatment of AlCl 3 loaded animals by FA showed simple atrophy as shrunken morphology saw in amyotrophic lateral sclerosis and a decrease in myeloid protein deposition. FA treatment of AlCl 3 loaded or irradiated animals represented a significant increase in serotonin concentration and ameliorated affects on oxidative stress markers, acetylcholinesterase activity and percentage of saturated fatty acids in plasma and brain tissue. In conclusion FA has a role in reducing the oxidative stress of AlCl 3 and γ- irradiation on brain tissue of rats

  17. Phasic changes of blood-brain-barrier permeability in mice after non-uniform γ-irradiation

    International Nuclear Information System (INIS)

    Ushakov, I.B.

    1986-01-01

    Early changes of blood-brain barrier (BBB) permeability in mice after irradiation of head or body were studied. The experiments were carried out on male-mice F 1 (C57xCBA) with medium mass of 25.1±0.8 g, irradiated in 2.58 C/kg dose to head or body. Correlation between BBB permeability decrease and radiation disease clinical manifestation frequency is determined. In early periods after irradiation, minimum two phases of BBB permeability change were observed: increase (0-2 h) and decrease (2-6 h) of permeability. BBB changes were expressed in later periods (24-120 h) as well. BBB permeability progressively increased after irradiation of head. According to the author's suggestion, this phenomenon gives evidence of generalization of vessel permeability disturbance (primarily of brain vessels) which leads to complete BBB dysfunction and to the loss of this morphofunctional formation's ability to perform its protective function. When considering BBB permeability connection with the frequency of neurologycal sign (tremor, ataxia) appearance, reversible correlation between these indicators is marked, beginning with the first period. The presence connection of fluid redistribution between blood and internal brain medium (edema growth) with the development of clinical manifestations of CNS affection is suggested

  18. WE-EF-BRA-10: Prophylactic Cranial Irradiation Reduces the Incidence of Brain Metastasis in a Mouse Model of Metastatic Breast Cancerr

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D; Debeb, B; Larson, R; Diagaradjane, P; Woodward, W [MD Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Prophylactic cranial irradiation (PCI) is a clinical technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with acute lymphoblastic leukemia and small-cell lung cancer. We examined whether PCI could benefit breast cancer patients at high risk of developing brain metastases. Methods: We utilized our mouse model in which 500k green fluorescent protein (GFP)-labeled breast cancer cells injected into the tail vein of SCID/Beige mice resulted in brain metastases in approximately two-thirds of untreated mice. To test the efficacy of PCI, one set of mice was irradiated five days after cell injection with a single fraction of 4-Gy (two 2-Gy opposing fields) whole-brain irradiation on the XRAD 225Cx small-animal irradiator. Four controls were included: a non-irradiated group, a group irradiated two days prior to cell injection, and two groups irradiated 3 or 6 weeks after cell injection. Mice were sacrificed four and eight weeks post-injection and were evaluated for the presence of brain metastases on a fluorescent stereomicroscope. Results: The incidence of brain metastasis in the non-irradiated group was 77% and 90% at four and eight weeks, respectively. The PCI group had a significantly lower incidence, 20% and 30%, whereas the other three control groups had incidence rates similar to the non-treated control (70% to 100%). Further, the number of metastases and the metastatic burden were also significantly lower in the PCI group compared to all other groups. Conclusion: The timing of irradiation to treat subclinical disease is critical, as a small dose of whole-brain irradiation given five days after cell injection abrogated tumor burden by greater than 90%, but had no effect when administered twenty-one days after cell injection. PCI is likely to benefit breast cancer patients at high risk of developing brain metastases and should be strongly considered in the clinic.

  19. Recall dermatitis caused by reexposition of decotaxel following irradiation of the brain. Case report and review of literature

    International Nuclear Information System (INIS)

    Giesel, B.U.; Kutz, G.G.; Thiel, H.J.

    2001-01-01

    Background: Together with radiation therapy the taxanes Paclitaxel and Docetaxel are more and more integrated into multimodal therapy regimens concerning breast- and lung cancer as well as squamous cell carcinoma of the head and neck. Especially in palliative situations we have to be aware of increasing side effects caused by interaction of the different treatment components. Therefore we report on a severe recall dermatitis that occurred in two breast-cancer patients following irradiation of the brain and reexposition to Docetaxel. Patients and method: From January until March 1999 tow female patients suffering from metastatic brest cancer and newly diagnosed cerebral metastases respectively carcinomatous meningitis underwent irradiation of the whole brain (2 Gy 5 days/week up to a reference dose of 50 Gy) in our department. Both patients had several courses of Docetaxel (Taxotere trademark ) 30 mg/m 2 BSA weekly respectively 100 mg/m 2 BSA/month since October and November 1998. After completion of radiotherapy chemotherapy with Docetaxel was continued. Results: Both patients tolerated Docetaxel well before and during radiotherapy. However, after having finished irradiation of the brain and receiving Docetaxel again a severe erythema of the irradiated skin and large areas of moist epitheliolysis with crust occurred (CTC grade IV). Conclusion: The dermatitis related to irradiation and reexposition to Docetaxel observed in our two cases is interpreted as a recall reaction. The basic initiating pathologic mechanism has not been solved completely. Further investigation is needed to find out how the taxanes can be used in combination radiochemotherapy regimens without causing severe toxicity to the irradiated skin or mucosa. (orig.) [de

  20. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2015-01-16

    Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

  1. Immunocytochemistry of formalin-fixed human brain tissues: microwave irradiation of free-floating sections.

    Science.gov (United States)

    Shiurba, R A; Spooner, E T; Ishiguro, K; Takahashi, M; Yoshida, R; Wheelock, T R; Imahori, K; Cataldo, A M; Nixon, R A

    1998-01-01

    antigens. Theory and practice of microwave antigen retrieval are covered extensively in the handbook Microwave Cookbook for Microscopists. A concise overview of microwave methods in the neurosciences has been published, and clinical applications have been reviewed. In this context, it should be noted that fresh tissues may be stabilized for immunocytochemistry by reversible, non-chemical binding processes such as cryosectioning after microwave treatment and freeze-drying. Thus, it may be possible to enhance immunostaining for some antigens by microwave irradiation of unfixed as well as fixed specimens. Parameters to be optimized for microwave retrieval of specific antigens include temperature, irradiation time, tissue buffer composition, salt concentration, and pH. Temperature, irradiation time, and pH are key variables. With this in mind, an optimal method was developed for retrieval of a wide variety of antigens in human brain tissues. Typical microwave protocols employ elevated temperatures that may reach 100 degrees C, where denaturation causes irreversible uncoiling and disruption of protein secondary and tertiary structures. Under these conditions, stable covalent bonds securing methylene crosslinks between polypeptides remain intact, but more reactive links formed by Schiff bases may be hydrolyzed. Resultant conformational changes presumably expose buried loops of continuous amino acids and protruding regions, increasing accessibility of their epitopes. Protein denaturation seems to be a reasonable explanation for the effects of microwaves on antigen retrieval. This idea is supported by the observation that denaturing solutions such as 6 M urea increase immunoreactivity of some antigens. Still, the molecular basis of these effects remains unresolved, in part due to the complex chemistry of formaldehyde reactions with tissue constituents. Indeed, some methylene bridges between similar groups such as NH2 and NH may be hydrolyzed by washing fixed tissues in distilled

  2. Electronmicroscopic study of gamma irradiated mouse spleen during primary immune response

    International Nuclear Information System (INIS)

    Burneva, V.G.; Gitsov, L.G.; Boyadzhieva-Mikhajlova, A.; Kyncheva, L.S.; Viklichka, St.

    1978-01-01

    An electronmicroscopic study of the mouse spleen immunocompetent cells during the productive phase of the primary immune response after sublethal gamma ray irradiation is carried out. For this purpose the animals were immunized with sheep red blood cells 24 hours after irradiation and sacrified on the 5th day after immunization. The number of small lymphocytes is reduced in all zones of the spleen. Only in the periarteriolar area the lymphoid sheaths are well outlines and the ultrastructure of the cells preserved. Three types of reticulohistocytic elements, according to their radiosensitivity are observed. The most radioresistant cells are the fixed ''dark'' reticular cells which do not complete phagocytosis. The ultrastructure of their nucleus and cytoplasm is not damaged. The macrophages are also quite resistant. The ''light'' reticular cells are the most radiosensitive. The chromatine of their nuclei is dispersed. The mitochondria are imbibed, with a reduced number of cristae. The cytoplasm contains many electron light vesicles, different in size. The changes in the processes of the dendridic cells in the spleen lymph follicles are of particular interest. Compared with the control animals the processes of dendritic reticular cells are markedly reduced. The postirradiation ultrastructural changes of the spleen cells indicate that parallel with the basic factor (the death of a considerable part of the small lymphocytes, precursors of the antibody-synthetizing cells) the reduced antibody-formation is due also to the limited capacity for ''traping'' the antigen on the processes of the dendritic follicular cells and to the reduced capacity of the reticulo-histocytic cells for antigen phagocytosis. The later is determined both by the damage of a considerable part of the phagocytes (radiosensitive ''light'' reticulo-histocytic cells) and by the blocking of the functionally undamaged phagocytes from ingested debris. (K.M.)

  3. Rapid decrease in brain enkephalin content after low-dose whole-body X-irradiation of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Miyachi, Yukihisa (Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab.); Ogawa, Norio; Mori, Akitane

    1992-03-01

    Methionine-eckephalin (ME) contents in the hypothalamus and other rat brain structures were measured immediately after 10 or 20 cGy whole-body X-irradiation. The ME contents of homogenates of the striatum, hypothalamus, midbrain + thalamus, hindbrain and pituitary were assayed radioimmunologically with {sup 125}I. The contents of all the structure, except the pituitary, decreased significantly after 20 cGy irradiation. The reduction in the hypothalamus was transient, ME content gradually recovering with time. These results suggest that the central nervous system of mammals is one of the most radiosensitive organs as judged by changes in stress-induced mediators such as ME. (author).

  4. Effects of low-dose X-irradiation on the developing brain, 19. Developmental disturbance of cerebral neocortex in rats. gamma. -irradiated on day 15 of gestation

    Energy Technology Data Exchange (ETDEWEB)

    Hoshino, K.; Fukui, Y.; Hayasaka, I.; Hayasaka, S.; Ito, Y.; Kameyama, Y.

    1987-03-01

    F344/DuCrj rats were irradiated with gamma-rays in a single dose of either 0.27 or 0.48 Gy at day 15 of gestation. Their neonates were autopsied at week 6 or 12 after birth for morphological observation of the cerebrum. The weight of brain had significantly decreased in a dose-dependent manner at weeks 6 and 12 in both irradiated groups. The thickness of the neocortex had also significantly decreased in both groups at week 6; however, the significant decrease at week 12 was confined to the group with 0.48 Gy. There was no difference in the cell density between the groups. Observations for dendrites in the base of pyramidal cells of the 5th layer of cerebral cortex showed that irradiation influenced the decrease in the number of dendrites directly arising in the reticulum, but did not influence the branching index. Electron microscopy showed that irradiation with 0.48 Gy influenced neither synapse density nor synaptic length.

  5. Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain

    Directory of Open Access Journals (Sweden)

    Julia F Alterman

    2015-01-01

    Full Text Available Applications of RNA interference for neuroscience research have been limited by a lack of simple and efficient methods to deliver oligonucleotides to primary neurons in culture and to the brain. Here, we show that primary neurons rapidly internalize hydrophobically modified siRNAs (hsiRNAs added directly to the culture medium without lipid formulation. We identify functional hsiRNAs targeting the mRNA of huntingtin, the mutation of which is responsible for Huntington's disease, and show that direct uptake in neurons induces potent and specific silencing in vitro. Moreover, a single injection of unformulated hsiRNA into mouse brain silences Htt mRNA with minimal neuronal toxicity. Thus, hsiRNAs embody a class of therapeutic oligonucleotides that enable simple and straightforward functional studies of genes involved in neuronal biology and neurodegenerative disorders in a native biological context.

  6. Effects of intravenous administration of bone marrow stromal stem cells on cognitive impairment of the whole-brain irradiated rat models

    International Nuclear Information System (INIS)

    Ding Weijun; Wang Jianhua; Zhu Min; Chen Baoguo; Wang Yang

    2007-01-01

    Objective: To explore the effect of intravenous infusion of bone marrow stromal stem cells(MSCs) on cognitive function of rats after whole brain irradiation. Methods: MSCs were isolated and cultured from adult rats. After Sprague-Dawly female rats were anaesthetized with chloral hydrate, their whole cerebrum was irradiated with a single dose of 20 Gy by 6 MV X-ray. Seven days after irradiation, 4 x 106 Hoechst33342-1abelled MSCs were intravenously injected into the tail vein of these rats. Four and 8 weeks after transplantation, the learning and memorizing ability was measured with the Y maze test. Immunohistochemical method was used to identify MSCs or ceils derived from MSCs in the brain. Results: The learning and memorizing ability of irradiation groups were significantly different from that of normal control group (P < 0.01). Significant improvement of cognitive impairment was observed in rats treated with MSCs at 4 and 8 weeks after transplantation as compared with the controll groups (P<0.05). This showed that the MSCs survived and were localized to the brain tissue. The number of Hoechst33342 immunohistofluorescence positive cells and double-immunostaining cells significantly decreased in 8 weeks group as compared with the 4 weeks group. Conclusion: Marrow stromal stem cells delivered to the irradiation brain tissue through intravenous route improve the cognitive impairment after whole brain irradiation. These cells may survive and differentiate in the brain tissue of irradiated rats. (authors)

  7. Regional differences in actomyosin contraction shape the primary vesicles in the embryonic chicken brain

    International Nuclear Information System (INIS)

    Filas, Benjamen A; Oltean, Alina; Majidi, Shabnam; Bayly, Philip V; Taber, Larry A; Beebe, David C

    2012-01-01

    In the early embryo, the brain initially forms as a relatively straight, cylindrical epithelial tube composed of neural stem cells. The brain tube then divides into three primary vesicles (forebrain, midbrain, hindbrain), as well as a series of bulges (rhombomeres) in the hindbrain. The boundaries between these subdivisions have been well studied as regions of differential gene expression, but the morphogenetic mechanisms that generate these constrictions are not well understood. Here, we show that regional variations in actomyosin-based contractility play a major role in vesicle formation in the embryonic chicken brain. In particular, boundaries did not form in brains exposed to the nonmuscle myosin II inhibitor blebbistatin, whereas increasing contractile force using calyculin or ATP deepened boundaries considerably. Tissue staining showed that contraction likely occurs at the inner part of the wall, as F-actin and phosphorylated myosin are concentrated at the apical side. However, relatively little actin and myosin was found in rhombomere boundaries. To determine the specific physical mechanisms that drive vesicle formation, we developed a finite-element model for the brain tube. Regional apical contraction was simulated in the model, with contractile anisotropy and strength estimated from contractile protein distributions and measurements of cell shapes. The model shows that a combination of circumferential contraction in the boundary regions and relatively isotropic contraction between boundaries can generate realistic morphologies for the primary vesicles. In contrast, rhombomere formation likely involves longitudinal contraction between boundaries. Further simulations suggest that these different mechanisms are dictated by regional differences in initial morphology and the need to withstand cerebrospinal fluid pressure. This study provides a new understanding of early brain morphogenesis. (paper)

  8. Distinct angiotensin II receptor in primary cultures of glial cells from rat brain

    International Nuclear Information System (INIS)

    Raizada, M.K.; Phillips, M.I.; Crews, F.T.; Sumners, C.

    1987-01-01

    Angiotensin II (Ang-II) has profound effects on the brain. Receptors for Ang-II have been demonstrated on neurons, but no relationship between glial cells and Agn-II has been established. Glial cells (from the hypothalamus and brain stem of 1-day-old rat brains) in primary culture have been used to demonstrate the presence of specific Ang-II receptors. Binding of 125 I-Ang-II to glial cultures was rapid, reversible, saturable, and specific for Ang-II. The rank order of potency of 125 I-Ang-II binding was determined. Scatchard analysis revealed a homogeneous population of high-affinity binding sites with a B/sub max/ of 110 fmol/mg of protein. Light-microscopic autoradiography of 125 I-Ang-II binding supported the kinetic data, documenting specific Ang-II receptors on the glial cells. Ang-II stimulated a dose-dependent hydrolysis of phosphatidylinositols in glial cells, an effect mediated by Ang-II receptors. However, Ang-II failed to influence [ 3 H] norepinephrine uptake, and catecholamines failed to regulate Ang-II receptors, effects that occur in neurons. These observations demonstrate the presence of specific Ang-II receptors on the glial cells in primary cultures derived from normotensive rat brain. The receptors are kinetically similar to, but functionally distinct from, the neuronal Ang-II receptors

  9. Increased CD147 and MMP-9 expression in the normal rat brain after gamma irradiation

    International Nuclear Information System (INIS)

    Li Hong; Wei Ming; Li Shenghui; Zhou Ziwei; Xu Desheng

    2013-01-01

    Radiation-induced vascular injury is a major complication of Gamma knife surgery (GKS). Previous studies have shown that CD147 and MMP-9 are closely associated with vascular remodeling and pathological angiogenesis. Thus, we analysed changes in CD147 and MMP-9 expression in the cerebral cortex to investigate the correlation between CD147 and MMP-9 in the rat following GKS. Adult male Wistar rats were subjected to GKS at a maximum dose of 75 Gy and then euthanized 1 to 12 weeks later. Using immunohistochemistry and western blot analysis, we found that CD147 and MMP-9 expression were markedly upregulated in the target area 8-12 weeks after GKS when compared with the control group. Immunofluorescent double staining demonstrated that CD147 signals colocalized with CD31, GFAP and MMP-9-positive cells. Importantly, CD147 levels correlated with increased MMP-9 expression in irradiated brain tissue. For the first time, these data demonstrate a potential relationship between CD147 and MMP-9 following GKS. In addition, our study also suggests that CD147 and MMP-9 may play a role in vascular injury after GKS. (author)

  10. Endocrine morbidity in adults treated with cerebral irradiation for brain tumours during childhood

    International Nuclear Information System (INIS)

    Shalet, S.M.; Beardwell, C.G.; MacFarlane, I.A.; Morris Jones, P.H.; Pearson, D.

    1977-01-01

    Hypothalamic-pituitary function was assessed in 20 adult subjects who were treated with cerebral irradiation for brain tumours during childhood between 8 and 32 years earlier. Nine patients showed impaired growth hormone (GH) responses to hypoglycaemia, of whom, 7 are below the third centile for standing height. All GH deficient subjects recieved more than 2950 rads to the hypothalamic-pituitary axis with a maximum dose of approximately 5000 rads being used in one case. Three subjects have an elevated basal serum thyroid stimulating hormone (TSH) level and 2 of these show an exaggerated TSH response to thyrotrophin releasing hormone (TRH) but no patient was clinically or biochemically hypothyroid. The rest of hypothalamic-pituitary function was essentially normal. This study shows that multiple pituitary hormone deficiencies do not develop with time when the radiation dose is below a critical level. Thus it appears that there is a gradation of radiation damage to the hypothalamic-pituitary axis which is dependent primarily on the dose received rather than the time interval after radiotherapy. (auth.)

  11. No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblasts after alpha particle irradiation

    Science.gov (United States)

    Hu, Burong; Zhu, Jiayun; Zhou, Hongning; Hei, Tom K.

    2013-02-01

    A major concern for bystander effects is the probability that normal healthy cells adjacent to the irradiated cells become genomically unstable and undergo further carcinogenesis after therapeutic irradiation or space mission where astronauts are exposed to low dose of heavy ions. Genomic instability is a hallmark of cancer cells. In the present study, two irradiation protocols were performed in order to ensure pure populations of bystander cells and the genomic instability in their progeny were investigated. After irradiation, chromosomal aberrations of cells were analyzed at designated time points using G2 phase premature chromosome condensation (G2-PCC) coupled with Giemsa staining and with multiplex fluorescent in situ hybridization (mFISH). Our Giemsa staining assay demonstrated that elevated yields of chromatid breaks were induced in the progeny of pure bystander primary fibroblasts up to 20 days after irradiation. mFISH assay showed no significant level of inheritable interchromosomal aberrations were induced in the progeny of the bystander cell groups, while the fractions of gross aberrations (chromatid breaks or chromosomal breaks) significantly increased in some bystander cell groups. These results suggest that genomic instability occurred in the progeny of the irradiation associated bystander normal fibroblasts exclude the inheritable interchromosomal aberration.

  12. Primary Dystonia: Conceptualizing the Disorder through a Structural Brain Imaging Lens

    Directory of Open Access Journals (Sweden)

    Kristina Simonyan

    2013-06-01

    Full Text Available Background: Dystonia is a hyperkinetic movement disorder of involuntary, twisting repetitive movements. The anatomical structures and pathways implicated in its pathogenesis as well as their relationship to the neurophysiological paradigm of abnormal surround inhibition, maladaptive plasticity and impaired sensorimotor integration remain not well delineated. Objective: We review the use of high-resolution structural brain imaging using voxel-based morphometry (VBM and diffusion tensor imaging (DTI techniques for evaluation of brain changes in primary torsion dystonia and their relationships to the pathophysiology of this disorder. Methods: A search in PubMed was conducted to identify the relevant literature. Discussion: Structural imaging has enhanced our understanding of the pathophysiological mechanisms of dystonia. In particular, VBM and DTI data have revealed microstructural disturbances in the basal ganglia, sensorimotor cortices and cerebellum along with aberrations in the cortico-striato-pallido-thalamic and cerebello-thalamo-cortical pathways.  When combined with functional brain imaging and neurophysiological modalities, a structure-function relationship can be established in the dystonia brain network at the sensorimotor, plasticity, cortical disinhibition and cerebellar outflow connectivity levels. Structural imaging highlighted new anatomical substrates and, with a combined structural-functional approach, has offered new opportunities for investigation of the neurodevelopmental, environmental and/or genetic interplay in the brain networks of dystonia patients. 

  13. Noninvasive imaging of brain oxygen metabolism in children with primary nocturnal enuresis during natural sleep.

    Science.gov (United States)

    Yu, Bing; Huang, Mingzhu; Zhang, Xu; Ma, Hongwei; Peng, Miao; Guo, Qiyong

    2017-05-01

    A series of studies have revealed that nocturnal enuresis is closely related to hypoxia in children with primary nocturnal enuresis (PNE). However, brain oxygen metabolism of PNE children has not been investigated before. The purpose of this study was to investigate changes in whole-brain cerebral metabolic rate of oxygen (CMRO 2 ), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) in children suffering from PNE. We used the newly developed T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging technique. Neurological evaluation, structural imaging, phase-contrast, and the TRUST imaging method were applied in children with PNE (n = 37) and healthy age- and sex-matched control volunteers (n = 39) during natural sleep to assess whole-brain CMRO 2 , CBF, OEF, and arousal from sleep scores. Results showed that whole-brain CMRO 2 and OEF values of PNE children were higher in controls, while there was no significant difference in CBF. Consequently, OEF levels of PNE children were increased to maintain oxygen supply. The elevation of OEF was positively correlated with the difficulty of arousal. Our results provide the first evidence that high oxygen consumption and high OEF values could make PNE children more susceptible to hypoxia, which may induce cumulative arousal deficits and make them more prone to nocturnal enuresis. Hum Brain Mapp 38:2532-2539, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Cellular proliferation and infiltration following interstitial irradiation of normal dog brain is altered by an inhibitor of polyamine synthesis

    International Nuclear Information System (INIS)

    Fike, John R.; Gobbel, Glenn T.; Chou, Dean; Wijnhoven, Bas P. L.; Bellinzona, Mattia; Nakagawa, Minoru; Seilhan, Theresa M.

    1995-01-01

    Purpose: The objectives of this study were to quantitatively define proliferative and infiltrative cell responses after focal 125 I irradiation of normal brain, and to determine the effects of an intravenous infusion of α-difluoromethylornithine (DFMO) on those responses. Methods and Materials: Adult beagle dogs were irradiated using high activity 125 I sources. Saline (control) or DFMO (150 mg/kg/day) was infused for 18 days starting 2 days before irradiation. At varying times up to 8 weeks after irradiation, brain tissues were collected and the cell responses in and around the focal lesion were quantified. Immunohistochemical stains were used to label astrocytes (GFAP), vascular endothelial cells (Factor VIII), polymorphonuclear leukocytes (PMNs; MAC 387) and cells synthesizing deoxyribonucleic acid (DNA) (BrdU). Cellular responses were quantified using a histomorphometric analysis. Results: After radiation alone, cellular events included a substantial acute inflammatory response followed by increased BrdU labeling and progressive increases in numbers of capillaries and astrocytes. α-Difluoromethylornithine treatment significantly affected the measured cell responses. As in controls, an early inflammatory response was measured, but after 2 weeks there were more PMNs/unit area than in controls. The onset of measurable BrdU labeling was delayed in DFMO-treated animals, and the magnitude of labeling was significantly reduced. Increases in astrocyte and vessel numbers/mm 2 were observed after a 2-week delay. At the site of implant, astrocytes from DFMO-treated dogs were significantly smaller than those from controls. Conclusions: There is substantial cell proliferation and infiltration in response to interstitial irradiation of normal brain, and these responses are significantly altered by DFMO treatment. Although the precise mechanisms by which DFMO exerts its effects in this model are not known, the results from this study suggest that modification of radiation

  15. Evaluation of immunological parameters during irradiation with combined chemotherapy in primary lung cancer

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Kimura, Shuji

    1980-01-01

    Changes of several immunological parameters in 52 cases of primary lung cancer treated with radiation combined chemotherapy were studied in the present paper. During the treatment, decreasing of absolute lymphocyte counts, PHA skin test reactivity and lymphocyte blastoid transformation with PHA were recognized. The decreasing of immunological capacities tested in the present investigation did not depend on among clinical stages or histologic types. But irradiation to mediastinum affected to immunological abilities. The values in some immunological parameter tested at pre-treatment or at post-treatment suggested the correlation with tumor regression, namely in the cases showed high values in absolute lymphocyte counts and PPD skin test reactivity at the time of pre-treatment and in the cases showed high reactivity in PHA skin test at post-treatment, tumor regression was significantly demonstrated compared with the other cases. The patients showed high values in absolute lymphocyte counts and PHA skin test at pretreatment time or showed high values in lymphocyte blastoid transformation with PHA at post-treatment demonstrated longer survival time. As a result, the test of immunological abilities obtained at pre-treatment time was reliable to forecast tumor regression and survival time. (author)

  16. Irradiation-injured brain tissues can self-renew in the absence of the pivotal tumor suppressor p53 in the medaka (Oryzias latipes) embryo

    International Nuclear Information System (INIS)

    Yasuda, Takako; Nagata, Kento; Igarashi, Kento; Watanabe-Asaka, Tomomi; Oda, Shoji; Mitani, Hiroshi; Kimori, Yoshitaka

    2016-01-01

    The tumor suppressor protein, p53, plays pivotal roles in regulating apoptosis and proliferation in the embryonic and adult central nervous system (CNS) following neuronal injuries such as those induced by ionizing radiation. There is increasing evidence that p53 negatively regulates the self-renewal of neural stem cells in the adult murine brain; however, it is still unknown whether p53 is essential for self-renewal in the injured developing CNS. Previously, we demonstrated that the numbers of apoptotic cells in medaka (Oryzias latipes) embryos decreased in the absence of p53 at 12-24 h after irradiation with 10-Gy gamma rays. Here, we used histology to examine the later morphological development of the irradiated medaka brain. In p53-deficient larvae, the embryonic brain possessed similar vacuoles in the brain and retina, although the vacuoles were much smaller and fewer than those found in wild-type embryos. At the time of hatching (6 days after irradiation), no brain abnormality was observed. In contrast, severe disorganized neuronal arrangements were still present in the brain of irradiated wild-type embryos. Our present results demonstrated that self-renewal of the brain tissue completed faster in the absence of p53 than wild type at the time of hatching because p53 reduces the acute severe neural apoptosis induced by irradiation, suggesting that p53 is not essential for tissue self-renewal in developing brain. (author)

  17. Hippocampal dose volume histogram predicts Hopkins Verbal Learning Test scores after brain irradiation

    Directory of Open Access Journals (Sweden)

    Catherine Okoukoni, PhD

    2017-10-01

    Full Text Available Purpose: Radiation-induced cognitive decline is relatively common after treatment for primary and metastatic brain tumors; however, identifying dosimetric parameters that are predictive of radiation-induced cognitive decline is difficult due to the heterogeneity of patient characteristics. The memory function is especially susceptible to radiation effects after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post–radiation therapy (RT memory impairment. Methods and materials: Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT in prospectively accrued clinical trials performed at our institution. Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at least 6 months after RT. Impairment was defined as an immediate recall score ≤15. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (VD(Gy with memory impairment. Results: Hippocampal V53.4Gy to V60.9Gy significantly predicted post-RT memory impairment (P < .05. Within this range, the hippocampal V55Gy was the most significant predictor (P = .004. Hippocampal V55Gy of 0%, 25%, and 50% was associated with tumor-induced impairment rates of 14.9% (95% confidence interval [CI], 7.2%-28.7%, 45.9% (95% CI, 24.7%-68.6%, and 80.6% (95% CI, 39.2%-96.4%, respectively. Conclusions: The hippocampal V55Gy is a significant predictor for impairment, and a limiting dose below 55 Gy may minimize radiation-induced cognitive impairment.

  18. Types and three-dimensional distribution of neuronal ectopias in the brain of mice prenatally subjected to X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xue-Zhi; Takahashi, Sentaro; Kubota, Yoshihisa; Sato, Hiroshi [National Inst. of Radiological Sciences, Chiba (Japan); Cui, Chun; Fukui, Yoshihiro [Tokushima Univ. (Japan). School of Medicine; Inouye, Minoru [Shin Nippon Biomedical Lab., Ltd., Miyanoura, Kagoshima (Japan)

    2002-03-01

    The types and three-dimensional distribution of neocortical ectopias following prenatal exposure to X-irradiation were studied by a histological examination and computer reconstruction techniques. Pregnant ICR mice were subjected to X-irradiation at a dose of 1.5 Gy on embryonic day 13. The brains from 30-day-old mice were serially sectioned on the frontal plane at 15 {mu}m, stained with HE and observed with a microscope. The image data for the sections were input to a computer, and then reconstructed to three-dimensional brain structures using the Magellan 3.6 program. Sectional images were then drawn on a computer display at 240 {mu}m intervals, and the positions of the different types of neocortical ectopias were marked using color coding. Three types of neocortical ectopias were recognized in the irradiated brains. Neocortical Lay I ectopias were identified as small patches in the caudal occipital cortex, and were located more laterally in the neocortex in caudal sections than in the rostral sections. Periventricular ectopias were located more rostrally than Lay I ectopias, and were found from the most caudal extent of the presumed motor cortex to the most caudal extent of the lateral ventricle. Hippocampal ectopias appeared as continuous linear bands, and were frequently associated with the anterior parts of the periventricular ectopias. (author)

  19. Coping and adaptive strategies of traumatic brain injury survivors and primary caregivers.

    Science.gov (United States)

    Adams, Deana; Dahdah, Marie

    2016-06-27

    Qualitative research methods allowed the investigator to contribute to the development of new theories and to examine change in processes over time, which added rich detail to existing knowledge of the use of coping and adaptive strategies by traumatic brain injury survivors and their primary caregivers (Ponsford, Sloan, & Snow, 2013). The advantages of phenomenological study were that it allows flexibility to explore and understand meanings attached by people to well-studied concepts such as coping, resiliency, and adaptation or compensation. Phenomenological study was sensitive to contextual factors. It also permitted the study of in-depth dynamics of coping and adaptive strategies of TBI survivors and primary caregivers, while understanding the social and psychological implications of the phenomenon. To explore the needs and deficits of adult traumatic brain injury (TBI) survivors and primary caregivers; and to identify their self-initiated coping and adaptive strategies. Significant to this study was the development of coping and adaptive strategies by the participants after their discharge from inpatient and rehabilitation treatment. The compensatory skills taught in treatment settings did not transfer to the home environment. Therefore, these strategies developed independently from previous treatment recommendations contributed to the development of theory related to rehabilitation and counseling. Distinctive to this study was the similarity of coping and adaptive strategies developed from both mild and severe traumatic brain injury survivors. This study consisted of eleven with TBI and six primary caregivers (N = 17), who participated in a series of semi-structured interviews aimed at discovering the coping and adaptive strategies utilized in dealing with the effects of brain injury. A Qualitative Phenomenological design was employed. Patience and understanding, support, and professional help were identified by TBI survivors and caregivers as being their

  20. Technical Note: Immunohistochemical evaluation of mouse brain irradiation targeting accuracy with 3D-printed immobilization device

    Energy Technology Data Exchange (ETDEWEB)

    Zarghami, Niloufar, E-mail: nzargham@uwo.ca; Jensen, Michael D. [Department of Medical Biophysics, The University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7 (Canada); Talluri, Srikanth; Dick, Frederick A. [Department of Biochemistry, The University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7 (Canada); London Regional Cancer Program, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 5W9 (Canada); Foster, Paula J. [Imaging Research Laboratories, Robarts Research Institute, 100 Perth Drive, London, Ontario N6A 5K8 (Canada); Department of Medical Biophysics, The University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7 (Canada); Chambers, Ann F. [Department of Medical Biophysics, The University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7 (Canada); Department of Oncology, The University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7 (Canada); London Regional Cancer Program, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 5W9 (Canada); Wong, Eugene [Department of Physics and Astronomy, The University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7 (Canada); Department of Medical Biophysics, The University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7 (Canada); Department of Oncology, The University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 3K7 (Canada); London Regional Cancer Program, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario N6A 5W9 (Canada)

    2015-11-15

    Purpose: Small animal immobilization devices facilitate positioning of animals for reproducible imaging and accurate focal radiation therapy. In this study, the authors demonstrate the use of three-dimensional (3D) printing technology to fabricate a custom-designed mouse head restraint. The authors evaluate the accuracy of this device for the purpose of mouse brain irradiation. Methods: A mouse head holder was designed for a microCT couch using CAD software and printed in an acrylic based material. Ten mice received half-brain radiation while positioned in the 3D-printed head holder. Animal placement was achieved using on-board image guidance and computerized asymmetric collimators. To evaluate the precision of beam localization for half-brain irradiation, mice were sacrificed approximately 30 min after treatment and brain sections were stained for γ-H2AX, a marker for DNA breaks. The distance and angle of the γ-H2AX radiation beam border to longitudinal fissure were measured on histological samples. Animals were monitored for any possible trauma from the device. Results: Visualization of the radiation beam on ex vivo brain sections with γ-H2AX immunohistochemical staining showed a sharp radiation field within the tissue. Measurements showed a mean irradiation targeting error of 0.14 ± 0.09 mm (standard deviation). Rotation between the beam axis and mouse head was 1.2° ± 1.0° (standard deviation). The immobilization device was easily adjusted to accommodate different sizes of mice. No signs of trauma to the mice were observed from the use of tooth block and ear bars. Conclusions: The authors designed and built a novel 3D-printed mouse head holder with many desired features for accurate and reproducible radiation targeting. The 3D printing technology was found to be practical and economical for producing a small animal imaging and radiation restraint device and allows for customization for study specific needs.

  1. Technical Note: Immunohistochemical evaluation of mouse brain irradiation targeting accuracy with 3D-printed immobilization device

    International Nuclear Information System (INIS)

    Zarghami, Niloufar; Jensen, Michael D.; Talluri, Srikanth; Dick, Frederick A.; Foster, Paula J.; Chambers, Ann F.; Wong, Eugene

    2015-01-01

    Purpose: Small animal immobilization devices facilitate positioning of animals for reproducible imaging and accurate focal radiation therapy. In this study, the authors demonstrate the use of three-dimensional (3D) printing technology to fabricate a custom-designed mouse head restraint. The authors evaluate the accuracy of this device for the purpose of mouse brain irradiation. Methods: A mouse head holder was designed for a microCT couch using CAD software and printed in an acrylic based material. Ten mice received half-brain radiation while positioned in the 3D-printed head holder. Animal placement was achieved using on-board image guidance and computerized asymmetric collimators. To evaluate the precision of beam localization for half-brain irradiation, mice were sacrificed approximately 30 min after treatment and brain sections were stained for γ-H2AX, a marker for DNA breaks. The distance and angle of the γ-H2AX radiation beam border to longitudinal fissure were measured on histological samples. Animals were monitored for any possible trauma from the device. Results: Visualization of the radiation beam on ex vivo brain sections with γ-H2AX immunohistochemical staining showed a sharp radiation field within the tissue. Measurements showed a mean irradiation targeting error of 0.14 ± 0.09 mm (standard deviation). Rotation between the beam axis and mouse head was 1.2° ± 1.0° (standard deviation). The immobilization device was easily adjusted to accommodate different sizes of mice. No signs of trauma to the mice were observed from the use of tooth block and ear bars. Conclusions: The authors designed and built a novel 3D-printed mouse head holder with many desired features for accurate and reproducible radiation targeting. The 3D printing technology was found to be practical and economical for producing a small animal imaging and radiation restraint device and allows for customization for study specific needs

  2. Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue.

    Science.gov (United States)

    Tamashiro, Tami T; Dalgard, Clifton Lee; Byrnes, Kimberly R

    2012-08-15

    Microglia account for approximately 12% of the total cellular population in the mammalian brain. While neurons and astrocytes are considered the major cell types of the nervous system, microglia play a significant role in normal brain physiology by monitoring tissue for debris and pathogens and maintaining homeostasis in the parenchyma via phagocytic activity. Microglia are activated during a number of injury and disease conditions, including neurodegenerative disease, traumatic brain injury, and nervous system infection. Under these activating conditions, microglia increase their phagocytic activity, undergo morpohological and proliferative change, and actively secrete reactive oxygen and nitrogen species, pro-inflammatory chemokines and cytokines, often activating a paracrine or autocrine loop. As these microglial responses contribute to disease pathogenesis in neurological conditions, research focused on microglia is warranted. Due to the cellular heterogeneity of the brain, it is technically difficult to obtain sufficient microglial sample material with high purity during in vivo experiments. Current research on the neuroprotective and neurotoxic functions of microglia require a routine technical method to consistently generate pure and healthy microglia with sufficient yield for study. We present, in text and video, a protocol to isolate pure primary microglia from mixed glia cultures for a variety of downstream applications. Briefly, this technique utilizes dissociated brain tissue from neonatal rat pups to produce mixed glial cell cultures. After the mixed glial cultures reach confluency, primary microglia are mechanically isolated from the culture by a brief duration of shaking. The microglia are then plated at high purity for experimental study. The principle and protocol of this methodology have been described in the literature. Additionally, alternate methodologies to isolate primary microglia are well described. Homogenized brain tissue may be separated

  3. Role of 18F-FDG PET/CT in primary brain lymphoma.

    Science.gov (United States)

    de-Bonilla-Damiá, Á; Fernández-López, R; Capote-Huelva, F J; de la Cruz-Vicente, F; Egea-Guerrero, J J; Borrego-Dorado, I

    To study the usefulness of 18 F-FDG PET/CT in the initial evaluation and in the response assessment in primary brain lymphoma. A retrospective analysis was carried out on 18 patients diagnosed with primary brain lymphoma, a histological subtype of diffuse large B-cell lymphoma, on whom an initial 18 F-FDG PET/CT and MRI was performed, with 7 of the cases being analysed after the completion of treatment in order to assess response and clinical follow up. Initial 18 F-FDG PET/CT showed 26 hypermetabolic foci, whereas 46 lesions were detected by MRI. The average SUV maximum of the lesions was 17.56 with T/N 3.55. The concordance of both tests for identifying the same number of lesions was moderate, obtaining a kappa index of 0.395 (P<.001). In the evaluation of treatment, MRI identified 16 lesions compared to 7 pathological accumulations observed by 18 F-FDG PET/CT. The concordance of both tests to assess type of response to treatment was moderate (kappa index 0.41) (P=.04). In both the initial evaluation and the assessment of the response to treatment, PET/CT led to a change strategy in 22% of patients who had lesions outside the cerebral parenchyma. MRI appears to be the method of choice for detecting brain disease in patients with primary brain lymphoma, whereas 18 F-FDG PET/CT seems to play a relevant role in the assessment of extra-cerebral disease. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  4. Discrimination of different brain metastases and primary CNS lymphomas using morphologic criteria and diffusion tensor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bette, S.; Wiestler, B.; Huber, T.; Boeckh-Behrens, T.; Zimmer, C.; Kirschke, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuroradiology; Delbridge, C. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuropathology; Meyer, B.; Gempt, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neurosurgery

    2016-12-15

    Brain metastases are a common complication of cancer and occur in about 15-40% of patients with malignancies. The aim of this retrospective study was to differentiate between metastases from different primary tumors/CNS lymphyomas using morphologic criteria, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Morphologic criteria such as hemorrhage, cysts, pattern of contrast enhancement and location were reported in 200 consecutive patients with brain metastases/primary CNS lymphomas. FA and ADC values were measured in regions of interest (ROIs) placed in the contrast-enhancing tumor part, the necrosis and the non-enhancing peritumoral region (NEPTR). Differences between histopathological subtypes of metastases were analyzed using non-parametric tests, decision trees and hierarchical clustering analysis. Significant differences were found in morphologic criteria such as hemorrhage or pattern of contrast enhancement. In diffusion measurements, significant differences between the different tumor entities were only found in ADC analyzed in the contrast-enhancing tumor part. Among single tumor entities, primary CNS lymphomas showed significantly lower median ADC values in the contrast-enhancing tumor part (ADC{sub lymphoma} 0.92 [0.83-1.07] vs. ADC{sub no} {sub lymphoma} 1.35 [1.10-1.64] P=0.001). Further differentiation between types of metastases was not possible using FA and ADC. There were morphologic differences among the main subtypes of brain metastases/CNS lymphomas. However, due to a high variability of common types of metastases and low specificity, prospective differentiation remained challenging. DTI including FA and ADC was not a reliable tool for differentiation between different histopathological subtypes of brain metastases except for CNS lymphomas showing lower ADC values. Biopsy, surgery and staging remain essential for diagnosis.

  5. Field-ion microscope studies of the defect structure of the primary state of damage of irradiated metals

    International Nuclear Information System (INIS)

    Seidman, D.N.

    1975-01-01

    A review is presented of field ion microscope applications in studies of point defect distribution in irradiated metals. FIM results on the primary state of radiation damage in neutron and ion-irradiated iridium and tungsten, at both room-temperature and 78 0 K, showed that it consists of: (1) isolated vacancies; (2) depleted zones; (3) compact vacancy clusters of voids; and (4) dislocation loops. The fraction of vacancies stored in the dislocation loops represented a small fraction of the total vacancy concentration; in the case of tungsten it was approximately 10 percent. These FIM observations provide a simple explanation of the low yield-factor, determined by transmission electron microscopy, for a number of ion-irradiated metals

  6. Craniospinal versus whole brain irradiation in Medulloblastoma patients, with introduction of utilizing a simple immobilization device

    Directory of Open Access Journals (Sweden)

    Haddad P

    2001-05-01

    Full Text Available Craniospinal irradiation plus posterior fossa boost (CS1 is the standard modality of post-operative treatment of patient with medulloblastoma, but considering the technical difficulties and limited facilities, often whole- brain irradiation plus posterior fossa boost (WBI had been used in our institution until 1991. Tust a retrospective study was undertaken to compare the patients treated by By WBI and CSI for recurrences and disease-free survival (DFS. Files of all medullobalstoma patients treated post-operatively in our department in the 10 – year period of 1986-1996 were reviewed. To obtain the best possible follow- up, a formal inquiry letter was mailed to all patients’ addresses.Total of 72 patients had been treated, with a mean age of 14.7 years and male-to-female ratio of 1.5:1 Thirty –seven patients had been treated by WBI and 35 by CS. A simple wooden device designed and made in our department was used for CSI patients’ set-up and immobilization. Mean radiation dose to posterior fossa was 4, 765 cGy in WBT and 5, 071 cGY in CSI (180-200 cGy fractions. Sixty-two patients (85% came back for follow-up, with 24 recurrences. Only 24% of CSI patients had recurrences, versus 51% in WBI Nearly all Wbi recurrences versus half of the CSI recurrences were spinal. DFS was 39 months in CSI and 26 months in WBI (P<0.001 . in multi-factorial analysis, only the extent of radiation (CSI versus WBI, P<0.001 was statistically significant. Mean age in our patients was higher than what is commonly reported in literature. The immobilization device introduce was a simple and useful accessory to CSI. Considering DFS, CSI in our department was acceptabley comparable to literature results and significantly superior to WBI. With regard to relatively high spinal recurrence rate even in CSI, the importance of suitable spinal cytological and imaging evaluation is again emphasized.

  7. Irradiation of rat brain reduces P-glycoprotein expression and function

    NARCIS (Netherlands)

    Bart, J.; Nagengast, W. B.; Coppes, R. P.; Wegman, T. D.; van der Graaf, W. T. A.; Groen, H. J. M.; Vaalburg, W.; de Vries, E. G. E.; Hendrikse, N. H.

    2007-01-01

    The blood - brain barrier ( BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P- glycoprotein ( P- gp), expressed on brain capillary endothelial cells, is part of the BBB. P- gp expression on capillary endothelium decreases 5 days after brain

  8. Expression and activity of the urokinase plasminogen activator system in canine primary brain tumors

    Directory of Open Access Journals (Sweden)

    Rossmeisl JH

    2017-04-01

    Full Text Available John H Rossmeisl,1–3 Kelli Hall-Manning,4 John L Robertson,1,3,5 Jamie N King,1,2 Rafael V Davalos,3,5 Waldemar Debinski,3 Subbiah Elankumaran6,† 1Veterinary and Comparative Neuro-Oncology Laboratory, 2Department of Small Animal Clinical Sciences, 3The Brain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC, 4Virginia Tech Animal Laboratory Services, Virginia-Maryland College of Veterinary Medicine, 5Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia Tech, 6Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA†The authors regret to advise of the passing of Dr Subbiah Elankumaran prior to publicationBackground: The expression of the urokinase plasminogen activator receptor (uPAR, a glycosylphosphatidylinositol-anchored protein family member, and the activity of its ligand, urokinase-type plasminogen activator (uPA, have been associated with the invasive and metastatic potentials of a variety of human brain tumors through their regulation of extracellular matrix degradation. Domesticated dogs develop naturally occurring brain tumors that share many clinical, phenotypic, molecular, and genetic features with their human counterparts, which has prompted the use of the dogs with spontaneous brain tumors as models to expedite the translation of novel brain tumor therapeutics to humans. There is currently little known regarding the role of the uPA system in canine brain tumorigenesis. The objective of this study was to characterize the expression of uPAR and the activity of uPA in canine brain tumors as justification for the development of uPAR-targeted brain tumor therapeutics in dogs.Methods: We investigated the expression of uPAR in 37 primary canine brain tumors using immunohistochemistry, Western blotting, real

  9. Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Rades, Dirk; Nadrowitz, Roger; Buchmann, Inga; Meller, Birgit; Hunold, Peter; Noack, Frank; Schild, Steven E.

    2010-01-01

    Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m 2 cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m 2 cetuximab (cold antibody) were given. Weekly doses of 250 mg/m 2 cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab ( 123 I-Erbi) on scintigraphy; 123 I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

  10. Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk; Nadrowitz, Roger [Dept. of Radiation Oncology, Univ. of Luebeck (Germany); Buchmann, Inga; Meller, Birgit [Section of Nuclear Medicine, Univ. of Luebeck (Germany); Hunold, Peter [Dept. of Radiology, Univ. of Luebeck (Germany); Noack, Frank [Inst. of Pathology, Univ. of Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2010-08-15

    Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m{sup 2} cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m{sup 2} cetuximab (cold antibody) were given. Weekly doses of 250 mg/m{sup 2} cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab ({sup 123}I-Erbi) on scintigraphy; {sup 123}I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

  11. Biogenic amines in brain areas of rats and response to varying dose levels of whole body gamma irradiation

    International Nuclear Information System (INIS)

    Abdelhamid, F.M.; Elmossalamy, N.; Othman, S.A.; Roushdy, H.M.; Abdelraheem, K.

    1994-01-01

    The levels of norepinephrine (NE), dopamine (DA), 5-hydroxy-tryptamine (5-HT) and 5-hydroxy-indole acetic acid (5-HIAA) were examined in the brain areas:cortex,: cerebellum, striatum and pons in rats exposed to whole body gamma-irradiation at the dose levels 6.5 and 10 Gy. The data obtained indicated that: 6.5 Gy induced in all brain areas, a slight increase in 5-HT concomitant with significant decrease in NE, DA levels, besides a significant increase in 5-HTAA in cerebellum and pons. After the dose 10 Gy the maximum excitation of 5-HT level was in striatum whereas declines in NE, DA were recorded in all brain areas. 5-HIAA displayed significant increase in cerebellum and pons and maximum decline in the cortex. 4 tab

  12. The research of morphological variations and sexual dimorphism of primary grooves on the medial side of brain hemispheres in humans

    Directory of Open Access Journals (Sweden)

    Spasojević Goran

    2012-01-01

    Full Text Available Morphological studies of the various parts of the brain show certain morphological and morphometric differences in correlation with sex, so-called sexual dimorphism of the brain. Our research has been done on the cerebral hemispheres, taken from cadavers of both sexes and different age without pathological processes in the brain. The sample comprised 26 male brains and 16 female brains. We studied three primary grooves (sulcus cinguli, sulcus parietooccipitalis and sulcus calcarinus of the medial surface of the human cerebral hemispheres. We conducted morphological typology of grooves and morphometric measurements of primary brain grooves length in relation to sex and side of hemisphere. The results showed a statistically significant sex difference in the cingulate sulcus length (p0,05. Determined morphometric sexual dimorphism in cingulate sulcus length is significant because it implies the correlation between morphology and function of the explored areas of the cerebral cortex.

  13. Use of primary cultures of Kenyon cells from bumblebee brains to assess pesticide side effects.

    Science.gov (United States)

    Wilson, Daniel E; Velarde, Rodrigo A; Fahrbach, Susan E; Mommaerts, Veerle; Smagghe, Guy

    2013-09-01

    Bumblebees are important pollinators in natural and agricultural ecosystems. The latter results in the frequent exposure of bumblebees to pesticides. We report here on a new bioassay that uses primary cultures of neurons derived from adult bumblebee workers to evaluate possible side-effects of the neonicotinoid pesticide imidacloprid. Mushroom bodies (MBs) from the brains of bumblebee workers were dissected and dissociated to produce cultures of Kenyon cells (KCs). Cultured KCs typically extend branched, dendrite-like processes called neurites, with substantial growth evident 24-48 h after culture initiation. Exposure of cultured KCs obtained from newly eclosed adult workers to 2.5 parts per billion (ppb) imidacloprid, an environmentally relevant concentration of pesticide, did not have a detectable effect on neurite outgrowth. By contrast, in cultures prepared from newly eclosed adult bumblebees, inhibitory effects of imidacloprid were evident when the medium contained 25 ppb imidacloprid, and no growth was observed at 2,500 ppb. The KCs of older workers (13-day-old nurses and foragers) appeared to be more sensitive to imidacloprid than newly eclosed adults, as strong effects on KCs obtained from older nurses and foragers were also evident at 2.5 ppb imidacloprid. In conclusion, primary cultures using KCs of bumblebee worker brains offer a tool to assess sublethal effects of neurotoxic pesticides in vitro. Such studies also have the potential to contribute to the understanding of mechanisms of plasticity in the adult bumblebee brain. © 2013 Wiley Periodicals, Inc.

  14. Role of Omega 3 Fatty Acids Against Ehrlich Ascites Carcinoma-Induced Hepatic and Brain Dysfunctions in Gamma Irradiated Mice

    International Nuclear Information System (INIS)

    El-Gharib, M.M.M.

    2014-01-01

    Cancer is a deadly disease that has touched the lives of many people in the world today. Omega 3 essential fatty acids (ω-3 FAs); found in high concentrations in fish oil, claim a plethora of health benefits. The present study aimed to evaluate the role of ω-3 FAs supplementation either alone or combined with fractionated γ-radiation exposure against Ehrlich solid tumor-induced inflammation, oxidative stress, biochemical alterations and histopathological changes in the liver, brain and tumor tissues of Albino mice. ω-3 FAs were orally administered via gavages to mice for a period of 30 consecutive days at a dose of 300 mg/kg body weight. On the 7th day of experiment, mice were subcutaneously transplanted in the neck region with 0.2 ml of Ehrlich ascites carcinoma cells for solid tumor induction and on the 17th and 25th days, mice were exposed to a fractionated whole body γ-radiation (0.5 Gy/week for two weeks). The results of the present work showed that Ehrlich carcinoma (EC) and/or γ-irradiation led to systemic inflammation (elevated TNF-α, TLC and CRP levels), hepatic oxidative stress (elevated TBARs level, decreased GSH, GSH-Px, CAT and SOD levels) and biochemical alterations in liver (elevated AST, ALT, ALP and LDH activities) and brain (dopamine, EP,NE and serotonin levels) tissues. On the other hand, ω-3 FAs supplementation to the experimentally irradiated EC-bearing mice, significantly reduced tumor size, depressed the concentrations of inflammatory markers, reduced oxidative stress and also ameliorated the biochemical alterations in liver and brain tissues. Histopathological examinations showed that treatment with ω-3 FAs recorded great destruction of tumor tissue, great disappearance of metastatic EC cells from the liver tissue and normal appearance in cerebrum and cerebellum of brain tissue layers in EC-bearing mice. Combined treatment of EC-bearing mice with ω-3 FAs and γ-irradiation showed necrotic cells and remnant tumor cells in tumor

  15. Feasibility of the evidence-based cognitive telerehabilitation program ReMind for patients with primary brain tumors

    NARCIS (Netherlands)

    van der Linden, S.D.; Sitskoorn, M.M.; Rutten, G.J.M.; Gehring, K.

    2018-01-01

    Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation

  16. Computed tomographic aspects of primary brain tumors in dogs and cats

    International Nuclear Information System (INIS)

    Babicsak, Viviam Rocco; Zardo, Karen Maciel; Santos, Debora Rodrigues dos; Silva, Luciana Carandina da; Machado, Vania Maria de Vasconcelos; Vulcano, Luiz Carlos

    2011-01-01

    Over the years, the Veterinary Medicine has made great advances, enabling thus the diagnosis of many diseases. As a result of this new situation, there was an increased expectation of life of animals resulting in an increase in the number of clinical care of older animals. Thus, diseases considered unusual in the past, begin to be diagnosed more frequently, as is the case of brain damage. Recently, computed tomography has been widely used in Brazil as a tool to aid in the diagnosis of several diseases. This noninvasive imaging technique allows the identification and evaluation of lesions of central nervous tissue such as brain tumors. This provides information about the size, shape and location of the lesion, in addition to the magnitude of compression and invasion of adjacent structures by the tumor and its side effects (such as the peritumoral edema and hydrocephalus). The image obtained from computed tomography may suggest the presence of a certain type brain tumor, data of great importance for the prognosis and treatment of the animal. This review covers the computed tomography aspects of primary brain tumors such as meningiomas, astrocytomas, oligodendrogliomas, choroid plexus tumors and ependymomas. However, despite the computed tomography provide much information about the changes inside the skull; no way replace histopathological examination in determining the definitive diagnosis. (author)

  17. Structural brain alterations in primary open angle glaucoma: a 3T MRI study

    Science.gov (United States)

    Wang, Jieqiong; Li, Ting; Sabel, Bernhard A.; Chen, Zhiqiang; Wen, Hongwei; Li, Jianhong; Xie, Xiaobin; Yang, Diya; Chen, Weiwei; Wang, Ningli; Xian, Junfang; He, Huiguang

    2016-01-01

    Glaucoma is not only an eye disease but is also associated with degeneration of brain structures. We now investigated the pattern of visual and non-visual brain structural changes in 25 primary open angle glaucoma (POAG) patients and 25 age-gender-matched normal controls using T1-weighted imaging. MRI images were subjected to volume-based analysis (VBA) and surface-based analysis (SBA) in the whole brain as well as ROI-based analysis of the lateral geniculate nucleus (LGN), visual cortex (V1/2), amygdala and hippocampus. While VBA showed no significant differences in the gray matter volumes of patients, SBA revealed significantly reduced cortical thickness in the right frontal pole and ROI-based analysis volume shrinkage in LGN bilaterally, right V1 and left amygdala. Structural abnormalities were correlated with clinical parameters in a subset of the patients revealing that the left LGN volume was negatively correlated with bilateral cup-to-disk ratio (CDR), the right LGN volume was positively correlated with the mean deviation of the right visual hemifield, and the right V1 cortical thickness was negatively correlated with the right CDR in glaucoma. These results demonstrate that POAG affects both vision-related structures and non-visual cortical regions. Moreover, alterations of the brain visual structures reflect the clinical severity of glaucoma. PMID:26743811

  18. Issues involved in food irradiation and its commercial application: a discussion paper prepared for the Primary and Allied Industries Council

    International Nuclear Information System (INIS)

    1988-01-01

    The Australian Department of Primary Industries and Energy's interest in food irradiation stems from its responsibilities under the Export Control Act (1982) and the Quarantine Act (1908) and the implications this process may have for Australian food exports and quarantine control. Food irradiation is regarded by the Department as a process which may provide an alternative to some existing conventional food treatments. It is not expected to replace completely other processes, but subject to the overseas acceptance of imported irradiated foods, it could offer Australian exporters an additional processing and/or quarantine treatment. The Department's position is that foods irradiated in approved facilities in Australia could be approved for export provided they comply with the regulatory requirements of the importing country and are appropriately labelled or identified. The Department maintains the view that the choice to use this technology is a commercial decision which will depend on many factors including: acceptability of the toxicological aspects, demand for benefits it provides, its cost and competitiveness with alternative treatments, approval by Australian and international regulatory authorities, and importantly, the willingness of consumers to buy irradiated foods

  19. U.V.-enhanced reactivation of u.v.-irradiated herpes virus by primary cultures of rat hepatocytes

    International Nuclear Information System (INIS)

    Zurlo, J.; Yager, J.D.

    1984-01-01

    Carcinogen treatment of cultured mammalian cells prior to infection with u.v.-irradiated virus results in enhanced virus survival and mutagenesis suggesting the induction of SOS-type processes. In this paper, we report the development of a primary rat hepatocyte culture system to investigate cellular responses to DNA damage which may be relevant to hepatocarcinogenesis in vivo. We have obtained data demonstrating that enhanced reactivation of u.v.-irradiated Herpes simplex virus type 1 (HSV-1) occurs in hepatocytes irradiated with u.v. Cultured hepatocytes were pretreated with u.v. at the time of enhanced DNA synthesis. These treatments caused an inhibition followed by a recovery of DNA synthesis. At various times after pretreatment, the hepatocytes were infected with control or u.v.-irradiated HSV-1 at low multiplicity, and virus survival was measured by direct plaque assay. U.v.-irradiated HSV-1 exhibited the expected two-component survival curve in control or u.v. pretreated hepatocytes. The magnitude of enhanced reactivation of HSV-1 was dependent on the u.v. dose to the hepatocytes, the time of infection following u.v. pretreatment, and the level of DNA synthesis at the time of pretreatment. These results suggest that u.v. treatment of rat hepatocytes causes the induction of SOS-type functions that may have a role in the initiation of hepatocarcinogenesis

  20. Enhancement of the efficacy of x-irradiation by pentobarbital in a rodent brain-tumor model

    International Nuclear Information System (INIS)

    Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H.

    1990-01-01

    Radiation therapy is an important component of brain tumor treatment, but its efficacy is limited by its toxicity to the surrounding normal tissue. Pentobarbital acts as a cerebral radioprotectant, but the selectivity of its protection for the central nervous system has not been demonstrated. To determine if pentobarbital also protects tumor against ionizing radiation, five groups of Fischer 344 rats were observed after exposure to varying combinations of the presence or absence of implanted tumor, pentobarbital, and radiation treatment. The first three groups underwent cerebral implantations of a suspension of 9L gliosarcoma cells. Group 1 was left untreated and served as tumor-bearing controls. Group 2 received 30 Gy of whole-brain x-irradiation without anesthesia 8 days after tumor implantation. Group 3 received the same radiation treatment 15 minutes after pretreatment with 60 mg/kg of pentobarbital intraperitoneally. Groups 4 and 5 served as radiation controls, receiving 30 Gy of x-irradiation while awake and 30 Gy of x-irradiation after pentobarbital administration, respectively. Survival was calculated from the death of the last tumor-bearing rat. The mean survival time in tumor-bearing control rats was 20.8 +/- 2.6 days (+/- standard deviation). X-irradiation alone significantly enhanced the period of survival in rats implanted with the 9L tumor (29.7 +/- 5.6 days, p less than 0.03). Further significant prolongation of survival was seen with the addition of pentobarbital to the treatment regimen (39.9 +/- 13.5 days, p less than 0.01). Nontumor-bearing rats irradiated while awake (Group 4) survived 30.9 +/- 2.3 days. All of their pentobarbital-anesthetized counterparts in Group 5 survived. If pentobarbital had offered radioprotection to the tumor, then Group 3 would have had a shorter survival period than Group 2

  1. Protective effects of hydroxysaffor yellow A on brain injury in mice irradiated by 300 MeV/n 12C6+ ions

    International Nuclear Information System (INIS)

    Gan Lu; Wang Zhenhua; Zhang Hong; Ma Chengjun; Li Guang

    2012-01-01

    Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction, to which no ideal prevention method is available until now. Hydroxysaffor yellow A (HSYA) is the main active ingredient of the traditional Chinese medicine safflower, with protective effects against cerebral ischemic injury. In this work, we investigated the protective effects of HSYA on brain injury in mice irradiated by 300 MeV/u 12 C 6+ ion beam. The whole head of male Kunming mouse was irradiated to 4.0 Gy after receiving daily intra-peritoneal injection HSYA for 3 d. One month later, the Morris water maze test was used to detect the spatial memory in mice. The Evans blue was used as the tracer to evaluate the permeability of blood-brain barrier. The SOD activity and MDA content in brain tissue were assayed by test kits. The results showed that the 12 C 6+ irradiation significantly impaired the spatial learning and memory in mice, increased the permeability of blood-brain barrier and the MDA content in brain tissue, whereas decreased the SOD activity in brain tissue. The pretreatment with HSYA could improve the spatial memory deficits and inhibit the changes of the blood-brain barrier, the SOD activity and the MDA content in brain tissue in mice. All these demonstrate that HSYA possesses the protective effect against brain injury induced by 12 C 6+ particle therapy. (authors)

  2. The toxicity of uranyl nitrate on primary brain cell culture of L. Hoevenii

    International Nuclear Information System (INIS)

    Ismail Bahari; Fauziah Mohd Noor

    1995-01-01

    In Malaysia, uranium is indirectly being concentrated by mining and petroleum industries that have no relevance to its use. Concentration of uranium and the production of TENORM may give rise to radiological risk to workers and the environment. A study was conducted to determine the toxicity of a uranium compound, uranyl nitrate. For this purpose a primary brain cell culture derived from L. hoevenii was used. The nature of uranil nitrate toxicity was determined by comparing with the effects induced by mitomycin C and gamma radiation. The toxicity of these agents were measured by observing changes in Unschedule DNA Synthesis (UDS) and the induction of micronucleus. Result from the study showed that UO sub 2 sup 2+ is UDS positive and is toxic to the primary brain cells of L. hoevenii. It gives a response profile that is almost similar to that induced by gamma radiation and mitomycin C. We believed that a low concentration, UO sub 2 sup 2+ acts as a chemo toxic agent rather than as an ionising radiation. At higher concentration the toxicity of UO sub 2 sup 2+ comes from both its chemo toxic and radiation effects. Results of this study also show the ability of the primary culture to carry out repair on its DNA damaged by the UDS positive agents

  3. Effect of MgSO4 on expression of NSE and S-100 in rats brain tissue irradiated by 6 MeV electron beam

    International Nuclear Information System (INIS)

    Zhou Juying; Wang Lili; Yu Zhiying; Qin Songbing; Xu Xiaoting; Li Li; Tu Yu

    2007-01-01

    Objective: To explore the protection of magnesium sulfate (MgSO 4 ) on radiation-induced acute brain injuries. Methods: Thirty six mature Sprague-Dawley rats were randomly divided into 3 groups: blank control group, experimental control group and experimental administered group. The whole brain of SD rats of experimental control group and experimental-therapeutic group were irradiated with a dose of 20 Gy using 6 MeV electron beam. Magnesium sulfate was injected intraperitoneally into the rats of experimental-therapeutic group before and after irradiation for five times. The brain tissue were taken on days 1, 7, 14 and 30 after irradiation. Immunohistochemical method was used to detect the expressions of NSE and S-100 in brain tissue. All data were processed statistically with One-ANOVA analysis. Results: The expressions of NSE and S-100 after whole brain irradiation were time-dependent. Compared with blank control group, the expression of NSE in brains of experimental control group decreased significantly (P 4 can inhibit the expression of S-100, but induce the expression of NSE on radiation-induced acute brain injury. MgSO 4 has a protective effect on radiation-induced acute brain injury. (authors)

  4. Occupational and environmental risk factors of adult primary brain cancers: a systematic review.

    Science.gov (United States)

    Gomes, J; Al Zayadi, A; Guzman, A

    2011-04-01

    The incidence of brain neoplasm has been progressively increasing in recent years in the industrialized countries. One of the reasons for this increased incidence could be better access to health care and improved diagnosis in the industrialized countries. It also appears that Caucasians have a higher incidence than blacks or Hispanics or Asians. A number of risk factors have been identified and described including the genetic, ethnic and age-based factors. Certain occupational and environmental factors are also believed to influence the risk of primary adult brain tumors. Potential occupational and environmental factors include exposure to diagnostic and therapeutic radiations, electromagnetic radiation from cellular phones and other wireless devices, infectious agents, air pollution and residence near landfills and high-voltage power lines and jobs as firefighters, farmers, physician, chemists and jobs in industries such as petrochemical, power generation, synthetic rubber manufacturing, agricultural chemicals manufacturing. The purpose of this systematic review is to examine occupational and environmental risk factors of brain neoplasm. A range of occupational and environmental exposures are evaluated for significance of their relationship with adult primary brain tumors. On the basis of this review we suggest a concurrent evaluation of multiple risk factors both within and beyond occupational and environmental domains. The concurrent approach needs to consider better exposure assessment techniques, lifetime occupational exposures, genotypic and phenotypic characteristics and lifestyle and dietary habits. This approach needs to be interdisciplinary with contributions from neurologists, oncologists, epidemiologists and molecular biologists. Conclusive evidence that has eluded multitude of studies with single focus and single exposure needs to multifaceted and multidisciplinary.

  5. Feasibility of the evidence-based cognitive telerehabilitation program Remind for patients with primary brain tumors.

    Science.gov (United States)

    van der Linden, Sophie D; Sitskoorn, Margriet M; Rutten, Geert-Jan M; Gehring, Karin

    2018-05-01

    Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation program developed by our group. We converted the program into the iPad-based cognitive rehabilitation program ReMind, to increase its accessibility. The app incorporates psychoeducation, strategy training and retraining. This pilot study in patients with primary brain tumors evaluates the feasibility of the use of the ReMind-app in a clinical (research) setting in terms of accrual, attrition, adherence and patient satisfaction. The intervention commenced 3 months after resective surgery and patients were advised to spend 3 h per week on the program for 10 weeks. Of 28 eligible patients, 15 patients with presumed low-grade glioma or meningioma provided informed consent. Most important reason for decline was that patients (7) experienced no cognitive complaints. Participants completed on average 71% of the strategy training and 76% of the retraining. Some patients evaluated the retraining as too easy. Overall, 85% of the patients evaluated the intervention as "good" or "excellent". All patients indicated that they would recommend the program to other patients with brain tumors. The ReMind-app is the first evidence-based cognitive telerehabilitation program for adult patients with brain tumors and this pilot study suggests that postoperative cognitive rehabilitation via this app is feasible. Based on patients' feedback, we have expanded the retraining with more difficult exercises. We will evaluate the efficacy of ReMind in an RCT.

  6. Role of prophylactic brain irradiation in limited stage small cell lung cancer: clinical, neuropsychologic, and CT sequelae

    International Nuclear Information System (INIS)

    Laukkanen, E.; Klonoff, H.; Allan, B.; Graeb, D.; Murray, N.

    1988-01-01

    Ninety-four patients with limited stage small cell lung cancer treated between 1981 and 1985 with a regimen including prophylactic brain irradiation (PBI) after combination chemotherapy were assessed for compliance with PBI, brain relapse, and neurologic morbidity. Seventy-seven percent of patients had PBI and of these, 22% developed brain metastases after a median time of 11 months post treatment. The brain was the apparent unique initial site of relapse in 10% of PBI cases but more commonly brain relapse was preceded or accompanied by failure at other sites, especially the chest. Brain metastases were the greatest cause of morbidity in 50% of PBI failures. Twelve of 14 PBI patients alive 2 years after treatment had oncologic, neurologic, and neuropsychological evaluation, and brain CT. All long-term survivors were capable of self care and none fulfilled diagnostic criteria for dementia, with three borderline cases. One third had pretreatment neurologic dysfunction and two thirds post treatment neurologic symptoms, most commonly recent memory loss. Fifty percent had subtle motor findings. Intellectual functioning was at the 38th percentile with most patients having an unskilled occupational history. Neuropsychologic impairment ratings were borderline in three cases and definitely impaired in seven cases. CT scans showed brain atrophy in all cases with mild progression in those having a pre-treatment baseline. Periventricular and subcortical low density lesions identical to the CT appearance of subcortical arteriosclerotic encephalopathy were seen in 82% of posttreatment CT studies, and lacunar infarcts in 54%. Neuropsychologic impairment scores and the extent of CT periventricular low density lesions were strongly associated

  7. CHOD/BVAM Chemotherapy and Whole-Brain Radiotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma

    International Nuclear Information System (INIS)

    Laack, Nadia N.; O'Neill, Brian Patrick; Ballman, Karla V.; O'Fallon, Judith Rich; Carrero, Xiomara W.; Kurtin, Paul J.; Scheithauer, Bernd W.; Brown, Paul D.; Habermann, Thomas M.; Colgan, Joseph P.; Gilbert, Mark R.; Hawkins, Roland B.; Morton, Roscoe F.; Windschitl, Harry E.; Fitch, Tom R.; Pajon, Eduardo R.

    2011-01-01

    Purpose: To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients 70 years old and younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint was 1-year survival. Results: Thirty-six patients (19 men, 17 women) enrolled between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty (83%) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1. All 36 patients were eligible for survival and response evaluations. Median time to progression was 12.3 months, and median survival was 18.5 months. The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%, respectively. The best response was complete response in 10 patients and immediate progression in 7 patients. Ten (28%) patients had at least one grade 3 or higher neurologic toxicity. Conclusions: This regimen did improve the survival of PCNSL patients but also caused substantial toxicity. The improvement in survival is less than that reported with high-dose methotrexate-based therapies.

  8. Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

    DEFF Research Database (Denmark)

    Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

    2016-01-01

    Background: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. Methods: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive...... lung cancer patients with brain metastases. Results: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p ... of peritumoral brain edema (p

  9. Enhanced Network Efficiency of Functional Brain Networks in Primary Insomnia Patients

    Directory of Open Access Journals (Sweden)

    Xiaofen Ma

    2018-02-01

    Full Text Available Accumulating evidence from neuroimaging studies suggests that primary insomnia (PI affects interregional neural coordination of multiple interacting functional brain networks. However, a complete understanding of the whole-brain network organization from a system-level perspective in PI is still lacking. To this end, we investigated in topological organization changes in brain functional networks in PI. 36 PI patients and 38 age-, sex-, and education-matched healthy controls were recruited. All participants underwent a series of neuropsychological assessments and resting-state functional magnetic resonance imaging scans. Individual whole-brain functional network were constructed and analyzed using graph theory-based network approaches. There were no significant differences with respect to age, sex, or education between groups (P > 0.05. Graph-based analyses revealed that participants with PI had a significantly higher total number of edges (P = 0.022, global efficiency (P = 0.014, and normalized global efficiency (P = 0.002, and a significantly lower normalized local efficiency (P = 0.042 compared with controls. Locally, several prefrontal and parietal regions, the superior temporal gyrus, and the thalamus exhibited higher nodal efficiency in participants with PI (P < 0.05, false discovery rate corrected. In addition, most of these regions showed increased functional connectivity in PI patients (P < 0.05, corrected. Finally, altered network efficiency was correlated with neuropsychological variables of the Epworth Sleepiness Scale and Insomnia Severity Index in patients with PI. PI is associated with abnormal organization of large-scale functional brain networks, which may account for memory and emotional dysfunction in people with PI. These findings provide novel implications for neural substrates associated with PI.

  10. Effect of gamma irradiation on the activity of alanine and aspartate transaminases in subcellular fractions of the brain and heart in white rats

    Energy Technology Data Exchange (ETDEWEB)

    Plenin, A E

    1973-01-01

    In experiments on rats, the activity of alanine (I) and aspartate transaminases (II) was studied in homogenates and subcellular fractions of the brain and myocardium under normal conditions and for 30 days after ..gamma.. irradiation at 40 rads. The activity of II in brain homogenates increased 1 hour after irradiation but decreased by 20 percent on day 3; it decreased again on days 7 and 15. The activity of brain I increased after 1 hour and 3 days but then returned to normal. The activity of I in heart homogenates increased in all the periods after irradiation. The subcellular fractions exhibited phase changes in the activity of the enzymes. These changes were different in nature from those observed after X and ..gamma.. irradiation at the same dose.

  11. Radioprotection by dipyridamole in the aging mouse. Effects on lipid peroxidation in mouse liver, spleen and brain after whole-body X-ray irradiation

    International Nuclear Information System (INIS)

    Seino, Noritaka

    1995-01-01

    To investigate the radioprotective effect of dipyridamole in the aging mouse, the lipid peroxide content in aging mouse liver, spleen and brain irradiated by X-ray were measured both before and after injection of dipyridamole. The lipid peroxide content increased with aging from 2 months old to 16 months old in the mouse liver, spleen and brain. The content of lipid peroxide in the liver and spleen of the aging mouse was significantly increased in 7 days after whole-body irradiation with 8 Gy, but was unchanged in the brain. Dipyridamole, given before irradiation, significantly inhibited the increase of lipid peroxide after irradiation. These results suggest that dipyridamole may have radioprotective effects on aging mouse liver and spleen as well as on young mouse, and that inhibition of lipid peroxidation is a possible factor in the radioprotective effect of dipyridamole. (author)

  12. Interstitial brachytherapy with 192-IR in treatment of recurrent malignant primary brain tumors

    International Nuclear Information System (INIS)

    Cardenes, R.; Martinez, R.; Victoria, C.; Nunez, L.; Clavo, B.; Sancedo, G.

    1994-01-01

    Seven patients with recurrent malignant primary brain tumors after surgery and radiation therapy were treated at the Clinica Puerta de Hierro (Madrid) by interstitial brachytherapy with 192-Ir sources. Implantations were performed using computerized tomography and dose prescription were determined following the Paris system rules for interstitial implants. The means dose deliberated was 50 to 65 Gy to the reference isodoses. At the last follow-up all patients except for one are alive and without evidence of progression of the disease. (Author) 35 refs

  13. High predictive value of brain MRI imaging in primary mitochondrial respiratory chain deficiency.

    Science.gov (United States)

    de Beaurepaire, Isaure; Grévent, David; Rio, Marlène; Desguerre, Isabelle; de Lonlay, Pascale; Levy, Raphaël; Dangouloff-Ros, Volodia; Bonnefont, Jean-Paul; Barcia, Giulia; Funalot, Benoit; Besmond, Claude; Metodiev, Metodi D; Ruzzenente, Benedetta; Assouline, Zahra; Munnich, Arnold; Rötig, Agnès; Boddaert, Nathalie

    2018-06-01

    Because the mitochondrial respiratory chain (RC) is ubiquitous, its deficiency can theoretically give rise to any symptom in any organ or tissue at any age with any mode of inheritance, owing to the twofold genetic origin of respiratory enzyme machinery, that is, nuclear and mitochondrial. Not all respiratory enzyme deficiencies are primary and secondary or artefactual deficiency is frequently observed, leading to a number of misleading conclusions and inappropriate investigations in clinical practice. This study is aimed at investigating the potential role of brain MRI in distinguishing primary RC deficiency from phenocopies and other aetiologies. Starting from a large series of 189 patients (median age: 3.5 years (8 days-56 years), 58% males) showing signs of RC enzyme deficiency, for whom both brain MRIs and disease-causing mutations were available, we retrospectively studied the positive predictive value (PPV) and the positive likelihood ratio (LR+) of brain MRI imaging and its ability to discriminate between two groups: primary deficiency of the mitochondrial RC machinery and phenocopies. Detection of (1) brainstem hyperintensity with basal ganglia involvement (P≤0.001) and (2) lactate peak with either brainstem or basal ganglia hyperintensity was highly suggestive of primary RC deficiency (P≤0.01). Fourteen items had a PPV>95% and LR+ was greater than 9 for seven signs. Biallelic SLC19A3 mutations represented the main differential diagnosis. Non-significant differences between the two groups were found for cortical/subcortical atrophy, leucoencephalopathy and involvement of caudate nuclei, spinothalamic tract and corpus callosum. Based on these results and owing to invasiveness of skeletal muscle biopsies and cost of high-throughput DNA sequencing, we suggest giving consideration to brain MRI imaging as a diagnostic marker and an informative investigation to be performed in patients showing signs of RC enzyme deficiency. © Article author(s) (or their

  14. Energy and glucose pathways in thiamine deficient primary rat brain microvascular endothelial cells.

    Science.gov (United States)

    Ham, D; Karska-Wysocki, B

    2005-12-01

    Thiamine deficiency (TD) results in lactate acidosis, which is associated with neurodegeneration. The aim of this study was to investigate this alteration in primary rat brain endothelia. Spectrophotometric analysis of culture media revealed that only a higher concentration of pyrithiamine, which accelerates the intracellular blocking of thiamine, significantly elevated the lactate level and lactate dehydrogenase activity within 7 days. The medium without pyrithiamine and with a thiamine concentration comparable to pathophysiological plasma levels mildly reduced only the activity of transketolase. This suggests that significant metabolic changes may not occur at the early phase of TD in cerebral capillary cells, while anaerobic glycolysis in capillaries may be mediated during late stage/chronic TD.

  15. [A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation].

    Science.gov (United States)

    Kakeya, Hiroshi; Inoue, Yuichi; Sawai, Toyomitsu; Ikuta, Yasushi; Ohno, Hideaki; Yanagihara, Katsunori; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Soda, Hiroshi; Tashiro, Takayoshi; Kohno, Shigeru

    2005-12-01

    A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.

  16. Differential gene expression in primary fibroblasts induced by proton and cobalt-60 beam irradiation

    DEFF Research Database (Denmark)

    Nielsen, Steffen; Bassler, Niels; Grzanka, Leszek

    2017-01-01

    profile: entrance, mid-SOBP and at the SOBP distal edge. Dose was delivered in three fractions × 3.5 Gy(RBE) (RBE 1.1). Cobalt-60 (Co-60) irradiation was used as reference. Real-time qPCR was performed to determine gene expression levels for 17 genes associated with inflammation response, fibrosis...... and angiogenesis. RESULTS: Differences in median gene expression levels were observed for multiple genes such as IL6, IL8 and CXCL12. Median IL6 expression was 30%, 24% and 47% lower in entrance, mid-SOBP and SOBP distal edge groups than in Co-60 irradiated cells. No genes were found to be oppositely regulated...... fibroblast cultures. Inflammatory factors were generally less extensively upregulated by proton irradiation compared with Co-60 photon irradiation. These effects may possibly influence the development of normal tissue damage in patients treated with proton beam therapy....

  17. Primary Observations on the Influence of 60Co Local Irradiation on Free Skin Flaps

    Institute of Scientific and Technical Information of China (English)

    杨建荣; 张园

    2002-01-01

    Objective To study the effect of postoperative radiation on free skin flaps.Methods Twenty-nine patients with free skin flaps applied to the plerosis of the postoperative defectwere followed up. Twenty-eight out of 29 patients received forearm free flaps while 1 had anterolater-al femoris skin flaps in a size ranging from 14 cm× 6 cm to 8 cm× 4 cm. These flaps were exposedto 60Co radiation ranging 40-69 Gy. Results Observation during irradiation: no visible changes ofskin flaps and oral mucous membrane were detected when irradiation dose was within 40 Gy; somechanges may be detected over 40 Gy. Observation 1 - 4 months after irradiation: pigmentations werefound in areas of erosion epidermis; skin flaps got dark but without evidence of necrosis. Observation2 years after irradiation: no necrosis happened in 29 skin flaps. Hairs were found on 15 of 29flaps. Sensation occurred within the margin of 1 cm. Conclusion Free skin flap can endure irradi-ation at the dose of 60 Gy.

  18. Effect of Omega-3 Fatty Acids on Neurotransmitters Level in the Brain of Male Albino Rats Exposed to Gamma Irradiation

    International Nuclear Information System (INIS)

    Saada, H.N.; Said, U.Z.; Shedid, S.M.; Mahdy, E.M.E.; Elmezayen, H.E.

    2014-01-01

    The omega-3 fatty acids are essential dietary nutrients, and one of their important roles is providing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for growth and function of nervous tissue. Reduced level of DHA in the brain induce dramatic changes in brain function including changes in size of neurons as well as changes in learning and memory. The objective of this study was to evaluate the role of fish oil rich in omega-3 fatty acids on γ-radiation-induced physiological changes in the brain cerebral hemispheres. Omega-3 fatty acids was supplemented daily by gavages to rats at a dose of 400 mg/ kg body wt for 7 days pre- and 21 days post-exposure to whole body fractionated gamma rays at doses of 2 Gy/week up to a total dose of 8 Gy. The results demonstrated that whole body γ-irradiation induced oxidative stress, de - creased the main polyunsaturated fatty acids; DHA and EPA, and induced neurotransmitters alteration in brain tissues. Oxidative stress was manifested by a significant increase in lipid peroxidation product malondialdehyde (MDA) and decrease in the activity of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Oxidative stress was accompanied by alterations in the level of the neurotransmitters manifested by a significant increase of glutamic and aspartic and a significant decrease of serotonin (5-HT) levels in brain cerebral hemispheres. Rats receiving fish oil 7 days before and 21 days after exposure to γ-radiation showed significant improvement in the levels of EPA and DHA associated with significant amelioration of oxidative stress and neurotransmitters alteration. It is concluded that fish oil protect the brain from radiation-induced physiological changes by protecting brain cellular membranes through counteracting the decrease of omega-3 fatty acids and minimizing oxidative stress

  19. Breast conserving surgery following primary irradiation in 3-7 cm breast cancer: pathologic response and outcome

    International Nuclear Information System (INIS)

    Saint-Gaudens, Anne Bareille; Vilcoq, Jacques R.; Campana, Francois; Gautier, Chantal; Asselain, Bernard; Rocherfordiere, Anne de la; Clough, Krishna B.; Fourquet, Alain

    1997-01-01

    Purpose: To retrospectively evaluate histologic response and outcome of patients treated by primary irradiation followed by conservative surgery. Materials and Methods: Between 1981 and 1993, 1742 patients (pts.) with large 3-7 cm invasive breast cancer were treated by primary breast and nodes irradiation in our institution. Of these, 311 pts. (18%) further underwent a wide excision of the residual tumor. Median age was 55 years (yrs.) (29 - 79 yrs.). Median breast tumor size was 40 mm (35 - 70mm). 149 pts. (48%) were premenopausal. 142 pts (46%) had clinically palpable axillary nodes. Diagnosis of invasive breast cancer was performed in all patients by drill biopsy. Following diagnosis, all 311 patients were treated by external irradiation to the breast and regional nodes. Median dose to the breast was 55 Gy (50 - 64 Gy) over 5.5 weeks. Following this irradiation, all patients underwent a wide surgical excision with (140 pts; 45%) or without (171 pts; 55%) axillary node dissection. In addition, 70 pts (22.5%) received adjuvant chemotherapy and 70 pts. received hormone therapy after local treatment. All patients were then regularly followed. Results: Median residual breast tumor size after completion of irradiation was 20 mm (0 - 50mm). On pathologic examination, 34 (11%) tumors had no residual malignant cells (complete response), 137 tumors (44%) had residual fibrosis with clusters of viable cells (partial response), and 138 tumors (45%) had residual viable malignant cells (no response). Median follow up was 106 months (10 - 188 months). Actuarial 9-year overall survival rate was 69 % ± 6%. The 9-year metastasis-free interval was 58 % ± 6%. The 9-year breast recurrence rate was 22 % ± 5 %. The 9-year breast preservation rate was 84% ± 5%. Pathologic response was not predictive of outcome, either distant or local. Conclusion: This retrospective study showed that in patients with tumors too large to be treated by upfront breast-conserving surgery, primary breast

  20. Hypothalamus-Related Resting Brain Network Underlying Short-Term Acupuncture Treatment in Primary Hypertension

    Directory of Open Access Journals (Sweden)

    Hongyan Chen

    2013-01-01

    Full Text Available The present study attempted to explore modulated hypothalamus-seeded resting brain network underlying the cardiovascular system in primary hypertensive patients after short-term acupuncture treatment. Thirty right-handed patients (14 male were divided randomly into acupuncture and control groups. The acupuncture group received a continuous five-day acupuncture treatment and undertook three resting-state fMRI scans and 24-hour ambulatory blood pressure monitoring (ABPM as well as SF-36 questionnaires before, after, and one month after acupuncture treatment. The control group undertook fMRI scans and 24-hour ABPM. For verum acupuncture, average blood pressure (BP and heart rate (HR decreased after treatment but showed no statistical differences. There were no significant differences in BP and HR between the acupuncture and control groups. Notably, SF-36 indicated that bodily pain (P = 0.005 decreased and vitality (P = 0.036 increased after acupuncture compared to the baseline. The hypothalamus-related brain network showed increased functional connectivity with the medulla, brainstem, cerebellum, limbic system, thalamus, and frontal lobes. In conclusion, short-term acupuncture did not decrease BP significantly but appeared to improve body pain and vitality. Acupuncture may regulate the cardiovascular system through a complicated brain network from the cortical level, the hypothalamus, and the brainstem.

  1. Brief descriptive epidemiology of primary malignant brain tumors from North-East India.

    Science.gov (United States)

    Krishnatreya, Manigreeva; Kataki, Amal Chandra; Sharma, Jagannath Dev; Bhattacharyya, Mouchumee; Nandy, Pintu; Hazarika, Munlima

    2014-01-01

    Brain tumors are a mixed group of neoplasms that originate from the intracranial tissues and the meninges with degrees of malignancy varying greatly from benign to aggressive. Not much is known about the epidemiology of primary malignant brain tumors (PMBTs) in our population in North-East India. In this analysis, an attempt was made to identify the age groups, gender distribution, topography and different histological types of PMBT with data from a hospital cancer registry. A total of 231 cases of PMBT were identified and included for the present analysis. Our analysis has shown that most of PMBT occur at 20-60 years of age, with a male to female ratio of 2.3:1. Some 70.5% of cases occurred in cerebral lobes except for the occipital lobe, and astrocytic tumors were the most common broad histological type. In our population the prevalence of PMBT is 1% of all cancers, mostly affecting young and middle aged patients. As brain tumors are rare, so case-control analytic epidemiological studies will be required to establish the risk factors prevalent in our population.

  2. A Case of Primary Central Nervous System Lymphoma Located at Brain Stem in a Child.

    Science.gov (United States)

    Kim, Jinho; Kim, Young Zoon

    2016-10-01

    Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's lymphoma that is confined to the brain, eyes, and/or leptomeninges without evidence of a systemic primary tumor. Although the tumor can affect all age groups, it is rare in childhood; thus, its incidence and prognosis in children have not been well defined and the best treatment strategy remains unclear. A nine-year old presented at our department with complaints of diplopia, dizziness, dysarthria, and right side hemiparesis. Magnetic resonance image suggested a diffuse brain stem glioma with infiltration into the right cerebellar peduncle. The patient was surgically treated by craniotomy and frameless stereotactic-guided biopsy, and unexpectedly, the histopathology of the mass was consistent with diffuse large B cell lymphoma, and immunohistochemical staining revealed positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for systemic lymphoma, but no evidence of lymphoma elsewhere in the body was obtained. In addition, she had a negative serologic finding for human immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL. She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis.

  3. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    International Nuclear Information System (INIS)

    Green, Daniel M.; Merchant, Thomas E.; Billups, Catherine A.; Stokes, Dennis C.; Broniscer, Alberto; Bartels, Ute; Chintagumpala, Murali; Hassall, Timothy E.; Gururangan, Sridharan; McCowage, Geoffrey B.; Heath, John A.; Cohn, Richard J.; Fisher, Michael J.; Srinivasan, Ashok; Robinson, Giles W.; Gajjar, Amar

    2015-01-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV 1 ] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO corr ]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m 2 (IQR, 15.7-16.0 g/m 2 ). At 24 and 60 months ACT, DLCO corr was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV 1 was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO corr was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO corr were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI. Continued monitoring of this cohort

  4. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Green, Daniel M., E-mail: daniel.green@stjude.org [Department of Epidemiology and Cancer Control, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Billups, Catherine A. [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Stokes, Dennis C. [Department of Pediatrics, University of Tennessee School of Medicine, Memphis, Tennessee (United States); Broniscer, Alberto [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Bartels, Ute [Department of Haematology and Oncology, The Hospital for Sick Children, Toronto, Ontario (Canada); Chintagumpala, Murali [Department of Pediatric Medicine, Texas Children' s Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas (United States); Hassall, Timothy E. [Department of Haematology and Oncology, Royal Children' s Hospital, Brisbane (Australia); Gururangan, Sridharan [Department of Pediatrics, Duke University Medical Center, Durham, North Carolina (United States); McCowage, Geoffrey B. [Department of Pediatrics, Children' s Hospital at Westmead, Sydney (Australia); Heath, John A. [Children' s Cancer Center, Royal Children' s Hospital Melbourne, Melbourne (Australia); Cohn, Richard J. [Department of Clinical Oncology, Sydney Children' s Hospital, Sydney (Australia); Fisher, Michael J. [Department of Pediatrics, Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Srinivasan, Ashok [Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Robinson, Giles W.; Gajjar, Amar [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2015-09-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV{sub 1}] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO{sub corr}]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m{sup 2} (IQR, 15.7-16.0 g/m{sup 2}). At 24 and 60 months ACT, DLCO{sub corr} was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV{sub 1} was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO{sub corr} was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO{sub corr} were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI

  5. Mutation induction in γ-irradiated primary human bronchial epithelial cells and molecular analysis of the HPRT- mutants

    International Nuclear Information System (INIS)

    Suzuki, Keiji; Hei, Tom K.

    1996-01-01

    We have examined various radiobiological parameters using commercially-available primary normal human bronchial epithelial (NHBE) cells, which can be subcultured more than 20 population doublings, and have established the mutation system in order to characterize the molecular changes in γ-irradiated primary cells. The survival curve, obtained after irradiation of cells with 137 Cs γ-rays, indicates that the D 0 , D q , and n values are 1.34 Gy, 1.12 Gy, and 2.3, respectively. The induction of HPRT - mutation was dose-dependent and the mutant fraction increased in a non-linear fashion. Since the doubling number of NHBE cells is limited, DNA was extracted directly from the single mutant colonies and alteration in the HPRT gene locus was analyzed using multiplex PCR technique. Among spontaneous mutants, the proportion with total and partial deletions of the gene was 10.0% (2/20) and 60.0% (12/20), respectively, while 30.0% (6/20) did not have any detectable changes in the nine exons examined. On the other hand, the fraction of total deletion increased by more than 2-fold among mutants induced by γ-rays in that 26.3% (10/38) of them showed the total gene deletions. Twenty-five out of 38 γ-induced mutants (65.8%) had partial deletions and 3 mutants (7.9%) had no detectable alteration. The present results showed that γ-irradiation efficiently induced HPRT gene mutation in primary human epithelial cells and that most of the induced mutants suffered larger deletions compared to that observed in spontaneous mutants. This system provides a useful tool for determination of mutagenicity and understanding the molecular mechanisms of environmental carcinogens in primary human bronchial cells

  6. Calculation of primary and secondary dose in proton therapy of brain tumors using Monte Carlo method

    International Nuclear Information System (INIS)

    Moghbel Esfahani, F.; Alamatsaz, M.; Karimian, A.

    2012-01-01

    High-energy beams of protons offer significant advantages for the treatment of deep-seated local tumors. Their physical depth-dose distribution in tissue is characterized by a small entrance dose and a distinct maximum - Bragg peak - near the end of range with a sharp falloff at the distal edge. Therefore, research must be done to investigate the possible negative and positive effects of using proton therapy as a treatment modality. In proton therapy, protons do account for the vast majority of dose. However, when protons travel through matter, secondary particles are created by the interactions of protons and matter en route to and within the patient. It is believed that secondary dose can lead to secondary cancer, especially in pediatric cases. Therefore, the focus of this work is determining both primary and secondary dose. Dose calculations were performed by MCNPX in tumoral and healthy parts of brain. The brain tumor has a 10 mm diameter and is located 16 cm under the skin surface. The brain was simulated by a cylindrical water phantom with the dimensions of 19 x 19cm 2 (length x diameter), with 0.5 cm thickness of plexiglass (C 4 H 6 O 2 ). Then beam characteristics were investigated to ensure the accuracy of the model. Simulations were initially validated with against packages such as SRIM/TRIM. Dose calculations were performed using different configurations to evaluate depth-dose profiles and dose 2D distributions.The results of the simulation show that the best proton energy interval, to cover completely the brain tumor, is from 152 to 154 MeV. (authors)

  7. Irradiation induced changes in endogenous regional distribution of catecholamines in rat brain and possible control through combined radioprotective treatments

    International Nuclear Information System (INIS)

    Hassan, S.H.M.; Elsayed, M.E.; Roushdy, H.M.; Maklaad, Y.A.

    1994-01-01

    The present study has been conducted aiming to evaluate the protective role of imidazole serotonin or their combination, on the radiation induced changes in the endogenous catecholamine contents in various areas of rat's brain : cortex, striatum, cerebellum, pons and medulla and thalamus and hypothalamus. Whole body gamma-irradiation (6 Gy) resulted in significant progressive decreases of catecholamine (epinephrine, norepinephrine and dopamine) contents, as investigated one and seven days post exposure. Administration of imidazole or serotonin showed to control radiation induced changes in catecholamine contents. Higher protection with lower potential risk of toxicity could be achieved by administration of lower doses of combined agents. The data suggest that, the endogenous concentration of catecholamines in the brain may play an important role in diagnosing the radiation hazard and evaluating the protective capacity of pharmacologic radioprotective. 2 figs

  8. Irradiation of the lymphatics in the primary treatment of breast cancer

    International Nuclear Information System (INIS)

    Levitt, S.H.

    1991-01-01

    Irradiation is a local treatment which must be delivered to the appropriate areas, with appropriate dosage and careful attention to avoiding excess dosage to normal tissues. Despite the negative reports of meta analyses of randomized adjuvant radiation trials, there has recently been a renewed interest in local regional irradiation by a number of factors: Adjuvant chemotherapy fails to affect the incidence of locoregional recurrences in patients with four or more positive nodes; the benefits in prospective randomized and non randomized trials of large numbers of patients who were not treated with chemotherapy are well documented; analysis of the Cuzick meta analysis and the recent long term reports of the CRC and Manchester studies have demonstrated that they are not reliable. Locoregional recurrences following adjuvant chemotherapy alone are in the chest wall, internal memory and supraclavicular areas. We recommand no nodal irradiation in node negative patients and internal mammary and supraclavicular irradiation in node positive patients. However, irradiation to the axilla is indicated in patients in whom the axilla has not been dissected, the nodes are large and/or the tumor has extended from the nodes into the axilla. 50 Gy target dose is to be delivered in 1.8-2.0 Gy fractions and an additional 10 Gy boost to areas with possible tumor invasion in more advanced cancers. (orig.) [de

  9. Acute response of mouse kidney clonogens to fractionated irradiation in situ and then assayed in primary culture

    International Nuclear Information System (INIS)

    Yeemin Jen; Hendry, J.H.

    1991-01-01

    The radiosensitivity of mouse kidney cells after in situ single-dose, 2, 8, and 16 fraction X-irradiations was measured in primary culture using a clonogenic assay. The assay was made 12 h after single doses or 12 h after the last dose of the multifraction regimens. When analysed using the linear-quadratic model, as predicted the individual α components for all the different fractionation schedules were not significantly different, and the changes in the β values were consistent with those expected on the basis of the reciprocal fraction numbers. When all four data sets were integrated to derive a common α/β ratio, the result was 4.4±1.3 (1SE) Gy, or 2.8±0.9 Gy (a better fit) if the single-dose data set was excluded. These values fall into the range reported for kidney using assays of tissue function at long times after irradiation. (author)

  10. Enzymatic method for the sensitive demonstration of postnatal effects caused by prenatal X-irradiation in mouse brain

    International Nuclear Information System (INIS)

    Weber, L.W.D.; Schmahl, W.G.; Kriegel, H.

    1982-01-01

    We have investigated the activities (per gram of wet tissue) of mouse brain acetylcholinesterase and Na, K-ATPase, with respect to the effects brought about by a prenatal X-ray dose. Pregnant NMRI mice received an X-ray dose of 0.24, 0.49, 0.95 or 1.9 Gy each on the 12th day of gestation. Investigations on the offspring were performed on the day of birth and the postnatal days 2, 5, 8, 12, 16, 23, 34, 48 and 64, respectively. The brain weights were reduced by the X-ray treatment dose - dependently and without recovery. This was well discernible after 0.24 Gy and reached about 40% reduction after 1.9 Gy. There were significant differences between irradiated and control enzyme activities on most of the days examined. On the 48th postnatal day both enzymes' activities were thoroughly elevated after 0.24 and 0.49 Gy. This could be reproduced in another test series with 0.49 Gy, but vanished when enzyme activities were related to the brain protein contents. As a more reliable parameter of the developmental age brain weights were compared to the corresponding enzyme activities. (orig./MG)

  11. A brief introduction of ICRP Publication 49: Developmental effects of irradiation on the brain of the embryo and fetus

    International Nuclear Information System (INIS)

    Kusama, Tomoko

    1988-01-01

    ICRP established a task group within its Committee 1 to carry out studies on the effects of irradiation on the central nerve system of embryos and fetuses. The present article summarizes the study results presented in the report, named ICRP Publication 49, published by the task group. Publication 49 consists of seven chapters dealing with the introduction, development of brain and auxiliary organs of embryo primates, retarded development of central nerve system, ionizing radiation as factor in teratogenesis of central nerve system, maximum susceptibility period, risk estimation for human being, and necessity of research. Radiation may cause either organogenetic or histological disturbances depending on the developmental stage of the brain. Results of animal tests can be applied to studies on the morphogenetic disturbances in human beings. Data on embryos and fetuses that received radiation in Hiroshima or Nagasaki are currently used for the estimation of the risk of disturbance in the brain of human embryos and fetuses. Risk estimation for the brain of human embryo exposed to radiation is discussed. (Nogami, K.)

  12. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation.

    Science.gov (United States)

    Plaga, Alexis; Shields, Lisa B E; Sun, David A; Vitaz, Todd W; Spalding, Aaron C

    2012-01-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  13. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    International Nuclear Information System (INIS)

    Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.; Vitaz, Todd W.; Spalding, Aaron C.

    2012-01-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  14. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Plaga, Alexis; Shields, Lisa B.E. [Norton Neuroscience Institute, Louisville, KY (United States); Sun, David A.; Vitaz, Todd W. [Norton Neuroscience Institute, Louisville, KY (United States); Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Spalding, Aaron C., E-mail: acspalding1@gmail.com [Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Norton Cancer Institute, Radiation Center, Kosair Children' s Hospital, Louisville, KY (United States)

    2012-10-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  15. Combination of neck dissection for cervical metastasis and irradiation of primary tumors for carcinomas of the mesopharynx, hypopharynx, and larynx

    International Nuclear Information System (INIS)

    Sato, Katsuro; Hanazawa, Hideyuki; Takahashi, Sugata; Watanabe, Jun; Tomita, Masahiko

    2006-01-01

    Carcinomas of the mesopharynx, hypopharynx, and larynx with early-stage primary tumor and with cervical lymph node metastasis, were treated by neck dissection for cervical metastasis and definitive irradiation of the primary tumor. In this study, the primary sites of the 16 cases were the mesopharynx (10), the hypopharynx (3), and the larynx (3). Twelve cases of early T stages (T1 or T2) and 15 cases of advanced N stages (N2 or N3) were chosen for this treatment concept. Neck lesions were controlled in all cases and all the primary tumors showed complete response at the end of the initial treatment. One case of mesopharyngeal cancer died due to recurrence of the primary tumor and one case of hypopharyngeal cancer died due to complicated lung cancer. The treatment modality for cases of early primary cancer and advanced cervical lymph node metastasis requires well-balanced strategies for both lesions. In these cases, optimal prognosis was obtained because of careful patient selection. The treatment strategy described in this paper should be considered for cases of early T tumors and advanced N tumors. (author)

  16. Rat behaviour reactions and brain synaptic membrane lipids under the chronical gamma-irradiation

    International Nuclear Information System (INIS)

    Semenova, T.P.; Medvinskaya, N.I.; Potekhina, N.I.; Kolomijtseva, I.K.

    1997-01-01

    The effects of low level chronical ionising irradiation (12.9 cGy/day on the sensory attention to the stimuli of different modalities (somatosensor, visual, odor) of Wistar rats were studied. Analysis of animals behaviour was made after they had received the different doses of irradiation: 4, 6, 8, 10, 15 and 20 Gy. It was founded, that the attention and exploratory activity of rats is significantly decreased up to 20-30% after 4-6 Gy. The irradiation doses 8 Gy did not change animal behaviour as compared to control animals, but doses 10, 15 and 20 Gy decreased the exploratory activity as well as sensory attention of rats to 3-5-times as compared to previous dose. Such a wave-like way of behaviour reflects the functioning of an adaptive mechanism. Biochemical data indicated that after 5 months of the irradiation (dose 20 Gy) the level of phospholipids, lysophosphatidylcholine, phosphatdylethanolamine, phosphatidylcholine, cholesterol were decreased

  17. Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat

    DEFF Research Database (Denmark)

    Madsen, Torsten Meldgaard; Kristjansen, P.E.G.; Bolwig, Tom Gert

    2003-01-01

    irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21...... that blocked neurogenesis contributes to the reported deleterious side effects of this treatment, consisting of memory impairment, dysphoria and lethargy....

  18. Radiobiological effect of different irradiation fractionated regimens in human brain glioma

    International Nuclear Information System (INIS)

    Gai Xue; Yang Weizhi; Gao Li; Jiang Heng; Wang Mianrong; Shi Huizhen

    2010-01-01

    Objective: To evaluate the radiobiological effect of different irradiation fractionated regimens in human glioma cells (BT 325 cell line). Methods: The xenografts in Balb/c-nude mice were irradiated with different single and fractionated regimens. The single fraction dose was 10, 20, 30, 40 and 60 Gy, respectively. The fractionated regimens were 2 Gy x 5 fractions ( irradiated every day), and 3 Gy x 3 fractions (irradiated every other day), 3 Gy x 5 fractions (irradiated every day) and 4 Gy x 3 fractions (irradiated every other day), with total doses of 125 Gy, 114 Gy, 126 Gy and 112 Gy, respectively. The growth curve was used to evaluate the tumor doubling time. clonogenic assays was performed to draw the cell survival curve and analyze the radiobiological parameters with doses of 1, 2, 4, 6, 8 and 10 Gy. T 1/2 was measured by comet assay. Results: Tumor regression were not observed by single fraction irradiation, 2 Gy x 5 fractions and 3 Gy x 3 fractions irradiation regimens. The tumor regress was more significant with the increas of fraction dose. The 4 Gy x 3 fractions inhibited tumor more though not curing tumor. The cell doubling time of the BT 325 cell was 30. 16 h and the tumor doubling time of the xenograft was 43 days.When fitted with L-Q model, α was 0. 36 Gy -1 and β was 0. 057 Gy -2 . When fitted with the single-hit multi target model, D 0 was 1. 394 Gy, Dq was 2. 127 Gy and SF 2 was 0.714, respectively. The T 1/2 was 9.999 min. Conclusions: Glioma is a radioresistant tumor. Increase of the fraction dose improves recent effect.Further study is needed to control the tumor stem cells. (authors)

  19. Preliminary study of haemostasis in irradiated-enterectomised dog. Primary haemostasis, coagulation, plasma factors exploration

    International Nuclear Information System (INIS)

    Dubos, M.; Niaussat, P.M.; Neveux, Y.; Nguyen, T.L.; Drouet, J.; Bac, P.

    Some hematological changes due to the combined effects of ionizing radiations and surgery were studied in dogs irradiated at 250, 300 and 350R. A constant hemorrhagic syndrome was observed with an impairment of the platelets functions and a depletion of several coagulation factors [fr

  20. Anticonvulsant action of gamma-irradiated diazepam with correlation to certain brain amino acids and electrocorticogram activity in experimental animals

    International Nuclear Information System (INIS)

    Saad, S.F.; Roushdy, H.M.; Hassan, S.H.M.; Elkashef, H.S.; Mahdy, A.M.; Elsayeh, B.M.

    1994-01-01

    The effect of sterilization by gamma irradiation (215 KGy) of diazepam on is anticonvulsant action, on norma and depleted cerebral gamma aminobutyric acid (GABA), on glutamic acid, as well as electrocorticogram activity (ECOG) was determined in the experimental animals. For the evaluation of the anticonvulsant action of either diazepam (D) or irradiated diazepam (ID), pentyl ene tetrazole seizure test, was used and the protective dose 50 (PD50) was determined in adult male mice. GABA, the main central inhibitory transmitter which is implicated in the mechanism of the anticonvulsant action of D and its precursor glutamic acid, were electrophoretically separated and spectrophotometrical evaluated. Moreover, brain electrical activity was recorded using an electroencephalograph apparatus. Although the PD50 of ID as well the effect on normal brain cerebral GABA and glutamic acids did not differ significantly from that of D, yet there was certain variabilities. Thus, the effect of D was about 4 times more potent than the ID on elevating depleted cerebral GABA. Also, electrocorticogram records demonstrated that D produced a slight inhibition while ID induced a decrease in B rhythm with remarkable in the amplitude of ECOG waves. The same pattern of effects were obtained when D or ID were used in combination with INH (250 mg kg-1). 1 tab. 1 fig

  1. The study of low level laser irradiation therapy on brain infarction with SPECT

    Institute of Scientific and Technical Information of China (English)

    Xiao Xuechang; Jia Shaowei; Zleng Xiyuan

    2000-01-01

    Objective: Effect of rCBF and brain function on ILIB treating brain infarction will be investigated by SPECT brain perfusion imaging. Method: 3 1 patients with brain infarction, 17 patients were treated by ILIB on standard pharmaceutial treatment. SPECT brain perfusion imaging was performed before and after ILIB therapy with comparison of oneself. They were quantified with BFCR% model effect during ILIB in 14 patients were observed. Result: ILIB 30 rnme SPECT showed the improvement of rCBF and cerebral function in 14 patients with brain infarction, and in 17 patients locus were prominence than mirror regions att er ILIB therapy, both are higher singnitficant difference ( t=4.4052, P<0.0001 ), but mirror regions were not singnificant difference before and after ILIB (t=1.6995, P>0.05). BFCR% quantitative results of locus were higher mirror regions, and higher singnificant difference (t=4.5278 p<0.0001 )。 Conclusion: ILIB can improve the rCBF and cerebral function of patients with brain infarction, and provoke function of brain cells. Some new evidence was provided for ILIB treatment of cerebral ischemia

  2. Prognostic factors for survival and intracerebral control after irradiation for brain metastases from gynecological cancer

    NARCIS (Netherlands)

    Rades, Dirk; Fischer, Dorothea; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.

    2009-01-01

    The most appropriate treatment for the individual patient with brain metastases from gynecological cancer is unclear. Most of these patients receive whole-brain radiotherapy (WBRT) alone. Prognostic factors predicting the outcomes of these patients may guide the physician to select the appropriate

  3. Helical Tomotherapy for Whole-Brain Irradiation With Integrated Boost to Multiple Brain Metastases: Evaluation of Dose Distribution Characteristics and Comparison With Alternative Techniques

    International Nuclear Information System (INIS)

    Levegrün, Sabine; Pöttgen, Christoph; Wittig, Andrea; Lübcke, Wolfgang; Abu Jawad, Jehad; Stuschke, Martin

    2013-01-01

    Purpose: To quantitatively evaluate dose distribution characteristics achieved with helical tomotherapy (HT) for whole-brain irradiation (WBRT) with integrated boost (IB) to multiple brain metastases in comparison with alternative techniques. Methods and Materials: Dose distributions for 23 patients with 81 metastases treated with WBRT (30 Gy/10 fractions) and IB (50 Gy) were analyzed. The median number of metastases per patient (N mets ) was 3 (range, 2-8). Mean values of the composite planning target volume of all metastases per patient (PTV mets ) and of the individual metastasis planning target volume (PTV ind met ) were 8.7 ± 8.9 cm 3 (range, 1.3-35.5 cm 3 ) and 2.5 ± 4.5 cm 3 (range, 0.19-24.7 cm 3 ), respectively. Dose distributions in PTV mets and PTV ind met were evaluated with respect to dose conformity (conformation number [CN], RTOG conformity index [PITV]), target coverage (TC), and homogeneity (homogeneity index [HI], ratio of maximum dose to prescription dose [MDPD]). The dependence of dose conformity on target size and N mets was investigated. The dose distribution characteristics were benchmarked against alternative irradiation techniques identified in a systematic literature review. Results: Mean ± standard deviation of dose distribution characteristics derived for PTV mets amounted to CN = 0.790 ± 0.101, PITV = 1.161 ± 0.154, TC = 0.95 ± 0.01, HI = 0.142 ± 0.022, and MDPD = 1.147 ± 0.029, respectively, demonstrating high dose conformity with acceptable homogeneity. Corresponding numbers for PTV ind met were CN = 0.708 ± 0.128, PITV = 1.174 ± 0.237, TC = 0.90 ± 0.10, HI = 0.140 ± 0.027, and MDPD = 1.129 ± 0.030, respectively. The target size had a statistically significant influence on dose conformity to PTV mets (CN = 0.737 for PTV mets ≤4.32 cm 3 vs CN = 0.848 for PTV mets >4.32 cm 3 , P=.006), in contrast to N mets . The achieved dose conformity to PTV mets , assessed by both CN and PITV, was in all investigated volume strata

  4. Estimating Oceanic Primary Production Using Vertical Irradiance and Chlorophyll Profiles from Ocean Gliders in the North Atlantic.

    Science.gov (United States)

    Hemsley, Victoria S; Smyth, Timothy J; Martin, Adrian P; Frajka-Williams, Eleanor; Thompson, Andrew F; Damerell, Gillian; Painter, Stuart C

    2015-10-06

    An autonomous underwater vehicle (Seaglider) has been used to estimate marine primary production (PP) using a combination of irradiance and fluorescence vertical profiles. This method provides estimates for depth-resolved and temporally evolving PP on fine spatial scales in the absence of ship-based calibrations. We describe techniques to correct for known issues associated with long autonomous deployments such as sensor calibration drift and fluorescence quenching. Comparisons were made between the Seaglider, stable isotope ((13)C), and satellite estimates of PP. The Seaglider-based PP estimates were comparable to both satellite estimates and stable isotope measurements.

  5. Expression and deposition of basement membrane proteins by brain capillary endothelial cells in a primary murine model of the blood-brain barrier

    DEFF Research Database (Denmark)

    Thomsen, Maj Schneider; Birkelund, Svend; Larsen, Annette Burkhart

    2016-01-01

    The blood-brain barrier (BBB) represents the interface between the blood and the brain parenchyma and consists of endothelial cells which are tightly sealed together by tight junction proteins. The endothelial cells are in addition supported by pericytes, which are embedded in the vascular basement...... of the present study was to create four different in vitro constructs of the murine BBB to characterise if the expression and secretion of basement membrane proteins by the murine brain capillary endothelial cells (mBCECs) was affected by co-culturing with pericytes, mixed glial cells, or both. Primary m......BCECs and pericytes were isolated from brains of adult mice. Mixed glial cells were prepared from cerebral cortices of newborn mice. The mBCECs were grown as mono-culture, or co-cultured with pericytes, mixed glial cells, or both. To study the expression of basement membrane proteins RT-qPCR, mass spectrometry...

  6. Effect of activation cross section uncertainties in the assessment of primary damage for MFE/IFE low-activation steels irradiated in IFMIF

    International Nuclear Information System (INIS)

    Cabellos, O.; Sanz, J.; Garcia-Herranz, N.; Otero, B.

    2009-01-01

    The present study is mainly aimed to provide the primary damage (displacements per atom, generation of solid transmutants and gas production rates) of structural materials irradiated in the high and medium flux test modules of the International Fusion Materials Irradiation Facility (IFMIF). We have investigated if the change of the composition during the irradiation time has effect on the prediction of the atomic displacements. The effect of the activation cross section uncertainties in the assessment of both solid transmutants and hydrogen and helium production is also analyzed. The results are provided element-by-element, so that the primary damage of any material irradiated in such neutron environments can be easily assessed; in this paper, we have predicted the primary damage of the low activation steel Eurofer.

  7. Effect of activation cross section uncertainties in the assessment of primary damage for MFE/IFE low-activation steels irradiated in IFMIF

    Energy Technology Data Exchange (ETDEWEB)

    Cabellos, O. [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid (UPM), C/Jose Gutierrez Abascal, n2, 28006 Madrid (Spain); Dept. de Ingenieria Nuclear, Universidad Politecnica de Madrid, 28006 Madrid (Spain)], E-mail: cabellos@din.upm.es; Sanz, J. [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid (UPM), C/Jose Gutierrez Abascal, n2, 28006 Madrid (Spain); Dept. de Ingenieria Energetica, Universidad Nacional de Educacion a Distancia, 28045 Madrid (Spain); Garcia-Herranz, N. [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid (UPM), C/Jose Gutierrez Abascal, n2, 28006 Madrid (Spain); Dept. de Ingenieria Nuclear, Universidad Politecnica de Madrid, 28006 Madrid (Spain); Otero, B. [Dept. de Ingenieria Nuclear, Universidad Politecnica de Madrid, 28006 Madrid (Spain)

    2009-04-30

    The present study is mainly aimed to provide the primary damage (displacements per atom, generation of solid transmutants and gas production rates) of structural materials irradiated in the high and medium flux test modules of the International Fusion Materials Irradiation Facility (IFMIF). We have investigated if the change of the composition during the irradiation time has effect on the prediction of the atomic displacements. The effect of the activation cross section uncertainties in the assessment of both solid transmutants and hydrogen and helium production is also analyzed. The results are provided element-by-element, so that the primary damage of any material irradiated in such neutron environments can be easily assessed; in this paper, we have predicted the primary damage of the low activation steel Eurofer.

  8. Assessment of the long-term effects of primary radiation therapy for brain tumors in children

    International Nuclear Information System (INIS)

    Danoff, B.F.; Cowchock, F.S.; Marquette, C.; Mulgrew, L.; Kramer, S.

    1982-01-01

    One-hundred-twelve children with primary brain tumors received definitive radiotherapy between the years 1958-1979. Sixty-nine patients were alive at intervals of 1-21 years. Thirty-eight patients underwent neurologic and endocrine evaluation, psychologic and intelligence testing, and assessment for second malignancy post-treatment. A second intracranial malgnancy developed in one child, for an incidence of 1.6%. Performance status was good to excellent in 89% of the patients studied. Seventeen percent of the group were mentally retarded. Behavioral disorders were identified in 39% of the patients, 59% of the mothers, and 43% of the fathers. Of the 23 patients with nonparasellar tumors, six were found to have growth hormone deficiency, including two patients with panhypopituitarism. Disability was related to age under 3 years at the time of treatment and tumor extension to the hypothalamus

  9. Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus

    Directory of Open Access Journals (Sweden)

    Olga M. Pulido

    2008-02-01

    Full Text Available Domoic acid is a marine biotoxin associated with harmful algal blooms and is the causative agent of amnesic shellfish poisoning in marine animals and humans. It is also an excitatory amino acid analog to glutamate and kainic acid which acts through glutamate receptors eliciting a very rapid and potent neurotoxic response. The hippocampus, among other brain regions, has been identified as a specific target site having high sensitivity to DOM toxicity. Histopathology evidence indicates that in addition to neurons, the astrocytes were also injured. Electron microscopy data reported in this study further supports the light microscopy findings. Furthermore, the effect of DOM was confirmed by culturing primary astrocytes from the hippocampus and the brain stem and subsequently exposing them to domoic acid. The RNA was extracted and used for biomarker analysis. The biomarker analysis was done for the early response genes including c-fos, c-jun, c-myc, Hsp-72; specific marker for the astrocytes- GFAP and the glutamate receptors including GluR 2, NMDAR 1, NMDAR 2A and B. Although, the astrocyte-GFAP and c-fos were not affected, c-jun and GluR 2 were down-regulated. The microarray analysis revealed that the chemokines / cytokines, tyrosine kinases (Trk, and apoptotic genes were altered. The chemokines that were up-regulated included - IL1-a, IL-1B, IL-6, the small inducible cytokine, interferon protein IP-10, CXC chemokine LIX, and IGF binding proteins. The Bax, Bcl-2, Trk A and Trk B were all downregulated. Interestingly, only the hippocampal astrocytes were affected. Our findings suggest that astrocytes may present a possible target for pharmacological interventions for the prevention and treatment of amnesic shellfish poisoning and for other brain pathologies involving excitotoxicity

  10. "Unusual brain stone": heavily calcified primary neoplasm with some features suggestive of angiocentric glioma.

    Science.gov (United States)

    Sajjad, Jahangir; Kaliaperumal, Chandrasekaran; Bermingham, Niamh; Marks, Charles; Keohane, Catherine

    2015-11-01

    This 40-year-old man presented with a 5-month history of progressive right-sided headache associated with visual blurring. He also had a history of epilepsy but had been seizure free with medication for the past 10 years. An initial CT scan of his brain performed 16 years previously had revealed a small area of calcification in the right parietal region. In the current presentation, he had a left-sided homonymous hemianopia but no other neurological deficits. A CT scan of his brain showed a much larger calcified, partly cystic lesion in the right parietal region. Because he was symptomatic, the lesion was excised and the cyst was drained. Histological examination of the excised tissue showed an unusual primary tumor that was difficult to classify but had some features of angiocentric glioma. The heavy calcification, mixed-density cell population, and regions with features of angiocentric glioma were most unusual. The patient remained asymptomatic 5 years after surgery, and follow-up scans did not show recurrence.

  11. Factors affecting 18 F FDOPA standardized uptake value in patients with primary brain tumors after treatment

    International Nuclear Information System (INIS)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Villani, Veronica; Carapella, Carmine; Pace, Andrea; Di Pietro, Barbara; Di Russo, Carmen; Palumbo, Barbara; Floris, Roberto; Schillaci, Orazio

    2015-01-01

    Aim: To investigate the factors affecting 18 F FDOPA uptake in patients with primary brain tumors (PBT) after treatment. Materials and methods: 97 patients with PBT (6 were grade I, 40 were grade II, 29 were grade III and 22 were grade IV) underwent 18 F FDOPA positron emission tomography/computed tomography (PET/CT) after treatment. Intervals from surgery, chemotherapy (CHT) and radiotherapy (RT) were 41.48 (± 42.27), 16.04 (± 29.08) and 28.62 (± 34.49) months respectively. Results: 18 F FDOPA uptake in the site of recurrence was not related to the interval from surgery and CHT while a significant relationship has been found with the interval from RT and tumor grade. Conclusions: The results of our study show that the interval from RT and the grade of PBT should be considered carefully when evaluating brain PET/CT scans since these factors could directly affect 18 F FDOPA uptake

  12. Clinical outcomes from maximum-safe resection of primary and metastatic brain tumors using awake craniotomy.

    Science.gov (United States)

    Groshev, Anastasia; Padalia, Devang; Patel, Sephalie; Garcia-Getting, Rosemarie; Sahebjam, Solmaz; Forsyth, Peter A; Vrionis, Frank D; Etame, Arnold B

    2017-06-01

    To retrospectively analyze outcomes in patients undergoing awake craniotomies for tumor resection at our institution in terms of extent of resection, functional preservation and length of hospital stay. All cases of adults undergoing awake-craniotomy from September 2012-February 2015 were retrospectively reviewed based on an IRB approved protocol. Information regarding patient age, sex, cancer type, procedure type, location, hospital stay, extent of resection, and postoperative complications was extracted. 76 patient charts were analyzed. Resected cancer types included metastasis to the brain (41%), glioblastoma (34%), WHO grade III anaplastic astrocytoma (18%), WHO grade II glioma (4%), WHO grade I glioma (1%), and meningioma (1%). Over a half of procedures were performed in the frontal lobes, followed by temporal, and occipital locations. The most common indication was for motor cortex and primary somatosensory area lesions followed by speech. Extent of resection was gross total for 59% patients, near-gross total for 34%, and subtotal for 7%. Average hospital stay for the cohort was 1.7days with 75% of patients staying at the hospital for only 24h or less post surgery. In the postoperative period, 67% of patients experienced improvement in neurological status, 21% of patients experienced no change, 7% experienced transient neurological deficits, which resolved within two months post op, 1% experienced transient speech deficit, and 3% experienced permanent weakness. In a consecutive series of 76 patients undergoing maximum-safe resection for primary and metastatic brain tumors, awake-craniotomy was associated with a short hospital stay and low postoperative complications rate. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

    Science.gov (United States)

    Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

    2014-01-06

    Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

  14. Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS

    Energy Technology Data Exchange (ETDEWEB)

    Shultz, David B.; Modlin, Leslie A.; Jayachandran, Priya; Von Eyben, Rie; Gibbs, Iris C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Choi, Clara Y.H. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Department of Radiation Oncology, Santa Clara Valley Medical Center, San Jose, California (United States); Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Adler, John R. [Department of Neurosurgery, Stanford University School of Medicine, Stanford, California (United States); Hancock, Steven L. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Soltys, Scott G., E-mail: sgsoltys@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2015-08-01

    Purpose: To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS). Patients and Methods: We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS. Results: Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites. Conclusion: Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.

  15. Focused microwave irradiation-assisted immunohistochemistry to study effects of ketamine on phospho-ERK expression in the mouse brain.

    Science.gov (United States)

    Fernandes, Alda; Li, Yu-Wen

    2017-09-01

    Ketamine produces rapid and long-lasting antidepressant effects in depressive patients. Preclinical studies demonstrate that ketamine stimulates AMPA receptor transmission and activates BDNF/TrkB-Akt/ERK-mTOR signaling cascades, leading to a sustained increase in synaptic protein synthesis and strengthening of synaptic plasticity, a potential mechanism underlying the antidepressant effects. The purpose of this study was to develop an immunohistochemistry (IHC) assay to map the distribution of extracellular signal-regulated kinase (ERK) phosphorylation in the mouse brain in response to systemic ketamine treatment. We established a focused microwave irradiation-assisted IHC assay to detect phosphorylated (phospho) proteins including phospho-ERK, phospho- cAMP-response- element-binding protein (CREB), phospho- glutamate receptor 1 (GluR1) and phospho- calcium/calmodulin-dependent protein kinase II (CaMKII) with greater sensitivity and reproducibility in comparison to conventional IHC methods. A single dose of ketamine produced a robust, dose- and time-dependent increase in phospho-ERK immunoreactive (phospho-ERK-ir) neurons in the medial prefrontal cortex (mPFC) and the central nucleus of the amygdala. Phospho-ERK-ir neurons in the mPFC were primarily located in the prelimbic and anterior cingulate subregions with the morphology resembling pyramidal neurons. An increase in phospho-ERK-ir was also observed in the brainstem dorsal raphe nucleus and locus coeruleus. The NMDA GluN2B subtype receptor antagonist Ro 25-6981 increased phospho-ERK expression in the brain in a similar pattern as ketamine. In summary, we have established a sensitive and reliable focused microwave irradiation-assisted IHC assay, and defined the activation pattern of ERK, in response to systemic ketamine and Ro 25-6981 treatment, in brain regions that are potentially responsible for mediating the antidepressant effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females

    International Nuclear Information System (INIS)

    Silasi, Greg; Diaz-Heijtz, Rochellys; Besplug, Jill; Rodriguez-Juarez, Rocio; Titov, Viktor; Kolb, Bryan; Kovalchuk, Olga

    2004-01-01

    Radiation exposure is known to have profound effects on the brain, leading to precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8 (2002) 955]. Although a plethora of data exist on the effects of high radiation doses, the effects of low-dose irradiation, such as ones received during repetitive diagnostic and therapeutic exposures, are still under-investigated [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889; Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological effects of ionizing radiation have been performed using a single acute dose, while clinically and environmentally relevant exposures occur predominantly under chronic/repetitive conditions. Here, we have used a mouse model to compare the effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5 Gy) to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44 MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have been previously shown to be crucial for neuronal survival upon irradiation. We report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive low-dose exposure in the hippocampus and frontal cortex of mice. These studies were paralleled by the analysis of radiation effects on neurogenesis and cellular proliferation. Repetitive exposure had a much more pronounced effect on cellular signaling and neurogenesis than acute exposure. These results suggest that studies of single acute exposures might be limited in terms of their predictive value. We also present the first evidence of sex differences in radiation-induced signaling in the hippocampus and frontal cortex. We show the role of estrogens in brain radiation responses and discuss the implications of the observed changes

  17. Use of primary cell cultures to measure the late effects in the skins of rhesus monkeys irradiated with protons

    Science.gov (United States)

    Cox, A. B.; Wood, D. H.; Lett, J. T.

    Previous pilot investigations of the uses of primary cell cultures to study late damage in stem cells of the skin of the New Zealand white (NZW) rabbit and the rhesus monkey /1-3/, have been extended to individual monkeys exposed to 55 MeV protons. Protons of this energy have a larger range in tissue of (~2.6 cm) than the 32 MeV protons (~0.9 cm) to which the animals in our earlier studies had been exposed. Although the primary emphases in the current studies were improvement and simplification in the techniques and logistics of transportation of biopsies to a central analytical facility, comparison of the quantitative measurements obtained thus far for survival of stem cells in the skins from animals irradiated 21 years ago reveals that the effects of both proton energies are similar.

  18. Effects of X-irradiation on glial cells in the developing rat brain

    International Nuclear Information System (INIS)

    Ferrer, I.; Borras, D.

    1994-01-01

    Sprague-Dawley rats were given a single dose of 2Gy X-rays when 1 or 3 days of age. Dying cells in the germinal layer of the telencephalon reached peak values 6h after irradiation; dead cells were cleared 48h later. These effects were almost abolished with the injection of cyclohexamide (1 μg/g body weight) given at the time of irradiation. PCNA-immunoreactive cells (cells in late G 1 and S phases of the cell cycle) and PCNA-negative cells were sensitive to X-rays. Long-term effects on glial cell populations in the subcortical white matter of the cingulum were examined in irradiated rats, killed at postnatal day 30 (P30), by means of glial fibrillary acidic protein, vimentin and S-100 immunohistochemistry, as well as with anti-TGF-α (transformerly growth factor) antibodies that are used as putative oligodendrogial cell markers in the white matter of rat. (author)

  19. Effect of γ-ray Irradiation On the Activities of Monoamine Oxidase in Rat Brain and Liver

    International Nuclear Information System (INIS)

    Kim, Joo Young; Choi, Myung Sun; Choi, Myung Un

    1993-01-01

    In order to evaluate the effects of radiation on mammalian neuronal system, we have examined the effect of gamma-ray radiation on the monoamine oxidase(MAO) activity in monoaminergic neurons. Following the whole body irradiation, MAO activity in the rat brain was measured as well as in the liver for the comparative studies between the neuronal and nonneuronal system. The effects of some radiation protectors and sensitizers were also examined in addition to the O2 effect. The results can be summarized as follows. 1) The MAO activity of rat brain was minimally affected by the radiation dose up to 1,700 cGy. Radiation dose above 2,500 cGy inhibited the brain MAO activity by no less than 10%. MAO-A form was found to be particularly sensitive to radiation. The liver MAO was somewhat inhibited(by about 5%) but hard1y dependent on the dose of radiation. 2) The inhibitory effect on the brain was initiated immediately by the radiation dose of 2,500 cGy. On the contrary, for the liver, the inhibitory effect became apparent only 2 days after irradiation. 3) Two days after a dose of 2,500 cGy, Vmax and Km of the brain mitochondrial MAO decreased. for liver, Vmax decreased while Km increased, which indicates the kinetic patterns for the neuronal and nonneruronal systems are not affected similarly by radiation. 4) The effect of several known radiation protectors and sensitizers on MAO activity was tested but no definite results were obtained. The level of -SH group increased in some degree upon radiation but not by the compounds. 5) MAO activity was not affected by O2 concentration, while an elevated level of lipid peroxidase was found udder the same condition. The results described here indicate that characteristics of MAO, one of the most important central nervous system enzymes, are liable to radiation, which is partially differentiated from the liver MAO. Also indicated are that the -SH groups are hardly related to the effect of radiation but the production of the lipid

  20. Analysis of diffuse brain injury with primary brainstem lesion on MRI

    International Nuclear Information System (INIS)

    Shibata, Masayoshi; Matsumae, Mitsunori; Shimoda, Masami; Ishizaka, Hideo; Shiramizu, Hideki; Morita, Seiji; Tsugane, Ryuichi

    2003-01-01

    It has been reported that diffuse brain injury patients with primary brainstem lesions have a poor prognosis. Predicting the existence of brainstem injury at hospital arrival is problematic in actual clinical practice. We conducted magnetic resonance imaging (MRI), to visualize brainstem lesions clearly, and retrospectively analyzed predictive factors of brainstem lesions by stepwise multiple logistic regression analysis of patient characteristics, neurological findings, laboratory data, and CT findings at arrival in each case. We compared 24 patients with brainstem lesion and 60 without using MRI obtained less than 3 weeks after admission. Items investigated were blood pressure immediately after hospital arrival, arterial blood gas analysis, existence of abnormal respiration, blow direction, Glasgow coma scale (GCS), light reflex, oculocephalic reflex, corneal reflex, intracranial pressure, jugular venous oxygen saturation, and CT findings such as existence of subarachnoid hemorrhage at the suprasellar cistern, perimesencephalic cistern and convexity, lesions on the thalamus and basal ganglia, gliding contusion, intraventricular hemorrhage and Traumatic Coma Data Bank classification. Independent predictive factors of primary brainstem lesion included impaired light reflex (odds ratio: 2.269), subarachnoid hemorrhage at convexity (odds ratio: 3.592) and suprasellar cistern (odds ratio: 2.458), and Traumatic Coma Data Bank group III (odds ratio: 11.062). (author)

  1. Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial.

    Science.gov (United States)

    Yang, Jin-Ji; Zhou, Caicun; Huang, Yisheng; Feng, Jifeng; Lu, Sun; Song, Yong; Huang, Cheng; Wu, Gang; Zhang, Li; Cheng, Ying; Hu, Chengping; Chen, Gongyan; Zhang, Li; Liu, Xiaoqing; Yan, Hong Hong; Tan, Fen Lai; Zhong, Wenzhao; Wu, Yi-Long

    2017-09-01

    For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China. Eligible participants were patients with NSCLC with EGFR mutations, who were naive to treatment with EGFR-TKIs or radiotherapy, and had at least three metastatic brain lesions. We randomly assigned participants (1:1) to either icotinib 125 mg orally (three times per day) or WBI (30 Gy in ten fractions of 3 Gy) plus concurrent or sequential chemotherapy for 4-6 cycles, until unacceptable adverse events or intracranial disease progression occurred. The randomisation was done by the Chinese Thoracic Oncology Group with a web-based allocation system applying the Pocock and Simon minimisation method; groups were stratified by EGFR gene mutation status, treatment line (first line or second line), brain metastases only versus both intracranial and extracranial metastases, and presence or absence of symptoms of intracranial hypertension. Clinicians and patients were not masked to treatment assignment, but individuals involved in the data analysis did not participate in the treatments and were thus masked to allocation. Patients receiving icotinib who had intracranial progression only were switched to WBI plus either icotinib or chemotherapy until further progression; those receiving icotinib who had extracranial progression only were switched to icotinib plus chemotherapy. Patients receiving WBI who progressed were switched to icotinib until further progression. Icotinib could be continued beyond progression if a clinical benefit

  2. Saffron extracts effect on processes in brain structures under exposure to x-ray irradiation of medium dose

    International Nuclear Information System (INIS)

    Rzaeva, A.

    2012-01-01

    Full text : Process of ionizing radiation on live organism is accompanied by interaction of free radicals (FR) with molecules of proteins, nucleic acids and lipids. In its turn, FR occurs subsequently by excitation and ionization of molecules. Besides all, ionizing radiation becomes the reason of accumulation in body tissues of toxic products (radio toxic) that strengthen beam effect. Endogenous antioxidatic system (EAS) of an organism plays a significant role in detoxication of redundant quantity of FR formed in cells. Ionizing radiation influences negatively to high-grade functioning of basic EAS enzymes. Besides, during radiation injuries, the level of FR increases. In case of its exhaustion and lack insertion of natural antioxidants (bioantioxidants) to organism plays a therapeutic role. Thus, in our work we used saffron extract in experiments with the purpose of studying its effect on the activity of antioxidant enzymes at radiation influence. Determination of proteins has been carried out with Lowry method. In the result of carried-out researches, it has been detected fixed dynamics of activity change of antioxidant enzymes in various brain structures of white rats within x-ray irradiation at medium dose, and joint impact of x-ray radiation of saffron extract. Under exposure to X-ray irradiation of medium dose in some brain structures decreasing of catalase activity was revealed. Tendency towards decreasing is more developed on the 3th day of irradiation. As opposed to catalase activity GPO activity was increased. Insertion of saffron extract to experimental animals (for 21 days before irradiation) conducive to prevention the decreasing of catalase activity stabilizes GPO activity and exerts an effective influence. Thereby, bioantioxidants have significant role in the regulation of processes occurred in tissues and cells under the influence of extreme factors. Antioxidant protection system of organism carries out continuous protection of organism from toxic

  3. Parameterization of surface irradiance and primary production in Århus Bay, SW Kattegat, Baltic Sea

    DEFF Research Database (Denmark)

    Lund-Hansen, Lars Chresten; Sørensen, Helene Munk

    2009-01-01

    . The study is based on a one year long time-series of PAR, CTD-casts (n = 45), and primary production measurements (n = 24) from Århus Bay (56°09′ N; 10°20′ E), south west Kattegat. Results showed a high and positive correlation between observed and calculated primary production in the bay, as based...

  4. Role of hormonal factor in development of primary and secondary tumorous process in the brain

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    Full Text Available Introduction. Causes of the development onset of primary malignant cerebral neoplasms have not yet been determined. Not excluded is a possibility of unfavorable effect of the environment, genetic abnormalities, changes alterations in the hormonal background as well as metabolism, ionizing radiation: possible is also the role of viral infections and injuries. One of the main most severest complications of malignant tumors remain are metastatic lesions of the central nervous system whose proportion increases as with the patients’ longlivity. Cerebral metastases of malignant tumors are encountered more often than primary neoplasms of the central nervous system. The brain is not only a hormone-dependent organ the effect of sex hormones as early the embryonic state conditions normal development of the body as a whole and controls the sex related differentiation. It is known that neurons and glyocites like gonads and adrenal glands are able to produce steroid hormones. The enzymes responsible for the synthesis of neurosteroids were detected in the brain tissue in the embryonic period of the development. The human brain is not only a hormone-dependent organ effect influence of sex hormones as early as in the embrional state conditiones normal development of the body as a whole and controls sexual gender differentiation. It is known that neurons and glyocytes like gonads and adrenal glands are able to produce steroid hormones. Enzymes responsible for synthesis of neurosteroids were revealed in cerebral tissue both in during the embryonic period of the development and in adult condition. Besides there are have been obtained large amount of data on the presence in the cerebral cells of receptors to steroidal hormones. In various periods of life the influence effect exerted by steroids on nervous cells can change the morphofunctional state of the brain and manifests as altering myelinization, neuronal growth, and differentiation of nerve cells

  5. C3 deficiency ameliorates the negative effects of irradiation of the young brain on hippocampal development and learning.

    Science.gov (United States)

    Kalm, Marie; Andreasson, Ulf; Björk-Eriksson, Thomas; Zetterberg, Henrik; Pekny, Milos; Blennow, Kaj; Pekna, Marcela; Blomgren, Klas

    2016-04-12

    Radiotherapy in the treatment of pediatric brain tumors is often associated with debilitating late-appearing adverse effects, such as intellectual impairment. Areas in the brain harboring stem cells are particularly sensitive to irradiation (IR) and loss of these cells may contribute to cognitive deficits. It has been demonstrated that IR-induced inflammation negatively affects neural progenitor differentiation. In this study, we used mice lacking the third complement component (C3-/-) to investigate the role of complement in a mouse model of IR-induced injury to the granule cell layer (GCL) of the hippocampus. C3-/- and wild type (WT) mice received a single, moderate dose of 8 Gy to the brain on postnatal day 10. The C3-/- mice displayed 55 % more microglia (Iba-1+) and a trend towards increase in proliferating cells in the GCL compared to WT mice 7 days after IR. Importantly, months after IR C3-/- mice made fewer errors than WT mice in a reversal learning test indicating better learning capacity in C3-/- mice after IR. Notably, months after IR C3-/- and WT mice had similar GCL volumes, survival of newborn cells (BrdU), microglia (Iba-1) and astrocyte (S100β) numbers in the GCL. In summary, our data show that the complement system contributes to IR-induced loss of proliferating cells and maladaptive inflammatory responses in the acute phase after IR, leading to impaired learning capacity in adulthood. Targeting the complement system is hence promising for future strategies to reduce the long-term adverse consequences of IR in the young brain.

  6. A phase II trial with bevacizumab and irinotecan for patients with primary brain tumors and progression after standard therapy

    DEFF Research Database (Denmark)

    Møller, Søren; Grunnet, Kirsten; Hansen, Steinbjørn

    2012-01-01

    The combination of irinotecan and bevacizumab has shown efficacy in the treatment of recurrent glioblastoma multiforme (GBM). A prospective, phase II study of 85 patients with various recurrent brain tumors was carried out. Primary endpoints were progression free survival (PFS) and response rate....

  7. Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Megan C. Mladinich

    2017-07-01

    Full Text Available Zika virus (ZIKV is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons. We found that ZIKV (strain PRVABC59 persistently infects and continuously replicates in primary human brain microvascular ECs (hBMECs, without cytopathology, for >9 days and following hBMEC passage. ZIKV did not permeabilize hBMECs but was released basolaterally from polarized hBMECs, suggesting a direct mechanism for ZIKV to cross the BBB. ZIKV-infected hBMECs were rapidly resistant to alpha interferon (IFN-α and transiently induced, but failed to secrete, IFN-β and IFN-λ. Global transcriptome analysis determined that ZIKV constitutively induced IFN regulatory factor 7 (IRF7, IRF9, and IFN-stimulated genes (ISGs 1 to 9 days postinfection, despite persistently replicating in hBMECs. ZIKV constitutively induced ISG15, HERC5, and USP18, which are linked to hepatitis C virus (HCV persistence and IFN regulation, chemokine CCL5, which is associated with immunopathogenesis, as well as cell survival factors. Our results reveal that hBMECs act as a reservoir of persistent ZIKV replication, suggest routes for ZIKV to cross hBMECs into neuronal compartments, and define novel mechanisms of ZIKV persistence that can be targeted to restrict ZIKV spread.

  8. Frequency, clinical correlates and rating of behavioural changes in primary brain tumour patients: A preliminary investigation.

    Directory of Open Access Journals (Sweden)

    Grahame K Simpson

    2015-04-01

    Full Text Available PurposeFew studies have addressed the specific behavioural changes associated with primary brain tumour (PBT. This paper will report on the frequency and demographic/clinical correlates of such behaviours, and the reliability of rating such behaviours amongst people with PBT, family informants and clinicians. The association of behavioural changes and patient functional status will also be discussed.MethodsA total of 57 patients with 37 family informants were recruited from two large Australian metropolitan hospitals. Each completed three neuro-behavioural self-report measures. Patients also completed a depression symptom measure. Functional status was defined by clinician-rated Karnofsky Performance Status.ResultsPatients were on average 52 years old, a median of four months (range 1-82 post-diagnosis, with high grade (39%, low grade (22% or benign tumours (39%. Patients reported frequency rates of 7-40% across various behavioural domains including anger, inappropriate behaviour, apathy, inertia and executive impairment. The presence of epileptic seizures was associated with significantly higher levels of behavioural changes. Notably, behaviour did not correlate with tumour grade or treatment modality. There was moderate agreement between patients and relatives on the presence or absence of behavioural changes, and substantial agreement between relative and clinician ratings. Depressed patients did not generally report more changes than non-depressed patients. Increases in the relative and clinician-rated behaviour scores were significantly correlated with decreasing functional status in the patient.ConclusionsBehavioural changes were a common sequela of both benign and malignant PBT. Larger scale studies are required to confirm these results. The results suggest the importance of including behaviour in brain cancer psychosocial assessments and the need to develop interventions to treat these patients and reduce the burden of care on families.

  9. Long-term memory shapes the primary olfactory center of an insect brain.

    Science.gov (United States)

    Hourcade, Benoît; Perisse, Emmanuel; Devaud, Jean-Marc; Sandoz, Jean-Christophe

    2009-10-01

    The storage of stable memories is generally considered to rely on changes in the functional properties and/or the synaptic connectivity of neural networks. However, these changes are not easily tractable given the complexity of the learning procedures and brain circuits studied. Such a search can be narrowed down by studying memories of specific stimuli in a given sensory modality and by working on networks with a modular and relatively simple organization. We have therefore focused on associative memories of individual odors and the possible related changes in the honeybee primary olfactory center, the antennal lobe (AL). As this brain structure is organized in well-identified morpho-functional units, the glomeruli, we looked for evidence of structural and functional plasticity in these units in relation with the bees' ability to store long-term memories (LTMs) of specific odors. Restrained bees were trained to form an odor-specific LTM in an appetitive Pavlovian conditioning protocol. The stability and specificity of this memory was tested behaviorally 3 d after conditioning. At that time, we performed both a structural and a functional analysis on a subset of 17 identified glomeruli by measuring glomerular volume under confocal microscopy, and odor-evoked activity, using in vivo calcium imaging. We show that long-term olfactory memory for a given odor is associated with volume increases in a subset of glomeruli. Independent of these structural changes, odor-evoked activity was not modified. Lastly, we show that structural glomerular plasticity can be predicted based on a putative model of interglomerular connections.

  10. Long-term effects of cranial irradiation on endocrine function in children with brain tumors. A prospective study

    International Nuclear Information System (INIS)

    Duffner, P.K.; Cohen, M.E.; Voorhess, M.L.; MacGillivray, M.H.; Brecher, M.L.; Panahon, A.; Gilani, B.B.

    1985-01-01

    This study prospectively evaluated the endocrine function of 11 children treated with cranial irradiation (CRT) for brain tumors. All tumors were remote from the hypothalamic-pituitary axis. Children were studied before treatment and at 3, 6, and 12 months after the completion of CRT. T4, thyroid-stimulating hormone, prolactin, plasma cortisol, and urinary follicle-stimulating hormone and luteinizing hormone values were normal before and after treatment in all patients. Growth hormone (GH) deficiency was identified in 0 of 7 patients before treatment, in 2 of 7 patients 3 months post-CRT, in 9 of 11 patients 6 months post-CRT, and in 7 of 8 patients 12 months post-CRT. Growth deceleration was identified in five of seven prepubertal patients. GH deficiency is an extremely common sequelae of CRT, beginning as early as 3 months after the completion of CRT. The deficit is progressive over time

  11. Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome.

    Science.gov (United States)

    Gu, Li-Na; Zhang, Min; Zhu, Hui; Liu, Jing-Yao

    2016-10-01

    Neuromyelitis optica spectrum disorder often co-exists with primary Sjögren's syndrome. We compared the clinical features of 16 neuromyelitis optica spectrum disorder patients with ( n = 6) or without primary Sjögren's syndrome ( n = 10). All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinuclear autoantibody, anti-Sjögren's-syndrome-related antigen A antibodies, anti-Sjögren's-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjögren's syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% (4/6) of patients with primary Sjögren's syndrome and in 60% (6/10) of patients without primary Sjögren's syndrome. More brain abnormalities were observed in patients without primary Sjögren's syndrome than in those with primary Sjögren's syndrome. Segments lesions (> 3 centrum) were noted in 50% (5/10) of patients without primary Sjögren's syndrome and in 67% (4/6) of patients with primary Sjögren's syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjögren's syndrome are similar. However, neuromyelitis optica spectrum disorder patients without primary Sjögren's syndrome have a high frequency of brain abnormalities.

  12. Primary brain tumors treated with steroids and radiotherapy: Low CD4 counts and risk of infection

    International Nuclear Information System (INIS)

    Hughes, Michael A.; Parisi, Michele; Grossman, Stuart; Kleinberg, Lawrence

    2005-01-01

    Purpose: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. Methods and Materials: CD4 counts were measured during RT in 70 of 76 consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. Results: CD4 counts decreased to 3 in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm 3 before RT, but 6 (24%) of 25 fell to 3 during RT. Patients with counts 3 were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of steroids, mean minimal white blood cell count

  13. Low-level x-irradiation of the brain during development: morphological, physiological, and behavioral consequences. Progress report, September 1, 1974--August 31, 1975

    International Nuclear Information System (INIS)

    Altman, J.

    1975-01-01

    Progress is reported on studies on the effects of exposure to low-dose x radiation on the developing brain of rats. Brief summaries of results of morphological, physiological, and behavioral studies on rats exposed using various x-irradiation schedules are included. A list of papers published and submitted for publication during the period is included. (U.S.)

  14. Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner

    International Nuclear Information System (INIS)

    Kim, Haksoo; Welford, Scott; Fabien, Jeffrey; Zheng, Yiran; Yuan, Jake; Brindle, James; Yao, Min; Lo, Simon; Wessels, Barry; Machtay, Mitchell; Sohn, Jason W.; Sloan, Andrew

    2014-01-01

    Purpose: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. Methods: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, with radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning system—MultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 × 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was “printed” using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. Results: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm). A

  15. Establishing a process of irradiating small animal brain using a CyberKnife and a microCT scanner

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Haksoo; Welford, Scott [Department of Radiation Oncology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106 (United States); Fabien, Jeffrey; Zheng, Yiran; Yuan, Jake; Brindle, James; Yao, Min; Lo, Simon; Wessels, Barry; Machtay, Mitchell; Sohn, Jason W., E-mail: jason.sohn@case.edu [Department of Radiation Oncology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106 and University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44106 (United States); Sloan, Andrew [Department of Neurosurgery, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106 (United States)

    2014-02-15

    Purpose: Establish and validate a process of accurately irradiating small animals using the CyberKnife G4 System (version 8.5) with treatment plans designed to irradiate a hemisphere of a mouse brain based on microCT scanner images. Methods: These experiments consisted of four parts: (1) building a mouse phantom for intensity modulated radiotherapy (IMRT) quality assurance (QA), (2) proving usability of a microCT for treatment planning, (3) fabricating a small animal positioning system for use with the CyberKnife's image guided radiotherapy (IGRT) system, and (4)in vivo verification of targeting accuracy. A set of solid water mouse phantoms was designed and fabricated, with radiochromic films (RCF) positioned in selected planes to measure delivered doses. After down-sampling for treatment planning compatibility, a CT image set of a phantom was imported into the CyberKnife treatment planning system—MultiPlan (ver. 3.5.2). A 0.5 cm diameter sphere was contoured within the phantom to represent a hemispherical section of a mouse brain. A nude mouse was scanned in an alpha cradle using a microCT scanner (cone-beam, 157 × 149 pixels slices, 0.2 mm longitudinal slice thickness). Based on the results of our positional accuracy study, a planning treatment volume (PTV) was created. A stereotactic body mold of the mouse was “printed” using a 3D printer laying UV curable acrylic plastic. Printer instructions were based on exported contours of the mouse's skin. Positional reproducibility in the mold was checked by measuring ten CT scans. To verify accurate dose delivery in vivo, six mice were irradiated in the mold with a 4 mm target contour and a 2 mm PTV margin to 3 Gy and sacrificed within 20 min to avoid DNA repair. The brain was sliced and stained for analysis. Results: For the IMRT QA using a set of phantoms, the planned dose (6 Gy to the calculation point) was compared to the delivered dose measured via film and analyzed using Gamma analysis (3% and 3 mm

  16. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    NARCIS (Netherlands)

    Verhoeff, Joost J. C.; Stalpers, Lukas J. A.; Coumou, Annet W.; Koedooder, Kees; Lavini, Cristina; van Noorden, Cornelis J. F.; Haveman, Jaap; Vandertop, William P.; van Furth, Wouter R.

    2007-01-01

    BACKGROUND: High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models- high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a

  17. Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases

    International Nuclear Information System (INIS)

    Rojas-Puentes, Luis L; Gonzalez-Pinedo, Marcelino; Crismatt, Alejando; Ortega-Gomez, Alette; Gamboa-Vignolle, Carlos; Nuñez-Gomez, Rodrigo; Dorantes-Gallareta, Yusmiren; Arce-Salinas, Claudia; Arrieta, Oscar

    2013-01-01

    Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors. Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) before beginning radiotherapy and one month later. The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms. Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings

  18. Advances in Diagnosis and Treatment of Brain Metastases from the Primary Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yi LIU

    2013-07-01

    Full Text Available Lung cancer with brain metastasis was 23% to 65%, and is the most common type in brain metastasis tumors with the poor prognosis. At present, diagnosis and treatment of brain metastases from lung carcinoma and its molecular mechanism have become one hot spot of amount researches. Here, we made a systematic review of the progress of the clinical features, diagnosis and treatment of brain metastases from lung and its molecular mechanism.

  19. Evaluation of primary tooth enamel surface morphology and microhardness after Nd:YAG laser irradiation and APF gel treatment--an in vitro study.

    Science.gov (United States)

    Banda, Naveen Reddy; Vanaja Reddy, G; Shashikiran, N D

    2011-01-01

    Laser irradiation and fluoride has been used as a preventive tool to combat dental caries in permanent teeth, but little has been done for primary teeth which are more prone to caries. The purpose of this study was to evaluate microhardness alterations in the primary tooth enamel after Nd-YAG laser irradiation alone and combined with topical fluoride treatment either before or after Nd-YAG laser irradiation. Ten primary molars were sectioned and assigned randomly to: control group, Nd-YAG laser irradiation, Nd-YAG lasing before APF and APF followed by Nd-YAG lasing. The groups were evaluated for microhardness. Surface morphological changes were observed using SEM. Statistical comparisons were performed. The control group's SEM showed a relatively smooth enamel surface and lasing group had fine cracks and porosities. In the lasing + fluoride group a homogenous confluent surface was seen. In the fluoride + lasing group an irregular contour with marked crack propagation was noted. There was a significant increase in the microhardness of the treatment groups. Nd-YAG laser irradiation and combined APF treatment of the primary tooth enamel gave morphologically hardened enamel surface which can be a protective barrier against a cariogenic attack.

  20. Focused ion beam (FIB) milling of electrically insulating specimens using simultaneous primary electron and ion beam irradiation

    International Nuclear Information System (INIS)

    Stokes, D J; Vystavel, T; Morrissey, F

    2007-01-01

    There is currently great interest in combining focused ion beam (FIB) and scanning electron microscopy technologies for advanced studies of polymeric materials and biological microstructures, as well as for sophisticated nanoscale fabrication and prototyping. Irradiation of electrically insulating materials with a positive ion beam in high vacuum can lead to the accumulation of charge, causing deflection of the ion beam. The resultant image drift has significant consequences upon the accuracy and quality of FIB milling, imaging and chemical vapour deposition. A method is described for suppressing ion beam drift using a defocused, low-energy primary electron beam, leading to the derivation of a mathematical expression to correlate the ion and electron beam energies and currents with other parameters required for electrically stabilizing these challenging materials

  1. Malignant primary germ-cell tumor of the brain: case report

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh (Kobe Municipal Central Hospital (Japan))

    1983-04-01

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported. The first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe. Total removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule. Histological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma. Primary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma. In this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy.

  2. Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

    Science.gov (United States)

    Napoli, Alessandro; Obeid, Iyad

    2016-03-01

    Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

  3. Elective Nodal Irradiation and Patterns of Failure in Head and Neck Cancer After Primary Radiation Therapy

    DEFF Research Database (Denmark)

    Kjems, Julie; Gothelf, Anita B; Håkansson, Katrin

    2016-01-01

    on recurrence in the retropharyngeal region and level IB. METHODS AND MATERIALS: From 2005 to 2012, 942 patients with oropharyngeal, hypopharyngeal, laryngeal or oral cavity carcinomas were curatively treated with primary radiation therapy. The median follow-up period was 34 months, and 77% of the patients...... underwent intensity modulated radiation therapy. The retropharyngeal region was only routinely included in cases of involvement of the posterior pharynx wall and level IB only in cases of involvement of the oral cavity. In patients with regional recurrence, the anatomic site of the recurrence was assessed...... likely to develop recurrence in distant sites. CONCLUSIONS: Retropharyngeal or level IB recurrence after primary HNC radiation therapy is rare. Thus, inclusion of these regions in the elective treatment volumes should be limited to patients with involvement of the posterior pharyngeal wall or oral cavity....

  4. Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Groothuis, D.R.; Mikhael, M.A.

    1986-06-01

    In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system.

  5. Focal cerebral vasculitis associated with circulating immune complexes and brain irradiation

    International Nuclear Information System (INIS)

    Groothuis, D.R.; Mikhael, M.A.

    1986-01-01

    In this report we describe a patient with a benign glioma treated with surgery and radiation. After a period of stability he developed subacute bacterial endocarditis, and deteriorated neurologically. Computed tomographic scans did not show recurrent tumor. An angiogram showed vasculitis restricted to the previously irradiated area. Secondary to subacute bacterial endocarditis was the presence of high levels of circulating immune complexes. His neurological status was unchanged after antibiotics, but improved after treatment with dexamethasone. We interpret the clinical course as an immune-complex-mediated vasculitis superimposed on a subclinical radiation vasculitis. This case supports the hypothesis that immune mechanisms may be involved in delayed radiation injury to the nervous system

  6. 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.

  7. Relationships between primary production and irradiance in coral reef algal communities

    International Nuclear Information System (INIS)

    Anon.

    1985-01-01

    Shallow water algal turf communities are the major primary producers on coral reefs. High rates of primary production are maintained despite extremely high light intensities and exposure to ultraviolet wavelengths. The relationships between the light intensity and primary production in these assemblages are typical of algae adapted to a high light environment [low α (initial slope), high I/sub k/ (saturating light intensity), and high I/sub c/ (compensation point light intensity)]. Seasonal variations in algal standing crop due to herbivory and daylength result in some characteristic photoadaptive changes in α I/sub k/, and I/sub c/ and changes in Pnet/sub max/ rates (maximum net photosynthetic rate achieved at light saturation) on both a chlorophyll α and an areal basis. Exposure to UV wavelength results in significantly higher respiration rates but no changes in α, Pnet/sub max/, or I/sub k/, when compared with these parameters for the same algal communities incubated at the same light intensities without UV wavelengths. The apparent lack of photoinhibition in these algae allows calculation of the daily integrated production from the P vs. I parameters. This integrated production is highest in July (3.1 +/- 0.2 g C m -2 d -1 ) and is reduced by 30% from this maximum in December (2.1 +/- 0.1 g C m -2 d -1 )

  8. Improved precision of interstitial brain tumor irradiation using the BRW CT stereotaxic guidance system

    International Nuclear Information System (INIS)

    Sapozink, M.D.; Moeller, J.M.; McDonald, P.N.; Heilbrun, M.P.

    1987-01-01

    A technique is described which enables precise temporary interstitial volume implantation of brain tumors using a CT stereotaxic guidance system. This technique has the advantages of designing irregular isodose distributions during the preplanning stage. Although the preplanning stage can be time-consuming, this is performed while the patient is in the hospital room and CT scanner time, anesthesia time, and operating room time is minimized for individual patients

  9. Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M. (University Coll. Hospital, London (United Kingdom)); Blackman, G. (Middlesex Hospital, London (United Kingdom))

    1993-01-01

    Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received [alpha]IFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. [alpha]IFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance [alpha]IFN therapy could not be fully evaluated. (author).

  10. Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

    International Nuclear Information System (INIS)

    McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M.; Blackman, G.

    1993-01-01

    Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received αIFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. αIFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance αIFN therapy could not be fully evaluated. (author)

  11. Melanosomes are a primary target of Q-switched ruby laser irradiation in guinea pig skin

    Energy Technology Data Exchange (ETDEWEB)

    Polla, L.L.; Margolis, R.J.; Dover, J.S.; Whitaker, D.; Murphy, G.F.; Jacques, S.L.; Anderson, R.R.

    1987-09-01

    The specific targeting of melanosomes may allow for laser therapy of pigmented cutaneous lesions. The mechanism of selective destruction of pigmented cells by various lasers, however, has not been fully clarified. Black, brown, and albino guinea pigs were exposed to optical pulses at various radiant exposure doses from a Q-switched, 40 nsec, 694 nm ruby laser. Biopsies were analyzed by light and electron microscopy (EM). Albino animals failed to develop clinical or microscopic evidence of cutaneous injury after irradiation. In both black and brown animals, the clinical threshold for gross change was 0.4 J/cm2, which produced an ash-white spot. By light microscopy, alterations appeared at 0.3 J/cm2 and included separation at the dermoepidermal junction, and the formation of vacuolated epidermal cells with a peripheral cytoplasmic condensation of pigment. By EM, enlarged melanosomes with a central lucent zone were observed within affected epidermal cells at 0.3 J/cm2. At 0.8 and 1.2 J/cm2, individual melanosomes were more intensely damaged and disruption of melanosomes deep in the hair papillae was observed. Dermal-epidermal blisters were formed precisely at the lamina lucida, leaving basal cell membranes and hemidesmosomes intact. Possible mechanisms for melanosomal injury are discussed. These observations show that the effects of the Q-switched ruby laser are melanin-specific and melanin-dependent, and may be useful in the selective destruction of pigmented as well as superficial cutaneous lesions.

  12. Autoradiographic studies on the cell kinetics after the whole body X-irradiation. 2. Regularities of the post-irradiation death of differentiating and proliferating cells of the rat brain subependimal zone

    International Nuclear Information System (INIS)

    Gracheva, N.D.

    1982-01-01

    A wave-like character of death of proliferating and differentiating (D) cells is shown autoradiographically using 3 H-thymidine introduced 60-80 min before the whole body X-ray irradiation in doses of 50, 150 or 300 R on subependymal cells of rat brain. Lethally damaged cells irradiated in G 2 and S-phases, resulted in 4 peaks of death in mitosis by following the first postradiational mitotic cycle (MC). Lethally damaged cells irradiated in G 1 -phase lost ability for DNA synthesis as cells irradiated in a dose of 300 R did not include additionally introduced (3 hrs before death) 14 C-thymidine from 12 to 17 hrs after 3 H-thymidine injection. However, in the first 4 hrs after irradiation there were no cells irradiated in G 1 -phase among dead ones, as indirec showed the calculations of data obtained tly/ while studying Pliss lymphosarcoma. A supposition is made that the death of cells irradiated in G 1 -phase is attributed to mitotic phase of the first MC after irradiation. Waves of death of lethally damaged D-cells repeated the peaks of death and corresponded to the mitotic peaks of proliferating cells, which permitted to presuppose the presence of ''short cycle'' (SC) in D-cells, which have the rhythm similar to MC and their death has been attributed to the final SC phase, which corresponds to MC mitotic phase in time. According to the peaks of cell death position of one hour block independent of dose in six MC(SC) points is determined. The cells have experienced the block in the point of MC(SC) in subphase of which they were caught by irradiation. Dose effect is manifested in the number of dead cells

  13. Comparison of a Rat Primary Cell-Based Blood-Brain Barrier Model With Epithelial and Brain Endothelial Cell Lines: Gene Expression and Drug Transport

    Directory of Open Access Journals (Sweden)

    Szilvia Veszelka

    2018-05-01

    Full Text Available Cell culture-based blood-brain barrier (BBB models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC, ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models. To establish a primary BBB model rat brain capillary endothelial cells were co-cultured with rat pericytes and astrocytes (EPA. As other BBB and surrogate models four brain endothelial cells lines, rat GP8 and RBE4 cells, and human hCMEC/D3 cells with or without lithium treatment (D3 and D3L, and four epithelial cell lines, native human intestinal Caco-2 and high P-glycoprotein expressing vinblastine-selected VB-Caco-2 cells, native MDCK and MDR1 transfected MDCK canine kidney cells were used. To test transporter functionality, the permeability of 12 molecules, glucopyranose, valproate, baclofen, gabapentin, probenecid, salicylate, rosuvastatin, pravastatin, atorvastatin, tacrine, donepezil, was also measured in the EPA and epithelial models. Among the junctional protein genes, the expression level of occludin was high in all models except the GP8 and RBE4 cells, and each model expressed a unique claudin pattern. Major BBB efflux (P-glycoprotein or ABCB1 and influx transporters (GLUT-1, LAT-1 were present in all models at mRNA levels. The transcript of BCRP (ABCG2 was not expressed in MDCK, GP8 and RBE4 cells. The absence of gene expression of important BBB efflux and influx transporters BCRP, MRP6, -9, MCT6, -8, PHT2, OATPs in one or both types of epithelial models suggests that Caco-2 or MDCK models are not suitable to test drug candidates which

  14. Characterisation of an in vitro blood-brain barrier model based on primary porcine capillary endothelial cells in monoculture or co-culture with primary rat or porcine astrocytes and pericytes

    DEFF Research Database (Denmark)

    Thomsen, Louiza Bohn; Larsen, Annette Burkhart; Moos, Torben

    to in vivo such as efflux transporters, tight junction proteins, and high transendothelial electric resistance (TEER). Primary BCECs are isolated from a variety of mammals such as rats, mice, cattle and pigs. Often bovine and porcine BCECs are cultured in monoculture or in co-culture with rat astrocytes......In vitro blood-brain barrier (BBB) models based on primary brain capillary endothelial cells (BCECs) in monoculture or in co-culture with primary astrocytes and pericytes are often applied for studying physiology of the BBB. Primary BCECs retain many morphological and biochemical properties similar...... obtained from neonatal rats which have been shown to strengthen the barrier properties of the BCECs. In this study, brain endothelial cells (PBECs), astrocytes and pericytes are isolated from pig brains donated by the local abattoir. The brains are from 6 month old domestic pigs. The availability and high...

  15. Mechanisms of growth inhibition of primary prostate epithelial cells following gamma irradiation or photodynamic therapy include senescence, necrosis, and autophagy, but not apoptosis

    International Nuclear Information System (INIS)

    Frame, Fiona M.; Savoie, Huguette; Bryden, Francesca; Giuntini, Francesca; Mann, Vincent M.; Simms, Matthew S.; Boyle, Ross W.; Maitland, Norman J.

    2015-01-01

    In comparison to more differentiated cells, prostate cancer stem-like cells are radioresistant, which could explain radio-recurrent prostate cancer. Improvement of radiotherapeutic efficacy may therefore require combination therapy. We have investigated the consequences of treating primary prostate epithelial cells with gamma irradiation and photodynamic therapy (PDT), both of which act through production of reactive oxygen species (ROS). Primary prostate epithelial cells were cultured from patient samples of benign prostatic hyperplasia and prostate cancer prior to treatment with PDT or gamma irradiation. Cell viability was measured using MTT and alamar blue assay, and cell recovery by colony-forming assays. Immunofluorescence of gamma-H2AX foci was used to quantify DNA damage, and autophagy and apoptosis were assessed using Western blots. Necrosis and senescence were measured by propidium iodide staining and beta-galactosidase staining, respectively. Both PDT and gamma irradiation reduced the colony-forming ability of primary prostate epithelial cells. PDT reduced the viability of all types of cells in the cultures, including stem-like cells and more differentiated cells. PDT induced necrosis and autophagy, whereas gamma irradiation induced senescence, but neither treatment induced apoptosis. PDT and gamma irradiation therefore inhibit cell growth by different mechanisms. We suggest these treatments would be suitable for use in combination as sequential treatments against prostate cancer

  16. Automated delineation of brain structures in patients undergoing radiotherapy for primary brain tumors: From atlas to dose–volume histograms

    International Nuclear Information System (INIS)

    Conson, Manuel; Cella, Laura; Pacelli, Roberto; Comerci, Marco; Liuzzi, Raffaele; Salvatore, Marco; Quarantelli, Mario

    2014-01-01

    Purpose: To implement and evaluate a magnetic resonance imaging atlas-based automated segmentation (MRI-ABAS) procedure for cortical and sub-cortical grey matter areas definition, suitable for dose-distribution analyses in brain tumor patients undergoing radiotherapy (RT). Patients and methods: 3T-MRI scans performed before RT in ten brain tumor patients were used. The MRI-ABAS procedure consists of grey matter classification and atlas-based regions of interest definition. The Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm was applied to structures manually delineated by four experts to generate the standard reference. Performance was assessed comparing multiple geometrical metrics (including Dice Similarity Coefficient – DSC). Dosimetric parameters from dose–volume-histograms were also generated and compared. Results: Compared with manual delineation, MRI-ABAS showed excellent reproducibility [median DSC ABAS = 1 (95% CI, 0.97–1.0) vs. DSC MANUAL = 0.90 (0.73–0.98)], acceptable accuracy [DSC ABAS = 0.81 (0.68–0.94) vs. DSC MANUAL = 0.90 (0.76–0.98)], and an overall 90% reduction in delineation time. Dosimetric parameters obtained using MRI-ABAS were comparable with those obtained by manual contouring. Conclusions: The speed, reproducibility, and robustness of the process make MRI-ABAS a valuable tool for investigating radiation dose–volume effects in non-target brain structures providing additional standardized data without additional time-consuming procedures

  17. Healthy brain connectivity predicts atrophy progression in non-fluent variant of primary progressive aphasia.

    Science.gov (United States)

    Mandelli, Maria Luisa; Vilaplana, Eduard; Brown, Jesse A; Hubbard, H Isabel; Binney, Richard J; Attygalle, Suneth; Santos-Santos, Miguel A; Miller, Zachary A; Pakvasa, Mikhail; Henry, Maya L; Rosen, Howard J; Henry, Roland G; Rabinovici, Gil D; Miller, Bruce L; Seeley, William W; Gorno-Tempini, Maria Luisa

    2016-10-01

    longitudinal grey matter changes in the non-fluent/agrammatic variant of primary progressive aphasia. Graph theoretical analysis of the speech/language network showed that regions with shorter functional paths to the epicentre exhibited greater longitudinal atrophy. The network contained three modules, including a left inferior frontal gyrus/supplementary motor area, which was most strongly connected with the epicentre. The aslant tract was the white matter pathway connecting these two regions and showed the most significant correlation between fractional anisotropy and white matter longitudinal atrophy changes. This study showed that the pattern of longitudinal atrophy progression in the non-fluent/agrammatic variant of primary progressive aphasia relates to the strength of connectivity in pre-determined functional and structural large-scale speech production networks. These findings support the hypothesis that the spread of neurodegeneration occurs by following specific anatomical and functional neuronal network architectures. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. The effect of irradiation and cis-diamminedichloroplatinum(II) in the rat brain : analysis of histopathology at 3 and 6 months after treatment

    International Nuclear Information System (INIS)

    Lee, Kyung Ja; Chang, Seung Hee; Koo, Hea Soo

    1998-01-01

    To evalute the late effect(3 and 6 months) of cis-diamminedichloroplatinum(II)(cisplatin) on the radiation brain damage when the cisplatin was intraperitoneally infused immediately after whole brain irradiation in the rats. The histolopathological findings of the brain were examined in rat brains at 3 and 6 months after the treatment. The rats were irradiated(20 or 22.5 Gy, RT) or cisplatin was injected intraperitoneally(2, 4, or 8mg/kg, CT) and in combined treatment group, cisplatin(2mg/kg) was injected immediately after irradiation (20 or 22.5 Gy). Histopathological examination was done mostly in irradiation or cisplatin alone groups, because the rats in combined group died during experimental period except 2 rats. The rats treated with cisplatin showed marked epithelial vacuolation with perivascular edema and vascular dilatation in choroid plexus at 3 months as well as multifocal necrosis involving fimbria and cerebellar hemispheres at 3 and 6 months. The changes were more prominent in rats with 2mg/kg injection compared to rats with 8mg/kg injection. The rats with RT and combined CT and RT showed characteristic delayed irradiation effects such as focal coagulation necrosis and vascular changes, which were more marked than previous reports. Prominent perivascular and leptomeningeal astrocytic proliferation was well documented by anti-GFAP antibody. Cisplatin treatment did not enhance the effect of radiation -induced changes of blood vessels and astrocytic proliferation. The focal necrosis was the most consistently noted finding in this study, it suggested the possibility to use this as an evaluation factor for combined effects of RT and cisplatin

  19. Aberrant whole-brain functional connectivity and intelligence structure in children with primary nocturnal enuresis.

    Directory of Open Access Journals (Sweden)

    Bing Yu

    Full Text Available AIM: To assess the potential relationship between intelligence structure abnormalities and whole-brain functional connectivity in children with primary nocturnal enuresis (PNE with resting-state functional magnetic resonance imaging (fMRI to provide insights into the association between these two seemingly unrelated conditions. METHODS: Intelligence testing and fMRI data were obtained from 133 right-handed children, including 67 PNE children (M/F, 39:28; age, 10.5 ± 1.2 y and 66 age-matched healthy controls (M/F, 37:29; age, 10.1 ± 1.1 y. All intelligence tests were performed using the China-Wechsler Intelligence Scale for Children (C-WISC. Each subject's full intelligence quotient (FIQ, verbal IQ (VIQ, performance IQ (PIQ, and memory/caution (M/C factor was measured and recorded. Resting state fMRI scans were performed on a 3.0-T MR scanner and post-processed using REST software. Comparisons of z-score correlation coefficients between distinct cerebral regions were used to identify altered functional connectivity in PNE children. RESULTS: The PNE group had normal FIQ, VIQ, and PIQ values, indicating no significant variation from the control group. However, the M/C factor was significantly lower in the PNE group. Compared to the control group, PNE children exhibited overall lower levels of functional connectivity that were most apparent in the cerebello-thalamo-frontal pathway. The M/C factor significantly correlated with z-scores representing connectivity between Cerebellum_Crus1_L and Frontal_Mid_R. CONCLUSION: PNE children exhibit intelligence structure imbalance and attention deficits. Our findings suggest that cerebello-thalamo-frontal circuit abnormalities are likely to be involved in the onset and progression of attention impairment in PNE children.

  20. Increased expression of EMMPRIN and VEGF in the rat brain after gamma irradiation.

    Science.gov (United States)

    Wei, Ming; Li, Hong; Huang, Huiling; Xu, Desheng; Zhi, Dashi; Liu, Dong; Zhang, Yipei

    2012-03-01

    The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.

  1. A consecutive series of patients with laryngeal carcinoma treated by primary irradiation

    International Nuclear Information System (INIS)

    Greisen, O.; Carl, J.; Pedersen, M.

    1997-01-01

    In Denmark there is an increasing frequency of laryngeal carcinoma, in particular in women and among these especially in supraglottic tumours. The incidence during the past 20 years has risen from about 40 to 60 cases per million per year. A series of 335 consecutive patients treated with primary radiation is presented. In one-third of all patients the tumour was localized in the supraglottic area; in women in more than half and in men in about one-fourth of the cases. The frequency of primary lymph node metastases in the supraglottic and the glottic tumours was 24% and 2% respectively. A multivariate analysis identified sex and tumour size as independent prognostic parameters of local control. Five-year survival corrected for intercurrent deaths was obtained in 59% of all cases, in 56% of supraglottic and in 92% of glottic tumours. A multivariate analysis defined localization, tumour grade and stage as independent prognostic parameters of survival. Salvage surgery was performed in about 32% of the cases, total laryngectomy in 26%, and partial laryngectomy in 6%. The survival rate among all total laryngectomies was 55%. A tracheostomy during or before radiation treatment prior to total laryngectomy had no influence on complication rate, admission time or recurrence rate. The frequency of pharyngo-cutaneous fistulae in the entire series was 11.5%; after routine use of metronidazol, however, only 5.7%. Radical neck dissection was carried out in 7.8% of the cases, by far most in the supraglottic group, only a few in the glottic carcinomas, in three-fourth in connection with a laryngectomy and in one-fourth without local recurrence in the larynx. (orig.)

  2. A consecutive series of patients with laryngeal carcinoma treated by primary irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Greisen, O. [ENT Dept. and the Oncological Dept., Aalborg Sygehus (Denmark); Carl, J. [ENT Dept. and the Oncological Dept., Aalborg Sygehus (Denmark); Pedersen, M. [ENT Dept. and the Oncological Dept., Aalborg Sygehus (Denmark)

    1997-09-01

    In Denmark there is an increasing frequency of laryngeal carcinoma, in particular in women and among these especially in supraglottic tumours. The incidence during the past 20 years has risen from about 40 to 60 cases per million per year. A series of 335 consecutive patients treated with primary radiation is presented. In one-third of all patients the tumour was localized in the supraglottic area; in women in more than half and in men in about one-fourth of the cases. The frequency of primary lymph node metastases in the supraglottic and the glottic tumours was 24% and 2% respectively. A multivariate analysis identified sex and tumour size as independent prognostic parameters of local control. Five-year survival corrected for intercurrent deaths was obtained in 59% of all cases, in 56% of supraglottic and in 92% of glottic tumours. A multivariate analysis defined localization, tumour grade and stage as independent prognostic parameters of survival. Salvage surgery was performed in about 32% of the cases, total laryngectomy in 26%, and partial laryngectomy in 6%. The survival rate among all total laryngectomies was 55%. A tracheostomy during or before radiation treatment prior to total laryngectomy had no influence on complication rate, admission time or recurrence rate. The frequency of pharyngo-cutaneous fistulae in the entire series was 11.5%; after routine use of metronidazol, however, only 5.7%. Radical neck dissection was carried out in 7.8% of the cases, by far most in the supraglottic group, only a few in the glottic carcinomas, in three-fourth in connection with a laryngectomy and in one-fourth without local recurrence in the larynx. (orig.).

  3. Classifying brain metastases by their primary site of origin using a radiomics approach based on texture analysis: a feasibility study.

    Science.gov (United States)

    Ortiz-Ramón, Rafael; Larroza, Andrés; Ruiz-España, Silvia; Arana, Estanislao; Moratal, David

    2018-05-14

    To examine the capability of MRI texture analysis to differentiate the primary site of origin of brain metastases following a radiomics approach. Sixty-seven untreated brain metastases (BM) were found in 3D T1-weighted MRI of 38 patients with cancer: 27 from lung cancer, 23 from melanoma and 17 from breast cancer. These lesions were segmented in 2D and 3D to compare the discriminative power of 2D and 3D texture features. The images were quantized using different number of gray-levels to test the influence of quantization. Forty-three rotation-invariant texture features were examined. Feature selection and random forest classification were implemented within a nested cross-validation structure. Classification was evaluated with the area under receiver operating characteristic curve (AUC) considering two strategies: multiclass and one-versus-one. In the multiclass approach, 3D texture features were more discriminative than 2D features. The best results were achieved for images quantized with 32 gray-levels (AUC = 0.873 ± 0.064) using the top four features provided by the feature selection method based on the p-value. In the one-versus-one approach, high accuracy was obtained when differentiating lung cancer BM from breast cancer BM (four features, AUC = 0.963 ± 0.054) and melanoma BM (eight features, AUC = 0.936 ± 0.070) using the optimal dataset (3D features, 32 gray-levels). Classification of breast cancer and melanoma BM was unsatisfactory (AUC = 0.607 ± 0.180). Volumetric MRI texture features can be useful to differentiate brain metastases from different primary cancers after quantizing the images with the proper number of gray-levels. • Texture analysis is a promising source of biomarkers for classifying brain neoplasms. • MRI texture features of brain metastases could help identifying the primary cancer. • Volumetric texture features are more discriminative than traditional 2D texture features.

  4. Stress corrosion cracking of irradiated stainless steels in primary water: experimental studies and model development in the FP7 PERFECT IP

    International Nuclear Information System (INIS)

    Van Dyck, S.

    2009-01-01

    The long term behaviour of the internal structures, surrounding the core of nuclear reactors, is a concern within the general framework of plant life management. Due to their positioning in the reactor, the internal structures of a pressurised water reactor (PWR) receive a high neutron irradiation dose during their exposure to the primary environment. The irradiation induced changes in the material and environment may cause or accelerate stress corrosion cracking of stainless steel internals, otherwise insensitive to stress corrosion in primary environment. This phenomenon of irradiation assisted stress corrosion cracking (IASCC) is currently not well quantified. At this stage, the understanding of the underlying mechanisms of IASCC is qualitative at best and no systematic database and descriptive model are available for IASCC in PWR conditions. Since 2004, a concerted European effort is ongoing within the framework 7 PERFECT integrated project to investigate and model IASCC

  5. Vascular targeting of LIGHT normalizes blood vessels in primary brain cancer and induces intratumoural high endothelial venules.

    Science.gov (United States)

    He, Bo; Jabouille, Arnaud; Steri, Veronica; Johansson-Percival, Anna; Michael, Iacovos P; Kotamraju, Venkata Ramana; Junckerstorff, Reimar; Nowak, Anna K; Hamzah, Juliana; Lee, Gabriel; Bergers, Gabriele; Ganss, Ruth

    2018-06-01

    High-grade brain cancer such as glioblastoma (GBM) remains an incurable disease. A common feature of GBM is the angiogenic vasculature, which can be targeted with selected peptides for payload delivery. We assessed the ability of micelle-tagged, vascular homing peptides RGR, CGKRK and NGR to specifically bind to blood vessels in syngeneic orthotopic GBM models. By using the peptide CGKRK to deliver the tumour necrosis factor (TNF) superfamily member LIGHT (also known as TNF superfamily member 14; TNFSF14) to angiogenic tumour vessels, we have generated a reagent that normalizes the brain cancer vasculature by inducing pericyte contractility and re-establishing endothelial barrier integrity. LIGHT-mediated vascular remodelling also activates endothelia and induces intratumoural high endothelial venules (HEVs), which are specialized blood vessels for lymphocyte infiltration. Combining CGKRK-LIGHT with anti-vascular endothelial growth factor and checkpoint blockade amplified HEV frequency and T-cell accumulation in GBM, which is often sparsely infiltrated by immune effector cells, and reduced tumour burden. Furthermore, CGKRK and RGR peptides strongly bound to blood vessels in freshly resected human GBM, demonstrating shared peptide-binding activities in mouse and human primary brain tumour vessels. Thus, peptide-mediated LIGHT targeting is a highly translatable approach in primary brain cancer to reduce vascular leakiness and enhance immunotherapy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex

    OpenAIRE

    Scott, Gregory D.; Karns, Christina M.; Dow, Mark W.; Stevens, Courtney; Neville, Helen J.

    2014-01-01

    Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants wer...

  7. Transfection of primary brain capillary endothelial cells for protein synthesis and secretion of recombinant erythropoietin: a strategy to enable protein delivery to the brain

    DEFF Research Database (Denmark)

    Burkhart, Annette; Andresen, Thomas Lars; Aigner, Achim

    2017-01-01

    , as turning BCECs into recombinant protein factories by transfection could result in protein secretion further into the brain. The present study aims to investigate the possibility of transfecting primary rat brain endothelial cells (RBECs) for recombinant protein synthesis and secretion...... of the neuroprotective protein erythropoietin (EPO). We previously showed that 4% of RBECs with BBB properties can be transfected without disrupting the BBB integrity in vitro, but it can be questioned whether this is sufficient to enable protein secretion at therapeutic levels. The present study examined various......-derived neurotropic factor (BDNF). In conclusion, non-viral gene therapy to RBECs leads to protein secretion and signifies a method for therapeutic proteins to target cells inside the CNS otherwise omitted due to the BBB....

  8. Effect of 710 nm visible light irradiation on neurite outgrowth in primary rat cortical neurons following ischemic insult

    International Nuclear Information System (INIS)

    Choi, Dong-Hee; Lee, Kyoung-Hee; Kim, Ji-Hye; Kim, Moon Young; Lim, Jeong Hoon; Lee, Jongmin

    2012-01-01

    Highlights: ► 710 nm wavelength light (LED) has a protective effect in the stroke animal model. ► We determined the effects of LED irradiation in vitro stroke model. ► LED treatment promotes the neurite outgrowth through MAPK activation. ► The level of synaptic markers significantly increased with LED treatment. ► LED treatment protects cell death in the in vitro stroke model. -- Abstract: Objective: We previously reported that 710 nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710 nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model. Materials and methods: Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm 2 and 50 mW/cm 2 ) were given once to four times within 8 h at 2 h intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axio Vision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting. Results: Images captured after MAP2 immunocytochemistry showed significant (p < 0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly increased with LED treatment in both OGD-exposed and normal cells (p < 0.05). Conclusion: Our data suggest that LED treatment may promote

  9. Effect of 710 nm visible light irradiation on neurite outgrowth in primary rat cortical neurons following ischemic insult

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Dong-Hee [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Department of Medical Science, Konkuk University School of Medicine, Seoul (Korea, Republic of); Lee, Kyoung-Hee; Kim, Ji-Hye; Kim, Moon Young [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Lim, Jeong Hoon [Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of); Rehabilitation Medicine, Division of Neurology, Department of Medicine, National University Hospital, National University Health System (Singapore); Lee, Jongmin, E-mail: leej@kuh.ac.kr [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer 710 nm wavelength light (LED) has a protective effect in the stroke animal model. Black-Right-Pointing-Pointer We determined the effects of LED irradiation in vitro stroke model. Black-Right-Pointing-Pointer LED treatment promotes the neurite outgrowth through MAPK activation. Black-Right-Pointing-Pointer The level of synaptic markers significantly increased with LED treatment. Black-Right-Pointing-Pointer LED treatment protects cell death in the in vitro stroke model. -- Abstract: Objective: We previously reported that 710 nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710 nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model. Materials and methods: Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm{sup 2} and 50 mW/cm{sup 2}) were given once to four times within 8 h at 2 h intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axio Vision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting. Results: Images captured after MAP2 immunocytochemistry showed significant (p < 0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly

  10. Developmental effects of irradiation on the brain of the embryo and fetus

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    This publication represents an evaluation of the data relating to radiation-induced effects on the central nervous system, especially radiation-induced mental retardation;assesses the gestational age at risk and the quantitative risk at low doses;analyses these effects in the light of what is known about cell survival, proliferation, repopulation and differentiation in the development of the fetal rain;and identifies the needs for future research. Contents: Preface;Introduction;Prenatal development of the primate brain and cerebral adnexa;Developmental disorders of the central nervous system;Ionizing radiation as a central nervous system teratogen;Periods of maximum sensitivity;Risk estimates in humans;Research needs;References

  11. Chronic irradiation and brain development. Progress report, February 15, 1976--February 15, 1977

    International Nuclear Information System (INIS)

    Zamenhof, S.

    1977-01-01

    Tritiated water ( 3 HOH) ingested by the female rats in the dose as low as 3 μCi/ml drinking water (69 μCi/day) produced highly significant decreases in body weight, cerebral weight, cerebral DNA (cell number), and cerebral protein, of the offspring at birth. These effects of such a low dose on fetal brain development were not demonstrated before. Administration of 3 HOH before mating (and during pregnancy) seemed to be necessary for this damage; a disturbance of ovarian maturation is implicated. Chronic administration of 3 HOH until birth of F 2 generation did not result in more damage in F 2 than in F 1 ; high mortality and a selection of individuals less suceptible to radiation may be implicated

  12. Purification of cells from fresh human brain tissue: primary human glial cells.

    NARCIS (Netherlands)

    Mizee, Mark R; van der Poel, Marlijn; Huitinga, I.; Huitinga, I.; Webster, M.J.

    2018-01-01

    In order to translate the findings obtained from postmortem brain tissue samples to functional biologic mechanisms of central nervous system disease, it will be necessary to understand how these findings affect the different cell populations in the brain. The acute isolation and analysis of pure

  13. Expression of Shiga toxin 2e glycosphingolipid receptors of primary porcine brain endothelial cells and toxin-mediated breakdown of the blood-brain barrier.

    Science.gov (United States)

    Meisen, Iris; Rosenbrück, Regina; Galla, Hans-Joachim; Hüwel, Sabine; Kouzel, Ivan U; Mormann, Michael; Karch, Helge; Müthing, Johannes

    2013-06-01

    Shiga toxin (Stx) 2e, released by certain Stx-producing Escherichia coli, is presently the best characterized virulence factor responsible for pig edema disease, which is characterized by hemorrhagic lesions, neurological disorders and often fatal outcomes. Although Stx2e-mediated brain vascular injury is the key event in development of neurologic signs, the glycosphingolipid (GSL) receptors of Stx2e and toxin-mediated impairment of pig brain endothelial cells have not been investigated so far. Here, we report on the detailed structural characterization of Stx2e receptors globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), which make up the major neutral GSLs in primary porcine brain capillary endothelial cells (PBCECs). Various Gb3Cer and Gb4Cer lipoforms harboring sphingenine (d18:1) or sphinganine (d18:0) and mostly a long-chain fatty acid (C20-C24) were detected. A notable batch-to-batch heterogeneity of primary endothelial cells was observed regarding the extent of ceramide hydroxylation of Gb3Cer or Gb4Cer species. Gb3Cer, Gb4Cer and sphingomyelin preferentially distribute to detergent-resistant membrane fractions and can be considered lipid raft markers in PBCECs. Moreover, we employed an in vitro model of the blood-brain barrier (BBB), which exhibited strong cytotoxic effects of Stx2e on the endothelial monolayer and a rapid collapse of the BBB. These data strongly suggest the involvement of Stx2e in cerebral vascular damage with resultant neurological disturbance characteristic of edema disease.

  14. Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Karunamuni, Roshan [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Bartsch, Hauke; White, Nathan S. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Moiseenko, Vitali; Carmona, Ruben; Marshall, Deborah C.; Seibert, Tyler M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Psychiatry, University of California San Diego, La Jolla, California (United States); Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua [Department of Radiology, University of California San Diego, La Jolla, California (United States); Mell, Loren [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Brewer, James B.; Dale, Anders M. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2016-02-01

    Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thickness between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.

  15. Complex treatment of primary brain neuroblastoma with four local recurrences for period of 5 years -clinical case from our practice

    International Nuclear Information System (INIS)

    Marinova, L.; Georgiev, R.; Mihaylova, I.; Belcheva, M.

    2017-01-01

    We present a clinical case of 17 years old girl with primary brain neuroblastoma (supratentorial primitive neuro-ectodermal tumor - PNET in right temporo-parietal brain region). Complex treatment has been applied, including subtotal operation, standard fractioned cranio-spinal external beam radiotherapy with boost up to 56 Gy in the locus of the tumor remnant and 6 courses of adjuvant chemotherapy with Carboplatin and Etoposide. Despite the applied local treatment methods (radical surgery, standard fractioned cranio-spinal external beam radiotherapy and radio-surgery with single total dose of 14 Gy), four recurrences have appeared for period of 5 years in the locus of the primary tumor. The risk of appearance of local recurrences, necessitating re-operations, chemotherapy, bone marrow transplantation of stem cells and radio-surgery was discussed. We are also discussing the radio sensitivity of the PNET and the possibilities for overcoming it with implementation of hyper fractioned cranio-spinal external beam radiotherapy in combination with chemotherapy, followed by bone marrow transplantation of stem cells. Key words: Primary Brain Neuroblastoma. Radio Sensitivity. Cranio-Spinal External Beam Radiotherapy. Adjuvant Chemotherapy [bg

  16. Evaluation of FSE and FSPGR MRI imaging methods for planning cranial stereotactic irradiation of a metastatic brain tumor

    International Nuclear Information System (INIS)

    Terada, Masaki; Tanoi, Chiharu

    2003-01-01

    Cranial stereotactic irradiation (STI) of a metastatic brain tumor (BT) was planned by fusing CT images with MRI images using the landmark method of the X-Knife System. The MRI images revealed the BT, the critical optic nerve and brain stem of structures and the eyeball and blood vessels that are landmarks. It was important to improve visibility of the BT with sufficient contrast. Therefore, comparison examinations were performed using the two dimensions fast spin echo (2DFSE), the two dimensions fast spoiled gradient echo (2DFSPGR), and the three dimensions fast spoiled gradient echo (3DFSPGR) methods of T1-weighted imaging with Gd-DTPA contrast. Critical structures and the internal structures of the landmark method were suitable for planning STI when the results of three or more points were combined in visual evaluations. However, the 2DFSE method could showed three or more points. The BT also be visually evaluated using three or less points by the FSPGR method, but had reduced visibility. From detailed contents, the fall of visual evaluation by the small thin and solid BT of the diameter of a BT was characteristic. In the whole signal noise ratio (SNR), the 3DFSPGR method is excellent in images analysis, and the 2DFSE method was excellent in contrast noise ratio (CNR) of a BT. The cystic BT accompanied by dropsy was images with clear and good depiction in all scan parameter. However, the FSPGR method was the boundary not clear in the small solid BT, the FSE method was able to recognize the maximum of the diameter of BT most, and depiction was good. Artifacts of blood flow and motion of the FSE method is a fault. However, the FSE method had the highest useful depiction ability of all BT in the STI plan. (author)

  17. 5-Fluorouracil and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) followed by hydroxyurea, misonidazole, and irradiation for brain stem gliomas: a pilot study of the Brain Tumor Research Center and the Childrens Cancer Group

    International Nuclear Information System (INIS)

    Levin, V.A.; Edwards, M.S.; Wara, W.M.; Allen, J.; Ortega, J.; Vestnys, P.

    1984-01-01

    Twenty-eight evaluable children with the diagnosis of brain stem glioma were treated with 5-fluorouracil and CCNU before posterior fossa irradiation (5500 rads); during irradiation, the children received hydroxyurea and misonidazole. The treatment was well tolerated, and minimal toxicity was produced. The median relapse-free survival was 32 weeks, and the median survival was 44 weeks. Analysis of covariates showed that, in patients between the ages of 2 and 19 years, survival was longest in the older children (P less than 0.02). Tumor histology, sex, extent of operation (if any), Karnofsky score, and radiation dose did not correlate with survival

  18. The value of intraoperative ultrasonography during the resection of relapsed irradiated malignant gliomas in the brain

    International Nuclear Information System (INIS)

    Mursch, Kay; Mursch, Julianne Behnke; Scholz, Martin; Brueck, Wolfgang

    2017-01-01

    The aim of this study was to investigate whether intraoperative ultrasonography (IOUS) helped the surgeon navigate towards the tumor as seen in preoperative magnetic resonance imaging and whether IOUS was able to distinguish between tumor margins and the surrounding tissue. Twenty-five patients suffering from high-grade gliomas who were previously treated by surgery and radiotherapy were included. Intraoperatively, two histopathologic samples were obtained a sample of unequivocal tumor tissue (according to anatomical landmarks and the surgeon's visual and tactile impressions) and a small tissue sample obtained using a navigated needle when the surgeon decided to stop the resection. This specimen was considered to be a boundary specimen, where no tumor tissue was apparent. The decision to take the second sample was not influenced by IOUS. The effect of IOUS was analyzed semi-quantitatively. All 25 samples of unequivocal tumor tissue were histopathologically classified as tumor tissue and were hyperechoic on IOUS. Of the boundary specimens, eight were hypoechoic. Only one harbored tumor tissue (P=0.150). Seventeen boundaries were moderately hyperechoic, and these samples contained all possible histological results (i.e., tumor, infiltration, or no tumor). During surgery performed on relapsed, irradiated, high-grade gliomas, IOUS provided a reliable method of navigating towards the core of the tumor. At borders, it did not reliably distinguish between remnants or tumor-free tissue, but hypoechoic areas seldom contained tumor tissue

  19. The value of intraoperative ultrasonography during the resection of relapsed irradiated malignant gliomas in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Mursch, Kay; Mursch, Julianne Behnke [Dept. of Neurosurgery, Zentralklinik, Bad Berka (Germany); Scholz, Martin [Dept. of Neurosurgery, Klinikum Duisburg, Duisburg (Germany); Brueck, Wolfgang [Dept. of Neuropathology, Georg August Universitaet, Goettingen (Germany)

    2017-01-15

    The aim of this study was to investigate whether intraoperative ultrasonography (IOUS) helped the surgeon navigate towards the tumor as seen in preoperative magnetic resonance imaging and whether IOUS was able to distinguish between tumor margins and the surrounding tissue. Twenty-five patients suffering from high-grade gliomas who were previously treated by surgery and radiotherapy were included. Intraoperatively, two histopathologic samples were obtained a sample of unequivocal tumor tissue (according to anatomical landmarks and the surgeon's visual and tactile impressions) and a small tissue sample obtained using a navigated needle when the surgeon decided to stop the resection. This specimen was considered to be a boundary specimen, where no tumor tissue was apparent. The decision to take the second sample was not influenced by IOUS. The effect of IOUS was analyzed semi-quantitatively. All 25 samples of unequivocal tumor tissue were histopathologically classified as tumor tissue and were hyperechoic on IOUS. Of the boundary specimens, eight were hypoechoic. Only one harbored tumor tissue (P=0.150). Seventeen boundaries were moderately hyperechoic, and these samples contained all possible histological results (i.e., tumor, infiltration, or no tumor). During surgery performed on relapsed, irradiated, high-grade gliomas, IOUS provided a reliable method of navigating towards the core of the tumor. At borders, it did not reliably distinguish between remnants or tumor-free tissue, but hypoechoic areas seldom contained tumor tissue.

  20. The value of intraoperative ultrasonography during the resection of relapsed irradiated malignant gliomas in the brain

    Directory of Open Access Journals (Sweden)

    Kay Mursch

    2017-01-01

    Full Text Available Purpose The aim of this study was to investigate whether intraoperative ultrasonography (IOUS helped the surgeon navigate towards the tumor as seen in preoperative magnetic resonance imaging and whether IOUS was able to distinguish between tumor margins and the surrounding tissue. Methods Twenty-five patients suffering from high-grade gliomas who were previously treated by surgery and radiotherapy were included. Intraoperatively, two histopathologic samples were obtained a sample of unequivocal tumor tissue (according to anatomical landmarks and the surgeon’s visual and tactile impressions and a small tissue sample obtained using a navigated needle when the surgeon decided to stop the resection. This specimen was considered to be a boundary specimen, where no tumor tissue was apparent. The decision to take the second sample was not influenced by IOUS. The effect of IOUS was analyzed semi-quantitatively. Results All 25 samples of unequivocal tumor tissue were histopathologically classified as tumor tissue and were hyperechoic on IOUS. Of the boundary specimens, eight were hypoechoic. Only one harbored tumor tissue (P=0.150. Seventeen boundaries were moderately hyperechoic, and these samples contained all possible histological results (i.e., tumor, infiltration, or no tumor. Conclusion During surgery performed on relapsed, irradiated, high-grade gliomas, IOUS provided a reliable method of navigating towards the core of the tumor. At borders, it did not reliably distinguish between remnants or tumor-free tissue, but hypoechoic areas seldom contained tumor tissue.

  1. Transfection of primary brain capillary endothelial cells for protein synthesis and secretion of recombinant erythropoietin: a strategy to enable protein delivery to the brain.

    Science.gov (United States)

    Burkhart, Annette; Andresen, Thomas Lars; Aigner, Achim; Thomsen, Louiza Bohn; Moos, Torben

    2017-07-01

    Treatment of chronic disorders affecting the central nervous system (CNS) is complicated by the inability of drugs to cross the blood-brain barrier (BBB). Non-viral gene therapy applied to brain capillary endothelial cells (BCECs) denotes a novel approach to overcome the restraints in this passage, as turning BCECs into recombinant protein factories by transfection could result in protein secretion further into the brain. The present study aims to investigate the possibility of transfecting primary rat brain endothelial cells (RBECs) for recombinant protein synthesis and secretion of the neuroprotective protein erythropoietin (EPO). We previously showed that 4% of RBECs with BBB properties can be transfected without disrupting the BBB integrity in vitro, but it can be questioned whether this is sufficient to enable protein secretion at therapeutic levels. The present study examined various transfection vectors, with regard to increasing the transfection efficiency without disrupting the BBB integrity. Lipofectamine 3000™ was the most potent vector compared to polyethylenimine (PEI) and Turbofect. When co-cultured with astrocytes, the genetically modified RBECs secreted recombinant EPO into the cell culture medium both luminally and abluminally, and despite lower levels of EPO reaching the abluminal chamber, the amount of recombinant EPO was sufficient to evolve a biological effect on astrocytes cultured at the abluminal side in terms of upregulated gene expression of brain-derived neurotropic factor (BDNF). In conclusion, non-viral gene therapy to RBECs leads to protein secretion and signifies a method for therapeutic proteins to target cells inside the CNS otherwise omitted due to the BBB.

  2. Revised and updated recommendations for the establishment of primary stroke centers: a summary statement from the brain attack coalition.

    Science.gov (United States)

    Alberts, Mark J; Latchaw, Richard E; Jagoda, Andy; Wechsler, Lawrence R; Crocco, Todd; George, Mary G; Connolly, E S; Mancini, Barbara; Prudhomme, Stephen; Gress, Daryl; Jensen, Mary E; Bass, Robert; Ruff, Robert; Foell, Kathy; Armonda, Rocco A; Emr, Marian; Warren, Margo; Baranski, Jim; Walker, Michael D

    2011-09-01

    The formation and certification of Primary Stroke Centers has progressed rapidly since the Brain Attack Coalition's original recommendations in 2000. The purpose of this article is to revise and update our recommendations for Primary Stroke Centers to reflect the latest data and experience. We conducted a literature review using MEDLINE and PubMed from March 2000 to January 2011. The review focused on studies that were relevant for acute stroke diagnosis, treatment, and care. Original references as well as meta-analyses and other care guidelines were also reviewed and included if found to be valid and relevant. Levels of evidence were added to reflect current guideline development practices. Based on the literature review and experience at Primary Stroke Centers, the importance of some elements has been further strengthened, and several new areas have been added. These include (1) the importance of acute stroke teams; (2) the importance of Stroke Units with telemetry monitoring; (3) performance of brain imaging with MRI and diffusion-weighted sequences; (4) assessment of cerebral vasculature with MR angiography or CT angiography; (5) cardiac imaging; (6) early initiation of rehabilitation therapies; and (7) certification by an independent body, including a site visit and disease performance measures. Based on the evidence, several elements of Primary Stroke Centers are particularly important for improving the care of patients with an acute stroke. Additional elements focus on imaging of the brain, the cerebral vasculature, and the heart. These new elements may improve the care and outcomes for patients with stroke cared for at a Primary Stroke Center.

  3. Treatment of primary brain lymphoma without immune deficiency, The importance of chemotherapy before radiotherapy

    Directory of Open Access Journals (Sweden)

    Keihani M

    1999-09-01

    Full Text Available The purpose of this study was to find a more efficacious treatment for patients with primary central nervous system Lymphoma using chemotherapy. The objective was to determine the optimal time for radiotherapy treatment in relation to chemotherapy. Retrospective evaluation in patients with brain lymphoma was conducted from 1992 to 1998. Twenty-three patients were evaluated. Patients were divided into two groups based on the timing of radiotherapy in relation to the chemotherapy. The first group of patients (n=13 initially received radiotherapy followed by chemotherapy. Five of these patients receied classic CHOP (cyclophosphamide, Doxorubicine, Vincistine and Prednisone, six patients received Cis-platin (60 Megs/M2 and Etoposide (120 Megs/M2 and two patients received Cis-platin (60 Megs/M2, Etoposide (120 Megs/M2 and Cytarabine (600 Megs/M2 every 2 to 3 weeks. The second group of patients (Group II, n=10 received the followeing treatment regimen: a course of BCNU 120 Megs/M2 with Ifosfamide 1200 Megs/M2, Mesna and Etoposide 120 Megs/M2 on the first day of treatment (course A. Two weeks later, treatment was continued with a course of Cis-platin 35 Megs/M2 and Cytarabine 600 Megs/M2 (course B. The treatment was continued 14 days later with a course of Mitoxantron 12 Megs/M2, Ifosfamide 1200 Megs/M2 puls Mesna (course C. After the fourth week of chemotherapy, these patients received radiotherapy to the brain (5000 RADS in 4 weeks. During radiotherapy and at the beginning of course chemotherapy, intrathecal therapy with Methorexate 12 Megs/M2 and Cytarabine 60 Megs/M2 was given. Immediately after radiotherapy, the same chemothotrexate 12 Megs/M2 and Cytarabine 60 Megs/M2 was given. Immediately after radiotherapy, the same chemotherapy treatment was repeated to a total of 3 times. After complete clearance of the tumor determined by MRI and absence of tumor cells in the spinal fluid, the chemotherapeutic regimen was repeated one last time. The

  4. Differential Motion Between Mediastinal Lymph Nodes and Primary Tumor in Radically Irradiated Lung Cancer Patients

    International Nuclear Information System (INIS)

    Schaake, Eva E.; Rossi, Maddalena M.G.; Buikhuisen, Wieneke A.; Burgers, Jacobus A.; Smit, Adrianus A.J.; Belderbos, José S.A.; Sonke, Jan-Jakob

    2014-01-01

    Purpose/Objective: In patients with locally advanced lung cancer, planning target volume margins for mediastinal lymph nodes and tumor after a correction protocol based on bony anatomy registration typically range from 1 to 1.5 cm. Detailed information about lymph node motion variability and differential motion with the primary tumor, however, is lacking from large series. In this study, lymph node and tumor position variability were analyzed in detail and correlated to the main carina to evaluate possible margin reduction. Methods and Materials: Small gold fiducial markers (0.35 × 5 mm) were placed in the mediastinal lymph nodes of 51 patients with non-small cell lung cancer during routine diagnostic esophageal or bronchial endoscopic ultrasonography. Four-dimensional (4D) planning computed tomographic (CT) and daily 4D cone beam (CB) CT scans were acquired before and during radical radiation therapy (66 Gy in 24 fractions). Each CBCT was registered in 3-dimensions (bony anatomy) and 4D (tumor, marker, and carina) to the planning CT scan. Subsequently, systematic and random residual misalignments of the time-averaged lymph node and tumor position relative to the bony anatomy and carina were determined. Additionally, tumor and lymph node respiratory amplitude variability was quantified. Finally, required margins were quantified by use of a recipe for dual targets. Results: Relative to the bony anatomy, systematic and random errors ranged from 0.16 to 0.32 cm for the markers and from 0.15 to 0.33 cm for the tumor, but despite similar ranges there was limited correlation (0.17-0.71) owing to differential motion. A large variability in lymph node amplitude between patients was observed, with an average motion of 0.56 cm in the cranial-caudal direction. Margins could be reduced by 10% (left-right), 27% (cranial-caudal), and 10% (anteroposterior) for the lymph nodes and −2%, 15%, and 7% for the tumor if an online carina registration protocol replaced a

  5. Apoptosis Induced in The Brain and Liver of Fetuses And Placenta of Irradiated Pregnant Rats Treated With Antacid Containing Aluminum

    International Nuclear Information System (INIS)

    Ramadan, F.L.; Madkour, N.K.

    2012-01-01

    Aluminum (Al) is widely used in antacid medicine which frequently used by pregnant women. It is of great importance to increase the knowledge about its harmful effects on the fetuses. The present study clarified that administration of antacid containing Al and/or exposure to gamma radiation induced maternal and fetal detrimental impact. Pregnant albino rats were administered antacid containing Al on the gestational days 5th, 7th, 9th, 11th, 13th, 15th and 17th at a dose of 4.5 mg/g and exposed to whole body fractionated gamma radiation (2 Gy) at a dose of 0.5 Gy for 4 times on gestational days 6th, 8th, 10th and 12th of pregnancy. Morphological, biochemical and molecular changes were studied. The investigation was carried out one day prior to parturition (the 20th day of gestation). Antacid containing Al and/or radiation induced growth retardation, intrauterine death, malformations and embryonic resorption. The extent of lipid peroxidase formation as well as glutathione content in the brain and liver tissues of rat fetuses and placenta of pregnant rats were used as sensitive parameters to evaluate tissues damage. Antacid containing Al and/or radiation treatment resulted in decreased total protein content in the maternal placenta tissue. Moreover, the elevation in the lipid peroxidase (malondialdehyde; MDA) was accompanied with decline in the glutathione content (GSH) in the brain and liver tissues of rat fetuses. The activity of a key enzyme of apoptosis namely the caspase-3 was analyzed, which its activation represent a point of no return in apoptosis induction. Apoptosis was confirmed by another important hallmark of programmed cell death such as the DNA fragmentation. Treatment with antacid containing Al and/or gamma irradiation significantly increased caspase-3 activity and DNA fragmentation in maternal placental tissue and fetal brain and liver tissues as compared to control animals. In conclusion, the present investigation showed that the deleterious

  6. Influence of family history, irradiation and anti-cancer drug (mitomycin C) on the occurrence of multiple primary neoplasms in breast carcinoma patients

    International Nuclear Information System (INIS)

    Yoshimoto, Masataka; Sakamoto, Goi; Sugano, Haruo; Kasumi, Fujio; Fukami, Atsuo; Kuno, Keijiro.

    1984-01-01

    The influence of family history, irradiation and anti-cancer drug (Mitomycin C) on the occurrence of multiple primary neoplasms was analysed using the person-year method in 1359 Japanese breast carcinoma patients. There were 111 multiple primary neoplasms, including bilaterl breast cancer, in 109 patients; the incidence rate was 0.0072 per person-year. The incidence rate in patients with a family history of cancer was 1.29 times higher than in those without. In the bilateral breast cancer group there was about a 3 times higher frequency of family history of breast cancer. Irradiation therapy raised the occurrence of multiple primary neoplasms 1.28 fold, and Mitomycin C (40 mg) had no effect on the occurrence of neoplasms during a 10-year observation period. (author)

  7. Effects of prenatal brain irradiation as a result of the Chernobyl accident

    International Nuclear Information System (INIS)

    Nyagu, A.I.; Loganovsky, K.N.; Repin, V.S.; Bomko, M.A.; Pott-Born, R.

    2004-01-01

    A cohort of 154 children born between April 26, 1986 and February 26, 1987 to mothers who had been evacuated from Pripyat to Kiev, and 143 classmates from Kiev were examined. Individual dose reconstruction of the children exposed in utero was carried out considering internal and external exposure. Prenatal equivalent brain doses were 19.2 ± 11.3 mSv and 0.8 ± 0.2 mSv for the exposed and control groups, respectively. Thyroid doses in utero were 760.4 ± 631.8.1 mSv and 44.5 ± 43.3 mSv for the exposed and control groups, correspondingly. There were 20 children from Pripyat town (13.2%) who had been exposed in utero to thyroid doses >1 Sv. The prenatally exposed children show significantly more diseases of the nervous system and mental disorders. Among mothers of the exposed group of children with the neuropsychiatric disorders there are much more depression and somatization, as well as mental disorders

  8. Long-term follow-up of young children with brain tumors after irradiation

    International Nuclear Information System (INIS)

    Syndikus, I.; Tait, D.; Ashley, S.

    1994-01-01

    Young children with brain tumors are at high risk of developing late sequelae after curative radiotherapy. A retrospective study was undertaken to determine the frequency and severity of neurological deficits, endocrine dysfunction, and intellectual disabilities. One hundred and fifty-six children age ≥ 3 years were treated between 1952 and 1986 with radiotherapy. Of the 57 survivors, 47 had surgery, 12 chemotherapy and 24 children received cranio-spinal radiotherapy. Late radiation side effects were assessed with a clinical examination, blood tests and an interview. The median follow-up was 13 years and the actuarial survival at 5 and 10 years was 49% and 44%, respectively. No, or only a mild, handicap was noted in 24 patients, while 21 had moderately severe and 16 severe disabilities. Children with supratentorial tumors had more abnormal neurological findings compared to those with infratentorial malignancies (p<0.001). Eighty percent of children had endocrine abnormalities, which were more marked in children with parasellar tumors (p<0.001). Twenty-one children were mentally retarded. In a multivariate analysis epilepsy emerged as the only significant variable independently associated with poor cognitive function. Long-term morbidity was found to be disabling in 58% of the surviving children. These findings encourage the development of treatment strategies designed to reduce toxity. 34 refs., 3 figs., 5 tabs

  9. Advance care planning in patients with primary malignant brain tumours: a systematic review

    Directory of Open Access Journals (Sweden)

    Krystal Song

    2016-10-01

    Full Text Available Advance care planning (ACP is a process of reflection and communication of a person’s future health care preferences, and has been shown to improve end-of-life care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumours (pmBT. A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus and Web of Science up to July 2016. Manual search of bibliographies of articles and grey literature search were also conducted. Two independent reviewers selected studies, extracted data and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program’s appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included (1 RCT, 17 cohort studies, 1 qualitative study with 4686 participants. All studies scored low to moderate on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision–making. However, the effect of the intervention on quality of life and care at the end-of-life were unclear. There was a low rate of use of ACP discussions at the end-of-life. Advance Directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with lack of

  10. Infratentorial brain tumors in children and adolescents - the significance of MRI in the diagnosis of primary and recurrent tumors

    International Nuclear Information System (INIS)

    Engelbrecht, V.; Kahn, T.; Moedder, U.

    1994-01-01

    MRI is the current method of choice for the diagnosis of infratentorial tumors in children and adolescents. The present article discusses the individual tumor entities on the basis of their magnetic resonance imaging characteristics in the patient pool of 1991/1992. New magnetic resonance imaging procedures are considered for infratentorial vascular anomalies. In addition to its use in the primary diagnosis, the significance of MRI for the detection of recurrences is discussed. Problems arising after prior surgery and irradiation as well as metastasization through CSF pathways are also mentioned. (orig.) [de

  11. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    International Nuclear Information System (INIS)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  12. Design, construction, and in vivo feasibility of a positioning device for irradiation of mice brains using a clinical linear accelerator and intensity modulated radiation therapy.

    Science.gov (United States)

    Rancilio, Nicholas J; Dahl, Shaun; Athanasiadi, Ilektra; Perez-Torres, Carlos J

    2017-12-01

    The goal of this study was to design a positioning device that would allow for selective irradiation of the mouse brain with a clinical linear accelerator. We designed and fabricated an immobilization fixture that incorporates three functions: head stabilizer (through ear bars and tooth bar), gaseous anesthesia delivery and scavenging, and tissue mimic/bolus. Cohorts of five mice were irradiated such that each mouse in the cohort received a unique dose between 1000 and 3000 cGy. DNA damage immunohistochemistry was used to validate an increase in biological effect as a function of radiation dose. Mice were then followed with hematoxylin and eosin (H&E) and anatomical magnetic resonance imaging (MRI). There was evidence of DNA damage throughout the brain proportional to radiation dose. Radiation-induced damage at the prescribed doses, as depicted by H&E, appeared to be constrained to the white matter consistent with radiological observation in human patients. The severity of the damage correlated with the radiation dose as expected. We have designed and manufactured a device that allows us to selectively irradiate the mouse brain with a clinical linear accelerator. However, some off-target effects are possible with large prescription doses.

  13. Dose planning with comparison to in vivo dosimetry for epithermal neutron irradiation of the dog brain

    International Nuclear Information System (INIS)

    Seppaelae, Tiina; Auterinen, Iiro; Aschan, Carita; Seren, Tom; Benczik, Judit; Snellman, Marjatta; Huiskamp, Rene; Ramadan, Usama Abo; Kankaanranta, Leena; Joensuu, Heikki; Savolainen, Sauli

    2002-01-01

    Boron neutron capture therapy (BNCT) is an experimental type of radiotherapy, presently being used to treat glioblastoma and melanoma. To improve patient safety and to determine the radiobiological characteristics of the epithermal neutron beam of Finnish BNCT facility (FiR 1) dose-response studies were carried on the brain of dogs before starting the clinical trials. A dose planning procedure was developed and uncertainties of the epithermal neutron-induced doses were estimated. The accuracy of the method of computing physical doses was assessed by comparing with in vivo dosimetry. Individual radiation dose plans were computed using magnetic resonance images of the heads of 15 Beagle dogs and the computational model of the FiR 1 epithermal neutron beam. For in vivo dosimetry, the thermal neutron fluences were measured using Mn activation foils and the gamma-ray doses with MCP-7s type thermoluminescent detectors placed both on the skin surface of the head and in the oral cavity. The degree of uncertainty of the reference doses at the thermal neutron maximum was estimated using a dose-planning program. The estimated uncertainty (±1 standard deviation) in the total physical reference dose was ±8.9%. The calculated and the measured dose values agreed within the uncertainties at the point of beam entry. The conclusion is that the dose delivery to the tissue can be verified in a practical and reliable fashion by placing an activation dosimeter and a TL detector at the beam entry point on the skin surface with homogeneous tissues below. However, the point doses cannot be calculated correctly in the inhomogeneous area near air cavities of the head model with this type of dose-planning program. This calls for attention in dose planning in human clinical trials in the corresponding areas

  14. The Case for DUF1220 Domain Dosage as a Primary Contributor to Anthropoid Brain Expansion

    Directory of Open Access Journals (Sweden)

    Jonathon eKeeney

    2014-06-01

    Full Text Available Here we present the hypothesis that increasing copy number (dosage of sequences encoding DUF1220 protein domains is a major contributor to the evolutionary increase in brain size, neuron number and cognitive capacity that is associated with the primate order. We further propose that this relationship is restricted to the anthropoid sub-order of primates, with DUF1220 copy number markedly increasing in monkeys, further in apes, and most extremely in humans where the greatest number of copies (~272 haploid copies is found. We show that this increase closely parallels the increase in brain size and neuron number that has occurred among anthropoid primate species. We also provide evidence linking DUF1220 copy number to brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly. While we believe these and other findings presented here strongly suggest increase in DUF1220 copy number is a key contributor to anthropoid brain expansion, the data currently available rely on correlative measures that, though considerable, do not yet provide direct evidence for a causal connection. Nevertheless, we believe the evidence presented is sufficient to provide the basis for a testable model which proposes that DUF1220 protein domain dosage increase is a main contributor to the increase in brain size and neuron number found among the anthropoid primate species and that is at its most extreme in human.

  15. Effects of naltrexone in postnatal rats on the recovery of disturbed brain and lymphatic tissues after X-irradiation or ethylnitrosourea treatment in utero

    International Nuclear Information System (INIS)

    Schmahl, W.G.; Plendl, J.; Reinoehl-Kompa, S.

    1987-01-01

    The role of endogenous opioid systems in preweaning development after intrauterine exposure to X-irradiation or ethylnitrosourea (ENU) was explored in rats using naltrexone, a potent antagonist of beta-endorphin. After daily s.c. injections of 50 mg/kg naltrexone only the prenatally untreated controls had body weights increased by 11% from control level on day 28 (weaning). In the X-irradiated as well as the ENU-treated pups no significant effects of naltrexone on body weight gain were observed. However, brain weight increased in all animals under the influence of naltrexone, irrespective of prenatal treatment or the severity of brain lesions: 9.5% above control values in untreated offspring and 14% after X-irradiation (1 Gy) on gestation day 14. The brain weight of ENU-treated rats (50 mg/kg on gest. day 14) was 13% higher after postnatal naltrexone application than that of their postnatally untreated counterparts. ENU (80 mg/kg) effects on the brain when given on gestation day 18 were ameliorated to 9.2% by naltrexone in the weaning period. Naltrexone significantly increased the thymus weight in controls. Prenatally treated animals also showed an increased thymus weight at weaning, presumably due to compensatory growth. In these cases naltrexone revealed a suppressive effect on the thymus, whereas spleen weight was apparently not influenced by naltrexone treatment. These results provide compelling evidence that endogenous opioid systems play a crucial role not only in normal development, but also in reparative growth events of the brain after prenatal injuries. The thymus, predominantly containing T-lymphocytes, seems to represent another sensitive system which is regulated under the influence of opioids

  16. Effects of naltrexone in postnatal rats on the recovery of disturbed brain and lymphatic tissues after X-irradiation or ethylnitrosourea treatment in utero

    Energy Technology Data Exchange (ETDEWEB)

    Schmahl, W.G.; Plendl, J.; Reinoehl-Kompa, S.

    1987-01-01

    The role of endogenous opioid systems in preweaning development after intrauterine exposure to X-irradiation or ethylnitrosourea (ENU) was explored in rats using naltrexone, a potent antagonist of beta-endorphin. After daily s.c. injections of 50 mg/kg naltrexone only the prenatally untreated controls had body weights increased by 11% from control level on day 28 (weaning). In the X-irradiated as well as the ENU-treated pups no significant effects of naltrexone on body weight gain were observed. However, brain weight increased in all animals under the influence of naltrexone, irrespective of prenatal treatment or the severity of brain lesions: 9.5% above control values in untreated offspring and 14% after X-irradiation (1 Gy) on gestation day 14. The brain weight of ENU-treated rats (50 mg/kg on gest. day 14) was 13% higher after postnatal naltrexone application than that of their postnatally untreated counterparts. ENU (80 mg/kg) effects on the brain when given on gestation day 18 were ameliorated to 9.2% by naltrexone in the weaning period. Naltrexone significantly increased the thymus weight in controls. Prenatally treated animals also showed an increased thymus weight at weaning, presumably due to compensatory growth. In these cases naltrexone revealed a suppressive effect on the thymus, whereas spleen weight was apparently not influenced by naltrexone treatment. These results provide compelling evidence that endogenous opioid systems play a crucial role not only in normal development, but also in reparative growth events of the brain after prenatal injuries. The thymus, predominantly containing T-lymphocytes, seems to represent another sensitive system which is regulated under the influence of opioids.

  17. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex

    Directory of Open Access Journals (Sweden)

    Gregory D. Scott

    2014-03-01

    Full Text Available Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl’s gyrus. In addition to reorganized auditory cortex (cross-modal plasticity, a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case, as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral versus perifoveal visual stimulation (11-15° vs. 2°-7° in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl’s gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl’s gyrus indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral versus perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory and multisensory and/or supramodal regions, such as posterior parietal cortex, frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal and multisensory regions, to altered visual processing in

  18. Isolation of primary microglia from the human post-mortem brain: effects of ante- and post-mortem variables.

    Science.gov (United States)

    Mizee, Mark R; Miedema, Suzanne S M; van der Poel, Marlijn; Adelia; Schuurman, Karianne G; van Strien, Miriam E; Melief, Jeroen; Smolders, Joost; Hendrickx, Debbie A; Heutinck, Kirstin M; Hamann, Jörg; Huitinga, Inge

    2017-02-17

    Microglia are key players in the central nervous system in health and disease. Much pioneering research on microglia function has been carried out in vivo with the use of genetic animal models. However, to fully understand the role of microglia in neurological and psychiatric disorders, it is crucial to study primary human microglia from brain donors. We have developed a rapid procedure for the isolation of pure human microglia from autopsy tissue using density gradient centrifugation followed by CD11b-specific cell selection. The protocol can be completed in 4 h, with an average yield of 450,000 and 145,000 viable cells per gram of white and grey matter tissue respectively. This method allows for the immediate phenotyping of microglia in relation to brain donor clinical variables, and shows the microglia population to be distinguishable from autologous choroid plexus macrophages. This protocol has been applied to samples from over 100 brain donors from the Netherlands Brain Bank, providing a robust dataset to analyze the effects of age, post-mortem delay, brain acidity, and neurological diagnosis on microglia yield and phenotype. Our data show that cerebrospinal fluid pH is positively correlated to microglial cell yield, but donor age and post-mortem delay do not negatively affect viable microglia yield. Analysis of CD45 and CD11b expression showed that changes in microglia phenotype can be attributed to a neurological diagnosis, and are not influenced by variation in ante- and post-mortem parameters. Cryogenic storage of primary microglia was shown to be possible, albeit with variable levels of recovery and effects on phenotype and RNA quality. Microglial gene expression substantially changed due to culture, including the loss of the microglia-specific markers, showing the importance of immediate microglia phenotyping. We conclude that primary microglia can be isolated effectively and rapidly from human post-mortem brain tissue, allowing for the study of the

  19. Whole-brain Irradiation Field Design: A Comparison of Parotid Dose

    International Nuclear Information System (INIS)

    Wu, Cheng-Chia; Wuu, Yen-Ruh; Jani, Ashish; Saraf, Anurag; Tai, Cheng-Hung; Lapa, Matthew E.; Andrew, Jacquelyn I.S.; Tiwari, Akhil; Saadatmand, Heva J.; Isaacson, Steven R.; Cheng, Simon K.; Wang, Tony J.C.

    2017-01-01

    Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: mean <26 Gy, volume constraint at 20 Gy (V20) < 20 cc, and dose at 50% of the parotid volume (D50) < 30 Gy. Biologically effective dose (BED) conversions with an α/β of 3 for normal parotid were performed to compare with 10-fraction and 15-fraction treatments of WBRT. The constraints are as follows: mean < BED 32.83 Gy, V15.76 (for 10-fraction WBRT) or V17.35 (for 15-fraction WBRT) < 20 cc, and D50 < BED 39.09 Gy. Nineteen patients treated to C1 and 26 patients treated to C2 were analyzed. Comparing WBRT to C1 with WBRT to C2, the mean left, right, and both parotids' doses were lower when treated to C1. Converting mean dose to BED 3 , the parotid doses were lower than BED 3 constraint of 32.83 Gy: left (30.12 Gy), right (30.69 Gy), and both parotids (30.32 Gy). V20 to combined parotids was lower in patients treated to C1. When accounting for fractionation of WBRT received, the mean corrected V20 volume was less than 20 cc when treating to C1. D50 for C1 was lower than C2 for the left parotid, right parotid, and both parotids. BED 3 conversion for the mean D50 of the left, right, and both parotids was less than 39.09 Gy. In conclusion, WBRT to C1 limits parotid dose, and parotid dose constraints are achievable compared with inferior border at C2. A possible mean parotid dose constraint with BED

  20. Whole-brain Irradiation Field Design: A Comparison of Parotid Dose

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cheng-Chia; Wuu, Yen-Ruh; Jani, Ashish; Saraf, Anurag; Tai, Cheng-Hung; Lapa, Matthew E.; Andrew, Jacquelyn I.S.; Tiwari, Akhil; Saadatmand, Heva J. [Department of Radiation Oncology, Columbia University Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032 (United States); Isaacson, Steven R. [Department of Radiation Oncology, Columbia University Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032 (United States); Department of Neurological Surgery, Columbia University Medical Center, New York, NY 10032 (United States); Cheng, Simon K., E-mail: sc3225@cumc.columbia.edu [Department of Radiation Oncology, Columbia University Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032 (United States); Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032 (United States); Wang, Tony J.C., E-mail: tjw2117@cumc.columbia.edu [Department of Radiation Oncology, Columbia University Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032 (United States); Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032 (United States)

    2017-07-01

    Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: mean <26 Gy, volume constraint at 20 Gy (V20) < 20 cc, and dose at 50% of the parotid volume (D50) < 30 Gy. Biologically effective dose (BED) conversions with an α/β of 3 for normal parotid were performed to compare with 10-fraction and 15-fraction treatments of WBRT. The constraints are as follows: mean < BED 32.83 Gy, V15.76 (for 10-fraction WBRT) or V17.35 (for 15-fraction WBRT) < 20 cc, and D50 < BED 39.09 Gy. Nineteen patients treated to C1 and 26 patients treated to C2 were analyzed. Comparing WBRT to C1 with WBRT to C2, the mean left, right, and both parotids' doses were lower when treated to C1. Converting mean dose to BED{sub 3}, the parotid doses were lower than BED{sub 3} constraint of 32.83 Gy: left (30.12 Gy), right (30.69 Gy), and both parotids (30.32 Gy). V20 to combined parotids was lower in patients treated to C1. When accounting for fractionation of WBRT received, the mean corrected V20 volume was less than 20 cc when treating to C1. D50 for C1 was lower than C2 for the left parotid, right parotid, and both parotids. BED{sub 3} conversion for the mean D50 of the left, right, and both parotids was less than 39.09 Gy. In conclusion, WBRT to C1 limits parotid dose, and parotid dose constraints are achievable compared with inferior border at C2. A possible mean parotid dose

  1. Mice knocked out for the primary brain calcification associated gene Slc20a2 show unimpaired pre-natal survival but retarded growth and nodules in the brain that grow and calcify over time

    DEFF Research Database (Denmark)

    Jensen, Nina; Schrøder, Henrik Daa; Kildall Hejbøl, Eva

    2018-01-01

    Brain calcification of especially the basal ganglia characterises primary familial brain calcification (PFBC). PFBC is a rare neurodegenerative disorder with neuropsychiatric and motor symptoms, and only symptomatic treatment is available. Four PFBC-associated genes are known; about 40% of patien...

  2. Whole-brain radiotherapy with 20 Gy in 5 fractions for brain metastases in patients with cancer of unknown primary (CUP)

    International Nuclear Information System (INIS)

    Rades, D.; Bohlen, G.; Dunst, J.; Lohynska, R.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.

    2007-01-01

    Background: Whole brain radiotherapy (WBRT) is the most common treatment for brain metastases. Survival of patients with cancer of unknown primary (CUP) presenting with brain metastases is extremely poor. A radiation program with a short overall treatment time (short-course RT) would be preferable to longer programs if it provides similar outcomes. This study compares short-course RT with 20 Gy in 5 fractions (5 x 4 Gy) given over 5 days to longer programs in CUP patients. Patients and Methods: Data regarding 101 CUP patients who received either short course WBRT (n = 34) with 5 x 4 Gy or long-course WBRT (n = 67) with 10 x 3 Gy given over 2 weeks or 20 x 2 Gy given over 4 weeks for brain metastases were analyzed retrospectively. Six additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, RPA-(Recursive Partitioning Analysis-)class. Results: On univariate analysis, the radiation program was not associated with survival (p = 0.88) nor intracerebral control (p = 0.36). Improved survival was associated with KPS ≥ 70 (p < 0.001), absence of extracranial metastases (p < 0.001), and RPA-class 1 (p < 0.001). On multivariate analyses, KPS (risk ratio [RR]: 4.55; p < 0.001), extracranial metastases (RR: 1.70; p = 0.018), and RPA-class (RR: 2.86; p < 0.001) maintained significance. On univariate analysis, KPS (p < 0.001) and RPA-class (p < 0.001) were significantly associated with intracerebral control. On multivariate analyses, KPS (RR: 2.72; p < 0.001) and RPA-class (RR: 2.09; p < 0.001) remained significant. Conclusion: Short-course WBRT with 5 x 4 Gy provided similar intracerebral control and survival as longer programs for the treatment of brain metastases in CUP patients. 5 x 4 Gy appears preferable because it is more convenient for patients. (orig.)

  3. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  4. Assessment of cognitive functions after prophylactic and therapeutic whole brain irradiation using neuropsychological testing; Erfassung kognitiver Funktionen nach prophylaktischer und therapeutischer Ganzhirnbestrahlung mittels neuropsychologischer Testverfahren

    Energy Technology Data Exchange (ETDEWEB)

    Penitzka, S.; Wannenmacher, M. [Universitaetsklinikum Heidelberg (Germany). Abt. Klinische Radiologie; Steinvorth, S. [Universitaetsklinikum Heidelberg (Germany). Abt. Klinische Radiologie; MIT, Cambridge, MT (United States). Dept. of Brain and Cognitive Sciences; Sehlleier, S. [Universitaetsklinikum Heidelberg (Germany). Abt. Klinische Radiologie; Universitaetsklinikum Wuerzburg (Germany). Abt. Strahlentherapie; Fuss, M. [Universitaetsklinikum Heidelberg (Germany). Abt. Klinische Radiologie; Texas Univ., San Antonio, TX (United States). Health Science Center; Wenz, F. [Universitaetsklinikum Heidelberg (Germany). Abt. Klinische Radiologie; Universitaetsklinikum Mannheim (Germany). Sektion Radioonkologie

    2002-05-01

    Purpose: Aim of this study was the assessment of neuropsychological changes after whole brain irradiation. Patients and Method: 64 patients were tested before, and 29 after whole brain irradiation, including 28 patients with small cell lung cancer (SCLC) before prophylactic cranial irradiation (PCI) and 36 patients with cerebral metastases before therapeutic cranial irradiation (TCI), as well as 14 patients after PCI and 15 after TCI (Table 1). Intelligence, attention and memory were assessed applying a 90-minute test battery of standardized, neuropsychological tests (Table 3). Results: Patients with SCLC showed test results significantly below average before PCI (n=28, mean IQ=83, SD=17). Neither after PCI, nor after TCI the tested neuropsychological functions decreased significantly (Tables 4, 5). A comparison between SCLC-patients with and without cerebral metastases before whole brain irradiation showed better test-results in patients with cerebral metastases and fewer cycles of preceding chemotherapy (Table 7). Conclusion: Neuropsychological capacity in patients with SCLC was impaired even before PCI. Possible reason is the preceding chemotherapy. Whole brain irradiation did not induce a significant decline of cognitive functions in patients with PCI or TCI. A decline in a longer follow-up nevertheless seems possible. (orig.) [German] Zielsetzung: Ziel der Studie war die Erfassung moeglicher Veraenderungen der neuropsychologischen Leistungsfaehigkeit nach Ganzhirnbestrahlung. Patienten und Methode: Untersucht wurden 64 Patienten vor und 29 Patienten nach Ganzhirnbestrahlung. Es handelte sich um 28 Patienten mit kleinzelligem Bronchialkarzinom (SCLC) vor prophylaktischer Ganzhirnbestrahlung (PCI) und um 36 Patienten mit Hirnmetastasen vor therapeutischer Ganzhirnbestrahlung (TCI). Es wurden 14 Patienten nach PCI und 15 Patienten nach TCI getestet. Zur Anwendung kam eine 90-minuetige Testbatterie standardisierter, neuropsychologischer Testverfahren zur Messung

  5. Craniofacial and brain abnormalities in Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Kornreich, L; Horev, G; Schwarz, M; Karmazyn, B; Laron, Z

    2002-04-01

    To investigate abnormalities in the craniofacial structures and in the brain in patients with Laron syndrome. Eleven patients with classical Laron syndrome, nine untreated adults aged 36-68 years and two children aged 4 and 9 years (the latter treated by IGF-I), were studied. Magnetic resonance images of the brain were obtained in all the patients. One patient also underwent computed tomography. The maximal diameter of the maxillary and frontal sinuses was measured and compared with reference values, the size of the sphenoid sinus was evaluated in relation to the sella, and the mastoids were evaluated qualitatively (small or normal). The brain was evaluated for congenital anomalies and parenchymal lesions. In the adult untreated patients, the paranasal sinuses and mastoids were small; in six patients, the bone marrow in the base of the skull was not mature. The diploe of the calvaria was thin. On computed tomography in one adult patient, the sutures were still open. A minimal or mild degree of diffuse brain parenchymal loss was seen in ten patients. One patient demonstrated a lacunar infarct and another periventricular high signals on T2-weighted images. Two patients had cerebellar atrophy. The present study has demonstrated the important role IGF-I plays in the development of the brain and bony structures of the cranium.

  6. Clinical Outcome in Gamma Knife Radiosurgery for Metastatic Brain Tumors from the Primary Breast Cancer : Prognostic Factors in Local Treatment Failure and Survival

    OpenAIRE

    Choi, Seung Won; Kwon, Do Hoon; Kim, Chang Jin

    2013-01-01

    Objective Brain metastases in primary breast cancer patients are considerable sources of morbidity and mortality. Gamma knife radiosurgery (GKRS) has gained popularity as an up-front therapy in treating such metastases over traditional radiation therapy due to better neurocognitive function preservation. The aim of this study was to clarify the prognostic factors for local tumor control and survival in radiosurgery for brain metastases from primary breast cancer. Methods From March 2001 to Ma...

  7. Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli

    Science.gov (United States)

    Field, Brent A.; Buck, Cara L.; McClure, Samuel M.; Nystrom, Leigh E.; Kahneman, Daniel; Cohen, Jonathan D.

    2015-01-01

    Studies of subjective well-being have conventionally relied upon self-report, which directs subjects’ attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure) by using functional magnetic resonance imaging (fMRI) to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly) the activity of brain mechanisms thought to represent hedonic value. PMID:26158468

  8. Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli.

    Directory of Open Access Journals (Sweden)

    Brent A Field

    Full Text Available Studies of subjective well-being have conventionally relied upon self-report, which directs subjects' attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure by using functional magnetic resonance imaging (fMRI to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly the activity of brain mechanisms thought to represent hedonic value.

  9. Association of Ki-67, p53, and bcl-2 expression of the primary non-small-cell lung cancer lesion with brain metastatic lesion

    International Nuclear Information System (INIS)

    Bubb, Robbin S.; Komaki, Ritsuko; Hachiya, Tsutomu; Milas, Ivan; Ro, Jae Y.; Langford, Lauren; Sawaya, Raymond; Putnam, Joe B.; Allen, Pamela; Cox, James D.; McDonnell, Timothy J.; Brock, William; Hong, Waun K.; Roth, Jack A.; Milas, Luka

    2002-01-01

    Purpose: The study was conducted to determine whether immunohistochemical analysis of Ki-67, p53, and bcl-2 in patients with non-small-cell lung cancer is associated with a higher rate of brain metastases and whether the intrapatient expression of these biomarkers (in the primary tumors vs. brain lesions) is similar. Methods and Materials: At the M. D. Anderson Cancer Center, tumors from 29 case patients with primary lung tumor and brain metastasis and 29 control patients with primary lung tumor but no brain metastasis were resected and examined for immunohistochemical expression. Ki-67, p53, and bcl-2 were analyzed in resected primary lung, lymph node, and metastatic brain tumors. Each control patient was matched by age, gender, and histology to a patient with brain metastasis. Results: No significant differences in patient survival characteristics were detected between the case group and control group. Also, difference in patient outcome between the two groups was not generally predicted by biomarker analysis. However, when the groups were combined, the biomarker analysis was predictive for certain patient outcome end points. Using median values as cutoff points between low and high expression of biomarkers, it was observed that high expression of Ki-67 (>40%) in lung primaries was associated with poorer disease-free survival (p=0.04), whereas low expression of p53 in lung primaries was associated with poorer overall survival (p=0.04), and these patients had a higher rate of nonbrain distant metastases (p=0.02). The patients with brain metastases were particularly prone to developing nonbrain distant metastases if the percentage of p53-positive cells in brain metastases was low (p=0.01). There was a positive correlation in the expression of Ki-67 (p=0.02) (r 2 =0.1608), as well as p53 (p 2 =0.7380), between lung primaries and brain metastases. Compared to Ki-67 and p53, bcl-2 was the least predictive. Conclusion: Differences in biomarker expression between the

  10. Reversible brain atrophy and cognitive impairment in an adolescent Japanese patient with primary adrenal Cushing's syndrome.

    Science.gov (United States)

    Ohara, Nobumasa; Suzuki, Hiroshi; Suzuki, Akiko; Kaneko, Masanori; Ishizawa, Masahiro; Furukawa, Kazuo; Abe, Takahiro; Matsubayashi, Yasuhiro; Yamada, Takaho; Hanyu, Osamu; Shimohata, Takayoshi; Sone, Hirohito

    2014-01-01

    Endogenous Cushing's syndrome is an endocrine disease resulting from chronic exposure to excessive glucocorticoids produced in the adrenal cortex. Although the ultimate outcome remains uncertain, functional and morphological brain changes are not uncommon in patients with this syndrome, and generally persist even after resolution of hypercortisolemia. We present an adolescent patient with Cushing's syndrome who exhibited cognitive impairment with brain atrophy. A 19-year-old Japanese male visited a local hospital following 5 days of behavioral abnormalities, such as money wasting or nighttime wandering. He had hypertension and a 1-year history of a rounded face. Magnetic resonance imaging (MRI) revealed apparently diffuse brain atrophy. Because of high random plasma cortisol levels (28.7 μg/dL) at 10 AM, he was referred to our hospital in August 2011. Endocrinological testing showed adrenocorticotropic hormone-independent hypercortisolemia, and abdominal computed tomography demonstrated a 2.7 cm tumor in the left adrenal gland. The patient underwent left adrenalectomy in September 2011, and the diagnosis of cortisol-secreting adenoma was confirmed histologically. His hypertension and Cushingoid features regressed. Behavioral abnormalities were no longer observed, and he was classified as cured of his cognitive disturbance caused by Cushing's syndrome in February 2012. MRI performed 8 months after surgery revealed reversal of brain atrophy, and his subsequent course has been uneventful. In summary, the young age at onset and the short duration of Cushing's syndrome probably contributed to the rapid recovery of both cognitive dysfunction and brain atrophy in our patient. Cushing's syndrome should be considered as a possible etiological factor in patients with cognitive impairment and brain atrophy that is atypical for their age.

  11. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  12. Prolonged survival after resection and radiotherapy for solitary brain metastases from non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Chee, R. J.; Bydder, S.; Cameron, F.

    2007-01-01

    Selected patients with brain metastases from non-small-cell lung cancer benefit from aggressive treatment. This report describes three patients who developed solitary brain metastases after previous resection of primary adenocarcinoma of the lung. Each underwent surgical resection of their brain metastasis followed by cranial irradiation and remain disease free 10 or more years later. Two patients developed cognitive impairment approximately 8 years after treatment of their brain metastasis, which was felt to be due to their previous brain irradiation. Here we discuss the treatment of solitary brain metastasis, particularly the value of combined method approaches in selected patients and dose-volume considerations

  13. Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: Mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05)

    International Nuclear Information System (INIS)

    Roos, Daniel E.; Wirth, Andrew; Burmeister, Bryan H.; Spry, Nigel A.; Drummond, Katharine J.; Beresford, Jennifer A.; McClure, Beverley E.

    2006-01-01

    We evaluated the effect of adjuvant whole brain irradiation (WBI) after surgery or radiosurgery for solitary brain metastases in a Phase III multicentre trial with randomization to 30-36 Gy WBI or observation. The study was closed early due to slow accrual after 19 patients (WBI 10, observation 9). There was no difference in CNS failure-free survival or overall survival between the arms. There was a trend to reduced CNS relapse with WBI (30% versus 78%, P = 0.12). Limited analysis of quality of life and neurocognitive function data revealed no evidence of difference between the arms. Our results are not inconsistent with two larger randomized trials and support the use of upfront WBI to decrease brain recurrence in this setting

  14. Long-Term Memory Shapes the Primary Olfactory Center of an Insect Brain

    Science.gov (United States)

    Hourcade, Benoit; Perisse, Emmanuel; Devaud, Jean-Marc; Sandoz, Jean-Christophe

    2009-01-01

    The storage of stable memories is generally considered to rely on changes in the functional properties and/or the synaptic connectivity of neural networks. However, these changes are not easily tractable given the complexity of the learning procedures and brain circuits studied. Such a search can be narrowed down by studying memories of specific…

  15. Vitamins and nutrients as primary treatments in experimental brain injury: Clinical implications for nutraceutical therapies.

    Science.gov (United States)

    Vonder Haar, Cole; Peterson, Todd C; Martens, Kris M; Hoane, Michael R

    2016-06-01

    With the numerous failures of pharmaceuticals to treat traumatic brain injury in humans, more researchers have become interested in combination therapies. This is largely due to the multimodal nature of damage from injury, which causes excitotoxicity, oxidative stress, edema, neuroinflammation and cell death. Polydrug treatments have the potential to target multiple aspects of the secondary injury cascade, while many previous therapies focused on one particular aspect. Of specific note are vitamins, minerals and nutrients that can be utilized to supplement other therapies. Many of these have low toxicity, are already FDA approved and have minimal interactions with other drugs, making them attractive targets for therapeutics. Over the past 20 years, interest in supplementation and supraphysiologic dosing of nutrients for brain injury has increased and indeed many vitamins and nutrients now have a considerable body of the literature backing their use. Here, we review several of the prominent therapies in the category of nutraceutical treatment for brain injury in experimental models, including vitamins (B2, B3, B6, B9, C, D, E), herbs and traditional medicines (ginseng, Gingko biloba), flavonoids, and other nutrients (magnesium, zinc, carnitine, omega-3 fatty acids). While there is still much work to be done, several of these have strong potential for clinical therapies, particularly with regard to polydrug regimens. This article is part of a Special Issue entitled SI:Brain injury and recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. An Increasing of Primary School Teachers' Competency in Brain-Based Learning

    Science.gov (United States)

    Waree, Chaiwat

    2017-01-01

    The purpose of the study was to develop a powerful and empowering guide (CBT) of elementary school teachers, to compare the ability of elementary school teachers. Management learning uses brain as a base. The experimental group with a control group the experimental group used in this research was a teacher at the grade level. 4-6 in province By…

  17. Expression of CD44 splice variants in human primary brain tumors

    NARCIS (Netherlands)

    Kaaijk, P.; Troost, D.; Morsink, F.; Keehnen, R. M.; Leenstra, S.; Bosch, D. A.; Pals, S. T.

    1995-01-01

    Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastatic potential in a number of different animal and human cancers. Although differential expression of CD44 standard epitopes (CD44s) in human brain tumors has been reported, the expression of

  18. Administration of the peroxisomal proliferator-activated receptor γ agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment

    International Nuclear Information System (INIS)

    Zhao Weiling; Payne, Valerie; Tommasi, Ellen; Diz, Debra I.; Hsu, F.-C.; Robbins, Mike E.

    2007-01-01

    Purpose: We hypothesized that administration of the anti-inflammatory peroxisomal proliferator-activated receptor γ (PPARγ) agonist pioglitazone (Pio) to adult male rats would inhibit radiation-induced cognitive impairment. Methods and Materials: Young adult male F344 rats received one of the following: (1) fractionated whole brain irradiation (WBI); 40 or 45 Gy γ-rays in 4 or 4.5 weeks, respectively, two fractions per week and normal diet; (2) sham-irradiation and normal diet; (3) WBI plus Pio (120 ppm) before, during, and for 4 or 54 weeks postirradiation; (4) sham-irradiation plus Pio; or (5) WBI plus Pio starting 24h after completion of WBI. Results: Administration of Pio before, during, and for 4 or 54 weeks after WBI prevented Radiation-induced cognitive impairment. Administration of Pio for 54 weeks starting after completion of fractionated WBI substantially but not significantly reduced Radiation-induced cognitive impairment. Conclusions: These findings offer the promise of improving the quality of life and increasing the therapeutic window for brain tumor patients

  19. Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small-cell lung cancer: A Cochrane Review

    International Nuclear Information System (INIS)

    Lester, Jason Francis; MacBeth, Fergus R.; Coles, Bernadette

    2005-01-01

    Purpose: To investigate whether prophylactic cranial irradiation (PCI) has a role in the management of patients with non-small-cell lung cancer (NSCLC) treated with curative intent. Methods and Materials: A search strategy was designed to identify randomized controlled trials (RCTs) comparing PCI with no PCI in NSCLC patients treated with curative intent. The electronic databases MEDLINE, EMBASE, LILACS, and Cancerlit were searched, along with relevant journals, books, and review articles to identify potentially eligible trials. Four RCTs were identified and reviewed. A total of 951 patients were randomized in these RCTs, of whom 833 were evaluable and reported. Forty-two patients with small-cell lung cancer were excluded, leaving 791 patients in total. Because of the small patient numbers and trial heterogeneity, no meta-analysis was attempted. Results: Prophylactic cranial irradiation did significantly reduce the incidence of brain metastases in three trials. No trial reported a survival advantage with PCI over observation. Toxicity data were poorly collected and no quality of life assessments were carried out in any trial. Conclusion: Prophylactic cranial irradiation may reduce the incidence of brain metastases, but there is no evidence of a survival benefit. It was not possible to evaluate whether any radiotherapy regimen is superior, and the effect of PCI on quality of life is not known. There is insufficient evidence to support the use of PCI in clinical practice. Where possible, patients should be offered entry into a clinical trial

  20. Effects of chronic postnatal opioid receptor blockade by naltrexone upon proliferation capacity in the prenatally x-irradiated brain of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Schmahl, W.; Miaskowski, U. (Department of Pathology, Gesellschaft fuer Strahlen-und Umweltforschung mbh Muechen, Neuherberg (West Germany))

    1991-01-01

    We recently reported that in rats prenatally x-irradiated on gestation day 14 with 1 Gy, postnatal chronic application of the opioid antagonist naltrexone (Nx) led to a remarkable growth spurt o