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Sample records for delayed radiation necrosis

  1. A histological and flow cytometric study of dog brain endothelial cell injuries in delayed radiation necrosis

    SciTech Connect

    Yamaguchi, N.; Yamashima, T.; Yamashita, J. )

    1991-04-01

    The pathogenesis of delayed cerebral radiation necrosis was studied histologically and biochemically in 25 dogs with special attention to vascular endothelial cell injuries. The dogs were sacrificed 3 to 30 months after irradiation with a single dose of 15 Gy to the head. Brain specimens were appropriately fixed for light and electron microscopic studies, and capillary endothelial cells were isolated for flow cytometric study. The endothelial cells were stained with acridine orange, then the cell ratios in the reproductive phase (S + G2 + M) were investigated with flow cytometry. Thereafter, Feulgen hydrolysis and computer analysis of the hydrolysis curves were performed to examine the qualitative changes in deoxyribonucleic acid (DNA) of endothelial cells after irradiation. Under light microscopy, spongy degeneration with small cell infiltration was observed, especially in the frontal white matter, at 6 months after irradiation. At 9 months, necrotic foci appeared and developed until 15 months after irradiation. Blood vessels around the necrotic area showed luminal narrowing with endothelial hyperplasia and proliferation. At 30 months, no fresh necrotic lesions were observed. Under electron microscopy, endothelial cells of capillaries and small vessels around the necrotic area showed an increase of pinocytosis, and in the nuclei there was an increase of infoldings and euchromatin. The cell ratios in the reproductive phase were 14.5% to 23.3% (maximum at 9 months) in the irradiated group compared to 6.4% in the control group. The rate constant of apurinic acid production, a parameter correlating with DNA transcriptional activity, was minimum at 3 months and maximum at 9 months after irradiation. The data suggest that impairment of the microcirculation plays an important role in the pathogenesis of delayed radiation necrosis.

  2. Hyperbaric oxygen therapy and delayed radiation injuries (soft tissue and bony necrosis): 2012 update.

    PubMed

    Feldmeier, John J

    2012-01-01

    Informal surveys at CME meetings have shown that approximately one-third of patients in the United States receive hyperbaric oxygen (HBO2) for delayed radiation injury. More than 600,000 patients receive radiation for malignancy in our country annually, and about one-half will be long-term survivors. Serious radiation complications occur in 5-10% of survivors. A large population of patients is therefore at risk for radiation injury. HBO2 has been applied to treat patients with radiation injury since the mid-1970s. Published results are consistently positive, but the level of evidence for individual publications is usually not high level, consisting mostly of case series and case reports. Only a rare randomized controlled trial has been accomplished. Radiation injury is one of the UHMS "approved" indications, and third-party payors will usually reimburse for this application. This updated review summarizes the publications available reporting results in treating radiation-injured patients. Mechanisms of HBO2 in radiation injury are discussed briefly. Outcome is reported on a mostly anatomic basis though due to the nature of the injury a positive outcome at one anatomic site is supportive of HBO2 at other sites. The potential benefit of prophylactic HBO2 before frank damage is also discussed in high-risk patients. The concerns of HBO2 enhancing growth of or precipitating recurrence of malignancy is discussed and largely refuted. PMID:23342770

  3. Delayed cerebral radiation necrosis after neutron beam radiation of a parotid adenocarcinoma: a case report and review of the literature.

    PubMed

    Hong, Christopher S; Gokozan, Hamza N; Otero, José J; Guiou, Michael; Elder, J Bradley

    2014-01-01

    Cerebral radiation necrosis (CRN) is a well described possible complication of radiation for treatment of intracranial pathology. However, CRN as sequelae of radiation to extracranial sites is rare. Neutron beam radiation is a highly potent form of radiotherapy that may be used to treat malignant tumors of the salivary glands. This report describes a patient who underwent neutron beam radiation for a parotid adenocarcinoma and who developed biopsy-confirmed temporal lobe radiation necrosis thirty months later. This represents the longest time interval described to date, from initial neutron radiation for extracranial pathology to development of CRN. Two other detailed case studies exist in the literature and are described in this report. These reports as well as our patient's case are reviewed, and additional recommendations are made to minimize the development of CRN after extracranial neutron beam radiation. Physicians should include the possible diagnosis of CRN in any patient with new neurologic signs or symptoms and a history of head and neck radiation that included planned fields extending to the base of the skull. Counseling of patients prior to neutron beam radiation should include potential neurologic complications associated with CRN and risks of treatment for CRN including neurosurgical intervention. PMID:25349750

  4. Cerebral radiation necrosis in pediatric patients.

    PubMed

    Plimpton, S Reed; Stence, Nicholas; Hemenway, Molly; Hankinson, Todd C; Foreman, Nicholas; Liu, Arthur K

    2015-02-01

    Radiation necrosis is a well-described toxicity following radiation therapy in the brain. There is little data regarding the incidence of radiation necrosis in pediatric patients. We retrospectively reviewed our experience with 101 children with solid brain tumors. Radiation necrosis was diagnosed by examination of magnetic resonance imaging. Median follow-up for all patients was 13 months (range 3-51). Radiation necrosis occurred in 5% (5/101) of cases with a median time to onset of 1.2 months. In three of these children, the child was symptomatic, requiring management with steroids and bevacizumab. Radiation necrosis did not correlate with the administration of chemotherapy, age at treatment, or planning treatment volume. Our experience with pediatric patients treated with radiotherapy for solid brain tumor suggests that children may have an increased likelihood to develop radiation necrosis compared to adults. PMID:23647507

  5. Ketoconazole attenuates radiation-induction of tumor necrosis factor

    SciTech Connect

    Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R.

    1994-07-01

    Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

  6. Pathophysiology, Diagnosis, and Treatment of Radiation Necrosis in the Brain

    PubMed Central

    MIYATAKE, Shin-Ichi; NONOGUCHI, Noasuke; FURUSE, Motomasa; YORITSUNE, Erina; MIYATA, Tomo; KAWABATA, Shinji; KUROIWA, Toshihiko

    2015-01-01

    New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient’s quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain. PMID:25744350

  7. Response-driven Imaging Biomarkers for Predicting Radiation Necrosis of the Brain

    PubMed Central

    Nazem-Zadeh, Mohammad-Reza; Chapman, Christopher H.; Chenevert, Thomas; Lawrence, Theodore S.; Ten Haken, Randall K.; Tsien, Christina I.; Cao, Yue

    2014-01-01

    Purpose Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy. Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Methods and Materials Twenty-nine patients with glioblastoma received six weeks of intensity modulated radiation therapy (RT) and concurrent temozolamide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Results Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p=0.05 and p=0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Conclusions Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid in predicting delayed radiation necrosis, which could provide guidance in dose-escalation trials. PMID:24778364

  8. Response-driven imaging biomarkers for predicting radiation necrosis of the brain

    NASA Astrophysics Data System (ADS)

    Nazem Zadeh, Mohammad-Reza; Chapman, Christopher H.; Chenevert, Thomas; Lawrence, Theodore S.; Ten Haken, Randall K.; Tsien, Christina I.; Cao, Yue

    2014-05-01

    Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy (RT). Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Twenty-nine patients with glioblastoma received six weeks of intensity modulated RT and concurrent temozolomide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p = 0.05 and p = 0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid the prediction of delayed radiation necrosis, which could provide guidance in dose-escalation trials.

  9. Challenges With the Diagnosis and Treatment of Cerebral Radiation Necrosis

    SciTech Connect

    Chao, Samuel T.; Ahluwalia, Manmeet S.; Barnett, Gene H.; Stevens, Glen H.J.; Murphy, Erin S.; Stockham, Abigail L.; Shiue, Kevin; Suh, John H.

    2013-11-01

    The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis.

  10. Delayed Radiation-Induced Vasculitic Leukoencephalopathy

    SciTech Connect

    Rauch, Philipp J.; Park, Henry S.; Knisely, Jonathan P.S.; Chiang, Veronica L.; Vortmeyer, Alexander O.

    2012-05-01

    Purpose: Recently, single-fraction, high-dosed focused radiation therapy such as that administered by Gamma Knife radiosurgery has been used increasingly for the treatment of metastatic brain cancer. Radiation therapy to the brain can cause delayed leukoencephalopathy, which carries its own significant morbidity and mortality. While radiosurgery-induced leukoencephalopathy is known to be clinically different from that following fractionated radiation, pathological differences are not well characterized. In this study, we aimed to integrate novel radiographic and histopathologic observations to gain a conceptual understanding of radiosurgery-induced leukoencephalopathy. Methods and Materials: We examined resected tissues of 10 patients treated at Yale New Haven Hospital between January 1, 2009, and June 30, 2010, for brain metastases that had been previously treated with Gamma Knife radiosurgery, who subsequently required surgical management of a symptomatic regrowing lesion. None of the patients showed pathological evidence of tumor recurrence. Clinical and magnetic resonance imaging data for each of the 10 patients were then studied retrospectively. Results: We provide evidence to show that radiosurgery-induced leukoencephalopathy may present as an advancing process that extends beyond the original high-dose radiation field. Neuropathologic examination of the resected tissue revealed traditionally known leukoencephalopathic changes including demyelination, coagulation necrosis, and vascular sclerosis. Unexpectedly, small and medium-sized vessels revealed transmural T-cell infiltration indicative of active vasculitis. Conclusions: We propose that the presence of a vasculitic component in association with radiation-induced leukoencephalopathy may facilitate the progressive nature of the condition. It may also explain the resemblance of delayed leukoencephalopathy with recurring tumor on virtually all imaging modalities used for posttreatment follow-up.

  11. Effect of bevacizumab on radiation necrosis of the brain

    SciTech Connect

    Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A. . E-mail: vlevin@mdanderson.org

    2007-02-01

    Purpose: Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis. Patients and Methods: Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination for their tumor on either a 5 mg/kg/2-week or 7.5 mg/kg/3-week schedule. Radiation necrosis was diagnosed in 8 of these patients on the basis of magnetic resonance imaging (MRI) and biopsy. MRI studies were obtained before treatment and at 6-week to 8-week intervals. Results: Of the 8 patients with radiation necrosis, posttreatment MRI performed an average of 8.1 weeks after the start of bevacizumab therapy showed a reduction in all 8 patients in both the MRI fluid-attenuated inversion-recovery (FLAIR) abnormalities and T1-weighted post-Gd-contrast abnormalities. The average area change in the T1-weighted post-Gd-contrast abnormalities was 48% ({+-}22 SD), and the average change in the FLAIR images was 60% ({+-}18 SD). The average reduction in daily dexamethasone requirements was 8.6 mg ({+-}3.6). Conclusion: Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment.

  12. Radiation necrosis after treatment of solitary intracranial metastases

    SciTech Connect

    Sundaresan, N.; Galicich, J.H.; Deck, M.D.; Tomita, T.

    1981-03-01

    During the period from July 1977 to June 1980, 75 patients underwent the surgical excision of solitary brain metastases, and 61 of these patients received whole brain radiation. Three patients developed chronic radiation necrosis. In the 3 patients with necrosis, computed tomography suggested recurrent tumor; the histological diagnosis of necrosis only was obtained at operation in 2 of these patients and by autopsy in the third. Radiation damage resulted in the death of 1 patient, a chronic vegetative state in another, and severe neurological deficit in the third. An additional 4 patients had neurological complications probably related to radiation therapy. As the survival of such patients is prolonged by aggressive treatment, the incidence of radiation-induced complications is likely to increase. The optimal dose of radiation necessary to destroy microscopic foci of tumor after the surgical resection of a single brain metastasis is unknown. Because of the significant incidence of damage after radiation as currently delivered, studies using graded, lower doses are indicated.

  13. A GSK-3β Inhibitor Protects Against Radiation Necrosis in Mouse Brain

    SciTech Connect

    Jiang, Xiaoyu; Perez-Torres, Carlos J.; Thotala, Dinesh; Engelbach, John A.; Yuan, Liya; Cates, Jeremy; Gao, Feng; Drzymala, Robert E.; Rich, Keith M.; Schmidt, Robert E.; Ackerman, Joseph J.H.; Hallahan, Dennis E.; Garbow, Joel R.

    2014-07-15

    Purpose: To quantify the effectiveness of SB415286, a specific inhibitor of GSK-3β, as a neuroprotectant against radiation-induced central nervous system (brain) necrosis in a mouse model. Methods and Materials: Cohorts of mice were treated with SB415286 or dimethyl sulfoxide (DMSO) prior to irradiation with a single 45-Gy fraction targeted to the left hemisphere (brain) using a gamma knife machine. The onset and progression of radiation necrosis (RN) were monitored longitudinally by noninvasive in vivo small-animal magnetic resonance imaging (MRI) beginning 13 weeks postirradiation. MRI-derived necrotic volumes for SB415286- and DMSO-treated mice were compared. MRI results were supported by correlative histology. Results: Mice treated with SB415286 showed significant protection from radiation-induced necrosis, as determined by in vivo MRI with histologic validation. MRI-derived necrotic volumes were significantly smaller at all postirradiation time points in SB415286-treated animals. Although the irradiated hemispheres of the DMSO-treated mice demonstrated many of the classic histologic features of RN, including fibrinoid vascular necrosis, vascular telangiectasia, hemorrhage, and tissue loss, the irradiated hemispheres of the SB415286-treated mice consistently showed only minimal tissue damage. These studies confirmed that treatment with a GSK-3β inhibitor dramatically reduced delayed time-to-onset necrosis in irradiated brain. Conclusions: The unilateral cerebral hemispheric stereotactic radiation surgery mouse model in concert with longitudinal MRI monitoring provided a powerful platform for studying the onset and progression of RN and for developing and testing new neuroprotectants. Effectiveness of SB415286 as a neuroprotectant against necrosis motivates potential clinical trials of it or other GSK-3β inhibitors.

  14. Delayed-type Necrosis after Soft-tissue Augmentation with Hyaluronic Acid.

    PubMed

    Souza Felix Bravo, Bruna; Klotz De Almeida Balassiano, Laila; Roos Mariano Da Rocha, Camila; Barbosa De Sousa Padilha, Carolina; Martinezt Torrado, Carolina; Teixeira Da Silva, Roberta; Carlos Regazzi Avelleira, João

    2015-12-01

    The growing use of dermal fillers, specifically the use of hyaluronic acid, can be explained by their effectiveness and versatility as well as their favorable safety profiles. Nevertheless, early and late complications with varying levels of severity may occur. The incidence of complications is low and the majority of adverse events are mild (edema, erythema, and local ecchymosis) and of limited duration. However, more severe events, such as ischemia and necrosis, may occur. The symptoms of ischemia can occur immediately after the injection or several hours after the procedure. Here, the authors report three cases of necrosis after hyaluronic acid injection with the first symptoms presenting only several hours after the procedure. The patients were treated immediately after the diagnosis. The aim of this review is to communicate the possibility of the delayed-type presentation of necrosis, present the signs and symptoms that lead to early diagnosis, and review the treatment possibilities of this severe complication. PMID:26705447

  15. Delayed-type Necrosis after Soft-tissue Augmentation with Hyaluronic Acid

    PubMed Central

    Klotz De Almeida Balassiano, Laila; Roos Mariano Da Rocha, Camila; Barbosa De Sousa Padilha, Carolina; Martinezt Torrado, Carolina; Teixeira Da Silva, Roberta; Carlos Regazzi Avelleira, João

    2015-01-01

    The growing use of dermal fillers, specifically the use of hyaluronic acid, can be explained by their effectiveness and versatility as well as their favorable safety profiles. Nevertheless, early and late complications with varying levels of severity may occur. The incidence of complications is low and the majority of adverse events are mild (edema, erythema, and local ecchymosis) and of limited duration. However, more severe events, such as ischemia and necrosis, may occur. The symptoms of ischemia can occur immediately after the injection or several hours after the procedure. Here, the authors report three cases of necrosis after hyaluronic acid injection with the first symptoms presenting only several hours after the procedure. The patients were treated immediately after the diagnosis. The aim of this review is to communicate the possibility of the delayed-type presentation of necrosis, present the signs and symptoms that lead to early diagnosis, and review the treatment possibilities of this severe complication. PMID:26705447

  16. Subcutaneous Fat Necrosis of the Neonate with a Delayed Second Eruption.

    PubMed

    Thomas, Justyn M; Bhandari, Jasjit; Rytina, Ed; Gass, Julia K; Williams, Rachel M; Burrows, Nigel P

    2016-01-01

    Subcutaneous fat necrosis (SCFN) of the neonate is a rare panniculitis of early life that occurs in association with gestational diabetes and preeclampsia, as well as perinatal asphyxia, hypothermia, and trauma. A characteristic feature of this condition is its self-limiting and monophasic nature. We report a highly unusual case of delayed SCFN in a male neonate involving an anatomically discrete eruption, reminiscent of erythema nodosum, occurring many weeks after his original eruption had resolved. PMID:26821771

  17. Analysis of risk and predictors of brain radiation necrosis after radiosurgery

    PubMed Central

    Zhuang, Hongqing; Zheng, Yi; Wang, Junjie; Chang, Joe Y.; Wang, Xiaoguang; Yuan, Zhiyong; Wang, Ping

    2016-01-01

    In this study, we examined the factors contributing to brain radiation necrosis and its predictors of patients treated with Cyberknife radiosurgery. A total of 94 patients with primary or metastatic brain tumours having been treated with Cyberknife radiotherapy from Sep. 2006 to Oct. 2011 were collected and retrospectively analyzed. Skull based tracking was used to deliver radiation to 104 target sites. and the prescribed radiation doses ranged from 1200 to 4500 cGy in 1 to 8 fractions with a 60% to 87% isodose line. Radiation necrosis was confirmed by imaging or pathological examination. Associations between cerebral radiation necrosis and factors including diabetes, cardio-cerebrovascular disease, target volume, isodose line, prescribed dosage, number of fractions, combination with whole brain radiation and biologically equivalent dose (BED) were determined by logistic regression. ROC curves were created to measure the predictive accuracy of influence factors and identify the threshold for brain radiation necrosis. Our results showed that radiation necrosis occurred in 12 targets (11.54%). Brain radiation necrosis was associated by BED, combination with whole brain radiotherapy, and fractions (areas under the ROC curves = 0.892±0.0335, 0.650±0.0717, and 0.712±0.0637 respectively). Among these factors, only BED had the capability to predict brain radiation necrosis, and the threshold dose was 7410 cGy. In conclusion, BED is the most effective predictor of brain radiation necrosis, with a dose of 7410 cGy being identified as the threshold. PMID:26675376

  18. Analysis of risk and predictors of brain radiation necrosis after radiosurgery.

    PubMed

    Zhuang, Hongqing; Zheng, Yi; Wang, Junjie; Chang, Joe Y; Wang, Xiaoguang; Yuan, Zhiyong; Wang, Ping

    2016-02-16

    In this study, we examined the factors contributing to brain radiation necrosis and its predictors of patients treated with Cyberknife radiosurgery. A total of 94 patients with primary or metastatic brain tumours having been treated with Cyberknife radiotherapy from Sep. 2006 to Oct. 2011 were collected and retrospectively analyzed. Skull based tracking was used to deliver radiation to 104 target sites. and the prescribed radiation doses ranged from 1200 to 4500 cGy in 1 to 8 fractions with a 60% to 87% isodose line. Radiation necrosis was confirmed by imaging or pathological examination. Associations between cerebral radiation necrosis and factors including diabetes, cardio-cerebrovascular disease, target volume, isodose line, prescribed dosage, number of fractions, combination with whole brain radiation and biologically equivalent dose (BED) were determined by logistic regression. ROC curves were created to measure the predictive accuracy of influence factors and identify the threshold for brain radiation necrosis. Our results showed that radiation necrosis occurred in 12 targets (11.54%). Brain radiation necrosis was associated by BED, combination with whole brain radiotherapy, and fractions (areas under the ROC curves = 0.892±0.0335, 0.650±0.0717, and 0.712±0.0637 respectively). Among these factors, only BED had the capability to predict brain radiation necrosis, and the threshold dose was 7410 cGy. In conclusion, BED is the most effective predictor of brain radiation necrosis, with a dose of 7410 cGy being identified as the threshold. PMID:26675376

  19. RIP1 and RIP3 complex regulates radiation-induced programmed necrosis in glioblastoma.

    PubMed

    Das, Arabinda; McDonald, Daniel G; Dixon-Mah, Yaenette N; Jacqmin, Dustin J; Samant, Vikram N; Vandergrift, William A; Lindhorst, Scott M; Cachia, David; Varma, Abhay K; Vanek, Kenneth N; Banik, Naren L; Jenrette, Joseph M; Raizer, Jeffery J; Giglio, Pierre; Patel, Sunil J

    2016-06-01

    Radiation-induced necrosis (RN) is a relatively common side effect of radiation therapy for glioblastoma. However, the molecular mechanisms involved and the ways RN mechanisms differ from regulated cell death (apoptosis) are not well understood. Here, we compare the molecular mechanism of cell death (apoptosis or necrosis) of C6 glioma cells in both in vitro and in vivo (C6 othotopically allograft) models in response to low and high doses of X-ray radiation. Lower radiation doses were used to induce apoptosis, while high-dose levels were chosen to induce radiation necrosis. Our results demonstrate that active caspase-8 in this complex I induces apoptosis in response to low-dose radiation and inhibits necrosis by cleaving RIP1 and RI. When activation of caspase-8 was reduced at high doses of X-ray radiation, the RIP1/RIP3 necrosome complex II is formed. These complexes induce necrosis through the caspase-3-independent pathway mediated by calpain, cathepsin B/D, and apoptosis-inducing factor (AIF). AIF has a dual role in apoptosis and necrosis. At high doses, AIF promotes chromatinolysis and necrosis by interacting with histone H2AX. In addition, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. Analysis of inflammatory markers in matched plasma and cerebrospinal fluid (CSF) isolated from in vivo specimens demonstrated the upregulation of chemokines and cytokines during the necrosis phase. Using RIP1/RIP3 kinase specific inhibitors (Nec-1, GSK'872), we also establish that the RIP1-RIP3 complex regulates programmed necrosis after either high-dose radiation or TNF-α-induced necrosis requires RIP1 and RIP3 kinases. Overall, our data shed new light on the relationship between RIP1/RIP3-mediated programmed necrosis and AIF-mediated caspase-independent programmed necrosis in glioblastoma. PMID:26684801

  20. Acquired-resistance of bevacizumab treatment for radiation brain necrosis: a case report

    PubMed Central

    Sun, Dayong; Bian, Jianliang; Chang, Joe Y.; Yuan, Zhiyong; Wang, Ping

    2016-01-01

    The case study reported on acquired bevacizumab resistance in one patient receiving re-treatment with bevacizumab following radiation brain necrosis progression after bevacizumab was discontinued. This case offers novel and additional insight for bevacizumab treatment. Low-dose bevacizumab is effective for radiation brain necrosis, and radiation brain necrosis may progress after bevacizumab discontinuation, whereas too many cycles of bevacizumab treatment may induce drug-resistance and re-treatment failure following the progression. Therefore, more rational administration for radiation brain necrosis with bevacizumab may include three aspects: short-course treatment, timely discontinuation upon obtaining satisfactory effects (to prevent long-term medication associated resistance) and re-treatment after brain necrosis progression. PMID:26933810

  1. Bevacizumab as Therapy for Radiation Necrosis in Four Children With Pontine Gliomas

    SciTech Connect

    Liu, Arthur K.; Macy, Margaret E.; Foreman, Nicholas K.

    2009-11-15

    Purpose: Diffuse pontine gliomas are a pediatric brain tumor that is fatal in nearly all patients. Given the poor prognosis for patients with this tumor, their quality of life is very important. Radiation therapy provides some palliation, but can result in radiation necrosis and associated neurologic decline. The typical treatment for this necrosis is steroid therapy. Although the steroids are effective, they have numerous side effects that can often significantly compromise quality of life. Bevacizumab, an antibody against vascular endothelial growth factor, has been suggested as a treatment for radiation necrosis. We report on our initial experience with bevacizumab therapy for radiation necrosis in pediatric pontine gliomas. Materials and Methods: Four children with pontine gliomas treated at the Children's Hospital in Denver and the University of Colorado Denver developed evidence of radiation necrosis both clinically and on imaging. Those 4 children then received bevacizumab as a treatment for the radiation necrosis. We reviewed the clinical outcome and imaging findings. Results: After bevacizumab therapy, 3 children had significant clinical improvement and were able to discontinue steroid use. One child continued to decline, and, in retrospect, had disease progression, not radiation necrosis. In all cases, bevacizumab was well tolerated. Conclusions: In children with pontine gliomas, bevacizumab may provide both therapeutic benefit and diagnostic information. More formal evaluation of bevacizumab in these children is needed.

  2. [Brain MR perfusion and MR spectroscopy in differentiation of radiation necrosis from tumor recurrence (case report)].

    PubMed

    Tekşam, Mehmet; Kayahan, Esra Meltem; Yerli, Hasan; Ağildere, A Muhteşem

    2004-12-01

    It is not always possible to differentiate tumor recurrence from radiation necrosis using conventional MR images. In this report we present a case of pathologically proven radiation necrosis which appeared as nodular contrast enhancement on conventional MR images in a patient who was surgically treated for grade II astrocytoma 5 years ago. There were decreased choline, creatine and N-acetyl aspartate peaks and significantly increased lipid peak on multivoxel H1-MR spectroscopy while there was no significant perfusion increase on MR perfusion. These findings suggested changes secondary to radiation necrosis. PMID:15611913

  3. Accuracy of magnetic resonance spectroscopy in distinction between radiation necrosis and recurrence of brain tumors

    PubMed Central

    Anbarloui, Mousa Reza; Ghodsi, Seyed Mohammad; Khoshnevisan, Alireza; Khadivi, Masoud; Abdollahzadeh, Sina; Aoude, Ahmad; Naderi, Soheil; Najafi, Zeynab; Faghih-Jouibari, Morteza

    2015-01-01

    Background: Distinction between radiation necrosis and recurrence of intraparenchymal tumors is necessary to select the appropriate treatment, but it is often difficult based on imaging features alone. We developed an algorithm for analyzing magnetic resonance spectroscopy (MRS) findings and studied its accuracy in differentiation between radiation necrosis and tumor recurrence. Methods: Thirty-three patients with a history of intraparenchymal brain tumor resection and radiotherapy, which had developed new enhancing lesion were evaluated by MRS and subsequently underwent reoperation. Lesions with Choline (Cho)/N-acetyl aspartate (NAA) > 1.8 or Cho/Lipid > 1 were considered as tumor recurrence and the remaining as radiation necrosis. Finally, pre-perative MRS diagnoses were compared with histopathological report. Results: The histological diagnosis was recurrence in 25 patients and necrosis in 8 patients. Mean Cho/NAA in recurrent tumors was 2.72, but it was 1.46 in radiation necrosis (P < 0.01). Furthermore, Cho/Lipid was significantly higher in recurrent tumors (P < 0.01) with the mean of 2.78 in recurrent tumors and 0.6 in radiation necrosis. Sensitivity, specificity, and diagnostic accuracy of the algorithm for detecting tumor recurrence were 84%, 75% and 81%, respectively. Conclusion: MRS is a safe and informative tool for differentiating between tumor recurrence and radiation necrosis. PMID:25874054

  4. [Brain radiation necrosis after stereotactic radiotherapy of the resection cavity for intracranial metastases: analysis of the literature from four cases].

    PubMed

    Doré, M; Lefebvre, L; Delpon, G; Thillays, F

    2015-04-01

    Stereotactic hypofractionated radiotherapy after resection of brain metastasis is an alternative to whole brain radiotherapy. A high dose per fraction is associated with a risk of radiation necrosis. We present four cases of confirmed histological radiation necrosis. Differentiating recurrent tumour from radiation necrosis in this scenario is challenging. An enhancing area in magnetic resonance imaging (MRI) with a "cut bell pepper" appearance may suggest radiation necrosis. Advanced imaging modalities such as perfusion MR imaging and positron emission tomography can be useful. Dosimetric predictors of the occurrence of radiation necrosis after stereotactic hypofractionated radiotherapy are poorly understood and require prospective studies on larger cohorts. PMID:25573799

  5. Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation.

    PubMed

    Ou, Sai-Hong Ignatius; Weitz, Michael; Jalas, John R; Kelly, Daniel F; Wong, Vanessa; Azada, Michele C; Quines, Oliver; Klempner, Samuel J

    2016-06-01

    Alectinib is a second generation ALK inhibitor that has significant clinical activity in central nervous system (CNS) metastases in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Pseudoprogression (PsP) due to radiation necrosis during alecitnib treatment of central nervous system (CNS) metastases from ALK-rearranged NSCLC as been reported. Hence, distinguishing radiation-related PsP from alectinib-induced radiographic changes is important to avoid erroneous early trial discontinuation and abandonment of an effective treatment. However, it remains difficult to assess casuality of radiation necrosis is related to recent direct radiation or induced by alectinib treatment or both. It is also unknown how long from previous radiation can alectinib still induce radiation necrosis. Here we reported a crizotinib-refractory ALK-positive NSCLC patient who develop radiation necrosis in one of his metastatic CNS lesions after approximately 12 months of alectinib treatment who otherwise had on-going CNS response on alectinib. His most recent radiation to his CNS metastases was 7 years prior to the start of alectinib. This case illustrates that in the setting of pror CNS radiation, given the significant clinical activity of alectinib in CNS metastases in ALK-positive NSCLC patients the risk of CNS radiation necrosis remains long after previous radiation to the CNS metastases has been completed and can occur after durable response of treatment. PMID:27133743

  6. Dose–Volume Relationships Associated With Temporal Lobe Radiation Necrosis After Skull Base Proton Beam Therapy

    SciTech Connect

    McDonald, Mark W.; Linton, Okechukwu R.; Calley, Cynthia S.J.

    2015-02-01

    Purpose: We evaluated patient and treatment parameters correlated with development of temporal lobe radiation necrosis. Methods and Materials: This was a retrospective analysis of a cohort of 66 patients treated for skull base chordoma, chondrosarcoma, adenoid cystic carcinoma, or sinonasal malignancies between 2005 and 2012, who had at least 6 months of clinical and radiographic follow-up. The median radiation dose was 75.6 Gy (relative biological effectiveness [RBE]). Analyzed factors included gender, age, hypertension, diabetes, smoking status, use of chemotherapy, and the absolute dose:volume data for both the right and left temporal lobes, considered separately. A generalized estimating equation (GEE) regression analysis evaluated potential predictors of radiation necrosis, and the median effective concentration (EC50) model estimated dose–volume parameters associated with radiation necrosis. Results: Median follow-up time was 31 months (range 6-96 months) and was 34 months in patients who were alive. The Kaplan-Meier estimate of overall survival at 3 years was 84.9%. The 3-year estimate of any grade temporal lobe radiation necrosis was 12.4%, and for grade 2 or higher radiation necrosis was 5.7%. On multivariate GEE, only dose–volume relationships were associated with the risk of radiation necrosis. In the EC50 model, all dose levels from 10 to 70 Gy (RBE) were highly correlated with radiation necrosis, with a 15% 3-year risk of any-grade temporal lobe radiation necrosis when the absolute volume of a temporal lobe receiving 60 Gy (RBE) (aV60) exceeded 5.5 cm{sup 3}, or aV70 > 1.7 cm{sup 3}. Conclusions: Dose–volume parameters are highly correlated with the risk of developing temporal lobe radiation necrosis. In this study the risk of radiation necrosis increased sharply when the temporal lobe aV60 exceeded 5.5 cm{sup 3} or aV70 > 1.7 cm{sup 3}. Treatment planning goals should include constraints on the volume of temporal lobes receiving

  7. Effect of genetic disruption of poly (ADP-ribose) synthetase on delayed production of inflammatory mediators and delayed necrosis during myocardial ischemia-reperfusion injury.

    PubMed

    Yang, Z; Zingarelli, B; Szabó, C

    2000-01-01

    The nuclear enzyme poly (ADP ribose) synthetase (PARS) has been shown to play an important role in the pathogenesis of various forms of ischemia or reperfusion injury and circulatory shock. Recent studies demonstrated that inhibition or genetic inactivation of PARS is beneficial in the early phase of myocardial reperfusion injury. The aim of the present study was to investigate whether inactivation of PARS influences the delayed myocardial necrosis and the production of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha), the anti-inflammatory cytokine interleukin-10 (IL-10), and the free radical nitric oxide in the late stage of myocardial reperfusion injury. The results demonstrate that genetic disruption of PARS provides marked protection against the delayed myocardial ischemia and reperfusion injury. In addition, in the absence of functional PARS, a suppression of TNFalpha, IL-10, and nitric oxide production was found. These findings provide direct evidence that PARS activation participates in the development of delayed cell injury and delayed mediator production in myocardial reperfusion injury. PMID:10638671

  8. A Novel Murine Model for Localized Radiation Necrosis and its Characterization Using Advanced Magnetic Resonance Imaging

    SciTech Connect

    Jost, Sarah C.; Hope, Andrew; Kiehl, Erich; Perry, Arie; Travers, Sarah; Garbow, Joel R.

    2009-10-01

    Purpose: To develop a murine model of radiation necrosis using fractionated, subtotal cranial irradiation; and to investigate the imaging signature of radiation-induced tissue damage using advanced magnetic resonance imaging techniques. Methods and Materials: Twenty-four mice each received 60 Gy of hemispheric (left) irradiation in 10 equal fractions. Magnetic resonance images at 4.7 T were subsequently collected using T1-, T2-, and diffusion sequences at selected time points after irradiation. After imaging, animals were killed and their brains fixed for correlative histologic analysis. Results: Contrast-enhanced T1- and T2-weighted magnetic resonance images at months 2, 3, and 4 showed changes consistent with progressive radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 {mu}m{sup 2}/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 {mu}m{sup 2}/ms) (p < 0.0001). Histology reflected changes typically seen in radiation necrosis. Conclusions: This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that diffusion-weighted imaging may be helpful in answering this diagnostic question in clinical settings.

  9. Semiquantitative Analysis Using Thallium-201 SPECT for Differential Diagnosis Between Tumor Recurrence and Radiation Necrosis After Gamma Knife Surgery for Malignant Brain Tumors

    SciTech Connect

    Matsunaga, Shigeo; Shuto, Takashi; Takase, Hajime; Ohtake, Makoto; Tomura, Nagatsuki; Tanaka, Takahiro; Sonoda, Masaki

    2013-01-01

    Purpose: Semiquantitative analysis of thallium-201 chloride single photon emission computed tomography ({sup 201}Tl SPECT) was evaluated for the discrimination between recurrent brain tumor and delayed radiation necrosis after gamma knife surgery (GKS) for metastatic brain tumors and high-grade gliomas. Methods and Materials: The medical records were reviewed of 75 patients, including 48 patients with metastatic brain tumor and 27 patients with high-grade glioma who underwent GKS in our institution, and had suspected tumor recurrence or radiation necrosis on follow-up neuroimaging and deteriorating clinical status after GKS. Analysis of {sup 201}Tl SPECT data used the early ratio (ER) and the delayed ratio (DR) calculated as tumor/normal average counts on the early and delayed images, and the retention index (RI) as the ratio of DR to ER. Results: A total of 107 tumors were analyzed with {sup 201}Tl SPECT. Nineteen lesions were removed surgically and histological diagnoses established, and the other lesions were evaluated with follow-up clinical and neuroimaging examinations after GKS. The final diagnosis was considered to be recurrent tumor in 65 lesions and radiation necrosis in 42 lesions. Semiquantitative analysis demonstrated significant differences in DR (P=.002) and RI (P<.0001), but not in ER (P=.372), between the tumor recurrence and radiation necrosis groups, and no significant differences between metastatic brain tumors and high-grade gliomas in all indices (P=.926 for ER, P=.263 for DR, and P=.826 for RI). Receiver operating characteristics analysis indicated that RI was the most informative index with the optimum threshold of 0.775, which provided 82.8% sensitivity, 83.7% specificity, and 82.8% accuracy. Conclusions: Semiquantitative analysis of {sup 201}Tl SPECT provides useful information for the differentiation between tumor recurrence and radiation necrosis in metastatic brain tumors and high-grade gliomas after GKS, and the RI may be the most

  10. Radiation Damage to the Nervous System: a delayed therapeutic hazard

    SciTech Connect

    Gilbert, H.A.; Kagan, A.R.

    1980-01-01

    This volume represents a good overview of an important issue - late effects of radiation on the nervous system, a topic of interest to everybody who deals with neurooncologic problems. The book is well edited and includes almost all relevant subjects ranging from diagnostic and dosimetric considerations to treatment of radiation brain necrosis.

  11. Radiation necrosis causing failure of automatic ventilation during sleep with central sleep apnea

    SciTech Connect

    Udwadia, Z.F.; Athale, S.; Misra, V.P.; Wadia, N.H.

    1987-09-01

    A patient operated upon for a midline cerebellar hemangioblastoma developed failure of automatic respiration during sleep, together with central sleep apnea syndrome, approximately two years after receiving radiation therapy to the brain. Clinical and CT scan findings were compatible with a diagnosis of radiation necrosis as the cause of his abnormal respiratory control.

  12. A Novel Murine Model for Localized Radiation Necrosis and its Characterization using Advanced Magnetic Resonance Imaging

    PubMed Central

    Jost, Sarah C.; Hope, Andrew; Kiehl, Erich; Perry, Arie; Travers, Sarah; Garbow, Joel R.

    2013-01-01

    Introduction Magnetic resonance (MR) images following external beam radiotherapy for brain tumors often display signal changes characteristic of either tumor progression and/or radiation injury. No non-invasive diagnostic biomarkers have been identified that clearly distinguish between these two disease processes. This study’s objective was to develop a murine model of radiation necrosis using fractionated, sub-total cranial irradiation and to investigate the imaging signature of radiation-induced tissue damage using advanced MR imaging techniques. Methods Twenty four mice each received 60 Gy of hemispheric (left) irradiation in ten equal fractions. MR images at 4.7 T were subsequently collected using T1-, T2- and diffusion-sequences at selected time points following irradiation or implantation. Following imaging, animals were euthanized and their brains were fixed for correlative histology. Results Contrast-enhanced T1- and T2-weighted MR images at months 2, 3, and 4 showed changes consistent with progressive radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 μm2/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 μm2/ms) (p<0.0001). Histology reflected changes typically seen in radiation necrosis. Conclusions This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that DWI may be helpful in answering this diagnostic question in clinical settings. PMID:19735877

  13. Brain necrosis after fractionated radiation therapy: Is the halftime for repair longer than we thought?

    SciTech Connect

    Bender, Edward T.

    2012-11-15

    Purpose: To derive a radiobiological model that enables the estimation of brain necrosis and spinal cord myelopathy rates for a variety of fractionation schemes, and to compare repair effects between brain and spinal cord. Methods: Sigmoidal dose response relationships for brain radiation necrosis and spinal cord myelopathy are derived from clinical data using nonlinear regression. Three different repair models are considered and the repair halftimes are included as regression parameters. Results: For radiation necrosis, a repair halftime of 38.1 (range 6.9-76) h is found with monoexponential repair, while for spinal cord myelopathy, a repair halftime of 4.1 (range 0-8) h is found. The best-fit alpha beta ratio is 0.96 (range 0.24-1.73)Conclusions: A radiobiological model that includes repair corrections can describe the clinical data for a variety of fraction sizes, fractionation schedules, and total doses. Modeling suggests a relatively long repair halftime for brain necrosis. This study suggests that the repair halftime for late radiation effects in the brain may be longer than is currently thought. If confirmed in future studies, this may lead to a re-evaluation of radiation fractionation schedules for some CNS diseases, particularly for those diseases where fractionated stereotactic radiation therapy is used.

  14. Inertia, gravitation, and radiation time delays

    SciTech Connect

    Graneau, P.

    1987-05-01

    This note explains how an instantaneous action-at-a-distance theory gives rise to time delays between a cause in one location and its effect at another. The key to this is a suitable law of induction which itself does not produce the time delay, but contains the cause in the form of a time derivative. The many-body solution process for an array of simultaneous induction equations then reveals retardation between cause and effect without the transport of energy at finite velocity. It is suggested that a suitable law of induction of inertia applied to an object in the solar system and the many-body universe may furnish the quantitative connection between inertia and Newtonian gravitation.

  15. A study on the evaluation method and recent clinical efficacy of bevacizumab on the treatment of radiation cerebral necrosis

    PubMed Central

    Zhuang, Hongqing; Yuan, Xiangkun; Zheng, Yi; Li, Xubin; Chang, Joe Y.; Wang, Junjie; Wang, Xiaoguang; Yuan, Zhiyong; Wang, Ping

    2016-01-01

    In order to investigate the efficacy of bevacizumab on the treatment of radiation cerebral necrosis, patients who were diagnosed with radiation cerebral necrosis by imaging after stereotactic radiotherapy were collected. Bevacizumab was applied at a dose of 5 mg/kg once every three weeks at least three times. The changes in cerebral necrosis symptoms before and after treatment, the cerebral edema volume, the cerebral necrosis volume, and the changes in magnetic resonance imaging (MRI) strengthening phase signals of cerebral necrosis were used as the first observation point. The side effects of bevacizumab were used as the second observation point. Total of 14 radiation cerebral necrosis patients were treated with bevacizumab between June 2011 and February 2013 were collected. There were 12 symptomatic patients, of whom 10 patients (83.3%) had reduced symptoms. The edema index grades of nine patients (64.29%) improved. The cerebral necrosis volumes of 13 patients (92.86%) decreased. The T1 phase signal strengths of the intracranial enhanced MRIs of 12 patients (85.71%) significantly decreased. The clinical side effects of bevacizumab were mild. In conclusion, Preliminary results showed that treatment of radiation cerebral necrosis using bevacizumab was safe and effective. This treatment measure is worthy of further study. PMID:27067388

  16. Radiation dependence of inverter propagation delay from timing sampler measurements

    NASA Technical Reports Server (NTRS)

    Buehler, M. G.; Blaes, B. R.; Lin, Y.-S.

    1989-01-01

    A timing sampler consisting of 14 four-stage inverter-pair chains with different load capacitances was fabricated in 1.6-micron n-well CMOS and irradiated with cobalt-60 at 10 rad(Si)/s. For this CMOS process the measured results indicate that the rising delay increases by about 2.2 ns/Mrad(Si) and the falling delay increase is very small, i.e., less than 300 ps/Mrad(Si). The amount of radiation-induced delay depends on the size of the load capacitance. The maximum value observed for this effect was 5.65 ns/pF-Mrad(Si). Using a sensitivity analysis, the sensitivity of the rising delay to radiation can be explained by a simple timing model and the radiation sensitivity of dc MOSFET parameters. This same approach could not explain the insensitivity of the falling delay to radiation. This may be due to a failure of the timing model and/or trapping effects.

  17. Unexpected radiation laryngeal necrosis after carbon ion therapy using conventional dose fractionation for laryngeal cancer.

    PubMed

    Demizu, Yusuke; Fujii, Osamu; Nagano, Fumiko; Terashima, Kazuki; Jin, Dongcun; Mima, Masayuki; Oda, Naoharu; Takeuchi, Kaoru; Takeda, Makiko; Ito, Kazuyuki; Fuwa, Nobukazu; Okimoto, Tomoaki

    2015-11-01

    Carbon ion therapy is a type of radiotherapy that can deliver high-dose radiation to a tumor while minimizing the dose delivered to organs at risk. Moreover, carbon ions are classified as high linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. A 73-year-old man with glottic squamous cell carcinoma, T3N0M0, refused laryngectomy and received carbon ion therapy of 70 Gy (relative biological effectiveness) in 35 fractions. Three months after the therapy, the patient had an upper airway inflammation, and then laryngeal edema and pain occurred. Five months after the therapy, the airway stenosis was severe and computed tomography showed lack of the left arytenoid cartilage and exacerbation of laryngeal necrosis. Despite the treatment, 5 and a half months after the therapy, the laryngeal edema and necrosis had become even worse and the surrounding mucosa was edematous and pale. Six months after the therapy, pharyngolaryngoesophagectomy and reconstruction with free jejunal autograft were performed. The surgical specimen pathologically showed massive necrosis and no residual tumor. Three years after the carbon ion therapy, he is alive without recurrence. The first reported laryngeal squamous cell carcinoma case treated with carbon ion therapy resulted in an unexpected radiation laryngeal necrosis. Tissue damage caused by carbon ion therapy may be difficult to repair even for radioresistant cartilage; therefore, hollow organs reinforced by cartilage, such as the larynx, may be vulnerable to carbon ion therapy. Caution should be exercised when treating tumors in or adjacent to such organs with carbon ion therapy. PMID:26355161

  18. Delayed radiation encephalopathy after radiotherapy for nasopharyngeal cancer: A CT study of 45 cases

    SciTech Connect

    Hu, J.Q.; Guan, Y.H.; Zhao, L.Z.; Xie, S.X.; Guo, Z.; Liang, Z.H. )

    1991-03-01

    The CT features of 45 cases of delayed radiation encephalopathy (including radiation necrosis) following radiotherapy for nasopharyngeal carcinoma are reported. The brain lesions were uni- or bilateral and involved mainly the white matter and subsequently the gray matter of the lower portion of the brain included within the portals of irradiation and its vicinity. The lesions were edematous and hypodense on CT and showed postcontrast enhancement in 50% of the cases. Within the period of follow-up (1-5 years), the lesions showed remissions and exacerbations and in some cases stabilized. In addition, there was progressive cerebral atrophy, manifesting itself mainly as dilatation of the temporal horns, the neighboring cisterns, and sylvian fissures. In some cases that were followed for a long time, the cerebral lesions showed either foci of calcification or encephalomalacia and/or porencephaly.

  19. Assessment of MRI Parameters as Imaging Biomarkers for Radiation Necrosis in the Rat Brain

    SciTech Connect

    Wang Silun; Tryggestad, Erik; Zhou Tingting; Armour, Michael; Wen Zhibo; Fu Dexue; Ford, Eric; Zijl, Peter C.M. van; Zhou Jinyuan

    2012-07-01

    Purpose: Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T{sub 1}, T{sub 2}, apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Methods and Materials: Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 Multiplication-Sign 10 mm{sup 2}) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at {approx}25 weeks' postradiation. The MRI signals of necrotic cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. Results: ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T{sub 1}, T{sub 2}, MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T{sub 1}, T{sub 2}, MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. Conclusion: ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores.

  20. Radiation recall dermatitis with soft tissue necrosis following pemetrexed therapy: a case report

    PubMed Central

    2009-01-01

    Introduction Radiation recall dermatitis is a well known but still poorly understood inflammatory reaction. It can develop in previously irradiated areas and has been shown to be triggered by a variety of different drugs, including cytostatic agents. Pemetrexed may cause radiation recall dermatitis in pre-irradiated patients. Case presentation We present the case of a 49-year-old Caucasian woman with non-small cell lung cancer who was initially treated with carboplatin and paclitaxel concomitant with radiotherapy after suffering a painful plexus brachialis infiltration. Due to disease progression, a second-line treatment with pemetrexed was started. A severe soft tissue necrosis developed despite steroid treatment and plastic surgery. Conclusion To the best of our knowledge, we present the first case of a patient with severe soft tissue necrosis in a pre-irradiated area after pemetrexed therapy. We believe that physicians treating patients with pemetrexed should be aware of the severe, possibly life-threatening effects that may be induced by pemetrexed after previous radiation therapy. PMID:19946510

  1. Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

    SciTech Connect

    Levin, Victor A.; Bidaut, Luc; Hou, Ping; Kumar, Ashok J.; Wefel, Jeffrey S.; Bekele, B. Nebiyou; Prabhu, Sujit; Loghin, Monica; Gilbert, Mark R.; Jackson, Edward F.

    2011-04-01

    Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T{sub 2}-weighted fluid-attenuated inversion recovery and T{sub 1}-weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with

  2. Severe Radiation Necrosis Successfully Treated With Bevacizumab in an Infant with Low-Grade Glioma and Tumor-Associated Intractable Trigeminal Neuralgia.

    PubMed

    Pillay Smiley, Natasha; Alden, Tord; Hartsell, William; Fangusaro, Jason

    2016-09-01

    We present a unique case of radiation necrosis in a child with brain stem low-grade glioma (LGG) presenting with trigeminal neuralgia. Despite extensive therapies, severe pain persisted. She received proton beam radiation with significant improvement. However, she developed radiation necrosis and hydrocephalus. Despite surgical correction of hydrocephalus, the patient remained critically ill. She was treated with dexamethasone and bevacizumab with rapid clinical improvement. Subsequent MRIs revealed almost complete resolution of the necrosis. This case illustrates the successful treatment of trigeminal neuralgia with radiation and a rare case of radiation necrosis in an LGG successfully treated with bevacizumab and dexamethasone. PMID:27187113

  3. Delayed effects of ionizing radiation on the ear

    SciTech Connect

    Bohne, B.A.; Marks, J.E.; Glasgow, G.P.

    1985-07-01

    The question of damage to the ear from exposure to ionizing radiation was addressed by exposing groups of chinchillas to fractioned doses of radiation (2 Gy per day) for total doses ranging from 40 to 90 Gy. In order to allow any delayed effects of radiation to become manifest, the animals were sacrificed two years after completion of treatment and their temporal bones were prepared for microscopic examination. The most pronounced effect of treatment was degeneration of sensory and supporting cells and loss of eighth nerve fibers in the organ of Corti. Damage increased with increasing dose of radiation. The degree of damage found in many of these ears was of sufficient magnitude to produce a permanent sensorineural hearing loss.

  4. BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis

    PubMed Central

    Patel, Kirtesh R.; Chowdhary, Mudit; Switchenko, Jeffrey M.; Kudchadkar, Ragini; Lawson, David H.; Cassidy, Richard J.; Prabhu, Roshan S.; Khan, Mohammad K.

    2016-01-01

    We retrospectively compared the outcomes and toxicities of melanoma brain metastases (MBM) patients treated with BRAF inhibitors (BRAFi) and stereotactic radiosurgery (SRS) with SRS alone. We identified 87 patients with 157 MBM treated with SRS alone from 2005 to 2013. Of these, 15 (17.2%) patients with 32 MBM (21.4%) received BRAFi therapy: three (20.0%) before SRS, two (13.3%) concurrent, and 10 (66.7%) after SRS. Overall survival (OS) was compared between cohorts using the product limit method. Intracranial outcomes were compared using cumulative incidence with competing risk for death. Baseline patient characteristics were similar between groups, except for the SRS cohort, which had higher rates of chemotherapy and more recent year of diagnosis. Radiation characteristics, including dose per fraction, total dose, gross tumor volume size, and prescription isodose, were also similar between cohorts. One-year outcomes – OS (64.3 vs. 40.4%, P =0.205), local failure (3.3 vs. 9.6%, P =0.423), and distant intracranial failure (63.9 vs. 65.1%, P =0.450) were not statistically different between the SRS + BRAFi and SRS-alone groups, respectively. The SRS + BRAFi group showed higher rates of radiographic radiation necrosis (RN) (22.2 vs. 11.0% at 1 year, P <0.001) and symptomatic radiation necrosis (SRN) (28.2 vs. 11.1% at 1 year, P <0.001). Multivariable analysis showed that BRAFi predicted an increased risk of both radiographic and SRN. SRS and BRAFi predicted for an increased risk of radiographic and SRN compared with SRS alone. Approaches to mitigate RN for patients receiving SRS and BRAFi should be considered until the clinical trial (http//:www.clinicaltrials.gov: NCT01721603) evaluating this treatment regimen is completed. PMID:27223498

  5. CN-04TREATMENT OF PEDIATRIC CEREBRAL RADIATION NECROSIS: A META-ANALYSIS

    PubMed Central

    Drezner, Nicole; Wells, Elizabeth; Vezina, Gilbert; Ho, Cheng-ying; Packer, Roger; Hwang, Eugene

    2014-01-01

    BACKGROUND: Cerebral radiation necrosis (CRN) is a well-characterized toxicity of radiation therapy that can result in significant neurologic deficits and be life threatening. Treatment for CRN has included surgical resection, corticosteroids, hyperbaric oxygen therapy (HBOT), and bevacizumab among other modalities, but no consensus approach has been identified. Given the paucity of pediatric CRN data, we sought to codify the approaches to treatment of radiation necrosis in pediatric patients. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL) and Ovid MEDLINE were searched to identify all relevant pediatric reports. RESULTS: Thirty-one pediatric patients, twenty-six with primary central nervous system tumors and four with arteriovenous malformations developed CRN, diagnosed by characteristic MRI findings, most (n = 28) with accompanying neurologic deficits. Patients received treatment with steroids alone (n = 5) or steroids followed by bevacizumab (n = 11) or HBOT (n = 12). Three asymptomatic patients did not receive intervention. 10/11 patients treated with steroids and bevacizumab, and 11/12 treated with steroids and HBOT improved. In all cases of steroid-resistent CRN, addition of bevacizumab induced improvement except in one case of disease progression. One patient treated with steroids alone died with progressive neurologic deterioration. With the exception of steroid-related adverse events, there were no reported significant side effects. CONCLUSIONS: Due to the small numbers of pediatric patients with CRN, analysis of treatment modalities is confined to limited reports. Furthermore, cases of CRN are likely underreported as we have seen much higher rates of CRN than the 3-5% reported in the literature at our institution in the past five years. The most common treatment following steroid initiation is addition of either bevacizumab or HBOT with good success. However, larger randomized controlled trials are needed to establish a definitive

  6. BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis.

    PubMed

    Patel, Kirtesh R; Chowdhary, Mudit; Switchenko, Jeffrey M; Kudchadkar, Ragini; Lawson, David H; Cassidy, Richard J; Prabhu, Roshan S; Khan, Mohammad K

    2016-08-01

    We retrospectively compared the outcomes and toxicities of melanoma brain metastases (MBM) patients treated with BRAF inhibitors (BRAFi) and stereotactic radiosurgery (SRS) with SRS alone. We identified 87 patients with 157 MBM treated with SRS alone from 2005 to 2013. Of these, 15 (17.2%) patients with 32 MBM (21.4%) received BRAFi therapy: three (20.0%) before SRS, two (13.3%) concurrent, and 10 (66.7%) after SRS. Overall survival (OS) was compared between cohorts using the product limit method. Intracranial outcomes were compared using cumulative incidence with competing risk for death. Baseline patient characteristics were similar between groups, except for the SRS cohort, which had higher rates of chemotherapy and more recent year of diagnosis. Radiation characteristics, including dose per fraction, total dose, gross tumor volume size, and prescription isodose, were also similar between cohorts. One-year outcomes - OS (64.3 vs. 40.4%, P=0.205), local failure (3.3 vs. 9.6%, P=0.423), and distant intracranial failure (63.9 vs. 65.1%, P=0.450) were not statistically different between the SRS+BRAFi and SRS-alone groups, respectively. The SRS+BRAFi group showed higher rates of radiographic radiation necrosis (RN) (22.2 vs. 11.0% at 1 year, P<0.001) and symptomatic radiation necrosis (SRN) (28.2 vs. 11.1% at 1 year, P<0.001). Multivariable analysis showed that BRAFi predicted an increased risk of both radiographic and SRN. SRS and BRAFi predicted for an increased risk of radiographic and SRN compared with SRS alone. Approaches to mitigate RN for patients receiving SRS and BRAFi should be considered until the clinical trial (http//:www.clinicaltrials.gov: NCT01721603) evaluating this treatment regimen is completed. PMID:27223498

  7. Tumor necrosis factor gene expression is mediated by protein kinase C following activation by ionizing radiation.

    SciTech Connect

    Hallahan, D. E.; Virudachalam, S.; Sherman, M. L.; Huberman, E.; Kufe, D. W.; Weichselbaum, R. R.; Univ. of Chicago; Dana-Farber Cancer Inst.; Univ. of Chicago

    1991-01-01

    Tumor necrosis factor (TNF) production following X-irradiation has been implicated in the biological response to ionizing radiation. Protein kinase C (PKC) is suggested to participate in TNF transcriptional induction and X-ray-mediated gene expression. We therefore studied radiation-mediated TNF expression in HL-60 cells with diminished PKC activity produced by either pretreatment with protein kinase inhibitors or prolonged 12-O-tetradecanoylphorbol-13-acetate treatment. Both treatments resulted in attenuation of radiation-mediated TNF induction. Consistent with these results, we found no detectable induction of TNF expression following X-irradiation in the HL-60 variant deficient in PKC-mediated signal transduction. The rapid activation of PKC following {gamma}-irradiation was established using an in vitro assay measuring phosphorylation of a PKC specific substrate. A 4.5-fold increase in PKC activity occurred 15 to 30 s following irradiation, which declined to baseline at 60 s. Two-dimensional gel electrophoresis of phosphoproteins extracted from irradiated cells demonstrated in vivo phosphorylation of the PKC specific substrate Mr 80,000 protein at 45 s following X-irradiation. These findings indicate that signal transduction via the PKC pathway is required for the induction of TNF gene expression by ionizing radiation.

  8. UVB Radiation Delays Tribolium castaneum Metamorphosis by Influencing Ecdysteroid Metabolism

    PubMed Central

    Sang, Wen; Yu, Lin; He, Li; Ma, Wei-Hua; Zhu, Zhi-Hui; Zhu, Fen; Wang, Xiao-Ping; Lei, Chao-Liang

    2016-01-01

    Ultraviolet B (UVB) radiation is an important environmental factor. It is generally known that UVB exhibits high genotoxicity due to causing DNA damage, potentially leading to skin carcinogenesis and aging in mammals. However, little is known about the effects of UVB on the development and metamorphosis of insects, which are the most abundant terrestrial animals. In the present study, we performed dose-response analyses of the effects UVB irradiation on Tribolium castaneum metamorphosis, assessed the function of the T. castaneum prothoracicotropic hormone gene (Trcptth), and analyzed ecdysteroid pathway gene expression profile and ecdysterone titers post-UVB irradiation. The results showed that UVB not only caused death of T. castaneum larvae, but also delayed larval-pupal metamorphosis and reduced the size and emergence rate of pupae. In addition, we verified the function of Trcptth, which is responsible for regulating metamorphosis. It was also found that the expression profiles of Trcptth as well as ecdysteroidogenesis and response genes were influenced by UVB radiation. Therefore, a disturbance pulse of ecdysteroid may be involved in delaying development under exposure to irradiation. To our knowledge, this is the first report indicating that UVB can influence the metamorphosis of insects. This study will contribute to a better understanding of the impact of UVB on signaling mechanisms in insect metamorphosis. PMID:26986217

  9. UVB Radiation Delays Tribolium castaneum Metamorphosis by Influencing Ecdysteroid Metabolism.

    PubMed

    Sang, Wen; Yu, Lin; He, Li; Ma, Wei-Hua; Zhu, Zhi-Hui; Zhu, Fen; Wang, Xiao-Ping; Lei, Chao-Liang

    2016-01-01

    Ultraviolet B (UVB) radiation is an important environmental factor. It is generally known that UVB exhibits high genotoxicity due to causing DNA damage, potentially leading to skin carcinogenesis and aging in mammals. However, little is known about the effects of UVB on the development and metamorphosis of insects, which are the most abundant terrestrial animals. In the present study, we performed dose-response analyses of the effects UVB irradiation on Tribolium castaneum metamorphosis, assessed the function of the T. castaneum prothoracicotropic hormone gene (Trcptth), and analyzed ecdysteroid pathway gene expression profile and ecdysterone titers post-UVB irradiation. The results showed that UVB not only caused death of T. castaneum larvae, but also delayed larval-pupal metamorphosis and reduced the size and emergence rate of pupae. In addition, we verified the function of Trcptth, which is responsible for regulating metamorphosis. It was also found that the expression profiles of Trcptth as well as ecdysteroidogenesis and response genes were influenced by UVB radiation. Therefore, a disturbance pulse of ecdysteroid may be involved in delaying development under exposure to irradiation. To our knowledge, this is the first report indicating that UVB can influence the metamorphosis of insects. This study will contribute to a better understanding of the impact of UVB on signaling mechanisms in insect metamorphosis. PMID:26986217

  10. Delay-Line Three-Dimensional Position Sensitive Radiation Detection

    NASA Astrophysics Data System (ADS)

    Jeong, Manhee

    High-resistivity silicon(Si) in large volumes and with good charge carrier transport properties has been produced and achieved success as a radiation detector material over the past few years due to its relatively low cost as well as the availability of well-established processing technologies. One application of that technology is in the fabrication of various position-sensing topologies from which the incident radiation's direction can be determined. We have succeeded in developing the modeling tools for investigating different position-sensing schemes and used those tools to examine both amplitude-based and time-based methods, an assessment that indicates that fine position-sensing can be achieved with simpler readout designs than are conventionally deployed. This realization can make ubiquitous and inexpensive deployment of special nuclear materials (SNM) detecting technology becomes more feasible because if one can deploy position-sensitive semiconductor detectors with only one or two contacts per side. For this purpose, we have described the delay-line radiation detector and its optimized fabrication. The semiconductor physics were simulated, the results from which guided the fabrication of the guard ring structure and the detector electrode, both of which included metal-field-plates. The measured improvement in the leakage current was confirmed with the fabricated devices, and the structures successfully suppressed soft-breakdown. We also demonstrated that fabricating an asymmetric strip-line structure successfully minimizing the pulse shaping and increases the distance through which one can propagate the information of the deposited charge distribution. With fabricated delay-line detectors we can acquire alpha spectra (Am-241) and gamma spectra (Ba-133, Co-57 and Cd-109). The delay-line detectors can therefore be used to extract the charge information from both ion and gamma-ray interactions. Furthermore, standard charge-sensitive circuits yield high SNR

  11. Tumor necrosis factor beta and ultraviolet radiation are potent regulators of human keratinocyte ICAM-1 expression

    SciTech Connect

    Krutmann, J.; Koeck, A.S.; Schauer, E.; Parlow, F.; Moeller, A.K.; Kapp, A.; Foerster, E.S.; Schoepf, E.L.; Luger, T.A. )

    1990-08-01

    Intercellular adhesion molecule-1 (ICAM-1) functions as a ligand of leukocyte function-associated antigen-1 (LFA-1), as well as a receptor for human picorna virus, and its regulation thus affects various immunologic and inflammatory reactions. The weak, constitutive ICAM-1 expression on human keratinocytes (KC) can be up-regulated by cytokines such as interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha). In order to further examine the regulation of KC ICAM-1 expression, normal human KC or epidermoid carcinoma cells (KB) were incubated with different cytokines and/or exposed to ultraviolet (UV) radiation. Subsequently, ICAM-1 expression was monitored cytofluorometrically using a monoclonal anti-ICAM-1 antibody. Stimulation of cells with recombinant human (rh) interleukin (IL) 1 alpha, rhIL-4, rhIL-5, rhIL-6, rh granulocyte/macrophage colony-stimulating factor (GM-CSF), rh interferon alpha (rhIFN alpha), and rh transforming growth factor beta (TGF beta) did not increase ICAM-1 surface expression. In contrast, rhTNF beta significantly up-regulated ICAM-1 expression in a time- and dose-dependent manner. Moreover, the combination of rhTNF beta with rhIFN gamma increased the percentage of ICAM-1-positive KC synergistically. This stimulatory effect of rhTNF beta was further confirmed by the demonstration that rhTNF beta was capable of markedly enhancing ICAM-1 mRNA expression in KC. Finally, exposure of KC in vitro to sublethal doses of UV radiation (0-100 J/m2) prior to cytokine (rhIFN tau, rhTNF alpha, rhTNF beta) stimulation inhibited ICAM-1 up-regulation in a dose-dependent fashion. These studies identify TNF beta and UV light as potent regulators of KC ICAM-1 expression, which may influence both attachment and detachment of leukocytes and possibly viruses to KC.

  12. Delayed effects of external radiation exposure: a brief history.

    PubMed

    Miller, R W

    1995-11-01

    Within months of Roentgen's discovery of X rays, severe adverse effects were reported, but not well publicized. As a result, over the next two decades, fluoroscope operators suffered lethal skin carcinomas. Later, case reports appeared concerning leukemia in radiation workers, and infants born with severe mental retardation after their mothers had been given pelvic radiotherapy early in pregnancy. Fluoroscopy and radiotherapy for benign disorders continued to be used with abandon until authoritative reports were published on the adverse effects of ionizing radiation by the U.S. NAS-NRC and the UK MRC in 1956. Meanwhile, exposure to the atomic bombs in Japan had occurred and epidemics of delayed effects began to be recognized among the survivors: cataracts (1949), leukemia (1952) and severe mental retardation among newborn infants after intrauterine exposure (1952). No statistically significant excess of germ-cell genetic effects was detected by six clinical measurements (1956), the F1 mortality (1981), cytogenetic studies (1987) or biochemical genetic studies (1988). Somatic cell effects were revealed by long-lasting chromosomal aberrations in peripheral lymphocytes (1968), and somatic cell mutations were found at the glycophorin A locus in erythrocytes (1992). Molecular biology is a likely focus of new studies based on the function of the gene for ataxia telangiectasia (1995), a disorder in which children have severe, even lethal acute radiation reactions when given conventional doses of radiotherapy for lymphoma, to which they are prone. Also, obligate heterozygote female relatives can be studied for increased susceptibility to radiation-induced breast cancer, as suggested by clinical studies. The tumor registries in Hiroshima and Nagasaki now provide incidence data that show the extent of increases in eight common cancers and no increase in eight others (1994). The possibility of very late effects of A-bomb exposure is suggested by recent reports of increased

  13. Clinical Outcomes of 174 Nasopharyngeal Carcinoma Patients With Radiation-Induced Temporal Lobe Necrosis

    SciTech Connect

    Lam, Tai-Chung; Wong, Frank C.S.; Leung, To-Wai; Ng, S.H.; Tung, Stewart Y.

    2012-01-01

    Purpose: To retrospectively study the clinical outcomes of nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis (TLN) treated with steroids, surgery, or observation only. Methods and Patients: We performed a retrospective analysis of 174 consecutive patients diagnosed with TLN between 1990 and 2008. Before 1998, symptomatic patients were treated with oral steroids, while asymptomatic patients were treated conservatively. After 1998, most symptomatic and asymptomatic patients with a large volume of necrosis were treated by intravenously pulsed-steroid therapy with a standardized protocol. We examined factors affecting grade 4 complication-free survival and overall survival. Outcomes of the three treatment groups, those receiving conservative treatment, those receiving oral steroid, and those receiving intravenous pulse steroid, were compared. Results: The mean follow-up time was 115 months. Rates of grade 4 complication-free survival at 2 years and at 5 years after diagnosis of TLN were 72.2% and 54.1%, respectively. The 2-year and 5-year overall survival rates were 57.5% and 35.4%, respectively. Multivariate analysis revealed that being symptomatic at diagnosis (relative risk [RR], 4.5; p = 0.0001), re-irradiation of the nasopharynx (NP) (RR, 1.56; p = 0.008), salvage brachytherapy to the NP (RR, 1.75; p = 0.012), and a short latency period before the diagnosis of TLN (RR, 0.96, p < 0.0001) were independent prognosticators of poor grade 4 complication-free survival. Patients with all four factors had a 100% risk of developing grade 4 complications within 5 years; whereas if no factor was present, the risk was 12.5%. Intravenous pulse steroid therapy was associated with a higher clinical response rate compared with conventional steroid therapy (p < 0.0001); however, it did not affect complication-free survival in multivariate analysis. Conclusions: TLN patients with good prognosticators could be observed without active treatment. Although

  14. Texture descriptors to distinguish radiation necrosis from recurrent brain tumors on multi-parametric MRI

    NASA Astrophysics Data System (ADS)

    Tiwari, Pallavi; Prasanna, Prateek; Rogers, Lisa; Wolansky, Leo; Badve, Chaitra; Sloan, Andrew; Cohen, Mark; Madabhushi, Anant

    2014-03-01

    Di erentiating radiation necrosis (a radiation induced treatment e ect) from recurrent brain tumors (rBT) is currently one of the most clinically challenging problems in care and management of brain tumor (BT) patients. Both radiation necrosis (RN), and rBT exhibit similar morphological appearance on standard MRI making non-invasive diagnosis extremely challenging for clinicians, with surgical intervention being the only course for obtaining de nitive ground truth". Recent studies have reported that the underlying biological pathways de n- ing RN and rBT are fundamentally di erent. This strongly suggests that there might be phenotypic di erences and hence cues on multi-parametric MRI, that can distinguish between the two pathologies. One challenge is that these di erences, if they exist, might be too subtle to distinguish by the human observer. In this work, we explore the utility of computer extracted texture descriptors on multi-parametric MRI (MP-MRI) to provide alternate representations of MRI that may be capable of accentuating subtle micro-architectural di erences between RN and rBT for primary and metastatic (MET) BT patients. We further explore the utility of texture descriptors in identifying the MRI protocol (from amongst T1-w, T2-w and FLAIR) that best distinguishes RN and rBT across two independent cohorts of primary and MET patients. A set of 119 texture descriptors (co-occurrence matrix homogeneity, neighboring gray-level dependence matrix, multi-scale Gaussian derivatives, Law features, and histogram of gradient orientations (HoG)) for modeling di erent macro and micro-scale morphologic changes within the treated lesion area for each MRI protocol were extracted. Principal component analysis based variable importance projection (PCA-VIP), a feature selection method previously developed in our group, was employed to identify the importance of every texture descriptor in distinguishing RN and rBT on MP-MRI. PCA-VIP employs regression analysis to provide

  15. Texture Descriptors to distinguish Radiation Necrosis from Recurrent Brain Tumors on multi-parametric MRI.

    PubMed

    Pallavi, Tiwari; Prateek, Prasanna; Lisa, Rogers; Leo, Wolansky; Chaitra, Badve; Andrew, Sloan; Mark, Cohen; Anant, Madabhushi

    2014-01-01

    Differentiating radiation necrosis (a radiation induced treatment effect) from recurrent brain tumors (rBT) is currently one of the most clinically challenging problems in care and management of brain tumor (BT) patients. Both radiation necrosis (RN), and rBT exhibit similar morphological appearance on standard MRI making non-invasive diagnosis extremely challenging for clinicians, with surgical intervention being the only course for obtaining definitive "ground truth". Recent studies have reported that the underlying biological pathways defining RN and rBT are fundamentally different. This strongly suggests that there might be phenotypic differences and hence cues on multi-parametric MRI, that can distinguish between the two pathologies. One challenge is that these differences, if they exist, might be too subtle to distinguish by the human observer. In this work, we explore the utility of computer extracted texture descriptors on multi-parametric MRI (MP-MRI) to provide alternate representations of MRI that may be capable of accentuating subtle micro-architectural differences between RN and rBT for primary and metastatic (MET) BT patients. We further explore the utility of texture descriptors in identifying the MRI protocol (from amongst T1-w, T2-w and FLAIR) that best distinguishes RN and rBT across two independent cohorts of primary and MET patients. A set of 119 texture descriptors (co-occurrence matrix homogeneity, neighboring gray-level dependence matrix, multi-scale Gaussian derivatives, Law features, and histogram of gradient orientations (HoG)) for modeling different macro and micro-scale morphologic changes within the treated lesion area for each MRI protocol were extracted. Principal component analysis based variable importance projection (PCA-VIP), a feature selection method previously developed in our group, was employed to identify the importance of every texture descriptor in distinguishing RN and rBT on MP-MRI. PCA-VIP employs regression analysis to

  16. Delayed effects of external radiation exposure: A brief history

    SciTech Connect

    Miller, R.W.

    1995-11-01

    Within months of Roentgen`s discovery of X rays, severe adverse effects were reported, but not well publicized. As a result, over the next two decades, fluoroscope operators suffered lethal skin carcinomas. Later, case reports appeared concerning leukemia in radiation workers, and infants born with severe mental retardation after their mothers had been given pelvic radiotherapy early in pregnancy. Fluoroscopy and radiotherapy for benign disorders continued to be used with abandon until authoritative reports were published on the adverse effects of ionizing radiation by the U.S. NAS-NRC and the UK MRC in 1956. Meanwhile, exposure to the atomic bombs in Japan had occurred and epidemics of delayed effects began to be recognized among the survivors: cataracts, leukemia and severe mental retardation among newborn infants after intra-uterine exposure. No statistically significant excess of germ-cell genetic effects was detected by six clinical measurements, the F{sub 1} mortality, cytogenetic studies or biochemical genetic studies. Somatic cell effects were revealed by long-lasting chromosomal aberrations in peripheral lymphocytes, and somatic cell mutations were found at the glycophorin A locus in erythrocytes. Molecular biology is a likely focus of new studies based on the function of the gene for ataxia telangiectasia, a disorder in which children have severe, even lethal acute radiation reactions when given conventional doses of radiotherapy for lymphoma, to which they are prone. The tumor registries in Hiroshima and Nagasaki now provide incidence data that show the extent of increases in eight common cancers and no increase in eight others. The possibility of very late effects of A-bomb exposure is suggested by recent reports of increased frequencies of hyperparathyroidism, parathyroid cancers and certain causes of death other than cancer. 88 refs., 1 fig.

  17. 12 Gy gamma knife radiosurgical volume is a predictor for radiation necrosis in non-AVM intracranial tumors

    SciTech Connect

    Korytko, Timothy; Radivoyevitch, Tomas; Colussi, Valdir; Wessels, Barry W.; Pillai, Kunjan; Maciunas, Robert J.; Einstein, Douglas B. . E-mail: Douglas.Einstein@uhhs.com

    2006-02-01

    Purpose: To determine whether the 12-Gy radiosurgical volume (12-GyV) correlates with the development of postradiosurgical imaging changes suggestive of radiation necrosis in patients treated for non-arteriovenous malformation (non-AVM) intracranial tumors with gamma knife stereotactic radiosurgery (GKSRS). Methods and Materials: A retrospective single-institution review of 129 patients with 198 separate non-AVM tumors was performed. Patients were followed with magnetic resonance imaging (MRI) and physical examinations at 3- to 6-month intervals. Patients who developed postradiosurgical MRI changes suggestive of radiation necrosis were labeled as having either symptomatic radiation necrosis (S-NEC) if they experienced any decline in neurologic examination associated with the imaging changes, or asymptomatic radiation necrosis (A-NEC) if they had a stable or improving neurologic examination. Results: 12-GyV correlated with risk of S-NEC, which was 23% (for 12-GyV of 0-5 cc), 20% (5-10 cc), 54% (10-15 cc), and 57% (>15 cc). The risk of A-NEC did not significantly change with 12-GyV. Logistic regression analyses showed that the following factors were associated with the development of S-NEC: 12-GyV (p < 0.01), occipital and temporal lesions (p < 0.01), previous whole-brain radiotherapy (p = 0.03), and male sex (p 0.03). Radiosurgical plan conformality did not correlate with the development of S-NEC. Conclusion: The risk of S-NEC, but not A-NEC after GKSRS for non-AVM tumors correlates with 12-GyV, and increases significantly for 12-GyV >10 cc.

  18. Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases?

    PubMed

    Colaco, Rovel J; Martin, Pierre; Kluger, Harriet M; Yu, James B; Chiang, Veronica L

    2016-07-01

    OBJECT Radiation necrosis (RN), or its imaging equivalent, treatment-related imaging changes (TRIC), is an inflammatory reaction to high-dose radiation in the brain. The authors sought to investigate the hypothesis that immunotherapy increases the risk of developing RN/TRIC after stereotactic Gamma Knife (GK) radiosurgery for brain metastases. METHODS A total of 180 patients who underwent GK surgery for brain metastases between 2006 and 2012 were studied. The systemic therapy they received was classified as cytotoxic chemotherapy (CT), targeted therapy (TT), or immunotherapy (IT). The timing of systemic therapy in relation to GK treatment was also recorded. Logistic regression was used to calculate the odds of developing RN according to type of systemic therapy received. RESULTS The median follow-up time was 11.7 months. Of 180 patients, 39 (21.7%) developed RN/TRIC. RN/TRIC rates were 37.5% (12 of 32) in patients who received IT alone, 16.9% (14 of 83) in those who received CT only, and 25.0% (5 of 20) in those who received TT only. Median overall survival was significantly longer in patients who developed RN/TRIC (23.7 vs 9.9 months, respectively). The RN/TRIC rate was increased significantly in patients who received IT alone (OR 2.40 [95% CI 1.06-5.44]; p = 0.03), whereas receipt of any CT was associated with a lower risk of RN/TRIC (OR 0.38 [95% CI 0.18-0.78]; p = 0.01). The timing of development of RN/TRIC was not different between patients who received IT and those who received CT. CONCLUSIONS Patients who receive IT alone may have an increased rate of RN/TRIC compared with those who receive CT or TT alone after stereotactic radiosurgery, whereas receiving any CT may in fact be protective against RN/TRIC. As the use of immunotherapies increases, the rate of RN/TRIC may be expected to increase compared with rates in the chemotherapy era. PMID:26544782

  19. Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

    PubMed Central

    Freund, Derek; Zhang, Rui; Sanders, Mary; Newhauser, Wayne

    2015-01-01

    Cancer of the brain and central nervous system (CNS) is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN) can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT) compared to passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT). Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV) and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis. PMID:25866999

  20. Effect of caffeine on radiation-induced mitotic delay: delayed expression of G/sub 2/ arrest

    SciTech Connect

    Rowley, R.; Zorch, M.; Leeper, D.B.

    1984-01-01

    In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G/sub 2/ cells progressed to mitosis in register and without arrest in G/sub 2/. Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G/sub 2/ arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delay suggests a common basis for delay induction in S and G/sub 2/ phases.

  1. Replication-induced DNA damage after PARP inhibition causes G2 delay, and cell line-dependent apoptosis, necrosis and multinucleation

    PubMed Central

    Dale Rein, Idun; Solberg Landsverk, Kirsti; Micci, Francesca; Patzke, Sebastian; Stokke, Trond

    2015-01-01

    PARP inhibitors have been approved for treatment of tumors with mutations in or loss of BRCA1/2. The molecular mechanisms and particularly the cellular phenotypes resulting in synthetic lethality are not well understood and varying clinical responses have been observed. We have investigated the dose- and time-dependency of cell growth, cell death and cell cycle traverse of 4 malignant lymphocyte cell lines treated with the PARP inhibitor Olaparib. PARP inhibition induced a severe growth inhibition in this cell line panel and increased the levels of phosphorylated H2AX-associated DNA damage in S phase. Repair of the remaining replication related damage caused a G2 phase delay before entry into mitosis. The G2 delay, and the growth inhibition, was more pronounced in the absence of functional ATM. Further, Olaparib treated Reh and Granta-519 cells died by apoptosis, while U698 and JVM-2 cells proceeded through mitosis with aberrant chromosomes, skipped cytokinesis, and eventually died by necrosis. The TP53-deficient U698 cells went through several rounds of DNA replication and mitosis without cytokinesis, ending up as multinucleated cells with DNA contents of up to 16c before dying. In summary, we report here for the first time cell cycle-resolved DNA damage induction, and cell line-dependent differences in the mode of cell death caused by PARP inhibition. PMID:26312527

  2. Replication-induced DNA damage after PARP inhibition causes G2 delay, and cell line-dependent apoptosis, necrosis and multinucleation.

    PubMed

    Dale Rein, Idun; Solberg Landsverk, Kirsti; Micci, Francesca; Patzke, Sebastian; Stokke, Trond

    2015-01-01

    PARP inhibitors have been approved for treatment of tumors with mutations in or loss of BRCA1/2. The molecular mechanisms and particularly the cellular phenotypes resulting in synthetic lethality are not well understood and varying clinical responses have been observed. We have investigated the dose- and time-dependency of cell growth, cell death and cell cycle traverse of 4 malignant lymphocyte cell lines treated with the PARP inhibitor Olaparib. PARP inhibition induced a severe growth inhibition in this cell line panel and increased the levels of phosphorylated H2AX-associated DNA damage in S phase. Repair of the remaining replication related damage caused a G2 phase delay before entry into mitosis. The G2 delay, and the growth inhibition, was more pronounced in the absence of functional ATM. Further, Olaparib treated Reh and Granta-519 cells died by apoptosis, while U698 and JVM-2 cells proceeded through mitosis with aberrant chromosomes, skipped cytokinesis, and eventually died by necrosis. The TP53-deficient U698 cells went through several rounds of DNA replication and mitosis without cytokinesis, ending up as multinucleated cells with DNA contents of up to 16c before dying. In summary, we report here for the first time cell cycle-resolved DNA damage induction, and cell line-dependent differences in the mode of cell death caused by PARP inhibition. PMID:26312527

  3. Delayed gamma radiation from lightning induced nuclear reactions

    NASA Astrophysics Data System (ADS)

    Greenfield, M. B.; Sakuma, K.; Ikeda, Y.; Kubo, K.

    2004-03-01

    An increase in atmospheric gamma radiation observed with NaI and Ge detectors positioned about 15 m above ground was observed following natural lightning near Tokyo, Japan [1]. Background subtracted gamma ray rates GRR following numerous lightning strokes observed since 2001 persisted for a few hours and subsequently decayed with a half-life of about 50 minutes. Using a 3x3 Ge detector, with 2 KeV resolution, positioned about 2 m from one of the NaI detectors increases in GRR were observed minutes after the onset of lightning with a delayed 50 min exponential decay. Although most of the increase in activity occured at less than a few 100 KeV, on July 11, 2003 a 1267 +/-2 KeV line was observed. Although the statistics of this event were poor, the appearance of this line with an exponential decay of 50 min half-life suggests the possibility that it may be due to 39Cl (1267 MeV; half-life = 55.5 min) via the 40Ar(gamma,p)39Cl, 40Ar(p,2p)39Cl and/or 40Ar(n,d)39Cl reactions. Observations of > 10 MeV gamma rays observed in NaI detectors within 10s of meters from and coincident with rocket-triggered lightning at the International Center for Lightning Research and Testing suggest that charged particles accelerated in intense electric fields associated with lightning give rise to photons with sufficient energy to initiate nuclear reactions [2]. Further work to explain the cause of this anomalous activity is underway using natural and triggered lightning. 1. M. B. Greenfield et al., Journal of Applied Physics 93 no. 3 (2003) pp 1839-184. 2. J. R. Dwyer et al., Science 299, (2003), pp 694-697 and recent communications

  4. Electrical delay line multiplexing for pulsed mode radiation detectors

    PubMed Central

    Vinke, Ruud; Yeom, Jung Yeol; Levin, Craig S.

    2015-01-01

    Medical imaging systems are composed of a large number of position sensitive radiation detectors to provide high resolution imaging. For example, whole-body Positron Emission Tomography (PET) systems are typically composed of thousands of scintillation crystal elements, which are coupled to photosensors. Thus, PET systems greatly benefit from methods to reduce the number of data acquisition channels, in order to reduce the system development cost and complexity. In this paper we present an electrical delay line multiplexing scheme that can significantly reduce the number of readout channels, while preserving the signal integrity required for good time resolution performance. We experimented with two 4 × 4 LYSO crystal arrays, with crystal elements having 3 mm × 3 mm × 5 mm and 3 mm × 3 mm × 20 mm dimensions, coupled to 16 Hamamatsu MPPC S10931-050P SiPM elements. Results show that each crystal could be accurately identified, even in the presence of scintillation light sharing and inter-crystal Compton scatter among neighboring crystal elements. The multiplexing configuration degraded the coincidence timing resolution from ~ 243 ps FWHM to ~272 ps FWHM when 16 SiPM signals were combined into a single channel for the 4 × 4 LYSO crystal array with 3 mm × 3 mm × 20 mm crystal element dimensions, in coincidence with a 3 mm × 3 mm × 5 mm LYSO crystal pixel. The method is exible to allow multiplexing configurations across different block detectors, and is scalable to an entire ring of detectors. PMID:25768002

  5. Electrical delay line multiplexing for pulsed mode radiation detectors

    NASA Astrophysics Data System (ADS)

    Vinke, Ruud; Yeom, Jung Yeol; Levin, Craig S.

    2015-04-01

    Medical imaging systems are composed of a large number of position sensitive radiation detectors to provide high resolution imaging. For example, whole-body Positron Emission Tomography (PET) systems are typically composed of thousands of scintillation crystal elements, which are coupled to photosensors. Thus, PET systems greatly benefit from methods to reduce the number of data acquisition channels, in order to reduce the system development cost and complexity. In this paper we present an electrical delay line multiplexing scheme that can significantly reduce the number of readout channels, while preserving the signal integrity required for good time resolution performance. We experimented with two 4 × 4 LYSO crystal arrays, with crystal elements having 3 mm × 3 mm × 5 mm and 3 mm × 3 mm × 20 mm dimensions, coupled to 16 Hamamatsu MPPC S10931-050P SiPM elements. Results show that each crystal could be accurately identified, even in the presence of scintillation light sharing and inter-crystal Compton scatter among neighboring crystal elements. The multiplexing configuration degraded the coincidence timing resolution from ∼243 ps FWHM to ∼272 ps FWHM when 16 SiPM signals were combined into a single channel for the 4 × 4 LYSO crystal array with 3 mm × 3 mm × 20 mm crystal element dimensions, in coincidence with a 3 mm × 3 mm × 5 mm LYSO crystal pixel. The method is flexible to allow multiplexing configurations across different block detectors, and is scalable to an entire ring of detectors.

  6. Electrical delay line multiplexing for pulsed mode radiation detectors.

    PubMed

    Vinke, Ruud; Yeom, Jung Yeol; Levin, Craig S

    2015-04-01

    Medical imaging systems are composed of a large number of position sensitive radiation detectors to provide high resolution imaging. For example, whole-body Positron Emission Tomography (PET) systems are typically composed of thousands of scintillation crystal elements, which are coupled to photosensors. Thus, PET systems greatly benefit from methods to reduce the number of data acquisition channels, in order to reduce the system development cost and complexity. In this paper we present an electrical delay line multiplexing scheme that can significantly reduce the number of readout channels, while preserving the signal integrity required for good time resolution performance. We experimented with two 4 × 4 LYSO crystal arrays, with crystal elements having 3 mm × 3 mm × 5 mm and 3 mm × 3 mm × 20 mm dimensions, coupled to 16 Hamamatsu MPPC S10931-050P SiPM elements. Results show that each crystal could be accurately identified, even in the presence of scintillation light sharing and inter-crystal Compton scatter among neighboring crystal elements. The multiplexing configuration degraded the coincidence timing resolution from ∼243 ps FWHM to ∼272 ps FWHM when 16 SiPM signals were combined into a single channel for the 4 × 4 LYSO crystal array with 3 mm × 3 mm × 20 mm crystal element dimensions, in coincidence with a 3 mm × 3 mm × 5 mm LYSO crystal pixel. The method is flexible to allow multiplexing configurations across different block detectors, and is scalable to an entire ring of detectors. PMID:25768002

  7. SU-E-T-549: Modeling Relative Biological Effectiveness of Protons for Radiation Induced Brain Necrosis

    SciTech Connect

    Mirkovic, D; Peeler, C; Grosshans, D; Titt, U; Taleei, R; Mohan, R

    2015-06-15

    Purpose: To develop a model of the relative biological effectiveness (RBE) of protons as a function of dose and linear energy transfer (LET) for induction of brain necrosis using clinical data. Methods: In this study, treatment planning information was exported from a clinical treatment planning system (TPS) and used to construct a detailed Monte Carlo model of the patient and the beam delivery system. The physical proton dose and LET were computed in each voxel of the patient volume using Monte Carlo particle transport. A follow-up magnetic resonance imaging (MRI) study registered to the treatment planning CT was used to determine the region of the necrosis in the brain volume. Both, the whole brain and the necrosis volumes were segmented from the computed tomography (CT) dataset using the contours drawn by a physician and the corresponding voxels were binned with respect to dose and LET. The brain necrosis probability was computed as a function of dose and LET by dividing the total volume of all necrosis voxels with a given dose and LET with the corresponding total brain volume resulting in a set of NTCP-like curves (probability as a function of dose parameterized by LET). Results: The resulting model shows dependence on both dose and LET indicating the weakness of the constant RBE model for describing the brain toxicity. To the best of our knowledge the constant RBE model is currently used in all clinical applications which may Result in increased rate of brain toxicities in patients treated with protons. Conclusion: Further studies are needed to develop more accurate brain toxicity models for patients treated with protons and other heavy ions.

  8. In Vitro Studies on Space Radiation-Induced Delayed Genetic Responses: Shielding Effects

    NASA Technical Reports Server (NTRS)

    Kadhim, Munira A.; Green, Lora M.; Gridley, Daila S.; Murray, Deborah K.; Tran, Da Thao; Andres, Melba; Pocock, Debbie; Macdonald, Denise; Goodhead, Dudley T.; Moyers, Michael F.

    2003-01-01

    Understanding the radiation risks involved in spaceflight is of considerable importance, especially with the long-term occupation of ISS and the planned crewed exploration missions. Several independent causes may contribute to the overall risk to astronauts exposed to the complex space environment, such as exposure to GCR as well as SPES. Protons and high-Z energetic particles comprise the GCR spectrum and may exert considerable biological effects even at low fluence. There are also considerable uncertainties associated with secondary particle effects (e.g. HZE fragments, neutrons etc.). The interaction of protons and high-LET particles with biological materials at all levels of biological organization needs to be investigated fully in order to establish a scientific basis for risk assessment. The results of these types of investigation will foster the development of appropriately directed countermeasures. In this study, we compared the biological responses to proton irradiation presented to the target cells as a monoenergetic beam of particles of complex composition delivered to cells outside or inside a tissue phantom head placed in the United States EVA space suit helmet. Measurements of chromosome aberrations, apoptosis, and the induction of key proteins were made in bone marrow from CBA/CaJ and C57BL/6 mice at early and late times post exposure to radiation at 0, 0.5, 1 and 2 Gy while inside or outside of the helmet. The data showed that proton irradiation induced transmissible chromosomal/genomic instability in haematopoietic stem cells in both strains of mice under both irradiation conditions and especially at low doses. Although differences were noted between the mouse strains in the degree and kinetics of transforming growth factor-beta 1 and tumor necrosis factor-alpha secretion, there were no significant differences observed in the level of the induced instability under either radiation condition, or for both strains of mice. Consequently, when

  9. Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy.

    PubMed

    Detappe, Alexandre; Kunjachan, Sijumon; Sancey, Lucie; Motto-Ros, Vincent; Biancur, Douglas; Drane, Pascal; Guieze, Romain; Makrigiorgos, G Mike; Tillement, Olivier; Langer, Robert; Berbeco, Ross

    2016-09-28

    Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The high atomic number of gadolinium provides a large photoelectric cross-section for increased photon interaction, even for high-energy clinical radiation beams. Imaging and therapy functionality of SiGdNP were tested in cynomolgus monkeys and pancreatic tumor-bearing mice models, respectively. A significant improvement in tumor cell damage (double strand DNA breaks), growth suppression, and overall survival under clinical radiation therapy conditions were observed in a human pancreatic xenograft model. For the first time, safe systemic administration and systematic renal clearance was demonstrated in both tested species. These findings strongly support the translational potential of SiGdNP for MR-guided radiation therapy in cancer treatment. PMID:27423325

  10. Combined effects of tumor necrosis factor alpha and radiation in the treatment of renal cell carcinoma grown as radia spheroids.

    PubMed

    Van Moorselaar, R J; Schwachöfer, J H; Crooijmans, R P; Van Stratum, P; Debruyne, F M; Schalken, J A

    1990-01-01

    We have investigated the antiproliferative effects of Tumor Necrosis Factor Alpha (TNF) and radiation on a recently described rat renal cell tumor line grown as multicellular tumor spheroids (MTS). Treatment commenced when the spheroids had reached a diameter of 250 microns. TNF was diluted in the tissue culture medium in different concentrations, ranging from 250-1000 ng/ml. TNF monotherapy had a dose-dependent inhibiting effect on spheroid growth. Single-dose irradiation with 2, 4 or 6 Gy also retarded spheroids significantly in their growth. In the combination treatment the highest dose of TNF (1000 ng/ml) was added 4 hours prior to radiation. TNF could not induce a potentiation of the radiation injury at 2 Gy. The combination with 4 Gy, however, had additive and the combination with 6 Gy synergistic antiproliferative effects; in these treatment regimens respectively 2 and 5 out of 24 spheroids were controlled, i.e. cured. These experiments suggest that TNF in combination with radiotherapy may be beneficial for the treatment of renal cell carcinoma or cancer in general. PMID:2285257

  11. Toward Distinguishing Recurrent Tumor From Radiation Necrosis: DWI and MTC in a Gamma Knife–Irradiated Mouse Glioma Model

    SciTech Connect

    Perez-Torres, Carlos J.; Engelbach, John A.; Cates, Jeremy; Thotala, Dinesh; Yuan, Liya; Schmidt, Robert E.; Rich, Keith M.; Drzymala, Robert E.; Ackerman, Joseph J.H.; Garbow, Joel R.

    2014-10-01

    Purpose: Accurate noninvasive diagnosis is vital for effective treatment planning. Presently, standard anatomical magnetic resonance imaging (MRI) is incapable of differentiating recurring tumor from delayed radiation injury, as both lesions are hyperintense in both postcontrast T1- and T2-weighted images. Further studies are therefore necessary to identify an MRI paradigm that can differentially diagnose these pathologies. Mouse glioma and radiation injury models provide a powerful platform for this purpose. Methods and Materials: Two MRI contrasts that are widely used in the clinic were chosen for application to a glioma/radiation-injury model: diffusion weighted imaging, from which the apparent diffusion coefficient (ADC) is obtained, and magnetization transfer contrast, from which the magnetization transfer ratio (MTR) is obtained. These metrics were evaluated longitudinally, first in each lesion type alone–glioma versus irradiation – and then in a combined irradiated glioma model. Results: MTR was found to be consistently decreased in all lesions compared to nonlesion brain tissue (contralateral hemisphere), with limited specificity between lesion types. In contrast, ADC, though less sensitive to the presence of pathology, was increased in radiation injury and decreased in tumors. In the irradiated glioma model, ADC also increased immediately after irradiation, but decreased as the tumor regrew. Conclusions: ADC is a better metric than MTR for differentiating glioma from radiation injury. However, MTR was more sensitive to both tumor and radiation injury than ADC, suggesting a possible role in detecting lesions that do not enhance strongly on T1-weighted images.

  12. Radiation-induced cell cycle delay measured in two mouse tumors in vivo using bromodeoxyuridine

    SciTech Connect

    Wilson, G.D.; Martindale, C.A.; Soranson, J.A.; Bourhis, J.; Carl, U.M.; McNally, N.J. )

    1994-02-01

    The magnitude of the delay of cells in the phases of the cell cycle after irradiation may be related to the radioresponsiveness of tumor cell populations. In this study we have quantified division delay in two mouse tumors in vivo after single and fractionated doses of X rays and single doses of neutrons. The incorporation of bromodeoxyuridine and flow cytometry provided a sensitive and quantitative method to detect cell cycle perturbations after radiation treatment. The more rapidly growing SAF tumor showed less G[sub 2]-phase delay per gray than a more slowly proliferating tumor, the Rh (0.9 vs 1.8 h). In addition, the SAF tumor failed to show any G[sub 1]/S-phase delay while the Rh tumor experienced a longer G[sub 1]-phase delay while the Rh tumor experienced a longer G[sub 1]-phase delay than that measured for G[sub 2] phase (3.1 vs 1.8 h). There was a trend in both tumors for lower doses to be more effective in producing cell cycle delays. Neutrons caused longer G[sub 2]-phase delays on a unit dose basis, 2.5 and 5.4 h for the SAF and Rh tumors, respectively. The RBE for neutrons for division delay was found to be 2.9 and 2.8 for the SAF and Rh tumors, while the RBE for growth delay was 3.4 and 3.5. Fractionation of the X-ray dose caused a reduction in division delay at higher total doses (10 or 12 Gy) but was without effect at the lower dose studied (6 Gy). These studies show the feasibility of measuring cell cycle delays in vivo, and future developments are suggested for a possible predictive test in patients receiving radiotherapy. 17 refs., 6 figs., 2 tabs.

  13. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation.

    PubMed

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-12-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts. PMID:26633443

  14. Delayed Numerical Chromosome Aberrations in Human Fibroblasts by Low Dose of Radiation

    PubMed Central

    Cho, Yoon Hee; Kim, Su Young; Woo, Hae Dong; Kim, Yang Jee; Ha, Sung Whan; Chung, Hai Won

    2015-01-01

    Radiation-induced genomic instability refers to a type of damage transmitted over many generations following irradiation. This delayed impact of radiation exposure may pose a high risk to human health and increases concern over the dose limit of radiation exposure for both the public and radiation workers. Therefore, the development of additional biomarkers is still needed for the detection of delayed responses following low doses of radiation exposure. In this study, we examined the effect of X-irradiation on delayed induction of numerical chromosomal aberrations in normal human fibroblasts irradiated with 20, 50 and 100 cGy of X-rays using the micronucleus-centromere assay. Frequencies of centromere negative- and positive-micronuclei, and aneuploidy of chromosome 1 and 4 were analyzed in the surviving cells at 28, 88 and 240 h after X-irradiation. X-irradiation increased the frequency of micronuclei (MN) in a dose-dependent manner in the cells at all measured time-points, but no significant differences in MN frequency among cell passages were observed. Aneuploid frequency of chromosomes 1 and 4 increased with radiation doses, and a significantly higher frequency of aneuploidy was observed in the surviving cells analyzed at 240 h compared to 28 h. These results indicate that low-dose of X-irradiation can induce delayed aneuploidy of chromosomes 1 and 4 in normal fibroblasts. PMID:26633443

  15. Potentiation of radiation-induced regrowth delay in murine tumors by fludarabine.

    PubMed

    Grégoire, V; Hunter, N; Milas, L; Brock, W A; Plunkett, W; Hittelman, W N

    1994-01-15

    Fludarabine (9-beta-D-arabinofuranosyl-2-fluoroadenine-5'-monophosphate), an adenine nucleoside analogue, has previously been shown to inhibit the repair of radiation-induced chromosome damage. Thus fludarabine may have therapeutic utility in combination with photon irradiation. The purpose of this study was to determine whether fludarabine could enhance radiation-induced murine tumor regrowth delay and to determine the most effective dose and schedule of the combination. A significant (P < 0.05) absolute regrowth delay enhancement was observed in three murine tumor models (SA-NH, a sarcoma; and MCA-K and MCA-4, mammary carcinomas) when fludarabine (800 mg/kg) was given 1 h prior to 25 Gy gamma-irradiation. While fludarabine enhanced radiation-induced tumor regrowth delay when given between -36 h and +6 h of radiation (SA-NH tumor), the greatest enhancement was observed when fludarabine was given at -24 h prior to irradiation (radiation dose modification factor of 1.82 at -24 h compared to 1.57 at -3 h prior to radiation). The degree of fludarabine enhancement (at -3 or -24 h) was dose dependent at doses above 200 mg/kg. When fludarabine and radiation were administered on a fractionated schedule (fludarabine given 3 h prior to radiation each day for 4 days), the dose modification factor increased to 2.14 (1.63 if the effect of fludarabine alone is subtracted). These results suggest that fludarabine enhances radiation-induced tumor regrowth delay in a more than additive fashion after both single and fractionated treatments, and the degree of enhancement is dependent on the sequence and timing of administration, the fludarabine dose, and the tumor type. Thus, fludarabine may have clinical potential as a radiation enhancer in the treatment of solid tumors. PMID:8275483

  16. Evaluation of delayed effects of ionizing radiation: an historical perspective.

    PubMed

    Stewart, A M

    1991-01-01

    It is widely assumed that after the bombing of Hiroshima and Nagasaki there were no lasting effects of the acute injuries (which included extensive damage to blood forming tissues by the radiation) or the massively high death rate (which was caused by environmental effects of the blast as well as personal injuries). However, close inspection of the dose response curves for non-cancer deaths has shown that this could be a false impression caused by one effect of marrow aplasia being confused with leukemia (defective erythropoiesis) and a second effect being confused with early selection in favor of general fitness (defective immune responses). Possible consequences of such confusion (for cancer risk coefficients) are discussed in relation to what is known about late effects of prenatal x-rays and occupational exposures to radiation. PMID:1805618

  17. Influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig

    SciTech Connect

    Morison, W.L.; Parrish, J.A.; Woehler, M.E.; Krugler, J.I.; Bloch, K.J.

    1981-06-01

    Exposure of guinea pigs to UVA (320--400 nm) radiation following administration of 8-methoxypsoralen by gavage (referred to by the acronym, PUVA) or exposure to UVB (290--320 nm) radiation, produced suppression of the cutaneous delayed hypersensitivity reaction at the site of exposure to radiation and at distant nonexposed sites. In these experiments, the animals were immunized by injection of dinitrophenyl-bovine gamma-globulin (DNP-BGG) in complete Freund's adjuvant and delayed hypersensitivity responses were provoked by intradermal injections of DNP-BGG, DNP and BGG on the flanks. Exposure to erythemogenic doses of either PUVA or UVB radiation for 7 days prior to immunization and for the 7 days between immunization and challenge (total period of radiation: 14 days) produced inhibiton of responses to each of the test substances. In addition, treatment with erythemogenic doses of PUVA either for 7 days prior to immunization or during the interval between immunization and challenge with DNP-BGG, inhibited the delayed hypersensitivity responses at the site of irradiation and at a nonexposed site. These findings suggest that in vivo exposure to nonionizing radiation leads to both local and systemic alteration of certain immune responses.

  18. Influence of the circadian rhythm in cell division on radiation-induced mitotic delay in vivo

    SciTech Connect

    Rubin, N.H.

    1982-01-01

    Mitotic delay is described as a classical response to radiation; however, circadian rhythmicity in cell division in vivo has not been considered by many authors. The present study investigated the relation between fluctuations reported as mitotic delay and recovery in vivo and circadian oscillations in mitotic index in mouse corneal epithelium. One aspect involved single doses (approximately 600 rad) given to mice at different circadian stages. The normal circadian rhythm in cell division was never obliterated. Inhibition of mitosis was evident but unpredictable, ranging from 6 to 15 hr after irradiation. Recovery was evident only during the daily increase in mitotic index of controls. The classical interpretation of recovery from mitotic delay may be in an in vitro phenomenon not reflecting in vivo responses, which are apparently strongly circadian stage dependent. The second portion of the study demonstrated a dose-response effect on length of mitotic delay and, to a lesser extent, degree of recovery.

  19. Epidermal Platelet-activating Factor Receptor Activation and Ultraviolet B Radiation Result in Synergistic Tumor Necrosis Factor-alpha Production

    PubMed Central

    Wolverton, Jay E.; Al-Hassani, Mohammed; Yao, Yongxue; Zhang, Qiwei; Travers, Jeffrey B.

    2010-01-01

    Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine production which has been implicated in photoaggravated dermatoses. In addition to cytokines such as tumor necrosis factor-α (TNF-α), UVB generates bioactive lipids including platelet-activating factor (PAF). Our previous studies have demonstrated that UVB-mediated production of keratinocyte TNF-α is in part due to PAF. The current studies use a human PAF-receptor (PAF-R) negative epithelial cell line transduced with PAF-Rs and PAF–R-deficient mice to demonstrate that activation of the epidermal PAF-R along with UVB irradiation results in a synergistic production of TNF-α. It should be noted that PAF-R effects are mimicked by the protein kinase C (PKC) agonist phorbol myristic acetate, and are inhibited by pharmacological antagonists of the PKC gamma isoenzyme. These studies suggest that concomitant PAF-R activation and UVB irradiation results in a synergistic production of the cytokine TNF-α which is mediated in part via PKC. These studies provide a novel potential mechanism for photosensitivity responses. PMID:19769579

  20. Radiation-guided drug delivery to tumor blood vessels results in improved tumor growth delay.

    PubMed

    Geng, Ling; Osusky, Katherine; Konjeti, Sekhar; Fu, Allie; Hallahan, Dennis

    2004-10-19

    Tumor blood vessels are biological targets for cancer therapy. In this study, a tumor vasculature targeting system that consisted of liposomes and lectin (WGA) was built. Liposomes were used to carry a number of liposome-friendly anti-tumoral agents along with WGA, a lectin which posseses a specific affinity for binding to inflamed endothelial cells. In order to target tumor vasculature, inflammation of endothelial cells was induced by radiation. Because ionizing radiation induces an inflammatory response in tumor vasculature, lectin-conjugates were utilized to determine whether radiation can be used to target drug delivery to tumor vessels. Wheat germ agglutinin (WGA) is one such lectin that binds to inflamed microvasculature. WGA was conjugated to liposomes containing cisplatin and administered to tumor bearing mice. Tumor growth delay was used to analyze the efficacy of cytotoxicity. FITC-conjugated WGA accumulated within irradiated tumor microvasculature. WGA was conjugated to liposomes and labeled with 111In. This demonstrated radiation-inducible tumor-selective binding. WGA-liposome-conjugates were loaded with Cisplatin and administered to mice bearing irradiated tumors. Tumors treated with a combination of liposome encapsulated cisplatin together with radiation showed a significant increase in tumor growth delay as compared to radiation alone. These findings demonstrate that ionizing radiation can be used to guide drug delivery to tumor microvasculature. PMID:15451595

  1. Increased radiation dose at mammography due to prolonged exposure, delayed processing, and increased film darkening

    SciTech Connect

    Kimme-Smith, C.; Bassett, L.W.; Gold, R.H.; Chow, S. )

    1991-02-01

    Four single-emulsion films introduced over the past 2 years--Du Pont Microvision, Fuji MiMa, Konica CM, and Eastman Kodak OM--were compared with Eastman Kodak OM SO-177 (Min-RE) film to evaluate their varying effects on mean glandular dose of reciprocity law failure due to prolonged exposure, delayed processing, and increased film darkening as a result of increased radiation exposure to improve penetration of glandular tissue. Exposures over 1.3 seconds led to increased radiation doses of 20%-30%. Delays in processing of 6 hours decreased processing speed by 11%-32% for all films except Du Pont Microvision. Optical density increases of 0.40 required 20%-30% more skin exposure for all five films. Optimal viewing densities were also evaluated and found to be different for each of the five films. Mammographers need to be aware of these differences in mammographic films to achieve maximum contrast at mammography.

  2. UV Radiation Induces Delayed Hyperrecombination Associated with Hypermutation in Human Cells†

    PubMed Central

    Durant, Stephen T.; Paffett, Kimberly S.; Shrivastav, Meena; Timmins, Graham S.; Morgan, William F.; Nickoloff, Jac A.

    2006-01-01

    Ionizing radiation induces delayed genomic instability in human cells, including chromosomal abnormalities and hyperrecombination. Here, we investigate delayed genome instability of cells exposed to UV radiation. We examined homologous recombination-mediated reactivation of a green fluorescent protein (GFP) gene in p53-proficient human cells. We observed an ∼5-fold enhancement of delayed hyperrecombination (DHR) among cells surviving a low dose of UV-C (5 J/m2), revealed as mixed GFP+/− colonies. UV-B did not induce DHR at an equitoxic (75 J/m2) dose or a higher dose (150 J/m2). UV is known to induce delayed hypermutation associated with increased oxidative stress. We found that hypoxanthine phosphoribosyltransferase (HPRT) mutation frequencies were ∼5-fold higher in strains derived from GFP+/− (DHR) colonies than in strains in which recombination was directly induced by UV (GFP+ colonies). To determine whether hypermutation was directly caused by hyperrecombination, we analyzed hprt mutation spectra. Large-scale alterations reflecting large deletions and insertions were observed in 25% of GFP+ strains, and most mutants had a single change in HPRT. In striking contrast, all mutations arising in the hypermutable GFP+/− strains were small (1- to 2-base) changes, including substitutions, deletions, and insertions (reminiscent of mutagenesis from oxidative damage), and the majority were compound, with an average of four hprt mutations per mutant. The absence of large hprt deletions in DHR strains indicates that DHR does not cause hypermutation. We propose that UV-induced DHR and hypermutation result from a common source, namely, increased oxidative stress. These two forms of delayed genome instability may collaborate in skin cancer initiation and progression. PMID:16880516

  3. Model-Based Radiation Dose Correction for Yttrium-90 Microsphere Treatment of Liver Tumors With Central Necrosis

    SciTech Connect

    Liu, Ching-Sheng; Lin, Ko-Han; Lee, Rheun-Chuan; Tseng, Hsiou-Shan; Wang, Ling-Wei; Huang, Pin-I; Chao, Liung-Sheau; Chang, Cheng-Yen; Yen, Sang-Hue; Tung, Chuan-Jong; Wang, Syh-Jen; Oliver Wong, Ching-yee

    2011-11-01

    Purpose: The objectives of this study were to model and calculate the absorbed fraction {phi} of energy emitted from yttrium-90 ({sup 90}Y) microsphere treatment of necrotic liver tumors. Methods and Materials: The tumor necrosis model was proposed for the calculation of {phi} over the spherical shell region. Two approaches, the semianalytic method and the probabilistic method, were adopted. In the former method, the range--energy relationship and the sampling of electron paths were applied to calculate the energy deposition within the target region, using the straight-ahead and continuous-slowing-down approximation (CSDA) method. In the latter method, the Monte Carlo PENELOPE code was used to verify results from the first method. Results: The fraction of energy, {phi}, absorbed from {sup 90}Y by 1-cm thickness of tumor shell from microsphere distribution by CSDA with complete beta spectrum was 0.832 {+-} 0.001 and 0.833 {+-} 0.001 for smaller (r{sub T} = 5 cm) and larger (r{sub T} = 10 cm) tumors (where r is the radii of the tumor [T] and necrosis [N]). The fraction absorbed depended mainly on the thickness of the tumor necrosis configuration, rather than on tumor necrosis size. The maximal absorbed fraction {phi} that occurred in tumors without central necrosis for each size of tumor was different: 0.950 {+-} 0.000, and 0.975 {+-} 0.000 for smaller (r{sub T} = 5 cm) and larger (r{sub T} = 10 cm) tumors, respectively (p < 0.0001). Conclusions: The tumor necrosis model was developed for dose calculation of {sup 90}Y microsphere treatment of hepatic tumors with central necrosis. With this model, important information is provided regarding the absorbed fraction applicable to clinical {sup 90}Y microsphere treatment.

  4. Favorable Prognosis in Patients With High-Grade Glioma With Radiation Necrosis: The University of Colorado Reoperation Series

    SciTech Connect

    Rusthoven, Kyle E.; Olsen, Christine; Franklin, Wilbur; Kleinschmidt-DeMasters, B.K.; Kavanagh, Brian D.; Gaspar, Laurie E.; Lillehei, Kevin; Waziri, Allen; Damek, Denise M.; Chen, Changhu

    2011-09-01

    Purpose: To analyze the pathology, outcomes, and prognostic factors in patients with high-grade glioma undergoing reoperation after radiotherapy (RT). Methods and Materials: Fifty-one patients with World Health Organization Grade 3-4 glioma underwent reoperation after prior RT. The median dose of prior RT was 60 Gy, and 84% received chemotherapy as part of their initial treatment. Estimation of the percentage of necrosis and recurrent tumor in each reoperation specimen was performed. Pathology was classified as RT necrosis if {>=}80% of the specimen was necrotic and as tumor recurrence if {>=}20% was tumor. Predictors of survival were analyzed using log-rank comparisons and Cox proportional hazards regression. Results: The median interval between the completion of RT and reoperation was 6.7 months (range, 1-59 months). Pathologic analysis showed RT necrosis in 27% and recurrence in 73% of cases. Thirteen patients required a reoperation for uncontrolled symptoms. Among them, 1 patient (8%) had pathology showing RT necrosis, and 12 (92%) had tumor recurrence. Median survival after reoperation was longer for patients with RT necrosis (21.8 months vs. 7.0 months, p = 0.047). In 7 patients with Grade 4 tumors treated with temozolomide-based chemoradiation with RT necrosis, median survival from diagnosis and reoperation were 30.2 months and 21.8 months, respectively. Conclusions: Patients with RT necrosis at reoperation have improved survival compared with patients with tumor recurrence. Future efforts to intensify local therapy and increase local tumor control in patients with high-grade glioma seem warranted.

  5. The 55-kD tumor necrosis factor receptor on human keratinocytes is regulated by tumor necrosis factor-alpha and by ultraviolet B radiation.

    PubMed Central

    Trefzer, U; Brockhaus, M; Lötscher, H; Parlow, F; Budnik, A; Grewe, M; Christoph, H; Kapp, A; Schöpf, E; Luger, T A

    1993-01-01

    In previous studies we showed that cultured human keratinocytes expressed the 55-kD TNF receptor (TNFR) and that its expression the important for TNF alpha-mediated upregulation of intercellular adhesion molecule-1 (ICAM-1) expression on keratinocytes. Because factors that either reduce or enhance TNFR expression are likely to have a major impact on the biological effects of TNF alpha on keratinocytes, these studies were conducted to determine the factors that regulate its expression on keratinocytes. Using reverse transcriptase polymerase chain reaction, human keratinocytes were shown to lack 75-kD TNFR expression, indicating that TNF responsiveness of human keratinocytes critically depended on regulation of 55-kD TNFR expression. Human keratinocyte 55-kD TNFR surface and mRNA expression was found to be regulated in vitro by recombinant human (rh) TNF alpha. Stimulation of keratinocytes with rhTNF alpha initially decreased, but later increased, 55-kD TNFR surface expression. This biphasic modulation of 55-kD TNFR surface expression was associated with concomitant changes in 55-kD TNFR mRNA expression. Ultraviolet B (UVB) radiation, a well-known inducer of synthesis and secretion of TNF alpha by human keratinocytes, was found to mimic TNF alpha-induced modulation of 55-kD TNFR surface and mRNA expression via a TNF alpha-mediated autocrine regulatory mechanism. Production of soluble 55-kD TNFR by human keratinocytes remained unaffected by TNF alpha stimulation or UVB irradiation. These studies provide clear evidence that membrane expression of the human 55-kD TNFR may be regulated in human keratinocytes by the ligand itself: TNF alpha. Since in previous studies UVB irradiation transiently inhibited TNF alpha-induced human keratinocyte ICAM-1 expression, it is proposed that UVB radiation-induced biphasic modulation of human keratinocyte 55-kD TNFR expression may affect the capacity of these cells to respond to TNF alpha. Images PMID:8392091

  6. NOS Inhibition Modulates Immune Polarization and Improves Radiation-Induced Tumor Growth Delay.

    PubMed

    Ridnour, Lisa A; Cheng, Robert Y S; Weiss, Jonathan M; Kaur, Sukhbir; Soto-Pantoja, David R; Basudhar, Debashree; Heinecke, Julie L; Stewart, C Andrew; DeGraff, William; Sowers, Anastasia L; Thetford, Angela; Kesarwala, Aparna H; Roberts, David D; Young, Howard A; Mitchell, James B; Trinchieri, Giorgio; Wiltrout, Robert H; Wink, David A

    2015-07-15

    Nitric oxide synthases (NOS) are important mediators of progrowth signaling in tumor cells, as they regulate angiogenesis, immune response, and immune-mediated wound healing. Ionizing radiation (IR) is also an immune modulator and inducer of wound response. We hypothesized that radiation therapeutic efficacy could be improved by targeting NOS following tumor irradiation. Herein, we show enhanced radiation-induced (10 Gy) tumor growth delay in a syngeneic model (C3H) but not immunosuppressed (Nu/Nu) squamous cell carcinoma tumor-bearing mice treated post-IR with the constitutive NOS inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME). These results suggest a requirement of T cells for improved radiation tumor response. In support of this observation, tumor irradiation induced a rapid increase in the immunosuppressive Th2 cytokine IL10, which was abated by post-IR administration of L-NAME. In vivo suppression of IL10 using an antisense IL10 morpholino also extended the tumor growth delay induced by radiation in a manner similar to L-NAME. Further examination of this mechanism in cultured Jurkat T cells revealed L-NAME suppression of IR-induced IL10 expression, which reaccumulated in the presence of exogenous NO donor. In addition to L-NAME, the guanylyl cyclase inhibitors ODQ and thrombospondin-1 also abated IR-induced IL10 expression in Jurkat T cells and ANA-1 macrophages, which further suggests that the immunosuppressive effects involve eNOS. Moreover, cytotoxic Th1 cytokines, including IL2, IL12p40, and IFNγ, as well as activated CD8(+) T cells were elevated in tumors receiving post-IR L-NAME. Together, these results suggest that post-IR NOS inhibition improves radiation tumor response via Th1 immune polarization within the tumor microenvironment. PMID:25990221

  7. Evidence for factors modulating radiation-induced G2-delay: potential application as radioprotectors

    NASA Technical Reports Server (NTRS)

    Cheong, N.; Zeng, Z. C.; Wang, Y.; Iliakis, G.

    2001-01-01

    Manipulation of checkpoint response to DNA damage can be developed as a means for protecting astronauts from the adverse effects of unexpected, or background exposures to ionizing radiation. To achieve this goal reagents need to be developed that protect cells from radiation injury by prolonging checkpoint response, thus promoting repair. We present evidence for a low molecular weight substance excreted by cells that dramatically increases the duration of the G2-delay. This compound is termed G2-Arrest Modulating Activity (GAMA). A rat cell line (A1-5) generated by transforming rat embryo fibroblasts with a temperature sensitive form of p53 plus H-ras demonstrates a dramatic increase in radiation resistance after exposure to low LET radiation that is not associated with an increase in the efficiency of rejoining of DNA double strand breaks. Radioresistance in this cell line correlates with a dramatic increase in the duration of the G2 arrest that is modulated by a GAMA produced by actively growing cells. The properties of GAMA suggest that it is a low molecular weight heat-stable peptide. Further characterization of this substance and elucidation of its mechanism of action may allow the development of a biological response modifier with potential applications as a radioprotector. GAMA may be useful for protecting astronauts from radiation injury as preliminary evidence suggests that it is able to modulate the response of cells exposed to heavy ion radiation, similar to that encountered in outer space.

  8. Biophysical modelling of early and delayed radiation damage at chromosome level

    NASA Astrophysics Data System (ADS)

    Andreev, S.; Eidelman, Y.

    Exposure by ionising radiation increases cancer risk in human population Cancer is thought to originate from an altered expression of certain number of specific genes It is now widely recognised that chromosome aberrations CA are involved in stable change in expression of genes by gain or loss of their functions Thus CA can contribute to initiation or progression of cancer Therefore understanding mechanisms of CA formation in the course of cancer development might be valuable tool for quantification and prognosis of different stages of radiation carcinogenesis Early CA are defined as aberrations induced in first post-irradiation mitotic cycle The present work describes the original biophysical technique for early CA modelling It includes the following simulation steps the ionising particle track structure the structural organisation of all chromosomes in G 0 G 1 cell nucleus spatial distribution of radiation induced DNA double-strand breaks dsb within chromosomes dsb rejoining and misrejoining modelling cell cycle taking into account mitotic delay which results in complex time dependence of aberrant cells in first mitosis The results on prediction of dose-response curves for simple and complex CA measured in cells undergoing first division cycle are presented in comparison with recent experimental data There is increasing evidence that CA are also observed in descendents of irradiated cells many generations after direct DNA damage These delayed CA or chromosome instability CI are thought to be a manifestation of genome

  9. Action Spectrum for Growth Delay Induced in Escherichia coli B/r by Far-Ultraviolet Radiation

    PubMed Central

    Takebe, Hiraku; Jagger, John

    1969-01-01

    An action spectrum for growth delay induced in Escherichia coli B/r by far-ultraviolet radiation (230 to 295 nm) was obtained. It resembles the action spectrum for killing obtained in the same experiments, indicating that the chromophore for growth delay is probably the same as the chromophore for killing. Another action spectrum for killing, obtained under conditions more suitable for chromophore identification, suggests that nucleic acid, either deoxyribonucleic acid or ribonucleic acid, is the chromophore for growth delay induced by far ultraviolet. Isoprenoid quinones, which seem to be important chromophores for growth delay induced by near-ultraviolet radiation (above 300 nm), appear to play a negligible role in growth delay induced by wavelengths below 300 nm. PMID:4891265

  10. Comparative study of cell cycle kinetics and induction of apoptosis or necrosis after exposure of human Mono Mac 6 cells to radiofrequency radiation.

    PubMed

    Lantow, M; Viergutz, T; Weiss, D G; Simkó, M

    2006-09-01

    The possible harmful effects of radiofrequency electromagnetic fields (RF EMFs) are controversial. We have used human Mono Mac 6 cells to investigate the influence of RF EMFs in vitro on cell cycle alterations and BrdU uptake, as well as the induction of apoptosis and necrosis in human Mono Mac 6 cells, using flow cytometry after exposure to a 1,800 MHz, 2 W/kg specific absorption rate (SAR), GSM-DTX signal for 12 h. No statistically significant differences in the induction of apoptosis or necrosis, cell cycle kinetics, or BrdU uptake were detected after RF EMF exposure compared to sham or incubator controls. However, in the positive control cells treated with gliotoxin and PMA (phorbol 12 myristate-13 acetate), a significant increase in apoptotic and necrotic cells was seen. Cell cycle analysis or BrdU incorporation for 72 h showed no differences between RF EMF- or sham-exposed cells, whereas PMA treatment induced a significant accumulation of cells in G(0)/G(1)-phase and a reduction in S-phase cells. RF EMF radiation did not induce cell cycle alterations or changes in BrdU incorporation or induce apoptosis and necrosis in Mono Mac 6 cells under the exposure conditions used. PMID:16953672

  11. Successful Mitigation of Delayed Intestinal Radiation Injury Using Pravastatin is not Associated with Acute Injury Improvement or Tumor Protection

    SciTech Connect

    Haydont, Valerie; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine |. E-mail: vozenin@igr.fr

    2007-08-01

    Purpose: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition. Methods and Materials: Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments. Results: Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury. Conclusion: Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible.

  12. Mechanism of growth delay induced in Escherichia coli by near ultraviolet radiation.

    PubMed Central

    Ramabhadran, T V; Jagger, J

    1976-01-01

    Continuously growing cultures of E. coli B/r were irradiated with a fluence of broad-band near-ultraviolet radiation (315-405 nm) sufficient to cause extensive growth delay and complete cessation of net RNA synthesis. Chloramphenicol treatment was found to stimulate resumption of RNA synthesis, similar to that observed with chloramphenicol treatment after amino-acid starvation. E. coli strains in which amino-acid starvation does not result in cessation of RNA synthesis ("relaxed" or rel- strains) show no cessation of growth and only a slight effect on the rate of growth or of RNA synthesis. These findings show that such near-UV fluences do not inactivate the RNA synthetic machinery but affect the regulation of RNA synthesis, in a manner similat to that produced by amino-acid starvation. Such regulation is believed to be mediated through alterations in concentration of guanosine tetraphosphate (ppGpp), and our estimations of ppGpp after near-UV irradiation are consistent with such an interpretation. These data, combined with earlier published data, strongly suggest that the mechanism of near-UV-induced growth delay in E. coli involves partial inactivation of certain tRNA species, which is interpreted by the cell in a manner similar to that of amino-acid starvation, causing a rise in ppGpp levels, a shut-off of net RNA synthesis, and the induction of a growth delay. Images PMID:1108019

  13. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    A long-standing dogma in the radiation sciences is that energy from radiation must be deposited in the cell nucleus to elicit a biological effect. A number of non-targeted, delayed effects of ionizing radiation have been described that challenge this dogma and pose new challenges to evaluating potential hazards associated with radiation exposure. These effects include induced genomic instability and non-targeted bystander effects. The in vitro evidence for non-targeted effects in radiation biology will be reviewed, but the question as to how one extrapolates from these in vitro observations to the risk of radiation-induced adverse health effects such as cancer remains open.

  14. Asymptomatic Evolution and Regression of Temporal Lobe Necrosis After Adjuvant Radiation for Skin Cancer: A Case Report and Review of Literature

    PubMed Central

    Bahl, Gaurav

    2016-01-01

    Temporal Lobe Necrosis (TLN) is not an expected complication of adjuvant radiation therapy (RT) for skin cancers and has become uncommon otherwise in daily practice due to improved RT planning and modern delivery techniques. TLN is a great mimic and can be mistaken for disease recurrence, metastasis to the brain, or high grade primary brain tumor. This case report demonstrates the importance of diagnosing the entity, its natural evolution, and dosimetric correlation with published constraints.​ It emphasizes the importance of thorough clinical examination on follow-up and review of previous radiation plan when encountered with challenging differentials. We also provide a review of clinical presentations, imaging modalities, and management options for patients with suspected TLN. PMID:27226935

  15. Delayed Workforce Entry and High Emigration Rates for Recent Canadian Radiation Oncology Graduates

    SciTech Connect

    Loewen, Shaun K.; Halperin, Ross; Lefresne, Shilo; Trotter, Theresa; Stuckless, Teri; Brundage, Michael

    2015-10-01

    Purpose: To determine the employment status and location of recent Canadian radiation oncology (RO) graduates and to identify current workforce entry trends. Methods and Materials: A fill-in-the-blank spreadsheet was distributed to all RO program directors in December 2013 and June 2014, requesting the employment status and location of their graduates over the last 3 years. Visa trainee graduates were excluded. Results: Response rate from program directors was 100% for both survey administrations. Of 101 graduates identified, 99 (98%) had known employment status and location. In the December survey, 5 2013 graduates (16%), 17 2012 graduates (59%), and 18 2011 graduates (75%) had permanent staff employment. Six months later, 5 2014 graduates (29%), 15 2013 graduates (48%), 24 2012 graduates (83%), and 21 2011 graduates (88%) had secured staff positions. Fellowships and temporary locums were common for those without staff employment. The proportion of graduates with staff positions abroad increased from 22% to 26% 6 months later. Conclusions: Workforce entry for most RO graduates was delayed but showed steady improvement with longer time after graduation. High emigration rates for jobs abroad signify domestic employment challenges for newly certified, Canadian-trained radiation oncologists. Coordination on a national level is required to address and regulate radiation oncologist supply and demand disequilibrium in Canada.

  16. Penile necrosis requiring penectomy complicating recto-urethral fistula post prostate cancer external beam radiation and brachytherapy.

    PubMed

    Kinahan, John; Pai, Howard; Martens, Mildred; Gray, Jason; Biberdorf, Darren; Mihailovic, Alex; McAuley, Iain

    2014-01-01

    Radiation therapy is a well-recognized treatment for unfavourable risk localized prostate cancer. Radiation induced recto-urethral fistulae are known rare complications particularly from brachytherapy. We report a case of a recto-urethral fistula 7 years post-external beam radiation and I-125 brachytherapy, which was complicated by a severe polymicrobial soft tissue infection. This infection required penectomy and pelvic exenteration with diverting colostomy, Indiana pouch urinary diversion and gracilis myo-cutaneuos flap closure of the perineum. PMID:24454604

  17. Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects

    NASA Technical Reports Server (NTRS)

    Morgan, William F.

    2003-01-01

    The goal of this review is to summarize the evidence for non-targeted and delayed effects of exposure to ionizing radiation in vivo. Currently, human health risks associated with radiation exposures are based primarily on the assumption that the detrimental effects of radiation occur in irradiated cells. Over the years a number of non-targeted effects of radiation exposure in vivo have been described that challenge this concept. These include radiation-induced genomic instability, bystander effects, clastogenic factors produced in plasma from irradiated individuals that can cause chromosomal damage when cultured with nonirradiated cells, and transgenerational effects of parental irradiation that can manifest in the progeny. These effects pose new challenges to evaluating the risk(s) associated with radiation exposure and understanding radiation-induced carcinogenesis.

  18. Time delays in the nonthermal radiation of solar flares according to observations of the CORONAS-F satellite

    NASA Astrophysics Data System (ADS)

    Tsap, Yu. T.; Stepanov, A. V.; Kashapova, L. K.; Myagkova, I. N.; Bogomolov, A. V.; Kopylova, Yu. G.; Goldvarg, T. B.

    2016-07-01

    In 2001-2003, the X-ray and microwave observations of ten solar flares of M- and X-classes were carried out by the CORONAS-F orbital station, the RSTN Sun service, and Nobeyama radio polarimeters. Based on these observations, a correlation analysis of time profiles of nonthermal radiation was performed. On average, hard X-ray radiation outstrips the microwave radiation in 9 events, i.e., time delays are positive. The appearance of negative delays is associated with effective scattering of accelerated electrons in pitch angles, where the length of the free path of a particle is less than the half-length of a flare loop. The additional indications are obtained in favor of the need to account for the effect of magnetic mirrors on the dynamics of energetic particles in the coronal arches.

  19. Modulation expression of tumor necrosis factor α in the radiation-induced lung injury by glycyrrhizic acid

    PubMed Central

    Refahi, Soheila; Pourissa, Masoud; Zirak, Mohammad Reza; Hadadi, GholamHassan

    2015-01-01

    To evaluate the ability of glycyrrhizic acid (GLA) to reduce the tumor necrosis factor α (TNF-α), release on messenger ribonucleic acid (mRNA) and protein production in the lungs using GLA in response to irradiation were studied. The animals were divided into four groups: No treatment (NT group), GLA treatment only (GLA group), irradiation only (XRT group), and GLA treatment plus irradiation (GLA/XRT group). Rats were killed at different time points. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of TNF-α in the lungs (compared with non-irradiated lungs). An enzyme-linked immunosorbant assay (ELISA) assay was used to measure the TNF-α protein level. The TNF-α mRNA expression in the lungs of the XRT rats was clearly higher at all-time points compared to the NT rats. The TNF-α mRNA expression in the lungs of the GLA/XRT rats was lower at all-time points compared to the XRT rats. Release of the TNF-α on protein level in the lungs of the XRT rats increased at all-time points compared to the NT rats. In contrast to the XRT rats, the lungs of the GLA/XRT rats revealed a reduction on TNF-α protein level at 6 h after irradiation. This study has clearly showed the immediate down-regulation of the TNF-α mRNA and protein production in the lungs using GLA in response to irradiation. PMID:26170556

  20. Detection of microvasculature alterations by synchrotron radiation in murine with delayed jellyfish envenomation syndrome.

    PubMed

    Wang, Beilei; Zhang, Bo; Huo, Hua; Wang, Tao; Wang, Qianqian; Wu, Yuanlin; Xiao, Liang; Ren, Yuqi; Zhang, Liming

    2014-04-01

    Using the tentacle extract (TE) from the jellyfish Cyanea capillata, we have previously established a delayed jellyfish envenomation syndrome (DJES) model, which is meaningful for clinical interventions against jellyfish stings. However, the mechanism of DJES still remains unclear. Thus, this study aimed to explore its potential mechanism by detecting TE-induced microvasculature alterations in vivo and ex vivo. Using a third-generation synchrotron radiation facility, we, for the first time, directly observed the blood vessel alterations induced by jellyfish venom in vivo and ex vivo. Firstly, microvasculature imaging of whole-body mouse in vivo indicated that the small blood vessel branches in the liver and kidney in the TE-treated group, seemed much thinner than those in the control group. Secondly, 3D imaging of kidney ex vivo showed that the kidneys in the TE-treated group had incomplete vascular trees where distal vessel branches were partly missing and disorderly disturbed. Finally, histopathological analysis found that obvious morphological changes, especially hemorrhagic effects, were also present in the TE-treated kidney. Thus, TE-induced microvasculature changes might be one of the important mechanisms of multiple organ dysfunctions in DJES. In addition, the methods we employed here will probably facilitate further studies on developing effective intervention strategies against DJES. PMID:24508769

  1. Effect of Dosimetric Factors on Occurrence and Volume of Temporal Lobe Necrosis Following Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma: A Case-Control Study

    SciTech Connect

    Zhou, Xin; Ou, Xiaomin; Xu, Tingting; Wang, Xiaosheng; Shen, Chunying; Ding, Jianhui; Hu, Chaosu

    2014-10-01

    Purpose: To determine dosimetric risk factors for the occurrence of temporal lobe necrosis (TLN) among nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT) and to investigate the impact of dose-volume histogram (DVH) parameters on the volume of TLN lesions (V-N). Methods and Materials: Forty-three NPC patients who had developed TLN following IMRT and 43 control subjects free of TLN were retrospectively assessed. DVH parameters included maximum dose (Dmax), minimum dose (Dmin), mean dose (Dmean), absolute volumes receiving specific dose (Vds) from 20 to 76 Gy (V20-V76), and doses covering certain volumes (Dvs) from 0.25 to 6.0 cm{sup 3} (D0.25-D6.0). V-Ns were quantified with axial magnetic resonance images. Results: DVH parameters were ubiquitously higher in temporal lobes with necrosis than in healthy temporal lobes. Increased Vds and Dvs were significantly associated with higher risk of TLN occurrence (P<.05). In particular, Vds at a dose of ≥70 Gy were found with the highest odds ratios. A common increasing trend was detected between V-N and DVH parameters through trend tests (P for trend of <.05). Linear regression analysis showed that V45 had the strongest predictive power for V-N (adjusted R{sup 2} = 0.305, P<.0001). V45 of <15.1 cm{sup 3} was relatively safe as the dose constraint for preventing large TLN lesions with V-N of >5 cm{sup 3}. Conclusions: Dosimetric parameters are significantly associated with TLN occurrence and the extent of temporal lobe injury. To better manage TLN, it would be important to avoid both focal high dose and moderate dose delivered to a large area in TLs.

  2. Validation of the cell cycle G2 delay assay in assessing ionizing radiation sensitivity and breast cancer risk

    PubMed Central

    Hill, Jeff W; Tansavatdi, Kristina; Lockett, Kristin L; Allen, Glenn O; Takita, Cristiane; Pollack, Alan; Hu, Jennifer J

    2009-01-01

    Genetic variations in cell cycle checkpoints and DNA repair genes are associated with prolonged cell cycle G2 delay following ionizing radiation (IR) treatment and breast cancer risk. However, different studies reported conflicting results examining the association between post-IR cell cycle delay and breast cancer risk utilizing four different parameters: cell cycle G2 delay index, %G2–M, G2/G0–G1, and (G2/G0–G1)/S. Therefore, we evaluated whether different parameters may influence study results using a data set from 118 breast cancer cases and 225 controls as well as lymphoblastoid and breast cancer cell lines with different genetic defects. Our results suggest that cell cycle G2 delay index may serve as the best parameter in assessing breast cancer risk, genetic regulation of IR-sensitivity, and mutations of ataxia telangiectasia mutated (ATM) and TP53. Cell cycle delay in 21 lymphoblastoid cell lines derived from BRCA1 mutation carriers was not different from that in controls. We also showed that IR-induced DNA-damage signaling, as measured by phosphorylation of H2AX on serine 139 (γ-H2AX) was inversely associated with cell cycle G2 delay index. In summary, the cellular responses to IR are extremely complex; mutations or genetic variations in DNA damage signaling, cell cycle checkpoints, and DNA repair contribute to cell cycle G2 delay and breast cancer risk. The cell cycle G2 delay assay characterized in this study may help identify subpopulations with elevated risk of breast cancer or susceptibility to adverse effects in normal tissue following radiotherapy. PMID:21188122

  3. Variable ultrasound trigger delay for improved magnetic resonance acoustic radiation force imaging

    NASA Astrophysics Data System (ADS)

    Mougenot, Charles; Waspe, Adam; Looi, Thomas; Drake, James M.

    2016-01-01

    Magnetic resonance acoustic radiation force imaging (MR-ARFI) allows the quantification of microscopic displacements induced by ultrasound pulses, which are proportional to the local acoustic intensity. This study describes a new method to acquire MR-ARFI maps, which reduces the measurement noise in the quantification of displacement as well as improving its robustness in the presence of motion. Two MR-ARFI sequences were compared in this study. The first sequence ‘variable MSG’ involves switching the polarity of the motion sensitive gradient (MSG) between odd and even image frames. The second sequence named ‘static MSG’ involves a variable ultrasound trigger delay to sonicate during the first or second MSG for odd and even image frames, respectively. As previously published, the data acquired with a variable MSG required the use of reference data acquired prior to any sonication to process displacement maps. In contrary, data acquired with a static MSG were converted to displacement maps without using reference data acquired prior to the sonication. Displacement maps acquired with both sequences were compared by performing sonications for three different conditions: in a polyacrylamide phantom, in the leg muscle of a freely breathing pig and in the leg muscle of pig under apnea. The comparison of images acquired at even image frames and odd image frames indicates that the sequence with a static MSG provides a significantly better steady state (p  <  0.001 based on a Student’s t-test) than the images acquired with a variable MSG. In addition no reference data prior to sonication were required to process displacement maps for data acquired with a static MSG. The absence of reference data prior to sonication provided a 41% reduction of the spatial distribution of noise (p  <  0.001 based on a Student’s t-test) and reduced the sensitivity to motion for displacements acquired with a static MSG. No significant differences were expected and

  4. Development and Characterization of a High Throughput Screen to investigate the delayed Effects of Radiations Commonly Encountered in Space

    NASA Astrophysics Data System (ADS)

    Morgan, W. F.

    Astronauts based on the space station or on long-term space missions will be exposed to high Z radiations in the cosmic environment In order to evaluate the potentially deleterious effects of exposure to radiations commonly encountered in space we have developed and characterized a high throughput assay to detect mutation deletion events and or hyperrecombination in the progeny of exposed cells This assay is based on a plasmid vector containing a green fluorescence protein reporter construct We have shown that after stable transfection of the vector into human or hamster cells this construct can identify mutations specifically base changes and deletions as well as recombination events e g gene conversion or homologous recombination occurring as a result of exposure to ionizing radiation Our focus has been on those events occurring in the progeny of an irradiated cell that are potentially associated with radiation induced genomic instability rather than the more conventional assays that evaluate the direct immediate effects of radiation exposure Considerable time has been spent automating analysis of surviving colonies as a function of time after irradiation in order to determine when delayed instability is induced and the consequences of this delayed instability The assay is now automated permitting the evaluation of potentially rare events associated with low dose low dose rate radiations commonly encountered in space

  5. Soft Tissue Necrosis in Head and Neck Cancer Patients After Transoral Robotic Surgery or Wide Excision With Primary Closure Followed by Radiation Therapy

    PubMed Central

    Yun Hee, Lee; Kim, Yeon Sil; Chung, Mi Joo; Yu, Mina; Jung, So Lyung; Yoo, Ie Ryung; Lee, Youn Soo; Kim, Min Sik; Sun, Dong Il; Kang, Jin Hyung

    2016-01-01

    Abstract Risk factors were evaluated for surgical bed soft tissue necrosis (STN) in head and neck cancer patients treated with postoperative radiation therapy (PORT) after transoral robotic surgery (TORS) or wide excision with primary closure. Sixty-seven patients were evaluated. STN was defined as ulceration and necrosis of the surgical bed or persistently unhealed high-grade acute mucositis with pain after PORT. The median RT dose of primary site was 63.6 Gy (range, 45–67.15 Gy) with 2 Gy/fx (range 1.8–2.2 Gy/fx). Total 41 patients (61.2%) were treated with concurrent chemoradiotherapy. The median follow-up period was 26 months. STN was diagnosed in 13 patients (19.4%). Most of the patients were treated with oral steroids, antibiotics, and analgesics and the lesions were eventually improved (median of 6 months after PORT). STN did not influence local control. A depth of invasion (DOI > 1.4 cm, odds ratio [OR] 14.04, p = 0.004) and maximum dose/fraction (CTVpmax/fx > 2.3 Gy, OR 6.344, p = 0.043) and grade 3 acute mucositis (OR 6.090, p = 0.054) were related to STN. The 12 (23.5%) of 51 oropharyngeal cancer patients presented STN, and the risk factors were DOI > 1.2 cm (OR 21.499, P = 0.005), CTVpmax/fx > 2.3 Gy (OR 12.972, P = 0.021) and grade 3 acute mucositis (OR 10.537, P = 0.052). Patients treated with TORS or WE with primary closure followed by PORT had a high risk of surgical bed STN. STN risk factors included DOI (>1.2–1.4 cm) and CTVpmax/fx (>2.3 Gy). Radiation therapy after TORS must be carefully designed to prevent STN. PMID:26945367

  6. Optically-switched submillimeter-wave oscillator and radiator having a switch-to-switch propagation delay

    NASA Technical Reports Server (NTRS)

    Spencer, Michael G. (Inventor); Maserjian, Joseph (Inventor)

    1995-01-01

    A submillimeter wave-generating integrated circuit includes an array of N photoconductive switches biased across a common voltage source and an optical path difference from a common optical pulse of repetition rate f sub 0 providing a different optical delay to each of the switches. In one embodiment, each incoming pulse is applied to successive ones of the N switches with successive delays. The N switches are spaced apart with a suitable switch-to-switch spacing so as to generate at the output load or antenna radiation of a submillimeter wave frequency f on the order of N f sub 0. Preferably, the optical pulse has a repetition rate of at least 10 GHz and N is of the order of 100, so that the circuit generates radiation of frequency of the order of or greater than 1 Terahertz.

  7. Identification and Characterization of Soluble Factors Involved in Delayed Effects of Low Dose Radiation. Final report

    SciTech Connect

    Baulch, Janet

    2013-09-11

    This is a 'glue grant' that was part of a DOE Low Dose project entitled 'Identification and Characterization of Soluble Factors Involved in Delayed Effects of Low Dose Radiation'. This collaborative program has involved Drs. David L. Springer from Pacific Northwest National Laboratory (PNNL), John H. Miller from Washington State University, Tri-cities (WSU) and William F. Morgan then from the University of Maryland, Baltimore (UMB). In July 2008, Dr. Morgan moved to PNNL and Dr. Janet E. Baulch became PI for this project at University of Maryland. In November of 2008, a one year extension with no new funds was requested to complete the proteomic analyses. The project stemmed from studies in the Morgan laboratory demonstrating that genomically unstable cells secret a soluble factor or factors into the culture medium, that cause cytogenetic aberrations and apoptosis in normal parental GM10115 cells. The purpose of this project was to identify the death inducing effect (DIE) factor or factors, estimate their relative abundance, identify the cell signaling pathways involved and finally recapitulate DIE in normal cells by exogenous manipulation of putative DIE factors in culture medium. As reported in detail in the previous progress report, analysis of culture medium from the parental cell line, and stable and unstable clones demonstrated inconsistent proteomic profiles as relate to candidate DIE factors. While the proposed proteomic analyses did not provide information that would allow DIE factors to be identified, the analyses provided another important set of observations. Proteomic analysis suggested that proteins associated with the cellular response to oxidative stress and mitochondrial function were elevated in the medium from unstable clones in a manner consistent with mitochondrial dysfunction. These findings correlate with previous studies of these clones that demonstrated functional differences between the mitochondria of stable and unstable clones. These

  8. High-Precision Time Delay Control with Continuous Phase Shifter for Pump-Probe Experiments Using Synchrotron Radiation Pulses

    SciTech Connect

    Tanaka, Yoshihito; Ohshima, Takashi; Moritomo, Yutaka; Tanaka, Hitoshi; Takata, Masaki

    2010-06-23

    Brilliant pulsed x-ray synchrotron radiation (SR) is useful for pump-probe experiment such as time-resolved x-ray diffraction, x-ray absorption fine structure, and x-ray spectroscopy. For laser pump-SR x-ray probe experiments, short pulsed lasers are generally synchronized to the SR master oscillator controlling the voltage for acceleration of electron bunches in an accelerator, and the interval between the laser and the SR pulses is changed around the time scale of target phenomenon. Ideal delay control produces any time delay as keeping the time-precision and pointing-stability of optical pulses at a sample position. We constructed the time delay control module using a continuous phase shifter of radio frequency signal and a frequency divider, which can produce the delayed trigger pulses to the laser without degradation of the time precision and the pointing stability. A picoseconds time-resolved x-ray diffraction experiment was demonstrated at SPring-8 storage ring for fast lattice response by femtosecond pulsed laser irradiation, and suggested the possibility of accurate sound velocity measurement. A delay control unit operating with subpicosecond precision has also been designed for femtosecond pump-probe experiments using a free electron laser at SPring-8 campus.

  9. Late Consequential Surgical Bed Soft Tissue Necrosis in Advanced Oropharyngeal Squamous Cell Carcinomas Treated With Transoral Robotic Surgery and Postoperative Radiation Therapy

    SciTech Connect

    Lukens, J. Nicholas; Lin, Alexander; Gamerman, Victoria; Mitra, Nandita; Grover, Surbhi; McMenamin, Erin M.; Weinstein, Gregory S.; O'Malley, Bert W.; Cohen, Roger B.; Orisamolu, Abimbola; Ahn, Peter H.; Quon, Harry

    2014-08-01

    Purpose: A subset of patients with oropharyngeal squamous cell carcinoma (OP-SCC) managed with transoral robotic surgery (TORS) and postoperative radiation therapy (PORT) developed soft tissue necrosis (STN) in the surgical bed months after completion of PORT. We investigated the frequency and risk factors. Materials and Methods: This retrospective analysis included 170 consecutive OP-SCC patients treated with TORS and PORT between 2006 and 2012, with >6 months' of follow-up. STN was defined as ulceration of the surgical bed >6 weeks after completion of PORT, requiring opioids, biopsy, or hyperbaric oxygen therapy. Results: A total of 47 of 170 patients (28%) had a diagnosis of STN. Tonsillar patients were more susceptible than base-of-tongue (BOT) patients, 39% (41 of 104) versus 9% (6 of 66), respectively. For patients with STN, median tumor size was 3.0 cm (range 1.0-5.6 cm), and depth of resection was 2.2 cm (range 1.0-5.1 cm). Median radiation dose and dose of fraction to the surgical bed were 6600 cGy and 220 cGy, respectively. Thirty-one patients (66%) received concurrent chemotherapy. Median time to STN was 2.5 months after PORT. All patients had resolution of STN after a median of 3.7 months. Multivariate analysis identified tonsillar primary (odds ratio [OR] 4.73, P=.01), depth of resection (OR 3.12, P=.001), total radiation dose to the resection bed (OR 1.51 per Gy, P<.01), and grade 3 acute mucositis (OR 3.47, P=.02) as risk factors for STN. Beginning May 2011, after implementing aggressive avoidance of delivering >2 Gy/day to the resection bed mucosa, only 8% (2 of 26 patients) experienced STN (all grade 2). Conclusions: A subset of OP-SCC patients treated with TORS and PORT are at risk for developing late consequential surgical bed STN. Risk factors include tonsillar location, depth of resection, radiation dose to the surgical bed, and severe mucositis. STN risk is significantly decreased with carefully avoiding a radiation dosage of >2 Gy/day to the

  10. Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids

    SciTech Connect

    Roden, D.; Bosley, T.M.; Fowble, B.; Clark, J.; Savino, P.J.; Sergott, R.C.; Schatz, N.J. )

    1990-03-01

    Thirteen patients with delayed radiation injury to the optic nerves and chiasm were treated with hyperbaric oxygen (HBO) and corticosteroids. These patients experienced painless, abrupt loss of vision in one (6 patients) or both (7 patients) eyes between 4 and 35 months after receiving radiation doses of at least 4500 cGy to the region of the chiasm. Diagnostic evaluation including neuro-imaging and lumbar puncture showed no recurrent tumor and no other cause for visual loss. No patient's vision improved during treatment or follow-up lasting between 1 and 4 years. There were no serious complications of treatment.

  11. The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor beta1 and tumor necrosis factor alpha.

    PubMed

    Xia, De-Hong; Xi, Lei; Xv, Chen; Mao, Wei-Dong; Shen, Wei-Sheng; Shu, Zhong-Qin; Yang, Hong-Zhi; Dai, Min

    2010-09-01

    The aim of this article was to investigate the effect of ambroxol on radiation lung injury and the expression of transforming growth factor beta(1) (TGF-beta(1)), as well as tumor necrosis factor alpha (TNF-alpha) in plasma. Totally, 120 patients with locally advanced lung cancer in radiotherapy were randomized into treatment and control groups. Patients in the treatment group took ambroxol orally at a dosage of 90 mg, three times per day for 3 months from the beginning of radiotherapy. The expression of TGF-beta(1) and TNF-alpha in plasma was analyzed. The clinical symptoms and lung diffusing capacity were monitored using high resolving power computed tomography. The level of TGF-beta(1) in the control group was increased (11.8 +/- 5.5 ng/ml), whereas in ambroxol-treated patients, the increase was not significant (5.6 +/- 2.6 ng/ml, P < 0.001). Radiotherapy-induced elevation of TNF-alpha levels, seen in control patients, was also abolished after treatment with ambroxol (5.1 +/- 1.0 vs. 2.4 +/- 0.8 ng/ml, P < 0.001). In the treatment group, carbon monoxide diffusion capacity was not significantly decreased at 6, 12, and 18 months post-radiotherapy, compared with the control group (P < 0.05). Ambroxol decreased the expression of TGF-beta(1) and TNF-alpha, and minimized the diminishment of lung diffusion capacity after radiotherapy. PMID:19636975

  12. Gating delays for two respiratory motion sensors in scanned particle radiation therapy

    NASA Astrophysics Data System (ADS)

    Steidl, P.; Haberer, T.; Durante, M.; Bert, C.

    2013-11-01

    Gating is one option for radiotherapy of tumours that move intrafractionally due to respiration. Delays of the motion monitoring system can lead to a shift of the gating window and thus slightly shifted dose distributions. We studied the delay of two motion monitoring systems which use the motion of the chest wall as surrogate for tumour motion. Delays and their dosimetric influence were determined against a precise motion acquisition system in a phantom study. The measurement data were supplemented by dedicated simulations of the experimental setup. Finally, the dosimetric influence for patient treatments was estimated for a lung tumour case using the extreme situation of a radiosurgery setting with a single field. We determined delays of 132 ± 18 ms and 103 ± 22 ms for the two systems. There was no significant difference between beam start and beam stop delay. Even for delays of 200 ms the dosimetric influence in a single-field radiosurgery setting is moderate (V95 = 96.5%, V107 = 8.5%, D5-D95 = 13%). We conclude, that the delay of the motion monitoring system should be part of the commissioning process for gated treatments. The dosimetric impact should be studied in detail prior treatments with a scanned ion beam.

  13. Role of tumor necrosis factor-alpha and TRAIL in high-dose radiation-induced bystander signaling in lung adenocarcinoma.

    PubMed

    Shareef, Mohammed M; Cui, Nuan; Burikhanov, Ravshan; Gupta, Seema; Satishkumar, Sabapathi; Shajahan, Shahin; Mohiuddin, Mohammed; Rangnekar, Vivek M; Ahmed, Mansoor M

    2007-12-15

    In the present study, ionizing radiation (IR)-induced bystander effects were investigated in two lung cancer cell lines. A549 cells were found to be more resistant to radiation-conditioned medium (RCM) obtained from A549 cells when compared with the H460 exposed to RCM procured from H460 cells. Significant release of tumor necrosis factor-alpha (TNF-alpha) was observed in A549 cells after IR/RCM exposure, and the survival was reversed with neutralizing antibody against TNF-alpha. In H460 cells, significant release of TNF-related apoptosis-inducing ligand (TRAIL), but not TNF-alpha, was observed in response to IR, RCM exposure, or RCM + 2Gy, and neutralizing antibody against TRAIL diminished clonogenic inhibition. Mechanistically, TNF-alpha present in RCM of A549 was found to mediate nuclear factor-kappaB (NF-kappaB) translocation to nucleus, whereas the soluble TRAIL present in RCM of H460 cells mobilized the nuclear translocation of PAR-4 (a proapoptotic protein). Analysis of IR-inducible early growth response-1 (EGR-1) function showed that EGR-1 was functional in A549 cells but not in H460 cells. A significant decrease in RCM-mediated apoptosis was observed in both A549 cells stably expressing small interfering RNA EGR-1 and EGR-1(-/-) mouse embryonic fibroblast cells. Thus, the high-dose IR-induced bystander responses in A549 may be dependent on the EGR-1 function and its target gene TNF-alpha. These findings show that the reduced bystander response in A549 cells is due to activation of NF-kappaB signaling by TNF-alpha, whereas enhanced response to IR-induced bystander signaling in H460 cells was due to release of TRAIL associated with nuclear translocation of PAR-4. PMID:18089811

  14. Innovative Hypofractionated Stereotactic Regimen Achieves Excellent Local Control with No Radiation Necrosis: Promising Results in the Management of Patients with Small Recurrent Inoperable GBM

    PubMed Central

    Pannullo, Susan C.; Minkowitz, Shlomo; Taube, Shoshana; Chang, Jenghwa; Parashar, Bhupesh; Christos, Paul; Wernicke, A.Gabriella

    2016-01-01

    Management of recurrent glioblastoma multiforme (GBM) remains a challenge. Several institutions reported that a single fraction of ≥ 20 Gy for small tumor burden results in excellent local control; however, this is at the expense of a high incidence of radiation necrosis (RN). Therefore, we developed a hypofractionation pattern of 33 Gy/3 fractions, which is a radiobiological equivalent of 20 Gy, with the aim to lower the incidence of RN. We reviewed records of 21 patients with recurrent GBM treated with hypofractionated stereotactic radiation therapy (HFSRT) to their 22 respective lesions. Sixty Gy fractioned external beam radiotherapy was performed as first-line treatment. Median time from primary irradiation to HFSRT was 9.6 months (range: 3.1 – 68.1 months). In HFSRT, a median dose of 33 Gy in 11 Gy fractions was delivered to the 80% isodose line that encompassed the target volume. The median tumor volume was 1.07 cm3 (range: 0.11 – 16.64 cm3). The median follow-up time after HFSRT was 9.3 months (range: 1.7 – 33.6 months). Twenty-one of 23 lesions treated (91.3%) achieved local control while 2/23 (8.7%) progressed. Median time to progression outside of the treated site was 5.2 months (range: 2.2 – 9.6 months). Progression was treated with salvage chemotherapy. Five of 21 patients (23.8%) were alive at the end of this follow-up; two patients remain disease-free. The remaining 16/21 patients (76.2%) died of disease. Treatment was well tolerated by all patients with no acute CTC/RTOG > Grade 2. There was 0% incidence of RN. A prospective trial will be underway to validate these promising results. PMID:27096136

  15. Can brain thallium 201 SPECT substitute for F-18-FDG PET in detecting recurrent brain tumor in the presence of radiation necrosis; correlation with biopsy/surgery results

    SciTech Connect

    Antar, M.A.; Barnett, G.H.; McIntyre, W.J.

    1994-05-01

    F-18-FDG PET man has been largely successful in differentiating between radiation necrosis and recurrent brain tumors. Because of the expense and unavailability of PET scanners in most clinical centers, Tl-201 SPECT scan may offer an alternative. Therefore, we have evaluated both techniques in 18 patients (13 men and 5 women) whose ages range from 28 to 74 year old. Eleven patients had glioblastoma multiformi and 4 patients high grade astrocytoma and 3 patient meningiosarcoma. All patients received radiation therapy (5500-6000 Rad) and 13 patients received also chemotherapy. PET scan was performed 40-60 min. after 5-10 mCi of F-18 FDG (i.v.) and SPECT 30 min. after 4.6 mCi of Tl-201 chloride (i.v.). Severe FDG hypometabolism was evident in the irradiated regions, in all patients. Evidence of tumor recurrence was seen in 15 patients by both FDG PET and Thallium 201 SPECT. The ratio of peak pixel uptake of suspected tumor to that of normal cortex for FDG ranged from 0.67 to 1.5 with a mean of 1.02. The ratio of peak pixel uptake of thallium 201 in the suspected lesion to that of the contralateral scalp area ranges from 0.8 to 1.9 with mean of 1.1. There was concordance between the findings of PET and SPECT in 16/18 patients. However, the volume of involvement differs in these patients; most likely secondary to different mechanisms of uptake and both studies may complement each other. Subsequent biopsy/surgery in 11 patients confirmed tumor recurrence in 10 out of 11 patients. The findings suggest that thallium 201 brain SPECT scan can provide similar (but not identical) information regarding brain tumor recurrence in these patients.

  16. Innovative Hypofractionated Stereotactic Regimen Achieves Excellent Local Control with No Radiation Necrosis: Promising Results in the Management of Patients with Small Recurrent Inoperable GBM.

    PubMed

    Jia, Angela; Pannullo, Susan C; Minkowitz, Shlomo; Taube, Shoshana; Chang, Jenghwa; Parashar, Bhupesh; Christos, Paul; Wernicke, A Gabriella

    2016-01-01

    Management of recurrent glioblastoma multiforme (GBM) remains a challenge. Several institutions reported that a single fraction of ≥ 20 Gy for small tumor burden results in excellent local control; however, this is at the expense of a high incidence of radiation necrosis (RN). Therefore, we developed a hypofractionation pattern of 33 Gy/3 fractions, which is a radiobiological equivalent of 20 Gy, with the aim to lower the incidence of RN. We reviewed records of 21 patients with recurrent GBM treated with hypofractionated stereotactic radiation therapy (HFSRT) to their 22 respective lesions. Sixty Gy fractioned external beam radiotherapy was performed as first-line treatment. Median time from primary irradiation to HFSRT was 9.6 months (range: 3.1 - 68.1 months). In HFSRT, a median dose of 33 Gy in 11 Gy fractions was delivered to the 80% isodose line that encompassed the target volume. The median tumor volume was 1.07 cm3 (range: 0.11 - 16.64 cm3). The median follow-up time after HFSRT was 9.3 months (range: 1.7 - 33.6 months). Twenty-one of 23 lesions treated (91.3%) achieved local control while 2/23 (8.7%) progressed. Median time to progression outside of the treated site was 5.2 months (range: 2.2 - 9.6 months). Progression was treated with salvage chemotherapy. Five of 21 patients (23.8%) were alive at the end of this follow-up; two patients remain disease-free. The remaining 16/21 patients (76.2%) died of disease. Treatment was well tolerated by all patients with no acute CTC/RTOG > Grade 2. There was 0% incidence of RN. A prospective trial will be underway to validate these promising results. PMID:27096136

  17. Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic Catastrophe and Tumor Growth Delay in Glioblastoma.

    PubMed

    Gordon, Ira K; Lu, Jie; Graves, Christian A; Huntoon, Kristin; Frerich, Jason M; Hanson, Ryan H; Wang, Xiaoping; Hong, Christopher S; Ho, Winson; Feldman, Michael J; Ikejiri, Barbara; Bisht, Kheem; Chen, Xiaoyuan S; Tandle, Anita; Yang, Chunzhang; Arscott, W Tristram; Ye, Donald; Heiss, John D; Lonser, Russell R; Camphausen, Kevin; Zhuang, Zhengping

    2015-07-01

    Protein phosphatase 2A (PP2A) is a tumor suppressor whose function is lost in many cancers. An emerging, though counterintuitive, therapeutic approach is inhibition of PP2A to drive damaged cells through the cell cycle, sensitizing them to radiotherapy. We investigated the effects of PP2A inhibition on U251 glioblastoma cells following radiation treatment in vitro and in a xenograft mouse model in vivo. Radiotherapy alone augmented PP2A activity, though this was significantly attenuated with combination LB100 treatment. LB100 treatment yielded a radiation dose enhancement factor of 1.45 and increased the rate of postradiation mitotic catastrophe at 72 and 96 hours. Glioblastoma cells treated with combination LB100 and radiotherapy maintained increased γ-H2AX expression at 24 hours, diminishing cellular repair of radiation-induced DNA double-strand breaks. Combination therapy significantly enhanced tumor growth delay and mouse survival and decreased p53 expression 3.68-fold, compared with radiotherapy alone. LB100 treatment effectively inhibited PP2A activity and enhanced U251 glioblastoma radiosensitivity in vitro and in vivo. Combination treatment with LB100 and radiation significantly delayed tumor growth, prolonging survival. The mechanism of radiosensitization appears to be related to increased mitotic catastrophe, decreased capacity for repair of DNA double-strand breaks, and diminished p53 DNA-damage response pathway activity. PMID:25939762

  18. Renal papillary necrosis

    MedlinePlus

    ... your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Ruggenenti P, Cravedi P, Remuzzi G. Microvascular and macrovascular diseases of the kidney. In: Taal MW, Chertow GM, ...

  19. Ionizing radiation accelerates Drp1-dependent mitochondrial fission, which involves delayed mitochondrial reactive oxygen species production in normal human fibroblast-like cells

    SciTech Connect

    Kobashigawa, Shinko; Suzuki, Keiji; Yamashita, Shunichi

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer We report first time that ionizing radiation induces mitochondrial dynamic changes. Black-Right-Pointing-Pointer Radiation-induced mitochondrial fission was caused by Drp1 localization. Black-Right-Pointing-Pointer We found that radiation causes delayed ROS from mitochondria. Black-Right-Pointing-Pointer Down regulation of Drp1 rescued mitochondrial dysfunction after radiation exposure. -- Abstract: Ionizing radiation is known to increase intracellular level of reactive oxygen species (ROS) through mitochondrial dysfunction. Although it has been as a basis of radiation-induced genetic instability, the mechanism involving mitochondrial dysfunction remains unclear. Here we studied the dynamics of mitochondrial structure in normal human fibroblast like cells exposed to ionizing radiation. Delayed mitochondrial O{sub 2}{sup {center_dot}-} production was peaked 3 days after irradiation, which was coupled with accelerated mitochondrial fission. We found that radiation exposure accumulated dynamin-related protein 1 (Drp1) to mitochondria. Knocking down of Drp1 expression prevented radiation induced acceleration of mitochondrial fission. Furthermore, knockdown of Drp1 significantly suppressed delayed production of mitochondrial O{sub 2}{sup {center_dot}-}. Since the loss of mitochondrial membrane potential, which was induced by radiation was prevented in cells knocking down of Drp1 expression, indicating that the excessive mitochondrial fission was involved in delayed mitochondrial dysfunction after irradiation.

  20. Prevention of ultraviolet radiation-induced immunosuppression by sunscreen in Candida albicans-induced delayed-type hypersensitivity

    PubMed Central

    CHEN, QUAN; LI, RUNXIANG; ZHAO, XIAOXIA; LIANG, BIHUA; MA, SHAOYIN; LI, ZHENJIE; ZHU, HUILAN

    2016-01-01

    Ultraviolet (UV) radiation-induced immunosuppression leading to skin cancer has received increased attention in previous years. The present study aimed to investigate the immunoprotection offered by Anthelios sunscreen in a mouse model of Candida albicans-induced delayed-type hypersensitivity. Anthelios sunscreen was applied to the skin on the dorsal skin of BALB/c mice treated with a sub-erythema dose of solar-simulated radiation. Delayed-type hypersensitivity was induced by immunization with Candida albicans. Changes in the skin thickness of the foot pads were measured, and immunosuppression rates were also evaluated. The expression levels of CD207, CD80 and CD86 in the Langerhans cells were semi-quantitatively detected using Western blotting and immunohistochemical assays. The delayed-type hypersensitivity mouse model was successfully established. The minimal erythema doses of UVA and UVB exposure to the mice were 2,000 and 145 mJ/cm2, respectively. The immunosuppression rates in the sunscreen group and non-sunscreen group were 24.39 and 65.85%, respectively (P<0.01). The results of the Western blotting and immunohistochemistry showed that the expression levels of CD207 (P<0.01), CD80 (P<0.05) and CD86 (P<0.01) were higher in the sunscreen group, compared with those in the non-sunscreen group. UV exposure reduced Candida albicans antigen-induced delayed-type hypersensitivity. Anthelios sunscreen was found to protect the skin from immunosuppression through the activation of epidermal Langerhans cells. PMID:27175551

  1. Ultraviolet radiation-induced tumor necrosis factor alpha, which is linked to the development of cutaneous SCC, modulates differential epidermal microRNAs expression.

    PubMed

    Singh, Ashok; Willems, Estelle; Singh, Anupama; Hafeez, Bilal Bin; Ong, Irene M; Mehta, Suresh L; Verma, Ajit Kumar

    2016-04-01

    Chronic exposure to ultraviolet radiation (UVR) is linked to the development of cutaneous squamous cell carcinoma (SCC), a non-melanoma form of skin cancer that can metastasize. Tumor necrosis factor-alpha (TNFα), a pro-inflammatory cytokine, is linked to UVR-induced development of SCC. To find clues about the mechanisms by which TNFα may promote UVR-induced development of SCC, we investigated changes in the expression profiling of microRNAs (miRNA), a novel class of short noncoding RNAs, which affects translation and stability of mRNAs. In this experiment, TNFα knockout (TNFα KO) mice and their wild type (WT) littermates were exposed to acute UVR (2.0 kJ/m2) and the expression profiling of epidermal miRNA was determined 4hr post UVR exposure. TNFα deletion in untreated WT mice resulted in differential expression (log fold change>1) of seventeen miRNA. UVR exposure in WT mice induced differential expression of 22 miRNA. However, UVR exposure in TNFα KO mice altered only two miRNAs. Four miRNA, were differentially expressed between WT+UVR and TNFα KO+UVR groups. Differentially expressed selected miRNAs were further validated using real time PCR. Few of the differentially expressed miRNAs (miR-31-5p, miR-196a-5p, miR-127-3p, miR-206-3p, miR-411-5p, miR-709, and miR-322-5p) were also observed in UVR-induced SCC. Finally, bio-informatics analysis using DIANA, MIRANDA, Target Scan, and miRDB algorithms revealed a link with major UVR-induced pathways (MAPK, PI3K-Akt, transcriptional mis-regulation, Wnt, and TGF-beta). PMID:26918454

  2. Ultraviolet radiation-induced tumor necrosis factor alpha, which is linked to the development of cutaneous SCC, modulates differential epidermal microRNAs expression

    PubMed Central

    Singh, Ashok; Willems, Estelle; Singh, Anupama; Hafeez, Bilal Bin; Ong, Irene M.; Mehta, Suresh L.; Verma, Ajit Kumar

    2016-01-01

    Chronic exposure to ultraviolet radiation (UVR) is linked to the development of cutaneous squamous cell carcinoma (SCC), a non-melanoma form of skin cancer that can metastasize. Tumor necrosis factor-alpha (TNFα), a pro-inflammatory cytokine, is linked to UVR-induced development of SCC. To find clues about the mechanisms by which TNFα may promote UVR-induced development of SCC, we investigated changes in the expression profiling of microRNAs (miRNA), a novel class of short noncoding RNAs, which affects translation and stability of mRNAs. In this experiment, TNFα knockout (TNFα KO) mice and their wild type (WT) littermates were exposed to acute UVR (2.0 kJ/m2) and the expression profiling of epidermal miRNA was determined 4hr post UVR exposure. TNFα deletion in untreated WT mice resulted in differential expression (log fold change>1) of seventeen miRNA. UVR exposure in WT mice induced differential expression of 22 miRNA. However, UVR exposure in TNFα KO mice altered only two miRNAs. Four miRNA, were differentially expressed between WT+UVR and TNFα KO+UVR groups. Differentially expressed selected miRNAs were further validated using real time PCR. Few of the differentially expressed miRNAs (miR-31-5p, miR-196a-5p, miR-127-3p, miR-206-3p, miR-411-5p, miR-709, and miR-322-5p) were also observed in UVR-induced SCC. Finally, bio-informatics analysis using DIANA, MIRANDA, Target Scan, and miRDB algorithms revealed a link with major UVR-induced pathways (MAPK, PI3K-Akt, transcriptional mis-regulation, Wnt, and TGF-beta). PMID:26918454

  3. Radiation necrosis of the optic chiasm, optic tract, hypothalamus, and upper pons after radiotherapy for pituitary adenoma, detected by gadolinium-enhanced, T1-weighted magnetic resonance imaging: Case report

    SciTech Connect

    Tachibana, O.; Yamaguchi, N.; Yamashima, T.; Yamashita, J. )

    1990-10-01

    A 26-year-old woman was treated for a prolactin secreting pituitary adenoma by surgery and radiotherapy (5860 rads). Fourteen months later, she developed right hemiparesis and dysarthria. A T1-weighted magnetic resonance imaging scan using gadolinium contrast showed a small, enhanced lesion in the upper pons. Seven months later, she had a sudden onset of loss of vision, and radiation optic neuropathy was diagnosed. A T1-weighted magnetic resonance imaging scan showed widespread gadolinium-enhanced lesions in the optic chiasm, optic tract, and hypothalamus. Magnetic resonance imaging is indispensable for the early diagnosis of radiation necrosis, which is not visualized by radiography or computed tomography.

  4. Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

    SciTech Connect

    Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin . E-mail: mhjensen@life.uams.edu

    2006-04-01

    Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor {beta} immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent.

  5. Delayed vaginal reconstruction in the fibrotic pelvis following radiation or previous reconstruction

    SciTech Connect

    Berek, J.S.; Hacker, N.F.; Lagasse, L.D.; Smith, M.L.

    1983-06-01

    Vaginal reconstruction was performed in 14 patients who had developed vaginal stenosis secondary to extensive pelvic fibrosis after pelvic radiation therapy (12 patients) or prior vaginal reconstruction (2 patients). Sixteen procedures were performed using a split-thickness skin graft. All patients had satisfactory vaginal restoration, and 12 patients reported good vaginal function. No fistula developed as a result of the operative procedure, but one patient later developed a rectovaginal fistula resulting from tumor recurrence. Successful vaginal reconstruction can be achieved even years after initial therapy in patients who develop an obliterated vagina from previous radiation or surgery.

  6. Elevated levels of plasminogen activators in the pathogenesis of delayed radiation damage in rat cervical spinal cord in vivo

    SciTech Connect

    Sawaya, R.; Rayford, A.; Kono, S.; Rao, J.S.; Ang, K.K.; Feng, Y.; Stephens, L.C.

    1994-06-01

    The pathophysiology of the cellular basis of radiation-induced demyelination and white-matter necrosis of the central nervous system (CNS) is poorly understood. Preliminary data suggest that tissue damage is partly mediated through changes in the proteolytic enzymes. In this study, we irradiated rat cervical spinal cords with single doses of 24 Gy of 18 MV photons or 20 MeV electrons and measured the levels of plasminogen activators at days 2, 7, 30, 60, 90, 120, 130 and 145 after irradiation, using appropriate controls at each time. Fibrin zymography revealed fibrinolytic bands representing molecular weights of 68,000 and 48,000 in controls and irradiated samples; these bands increased significantly at days 120, 130 and 145 after irradiation. Inhibition of these enzymatic bands with specific antibodies against tissue-type plasminogen activator (tPA) and amiloride, an inhibitor for urokinase plasminogen activator (uPA), confirmed that these bands were tPA and uPA. Enzymatic levels quantified by densitometry showed a twofold elevation in the levels of tPA and more than a tenfold increase in uPA after 120 days` irradiation. Activity of uPA was increased threefold by day 2 and increased steadily with time compared to nonirradiated control samples. Enzyme-linked immunosorbent assay (ELISA) also showed a threefold increase in the tPA content in the extracts of irradiated rat cervical spinal cords at days 120, 130 and 145. This study adds additional information to the proposed role of plasminogen activators in the pathogenic pathways of radiation damage in the CNS. 38 refs., 6 figs.

  7. Deflection of polarised radiation - Relative phase delay technique. [photon geodesic motion variations

    NASA Technical Reports Server (NTRS)

    Dennison, B.; Melnick, G.; Harwit, M.; Sato, T.; Stelzried, C. T.; Jauncey, D.

    1978-01-01

    The article discusses the geodesic motion of photons, considering particularly whether oppositely polarized photons fall at the same rate. It is assumed that orthogonally polarized photons would be equally deflected by the gravitational field of a nonrotating mass. Upon the introduction of rotation, the angular momentum of the deflecting source couples to the photon spin through gravitational field action. Thus there arise separate trajectories for orthogonal polarizations. Searching for changes in polarization in a deflected beam is accomplished by a relative phase delay technique. If the beam is split into orthogonal linear polarization, final polarization is elliptical. Experiments have been performed on searching for ellipticity developments in the linearly polarized carrier waves from Helios 1 and 2, and the results are presented.

  8. Generation of chaotic radiation in a driven traveling wave tube amplifier with time-delayed feedback

    SciTech Connect

    Marchewka, Chad; Larsen, Paul; Bhattacharjee, Sudeep; Booske, John; Sengele, Sean; Ryskin, Nikita; Titov, Vladimir

    2006-01-15

    The application of chaos in communications and radar offers new and interesting possibilities. This article describes investigations on the generation of chaos in a traveling wave tube (TWT) amplifier and the experimental parameters responsible for sustaining stable chaos. Chaos is generated in a TWT amplifier when it is made to operate in a highly nonlinear regime by recirculating a fraction of the TWT output power back to the input in a delayed feedback configuration. A driver wave provides a constant external force to the system making it behave like a forced nonlinear oscillator. The effects of the feedback bandwidth, intensity, and phase are described. The study illuminates the different transitions to chaos and the effect of parameters such as the frequency and intensity of the driver wave. The detuning frequency, i.e., difference frequency between the driver wave and the natural oscillation of the system, has been identified as being an important physical parameter for controlling evolution to chaos. Among the observed routes to chaos, besides the more common period doubling, a new route called loss of frequency locking occurs when the driving frequency is adjacent to a natural oscillation mode. The feedback bandwidth controls the nonlinear dynamics of the system, particularly the number of natural oscillation modes. A computational model has been developed to simulate the experiments and reasonably good agreement is obtained between them. Experiments are described that demonstrate the feasibility of chaotic communications using two TWTs, where one is operated as a driven chaotic oscillator and the other as a time-delayed, open-loop amplifier.

  9. Cyclic nucleotide responses and radiation-induced mitotic delay in Physarum polycephalum

    SciTech Connect

    Daniel, J.W.; Oleinick, N.L.

    1984-02-01

    The response of the plasmodial levels of cyclic AMP and cyclic GMP in Physarum polycephalum to several putative phosphodiesterase inhibitors and to ionizing radiation has been measured. Isobutylmethylxanthine (2 mM) induces a rapid transient threefold elevation of cyclic AMP alone, with maximum response in about 10 min and return to the base line in about 30 min. Theophylline (2 mM) induces a rapid, sustained twofold elevation of cyclic GMP only. Caffeine (2mM) and Ro-20-1724 (18 ..mu..M) both elicit a rapid transient rise in cyclic AMP, resembling the isobutylmethylxanthine response, and a slow transient elevation of the cyclic GMP level. Of particular interest is the rapid threefold transient elevation of the cyclic AMP, but not of the cyclic GMP, level by ..gamma.. radiation.

  10. The reduction of radiation damage to the spinal cord by post-irradiation administration of vasoactive drugs

    SciTech Connect

    Hornsey, S.; Myers, R.; Jenkinson, T. )

    1990-06-01

    Radiation induced white matter necrosis in the rat spinal cord is preceded by changes in permeability of the blood brain-barrier, reduced blood flow, and infarction so that the necrosis is an ischemic necrosis. Attempts have been made to modify this developing pathology by the administration of drugs post-irradiation but just prior to the changes in vascular permeability. Verapamyl, a calcium channel blocker, had no effect on the development of ataxia. Dipyridamole, a drug which increases blood flow and reduces thrombosis, delayed and reduced the onset of ataxia. A low iron diet and desferrioxamine which reduces reperfusion injury also delayed and reduced ataxia. These results support the thesis that vascular changes are an important pathway in the development of radiation necrosis and that reperfusion injury is an important factor in the development and exacerbation of radiation damage to the spinal cord.

  11. Modelling radiation-induced cell death and tumour re-oxygenation: local versus global and instant versus delayed cell death

    NASA Astrophysics Data System (ADS)

    Gago-Arias, Araceli; Aguiar, Pablo; Espinoza, Ignacio; Sánchez-Nieto, Beatriz; Pardo-Montero, Juan

    2016-02-01

    The resistance of hypoxic cells to radiation, due to the oxygen dependence of radiosensitivity, is well known and must be taken into account to accurately calculate the radiation induced cell death. A proper modelling of the response of tumours to radiation requires deriving the distribution of oxygen at a microscopic scale. This usually involves solving the reaction-diffusion equation in tumour voxels using a vascularization distribution model. Moreover, re-oxygenation arises during the course of radiotherapy, one reason being the increase of available oxygen caused by cell killing, which can turn hypoxic tumours into oxic. In this work we study the effect of cell death kinetics in tumour oxygenation modelling, analysing how it affects the timing of re-oxygenation, surviving fraction and tumour control. Two models of cell death are compared, an instantaneous cell killing, mimicking early apoptosis, and a delayed cell death scenario in which cells can die shortly after being damaged, as well as long after irradiation. For each of these scenarios, the decrease in oxygen consumption due to cell death can be computed globally (macroscopic voxel average) or locally (microscopic). A re-oxygenation model already used in the literature, the so called full re-oxygenation, is also considered. The impact of cell death kinetics and re-oxygenation on tumour responses is illustrated for two radiotherapy fractionation schemes: a conventional schedule, and a hypofractionated treatment. The results show large differences in the doses needed to achieve 50% tumour control for the investigated cell death models. Moreover, the models affect the tumour responses differently depending on the treatment schedule. This corroborates the complex nature of re-oxygenation, showing the need to take into account the kinetics of cell death in radiation response models.

  12. Mathematics of Radiation Propagation in Planetary Atmospheres: Absorption, Refraction, Time Delay, Occultation, and Abel Inversion

    NASA Astrophysics Data System (ADS)

    Huestis, D. L.

    Forward integration calculation of air mass, refraction, and time delay requires care even for very smooth model atmospheres. The literature abounds in examples of injudicious approximations, assumptions, transformations, variable substitutions, and failures to verify that the formulas work with unlimited accuracy for simple cases and also survive challenges from mathematically pathological but physically realizable cases. A few years ago we addressed the problem of evaluation of the Chapman function for attenuation along a straight line path in an exponential atmosphere. In this presentation we will describe issues and approaches for integration over light paths curved by refraction. The inverse problem, determining the altitude profile of mass density (index of refraction) or the concentration of an individual chemical species (absorption), from occultation data, also has its mathematically interesting (i.e., difficult) aspects. Now we automatically have noise and thus statistical analysis is just as important as calculus and numerical analysis. Here we will describe a new approach of least-squares fitting occultation data to an expansion over compact basis functions. This approach, which avoids numerical differentiation and singular integrals, was originally developed to analyze laboratory imaging data.Forward integration calculation of air mass, refraction, and time delay requires care even for very smooth model atmospheres. The literature abounds in examples of injudicious approximations, assumptions, transformations, variable substitutions, and failures to verify that the formulas work with unlimited accuracy for simple cases and also survive challenges from mathematically pathological but physically realizable cases. A few years ago we addressed the problem of evaluation of the Chapman function for attenuation along a straight line path in an exponential atmosphere. In this presentation we will describe issues and approaches for integration over light paths

  13. Fat Necrosis and Oil Cysts

    MedlinePlus

    ... Previous Topic Granular cell tumors Next Topic Mastitis Fat necrosis and oil cysts Fat necrosis happens when ... lumpy area if it becomes bothersome. How do fat necrosis and oil cysts affect your risk for ...

  14. Cortical laminar necrosis following myocardial infarction.

    PubMed

    Lattanzi, Simona; Silvestrini, Mauro; Provinciali, Leandro

    2016-01-01

    The cortical laminar necrosis (CLN) is a permanent injury characterized by the selective delayed necrosis of the cerebral cortex, mainly of the third layer, and usually greater in the depths and sides of the sulci than over the crest of the gyri. The damage involves all cellular components - either neurons, glia cells and blood vessels - and results in a focal cortical band of pan-necrosis detectable in late sub-acute or chronic stages of reduced energy supply to the brain. The CLN has been described in different conditions as hypoxia, hypoglycemia and status epilepticus. At brain CT or MR scans it appears with pathognomonic highly hyperdense or T1-hyperintense lesions following the gyral anatomy of the cerebral cortex. We reported a case of CLN associated to myocardial infarct and discussed the underlying mechanisms. PMID:27375142

  15. Delayed activation of human microglial cells by high dose ionizing radiation.

    PubMed

    Chen, Hongxin; Chong, Zhao Zhong; De Toledo, Sonia M; Azzam, Edouard I; Elkabes, Stella; Souayah, Nizar

    2016-09-01

    Recent studies have shown that microglia affects the fate of neural stem cells in response to ionizing radiation, which suggests a role for microglia in radiation-induced degenerative outcomes. We therefore investigated the effects of γ-irradiation on cell survival, proliferation, and activation of microglia and explored associated mechanisms. Specifically, we evaluated cellular and molecular changes associated with exposure of human microglial cells (CHME5) to low and high doses of acute cesium-137 γ rays. Twenty-four hours after irradiation, cell cycle analyses revealed dose-dependent decreases in the fraction of cells in S and G2/M phase, which correlated with significant oxidative stress. By one week after irradiation, 20-30% of the cells exposed to high doses of γ rays underwent apoptosis, which correlated with significant concomitant decrease in metabolic activity as assessed by the MTT assay, and microglial activation as judged by both morphological changes and increased expression of Glut-5 and CR43. These changes were associated with increases in the mRNA levels for IL-1α, IL-10 and TNFα. Together, the results show that human CHME5 microglia are relatively resistant to low and moderate doses of γ rays, but are sensitive to acute high doses, and that CHME5 cells are a useful tool for in vitro study of human microglia. PMID:27265419

  16. Renal papillary necrosis

    MedlinePlus

    ... renal papillary necrosis, especially after taking over-the-counter pain medicines ... diabetes or sickle cell anemia may reduce your risk. To prevent renal ... over-the-counter pain relievers. Do not take more than the ...

  17. Gravitational time delay in orthogonally polarized radiation passing by the sun

    NASA Technical Reports Server (NTRS)

    Harwit, M.

    1979-01-01

    Two parallel investigations into the degree, if any, to which orthogonally polarized rays are deflected differently on passing through the gravitational field of the sun were previously conducted. The first involved very long and intermediate length baseline radio interferometry. The second was initially based on observations of radiation transmitted by the Pioneer 6 spacecraft, on passing behind the sun in 1968. This work was extended by using Helios-A and Helios-B spacecraft. It was calculated that the differential deflection between orthogonally polarized components is less than one part in 10 to the 7th power of the total gravitational deflection, or less than about 10 to the -7th power arc sec, in total.

  18. Gamma radiation and magnetic field mediated delay in effect of accelerated ageing of soybean.

    PubMed

    Kumar, Mahesh; Singh, Bhupinder; Ahuja, Sumedha; Dahuja, Anil; Anand, Anjali

    2015-08-01

    Soybean seeds were exposed to gamma radiation (0.5, 1, 3 and 5 kGy), static magnetic field (50, 100 and 200 mT) and a combination of gamma radiation and magnetic energy (0.5 kGy + 200 mT and 5 kGy + 50 mT) and stored at room temperature for six months. These seeds were later subjected to accelerated ageing treatment at 42 °C temperature and 95-100 % relative humidity and were compared for various physical and biochemical characteristics between the untreated and the energized treatments. Energy treatment protected the quality of stored seeds in terms of its protein and oil content . Accelerated aging conditions, however, affected the oil and protein quantity and quality of seed negatively. Antioxidant enzymes exhibited a decline in their activity during aging while the LOX activity, which reflects the rate of lipid peroxidation, in general, increased during the aging. Gamma irradiated (3 and 5 kGy) and magnetic field treated seeds (100 and 200 mT) maintained a higher catalase and ascorbate peroxidase activity which may help in efficient scavenging of deleterious free radical produced during the aging. Aging caused peroxidative changes to lipids, which could be contributed to the loss of oil quality. Among the electromagnetic energy treatments, a dose of 1-5 kGy of gamma and 100 mT, 200 mT magnetic field effectively slowed the rate of biochemical degradation and loss of cellular integrity in seeds stored under conditions of accelerated aging and thus, protected the deterioration of seed quality. Energy combination treatments did not yield any additional protection advantage. PMID:26243899

  19. Pancreatography after recovery from massive pancreatic necrosis.

    PubMed

    Howard, J M; Wagner, S M

    1989-01-01

    Massive retroperitoneal necrosis may follow life-threatening acute pancreatitis. At delayed operation, the surgeon may not be able to delineate dead pancreas from dead adipose tissue. The question arises: has "gloved hand" debridement resulted in pancreatectomy? The histologists report only "necrotic debris, of uncertain origin." To obtain objective data, pancreatography was performed in 13 patients, 10 weeks to 23 months after onset of massive pancreatic necrosis. Each patient had required delayed laparotomy for debridement and external drainage at some earlier stage of their illness. Pancreatography was correlated with the clinical assessment of diabetes and steatorrhea. Except in specific cases involving internal fistulae, pancreatography has not been previously reported in such patients. The results demonstrate that the main pancreatic duct usually maintained its normal length and configuration. Necrosis or stricture of the main duct, if it occurred, was more likely to be followed by diabetes. Steatorrhea was clinically detected in a single patient only. The necrotic tissue, up to several kilograms in wet weight, is largely dead adipose tissue. The pancreas, especially its head, is resistant to necrosis, much more resistant than is the retroperitoneal fat. PMID:2910213

  20. Correlations between radiation-induced double strand breaks, cell division delay, and cyclin-dependent signaling in x-irradiated NIH3T3 fibroblasts

    NASA Astrophysics Data System (ADS)

    Cariveau, Mickael J.

    2005-07-01

    Molecular responses to radiation-induced DNA double strand breaks (DSB) are mediated by the phosphorylation of the histone variant H2AX which forms identifiable gamma-H2AX foci at the site of the DSB. This event is thought to be linked with the down-regulation of signaling proteins contributing to the checkpoints regulating cell cycle progression and, vis-a-vis , the induction of cell division delay. However, it is unclear whether this division delay is directly related to the number of DSB (gamma-H2AX foci) sustained by an irradiated cell and, if so, whether this number drives cells into cell cycle delay or apoptosis. For this reason, studies were conducted in the immortalized NIH/3T3 fibroblast cell in order to establish correlations between the temporal appearance of the gamma-H2AX foci (a DSB) and the expression of the cell cycle regulatory proteins, cyclin E, A, B1, and their cyclin kinase inhibitor, p21. Cell cycle kinetics and flow cytometry were used to establish radiation-induced division delay over a dose range of 1--6 Gy where a mitotic delay of 2.65 min/cGy was established. Correlations between the expression of cyclin E, A, B1, p21, and the generation of DSB were established in NIH/3T3 cells exposed to 2 or 4 Gy x-irradiation. The data suggest that the G1/S and S phase delay (cyclin E and cyclin A protein levels) are dependent on the dose of radiation while the G2/M (cyclin B1 protein levels) delay is dependent on the quantity of DSB sustained by the irradiated cell.

  1. Radiation cataracts: mechanisms involved in their long delayed occurrence but then rapid progression

    PubMed Central

    Pendergrass, William; Singh, Narendra; Schwartz, Jeffrey

    2008-01-01

    Purpose This study was directed to assess the DNA damage and DNA repair response to X-ray inflicted lens oxidative damage and to investigate the subsequent changes in lens epithelial cell (LEC) behavior in vivo that led to long delayed but then rapidly developing cataracts. Methods Two-month-old C57Bl/6 female mice received 11 Grays (Gy) of soft x-irradiation to the head only. The animals’ eyes were examined for cataract status in 30 day intervals by slit lamp over an 11 month period post-irradiation. LEC migration, DNA fragment, free DNA retention, and reactive oxygen species (ROS) presence were established in the living lenses with fluorescent dyes using laser scanning confocal microscopy (LSCM). The extent and removal of initial LEC DNA damage were determined by comet assay. Immunohistochemistry was used to determine the presence of oxidized DNA and the response of a DNA repair protein in the lenses. Results This treatment resulted in advanced cortical cataracts that developed 5–11 months post-irradiation but then appeared suddenly within a 30 day period. The initially incurred DNA strand breaks were repaired within 30 min, but DNA damage remained as shown 72 h post-irradiation by the presence of the DNA adduct, 8-hydroxyguanosine (8-OHG), and a DNA repair protein, XRCC1. This was followed months later by abnormal behavior by LEC descendant cells with abnormal differentiation and migration patterns as seen with LSCM and fluorescent dyes. Conclusions The sudden development of cortical cataracts several months post-irradiation coupled with the above findings suggests an accumulation of damaged descendants from the initially x-irradiated LECs. As these cells migrate abnormally and leave acellular lens surface sites, eventually a crisis point may arrive for lens entry of environmental O2 with resultant ROS formation that overwhelms protection by resident antioxidant enzymes and results in the coagulation of lens proteins. The events seen in this study indicate

  2. Diffusion Tensor Imaging of Normal-Appearing White Matter as Biomarker for Radiation-Induced Late Delayed Cognitive Decline

    SciTech Connect

    Chapman, Christopher H.; Nagesh, Vijaya; Sundgren, Pia C.; Buchtel, Henry; Chenevert, Thomas L.; Junck, Larry; Lawrence, Theodore S.; Tsien, Christina I.; Cao, Yue

    2012-04-01

    Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). Methods and Materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. Results: In both structures, longitudinal diffusivity ({lambda}{sub Double-Vertical-Line }) decreased and perpendicular diffusivity ({lambda}{sub Up-Tack }) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum {lambda}{sub Up-Tack} at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in {lambda}{sub Up-Tack} at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum {lambda}{sub Double-Vertical-Line} (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum {lambda}{sub Double-Vertical-Line} changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.

  3. Radiative transfer theory with time delay for the effect of pulse entrapping in a resonant random medium: general transfer equation and point-like scatterer model

    NASA Astrophysics Data System (ADS)

    Barabanenkov, Yu N.; Barabanenkov, M. Yu

    1997-10-01

    A pulse propagation of a vector electromagnetic wave field in a discrete random medium under the condition of Mie resonant scattering is considered on the basis of the Bethe - Salpeter equation in the two-frequency domain in the form of an exact kinetic equation which takes into account the energy accumulation inside scatterers. The kinetic equation is simplified using the transverse field and far wave zone approximations which give a new general tensor radiative transfer equation with strong time delay by resonant scattering. This new general radiative transfer equation, being specified in terms of the low-density limit and the resonant point-like scatterer model, takes the form of a new tensor radiative transfer equation with three Lorentzian time-delay kernels by resonant scattering. In contrast to the known phenomenological scalar Sobolev equation with one Lorentzian time-delay kernel, the derived radiative transfer equation does take into account effects of (i) the radiation polarization, (ii) the energy accumulation inside scatterers, (iii) the time delay in three terms, namely in terms with the Rayleigh phase tensor, the extinction coefficient and a coefficient of the energy accumulation inside scatterers, respectively (i.e. not only in a term with the Rayleigh phase tensor). It is worth noting that the derived radiative transfer equation is coordinated with Poynting's theorem for non-stationary radiation, unlike the Sobolev equation. The derived radiative transfer equation is applied to study the Compton - Milne effect of a pulse entrapping by its diffuse reflection from the semi-infinite random medium when the pulse, while propagating in the medium, spends most of its time inside scatterers. This specific albedo problem for the derived radiative transfer equation is resolved in scalar approximation using a version of the time-dependent invariance principle. In fact, the scattering function of the diffusely reflected pulse is expressed in terms of a

  4. [Acute retinal necrosis].

    PubMed

    Lucke, K; Reinking, U; el-Hifnawi, E; Dennin, R H; Laqua, H

    1988-12-01

    The authors report on three patients with acute retinal necrosis who were treated with the virostatic agent Acyclovir and who underwent vitreoretinal surgery with silicone oil filling for total retinal detachment. In two eyes the retina was reattached, but useful vision was only preserved in one patient. Titers from blood and the vitreous, as well as microscopic findings in retinal biopsies, support the view that the necrosis is caused by a herpes simplex virus infection. After therapy with Acyclovir was instituted no further progression on the necrosis was observed. However, the development of retinal detachment could not be prevented. Early diagnosis and antiviral therapy are essential to improve the otherwise poor prognosis in this rare syndrome. PMID:3221657

  5. Lumbar corpectomy for correction of degenerative scoliosis from osteoradionecrosis reveals a delayed complication of lumbar myxopapillary ependymoma.

    PubMed

    Palejwala, Sheri K; Lawson, Kevin A; Kent, Sean L; Martirosyan, Nikolay L; Dumont, Travis M

    2016-08-01

    Osteoradionecrosis is a known complication following radiation therapy, presenting most commonly in the cervical spine as a delayed consequence of radiation that is often necessary in the management of head and neck cancers. In contrast, osteoradionecrosis has rarely been described in the lumbar spine. Here we describe, to our knowledge, the first reported case of lumbar spine osteoradionecrosis, after adjuvant radiation for a primary spinal cord tumor, leading to progressive degenerative scoliosis which required subsequent operative management. Established guidelines recommend that mature bone can tolerate a dose of up to 6000 cGy without injury. However, once bone has been exposed to radiation over this level progressive soft tissue changes may lead to devascularization, leaving the bone vulnerable to osteonecrosis, specifically when manipulated. Radiation necrosis can be progressive and lead to eventual mechanical instability requiring debridement and surgical fixation. In the setting of the lumbar spine, osseous necrosis can lead to biomechanical instability, deformity, pain, and neurologic deficit. PMID:27056674

  6. Subcutaneous encapsulated fat necrosis.

    PubMed

    Aydin, Dogu; Berg, Jais O

    2016-04-01

    We have described subcutaneous encapsulated fat necrosis, which is benign, usually asymptomatic and underreported. Images have only been published on two earlier occasions, in which the necrotic nodules appear "pearly" than the cloudy yellow surface in present case. The presented image may help future surgeons to establish the diagnosis peroperatively. PMID:27099753

  7. AT-41MULTI-CENTER CLINICAL TRIAL OF INTRAVENOUS ADMINISTRATION OF BEVACIZUMAB FOR THE TREATMENT OF RADIATION NECROSIS IN THE BRAIN TO OBTAIN NDA APPLICATION FOR ON LABEL USE IN JAPAN

    PubMed Central

    Miyatake, Shin-Ichi; Arakawa, Yoshiki; Miwa, Kazuhiro; Tsuboi, Koji; Iuchi, Toshihiko; Terasaka, Shunsuke; Tabei, Yusuke; Nakamura, Hideo; Nagane, Motoo; Sugiyama, Kazuhiko; Terasaki, Mizuhiko; Abe, Tatsuya; Mukasa, Akitake; Beppu, Takaaki; Furuse, Motomasa

    2014-01-01

    Recent radiotherapeutic modalities including particle radiotherapy, IMRT, and SRS are able to irradiate tumor tissue with high absorbed doses. These radiation therapies are promising to provide a longer survival in patients with CNS malignant tumors, compared to conventional X-ray radiotherapy. Simultaneously radiation necrosis (RN) has been a serious problem in such patients. However, there is no effective treatment for progressive RN so far. VEGF has been reported to play an important role in the progression of RN. Some clinical reports including ours demonstrate good results of bevacizumab treatment for RN. However, so far, no country gives a permission to use bevacizumab for symptomatic radiation necrosisin the brain as on label use. We initiated a nation-wide multicenter clinical trial in Japan, with the correct diagnosis of RN by amino-acid PET, to obtain a new drug approval (NDA) applications from Japanese FDA, based on public knowledge. Primary endpoint was the improvement of cerebral edema in periodic MRI. Secondary endpoint were safety, reduction of steroids, improvement of KPS and recurrence rate of RN within a year. The back ground of the patients are as follows; primary brain tumors such as GBM, metastatic brain tumors and head and neck cancers are 28 cases (68.3%), 12 cases (29.3%) and 1 case (2.4%), respectively. Applied radiation modalities are as follows; external beam radio-therapy 17 cases, SES 29 cases, hypo-fractionated IMRT 4 cases, proton beam particle radiation 3 cases and boron neutron capture therapy 1 case. Totally 41 cases of patients' enrollment finished. Last patient, last visit was in April 2014. The results are now opening and hopefully we can present them in SNO meeting.

  8. Delayed radiation-induced inflammation accompanying a marked carbohydrate antigen 19-9 elevation in a patient with resected pancreatic cancer

    PubMed Central

    Mattes, Malcolm D.; Cardinal, Jon S.; Jacobson, Geraldine M.

    2016-01-01

    Although carbohydrate antigen (CA) 19-9 is a useful tumor marker for pancreatic cancer, it can also become elevated from a variety of benign and malignant conditions. Herein we describe an unusual presentation of elevated CA 19-9 in an asymptomatic patient who had previously undergone adjuvant chemotherapy and radiation therapy for resected early stage pancreatic cancer. The rise in CA 19-9 might be due to delayed radiation-induced inflammation related to previous intra-abdominal radiation therapy with or without radiation recall induced by gemcitabine. After treatment with corticosteroids the CA 19-9 level decreased to normal, and the patient has not developed any evidence of recurrent cancer to date. PMID:27306770

  9. New cancer therapies and jaw necrosis.

    PubMed

    Patel, V; Kelleher, M; Sproat, C; Kwok, J; McGurk, M

    2015-09-11

    Osteonecrosis of the jaw (ONJ) has a number of causes, the most familiar being radiation or bisphosphonate induced. Various other novel anti-neoplastic and bone-targeting therapies that can also cause jaw necrosis have recently become available. This has led to the suggested acronym MRONJ for medication-related osteonecrosis of the jaw. This article summarises the available information on these drugs and their implications for the dental surgeon. PMID:26361116

  10. Delayed ejaculation

    MedlinePlus

    Ejaculatory incompetence; Sex - delayed ejaculation; Retarded ejaculation; Anejaculation; Infertility - delayed ejaculation ... include: Religious background that makes the person view sex as sinful Lack of attraction for a partner ...

  11. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

    SciTech Connect

    Heravi, Mitra; Kumala, Slawomir; Rachid, Zakaria; Jean-Claude, Bertrand J.; Radzioch, Danuta; Muanza, Thierry M.

    2015-06-01

    Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Western blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.

  12. Slow gamma photon with a doublet structure: Time delay via a transition from destructive to constructive interference of collectively scattered radiation with the incoming photon

    SciTech Connect

    Shakhmuratov, R. N.; Odeurs, J.; Kocharovskaya, O.

    2009-12-15

    Single gamma photon propagation in a dense absorptive medium with two widely spaced resonances is experimentally studied. After an initial fast decay, a revival of the photon amplitude in the form of a bump, exceeding the probability amplitude of the incident photon, is observed. The irradiation time of this bump delays approximately by the lifetime of the excited nuclei in the absorber. This effect is explained by the interference of the incoming radiation with the collectively scattered radiation, the phase of which is modulated with the frequency of the doublet splitting. Initially, the destructive interference changes to a constructive one, distinguishing the storage and retrieval stages of the photon propagation in a dense medium, i.e., the collective absorption and collective re-emission processes.

  13. Studies on the mechanism of systemic suppression of contact hypersensitivity by UVB radiation. II. Differences in the suppression of delayed and contact hypersensitivity in mice.

    PubMed

    Kripke, M L; Morison, W L

    1986-05-01

    Exposing mice to UV radiation in the UVB range (280-320 nm) causes a selective immune suppression that contributes to the development of UVB-induced skin cancers. Among the immune responses suppressed by UVB irradiation are contact and delayed hypersensitivity reactions to haptens administered at unexposed sites. In these studies we provide evidence that delayed and contact hypersensitivity to the same hapten are not equivalent reactions and that they are suppressed in UVB-irradiated mice by 2 different mechanisms. This conclusion is based on the findings that: suppression of contact hypersensitivity could not be overcome by immunizing UVB-irradiated mice with hapten-coupled antigen-presenting cells derived from normal donors; and treatment of UVB-irradiated mice with methylprednisolone before immunization prevented the suppression of delayed hypersensitivity but had no effect on the suppression of contact hypersensitivity. The decreased ability to induce contact hypersensitivity in UVB-irradiated mice could be transferred to x-irradiated mice by reconstituting them with spleen cells from UVB-irradiated donors. The induction of hapten-specific suppressor cells, however, required both UVB irradiation and priming with hapten. Based on these results, we postulate that UVB irradiation induces a population of suppressor-inducer cells with specificity for a modified skin antigen and that this antigen serves as a carrier molecule for haptens that induce contact hypersensitivity and for tumor-specific transplantation antigens on UVB-induced tumors. PMID:3745963

  14. Delayed massive soft tissue uptake of Tc-99m MDP after radiation therapy for cancer of the breast

    SciTech Connect

    Morrison, R.T.; Steuart, R.D.

    1995-09-01

    A patient with a history of breast cancer and known lung metastases was referred for a bone scan to investigate the cause of severe neck and right shoulder pain. The bone scan showed massive uptake of the radiopharmaceutical in the soft tissue surrounding the right shoulder. A review of the patient`s history indicated that the patient had undergone radiation therapy to the right upper thorax and breast area 14 months previously and an acute radiation dermatitis of the proximal right arm and shoulder had developed. This had long since resolved. Physical examination and plain radiographs of the right shoulder and humerus failed to demonstrated any abnormality. 6 refs., 1 fig.

  15. Delayed effects of low-dose radiation on cellular immunity in atomic bomb survivors residing in the United States.

    PubMed

    Bloom, E T; Akiyama, M; Kusunoki, Y; Makinodan, T

    1987-05-01

    Several parameters of cellular immune function were assessed among persons who survived the 1945 atomic bombs in Hiroshima and Nagasaki but who now reside in the United States. The subjects in this study were exposed to various low doses (T65D) of radiation at the time of the bomb. More than half received an estimated 0 Gy (S0 group). Of those exposed to more radiation (S+ group), nearly 90% received less than 0.50 Gy (50 rad). Lymphocytes were isolated from the peripheral blood of these individuals and were assessed for the following parameters of cellular immunity: mitogenic response to phytohemagglutinin, mitogenic response to allogeneic lymphocytes, natural cell-mediated cytotoxicity (NCMC), and interferon production. In every case, the response of the S+ group was greater than that of the S0 group, although only the difference for NCMC was statistically significant. Results of studies presently being performed on A-bomb survivors residing in Hiroshima do not confirm this difference. Therefore, it is difficult to say whether the increase in natural cytotoxicity observed among the American and not the Japanese A-bomb survivors exposed to very low doses of radiation is a hormetic effect which was modulated by post-radiation environmental conditions or a result of selective migration. PMID:3570796

  16. Walled-off pancreatic necrosis.

    PubMed

    Ramia, J M; de la Plaza, R; Quiñones-Sampedro, J E; Ramiro, C; Veguillas, P; García-Parreño, J

    2012-05-01

    Acute severe pancreatitits may be complicated by the development of 'walled-off pancreatic necrosis' (WOPN), which is characterised by a mixture of solid components and fluids on imaging studies as a consequence of organised pancreatic tissue necrosis. We present here an overview of the definition, clinical features, and diagnostic and therapeutic management of this clinical condition, which is mostly based on consensus as adequate clinical trials are lacking. PMID:22641624

  17. Delayed ejaculation

    MedlinePlus

    Ejaculatory incompetence; Sex - delayed ejaculation; Retarded ejaculation; Anejaculation ... include: Religious background that makes the person view sex as sinful Lack of attraction for a partner ...

  18. Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats

    PubMed Central

    Lybaert, Kelly; Moerman, Lieselotte; Descamps, Benedicte; Deblaere, Karel; Boterberg, Tom; Kalala, Jean-Pierre; Van den Broecke, Caroline; De Vos, Filip; Vanhove, Christian; Goethals, Ingeborg

    2016-01-01

    Background Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results. Methods Dynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed. Results The influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k3) in GB (0.07 min-1) compared to RN (0.04 min-1) (p = 0.017). K1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p = 0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN. Conclusions Based on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Using a 2-CM model more trapping of 18F-FDG was found in GB compared to RN. Secondly, the influx of 18F-FET was higher in GB compared to RN using a 1-CM model. Important correlations were found between SUV and kinetic or graphical measures for 18F-FDG and 18F-FET. 18F-FCho PET did not allow discrimination between GB and RN. PMID:27559736

  19. [Renal ultrasound in fat necrosis].

    PubMed

    Tizki, S; Lasry, F; Elftoiki, F Z; Hadj Khalifa, H; Itri, M; Khadir, K; Benchikhi, H

    2013-07-01

    Subcutaneous fat necrosis is an uncommon disease that may be complicated with potentially fatal hypercalcemia or with nephrocalcinosis. We report on the case of a patient with a history of significant perinatal asphyxia, hospitalized for a urinary tract infection. Lesions of subcutaneous fat necrosis were noted, with asymptomatic hypercalcemia at 3.9mmol/L. A renal ultrasound was performed and showed echogenic medullary pyramids bilaterally, consistent with nephrocalcinosis and left nephrolithiasis. The treatment of hypercalcemia included hyperhydration, a diuretic and corticosteroids. Progression was characterized by the total regression of skin lesions and normalization of serum calcium. Hypercalcemia is a rare complication of subcutaneous fat necrosis. It develops within days to weeks after the appearance of skin lesions. Nephrocalcinosis appears after several weeks or months. Hypercalcemia must be treated in due time to avoid the impact on the kidney. PMID:23726682

  20. Prevention of skin flap necrosis by a course of treatment with vasodilator drugs.

    PubMed

    Finseth, F; Adelberg, M G

    1978-05-01

    Large island skin flaps, comprising the entire abdominal covering in rats, were raised on one neurovascular pedicle in the groin. A standard area of necrosis was produced on the other side from the pedicle. However, when the animals were treated with certain vasodilator drugs for 15 days before and 7 days after the flaps were raised, there was little or no necrosis. The effect of the drug therapy was the same as a surgical delay. PMID:347479

  1. Widespread marrow necrosis during pregnancy

    SciTech Connect

    Knickerbocker, W.J.; Quenville, N.F.

    1982-11-01

    Recently, a 22-year-old Caucasian female was referred to our Hospital two days post-partum. She had been feeling unwell during the last few days of her pregnancy and complained of multiple aches and pains, worst in the abdomen and lower back. Her admission platelet count was severely depressed and a bone biopsy showed extensive marrow necrosis with viable bony trabeculae. There was no evidence of vasculitis, vascular thrombosis, or malignancy. Widespread marrow necrosis in pregnancy followed by recovery, to our knowledge, has not been previously reported.

  2. Black Anal Canal: Acute Necrosis

    PubMed Central

    Martins, Catarina; Gonçalves, Cláudia; Alves, Paulo; Gil, Inês; Canhoto, Manuela; Silva, Filipe; Cotrim, Isabel; Amado, Cristina; Eliseu, Liliana; Vasconcelos, Helena

    2016-01-01

    Acute ischemia of the rectum or anal canal resulting in necrosis is extremely uncommon because both the rectum and the anal canal have excellent blood supplies. We present a case with spontaneous necrosis of the anal canal without rectal involvement. Surgical debridement was accomplished, and the recovery was uneventful. The patient was elderly, with probable atherosclerotic arterial disease, and presented with hypotension. Due to the lack of other precipitating factors, the hypoperfusion hypothesis seems to be the most suitable in this case. To the best of our knowledge, no similar cases have been reported in the literature on this subject.

  3. Delayed discharge.

    PubMed

    Allen, Daniel

    2016-07-01

    Essential facts Delays in discharging older peo ple from hospital cost the NHS £820 million a year, according to a report from the National Audit Office (NAO). Last year in acute hospitals, 1.15 million bed days were lost to delayed transfers of care, an increase of 31% since 2013. The NAO says rising demand for NHS services is compounded by reduced local authority spending on adult social care - down by 10% since 2009-10. PMID:27380673

  4. Acute Esophageal Necrosis: An Update

    PubMed Central

    Inayat, Faisal; Hurairah, Abu; Virk, Hafeez Ul Hassan

    2016-01-01

    Acute esophageal necrosis (AEN) or “black esophagus” is a rare clinical entity with an unclear etiology. It is diagnosed at upper gastrointestinal endoscopy with the presence of strikingly black necrotic esophagus. The treatment is primarily medical, but the prognosis is generally poor due to advanced age and comorbid illnesses in patients who develop AEN. Herein, we discussed the implications of poor glycemic control in regards with AEN and undertook a literature review of this rare diagnosis. PMID:27583242

  5. [Talus necrosis and its treatment].

    PubMed

    Trauth, J; Bläsius, K

    1988-08-01

    Aetiopathogenesis of the necrosis of the talus has not yet been definitely clarified, and neither has that of the other aseptic necroses. We were able to study the aetiopathogenesis, course of the disease and therapy in 20 of our own patients by follow-up; two of these developed necrosis of the talus in both feet. We definitely excluded patients suffering from osteochondrosis dissecans. Even though fracture of the talus is on the whole relatively rare, it remains the most frequent cause of necrosis of the talus. We also found talonecrosis after surgical correction of clubfoot, after Sudeck's disease (Sudeck-Leriche syndrome, Sudeck's atrophy or dystrophy), suppurative arthritis of the ankle joint, subtalar luxation and haematogenic osteomyelitis. Only few patients required surgery. In most cases a special boot constructed for arthrodesis patients proved sufficient. Each patient developed arthrodesis to a different degree. Depending upon the complaints and stiffening of the ankle joint or of the talo-calcanonavicular joint, the capacity of the patients to be gainfully employed was reduced by an amount between 20 and 30 per cent. PMID:2905578

  6. Developmental delay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrition support is essential for the care of the child with developmental delay. After a thorough evaluation, an individualized intervention plan that accounts for the child’s nutrition status, feeding ability, and medical condition may be determined. Nutrition assessments may be performed at leas...

  7. [Evaluation of the risk of delayed adverse effects of chronic combined exposure to radiation and chemical factors with the purpose to ensure safety in orbital and exploration space missions].

    PubMed

    Shafirkin, A V; Mukhamedieva, L N; Tatarkin, S V; Barantseva, M Iu

    2012-01-01

    The work had the aim to anatomize the existing issues with providing safety in extended orbital and exploration missions for ensuing estimation of actual values of the total radiation risk for the crew, and risks of other delayed effects of simultaneous exposure to ionizing radiation and chemical pollutants in cabin air, and a number of other stressful factors inevitable in space flight. The flow of chronic experiments for separate and combined studies with reproduction of air makeup and radiation doses in actual orbital and predicted exploration missions is outlined. To set safety limits, new approaches should be applied to the description of gradual norm degradation to pathologies in addition to several generalized quantitative indices of adaptation and straining of the regulatory systems, as well as of effectiveness of the compensatory body reserve against separate and combined exposure. PMID:22624477

  8. Localized dose delivering by ion beam irradiation for experimental trial of establishing brain necrosis model.

    PubMed

    Takata, Takushi; Kondo, Natsuko; Sakurai, Yoshinori; Tanaka, Hiroki; Hasegawa, Takashi; Kume, Kyo; Suzuki, Minoru

    2015-11-01

    Localized dose delivery techniques to establish a brain radiation necrosis model are described. An irradiation field was designed by using accelerated protons or helium ions with a spread-out Bragg peak. Measurement of the designed field confirmed that a high dose can be confined to a local volume of an animal brain. The irradiation techniques described here are very useful for establishing a necrosis model without existence of extraneous complications. PMID:26454176

  9. Phosphorus Necrosis of the Jaw: A Present-day Study

    PubMed Central

    Hughes, J. P. W.; Baron, R.; Buckland, D. H.; Cooke, M. A.; Craig, J. D.; Duffield, D. P.; Grosart, A. W.; Parkes, P. W. J.; Porter, A.

    1962-01-01

    A historical note on the aetiology of phossy jaw shows that present-day knowledge is little greater than it was a century ago. The varied clinical course of the disease is described together with a report of 10 classical cases not previously reported. Six cases, not amounting to true necrosis but in which healing after dental extraction was delayed, and described, and mention is made of the noticeable differences in the oral state and appearances of tartar of healthy workmen exposed to phosphorus compared with healthy workmen not exposed. But no systematic differences of any kind were found in the incidence of general infections, fractures of bones, haematological findings, and biochemical studies of blood and urine in two groups of healthy men most exposed and least exposed to phosphorous in the same factory. An intensive study in hospital of a case of classical necrosis showed no departure from normal, except delayed healing following bone biopsy from the iliac crest, and a reversed polymorphonuclear/lymphocyte ratio. In the discussion the time of onset of necrosis after first exposure to phosphorus, clinical and radiological diagnosis, the organisms present, personal susceptibility, the appearance of the sequestra, and regeneration of bone are considered. An up-to-date note on prevention of the disease is given, although this has met with only partial success. Some persons are highly susceptible and, whilst complete protection is impossible in the light of our present knowledge, early diagnosis and modern treatment have robbed the disease of its terrible manifestations of Victorian times and turned it into a minor, although often uncomfortable complaint, with little or no resulting disability. Images PMID:14449812

  10. Acute oesophageal necrosis (black oesophagus).

    PubMed

    Galtés, Ignasi; Gallego, María Ángeles; Esgueva, Raquel; Martin-Fumadó, Carles

    2016-03-01

    A 54-year-old man was admitted to hospital after being found unconscious in his home. He had a history of alcoholism, multiple drug addictions, and type I diabetes mellitus. At admission, he had hyperglycaemia (550 mg/dL) with glucosuria and ketone bodies in the urine, along with septic shock refractory to bilateral alveolar infiltrates and severe respiratory failure. The patient died 24 hours post admission due to multiple organ failure, with diabetic ketoacidosis decompensated by possible respiratory infection in a patient with polytoxicomania. The autopsy confirmed the presence of acute bilateral bronchopneumonia, chronic pancreatitis, severe hepatic steatosis, and generalized congestive changes. At the oesophagus, acute oesophageal necrosis was evident. PMID:26949146

  11. Delaying obsolescence.

    PubMed

    Lawlor, Rob

    2015-04-01

    This paper argues that those who emphasise that designers and engineers need to plan for obsolescence are too conservative. Rather, in addition to planning for obsolescence, designers and engineers should also think carefully about what they could do in order delay obsolescence. They should so this by thinking about the design itself, thinking of ways in which products could be useful and appealing for longer before becoming obsolete, as well thinking about the wider context in terms of the marketing of products, and also the social and legal. The paper also considers objections that these suggestions are unrealistically idealistic, failing to recognise the economic realities. I respond to these objections appealing to research in advertising, psychology, cognitive linguistics, philosophy, history, and economics, as well as drawing on the Statement of Ethical Principles developed by the Royal Academy of Engineering and the Engineering Council. PMID:24792878

  12. Cell cycle delay in murine pre-osteoblasts is more pronounced after exposure to high-LET compared to low-LET radiation.

    PubMed

    Hu, Yueyuan; Hellweg, Christine E; Baumstark-Khan, Christa; Reitz, Günther; Lau, Patrick

    2014-03-01

    Space radiation contains a complex mixture of particles comprised primarily of protons and high-energy heavy ions. Radiation risk is considered one of the major health risks for astronauts who embark on both orbital and interplanetary space missions. Ionizing radiation dose-dependently kills cells, damages genetic material, and disturbs cell differentiation and function. The immediate response to ionizing radiation-induced DNA damage is stimulation of DNA repair machinery and activation of cell cycle regulatory checkpoints. To date, little is known about cell cycle regulation after exposure to space-relevant radiation, especially regarding bone-forming osteoblasts. Here, we assessed cell cycle regulation in the osteoblastic cell line OCT-1 after exposure to various types of space-relevant radiation. The relative biological effectiveness (RBE) of ionizing radiation was investigated regarding the biological endpoint of cellular survival ability. Cell cycle progression was examined following radiation exposure resulting in different RBE values calculated for a cellular survival level of 1 %. Our findings indicate that radiation with a linear energy transfer (LET) of 150 keV/μm was most effective in inducing reproductive cell killing by causing cell cycle arrest. Expression analyses indicated that cells exposed to ionizing radiation exhibited significantly up-regulated p21(CDKN1A) gene expression. In conclusion, our findings suggest that cell cycle regulation is more sensitive to high-LET radiation than cell survival, which is not solely regulated through elevated CDKN1A expression. PMID:24240273

  13. Thermal inactivation of infectious hematopoietic necrosis and infectious pancreatic necrosis virus

    USGS Publications Warehouse

    Gosting, L.; Gould, R.W.

    1981-01-01

    A plaque assay was used to follow the inactivation kinetics of infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus in cell culture media at various temperatures. Inactivation of infectious hematopoietic necrosis virus in a visceral organ slurry was compared with that in culture media.

  14. Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells

    PubMed Central

    Luce, Audrey; Courtin, Aurélie; Levalois, Céline; Altmeyer-Morel, Sandrine; Romeo, Paul-Henri; Lebeau, Jérôme

    2009-01-01

    Delayed cell death by mitotic catastrophe is a frequent mode of solid tumor cell death after γ-irradiation, a widely used treatment of cancer. Whereas the mechanisms that underlie the early γ-irradiation-induced cell death are well documented, those that drive the delayed cell death are largely unknown. Here we show that the Fas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and tumor necrosis factor (TNF)-α death receptor pathways mediate the delayed cell death observed after γ-irradiation of breast cancer cells. Early after irradiation, we observe the increased expression of Fas, TRAIL-R and TNF-R that first sensitizes cells to apoptosis. Later, the increased expression of FasL, TRAIL and TNF-α permit the apoptosis engagement linked to mitotic catastrophe. Treatments with TNF-α, TRAIL or anti-Fas antibody, early after radiation exposure, induce apoptosis, whereas the neutralization of the three death receptors pathways impairs the delayed cell death. We also show for the first time that irradiated breast cancer cells excrete soluble forms of the three ligands that can induce the death of sensitive bystander cells. Overall, these results define the molecular basis of the delayed cell death of irradiated cancer cells and identify the death receptors pathways as crucial actors in apoptosis induced by targeted as well as non-targeted effects of ionizing radiation. PMID:19126655

  15. Time-Delay Interferometry

    NASA Astrophysics Data System (ADS)

    Dhurandhar, Sanjeev V.; Tinto, Massimo

    2005-07-01

    Equal-arm interferometric detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set the overall performance. If, however, the two arms have different lengths (as will necessarily be the case with space-borne interferometers), the laser noise experiences different delays in the two arms and will hence not directly cancel at the detector. In order to solve this problem, a technique involving heterodyne interferometry with unequal arm lengths and independent phase-difference readouts has been proposed. It relies on properly time-shifting and linearly combining independent Doppler measurements, and for this reason it has been called Time-Delay Interferometry (TDI). This article provides an overview of the theory and mathematical foundations of TDI as it will be implemented by the forthcoming space-based interferometers such as the Laser Interferometer Space Antenna (LISA) mission. We have purposely left out from this first version of our "Living Review" article on TDI all the results of more practical and experimental nature, as well as all the aspects of TDI that the data analysts will need to account for when analyzing the LISA TDI data combinations. Our forthcoming "second edition" of this review paper will include these topics.

  16. Delayed effects of neutron irradiation on central nervous system microvasculature in the rat

    SciTech Connect

    Goodman, J.H.; McGregor, J.M.; Clendenon, N.R.; Gordon, W.A.; Yates, A.J.; Gahbauer, R.A.; Barth, R.F.; Fairchild, R.G.

    1988-01-01

    Pathologic examination of a series of 14 patients with malignant gliomas treated with BNCT showed well demarcated zones of radiation damage characterized by coagulation necrosis. Beam attenuation was correlated with edema, loss of parenchymal elements, demyelination, leukocytosis, and peripheral gliosis. Vascular disturbances consisted of endothelial swelling, medial and adventitial proliferation, fibrin impregnation, frequent thrombosis, and perivascular inflammation. Radiation changes appeared to be acute and delayed. The outcome of the patients in this series was not significantly different from the natural course of the disease, even though two of the patients had no residual tumor detected at the time of autopsy. The intensity of the vascular changes raised a suspicion that boron may have sequestered in vessel walls, resulting in selectively high doses of radiation to these structures (Asbury et al., 1972), or that there may have been high blood concentrations of boron at the time of treatment. The potential limiting effects of a vascular ischemic reaction in Boron Neutron Capture Therapy (BNCT) prompted the following study to investigate the delayed response of microvascular structures in a rat model currently being used for pre-clinical investigations. 8 refs., 3 figs., 1 tab.

  17. Prediction of pancreatic necrosis by dynamic pancreatography.

    PubMed Central

    Bradley, E L; Murphy, F; Ferguson, C

    1989-01-01

    Parenchymal necrosis has recently been recognized as the principal determinant of the incidence of secondary infection in acute pancreatitis. Because secondary infection of pancreatic necrosis accounts for more than 80% of all deaths from acute pancreatitis, a method for determining the presence or absence of parenchymal necrosis would offer considerable prognostic and therapeutic information. Thirty seven patients with unequivocal acute pancreatitis and five normal controls were prospectively studied with intravenous bolus, contrast-enhanced computed tomography (dynamic pancreatography). In the absence of pancreatic necrosis, there were no significant differences in parenchymal enhancement between any of the following patient groups: controls (5), uncomplicated pancreatitis (20), pancreatic abscess (7), or peripancreatic necrosis (4)(p less than 0.05). On the other hand, pancreatic parenchymal enhancement was significantly reduced or absent in all six patients with segmental or diffuse pancreatic necrosis (p less than 0.05). Postcontrast pancreatic parenchymal enhancement was also found to be inversely correlated with the number of Ranson signs (p less than 0.001). Dynamic pancreatography offers prognostic information and is a safe and reliable technique for predicting the presence or absence of pancreatic parenchymal necrosis. Images Figs. 1A and B. Figs. 3A and B. Figs. 4A and B. Fig. 5. Figs. 6A and B. Fig. 7. PMID:2802834

  18. Ionizing radiation potentiates the induction of nitric oxide synthase by interferon-gamma and/or lipopolysaccharide in murine macrophage cell lines. Role of tumor necrosis factor-alpha.

    PubMed

    McKinney, L C; Aquilla, E M; Coffin, D; Wink, D A; Vodovotz, Y

    2000-01-01

    Macrophages respond to infection or injury by changing from a "resting" cellular phenotype to an "activated" state defined by the expression of various cytotoxic effector functions. Regulation of the transition from a resting to an activated state is effected by cytokine and/or pathogenic signals. Some signals do not directly induce activation, but instead "prime" the macrophage to respond more vigorously to a second signal. One example of this priming phenomenon involves induction of nitric oxide (NO) synthesis by the enzyme nitric oxide synthase (NOS2). Our experiments indicate that low doses (1-5 Gy) of ionizing radiation can enhance the induction of enzymatically active NOS2 by IFN-gamma or LPS in J774.1 and RAW264.7 murine macrophage cell lines. Radiation alone did not produce this induction, rather, it was effective as a priming signal; cells exposed to radiation produced more NO when a second signal, either IFN-gamma or LPS, was applied 24 h later. PMID:10863529

  19. Radiation enteritis and radiation scoliosis

    SciTech Connect

    Shah, M.; Eng, K.; Engler, G.L.

    1980-09-01

    Any patient with radiation scoliosis should be suspected of having a visceral lesion as well. Chronic radiation enteritis may be manifested by intestinal obstruction, fistulas, perforation, and hemorrhage. Intestinal obstruction is the most common complication, and must be differentiated from postoperative cast or from spinal-traction syndrome. Obstruction that does not respond promptly to conservative measures must be treated surgically. Irradiated bowel is ischemic, and necrosis with spontaneous perforation can only be avoided with early diagnosis and surgical intervention.

  20. Experimental Papillary Necrosis of the Kidney

    PubMed Central

    Wyllie, R. G.; Hill, G. S.; Murray, G.; Ramsden, P. W.; Heptinstall, R. H.

    1972-01-01

    Reserpine is able to exert a pronounced inhibitory effect on the development of papillary necrosis following the administration of bromoethylamine hydrobromide to the rat. This inhibitory effect has been observed using light microscopy, histochemistry, indigo carmine excretion and urine output. These observations suggest that vasoconstriction may play a significant role in the pathogenesis of papillary necrosis, but the evidence for this is incomplete. ImagesFig 1Fig 2Fig 3Fig 4Fig 5Fig 6 PMID:4114974

  1. Cortical necrosis in a renal transplant

    SciTech Connect

    Blumhardt, R.; Growcock, G.; Lasher, J.C.

    1983-07-01

    The /sup 99m/Tc-DTPA renogram is a well extabished noninvasive method for evaluating and following transplanted kidneys. The examination is useful in distinguishing rejection from acute tubular necrosis as well as demonstrating several less common complications such as vascular occlusion, urinary extravasation, obstruction, and lymphocele. A previously unreported condition involving a transplant kidney (i.e., renal cortical necrosis) is described which was diagnosed with renal scintigraphy in combination with sonography.

  2. [Palatal necrosis in children. Case report].

    PubMed

    Sancho, M A; Parri, F J; Raigosa, J M; Lerena, J; Cacéres, F; Muñoz, M E

    2006-04-01

    Palate necrosis as a consequence of palate infection it's an exceptional condition about there's not too much references at literature. We present a case of a 6 months old child who present a palatal necrosis after a supurative medial otitis that involved hard and soft palate, with positive culture for Pseudomona aeruginosa causing a almost complete absence of the palate that simulate a bilateral palatal cleft. PMID:16846136

  3. Imaging Tumor Necrosis with Ferumoxytol

    PubMed Central

    Aghighi, Maryam; Golovko, Daniel; Ansari, Celina; Marina, Neyssa M.; Pisani, Laura; Kurlander, Lonnie; Klenk, Christopher; Bhaumik, Srabani; Wendland, Michael; Daldrup-Link, Heike E.

    2015-01-01

    showed similar findings with high T1 signal in areas of tumor necrosis and low signal in areas of intracellularly compartmentalized iron. Conclusion Differential T1- and T2-enhancement patterns of USPIO in tumors enable conclusions about their intracellular and extracellular location. This information can be used to characterize the composition of the tumor microenvironment. PMID:26569397

  4. Radiation

    NASA Video Gallery

    Outside the protective cocoon of Earth's atmosphere, the universe is full of harmful radiation. Astronauts who live and work in space are exposed not only to ultraviolet rays but also to space radi...

  5. Time delay and distance measurement

    NASA Technical Reports Server (NTRS)

    Abshire, James B. (Inventor); Sun, Xiaoli (Inventor)

    2011-01-01

    A method for measuring time delay and distance may include providing an electromagnetic radiation carrier frequency and modulating one or more of amplitude, phase, frequency, polarization, and pointing angle of the carrier frequency with a return to zero (RZ) pseudo random noise (PN) code. The RZ PN code may have a constant bit period and a pulse duration that is less than the bit period. A receiver may detect the electromagnetic radiation and calculate the scattering profile versus time (or range) by computing a cross correlation function between the recorded received signal and a three-state RZ PN code kernel in the receiver. The method also may be used for pulse delay time (i.e., PPM) communications.

  6. Hyperglycemia Increases Susceptibility to Ischemic Necrosis

    PubMed Central

    Lévigne, D.; Tobalem, M.; Modarressi, A.; Pittet-Cuénod, B.

    2013-01-01

    Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.). In this study, we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia. PMID:23509730

  7. Renal Papillary Necrosis: Role of Radiology

    PubMed Central

    Pandya, Vaidehi K.

    2016-01-01

    Renal Papillary Necrosis (RPN) is idefined as Ischemic necrobiosis of the papilla in the medulla of the kidneys. Variety of etiological factors are recognized which cause papillary necrosis, such as analgesic nephropathy, diabetes mellitus, urinary obstruction and sickle cell haemoglobinopathy. The early diagnosis of RPN is important to improve prognosis and reduce morbidity. Radiological Imaging offers early diagnosis and can guide prompt treatment of papillary necrosis and can minimize a decline in renal function. Here we report three cases of RPN with typical imaging findings. One of them was diabetic and hypertensive female with recurrent Urinary tract Infections and other was a male with no known co-morbidity. Both of them were diagnosed to have renal papillary necrosis on CT scan and were managed operatively and conservatively, respectively. Third case was a healthy female being investigated to be renal donor for her son. Here RPN was an incidental finding and was treated conservatively. Thus CT scan could detect it pre-operatively and complications due to transplantation of a kidney with papillary necrosis were avoided. So, we want to emphasize the importance of Radiology, particularly CT scanning in detection of RPN and to guide early and prompt treatment. PMID:26894147

  8. Diverse delayed effects in human lymphoblastoid cells surviving exposure to high-LET (56)Fe particles or low-LET (137)Cs gamma radiation

    NASA Technical Reports Server (NTRS)

    Evans, H. H.; Horng, M. F.; Ricanati, M.; Diaz-Insua, M.; Jordan, R.; Schwartz, J. L.

    2001-01-01

    To obtain information on the origin of radiation-induced genomic instability, we characterized a total of 166 clones that survived exposure to (56)Fe particles or (137)Cs gamma radiation, isolated approximately 36 generations after exposure, along with their respective control clones. Cytogenetic aberrations, growth alterations, responses to a second irradiation, and mutant frequencies at the Na(+)/K(+) ATPase and thymidine kinase loci were determined. A greater percentage of clones that survived exposure to (56)Fe particles exhibited instability (defined as clones showing one or more outlying characteristics) than in the case of those that survived gamma irradiation. The phenotypes of the unstable clones that survived exposure to (56)Fe particles were also qualitatively different from those of the clones that survived gamma irradiation. A greater percentage (20%) of the unstable clones that survived gamma irradiation than those that survived exposure to (56)Fe particles (4%) showed an altered response to the second irradiation, while an increase in the percentage of clones that had an outlying frequency of ouabain-resistant and thymidine kinase mutants was more evident in the clones exposed to (56)Fe particles than in those exposed to gamma rays. Growth alterations and increases in dicentric chromosomes were found only in clones with more than one alteration. These results underscore the complex nature of genomic instability and the likelihood that radiation-induced genomic instability arises from different original events.

  9. Reprint of localized dose delivering by ion beam irradiation for experimental trial of establishing brain necrosis model.

    PubMed

    Takata, Takushi; Kondo, Natsuko; Sakurai, Yoshinori; Tanaka, Hiroki; Hasegawa, Takashi; Kume, Kyo; Suzuki, Minoru

    2015-12-01

    Localized dose delivery techniques to establish a brain radiation necrosis model are described. An irradiation field was designed by using accelerated protons or helium ions with a spread-out Bragg peak. Measurement of the designed field confirmed that a high dose can be confined to a local volume of an animal brain. The irradiation techniques described here are very useful for establishing a necrosis model without existence of extraneous complications. PMID:26515136

  10. Phosphorescence or Thermally Activated Delayed Fluorescence? Intersystem Crossing and Radiative Rate Constants of a Three-Coordinate Copper(I) Complex Determined by Quantum-Chemical Methods.

    PubMed

    Föller, Jelena; Kleinschmidt, Martin; Marian, Christel M

    2016-08-01

    The photophysical properties of a cationic three-coordinate copper(I) complex with a monodentate N-heterocyclic carbene ligand and a bidentate phenanthroline ligand have been investigated by employing computational chemistry methods. The absorption spectrum, calculated with the combined density functional theory and multireference configuration interaction method, matches experimentally available data perfectly, thus corroborating the validity of our applied theoretical approach. On the basis of our calculated singlet-triplet gap of 650 cm(-1) and the (reverse) intersystem crossing rates that are both larger than the fluorescence and phosphorescence rates at room temperature, we conclude that thermally activated delayed fluorescence should be observable for this complex in addition to phosphorescence. Torsion of the ligands has only a small impact on the singlet-triplet gap. However, the electronic coupling between the S1 and T1 states-and hence the probability for (reverse) intersystem crossing-is seen to increase substantially when moving from a coplanar to a perpendicular arrangement of the ligands. PMID:27428010

  11. [Digital necrosis in hand by uncommon mechanism].

    PubMed

    Leroux, Maria Bibiana; Lashak, Celina; Mazzurco, Martin

    2013-07-01

    A 43-year-old, non-smoking man presented with acute ischemic lesions of his left hand. He had been taking beta-blockers for his arterial hypertension. The day before the occurrence of these acute lesions, he self medicated with a drug containing ergotamine and caffeine because of a headache. About one hour after mild trauma to the hand, he noticed intense cyanosis accompanied by severe pain in the fingers that progressed to digital necrosis. Hematological tests, hand radiography, echo Doppler, and nailfold videocapillaroscopy were performed. Digital necrosis owing to an unusual combination of ischemic mechanisms is assumed. PMID:24010508

  12. Effects of high dose intraperitoneal cytosine arabinoside on the radiation tolerance of the rat spinal cord

    SciTech Connect

    Menten, J.; Landuyt, W.; van der Kogel, A.J.; Ang, K.K.; van der Schueren, E.

    1989-07-01

    The effect of intraperitoneal high dose (9 g/kg) cytosine arabinoside (Ara-C) on the early delayed radiation response of the rat cervical spinal cord has been studied. When given 2 hrs before irradiation, systemically administered Ara-C significantly reduces the isoeffect doses for the induction of paralysis due to white matter necrosis by a factor of approximately 1.2 for both a single irradiation treatment and for a two fraction irradiation with 24 hr interval. No effect on the latency time to develop paralysis was recorded.

  13. The Delayed Effects of Acute Radiation Syndrome: Evidence of Long-Term Functional Changes in the Clonogenic Cells of the Small Intestine.

    PubMed

    Booth, Catherine; Tudor, Gregory L; Katz, Barry P; MacVittie, Thomas J

    2015-11-01

    Long term or residual damage post-irradiation has been described for many tissues. In hematopoietic stem cells (HSC), this is only revealed when the HSC are stressed and required to regenerate and repopulate a myeloablated host. Such an assay cannot be used to assess the recovery potential of previously irradiated intestinal stem cells (ISC) due to their incompatibility with transplantation. The best approximation to the HSC assay is the crypt microcolony assay, also based on clonogen survival. In the current study, the regenerative capacity of intestinal clonogenic cells in mice that had survived 13 Gy irradiation (with 5% bone marrow shielding to allow survival through the hematopoietic syndrome) and were then aged for 200 d was compared to previously unirradiated age-matched controls. Interestingly, at 200 d following 13 Gy, there remained a statistically significant reduction in crypts present in the various small intestinal regions (illustrating that the gastrointestinal epithelium had not fully recovered despite the 200-d interval). However, upon re-irradiation on day 196, those mice previously irradiated had improved crypt survival and regeneration compared to the age-matched controls. This was evident in all regions of the small intestine following 11-13 Gy re-exposure. Thus, there were either more clonogens per crypt within those previously irradiated and/or those that were present were more radioresistant (possibly because a subpopulation was more quiescent). This is contrary to the popular belief that previously irradiated animals may have an impaired/delayed regenerative response and be more radiosensitive. PMID:26425901

  14. Epinephrine Injection Associated Scrotal Skin Necrosis

    PubMed Central

    Gul, Murat; Kaynar, Mehmet; Sekmenli, Tamer; Ciftci, Ilhan; Goktas, Serdar

    2015-01-01

    Male circumcision is among the most frequent surgical interventions throughout history. Although considered as a minor intervention, it may have complications ranging from insignificant to catastrophic. These complications can be attributed to the surgical procedure and anesthesia. In this report we present two cases of scrotal skin necrosis after lidocaine with epinephrine injection using subcutaneous ring block technique prior to circumcision. PMID:26185706

  15. Pythium Root Rot (and Feeder Root Necrosis)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pythium species cause a number of diseases on corn. Among the Pythium diseases, root rot presents the least conspicuous aboveground symptoms. Broadly defined, root rot also includes feeder root necrosis. At least 16 species of Pythium are known to cause root rot of corn. These include P. acanthicu...

  16. Delayed orgasm and anorgasmia.

    PubMed

    Jenkins, Lawrence C; Mulhall, John P

    2015-11-01

    Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies, which include medications, penile sensation loss, endocrinopathies, penile hyperstimulation, and psychological etiologies. Unfortunately, there are no excellent pharmacotherapies for delayed orgasm/anorgasmia, and treatment revolves largely around addressing potential causative factors and psychotherapy. PMID:26439762

  17. Speech and Language Delay

    MedlinePlus

    MENU Return to Web version Speech and Language Delay Overview How do I know if my child has speech delay? Every child develops at his or her ... of the same age, the problem may be speech delay. Your doctor may think your child has ...

  18. Delay Discounting and Gambling

    PubMed Central

    Madden, Gregory J.; Francisco, Monica T.; Brewer, Adam T.; Stein, Jeffrey S.

    2011-01-01

    Delay discounting describes the decline in the value of a reinforcer as the delay to that reinforcer increases. A review of the available studies revealed that steep delay discounting is positively correlated with problem or pathological gambling. One hypothesis regarding this correlation derives from the discounting equation proposed by Mazur (1989). According to the equation, steeper discounting renders the difference between fixed-delayed rewards and gambling-like variable-delayed rewards larger; with the latter being more valuable. The present study was designed to test this prediction by first assessing rats’ impulsive choices across four delays to a larger-later reinforcer. A second condition quantified strength of preference for mixed- over fixed-delays, with the duration of the latter adjusted between sessions to achieve indifference. Strength of preference for the mixed-delay alternative is given by the fixed delay at indifference (lower fixed-delay values reflect stronger preferences). Percent impulsive choice was not correlated with the value of the fixed delay at indifference and, therefore, the prediction of the hyperbolic model of gambling was not supported. A follow-up assessment revealed a significant decrease in impulsive choice after the second condition. This shift in impulsive choice could underlie the failure to observe the predicted correlation between impulsive choice and degree of preference for mixed- over fixed delays. PMID:21352902

  19. Postprimary Tuberculosis and Macrophage Necrosis: Is There a Big ConNECtion?

    PubMed Central

    2016-01-01

    ABSTRACT Adult or postprimary tuberculosis (TB) accounts for most TB cases. Its hallmark is pulmonary cavitation, which occurs as a result of necrosis in the lung in individuals with tuberculous pneumonia. Postprimary TB has previously been known to be associated with vascular thrombosis and delayed-type hypersensitivity, but their roles in pulmonary cavitation are unclear. A necrosis-associated extracellular cluster (NEC) refers to a cluster of drug-tolerant Mycobacterium tuberculosis attached to lysed host materials and is proposed to contribute to granulomatous TB. Here we suggest that NECs, perhaps due to big size, produce a distinct host response leading to postprimary TB. We propose that vascular thrombosis and pneumonia arise from NEC and that these processes are promoted by inflammatory cytokines produced from cell-mediated delayed-type hypersensitivity, such as interleukin-17 and gamma interferon, eventually triggering necrosis in the lung and causing cavitation. According to this view, targeting NEC represents a necessary strategy to control adult TB. PMID:26758178

  20. Postprimary Tuberculosis and Macrophage Necrosis: Is There a Big ConNECtion?

    PubMed

    Wong, Ka-Wing; Jacobs, William R

    2016-01-01

    Adult or postprimary tuberculosis (TB) accounts for most TB cases. Its hallmark is pulmonary cavitation, which occurs as a result of necrosis in the lung in individuals with tuberculous pneumonia. Postprimary TB has previously been known to be associated with vascular thrombosis and delayed-type hypersensitivity, but their roles in pulmonary cavitation are unclear. A necrosis-associated extracellular cluster (NEC) refers to a cluster of drug-tolerant Mycobacterium tuberculosis attached to lysed host materials and is proposed to contribute to granulomatous TB. Here we suggest that NECs, perhaps due to big size, produce a distinct host response leading to postprimary TB. We propose that vascular thrombosis and pneumonia arise from NEC and that these processes are promoted by inflammatory cytokines produced from cell-mediated delayed-type hypersensitivity, such as interleukin-17 and gamma interferon, eventually triggering necrosis in the lung and causing cavitation. According to this view, targeting NEC represents a necessary strategy to control adult TB. PMID:26758178

  1. Delayed chromosomal instability induced by DNA damage.

    PubMed Central

    Marder, B A; Morgan, W F

    1993-01-01

    DNA damage induced by ionizing radiation can result in gene mutation, gene amplification, chromosome rearrangements, cellular transformation, and cell death. Although many of these changes may be induced directly by the radiation, there is accumulating evidence for delayed genomic instability following X-ray exposure. We have investigated this phenomenon by studying delayed chromosomal instability in a hamster-human hybrid cell line by means of fluorescence in situ hybridization. We examined populations of metaphase cells several generations after expanding single-cell colonies that had survived 5 or 10 Gy of X rays. Delayed chromosomal instability, manifested as multiple rearrangements of human chromosome 4 in a background of hamster chromosomes, was observed in 29% of colonies surviving 5 Gy and in 62% of colonies surviving 10 Gy. A correlation of delayed chromosomal instability with delayed reproductive cell death, manifested as reduced plating efficiency in surviving clones, suggests a role for chromosome rearrangements in cytotoxicity. There were small differences in chromosome destabilization and plating efficiencies between cells irradiated with 5 or 10 Gy of X rays after a previous exposure to 10 Gy and cells irradiated only once. Cell clones showing delayed chromosomal instability had normal frequencies of sister chromatid exchange formation, indicating that at this cytogenetic endpoint the chromosomal instability was not apparent. The types of chromosomal rearrangements observed suggest that chromosome fusion, followed by bridge breakage and refusion, contributes to the observed delayed chromosomal instability. Images PMID:8413263

  2. Perfusion delay causes unintentional ischemic preconditioning in isolated heart preparation.

    PubMed

    Minhaz, U; Koide, S; Shohtsu, A; Fujishima, M; Nakazawa, H

    1995-01-01

    This study sought to show that unintentional preconditioning can be induced in the isolated perfused heart during the preparation procedure. The following four groups were compared: hearts were placed in ice cold saline and cooled for 15 s and then mounted to the Langendorff apparatus (n = 5; cool immediate group); hearts were cooled for 60 s and mounted (n = 5; cool delay group); hearts were mounted directly to the apparatus within 15 s after the isolation without cooling (n = 5; noncool immediate group); hearts were mounted without cooling, but the mounting was delayed for 60 s after the isolation (n = 5; noncool delay group). All hearts were paced at a fixed rate of 300 bpm, and an occlusion of left coronary (LCA) for 60 min was performed, which was followed by reperfusion for another 60 min. Coronary flow (CBF), left ventricular developed pressure (LVDP), and creatine phosphokinase (CPK) release did not change among the four groups during ischemia. At the end of reperfusion the LVDP values were 70 +/- 1%, 66 +/- 2%, 62 +/- 3%, and 73 +/- 2% of preischemic values in cool immediate, cool delay, noncool immediate, and noncool delay groups, respectively. CPK values were 116 +/- 4, 121 +/- 7, 138 +/- 6, and 29 +/- 1 x 10(3) U/g myocardium, and percentage necrosis/risk areas were 24 +/- 1.0%, 21 +/- 1.7%, 38 +/- 2.6%, and 13 +/- 0.5% in cool immediate, cool delay, noncool immediate, and noncool delay groups, respectively. The noncool delay group demonstrated high LVDP, least amount of CPK release, and smallest size of necrosis. These results indicate that an unintentional preconditioning effect can be induced when the cooling procedure is not applied and perfusion is delayed. PMID:8585864

  3. Regulated necrosis and its implications in toxicology.

    PubMed

    Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi

    2015-07-01

    Recent research developments have revealed that caspase-dependent apoptosis is not the sole form of regulated cell death. Caspase-independent, but genetically regulated, forms of cell death include pyroptosis, necroptosis, parthanatos, and the recently discovered ferroptosis and autosis. Importantly, regulated necrosis can be modulated by small molecule inhibitors/activators, confirming the cell autonomous mechanism of these forms of cell death. The success of small molecule-mediated manipulation of regulated necrosis has produced great changes in the field of cell death research, and has also brought about significant changes in the fields of pharmacology as well as toxicology. In this review, we intend to summarize the modes of regulated cell death other than apoptosis, and discuss their implications in toxicology. PMID:25865964

  4. Giant cell arteritis presenting as scalp necrosis.

    PubMed

    Maidana, Daniel E; Muñoz, Silvia; Acebes, Xènia; Llatjós, Roger; Jucglà, Anna; Alvarez, Alba

    2011-01-01

    The differential of scalp ulceration in older patients should include several causes, such as herpes zoster, irritant contact dermatitis, ulcerated skin tumors, postirradiation ulcers, microbial infections, pyoderma gangrenosum, and giant cell arteritis. Scalp necrosis associated with giant cell arteritis was first described in the 1940s. The presence of this dermatological sign within giant cell arteritis represents a severity marker of this disease, with a higher mean age at diagnosis, an elevated risk of vision loss and tongue gangrene, as well as overall higher mortality rates, in comparison to patients not presenting this manifestation. Even though scalp necrosis due to giant cell arteritis is exceptional, a high level of suspicion must be held for this clinical finding, in order to initiate prompt and proper treatment and avoid blindness. PMID:21789466

  5. Radiation dermatitis

    SciTech Connect

    Shack, R.B.; Lynch, J.B.

    1987-04-01

    Even in this era of modern radiotherapy, injuries associated with the medical and industrial use of radiation devices will continue to pose a difficult problem for the reconstructive surgeon. It must be borne in mind that the single most serious hazard to surgery in irradiated tissue is the lodgement of bacteria in tissue rendered avascular by the radiation and the secondary necrosis from the infection itself. The basic principles of wound management must be augmented by thorough knowledge of the use of well-vascularized muscle and musculocutaneous flap to provide adequate, blood-rich, soft-tissue coverage.

  6. Uterine Necrosis Associated with Fusobacterium necrophorum Infection

    PubMed Central

    Widelock, T.; Elkattah, R.; Gibbs, S.; Mashak, Z.; Mohling, S.; DePasquale, S.

    2015-01-01

    Fusobacterium necrophorum is infrequently implicated as a pathogenic organism. When pathogenic, the typical clinical presentation is that of pharyngitis, cervical adenopathy, and unilateral thrombophlebitis of the internal jugular vein. Infections caused by Fusobacterium necrophorum within the fields of obstetrics and gynecology have been infrequently reported. We describe a 19-year-old woman who underwent a cesarean delivery complicated by sepsis and purulent uterine necrosis secondary to Fusobacterium necrophorum infection. PMID:26000185

  7. Idiopathic incus necrosis: Analysis of 4 cases.

    PubMed

    Kansu, Leyla; Yilmaz, Ismail; Akdogan, Volkan; Avci, Suat; Ozluoglu, Levent

    2013-02-01

    We evaluated ossicular chain reconstruction in patients with idiopathic incus necrosis who have conductive hearing loss and an intact ear drum. The study included four patients (3 women and 1 man; the ages of the patients were 22, 31, 35, and 56 years, respectively) with unilateral conductive hearing loss, no history of chronic serous otitis media, an intact ear drum, normal middle ear mucosa, and necrosis of the long processes of the incus. On preoperative pure tone audiometry, air-bone gaps were 24, 25, 38, and 33 dB. Bilateral tympanometry and temporal bone computed tomography results were normal. All 4 patients underwent an exploratory tympanotomy. During the operation, the mucosa of the middle ear was normal, with a mobile stapes foot plate and malleus. No evidence of any granulation tissue was found; however, necrosis of the incus long processes was seen. For ossicular reconstruction, we used tragal cartilage between the incus and the stapes in 1 patient; in the other 3 patients, glass ionomer bone cement was used (an interposition cartilage graft also was used in the patients who received the glass ionomer bone cement). In all patients, air-bone gaps under 20 dB were established in the first year after surgery. In the ossicular disorders within the middle ear, the incus is the most commonly affected ossicle. While, the most common cause of these disorders is chronic otitis media, it may be idiopathic rarely. Several ossicular reconstruction techniques have been used to repair incudostapedial discontinuity. PMID:23460219

  8. Oxidative stress signalling: a potential mediator of tumour necrosis factor alpha-induced genomic instability in primary vascular endothelial cells.

    PubMed

    Natarajan, M; Gibbons, C F; Mohan, S; Moore, S; Kadhim, M A

    2007-09-01

    Studying the potential role of tumour necrosis factor (TNF)alpha in the initiation of genomic instability is necessary to understand whether TNFalpha can serve as a signalling mediator of radiation-induced genomic instability in non-irradiated bystander cells. In this study, we examined whether TNFalpha could initiate processes through oxidative stress signalling that lead to DNA damage and genomic instability in primary vascular endothelium. In these cells, low linear energy transfer (LET) radiation (0.1-2 Gy) induced the secretion of TNFalpha into the culture medium. When added ectopically, TNFalpha at concentrations ranging from 0.1 ng ml(-1) to 10 ng ml(-1) increased (twofold to threefold) intracellular oxidative stress. Next, to examine whether TNFalpha induces genetic damage, cells were treated with TNFalpha for 5 h and analysed immediately using the single cell gel electrophoresis assay or after 3 days, 12 days and 20 days using solid stain chromosomal analysis. Cells exposed to 0.1 Gy, 1 Gy or 2 Gy or treated with 100 microM H2O2 were used as positive controls. The results showed that TNFalpha as low as 0.1 ng ml(-1) could initiate increased DNA damage compared with untreated controls. When examined in the progeny cells after several generations, the chromosomal instability appeared to be carried over even after day 12 and day 20. The increased genetic damage is inhibited in cells that are pre-incubated with the antioxidant enzyme catalase, the antioxidant N-acetyl-L-cysteine or the metal chelator pyrrolidine dithiocarbamate. These results clearly indicate that TNFalpha at concentrations at which no cytotoxicity is observed could induce genetic damage through free radical generation, which could, in turn, lead to the delayed events associated with genomic instability. PMID:17704321

  9. CGI delay compensation

    NASA Technical Reports Server (NTRS)

    Mcfarland, Richard E.

    1986-01-01

    Computer-generated graphics in real-time helicopter simulation produces objectionable scene-presentation time delays. In the flight simulation laboratory at Ames Research Center, it has been determined that these delays have an adverse influence on pilot performance during aggressive tasks such as nap-of-the-earth (NOE) maneuvers. Using contemporary equipment, computer-generated image (CGI) time delays are an unavoidable consequence of the operations required for scene generation. However, providing that magnitide distortions at higher frequencies are tolerable, delay compensation is possible over a restricted frequency range. This range, assumed to have an upper limit of perhaps 10 or 15 rad/sec, conforms approximately to the bandwidth associated with helicopter handling qualities research. A compensation algorithm is introduced here and evaluated in terms of tradeoffs in frequency responses. The algorithm has a discrete basis and accommodates both a large, constant transport delay interval and a periodic delay interval, as associated with asynchronous operations.

  10. VARIABLE TIME DELAY MEANS

    DOEpatents

    Clemensen, R.E.

    1959-11-01

    An electrically variable time delay line is described which may be readily controlled simuitaneously with variable impedance matching means coupied thereto such that reflections are prevented. Broadly, the delay line includes a signal winding about a magnetic core whose permeability is electrically variable. Inasmuch as the inductance of the line varies directly with the permeability, the time delay and characteristic impedance of the line both vary as the square root of the permeability. Consequently, impedance matching means may be varied similariy and simultaneously w:th the electrically variable permeability to match the line impedance over the entire range of time delay whereby reflections are prevented.

  11. Radiation protection in space.

    PubMed

    Reitz, G; Facius, R; Sandler, H

    1995-01-01

    Radiation environment, basic concepts of radiation protection, and specific aspects of the space radiation field are reviewed. The discussion of physico-chemical and subcellular radiation effects includes mechanisms of radiation action and cellular consequences. The discussion of radiobiological effects includes unique aspects of HZE particle effects, space flight findings, terrestrial findings, analysis of somatic radiation effects and effects on critical organs, and early and delayed effects. Other topics include the impact of the space flight environment, measurement of radiation exposure, establishing radiation protection limits, limitations in establishing space-based radiation exposure limits, radiation protection measures, and recommendations. PMID:11541474

  12. Multiple roles of tumor necrosis factor-alpha in fracture healing.

    PubMed

    Karnes, Jonathan M; Daffner, Scott D; Watkins, Colleen M

    2015-09-01

    This review presents a summary of basic science evidence examining the influence of tumor necrosis factor-alpha (TNF-α) on secondary fracture healing. Multiple studies suggest that TNF-α, in combination with the host reservoir of peri-fracture mesenchymal stem cells, is a main determinant in the success of bone healing. Disease states associated with poor bone healing commonly have inappropriate TNF-α responses, which likely contributes to the higher incidence of delayed and nonunions in these patient populations. Appreciation of TNF-α in fracture healing may lead to new therapies to augment recovery and reduce the incidence of complications. PMID:25959413

  13. Delayed recombination and standard rulers

    SciTech Connect

    De Bernardis, Francesco; Melchiorri, Alessandro; Bean, Rachel; Galli, Silvia; Silk, Joseph I.; Verde, Licia

    2009-02-15

    Measurements of baryonic acoustic oscillations (BAOs) in galaxy surveys have been recognized as a powerful tool for constraining dark energy. However, this method relies on the knowledge of the size of the acoustic horizon at recombination derived from cosmic microwave background (CMB) anisotropy measurements. This estimate is typically derived assuming a standard recombination scheme; additional radiation sources can delay recombination altering the cosmic ionization history and the cosmological inferences drawn from CMB and BAO data. In this paper we quantify the effect of delayed recombination on the determination of dark energy parameters from future BAO surveys such as the Baryon Oscillation Spectroscopic Survey and the Wide-Field Multi-Object Spectrograph. We find the impact to be small but still not negligible. In particular, if recombination is nonstandard (to a level still allowed by CMB data), but this is ignored, future surveys may incorrectly suggest the presence of a redshift-dependent dark energy component. On the other hand, in the case of delayed recombination, adding to the analysis one extra parameter describing deviations from standard recombination does not significantly degrade the error bars on dark energy parameters and yields unbiased estimates. This is due to the CMB-BAO complementarity.

  14. Mycobacterium tuberculosis PPE68 and Rv2626c genes contribute to the host cell necrosis and bacterial escape from macrophages.

    PubMed

    Danelishvili, Lia; Everman, Jamie; Bermudez, Luiz E

    2016-01-01

    Alveolar macrophages are the main line of innate immune response against M. tuberculosis (Mtb) infection. However, these cells serve as the major intracellular niche for Mtb enhancing its survival, replication and, later on, cell-to-cell spread. Mtb-associated cytotoxicity of macrophages has been well documented, but limited information exists about mechanisms by which the pathogen induces cell necrosis. To identify virulence factors involved in the induction of necrosis, we screened 5,000 transposon mutants of Mtb for clones that failed to promote the host cell necrosis in a similar manner as the wild-type bacterium. Five Mtb mutants were identified as potential candidates inducing significantly lower levels of THP-1 cell damage in contrast to the H37Rv wild-type infection. Reduced levels of the cell damage by necrosis deficient mutants (NDMs) were also associated with delayed damage of mitochondrial membrane permeability when compared with the wild-type infection over time. Two knockout mutants of the Rv3873 gene, encoding a cell wall PPE68 protein of RD1 region, were identified out of 5 NDMs. Further investigation lead to the observation that PPE68 protein interacts and exports several unknown or known surface/secreted proteins, among them Rv2626c is associated with the host cell necrosis. When the Rv2626c gene is deleted from the genome of Mtb, the bacterium displays significantly less necrosis in THP-1 cells and, conversely, the overexpression of Rv2626c promotes the host cell necrosis at early time points of infections in contrast to the wild-type strain. PMID:26605666

  15. Digital time delay

    DOEpatents

    Martin, A.D.

    1986-05-09

    Method and apparatus are provided for generating an output pulse following a trigger pulse at a time delay interval preset with a resolution which is high relative to a low resolution available from supplied clock pulses. A first lumped constant delay provides a first output signal at predetermined interpolation intervals corresponding to the desired high resolution time interval. Latching circuits latch the high resolution data to form a first synchronizing data set. A selected time interval has been preset to internal counters and corrected for circuit propagation delay times having the same order of magnitude as the desired high resolution. Internal system clock pulses count down the counters to generate an internal pulse delayed by an internal which is functionally related to the preset time interval. A second LCD corrects the internal signal with the high resolution time delay. A second internal pulse is then applied to a third LCD to generate a second set of synchronizing data which is complementary with the first set of synchronizing data for presentation to logic circuits. The logic circuits further delay the internal output signal with the internal pulses. The final delayed output signal thereafter enables the output pulse generator to produce the desired output pulse at the preset time delay interval following input of the trigger pulse.

  16. Delayed recombination and cosmic parameters

    NASA Astrophysics Data System (ADS)

    Galli, Silvia; Bean, Rachel; Melchiorri, Alessandro; Silk, Joseph

    2008-09-01

    Current cosmological constraints from cosmic microwave background anisotropies are typically derived assuming a standard recombination scheme, however additional resonance and ionizing radiation sources can delay recombination, altering the cosmic ionization history and the cosmological inferences drawn from the cosmic microwave background data. We show that for recent observations of the cosmic microwave background anisotropy, from the Wilkinson microwave anisotropy probe satellite mission (WMAP) 5-year survey and from the arcminute cosmology bolometer array receiver experiment, additional resonance radiation is nearly degenerate with variations in the spectral index, ns, and has a marked effect on uncertainties in constraints on the Hubble constant, age of the universe, curvature and the upper bound on the neutrino mass. When a modified recombination scheme is considered, the redshift of recombination is constrained to z*=1078±11, with uncertainties in the measurement weaker by 1 order of magnitude than those obtained under the assumption of standard recombination while constraints on the shift parameter are shifted by 1σ to R=1.734±0.028. From the WMAP5 data we obtain the following constraints on the resonance and ionization sources parameters: γα<0.39 and γi<0.058 at 95% c.l.. Although delayed recombination limits the precision of parameter estimation from the WMAP satellite, we demonstrate that this should not be the case for future, smaller angular scales measurements, such as those by the Planck satellite mission.

  17. Delayed recombination and cosmic parameters

    SciTech Connect

    Galli, Silvia; Melchiorri, Alessandro; Bean, Rachel; Silk, Joseph

    2008-09-15

    Current cosmological constraints from cosmic microwave background anisotropies are typically derived assuming a standard recombination scheme, however additional resonance and ionizing radiation sources can delay recombination, altering the cosmic ionization history and the cosmological inferences drawn from the cosmic microwave background data. We show that for recent observations of the cosmic microwave background anisotropy, from the Wilkinson microwave anisotropy probe satellite mission (WMAP) 5-year survey and from the arcminute cosmology bolometer array receiver experiment, additional resonance radiation is nearly degenerate with variations in the spectral index, n{sub s}, and has a marked effect on uncertainties in constraints on the Hubble constant, age of the universe, curvature and the upper bound on the neutrino mass. When a modified recombination scheme is considered, the redshift of recombination is constrained to z{sub *}=1078{+-}11, with uncertainties in the measurement weaker by 1 order of magnitude than those obtained under the assumption of standard recombination while constraints on the shift parameter are shifted by 1{sigma} to R=1.734{+-}0.028. From the WMAP5 data we obtain the following constraints on the resonance and ionization sources parameters: {epsilon}{sub {alpha}}<0.39 and {epsilon}{sub i}<0.058 at 95% c.l.. Although delayed recombination limits the precision of parameter estimation from the WMAP satellite, we demonstrate that this should not be the case for future, smaller angular scales measurements, such as those by the Planck satellite mission.

  18. Tracheal necrosis with surgical emphysema following thyroidectomy.

    PubMed

    Chauhan, A; Ganguly, M; Saidha, N; Gulia, P

    2009-01-01

    Tracheal necrosis after thyroidectomy is an extremely rare event with only a few published reports. We present a case of a 65-year-old male who developed rapidly progressive surgical emphysema of face and upper thorax on the seventh day following total thyroidectomy. Prompt surgical exploration of neck revealed a tracheal rent at the level of the second tracheal ring. This hole was then refashioned into a formal tracheostomy. Patient had an eventful recovery. Tracheostomy was closed by the 14th day. The complication was probably related to tracheal injury sustained due to electro-coagulation and subsequent secondary infection. PMID:19884745

  19. Combination of Anti-IGF-1R Antibody A12 and Ionizing Radiation in Upper Respiratory Tract Cancers

    SciTech Connect

    Riesterer, Oliver; Yang Qiuan; Raju, Uma; Torres, Mylin; Molkentine, David; Patel, Nalini; Valdecanas, David; Milas, Luka; Ang, K. Kian

    2011-03-15

    Purpose: The IGF1/IGF-1R signaling pathway has emerged as a potential determinant of radiation resistance in human cancer cell lines. Therefore we investigated the potency of monoclonal anti-IGF-1R antibody, A12, to enhance radiation response in upper respiratory tract cancers. Methods and Materials: Cell lines were assessed for IGF-1R expression and IGF1-dependent response to A12 or radiation using viability and clonogenic cancer cell survival assays. In vivo response of tumor xenografts to 10 or 20 Gy and A12 (0.25-2 mg x 3) was assessed using growth delay assays. Combined treatment effects were also analyzed by immunohistochemical assays for tumor cell proliferation, apoptosis, necrosis, and vascular endothelial growth factor expression at Days 1 and 6 after start of treatment. Results: A12 enhanced the radiosensitivity of HN5 and FaDu head-and-neck carcinomas in vitro (p < 0.05) and amplified the radioresponse of FaDu xenografts in a dose-dependent manner, with enhancement factors ranging from 1.2 to 1.8 (p < 0.01). Immunohistochemical analysis of FaDu xenografts demonstrated that A12 inhibited tumor cell proliferation (p < 0.05) and vascular endothelial growth factor expression. When A12 was combined with radiation, this resulted in apoptosis induction that persisted until 6 days from the start of treatment and in increased necrosis at Day 1 (p < 0.01, respectively). Combined treatment with A12 and radiation resulted in additive or subadditive growth delay in H460 or A549 xenografts, respectively. Conclusions: The results of this study strengthen the evidence for investigating how anti-IGF-1R strategies can be integrated into radiation and radiation-cetuximab regimen in the treatment of cancer of the upper aerodigestive tract cancers.

  20. Until Death Do Us Part: Necrosis and Oxidation Promote the Tumor Microenvironment

    PubMed Central

    Lotfi, Ramin; Kaltenmeier, Christof; Lotze, Michael T.; Bergmann, Christoph

    2016-01-01

    Summary Tumor proliferation is concomitant with autophagy, limited apoptosis, and resultant necrosis. Necrosis is associated with the release of damage-associated molecular pattern molecules (DAMPs), which act as ‘danger signals’, recruiting inflammatory cells, inducing immune responses, and promoting wound healing. Most of the current treatment strategies for cancer (chemotherapy, radiation therapy, hormonal therapy) promote DAMP release following therapy-induced tumor death by necroptosis and necrosis. Myeloid cells (monocytes, dendritic cells (DCs), and granulocytes), as well as mesenchymal stromal cells (MSCs) belong to the early immigrants in response to unscheduled cell death, initiating and modulating the subsequent inflammatory response. Responding to DAMPs, MSCs, and DCs promote an immunosuppressive milieu, while eosinophils induce oxidative conditions limiting the biologic activity of DAMPs over time and distance. Regulatory T cells are strongly affected by pattern recognition receptor signaling in the tumor microenvironment and limit immune reactivity coordinately with myeloid-derived suppressor cells. Means to ‘aerobically’ oxidize DAMPs provide a novel strategy for limiting tumor progression. The present article summarizes our current understanding of the impact of necrosis on the tumor microenvironment and the influence of oxidative conditions found within this setting. PMID:27226794

  1. Restriction-Spectrum Imaging of Bevacizumab-Related Necrosis in a Patient with GBM

    PubMed Central

    Farid, Nikdokht; Almeida-Freitas, Daniela B.; White, Nathan S.; McDonald, Carrie R.; Muller, Karra A.; VandenBerg, Scott R.; Kesari, Santosh; Dale, Anders M.

    2013-01-01

    Importance: With the increasing use of antiangiogenic agents in the treatment of high-grade gliomas, we are becoming increasingly aware of distinctive imaging findings seen in a subset of patients treated with these agents. Of particular interest is the development of regions of marked and persistent restricted diffusion. We describe a case with histopathologic validation, confirming that this region of restricted diffusion represents necrosis and not viable tumor. Observations: We present a case report of a 52-year-old man with GBM treated with temozolomide, radiation, and concurrent bevacizumab following gross total resection. The patient underwent sequential MRI’s which included restriction-spectrum imaging (RSI), an advanced diffusion-weighted imaging (DWI) technique, and MR perfusion. Following surgery, the patient developed an area of restricted diffusion on RSI which became larger and more confluent over the next several months. Marked signal intensity on RSI and very low cerebral blood volume (CBV) on MR perfusion led us to favor bevacizumab-related necrosis over recurrent tumor. Subsequent histopathologic evaluation confirmed coagulative necrosis. Conclusion and Relevance: Our report increases the number of pathologically proven cases of bevacizumab-related necrosis in the literature from three to four. Furthermore, our case demonstrates this phenomenon on RSI, which has been shown to have good sensitivity to restricted diffusion. PMID:24137566

  2. Bilateral putaminal necrosis and bronopol toxicity.

    PubMed

    Trivisano, Marina; Carapelle, Elena; Martino, Tommaso; Specchio, Luigi Maria

    2015-01-01

    Among alcohols, methanol intoxication is the most frequently associated with cerebral toxicity, causing retinal damage and putaminal necrosis. This consequence is believed to be due to the transformation of methanol into formic acid. We describe the case of a patient who presented with acute impairment of consciousness and tetraparesis after she had been drinking several bottles of a topical antiseptic solution (Lysoform Medical) containing 2-bromo-2-nitro-1,3-propandiol (bronopol) among excipients, in order to lose weight during previous months. Moreover, she had been on a strict slimming diet. Soon after admission, a severe respiratory and metabolic impairment became rapidly evident, requiring an intensive care unit admission. Cerebral MRI showed the presence of bilateral putaminal necrosis. She recovered in 10 days, surprisingly, without any evident clinical neurological signs. Methanol, also bronopol, when diluted in aqueous solution, at warm temperature and/or higher pH, may release formaldehyde, which is converted into formic acid, a basal ganglia toxic compound. PMID:25697297

  3. Mechanisms of Acetaminophen-Induced Liver Necrosis

    PubMed Central

    Roberts, Dean W.; James, Laura P.

    2010-01-01

    Although considered safe at therapeutic doses, at higher doses, acetaminophen produces a centrilobular hepatic necrosis that can be fatal. Acetaminophen poisoning accounts for approximately one-half of all cases of acute liver failure in the United States and Great Britain today. The mechanism occurs by a complex sequence of events. These events include: (1) CYP metabolism to a reactive metabolite which depletes glutathione and covalently binds to proteins; (2) loss of glutathione with an increased formation of reactive oxygen and nitrogen species in hepatocytes undergoing necrotic changes; (3) increased oxidative stress, associated with alterations in calcium homeostasis and initiation of signal transduction responses, causing mitochondrial permeability transition; (4) mitochondrial permeability transition occurring with additional oxidative stress, loss of mitochondrial membrane potential, and loss of the ability of the mitochondria to synthesize ATP; and (5) loss of ATP which leads to necrosis. Associated with these essential events there appear to be a number of inflammatory mediators such as certain cytokines and chemokines that can modify the toxicity. Some have been shown to alter oxidative stress, but the relationship of these modulators to other critical mechanistic events has not been well delineated. In addition, existing data support the involvement of cytokines, chemokines, and growth factors in the initiation of regenerative processes leading to the reestablishment of hepatic structure and function. PMID:20020268

  4. Necrosis Avidity: A Newly Discovered Feature of Hypericin and its Preclinical Applications in Necrosis Imaging

    PubMed Central

    Jiang, Binghu; Wang, Jichen; Ni, Yicheng; Chen, Feng

    2013-01-01

    Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [123I]iodohypericin, [124I]iodohypericin, and [131I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin. PMID:24052807

  5. Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model.

    PubMed

    Bohr, Stefan; Patel, Suraj J; Sarin, Dhruv; Irimia, Daniel; Yarmush, Martin L; Berthiaume, Francois

    2013-01-01

    Deep partial thickness burns are subject to delayed necrosis of initially viable tissues surrounding the primary zone of thermally induced coagulation, which results in an expansion of the burn wound, both in area and depth, within 48 hours postburn. Neutrophil sequestration and activation leading to microvascular damage is thought to mediate this secondary tissue damage. Resolvins, a class of endogenous mediators derived from omega-3 polyunsaturated fatty acids, have been shown to regulate the resolution of inflammation. We hypothesized that exogenous resolvins could mitigate the deleterious impact of the inflammatory response in burn wounds. Using two different mouse burn injury models involving significant partial thickness injuries, we found that a systemically administered single dose of resolvin D2 (RvD2) as low as 25 pg/g bw given within an interval of up to 4 hours postburn effectively prevented thrombosis of the deep dermal vascular network and subsequent dermal necrosis. By preserving the microvascular network, RvD2 enhanced neutrophil access to the dermis, but prevented neutrophil-mediated damage through other anti-inflammatory actions, including inhibition of tumor necrosis factor-α, interleukin-1β, and neutrophil platelet-endothelial cell adhesion molecule-1. In a clinical context, RvD2 may be therapeutically useful by reducing the need for surgical debridement and the area requiring skin grafting. PMID:23110665

  6. Centrilobular zonal necrosis as a hallmark of a distinctive subtype of autoimmune hepatitis

    PubMed Central

    Abe, Hiroshi; Sugita, Tomonori; Seki, Nobuyoshi; Chuganji, Yoshimichi; Furumoto, Youhei; Sakata, Akihiko

    2016-01-01

    Background and aim Centrilobular zonal necrosis (CZN) is a known histological variant of autoimmune hepatitis (AIH). However, the significance of CZN is yet to be fully elucidated. This study aimed to determine whether CZN is a hallmark of a distinctive subtype of AIH. Methods Histological changes in the centrilobular zones of liver biopsies from 113 AIH patients were assessed by a single pathologist and classified into three categories: typical zonal necrosis defined as CZN (15 patients); other necroinflammatory change (NIC; 24 patients); and absence of necrosis (non-NIC; 74 patients). The clinicopathological features and immunogenetic background of CZN patients were then assessed. Results The clinicopathological features of AIH with CZN were distinct from other types of AIH, including a higher frequency of acute onset, lower frequency of antinuclear antibodies, lower antinuclear antibody titers, lower serum immunoglobulin G levels, lower grade interface hepatitis, less prominent lymphoplasmacytic infiltration, and lower AIH score. Increased and decreased frequencies of HLA-DR9 and HLA-DR4, respectively, were identified as immunogenetic features of AIH with CZN. Conversely, the clinicopathological characteristics of AIH with NIC were similar to those of non-NIC AIH, including the majority of the AIH patients. The therapeutic outcomes of AIH with CZN were excellent when precise diagnoses were made without delay. Conclusion The clinicopathological features and immunogenetic background of AIH with CZN differed from AIH without CZN. CZN may be a hallmark of a distinct subtype of AIH. PMID:26657454

  7. Fat Embolism Syndrome Secondary to Bone Marrow Necrosis in Patients with Hemoglobinopathies.

    PubMed

    Gangaraju, Radhika; Reddy, Vishnu V B; Marques, Marisa B

    2016-09-01

    Bone marrow necrosis with subsequent embolization of the fat and necrotic tissues into the systemic circulation causing fat embolism syndrome and multiorgan failure is a rare complication of patients with hemoglobinopathies. The exact etiology of this condition is not known. Because it occurs more often in patients with compound heterozygous conditions than in sickle cell disease, some patients are unaware of their predisposition. The initial symptoms are nonspecific, such as back and/or abdominal pain, fever, and fatigue, which may rapidly progress to respiratory failure and severe neurologic compromise. Common laboratory tests reveal anemia without reticulocytosis, thrombocytopenia, leukoerythroblastic picture with immature white cells and nucleated red blood cells, increased lactate dehydrogenase, high ferritin, and, sometimes increased creatinine. The diagnosis can be delayed because of an apparent lack of awareness about bone marrow necrosis with fat embolism syndrome, its rarity, and its similarities with other conditions such as thrombotic thrombocytopenic purpura. Although a bone marrow biopsy is diagnostic, waiting for it delays definitive treatment, which appears to be essential for the recovery of end-organ damage, such as neurologic and pulmonary damage. In our experience, either multiple units of red blood cell transfusion or, preferably, red cell exchange initiated promptly, is lifesaving. PMID:27598359

  8. Delayed emergence after anesthesia.

    PubMed

    Tzabazis, Alexander; Miller, Christopher; Dobrow, Marc F; Zheng, Karl; Brock-Utne, John G

    2015-06-01

    In most instances, delayed emergence from anesthesia is attributed to residual anesthetic or analgesic medications. However, delayed emergence can be secondary to unusual causes and present diagnostic dilemmas. Data from clinical studies is scarce and most available published material is comprised of case reports. In this review, we summarize and discuss less common and difficult to diagnose reasons for delayed emergence and present cases from our own experience or reference published case reports/case series. The goal is to draw attention to less common reasons for delayed emergence, identify patient populations that are potentially at risk and to help anesthesiologists identifying a possible cause why their patient is slow to wake up. PMID:25912729

  9. Quantitation of Acute Necrosis After Experimental Myocardial Infarction

    PubMed Central

    Yeap, Xin-Yi; Dehn, Shirley; Adelman, Jeremy; Lipsitz, Jeremy; Thorp, Edward B.

    2016-01-01

    Myocardial infarction (MI) is death and necrosis of myocardial tissue secondary to ischemia. MI is associated with adverse cardiac remodeling, progressive heart chamber dilation, ventricular wall thinning, and loss of cardiac function. Myocardial necrosis can be experimentally induced in rodents to simulate human MI by surgical occlusion of coronary arteries. When induced in knockout or transgenic mice, this model is useful for the identification of molecular modulators of cell death, cardiac remodeling, and preclinical therapeutic potential. Herein we outline in tandem, methods for microsurgical ligation of the left anterior descending artery followed by quantitation of myocardial necrosis. Necrosis is quantified after staining the heart with triphenyltetrazolium chloride. PMID:23733573

  10. The interplay between regulated necrosis and bacterial infection.

    PubMed

    Blériot, Camille; Lecuit, Marc

    2016-06-01

    Necrosis has long been considered as a passive event resulting from a cell extrinsic stimulus, such as pathogen infection. Recent advances have refined this view and it is now well established that necrosis is tightly regulated at the cell level. Regulated necrosis can occur in the context of host-pathogen interactions, and can either participate in the control of infection or favor it. Here, we review the two main pathways implicated so far in bacteria-associated regulated necrosis: caspase 1-dependent pyroptosis and RIPK1/RIPK3-dependent necroptosis. We present how these pathways are modulated in the context of infection by a series of model bacterial pathogens. PMID:27048818

  11. Time delay spectrum conditioner

    DOEpatents

    Greiner, Norman R.

    1980-01-01

    A device for delaying specified frequencies of a multiple frequency laser beam. The device separates the multiple frequency beam into a series of spatially separated single frequency beams. The propagation distance of the single frequency beam is subsequently altered to provide the desired delay for each specific frequency. Focusing reflectors can be utilized to provide a simple but nonadjustable system or, flat reflectors with collimating and focusing optics can be utilized to provide an adjustable system.

  12. Mitochondria-targeted antioxidants do not prevent tumour necrosis factor-induced necrosis of L929 cells.

    PubMed

    Jarvis, Reagan M; Göttert, Jana; Murphy, Michael P; Ledgerwood, Elizabeth C

    2007-09-01

    Mitochondrial production of reactive oxygen species (ROS) is widely reported as a central effector during TNF-induced necrosis. The effect of a family of mitochondria-targeted antioxidants on TNF-induced necrosis of L929 cells was studied. While the commonly used lipid-soluble antioxidant BHA effectively protected cells from TNF-induced necrosis, the mitochondria-targeted antioxidants MitoQ(3), MitoQ(5), MitoQ(10) and MitoPBN had no effect on TNF-induced necrosis. Since BHA also acts as an uncoupler of mitochondrial membrane potential, two additional uncouplers were tested. FCCP and CCCP both provided dose-dependent inhibition of TNF-induced necrosis. In conclusion, the generation of mitochondrial ROS may not be necessary for TNF-induced necrosis. Instead, these results suggest alternative mitochondrial functions, such as a respiration-dependent process, are critical for necrotic death. PMID:17729122

  13. Delayed voice communication

    NASA Astrophysics Data System (ADS)

    Love, Stanley G.; Reagan, Marcum L.

    2013-10-01

    We present results from simulated deep-space exploration missions that investigated voice communication with significant time delays. The simulations identified many challenges: confusion of sequence, blocked calls, wasted crew time, impaired ability to provide relevant information to the other party, losing track of which messages have reached the other party, weakened rapport between crew and ground, slow response to rapidly changing situations, and reduced situational awareness. These challenges were met in part with additional training; greater attention and foresight; longer, less frequent transmissions; meticulous recordkeeping and timekeeping; and specific alerting and acknowledging calls. Several simulations used both delayed voice and text messaging. Text messaging provided a valuable record of transmissions and allowed messages to be targeted to subsets of the flight and ground crew, but it was a poor choice for high-workload operators such as vehicle drivers and spacewalkers. Even with the foregoing countermeasures, delayed voice communication is difficult. Additional aids such as automatic delay timers and voice-to-text transcription would help. Tests comparing delays of 50 and 300 s unexpectedly revealed that communicating with the shorter delay was just as challenging as with the longer one.

  14. Severe Hepatic Necrosis Associated with Methyldopa

    PubMed Central

    Cameron, Ian A.; Achord, James L.; Bartee, Harry

    1981-01-01

    Family physicians should carefully follow their patients receiving methyldopa for liver toxicity. Methyldopa is commonly used in treating hypertension and its hepatotoxic potential is frequently overlooked. This point is illustrated in the following case report involving a 45-year-old black female. The patient had been receiving oral methyldopa for 7.5 months prior to hospitalization for control of severe hypertension. Methyldopa was discontinued on her second hospital day when her liver tests were found to be abnormal. She developed progressive liver failure and lapsed into hepatic coma. Subsequently, her liver biopsy showed severe hepatic necrosis. She slowly improved with medical management. Her liver tests returned to normal; she resumed work and at 14 months follow up her liver biopsy showed no evidence of chronic active liver disease. Monitoring for methyldopa toxicity as outlined in this article could have prevented this costly and near lethal side effect. ImagesFig. 1Fig. 2 PMID:21289717

  15. Eosinophilic Gastritis Presenting as Tissue Necrosis

    PubMed Central

    Jo, Yong Min; Jang, Jin Seok; Han, Seung Hee; Kang, Sang Hyun; Kim, Woo Jae; Jeong, Jin Sook

    2015-01-01

    Eosinophilic gastroenteritis is very rare disorder that is characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of any definite causes of eosinophilia. It is associated with various clinical gastrointestinal manifestations, and depends on the involved layer and site. We report a case of eosinophilic gastritis presenting with severe necrosis. The symptoms disappeared immediately after beginning steroid treatment, and the eosinophil count decreased to the reference range. The patient showed eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis. It is a unique presentation of eosinophilic gastritis. To the best of our knowledge, no case of eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis has been previously reported in Korea. PMID:26668805

  16. Complete spontaneous necrosis of hepatocellular carcinoma confirmed on resection: A case report

    PubMed Central

    Saito, Ryusuke; Amano, Hironobu; Abe, Tomoyuki; Fujikuni, Nobuaki; Nakahara, Masahiro; Yonehara, Shuji; Teramen, Kazushi; Noriyuki, Toshio

    2016-01-01

    Introduction Complete spontaneous necrosis of hepatocellular carcinoma (HCC) without any pretreatment or angiography is rare. We present a rare case of spontaneous complete necrosis of HCC, as confirmed after hepatectomy. Presentation of case The patient, a 74-year-old man with a history of alcoholic hepatitis, was referred to our hospital for confirmation of suspected HCC. In March 2015, abdominal ultrasonography detected a low echoic mass in segment 8 (S8) of the liver. Contrast-enhanced computed tomography (CT) imaging revealed interval growth of this tumor and showed that the tumor was well enhanced in the arterial phase and washed out in the portal and delayed phases. The serum alpha-fetoprotein level was elevated at 30.8 ng/mL and the percentage of the L3 isoform was 25.5%. Two months later, CT imaging showed that the tumor was of low density and had decreased in size; no contrast enhancement of the tumor was seen. Spontaneous necrosis of the HCC was considered; however, as we could not exclude viable malignant cells in the tumor, we performed S8 segmentectomy of the liver. The resected tumor specimen had a thick fibrous capsule. Histopathological findings showed only granulation and necrotic tissue accompanied by bleeding and hemosiderosis. No viable tumor cells were observed. The serum alpha-fetoprotein level returned to the normal range one month after surgery. Discussion If spontaneous regression has occurred, there is a possibility of HCC recurrence and of remnant viable tumor cells. Conclusion We present a rare case of complete spontaneous necrosis of HCC and strongly recommended surgical intervention. PMID:27060644

  17. Photosensitizer absorption coefficient modeling and necrosis prediction during Photodynamic Therapy.

    PubMed

    Salas-García, Irene; Fanjul-Vélez, Félix; Arce-Diego, José Luis

    2012-09-01

    The development of accurate predictive models for Photodynamic Therapy (PDT) has emerged as a valuable tool to adjust the current therapy dosimetry to get an optimal treatment response, and definitely to establish new personal protocols. Several attempts have been made in this way, although the influence of the photosensitizer depletion on the optical parameters has not been taken into account so far. We present a first approach to predict the spatio-temporal variation of the photosensitizer absorption coefficient during PDT applied to dermatological diseases, taking into account the photobleaching of a topical photosensitizer. This permits us to obtain the photons density absorbed by the photosensitizer molecules as the treatment progresses and to determine necrosis maps to estimate the short term therapeutic effects in the target tissue. The model presented also takes into account an inhomogeneous initial photosensitizer distribution, light propagation in biological media and the evolution of the molecular concentrations of different components involved in the photochemical reactions. The obtained results allow to investigate how the photosensitizer depletion during the photochemical reactions affects light absorption by the photosensitizer molecules as the optical radiation propagates through the target tissue, and estimate the necrotic tumor area progression under different treatment conditions. PMID:22704663

  18. United Kingdom nationwide study of avascular necrosis of the jaws including bisphosphonate-related necrosis.

    PubMed

    Rogers, S N; Palmer, N O A; Lowe, D; Randall, C

    2015-02-01

    We aimed to record all new patients who presented to departments of oral surgery, oral medicine, and oral and maxillofacial surgery, and to dental hospitals in the UK, with avascular necrosis of the jaws including bisphosphonate-related necrosis (BRONJ) over a 2-year period (1 June 2009-31 May 2011). They were eligible irrespective of age, cause, or coexisting conditions. Data on incidence, clinical characteristics, risk factors, and coexisting conditions were collected. A total of 383 cases were registered: 369 were described as BRONJ, 5 as avascular necrosis, and 9 were unknown. Bisphosphonates had been given orally in 207 (56%), intravenously in 125 (34%), both orally and intravenously in 27 (7%), and was unknown in 9 (2%); one had been given denosumab. The main risk factor was dental extraction, and the mandible was commonly affected. The median duration of administration until onset of BRONJ was 3 years in those treated intravenously and 4 years in those treated orally. Levels of engagement with the study varied between regions, and extrapolation from the 2 most involved (Merseyside and Northern Ireland) found around 8.2-12.8 cases/million/year, which is 508-793 patients/year across the UK. To our knowledge this is one of the first studies to estimate national rates of BRONJ. It confirms that the risk and incidence are low. With changes in trends for antiresorptive bone medication, and increasing numbers of elderly people, it would be useful to repeat the registration in the future. PMID:25497376

  19. Contrast-Enhanced Ultrasonography of Hepatocellular Carcinoma After Chemoembolisation Using Drug-Eluting Beads: A Pilot Study Focused on Sustained Tumor Necrosis

    SciTech Connect

    Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina Georgiou; Kornezos, Ioannis Matsaidonis, Dimitrios

    2010-10-15

    The purpose of this study was to assess the use of contrast-enhanced ultrasonography (CEUS) and the sustained antitumor effect of drug-eluting beads used for transarterial chemoembolisation (TACE) of unresectable hepatocellular carcinoma (HCC). Ten patients with solitary, unresectable HCC underwent CEUS before, 2 days after, and 35 to 40 days after TACE using a standard dose (4 ml) of drug-eluting beads (DC Beads; Biocompatibles, Surrey, UK) preloaded with doxorubicin (25 mg doxorubicin/ml hydrated beads). For CEUS, a second-generation contrast agent (SonoVue, Bracco, Milan, Italy) and a low mechanical-index technique were used. A part of the tumor was characterized as necrotic if it showed complete lack of enhancement. The percentage of necrosis was calculated at the sonographic section that depicted the largest diameter of the tumor. Differences in the extent of early (2 days after TACE) and delayed (35 to 40 days after TACE) necrosis were quantitatively and subjectively assessed. Early post-TACE tumor necrosis ranged from 21% to 70% (mean 43.5% {+-} 19%). There was a statistically significant (p = 0.0012, paired Student t test) higher percentage of delayed tumor necrosis, which ranged from 24% to 88% (mean 52.3% {+-} 20.3%). Subjective evaluation showed a delayed obvious increase of the necrotic areas in 5 patients. In 2 patients, tumor vessels that initially remained patent disappeared on the delayed follow-up. A part of tumor necrosis after chemoembolisation of HCC with DEB seems to take place later than 2 days after TACE. CEUS may provide evidence for the sustained antitumor effect of DEB-TACE. Nevertheless, the ideal time for the imaging evaluation of tumor response remains to be defined.

  20. Downhole delay assembly for blasting with series delay

    DOEpatents

    Ricketts, Thomas E.

    1982-01-01

    A downhole delay assembly is provided which can be placed into a blasthole for initiation of explosive in the blasthole. The downhole delay assembly includes at least two detonating time delay devices in series in order to effect a time delay of longer than about 200 milliseconds in a round of explosions. The downhole delay assembly provides a protective housing to prevent detonation of explosive in the blasthole in response to the detonation of the first detonating time delay device. There is further provided a connection between the first and second time delay devices. The connection is responsive to the detonation of the first detonating time delay device and initiates the second detonating time delay device. A plurality of such downhole delay assemblies are placed downhole in unfragmented formation and are initiated simultaneously for providing a round of explosive expansions. The explosive expansions can be used to form an in situ oil shale retort containing a fragmented permeable mass of formation particles.

  1. Coagulopathy and encephalopathy in a dog with acute hepatic necrosis.

    PubMed

    Strombeck, D R; Krum, S; Rogers, Q

    1976-10-15

    Disseminated intravascular coagulation developed secondary to hepatic necrosis in a 5-year-old Saint Bernard. Although the coagulopathy responded to treatment with heparin, the dog died from the combined effects of gastric hemorrhage and encephalopathy, both of which are complications of hepatic necrosis. PMID:977448

  2. The Vernier delay unit

    SciTech Connect

    Pierce, W.B.

    1985-02-01

    One of the most critical timing specifications for the SLC machine occurs at the injector and ejector magnets for the Damping Ring. It has been determined that the trigger pulses to the magnets must be controlled to 0.1 ns. The primary source for all trigger pulses for the SLC machine is the Programmable Delay Unit (PDU). The PDU generates a 67.2 ns wide pulse with delay increments of 8.7 ns. The gap between the required accuracy and that available from the PDU requires the design of a new module that is called the Vernier Delay Unit (VDU). This module accepts the 67.2 ns pulse from the PDU and is capable of increasing the delay in steps of 0.1 ns from 0 to 10.7 ns plus the minimum 9 ns delay. The module has two totally independent channels. The pulse input to the module is software selectable from either the auxiliary backplane or a front panel Lemo connector. The auxiliary backplane pulses are to be the 67 ns differential ECL pulses from the PDU. The front panel input is to be a NIM level (-0.7 V 50 termination).

  3. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

    PubMed Central

    Noel, Pawan; Patel, Krutika; Durgampudi, Chandra; Trivedi, Ram N; de Oliveira, Cristiane; Crowell, Michael D; Pannala, Rahul; Lee, Kenneth; Brand, Randall; Chennat, Jennifer; Slivka, Adam; Papachristou, Georgios I; Khalid, Asif; Whitcomb, David C; DeLany, James P; Cline, Rachel A; Acharya, Chathur; Jaligama, Deepthi; Murad, Faris M; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay P

    2016-01-01

    Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP. PMID:25500204

  4. [Programmed necrosis: a new target for
ischemia reperfusion injury].

    PubMed

    Li, Xiaojing; Ming, Yingzi; Niu, Ying; Liu, Qianwen; Ye, Qifa

    2016-07-01

    Recent years, the researchers have found a new type of cell death, referred to programmed necrosis or necroptosis, which involves the death receptor and the ligand binds and is initiated under the inhibition of apoptosis pathway. Programmed necrosis possesses the morphological features of typical necrosis accompanied by inflammation. The receptor interacting protein kinase 1/3(RIPK1/3) can be inhibited by the specific inhibitors, such as necrostatin-1. RIPK1/3 could regulate programmed necrosis and play a key role in the process. The significance of programmed necrosis in ischemia-reperfusion injury (IRI) has been attracted great attention at present. Simultaneously, a series of studies have found it also involves in the IRI of heart, kidney, brain and retina. PMID:27592584

  5. Plasma intestinal alkaline phosphatase isoenzymes in neonates with bowel necrosis.

    PubMed Central

    McLachlan, R; Coakley, J; Murton, L; Campbell, N

    1993-01-01

    AIM--To determine if the intestinal isoenzymes of alkaline phosphatase (ALP) are biochemical markers of bowel necrosis in neonates. METHODS--Plasma ALP isoenzymes were measured in 22 babies with bowel necrosis, histologically confirmed, and in 22 matched controls. The isoenzymes were also measured in 16 infants with signs of necrotising enterocolitis, who recovered without histological confirmation of bowel necrosis. The isoenzymes were separated by polyacrylamide gel electrophoresis. Auxiliary tests for identification included neuraminidase digestion and treatment with monoclonal and polyclonal antiplacental antibodies. RESULTS--Intestinal ALP was detected in 16 infants with bowel necrosis--13 had fetal intestinal ALP (FI-ALP) and three had adult intestinal ALP (AI-ALP). FI-ALP was detected in nine of the controls. In the babies with bowel necrosis intestinal ALP was found over all gestations, but in the controls only in those less than 34 weeks. The percentages of total ALP activity due to intestinal ALP were significantly higher in those with bowel necrosis compared with matched controls (p = 0.028). In babies of all gestations diagnostic sensitivity for the presence of intestinal ALP as a marker of bowel necrosis was 73% and diagnostic specificity 59%. In babies greater than 34 weeks' gestation, diagnostic sensitivity fell to 60% but the test became completely specific. In two babies FI-ALP increased from zero/trace to high activity coincident with the episode of bowel necrosis. In 16 babies with signs of necrotising enterocolitis but unconfirmed bowel necrosis FI-ALP was detected in four. CONCLUSION--Intestinal ALP seems to be released into the circulation in some babies with bowel necrosis, but its detection does not have the diagnostic sensitivity and specificity to be a reliable biochemical marker of the condition. Images PMID:8157755

  6. Immunization with viral antigens: infectious haematopoietic necrosis.

    PubMed

    Winton, J R

    1997-01-01

    Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease. PMID:9270850

  7. Clinical studies with tumour necrosis factor.

    PubMed

    Spriggs, D R; Sherman, M L; Frei, E; Kufe, D W

    1987-01-01

    The mechanism of tumour necrosis factor (TNF) cytotoxicity remains unknown. The in vivo antitumour effects of TNF may be related to direct cytotoxicity, immunomodulatory effects or endothelial effects on tumour vasculature. Phase I and early Phase II clinical trials of human recombinant TNF are under way in Japan, the USA, the UK and Germany. The maximum Phase II dose for TNF has not been established. The clinical toxicity of TNF is generally similar to that of other biological agents. Systemic toxicity, including fever, chills, anorexia and nausea, has been seen in most patients treated with TNF and has not been clearly related to dose. Other toxicities have included liver function abnormalities, hypotension, transient neurological changes and haematological abnormalities. Few clinical responses have been reported but organized Phase II testing remains to be completed. Combination trials with interferons have recently been initiated. Phase II efficacy studies of TNF as a single agent and in combination are needed for an assessment of the value of this agent in cancer therapy. PMID:3330011

  8. Pyelo-ureteral necrosis after renal transplantation.

    PubMed

    Spasovski, Goce B; Masin-Spasovska, Jelka; Stavridis, Sotir; Saiti, Skender; Lekovski, Ljupco

    2008-01-01

    Because of the limited chance of receiving a kidney transplant (for several well-known reasons), a lot of desperate dialysis patients procure an unrelated donor kidney transplant against all medical advice. This type of renal paid transplantation is associated with many surgical complications and invasive opportunistic infections that increase the morbidity and mortality in this group of transplant recipients. In this report, we describe a case of a 22-year-old girl with a segmental infarction of the graft lower pole and a complete pyelo-ureteral necrosis as a consequence of some vascular damage, complicated by a pathohistological finding of an invasive candidiasis. Despite the successful surgical pyelovesical anastomosis and the good recovery of the patient and the kidney, long-term prognosis remains poor. The lack of information from the transplanting center regarding both donor and recipient and the associated, unacceptable risks on the graft and patient survival in unrelated, paid transplant recipients reinforce the standpoint that this practice should be abandoned. PMID:18204913

  9. [An infected necrosis of the chin].

    PubMed

    Muller, B S; van Goor, H F; Rosenberg, A J W P

    2016-07-01

    A 51-year-old man was referred by his dentist to a maxillofacial surgeon with complaints of illness and pain in the mandible, associated with a rapidly expanding area of black gingiva and mucosa surrounding the lower front teeth. Clinically and radiographically there was evidence of an infected necrosis of the chin and floor of mouth. Following debridement at the operating room, the patient was treated at the intensive care unit for septic shock leading to prolonged hospitalisation. Investigation of the bone marrow did not provide an explanation for pancytopenia or the severity of the illness. In addition, genetic investigation of thiopurine S-methyltransferase gene showed no mutations. This gene codes for an identically named protein enzyme that contributes in the metabolising of the medicine azathioprine, used daily for an autoimmune disease. A combination of the use of azathioprine, a folic acid deficiency and sepsis led to this exceptional course of illness. Therapeutic intervention consisted of surgical debridement and treatment of the bacteraemia. Afterwards several corrective surgeries were necessary to restore oral functions. PMID:27430038

  10. Estimating Delays In ASIC's

    NASA Technical Reports Server (NTRS)

    Burke, Gary; Nesheiwat, Jeffrey; Su, Ling

    1994-01-01

    Verification is important aspect of process of designing application-specific integrated circuit (ASIC). Design must not only be functionally accurate, but must also maintain correct timing. IFA, Intelligent Front Annotation program, assists in verifying timing of ASIC early in design process. This program speeds design-and-verification cycle by estimating delays before layouts completed. Written in C language.