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

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com; Indiana University Health Proton Therapy Center, Bloomington, Indiana; Linton, Okechukwu R.

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 evaluatedmore » 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

Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis.

PubMed

Borab, Zachary; Mirmanesh, Michael D; Gantz, Madeleine; Cusano, Alessandro; Pu, Lee L Q

2017-04-01

Every year, 1.2 million cancer patients receive radiation therapy in the United States. Late radiation tissue injury occurs in an estimated 5-15% of these patients. Tissue injury can include skin necrosis, which can lead to chronic nonhealing wounds. Despite many treatments available to help heal skin necrosis such as hyperbaric oxygen therapy, no clinical guidelines exist and evidence is lacking. The purpose of this review is to identify and comprehensively summarize studies published to date to evaluate the effectiveness of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. Adhering to PRISMA guidelines, a systematic review of currently published articles was performed, evaluating the use of hyperbaric oxygen to treat skin necrosis. Eight articles were identified, including one observational cohort, five case series, and two case reports. The articles describe changes in symptoms and alteration in wound healing of radiation-induced skin necrosis after treatment with hyperbaric oxygen therapy. Hyperbaric oxygen therapy is a safe intervention with promising outcomes; however, additional evidence is needed to endorse its application as a relevant therapy in the treatment of radiation-induced skin necrosis. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Angiographic delay: a viable alternative to surgical delay.

PubMed

Aboutanos, Sharline Z; Spinos, Efstathios; Blanchet, Nadia P

2012-06-01

Selective embolization of the inferior epigastric arteries can serve as a method for transverse rectus abdominis musculocutaneous (TRAM) flap delay. The purpose of this study was to determine whether delay by selective arterial embolization is comparable to traditionally surgically delayed TRAM flaps as reported in the literature, in terms of skin and fat necrosis, and to examine whether certain risk factors play a role in TRAM flap fat necrosis despite angiographic delay. Retrospective chart review was performed for 88 consecutive patients who underwent unilateral TRAM flap breast reconstruction after selective embolization of bilateral inferior epigastric arteries. Between 1997 and 2009, 88 pedicled TRAM flaps were performed for breast reconstruction in women with a mean age of 49.7 years. No patients had flap skin necrosis or total flap loss. In all, 13.6% patients had TRAM flap fat necrosis. Two patients in the TRAM fat necrosis group (16.7%) had a positive history of smoking, which was a statistically significant risk factor for necrosis (P = 0.048). Outcomes of pedicled TRAM flaps delayed by selective arterial embolization are comparable to historical controls of those delayed by traditional surgical means (ligation of artery and vein) and better than nondelayed flaps. Smoking remains a significant risk factor for TRAM flap fat necrosis despite the benefit of delay.

Novel biomarker identification using metabolomic profiling to differentiate radiation necrosis and recurrent tumor following Gamma Knife radiosurgery.

PubMed

Lu, Alex Y; Turban, Jack L; Damisah, Eyiyemisi C; Li, Jie; Alomari, Ahmed K; Eid, Tore; Vortmeyer, Alexander O; Chiang, Veronica L

2017-08-01

OBJECTIVE Following an initial response of brain metastases to Gamma Knife radiosurgery, regrowth of the enhancing lesion as detected on MRI may represent either radiation necrosis (a treatment-related inflammatory change) or recurrent tumor. Differentiation of radiation necrosis from tumor is vital for management decision making but remains difficult by imaging alone. In this study, gas chromatography with time-of-flight mass spectrometry (GC-TOF) was used to identify differential metabolite profiles of the 2 tissue types obtained by surgical biopsy to find potential targets for noninvasive imaging. METHODS Specimens of pure radiation necrosis and pure tumor obtained from patient brain biopsies were flash-frozen and validated histologically. These formalin-free tissue samples were then analyzed using GC-TOF. The metabolite profiles of radiation necrosis and tumor samples were compared using multivariate and univariate statistical analysis. Statistical significance was defined as p ≤ 0.05. RESULTS For the metabolic profiling, GC-TOF was performed on 7 samples of radiation necrosis and 7 samples of tumor. Of the 141 metabolites identified, 17 (12.1%) were found to be statistically significantly different between comparison groups. Of these metabolites, 6 were increased in tumor, and 11 were increased in radiation necrosis. An unsupervised hierarchical clustering analysis found that tumor had elevated levels of metabolites associated with energy metabolism, whereas radiation necrosis had elevated levels of metabolites that were fatty acids and antioxidants/cofactors. CONCLUSIONS To the authors' knowledge, this is the first tissue-based metabolomics study of radiation necrosis and tumor. Radiation necrosis and recurrent tumor following Gamma Knife radiosurgery for brain metastases have unique metabolite profiles that may be targeted in the future to develop noninvasive metabolic imaging techniques.

Delayed-onset heparin-induced skin necrosis: a rare complication of perioperative heparin therapy.

PubMed

Gan, Weh Kiat

2017-11-03

An uncommon case of delayed-onset dalteparin-induced skin necrosis in an 83-year-old Caucasian female patient associated with heparin-induced thrombocytopaenia (HIT) presenting on day 30 following dalteparin therapy is reported. Investigations revealed mild thrombocytopaenia with normal protein C, protein S, coagulation screen and positive test for heparin-platelet factor-4 antibody. Clinical diagnosis of heparin-induced skin necrosis with HIT was made. Dalteparin injection was discontinued promptly and substituted with fondaparinux therapy. The patient achieved good recovery following cessation of dalteparin therapy and was subsequently discharged. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jost, Sarah C.; Hope, Andrew; Kiehl, Erich

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 progressivemore » 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.« less

Surgical techniques in radiation induced temporal lobe necrosis in nasopharyngeal carcinoma patients.

PubMed

Alfotih, Gobran Taha Ahmed; Zheng, Mei Guang; Cai, Wang Qing; Xu, Xin Ke; Hu, Zhen; Li, Fang Cheng

2016-01-01

Radiation induced brain injury ranges from acute reversible edema to late, irreversible radiation necrosis. Radiation induced temporal lobe necrosis is associated with permanent neurological deficits and occasionally progresses to death. We present our experience with surgery on radiation induced temporal lobe necrosis (RTLN) in nasopharyngeal carcinoma (NPC) patients with special consideration of clinical presentation, surgical technique, and outcomes. This retrospective study includes 12 patients with RTLN treated by the senior author between January 2010 and December 2014. Patients initially sought medical treatment due to headache; other symptoms were hearing loss, visual deterioration, seizure, hemiparesis, vertigo, memory loss and agnosia. A temporal approach through a linear incision was performed for all cases. RTLN was found in one side in 7 patients, and bilaterally in 5. 4 patients underwent resection of necrotic tissue bilaterally and 8 patients on one side. No death occurred in this series of cases. There were no post-operative complications, except 1 patient who developed aseptic meningitis. All 12 patients were free from headache. No seizure occurred in patients with preoperative epilepsy. Other symptoms such as hemiparesis and vertigo improved in all patients. Memory loss, agnosia and hearing loss did not change post-operatively in all cases. The follow-up MR images demonstrated no recurrence of necrotic lesions in all 12 patients. Neurosurgical intervention through a temporal approach with linear incision is warranted in patients with radiation induced temporal lobe necrosis with significant symptoms and signs of increased intracranial pressure, minimum space occupying effect on imaging, or neurological deterioration despite conservative management. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bender, Edward T.

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) hmore » 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.« less

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

PubMed

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

2016-04-12

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.

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levin, Victor A., E-mail: vlevin49@comcast.ne; Bidaut, Luc; Hou, Ping

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 weeksmore » 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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Udwadia, Z.F.; Athale, S.; Misra, V.P.

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.

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.

O2 -sensitive MRI distinguishes brain tumor versus radiation necrosis in murine models.

PubMed

Beeman, Scott C; Shui, Ying-Bo; Perez-Torres, Carlos J; Engelbach, John A; Ackerman, Joseph J H; Garbow, Joel R

2016-06-01

The goal of this study was to quantify the relationship between the (1) H longitudinal relaxation rate constant, R1 , and oxygen (O2 ) concentration (relaxivity, r1 ) in tissue and to quantify O2 -driven changes in R1 (ΔR1 ) during a breathing gas challenge in normal brain, radiation-induced lesions, and tumor lesions. R1 data were collected in control-state mice (n = 4) during three different breathing gas (and thus tissue O2 ) conditions. In parallel experiments, pO2 was measured in the thalamus of control-state mice (n = 4) under the same breathing gas conditions using an O2 -sensitive microprobe. The relaxivity of tissue O2 was calculated using the R1 and pO2 data. R1 data were collected in control-state (n = 4) mice, a glioma model (n = 7), and a radiation necrosis model (n = 6) during two breathing gas (thus tissue O2 ) conditions. R1 and ΔR1 were calculated for each cohort. O2 r1 in the brain was 9 × 10(-4)  ± 3 × 10(-4) mm Hg(-1) · s(-1) at 4.7T. R1 and ΔR1 measurements distinguished radiation necrosis from tumor (P< 0.03 and P< 0.01, respectively). The relaxivity of O2 in the brain is determined. R1 and ΔR1 measurements differentiate tumor lesions from radiation necrosis lesions in the mouse models. These pathologies are difficult to distinguish by traditional imaging techniques; O2 -driven changes in R1 holds promise in this regard. Magn Reson Med 75:2442-2447, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Extensive Necrosis After Radiation for Cancer: Experiences in Surgical Management

DOE Office of Scientific and Technical Information (OSTI.GOV)

BENNETT, JAMES E.

1963-06-01

Radionecrosis in skin and deeper tissues and its surgical repair are described in 16 cases. The observed epithelial changes included both atrophy and hypertrophy, but atrophy was the dominant feature. Epidermal hypertrophy, which preceded malignant change, developed more slowly and was less likely to occur in areas subjected to deep irradiation than in skin treated with multiple small doses of x-ray over a long period. The indolent ulceration that developed in skin augmented the changes in underlying tissues so that successful management of these ulcerations required adequate excision of the damaged area and replacement with fat-bearing pedicle flap tissue. Whenmore » adjacent flaps were used, permanent blood supply to the region was assured. In cases of radiotherapy for basal cell carcinoma of the scalp, skin necrosis resulted in skull exposure with subsequent osteomyelitis and/or bone necrosis. Excision included the full thickness of the skull, and pedicle flap tissue from the scalp was used for coverage. Cranioplasty was performed after good skin and soft tissue cover had been obtained. Therapeutic radiation of the neck invariably produces marked skin changes, and when ulceration occurs, the vulnerability of underlying structures demands surgical treatment. Lesions of the upper extremity can be excised and covered with direct pedicle flaps from the trunk. Therapeutic radiation of the retroperitoneal area may produce extensive visceral damage as well as injury to the anterior abdominal wall, and anterior suprapubic ulcerations are particularly difficult to deal with since mobile adjacent tissue is scarce. The avascular midline is a limiting factor in flap design. Abdominal flaps extending onto the thigh can be used, but these require multiple delaying procedures to insure adequate blood supply. Patients being managed by these procedures are described. Most patients underwent their operative procedures with few serious complications. While postoperative bleeding

Comparison between nonspecific and necrosis-avid gadolinium contrast agents in vascular disrupting agent-induced necrosis of rodent tumors at 3.0T.

PubMed

Wang, Huaijun; Miranda Cona, Marlein; Chen, Feng; Li, Junjie; Yu, Jie; Feng, Yuanbo; Peeters, Ronald; De Keyzer, Frederik; Marchal, Guy; Ni, Yicheng

2011-09-01

: To compare a commercial contrast agent (CA) Dotarem and a necrosis-avid CA (NACA) for their ability to evaluate the therapeutic necrosis with a vascular disrupting agent (VDA) on magnetic resonance imaging in rodent liver tumors to determine which could better correlate with the histopathologic outcome. : After the VDA treatment, 16 rats with 32 liver rhabdomyosarcomas were randomized into Dotarem and NACA groups (n = 8 per group) for both interindividual and intraindividual comparisons. T2-weighted imaging, T1-weighted imaging (T1WI), contrast-enhanced T1-weighted imaging (CE-T1WI), and diffusion-weighted imaging were performed at baseline, after VDA treatment and CA injections. The enhancing efficacy of CAs at immediate and delayed enhancement on CE-T1WI in viable tumor and necrosis was compared. Tumor necrosis ratios calculated from NACA and Dotarem were compared and correlated with gold-standard histopathology. : On the immediate CE-T1WI, viable tumor was enhanced by either CA. On the delayed CE-T1WI at 30 minutes, both CAs failed to demarcate viable tumor from necrosis. At 24 hours post-NACA, the necrosis was clearly distinguished from viable tumor and thus derived necrosis ratio matched that from histopathology (P = 0.99); necrosis ratio from Dotarem was significantly lower than that from NACA and histopathology (P < 0.05, both), with a higher correlation of NACA than that of Dotarem with histopathology (r = 0.99 vs. r = 0.82). : NACA better evaluated VDA-induced tumor necrosis than nonspecific CA on T1WI in tumor models of rat liver. NACA showed a closer correlation with histopathology than nonspecific CA for the delineation of true necrosis. Delayed enhancement on T1WI with nonspecific CA is not suitable for the assessment of VDA-induced tumor necrosis.

Assessment of MRI parameters as imaging biomarkers for radiation necrosis in the rat brain.

PubMed

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

2012-07-01

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(1), T(2), apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 × 10 mm(2)) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at ~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. ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T(1), T(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(1), T(2), MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores. Copyright © 2012 Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Silun; Tryggestad, Erik; Zhou Tingting

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 necroticmore » 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.« less

Differentiating radiation necrosis from tumor progression in brain metastases treated with stereotactic radiotherapy: utility of intravoxel incoherent motion perfusion MRI and correlation with histopathology.

PubMed

Detsky, Jay S; Keith, Julia; Conklin, John; Symons, Sean; Myrehaug, Sten; Sahgal, Arjun; Heyn, Chinthaka C; Soliman, Hany

2017-09-01

Radiation necrosis is a serious potential adverse event of stereotactic radiosurgery that cannot be reliably differentiated from recurrent tumor using conventional imaging techniques. Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) based method that uses a diffusion-weighted sequence to estimate quantitative perfusion and diffusion parameters. This study evaluated the IVIM-derived apparent diffusion coefficient (ADC) and perfusion fraction (f), and compared the results to the gold standard histopathological-defined outcomes of radiation necrosis or recurrent tumor. Nine patients with ten lesions were included in this study; all lesions exhibited radiographic progression after stereotactic radiosurgery for brain metastases that subsequently underwent surgical resection due to uncertainty regarding the presence of radiation necrosis versus recurrent tumor. Pre-surgical IVIM was performed to obtain f and ADC values and the results were compared to histopathology. Five lesions exhibited pathological radiation necrosis and five had predominantly recurrent tumor. The IVIM perfusion fraction reliably differentiated tumor recurrence from radiation necrosis (f mean  = 10.1 ± 0.7 vs. 8.3 ± 1.2, p = 0.02; cutoff value of 9.0 yielding a sensitivity/specificity of 100%/80%) while the ADC did not distinguish between the two (ADC mean  = 1.1 ± 0.2 vs. 1.2 ± 0.4, p = 0.6). IVIM shows promise in differentiating recurrent tumor from radiation necrosis for brain metastases treated with radiosurgery, but needs to be validated in a larger cohort.

SU-G-TeP3-12: Retrospective Assessment of R2star Using Ultra-High Field MRI in a Rodent Model of Radiation Necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belliveau, J; Menon, R

Purpose: To establish a quantitative MRI method that would be capable of predicting radiation necrosis without using a contrast agent. Methods: Healthy male Fischer 344 rats were irradiated using an animal irradiator capable of delivering 2.3 Gy/min with a kVp of 225 V. A dose of 40 Gy was given to half the brain in a single session. Rats were scanned using a 9.4 T animal MRI before irradiation and every two weeks following radiation until either necrosis developed or they were sacrificed for health reasons. A multi-echo gradient-echo sequence was acquired at every time point and the apparent transversemore » relaxation rate R{sub 2}* was calculated based on the measured signal decay. At the last time point, an ROI mask with an R{sub 2}* value of greater than 45 s{sup −1} was applied in the area of the external and internal capsule where radiation necrosis was confirmed. A retrospective analysis was performed to determine whether R{sub 2}* values would be able to predict where radiation necrosis would occur. Results: Radiation necrosis was morphologically visible between weeks 22–24 following treatment. Gadolinium MRI and histology confirmed radiation necrosis in the area of MRI enhancement. Our data suggests that there is a trend towards significance in the lesion as early as 12 weeks prior to morphological changes on MRI with significance occurring 6 weeks prior (p≤0.05, p≤0.01 at week 24). Measurements of the R{sub 2}* in the hippocampus did not show any significant difference; however, there are areas of visible R{sub 2}* change within sub-hippocampal regions. Conclusion: R{sub 2}* is a promising method that could be able to predict an underlying disease process that occurs prior to radiation necrosis. The constant increase in R{sub 2}* values suggests a possible neuroinflammatory mechanism rather than an acute vascular event where R{sub 2}* would tend to decrease in the area.« less

Prediction of radiation necrosis in a rodent model using magnetic resonance imaging apparent transverse relaxation (R_{2}^{*} )

NASA Astrophysics Data System (ADS)

Belliveau, Jean-Guy; Jensen, Michael D.; Stewart, James M. P.; Solovey, Igor; Klassen, L. Martyn; Bauman, Glenn S.; Menon, Ravi S.

2018-02-01

Background and purpose. Radiation necrosis remains an irreversible long-term side-effect following radiotherapy to the brain. The ability to predict areas that could ultimately develop into necrosis could lead to prevention and management of radiation necrosis. Materials and Methods. Fischer 344 rats were irradiated using two platforms (micro-CT irradiator and x-Rad 225 IGRT) with radiation up to 30 Gy for the micro-CT and 40 Gy for the xRAD-224 to half the brain. Animals were subsequently imaged using a 9.4 T MRI scanner every 2-4 weeks for up to 28 weeks using a 7-echo gradient echo sequence. The apparent transverse relaxation constant (R2* ) was calculated and retrospectively analyzed. Results. Animals irradiated with the low-dose rate micro-CT did not exhibit any symptoms or imaging changes associated with RN. Animals irradiated with the xRAD-225 exhibited imaging changes consistent with RN at week 24. Analysis of the R2* coefficient within the lesion and hippocampus shows the potential for detection of RN up to 10 weeks prior to morphological changes. Conclusions. The ability to predict areas of RN and increases of R2* within the hippocampus provides a method for long-term monitoring and prediction of RN.

Combination of Gold Nanoparticle-Conjugated Tumor Necrosis Factor-α and Radiation Therapy Results in a Synergistic Antitumor Response in Murine Carcinoma Models.

PubMed

Koonce, Nathan A; Quick, Charles M; Hardee, Matthew E; Jamshidi-Parsian, Azemat; Dent, Judith A; Paciotti, Giulio F; Nedosekin, Dmitry; Dings, Ruud P M; Griffin, Robert J

2015-11-01

Although remarkable preclinical antitumor effects have been shown for tumor necrosis factor-α (TNF) alone and combined with radiation, its clinical use has been hindered by systemic dose-limiting toxicities. We investigated the physiological and antitumor effects of radiation therapy combined with the novel nanomedicine CYT-6091, a 27-nm average-diameter polyethylene glycol-TNF-coated gold nanoparticle, which recently passed through phase 1 trials. The physiologic and antitumor effects of single and fractionated radiation combined with CYT-6091 were studied in the murine 4T1 breast carcinoma and SCCVII head and neck tumor squamous cell carcinoma models. In the 4T1 murine breast tumor model, we observed a significant reduction in the tumor interstitial fluid pressure (IFP) 24 hours after CYT-6091 alone and combined with a radiation dose of 12 Gy (P<.05 vs control). In contrast, radiation alone (12 Gy) had a negligible effect on the IFP. In the SCCVII head and neck tumor model, the baseline IFP was not markedly elevated, and little additional change occurred in the IFP after single-dose radiation or combined therapy (P>.05 vs control) despite extensive vascular damage observed. The IFP reduction in the 4T1 model was also associated with marked vascular damage and extravasation of red blood cells into the tumor interstitium. A sustained reduction in tumor cell density was observed in the combined therapy group compared with all other groups (P<.05). Finally, we observed a more than twofold delay in tumor growth when CYT-6091 was combined with a single 20-Gy radiation dose-notably, irrespective of the treatment sequence. Moreover, when hypofractionated radiation (12 Gy × 3) was applied with CYT-6091 treatment, a more than five-fold growth delay was observed in the combined treatment group of both tumor models and determined to be synergistic. Our results have demonstrated that TNF-labeled gold nanoparticles combined with single or fractionated high-dose radiation

Combination of Gold Nanoparticle-Conjugated Tumor Necrosis Factor-α and Radiation Therapy Results in a Synergistic Antitumor Response in Murine Carcinoma Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koonce, Nathan A.; Quick, Charles M.; Hardee, Matthew E.

Purpose: Although remarkable preclinical antitumor effects have been shown for tumor necrosis factor-α (TNF) alone and combined with radiation, its clinical use has been hindered by systemic dose-limiting toxicities. We investigated the physiological and antitumor effects of radiation therapy combined with the novel nanomedicine CYT-6091, a 27-nm average-diameter polyethylene glycol-TNF-coated gold nanoparticle, which recently passed through phase 1 trials. Methods and Materials: The physiologic and antitumor effects of single and fractionated radiation combined with CYT-6091 were studied in the murine 4T1 breast carcinoma and SCCVII head and neck tumor squamous cell carcinoma models. Results: In the 4T1 murine breast tumormore » model, we observed a significant reduction in the tumor interstitial fluid pressure (IFP) 24 hours after CYT-6091 alone and combined with a radiation dose of 12 Gy (P<.05 vs control). In contrast, radiation alone (12 Gy) had a negligible effect on the IFP. In the SCCVII head and neck tumor model, the baseline IFP was not markedly elevated, and little additional change occurred in the IFP after single-dose radiation or combined therapy (P>.05 vs control) despite extensive vascular damage observed. The IFP reduction in the 4T1 model was also associated with marked vascular damage and extravasation of red blood cells into the tumor interstitium. A sustained reduction in tumor cell density was observed in the combined therapy group compared with all other groups (P<.05). Finally, we observed a more than twofold delay in tumor growth when CYT-6091 was combined with a single 20-Gy radiation dose—notably, irrespective of the treatment sequence. Moreover, when hypofractionated radiation (12 Gy × 3) was applied with CYT-6091 treatment, a more than five-fold growth delay was observed in the combined treatment group of both tumor models and determined to be synergistic. Conclusions: Our results have demonstrated that TNF-labeled gold

Temporal Cerebral Microbleeds Are Associated With Radiation Necrosis and Cognitive Dysfunction in Patients Treated for Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Qingyu; Department of Neurology, Zengcheng People's Hospital, Guangzhou; Lin, Focai

Purpose: Radiation therapy for patients with nasopharyngeal carcinoma (NPC) may be complicated with radiation-induced brain necrosis (RN), resulting in deteriorated cognitive function. However, the underlying mechanism of this phenomenon remains unclear. This study attempts to elucidate the association between cerebral microbleeds (CMBs) and radiation necrosis and cognitive dysfunction in NPC patients treated with radiation therapy. Methods and Materials: This cross-sectional study included 106 NPC patients who were exposed to radiation therapy (78 patients with RN and 28 without RN). Sixty-six patients without discernable intracranial pathology were included as the control group. CMBs were confirmed using susceptibility-weighted magnetic resonance imaging. Cognitivemore » function was accessed using Montreal Cognitive Assessment. Patients with a total score below 26 were defined as cognitively dysfunction. Results: Seventy-seven patients (98.7%) in the RN group and 12 patients (42.9%) in the non-RN group had at least 1 CMB. In contrast, only 14 patients (21.2%) in the control group had CMBs. In patients with a history of radiation therapy, CMBs most commonly presented in temporal lobes (76.4%) followed by cerebellum (23.7%). Patients with RN had more temporal CMBs than those in the non-RN group (37.7 ± 51.9 vs 3.8 ± 12.6, respectively; P<.001). The number of temporal lobe CMBs was predictive for larger volume of brain necrosis (P<.001) in multivariate linear regression analysis. Although cognitive impairment was diagnosed in 55.1% of RN patients, only 7.1% of non-RN patients sustained cognitive impairment (P<.001). After adjusting for age, sex, education, period after radiation therapy, CMBs in other lobes, and RN volume, the number of temporal CMBs remained an independent risk factor for cognitive dysfunction (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04; P=.003). Conclusions: CMBs is a common radiological manifestation in NPC patients

Radiation necrosis presenting as pseudoprogression (PsP) during alectinib treatment of previously radiated brain metastases in ALK-positive NSCLC: Implications for disease assessment and management.

PubMed

Ou, Sai-Hong Ignatius; Klempner, Samuel J; Azada, Michele C; Rausei-Mills, Veronica; Duma, Christopher

2015-06-01

Radiation necrosis presenting as pseudoprogression (PsP) is relatively common after radiation and temozolomide (TMZ) treatment in glioblastoma multiforme (GBM), especially among patients with GBM that harbors intrinsic increased responsiveness to TMZ (methylated O6-methylguanine-DNA methyltransferase [MGMT] promoter). Alectinib is a second generation ALK inhibitor that has significant CNS activity against brain metastases in anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients. We report 2 ALK+ NSCLC patients who met RECIST criteria for progressive disease by central radiologic review due to increased in size from increased contrast enhancement in previously stereotactically radiated brain metastases with ongoing extra-cranial response to alectinib. In both patients alectinib was started within 4 months of completing stereotactic radiosurgery (SRS). The enlarging lesions in both patients were resected and found to have undergone extensive necrosis with no residual tumor pathologically. PsP was incorrectly classified as progressive disease even by central independent imaging review. Treatment-related necrosis of previously SRS-treated brain metastasis during alectinib treatment can present as PsP. It may be impossible to distinguish PsP from true disease progression without a pathologic examination from resected sample. High degree of clinical suspicion, close monitoring and more sensitive imaging modalities may be needed to distinguish PsP versus progression in radiated brain lesions during alectinib treatment especially if there is no progression extra-cranially. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 delaymore » suggests a common basis for delay induction in S and G/sub 2/ phases.« less

Detection of radiation-induced brain necrosis in live rats using label-free time-resolved fluorescence spectroscopy (TRFS) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hartl, Brad A.; Ma, Htet S. W.; Sridharan, Shamira; Hansen, Katherine; Klich, Melanie; Perks, Julian; Kent, Michael; Kim, Kyoungmi; Fragoso, Ruben; Marcu, Laura

2017-02-01

Differentiating radiation-induced necrosis from recurrent tumor in the brain remains a significant challenge to the neurosurgeon. Clinical imaging modalities are not able to reliably discriminate the two tissue types, making biopsy location selection and surgical management difficult. Label-free fluorescence lifetime techniques have previously been shown to be able to delineate human brain tumor from healthy tissues. Thus, fluorescence lifetime techniques represent a potential means to discriminate the two tissues in real-time during surgery. This study aims to characterize the endogenous fluorescence lifetime signatures from radiation induced brain necrosis in a tumor-free rat model. Fischer rats received a single fraction of 60 Gy of radiation to the right hemisphere using a linear accelerator. Animals underwent a terminal live surgery after gross necrosis had developed, as verified with MRI. During surgery, healthy and necrotic brain tissue was measured with a fiber optic needle connected to a multispectral fluorescence lifetime system. Measurements of the necrotic tissue showed a 48% decrease in intensity and 20% increase in lifetimes relative to healthy tissue. Using a support vector machine classifier and leave-one-out validation technique, the necrotic tissue was correctly classified with 94% sensitivity and 97% specificity. Spectral contribution analysis also confirmed that the primary source of fluorescence contrast lies within the redox and bound-unbound population shifts of nicotinamide adenine dinucleotide. A clinical trial is presently underway to measure these tissue types in humans. These results show for the first time that radiation-induced necrotic tissue in the brain contains significantly different metabolic signatures that are detectable with label-free fluorescence lifetime techniques.

Incidence and dosimetric parameters for brainstem necrosis following intensity modulated radiation therapy in nasopharyngeal carcinoma.

PubMed

Li, Yang-Chan; Chen, Fo-Ping; Zhou, Guan-Qun; Zhu, Jin-Han; Hu, Jiang; Kang, De-Hua; Wu, Chen-Fei; Lin, Li; Wang, Xiao-Ju; Ma, Jun; Sun, Ying

2017-10-01

To clarify the incidence of brainstem toxicity and perform a dose-volume analysis for the brainstem after long-term follow-up of a large cohort of nasopharyngeal carcinoma (NPC) patients who underwent intensity-modulated radiation therapy (IMRT). All patients with NPC treated with IMRT at Sun Yat-sen University Cancer Center between April 2009 and March 2012 were retrospectively reviewed. A total of 1544 patients with follow-up >12months and detailed treatment plan data were included. Radiotherapy was administered using the simultaneous integrated boost technique in 2.0-2.48Gy per fractions/28-33 fractions. Brainstem necrosis was defined as lesions with high signal intensity on T2-weighted images and low signal intensity on T1-weighted images, with or without enhancement after administration of contrast in follow-up MRI. After median follow-up of 79.7months (range, 12.2-85.6months), 2/1544 (0.13%) patients developed brainstem necrosis after intervals of 12.3 and 18.5months. Actuarial incidence of brainstem necrosis was 0.07%, 0.13%, 0.13% and 0.13% after 1, 2, 3 and 5years, respectively. Overall, 384 (24.9%), 153 (9.9%), 67 (4.3%), 39 (2.5%), 78 (5.1%), and 114 (7.4%) patients had excessive doses of D max ≥64Gy, D1cc>59Gy, D2cc>59Gy, aV50>5.9cc, aV55>2.7cc and aV60>0.9cc respectively, of whom only two developed brainstem necrosis. Brainstem necrosis is rare in NPC. The definitive criteria based on conventional radiotherapy cannot accurately predict the occurrence of brainstem necrosis after IMRT, thus more flexible definitive criteria with strict restrictions need to be defined. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reenlargement of radiation necrosis after stereotactic radiotherapy for brain metastasis from lung cancer during bevacizumab treatment.

PubMed

Furuuchi, Koji; Nishiyama, Akihiro; Yoshioka, Hiroshige; Yokoyama, Toshihide; Ishida, Tadashi

2017-03-01

We describe a 55-year-old man who received stereotactic radiotherapy (SRT) for the treatment of brain metastasis from lung adenocarcinoma. Fourteen months after SRT, right-sided hemiparesis developed, and magnetic resonance imaging revealed progression of perifocal edema and an enhanced lesion. Cerebral radiation necrosis was diagnosed, and treatment with bevacizumab was initiated. The lesion clearly responded to bevacizumab therapy, but reenlarged 8 months later and was surgically resected. Histopathological analysis of the resected specimen revealed large areas of necrosis; however, viable tumor cells were detected in the necrotic areas. Reenlargement of the necrotic lesion was attributed to the recurrence of lung cancer. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Histopathology of radiation necrosis with severe peritumoral edema after gamma knife radiosurgery for parasagittal meningioma. A report of two cases.

PubMed

Chen, Chien-hua; Shen, Chiung-chyi; Sun, Ming-hsi; Ho, William L; Huang, Chuan-fu; Kwan, Po-cheung

2007-01-01

Gamma knife radiosurgery (GKS) has been an effective treatment for meningiomas. Nevertheless, it still has certain risks. We present 2 cases of parasagittal meningioma after GKS complicated with radiation necrosis and peritumoral edema. The results of histologic examination are discussed. Two cases of parasagittal meningioma received GKS. Symptomatic peritumoral edema developed 3-4 months after GKS. Both of them underwent surgical resection of their tumor afterwards. Histologic examination showed necrotic change inside the tumor and infiltration of inflammatory cells in both cases. Hyalinization of blood vessels was seen in the 2nd case. The patients had improvement of neurologic function after surgical resection. Imaging performed 3 months after surgical resection showed alleviation of brain edema. After radiosurgery peritumoral edema tends to occur in meningiomas with a parasagittal position. Radiation necrosis, infiltration of inflammatory cells, and radiation injury to the vasculature causing hyalinization of blood vessels are suggested as the underlying histopathology. (c) 2007 S. Karger AG, Basel.

Radiation hard programmable delay line for LHCb calorimeter upgrade

NASA Astrophysics Data System (ADS)

Mauricio, J.; Gascón, D.; Vilasís, X.; Picatoste, E.; Machefert, F.; Lefrancois, J.; Duarte, O.; Beigbeder, C.

2014-01-01

This paper describes the implementation of a SPI-programmable clock delay chip based on a Delay Locked Loop (DLL) in order to shift the phase of the LHC clock (25 ns) in steps of 1ns, with less than 5 ps jitter and 23 ps of DNL. The delay lines will be integrated into ICECAL, the LHCb calorimeter front-end analog signal processing ASIC in the near future. The stringent noise requirements on the ASIC imply minimizing the noise contribution of digital components. This is accomplished by implementing the DLL in differential mode. To achieve the required radiation tolerance several techniques are applied: double guard rings between PMOS and NMOS transistors as well as glitch suppressors and TMR Registers. This 5.7 mm2 chip has been implemented in CMOS 0.35 μm technology.

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

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

Effect of edaravone on radiation-induced brain necrosis in patients with nasopharyngeal carcinoma after radiotherapy: a randomized controlled trial.

PubMed

Tang, Yamei; Rong, Xiaoming; Hu, Weihan; Li, Guoqian; Yang, Xiaoxia; Yang, Jianhua; Xu, Pengfei; Luo, Jinjun

2014-11-01

Excessive generation of free radicals plays a critical role in the pathogenesis of radiation-induced brain injury. This study was designed to evaluate the protective effect of edaravone, a free radical scavenger, on radiation-induced brain necrosis in patients with nasopharyngeal carcinoma. Eligible patients were randomized 1:1 to the control group and the edaravone group (intravenous 30 mg twice per day for 2 weeks). Both groups received intravenous conventional steroid therapy and were monitored by brain MRI and LENT/SOMA scales prior to the entry of the trial and at 3-months after completing the trial. The primary end point was a 3-month response rate of the proportional changes determined by MRI. The trial is registered at Clinicaltrials.gov Identifier: NCT01865201. Between 2009 and 2012, we enrolled 154 patients. Of whom 137 were eligible for analysis. The volumes of necrosis estimated on T(2)-weighted image showed that 55.6 % edaravone-treated patients (40 out of 72) showed edema decreases ≥25 %, which was significantly higher than that in the control group (35.4 %, 23 out of 65, p = 0.025). Forty-four patients treated with edaravone (61.1 %) reported improvement in neurologic symptoms and signs evaluated by LENT/SOMA scales, while the rate was 38.5 % in the control group (p = 0.006). MRI of the edaravone group showed a significant decrease in area of T(1)-weighted contrast enhancement (1.67 ± 4.69 cm(2), p = 0.004) and the T(2)-weighted edema (5.08 ± 10.32 cm(2), p = 0.000). Moreover, compared with those in control group, patients with edaravone exhibited significantly better radiological improvement measured by T(2)-weighted image (p = 0.042). Administration of edaravone, in adjunct to steroid regimen, might provide a better outcome in patients with radiation-induced brain necrosis.

Late temporal lobe necrosis after conventional radiotherapy for carcinoma of maxillary sinus.

PubMed

Kanakamedala, Madhava R; Mahta, Ali; Liu, Jianlin; Kesari, Santosh

2012-12-01

Cerebral radiation necrosis is a serious late complication after conventional radiotherapy that can present with focal neurologic deficits or with more generalized signs and symptoms of increased intracranial pressure, depending on the location. The incidence and severity of radionecrosis are dose-volume dependent. We report a case of cerebral radiation necrosis 5 years after radiotherapy for a maxillary sinus carcinoma.

Delayed hemorrhage after surgery and radiation in suprasellar pilocytic astrocytomas

PubMed Central

Turel, Mazda K.; Kiehl, Tim-Rasmus; Gentili, Fred

2016-01-01

Delayed intracranial hemorrhage is a rare complication of treatment for central nervous system tumors. This may be secondary to malignant transformation of the tumor or vasculopathy related to radiation therapy (RT). While most reports on radiation-induced vasculopathy in children with optic pathway gliomas are associated with ischemic complications, there are only two reports of hemorrhagic complications in these patients. In both cases, the hemorrhage was asymptomatic and remote from the site of the original tumor but within the field of irradiation. We describe a female patient who underwent surgery for an optico-chiasmatic pilocytic astrocytoma (PA) at the age of 12 followed by RT at the age of 17 for tumor progression. The patient was followed with serial magnetic resonance imaging (MRI) scans showing marginal regression and no subsequent evidence of tumor recurrence, including the most recent MRI done only 6 months before the latest presentation. She then developed a symptomatic intratumoral hemorrhage at the age of 32 for which she underwent emergent surgery. To our knowledge, this is the first report of a nonaneurysmal-delayed hemorrhage within the site of previous surgery, several years after RT for a suprasellar PA. We review literature on delayed vasculopathy following the treatment of pediatric optic pathway gliomas and discuss the possible mechanisms of hemorrhage in our case. These long-term follow-up outcomes add significant insight and have implications in patient management. PMID:27857781

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.

Management of Cerebral Radiation Necrosis: A Retrospective Study of 12 Patients.

PubMed

Liao, Chenlong; Visocchi, Massimiliano; Zhang, Wenchuan; Yang, Min; Zhong, Wenxiang; Liu, Pengfei

2017-01-01

Cerebral radiation necrosis (RN) is a severe complication of radiotherapy for cerebral pathologies. This study discusses the radiographic and pathological features of 12 patients with RN and investigates the management strategy. Eleven patients with brain tumors, and one with cerebral cavernous angioma, treated by surgical resection or Gamma Knife alone before radiotherapy developed RN during follow-up. Surgical resection for the cerebral RN was performed in nine patients, and the other three patients received medical treatment. The clinical features, magnetic resonance imaging (MRI), surgical findings, and pathological sections are reviewed. The diagnosis of RN was confirmed by histological study in all the patients; those with surgical and medical treatment recovered. As a major complication of radiotherapy, from the clinical and neuroradiological points of view, RN may simulate tumor recurrence. Due to the increasing number of patients with RN who will need to be treated in future years, the definite diagnosis and appropriate treatment of RN remain critical.

Fibrinogen deficiency suppresses the development of early and delayed radiation enteropathy

PubMed Central

Wang, Junru; Pathak, Rupak; Garg, Sarita; Hauer-Jensen, Martin

2017-01-01

AIM To determine the mechanistic role of fibrinogen, a key regulator of inflammation and fibrosis, in early and delayed radiation enteropathy. METHODS Fibrinogen wild-type (Fib+/+), fibrinogen heterozygous (Fib+/-), and fibrinogen knockout (Fib-/-) mice were exposed to localized intestinal irradiation and assessed for early and delayed structural changes in the intestinal tissue. A 5-cm segment of ileum of mice was exteriorized and exposed to 18.5 Gy of x-irradiation. Intestinal tissue injury was assessed by quantitative histology, morphometry, and immunohistochemistry at 2 wk and 26 wk after radiation. Plasma fibrinogen level was measured by enzyme-linked immunosorbent assay. RESULTS There was no difference between sham-irradiated Fib+/+ and Fib+/- mice in terms of fibrinogen concentration in plasma and intestinal tissue, intestinal histology, morphometry, intestinal smooth muscle cell proliferation, and neutrophil infiltration. Therefore, Fib+/- mice were used as littermate controls. Unlike sham-irradiated Fib+/+ and Fib+/- mice, no fibrinogen was detected in the plasma and intestinal tissue of sham-irradiated Fib-/- mice. Moreover, fibrinogen level was not elevated after irradiation in the intestinal tissue of Fib-/- mice, while significant increase in intestinal fibrinogen level was noticed in irradiated Fib+/+ and Fib+/- mice. Importantly, irradiated Fib-/- mice exhibited substantially less overall intestinal structural injury (RIS, P = 0.000002), intestinal wall thickness (P = 0.003), intestinal serosal thickness (P = 0.009), collagen deposition (P = 0.01), TGF-β immunoreactivity (P = 0.03), intestinal smooth muscle proliferation (P = 0.046), neutrophil infiltration (P = 0.01), and intestinal mucosal injury (P = 0.0003), compared to irradiated Fib+/+ and Fib+/- mice at both 2 wk and 26 wk. CONCLUSION These data demonstrate that fibrinogen deficiency directly attenuates development of early and delayed radiation enteropathy. Fibrinogen could be a novel target

Diagnostic Accuracy of Centrally Restricted Diffusion in the Differentiation of Treatment-Related Necrosis from Tumor Recurrence in High-Grade Gliomas.

PubMed

Zakhari, N; Taccone, M S; Torres, C; Chakraborty, S; Sinclair, J; Woulfe, J; Jansen, G H; Nguyen, T B

2018-02-01

Centrally restricted diffusion has been demonstrated in recurrent high-grade gliomas treated with bevacizumab. Our purpose was to assess the accuracy of centrally restricted diffusion in the diagnosis of radiation necrosis in high-grade gliomas not treated with bevacizumab. In this prospective study, we enrolled patients with high-grade gliomas who developed a new ring-enhancing necrotic lesion and who underwent re-resection. The presence of a centrally restricted diffusion within the ring-enhancing lesion was assessed visually on diffusion trace images and by ADC measurements on 3T preoperative diffusion tensor examination. The percentage of tumor recurrence and radiation necrosis in each surgical specimen was defined histopathologically. The association between centrally restricted diffusion and radiation necrosis was assessed using the Fisher exact test. Differences in ADC and the ADC ratio between the groups were assessed via the Mann-Whitney U test, and receiver operating characteristic curve analysis was performed. Seventeen patients had re-resected ring-enhancing lesions: 8 cases of radiation necrosis and 9 cases of tumor recurrence. There was significant association between centrally restricted diffusion by visual assessment and radiation necrosis ( P = .015) with a sensitivity of 75% and a specificity of 88.9%, a positive predictive value 85.7%, and a negative predictive value of 80% for the diagnosis of radiation necrosis. There was a statistically significant difference in the ADC and ADC ratio between radiation necrosis and tumor recurrence ( P = .027). The presence of centrally restricted diffusion in a new ring-enhancing lesion might indicate radiation necrosis rather than tumor recurrence in high-grade gliomas previously treated with standard chemoradiation without bevacizumab. © 2018 by American Journal of Neuroradiology.

Poly[ADP-ribose] polymerase-1 expression is related to cold ischemia, acute tubular necrosis, and delayed renal function in kidney transplantation.

PubMed

O'Valle, Francisco; Del Moral, Raimundo G M; Benítez, María del Carmén; Martín-Oliva, David; Gómez-Morales, Mercedes; Aguilar, David; Aneiros-Fernández, José; Hernández-Cortés, Pedro; Osuna, Antonio; Moreso, Francesc; Serón, Daniel; Oliver, Francisco J; Del Moral, Raimundo G

2009-09-28

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.

Long-Term Follow-up of the Delayed Effects of Acute Radiation Exposure in Primates

DTIC Science & Technology

2016-10-01

MV, Katz BP, Smith CP, Jackson W 3rd, Cohen DM, et al. A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management...subsyndrome of the acute radiation syndrome : a rhesus macaque model. Health Phys 2012; 103:411–26. 32. Robbins ME, Bourland JD, Cline JM, Wheeler KT, Deadwyler...AD______________ AWARD NUMBER: W81XWH-15-1-0574 TITLE: Long-Term Follow-up of the Delayed Effects of Acute Radiation Exposure in Primates

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.

[Avascular necrosis of the femoral head].

PubMed

Porubský, Peter; Trč, Tomáš; Havlas, Vojtěch; Smetana, Pavel

Avascular necrosis of the femoral head in adults is not common, but not too rare diseases. In orthopedic practice, it is one of the diseases that are causing implantation of hip replacement at a relatively early age. In the early detection and initiation of therapy can delay the implantation of prosthesis for several years, which is certainly more convenient for the patient and beneficial. This article is intended to acquaint the reader with the basic diagnostic procedures and therapy.

Models of CNS radiation damage during space flight

NASA Astrophysics Data System (ADS)

Hopewell, J. W.

1994-10-01

The primary structural and functional arrangement of the different cell types within the CNS are reviewed. This was undertaken with a view to providing a better understanding of the complex interrelationships that may contribute to the pathogenesis of lesions in this tissue after exposure to ionizing radiation. The spectrum of possible CNS radiation-induced syndromes are discussed although not all have an immediate relevance to exposure during space flight. The specific characteristics of the lesions observed would appear to be dose related. Very high doses may produce an acute CNS syndrome that can cause death. Of the delayed lesions, selective coagulation necrosis of white matter and a later appearing vascular microangiopathy, have been reported in patients after cancer therapy doses. Lower doses, perhaps very low doses, may produce a delayed generalised CNS atrophy; this effect and the probability of the induction of CNS tumors could potentially have the greatest significance for space flight.

Imaging of endoscopic cystogastrostomy in pancreatic walled-off necrosis: what the radiologist needs to know.

PubMed

Abou Karam, Anthony; Bagherpour, Arya; Calleros, Jesus; Laks, Shaked

2018-04-04

Acute pancreatitis is a frequent entity encountered by radiologists. In 2012, the Atlanta criteria were revised to help radiologists use a common nomenclature when describing acute pancreatitis and its complications. One delayed complication of acute necrotizing pancreatitis in walled-off necrosis, a collection seen at least 4 weeks after an episode of acute pancreatic necrosis and/or acute peripancreatic necrosis. Multiple treatments have been adapted in the setting of walled-off necrosis, including endoscopic cystogastrostomy. The focus of this article is to familiarize the radiologist with the imaging appearance of this procedure as well as, review the outcomes and potential complications of endoscopic cystogastrostomy.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kobashigawa, Shinko, E-mail: kobashin@nagasaki-u.ac.jp; 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{submore » 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.« less

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

Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

PubMed Central

O'Valle, Francisco; Del Moral, Raimundo G. M.; Benítez, María del Carmén; Martín-Oliva, David; Gómez-Morales, Mercedes; Aguilar, David; Aneiros-Fernández, José; Hernández-Cortés, Pedro; Osuna, Antonio; Moreso, Francesc; Serón, Daniel; Oliver, Francisco J.; Del Moral, Raimundo G.

2009-01-01

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). Materials and Methods Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. Results PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function. PMID:19784367

Targeted delayed scanning at CT urography: a worthwhile use of radiation?

PubMed

Hack, Kalesha; Pinto, Patricia A; Gollub, Marc J

2012-10-01

To determine whether ureteral segments not filled with contrast material at computed tomographic (CT) urography ever contain tumor detectable only by filling these segments with contrast material. In this institutional review board-approved, HIPAA-compliant retrospective study, with waiver of informed consent, databases were searched for all patients who underwent heminephroureterectomy or ureteroscopy between January 1, 2001, and December 31, 2009, with available CT urography findings in the 12 months prior to surgery or biopsy and patients who had undergone at least two CT urography procedures with a minimum 5-year follow-up between studies. One of two radiologists blinded to results of pathologic examination recorded location of unfilled segments, time of scan, subsequent filling, and pathologic or 5-year follow-up CT urography results. Tumors were considered missed in an unfilled segment if tumor was found at pathologic examination or follow-up CT urography in the same one-third of the ureter and there were no secondary signs of a mass with other index CT urography sequences. Estimated radiation dose for additional delayed sequences was calculated with a 32-cm phantom. In 59 male and 33 female patients (mean age, 66 years) undergoing heminephroureterectomy, 27 tumors were present in 41 partially nonopacified ureters in 20 patients. Six tumors were present in nonopacified segments (one multifocal, none bilateral); all were identifiable by means of secondary signs present with earlier sequences. Among 182 lesions biopsied at ureteroscopy in 124 male and 53 female patients (mean age, 69 years), 28 tumors were present in nonopacified segments in 25 patients (four multifocal, none bilateral), all with secondary imaging signs detectable without delayed scanning. In 64 male and 29 female patients (mean age, 69 years) who underwent 5-year follow-up CT urography, three new tumors were revealed in three patients; none occurred in the unfilled ureter at index CT urography

Membrane-derived second messenger regulates x-ray-mediated tumor necrosis factor alpha gene induction.

PubMed Central

Hallahan, D E; Virudachalam, S; Kuchibhotla, J; Kufe, D W; Weichselbaum, R R

1994-01-01

Cells adapt to adverse environmental conditions through a wide range of responses that are conserved throughout evolution. Physical agents such as ionizing radiation are known to initiate a stress response that is triggered by the recognition of DNA damage. We have identified a signaling pathway involving the activation of phospholipase A2 and protein kinase C in human cells that confers x-ray induction of the tumor necrosis factor alpha gene. Treatment of human cells with ionizing radiation or H2O2 was associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolished radiation-mediated arachidonate production as well as the subsequent activation of protein kinase C and tumor necrosis factor alpha gene expression. These findings demonstrate that ionizing radiation-mediated gene expression in human cells is regulated in part by extranuclear signal transduction. One practical application of phospholipase A2 inhibitors is to ameliorate the adverse effects of radiotherapy associated with tumor necrosis factor alpha production. Images PMID:8197153

Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum.

PubMed

Inouye, M; Yamamura, H; Nakano, A

1995-09-01

Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 mumol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 micrograms/g at the time of irradiation and remaining at more than 40 micrograms/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositidemediated signaling systems regulate radiation-induced apoptosis.

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.

Methods to Differentiate Radiation Necrosis and Recurrent Disease in Gliomas

NASA Astrophysics Data System (ADS)

Ewell, Lars

2007-03-01

Given the difficulty in differentiating Radiation Induced Necrosis (RIN) and recurrent disease in glioma patients using conventional techniques (CT scans, MRI scans), researchers have looked for different imaging modalities. Among these different modalities are Diffusion Weighted Magnetic Resonance Imaging (DWMRI) and Magnetic Resonance Spectroscopy (MRS). In DWMRI, an Apparent Diffusion Coefficient (ADC) is calculated for a Region Of Interest (ROI), and then monitored over time (longitudinally). In the brain, different anatomical features can complicate the interpretation of ADCs. In particular, the density and spatial variation of the cerebral spinal fluid filled fissures known as sulci can influence how a change in an ADC is explained. We have used the covariance of pixel intensity in T1 weighted MRI scans to study how intra-patient and inter-patient sulci density varies, and will present these results. MRS uses the shift in the MR signal due to the local chemical environment to determine the concentration of brain metabolites like choline and creatin. The ratio of metabolites such as these has been shown to have the power to discriminate between RIN and recurrent disease in glioma patients. At our institution, we have initiated a protocol whereby we will use DWMRI and MRS to study how best to utilize these complimentary forms of imaging.

Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-β and fibroblast growth factor production.

PubMed

Atiba, Ayman; Nishimura, Mayumi; Kakinuma, Shizuko; Hiraoka, Takeshi; Goryo, Masanobu; Shimada, Yoshiya; Ueno, Hiroshi; Uzuka, Yuji

2011-06-01

Delayed wound healing is a significant clinical problem in patients who have had previous irradiation. This study investigated the effectiveness of Aloe vera (Av) on acute radiation-delayed wound healing. The effect of Av was studied in radiation-exposed rats compared with radiation-only and control rats. Skin wounds were excised on the back of rats after 3 days of local radiation. Wound size was measured on days 0, 3, 6, 9, and 12 after wounding. Wound tissues were examined histologically and the expressions of transforming growth factor β-1 (TGF-β-1) and basic fibroblast growth factor (bFGF) were examined by immunohistochemistry and reverse-transcription polymerase chain reaction. Wound contraction was accelerated significantly by Av on days 6 and 12 after wounding. Furthermore, the inflammatory cell infiltration, fibroblast proliferation, collagen deposition, angiogenesis, and the expression levels of TGF-β-1 and bFGF were significantly higher in the radiation plus Av group compared with the radiation-only group. These data showed the potential application of Av to improve the acute radiation-delayed wound healing by increasing TGF-β-1 and bFGF production. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

TU-D-207B-01: A Prediction Model for Distinguishing Radiation Necrosis From Tumor Progression After Gamma Knife Radiosurgery Based On Radiomics Features From MR Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Z; MD Anderson Cancer Center, Houston, TX; Ho, A

Purpose: To develop and validate a prediction model using radiomics features extracted from MR images to distinguish radiation necrosis from tumor progression for brain metastases treated with Gamma knife radiosurgery. Methods: The images used to develop the model were T1 post-contrast MR scans from 71 patients who had had pathologic confirmation of necrosis or progression; 1 lesion was identified per patient (17 necrosis and 54 progression). Radiomics features were extracted from 2 images at 2 time points per patient, both obtained prior to resection. Each lesion was manually contoured on each image, and 282 radiomics features were calculated for eachmore » lesion. The correlation for each radiomics feature between two time points was calculated within each group to identify a subset of features with distinct values between two groups. The delta of this subset of radiomics features, characterizing changes from the earlier time to the later one, was included as a covariate to build a prediction model using support vector machines with a cubic polynomial kernel function. The model was evaluated with a 10-fold cross-validation. Results: Forty radiomics features were selected based on consistent correlation values of approximately 0 for the necrosis group and >0.2 for the progression group. In performing the 10-fold cross-validation, we narrowed this number down to 11 delta radiomics features for the model. This 11-delta-feature model showed an overall prediction accuracy of 83.1%, with a true positive rate of 58.8% in predicting necrosis and 90.7% for predicting tumor progression. The area under the curve for the prediction model was 0.79. Conclusion: These delta radiomics features extracted from MR scans showed potential for distinguishing radiation necrosis from tumor progression. This tool may be a useful, noninvasive means of determining the status of an enlarging lesion after radiosurgery, aiding decision-making regarding surgical resection versus conservative

Avascular Necrosis

MedlinePlus

... Financial Reports Watchdog Ratings Feedback Contact Select Page Avascular Necrosis Home > Cancer Resources > Late Effects of Treatment > Avascular Necrosis Avascular necrosis (AVN) is a disorder resulting from ...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina Georgiou

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 ifmore » 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.« less

Delayed Surgical Debridement and Use of Semiocclusive Dressings for Salvage of Fingers After Purpura Fulminans.

PubMed

Pino, Paula A; Román, Javier A; Fernández, Felipe

2016-12-01

Background: Purpura fulminans is a condition characterized by rapidly evolving skin necrosis and disseminated intravascular coagulation. Early recognition and aggressive supportive management has led to a decrease in its mortality rate, but most of these patients must undergo extensive soft tissue debridement and partial or total limb amputation. There is controversial evidence about the timing of surgery, suggesting that some patients may benefit from delayed debridement with limb preservation. Methods: We present a case of an 86-year-old patient who developed skin necrosis of his four limbs after infectious purpura fulminans. He was treated in the ICU with supportive measures and antibiotic treatment. Surgical debridement was delayed for 4 weeks until necrosis delimitation. Results: Only upper extremity debridement was necessary. Four fingers, including one thumb, were salvaged and successfully treated with semi-occlusive dressing without complications. Conclusion: Early recognition of infectious PF and timely supportive management are important pillars of its treatment. Delayed surgical debridement allows for less aggressive resection and good functional outcome.

Coupling of Rigor Mortis and Intestinal Necrosis during C. elegans Organismal Death.

PubMed

Galimov, Evgeniy R; Pryor, Rosina E; Poole, Sarah E; Benedetto, Alexandre; Pincus, Zachary; Gems, David

2018-03-06

Organismal death is a process of systemic collapse whose mechanisms are less well understood than those of cell death. We previously reported that death in C. elegans is accompanied by a calcium-propagated wave of intestinal necrosis, marked by a wave of blue autofluorescence (death fluorescence). Here, we describe another feature of organismal death, a wave of body wall muscle contraction, or death contraction (DC). This phenomenon is accompanied by a wave of intramuscular Ca 2+ release and, subsequently, of intestinal necrosis. Correlation of directions of the DC and intestinal necrosis waves implies coupling of these death processes. Long-lived insulin/IGF-1-signaling mutants show reduced DC and delayed intestinal necrosis, suggesting possible resistance to organismal death. DC resembles mammalian rigor mortis, a postmortem necrosis-related process in which Ca 2+ influx promotes muscle hyper-contraction. In contrast to mammals, DC is an early rather than a late event in C. elegans organismal death. VIDEO ABSTRACT. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riesterer, Oliver; Yang Qiuan; Raju, Uma

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,more » 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.« less

Avascular Necrosis

MedlinePlus

Avascular necrosis Overview Avascular necrosis is the death of bone tissue due to a lack of blood supply. Also called osteonecrosis, it can lead to ... blood flow to a section of bone. Avascular necrosis is also associated with long-term use of ...

DELAY OF CLEAVAGE OF THE ARBACIA EGG BY ULTRAVIOLET RADIATION

PubMed Central

Blum, Harold F.; Price, Judith P.

1950-01-01

While our data do not permit us to state the exact locus or mode of action of ultraviolet radiation in the Arbacia egg, certain general conclusions may be reached. The amount of delay of cleavage of these eggs is determined by two principal factors: (1) The extent of an effect, resulting from photochemical action induced by ultraviolet radiation, which is reversible in a biological sense, the reversibility not being directly dependent upon the process of cell division. (2) The sensitivity of the cell division process to the effects of the ultraviolet-induced photochemical reaction. This factor varies with the stage of cell division, the cell being insensitive during a period corresponding to most of mitosis. It seems likely that these findings may apply to cell division in general, but, since the quantitative relationships observed must, in this case, reflect the integration of two semi-independent factors, the over-all picture may appear quite different for different kinds of cells. PMID:15410486

[Seasonal changes in tumor necrosis factor production in hibernating animals in normal conditions and under the effects of electromagnetic and ionizing radiation].

PubMed

Ogaĭ, V B; Novoselova, E G; Makar, V R; Kolaeva, S G

2002-01-01

Production of tumor necrosis factor (TNF) has been investigated in peritoneal macrophages and splenic T cells of Arctic Yakutian ground squirrel (Citellus Undulatus Pallas) upon in vitro action of electromagnetic and ionizing radiation during annual cycle. The significant activation of TNF production in the cells of awaken ground squirrels in winter and increasing level of the lymphokine production at spring-summer period has been indicated. The level of TNF production in splenic T cells was not changed during whole year. The electromagnetic radiation (EMR) of low intensity (8.15-18 GHz, 1 microW/cm2) induced an augmentation of both secretory and proliferative activity in TNF-producing cells. Ionizing radiation suppressed T cell proliferation, but the doses 2 and 5 Gy resulted in a significant stimulation of TNF production in T cells and macrophages.

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

Stereotactic robot-assisted MRI-guided laser thermal ablation of radiation necrosis in the posterior cranial fossa: technical note.

PubMed

Chan, Alvin Y; Tran, Diem Kieu T; Gill, Amandip S; Hsu, Frank P K; Vadera, Sumeet

2016-10-01

Laser interstitial thermal therapy (LITT) is a minimally invasive procedure used to treat a variety of intracranial lesions. Utilization of robotic assistance with stereotactic procedures has gained attention due to potential for advantages over conventional techniques. The authors report the first case in which robot-assisted MRI-guided LITT was used to treat radiation necrosis in the posterior fossa, specifically within the cerebellar peduncle. The use of a stereotactic robot allowed the surgeon to perform LITT using a trajectory that would be extremely difficult with conventional arc-based techniques. A 60-year-old man presented with facial weakness and brainstem symptoms consistent with radiation necrosis. He had a history of anaplastic astrocytoma that was treated with CyberKnife radiosurgery 1 year prior to presentation, and he did well for 11 months until his symptoms recurred. The location and form of the lesion precluded excision but made the patient a suitable candidate for LITT. The location and configuration of the lesion required a trajectory for LITT that was too low for arc-based stereotactic navigation, and thus the ROSA robot (Medtech) was used. Using preoperative MRI acquisitions, the lesion in the posterior fossa was targeted. Bone fiducials were used to improve accuracy in registration, and the authors obtained an intraoperative CT image that was then fused with the MR image by the ROSA robot. They placed the laser applicator and then ablated the lesion under real-time MR thermometry. There were no complications, and the patient tolerated the procedure well. Postoperative 2-month MRI showed complete resolution of the lesion, and the patient had some improvement in symptoms.

[Complete necrosis of the penis and testes by strangulation in a psychotic patient].

PubMed

Bart, S; Culty, T; Pizzoferrato, A-C; Thibault, F; Girault, N; Chartier-Kastler, E; Richard, F

2008-07-01

Complete necrosis of the penis and scrotum due to strangulation of the external genitalia is unusually encountered in urologic emergencies. Urological conservative management is recommended. Delayed presentation is a major source of complications. We report the case of a psychotic patient, who was transferred from the emergency department in a context of complete necrosis of the external genitalia. This patient's history included chronic psychotic disorder and positive HIV serology, but he refused to take either neuroleptic or antiretroviral therapy. Complete amputation of the penis and bilateral orchidectomy were performed. We report the first six months of medical management.

Diffusion Weighted MRI and MRS to Differentiate Radiation Necrosis and Recurrent Disease in Gliomas

NASA Astrophysics Data System (ADS)

Ewell, Lars

2006-03-01

A difficulty encountered in the diagnosis of patients with gliomas is the differentiation between recurrent disease and Radiation Induced Necrosis (RIN). Both can appear as ‘enhancing lesions’ on a typical T2 weighted MRI scan. Magnetic Resonance Spectroscopy (MRS) and Diffusion Weighted MRI (DWMRI) have the potential to be helpful regarding this differentiation. MRS has the ability to measure the concentration of brain metabolites, such as Choline, Creatin and N- Acetyl Aspartate, the ratios of which have been shown to discriminate between RIN and recurrent disease. DWMRI has been linked via a rise in the Apparent Diffusion Coefficient (ADC) to successful treatment of disease. Using both of these complimentary non-invasive imaging modalities, we intend to initiate an imaging protocol whereby we will study how best to combine metabolite ratios and ADC values to obtain the most useful information in the least amount of scan time. We will look for correlations over time between ADC values, and MRS, among different sized voxels.

Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Guanghui; Zhang Yaping; Tang Jinliang

2010-08-01

Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-{alpha}, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT.more » The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-{alpha}, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.« less

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.

Predictors of Postoperative Wound Necrosis Following Primary Wound Closure of Open Ankle Fractures.

PubMed

Ovaska, Mikko T; Madanat, Rami; Mäkinen, Tatu J

2016-04-01

Most open malleolar ankle fracture wounds can be closed primarily after meticulous debridement. However, the development of wound necrosis following operative treatment of open malleolar ankle fractures can have catastrophic consequences. The aim of this study was to identify risk factors predisposing to postoperative wound necrosis following primary wound closure of open malleolar ankle fractures. A total of 137 patients with open malleolar ankle fractures were identified. The open fracture wound was primarily closed in 110 of 137 (80%) patients, and postoperative wound necrosis occurred in 18 (16%) of these patients. These patients were compared to the open fracture patients without wound necrosis. Twenty possible risk factors for the development of wound necrosis were studied with logistic regression analysis. The variables that were independently associated with an increased risk for postoperative wound necrosis included ASA class ≥2, Gustilo grade III open injury, and the use of pulsatile lavage at index surgery. Our study showed that ASA class ≥2, Gustilo grade III open injury, and the use of pulsatile lavage at index surgery were the most important factors predisposing to postoperative wound necrosis following primary wound closure of open malleolar ankle fractures. The findings warrant a further study specifically comparing primary and delayed wound closure in patients with Gustilo grade III open malleolar ankle fractures and different ASA classes. Also, the role of pulsatile lavage should be re-evaluated. Level III, retrospective comparative series. © The Author(s) 2016.

Using computed tomography to assist with diagnosis of avascular necrosis complicating chronic scaphoid nonunion.

PubMed

Smith, Michael L; Bain, Gregory I; Chabrel, Nick; Turner, Perry; Carter, Chris; Field, John

2009-01-01

The primary aim of our study was to investigate use of long axis computed tomography (CT) in predicting avascular necrosis of the proximal pole of the scaphoid and subsequent fracture nonunion after internal fixation. In addition, we describe a new technique of measuring the position of a scaphoid fracture and provide data on its reproducibility. Thirty-one patients operated on by the senior author for delayed union or nonunion of scaphoid fracture were included. Preoperative CT scans were independently assessed for increased radiodensity of the proximal pole, converging trabeculae, degree of deformity, comminution, and fracture position. Intraoperative biopsies of the proximal pole were obtained and histologically assessed for evidence of avascular necrosis. The radiologic variables were statistically compared with the histologic findings. The presence of avascular necrosis was also compared with postoperative union status, identified on longitudinal CT scans. Preoperative CT features that statistically correlated with histologic evidence of avascular necrosis were increased radiodensity of the proximal pole and the absence of any converging trabeculae between the fracture fragments. The radiologic changes of avascular necrosis and the histologic confirmation of avascular necrosis were associated with persistent nonunion. Preoperative longitudinal CT of scaphoid nonunion is of great value in identifying avascular necrosis and predicting subsequent fracture union. If avascular necrosis is suspected based on preoperative CT, management options include vascularized bone grafts and bone morphogenic protein for younger patients and limited wrist arthrodesis for older patients. Diagnostic II.

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lam, Tai-Chung, E-mail: lamtaichung@gmail.com; Wong, Frank C.S.; Leung, To-Wai

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 receivingmore » 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

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.

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ching-Sheng; Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Lin, Ko-Han

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 wasmore » 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.« less

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

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusthoven, Kyle E.; Olsen, Christine; Franklin, Wilbur

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 andmore » 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.« less

[Avascular necrosis of the femoral head in a patient with severe aplastic anaemia].

PubMed

Plichta, Piotr; Pawelec, Katarzyna

2011-01-01

Avascular necrosis (AVN) is a pathological condition associated with numerous processes. Most frequent causes of ischaemia of the femoral head include trauma, corticosteroid therapy, radiation therapy, alcoholism, Gaucher's disease, systemic lupus erythematosus, rheumatoid arthritis. Corticosteroid therapy is considered the most frequent risk factor for developing avascular necrosis. In this paper we report a case of a 19-year old female patient who developed avascular necrosis of the right femoral head following treatment of severe aplastic anaemia. Clinical symptoms included groin pain and fever, painful abduction and internal rotation, tenderness over the right hip joint. The plain X-ray was not specific. However magnetic resonance imaging of the hip revealed changes characteristic for avascular necrosis. Conservative treatment was administrated. Two years after the onset of first clinical symptoms the patient is able to walk without pain, although the range of motion of the right hip joint is partially diminished. We evaluated the possible risk factors of AVN, diagnostic methods and prognosis. The onset of avascular necrosis should be considered as one of the relevant complications in patients with severe aplastic anaemia following immunosuppressive treatment.

Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs.

PubMed

Fish, Brian L; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R; Cohen, Eric P; Moulder, John E; Orschell, Christie M; Medhora, Meetha

2016-11-01

The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.

[Cutaneous radiation syndrome after accidental skin exposure to ionizing radiation].

PubMed

Peter, R U

2013-12-01

Accidental exposure of the human skin to single doses of ionizing radiation greater than 3 Gy results in a distinct clinical picture, which is characterized by a transient and faint erythema after a few hours, then followed by severe erythema, blistering and necrosis. Depending on severity of damage, the latter generally occurs 10-30 days after exposure, but in severe cases may appear within 48 hrs. Between three and 24 months after exposure, epidermal atrophy combined with progressive dermal and subcutaneous fibrosis is the predominant clinical feature. Even years and decades after exposure, atrophy of epidermis, sweat and sebaceous glands; telangiectases; and dermal and subcutaneous fibrosis may be found and even continue to progress. For this distinct pattern of deterministic effects following cutaneous accidental radiation exposure the term "cutaneous radiation syndrome (CRS)" was coined in 1993 and has been accepted by all international authorities including IAEA and WHO since 2000. In contrast to the classical concept that inhibition of epidermal stem cell proliferation accounts for the clinical symptomatology, research of the last three decades has demonstrated the additional crucial role of inflammatory processes in the etiology of both acute and chronic sequelae of the CRS. Therefore, therapeutic approaches should include topical and systemic anti-inflammatory measures at the earliest conceivable point, and should be maintained throughout the acute and subacute stages, as this reduces the need for surgical intervention, once necrosis has occurred. If surgical intervention is planned, it should be executed with a conservative approach; no safety margins are needed. Antifibrotic measures in the chronic stage should address the chronic inflammatory nature of this process, in which over-expression TGF beta-1 may be a target for therapeutic intervention. Life-long follow-up often is required for management of delayed effects and for early detection of secondary

Delayed repair of radiation induced clustered DNA damage: Friend or foe?

PubMed Central

Eccles, Laura J.; O’Neill, Peter; Lomax, Martine E.

2011-01-01

A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a “friend”, leading to cell killing in tumour cells or as a “foe”, resulting in the formation of mutations and genetic instability in normal tissue. PMID:21130102

Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery

PubMed Central

Okwan-Duodu, Derick; Switchenko, Jeffrey M.; Press, Robert H.; Jhaveri, Jaymin; Buchwald, Zachary S.; Zhong, Jim; Chapman, Bhavana V.; Bindra, Ranjit S.; Contessa, Joseph N.; Park, Henry S.; Yu, James B.; Decker, Roy H.; Olson, Jeffrey J.; Oyesiku, Nelson M.; Abrams, Ross A.; Shu, Hui-Kuo G.; Curran, Walter J.; Crocker, Ian R.

2018-01-01

Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-month follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes. 228 consecutive patients were treated with SRS: 111 with rBM and 117 with AVM. Overall, 51 (22.4%) patients were in the ABT group: 32 (28.8%) in the rBM and 19 (16.2%) in AVM cohorts. Baseline characteristics were similar, except for higher Graded Prognostic Analysis (3–4) in the rBM (ABT: 25.0% vs. non-ABT: 49.0%, p = 0.033) and median age in the AVM (ABT: 51.4 vs. non-ABT: 35.4, p < 0.001) cohorts. In both populations, OS and intracranial efficacy (rBM—local control; AVM—obliteration rates) were statistically similar between the cohorts. ABT was associated with lower 1-year SRN rates in both populations: rBM, 3.1 versus 25.3% (p = 0.003); AVM, 6.7 vs. 14.6% (p = 0.063). On multivariate analysis, ABT was a significant predictive factor for rBM (HR: 0.17; 95% CI 0.03–0.88, p = 0.035), but did not reach statistical significance for AVM (HR: 0.36; 95% CI 0.09–1.52, p = 0.165). ABT use appears to be associated with a reduced risk of SRN following SRS, without detriment to OS or intracranial efficacy. A prospective trial to validate these findings is warranted. PMID:29124649

Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery.

PubMed

Chowdhary, Mudit; Okwan-Duodu, Derick; Switchenko, Jeffrey M; Press, Robert H; Jhaveri, Jaymin; Buchwald, Zachary S; Zhong, Jim; Chapman, Bhavana V; Bindra, Ranjit S; Contessa, Joseph N; Park, Henry S; Yu, James B; Decker, Roy H; Olson, Jeffrey J; Oyesiku, Nelson M; Abrams, Ross A; Shu, Hui-Kuo G; Curran, Walter J; Crocker, Ian R; Patel, Kirtesh R

2018-01-01

Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-month follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes. 228 consecutive patients were treated with SRS: 111 with rBM and 117 with AVM. Overall, 51 (22.4%) patients were in the ABT group: 32 (28.8%) in the rBM and 19 (16.2%) in AVM cohorts. Baseline characteristics were similar, except for higher Graded Prognostic Analysis (3-4) in the rBM (ABT: 25.0% vs. non-ABT: 49.0%, p = 0.033) and median age in the AVM (ABT: 51.4 vs. non-ABT: 35.4, p < 0.001) cohorts. In both populations, OS and intracranial efficacy (rBM-local control; AVM-obliteration rates) were statistically similar between the cohorts. ABT was associated with lower 1-year SRN rates in both populations: rBM, 3.1 versus 25.3% (p = 0.003); AVM, 6.7 vs. 14.6% (p = 0.063). On multivariate analysis, ABT was a significant predictive factor for rBM (HR: 0.17; 95% CI 0.03-0.88, p = 0.035), but did not reach statistical significance for AVM (HR: 0.36; 95% CI 0.09-1.52, p = 0.165). ABT use appears to be associated with a reduced risk of SRN following SRS, without detriment to OS or intracranial efficacy. A prospective trial to validate these findings is warranted.

Renal papillary necrosis

MedlinePlus

... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

Enhancement of radiation therapy by the novel vascular targeting agent ZD6126.

PubMed

Siemann, Dietmar W; Rojiani, Amyn M

2002-05-01

The aim of this study was to evaluate the antitumor efficacy of the novel vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) in the rodent KHT sarcoma model, either alone or in combination with single- or fractionated-dose radiation therapy. C3H/HeJ mice bearing i.m. KHT tumors were injected i.p. with ZD6126 doses ranging from 10 to 150 mg/kg. Tumors were irradiated locally in unanesthetized mice using a linear accelerator. Tumor response to ZD6126 administered alone or in combination with radiation was assessed by clonogenic cell survival assay or tumor growth delay. Treatment with ZD6126 led to a rapid tumor vascular shutdown as determined by Hoechst 33342 diffusion. Histologic evaluation showed morphologic damage of tumor cells within a few hours after drug exposure, followed by extensive central tumor necrosis and neoplastic cell death as a result of prolonged ischemia. When combined with radiation, a 150 mg/kg dose of ZD6126 reduced tumor cell survival 10-500-fold compared with radiation alone. These enhancements in tumor cell killing could be achieved for ZD6126 given both before and after radiation exposure. Further, the shape of the cell survival curve observed after the combination therapy suggested that including ZD6126 in the treatment had a major effect on the radiation-resistant hypoxic cell subpopulation associated with this tumor. Finally, when given on a once-weekly basis in conjunction with fractionated radiotherapy, ZD6126 treatment was found to significantly increase the tumor response to daily 2.5 Gy fractions. The present results demonstrated that in the KHT sarcoma, ZD6126 caused rapid tumor vascular shutdown, induction of central tumor necrosis, tumor cell death secondary to ischemia, and enhancement of the antitumor effects of radiation therapy.

Acute massive gastric dilatation causing ischaemic necrosis and perforation of the stomach.

PubMed

Moslim, Maitham A; Mittal, Jay; Falk, Gavin A; Ustin, Jeffrey S; Morris-Stiff, Gareth

2017-06-15

Acute massive gastric dilatation (AMGD) is a rare distinctive condition but associates with high morbidity and mortality. Though usually seen in patients with eating disorders, many aetiologies of AMGD have been described. The distension has been reported to cause gastric necrosis with or without perforation, usually within 1-2 days of an inciting event of AMGD.We report the case of a 58-year-old male who presented with gastric perforation associated with AMGD 11 days after surgical relief of a proximal small bowel obstruction. The AMGD arose from a closed loop obstruction between a tumour at the gastro-oesophageal junction and a small bowel obstruction as a result of volvulus around a jejunal feeding tube.To our knowledge, this is the first case of a closed loop obstruction of this aetiology reported in the literature, and the presentation of this patient's AMGD was notable for the delayed onset of gastric necrosis. The patient underwent an exploratory laparotomy and a partial gastrectomy to excise a portion of his perforated stomach. Surgeons should be aware of the possibility of delayed ischaemic gastric perforation in cases of AMGD. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mirkovic, D; Peeler, C; Grosshans, D

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 tomore » 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.« less

Inhibitors of HIF-1α and CXCR4 Mitigate the Development of Radiation Necrosis in Mouse Brain.

PubMed

Yang, Ruimeng; Duan, Chong; Yuan, Liya; Engelbach, John A; Tsien, Christina I; Beeman, Scott C; Perez-Torres, Carlos J; Ge, Xia; Rich, Keith M; Ackerman, Joseph J H; Garbow, Joel R

2018-03-15

There is mounting evidence that, in addition to angiogenesis, hypoxia-induced inflammation via the hypoxia-inducible factor 1α (HIF-1α)-CXC chemokine receptor 4 (CXCR4) pathway may contribute to the pathogenesis of late-onset, irradiation-induced necrosis. This study investigates the mitigative efficacy of an HIF-1α inhibitor, topotecan, and a CXCR4 antagonist, AMD3100, on the development of radiation necrosis (RN) in an intracranial mouse model. Mice received a single-fraction, 50-Gy dose of hemispheric irradiation from the Leksell Gamma Knife Perfexion and were then treated with either topotecan, an HIF-1α inhibitor, from 1 to 12 weeks after irradiation, or AMD3100, a CXCR4 antagonist, from 4 to 12 weeks after irradiation. The onset and progression of RN were monitored longitudinally via noninvasive, in vivo magnetic resonance imaging (MRI) from 4 to 12 weeks after irradiation. Conventional hematoxylin-eosin staining and immunohistochemistry staining were performed to evaluate the treatment response. The progression of brain RN was significantly mitigated for mice treated with either topotecan or AMD3100 compared with control animals. MRI-derived lesion volumes were significantly smaller for both of the treated groups, and histologic findings correlated well with the MRI data. By hematoxylin-eosin staining, both treated groups demonstrated reduced irradiation-induced tissue damage compared with controls. Furthermore, immunohistochemistry results revealed that expression levels of vascular endothelial growth factor, CXC chemokine ligand 12, CD68, CD3, and tumor necrosis factor α in the lesion area were significantly lower in treated (topotecan or AMD3100) brains versus control brains, while ionized calcium-binding adapter molecule 1 (Iba1) and HIF-1α expression was similar, though somewhat reduced. CXCR4 expression was reduced only in topotecan-treated mice, while interleukin 6 expression was unaffected by either topotecan or AMD3100. By reducing

Surgical management of pancreatic necrosis: A practice management guideline from the Eastern Association for the Surgery of Trauma.

PubMed

Mowery, Nathan T; Bruns, Brandon R; MacNew, Heather G; Agarwal, Suresh; Enniss, Toby M; Khan, Mansoor; Guo, Weidun Alan; Cannon, Jeremy W; Lissauer, Matthew E; Duane, Therese M; Hildreth, Amy N; Pappas, Peter A; Gries, Lynn M; Kaiser, Meghann; Robinson, Bryce R H

2017-08-01

Pancreatic or peripancreatic tissue necrosis confers substantial morbidity and mortality. New modalities have created a wide variation in approaches and timing of interventions for necrotizing pancreatitis. As acute care surgery evolves, its practitioners are increasingly being called upon to manage these complex patients. A systematic review of the MEDLINE database using PubMed was performed. English language articles regarding pancreatic necrosis from 1980 to 2014 were included. Letters to the editor, case reports, book chapters, and review articles were excluded. Topics of investigation included operative timing, the use of adjuvant therapy and the type of operative repair. Grading of Recommendations, Assessment, Development and Evaluations methodology was applied to question development, outcome prioritization, evidence quality assessments, and recommendation creation. Eighty-eight studies were included and underwent full review. Increasing the time to surgical intervention had an improved outcome in each of the periods evaluated (72 hours, 12-14 days, 30 days) with a significant improvement in outcomes if surgery was delayed 30 days. The use of percutaneous and endoscopic procedures was shown to postpone surgery and potentially be definitive. The use of minimally invasive surgery for debridement and drainage has been shown to be safe and associated with reduced morbidity and mortality. Acute Care Surgeons are uniquely trained to care for those with pancreatic necrosis due their training in critical care and complex surgery with ongoing shock. In adult patients with pancreatic necrosis, we recommend that pancreatic necrosectomy be delayed until at least day 12. During the first 30 days of symptoms with infected necrotic collections, we conditionally recommend surgical debridement only if the patients fail to improve after radiologic or endoscopic drainage. Finally, even with documented infected necrosis, we recommend that patients undergo a step-up approach to

Can anti-vascular endothelial growth factor antibody reverse radiation necrosis? A preclinical investigation.

PubMed

Duan, Chong; Perez-Torres, Carlos J; Yuan, Liya; Engelbach, John A; Beeman, Scott C; Tsien, Christina I; Rich, Keith M; Schmidt, Robert E; Ackerman, Joseph J H; Garbow, Joel R

2017-05-01

Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising new treatment for late time-to-onset radiation-induced necrosis (RN). We sought to evaluate and validate the response to anti-VEGF antibody in a mouse model of RN. Mice were irradiated with the Leksell Gamma Knife Perfexion™ and then treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN progression was monitored via anatomic and diffusion MRI from weeks 4-12 PIR. Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry staining were used to validate the response to treatment. After treatment, both post-contrast T1-weighted and T2-weighted image-derived lesion volumes decreased (P < 0.001), while the lesion volumes for the control group increased. The abnormally high apparent diffusion coefficient (ADC) for RN also returned to the ADC range for normal brain following treatment (P < 0.001). However, typical RN pathology was still present histologically. Large areas of focal calcification were observed in ~50% of treated mouse brains. Additionally, VEGF and hypoxia-inducible factor 1-alpha (HIF-1α) were continually upregulated in both the anti-VEGF and control groups. Despite improvements observed radiographically following anti-VEGF treatment, lesions were not completely resolved histologically. The subsequent calcification and the continued upregulation of VEGF and HIF-1α merit further preclinical/clinical investigation.

Can anti-Vascular Endothelial Growth Factor Antibody Reverse Radiation Necrosis? A Preclinical Investigation

PubMed Central

Duan, Chong; Perez-Torres, Carlos J; Yuan, Liya; Engelbach, John A; Beeman, Scott C; Tsien, Christina I; Rich, Keith M; Schmidt, Robert E; Ackerman, Joseph JH; Garbow, Joel R

2017-01-01

Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising new treatment for late time-to-onset radiation-induced necrosis (RN). We sought to evaluate and validate the response to anti-VEGF antibody in a mouse model of RN. Mice were irradiated with the Leksell Gamma Knife PerfexionTM and then treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN progression was monitored via anatomic and diffusion MRI from weeks 4 to 12 PIR. Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry staining were used to validate the response to treatment. After treatment, both post-contrast T1-weighted and T2-weighted image-derived lesion volumes decreased (P<0.001), while the lesion volumes for the control group increased. The abnormally high apparent diffusion coefficient (ADC) for RN also returned to the ADC range for normal brain following treatment (P<0.001). However, typical RN pathology was still present histologically. Large areas of focal calcification were observed in ~50% of treated mouse brains. Additionally, VEGF and hypoxia-inducible factor 1-alpha (HIF-1α) were continually upregulated in both the anti-VEGF and control groups. Despite improvements observed radiographically following anti-VEGF treatment, lesions were not completely resolved histologically. The subsequent calcification and the continued upregulation of VEGF and HIF-1α merit further preclinical/clinical investigation. PMID:28425047

Tissue necrosis following extravasation of acyclovir in an adolescent: A case report.

PubMed

Neocleous, Charalambos; Andonopoulou, Eleni; Adramerina, Alkistis; Pegkou, Antigoni; Savelieva, Olga; Georgiadou, Petroula; Drikos, Ioannis

2017-05-01

Extravasation of intravenously infused vesicant solutions is a common problem in medical practice, which can lead to severe and progressive tissue dysfunction, ranging from persistent tissue oedema and fibrosis to delayed tissue necrosis. Acyclovir is a known vesicant medication administrated in paediatric patients, which appears to irritate venous and soft tissue if extravasated. We present the first case involving the extravasation of intravenously infused acyclovir in a female adolescent patient, which caused tissue necrosis and left behind a residual scar lesion. Nursing and medical staff should be aware of the potential dermatological side effects of intravenously infused acyclovir and other medications, even a long time after infusion, and the possible lack of initial local symptoms and signs. Early recognition of extravasation and prompt management are critical in preventing further morbidity, and optimizing outcomes. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Spontaneous complete necrosis of advanced hepatocellular carcinoma.

PubMed

Yokoyama, Tadashi; Yoshida, Hiroshi; Hirakata, Atsushi; Makino, Hiroshi; Maruyama, Hiroshi; Suzuki, Seiji; Matsutani, Takeshi; Hayakawa, Tomohiro; Hosone, Masaru; Uchida, Eiji

2012-01-01

We present a rare case of hepatocellular carcinoma (HCC) in which spontaneous complete necrosis was confirmed with surgical resection. An 80-year-old man with HCC was referred to Nippon Medical School Tama Nagayama Hospital. The medical history included hypertension, managed with medication, and partial lobectomy of the lung owing to a lung schwannoma. A previously untreated abdominal aortic aneurysm, 51 mm in maximum diameter, was detected. The serum concentration of proteins induced by vitamin k antagonism or absence (PIVKA-2) was 14,300 mAU/mL, and that of alpha-fetoprotein was 184.2 ng/mL. Antibodies against hepatitis B surface antigens and hepatitis C virus were not detected in the serum. Computed tomography (CT) demonstrated a hypervascular tumor, 68 mm in diameter, in the left paramedian sector of the liver with washout of contrast medium in the delayed phase. An HCC in the left paramedian sector was diagnosed. Laparotomy was performed 40 days after CT scanning. Intraoperative ultrasonography showed that the HCC had shrunk to 30 mm in diameter. A left paramedian sectionectomy was performed. On macroscopic examination the surgical specimen was a firm mass, 30 mm in diameter, with a fibrous capsule. Histologic examination showed that the tumor in the cirrhotic liver had been completely replaced by central coagulative necrosis, circumferential fibrosis, and dense infiltrates of inflammatory cells. No viable HCC cells were observed in the coagulative necrosis. Organized thrombi in the hepatic artery were detected in the tumor. The tumor also contained multiple foci of old hemorrhage, ductular proliferation, and granulation tissue. The patient was discharged 10 days after the operation. After 1 month, the serum concentrations of PIVKA-2 (25 mAU/mL) and alpha-fetoprotein (5.9 ng/mL) had decreased to within their normal ranges.

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

PubMed

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

2015-10-01

To determine the employment status and location of recent Canadian radiation oncology (RO) graduates and to identify current workforce entry trends. 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. 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. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez-Torres, Carlos J.; Engelbach, John A.; Cates, Jeremy

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) ismore » 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.« less

Radiation enteritis and radiation scoliosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.

Rhabdomyolysis with acute tubular necrosis following occupational inhalation of thinners.

PubMed

Ngajilo, D; Ehrlich, R

2017-07-01

Thinners are mixtures of organic solvents commonly containing toluene, xylene, acetone, hexane, benzene and methyl isobutyl ketone. This report describes a case of rhabdomyolysis with acute tubular necrosis and renal failure, most likely attributable to toluene, following occupational exposure to thinners while cleaning a steel water tank. These adverse health effects have previously been reported following acute poisoning or intentional inhalation by drug abusers, but rarely in the occupational setting. Poor working conditions, lack of health and safety training and delayed treatment contributed to the onset and severity of the patient's complications. This case emphasizes the need for strict control measures, including adequate ventilation, training on working in confined spaces, appropriate personal protective equipment and emergency rescue procedures in such settings. In addition, rhabdomyolysis, acute tubular necrosis and renal failure should be added to safety data material as possible complications of excessive inhalation of thinners. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates.

PubMed

Andrews, Rachel N; Metheny-Barlow, Linda J; Peiffer, Ann M; Hanbury, David B; Tooze, Janet A; Bourland, J Daniel; Hampson, Robert E; Deadwyler, Samuel A; Cline, J Mark

2017-05-01

Fractionated whole-brain irradiation (fWBI) is a mainstay of treatment for patients with intracranial neoplasia; however late-delayed radiation-induced normal tissue injury remains a major adverse consequence of treatment, with deleterious effects on quality of life for affected patients. We hypothesize that cerebrovascular injury and remodeling after fWBI results in ischemic injury to dependent white matter, which contributes to the observed cognitive dysfunction. To evaluate molecular effectors of radiation-induced brain injury (RIBI), real-time quantitative polymerase chain reaction (RT-qPCR) was performed on the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46), hippocampus and temporal white matter of 4 male Rhesus macaques (age 6-11 years), which had received 40 Gray (Gy) fWBI (8 fractions of 5 Gy each, twice per week), and 3 control comparators. All fWBI animals developed neurologic impairment; humane euthanasia was elected at a median of 6 months. Radiation-induced brain injury was confirmed histopathologically in all animals, characterized by white matter degeneration and necrosis, and multifocal cerebrovascular injury consisting of perivascular edema, abnormal angiogenesis and perivascular extracellular matrix deposition. Herein we demonstrate that RIBI is associated with white matter-specific up-regulation of hypoxia-associated lactate dehydrogenase A (LDHA) and that increased gene expression of fibronectin 1 (FN1), SERPINE1 and matrix metalloprotease 2 (MMP2) may contribute to cerebrovascular remodeling in late-delayed RIBI. Additionally, vascular stability and maturation associated tumor necrosis super family member 15 (TNFSF15) and vascular endothelial growth factor beta (VEGFB) mRNAs were increased within temporal white matter. We also demonstrate that radiation-induced brain injury is associated with decreases in white matter-specific expression of neurotransmitter receptors SYP, GRIN2A and GRIA4. We additionally provide evidence that

Evaluation of a metalloporphyrin (THPPMnCl) for necrosis-affinity in rat models of necrosis.

PubMed

Li, Yue; Liu, Xuejiao; Zhang, Dongjian; Lou, Bin; Peng, Fei; Wang, Xiaoning; Shan, Xin; Jiang, Cuihua; Gao, Meng; Sun, Ziping; Ni, Yicheng; Huang, Dejian; Zhang, Jian

2015-12-01

The combination of an (13I)I-labeled necrosis-targeting agent (NTA) with a vascular disrupting agent is a novel and potentially powerful technique for tumor necrosis treatment (TNT). The purpose of this study was to evaluate a NTA candidate, THPPMnCl, using (131)I isotope for tracing its biodistribution and necrosis affinity. (131)I-THPPMnCl was intravenously injected in rat models with liver, muscle, and tumor necrosis and myocardial infarction (MI), followed by investigations with macroscopic autoradiography, triphenyltetrazolium chloride (TTC) histochemical staining, fluorescence microscopy and H&E stained histology for up to 9 days. (131)I-THPPMnCl displayed a long-term affinity for all types of necrosis and accumulation in the mononuclear phagocytic system especially in the liver. Autoradiograms and TTC staining showed a good targetability of (131)I-THPPMnCl for MI. These findings indicate the potential of THPPMnCl for non-invasive imaging assessment of necrosis, such as in MI. However, (13I)I-THPPMnCl is unlikely suitable for TNT due to its long-term retention in normal tissues.

Radiation Hardened Structured ASIC Platform with Compensation of Delay for Temperature and Voltage Variations for Multiple Redundant Temporal Voting Latch Technology

NASA Technical Reports Server (NTRS)

Ardalan, Sasan (Inventor)

2018-01-01

The invention relates to devices and methods of maintaining the current starved delay at a constant value across variations in voltage and temperature to increase the speed of operation of the sequential logic in the radiation hardened ASIC design.

Methotrexate-induced epidermal necrosis: A case series of 24 patients.

PubMed

Chen, Ting-Jui; Chung, Wen-Hung; Chen, Chun-Bing; Hui, Rosaline Chung-Yee; Huang, Yu-Huei; Lu, Yueh-Tsung; Wang, Chang-Wei; Wang, Kuo-Hsien; Yang, Li-Cheng; Hung, Shuen-Iu

2017-08-01

Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To investigate the clinicopathology, risk factors, and prognostic factors of MEN. We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX). Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN. The study was limited by the small sample size. MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Application of adipocyte-derived stem cells in treatment of cutaneous radiation syndrome.

PubMed

Riccobono, Diane; Agay, Diane; Scherthan, Harry; Forcheron, Fabien; Vivier, Mylène; Ballester, Bruno; Meineke, Viktor; Drouet, Michel

2012-08-01

Cutaneous radiation syndrome caused by local high dose irradiation is characterized by delayed outcome and incomplete healing. Recent therapeutic management of accidentally irradiated burn patients has suggested the benefit of local cellular therapy using mesenchymal stem cell grafting. According to the proposed strategy of early treatment, large amounts of stem cells would be necessary in the days following exposure and hospitalization, which would require allogeneic stem cells banking. In this context, the authors compared the benefit of local autologous and allogeneic adipocyte-derived stem cell injection in a large animal model. Minipigs were locally irradiated using a 60Co gamma source at a dose of 50 Gy and divided into three groups. Two groups were grafted with autologous (n = 5) or allogeneic (n = 5) adipocyte-derived stem cells four times after the radiation exposure, whereas the control group received the vehicle without cells (n = 8). A clinical score was elaborated to compare the efficiency of the three treatments. All controls exhibited local inflammatory injuries leading to a persistent painful necrosis, thus mimicking the clinical evolution in human victims. In the autologous adipocyte-derived stem cells group, skin healing without necrosis or uncontrollable pain was observed. In contrast, the clinical outcome was not significantly different in the adipocyte-derived stem cell allogeneic group when compared with controls. This study suggests that autologous adipocyte-derived stem cell grafting improves cutaneous radiation syndrome wound healing, whereas allogeneic adipocyte derived stem cells do not. Further studies will establish whether manipulation of allogeneic stem cells will improve their therapeutic potential.

Light-Cone Effect of Radiation Fields in Cosmological Radiative Transfer Simulations

NASA Astrophysics Data System (ADS)

Ahn, Kyungjin

2015-02-01

We present a novel method to implement time-delayed propagation of radiation fields in cosmo-logical radiative transfer simulations. Time-delayed propagation of radiation fields requires construction of retarded-time fields by tracking the location and lifetime of radiation sources along the corresponding light-cones. Cosmological radiative transfer simulations have, until now, ignored this "light-cone effect" or implemented ray-tracing methods that are computationally demanding. We show that radiative trans-fer calculation of the time-delayed fields can be easily achieved in numerical simulations when periodic boundary conditions are used, by calculating the time-discretized retarded-time Green's function using the Fast Fourier Transform (FFT) method and convolving it with the source distribution. We also present a direct application of this method to the long-range radiation field of Lyman-Werner band photons, which is important in the high-redshift astrophysics with first stars.

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.

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Necrosis

MedlinePlus

... Meningococcemia associated purpura Necrosis of the toes References Kumar V, Abbas AK, Aster JC. Cellular responses to ... and toxic insults: adaptation, injury, and death. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and ...

Targeting of regulated necrosis in kidney disease.

PubMed

Martin-Sanchez, Diego; Poveda, Jonay; Fontecha-Barriuso, Miguel; Ruiz-Andres, Olga; Sanchez-Niño, María Dolores; Ruiz-Ortega, Marta; Ortiz, Alberto; Sanz, Ana Belén

The term acute tubular necrosis was thought to represent a misnomer derived from morphological studies of human necropsies and necrosis was thought to represent an unregulated passive form of cell death which was not amenable to therapeutic manipulation. Recent advances have improved our understanding of cell death in acute kidney injury. First, apoptosis results in cell loss, but does not trigger an inflammatory response. However, clumsy attempts at interfering with apoptosis (e.g. certain caspase inhibitors) may trigger necrosis and, thus, inflammation-mediated kidney injury. Second, and most revolutionary, the concept of regulated necrosis emerged. Several modalities of regulated necrosis were described, such as necroptosis, ferroptosis, pyroptosis and mitochondria permeability transition regulated necrosis. Similar to apoptosis, regulated necrosis is modulated by specific molecules that behave as therapeutic targets. Contrary to apoptosis, regulated necrosis may be extremely pro-inflammatory and, importantly for kidney transplantation, immunogenic. Furthermore, regulated necrosis may trigger synchronized necrosis, in which all cells within a given tubule die in a synchronized manner. We now review the different modalities of regulated necrosis, the evidence for a role in diverse forms of kidney injury and the new opportunities for therapeutic intervention. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

[Programmed necrosis and necroptosis - molecular mechanisms].

PubMed

Giżycka, Agata; Chorostowska-Wynimko, Joanna

2015-12-16

Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor α, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis.

Delayed fixation of displaced bilateral, atraumatic, femoral neck fractures in a patient with pregnancy related osteomalacia.

PubMed

Docker, Charles; Starks, Ian; Wade, Roger; Wynn-Jones, Charles

2011-06-01

We present the case of a woman diagnosed with simultaneous displaced intracapsular femoral neck fractures following the birth of her second child. No traumatic event was identified. Diagnosis was delayed as the cause of her pain was thought to be non-skeletal in origin. Radiological and serological investigations were diagnostic of osteomalacia. Surgical fixation of her fractures was further delayed due to profound hypocalcaemia. Despite the delays, fixation with bilateral dynamic hip screws resulted in union with no evidence of avascular necrosis at 2 years follow-up. We believe this to be the first report of atraumatic bilateral femoral neck fractures and it shows that a good result can be achieved even in the presence of delayed fixation.

First Evaluation of Radioiodinated Flavonoids as Necrosis-Avid Agents and Application in Early Assessment of Tumor Necrosis.

PubMed

Liang, Jiajia; Sun, Ziping; Zhang, Dongjian; Jin, Qiaomei; Cai, Lingqiao; Ma, Lin; Liu, Wei; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

2018-01-02

A rapid and accurate identification of necrotic tissues is of great importance to define disease severity, predict prognosis, and monitor responses to therapies. To seek necrosis-avid agents with clinically translational potential, we first evaluated the necrosis avidity of flavonoids in rodent models of muscular, myocardial, and tumoral necrosis. In this study, the necrosis avidity of eight radioiodinated 5,7-dihydroxyflavones was tested by ex vivo gamma counting, histochemical staining, and autoradiography in mouse models of ethanol-induced muscular necrosis. The necrosis avidity of a lead tracer, 131 I-5, was further assessed in rat models of myocardial infarction and reperfusion. Therapy response was evaluated by 131 I-5 single photon emission computed tomography/computed tomography imaging 24 h after combretastatin A-4 disodium phosphate (CA4P) therapy on rats bearing W256 breast carcinomas. The necrosis avidity mechanism for the tracers was studied by in vitro DNA binding experiments of 12 5,7-dihydroxyflavones and in vivo blocking experiments of 131 I-5. In the results, all 131 I-5,7-dihydroxyflavones showed intense uptake to necrotic muscles, and 131 I-5 emerged as the most potential tracer among them. 131 I-5 obtained a necrotic-viable myocardium ratio of 5.0 ± 0.9 in post-mortem biodistribution on reperfused myocardial infarction models and achieved necrosis imaging on CA4P-treated W256 tumors 4 h after tracer injection. DNA binding studies suggested that necrosis avidity was related to DNA binding to a certain extent. The uptake of 131 I-5 in necrotic muscle was markedly blocked by excessive ethidium bromide and cold 5 with a 51.95% and 64.29% decline at 1 h after coinjection, respectively. In conclusion, flavonoids are necrosis-avid agents. Furthermore, 131 I-5 can serve as a promising necrosis-avid diagnostic tracer for the rapid imaging of necrotic tissues, supporting the further molecular design of radiotracer based on 5.

Late radiation side-effects in three patients undergoing parotid irradiation for benign disease.

PubMed

Armour, A; Ghanna, P; O'Rielly, B; Habeshaw, T; Symonds, P

2000-01-01

We report three patients in whom standard radiation therapy was given and serious late radiation damage was seen. The first patient suffered recurrent parotiditis and a parotid fistula. He was treated initially with 20 Gy in ten fractions via a 300 kV field. Further irradiation was required 1 year later and 40 Gy was given in 2 Gy fractions by an oblique anterior and posterior wedged photon pair. Ten years later he developed localized temporal bone necrosis. The second patient, with pleomorphic salivary adenoma, developed localized temporal bone necrosis 6 years after 60 Gy had been given using standard fractionation and technique. The third patient received 55 Gy in 25 fractions for a pleomorphic salivary adenoma and after 3 years developed temporal bone necrosis. Sixteen years later the same patient developed cerebellar and brainstem necrosis. All patients developed chronic persistent infection during or shortly after the radiation therapy, which increased local tissue sensitivity to late radiation damage. As a result, severe bone, cerebellar and brainstem necrosis was observed at doses that are normally considered safe. We therefore strongly recommend that any infection in a proposed irradiated area should be treated aggressively, with surgical debridement if necessary, before radiotherapy is administered, or that infection developing during or after irradiation is treated promptly.

Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates

PubMed Central

Andrews, Rachel N.; Metheny-Barlow, Linda J.; Peiffer, Ann M.; Hanbury, David B.; Tooze, Janet A.; Bourland, J. Daniel; Hampson, Robert E.; Deadwyler, Samuel A.; Cline, J. Mark

2017-01-01

Andrews, R. N., Metheny-Barlow, L. J., Peiffer, A. M., Hanbury, D. B., Tooze, J. A., Bourland, J. D., Hampson, R. E., Deadwyler, S. A. and Cline, J. M. Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates. Radiat. Res. 187, 599–611 (2017). Fractionated whole-brain irradiation (fWBI) is a mainstay of treatment for patients with intracranial neoplasia; however late-delayed radiation-induced normal tissue injury remains a major adverse consequence of treatment, with deleterious effects on quality of life for affected patients. We hypothesize that cerebrovascular injury and remodeling after fWBI results in ischemic injury to dependent white matter, which contributes to the observed cognitive dysfunction. To evaluate molecular effectors of radiation-induced brain injury (RIBI), real-time quantitative polymerase chain reaction (RT-qPCR) was performed on the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46), hippocampus and temporal white matter of 4 male Rhesus macaques (age 6–11 years), which had received 40 Gray (Gy) fWBI (8 fractions of 5 Gy each, twice per week), and 3 control comparators. All fWBI animals developed neurologic impairment; humane euthanasia was elected at a median of 6 months. Radiation-induced brain injury was confirmed histopathologically in all animals, characterized by white matter degeneration and necrosis, and multifocal cerebrovascular injury consisting of perivascular edema, abnormal angiogenesis and perivascular extracellular matrix deposition. Herein we demonstrate that RIBI is associated with white matter-specific up-regulation of hypoxia-associated lactate dehydrogenase A (LDHA) and that increased gene expression of fibronectin 1 (FN1), SERPINE1 and matrix metalloprotease 2 (MMP2) may contribute to cerebrovascular remodeling in late-delayed RIBI. Additionally, vascular stability and maturation associated tumor necrosis super family member 15 (TNFSF15) and

Delayed presentation of a bowel Bovie injury after laparoscopic ventral hernia repair.

PubMed

Bhullar, Jasneet Singh; Gayagoy, Jennifer; Chaudhary, Sushant; Kolachalam, Ramachandra B

2013-01-01

Bowel injury during laparoscopic surgery is a rare but serious complication. A Bovie injury to the bowel can cause delayed perforation of the viscus, thus increasing the possibility of a preventable morbidity. Patients presenting with perforation peritonitis within 24 hours and up to 2 to 3 weeks after laparoscopic Bovie injury to the bowel have been reported in the literature. A 74-year-old woman underwent a laparoscopic ventral hernia mesh repair. Intraoperatively, a small area of superficial Bovie injury to the small bowel was repaired with Lembert sutures and tissue glue. Postoperatively, the patient recovered well, but she presented with perforation peritonitis 3 months after surgery. An exploratory laparotomy showed a jejunal perforation in the same area that was injured with cautery and repaired during the previous surgery. The patient was only using inhaled steroids for asthma on and off but had a remote history of chemotherapy and radiation for colorectal cancer. Bovie injury to the bowel has a hidden depth, causing a slow transmural tissue necrosis, and it might also impair local healing and eventually lead to perforation. Thus, the patient may present later than the usual period for wound healing and remodeling as previously reported. Given the disastrous consequence, it is imperative to perform a good surgical repair of even a minor Bovie injury to the bowel. This is the first report of a delayed presentation (>1 month) of a Bovie injury of the bowel.

Delayed Presentation of a Bowel Bovie Injury After Laparoscopic Ventral Hernia Repair

PubMed Central

Gayagoy, Jennifer; Chaudhary, Sushant; Kolachalam, Ramachandra B.

2013-01-01

Introduction: Bowel injury during laparoscopic surgery is a rare but serious complication. A Bovie injury to the bowel can cause delayed perforation of the viscus, thus increasing the possibility of a preventable morbidity. Patients presenting with perforation peritonitis within 24 hours and up to 2 to 3 weeks after laparoscopic Bovie injury to the bowel have been reported in the literature. Case Description: A 74-year-old woman underwent a laparoscopic ventral hernia mesh repair. Intraoperatively, a small area of superficial Bovie injury to the small bowel was repaired with Lembert sutures and tissue glue. Postoperatively, the patient recovered well, but she presented with perforation peritonitis 3 months after surgery. An exploratory laparotomy showed a jejunal perforation in the same area that was injured with cautery and repaired during the previous surgery. The patient was only using inhaled steroids for asthma on and off but had a remote history of chemotherapy and radiation for colorectal cancer. Conclusion: Bovie injury to the bowel has a hidden depth, causing a slow transmural tissue necrosis, and it might also impair local healing and eventually lead to perforation. Thus, the patient may present later than the usual period for wound healing and remodeling as previously reported. Given the disastrous consequence, it is imperative to perform a good surgical repair of even a minor Bovie injury to the bowel. This is the first report of a delayed presentation (>1 month) of a Bovie injury of the bowel. PMID:24018096

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loewen, Shaun K., E-mail: shaun.loewen@cancercare.mb.ca; Halperin, Ross; Lefresne, Shilo

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%) hadmore » 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.« less

Visceral brown fat necrosis in postperinatal mortality.

PubMed Central

Stephenson, T J; Variend, S

1987-01-01

Fat necrosis was present in 22 of 400 cases of consecutive postperinatal mortalities investigated to assess the presence and pattern of deep fat necrosis. In just over 50% of the cases of fat necrosis the cause of death was categorised as sudden infant death syndrome, which also showed more severe degrees of necrosis. The mechanism of necrosis may be vascular hypoperfusion, possibly related to shock, and brown adipose tissue, on account of its high metabolic activity and rich capillary plexus, may be particularly vulnerable to infarction. The occurrence of fat necrosis in association with other causes of death did not provide any definite clue as to the nature of the alleged shock. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 PMID:3654989

Vascular delay of the latissimus dorsi muscle: an essential component of cardiomyoplasty.

PubMed

Carroll, S M; Carroll, C M; Stremel, R W; Heilman, S J; Tobin, G R; Barker, J H

1997-04-01

Cardiomyoplasty (CMP) uses the latissimus dorsi muscle (LDM) to assist the heart in cases of cardiac failure. Distal ischemia and necrosis of the LDM is a recognized complication of CMP that can reduce distal muscle function and the mechanical effectiveness of CMP. Canine (n = 9) LDMs were subjected to a 10-day period of vascular delay followed by a simulated CMP. Two weeks after simulated CMP (corresponding to the healing delay between CMP and the onset of LDM stimulation used in the clinical setting), LDM perfusion was measured in the distal, middle, and proximal segments of the muscle, and circumferential (distal and middle squeezing muscle function) and longitudinal (proximal pulling muscle function) force generation and fatigue rates were measured. The results were compared with the contralateral nondelayed simulated CMP. Muscle perfusion was significantly (p < 0.05) greater in the distal and middle segments of vascular-delayed LDMs. Circumferential muscle force generation and fatigue rates were significantly (p < 0.05) improved in the vascular-delayed LDMs. Vascular delay can significantly improve LDM perfusion and function in a model that closely reflects clinical CMP, and the use of vascular delay may improve clinical outcomes in CMP.

Application of ray-traced tropospheric slant delays to geodetic VLBI analysis

NASA Astrophysics Data System (ADS)

Hofmeister, Armin; Böhm, Johannes

2017-08-01

The correction of tropospheric influences via so-called path delays is critical for the analysis of observations from space geodetic techniques like the very long baseline interferometry (VLBI). In standard VLBI analysis, the a priori slant path delays are determined using the concept of zenith delays, mapping functions and gradients. The a priori use of ray-traced delays, i.e., tropospheric slant path delays determined with the technique of ray-tracing through the meteorological data of numerical weather models (NWM), serves as an alternative way of correcting the influences of the troposphere on the VLBI observations within the analysis. In the presented research, the application of ray-traced delays to the VLBI analysis of sessions in a time span of 16.5 years is investigated. Ray-traced delays have been determined with program RADIATE (see Hofmeister in Ph.D. thesis, Department of Geodesy and Geophysics, Faculty of Mathematics and Geoinformation, Technische Universität Wien. http://resolver.obvsg.at/urn:nbn:at:at-ubtuw:1-3444, 2016) utilizing meteorological data provided by NWM of the European Centre for Medium-Range Weather Forecasts (ECMWF). In comparison with a standard VLBI analysis, which includes the tropospheric gradient estimation, the application of the ray-traced delays to an analysis, which uses the same parameterization except for the a priori slant path delay handling and the used wet mapping factors for the zenith wet delay (ZWD) estimation, improves the baseline length repeatability (BLR) at 55.9% of the baselines at sub-mm level. If no tropospheric gradients are estimated within the compared analyses, 90.6% of all baselines benefit from the application of the ray-traced delays, which leads to an average improvement of the BLR of 1 mm. The effects of the ray-traced delays on the terrestrial reference frame are also investigated. A separate assessment of the RADIATE ray-traced delays is carried out by comparison to the ray-traced delays from the

Mastectomy Skin Necrosis After Breast Reconstruction: A Comparative Analysis Between Autologous Reconstruction and Implant-Based Reconstruction.

PubMed

Sue, Gloria R; Lee, Gordon K

2018-05-01

Mastectomy skin necrosis is a significant problem after breast reconstruction. We sought to perform a comparative analysis on this complication between patients undergoing autologous breast reconstruction and patients undergoing 2-stage expander implant breast reconstruction. A retrospective review was performed on consecutive patients undergoing autologous breast reconstruction or 2-stage expander implant breast reconstruction by the senior author from 2006 through 2015. Patient demographic factors including age, body mass index, history of diabetes, history of smoking, and history of radiation to the breast were collected. Our primary outcome measure was mastectomy skin necrosis. Fisher exact test was used for statistical analysis between the 2 patient cohorts. The treatment patterns of mastectomy skin necrosis were then analyzed. We identified 204 patients who underwent autologous breast reconstruction and 293 patients who underwent 2-stage expander implant breast reconstruction. Patients undergoing autologous breast reconstruction were older, heavier, more likely to have diabetes, and more likely to have had prior radiation to the breast compared with patients undergoing implant-based reconstruction. The incidence of mastectomy skin necrosis was 30.4% of patients in the autologous group compared with only 10.6% of patients in the tissue expander group (P < 0.001). The treatment of this complication differed between these 2 patient groups. In general, those with autologous reconstructions were treated with more conservative means. Although 37.1% of patients were treated successfully with local wound care in the autologous group, only 3.2% were treated with local wound care in the tissue expander group (P < 0.001). Less than half (29.0%) of patients in the autologous group were treated with an operative intervention for this complication compared with 41.9% in the implant-based group (P = 0.25). Mastectomy skin necrosis is significantly more likely to occur after

Quantitative survival impact of composite treatment delays in head and neck cancer.

PubMed

Ho, Allen S; Kim, Sungjin; Tighiouart, Mourad; Mita, Alain; Scher, Kevin S; Epstein, Joel B; Laury, Anna; Prasad, Ravi; Ali, Nabilah; Patio, Chrysanta; St-Clair, Jon Mallen; Zumsteg, Zachary S

2018-05-09

Multidisciplinary management of head and neck cancer (HNC) must reconcile increasingly sophisticated subspecialty care with timeliness of care. Prior studies examined the individual effects of delays in diagnosis-to-treatment interval, postoperative interval, and radiation interval but did not consider them collectively. The objective of the current study was to investigate the combined impact of these interwoven intervals on patients with HNC. Patients with HNC who underwent curative-intent surgery with radiation were identified in the National Cancer Database between 2004 and 2013. Multivariable models were constructed using restricted cubic splines to determine nonlinear relations with overall survival. Overall, 15,064 patients were evaluated. After adjustment for covariates, only prolonged postoperative interval (P < .001) and radiation interval (P < .001) independently predicted for worse outcomes, whereas the association of diagnosis-to-treatment interval with survival disappeared. By using multivariable restricted cubic spline functions, increasing postoperative interval did not affect mortality until 40 days after surgery, and each day of delay beyond this increased the risk of mortality until 70 days after surgery (hazard ratio, 1.14; 95% confidence interval, 1.01-1.28; P = .029). For radiation interval, mortality escalated continuously with each additional day of delay, plateauing at 55 days (hazard ratio, 1.25; 95% confidence interval, 1.11-1.41; P < .001). Delays beyond these change points were not associated with further survival decrements. Increasing delays in postoperative and radiation intervals are associated independently with an escalating risk of mortality that plateaus beyond certain thresholds. Delays in initiating therapy, conversely, are eclipsed in importance when appraised in conjunction with the entire treatment course. Such findings may redirect focus to streamlining those intervals that are most sensitive to delays when

IL-1 or TNF receptor gene deletion delays onset of encephalopathy and attenuates brain edema in experimental acute liver failure.

PubMed

Bémeur, Chantal; Qu, Hong; Desjardins, Paul; Butterworth, Roger F

2010-01-01

Previous reports suggested that brain-derived proinflammatory cytokines are involved in the pathogenesis of hepatic encephalopathy (HE) and brain edema in acute liver failure (ALF). To further address this issue, expression of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNAs were measured in the brains of mice with acute liver failure resulting from exposure to azoxymethane. In addition, time to severe encephalopathy (coma) was assessed in mice lacking genes coding for interferon-gamma, the tumor necrosis factor receptor-1 or the interleukin-1 type 1 receptor. Interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma expression were quantified using RT-PCR. Significant increases in interleukin-1beta and tumor necrosis factor-alpha mRNA were observed in the frontal cortex of azoxymethane-treated wild-type mice at coma stages of encephalopathy. Interferon-gamma, however, could not be detected in the brains of these animals. Onset of severe encephalopathy (coma) and brain edema in ALF mice were significantly delayed in interleukin-1 type 1 receptor or tumor necrosis factor receptor-1 knockout mice. Deletion of the interferon-gamma gene, on the other hand, had no significative effect on the neurological status or brain water content of acute liver failure mice. These results demonstrate that toxic liver injury resulting from exposure to azoxymethane is associated with selective induction of proinflammatory cytokines in the brain and that deletion of tumor necrosis factor receptor-1 or interlukin-1 type 1 receptor delays the onset of coma and brain edema in this model of acute liver failure. These findings further support a role for selective brain-derived cytokines in the pathogenesis of the cerebral complications in acute liver failure and suggest that anti-inflammatory strategies could be beneficial in their prevention. Copyright 2009 Elsevier Ltd. All rights reserved.

Accuracy of 18F-FDOPA Positron Emission Tomography and 18F-FET Positron Emission Tomography for Differentiating Radiation Necrosis from Brain Tumor Recurrence.

PubMed

Yu, Jun; Zheng, Jingwei; Xu, Weilin; Weng, Jiaqi; Gao, Liansheng; Tao, Li; Liang, Feng; Zhang, Jianmin

2018-06-01

Distinguishing radiation necrosis from brain tumor recurrence remains challenging. We performed a meta-analysis to assess the diagnostic accuracy of 2 different amino acid tracers used in positron emission tomography/computed tomography scans: 18 F-FDOPA (6-[18F]-fluoro-L-3,4-dihydroxyphenylalanine) and 18 F-FET (O-(2-18F-fluoroethyl)-L-tyrosine). We searched for studies in 3 databases: PubMed, Embase, and Chinese Biomedical databases. The data were extracted from eligible studies and then processed with heterogeneity test, threshold effect test, and calculations of sensitivity, specificity, and area under the summary receiver operating characteristic curve. Meta-regression and subgroup analyses were performed to explore the source of heterogeneity. A total of 48 studies ( 18 F-FDOPA, n = 21; 18 F-FET, n = 27) were included. Quantitative synthesis determined pooled weight values in the 18 F-FDOPA and 18 F-FET groups: sensitivity, 0.85 versus 0.82; specificity, 0.77 versus 0.80; diagnostic odds ratio, 21.7 versus 23.03; area under the curve (AUC) values, 0.8771 versus 0.8976 (P = 0.46). Moreover, the type of tumor was identified as the possible source of the significant heterogeneity (I 2  = 52%; P = 0.003) found in the 18 F-FDOPA group. In meta-regression and subgroup analyses, 18 F-FDOPA showed better diagnostic accuracy in patients with glioma compared with patients with brain metastases (AUC values, 0.9691 vs. 0.837; P < 0.01). 18 F-FDOPA also showed a significant advantage in the diagnosis of glioma recurrence compared with 18 F-FET (AUC values, 0.9691 vs. 0.9124; P = 0.015). Both 18 F-FDOPA and 18 F-FET exhibit moderate overall accuracy in diagnosing brain tumor recurrence from radiation necrosis. However, 18 F-FDOPA is more adept at diagnosing glioma recurrence compared with brain metastases, and it is more effective than 18 F-FET in diagnosing glioma recurrence. Copyright © 2018 Elsevier Inc. All rights reserved.

Avascular Necrosis of the Capitate

PubMed Central

Bekele, Wosen; Escobedo, Eva; Allen, Robert

2011-01-01

Avascular necrosis of the capitate is a rare entity. The most common reported etiology is trauma. We report a case of avascular necrosis of the capitate in a patient with chronic wrist pain that began after a single episode of remote trauma. PMID:22470799

Association Between Radiation Necrosis and Tumor Biology After Stereotactic Radiosurgery for Brain Metastasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Jacob A.; Bennett, Elizabeth E.; Xiao, Roy

Background: The primary dose-limiting toxicity of stereotactic radiosurgery (SRS) is radiation necrosis (RN), which occurs after approximately 5% to 10% of treatments. This adverse event may worsen neurologic deficits, increase the frequency and cost of imaging, and necessitate prolonged treatment with steroids or antiangiogenic agents. Previous investigations have primarily identified lesion size and dosimetric constraints as risk factors for RN in small populations. We hypothesized that disease histology, receptor status, and mutational status are associated with RN. Methods and Materials: All patients presenting with brain metastasis between 1997 and 2015 who underwent SRS and subsequent radiographic follow-up at a singlemore » tertiary-care institution were eligible for inclusion. The primary outcome was the cumulative incidence of radiographic RN. Multivariate competing risks regression was used to identify biological risk factors for RN. Results: 1939 patients (5747 lesions) were eligible for inclusion; 285 patients (15%) experienced radiographic RN after the treatment of 427 (7%) lesions. After SRS, the median time to RN was 7.6 months. After multivariate analysis, graded prognostic assessment, renal pathology, lesion diameter, and the heterogeneity index remained independently predictive of RN in the pooled cohort. In subset analyses of individual pathologies, HER2-amplified status (hazard ratio [HR] 2.05, P=.02), BRAF V600+ mutational status (HR 0.33, P=.04), lung adenocarcinoma histology (HR 1.89, P=.04), and ALK rearrangement (HR 6.36, P<.01) were also associated with RN. Conclusions: In the present investigation constituting the largest series of RN, several novel risk factors were identified, including renal histology, lung adenocarcinoma histology, HER2 amplification, and ALK/BRAF mutational status. These risk factors may be used to guide clinical trial design incorporating biological risk stratification or dose escalation. Future studies

NecroQuant: quantitative assessment of radiological necrosis

NASA Astrophysics Data System (ADS)

Hwang, Darryl H.; Mohamed, Passant; Varghese, Bino A.; Cen, Steven Y.; Duddalwar, Vinay

2017-11-01

Clinicians can now objectively quantify tumor necrosis by Hounsfield units and enhancement characteristics from multiphase contrast enhanced CT imaging. NecroQuant has been designed to work as part of a radiomics pipelines. The software is a departure from the conventional qualitative assessment of tumor necrosis, as it provides the user (radiologists and researchers) a simple interface to precisely and interactively define and measure necrosis in contrast-enhanced CT images. Although, the software is tested here on renal masses, it can be re-configured to assess tumor necrosis across variety of tumors from different body sites, providing a generalized, open, portable, and extensible quantitative analysis platform that is widely applicable across cancer types to quantify tumor necrosis.

The in vivo evidence for regulated necrosis.

PubMed

Tonnus, Wulf; Linkermann, Andreas

2017-05-01

Necrosis is a hallmark of several widespread diseases or their direct complications. In the past decade, we learned that necrosis can be a regulated process that is potentially druggable. RIPK3- and MLKL-mediated necroptosis represents by far the best studied pathway of regulated necrosis. During necroptosis, the release of damage-associated molecular patterns (DAMPs) drives a phenomenon referred to as necroinflammation, a common consequence of necrosis. However, most studies of regulated necrosis investigated cell lines in vitro in a cell autonomous manner, which represents a non-physiological situation. Conclusions based on such work might not necessarily be transferrable to disease states in which synchronized, non-cell autonomous effects occur. Here, we summarize the current knowledge of the pathophysiological relevance of necroptosis in vivo, and in light of this understanding, we reassess the morphological classification of necrosis that is generally used by pathologists. Along these lines, we discuss the paucity of data implicating necroptosis in human disease. Finally, the in vivo relevance of non-necroptotic forms of necrosis, such as ferroptosis, is addressed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Single-Fraction Versus Multifraction (3 × 9 Gy) Stereotactic Radiosurgery for Large (>2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it; IRCCS Neuromed, Pozzilli; Scaringi, Claudia

Purpose: To investigate the local control and radiation-induced brain necrosis in patients with brain metastases >2 cm in size who received single-fraction or multifraction stereotactic radiosurgery (SRS); factors associated with clinical outcomes and the development of brain radionecrosis were assessed. Methods and Materials: Two hundred eighty-nine consecutive patients with brain metastases >2.0 cm who received SRS as primary treatment at Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy, were analyzed. Cumulative incidence analysis was used to compare local control and radiation-induced brain necrosis between groups from the time of SRS. To achieve a balanced distribution of baseline covariates between treatment groups, amore » propensity score analysis was used. Results: The 1-year cumulative local control rates were 77% in the single-fraction SRS (SF-SRS) group and 91% in the multifraction SRS (MF-SRS) group (P=.01). Recurrences occurred in 25 and 11 patients who received SF-SRS or MF-SRS (P=.03), respectively. Thirty-one patients (20%) undergoing SF-SRS and 11 (8%) subjected to MF-SRS experienced brain radionecrosis (P=.004); the 1-year cumulative incidence rate of radionecrosis was 18% and 9% (P=.01), respectively. Significant differences between the 2 groups in terms of local control and risk of radionecrosis were maintained after propensity score adjustment. Conclusions: Multifraction SRS at a dose of 27 Gy in 3 daily fractions seems to be an effective treatment modality for large brain metastases, associated with better local control and a reduced risk of radiation-induced radionecrosis as compared with SF-SRS.« less

Robotic-assisted latissimus dorsi harvest in delayed-immediate breast reconstruction.

PubMed

Clemens, Mark W; Kronowitz, Steven; Selber, Jesse C

2014-02-01

For two-stage, implant-based, delayed-immediate reconstruction of the radiated breast, robotic-assisted latissimus dorsi harvest (RALDH) is a good option for patients who wish to avoid a traditional latissimus dorsi donor-site incision. The purpose of this study was to compare outcomes of RALDH and the traditional open technique (TOT) for patients undergoing delayed-immediate breast reconstruction following radiation therapy. A retrospective analysis of a prospective database of all consecutive patients undergoing latissimus dorsi harvest for radiated breast reconstruction between 2009 and 2013 was performed. Indications, surgical technique, complications, and outcomes were assessed. One hundred forty-six pedicled latissimus dorsi muscle flaps were performed for breast reconstruction and 17 were performed robotically during the study period (average follow-up 14.6 ± 7.3 mo). Latissimus dorsi breast reconstruction following radiation was performed in 64 patients using TOT and 12 using RALDH. Surgical complication rates were 37.5% in TOT versus 16.7% in RALDH (p = 0.31) including seroma (8.9% versus 8.3%), infection (14.1 versus 8.3%), delayed wound healing (7.8% versus 0), and capsular contracture (4.7% vs. 0). Robotic-assisted harvest of the latissimus dorsi muscle is associated with a low complication rate and reliable results for delayed reconstruction of the irradiated breast while eliminating the need for a donor-site incision.

Robotic-Assisted Latissimus Dorsi Harvest in Delayed-Immediate Breast Reconstruction

PubMed Central

Clemens, Mark W.; Kronowitz, Steven; Selber, Jesse C.

2014-01-01

For two-stage, implant-based, delayed-immediate reconstruction of the radiated breast, robotic-assisted latissimus dorsi harvest (RALDH) is a good option for patients who wish to avoid a traditional latissimus dorsi donor-site incision. The purpose of this study was to compare outcomes of RALDH and the traditional open technique (TOT) for patients undergoing delayed-immediate breast reconstruction following radiation therapy. A retrospective analysis of a prospective database of all consecutive patients undergoing latissimus dorsi harvest for radiated breast reconstruction between 2009 and 2013 was performed. Indications, surgical technique, complications, and outcomes were assessed. One hundred forty-six pedicled latissimus dorsi muscle flaps were performed for breast reconstruction and 17 were performed robotically during the study period (average follow-up 14.6 ± 7.3 mo). Latissimus dorsi breast reconstruction following radiation was performed in 64 patients using TOT and 12 using RALDH. Surgical complication rates were 37.5% in TOT versus 16.7% in RALDH (p = 0.31) including seroma (8.9% versus 8.3%), infection (14.1 versus 8.3%), delayed wound healing (7.8% versus 0), and capsular contracture (4.7% vs. 0). Robotic-assisted harvest of the latissimus dorsi muscle is associated with a low complication rate and reliable results for delayed reconstruction of the irradiated breast while eliminating the need for a donor-site incision. PMID:24872775

Minimally Invasive Radiation Biodosimetry and Evaluation of Organ Responses

DTIC Science & Technology

2016-10-01

radiation exposure, potentially leading to Acute Radiation Syndromes (ARS) and Delayed Effects of Acute ...underlying conditions and inherent variations. 2. KEYWORDS Radiation Biodosimetry, Radiation Biomarkers, microRNA, Acute Radiation Syndromes ... syndromes and delayed effects of acute radiation exposure. We expect to identify the circulating miRNA biomarkers as early predictors of late effects

An Aloe Vera-Based Cosmeceutical Cream Delays and Mitigates Ionizing Radiation-Induced Dermatitis in Head and Neck Cancer Patients Undergoing Curative Radiotherapy: A Clinical Study.

PubMed

Rao, Suresh; Hegde, Sanath Kumar; Baliga-Rao, Manjeshwar Poonam; Palatty, Princy Louis; George, Thomas; Baliga, Manjeshwar Shrinath

2017-06-24

Background: This study was planned to evaluate the efficacy of topical application of an Aloe vera -based cream (AVC) for the prevention of ionizing radiation (X ray)-induced dermatitis in head and neck cancer patients requiring therapeutic radiation treatment (>62 Gy). Methods: From July 2012 to December 2012, a total of 60 head and neck cancer patients requiring curative radiotherapy (RT) of more than 66 Gy were prospectively enrolled and treated with AVC or a comparator Johnson's Baby Oil (JBO). Acute skin reaction was monitored and classified according to the Radiation Therapy Oncology Group (RTOG) four-point rating scale on a weekly basis. Results: The results indicate that there was a statistically significant delay in the incidence ( p = 0.04) of dermatitis at week three in the AVC application group. Application of AVC reduced the incidence of Grade 1, 2, and 3 dermatitis at subsequent time points, while Grade 4 dermatitis was not seen in either cohort. The other most important observation was that the continued application of AVC two weeks after the completion of RT was effective in reducing the average grade of dermatitis and was statistically significant ( p < 0.02). Conclusions : Prophylactic use of an AVC-based cream is thus effective in delaying radiation dermatitis in head and neck cancer.

An Aloe Vera-Based Cosmeceutical Cream Delays and Mitigates Ionizing Radiation-Induced Dermatitis in Head and Neck Cancer Patients Undergoing Curative Radiotherapy: A Clinical Study

PubMed Central

Rao, Suresh; Hegde, Sanath Kumar; Baliga-Rao, Manjeshwar Poonam; Palatty, Princy Louis; George, Thomas; Baliga, Manjeshwar Shrinath

2017-01-01

Background: This study was planned to evaluate the efficacy of topical application of an Aloe vera-based cream (AVC) for the prevention of ionizing radiation (X ray)-induced dermatitis in head and neck cancer patients requiring therapeutic radiation treatment (>62 Gy). Methods: From July 2012 to December 2012, a total of 60 head and neck cancer patients requiring curative radiotherapy (RT) of more than 66 Gy were prospectively enrolled and treated with AVC or a comparator Johnson’s Baby Oil (JBO). Acute skin reaction was monitored and classified according to the Radiation Therapy Oncology Group (RTOG) four-point rating scale on a weekly basis. Results: The results indicate that there was a statistically significant delay in the incidence (p = 0.04) of dermatitis at week three in the AVC application group. Application of AVC reduced the incidence of Grade 1, 2, and 3 dermatitis at subsequent time points, while Grade 4 dermatitis was not seen in either cohort. The other most important observation was that the continued application of AVC two weeks after the completion of RT was effective in reducing the average grade of dermatitis and was statistically significant (p < 0.02). Conclusions: Prophylactic use of an AVC-based cream is thus effective in delaying radiation dermatitis in head and neck cancer. PMID:28930258

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heravi, Mitra; Department of Radiation Oncology, McGill University, Montreal; Segal Cancer Center, Jewish General Hospital, Montreal

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, Westernmore » 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.« less

Infectious haematopoietic necrosis virus: Chapter 2

USGS Publications Warehouse

Leong, Jo-Ann; Kurath, Gael

2017-01-01

Infectious haematopoietic necrosis virus (IHNV) is a Rhabdovirus that causes significant disease in Pacific salmon (Oncorhynchus spp.), Atlantic salmon (Salmo salar), and rainbow and steelhead trout (O. mykiss). IHNV causes necrosis of the haematopoietic tissues, and consequently it was named infectious haematopoietic necrosis. This virus is waterborne and may transmit horizontally and vertically through virus associated with seminal and ovarian fluids. The clinical signs of disease and diagnosis; pathology; pathophysiology; and control strategies against IHNV are discussed.

Intranasal hydrocodone-acetaminophen abuse induced necrosis of the nasal cavity and pharynx.

PubMed

Alexander, David; Alexander, Keith; Valentino, Joseph

2012-11-01

Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid transmucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Retrospective chart review. Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. The majority of patients will initially deny the behavior, frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow-up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented, with one resulting in death. The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue, which can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Acute Biological Effects of Simulating the Whole-Body Radiation Dose Distribution from a Solar Particle Event Using a Porcine Model

PubMed Central

Wilson, Jolaine M.; Sanzari, Jenine K.; Diffenderfer, Eric S.; Yee, Stephanie S.; Seykora, John T.; Maks, Casey; Ware, Jeffrey H.; Litt, Harold I.; Reetz, Jennifer A.; McDonough, James; Weissman, Drew; Kennedy, Ann R.; Cengel, Keith A.

2011-01-01

In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses. PMID:21859326

Regulation of Tumor Progression by Programmed Necrosis

PubMed Central

Jeon, Hyun Min; Jeong, Eui Kyong; Lee, Yig Ji; Kim, Cho Hee; Park, Hye Gyeong

2018-01-01

Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose) deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1), which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s) in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness. PMID:29636841

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

Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma.

PubMed

Atanasov, Georgi; Schierle, Katrin; Hau, Hans-Michael; Dietel, Corinna; Krenzien, Felix; Brandl, Andreas; Wiltberger, Georg; Englisch, Julianna Paulina; Robson, Simon C; Reutzel-Selke, Anja; Pascher, Andreas; Jonas, Sven; Pratschke, Johann; Benzing, Christian; Schmelzle, Moritz

2017-02-01

Tumor necrosis and peritumoral fibrosis have both been suggested to have a prognostic value in selected solid tumors. However, little is known regarding their influence on tumor progression and prognosis in hilar cholangiocarcinoma (HC). Surgically resected tumor specimens of HC (n = 47) were analyzed for formation of necrosis and extent of peritumoral fibrosis. Tumor necrosis and grade of fibrosis were assessed histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients' survival. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. Mild peritumoral fibrosis was evident in 12 tumor samples, moderate peritumoral fibrosis in 20, and high-grade fibrosis in 15. Necrosis was evident in 19 of 47 tumor samples. Patients with tumors characterized by necrosis showed a significantly decreased 5-year recurrence-free survival (37.9 vs. 25.7 %; p < .05) and a significantly decreased 5-year overall survival (42.6 vs. 12.4 %; p < .05), when compared with patients with tumors showing no necrosis. R status, tumor recurrence, and tumor necrosis were of prognostic value in the univariate analysis (all p < .05). Multivariate survival analysis confirmed tumor necrosis (p = .038) as the only independent prognostic variable. The assessment of tumor necrosis appears as a valuable additional prognostic tool in routine histopathological evaluation of HC. These observations might have implications for monitoring and more individualized multimodal therapeutic strategies.

Palatal Perforation: A Rare Complication of Postanesthetic Necrosis

PubMed Central

Gargi, Vidisha; Mohan, Ravi Prakash Sasankoti; Kamarthi, Nagaraju; Gupta, Swati

2017-01-01

The everyday practice of dentistry relies heavily on achieving adequate local anesthesia. Even though the safety record of local anesthetic agents is high, complications do occur. Palate is a favorable site for soft-tissue lesions. Various factors such as direct effects of the drug, blanching of the tissues during injection, relatively poor blood supply, and reactivation of the latent forms of herpes can all promote to tissue ischemia and a lesion in the palate. Among various complications, anesthetic necrotic ulcer is a rare and uncommon condition occurring mostly in the hard palate possibly after a local anesthetic infiltration. The ulceration is often deep and shows spontaneous but delayed healing. If proper treatment is not instituted on time, the necrosis can reach deep into the bone causing sequestrum formation and ultimately leading to palatal perforation. Here, we report a case of palatal perforation in a male patient followed by surgical interventions and follow-up. PMID:29042744

Revision Stapedectomy with Necrosis of the Long Process of the Incus: Does the Degree of Necrosis Matter? A Retrospective Clinical Study.

PubMed

Ghonim, Mohamed; Shabana, Yousef; Ashraf, Bassem; Salem, Mohamed

2017-04-01

To discuss the different modalities for managing necrosis of the long process of the incus in revision stapedectomy on the basis of the degree of necrosis and compare the results with those reported in the literature. Thirty-six patients underwent revision stapedectomy with the necrosis of the long process of the incus from 2009 to 2016. The patients were divided into three groups on the basis of the degree of necrosis. For group A (minimal necrosis), augmentation technique with bone cement was performed. For group B (partial necrosis), the cement plug technique was performed. For group C (sever necrosis), malleus relocation with malleovestibulopexy was performed using reshaped necrosed incus. Air and bone conduction thresholds at frequencies of 500-3000 Hz were reviewed pre- and postoperatively using conventional audiometry. The air-bone gap (ABG) and bone conduction thresholds were measured. Postoperative ABG was reduced to <10 dB in 28 cases (77.8%) and <20 dB in all cases (100%). There was no significant change in postoperative bone conduction thresholds. The mean patient follow-up duration was 23 (range, 18-36) months. The cement plug technique was used in 75% of cases. Managing necrosis of the long process of the incus in revision stapedectomy should be considered according to the degree of necrosis. The cement plug technique is considered to be a reasonable option in most cases. Malleus relocation with malleovestibulopexy is an effective alternative to prosthesis.

Recommendations from the INHAND Apoptosis/Necrosis Working Group.

PubMed

Elmore, Susan A; Dixon, Darlene; Hailey, James R; Harada, Takanori; Herbert, Ronald A; Maronpot, Robert R; Nolte, Thomas; Rehg, Jerold E; Rittinghausen, Susanne; Rosol, Thomas J; Satoh, Hiroshi; Vidal, Justin D; Willard-Mack, Cynthia L; Creasy, Dianne M

2016-02-01

Historically, there has been confusion relating to the diagnostic nomenclature for individual cell death. Toxicologic pathologists have generally used the terms "single cell necrosis" and "apoptosis" interchangeably. Increased research on the mechanisms of cell death in recent years has led to the understanding that apoptosis and necrosis involve different cellular pathways and that these differences can have important implications when considering overall mechanisms of toxicity, and, for these reasons, the separate terms of apoptosis and necrosis should be used whenever differentiation is possible. However, it is also recognized that differentiation of the precise pathway of cell death may not be important, necessary, or possible in routine toxicity studies and so a more general term to indicate cell death is warranted in these situations. Morphological distinction between these two forms of cell death can sometimes be straightforward but can also be challenging. This article provides a brief discussion of the cellular mechanisms and morphological features of apoptosis and necrosis as well as guidance on when the pathologist should use these terms. It provides recommended nomenclature along with diagnostic criteria (in hematoxylin and eosin [H&E]-stained sections) for the most common forms of cell death (apoptosis and necrosis). This document is intended to serve as current guidance for the nomenclature of cell death for the International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups and the toxicologic pathology community at large. The specific recommendations are:Use necrosis and apoptosis as separate diagnostic terms.Use modifiers to denote the distribution of necrosis (e.g., necrosis, single cell; necrosis, focal; necrosis, diffuse; etc.).Use the combined term apoptosis/single cell necrosis whenThere is no requirement or need to split the processes, orWhen the nature of cell death cannot be determined with certainty, orWhen both

Chronic retinal necrosis: cytomegalovirus necrotizing retinitis associated with panretinal vasculopathy in non-HIV patients.

PubMed

Schneider, Eric W; Elner, Susan G; van Kuijk, Frederik J; Goldberg, Naomi; Lieberman, Ronni M; Eliott, Dean; Johnson, Mark W

2013-10-01

To characterize a unique cytomegalovirus (CMV)-associated retinopathy in patients with limited immune dysfunction. Retrospective observational case series. CMV was confirmed as the pathogenic agent via polymerase chain reaction analysis of aqueous or vitreous humor samples or via immunohistochemical analysis of retinal biopsy specimens. Five non-HIV patients with granular necrotizing retinitis, vitritis, and severe occlusive vasculopathy were identified. Patient histories all suggested a basis for limited immune dysfunction including advanced age (n = 4), diabetes mellitus (n = 4), and noncytotoxic immunotherapy (n = 3). Diagnosis of CMV retinitis was delayed in all cases and patients received either no antiviral therapy (n = 2) or incorrect antiviral therapy (n = 3) for presumed herpes simplex/varicella zoster-related acute retinal necrosis. Retinitis subsequently regressed in all cases with introduction of systemic ganciclovir/valganciclovir (n = 5) and/or intravitreal foscarnet (n = 2). Four of five patients developed neovascularization because of extensive retinal ischemia. The clinical expression of CMV-associated retinopathy is strongly related to immune status. In patients with limited immune dysfunction, a mixed clinical picture of intraocular inflammation with panretinal occlusive vasculopathy, more characteristic of acute retinal necrosis, and peripheral slowly progressive granular retinitis, more characteristic of classic CMV retinitis, is observed. Recognition of this atypical clinical presentation, which the authors term chronic retinal necrosis, should prompt molecular testing for CMV to determine the appropriate antiviral therapy. Consideration should also be given to prophylactic panretinal photocoagulation in such eyes, given the high risk of neovascular complications.

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.

Standard cosmology delayed

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choudhury, Debajyoti; Ghoshal, Debashis; Sen, Anjan Ananda, E-mail: debajyoti.choudhury@gmail.com, E-mail: dghoshal@mail.jnu.ac.in, E-mail: anjan.ctp@jmi.ac.in

2012-02-01

The introduction of a delay in the Friedmann equation of cosmological evolution is shown to result in the very early universe undergoing the necessary accelerated expansion in the usual radiation (or matter) dominated phase. Occurring even without a violation of the strong energy condition, this expansion slows down naturally to go over to the decelerated phase, namely the standard Hubble expansion. This may obviate the need for a scalar field driven inflationary epoch.

The incidence of radiation necrosis following stereotactic radiotherapy for melanoma brain metastases: the potential impact of immunotherapy.

PubMed

Kaidar-Person, Orit; Zagar, Timothy M; Deal, Allison; Moschos, Stergios J; Ewend, Matthew G; Sasaki-Adams, Deanna; Lee, Carrie B; Collichio, Frances A; Fried, David; Marks, Lawrence B; Chera, Bhishamjit S

2017-07-01

Stereotactic radiotherapy (SRT) is the standard treatment for patients with limited number of brain metastases. In the past few years, newer immunotherapies (immune checkpoint inhibitors) have been proven to prolong survival in patients with metastatic melanoma. The safety of the combination of SRT and immunotherapy for brain metastases is unknown. We retrospectively identified patients with melanoma brain metastases treated with SRT between 2007 and 2015. Patients who did not have at least 3 months of follow-up with imaging after SRT were excluded from the analysis. Outcomes were compared between patients who were treated with or without immunotherapy. A total of 58 patients were included; of these, 29 were treated with SRT and immunotherapy. MAPK inhibitors (BRAF, MEK inhibitors) were used more often in the immunotherapy group (nine vs. two patients). There was a higher incidence of intracranial complications in patients treated with immunotherapy and SRT. Eight patients had radiation necrosis; all occurred in patients who were treated with immunotherapy. Nine patients had hemorrhage, of which seven occurred in patients who were treated with immunotherapy (P=0.08). However, patients treated with immunotherapy and SRT had a significant overall survival advantage compared with SRT without immunotherapy (15 vs. 6 months, P=0.0013). Patients treated with SRT and immunotherapy have a higher incidence/risk of intracranial complications, but a longer overall survival.

Effects of ultraviolet radiation, visible light, and infrared radiation on erythema and pigmentation: a review.

PubMed

Sklar, Lindsay R; Almutawa, Fahad; Lim, Henry W; Hamzavi, Iltefat

2013-01-01

The effects of ultraviolet radiation, visible light, and infrared radiation on cutaneous erythema, immediate pigment darkening, persistent pigment darkening, and delayed tanning are affected by a variety of factors. Some of these factors include the depth of cutaneous penetration of the specific wavelength, the individual skin type, and the absorption spectra of the different chromophores in the skin. UVB is an effective spectrum to induce erythema, which is followed by delayed tanning. UVA induces immediate pigment darkening, persistent pigment darkening, and delayed tanning. At high doses, UVA (primarily UVA2) can also induce erythema in individuals with skin types I-II. Visible light has been shown to induce erythema and a tanning response in dark skin, but not in fair skinned individuals. Infrared radiation produces erythema, which is probably a thermal effect. In this article we reviewed the available literature on the effects of ultraviolet radiation, visible light, and infrared radiation on the skin in regards to erythema and pigmentation. Much remains to be learned on the cutaneous effects of visible light and infrared radiation.

Intranasal Hydrocodone-Acetaminophen Abuse Induced Necrosis of the Nasal Cavity and Pharynx

PubMed Central

Alexander, David; Alexander, Keith; Valentino, Joseph

2012-01-01

Objectives Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid trans mucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Study Design Retrospective chart review. Methods Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. Results The majority of patients will initially deny the behavior frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented with one resulting in death. Conclusions The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue that can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Study Design Chart review, level of evidence: 4 PMID:22965281

First follow-up radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastases.

PubMed

Sharma, Mayur; Jia, Xuefei; Ahluwalia, Manmeet; Barnett, Gene H; Vogelbaum, Michael A; Chao, Samuel T; Suh, John H; Murphy, Erin S; Yu, Jennifer S; Angelov, Lilyana; Mohammadi, Alireza M

2017-09-01

Local progression (LP) and radiation necrosis (RN) occur in >20% of cases following stereotactic radiosurgery (SRS) for brain metastases (BM). Expected outcomes following SRS for BM include tumor control/shrinkage, local progression and radiation necrosis. 1427 patients with 4283 BM lesions were treated using SRS at Cleveland Clinic from 2000 to 2012. Clinical, imaging and radiosurgery data were collected from the database. Local tumor progression and RN were the primary end points and correlated with patient and tumor-related variables. 5.7% of lesions developed radiographic RN and 3.6% showed local progression at 6 months. Absence of new extracranial metastasis (P < 0.001), response to SRS at first follow-up scan (local progression versus stable size (P < 0.001), partial resolution versus complete resolution at first follow up [P = 0.009]), prior SRS to the same lesion (P < 0.001), IDL% (≤55; P < 0.001), maximum tumor diameter (>0.9 cm; P < 0.001) and MD/PD gradient index (≤1.8, P < 0.001) were independent predictors of high risk of local tumor progression. Absence of systemic metastases (P = 0.029), good neurological function at 1st follow-up (P ≤ 0.001), no prior SRS to other lesion (P = 0.024), low conformity index (≤1.9) (P = 0.009), large maximum target diameter (>0.9 cm) (P = 0.003) and response to SRS (tumor progression vs. stable size following SRS [P < 0.001]) were independent predictors of high risk of radiographic RN. Complete tumor response at first follow-up, maximum tumor diameter <0.9 cm, tumor volume <2.4 cc and no prior SRS to the index lesion are good prognostic factors with reduced risk of LP following SRS. Complete tumor response to SRS, poor neurological function at first follow-up, prior SRS to other lesions and high conformity index are favorable factors for not developing RN. Stable or partial response at first follow-up after SRS have same impact on local progression and RN compared to those with

Indomethacin induced avascular necrosis of head of femur

PubMed Central

Prathapkumar, K; Smith, I; Attara, G

2000-01-01

Chemically induced avascular necrosis of bone is a well documented entity. Indomethacin is one of the causes of this condition but is often difficult to recognise. Review of the literature shows that only one case of indomethacin induced avascular necrosis has been reported in the English language between 1966 and the present.
The case of a young healthy man, who developed avascular necrosis of head of femur after prolonged administration of indomethacin, is reported here.


Keywords: indomethacin; avascular necrosis PMID:10964124

Pharmacological doses of daily ascorbate protect tumors from radiation damage after a single dose of radiation in an intracranial mouse glioma model.

PubMed

Grasso, Carole; Fabre, Marie-Sophie; Collis, Sarah V; Castro, M Leticia; Field, Cameron S; Schleich, Nanette; McConnell, Melanie J; Herst, Patries M

2014-01-01

Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumor environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionizing radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumor, glioblastoma multiforme (GBM), is very resistant to radiation; radiosensitizing GBM cells will improve survival of GBM patients. Here, we demonstrate that a single fraction (6 Gy) of radiation combined with a 1 h exposure to ascorbate (5 mM) sensitized murine glioma GL261 cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy) of whole brain radiation combined with daily intraperitoneal injections of ascorbate (1 mg/kg) in an intracranial GL261 glioma mouse model. Tumor-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain 8 days after tumor implantation, a second group received daily intraperitoneal injections of ascorbate (day 8-45) after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumor progression, intraperitoneal ascorbate alone had no effect on tumor progression. Tumor progression was faster in tumor-bearing mice treated with radiation and daily ascorbate than in those treated with radiation alone. Histological analysis showed less necrosis in tumors treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumor microenvironment, which determines whether ascorbate remains outside the cell, acting as a pro-oxidant, or whether it enters the cells and acts as an anti-oxidant.

Principals Of Radiation Toxicology: Important Aspects.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

. 1990, 2012] Moderate and high doses of radiation induces necrosis of radiosensitive cells with the subsequent formation of radiation toxins and their induced acute inflammatory processes. Radiation necrosis is the most substantial and most severe form of radiation induced injury, and when widespread, has grave therapeutic implications. [D. Popov et al. 1990, 2012,Claudio A. et al. 2002, Robertson J. et al. 2002, ] Relatively small doses of Radiation Toxins induce apoptosis and high doses of Radiation Toxins induce necrosis. [Rastogi P. et al. 2009, D. Popov et al. 1990, 2012,] Threshold of Toxic Effects occurs and can be defined. [D. Popov et al. 2012, ] Radiation Toxins affects Somatic cells and Germ Cells. Radiation Toxins can induce teratogenic processes. Specific Toxicity of Radiation Toxins can affects developing fetus. Material and Methods, Results: http://www.intechopen.com/books/current-topics-in-ionizing-radiation-research/radiation-toxins-molecular-mechanisms-of-toxicity-and-radiomimetic-properties- Conclusion: Radiation is a physical agent - induce activation of some secretory proteins with high enzymatic activity. This proteins called as Radiation Toxins can produce specific for radiation biological and toxic effects after administration to radiation naive mammals. [V. Maliev et al. 2007, D. Popov et al. 1990, 2012] Radiation Toxins are teratogenic and oncogenic. Radiation Toxins effects depend on Administered Dose and Radiation effects depend on Exposure Dose and Absorbed Dose. The levels of Radiation Toxins correlates with Radiation Exposure.

Pseudotumoral encapsulated fat necrosis with diffuse pseudomembranous degeneration.

PubMed

Felipo, F; Vaquero, M; del Agua, C

2004-09-01

An extraordinary case of encapsulated fat necrosis characterized by its large size, diffuse formation of pseudomembranes, and tendency to recur after excision is reported. A 67-year-old Caucasian woman suffering from morbid obesity was admitted for diagnosis and surgical treatment of a soft tissue mass showing a longest diameter of 14 cm and lying adjacently to the scar from previous appendicectomy. Histopathologic features were consistent with a nodular-cystic encapsulated fat necrosis with diffuse pseudomembranous transformation. Eight months after surgery, a new larger mass (longest diameter of 18 cm) sharing identical histopathologic features appeared in the same location. Encapsulated fat necrosis is a well-defined entity even though several names have been proposed for this condition, including mobile encapsulated lipoma, encapsulated necrosis, or nodular-cystic fat necrosis. Its pathogenesis seems to be related to ischemic changes secondary to previous trauma. It may occasionally show degenerative changes, including dystrophic calcifications and presence of pseudomembranes. To our knowledge, these are the first reported cases of encapsulated fat necrosis presenting as lesions of such size and showing diffuse formation of pseudomembranes; these particular features made diagnosis difficult and led to consideration of a wide range of potential diagnostic possibilities. This case expands the clinico-pathologic spectrum of membranocystic fat necrosis, including the potential ability of this subcutaneous fatty tissue abnormality to recur after surgical excision. Felipo F, Vaquero M, del Agua C. Pseudotumoral encapsulated fat necrosis with diffuse pseudomembranous degeneration.

Using Feily's method prevented scalp necrosis in three patients incline to the scalp recipient necrosis; what is new in prevention of scalp necrosis?

PubMed

Feily, Amir; Feily, Ahmad

2017-01-01

Serious complications arising from surgical hair restoration are relatively uncommon following well-performed and well-planned surgery by skillful surgical techniques, good communication, and postoperative follow-up. Surgical complications often categorized as those which occur in the donor site and the recipient site. In this paper among recipient area complication we focused on recipient area necrosis that arises when an increased number of recipient grafts are utilized and de-vascularization of the scalp occurs as a result of the large wound area due to the dense packing splitting of recipient skin. Recently, Feily et al. explained an interesting method to prevent development of recipient area necrosis following a hair transplant procedure. Herein we reported three cases of dense hair transplantation using the Feilys method that after slitting they troubled by unusual long lasting dark areas on the scalp and they need more than 24 hr's patience for prevention of scalp necrosis. © 2016 Wiley Periodicals, Inc.

Post-pancreatitis Fat Necrosis Mimicking Carcinomatosis.

PubMed

Smith, Joshua P; Arnoletti, J Pablo; Varadarajulu, Shyam; Morgan, Desiree E

2008-01-01

Acute pancreatitis can result in retroperitoneal fat necrosis, typically occurring in the peripancreatic region, with extension into the transverse mesocolon, omentum and mesenteric root. When evaluated with contrast enhanced computed tomography (CECT), acute peripancreatic post necrotic collections typically become lower in attenuation over time, and often appear as homogeneous fluid collections. Saponification as a complication of fat necrosis in patients with acute pancreatitis is a well recognized clinical entity. While retroperitonal fat necrosis is commonly seen on CECT, saponification is not a prominent imaging feature. We present a case of acute pancreatitis complicated by extensive saponification of fat throughout the retroperitoneum and peritoneal lining, mimicking carcinomatosis.

Coherent nature of the radiation emitted in delayed luminescence of leaves

PubMed

Bajpai

1999-06-07

After exposure to light, a living system emits a photon signal of characteristic shape. The signal has a small decay region and a long tail region. The flux of photons in the decay region changes by 2 to 3 orders of magnitude, but remains almost constant in the tail region. The decaying part is attributed to delayed luminescence and the constant part to ultra-weak luminescence. Biophoton emission is the common name given to both kinds of luminescence, and photons emitted are called biophotons. The decay character of the biophoton signal is not exponential, which is suggestive of a coherent signal. We sought to establish the coherent nature by measuring the conditional probability of zero photon detection in a small interval Delta. Our measurements establish the coherent nature of biophotons emitted by different leaves at various temperatures in the range 15-50 degrees C. Our set up could measure the conditional probability for Deltaradiation of a light emitting diode along with a leaf for Delta in the range 10 &mgr;s-100 &mgr

Avascular necrosis of the femoral head in patients treated for leukaemia. Assessment of the need for a diagnostic protocol.

PubMed

Alguacil Pinel, J; Vila Vives, P; Salom Taverner, M

To evaluate the incidence of avascular necrosis of the hip in leukaemia patients treated in our hospital with high doses of corticosteroids in order to evaluate the necessity for an early detection protocol. Observational-descriptive and retrospective study from 2005 to 2016 of 253 patients diagnosed with paediatric leukaemia. Patients with musculoskeletal pathology were identified and patients with avascular necrosis were analysed. A total of 26 patients (10%) had musculoskeletal symptoms. Three patients with avascular necrosis (1.2%) were analysed. One girl, 7 years old, was treated conservatively with traction - suspension and discharge. Two boys, an 11 and a 15.4 year-old,who developed graft-versus-host disease secondary to bone marrow transplantation, and whose treatment included high doses of corticosteroids, developed avascular necrosis of the hip. One was treated with bisphosphonates and forage and the other ended up with a total hip arthroplasty. The occurrence of musculoskeletal symptoms during the treatment of leukaemia is different according to the bibliographic series (0.43 -12.6%). Some authors observe an increased risk in female patients between the ages of 10 and 17. A retrospective study reveals that there is a delay of 3.9 months in the diagnosis of CAP since the onset of pain. Other authors relate NAV to loading joints, age and high doses of corticosteroids. Based on the low incidence of avascular necrosis of the hip in our 14-year-old population treated for leukaemia, the creation of diagnostic protocols seems not to be necessary. However, close monitoring of patients with potential risk factors recognized in the literature, is advisable. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

LhnR and upstream operon LhnABC in Agrobacterium vitis regulate the induction of tobacco hypersensitive responses, grape necrosis and swarming motility.

PubMed

Zheng, Desen; Hao, Guixia; Cursino, Luciana; Zhang, Hongsheng; Burr, Thomas J

2012-09-01

The characterization of Tn5 transposon insertional mutants of Agrobacterium vitis strain F2/5 revealed a gene encoding a predicted LysR-type transcriptional regulator, lhnR (for 'LysR-type regulator associated with HR and necrosis'), and an immediate upstream operon consisting of three open reading frames (lhnABC) required for swarming motility, surfactant production and the induction of a hypersensitive response (HR) on tobacco and necrosis on grape. The operon lhnABC is unique to A. vitis among the sequenced members in Rhizobiaceae. Mutagenesis of lhnR and lhnABC by gene disruption and complementation of ΔlhnR and ΔlhnABC confirmed their roles in the expression of these phenotypes. Mutation of lhnR resulted in complete loss of HR, swarming motility, surfactant production and reduced necrosis, whereas mutation of lhnABC resulted in loss of swarming motility, delayed and reduced HR development and reduced surfactant production and necrosis. The data from promoter-green fluorescent protein (gfp) fusions showed that lhnR suppresses the expression of lhnABC and negatively autoregulates its own expression. It was also shown that lhnABC negatively affects its own expression and positively affects the transcription of lhnR. lhnR and lhnABC constitute a regulatory circuit that coordinates the transcription level of lhnR, resulting in the expression of swarming, surfactant, HR and necrosis phenotypes. © 2012 THE AUTHORS. MOLECULAR PLANT PATHOLOGY © 2012 BSPP AND BLACKWELL PUBLISHING LTD.

Generation of small molecules to interfere with regulated necrosis.

PubMed

Degterev, Alexei; Linkermann, Andreas

2016-06-01

Interference with regulated necrosis for clinical purposes carries broad therapeutic relevance and, if successfully achieved, has a potential to revolutionize everyday clinical routine. Necrosis was interpreted as something that no clinician might ever be able to prevent due to the unregulated nature of this form of cell death. However, given our growing understanding of the existence of regulated forms of necrosis and the roles of key enzymes of these pathways, e.g., kinases, peroxidases, etc., the possibility emerges to identify efficient and selective small molecule inhibitors of pathologic necrosis. Here, we review the published literature on small molecule inhibition of regulated necrosis and provide an outlook on how combination therapy may be most effective in treatment of necrosis-associated clinical situations like stroke, myocardial infarction, sepsis, cancer and solid organ transplantation.

CYLD Deubiquitinates RIP1 in the TNFα-Induced Necrosome to Facilitate Kinase Activation and Programmed Necrosis

PubMed Central

Moquin, David M.; McQuade, Thomas; Chan, Francis Ka-Ming

2013-01-01

Background Necroptosis/programmed necrosis is initiated by a macro-molecular protein complex termed the necrosome. Receptor interacting protein kinase 1 (RIPK1/RIP1) and RIP3 are key components of the necrosome. TNFα is a prototypic inducer of necrosome activation, and it is widely believed that deubiquitination of RIP1 at the TNFR-1 signaling complex precedes transition of RIP1 into the cytosol where it forms the RIP1-RIP3 necrosome. Cylindromatosis (CYLD) is believed to promote programmed necrosis by facilitating RIP1 deubiquitination at this membrane receptor complex. Methodology/Principal Findings We demonstrate that RIP1 is indeed the primary target of CYLD in TNFα-induced programmed necrosis. We observed that CYLD does not regulate RIP1 ubiquitination at the TNF receptor. TNF and zVAD-induced programmed necrosis was highly attenuated in CYLD-/- cells. However, in the presence of cycloheximide or SMAC mimetics, programmed necrosis was only moderately reduced in CYLD-/- cells. Under the latter conditions, RIP1-RIP3 necrosome formation is only delayed, but not abolished in CYLD-/- cells. We further demonstrate that RIP1 within the NP-40 insoluble necrosome is ubiquitinated and that CYLD regulates RIP1 ubiquitination in this compartment. Hence, RIP1 ubiquitination in this late-forming complex is greatly increased in CYLD-/- cells. Increased RIP1 ubiquitination impairs RIP1 and RIP3 phosphorylation, a signature of kinase activation. Conclusions/Significance Our results show that CYLD regulates RIP1 ubiquitination in the TNFα-induced necrosome, but not in the TNFR-1 signaling complex. In cells sensitized to programmed necrosis with SMAC mimetics, CYLD is not essential for necrosome assembly. Since SMAC mimetics induces the loss of the E3 ligases cIAP1 and cIAP2, reduced RIP1 ubiquitination could lead to reduced requirement for CYLD to remove ubiquitin chains from RIP1 in the TNFR-1 complex. As increased RIP1 ubiquitination in the necrosome correlates with

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lukens, J. Nicholas; Lin, Alexander, E-mail: alexander.lin@uphs.upenn.edu; Gamerman, Victoria

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%) hadmore » 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

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.

PubMed

Napoletano, Francesco; Gibert, Benjamin; Yacobi-Sharon, Keren; Vincent, Stéphane; Favrot, Clémentine; Mehlen, Patrick; Girard, Victor; Teil, Margaux; Chatelain, Gilles; Walter, Ludivine; Arama, Eli; Mollereau, Bertrand

2017-09-01

The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required for the programmed necrosis that occurs spontaneously in mitotic germ cells during spermatogenesis. This form of necrosis involved an atypical function of the initiator caspase Dronc/Caspase 9, independent of its catalytic activity. Prevention of p53-dependent necrosis resulted in testicular hyperplasia, which was reversed by restoring necrosis in spermatogonia. In mouse testes, p53 was required for heat-induced germ cell necrosis, indicating that regulation of necrosis is a primordial function of p53 conserved from invertebrates to vertebrates. Drosophila and mouse spermatogenesis will thus be useful models to identify inducers of necrosis to treat cancers that are refractory to apoptosis.

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis

PubMed Central

Napoletano, Francesco; Vincent, Stéphane; Favrot, Clémentine; Mehlen, Patrick; Girard, Victor; Chatelain, Gilles; Walter, Ludivine; Arama, Eli

2017-01-01

The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required for the programmed necrosis that occurs spontaneously in mitotic germ cells during spermatogenesis. This form of necrosis involved an atypical function of the initiator caspase Dronc/Caspase 9, independent of its catalytic activity. Prevention of p53-dependent necrosis resulted in testicular hyperplasia, which was reversed by restoring necrosis in spermatogonia. In mouse testes, p53 was required for heat-induced germ cell necrosis, indicating that regulation of necrosis is a primordial function of p53 conserved from invertebrates to vertebrates. Drosophila and mouse spermatogenesis will thus be useful models to identify inducers of necrosis to treat cancers that are refractory to apoptosis. PMID:28945745

Management of Necrotizing Fasciitis and Fecal Peritonitis following Ostomy Necrosis and Detachment by Using NPT and Flexi-Seal.

PubMed

Yetışır, Fahri; Şarer, Akgün Ebru; Acar, H Zafer

2015-01-01

Management of necrotizing fasciitis and severe faecal peritonitis following ostomy in elderly patient with comorbid disease is challenging. We would like to report management of frozen Open Abdomen (OA) with colonic fistula following ostomy necrosis and detachment in an elderly patient with comorbid disease and malignancy. 78-year-old woman with high stage rectum carcinoma was admitted to emergency department and underwent operation for severe peritonitis and sigmoid colonic perforation. Loop sigmoidostomy was performed. At postoperative 15th day, she was transferred to our clinic with necrotizing fasciitis and severe faecal peritonitis due to ostomy necrosis and detachment. Enteric effluent was removed from the OA wound by using the Flexi-Seal Fecal Management System (FMS) (ConvaTec) and pesser tube in deeply located colonic fistula in conjunction with Negative Pressure Therapy (NPT). Maturation of ostomy was facilitated by using second NPT on ostomy side. After source control, delayed abdominal closure was achieved by skin flap approximation.

Infected Peri-Pancreatic Necrosis Causing Gallbladder Necrosis by Direct Extension

PubMed Central

Assalia, Ahmad; Schmulevski, Pavel; Meislin, Vladimir; Hashmonai, Moshe

1993-01-01

Acute acalculous cholecystitis may develop in patients suffering from necrotizing pancreatitis. Conversely, acute pancreatitis may complicate acute gallbladder disease. We present a case that lends support to the existence of another possibility: gallbladder necrosis caused by direct extension of the necrotizing pancreatitic process. PMID:8260438

Experimental study of electrolysis-induced hepatic necrosis.

PubMed

Robertson, G S; Wemyss-Holden, S A; Dennison, A R; Hall, P M; Baxter, P; Maddern, G J

1998-09-01

One of the most promising but unexplored methods for treating patients with irresectable liver tumours is electrolysis. This study examined the effect of increasing 'current dose' on the volume of the lesion induced in normal rat liver. A direct current generator, connected to platinum electrodes implanted in the rat liver, was used to examine the effect of (1) varying current doses from 1 to 5 coulombs and (2) electrode separation (2 or 20 mm), on the volume of liver necrosis. There was a significant correlation (P < 0.001) between the current dose and the volume of necrosis produced for each electrode separation. Placing the electrodes 2 mm apart resulted in smaller total volumes of necrosis than placing them 20 mm apart when anode lesions were significantly larger than cathode lesions (P< 0.05). Liver enzymes (aspartate aminotransferase, alanine aminotransferase) were significantly raised 1 day after treatment (P < 0.001) and predicted the total volume of hepatic necrosis (P < 0.001). Predictable and reproducible areas of liver necrosis are produced with electrolysis. If these results extrapolate to larger animal models, this technique has potential for patients with irresectable primary and secondary liver tumours.

Clozapine-induced acute gastrointestinal necrosis: a case report.

PubMed

Osterman, Mark T; Foley, Caitlin; Matthias, Isaac

2017-09-23

Clozapine is known to cause fecal impaction and ileus with resultant colonic necrosis due to compression of colonic mucosa. There are rare reports of clozapine causing necrosis of other portions of the gastrointestinal tract unrelated to constipation. We describe a case of acute necrosis of the upper gastrointestinal tract and small bowel to due to clozapine and quetiapine. A 66-year-old white man with a past medical history of schizophrenia, maintained on clozapine and quetiapine, presented with hypoxic respiratory failure caused by aspiration of feculent emesis due to impacted stool throughout his colon. His constipation resolved with discontinuation of clozapine and quetiapine, and his clinical condition improved. These medicines were restarted after 2 weeks, resulting in acute gastrointestinal necrosis from the mid esophagus through his entire small bowel. He died due to septic shock with Gram-negative rod bacteremia. Clozapine may cause acute gastrointestinal necrosis.

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.

Early excision and grafting, an alternative approach to the surgical management of large body surface area levamisole-adulterated cocaine induced skin necrosis.

PubMed

Miner, Jason; Gruber, Paul; Perry, Travis L

2015-05-01

Levamisole-adulterated cocaine as a cause of retiform purpura progressing to full-thickness skin necrosis was first documented in 2003 and currently comprises over 200 reported cases. Whereas, its presentation, pathophysiology, and diagnostic workup have been reasonably well-defined, only one publication has significantly detailed its surgical management. For this reason there exists a relative absence of data in comparison to its reported incidence to suggest a preferred treatment strategy. In the case mentioned, treatment emphasized delayed surgical intervention while awaiting lesion demarcation and the monitoring of autoantibodies. At our institution we offer an alternative approach and present the case of a 34 year old female who presented with 49% TBSA, levamisole-induced skin necrosis managed with early surgical excision and skin grafting. The patient presented three days following cocaine exposure with painful, purpura involving the ears, nose, buttocks, and bilateral lower extremities which quickly progressed to areas of full-thickness necrosis. Lab analysis demonstrated elevated p-ANCA and c-ANCA, as well as leukopenia, decreased C4 complement, and urinalysis positive for levamisole, corroborating the diagnosis. Contrasting the most thoroughly documented case in which the patient underwent first surgical excision on hospital day 36 and underwent 18 total excisions, our patient underwent first excision on hospital day 10 and received only one primary excision prior to definitive autografting. To our knowledge, this is the largest surface area surgically treated that did not result in surgical amputation or autoamputation of limbs or appendages, respectively. We contend that early excision and grafting provides optimal surgical management of this syndrome while avoiding the morbidity seen with delayed intervention. Published by Elsevier Ltd.

Position-dependent radiative transfer as a tool for studying Anderson localization: Delay time, time-reversal and coherent backscattering

NASA Astrophysics Data System (ADS)

van Tiggelen, B. A.; Skipetrov, S. E.; Page, J. H.

2017-05-01

Previous work has established that the localized regime of wave transport in open media is characterized by a position-dependent diffusion coefficient. In this work we study how the concept of position-dependent diffusion affects the delay time, the transverse confinement, the coherent backscattering, and the time reversal of waves. Definitions of energy transport velocity of localized waves are proposed. We start with a phenomenological model of radiative transfer and then present a novel perturbational approach based on the self-consistent theory of localization. The latter allows us to obtain results relevant for realistic experiments in disordered quasi-1D wave guides and 3D slabs.

Efficacy of Liposuction as a Delay Method for Improving Flap Survival.

PubMed

Orhan, Erkan; Erol, Yağmur Reyyan; Deren, Orgun; Altun, Serdar; Erdoğan, Bülent

2016-12-01

Flaps are often used in repairing tissue defects and partial or full flap loss is still an important morbidity cause. Several techniques have been tried to increase flap circulation but none of these could replace the delay technique. Our goal in this study is to show the efficacy of liposuction in delay of dorsal rat cutaneous flaps and improvement in flap survival. Twenty-four Wistar rats were used. The rats in group 1 received 9 × 3-sized caudally-based random pattern skin flaps. In group 2, liposuction was done under the tissue island spotted as the flap and after 14 days, standard flap surgery was done. In group 3, surgical delay was done and after 14 days, standard flap surgery was done. In group 4, liposuction was done under the tissue island spotted as the flap and standard flap surgery was done right after the liposuction. The rate of necrotic tissue in group 3 (surgical delay; mean % 13.7) was less than the rate in group 2 (liposuction delay; mean % 15.1), although the difference was not statistically significant. The necrosis rates in group 3 (surgical delay) and group 2 (liposuction delay) were less than the rates in both group 1 (only flap; mean % 41.5) and group 4 (liposuction flap; mean % 40.0) and this difference was statistically significant (p < 0.0001). Liposuction can be an alternative to surgical delay as a less invasive method in the clinic. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Histologic morphometry confirms a prophylactic effect for hyperbaric oxygen in the prevention of delayed radiation enteropathy.

PubMed

Feldmeier, J J; Davolt, D A; Court, W S; Onoda, J M; Alecu, R

1998-01-01

In a previous publication (Feldmeier et al., Radiother Oncol 1995; 35:138-144) we reported our success in preventing delayed radiation enteropathy in a murine model by the application of hyperbaric oxygen (HBO2). In this study we introduce a histologic morphometric technique for assessing fibrosis in the submucosa of these same animal specimens and relate this assay to the previous results. The histologic morphometry, like the previous gross morphometry and compliance assays, demonstrates a significant protective effect for HBO2. The present assay is related to the previous assays in a statistically significant fashion. The predictive value for the histologic morphometric assay demonstrates a sensitivity of 75% and a specificity of 62.5%. The applicability of this assay to other organ systems and its potential superiority to the compliance assay are discussed.

Acute Esophageal Necrosis: A Case Series

PubMed Central

Mavilia, Marianna G; Gurvits, Grigoriy E

2018-01-01

Acute esophageal necrosis (AEN) is a particularly rare syndrome with an incidence of only 0.1-0.28%, whose appearance is notable for proximal extensions of black, necrotic appearing mucosa extending proximally in the esophagus and abruptly interrupted at the gastroesophageal junction. In this case series, we explore the cases of two males: one middle-aged and one elderly, who after presenting with emesis, were found to have acute esophageal necrosis on esophagogastroduodenoscopy. PMID:29850386

Papillary Necrosis in Experimental Analgesic Nephropathy

PubMed Central

Saker, B. M.; Kincaid-Smith, Priscilla

1969-01-01

A proprietary aspirin, phenacetin, and caffeine preparation given to rats in a dose equivalent to that taken by patients with analgesic nephropathy produced papillary necrosis in 55%. There was a higher incidence in rats deprived of fluids overnight. Papillary necrosis was not noted in rats receiving twice as much phenacetin. These findings support the argument that phenacetin should not be singled out as the substance responsible for analgesic nephropathy in man. PMID:5762278

Virus inhibition of RIP3-dependent necrosis.

PubMed

Upton, Jason W; Kaiser, William J; Mocarski, Edward S

2010-04-22

Viral infection activates cytokine expression and triggers cell death, the modulation of which is important for successful pathogenesis. Necroptosis is a form of programmed necrosis dependent on two related RIP homotypic interaction motif (RHIM)-containing signaling adaptors, receptor-interacting protein kinases (RIP) 1 and 3. We find that murine cytomegalovirus infection induces RIP3-dependent necrosis. Whereas RIP3 kinase activity and RHIM-dependent interactions control virus-associated necrosis, virus-induced death proceeds independently of RIP1 and is therefore distinct from TNFalpha-dependent necroptosis. Viral M45-encoded inhibitor of RIP activation (vIRA) targets RIP3 during infection and disrupts RIP3-RIP1 interactions characteristic of TNFalpha-induced necroptosis, thereby suppressing both death pathways. Importantly, attenuation of vIRA mutant virus in wild-type mice is normalized in RIP3-deficient mice. Thus, vIRA function validates necrosis as central to host defense against viral infections and highlights the benefit of multiple virus-encoded cell-death suppressors that inhibit not only apoptotic, but also necrotic mechanisms of virus clearance. Copyright 2010 Elsevier Inc. All rights reserved.

Impact of an angiotensin analogue in treating thermal and combined radiation injuries

NASA Astrophysics Data System (ADS)

Jadhav, Sachin Suresh

Background: In recent years there has been a growing concern regarding the use of nuclear weapons by terrorists. Such incidents in the past have shown that radiation exposure is often accompanied by other forms of trauma such as burns, wounds or infection; leading to increased mortality rates among the affected individuals. This increased risk with combined radiation injury has been attributed to the delayed wound healing observed in this injury. The Renin-Angiotensin System (RAS) has emerged as a critical regulator of wound healing. Angiotensin II (A-II) and Angiotensin (1-7) [A(1-7)] have been shown to accelerate the rate of wound healing in different animal models of cutaneous injury. Nor-Leu3-Angiotensin (1-7) [Nor-Leu3-A (1-7)], an analogue of A(1-7), is more efficient than both A-II and A(1-7) in its ability to improve wound healing and is currently in phase III clinical trials for the treatment of diabetic foot ulcers. Aims: The three main goals of this study were to; 1) Develop a combined radiation and burn injury (CRBI) model and a radiation-induced cutaneous injury model to study the pathophysiological effects of these injuries on dermal wound healing; 2) To treat thermal and CRBI injuries using Nor-Leu 3-A (1-7) and decipher the mechanism of action of this peptide and 3) Develop an in-vitro model of CRBI using dermal cells in order to study the effect of CRBI on individual cell types involved in wound healing. Results: CRBI results in delayed and exacerbated apoptosis, necrosis and inflammation in injured skin as compared to thermal injury by itself. Radiation-induced cutaneous injury shows a radiation-dose dependent increase in inflammation as well as a chronic inflammatory response in the higher radiation exposure groups. Nor-Leu3-A (1-7) can mitigate thermal and CRBI injuries by reducing inflammation, oxidative stress and DNA damage while increasing the rate of proliferation of dermal stem cells and re-epithelialization of injured skin. The in

Acute Necrotizing Esophagitis Followed by Duodenal Necrosis

PubMed Central

del Hierro, Piedad Magdalena

2011-01-01

Acute Necrotizing Esophagitis is an uncommon pathology, characterized by endoscopic finding of diffuse black coloration in esophageal mucosa and histological presence of necrosis in patients with upper gastrointestinal bleeding. The first case of acute necrotizing esophagitis followed by duodenal necrosis, in 81 years old woman with a positive history of Type 2 Diabetes Mellitus, Hypertension, and usual intake of Nonsteroidal Anti-inflammatory drugs, is reported. Although its etiology remains unknown, the duodenal necrosis suggests that ischemia could be the main cause given that the branches off the celiac axis provide common blood supply to the distal esophageal and duodenal tissue. The massive gastroesophagic reflux and NSAID intake could be involved. PMID:27957030

Cardiolipin plays a role in KCN-induced necrosis.

PubMed

Tsesin, Natalia; Khalfin, Boris; Nathan, Ilana; Parola, Abraham H

2014-10-01

Cardiolipin (CL) is a unique anionic, dimeric phospholipid found almost exclusively in the inner mitochondrial membrane and is essential for the function of numerous enzymes that are involved in mitochondrial energy metabolism. While the role of cardiolipin in apoptosis is well established, its involvement in necrosis is enigmatic. In the present study, KCN-induced necrosis in U937 cells was used as an experimental model to assess the role of CL in necrosis. KCN addition to U937 cells induced reactive oxygen species (ROS) formation, while the antioxidants inhibited necrosis, indicating that ROS play a role in KCN-induced cell death. Further, CL oxidation was confirmed by the monomer green fluorescence of 10-N-nonyl acridine orange (NAO) and by TLC. Utilizing the red fluorescence of the dimeric NAO, redistribution of CL in mitochondrial membrane during necrosis was revealed. We also showed that the catalytic activity of purified adenosine triphosphate (ATP) synthase complex, known to be modulated by cardiolipin, decreased following KCN treatment. All these events occurred at an early phase of the necrotic process prior to rupture of the cell membrane. Furthermore, CL-deficient HeLa cells were found to be resistant to KCN-induced necrosis as compared with the wild type cells. We suggest that KCN, an effective reversible inhibitor of cytochrome oxidase and thereby of the respiratory chain leads to ROS increase, which in turn oxidizes CL (amongst other membrane phospholipids) and leads to mitochondrial membrane lipid reorganization and loss of CL symmetry. Finally, the resistance of CL-deficient cells to necrosis further supports the notion that CL, which undergoes oxidation during necrotic cell death, is an integral part of the milieu of events taking place in mitochondria leading to membrane disorganization and mitochondrial dysfunction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

AICAR induces AMPK-independent programmed necrosis in prostate cancer cells.

PubMed

Guo, Feng; Liu, Shuang-Qing; Gao, Xing-Hua; Zhang, Long-Yang

2016-05-27

AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, which induces cytotoxic effect to several cancer cells. Its potential activity in prostate cancer cells and the underlying signaling mechanisms have not been extensively studied. Here, we showed that AICAR primarily induced programmed necrosis, but not apoptosis, in prostate cancer cells (LNCaP, PC-3 and PC-82 lines). AICAR's cytotoxicity to prostate cancer cells was largely attenuated by the necrosis inhibitor necrostatin-1. Mitochondrial protein cyclophilin-D (CYPD) is required for AICAR-induced programmed necrosis. CYPD inhibitors (cyclosporin A and sanglifehrin A) as well as CYPD shRNAs dramatically attenuated AICAR-induced prostate cancer cell necrosis and cytotoxicity. Notably, AICAR-induced cell necrosis appeared independent of AMPK, yet requiring reactive oxygen species (ROS) production. ROS scavengers (N-acetylcysteine and MnTBAP), but not AMPKα shRNAs, largely inhibited prostate cancer cell necrosis and cytotoxicity by AICAR. In summary, the results of the present study demonstrate mechanistic evidences that AMPK-independent programmed necrosis contributes to AICAR's cytotoxicity in prostate cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute Cutaneous Necrosis: A Guide to Early Diagnosis and Treatment.

PubMed

Karimi, Karen; Odhav, Ashika; Kollipara, Ramya; Fike, Jesse; Stanford, Carol; Hall, John C

Acute cutaneous necrosis is characterised by a wide range of aetiologies and is associated with significant morbidity and mortality, warranting complex considerations in management. Early recognition is imperative in diagnosis and management of sudden gangrenous changes in the skin. This review discusses major causes of cutaneous necrosis, examines the need for early assessment, and integrates techniques related to diagnosis and management. The literature, available via PubMed, on acute cutaneous necrotic syndromes was reviewed to summarise causes and synthesise appropriate treatment strategies to create a clinician's guide in the early diagnosis and management of acute cutaneous necrosis. Highlighted in this article are key features associated with common causes of acute cutaneous necrosis: warfarin-induced skin necrosis, heparin-induced skin necrosis, calciphylaxis, pyoderma gangrenosum, embolic phenomena, purpura fulminans, brown recluse spider bite, necrotising fasciitis, ecthyma gangrenosum, antiphospholipid syndrome, hypergammaglobulinemia, and cryoglobulinemia. This review serves to increase recognition of these serious pathologies and complications, allowing for prompt diagnosis and swift limb- or life-saving management.

Optimization of a simultaneous dual-isotope 201Tl/123I-MIBG myocardial SPECT imaging protocol with a CZT camera for trigger zone assessment after myocardial infarction for routine clinical settings: Are delayed acquisition and scatter correction necessary?

PubMed

D'estanque, Emmanuel; Hedon, Christophe; Lattuca, Benoît; Bourdon, Aurélie; Benkiran, Meriem; Verd, Aurélie; Roubille, François; Mariano-Goulart, Denis

2017-08-01

Dual-isotope 201 Tl/ 123 I-MIBG SPECT can assess trigger zones (dysfunctions in the autonomic nervous system located in areas of viable myocardium) that are substrate for ventricular arrhythmias after STEMI. This study evaluated the necessity of delayed acquisition and scatter correction for dual-isotope 201 Tl/ 123 I-MIBG SPECT studies with a CZT camera to identify trigger zones after revascularization in patients with STEMI in routine clinical settings. Sixty-nine patients were prospectively enrolled after revascularization to undergo 201 Tl/ 123 I-MIBG SPECT using a CZT camera (Discovery NM 530c, GE). The first acquisition was a single thallium study (before MIBG administration); the second and the third were early and late dual-isotope studies. We compared the scatter-uncorrected and scatter-corrected (TEW method) thallium studies with the results of magnetic resonance imaging or transthoracic echography (reference standard) to diagnose myocardial necrosis. Summed rest scores (SRS) were significantly higher in the delayed MIBG studies than the early MIBG studies. SRS and necrosis surface were significantly higher in the delayed thallium studies with scatter correction than without scatter correction, leading to less trigger zone diagnosis for the scatter-corrected studies. Compared with the scatter-uncorrected studies, the late thallium scatter-corrected studies provided the best diagnostic values for myocardial necrosis assessment. Delayed acquisitions and scatter-corrected dual-isotope 201 Tl/ 123 I-MIBG SPECT acquisitions provide an improved evaluation of trigger zones in routine clinical settings after revascularization for STEMI.

Biomechanical comparisons between a new avascular necrosis of femaral head stem based on Chinese patients with avascular necrosis and two other designs.

PubMed

Zhang, Qiang; Cheng, Cheng-Kung; Wei, Hung-Wen; Dong, Xiang; Chen, Yi-Ting; Lai, Yu-Shu; Wang, Yan

2013-01-01

There is a relatively high failure rate of the femoral component in patients with avascular necrosis at the intermediate-term follow-up. Improving the geometrical fit of the femoral stem against the medullary canal may help to provide long-term survivorship of the hip replacement for patients with avascular necrosis. We designed a specific stem, based on morphometric studies of proximal femoral canals in Chinese avascular necrosis patients and evaluated the stem by finite element analyses, comparing the novel stem with two commercially available and commonly used stems. The morphometric data from avascular necrosis patients showed specific geometric differences in the proximal femoral canal, including profile curves in both the sagittal and coronary planes than the patients with femoral neck fracture. The shorter stemmed prostheses (Fitmore(®) and our stem) performed better than the longer stemmed prosthesis (VerSys(®)). This is the first study to investigate the femoral geometries of Chinese avascular necrosis patients. Our stem provides better stability and is theoretically beneficial to bone ingrowth, which may increase the long-term stability and fixation of the implant.

Subcutaneous fat necrosis of the newborn.

PubMed

Oswalt, G C; Montes, L F; Cassady, G

1978-08-01

Subcutaneous fat necrosis of the newborn (SFNN) developed in a 1-week-old black boy. His mother had received numerous medications for eclampsia. Birth was by Caesarean section and complicated by meconium aspiration. There were numerous nodules over the back, buttocks and extremities that yielded a caseous-like material. Microscopically, these nodules showed crystallization and necrosis of the fat. Hypoglycemia, pneumonia, oliguria, thrombocytopenia, seizures and urinary infection were associated with the cutaneous problem and led to a fatal outcome 2 weeks after birth.

Tunable Optical True-Time Delay Devices Would Exploit EIT

NASA Technical Reports Server (NTRS)

Kulikov, Igor; DiDomenico, Leo; Lee, Hwang

2004-01-01

Tunable optical true-time delay devices that would exploit electromagnetically induced transparency (EIT) have been proposed. Relative to prior true-time delay devices (for example, devices based on ferroelectric and ferromagnetic materials) and electronically controlled phase shifters, the proposed devices would offer much greater bandwidths. In a typical envisioned application, an optical pulse would be modulated with an ultra-wideband radio-frequency (RF) signal that would convey the information that one seeks to communicate, and it would be required to couple differently delayed replicas of the RF signal to the radiating elements of a phased-array antenna. One or more of the proposed devices would be used to impose the delays and/or generate the delayed replicas of the RF-modulated optical pulse. The beam radiated or received by the antenna would be steered by use of a microprocessor-based control system that would adjust operational parameters of the devices to tune the delays to the required values. EIT is a nonlinear quantum optical interference effect that enables the propagation of light through an initially opaque medium. A suitable medium must have, among other properties, three quantum states (see Figure 1): an excited state (state 3), an upper ground state (state 2), and a lower ground state (state 1). These three states must form a closed system that exhibits no decays to other states in the presence of either or both of two laser beams: (1) a probe beam having the wavelength corresponding to the photon energy equal to the energy difference between states 3 and 1; and (2) a coupling beam having the wavelength corresponding to the photon energy equal to the energy difference between states 3 and 2. The probe beam is the one that is pulsed and modulated with an RF signal.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Xin; Ou, Xiaomin; Xu, Tingting

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).more » 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.« less

A Case of Trapezium Avascular Necrosis Treated Conservatively.

PubMed

Petsatodis, Evangelos; Ditsios, Konstantinos; Konstantinou, Panagiotis; Pinto, Iosafat; Kostretzis, Lazaros; Theodoroudis, Ioannis; Pilavaki, Mayia

2017-01-01

Avascular necrosis (AVN) of the bones of the wrist most commonly involves the lunate followed by the proximal pole of the scaphoid and the capitate. Trapezium avascular necrosis is extremely rare with only two cases reported in the literature, both of which were treated surgically. In this article, we report a unique case of trapezium avascular necrosis treated conservatively. A 38-year-old man complaining of a 4-month history of mild pain on the base of his right thumb. MRI scan was performed. The clinical presentation and the imaging findings indicated avascular osteonecrosis of the trapezium. The patient was treated with immobilization of the wrist joint for a period of six weeks. Three months later, the patient was free of symptoms and the MRI scan revealed a normal trapezium. AVN of trapezium is extremely rare. Our case shows that immobilization of an early stage avascular necrosis of the trapezium might be a treatment option.

Diagnostic delay in Crohn's disease is associated with a complicated disease course and increased operation rate.

PubMed

Schoepfer, Alain M; Dehlavi, Mohamed-Ali; Fournier, Nicolas; Safroneeva, Ekaterina; Straumann, Alex; Pittet, Valérie; Peyrin-Biroulet, Laurent; Michetti, Pierre; Rogler, Gerhard; Vavricka, Stephan R

2013-11-01

The impact of diagnostic delay (a period from appearance of first symptoms to diagnosis) on the clinical course of Crohn's disease (CD) is unknown. We examined whether length of diagnostic delay affects disease outcomes. Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). The frequencies of occurrence of bowel stenoses, internal fistulas, perianal fistulas, and CD-related surgery (intestinal and perianal) were analyzed. A total of 905 CD patients (53.4% female, median age at diagnosis 26 (20-36) years) were stratified into four groups according to the quartiles of diagnostic delay (0-3, 4-9, 10-24, and ≥25 months, respectively). Median diagnostic delay was 9 (3-24) months. The frequency of immunomodulator and/or antitumor necrosis factor drug use did not differ among the four groups. The length of diagnostic delay was positively correlated with the occurrence of bowel stenosis (odds ratio (OR) 1.76, P=0.011 for delay of ≥25 months) and intestinal surgery (OR 1.76, P=0.014 for delay of 10-24 months and OR 2.03, P=0.003 for delay of ≥25 months). Disease duration was positively associated and non-ileal disease location was negatively associated with bowel stenosis (OR 1.07, P<0.001, and OR 0.41, P=0.005, respectively) and intestinal surgery (OR 1.14, P<0.001, and OR 0.23, P<0.001, respectively). The length of diagnostic delay is correlated with an increased risk of bowel stenosis and CD-related intestinal surgery. Efforts should be undertaken to shorten the diagnostic delay.

Tumor necrosis factor and interleukin 1 as mediators of endotoxin-induced beneficial effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urbaschek, R.; Urbaschek, B.

Bacterial lipopolysaccharides or endotoxins are known to induce tumor necrosis; enhanced nonspecific resistance to bacterial, viral, and parasitic infections and to radiation sickness; and tolerance to lethal doses of endotoxin. These beneficial effects are achieved by pretreatment with minute amounts of endotoxin. Recombinant tumor necrosis factor (TNF) and interleukin 1 (IL-1) are among the mediators capable of invoking radioprotection or resistance to the consequences of cecal ligation and puncture. Both cytokines are potent inducers of serum colony-stimulating factor (CSF) in C3H/HeJ mice (low responders to endotoxin). The number of splenic granulocyte-macrophage precursors was found to increase 5 days after injectionmore » of TNF in these mice. Although with IL-1 no increase in the number of granulocyte-macrophage colonies occurred in culture in the presence of serum CSF, a marked stimulation was observed when TNF was added. This stimulation of myelopoiesis observed in vivo and in vitro may be related to the radioprotective effect of TNF. The data presented suggest that TNF and IL-1 released after injection of endotoxin participate in the mediation of endotoxin-induced enhancement of nonspecific resistance and stimulation of hematopoiesis. 76 references.« less

Tumour necrosis factor α secretion induces protease activation and acinar cell necrosis in acute experimental pancreatitis in mice.

PubMed

Sendler, Matthias; Dummer, Annegret; Weiss, Frank U; Krüger, Burkhard; Wartmann, Thomas; Scharffetter-Kochanek, Karin; van Rooijen, Nico; Malla, Sudarshan Ravi; Aghdassi, Ali; Halangk, Walter; Lerch, Markus M; Mayerle, Julia

2013-03-01

Acute pancreatitis has long been considered a disorder of pancreatic self-digestion, in which intracellular activation of digestive proteases induces tissue injury. Chemokines, released from damaged pancreatic cells then attract inflammatory cells, whose systemic action ultimately determines the disease severity. In the present work the opposite mechanism is investigated; that is, whether and how inflammatory cells can activate intracellular proteases. Using mice either deficient for the CD18-α subunit of the membrane attack complex-1 (MAC-1) complex or tumour necrosis factor (TNF)α, as well as after depletion of leucocyte subpopulations, pancreatitis was induced by 7-hourly caerulein injections (50 μg/kg, intraperitoneally). Pancreatic acini were coincubated in vitro from wild-type and cathepsin-B-deficient animals with phorbol-12-myristate-13-acetate (PMA)-activated neutrophils and macrophages, caerulein or TNFα, and activities of trypsin, cathepsin-B and caspase-3 were measured, as well as necrosis using fluorogenic substrates. TNFα was inhibited with monospecific antibodies. Deletion of CD18 prevented transmigration of leucocytes into the pancreas during pancreatitis, greatly reduced disease severity and abolished digestive protease activation. Depletion of neutrophils and macrophages equally reduced premature trypsinogen activation and disease severity. In vitro activated neutrophils and macrophages directly induced premature protease activation and cell death in pancreatic acini and stimulation of acini with TNFα induced caspase-3 activation and necrosis via a cathepsin-B and calcium-dependent mechanism. Neutralising antibodies against TNFα and genetic deletion of TNFα prevented leucocyte-induced trypsin activity and necrosis in isolated acini. The soluble inflammatory cell mediator TNFα directly induces premature protease activation and necrosis in pancreatic acinar cells. This activation depends on calcium and cathepsin-B activity. The findings

Chronic radiation-induced dermatitis: challenges and solutions.

PubMed

Spałek, Mateusz

2016-01-01

Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients' quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF). RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and radiomics that allow scientists and clinicians to select patients who are at risk of the development of chronic radiation dermatitis. Novel treatment methods and clinical

Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils.

PubMed

Zhu, Xiang; Hogan, Simon P; Molkentin, Jeffery D; Zimmermann, Nives

2016-04-15

Eosinophil degranulation and clusters of free extracellular granules are frequently observed in diverse diseases, including atopic dermatitis, nasal polyposis, and eosinophilic esophagitis. Whether these intact granules are released by necrosis or a biochemically mediated cytolysis remains unknown. Recently, a peptidyl-prolyl isomerase located within the mitochondrial matrix, cyclophilin D (PPIF), was shown to regulate necrotic, but not apoptotic, cell death in vitro in fibroblasts, hepatocytes, and cardiomyocytes. Whether cyclophilin D regulates necrosis in hematopoietic cells such as eosinophils remains unknown. We used PPIF-deficient (Ppif(-/-)) mice to test whether cyclophilin D is required for regulating eosinophil necrosis. PPIF deficiency did not affect eosinophil development or maturation at baseline. After in vitro ionomycin or H2O2 treatment, Ppif(-/-) eosinophils were significantly protected from Ca(2+) overload- or oxidative stress-induced necrosis. Additionally, Ppif(-/-) eosinophils demonstrated significantly decreased necrosis, but not apoptosis, in response to Siglec-F cross-linking, a stimulus associated with eosinophil-mediated processes in vitro and in vivo. When treated with apoptosis inducers, Ppif(+/+) and Ppif(-/-) eosinophils exhibited no significant difference in apoptosis or secondary necrosis. Finally, in a dextran sodium sulfate-induced colitis model, although levels of colitogenic cytokines and eosinophil-selective chemokines were comparable between Ppif(+/+) and Ppif(-/-) mice, the latter exhibited decreased clinical outcomes. This correlated with significantly reduced eosinophil cytolysis in the colon. Collectively, our present studies demonstrate that murine eosinophil necrosis is regulated in vitro and in vivo by cyclophilin D, at least in part, thus providing new insight into the mechanism of eosinophil necrosis and release of free extracellular granules in eosinophil-associated diseases. Copyright © 2016 the American

Avascular necrosis of the trapezoid bone following carpometacarpal arthroplasty.

PubMed

Kane, Patrick; Waryasz, Greg; Katarincic, Julie

2014-03-03

A 58-year-old female developed avascular necrosis of her trapezoid approximately 3 months after undergoing carpometacarpal arthroplasty. The patient was treated conservatively with immobilization and had complete resolution of her clinical symptoms during her year of follow-up. Additionally, radiographic examination showed complete restoration of the height of her trapezoid approximately 1 year after the index procedure. Avascular necrosis of the trapezoid is extremely rare with very few cases described in the literature. This is the first description of avascular necrosis following carpometacarpal arthroplasty.

Is it better to include necrosis in apparent diffusion coefficient (ADC) measurements? The necrosis/wall ADC ratio to differentiate malignant and benign necrotic lung lesions: Preliminary results.

PubMed

Karaman, Adem; Durur-Subasi, Irmak; Alper, Fatih; Durur-Karakaya, Afak; Subasi, Mahmut; Akgun, Metin

2017-10-01

To determine whether the use of necrosis/wall apparent diffusion coefficient (ADC) ratios in the differentiation of necrotic lung lesions is more reliable than measuring the wall alone. In this retrospective study, a total of 76 patients (54 males and 22 females, 71% vs. 29%, with a mean age of 53 ± 18 years, range, 18-84) were enrolled, 33 of whom had lung carcinoma and 43 had a benign necrotic lung lesion. A 3T scanner was used. The calculation of the necrosis/wall ADC ratio was based on ADC values measured from necrosis and the wall of the lesions by diffusion-weighted imaging (DWI). Statistical analyses were performed with the independent samples t-test and receiver operating characteristic analysis. Intraobserver and interobserver reliability were calculated for ADC values of wall and necrosis. The mean necrosis/wall ADC ratio was 1.67 ± 0.23 for malignant lesions and 0.75 ± 0.19 for benign lung lesions (P < 0.001). To estimate malignancy the area under the curve (AUC) values for necrosis ADC, wall ADC, and the necrosis/wall ADC ratio were 0.720, 0.073, and 0.997, respectively. A wall/necrosis ADC ratio cutoff value of 1.12 demonstrated a 100% sensitivity and 98% specificity in the estimation of malignancy. Positive predictive value was 100%, and negative predictive value 98% and diagnostic accuracy 99%. There was a good intraobserver and interobserver reliability for wall and necrosis. The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating lung carcinoma from benign necrotic lung lesions than measuring the wall alone. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1001-1006. © 2017 International Society for Magnetic Resonance in Medicine.

Umbilical necrosis rates after abdominal-based microsurgical breast reconstruction.

PubMed

Ricci, Joseph A; Kamali, Parisa; Becherer, Babette E; Curiel, Daniel; Wu, Winona; Tobias, Adam M; Lin, Samuel J; Lee, Bernard T

2017-07-01

Umbilical stalk necrosis represents a rare, yet important complication after abdominal-based microsurgical breast reconstruction, which is both underrecognized and understudied in the literature. Once identified, umbilical reconstruction can be an extremely challenging problem. All consecutive breast free flaps at a single institution from February 2004 to February 2016 were reviewed, excluding non-abdominal-based flaps. Patients were divided based on the development of umbilical necrosis postoperatively. Demographics, surgical characteristics, and other complications were compared between the groups. A total of 918 patients met the inclusion criteria, with 29 developing umbilical necrosis identified (3.2%). Patients developing necrosis tended to be older (49.4 yrs versus 52.9 yrs; P < 0.01); have higher BMI (31.3 versus 27.8; P < 0.01); and were more likely to be smokers (27.5% versus 11.6%; P = 0.01). Umbilical necrosis was also associated with increased flap weight (830 g versus 656 g; P < 0.01), decreased time of perforator dissection (151 min versus 169 min; P = 0.02); bilateral cases (68.9% versus 44.7%; P < 0.01), and increased number of perforators per flap (2.5 versus 2.2; P = 0.03). There was no association with flap type (deep inferior epigastric perforator, superficial inferior epigastric artery, or free TRAM), diabetes, previous abdominal surgery, or use of preoperative imaging. Umbilical necrosis was not associated with any concomitant complications. Umbilical stalk necrosis was found to occur in 3.2% of patients and was associated with several preoperative comorbidities and intraoperative characteristics. This information should help influence intraoperative decision-making to prevent the development of this undesirable complication. Copyright © 2017 Elsevier Inc. All rights reserved.

Fat necrosis in autologous abdomen-based breast reconstruction: a systematic review.

PubMed

Khansa, Ibrahim; Momoh, Adeyiza O; Patel, Priti P; Nguyen, John T; Miller, Michael J; Lee, Bernard T

2013-03-01

Fat necrosis is a common and potentially exasperating complication of autologous breast reconstruction. The authors performed a systematic review of the English literature on autologous breast reconstruction to determine significant patient and surgical factors that are predictors of postoperative fat necrosis. A PubMed search using the terms "fat necrosis" and "breast reconstruction" was conducted. Articles were screened using predetermined inclusion and exclusion criteria. Data collected included patient characteristics, reconstructive techniques used, and the specific postoperative morbidity of interest. Patient cohorts were pooled, and the incidence of fat necrosis was calculated in the presence and absence of each risk factor. Chi-square analysis was applied, and p < 0.05 was considered statistically significant. Of 172 articles found, 70 met the inclusion criteria. The mean rate of fat necrosis was 11.3 percent. Deep inferior epigastric artery perforator flaps had the highest rate of fat necrosis (14.4 percent), followed by pedicled transverse rectus abdominis musculocutaneous (12.3 percent), superficial inferior epigastric artery (8.1 percent), and free transverse rectus abdominis musculocutaneous flaps (6.9 percent). Significant predictors of fat necrosis included obesity (p = 0.035), prereconstruction irradiation (p = 0.022), postreconstruction irradiation (p < 0.001), active smoking (p < 0.001), and abdominal scars (p = 0.05). Protective factors included supercharging (p < 0.001) and bilateral reconstruction (p = 0.01). Although there is little agreement in the literature regarding risk factors for fat necrosis, the authors were able to demonstrate several significant predictors by systematically analyzing 70 articles. Improved knowledge of the risk factors for fat necrosis can help surgeons provide improved preoperative counseling and take measures to minimize the risk of this complication.

Atraumatic Pantalar Avascular Necrosis in a Patient With Alcohol Dependence.

PubMed

Callachand, Fayaz; Milligan, David; Wilson, Alistair

2016-01-01

In the United States, an estimated 10,000 to 20,000 new cases of avascular necrosis are diagnosed each year. We present an unusual case of atraumatic avascular necrosis with widespread hindfoot and midfoot involvement. A 62-year-old female with a history of alcohol dependence and smoking, who had previously been treated for avascular necrosis of the knee, presented with right-sided foot pain and difficulty weightbearing. Imaging studies revealed extensive avascular necrosis of the hindfoot and midfoot, which precluded simple surgical intervention. The patient was followed up for 18 months. In the last 8 months of the 18-month period, the patient managed her symptoms using an ankle-foot orthosis. A diagnosis of avascular necrosis should be considered in patients with atraumatic foot and ankle pain, especially in the presence of risk factors such as alcohol excess and smoking. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

The recent progress of the mechanism and regulation of tumor necrosis in colorectal cancer.

PubMed

Zhang, Xi; Chen, Lirong

2016-02-01

In colorectal cancer (CRC), despite the complex inducing and regulating mechanism in necrosis progress, the prognostic value of tumor necrosis has been reported. It is generally recognized that necrosis is associated with many process involving severe hypoxia, inflammatory responses and angiogenesis, all of which contribute to promote tumor growth and poor prognosis. In addition to local hypoxia, regulation by RIP kinase and the conversion from apoptosis to necrosis can result in necrosis also. Recent studies showed necrosis can be a histopathologic characteristic for special molecular phenotype of CRC. A novel and attractive complementary treatment, tumor necrosis therapy, using radiolabelled compounds avid for necrosis has emerged. However, the complicated regulatory mechanisms of tumor necrosis were rarely reported in CRC, and we collected and reviewed these effect and relevance in CRC.

An intracellular matrix metalloproteinase-2 isoform induces tubular regulated necrosis: implications for acute kidney injury.

PubMed

Ceron, Carla S; Baligand, Celine; Joshi, Sunil; Wanga, Shaynah; Cowley, Patrick M; Walker, Joy P; Song, Sang Heon; Mahimkar, Rajeev; Baker, Anthony J; Raffai, Robert L; Wang, Zhen J; Lovett, David H

2017-06-01

Acute kidney injury (AKI) causes severe morbidity, mortality, and chronic kidney disease (CKD). Mortality is particularly marked in the elderly and with preexisting CKD. Oxidative stress is a common theme in models of AKI induced by ischemia-reperfusion (I-R) injury. We recently characterized an intracellular isoform of matrix metalloproteinase-2 (MMP-2) induced by oxidative stress-mediated activation of an alternate promoter in the first intron of the MMP-2 gene. This generates an NH 2 -terminal truncated MMP-2 (NTT-MMP-2) isoform that is intracellular and associated with mitochondria. The NTT-MMP-2 isoform is expressed in kidneys of 14-mo-old mice and in a mouse model of coronary atherosclerosis and heart failure with CKD. We recently determined that NTT-MMP-2 is induced in human renal transplants with delayed graft function and correlated with tubular cell necrosis. To determine mechanism(s) of action, we generated proximal tubule cell-specific NTT-MMP-2 transgenic mice. Although morphologically normal at the light microscopic level at 4 mo, ultrastructural studies revealed foci of tubular epithelial cell necrosis, the mitochondrial permeability transition, and mitophagy. To determine whether NTT-MMP-2 expression enhances sensitivity to I-R injury, we performed unilateral I-R to induce mild tubular injury in wild-type mice. In contrast, expression of the NTT-MMP-2 isoform resulted in a dramatic increase in tubular cell necrosis, inflammation, and fibrosis. NTT-MMP-2 mice had enhanced expression of innate immunity genes and release of danger-associated molecular pattern molecules. We conclude that NTT-MMP-2 "primes" the kidney to enhanced susceptibility to I-R injury via induction of mitochondrial dysfunction. NTT-MMP-2 may be a novel AKI treatment target.

Endothelial necrosis at 1h post-burn predicts progression of tissue injury

PubMed Central

Hirth, Douglas; McClain, Steve A.; Singer, Adam J.; Clark, Richard A.F.

2013-01-01

Burn injury progression has not been well characterized at the cellular level. To define burn injury progression in terms of cell death, histopathologic spatiotemporal relationships of cellular necrosis and apoptosis were investigated in a validated porcine model of vertical burn injury progression. Cell necrosis was identified by High Mobility Group Box 1 protein and apoptosis by Caspase 3a staining of tissue samples taken 1h, 24h and 7 days post-burn. Level of endothelial cell necrosis at 1h was predictive of level of apoptosis at 24h (Pearson's r=0.87) and of level of tissue necrosis at 7 days (Pearson's r=0.87). Furthermore, endothelial cell necrosis was deeper than interstitial cell necrosis at 1h (p<0.001). Endothelial cell necrosis at 1h divided the zone of injury progression (Jackson's zone of stasis) into an upper subzone with necrotic endothelial cells and initially viable adnexal and interstitial cells at 1h that progressed to necrosis by 24h, and a lower zone with initially viable endothelial cells at 1h, but necrosis and apoptosis of all cell types by 24h. Importantly, this spatiotemporal series of events and rapid progression resembles myocardial infarction and stroke, and implicates mechanisms of these injuries, ischemia, ischemia reperfusion, and programmed cell death, in burn progression. PMID:23627744

The Extracellular Matrix Regulates Granuloma Necrosis in Tuberculosis.

PubMed

Al Shammari, Basim; Shiomi, Takayuki; Tezera, Liku; Bielecka, Magdalena K; Workman, Victoria; Sathyamoorthy, Tarangini; Mauri, Francesco; Jayasinghe, Suwan N; Robertson, Brian D; D'Armiento, Jeanine; Friedland, Jon S; Elkington, Paul T

2015-08-01

A central tenet of tuberculosis pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism of tuberculosis pathology and demonstrate that collagen destruction may be a critical initial event, causing caseous necrosis as opposed to resulting from it. In human tuberculosis granulomas, regions of extracellular matrix destruction map to areas of caseous necrosis. In mice, transgenic expression of human matrix metalloproteinase 1 causes caseous necrosis, the pathological hallmark of human tuberculosis. Collagen destruction is the principal pathological difference between humanised mice and wild-type mice with tuberculosis, whereas the release of proinflammatory cytokines does not differ, demonstrating that collagen breakdown may lead to cell death and caseation. To investigate this hypothesis, we developed a 3-dimensional cell culture model of tuberculosis granuloma formation, using bioelectrospray technology. Collagen improved survival of Mycobacterium tuberculosis-infected cells analyzed on the basis of a lactate dehydrogenase release assay, propidium iodide staining, and measurement of the total number of viable cells. Taken together, these findings suggest that collagen destruction is an initial event in tuberculosis immunopathology, leading to caseous necrosis and compromising the immune response, revealing a previously unappreciated role for the extracellular matrix in regulating the host-pathogen interaction. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

PubMed

Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

2018-01-20

The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

[Skin necrosis during long-term fluindione treatment revealing protein C deficiency].

PubMed

Merklen-Djafri, C; Mazurier, I; Samama, M-M; Alhenc-Gelas, M; Tortel, M-C; Cribier, B; Roth, B; Batard, M-L

2012-03-01

Cutaneous necrosis is a rare complication of vitamin K antagonist therapy. It presents as cutaneous hemorrhagic necrosis and usually occurs at the start of treatment. We describe an atypical case of recurrent skin necrosis after two years of treatment with fluindione. A 70-year old woman with a history of venous thromboembolism and obesity presented with a large haemorrhagic necrosis of the abdominal wall. She had been treated with fluindione for two years. Genetic protein C deficiency was discovered. Resumption of vitamin K antagonist therapy was followed by recurrence of skin necrosis despite concomitant administration of heparin. Treatment with vitamin K antagonists could not be continued. This observation is unusual due to the late onset of skin necrosis. The condition usually begins shortly after initiation of vitamin K antagonist therapy, generally between the third and the sixth day of treatment. It is due to a transient hypercoagulable state in patients with protein C deficiency or, in rare cases, protein S deficiency. This late-onset skin necrosis, occurring many years after initiation of anticoagulant therapy, may be explained by a sudden worsening of pre-existing protein C deficiency due to infectious and iatrogenic factors. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Fueling the Flames: Mammalian Programmed Necrosis in Inflammatory Diseases

PubMed Central

Chan, Francis Ka-Ming

2012-01-01

Programmed necrosis or necroptosis is an inflammatory form of cell death driven by TNF-like death cytokines, toll-like receptors, and antigen receptors. Unlike necrosis induced by physical trauma, a dedicated pathway is involved in programmed necrosis. In particular, a kinase complex composed of the receptor interacting protein kinase 1 (RIPK1) and RIPK3 is a central step in necrotic cell death. Assembly and activation of this RIPK1–RIPK3 “necrosome” is critically controlled by protein ubiquitination, phosphorylation, and caspase-mediated cleavage events. The molecular signals cumulate in formation of intracellular vacuoles, organelle swelling, internal membrane leakage, and eventually plasma membrane rupture. These morphological changes can result in spillage of intracellular adjuvants to promote inflammation and further exacerbate tissue injury. Because of the inflammatory nature of necrosis, it is an attractive pathway for therapeutic intervention in acute inflammatory diseases. PMID:23125016

Computed Tomography Evaluation of Esophagogastric Necrosis After Caustic Ingestion.

PubMed

Chirica, Mircea; Resche-Rigon, Matthieu; Zagdanski, Anne Marie; Bruzzi, Matthieu; Bouda, Damien; Roland, Eric; Sabatier, François; Bouhidel, Fatiha; Bonnet, Francine; Munoz-Bongrand, Nicolas; Marc Gornet, Jean; Sarfati, Emile; Cattan, Pierre

2016-07-01

Endoscopy is the standard of care for emergency patient evaluation after caustic ingestion. However, the inaccuracy of endoscopy in determining the depth of intramural necrosis may lead to inappropriate decision-making with devastating consequences. Our aim was to evaluate the use of computed tomography (CT) for the emergency diagnostic workup of patients with caustic injuries. In a prospective study, we used a combined endoscopy-CT decision-making algorithm. The primary outcome was pathology-confirmed digestive necrosis. The respective utility of CT and endoscopy in the decision-making process were compared. Transmural endoscopic necrosis was defined as grade 3b injuries; signs of transmural CT necrosis included absence of postcontrast gastric/ esophageal-wall enhancement, esophageal-wall blurring, and periesophageal-fat blurring. We included 120 patients (59 men, median age 44 years). Emergency surgery was performed in 24 patients (20%) and digestive resection was completed in 16. Three patients (3%) died and 28 patients (23%) experienced complications. Pathology revealed transmural necrosis in 9/11 esophagectomy and 16/16 gastrectomy specimens. Severe oropharyngeal injuries (P = 0.015), increased levels of blood lactate (P = 0.007), alanine aminotransferase (P = 0.027), bilirubin (P = 0.005), and low platelet counts (P > 0.0001) were predictive of digestive necrosis. Decision-making relying on CT alone or on a combined CT-endoscopy algorithm was similar and would have spared 19 unnecessary esophagectomies and 16 explorative laparotomies compared with an endoscopy-alone algorithm. Endoscopy did never rectify a wrong CT decision. Emergency decision-making after caustic injuries can rely on CT alone.

Practical quantification of necrosis in histological whole-slide images.

PubMed

Homeyer, André; Schenk, Andrea; Arlt, Janine; Dahmen, Uta; Dirsch, Olaf; Hahn, Horst K

2013-06-01

Since the histological quantification of necrosis is a common task in medical research and practice, we evaluate different image analysis methods for quantifying necrosis in whole-slide images. In a practical usage scenario, we assess the impact of different classification algorithms and feature sets on both accuracy and computation time. We show how a well-chosen combination of multiresolution features and an efficient postprocessing step enables the accurate quantification necrosis in gigapixel images in less than a minute. The results are general enough to be applied to other areas of histological image analysis as well. Copyright © 2013 Elsevier Ltd. All rights reserved.

Take my breath away: necrosis in kidney transplants kills the lungs!

PubMed

Vanden Berghe, Tom; Linkermann, Andreas

2015-04-01

Necrosis is not only a regulated process, it is an interconnected molecular network allowing different genetically encoded forms that are more or less immunogenic. Zhao et al. elegantly illustrate this concept, underscore the need for combination therapy to successfully interfere with regulated necrosis, and identify the role of regulated necrosis in the pathophysiology of remote lung injury.

Can Vascular Patterns on Preoperative Magnetic Resonance Imaging Help Predict Skin Necrosis after Nipple-Sparing Mastectomy?

PubMed

Bahl, Manisha; Pien, Irene J; Buretta, Kate J; Hwang, E Shelley; Greenup, Rachel A; Ghate, Sujata V; Hollenbeck, Scott T

2016-08-01

Nipple-areola complex (NAC) and skin flap ischemia and necrosis can occur after nipple-sparing mastectomy (NSM). The purpose of this study was to correlate vascular findings on MRI with outcomes in patients who underwent NSM. Female patients at a single institution who underwent NSM and had a preoperative breast MRI between 2010 and 2014 were identified. Medical records were reviewed for patient demographics, surgical factors, and complications. Magnetic resonance images were reviewed by 2 radiologists, blinded to outcomes, for the presence of dual vs single blood supply to the breast. The association between blood supply on MRI with ischemic and necrotic complications after NSM was analyzed. One hundred and sixty-four NSM procedures were performed in 105 patients (mean age 45.5 years, range 25 to 69 years) who had a preoperative MRI. The majority of procedures were performed for malignancy (89 of 164 [54.3%]) or prophylaxis (73 of 164 [44.5%]). Nipple-areola complex or skin flap ischemia or necrosis occurred in 40 (24.4%) breasts. Ischemia or necrosis after NSM was less likely to occur in breasts with dual compared with single blood supply (20.8% vs 38.2%; p = 0.03). There was no association between surgical complications and age, BMI, smoking history, previous radiation therapy, indication for NSM, surgical specimen weight, surgical incision type, reconstruction approach, or operating surgeon on univariate analysis. Preoperative MRI characterization of breast vascularity can be considered when planning NSM. The presence of a dual blood supply to the breast on MRI is associated with a decreased risk of nipple-areola complex and skin flap ischemia and necrosis after NSM. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Outcomes of Fat-Augmented Latissimus Dorsi (FALD) Flap Versus Implant-Based Latissimus Dorsi Flap for Delayed Post-radiation Breast Reconstruction.

PubMed

Demiri, Efterpi C; Dionyssiou, Dimitrios D; Tsimponis, Antonios; Goula, Christina-Olga; Pavlidis, Leonidas C; Spyropoulou, Georgia-Alexandra

2018-06-01

Although free abdominal flaps constitute the gold standard in post-radiation delayed breast reconstruction, latissimus dorsi-based methods offer alternative reconstructive options. This retrospective study aims to compare outcomes of delayed breast reconstruction using the fat-augmented latissimus dorsi (FALD) autologous reconstruction and the latissimus dorsi-plus-implant reconstruction in irradiated women. We reviewed the files of 47 post-mastectomy irradiated patients (aged 29-73 years), who underwent delayed latissimus dorsi-based breast reconstruction between 2010 and 2016. Twenty-three patients (Group A) had an extended FALD flap and twenty-four patients (Group B) an implant-based latissimus dorsi reconstruction. Patients' age, BMI, pregnancies, volume of injected fat, implant size, postoperative complications, and secondary surgical procedures were recorded and analyzed. Age, BMI, pregnancies, and donor-site complications were similar in both groups (p > 0.05). Mean fat volume injected initially was 254 cc (ranged 130-380 cc/session); mean implant volume was 323 cc (ranged 225-420 cc). Breast complications were significantly fewer in Group A (one wound dehiscence, two oily cysts) compared to Group B (three cases with wound dehiscence, two extrusions, thirteen severe capsular contractions). Non-statistically significant difference was documented for secondary procedures between groups; although the mean number of additional surgeries/patient was higher in Group A, they referred to secondary lipofilling, whereas in Group B they were revision surgeries for complications. The FALD flap constitutes an alternative method for delayed autologous reconstruction after post-mastectomy irradiation, avoiding implant-related complications. Although additional fat graft sessions might be required, it provides an ideal autogenous reconstructive option for thin nulliparous women, with a small opposite breast and adequate fat donor sites. This journal requires that

JNK1 and JNK3 play a significant role in both neuronal apoptosis and necrosis. Evaluation based on in vitro approach using tert-butylhydroperoxide induced oxidative stress in neuro-2A cells and perturbation through 3-aminobenzamide.

PubMed

Muthaiah, Vijaya Prakash Krishnan; Michael, Felicia Mary; Palaniappan, Tamilselvi; Rajan, Sridhar Skylab; Chandrasekar, Kirubhanand; Venkatachalam, Sankar

2017-06-01

In spinal cord injury (SCI), oxidative stress in the penumbra of the injury site is a characteristic feature. The predominance of necrosis over apoptosis in the ensuing delayed cell death results in progressive waves of necrosis affecting neighboring cells and thus exaggerates the severity of the lesion. Necrosis has been classified into subtypes based on the active molecular players and parthanatos is one among them, which is characterized by the over activation of PARP1 as the pre-mitochondrial event that triggers necrosis. Parthanatos being the necrosis mode reported in SCI, we intended to study the molecular players in the elusive pre-mitochondrial events of PARP1 over activation using an in vitro model. tert-Butylhydroperoxide (tBuOOH) was reported to induce oxidative stress in various cell types including Neuro-2A cells. Using a tailored protocol, a predominantly PARP1 mediated necrotic mode of cell death was obtained in Neuro-2A cells using tBuOOH. By perturbing the progress of necrosis using 3-amniobenzamide, a known PARP1 inhibitor, it was found that JNK1 and JNK3 but not JNK2 were involved in pre-mitochondrial stages of PARP1 mediated cell death. Given that JNK1 and JNK3 play a role in apoptosis also, they may serve as common targets to counter both apoptosis and necrosis. The in vitro model used in the present study may be useful in delineating molecular mechanisms in necrosis. Copyright © 2017 Elsevier B.V. All rights reserved.

77 FR 41417 - Regulatory Science Considerations for Medical Countermeasure Radiation Biodosimetry Devices

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... irradiation scenarios? F. How should the impact of delays in sampling, delays in testing, combined injury, and... biodosimeter for use in a mass exposure scenario, the development of proper radiation biodosimetry tools is a... clinical animal model testing might be necessary to demonstrate radiation biodosimeter performance? D...

Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.

PubMed

Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

2015-11-01

The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p < 0.01 vs. non-irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

RADIATION WAVE DETECTION

DOEpatents

Wouters, L.F.

1960-08-30

Radiation waves can be detected by simultaneously measuring radiation- wave intensities at a plurality of space-distributed points and producing therefrom a plot of the wave intensity as a function of time. To this end. a detector system is provided which includes a plurality of nuclear radiation intensity detectors spaced at equal radial increments of distance from a source of nuclear radiation. Means are provided to simultaneously sensitize the detectors at the instant a wave of radiation traverses their positions. the detectors producing electrical pulses indicative of wave intensity. The system further includes means for delaying the pulses from the detectors by amounts proportional to the distance of the detectors from the source to provide an indication of radiation-wave intensity as a function of time.

Immunological mechanism of low-dose priming radiation resistance in walker-256 tumor model mice

PubMed Central

Feng, Li; Qin, Ling; Guo, Dan; Deng, Daping; Lu, Feng; Li, Hailiang; Bao, Narisu; Yang, Xiting; Ding, Hongyu; Li, Jianguo

2017-01-01

The aim of the present study was to investigate whether low-dose priming radiation induces antitumor immunity that can be augmented by the modulation of natural killer (NK) cell and cytokine activity using a mouse tumor model. Walker-256 cells were injected into the right flank of male BALB/c mice. At 7 days after inoculation, mice were divided into three groups, including group 1,2,3. In group 1 the mice were without radiation, in group 2 the mice were received 2 Gy radiation only, and in group 3 the mice were radiated with a priming dose of 75 mGy followed by 2 Gy radiation after 24 h. On day 21 following the radiation, the tumors were removed and the tumor index (tumor weight as a percentage of body weight) was calculated. At 1, 7, 14 and 21 days following the 2 Gy radiation, mouse splenocytes were isolated to analyze the NK activity and measure the production of the cytokines interleukin-1β, interferon-γ and tumor necrosis factor-α by ELISA. Apoptosis was also measured by flow cytometry. The results demonstrated that priming radiation significantly delayed the tumor growth and prolonged the median survival time to 38 days compared with the 31-day survival in the 2 Gy radiation group. The percentage of apoptotic cells was significantly higher in the mice that received 75 mGy + 2 Gy radiation compared with that in the mice that received 2 Gy alone; by contrast, mice that were not irradiated exhibited a relatively low level of apoptosis. The primed mice had a higher level of NK activity as compared with the mice exposed to 2 Gy radiation only or mice that were not irradiated. Furthermore, cytokine expression remained at a higher level in mice receiving priming dose of radiation compared that in the mice receiving only 2 Gy radiation. In conclusion, the results indicated that low-dose priming X-ray radiation may enhance the NK activity and the levels of cytokines, and that the immune response serves an important role in anticancer therapy, including radiotherapy

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.

Genetics Home Reference: tumor necrosis factor receptor-associated periodic syndrome

MedlinePlus

... Email Facebook Twitter Home Health Conditions TRAPS Tumor necrosis factor receptor-associated periodic syndrome Printable PDF Open ... to view the expand/collapse boxes. Description Tumor necrosis factor receptor-associated periodic syndrome (commonly known as ...

Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Introduction: Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe in-jury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. The Syndrome clinical picture depends on a type, timing, and the doses of radiation. Four grades of the CvARS were defined: mild, moderate, severe, and extremely severe. Also, four stages of CvARS were developed: prodromal, latent, manifest, outcome -death. Duration of stages depends on the types, doses, and time of radiation. The CvARS clinical symptoms are: respiratory distress, hypotension, cerebral edema, severe disorder of cerebral blood microcirculation, and acute motor weakness. The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. Intracerebral hemorrhage can be a consequence of the damage of endothelial cells caused by radiation and the radiation tox-ins. Disruption of blood-brain barrier (BBB)and blood-cerebrospinal fluid barrier (BCFB)is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia. Dam-age of the pyramidal cells in layers 3 and 5 and Purkinje cell layer the cerebral cortex , damage of pyramidal cells in the hippocampus occur as a result of cerebral ischemia and intracerebral bleeding. Methods: Radiation Toxins of CV ARS are defined as glycoproteins with the molec-ular weight of RT toxins ranges from 200-250 kDa and with high enzymatic activity

Pancreatic Necrosis and Gas in the Retroperitoneum: Treatment with Antibiotics Alone.

PubMed

Rasslan, Roberto; da Costa Ferreira Novo, Fernando; Rocha, Marcelo Cristiano; Bitran, Alberto; de Souza Rocha, Manoel; de Oliveira Bernini, Celso; Rasslan, Samir; Utiyama, Edivaldo Massazo

2017-02-01

To present our experience in the management of patients with infected pancreatic necrosis without drainage. The records of patients with pancreatic necrosis admitted to our facility from 2011 to 2015 were retrospectively reviewed. We identified 61 patients with pancreatic necrosis. Six patients with pancreatic necrosis and gas in the retroperitoneum were treated exclusively with clinical support without any type of drainage. Only 2 patients had an APACHE II score >8. The first computed tomography scan revealed the presence of gas in 5 patients. The Balthazar computed tomography severity index score was >9 in 5 of the 6 patients. All patients were treated with antibiotics for at least 3 weeks. Blood cultures were positive in only 2 patients. Parenteral nutrition was not used in these patients. The length of hospital stay exceeded three weeks for 5 patients; 3 patients had to be readmitted. A cholecystectomy was performed after necrosis was completely resolved; pancreatitis recurred in 2 patients before the operation. No patients died. In selected patients, infected pancreatic necrosis (gas in the retroperitoneum) can be treated without percutaneous drainage or any additional surgical intervention. Intervention procedures should be performed for patients who exhibit clinical and laboratory deterioration.

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ionizing radiation and cell cycle progression in ataxia telangiectasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beamish, H.; Khanna, K.K.; Lavin, M.F.

1994-04-01

Exposure of mammalian cells to ionizing radiation causes delay in normal progress through the cell cycle at a number of different checkpoints. Abnormalities in these checkpoints have been described for ataxia telangiectasia cells after irradiation. In this report we show that these abnormalities occur at different phases in the cell cycle in several ataxia telangiectasia lymphoblastoid cells. Ataxia telangiectasia cells, synchronized in late G{sub 1} phase with either mimosine or aphidicolin and exposed to radiation, showed a reduced delay in entering S phase compared to irradiated control cells. Failure to exhibit G{sub 1}-phase delay in ataxia telangiectasia cells is accompaniedmore » by a reduced ability of radiation to activate the product of the tumor suppressor gene p53, a protein involved in G{sub 1}/S-phase delay. When the progress of irradiated G{sub 1}-phase cells was followed into the subsequent G{sub 2} and G{sub 1} phases ataxia telangiectasia cells showed a more pronounced accumulation in G{sub 2} phase than control cells. When cells were irradiated in S phase and extent of delay was more evident in G{sub 2} phase and ataxia telangiectasia cells were delayed to a greater extent. These results suggest that the lack of initial delay in both G{sub 1} and S phases to the radiosensitivity observed in this syndrome. 26 refs., 3 figs., 2 tabs.« less

Gastric Necrosis due to Acute Massive Gastric Dilatation.

PubMed

Aydin, Ibrahim; Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

2013-01-01

Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature.

Gastric Necrosis due to Acute Massive Gastric Dilatation

PubMed Central

Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

2013-01-01

Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature. PMID:23983714

Widespread Skin Necrosis Secondary to Gemcitabine Therapy.

PubMed

Zito, Patrick M; Gonzalez, Adrianna M; Fox, Joshua D; Cronin, Megan; Mackrides, Nicholas; Kirsner, Robert S; Nichols, Anna J

2018-05-01

Gemcitabine, a pyrimidine nucleoside analogue, is an oncologic agent used in the treatment of cutaneous T-cell lymphoma (CTCL). Common dermatologic reactions associated with gemcitabine include alopecia, mild skin rash, and mucositis but skin necrosis is exceptional. Herein we present an unusual case of widespread skin necrosis mimicking toxic epidermal necrolysis in a 45-year-old woman receiving gemcitabine therapy for stage IIIA cutaneous T-cell lymphoma. This is the first reported case of a TEN-like reaction subsequent to gemcitabine treatment. J Drugs Dermatol. 2018;17(5):582-585.

First-aid with warm water delays burn progression and increases skin survival.

PubMed

Tobalem, M; Harder, Y; Tschanz, E; Speidel, V; Pittet-Cuénod, B; Wettstein, R

2013-02-01

First aid treatment for thermal injuries with cold water removes heat and decreases inflammation. However, perfusion in the ischemic zone surrounding the coagulated core can be compromised by cold-induced vasoconstriction and favor burn progression. The aim of this study is to evaluate the effect of local warming on burn progression in the rat comb burn model. 24 male Wistar rats were randomly assigned to either no treatment (control) or application of cold (17 °C) or warm (37 °C) water applied for 20 min. Evolution of burn depth, interspace necrosis, and microcirculatory perfusion were assessed with histology, planimetry, respectively with Laser Doppler flowmetry after 1 h, as well as 1, 4, and 7 days. Consistent conversion from a superficial to a deep dermal burn within 24 h was obtained in control animals. Warm and cold water significantly delayed burn depth progression, however after 4 days the burn depth was similar in all groups. Interspace necrosis was significantly reduced by warm water treatment (62±4% vs. 69±5% (cold water) and 82±3% (control); p<0.05). This was attributed to the significantly improved perfusion after warming, which was present 1 h after burn induction and was maintained thereafter (103±4% of baseline vs. 91±3% for cold water and 80±2% for control, p<0.05). In order to limit damage after burn injury, burn progression has to be prevented. Besides delaying burn progression, the application of warm water provided an additional benefit by improving the microcirculatory perfusion, which translated into increased tissue survival. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

PubMed

Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

2011-03-01

The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.

Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

PubMed

Bahia, Malkeet S; Silakari, Om

2010-05-01

Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

Intraperitoneal administration of chitosan/DsiRNA nanoparticles targeting TNFα prevents radiation-induced fibrosis.

PubMed

Nawroth, Isabel; Alsner, Jan; Behlke, Mark A; Besenbacher, Flemming; Overgaard, Jens; Howard, Kenneth A; Kjems, Jørgen

2010-10-01

One of the most common and dose-limiting long-term adverse effects of radiation therapy is radiation-induced fibrosis (RIF), which is characterized by restricted tissue flexibility, reduced compliance or strictures, pain and in severe cases, ulceration and necrosis. Several strategies have been proposed to ameliorate RIF but presently no effective one is available. Recent studies have reported that tumor necrosis factor-α (TNFα) plays a role in fibrogenesis. Male CDF1 mice were radiated with a single dose of 45 Gy. Chitosan/DsiRNA nanoparticles targeting TNFα were intraperitoneal injected and late radiation-induced fibrosis (RIF) was assessed using a modification of the leg contracture model. Additionally, the effect of these nanoparticles on tumor growth and tumor control probability in the absence of radiation was examined in a C3H mammary carcinoma model. We show in this work, that targeting TNFα in macrophages by intraperitoneal administration of chitosan/DsiRNA nanoparticles completely prevented radiation-induced fibrosis in CDF1 mice without revealing any cytotoxic side-effects after a long-term administration. Furthermore, such TNFα targeting was selective without any significant influence on tumor growth or irradiation-related tumor control probability. This nanoparticle-based RNAi approach represents a novel approach to prevent RIF with potential application to improve clinical radiation therapeutic strategies. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Pancreatic necrosis in New World camelids: 11 cases (1990-1998).

PubMed

Pearson, E G; Snyder, S P

2000-07-15

To determine clinical, clinicopathologic, and postmortem abnormalities in New World camelids with pancreatic necrosis. Retrospective study. 10 llamas and 1 alpaca. Medical records of animals in which a diagnosis of pancreatic necrosis had been made on the basis of histologic examination of necropsy specimens or on the basis of clinical signs and results of clinicopathologic testing were reviewed. The initial owner complaint varied, and various other conditions were diagnosed. Clinical and clinicopathologic abnormalities were vague. Amylase activity was higher in abdominal fluid than in serum in 5 of 7 animals, and lipase activity was higher in abdominal fluid than in serum in all 7. Four animals survived, and 7 died or were euthanatized. Only 1 of the animals that died had marked inflammation of the pancreatic parenchyma. All 7 had necrosis and saponification of fat in and surrounding the pancreas. Results suggest that pancreatic necrosis may develop in New World camelids, but clinical signs are vague, and the condition may easily be confused with other diseases. The only laboratory test that appeared to be helpful in the antemortem diagnosis of pancreatic necrosis was comparison of amylase and lipase activities in abdominal fluid and serum.

An Overview of Pathways of Regulated Necrosis in Acute Kidney Injury.

PubMed

Kers, Jesper; Leemans, Jaklien C; Linkermann, Andreas

2016-05-01

Necrosis is the predominant form of regulated cell death in acute kidney injury (AKI) and represents results in the formation of casts that appear in the urine sedimentation, referred to as muddy brown casts, which are part of the diagnosis of AKI. Pathologists referred to this typical feature as acute tubular necrosis. We are only beginning to understand the dynamics and the molecular pathways that underlie such typical necrotic morphology. In this review, we provide an overview of candidate pathways and summarize the emerging evidence for the relative contribution of these pathways of regulated necrosis, such as necroptosis, ferroptosis, mitochondrial permeability transition-mediated regulated necrosis, parthanatos, and pyroptosis. Inhibitors of each of these pathways are available, and clinical trials may be started after the detection of the most promising drug targets, which will be discussed here. With the global burden of AKI in mind, inhibitiors of regulated necrosis represent promising means to prevent this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog.

PubMed

Nuttall, T J; Burrow, R; Fraser, I; Kipar, A

2005-05-01

An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition.

Bacteria-induced phagocyte secondary necrosis as a pathogenicity mechanism.

PubMed

Silva, Manuel T

2010-11-01

Triggering of phagocyte apoptosis is a major virulence mechanism used by some successful bacterial pathogens. A central issue in the apoptotic death context is that fully developed apoptosis results in necrotic cell autolysis (secondary necrosis) with release of harmful cell components. In multicellular animals, this occurs when apoptosing cells are not removed by scavengers, mainly macrophages. Secondary necrotic lysis of neutrophils and macrophages may occur in infection when extensive phagocyte apoptosis is induced by bacterial cytotoxins and removal of apoptosing phagocytes is defective because the apoptotic process exceeds the available scavenging capacity or targets macrophages directly. Induction of phagocyte secondary necrosis is an important pathogenic mechanism, as it combines the pathogen evasion from phagocyte antimicrobial activities and the release of highly cytotoxic molecules, particularly of neutrophil origin, such as neutrophil elastase. This pathogenicity mechanism therefore promotes the unrestricted multiplication of the pathogen and contributes directly to the pathology of several necrotizing infections, where extensive apoptosis and necrosis of macrophages and neutrophils are present. Here, examples of necrotizing infectious diseases, where phagocyte secondary necrosis is implicated, are reviewed.

Gastric volvulus with partial and complete gastric necrosis

PubMed Central

Shukla, Ram Mohan; Mandal, Kartik Chandra; Maitra, Sujay; Ray, Amit; Sarkar, Ruchirendu; Mukhopadhyay, Biswanath; Bhattacharya, Malay

2014-01-01

Here, we report two interesting cases of gastric necrosis in acute gastric volvulus due to eventration of the diaphragm. Both the cases presented with a significant challenge and were managed successfully. The management of the cases is presented and relevant literature is discussed. To the best of our knowledge, this is the first case report of gastric volvulus with gastric necrosis requiring complete and partial gastrectomy in the available English literature. PMID:24604987

Delayed neovascularization in free skin flap transfer to irradiated beds in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clarke, H.M.; Howard, C.R.; Pynn, B.R.

1985-04-01

A model for the study of neovascularization with a normal epigastric free flap set into an irradiated defect in the Fischer F344 rat is presented. In this model, both the administration of radiation and the flap transfer mimic the clinical situation. Significantly less tissue survives loss of the complete vascular pedicle at the second to fourth days following flap creation in rats with an irradiated bed. Later survival is not different from controls. Delayed neovascularization is proposed as the mechanism responsible for this effect during the period corresponding to the onset of the late phase of the response to skinmore » radiation in rats. That neovascularization does occur, although delayed, suggests that the induced endarteritis may not be as important as previously suggested.« less

Bladder necrosis: 'A man without a bladder'.

PubMed

Bosschieter, Judith; Oudshoorn, Frederik H K; Meuleman, Eric J H; Nieuwenhuijzen, Jakko A

2018-02-17

Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical impact and network of determinants of tumour necrosis in colorectal cancer

PubMed Central

Väyrynen, Sara A; Väyrynen, Juha P; Klintrup, Kai; Mäkelä, Jyrki; Karttunen, Tuomo J; Tuomisto, Anne; Mäkinen, Markus J

2016-01-01

Background: The disease outcome in colorectal cancer (CRC) can vary in a wide range within the same tumour stage. The aim of this study was to clarify the prognostic value and the determinants of tumour necrosis in CRC. Methods: The areal proportion (%) of tumour tissue showing coagulative necrosis was evaluated in a cohort of 147 CRC patients and correlated with basic clinicopathological characteristics, microvascular density (MVD), cell proliferation rate, KRAS and BRAF mutations, and survival. To validate the prognostic significance of tumour necrosis, an independent cohort of 418 CRC patients was analysed. Results: Tumour necrosis positively correlated with tumour stage (P=8.5E−4)—especially with T class (4.0E−6)—and inversely correlated with serrated histology (P=0.014), but did not significantly associate with cell proliferation rate, MVD, and KRAS or BRAF mutation. Abundant (10% or more) tumour necrosis associated with worse disease-free survival independent of stage and other biological or clinicopathological characteristics in both cohorts, and the adverse effect was directly related to its extent. High CD105 MVD was also a stage independent marker for worse disease-free survival. Conclusions: Tumour necrosis percentage is a relevant histomorphological prognostic indicator in CRC. More studies are needed to disclose the mechanisms of tumour necrosis. PMID:27195424

Mucoperiosteal Flap Necrosis after Primary Palatoplasty in Patients with Cleft Palate

PubMed Central

Cotrina-Rabanal, Omar; Barrenechea-Tarazona, Luis; Vargas-Chanduvi, Roberto; Paredes-Aponte, Luis; Romero-Narvaez, Carolina

2017-01-01

Background The prevalence of flap necrosis after palatoplasty in patients with cleft palate. The prevalence of mucoperiosteal flap necrosis after palatoplasty remains unknown, and this complication is rare. This event is highly undesirable for both the patient and the surgeon. We present here a new scale to evaluate the degree of hypoplasia of the palate and identify patients with cleft palate at high risk for the development of this complication. Methods In this case series, a 20-year retrospective analysis (1994–2014) identified patients from our records (medical records and screening day registries) with nonsyndromic cleft palate who underwent operations at 3 centers. All of these patients underwent operations using 2-flap palatoplasty and also underwent a physical examination with photographs and documentation of the presence of palatal flap necrosis after primary palatoplasty. Results Palatal flap necrosis was observed in 4 cases out of 1,174 palatoplasties performed at these centers. The observed prevalence of palatal flap necrosis in these groups was 0.34%. Conclusions The prevalence of flap necrosis can be reduced by careful preoperative planning, and prevention is possible. The scale proposed here may help to prevent this complication; however, further studies are necessary to validate its utility. PMID:28573096

Histopathological changes in the pancreas of cattle with abdominal fat necrosis

PubMed Central

TANI, Chikako; PRATAKPIRIYA, Watanyoo; TANI, Mineto; YAMAUCHI, Takenori; HIRAI, Takuya; YAMAGUCHI, Ryoji; ANO, Hitoshi; KATAMOTO, Hiromu

2016-01-01

The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process. PMID:27795463

Histopathological changes in the pancreas of cattle with abdominal fat necrosis.

PubMed

Tani, Chikako; Pratakpiriya, Watanyoo; Tani, Mineto; Yamauchi, Takenori; Hirai, Takuya; Yamaguchi, Ryoji; Ano, Hitoshi; Katamoto, Hiromu

2017-01-20

The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process.

[Effect of vascular endothelial growth factor and tumor necrosis factor receptor for treatment of avascular necrosis of the femoral head in rabbits].

PubMed

Hu, Zhi-ming; Zhou, Ming-qian; Gao, Ji-min

2008-12-01

To evaluate the therapeutic effect of vascular endothelial growth factor (VEGF) and tumor necrosis factor receptor (TNFR) on avascular necrosis of the femoral head in rabbits. Avascular necrosis of the femoral head was induced in 26 New Zealand white rabbits by injections of horse serum and prednisolone. The rabbits were then divided into VEGF/TNFR treatment group, VEGF treatment group, and untreated model group, with another 4 normal rabbits as the normal control group. In the two treatment groups, the therapeutic agents were injected percutaneously into the femoral head. Enzyme-linked immunosorbent assay was performed to determine the concentration of TNF-alpha in rabbit serum followed by pathological examination of the changes in the bone tissues, bone marrow hematopoietic tissue and the blood vessels in the femoral head. Compared with the model group, the rabbits with both VEGF and TNFR treatment showed decreased serum concentration of TNF-alpha with obvious new vessel formation, decreased empty bone lacunae in the femoral head and hematopoietic tissue proliferation in the bone marrow cavity. Percutaneous injection of VEGF and TNFR into the femoral head can significantly enhance bone tissue angiogenesis and ameliorate osteonecrosis in rabbits with experimental femoral head necrosis.

Delay Choice vs. Delay Maintenance: Different Measures of Delayed Gratification in Capuchin Monkeys (Cebus apella)

PubMed Central

Addessi, Elsa; Paglieri, Fabio; Beran, Michael J.; Evans, Theodore A.; Macchitella, Luigi; De Petrillo, Francesca; Focaroli, Valentina

2013-01-01

Delaying gratification involves two components: (i) delay choice (selecting a delayed reward over an immediate one), and (ii) delay maintenance (sustaining the decision to delay gratification even if the immediate reward is available during the delay). In primates, two tasks most commonly have explored these components, the Intertemporal choice task and the Accumulation task. It is unclear whether these tasks provide equivalent measures of delay of gratification. Here, we compared the performance of the same capuchin monkeys, belonging to two study populations, between these tasks. We found only limited evidence of a significant correlation in performance. Consequently, in contrast to what is often assumed, our data provide only partial support to the hypothesis that these tasks provide equivalent measures of delay of gratification. PMID:23544770

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. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Modeling delay in genetic networks: From delay birth-death processes to delay stochastic differential equations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Chinmaya; López, José Manuel; Azencott, Robert

Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemicalmore » Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.« less

AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay.

PubMed

Gersch, Robert P; Fourman, Mitchell S; Phillips, Brett T; Nasser, Ahmed; McClain, Steve A; Khan, Sami U; Dagum, Alexander B; Bui, Duc T

2015-08-01

Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (10(9) pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm(2), P < 0.01 and 12.4 ± 1.2 cm(2), P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm(2)). AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not.

AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay

PubMed Central

Gersch, Robert P.; Fourman, Mitchell S.; Phillips, Brett T.; Nasser, Ahmed; McClain, Steve A.; Khan, Sami U.; Dagum, Alexander B.

2015-01-01

Background: Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. Methods: Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (109 pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. Results: AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm2, P < 0.01 and 12.4 ± 1.2 cm2, P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm2). Conclusions: AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not. PMID:26495207

Delayed response to cold stress is characterized by successive metabolic shifts culminating in apple fruit peel necrosis.

PubMed

Gapper, Nigel E; Hertog, Maarten L A T M; Lee, Jinwook; Buchanan, David A; Leisso, Rachel S; Fei, Zhangjun; Qu, Guiqin; Giovannoni, James J; Johnston, Jason W; Schaffer, Robert J; Nicolaï, Bart M; Mattheis, James P; Watkins, Christopher B; Rudell, David R

2017-04-21

Superficial scald is a physiological disorder of apple fruit characterized by sunken, necrotic lesions appearing after prolonged cold storage, although initial injury occurs much earlier in the storage period. To determine the degree to which the transition to cell death is an active process and specific metabolism involved, untargeted metabolic and transcriptomic profiling was used to follow metabolism of peel tissue over 180 d of cold storage. The metabolome and transcriptome of peel destined to develop scald began to diverge from peel where scald was controlled using antioxidant (diphenylamine; DPA) or rendered insensitive to ethylene using 1-methylcyclopropene (1-MCP) beginning between 30 and 60 days of storage. Overall metabolic and transcriptomic shifts, representing multiple pathways and processes, occurred alongside α-farnesene oxidation and, later, methanol production alongside symptom development. Results indicate this form of peel necrosis is a product of an active metabolic transition involving multiple pathways triggered by chilling temperatures at cold storage inception rather than physical injury. Among multiple other pathways, enhanced methanol and methyl ester levels alongside upregulated pectin methylesterases are unique to peel that is developing scald symptoms similar to injury resulting from mechanical stress and herbivory in other plants.

Uterine necrosis following pelvic arterial embolization for post-partum hemorrhage: review of the literature.

PubMed

Poujade, Olivier; Ceccaldi, Pierre François; Davitian, Carine; Amate, Pascale; Chatel, Paul; Khater, Carine; Aflak, Nizar; Vilgrain, Valérie; Luton, Dominique

2013-10-01

Uterine necrosis is one of the rarest complications following pelvic arterial embolization for postpartum hemorrhage (PPH). With the increasing incidence of cesarean section and abnormal placental localization (placenta previa) or placental invasion (placenta accreta/increta/percreta), more and more cases of uterine necrosis after embolization are being diagnosed and reported. Pelvic computed tomography or magnetic resonance imaging provides high diagnostic accuracy, and surgical management includes hysterectomy. We performed a Medline database query following the first description of uterine necrosis after pelvic embolization (between January 1985 and January 2013). Medical subheading search words were the following: "uterine necrosis"; "embolization"; "postpartum hemorrhage". Seventeen citations reporting at least one case of uterine necrosis after pelvic embolization for PPH were included, with a total of 19 cases. This literature review discusses the etiopathogenesis, clinical and therapeutic aspects of uterine necrosis following pelvic arterial embolization, and guidelines are detailed. The mean time interval between pelvic embolization and diagnosis of uterine necrosis was 21 days (range 9-730). The main symptoms of uterine necrosis were fever, abdominal pain, menorrhagia and leukorrhea. Surgical management included total hysterectomy (n=15, 78%) or subtotal hysterectomy (n=2, 10%) and partial cystectomy with excision of the necrotic portion in three cases of associated bladder necrosis (15%). Uterine necrosis was partial in four cases (21%). Regarding the pathophysiology, four factors may be involved in uterine necrosis: the size and nature of the embolizing agent, the presence of the anastomotic vascular system and the embolization technique itself with the use of free flow embolization. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Hyperbaric Oxygen Therapy Registry

ClinicalTrials.gov

2018-04-30

Air or Gas Embolism; Carbon Monoxide Poisoning; Clostridial Myositis and Myonecrosis (Gas Gangrene); Crush Injury, Compartment Syndrome & Other Acute Traumatic Ischemias; Decompression Sickness; Peripheral Arterial Insufficiency and Central Retinal Artery Occlusion; Severe Anemia; Intracranial Abscess; Necrotizing Soft Tissue Infections; Osteomyelitis (Refractory); Delayed Radiation Injury (Soft Tissue and Bony Necrosis); Compromised Grafts and Flaps; Acute Thermal Burn Injury; Idiopathic Sudden Sensorineural Hearing Loss

miR-874 regulates myocardial necrosis by targeting caspase-8

PubMed Central

Wang, K; Liu, F; Zhou, L-Y; Ding, S-L; Long, B; Liu, C-Y; Sun, T; Fan, Y-Y; Sun, L; Li, P-F

2013-01-01

Cardiomyocyte death is an important reason for the cardiac syndromes, such as heart failure (HF) and myocardial infarction (MI). In the heart diseases, necrosis is one of the main forms of cell death. MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate post-transcriptional gene silencing. Hitherto, it is not yet clear whether miRNA can regulate necrosis in cardiomyocyte. In this work, we performed a microarray to detect miRNAs in response to H2O2 treatment, and the results showed that miR-874 was substantially increased. We further studied the function of miR-874, and observed that knockdown of miR-874 attenuated necrosis in the cellular model and also MI in the animal model. We searched for the downstream mediator of miR-874 and identified that caspase-8 was a target of miR-874. Caspase-8 was able to antagonize necrosis. When suppressed by miR-874, caspase-8 lost the ability to repress necrotic program. In exploring the molecular mechanism by which miR-874 expression is regulated, we identified that Foxo3a could transcriptionally repress miR-874 expression. Foxo3a transgenic or knockout mice exhibited a low or high expression level of miR-874, and a reduced or enhanced necrosis and MI. Our present study reveals a novel myocardial necrotic regulating model, which is composed of Foxo3a, miR-874 and caspase-8. Modulation of their levels may provide a new approach for tackling myocardial necrosis. PMID:23828572

Acute Esophageal Necrosis: “Black Esophagus”

PubMed Central

Weigel, Tracey L.

2007-01-01

Acute esophageal necrosis (AEN) is an uncommon event. We report a case of an 84-year-old female with a giant paraesophageal hernia who presented with coffee ground emesis and on esophagogastroduodenoscopy (EGD) demonstrated findings consistent with acute esophageal necrosis and a giant paraesophageal hernia with normal-appearing gastric mucosa. She was managed conservatively with bowel rest, parenteral nutrition, and continuous intravenous proton pump inhibitor (PPI). After significant improvement in the gross appearance of her esophageal mucosa, surgery was performed to reduce her giant paraesophageal hernia. The patient's postoperative course was uneventful, and she was discharged home on postoperative day 6, tolerating a normal diet. The percutaneous endoscopic gastrostomy (PEG) tube was removed in clinic 2 months postoperatively. PMID:17651583

Lysosome-dependent necrosis specifically evoked in cancer cells by gold nanorods.

PubMed

Zhang, Fulei; Chen, Di; Wang, Ying; Zhang, Li; Dong, Wei; Dai, Jianxin; Jin, Chong; Dong, Xia; Sun, Yun; Zhao, He; Fan, Kexin; Liu, Hui; Chen, Bingdi; Zou, Hao; Li, Wei

2017-07-01

This article aims to explain the necrosis mechanisms of cancer cells specifically induced by gold nanorods (GNRs). The intracellular route and location of GNRs, the interaction between GNRs and lysosome, lysosome damage, cathepsin B release, necrosis complex formation, receptor-interacting protein 1 and TNF-α expression were systematically investigated. The GNRs with serum corona were internalized quickly by cancer cells and finally taken up by lysosomes. The GNRs damaged the lysosomal membrane, resulting in the leakage of cathepsin B, which promoted the activation of receptor-interacting protein 1 and necrosomes formation. Necrotic cells and their debris or ill cellular contents were engulfed by macrophages resulting in high-level release of TNF-α, which further confirmed necrosis. GNRs can specifically trigger lysosome-dependent necrosis in cancer cells.

Linking surface-fire behavior, stem heating, and tissue necrosis

Treesearch

A.S. Bova; M.B. Dickinson; M.B. Dickinson

2005-01-01

Data from 69 experimental, small-plot fires are used to describe relationships among fire intensity, barksurface heat flux, and depth of necrosis in stem tissue for red maple (Acer rubrum L.) and chestnut oak (Quercus prinus L.j. A tetrazolium staining technique was used to determine the depth of necrosis in tree boles subjected to fires with intensities of 20 to 2000...

(18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors.

PubMed

Toyonaga, Takuya; Hirata, Kenji; Yamaguchi, Shigeru; Hatanaka, Kanako C; Yuzawa, Sayaka; Manabe, Osamu; Kobayashi, Kentaro; Watanabe, Shiro; Shiga, Tohru; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Kuge, Yuji; Tamaki, Nagara

2016-07-01

Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for

Cirrhosis is a risk factor for total hip arthroplasty for avascular necrosis.

PubMed

Deleuran, Thomas; Overgaard, Søren; Vilstrup, Hendrik; Jepsen, Peter

2016-06-01

Background and purpose - There are limited data on risk factors for avascular necrosis of the hip, but cirrhosis has been proposed as a risk factor. We examined the association between cirrhosis and incidence of total hip arthroplasty for avascular necrosis. Methods - We used nationwide healthcare data to identify all Danish residents diagnosed with cirrhosis in 1994-2011, and matched them 1:5 by age and sex to non-cirrhotic reference individuals from the general population. We excluded people with a previous total hip arthroplasty, a previous hip fracture, or a previous diagnosis of avascular necrosis. We used stratified Cox regression to estimate the hazard ratio (HR) for cirrhosis patients relative to reference individuals, adjusting for potential confounders. We used the cumulative incidence function to compute 5-year risks. Results - We included 25,421 cirrhosis patients and 114,052 reference individuals. Their median age was 57 years, and 65% were men. 45 cirrhosis patients and 44 reference individuals underwent total hip arthroplasty for avascular necrosis. Cirrhosis patients' HR for a total hip arthroplasty for avascular necrosis was 10 (95% CI: 6-17), yet their 5-year risk of avascular necrosis was only 0.2%. For the reference individuals, the 5-year risk was 0.02%. Interpretation - Cirrhosis is a strong risk factor for avascular necrosis of the hip, but it is rare even in cirrhosis patients.

Cirrhosis is a risk factor for total hip arthroplasty for avascular necrosis

PubMed Central

Deleuran, Thomas; Overgaard, Søren; Vilstrup, Hendrik; Jepsen, Peter

2016-01-01

Background and purpose There are limited data on risk factors for avascular necrosis of the hip, but cirrhosis has been proposed as a risk factor. We examined the association between cirrhosis and incidence of total hip arthroplasty for avascular necrosis. Methods We used nationwide healthcare data to identify all Danish residents diagnosed with cirrhosis in 1994–2011, and matched them 1:5 by age and sex to non-cirrhotic reference individuals from the general population. We excluded people with a previous total hip arthroplasty, a previous hip fracture, or a previous diagnosis of avascular necrosis. We used stratified Cox regression to estimate the hazard ratio (HR) for cirrhosis patients relative to reference individuals, adjusting for potential confounders. We used the cumulative incidence function to compute 5-year risks. Results We included 25,421 cirrhosis patients and 114,052 reference individuals. Their median age was 57 years, and 65% were men. 45 cirrhosis patients and 44 reference individuals underwent total hip arthroplasty for avascular necrosis. Cirrhosis patients’ HR for a total hip arthroplasty for avascular necrosis was 10 (95% CI: 6–17), yet their 5-year risk of avascular necrosis was only 0.2%. For the reference individuals, the 5-year risk was 0.02%. Interpretation Cirrhosis is a strong risk factor for avascular necrosis of the hip, but it is rare even in cirrhosis patients. PMID:26900635

Experimental evaluation of radioiodinated sennoside B as a necrosis-avid tracer agent.

PubMed

Zhang, Dongjian; Huang, Dejian; Ji, Yun; Jiang, Cuihua; Li, Yue; Gao, Meng; Yao, Nan; Liu, Xuejiao; Shao, Haibo; Jing, Su; Ni, Yicheng; Yin, Zhiqi; Zhang, Jian

2015-02-01

Necrosis-avid agents are a class of compounds that selectively accumulate in the necrotic tissues after systemic administration, which can be used for in vivo necrosis imaging and targeted therapies. In order to search for a necrosis-avid tracer agent with improved drugability, we labelled iodine-131 on sennoside B (SB) as a naturally occurring median dianthrone compound. The necrosis targetability and clearance properties of (131)I-SB were evaluated in model rats with liver and muscle necrosis. On SPECT/CT images, a "hot spot" in the infarcted liver lobe and necrotic muscle was persistently observed at 24 h and 72 h post-injection (p.i.). Gamma counting of the tissues of interest revealed a radioactivity ratio of necrotic to viable liver at 4.6 and 3.4 and of necrotic to viable muscle at 7.0 and 8.8 at 24 h and 72 h p.i., respectively. The good match of autoradiographs and fluoromicroscopic images with corresponding histochemical staining suggested preferential uptake of (131)I-SB in necrotic tissue. Pharmacokinetic study revealed that (131)I-SB has an elimination half-life of 8.6 h. This study indicates that (131)I-SB shows not only prominent necrosis avidity but also favourable pharmacokinetics, which may serve as a potential necrosis-avid diagnostic agent for assessment of tissue viability.

Fast Neutron Induced Autophagy Leads To Necrosis In Glioblastoma Multiforme Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yasui, Linda; Gladden, Samantha; Andorf, Christine

Fast neutrons are highly effective at killing glioblastoma multiforme (GBM), U87 and U251 cells. The mode of cell death was investigated using transmission electron microscopy (TEM) to identify the fraction of irradiated U87 or U251 cells having morphological features of autophagy and/or necrosis. U87 or U251 cells were irradiated with 2 Gy fast neturons or 10 Gy {gamma} rays. A majority of U87 and U251 cells exhibit features of cell death with autophagy after irradiation with either 10 Gy {gamma} rays or 2 Gy fast neutrons. Very few {gamma} irradiated cells had features of necrosis (U87 or U251 cell samplesmore » processed for TEM 1 day after 10 Gy {gamma} irradiation). In contrast, a significant increase was observed in necrotic U87 and U251 cells irradiated with fast neutrons. These results show a greater percentage of cells exhibit morphological evidence of necrosis induced by a lower dose of fast neutron irradiation compared to {gamma} irradiation. Also, the evidence of necrosis in fast neutron irradiated U87 and U251 cells occurs in a background of autophagy. Since autophagy is observed before necrosis, autophagy may play a role in signaling programmed necrosis in fast neutron irradiated U87 and U251 cells.« less

[The role of core decompression for the treatment of femoral head avascular necrosis in renal transplant recipients].

PubMed

Zivcić-Cosić, Stela; Stalekar, Hrvoje; Mamula, Mihaela; Miletić, Damir; Orlić, Lidija; Racki, Sanjin; Cicvarić, Tedi

2012-10-01

subchondral radiolucencies in the lateral part of the head circumference spreading into the proximal part of the neck of the right femur, which indicated the presence of aseptic necrosis, but these changes could have also been caused by coxarthrosis. Unexpectedly, magnetic resonance imaging (MRI) did not reveal changes characteristic for avascular bone necrosis. Due to the progressively worsening of pain and the radiographic finding, the patient was submitted to decompression surgery of the femoral head. The surgical procedure was performed under diascopic guidance (C-arm) which allowed the correct positioning of a Kuerschner wire. A cannulated drill (diameter 4.0 mm) was placed over the wire and we performed two drillings of the spongiosis of the femoral head through to the subchondral area. Postoperatively, the patient was soon verticalized and advised to walk with crooks during a period of six weeks. This time is necessary to allow the mineralisation and strengthening of the bone which is now better vascularised. The patient recovered well and had no more pain. In renal transplant recipients it is most important to raise suspicion and verify the presence of avascular bone necrosis early, because timely bone decompression surgery can eliminate pain and cure the patient or it can prevent or delay bone destruction. When clinical signs of avascular bone necrosis arise and radiographic or standard MRI findings are negative, additional investigations (i.e. SPECT or MRI with contrast) should be performed to confirm or exclude the diagnosis. In latter phases of the disease, surgical decompression of the femoral head cannot lead to permanent amelioration, and it is inevitable to perform more invasive surgical procedures like "resurfacing" or bone grafting in younger patients, or the implantation of total hip endoprotheses.

Effects of Ion Irradiation on Seedlings Growth Monitored by Ultraweak Delayed Luminescence

PubMed Central

Abe, Tomoko; Cirrone, Giuseppe A. P.; Cuttone, Giacomo; Gulino, Marisa; Musumeci, Francesco; Romano, Francesco; Ryuto, Hiromichi; Scordino, Agata

2016-01-01

The optical technique based on the measurement of delayed luminescence emitted from the biological samples has demonstrated its ability to provide valid and predictive information on the functional status of various biological systems. We want to extend this technique to study the effect of ionizing radiation on biological systems. In particular we are interested in the action of ion beams, used for therapeutic purposes or to increase the biological diversity. In general, the assessment of the damage that radiation produces both in the target objects and in the surrounding tissues, requires considerable time because is based on biochemical analysis or on the examination of the evolution of the irradiated systems. The delayed luminescence technique could help to simplify this investigation. We have so started our studies performing irradiations of some relatively simple vegetable models. In this paper we report results obtained from mung bean (Vigna radiata) seeds submitted to a 12C ion beam at the energy of 62 MeV/nucleon. The dry seeds were irradiated at doses from 50 to 7000 Gy. The photoinduced delayed luminescence of each seed before and after ion irradiation was measured. The growth of seedlings after irradiation was compared with that of untreated seeds. A growth reduction on increasing the dose was registered. The results show strong correlations between the ion irradiation dose, seeds growth and delayed luminescence intensity. In particular, the delayed luminescence intensity is correlated by a logistic function to the seedlings elongation and, after performing a suitable measurement campaign based on blind tests, it could become a tool able to predict the growth of seeds after ion irradiation. Moreover these results demonstrate that measurements of delayed luminescence could be used as a fast and non-invasive technique to check the effects of ion beams on relatively simple biological systems. PMID:27936220

Programmable Differential Delay Circuit With Fine Delay Adjustment

DOEpatents

DeRyckere, John F.; Jenkins, Philip Nord; Cornett, Frank Nolan

2002-07-09

Circuitry that provides additional delay to early arriving signals such that all data signals arrive at a receiving latch with same path delay. The delay of a forwarded clock reference is also controlled such that the capturing clock edge will be optimally positioned near quadrature (depending on latch setup/hold requirements). The circuitry continuously adapts to data and clock path delay changes and digital filtering of phase measurements reduce errors brought on by jittering data edges. The circuitry utilizes only the minimum amount of delay necessary to achieve objective thereby limiting any unintended jitter. Particularly, this programmable differential delay circuit with fine delay adjustment is designed to allow the skew between ASICS to be minimized. This includes skew between data bits, between data bits and clocks as well as minimizing the overall skew in a channel between ASICS.

Treatment of sickle cell disease's hip necrosis by core decompression: a prospective case-control study.

PubMed

Mukisi-Mukaza, M; Manicom, O; Alexis, C; Bashoun, K; Donkerwolcke, M; Burny, F

2009-11-01

The young age of patients, total arthroplasties complications risks, and implant costs justify evaluation of the results of core decompression in the treatment of sickle-cell disease avascular necrosis of the femoral head (ONFH). In sickle-cell disease necrosis, core decompression offers good relief from pain and delays the use of total arthroplasty in comparison to a conservatively treated control group by a simple non-weight bearing protocol. From 1994 to 2008, among 215 drepanocytic adults, 42 patients (22 genotype SS, 20 genotype SC; 15 men, 27 women) presented symptomatic ONFH. We report the data from a prospective study of two patients' groups: a non-operated group (16 patients aged 36.5+/-6.5 years, 23 hips) and an operated group (26 patients aged 30.3+/-2.8 years, 42 hips). The results were considered on the basis of change in clinical status according to the numeric evaluation of pain scale, the functional score of Merle d'Aubigné-Postel (MAP), the radiological progression of lesions, and the time delay to total arthroplasty. Twenty-three hips were conservatively treated by discharge (a pair of canes). After a follow-up period of 13.4+/-0.5 years, no pain improvement was noted (p=0.76), and MAP score was unchanged (p=0.27). Out of 23 hips managed by discharge, 9 stage IV hips (degenerative arthritis, 39.1%) underwent arthroplasty after an average delay of 2.6+/-2.4 years. Forty-two hips were treated by core decompression. The duration of follow-up was 11.3+/-1.8 years. Postoperatively, pain reduction and MAP score improvement were significant in 39 out of 42 hips (93%, p<0.0001). Twenty-nine out of these 42 hips had a favorable evolution. Ten hips (23.8%) progressed to total arthroplasty, after a period of 7.4+/-2.7 years, longer than the one of the non-operated group (p=0.0007). By comparing the two groups (operated and non-operated), the benefit of core decompression appeared very significant (p<0.0001). In addition to allocating patients osteonecrosis

[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.

Preoperative imaging and prediction of oesophageal conduit necrosis after oesophagectomy for cancer.

PubMed

Lainas, P; Fuks, D; Gaujoux, S; Machroub, Z; Fregeville, A; Perniceni, T; Mal, F; Dousset, B; Gayet, B

2017-09-01

Oesophageal conduit necrosis following oesophagectomy is a rare but life-threatening complication. The present study aimed to assess the impact of coeliac axis stenosis on outcomes after oesophagectomy for cancer. The study included consecutive patients who had an Ivor Lewis procedure with curative intent for middle- and lower-third oesophageal cancer at two tertiary referral centres. All patients underwent preoperative multidetector CT with arterial phase to detect coeliac axis stenosis. The coeliac artery was classified as normal, with extrinsic stenosis due to a median arcuate ligament or with intrinsic stenosis caused by atherosclerosis. Some 481 patients underwent an Ivor Lewis procedure. Of these, ten (2·1 per cent) developed oesophageal conduit necrosis after surgery. Coeliac artery evaluation revealed a completely normal artery in 431 patients (91·5 per cent) in the group without conduit necrosis and in one (10 per cent) with necrosis (P < 0·001). Extrinsic stenosis of the coeliac artery due to a median arcuate ligament was found in two patients (0·4 per cent) without conduit necrosis and five (50 per cent) with necrosis (P < 0·001). Intrinsic stenosis of the coeliac artery was found in 11 (2·3 per cent) and eight (80 per cent) patients respectively (P < 0·001). Eight patients without (1·7 per cent) and five (50 per cent) with conduit necrosis had a single and thin left gastric artery (P < 0·001). This study suggests that oesophageal conduit necrosis after oesophagectomy for cancer may be due to pre-existing coeliac axis stenosis. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Focal necrosis mimicking breast cancer following coronary bypass grafting.

PubMed

Coufal, Oldřich; Ostřížek, Tomáš; Krsička, Petr; Lžičařová, Eva; Nenutil, Rudolf; Procházková, Monika; Bencsiková, Beatrix; Grell, Peter; Šefr, Roman

2017-05-30

Breast cancer can be diagnosed easily in most cases. However, occasionally, we are faced with some conditions that can mimic it. These may include inflammations, benign tumors, cysts, hematomas, or, more rarely, focal necrosis. This report presents a case of focal breast necrosis following myocardial revascularization with the left internal mammary artery, which is a very rare condition, with only few cases described in the literature. The necrosis becomes usually apparent a few days or weeks after the surgery and is often coincidental with the dehiscence of sternotomy with necrosis of wound edges. As it mostly affects the skin, it can be easily recognized. Also, our patient developed a dehisced sternotomy shortly after the surgery but there were no obvious objective changes on the breast. The condition was first dominated only by non-specific subjective symptom-pain. Later, a lump in the breast occurred, when the sternotomy had already healed. Moreover, an enlarged lymph node was palpable in the axilla. Because of non-typical symptoms, the condition was suggestive of breast cancer for a relatively long time. The patient had suffered from a very strong pain until she was treated by mastectomy with a good clinical result. Mammary necrosis following the coronary artery bypass is rare. In most cases, it manifests on the skin shortly after the surgery concurrently with dehisced sternotomy, so it can be easily diagnosed. However, in sporadic cases, the symptoms may occur later and may mimic breast cancer. Our objective is to raise awareness of this rare condition.

Morphometric findings in avascular necrosis of the femoral head.

PubMed

Kamal, Diana; Trăistaru, Rodica; Alexandru, D O; Kamal, C K; Pirici, D; Pop, O T; Mălăescu, D Gh

2012-01-01

Avascular necrosis of the femoral head is an illness with a controversial etiology, the trigger event being the suppression of blood flow to the femoral head. The disease affects mostly young adults within their third and fifth decade, the majority of the patients being men. The main risk factors are trauma, chronic alcohol consumption, smoking, corticotherapy. The main goal of our study is to describe the morphometric changes found in the bone tissue of patients diagnosed with avascular necrosis of the femoral head, with different risk factors, by comparing the area of bone trabeculae inside the area of necrosis with that from the adjacent viable tissue. The morphometric study used biological material from 16 patients with ages between 29 and 57 years, who underwent surgery for avascular necrosis of the femoral head. They were admitted in the Orthopedics Department at the Emergency County Hospital in Craiova between 2010 and 2011 and were split into four groups. Group I presented trauma as the main risk factor, Group II had corticotherapy as the defining risk factor, Group III presented chronic alcohol consumption and Group IV was represented by the patients who smoked and exhibited chronic alcohol consumption. There was not a significant statistical difference between the areas of bone trabeculae of the four groups when we compared viable bone tissue to the necrotized one. Knowing the risk factors of the avascular necrosis of the femoral head is critical to the management of the disease, because diagnosing it in an early stage is a necessity for obtaining a good result for conservative treatment.

Bcl-xL mediates RIPK3-dependent necrosis in M. tuberculosis-infected macrophages

PubMed Central

Zhao, Xiaomin; Khan, Nargis; Gan, Huixian; Tzelepis, Fanny; Nishimura, Tomoyasu; Park, Seung-Yeol; Divangahi, Maziar; Remold, Heinz G.

2017-01-01

Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mφ, which is essential for successful pathogenesis. Here we demonstrate that necrosis of Mtb-infected Mφ is dependent on the action of the cytosolic kinase Receptor Interacting Protein 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma - extra large (Bcl-xL). RIPK3-deficient Mφ are able to better control bacterial growth in vitro and in vivo. Cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-xL. Furthermore, necrosis is associated with stabilization of hexokinase II on the mitochondria as well as cyclophilin D-dependent mitochondrial permeability transition (MPT). These events up-regulate the level of reactive oxygen species (ROS) to induce necrosis. Thus, in Mtb-infected Mφ mitochondria are an essential platform for induction of necrosis by activating RIPK3 function and preventing caspase 8 - activation. PMID:28401933

Bcl-xL mediates RIPK3-dependent necrosis in M. tuberculosis-infected macrophages.

PubMed

Zhao, X; Khan, N; Gan, H; Tzelepis, F; Nishimura, T; Park, S-Y; Divangahi, M; Remold, H G

2017-11-01

Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mϕ, which is essential for successful pathogenesis in tuberculosis. Here we demonstrate that necrosis of Mtb-infected Mϕ is dependent on the action of the cytosolic Receptor Interacting Protein Kinase 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma-extra large (Bcl-x L ). RIPK3-deficient Mϕ are able to better control bacterial growth in vitro and in vivo. Mechanistically, cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-x L . Furthermore, necrosis is associated with stabilization of hexokinase II on the mitochondria as well as cyclophilin D-dependent mitochondrial permeability transition. Collectively, these events upregulate the level of reactive oxygen species to induce necrosis. Thus, in Mtb-infected Mϕ, mitochondria are an essential platform for induction of necrosis by activating RIPK3 function and preventing caspase 8-activation.

Risk factors associated with intestinal necrosis in children with failed non-surgical reduction for intussusception.

PubMed

Huang, Hui-Ya; Huang, Xiao-Zhong; Han, Yi-Jiang; Zhu, Li-Bin; Huang, Kai-Yu; Lin, Jing; Li, Zhong-Rong

2017-05-01

Intestinal necrosis is the most serious complication of intussusception. The risk factors associated with intestinal necrosis in pediatric patients with intussusception have not been well characterized. This study aimed to investigate the risk factors associated with intestinal necrosis in pediatric patients with failed non-surgical reduction for intussusception. Hospitalized patients who failed the air-enema reduction for intussusception in the outpatient department and subsequently underwent surgery were retrospectively reviewed. All cases were categorized into two groups: intestinal necrosis group and non-intestinal necrosis group based on the surgical findings. Demographic and clinical features including the findings from the surgery were recorded and analyzed. Factors associated with intestinal necrosis were analyzed using univariate and multivariate unconditional logistic regression analyses. A total of 728 cases were included. Among them, 171 had intestinal necrosis at the time of surgery. The group with intestinal necrosis had a longer duration of symptom or length of illness (P = 0.000), and younger (P = 0.000) than the non-intestinal necrosis group. Complex/compound type of intussusceptions is more likely to have intestinal necrosis. Multivariate analysis showed that the presence of grossly bloody stool (OR = 2.12; 95% CI 1.19-3.76, P = 0.010) and duration of symptom (OR = 1.07; 95% CI 1.06-1.08, P = 0.000) were independent risk factors for intestinal necrosis in patients hospitalized for surgical reduction for intussusceptions. At time of admission, the presence of bloody stools and duration of symptom are the important risk factors for developing intestinal necrosis for those patients who failed non-surgical reduction. The length of illness has the highest sensitivity and specificity to correlate with intestinal necrosis. This finding may suggest that we should take the intussusception cases that have the longer duration of

Ionizing radiation from Chernobyl affects development of wild carrot plants.

PubMed

Boratyński, Zbyszek; Arias, Javi Miranda; Garcia, Cristina; Mappes, Tapio; Mousseau, Timothy A; Møller, Anders P; Pajares, Antonio Jesús Muñoz; Piwczyński, Marcin; Tukalenko, Eugene

2016-12-16

Radioactivity released from disasters like Chernobyl and Fukushima is a global hazard and a threat to exposed biota. To minimize the deleterious effects of stressors organisms adopt various strategies. Plants, for example, may delay germination or stay dormant during stressful periods. However, an intense stress may halt germination or heavily affect various developmental stages and select for life history changes. Here, we test for the consequence of exposure to ionizing radiation on plant development. We conducted a common garden experiment in an uncontaminated greenhouse using 660 seeds originating from 33 wild carrots (Daucus carota) collected near the Chernobyl nuclear power plant. These maternal plants had been exposed to radiation levels that varied by three orders of magnitude. We found strong negative effects of elevated radiation on the timing and rates of seed germination. In addition, later stages of development and the timing of emergence of consecutive leaves were delayed by exposure to radiation. We hypothesize that low quality of resources stored in seeds, damaged DNA, or both, delayed development and halted germination of seeds from plants exposed to elevated levels of ionizing radiation. We propose that high levels of spatial heterogeneity in background radiation may hamper adaptive life history responses.

Ionizing radiation from Chernobyl affects development of wild carrot plants

NASA Astrophysics Data System (ADS)

Boratyński, Zbyszek; Arias, Javi Miranda; Garcia, Cristina; Mappes, Tapio; Mousseau, Timothy A.; Møller, Anders P.; Pajares, Antonio Jesús Muñoz; Piwczyński, Marcin; Tukalenko, Eugene

2016-12-01

Radioactivity released from disasters like Chernobyl and Fukushima is a global hazard and a threat to exposed biota. To minimize the deleterious effects of stressors organisms adopt various strategies. Plants, for example, may delay germination or stay dormant during stressful periods. However, an intense stress may halt germination or heavily affect various developmental stages and select for life history changes. Here, we test for the consequence of exposure to ionizing radiation on plant development. We conducted a common garden experiment in an uncontaminated greenhouse using 660 seeds originating from 33 wild carrots (Daucus carota) collected near the Chernobyl nuclear power plant. These maternal plants had been exposed to radiation levels that varied by three orders of magnitude. We found strong negative effects of elevated radiation on the timing and rates of seed germination. In addition, later stages of development and the timing of emergence of consecutive leaves were delayed by exposure to radiation. We hypothesize that low quality of resources stored in seeds, damaged DNA, or both, delayed development and halted germination of seeds from plants exposed to elevated levels of ionizing radiation. We propose that high levels of spatial heterogeneity in background radiation may hamper adaptive life history responses.

Avascular necrosis of the femoral head presenting as trochanteric bursitis.

PubMed Central

Mandell, B F

1990-01-01

Five patients are described with avascular necrosis of the femoral head who presented with ipsilateral trochanteric bursitis, in the absence of clearcut hip joint disease. Avascular necrosis was indicated by magnetic resonance imaging. It is suggested that clinical trochanteric bursitis, especially when refractory to local corticosteroid treatment, may be the initial sign of hip disease. In the patient with risk factor(s) for avascular necrosis that diagnosis should be considered and evaluated with appropriate studies, such as magnetic resonance imaging, to prevent weight bearing at an early stage and permit possible surgical decompression in the hope of postponing or obviating the need for total hip replacement. PMID:2241294

Previously reported sonographic appearances of regional melanoma metastases are not likely due to necrosis.

PubMed

Catalano, Orlando; Voit, Christiane; Sandomenico, Fabio; Mandato, Ylenia; Petrillo, Mario; Franco, Renato; Botti, Gerardo; Caracò, Corrado; Mozzillo, Nicola; D'Errico, Adolfo Gallipoli

2011-08-01

Sonography has proven to be a reliable tool in early detection of lymph node and in-transit cutaneous-subcutaneous metastases. Those metastases normally appear as hypoechoic or even anechoic lesions on sonography. It has been assumed that this appearance is due to necrosis of the lesions, but so far, that assumption has never been proven. The purpose of this retrospective study was to evaluate whether the hypoechoic appearance of melanoma metastasis is really due to tumor necrosis. From a radiographic database, we retrieved 212 melanoma cases imaged with sonography over a 2-year period for disease staging or follow-up. We selected 37 positive cases with 84 nodal and extranodal (satellite and in-transit) metastatic lesions and reviewed the sonograms and pathologic slides (slides available for 40 of 84 lesions). We retrospectively assessed the vascularization pattern (color Doppler images available for 78 of 84 lesions), categorizing it as poor, intermediate, or consistent. We also looked for necrosis on the histopathologic material, categorizing it into scores of 0, 1, 2, and 3 for absence of necrosis, less than 20% necrosis, 20% to 40% necrosis, and greater than 40% necrosis, respectively. Despite their gray scale appearance, most melanoma lesions were vascularized on color Doppler imaging and showed limited necrosis at histopathologic analysis. Consistent vascularization on Doppler imaging, excluding substantial necrosis, was found in 44 of 78 lesions (56.4%). Poor vascularization on Doppler imaging, suggesting necrosis, was present in only 14% of the lesions. Substantial necrosis (scores of 2 and 3) was found pathologically in only 10% of the lesions. Necrosis seems to be an uncommon event in melanoma metastasis and is probably not the basis for its low-level echo pattern on sonography. The hypoechoic appearance is very typical of melanoma metastasis and is likely due to massive melanomatous infiltration (with the poor echo reflectivity of melanin). However

Avascular necrosis of the femoral head after osteosynthesis of femoral neck fracture.

PubMed

Min, Byung-Woo; Kim, Sung-Jin

2011-05-18

The reported incidence of avascular necrosis after femoral neck fracture fixation varies widely, and there is no consensus regarding its risk factors. We evaluated the incidence of avascular necrosis of the femoral head with the use of contemporary techniques for femoral neck fracture fixation. We then sought to determine what potential risk factors influenced the development of avascular necrosis.Between 1990 and 2005, one hundred sixty-three intracapsular femoral neck fractures in 163 patients were treated with internal fixation at our level-I trauma center. All patients were monitored until conversion to total hip arthroplasty or for a minimum of 2 years postoperatively. Ten patients (10 hips) died and 7 patients (7 hips) were lost to follow-up. The remaining 146 patients (146 hips) had a mean 5.2 years of follow-up (range, 3 months to 17 years). The incidence of avascular necrosis was 25.3% (37 hips). The average time to diagnosis of avascular necrosis was 18.8 months (range, 3-47 months). Patient sex, age, interval from injury to surgery, and mechanism of injury were statistically not associated with the development of avascular necrosis. The quality of fracture reduction, adequacy of fixation, degree of displacement, and comminution of the posterior cortex were significantly associated. After we controlled for patient and radiographic characteristics, multivariate analyses indicated that the important predictors for avascular necrosis are poor reduction (odds ratio=13.889) and initial displacement of the fracture (odds ratio=4.693). Copyright 2011, SLACK Incorporated.

Conservative management of distal leg necrosis in lung transplant recipients.

PubMed

Aigner, F; Husmann, M; Huber, L C; Benden, C; Schuurmans, M M

2017-05-01

Critical limb ischemia (CLI) with distal leg necrosis in lung transplant recipients (LTR) is associated with a high risk for systemic infection and sepsis. Optimal management of CLI has not been defined so far in LTR. In immunocompetent individuals with leg necrosis, surgical amputation would be indicated and standard care. We report on the outcome of four conservatively managed LTR with distal leg necrosis due to peripheral arterial disease (PAD) with medial calcification of the distal limb vessels. Time interval from lung transplantation to CLI ranged from four years (n = 1) to more than a decade (n = 3). In all cases a multimodal therapy with heparin, acetylsalicylic acid, iloprost and antibiotic therapy was performed, in addition to a trial of catheter-based revascularization. Surgical amputation of necrosis was not undertaken due to fear of wound healing difficulties under long-term immunosuppression and impaired tissue perfusion. Intensive wound care and selective debridement were performed. Two patients developed progressive gangrene followed by auto-amputation during a follow-up of 43 and 49 months with continued ambulation and two patients died of unrelated causes 9 and 12 months after diagnosis of CLI. In conclusion, we report a conservative treatment strategy for distal leg necrosis in LTR without surgical amputation and recommend this approach based on our experience. Copyright © 2017 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Delayed plumage maturation and delayed reproductive investment in birds.

PubMed

Hawkins, Gerard L; Hill, Geoffrey E; Mercadante, Austin

2012-05-01

Delayed plumage maturation is the delayed acquisition of a definitive colour and pattern of plumage until after the first potential breeding period in birds. Here we provide a comprehensive overview of the numerous studies of delayed plumage maturation and a revised theoretical framework for understanding the function of delayed plumage maturation in all birds. We first distinguish between hypotheses that delayed plumage maturation is attributable to a moult constraint with no adaptive function and hypotheses that propose that delayed plumage maturation is a component of an adaptive life-history strategy associated with delayed reproductive investment. We then recognize three potential benefits of delayed plumage maturation: crypsis, mimicry and status signaling. Evidence suggests that delayed plumage maturation is not a consequence of developmental constraints and instead represents a strategy to maximize reproductive success in circumstances where young adults cannot effectively compete with older adults for limited resources, particularly breeding opportunities. A multi-factorial explanation that takes into account lifespan and the degree of competition for limited breeding resources and that combines the benefits of an inconspicuous appearance with the benefits of honest signaling of reduced competitiveness provides a general explanation for the function of delayed plumage maturation in most bird species. Delayed plumage maturation should be viewed as a component of alternative reproductive strategies that can include delay in both plumage and sexual development. Such strategies are frequently facultative, with individuals breeding prior to the acquisition of definitive plumages when conditions are favourable. Presumably, the benefits of delayed plumage maturation ultimately enhance lifetime reproductive success, and studying delayed plumage maturation within the context of lifetime reproductive success should be a goal of future studies. © 2011 The Authors

Femoral Head Avascular Necrosis Is Not Caused by Arthroscopic Posterolateral Femoroplasty.

PubMed

Rupp, Robert E; Rupp, Sasha N

2016-05-01

This study was conducted to identify the risk of avascular necrosis of the femoral head after arthroscopic femoroplasty extending to the posterolateral femoral neck, the source of the primary blood supply to the femoral head. Cam lesions of femoroacetabular impingement are typically anterior along the junction of the femoral head and neck. However, anatomic variations can involve the posterolateral vascular region of the femoral head and neck. Femoroplasty involving this vascular region can lead to injury to the blood supply to the femoral head, with subsequent avascular necrosis. If the posterolateral portion of the cam lesion is preserved, persistent femoroacetabular impingement may occur. A retrospective review identified 112 patients who underwent arthroscopic femoroplasty for femoroacetabular impingement over a 2-year period. Of these patients, 14 had femoroplasty that extended to the posterolateral femoral head. Of this group, 5 had undergone magnetic resonance imaging (MRI) after femoroplasty and the other 9 were contacted to undergo MRI of the hip to evaluate for avascular necrosis. A radiologist and the senior author evaluated all MRI scans specifically for avascular necrosis of the femoral head. All procedures were performed by the senior author. Mean age of the 14 patients (8 women and 6 men) with femoroplasty that extended into the posterolateral vascular region of the femoral head was 44 years (range, 23-69 years). All 14 patients underwent MRI evaluation of the affected hip a mean of 25 months (range, 7-44 months) after femoroplasty. No MRI scans showed evidence of avascular necrosis of the femoral head. Femoroplasty of the posterolateral vascular region of the femoral head is not associated with avascular necrosis. Patients with femoroacetabular impingement and a cam lesion extending to the posterolateral femoral head can undergo femoroplasty of this region without the development of avascular necrosis. [Orthopedics. 2016; 39(3):177-180.]. Copyright

Dose-dependent effects of alpha-naphthylisothiocyanate disconnect biliary fibrosis from hepatocellular necrosis.

PubMed

Joshi, Nikita; Ray, Jessica L; Kopec, Anna K; Luyendyk, James P

2017-01-01

Exposure of rodents to the xenobiotic α-naphthylisothiocyanate (ANIT) is an established model of experimental intrahepatic bile duct injury. Administration of ANIT to mice causes neutrophil-mediated hepatocellular necrosis. Prolonged exposure of mice to ANIT also produces bile duct hyperplasia and liver fibrosis. However, the mechanistic connection between ANIT-induced hepatocellular necrosis and bile duct hyperplasia and fibrosis is not well characterized. We examined impact of two different doses of ANIT, by feeding chow containing ANIT (0.05%, 0.1%), on the severity of various liver pathologies in a model of chronic ANIT exposure. ANIT-elicited increases in liver inflammation and hepatocellular necrosis increased with dose. Remarkably, there was no connection between increased hepatocellular necrosis and bile duct hyperplasia and peribiliary fibrosis, as these pathologies increased similarly in mice exposed to either dose of ANIT. The results indicate that the severity of hepatocellular necrosis does not dictate the extent of bile duct hyperplasia/fibrosis in ANIT-exposed mice. © 2016 Wiley Periodicals, Inc.

Dose-Dependent Effects of Alpha-Naphthylisothiocyanate Disconnect Biliary Fibrosis from Hepatocellular Necrosis

PubMed Central

Joshi, Nikita; Ray, Jessica L.; Kopec, Anna K.; Luyendyk, James P.

2017-01-01

Exposure of rodents to the xenobiotic α-naphthylisothiocyanate (ANIT) is an established model of experimental intrahepatic bile duct injury. Administration of ANIT to mice causes neutrophil-mediated hepatocellular necrosis. Prolonged exposure of mice to ANIT also produces bile duct hyperplasia and liver fibrosis. However, the mechanistic connection between ANIT-induced hepatocellular necrosis and bile duct hyperplasia and fibrosis is not well-characterized. We examined impact of two different doses of ANIT, by feeding chow containing ANIT (0.05%, 0.1%), on the severity of various liver pathologies in a model of chronic ANIT exposure. ANIT-elicited increases in liver inflammation and hepatocellular necrosis increased with dose. Remarkably, there was no connection between increased hepatocellular necrosis and bile duct hyperplasia and peribiliary fibrosis, as these pathologies increased similarly in mice exposed to either dose of ANIT. The results indicate that the severity of hepatocellular necrosis does not dictate the extent of bile duct hyperplasia/fibrosis in ANIT-exposed mice. PMID:27605088

Inhibition of Prostaglandin D Synthase Suppresses Muscular Necrosis

PubMed Central

Mohri, Ikuko; Aritake, Kosuke; Taniguchi, Hidetoshi; Sato, Yo; Kamauchi, Shinya; Nagata, Nanae; Maruyama, Toshihiko; Taniike, Masako; Urade, Yoshihiro

2009-01-01

Duchenne muscular dystrophy is a fatal muscle wasting disease that is characterized by a deficiency in the protein dystrophin. Previously, we reported that the expression of hematopoietic prostaglandin D synthase (HPGDS) appeared in necrotic muscle fibers from patients with either Duchenne muscular dystrophy or polymyositis. HPGDS is responsible for the production of the inflammatory mediator, prostaglandin D2. In this paper, we validated the hypothesis that HPGDS has a role in the etiology of muscular necrosis. We investigated the expression of HPGDS/ prostaglandin D2 signaling using two different mouse models of muscle necrosis, that is, bupivacaine-induced muscle necrosis and the mdx mouse, which has a genetic muscular dystrophy. We treated each mouse model with the HPGDS-specific inhibitor, HQL-79, and measured both necrotic muscle volume and selected cytokine mRNA levels. We confirmed that HPGDS expression was induced in necrotic muscle fibers in both bupivacaine-injected muscle and mdx mice. After administration of HQL-79, necrotic muscle volume was significantly decreased in both mouse models. Additionally, mRNA levels of both CD11b and transforming growth factor β1 were significantly lower in HQL-79-treated mdx mice than in vehicle-treated animals. We also demonstrated that HQL-79 suppressed prostaglandin D2 production and improved muscle strength in the mdx mouse. Our results show that HPGDS augments inflammation, which is followed by muscle injury. Furthermore, the inhibition of HPGDS ameliorates muscle necrosis even in cases of genetic muscular dystrophy. PMID:19359520

Pharmacological interventions for the prevention of insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults.

PubMed

van den Blink, Qurrat U; Garcez, Kate; Henson, Caroline C; Davidson, Susan E; Higham, Claire E

2018-04-23

obtain missing data. Data were to be pooled using the random-effects model if study comparisons were similar, otherwise results were to be reported narratively. We included two RCTs (1167 participants). The first RCT compared zoledronic acid with placebo in 96 men undergoing pelvic radiotherapy for non-metastatic prostate cancer.The second RCT had four treatment arms, two of which evaluated zoledronic acid plus adjuvant androgen suppression compared with androgen suppression only in 1071 men undergoing pelvic radiotherapy for non-metastatic prostate cancer.Both studies were at a moderate to high risk of bias and all evidence was judged to be of very low certainty.The studies provided no evidence on the primary outcomes of the review and provided limited data in relation to secondary outcomes, such that meta-analyses were not possible. Both studies focused on interventions to improve bone health in relation to androgen deprivation rather than radiation-related insufficiency fractures and avascular necrosis. Few fractures were described in each study and those described were not specific to insufficiency fractures secondary to radiotherapy. Both studies reported that zoledronic acid in addition to androgen deprivation and pelvic radiotherapy led to improvements in BMD; however, the changes in BMD were measured and reported differently. There was no available evidence regarding adverse effects. The evidence relating to interventions to prevent insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults is of very low certainty. This review highlights the need for prospective clinical trials using interventions prior to and during radiotherapy to prevent radiation-related bone morbidity, insufficiency fractures and avascular necrosis. Future trials could involve prospective assessment of bone health including BMD and bone turnover markers prior to pelvic radiotherapy. The interventions for investigation could begin as radiotherapy commences

Radiation hepatology of the rat: The effects of the proliferation stimulus induced by subtotal hepatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geraci, J.P.; Mariano, M.S.

1994-11-01

The effect of an 80 to 90% hepatectomy in stimulating proliferation immediately after irradiation of the liver was studied. A dose of 15 Gy was not lethal for animals with intact livers, but all animals with subtotal hepatectomies exposed to this dose died from apparent liver failure 28 to 60 days after exposure. To elucidate the mechanism for this mortality, plasma aspartate aminotransferase, retention of intravenous injected rose bengal, liver weight and liver hydroxyproline content were measured 0 to 90 days after 15 Gy irradiation of the liver to determine temporal changes in necrosis, function, mass and fibrosis, respectively, inmore » animals with either intact livers or livers with subtotal resection. Irradiation of the liver had no significant effect on these parameters in animals with intact livers. In subtotally hepatectomized animals the same radiation dose that suppressed liver mass restoration significantly increased hepatocyte necrosis within 7 days, which was followed by increased liver hydroxyproline concentration and hepatic dysfunction. This radiation-induced temporal change in hepatic dysfunction correlated with increased concentration of hydroxyproline but not with liver mass, indicating that liver fibrosis was the cause of hepatic dysfunction. Since similar sequelae are produced in intact livers after higher doses and longer intervals after irradiation, the proliferation stimulus induced by partial hepatectomy must accelerate the expression of damage and lower the radiation tolerance of the liver. However, in subtotally hepatectomized animals radiation-induced hepatocyte necrosis precedes fibrosis, whereas the reverse is normally true for animals with intact livers. 35 refs., 5 figs.« less

[Uterine necrosis after arterial embolization for postpartum hemorrhage].

PubMed

Belghiti, J; Tassin, M; Raiffort, C; Zappa, M; Poujade, O; Bout, H; Mandelbrot, L

2014-02-01

Radiologic embolization of the uterine arteries is increasingly used to treat severe postpartum hemorrhage, as an alternative to surgical procedures. Guidelines have been published in order to standardize the indications as well as the technique. An important objective was to limit severe complications such as uterine necrosis. We report a case of a uterine necrosis after arterial embolization for severe postpartum hemorrhage due to uterine atony on a uterus with fibroids. This complication occurred despite the use of the recommended technique. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Phencyclidine-induced malignant hyperthermia causing submassive liver necrosis.

PubMed

Armen, R; Kanel, G; Reynolds, T

1984-07-01

This report describes three male patients arrested for aggressive and combative behavior, characteristic of phencyclidine intoxication, in whom severe hyperthermia, respiratory failure, and coma developed. Two days after the malignant hyperthermic event, serum transaminase levels rose acutely to extremely high levels with concomitant elevations in bilirubin levels and a fall in prothrombin activity. Liver biopsy specimens in two patients showed marked perivenular necrosis and collapse. No specific treatment was directed at the phencyclidine intoxication. Two of the three patients survived. Submassive liver necrosis caused by malignant hyperthermia is an unusual complication of phencyclidine abuse.

Effects of stochastic time-delayed feedback on a dynamical system modeling a chemical oscillator.

PubMed

González Ochoa, Héctor O; Perales, Gualberto Solís; Epstein, Irving R; Femat, Ricardo

2018-05-01

We examine how stochastic time-delayed negative feedback affects the dynamical behavior of a model oscillatory reaction. We apply constant and stochastic time-delayed negative feedbacks to a point Field-Körös-Noyes photosensitive oscillator and compare their effects. Negative feedback is applied in the form of simulated inhibitory electromagnetic radiation with an intensity proportional to the concentration of oxidized light-sensitive catalyst in the oscillator. We first characterize the system under nondelayed inhibitory feedback; then we explore and compare the effects of constant (deterministic) versus stochastic time-delayed feedback. We find that the oscillatory amplitude, frequency, and waveform are essentially preserved when low-dispersion stochastic delayed feedback is used, whereas small but measurable changes appear when a large dispersion is applied.

Effects of stochastic time-delayed feedback on a dynamical system modeling a chemical oscillator

NASA Astrophysics Data System (ADS)

González Ochoa, Héctor O.; Perales, Gualberto Solís; Epstein, Irving R.; Femat, Ricardo

2018-05-01

We examine how stochastic time-delayed negative feedback affects the dynamical behavior of a model oscillatory reaction. We apply constant and stochastic time-delayed negative feedbacks to a point Field-Körös-Noyes photosensitive oscillator and compare their effects. Negative feedback is applied in the form of simulated inhibitory electromagnetic radiation with an intensity proportional to the concentration of oxidized light-sensitive catalyst in the oscillator. We first characterize the system under nondelayed inhibitory feedback; then we explore and compare the effects of constant (deterministic) versus stochastic time-delayed feedback. We find that the oscillatory amplitude, frequency, and waveform are essentially preserved when low-dispersion stochastic delayed feedback is used, whereas small but measurable changes appear when a large dispersion is applied.

Mechanisms of Radiation Toxicity in Transformed and Non-Transformed Cells

PubMed Central

Panganiban, Ronald-Allan M.; Snow, Andrew L.; Day, Regina M.

2013-01-01

Radiation damage to biological systems is determined by the type of radiation, the total dosage of exposure, the dose rate, and the region of the body exposed. Three modes of cell death—necrosis, apoptosis, and autophagy—as well as accelerated senescence have been demonstrated to occur in vitro and in vivo in response to radiation in cancer cells as well as in normal cells. The basis for cellular selection for each mode depends on various factors including the specific cell type involved, the dose of radiation absorbed by the cell, and whether it is proliferating and/or transformed. Here we review the signaling mechanisms activated by radiation for the induction of toxicity in transformed and normal cells. Understanding the molecular mechanisms of radiation toxicity is critical for the development of radiation countermeasures as well as for the improvement of clinical radiation in cancer treatment. PMID:23912235

Diagnostic Delay Is Associated with a Greater Risk of Early Surgery in a French Cohort of Crohn's Disease Patients.

PubMed

Nahon, Stéphane; Lahmek, Pierre; Paupard, Thierry; Lesgourgues, Bruno; Chaussade, Stanislas; Peyrin-Biroulet, Laurent; Abitbol, Vered

2016-11-01

To investigate whether a diagnostic delay is associated with a poor outcome in Crohn's disease (CD). Medical and socioeconomic characteristics as well as medications and need for surgery of consecutive CD adults patients followed in three referral centers were prospectively recorded using an electronic database (Focus_MICI ® ). A long diagnostic delay was defined by the upper quartile. We compared patients with long diagnostic delay to those with earlier diagnosis regarding the time to: (1) first intestinal surgery, (2) first use of immunosuppressants (IMSs), and (3) first use of anti-tumor necrosis factor (anti-TNF) therapy using the Kaplan-Meier test and the log-rank test. A total of 497 patients with CD (53.6 % women) were analyzed. Median diagnostic delay was 5 months (IQR 25-75 %: 2-13 months). Median follow-up was 9 years (IQR 4-16.2), and 148 (29.8 %) patients had major surgery. There were no significant differences between patients with late and early diagnosis regarding age at diagnosis, disease phenotype, need for IMS therapy, and need for anti-TNF therapy. Time to first major surgery was shorter in patients with late diagnosis (p = 0.05). In this large multicenter prospective cohort of French CD patients, a long diagnostic delay (>13 months) increased the risk of early surgery. No associated factors could be identified in this study.

Gastric necrosis and perforation in a patient with Asperger's syndrome.

PubMed

Hicks, Georgina; D'Souza, Nigel; Thomas, Rhys; Brar, Ranjeet

2017-09-27

Acute gastric necrosis is a very rare but potentially fatal condition which has been reported in patients with abnormal eating behaviours.We describe the case of a 24-year-old female with a background of Asperger's syndrome, who presented with abdominal pain and gross distension. She underwent an emergency exploratory laparotomy and was found to have a massively distended, necrotic stomach. A total gastrectomy was performed with interval reconstruction planned. This case reports the surgical management of a rarely seen condition and highlights the importance of recognising gastric necrosis and its causes, which include patients with abnormal eating behaviours, the majority of whom are young females. This is the first report highlighting gastric necrosis in a patient with Asperger's syndrome and coincides with a growing recognition of the association between eating disorders and the autistic spectrum. It is also a rare example of patient survival following total gastric necrosis with perforation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Christopher H., E-mail: chchap@umich.edu; Nagesh, Vijaya; Sundgren, Pia C.

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:more » 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.« less

TAK1 kinase switches cell fate from apoptosis to necrosis following TNF stimulation.

PubMed

Morioka, Sho; Broglie, Peter; Omori, Emily; Ikeda, Yuka; Takaesu, Giichi; Matsumoto, Kunihiro; Ninomiya-Tsuji, Jun

2014-02-17

TNF activates three distinct intracellular signaling cascades leading to cell survival, caspase-8-mediated apoptosis, or receptor interacting protein kinase 3 (RIPK3)-dependent necrosis, also called necroptosis. Depending on the cellular context, one of these pathways is activated upon TNF challenge. When caspase-8 is activated, it drives the apoptosis cascade and blocks RIPK3-dependent necrosis. Here we report the biological event switching to activate necrosis over apoptosis. TAK1 kinase is normally transiently activated upon TNF stimulation. We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation. In addition, we also demonstrated that activation of RIPK1 and RIPK3 promoted TAK1 activation, suggesting a positive feedforward loop of RIPK1, RIPK3, and TAK1. Conversely, ablation of TAK1 caused caspase-dependent apoptosis, in which Ripk3 deletion did not block cell death either in vivo or in vitro. Our results reveal that TAK1 activation drives RIPK3-dependent necrosis and inhibits apoptosis. TAK1 acts as a switch between apoptosis and necrosis.

Bilateral striatal necrosis caused by ADAR mutations in two siblings with dystonia and freckles-like skin changes that should be differentiated from Leigh syndrome.

PubMed

Piekutowska-Abramczuk, Dorota; Mierzewska, Hanna; Bekiesińska-Figatowska, Monika; Ciara, Elżbieta; Trubicka, Joanna; Pronicki, Maciej; Rokicki, Dariusz; Rydzanicz, Małgorzata; Płoski, Rafał; Pronicka, Ewa

2016-01-01

Pathogenic molecular variants in the ADAR gene are a known cause of rare diseases, autosomal recessive Aicardi- Goutières syndrome type 6, severe infantile encephalopathy with intracranial calcifications and dominant dyschromatosis symmetrica hereditaria, demonstrated mainly in Asian adults. Recently, they have been also found in patients with nonsyndromic bilateral striatal necrosis accompanied by skin changes of the freckles-like type. Here, we present Polish siblings with acute onset and slowly progressive extrapyramidal syndrome with preserved intellectual abilities and basal ganglia changes found in MRI. A Leigh syndrome was considered for a long time as the most frequent cause of such lesions in children. Finally, two molecular variants in non-mitochondria-related ADAR gene c.3202+1G>A (p.?) and c.577C>G (p.Pro193Ala) were revealed by whole exome sequencing. We suggest that bilateral striatal necrosis should be always differentiated from LS to prevent the diagnosis delay. The striatal involvement accompanied by the presence of freckles-like skin changes should direct differential diagnosis to the ADAR gene mutations screening.

[Bilateral acute retinal necrosis in a patient with acquired immunodeficiency syndrome].

PubMed

Menerath, J M; Gerard, M; Laurichesse, H; Goldschmidt, P; Peigue-Lafeuille, H; Rozenberg, F; Beytout, J

1995-01-01

A case of bilateral progressive outer retinal necrosis occurred after herpes zoster ophthalmicus in a patient with acquired immunodeficiency syndrome. This case does not correspond to the classical picture of progressive outer retinal necrosis. The disease led to blindness despite intravenous therapy with acyclovir and foscarnet. PCR could not identify any virus in the aqueous humour, but VZV is evidenced in cerebrospinal fluid. Acute retinal necrosis is now clearly defined by the American Uveitis Society, which should allow to determine its incidence and risk factors. Herpes zoster usually precedes the acute outer retinal necrosis. The infectious theory (VZV, HSV, CMV) widely prevails over the immune theory. We prefer the virus genome identification in the aqueous humor or in the vitreous by PCR to confirm diagnosis rather than the specific antibody titration. Therapy consists in acyclovir, foscarnet and ganciclovir. But whatever the treatment, the visual prognosis is poor.

Computed tomography predictors of hepatocellular carcinoma tumour necrosis after chemoembolization

PubMed Central

Bryant, Mary K; Dorn, David P; Zarzour, Jessica; Smith, J Kevin; Redden, David T; Saddekni, Souheil; Aal, Ahmed Kamel Abdel; Gray, Stephen H; Eckhoff, Devin E; DuBay, Derek A

2014-01-01

Background Radiographical features associated with a favourable response to trans-arterial chemoembolization (TACE) are poorly defined for patients with hepatocellular carcinoma (HCC). Methods From 2008 to 2012, all first TACE interventions for HCC performed at the University of Alabama at Birmingham (UAB) were retrospectively reviewed. Only patients with a pre-TACE and a post-TACE computed tomography (CT) scan were included in the analyses (n = 115). HCC tumour response to TACE was quantified via the the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Univariate and multivariable analyses were constructed. Results The index HCC tumours experienced a > 90% or complete tumour necrosis in 59/115 (51%) of patients after the first TACE intervention. On univariate analysis, smaller tumour size, peripheral tumour location and arterial enhancement were associated with a > 90% or complete tumour necrosis, whereas, only smaller tumour size [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.48, 0.81] and peripheral location (OR 6.91; 95% CI 1.75, 27.29) were significant on multivariable analysis. There was a trend towards improved survival in the patients that experienced a > 90% or complete tumour necrosis (P = 0.08). Conclusions Peripherally located smaller HCC tumours are most likely to experience a > 90% or complete tumour necrosis after TACE. Surprisingly, arterial-phase enhancement and portal venous-phase washout were not significantly predictive of TACE-induced tumour necrosis. The TACE response was not statistically associated with improved survival. PMID:23980917

Synchrotron Radiation from Ultra-High Energy Protons and the Fermi Observations of GRB 080916C

DTIC Science & Technology

2010-01-01

compared with keV – MeV radiation. Here we show that synchrotron radiation from cosmic ray protons accelerated in GRBs, delayed by the proton synchrotron... cosmic rays from sources within 100 Mpc for nano-Gauss intergalactic magnetic fields. The total energy requirements in a proton synchrotron model are...component arising from cosmic - ray proton synchrotron radiation explains the delayed onset of the LAT emission. If GRBs accelerate UHECRs, then the

Pre-clinical Evaluation of a Cyanine-Based SPECT Probe for Multimodal Tumor Necrosis Imaging.

PubMed

Stammes, Marieke A; Knol-Blankevoort, Vicky T; Cruz, Luis J; Feitsma, Hans R I J; Mezzanotte, Laura; Cordfunke, Robert A; Sinisi, Riccardo; Dubikovskaya, Elena A; Maeda, Azusa; DaCosta, Ralph S; Bierau, Katja; Chan, Alan; Kaijzel, Eric L; Snoeks, Thomas J A; van Beek, Ermond R; Löwik, Clemens W G M

2016-12-01

Recently we showed that a number of carboxylated near-infrared fluorescent (NIRF) cyanine dyes possess strong necrosis avid properties in vitro as well as in different mouse models of spontaneous and therapy-induced tumor necrosis, indicating their potential use for cancer diagnostic- and prognostic purposes. In the previous study, the detection of the cyanines was achieved by whole body optical imaging, a technique that, due to the limited penetration of near-infrared light, is not suitable for investigations deeper than 1 cm within the human body. Therefore, in order to facilitate clinical translation, the purpose of the present study was to generate a necrosis avid cyanine-based NIRF probe that could also be used for single photon emission computed tomography (SPECT). For this, the necrosis avid NIRF cyanine HQ4 was radiolabeled with 111 indium, via the chelate diethylene triamine pentaacetic acid (DTPA). The necrosis avid properties of the radiotracer [ 111 In]DTPA-HQ4 were examined in vitro and in vivo in different breast tumor models in mice using SPECT and optical imaging. Moreover, biodistribution studies were performed to examine the pharmacokinetics of the probe in vivo. Using optical imaging and radioactivity measurements, in vitro, we showed selective accumulation of [ 111 In]DTPA-HQ4 in dead cells. Using SPECT and in biodistribution studies, the necrosis avidity of the radiotracer was confirmed in a 4T1 mouse breast cancer model of spontaneous tumor necrosis and in a MCF-7 human breast cancer model of chemotherapy-induced tumor necrosis. The radiotracer [ 111 In]DTPA-HQ4 possessed strong and selective necrosis avidity in vitro and in various mouse models of tumor necrosis in vivo, indicating its potential to be clinically applied for diagnostic purposes and to monitor anti-cancer treatment efficacy.

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn; National Institute of Biological Sciences, Beijing 102206; Jin, Wei

Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibitionmore » of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.« less

Macroscopic and microscopic findings in avascular necrosis of the femoral head.

PubMed

Kamal, Diana; Alexandru, D O; Kamal, C K; Streba, C T; Grecu, D; Mogoantă, L

2012-01-01

The avascular necrosis of the femoral head is an illness induced by the cutoff of blood flow to the femoral head and it affects mostly young adults between the ages of 30 and 50 years, raising therapeutic and diagnostic issues. Many risk factors are incriminated in the development of avascular necrosis of the femoral head like: trauma, chronic alcohol consumption, smoking, administration of corticosteroid drugs, most of the cases are considered to be idiopathic. The main goal of our paper is to describe the macroscopic and microscopic variations of the bone structure, which occur in patients with avascular necrosis of the femoral head. The biological material needed for our study was obtained following hip arthroplasty surgery in 26 patients between the ages of 29 and 59 years, which previously were diagnosed with avascular necrosis of the femoral head and admitted in the Orthopedics Department of the Emergency County Hospital of Craiova (Romania) between 2010 and 2011. From a macroscopic point of view, we found well defined areas of necrosis, most of which were neatly demarcated of the adjacent viable tissue by hyperemic areas, loss of shape and contour of the femoral head and transformations of the articular cartilage above the area of necrosis. When examined under the microscope, we found vast areas of fibrosis, narrow bone trabeculae, obstructed blood vessels or blood vessels with clots inside, hypertrophic fat cells, bone sequestration but also small cells and pyknotic nuclei. The microscopic and macroscopic findings on the femoral head sections varied with the patients and the stage of the disease.

Fine needle aspiration cytology of radiation-induced changes in nonneoplastic breast lesions. Possible pitfalls in cytodiagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterse, J.L.; Thunnissen, F.B.; van Heerde, P.

1989-03-01

The range of radiation-induced changes in fine needle aspiration (FNA) smears of the breast is described. In 41 of more than 800 patients who underwent breast-conserving treatment, a palpable breast lesion developed, and FNA was performed. In six cases, a recurrent carcinoma was present. In the remaining cases, three patterns of nonneoplastic lesions could be discerned: epithelial atypia (14 cases), fat necrosis (10 cases) and poorly cellular smears without epithelial atypia or fat necrosis (13 cases). It is important to be familiar with the patterns of radiation-induced epithelial atypia, since such atypia may lead to a misdiagnosis of recurrent carcinoma.more » These atypical cells may show impressive anisocytosis and anisonucleosis; however, the nuclear/cytoplasmic ratio remains normal and an admixture of bipolar cells is present. Cell dissociation and necrotic cell debris, as often seen in breast cancer smears, were never encountered in FNA smears from radiated nonneoplastic breasts.« less

Tumor necrosis factor-alpha inhibits differentiation of myogenic cells in human urethral rhabdosphincter.

PubMed

Shinohara, Mayuka; Sumino, Yasuhiro; Sato, Fuminori; Kiyono, Tohru; Hashimoto, Naohiro; Mimata, Hiromitsu

2017-06-01

To examine the inhibitory effects of tumor necrosis factor-α on myogenic differentiation of human urethral rhabdosphincter cells. A rhabdosphincter sample was obtained from a patient who underwent total cystectomy. To expand the lifespan of the primary cultured cells, rhabdosphincter myogenic cells were immortalized with mutated cyclin-dependent kinase 4, cyclin D1 and telomerase. The differential potential of the cells was investigated. The transfected human rhabdosphincter cells were induced for myogenic differentiation with recombinant human tumor necrosis factor-α and/or the tumor necrosis factor-α antagonist etanercept at different concentrations, and activation of signaling pathways was monitored. Human rhabdosphincter cells were selectively cultured for at least 40 passages. Molecular analysis confirmed the expression of myosin heavy chain, which is a specific marker of differentiated muscle cells, significantly increased after differentiation induction. Although tumor necrosis factor-α treatment reduced the myosin heavy chain expression in a concentration-dependent manner, etanercept inhibited this suppression. Tumor necrosis factor-α suppressed phosphorylation of protein kinase B and p38, whereas etanercept pretreatment promoted phosphorylation and myosin heavy chain expression in a concentration-dependent manner. Tumor necrosis factor-α inhibits differentiation of urethral rhabdosphincter cells in part through the p38 mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. Inhibition of tumor necrosis factor-α might be a useful strategy to treat stress urinary incontinence. © 2017 The Japanese Urological Association.

Novel treatment for radiation optic neuropathy with intravenous bevacizumab.

PubMed

Farooq, Osman; Lincoff, Norah S; Saikali, Nicolas; Prasad, Dheerendra; Miletich, Robert S; Mechtler, Laszlo L

2012-12-01

Radiation optic neuropathy is a devastating form of vision loss that can occur months to years after radiation therapy for tumors and other lesions located in close proximity to the visual pathways. We present the case of a 24-year-old woman who underwent external beam radiation for treatment of a tectal pilocytic astrocytoma, and 5 years later she developed bilateral radiation optic neuropathy and radiation necrosis of the right temporal lobe. We opted to treat her with intravenous bevacizumab with 3 doses every 3 weeks, as well as dexamethasone and pentoxifylline. After the first infusion of bevacizumab, the patient noted improvement in vision and color vision, and a follow-up magnetic resonance imaging study showed that the previous enhancement of the optic nerves and chiasm was diminishing. Her vision improved dramatically and has remained stable over a 3-year period.

Novel drug discovery strategies for atherosclerosis that target necrosis and necroptosis.

PubMed

Coornaert, Isabelle; Hofmans, Sam; Devisscher, Lars; Augustyns, Koen; Van Der Veken, Pieter; De Meyer, Guido R Y; Martinet, Wim

2018-06-01

Formation and enlargement of a necrotic core play a pivotal role in atherogenesis. Since the discovery of necroptosis, which is a regulated form of necrosis, prevention of necrotic cell death has become an attractive therapeutic goal to reduce plaque formation. Areas covered: This review highlights the triggers and consequences of (unregulated) necrosis and necroptosis in atherosclerosis. The authors discuss different pharmacological strategies to inhibit necrotic cell death in advanced atherosclerotic plaques. Expert opinion: Addition of a necrosis or necroptosis inhibitor to standard statin therapy could be a promising strategy for primary prevention of cardiovascular disease. However, a necrosis inhibitor cannot block all necrosis stimuli in atherosclerotic plaques. A necroptosis inhibitor could be more effective, because necroptosis is mediated by specific proteins, termed receptor-interacting serine/threonine-protein kinases (RIPK) and mixed lineage kinase domain-like pseudokinase (MLKL). Currently, only RIPK1 inhibitors have been successfully used in atherosclerotic mouse models to inhibit necroptosis. However, because RIPK1 is involved in both necroptosis and apoptosis, and also RIPK1-independent necroptosis can occur, we feel that targeting RIPK3 and MLKL could be a more attractive therapeutic approach to inhibit necroptosis. Therefore, future challenges will consist of developing RIPK3 and MLKL inhibitors applicable in both preclinical and clinical settings.

A novel role for the apoptosis inhibitor ARC in suppressing TNFα-induced regulated necrosis

PubMed Central

Kung, G; Dai, P; Deng, L; Kitsis, R N

2014-01-01

TNFα signaling can promote apoptosis or a regulated form of necrosis. ARC (apoptosis repressor with CARD (caspase recruitment domain)) is an endogenous inhibitor of apoptosis that antagonizes both the extrinsic (death receptor) and intrinsic (mitochondrial/ER) apoptosis pathways. We discovered that ARC blocks not only apoptosis but also necrosis. TNFα-induced necrosis was abrogated by overexpression of wild-type ARC but not by a CARD mutant that is also defective for inhibition of apoptosis. Conversely, knockdown of ARC exacerbated TNFα-induced necrosis, an effect that was rescued by reconstitution with wild-type, but not CARD-defective, ARC. Similarly, depletion of ARC in vivo exacerbated necrosis caused by infection with vaccinia virus, which elicits severe tissue damage through this pathway, and sensitized mice to TNFα-induced systemic inflammatory response syndrome. The mechanism underlying these effects is an interaction of ARC with TNF receptor 1 that interferes with recruitment of RIP1, a critical mediator of TNFα-induced regulated necrosis. These findings extend the role of ARC from an apoptosis inhibitor to a regulator of the TNFα pathway and an inhibitor of TNFα-mediated regulated necrosis. PMID:24440909

Fulminant bilateral acute retinal necrosis after chickenpox - a case report.

PubMed

Dascalu, Ana Maria; Stana, Daniela; Popa-Cherecheanu, Alina; Popa-Cherecheanu, Matei; Serban, Dragos

2016-01-01

We present the case of a 34-year-old male, admitted for progressive bilateral loss of vision after a recent episode of chickenpox. Ophthalmological exam revealed bilateral acute retinal necrosis. As the patient was following a drug detoxification program, he was tested for HIV, HVB, HVC, and results highly positive. Immediate intravenous therapy with high doses of acyclovir and methylprednisolone was initiated, but the evolution was extremely severe resulting in necrotic retinal detachment. Surgery was performed in right eye, but no improvement of visual acuity was observed. The fulminant evolution of bilateral acute retinal necrosis and the lack of response to maximal intravenous therapy were clinical elements indicating coexistent immunosuppressive disease. Very severe acute retinal necrosis may occur in immunosuppressed patients, leading to blindness.

Revisiting therapeutic strategies in radiation casualties.

PubMed

Hérodin, Francis; Grenier, Nancy; Drouet, Michel

2007-04-01

Nuclear/radiological threats have evolved and scenarios for terrorist attacks involving radioactive material have been identified as complex situations. Mass casualty scenarios may happen, and individuals may be exposed to intentionally hidden sources of high activity, resulting in delayed diagnosis and treatment of acute radiation syndrome (ARS). Moreover, ARS must be considered as an emergency in order to better anticipate delayed radiation toxicity. In this context, therapeutic strategies in radiation casualties have to be revisited and new pharmacological approaches developed. B6D2F1 mice were total-body irradiated (TBI) with a 9 Gy gamma dose and then received intraperitoneal doses of either early (stem cell factor + FLT-3 ligand + thrombopoietin + interleukin-3 [SFT3] +/- keratinocyte growth factor (KGF); stem cell factor + erythropoietin + Peg-filgrastim [SEG]) or delayed treatments (SFT3 +/- KGF, erythropoietin, or hyaluronic acid). Survival was monitored and bone marrow hematopoiesis evaluated at 300 days following early treatments. SFT3 anti-apoptotic cytokine combination administered early (2 hours and 24 hours) after lethal TBI induced 60% survival versus 5% in controls. Early SEG treatment may be an alternative to SFT3 in terms of survival (55%), but SEG benefit might be obtained at the expense of long-term hematopoiesis. SFT3 + KGF induced 75% survival. No effectiveness was observed, over antimicrobial supportive care, when administration of SFT3 or its tested combinations was delayed at 48 hours. As a potentially multi-organ failure, ARS requires global therapy, beyond the hematopoietic syndrome, which may include pleiotropic cytokines such as KGF.

Effects of disease severity and necrosis on pancreatic dysfunction after acute pancreatitis.

PubMed

Garip, Gokhan; Sarandöl, Emre; Kaya, Ekrem

2013-11-28

To evaluate the effects of disease severity and necrosis on organ dysfunctions in acute pancreatitis (AP). One hundred and nine patients treated as AP between March 2003 and September 2007 with at least 6 mo follow-up were included. Patients were classified according to severity of the disease, necrosis ratio and localization. Subjective clinical evaluation and fecal pancreatic elastase-I (FPE-I) were used for exocrine dysfunction evaluation, and oral glucose tolerance test was completed for endocrine dysfunction. The correlation of disease severity, necrosis ratio and localization with exocrine and endocrine dysfunction were investigated. There were 58 male and 51 female patients, and mean age was 56.5 ± 15.7. Of the patients, 35.8% had severe AP (SAP) and 27.5% had pancreatic necrosis. Exocrine dysfunction was identified in 13.7% of the patients [17.9% were in SAP, 11.4% were in mild AP (MAP)] and 34.7% of all of the patients had endocrine dysfunction (56.4% in SAP and 23.2% in MAP). In patients with SAP and necrotizing AP (NAP), FPE-Ilevels were lower than the others (P < 0.05 and 0.001 respectively) and in patients having pancreatic head necrosis or near total necrosis, FPE-1 levels were lower than 200 μg/g stool. Forty percent of the patients who had undergone necrosectomy developed exocrine dysfunction. Endocrine dysfunction was more significant in patients with SAP and NAP (P < 0.001). All of the patients in the necrosectomy group had endocrine dysfunction. Patients with SAP, NAP, pancreatic head necrosis and necrosectomy should be followed for pancreatic functions.

The effect of topical minoxidil pretreatment on nonsurgical delay of rat cutaneous flaps: further studies.

PubMed

Gümüş, Nazım; Odemiş, Yusuf; Tuncer, Ersin; Yılmaz, Sarper

2013-08-01

The purpose of this study was to determine the effectiveness of topically applied minoxidil in the pharmacological delay phenomenon and to demonstrate the comparable microscopic and macroscopic changes between minoxidil-pretreated flaps and surgically delayed flaps. A modified version of the McFarlane flap was used. Group 1 rats, in which a caudally based dorsal skin flap was raised and sutured back, were the control group. In group II, minoxidil solution was spread over the marked skin flap area for 7 days. On the 7th day, a caudally based dorsal skin flap was elevated and then sutured back. Group III rats underwent a surgical delay procedure alone. On the 7th day after flap elevation, evaluation was done by histologic examination and calculation of the flap survival areas in all groups. The lowest flap survival rate appeared in group I and was statistically different from groups II and III. The mean surviving skin flap area in the minoxidil-pretreated group was significantly larger than that in the control group. After histologic evaluation, moderate angiogenesis was also detected in group II. We also found that surgical delay significantly reduced flap necrosis when compared to the minoxidil pretreatment group. According to our study, minoxidil may be considered an effective vasoactive agent for the stimulation of angiogenesis in rat cutaneous flaps and capable of achieving pharmacological delay and increasing flap survival. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of Radiation on Rat Retina after 18 days of Space Flight

NASA Technical Reports Server (NTRS)

Philpott, D.; Corbett, R.; Turnbill, C.; Black, S.; Dayhoff, D.; McGourty, J.; Lee, R.; Harrison, G.; Savick, L.

1978-01-01

Although cumulative effects an retina from low-dose radiation during prolonged spaceflight are not known, ary impairment of vision could set limits for spaceflight duration. Cosmic rays are now considered to be the cause of the "light flashes" seen during spaceflight by activating retina cells as they pass through the photoreceptors. Previous studies have also shown retinal cellular alterations and cell necrosis from high-energy, particle (HZE) radiation. Ten rats, 5 centrifuged during flight (FC) to simulate gravity and 5 in-flight stationary (FS) experiencing hypogravity, orbited Earth for 18.5 days on Cosmos 936. The animals were sacrificed 25 days post-recovery and the eyes flown to Ames Res. Ctr. The pattern of cell necrosis in the retinas from the FC group showed the same response to radiation as the FS. This would indicate that hypogravity was not a factor in the observed results. Also the cellular response in the retinas exposed in the Berkeley accelerator again matched both the FC and FS eyes. Thus all three conditions provide comparable changes and indicate HZE particles as the possible cause of the cellular alterations, channels, and breakdown.

Diagnostic imaging in uterine incisional necrosis/dehiscence complicating cesarean section.

PubMed

Rivlin, Michel E; Patel, Rameshkumar B; Carroll, C Shannon; Morrison, John C

2005-12-01

To review the diagnostic imaging studies in patients with surgically proven uterine incisional necrosis/dehiscence complicating cesarean section and to compare these studies with the findings at surgery. Over a 6-year period, the records of 7 patients with imaging studies prior to surgery for uterine incisional necrosis/dehiscence complicating cesarean delivery were reviewed and compared with the findings at surgery. Four cases underwent computed tomography (CT) and sonography, 1 underwent CT only, and 2 underwent sonography only. Abnormal findings included abdominal free fluid in 4, pleural effusions in 3, dilated bowel in 3, possible bladder flap hematoma in 2 and single instances of liver abscess and retained products of conception. In no cases were all the studies normal, and necrosis/dehiscence was not demonstrated in any patient. Abdominal free fluid, bowel distension, pleural effusion and bladder flap hematoma seen on CT or sonogram in the postcesarean context suggest the possibility of uterine incisional necrosis/dehiscence. Magnetic resonance imaging (MRI) might then be indicated since MRI may be superior to CT in evaluating complications at the incisional site because of its multiplanar capability and greater degree of soft tissue contrast.

Acute Radiation Disease : Cutaneous Syndrome and Toxic properties of Radiomimetics -Radiation Neurotoxins and Hematotoxins.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Cutaneous injury is an important complication of a general or local acute irradiation. A type of a skin and tissues lesions depends on a type, intensity, and period of irradiation. Also, the clinical picture, signs, and manifestations of the cutaneous syndrome depend on a type of the radiation toxins circulated in lymph and blood of irradiated mammals. Radiation Toxins were isolated from lymph of the mammals that were irradiated and developed different forms of the Acute Radiation Syndromes (ARS) -Cerebrovascular, Cardiovascular, Gastrointestinal, and Hematopoietic. Radiation Toxins can be divided into the two important types of toxins (Neu-rotoxins and Hematotoxins) or four groups. The effects of Radiation Neurotoxins include severe damages and cell death of brain, heart, gastrointestinal tissues and endothelial cells of blood and lymphatic vessels. The hematotoxicity of Hematotoxic Radiation Toxins includes lym-phopenia, leukopenia, thrombocytopenia, and anemia in the blood circulation and transitory lymphocytosis and leukocytosis in the Central Lymphatic System. In all cases, administration of the Radiomimetics (Radiation Toxins) intramuscularly or intravenously to healthy, radiation naive mammals had induced and developed the typical clinical manifestations of the ARS. In all cases, administration of Radiomimetics by subtoxic doses had demonstrated development of typical clinical signs of the cutaneous syndrome such as hair loss, erythema, swelling, desqua-mation, blistering and skin necrosis. In animal-toxic models, we have activated development of the local skin and tissue injury after injection of Radiation Toxins with cytoxic properties.

Serum and Urinary Levels of Tumor Necrosis Factor-Alpha in Renal Transplant Patients.

PubMed

Senturk Ciftci, Hayriye; Demir, Erol; Savran Karadeniz, Meltem; Tefik, Tzevat; Yazici, Halil; Nane, Ismet; Savran Oguz, Fatma; Aydin, Filiz; Turkmen, Aydin

2017-12-18

Allograft rejection is an important cause of early and long-term graft loss in kidney transplant recipients. Tumor necrosis factor-alpha promotes T-cell activation, the key reaction leading to allograft rejection. Here, we investigated whether serum and urinary tumor necrosis factor-alpha levels can predict allograft rejection. This study included 65 living related-donor renal transplant recipients with mean follow-up of 26 ± 9 months. Serum and urinary tumor necrosis factor-alpha levels were measured at pretransplant and at posttransplant time points (days 1 and 7 and months 3 and 6); serum creatinine levels were also monitored during posttransplant follow-up. Standard enzyme-linked immunoabsorbent assay was used to detect tumor necrosis factor-alpha levels. Clinical variables were monitored. Nine of 65 patients (13.8%) had biopsy-proven rejection during follow-up. Preoperative serum and urinary tumor necrosis factor-alpha levels were not significantly different when we compared patients with and without rejection. Serum tumor necrosis factor-alpha levels (in pg/mL) were significantly higher in the allograft rejection versus nonrejection group at day 7 (11.5 ± 4.7 vs 15.4 ± 5.8; P = .029) and month 1 (11.1 ± 4.8 vs 17.8 ± 10.9; P =.003). Urinary tumor necrosis factor-alpha levels (in pg/mL) were also elevated in the allograft rejection versus the nonrejection group at days 1 (10.2 ± 2.5 vs 14.1 ± 6.8; P = .002) and 7 (9.8 ± 2.2 vs 14.5 ± 2.7; P < .001) and at months 1 (8.0 ± 1.7 vs 11.8 ± 2.4; P < .001), 3 (7.7 ± 1.6 vs 9.6 ± 1.7; P = .002), and 6 (7.4 ± 1.6 vs 8.9 ± 0.9; P = .005). Our preliminary findings suggest that tumor necrosis factor-alpha has a role in diagnosing renal transplant rejection. Serum and urinary tumor necrosis factor-alpha levels may be a possible predictor for allograft rejection.

Apoptosis and Necrosis in the Liver

PubMed Central

Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

2013-01-01

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

Apoptosis and necrosis in the liver.

PubMed

Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L; Gores, Gregory J

2013-04-01

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of "programmed" necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article.

Scattering and; Delay, Scale, and Sum Migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lehman, S K

How do we see? What is the mechanism? Consider standing in an open field on a clear sunny day. In the field are a yellow dog and a blue ball. From a wave-based remote sensing point of view the sun is a source of radiation. It is a broadband electromagnetic source which, for the purposes of this introduction, only the visible spectrum is considered (approximately 390 to 750 nanometers or 400 to 769 TeraHertz). The source emits an incident field into the known background environment which, for this example, is free space. The incident field propagates until it strikes anmore » object or target, either the yellow dog or the blue ball. The interaction of the incident field with an object results in a scattered field. The scattered field arises from a mis-match between the background refractive index, considered to be unity, and the scattering object refractive index ('yellow' for the case of the dog, and 'blue' for the ball). This is also known as an impedance mis-match. The scattering objects are referred to as secondary sources of radiation, that radiation being the scattered field which propagates until it is measured by the two receivers known as 'eyes'. The eyes focus the measured scattered field to form images which are processed by the 'wetware' of the brain for detection, identification, and localization. When time series representations of the measured scattered field are available, the image forming focusing process can be mathematically modeled by delayed, scaled, and summed migration. This concept of optical propagation, scattering, and focusing have one-to-one equivalents in the acoustic realm. This document is intended to present the basic concepts of scalar scattering and migration used in wide band wave-based remote sensing and imaging. The terms beamforming and (delayed, scaled, and summed) migration are used interchangeably but are to be distinguished from the narrow band (frequency domain) beamforming to determine the direction of arrival of a

Human-Specific Bacterial Pore-Forming Toxins Induce Programmed Necrosis in Erythrocytes

PubMed Central

LaRocca, Timothy J.; Stivison, Elizabeth A.; Hod, Eldad A.; Spitalnik, Steven L.; Cowan, Peter J.; Randis, Tara M.

2014-01-01

ABSTRACT A subgroup of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins (PFTs) has an unusually narrow host range due to a requirement for binding to human CD59 (hCD59), a glycosylphosphatidylinositol (GPI)-linked complement regulatory molecule. hCD59-specific CDCs are produced by several organisms that inhabit human mucosal surfaces and can act as pathogens, including Gardnerella vaginalis and Streptococcus intermedius. The consequences and potential selective advantages of such PFT host limitation have remained unknown. Here, we demonstrate that, in addition to species restriction, PFT ligation of hCD59 triggers a previously unrecognized pathway for programmed necrosis in primary erythrocytes (red blood cells [RBCs]) from humans and transgenic mice expressing hCD59. Because they lack nuclei and mitochondria, RBCs have typically been thought to possess limited capacity to undergo programmed cell death. RBC programmed necrosis shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and RIP1 phosphorylation, necrosome assembly, and restriction by caspase-8. Death due to programmed necrosis in RBCs is executed by acid sphingomyelinase-dependent ceramide formation, NADPH oxidase- and iron-dependent reactive oxygen species formation, and glycolytic formation of advanced glycation end products. Bacterial PFTs that are hCD59 independent do not induce RBC programmed necrosis. RBC programmed necrosis is biochemically distinct from eryptosis, the only other known programmed cell death pathway in mature RBCs. Importantly, RBC programmed necrosis enhances the growth of PFT-producing pathogens during exposure to primary RBCs, consistent with a role for such signaling in microbial growth and pathogenesis. PMID:25161188

Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma.

PubMed

Adams, Hugo J A; de Klerk, John M H; Fijnheer, Rob; Dubois, Stefan V; Nievelstein, Rutger A J; Kwee, Thomas C

2015-03-01

To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ=-0.042, P=0.765), categorized lactate dehydrogenase (LDH) ratio (ρ=0.201, P=0.156), extranodal disease in major organs (φ=-0.245, P=0.083), Ann Arbor stage III/IV disease (φ=-0.208, P=0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ=0.015, P=0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P=0.003) and overall survival (P=0.004). The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The proinflammatory cytokine tumor necrosis factor-α excites subfornical organ neurons.

PubMed

Simpson, Nick J; Ferguson, Alastair V

2017-09-01

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine implicated in cardiovascular and autonomic regulation via actions in the central nervous system. TNF-α -/- mice do not develop angiotensin II (ANG II)-induced hypertension, and administration of TNF-α into the bloodstream of rats increases blood pressure and sympathetic tone. Recent studies have shown that lesion of the subfornical organ (SFO) attenuates the hypertensive and autonomic effects of TNF-α, while direct administration of TNF-α into the SFO increases blood pressure, suggesting the SFO to be a key site for the actions of TNF-α. Therefore, we used patch-clamp techniques to examine both acute and long-term effects of TNF-α on the excitability of Sprague-Dawley rat SFO neurons. It was observed that acute bath application of TNF-α depolarized SFO neurons and subsequently increased action potential firing rate. Furthermore, the magnitude of depolarization and the proportion of depolarized SFO neurons were concentration dependent. Interestingly, following 24-h incubation with TNF-α, the basal firing rate of the SFO neurons was increased and the rheobase was decreased, suggesting that TNF-α elevates SFO neuron excitability. This effect was likely mediated by the transient sodium current, as TNF-α increased the magnitude of the current and lowered its threshold of activation. In contrast, TNF-α did not appear to modulate either the delayed rectifier potassium current or the transient potassium current. These data suggest that acute and long-term TNF-α exposure elevates SFO neuron activity, providing a basis for TNF-α hypertensive and sympathetic effects. NEW & NOTEWORTHY Considerable recent evidence has suggested important links between inflammation and the pathological mechanisms underlying hypertension. The present study describes cellular mechanisms through which acute and long-term exposure of tumor necrosis factor-α (TNF-α) influences the activity of subfornical organ neurons by

Pravastatin Protects Against Avascular Necrosis of Femoral Head via Autophagy.

PubMed

Liao, Yun; Zhang, Ping; Yuan, Bo; Li, Ling; Bao, Shisan

2018-01-01

Autophagy serves as a stress response and may contribute to the pathogenesis of avascular necrosis of the femoral head induced by steroids. Statins promote angiogenesis and ameliorate endothelial functions through apoptosis inhibition and necrosis of endothelial progenitor cells, however the process used by statins to modulate autophagy in avascular necrosis of the femoral head remains unclear. This manuscript determines whether pravastatin protects against dexamethasone-induced avascular necrosis of the femoral head by activating endothelial progenitor cell autophagy. Pravastatin was observed to enhance the autophagy activity in endothelial progenitor cells, specifically by upregulating LC3-II/Beclin-1 (autophagy related proteins), and autophagosome formation in vivo and in vitro . An autophagy inhibitor, 3-MA, reduced pravastatin protection in endothelial progenitor cells exposed to dexamethasone by attenuating pravastatin-induced autophagy. Adenosine monophosphate-activated protein kinase (AMPK) is a key autophagy regulator by sensing cellular energy changes, and indirectly suppressing activation of the mammalian target of rapamycin (mTOR). We found that phosphorylation of AMPK was upregulated however phosphorylation of mTOR was downregulated in pravastatin-treated endothelial progenitor cells, which was attenuated by AMPK inhibitor compound C. Furthermore, liver kinase B1 (a phosphorylase of AMPK) knockdown eliminated pravastatin regulated autophagy protein LC3-II in endothelial progenitor cells in vitro . We therefore demonstrated pravastatin rescued endothelial progenitor cells from dexamethasone-induced autophagy dysfunction through the AMPK-mTOR signaling pathway in a liver kinase B1-dependent manner. Our results provide useful information for the development of novel therapeutics for management of glucocorticoids-induced avascular necrosis of the femoral head.

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

McMillan, Matthew T.; Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Ojerholm, Eric

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiationmore » therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.« less

Gastric Volvulus with Segmental Necrosis Treated with Wedge Resection and Gastrogastrostomy.

PubMed

Merz, Alexa Elizabeth; Preston, Jennifer Francis

2017-12-01

Ischemic necrosis is a feared complication of acute gastric volvulus, occurring in 11% of patients presenting with the condition and responsible for mortality in 30%. In such cases, there are few well-validated options for surgical reconstruction. We present the case of a 77-year-old woman with intraabdominal mesenteroaxial gastric volvulus with segmental ischemic gastric necrosis who underwent wedge gastrectomy and hand-sewn gastrogastrostomy. She did well postoperatively and experienced no significant gastrointestinal complications. Gastric wedge resection with gastrogastrostomy presents a novel surgical intervention for a rare and highly morbid entity. We hope to add it to the repertoire of surgeons facing acute gastric volvulus complicated by segmental necrosis.

A case of systemic lupus erythematosus presenting as bilateral avascular necrosis of femur.

PubMed

Adikari, Madura; Gunawardane, Aloka; Illangantilaka, Sachithra; Atukorale, Himantha; Rubasinghe, Jeevanie

2016-08-05

Avascular necrosis occur as a result of diverse etiology. Chronic inflammatory conditions such as systemic lupus erythematosus considered as a recognize cause. Many cases were reported in systemic lupus erythematosus after treating with corticosteroids. We report a case of a corticosteroid naïve patient presented as bilateral avascular necrosis of femoral head and later progressed to a case of systemic lupus erythematosus. A 26 year old lady presented with right sided hip pain and diagnosed as avascular necrosis of the femoral head. After 6 months she presented a similar pain in left hip, which revealed avascular necrosis of left femoral head as well. A probable cause for her clinical presentation could not be found after extensive clinical and laboratory evaluation. Patient reported high erythrocyte sedimentation rate persistently, and over the next few years progressed as a case of systemic lupus erythematosus. Above case illustrated avascular necrosis could be an early musculoskeletal manifestation of systemic lupus erythematosus even in the absence of corticosteroid administration.

Atypical incus necrosis: a case report and literature review.

PubMed

Choudhury, N; Kumar, G; Krishnan, M; Gatland, D J

2008-10-01

We report an atypical case of ossicular necrosis affecting the incus, in the absence of any history of chronic serous otitis media. We also discuss the current theories of incus necrosis. A male patient presented with a history of right unilateral hearing loss and tinnitus. Audiometry confirmed right conductive deafness; tympanometry was normal bilaterally. He underwent a right exploratory tympanotomy, which revealed atypical erosion of the proximal long process of the incus. Middle-ear examination was otherwise normal, with a mobile stapes footplate. The redundant long process of the incus was excised and a partial ossicular replacement prosthesis was inserted, resulting in improved hearing. Ossicular pathologies most commonly affect the incus. The commonest defect is an absent lenticular and distal long process of the incus, which is most commonly associated with chronic otitis media. This is the first reported case of ossicular necrosis, particularly of the proximal long process of the incus, in the absence of chronic middle-ear pathology.

PARP1-mediated necrosis is dependent on parallel JNK and Ca2+/calpain pathways

PubMed Central

Douglas, Diana L.; Baines, Christopher P.

2014-01-01

ABSTRACT Poly(ADP-ribose) polymerase-1 (PARP1) is a nuclear enzyme that can trigger caspase-independent necrosis. Two main mechanisms for this have been proposed: one involving RIP1 and JNK kinases and mitochondrial permeability transition (MPT), the other involving calpain-mediated activation of Bax and mitochondrial release of apoptosis-inducing factor (AIF). However, whether these two mechanisms represent distinct pathways for PARP1-induced necrosis, or whether they are simply different components of the same pathway has yet to be tested. Mouse embryonic fibroblasts (MEFs) were treated with either N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) or β-Lapachone, resulting in PARP1-dependent necrosis. This was associated with increases in calpain activity, JNK activation and AIF translocation. JNK inhibition significantly reduced MNNG- and β-Lapachone-induced JNK activation, AIF translocation, and necrosis, but not calpain activation. In contrast, inhibition of calpain either by Ca2+ chelation or knockdown attenuated necrosis, but did not affect JNK activation or AIF translocation. To our surprise, genetic and/or pharmacological inhibition of RIP1, AIF, Bax and the MPT pore failed to abrogate MNNG- and β-Lapachone-induced necrosis. In conclusion, although JNK and calpain both contribute to PARP1-induced necrosis, they do so via parallel mechanisms. PMID:25052090

Ischemic necrosis of the tongue in surgical patients with septic shock: a case report.

PubMed

Cho, Jinbeom; Sung, Kiyoung; Lee, Dosang

2016-07-19

As the tongue is a well-vascularized organ, ischemic necrosis of the tongue is a rare disease entity. Critically ill patients with profound shock may experience end-organ hypoperfusion, which might result in tongue necrosis. However, to our best knowledge, there are no reports regarding ischemic necrosis of the tongue in surgical patients with septic shock. Two patients recently developed ischemic necrosis of the tongue in our surgical intensive care unit. Both patients had undergone emergent surgery for ischemic enteritis and developed postoperative septic shock. The first patient responded to critical treatment with a short period of circulatory shock, and the delivered dose of the vasopressor seemed to be acceptable. In contrast, the second patient developed postoperative refractory shock, and high-dose vasopressor treatment was required to maintain adequate tissue perfusion. Both patients developed ischemic necrosis of the tongue and died shortly after its emergence, despite vigorous resuscitation. We suggest that ischemic necrosis of the tongue is an under-reported manifestation of any type of circulatory shock, which may have a complex pathogenic mechanism. Clinicians should be aware of the possibility of ischemic necrosis of the tongue in patients with circulatory shock, even if the patient exhibits clinical improvement, as this awareness may facilitate estimation of their prognosis and preparation for clinical deterioration.

Simulation analysis of the effect of initial delay on flight delay diffusion

NASA Astrophysics Data System (ADS)

Que, Zufu; Yao, Hongguang; Yue, Wei

2018-01-01

The initial delay of the flight is an important factor affecting the spread of flight delays, so clarifying their relationship conduces to control flight delays in the aeronautical network. Through establishing a model of the chain aviation network and making simulation analysis of the effects of initial delay on the delay longitudinal diffusion, it’s found that the number of delayed airports in the air network, the total delay time and the average delay time of the delayed airport are generally positively correlated with the initial delay. This indicates that the occurrence of the initial delay should be avoided or reduced as much as possible to improve the punctuality of the flight.

Stability and delay sensitivity of neutral fractional-delay systems.

PubMed

Xu, Qi; Shi, Min; Wang, Zaihua

2016-08-01

This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

Superomedial pedicle reduction mammaplasty: increased resection weight does not increase nipple necrosis.

PubMed

Brownlee, Pamela; Chesire, David; Crandall, Marie; Murray, John

2017-11-01

The superomedial pedicle (SMP) reduction mammaplasty offers several advantages over more traditional operative techniques, such as retained sensation to the nipple areola complex (NAC) and improved preservation of long-term breast shape. However, many surgeons believe that using the SMP can cause an increase in NAC necrosis rates up to 13.1%, especially in large volume reductions. The aims of this paper are to determine the rate of nipple necrosis when performing an SMP reduction mammaplasty at our institution and establish if there is a difference in those rates based on the weight of tissue removed. We then compared our overall rate of nipple necrosis to those found using a systematic review of literature involving other pedicles to determine if this technique is equivalent to more commonly used methods. We performed a retrospective chart review of patients who underwent breast reduction surgery using SMP at a single institution between May 1, 2013, and May 1, 2015. Each breast was counted separately, and the weight of the tissue removed was recorded. Six-mo follow-up data were analyzed using the chi-square analysis to compare rates of NAC necrosis among our patients and historical cohorts. One hundred thirty-five breasts (70 patients) met inclusion criteria. Patients had a mean resection weight per breast of 1016.7 g (±478.3). There was an NAC necrosis rate of 0% in the groups where 1200 g or less of tissue were removed and 2.3% (n = 1) in the group where greater than 1200 g of tissue were removed. We found no statistically significant difference in the rate of NAC necrosis with increased resection weights, (P = 0.32). The overall rate of NAC necrosis for this study was 0.7% per breast, which is equivalent to the rates found during the systematic review of literature. In this study, the SMP breast reduction technique shows a low rate of NAC. We found no statistically significant increase in NAC necrosis rates as the volume of tissue removed increases

Scaling beta-delayed neutron measurements to large detector areas

NASA Astrophysics Data System (ADS)

Sutanto, F.; Nattress, J.; Jovanovic, I.

2017-08-01

We explore the performance of a cargo screening system that consists of two large-sized composite scintillation detectors and a high-energy neutron interrogation source by modeling and simulation. The goal of the system is to measure β-delayed neutron emission from an illicit special nuclear material by use of active interrogation. This task is challenging because the β-delayed neutron yield is small in comparison with the yield of the prompt fission secondary products, β-delayed neutrons are emitted with relatively low energies, and high neutron and gamma backgrounds are typically present. Detectors used to measure delayed neutron emission must exhibit high intrinsic efficiency and cover a large solid angle, which also makes them sensitive to background neutron radiation. We present a case study where we attempt to detect the presence of 5 kg-scale quantities of 235U in a standard air-filled cargo container using 14 MeV neutrons as a probe. We find that by using a total measurement time of ˜11.6 s and a dose equivalent of ˜1.7 mrem, the presence of 235U can be detected with false positive and false negative probabilities that are both no larger than 0.1%.

Radiation from lightning return strokes over a finitely conducting earth

NASA Technical Reports Server (NTRS)

Le Vine, D. M.; Gesell, L.; Kao, Michael

1986-01-01

The effects of the conductivity of the earth on radiation from lightning return strokes are examined theoretically using a piecewise linear transmission line model for the return stroke. First, calculations are made of the electric field radiated during the return stroke, and then this electric field is used to compute the response of conventional AM radio receivers and electric field change systems during the return stroke. The calculations apply to the entire transient waveform (they are not restricted to the initial portions of the return stroke) and yield fast field changes and RF radiation in agreement with measurements made during real lightning. This research was motivated by measurements indicating that a time delay exists between the time of arrival of the fast electric field change and the RF radiation from first return strokes. The time delay is on the order of 20 microsec for frequencies in the HF-UHF range for lightning in Florida. The time delay is obtained theoretically in this paper. It occurs when both the effects of attenuation due to conductivity of the earth, and the finite velocity of propagation of the current pulse up the return stroke channel, are taken into account in the model.

Histopathology of aseptic necrosis of the femoral head in sickle cell disease.

PubMed

Mukisi-Mukaza, Martin; Gomez-Brouchet, Anne; Donkerwolcke, Monique; Hinsenkamp, Maurice; Burny, Franz

2011-08-01

This study compares the histopathology of bone biopsies from patients suffering from sickle cell anaemia (homozygote SS) to heterozygote patients (SA) and homozygotes with aseptic osteonecrosis (AA). The sensitivity to bacterial infection of sickle cell patients raises the question of the aetiology of sepsis in the onset of the necrosis. To our knowledge this study is the first to analyse the histopathology of osteonecrosis of the femoral head, at its early stages, in sickle cell anaemia. At the University Hospital of Pointe-à-Pitre, from 1994 to 2007, 38 bone biopsies were obtained from adult patients with avascular necrosis of the femoral head at the time of a core decompression procedure (SS, SC: 27; AS: 5; AA: 6). The histology of the biopsies confirmed the necrosis; all bacteriological cultures were negative. Patients displaying one S gene (SS, SC, AS) compared to homozygote subjects (AA) showed a significant increase of a nonspecific inflammatory granulomatosis (p = 0.003). No relationship was observed between the radiological stages and the histology whatever the genotype (p = 0.1). Inflammatory histopathology without sepsis or advanced alteration characterises the early stages of sickle cell necrosis. This inflammatory process is absent in idiopathic avascular necrosis.

[RESEARCH PROGRESS OF EXPERIMENTAL ANIMAL MODELS OF AVASCULAR NECROSIS OF FEMORAL HEAD].

PubMed

Yu, Kaifu; Tan, Hongbo; Xu, Yongqing

2015-12-01

To summarize the current researches and progress on experimental animal models of avascular necrosis of the femoral head. Domestic and internation literature concerning experimental animal models of avascular necrosis of the femoral head was reviewed and analyzed. The methods to prepare the experimental animal models of avascular necrosis of the femoral head can be mainly concluded as traumatic methods (including surgical, physical, and chemical insult), and non-traumatic methods (including steroid, lipopolysaccharide, steroid combined with lipopolysaccharide, steroid combined with horse serum, etc). Each method has both merits and demerits, yet no ideal methods have been developed. There are many methods to prepare the experimental animal models of avascular necrosis of the femoral head, but proper model should be selected based on the aim of research. The establishment of ideal experimental animal models needs further research in future.

Prognostic significance of extensive necrosis in renal cell carcinoma.

PubMed

Collins, Jennifer; Epstein, Jonathan I

2017-08-01

Few studies using the current classification of renal cell carcinoma (RCC) have looked at a large number of cases with near total necrosis. We identified 21 cases of resections of RCC with >90% necrosis from the archives of Johns Hopkins Hospital between 2000 and 2015. Patients' mean age was 59 years (43-77) with 16 men (76%); 12 cases (57%) were papillary RCC, 4 clear cell papillary RCC (19%), 4 clear cell RCC (19%), and 1 unclassified with sarcomatoid differentiation (5%). International Society of Urological Pathology (ISUP) nucleolar grade was grade 1 (9 cases) or grade 2 (9 cases). Two cases were ISUP nucleolar grade 3, and 1 case was grade 4. Pathological stage was low (pT1-2) in 20 (95%) with the unclassified RCC with sarcomatoid differentiation RCC stage pT3a. Mean tumor size was 6.3 cm (1.2-17). In 52% (11) of cases, it was difficult to identify viable tumor, requiring multiple sections; 4 cases of papillary RCC were diagnosed in part due to necrotic tumor "ghost" architecture. Follow-up was available in 17 cases (81%) with a mean follow-up of 59 months. Thirteen patients (62%) are alive without disease. The patient with unclassified carcinoma with sarcomatoid differentiation died of cancer, and 2 died due to causes unrelated to cancer. One patient (5%) with low-grade clear cell RCC developed metastases but had a contralateral RCC. In the setting of a low-grade RCC, extensive necrosis does not have an adverse prognosis. In summary, our data, together with a prior study from our institution, comprise one of the largest cohorts of extensively (>90%) necrotic RCCs and suggests that in the setting of a low-grade RCC, it portends a good prognosis (only 2/36 cases showing progression (6%) on follow-up). However, we did identify a single case of high-grade RCC with an adverse prognosis and therefore, careful attention to tumor grade and classification is critical. The presence of tumor necrosis as a prognosticator in RCCs is complex, and despite its well

Is the necrosis/wall ADC ratio useful for the differentiation of benign and malignant breast lesions?

PubMed

Durur-Subasi, Irmak; Durur-Karakaya, Afak; Karaman, Adem; Seker, Mehmet; Demirci, Elif; Alper, Fatih

2017-05-01

To determine whether the necrosis/wall apparent diffusion coefficient (ADC) ratio is useful for the malignant-benign differentiation of necrotic breast lesions. Breast MRI was performed using a 3-T system. In this retrospective study, calculation of the necrosis/wall ADC ratio was based on ADC values measured from the necrosis and from the wall of malignant and benign breast lesions by diffusion-weighted imaging (DWI). By synchronizing post-contrast T 1 weighted images, the separate parts of wall and necrosis were maintained. All the diagnoses were pathologically confirmed. Statistical analyses were conducted using an independent sample t-test and receiver operating characteristic analysis. The intraclass and interclass correlations were evaluated. A total of 66 female patients were enrolled, 38 of whom had necrotic breast carcinomas and 28 of whom had breast abscesses. The ADC values were obtained from both the wall and necrosis. The mean necrosis/wall ADC ratio (± standard deviation) was 1.61 ± 0.51 in carcinomas, and it was 0.65 ± 0.33 in abscesses. The area under the curve values for necrosis ADC, wall ADC and the necrosis/wall ADC ratio were 0.680, 0.068 and 0.942, respectively. A wall/necrosis ADC ratio cut-off value of 1.18 demonstrated a sensitivity of 97%, specificity of 93%, a positive-predictive value of 95%, a negative-predictive value of 96% and an accuracy of 95% in determining the malignant nature of necrotic breast lesions. There was a good intra- and interclass reliability for the ADC values of both necrosis and wall. The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating breast carcinomas from abscesses using DWI. Advances in knowledge: ADC values of the necrosis obtained by DWI are valuable for malignant-benign differentiation in necrotic breast lesions. The necrosis/wall ADC ratio appears to be a reliable and promising tool in the breast imaging field.

Is the necrosis/wall ADC ratio useful for the differentiation of benign and malignant breast lesions?

PubMed Central

Durur-Karakaya, Afak; Karaman, Adem; Seker, Mehmet; Demirci, Elif; Alper, Fatih

2017-01-01

Objective: To determine whether the necrosis/wall apparent diffusion coefficient (ADC) ratio is useful for the malignant–benign differentiation of necrotic breast lesions. Methods: Breast MRI was performed using a 3-T system. In this retrospective study, calculation of the necrosis/wall ADC ratio was based on ADC values measured from the necrosis and from the wall of malignant and benign breast lesions by diffusion-weighted imaging (DWI). By synchronizing post-contrast T1 weighted images, the separate parts of wall and necrosis were maintained. All the diagnoses were pathologically confirmed. Statistical analyses were conducted using an independent sample t-test and receiver operating characteristic analysis. The intraclass and interclass correlations were evaluated. Results: A total of 66 female patients were enrolled, 38 of whom had necrotic breast carcinomas and 28 of whom had breast abscesses. The ADC values were obtained from both the wall and necrosis. The mean necrosis/wall ADC ratio (± standard deviation) was 1.61 ± 0.51 in carcinomas, and it was 0.65 ± 0.33 in abscesses. The area under the curve values for necrosis ADC, wall ADC and the necrosis/wall ADC ratio were 0.680, 0.068 and 0.942, respectively. A wall/necrosis ADC ratio cut-off value of 1.18 demonstrated a sensitivity of 97%, specificity of 93%, a positive-predictive value of 95%, a negative-predictive value of 96% and an accuracy of 95% in determining the malignant nature of necrotic breast lesions. There was a good intra- and interclass reliability for the ADC values of both necrosis and wall. Conclusion: The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating breast carcinomas from abscesses using DWI. Advances in knowledge: ADC values of the necrosis obtained by DWI are valuable for malignant-benign differentiation in necrotic breast lesions. The necrosis/wall ADC ratio appears to be a reliable and promising tool in the breast imaging field. PMID

Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones.

PubMed

Zhang, Dongjian; Jiang, Cuihua; Yang, Shengwei; Gao, Meng; Huang, Dejian; Wang, Xiaoning; Shao, Haibo; Feng, Yuanbo; Sun, Ziping; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

2016-01-01

Necrosis avid agents (NAAs) can be used for diagnose of necrosis-related diseases, evaluation of therapeutic responses and targeted therapeutics of tumor. In order to probe into the effects of molecular skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones, four dianthrone compounds with the same substituents but different skeletal structures, namely Hypericin (Hyp), protohypericin (ProHyp), emodin dianthrone mesomer (ED-1) and emodin dianthrone raceme (ED-2) were synthesized and radioiodinated. Then radioiodinated dianthrones were evaluated in vitro for their necrosis avidity in A549 lung cancer cells untreated and treated with H2O2. Their biodistribution and pharmacokinetic properties were determined in rat models of induced necrosis. In vitro cell assay revealed that destruction of rigid skeleton structure dramatically reduced their necrosis targeting ability. Animal studies demonstrated that destruction of rigid skeleton structure dramatically reduced the necrotic tissue uptake and speed up the clearance from the most normal tissues for the studied compounds. Among these (131)I-dianthrones, (131)I-Hyp exhibited the highest uptake and persistent retention in necrotic tissues. Hepatic infarction could be clearly visualized by SPECT/CT using (131)I-Hyp as an imaging probe. The results suggest that the skeleton structure of Hyp is the lead structure for further structure optimization of this class of NAAs.

Avascular Necrosis of the Femoral Head.

PubMed

Seijas, Roberto; Sallent, Andrea; Rivera, Eila; Ares, Oscar

2017-12-29

About 250000 patients are operated on annually for hip arthroplasty in the USA alone. Of this number, about 10% the cause of their osteoarthritis is the avascular necrosis of the femoral head. But the causes of necrosis are multiple and many of them are still unknown. That is why small advances in etiopathogenesis, diagnosis and treatment of different causes are very important in order to reduce the number of affected patients. It may seem that small changes, studies focused on the details of different diseases do not bring great changes to science, but it is these small changes that end up adding great evolutions in our knowledge. In addition, the changes of recent years, are not focused on our specialty in technical or anatomical evolutions exclusively, but are often based on biological bases, which is the branch that evolves more within trauma and orthopedics. That is why open and constant minds are what help us move forward.

Avascular Necrosis of Acetabulum: The Hidden Culprit of Resistant Deep Wound Infection and Failed Fixation of Fracture Acetabulum - A Case Report.

PubMed

K, Kandhari V; M, Desai M; S, Bava S; N, Wade R

2015-01-01

Chances of avascular necrosis of acetabulum are rare as it enjoys a rich blood supply. But cases of post - traumatic avascular necrosis of acetabulum following fracture of posterior column have been well documented. Importance of identifying and suspecting the avascular necrosis of acetabulum is essential in cases of failed fixation of fracture acetabulum, previously operated using extensile approach to acetabulum; either extended anterior ilio - femoral or tri - radiate approach. Such patients usually present with repeated deep bone infection or with early failure of fixation with aseptic loosening and migration of its components. We present a similar case. 40 years female presented with inadequately managed transverse fracture of left acetabulum done by anterior extended ilio-inguinal approach. The fixation failed. She presented 6 months later with painful hip. Cemented total hip replacement was performed with reconstruction of acetabulum by posterior column plating. Six months postoperatively patient presented with dislodgement of cup, pelvic discontinuity and sinus in the thigh. Two stage revision surgery was planned. First implant, removal; debridement and antibiotic spacer surgery was performed. At second stage of revision total hip replacement, patient had Paprosky grade IIIb defect in acetabulum. Spacer was removed through the posterior approach. Anterior approach was taken for anterior plating. Intra-operatively external iliac pulsations were found to be absent so procedure was abandoned after expert opinion. Postoperatively digital subtraction angiography demonstrated a chronic block in the external iliac artery and corona mortis was the only patent vascular channel providing vascular to the left lower limb. Thus, peripheral limb was stealing blood supply from the acetabulum to maintain perfusion. Patient was ultimately left with pelvic discontinuity, excision arthroplasty and pseudoarthrosis of the left hip. Avascular necrosis of acetabulum is a rare

Delayed Treatment Acceleration in Patients with Rheumatoid Arthritis Who Have Inadequate Response to Initial Tumor Necrosis Factor Inhibitors: Data from the Corrona Registry

PubMed Central

Pappas, Dimitrios A.; Gerber, Robert A.; Litman, Heather J.; Gruben, David; Geier, Jamie; Hua, Winnie D.; Chen, Connie; Li, Youfu; Kremer, Joel M.; Andrews, John S.; Bourret, Jeffrey A.

2018-01-01

Background The implementation of treat-to-target principles in rheumatoid arthritis (RA) has not been fully investigated in patients with inadequate response to tumor necrosis factor (TNF) inhibitor treatment. Objectives To evaluate the prevalence of an inadequate response to initial TNF inhibitor treatment at 6 and 12 months among patients with RA in a real-world patient registry, as well as the delay in therapy adjustment and its impact on disease activity and patient-reported outcome (PRO) measures. Methods This analysis is based on data of patients with moderate or severe disease activity (Clinical Disease Activity Index [CDAI] score >10) who were included in the Consortium of Rheumatology Researchers of North America (Corrona) RA registry, a prospective, observational database. The patients had never received treatment with a biologic disease-modifying antirheumatic drug (DMARD) and had initiated treatment with a TNF inhibitor (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) between October 2001 and December 2014. We evaluated treatment response (CDAI score ≤10), select PRO measures, and treatment changes at 6 months. Patients who had an inadequate response to TNF inhibitor therapy at 6 months and continued to use their initial TNF inhibitor were evaluated again at 12 months. Results This retrospective analysis included 2282 patients. At 6 months, 1732 (75.9%) of the patients continued to use their initial TNF inhibitor; of these, 803 (46.4%) patients had an inadequate response to treatment. Of the 803 patients who had an inadequate response at 6 months, 488 (60.8%) continued their initial treatment at 12 months. Of these 488 patients, 315 (64.5%) had an inadequate response at 12 months, and 173 (35.5%) had a response. Numerically greater improvements in all PRO measures were observed for patients who responded to therapy compared with patients with an inadequate response. Conclusions In this real-world analysis of data from the Corrona

The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games.

PubMed

Hehlgans, Thomas; Pfeffer, Klaus

2005-05-01

The members of the tumour necrosis factor (TNF)/tumour necrosis factor receptor (TNFR) superfamily are critically involved in the maintenance of homeostasis of the immune system. The biological functions of this system encompass beneficial and protective effects in inflammation and host defence as well as a crucial role in organogenesis. At the same time, members of this superfamily are responsible for host damaging effects in sepsis, cachexia, and autoimmune diseases. This review summarizes recent progress in the immunobiology of the TNF/TNFR superfamily focusing on results obtained from animal studies using gene targeted mice. The different modes of signalling pathways affecting cell proliferation, survival, differentiation, apoptosis, and immune organ development as well as host defence are reviewed. Molecular and cellular mechanisms that demonstrate a therapeutic potential by targeting individual receptors or ligands for the treatment of chronic inflammatory or autoimmune diseases are discussed.

Regulated necrosis and its implications in toxicology.

PubMed

Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi

2015-07-03

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Giant Cell Arteritis Presenting as Scalp Necrosis

PubMed Central

Maidana, Daniel E.; Muñoz, Silvia; Acebes, Xènia; Llatjós, Roger; Jucglà, Anna; Álvarez, 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

RF radiation from lightning

NASA Technical Reports Server (NTRS)

Levine, D. M.

1978-01-01

Radiation from lightning in the RF band from 3-300 MHz were monitored. Radiation in this frequency range is of interest as a potential vehicle for monitoring severe storms and for studying the lightning itself. Simultaneous measurements were made of RF radiation and fast and slow field changes. Continuous analogue recordings with a system having 300 kHz of bandwidth were made together with digital records of selected events (principally return strokes) at greater temporal resolution. The data reveal patterns in the RF radiation for the entire flash which are characteristic of flash type and independent of the frequency of observation. Individual events within the flash also have characteristic RF patterns. Strong radiation occurs during the first return strokes, but delayed about 20 micron sec with respect to the begining of the return stroke; whereas, RF radiation from subsequent return strokes tends to be associated with cloud processes preceding the flash with comparatively little radiation occurring during the return stroke itself.

Concurrent Acute Retinal Necrosis in a Patient With Iridocorneal Endothelial Syndrome.

PubMed

Vignesh, A P; Srinivasan, Renuka

2016-11-01

To report a rare case of concurrent acute retinal necrosis in a patient with iridocorneal endothelial syndrome (ICE). Case report. A 42-year-old woman showed acute diminution of vision in the right eye. Her fundus examination revealed features of acute retinal necrosis. She had also experienced gradual diminution of vision in her left eye for 5 years. The examination of her left eye revealed corneal edema with mild corectopia and increased intraocular pressure with abnormal endothelium on specular microscopy pointing to a diagnosis of ICE. This is a rare case where concurrent acute retinal necrosis and ICE syndrome are present in the same patient, possibly pointing to a common viral etiology causing both entities.

TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells

PubMed Central

2014-01-01

Background The cytokine TRAIL represents one of the most promising candidates for the apoptotic elimination of tumor cells, either alone or in combination therapies. However, its efficacy is often limited by intrinsic or acquired resistance of tumor cells to apoptosis. Programmed necrosis is an alternative, molecularly distinct mode of programmed cell death that is elicited by TRAIL under conditions when the classical apoptosis machinery fails or is actively inhibited. The potential of TRAIL-induced programmed necrosis in tumor therapy is, however, almost completely uncharacterized. We therefore investigated its impact on a panel of tumor cell lines of wide-ranging origin. Methods Cell death/viability was measured by flow cytometry/determination of intracellular ATP levels/crystal violet staining. Cell surface expression of TRAIL receptors was detected by flow cytometry, expression of proteins by Western blot. Ceramide levels were quantified by high-performance thin layer chromatography and densitometric analysis, clonogenic survival of cells was determined by crystal violet staining or by soft agarose cloning. Results TRAIL-induced programmed necrosis killed eight out of 14 tumor cell lines. Clonogenic survival was reduced in all sensitive and even one resistant cell lines tested. TRAIL synergized with chemotherapeutics in killing tumor cell lines by programmed necrosis, enhancing their effect in eight out of 10 tested tumor cell lines and in 41 out of 80 chemotherapeutic/TRAIL combinations. Susceptibility/resistance of the investigated tumor cell lines to programmed necrosis seems to primarily depend on expression of the pro-necrotic kinase RIPK3 rather than the related kinase RIPK1 or cell surface expression of TRAIL receptors. Furthermore, interference with production of the lipid ceramide protected all tested tumor cell lines. Conclusions Our study provides evidence that TRAIL-induced programmed necrosis represents a feasible approach for the elimination of

FOCAL OR INSULAR NECROSIS PRODUCED BY THE BACILLUS OF TUBERCULOSIS.

PubMed

Le Count, E R

1897-11-01

1. It must be accepted from a comparison between the histological changes described in the focal necroses due to abrin and ricin, diphtheria, eclampsia, blood-serum intoxication, typhoid fever, lobar pneumonia and glanders, and those described here in three cases of tuberculosis, that the last are also instances of focal necrosis. 2. It may be claimed that the areas of necrosis in the three cases of tuberculosis had their origin in ischaemia, for the reason that they were numerous in the spleen and were not found in the kidney. Against such an explanation of their causation are the facts: that other forms of necrosis affect frequently the spleen and seldom the kidney; that thrombosis of vessels or any fixed relation of the areas in the spleen to blood-vessels could not be established; that the tubercle bacilli were invariably present; and lastly and of no slight importance, that these necroses were all present in cases of marked marasmus. 3. That the areas of necrosis in these three cases might be phenomena resulting from a mixed infection with pyogenic bacteria is possible, but no groups, colonies or even single bodies could be found which answered to the requirements in shape or staining properties for such bacteria. Even were it the case that the focal necroses here presented are the histological lesions of a septicaemia occurring as a complication of tuberculosis, the presence of the bacillus of tuberculosis in the areas of necrosis would still require explanation. 4. Lastly, it is not unreasonable to suppose that a diminished resistance on the part of the tissues incidental to marasmus is an important factor in the production of these necrotic lesions.

Post Traumatic Avascular Necrosis of the Proximal Carpal Row--A Case Report.

PubMed

Manohara, Ruben; Sebastin, Sandeep Jacob; Puhaindran, Mark Edward

2015-10-01

We report a case of avascular necrosis of the scaphoid, lunate and triquetrum in a young 21-year-old patient, after a purely ligamentous peri-lunate dislocation of the wrist. He presented with a Mayfield III peri-lunate dislocation after a road traffic accident and underwent an open reduction and internal fixation. Post-operatively, the scapho-lunate gap widened after removal of the temporary K-wires, and he gradually developed avascular necrosis of the scaphoid, lunate and triquetrum, and osteoarthritis of his wrist. We present this unusual case of simultaneous avascular necrosis of multiple carpal bones and discuss the possible risk factors and subsequent management plans for this complex injury. Our patient has no identifiable contributing factors to developing avascular necrosis. We suspect that the violence of the injury and surgery may have compromised the circulation, and advise caution when treating and counseling these patients pre-operatively.

Pediatric Digital Necrosis Secondary to Dressing Application: A Case Series.

PubMed

Bjorklund, Kim A; Rice, Dahlia M; Amalfi, Ashley N

2018-04-01

Pediatric digital necrosis resulting in revision amputation is a devastating outcome following digital dressing application. We report a series of 4 pediatric patients (age: 21 months-11 years) who presented for surgical consultation related to digital ischemia and irreversible necrosis following the application of Coban digital dressings. A review of the literature demonstrated that such injuries had not previously been described. In our case series, Coban dressing was utilized as a deterrent for thumb sucking, fingertip tuft fractures with nail bed lacerations, and a phalanx fracture secondary to crush injury. All 4 children suffered digital necrosis secondary to Coban dressings and ultimately required revision amputation. We discuss risks factors, application practices, and strategies to minimize complications with digital dressings in the pediatric population with the intent of creating awareness among hand surgeons to help promote safe practices and improve patient outcomes.

International Retrospective Chart Review of Treatment Patterns in Severe Familial Mediterranean Fever, Tumor Necrosis Factor Receptor-Associated Periodic Syndrome, and Mevalonate Kinase Deficiency/Hyperimmunoglobulinemia D Syndrome.

PubMed

Ozen, Seza; Kuemmerle-Deschner, Jasmin B; Cimaz, Rolando; Livneh, Avi; Quartier, Pierre; Kone-Paut, Isabelle; Zeft, Andrew; Spalding, Steve; Gul, Ahmet; Hentgen, Veronique; Savic, Sinisa; Foeldvari, Ivan; Frenkel, Joost; Cantarini, Luca; Patel, Dony; Weiss, Jeffrey; Marinsek, Nina; Degun, Ravi; Lomax, Kathleen G; Lachmann, Helen J

2017-04-01

Periodic fever syndrome (PFS) conditions are characterized by recurrent attacks of fever and localized inflammation. This study examined the diagnostic pathway and treatments at tertiary centers for familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and mevalonate kinase deficiency (MKD)/hyperimmunoglobulinemia D syndrome (HIDS). PFS specialists at medical centers in the US, the European Union, and the eastern Mediterranean participated in a retrospective chart review, providing de-identified data in an electronic case report form. Patients were treated between 2008 and 2012, with at least 1 year of followup; all had clinical and/or genetically proven disease and were on/eligible for biologic treatment. A total of 134 patients were analyzed: FMF (n = 49), TRAPS (n = 47), and MKD/HIDS (n = 38). Fever was commonly reported as severe across all indications. Other frequently reported severe symptoms were serositis for FMF patients and elevated acute-phase reactants and gastrointestinal upset for TRAPS and MKD/HIDS. A long delay from disease onset to diagnosis was seen within TRAPS and MKD/HIDS (5.8 and 7.1 years, respectively) compared to a 1.8-year delay in FMF patients. An equal proportion of TRAPS patients first received anti-interleukin-1 (anti-IL-1) and anti-tumor necrosis factor (anti-TNF) biologic agents, whereas IL-1 blockade was the main choice for FMF patients resistant to colchicine and MKD/HIDS patients. For TRAPS patients, treatment with anakinra versus anti-TNF treatments as first biologic agent resulted in significantly higher clinical and biochemical responses (P = 0.03 and P < 0.01, respectively). No significant differences in responses were observed between biologic agents among other cohorts. Referral patterns and diagnostic delays highlight the need for greater awareness and improved diagnostics for PFS. This real-world treatment assessment supports the need for further

Tumor Necrosis Factor-α and Interleukin (IL)-1β, IL-6, and IL-8 Impair In Vitro Migration and Induce Apoptosis of Gingival Fibroblasts and Epithelial Cells, Delaying Wound Healing.

PubMed

Basso, Fernanda G; Pansani, Taisa N; Turrioni, Ana Paula S; Soares, Diana G; de Souza Costa, Carlos Alberto; Hebling, Josimeri

2016-08-01

Multiple factors affect oral mucosal healing, such as the persistence of an inflammatory reaction. The present study evaluates effects of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-6, and IL-8 on epithelial cells (ECs) and human gingival fibroblasts (GFs) in vitro. GFs and ECs were seeded in 96-well plates (1 × 10(4) cells/well) in plain culture medium (Dulbecco's modified Eagle's medium [DMEM]) containing 1% antibiotic/antimycotic solution and 10% fetal bovine serum, and incubated for 24 hours. Both cell lines were exposed for 24 hours to the following cytokines: 1) TNF-α (100 ng/mL); 2) IL-1β (1 ng/mL); 3) IL-6 (10 ng/mL); and 4) IL-8 (10 ng/mL). All cytokines were diluted in serum-free DMEM. Control cultures were exposed only to serum-free DMEM. Effects of exposure to inflammatory cytokines were determined by means of: 1) apoptosis (anexin V); 2) cell migration (wound healing assay); 3) inflammatory cytokine synthesis (enzyme-linked immunosorbent assay). Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests (α = 0.05). Increased apoptosis rates were noted when cells were exposed to inflammatory cytokines, except ECs exposed to IL-1β. Cell migration was negatively affected by all inflammatory cytokines for both cell lines. ECs and GFs exposed to IL-6 and IL-8 significantly increased synthesis of TNF-α and IL-1β. Demonstrated results indicate negative effects of tested inflammatory cytokines on ECs and GFs, inducing apoptosis and impairing cell migration. These results can justify delayed oral mucosa healing in the presence of inflammatory reaction.

EVALUATION OF CONTRAST-ENHANCED ULTRASONOGRAPHY AS A METHOD FOR DETECTING GALLBLADDER NECROSIS OR RUPTURE IN DOGS.

PubMed

Bargellini, Paolo; Orlandi, Riccardo; Paloni, Chiara; Rubini, Giuseppe; Fonti, Paolo; Peterson, Mark E; Rishniw, Mark; Boiti, Cristiano

2016-11-01

Gall bladder necrosis and rupture are life-threatening conditions in dogs requiring surgical intervention and early diagnosis is essential. Human patients with suspected gall bladder necrosis/rupture are commonly evaluated with contrast-enhanced ultrasonography (CEUS), however this procedure has not been described in dogs with suspected gall bladder necrosis/rupture. In a prospective diagnostic cohort study, CEUS (using SonoVue contrast medium) was performed in 93 dogs with gallbladder lesions identified by abdominal conventional ultrasonography. Necrosis/rupture was identified by CEUS as a focal lack of enhancement of the gallbladder wall. Dogs with positive CEUS finding for necrosis/rupture (complete lack of regional wall enhancement) underwent immediate surgery as did dogs with other biliary disorders requiring surgery. Dogs with negative CEUS findings or those not requiring surgery were managed medically. In cases undergoing surgery, necrosis/rupture was confirmed intraoperatively (and via histopathology). Absence of necrosis/rupture was confirmed either intraoperatively (via histopathology) or was assumed to be absent by complete recovery with medical management. Forty-nine dogs underwent surgery and cholecystectomy: 24 had necrosis/rupture. CEUS was more accurate (100% sensitive and specific) in diagnosing gallbladder wall necrosis/rupture than conventional ultrasonography (75% sensitive and 81% specific) (P < 0.03). In conclusion, CEUS provides accurate characterization of gallbladder wall integrity that can impact decisions regarding clinical management, either surgical or medical. © 2016 American College of Veterinary Radiology.

High serum creatinine in acute pancreatitis: a marker for pancreatic necrosis?

PubMed

Lankisch, Paul Georg; Weber-Dany, Bettina; Maisonneuve, Patrick; Lowenfels, Albert B

2010-05-01

High serum creatinine is a well-known unfavorable prognostic parameter in acute pancreatitis. Elevated creatinine at 48 h after admission was recently described as a marker for pancreatic necrosis. As pancreatic necrosis is a serious complication of acute pancreatitis and its identification by a simple single laboratory test would be very helpful, the aim of this study was to test that statement. In a prospective multicenter study of 462 patients with a first attack of acute pancreatitis, serum creatinine was determined on admission, and at 24 and 48 h thereafter, and compared with the findings of contrast-enhanced computed tomography (CT) performed within 96 h of admission. Pancreatic necrosis was present in 62 (13%) of the patients. Serum creatinine levels (abnormal > or = 2 mg/dl) on admission and after 24 and 48 h were evaluated vs. the presence or absence of pancreatic necrosis. Sensitivity rates varied between 14 and 23%, specificity between 95 and 97%, positive predictive values between 41 and 50%, and negative predictive values between 87 and 89%. Receiver operating characteristic curves revealed an area under the curve of between 0.604 and 0.669. An elevated serum creatinine concentration at any time during the first 48 h of admission is not a marker for pancreatic necrosis in a first attack of acute pancreatitis. If serum creatinine is normal, necrotizing pancreatitis is unlikely, and contrast-enhanced CT need not be performed unless complications occur and/or the patient's condition deteriorates.

Primary Tumor Necrosis Predicts Distant Control in Locally Advanced Soft-Tissue Sarcomas After Preoperative Concurrent Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDermed, Dhara M.; Miller, Luke L.; Peabody, Terrance D.

Purpose: Various neoadjuvant approaches have been evaluated for the treatment of locally advanced soft-tissue sarcomas. This retrospective study describes a uniquely modified version of the Eilber regimen developed at the University of Chicago. Methods and Materials: We treated 34 patients (28 Stage III and 6 Stage IV) with locally advanced soft-tissue sarcomas of an extremity between 1995 and 2008. All patients received preoperative therapy including ifosfamide (2.5 g/m2 per day for 5 days) with concurrent radiation (28 Gy in 3.5-Gy daily fractions), sandwiched between various chemotherapy regimens. Postoperatively, 47% received further adjuvant chemotherapy. Results: Most tumors (94%) were Grade 3,more » and all were T2b, with a median size of 10.3 cm. Wide excision was performed in 29 patients (85%), and 5 required amputation. Of the resected tumor specimens, 50% exhibited high (>=90%) treatment-induced necrosis and 11.8% had a complete pathologic response. Surgical margins were negative in all patients. The 5-year survival rate was 42.3% for all patients and 45.2% for Stage III patients. For limb-preservation patients, the 5-year local control rate was 89.0% and reoperation was required for wound complications in 17.2%. The 5-year freedom-from-distant metastasis rate was 53.4% (Stage IV patients excluded), and freedom from distant metastasis was superior if treatment-induced tumor necrosis was 90% or greater (84.6% vs. 19.9%, p = 0.02). Conclusions: This well-tolerated concurrent chemoradiotherapy approach yields excellent rates of limb preservation and local control. The resulting treatment-induced necrosis rates are predictive of subsequent metastatic risk, and this information may provide an opportunity to guide postoperative systemic therapies.« less

Rapid Detection of Necrosis in Breast Cancer with Desorption Electrospray Ionization Mass Spectrometry

PubMed Central

Tata, Alessandra; Woolman, Michael; Ventura, Manuela; Bernards, Nicholas; Ganguly, Milan; Gribble, Adam; Shrestha, Bindesh; Bluemke, Emma; Ginsberg, Howard J.; Vitkin, Alex; Zheng, Jinzi; Zarrine-Afsar, Arash

2016-01-01

Identification of necrosis in tumors is of prognostic value in treatment planning, as necrosis is associated with aggressive forms of cancer and unfavourable outcomes. To facilitate rapid detection of necrosis with Mass Spectrometry (MS), we report the lipid MS profile of necrotic breast cancer with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) imaging validated with statistical analysis and correlating pathology. This MS profile is characterized by (1) the presence of the ion of m/z 572.48 [Cer(d34:1) + Cl]− which is a ceramide absent from the viable cancer subregions; (2) the absence of the ion of m/z 391.25 which is present in small abundance only in viable cancer subregions; and (3) a slight increase in the relative intensity of known breast cancer biomarker ions of m/z 281.25 [FA(18:1)-H]− and 303.23 [FA(20:4)-H]−. Necrosis is accompanied by alterations in the tissue optical depolarization rate, allowing tissue polarimetry to guide DESI-MS analysis for rapid MS profiling or targeted MS imaging. This workflow, in combination with the MS profile of necrosis, may permit rapid characterization of necrotic tumors from tissue slices. Further, necrosis-specific biomarker ions are detected in seconds with single MS scans of necrotic tumor tissue smears, which further accelerates the identification workflow by avoiding tissue sectioning and slide preparation. PMID:27734938

Antiradiation Antitoxin IgG : Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Introduction: High doses of radiation induce apoptotic necrosis of radio-sensitive cells. Mild doses of radiation induce apoptosis or controlled programmed death of radio-sensitive cells with-out development of inflammation and formation of Radiation Toxins. Cell apoptotic necrosis initiates Radiation Toxins (RT)formation. Radiation Toxins play an important role as a trig-ger mechanism for inflammation development and cell lysis. If an immunotherapy approach to treatment of the acute radiation syndromes (ARS) were to be developed, a consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants-SRD) by specific antiradiation antibodies. Therapeutic neutralization effects of the blocking anti-radiation antibodies on the circulated RT had been studied. Radiation Toxins were isolated from the central lymph of irradiated animals with Cerebrovascular(Cv ARS),Cardiovascular (Cr ARS),Gastrointestinal(Gi ARS) and Haemopoietic (Hp ARS) forms of ARS. To accomplish this objective, irradiated animals were injected with a preparation of anti-radiation immunoglobulin G (IgG) obtained from hyperimmune donors. Radiation-induced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic) characteristics as well as specific antigenic properties. Depending on direct physiochemical radiation damage, they can induce development of many of the pathological processes associated with ARS. We have tested several specific hyperimmune IgG preparations against these radiation toxins and ob-served that their toxic properties were neutralized by the specific antiradiation IgGs. Material and Methods: A scheme of experiments was following: 1.Isolation of radiation toxins (RT) from the central lymph of irradiated animals with different form of ARS. 2.Transformation of a toxic form of the RT to a toxoid form of the RT. 3.Immunization of radiation naive animals. Four groups of rabbits were inoculated with a toxoid form of SRD

Immunodiagnosis of groundnut and watermelon bud necrosis viruses using polyclonal antiserum to recombinant nucleocapsid protein of Groundnut bud necrosis virus.

PubMed

Jain, R K; Pandey, Amar N; Krishnareddy, M; Mandal, Bikash

2005-12-01

In vitro gene expression strategy was used for the production of polyclonal antiserum to the nucleocapsid protein (NP) of Groundnut bud necrosis virus (GBNV). The GBNV NP gene from cowpea isolate was cloned into 6x His-tagged UA cloning vector and expressed in Escherichia coli [M15] cells. The fusion protein was detected in insoluble fraction and was purified by using Ni-NTA agarose resin. The purified 6x His-fusion protein ( approximately 32 kDa) was used for immunisation to produce a high titre polyclonal antiserum. The antiserum to the NP of GBNV at 1:4000 dilution detected successfully natural infection of GBNV and Watermelon bud necrosis virus in a wide range of cucurbitaceous, leguminous and solanaceous hosts from different locations.

Computed tomography findings of gaseous necrosis in epithelial ovarian cancer: a report of three cases.

PubMed

Cronin, Paul; Crosse, Barbara; Lane, Geoff; Spencer, John A

2002-01-01

Necrosis in pathologic specimens of ovarian cancer is well documented; however, computed tomography (CT) evidence of gaseous necrosis in the absence of fistulation with bowel has not yet been described. We report three cases of ovarian adenocarcinoma that on CT showed evidence of gross gaseous necrosis, mimicking a pelvic abscess.

Prospective evaluation of radionuclide scanning in detection of intestinal necrosis in neonatal necrotizing enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haase, G.M.; Sfakianakis, G.N.; Lobe, T.E.

1981-06-01

The ability of external imaging to demonstrate intestinal infarction in neonatal necrotizing enterocolitis (NEC) was prospectively evaluated. The radiopharmaceutical technetium--99m diphosphonate was injected intravenously and the patients subsequently underwent abdominal scanning. Clinical patient care and interpretation of the images were entirely independent throughout the study. Of 33 studies, 7 were positive, 4 were suspicious, and 22 were negative. One false positive study detected ischemia without transmural infarction. The second false positive scan occurred postoperatively and was due to misinterpretation of the hyperactivity along the surgical incision. None of the suspicious cases had damaged bowel. The two false negative studies clearlymore » failed to demonstrate frank intestinal necrosis. The presence of very small areas of infarction, errors in technical settings, subjective interpretation of scans and delayed clearance of the radionuclide in a critically ill neonate may all limit the accuracy of external abdominal scanning. However, in spite of an error rate of 12%, it is likely that this technique will enhance the present clinical, laboratory, and radiologic parameters of patient management in NEC.« less

Factors influencing notching and necrosis of Dracaena deremensis Warneckii foliage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conover, C.A.; Poole, R.T.

1973-01-01

Quality of Dracaena deremensis Warneckii Engler. cuttings imported from Puerto Rico deteriorated during propagation and growing in commercial nurseries in Apopka, Florida. Foliage became necrotic with reddish brown spots occurring along edges, particularly in the white areas. As plants increased in size, notches occurred in the leaves. Tissue analyses indicated that Ca and Cu content decreased, F increased and Mg, Fe, Zn and Mn increased then decreased with time from importation. To determine possible method of alleviating the notching and necrosis, three 3x2x2 factorial experiments were established in 3 shade levels. Varying rates of boron, Osmocote (18-6-12) and Perk, amore » micronutrient blend, were applied to rooted Warneckii. Osmocote and Perk levels had no effect on necrosis or notching. Increasing light increased necrosis and increasing B decreased no. of notched leaves of plants grown under 80% shade. 11 references, 4 tables.« less

In vitro and in vivo expression of interleukin-1alpha and tumor necrosis factor-alpha mRNA in pemphigus vulgaris: interleukin-1alpha and tumor necrosis factor-alpha are involved in acantholysis.

PubMed

Feliciani, C; Toto, P; Amerio, P; Pour, S M; Coscione, G; Shivji, G; Wang, B; Sauder, D N

2000-01-01

Keratinocyte-derived cytokines have been implicated in the pathogenesis of a number of skin diseases. In this study we examined the possible role of keratinocyte-derived cytokines in the development of acantholysis in pemphigus vulgaris. Nineteen patients with pemphigus vulgaris, demonstrating the characteristic clinical, pathologic, and immunopathologic findings were studied. In situ immunolabeling demonstrated the presence of two cytokines interleukin-1alpha and tumor necrosis factor-alpha, in lesional and perilesional areas. Results were confirmed by reverse transcriptase-polymerase chain reaction, demonstrating overexpression of both cytokines in vivo. To study the role of these cytokines in the pathogenesis of pemphigus vulgaris both in vitro and in vivo studies were performed. The results of the in vitro study demonstrated that pemphigus vulgaris IgG induced interleukin-1alpha and tumor necrosis factor-alpha mRNA in the skin. The potential pathogenic role of these mediators was demonstrated by a blocking study using antibodies against human interleukin-1alpha and tumor necrosis factor-alpha in keratinocytes cultures. A combination of anti-interleukin-1alpha and anti-tumor necrosis factor-alpha antibodies inhibited in vitro pemphigus vulgaris IgG induced acantholysis. To confirm the role of interleukin-1 and tumor necrosis factor-alpha in pemphigus, we utilized passive transfer studies using interleukin-1 deficient mice (ICE-/-, interleukin-1beta-/-) and tumor necrosis factor-alpha receptor deficient mice (TNFR1R2-/-). Both groups demonstrated a decreased susceptibility to the passive transfer of pemphigus. Our data support the role of cytokines interleukin-1 and tumor necrosis factor-alpha in the pathogenesis of pemphigus vulgaris.

SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis.

PubMed

Choi, Seon-Guk; Kim, Hyunjoo; Jeong, Eun Il; Lee, Ho-June; Park, Sungwoo; Lee, Song-Yi; Lee, Hyeon-Jeong; Lee, Seong Won; Chung, Chin Ha; Jung, Yong-Keun

2017-01-15

Fas-associated protein with death domain (FADD) plays a key role in extrinsic apoptosis. Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis caused by calcium ionophore A23187 and by ischemic damage. SUMOylated FADD bound to dynamin-related protein 1 (Drp1) in cells both in vitro and in ischemic tissue damage cores, thus promoting Drp1 recruitment by mitochondrial fission factor (Mff) to accomplish mitochondrial fragmentation. Mitochondrial-fragmentation-associated necrosis was blocked by FADD or Drp1 deficiency and SUMO-defective FADD expression. Interestingly, caspase-10, but not caspase-8, formed a ternary protein complex with SUMO-FADD/Drp1 on the mitochondria upon exposure to A23187 and potentiated Drp1 oligomerization for necrosis. Moreover, the caspase-10 L285F and A414V mutants, found in autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma, respectively, regulated this necrosis. Our study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis, providing insights into the mechanism of regulated necrosis by calcium overload and ischemic injury. Copyright © 2017 American Society for Microbiology.

SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis

PubMed Central

Choi, Seon-Guk; Kim, Hyunjoo; Jeong, Eun Il; Lee, Ho-June; Park, Sungwoo; Lee, Song-Yi; Lee, Hyeon-Jeong; Lee, Seong Won; Chung, Chin Ha

2016-01-01

ABSTRACT Fas-associated protein with death domain (FADD) plays a key role in extrinsic apoptosis. Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis caused by calcium ionophore A23187 and by ischemic damage. SUMOylated FADD bound to dynamin-related protein 1 (Drp1) in cells both in vitro and in ischemic tissue damage cores, thus promoting Drp1 recruitment by mitochondrial fission factor (Mff) to accomplish mitochondrial fragmentation. Mitochondrial-fragmentation-associated necrosis was blocked by FADD or Drp1 deficiency and SUMO-defective FADD expression. Interestingly, caspase-10, but not caspase-8, formed a ternary protein complex with SUMO-FADD/Drp1 on the mitochondria upon exposure to A23187 and potentiated Drp1 oligomerization for necrosis. Moreover, the caspase-10 L285F and A414V mutants, found in autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma, respectively, regulated this necrosis. Our study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis, providing insights into the mechanism of regulated necrosis by calcium overload and ischemic injury. PMID:27799292

Tumour necrosis factor-α/interleukin-10 ratio in patients with obstructive sleep apnoea hypopnoea syndrome.

PubMed

Jiang, H; Cao, H; Wang, P; Liu, W; Cao, F; Chen, J

2015-01-01

To explore the significance of the tumour necrosis factor-α/interleukin-10 ratio and the effect of continuous positive airway pressure in patients with different degrees of obstructive sleep apnoea hypopnoea syndrome severity. This study comprised 135 patients with obstructive sleep apnoea hypopnoea syndrome and 94 control subjects. Tumour necrosis factor-α and tumour necrosis factor-α/interleukin-10 ratio values were significantly higher in the obstructive sleep apnoea hypopnoea syndrome group than in the control group, but interleukin-10 was significantly lower. Tumour necrosis factor-α/interleukin-10 ratio values increased in line with the severity of obstructive sleep apnoea hypopnoea syndrome. In multivariate analysis, the tumour necrosis factor-α/interleukin-10 ratio correlated positively with the apnoea-hypopnoea index and all indices of obstructive sleep apnoea hypopnoea syndrome, except for age, body mass index and neck circumference. After one month of continuous positive airway pressure therapy, levels of tumour necrosis factor-α decreased; interleukin-10 showed no change. The results suggest that inflammation is activated and anti-inflammatory cytokines are decreased in obstructive sleep apnoea hypopnoea syndrome patients. Tumour necrosis factor-α/interleukin-10 ratio may prove useful for severity monitoring and management of obstructive sleep apnoea hypopnoea syndrome patients, and may reduce the need for polysomnography.

Navigation to the graveyard-induction of various pathways of necrosis and their classification by flow cytometry.

PubMed

Janko, Christina; Munoz, Luis; Chaurio, Ricardo; Maueröder, Christian; Berens, Christian; Lauber, Kirsten; Herrmann, Martin

2013-01-01

Apoptosis and necrosis reflect the program of cell death employed by a dying cell and the final stage of death, respectively. Whereas apoptosis is defined as a physiological, highly organized cell death process, necrosis is commonly considered to be accidental and uncontrolled. Physiological and weak pathological death stimuli preferentially induce apoptosis, while harsh non-physiological insults often immediately instigate (primary) necrosis. If an apoptosing cell transits into a phase of plasma membrane disintegration, this stage of death is referred to as secondary or post-apoptotic necrosis.Here, we present several conditions that stimulate primary and/or secondary necrosis and show that necrosis displays considerably different time courses. For subclassification of necrotic phenotypes we employed a flow cytometric single-tube 4-color staining technique including annexin A5-FITC, propidium iodide, DiIC1(5), and Hoechst 33342.

Protective effects of batimastat against hemorrhagic injuries in delayed jellyfish envenomation syndrome models.

PubMed

Wang, Beilei; Liu, Dan; Liu, Guoyan; Zhang, Xin; Wang, Qianqian; Zheng, Jiemin; Zhou, Yonghong; He, Qian; Zhang, Liming

2015-12-15

Previously, we established delayed jellyfish envenomation syndrome (DJES) models and proposed that the hemorrhagic toxins in jellyfish tentacle extracts (TE) play a significant role in the liver and kidney injuries of the experimental model. Further, we also demonstrated that metalloproteinases are the central toxic components of the jellyfish Cyanea capillata (C. capillata), which may be responsible for the hemorrhagic effects. Thus, metalloproteinase inhibitors appear to be a promising therapeutic alternative for the treatment of hemorrhagic injuries in DJES. In this study, we examined the metalloproteinase activity of TE from the jellyfish C. capillata using zymography analyses. Our results confirmed that TE possessed a metalloproteinase activity, which was also sensitive to heat. Then, we tested the effect of metalloproteinase inhibitor batimastat (BB-94) on TE-induced hemorrhagic injuries in DJES models. Firstly, using SR-based X-ray microangiography, we found that BB-94 significantly improved TE-induced hepatic and renal microvasculature alterations in DJES mouse model. Secondly, under synchrotron radiation micro-computed tomography (SR-μCT), we also confirmed that BB-94 reduced TE-induced hepatic and renal microvasculature changes in DJES rat model. In addition, being consistent with the imaging results, histopathological and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL)-like staining observations also clearly corroborated this hypothesis, as BB-94 was highly effective in neutralizing TE-induced extensive hemorrhage and necrosis in DJES rat model. Although it may require further clinical studies in the near future, the current study opens up the possibilities for the use of the metalloproteinase inhibitor, BB-94, in the treatment of multiple organ hemorrhagic injuries in DJES. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Focal neuronal gigantism: a rare complication of therapeutic radiation.

PubMed

Gaughen, J R; Bourne, T D; Aregawi, D; Shah, L M; Schiff, D

2009-11-01

Radiation therapy, a mainstay in the treatment of many brain tumors, results in a variety of well-documented acute and chronic complications. Isolated cortical damage following irradiation represents an extremely rare delayed therapeutic complication, described only twice in the medical literature. We report this rare delayed complication in a patient following treatment of a right frontal anaplastic oligodendroglioma.

Detection of contraband using microwave radiation

DOEpatents

Toth, Richard P.; Loubriel, Guillermo M.; Bacon, Larry D.; Watson, Robert D.

2002-01-01

The present invention relates to a method and system for using microwave radiation to detect contraband hidden inside of a non-metallic container, such as a pneumatic vehicle tire. The method relies on the attenuation, retardation, time delay, or phase shift of microwave radiation as it passes through the container plus the contraband. The method is non-invasive, non-destructive, low power, and does not require physical contact with the container.

RIP3: a molecular switch for necrosis and inflammation

PubMed Central

Moriwaki, Kenta; Chan, Francis Ka-Ming

2013-01-01

The receptor-interacting protein kinase 3 (RIP3/RIPK3) has emerged as a critical regulator of programmed necrosis/necroptosis, an inflammatory form of cell death with important functions in pathogen-induced and sterile inflammation. RIP3 activation is tightly regulated by phosphorylation, ubiquitination, and caspase-mediated cleavage. These post-translational modifications coordinately regulate the assembly of a macromolecular signaling complex termed the necrosome. Recently, several reports indicate that RIP3 can promote inflammation independent of its pronecrotic activity. Here, we review our current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases. PMID:23913919

Generation of tunable infrared radiation by stimulated Raman scattering on hydrogen in a prism-lens optical delay line

NASA Astrophysics Data System (ADS)

Andreev, R. B.; Butylkin, V. S.; Evtiushkin, V. A.; Fisher, P. S.; Khabarov, V. V.

1983-03-01

The threshold of stimulated Raman scattering was lowered by filling an optical delay line with hydrogen. Pumping was by a tunable neodymium laser. Lens-prism combinations were used as phase correctors in the delay line. The dependences of the energy of the Stokes component on the pump energy determined experimentally for different numbers of transits through the delay line were compared with the results of a calculation allowing for the losses in the components of this line. When the frequency conversion was by a factor of at least 2 and the tuning range was wide (tens of percent), the optimal performance was obtained from the optical delay line when total-internal-reflection prisms and lenses were combined in a single component and oriented at the Brewster angle.

[S3 Guideline. Part 3: Non-Traumatic Avascular Necrosis in Adults - Surgical Treatment of Atraumatic Avascular Femoral Head Necrosis in Adults].

PubMed

Maus, U; Roth, A; Tingart, M; Rader, C; Jäger, M; Nöth, U; Reppenhagen, S; Heiss, C; Beckmann, J

2015-10-01

The present article describes the guidelines for the surgical treatment of atraumatic avascular necrosis (aFKN). These include joint preserving and joint replacement procedures. As part of the targeted literature, 43 publications were included and evaluated to assess the surgical treatment. According to the GRADE and SIGN criteria level of evidence (LoE), grade of recommendation (EC) and expert consensus (EK) were listed for each statement and question. The analysed studies have shown that up to ARCO stage III, joint-preserving surgery can be performed. A particular joint-preserving surgery currently cannot be recommended as preferred method. The selection of the method depends on the extent of necrosis. Core decompression performed in stage ARCO I (reversible early stage) or stage ARCO II (irreversible early stage) with medial or central necrosis with an area of less than 30 % of the femoral head shows better results than conservative therapy. In ARCO stage III with infraction of the femoral head, the core decompression can be used for a short-term pain relief. For ARCO stage IIIC or stage IV core decompression should not be performed. In these cases, the indication for implantation of a total hip replacement should be checked. Additional therapeutic procedures (e.g., osteotomies) and innovative treatment options (advanced core decompression, autologous bone marrow, bone grafting, etc.) can be discussed in the individual case. In elective hip replacement complications and revision rates have been clearly declining for decades. In the case of an underlying aFKN, however, previous joint-preserving surgery (osteotomies and grafts in particular) can complicate the implantation of a THA significantly. However, the implant life seems to be dependent on the aetiology. Higher revision rates for avascular necrosis are particularly expected in sickle cell disease, Gaucher disease, or kidney transplantation patients. Furthermore, the relatively young age of the patient

Human-specific bacterial pore-forming toxins induce programmed necrosis in erythrocytes.

PubMed

LaRocca, Timothy J; Stivison, Elizabeth A; Hod, Eldad A; Spitalnik, Steven L; Cowan, Peter J; Randis, Tara M; Ratner, Adam J

2014-08-26

A subgroup of the cholesterol-dependent cytolysin (CDC) family of pore-forming toxins (PFTs) has an unusually narrow host range due to a requirement for binding to human CD59 (hCD59), a glycosylphosphatidylinositol (GPI)-linked complement regulatory molecule. hCD59-specific CDCs are produced by several organisms that inhabit human mucosal surfaces and can act as pathogens, including Gardnerella vaginalis and Streptococcus intermedius. The consequences and potential selective advantages of such PFT host limitation have remained unknown. Here, we demonstrate that, in addition to species restriction, PFT ligation of hCD59 triggers a previously unrecognized pathway for programmed necrosis in primary erythrocytes (red blood cells [RBCs]) from humans and transgenic mice expressing hCD59. Because they lack nuclei and mitochondria, RBCs have typically been thought to possess limited capacity to undergo programmed cell death. RBC programmed necrosis shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and RIP1 phosphorylation, necrosome assembly, and restriction by caspase-8. Death due to programmed necrosis in RBCs is executed by acid sphingomyelinase-dependent ceramide formation, NADPH oxidase- and iron-dependent reactive oxygen species formation, and glycolytic formation of advanced glycation end products. Bacterial PFTs that are hCD59 independent do not induce RBC programmed necrosis. RBC programmed necrosis is biochemically distinct from eryptosis, the only other known programmed cell death pathway in mature RBCs. Importantly, RBC programmed necrosis enhances the growth of PFT-producing pathogens during exposure to primary RBCs, consistent with a role for such signaling in microbial growth and pathogenesis. In this work, we provide the first description of a new form of programmed cell death in erythrocytes (RBCs) that occurs as a consequence of cellular attack by human-specific bacterial toxins. By defining a new RBC

Spinal bone marrow necrosis with vertebral compression fracture: differentiation of BMN from AVN.

PubMed

Nix, J S; Fitzgerald, R T; Samant, R S; Harrison, M; Angtuaco, E J

2014-09-01

Bone marrow necrosis (BMN) is a rare malignancy-associated hematologic disorder characterized by necrosis of myeloid and stromal marrow elements with preservation of cortical bone. Overlap between the imaging appearances of BMN and avascular necrosis (AVN) raises the potential for diagnostic confusion. We report a case of BMN presenting with a traumatic multi-level vertebral body collapse, and finding that may potentially confound distinction between the two entities. We discuss important pathophysiologic, clinical, and radiologic differences between BMN and AVN with emphasis on features important in the differential diagnosis.

Latitude-dependent delay in the responses of the equatorial electrojet and Sq currents to X-class solar flares

NASA Astrophysics Data System (ADS)

Nogueira, Paulo A. B.; Abdu, Mangalathayil A.; Souza, Jonas R.; Denardini, Clezio M.; Barbosa Neto, Paulo F.; Serra de Souza da Costa, João P.; Silva, Ana P. M.

2018-01-01

We have analyzed low-latitude ionospheric current responses to two intense (X-class) solar flares that occurred on 13 May 2013 and 11 March 2015. Sudden intensifications, in response to solar flare radiation impulses, in the Sq and equatorial electrojet (EEJ) currents, as detected by magnetometers over equatorial and low-latitude sites in South America, are studied. In particular we show for the first time that a 5 to 8 min time delay is present in the peak effect in the EEJ, with respect that of Sq current outside the magnetic equator, in response to the flare radiation enhancement. The Sq current intensification peaks close to the flare X-ray peak, while the EEJ peak occurs 5 to 8 min later. We have used the Sheffield University Plasmasphere-Ionosphere Model at National Institute for Space Research (SUPIM-INPE) to simulate the E-region conductivity enhancement as caused by the flare enhanced solar extreme ultraviolet (EUV) and soft X-rays flux. We propose that the flare-induced enhancement in neutral wind occurring with a time delay (with respect to the flare radiation) could be responsible for a delayed zonal electric field disturbance driving the EEJ, in which the Cowling conductivity offers enhanced sensitivity to the driving zonal electric field.

Aseptic Bone Necrosis Among U.S. Navy Divers: Survey of 934 Nonrandomly Selected Personnel

DTIC Science & Technology

1977-06-01

Health, Education, and Welfare, Washington, D.C. Kawashima, M., T. Torisu, K. Hayashi, and Y. Kamo. 1974. Avascular bone necrosis in Japanese diving...5ÜL ^4- P=- 7 RESEM^a^ATORY SUBMARINE BASE, GROTON, CONN. REPORT NUMBER 854 ASEPTIC BONE NECROSIS AMONG U. S. NAVY DIVERS: Survey of 934...Approved for public release; distribution unlimited SUMMARY PAGE THE PROBLEM Aseptic boire~ necrosis tABN) has beelTknown toT5e~ associated with

AGN Space Telescope and Optical Reverberation Mapping Project. IV. Velocity-Delay Mapping of Broad Emission Lines in NGC 5548

NASA Astrophysics Data System (ADS)

Horne, Keith D.; Agn Storm Team

2015-01-01

Two-dimensional velocity-delay maps of AGN broad emission line regions can be recovered by modelling observations of reverberating emission-line profiles on the assumption that the line profile variations are driven by changes in ionising radiation from a compact source near the black hole. The observable light travel time delay resolves spatial structure on iso-delay paraboloids, while the doppler shift resolves kinematic structure along the observer's line-of-sight. Velocity-delay maps will be presented and briefly discussed for the Lyman alpha, CIV and Hbeta line profiles based on the HST and ground-based spectrophotometric monitoring of NGC 5548 during the 2014 AGN STORM campaign.

Hydrodynamic Determinants of Cell Necrosis and Molecular Delivery Produced by Pulsed Laser Microbeam Irradiation of Adherent Cells

PubMed Central

Compton, Jonathan L.; Hellman, Amy N.; Venugopalan, Vasan

2013-01-01

Time-resolved imaging, fluorescence microscopy, and hydrodynamic modeling were used to examine cell lysis and molecular delivery produced by picosecond and nanosecond pulsed laser microbeam irradiation in adherent cell cultures. Pulsed laser microbeam radiation at λ = 532 nm was delivered to confluent monolayers of PtK2 cells via a 40×, 0.8 NA microscope objective. Using laser microbeam pulse durations of 180–1100 ps and pulse energies of 0.5–10.5 μJ, we examined the resulting plasma formation and cavitation bubble dynamics that lead to laser-induced cell lysis, necrosis, and molecular delivery. The cavitation bubble dynamics are imaged at times of 0.5 ns to 50 μs after the pulsed laser microbeam irradiation, and fluorescence assays assess the resulting cell viability and molecular delivery of 3 kDa dextran molecules. Reductions in both the threshold laser microbeam pulse energy for plasma formation and the cavitation bubble energy are observed with decreasing pulse duration. These energy reductions provide for increased precision of laser-based cellular manipulation including cell lysis, cell necrosis, and molecular delivery. Hydrodynamic analysis reveals critical values for the shear-stress impulse generated by the cavitation bubble dynamics governs the location and spatial extent of cell necrosis and molecular delivery independent of pulse duration and pulse energy. Specifically, cellular exposure to a shear-stress impulse J≳0.1 Pa s ensures cell lysis or necrosis, whereas exposures in the range of 0.035≲J≲0.1 Pa s preserve cell viability while also enabling molecular delivery of 3 kDa dextran. Exposure to shear-stress impulses of J≲0.035 Pa s leaves the cells unaffected. Hydrodynamic analysis of these data, combined with data from studies of 6 ns microbeam irradiation, demonstrates the primacy of shear-stress impulse in determining cellular outcome resulting from pulsed laser microbeam irradiation spanning a nearly two

Leveraging delay discounting for health: Can time delays influence food choice?

PubMed

Appelhans, Bradley M; French, Simone A; Olinger, Tamara; Bogucki, Michael; Janssen, Imke; Avery-Mamer, Elizabeth F; Powell, Lisa M

2018-07-01

Delay discounting, the tendency to choose smaller immediate rewards over larger delayed rewards, is theorized to promote consumption of immediately rewarding but unhealthy foods at the expense of long-term weight maintenance and nutritional health. An untested implication of delay discounting models of decision-making is that selectively delaying access to less healthy foods may promote selection of healthier (immediately available) alternatives, even if they may be less desirable. The current study tested this hypothesis by measuring healthy versus regular vending machine snack purchasing before and during the implementation of a 25-s time delay on the delivery of regular snacks. Purchasing was also examined under a $0.25 discount on healthy snacks, a $0.25 tax on regular snacks, and the combination of both pricing interventions with the 25-s time delay. Across 32,019 vending sales from three separate vending locations, the 25-s time delay increased healthy snack purchasing from 40.1% to 42.5%, which was comparable to the impact of a $0.25 discount (43.0%). Combining the delay and the discount had a roughly additive effect (46.0%). However, the strongest effects were seen under the $0.25 tax on regular snacks (53.7%) and the combination of the delay and the tax (50.2%). Intervention effects varied substantially between vending locations. Importantly, time delays did not harm overall vending sales or revenue, which is relevant to the real-world feasibility of this intervention. More investigation is needed to better understand how the impact of time delays on food choice varies across populations, evaluate the effects of time delays on beverage vending choices, and extend this approach to food choices in contexts other than vending machines. ClinicalTrials.gov, NCT02359916. Copyright © 2018 Elsevier Ltd. All rights reserved.

Trigger wrist caused by avascular necrosis of the capitate: a case report.

PubMed

Matsui, Yuichiro; Kawamura, Daisuke; Kida, Hiroaki; Hatanaka, Kanako C; Iwasaki, Norimasa

2018-03-27

Trigger wrist is a rare condition first described by Marti in 1960, and various causes have been reported. The condition mostly occurs with finger flexion and extension, and rarely with flexion and extension of the wrist itself. Avascular necrosis of the capitate is also a rare condition, first described by Jönsson in 1942. While some reports of this condition have been published, little is known about its etiology. Therefore, no established treatment exists. We report a case of trigger wrist caused by avascular necrosis of the capitate. A 16-year-old right-handed male who was a high school handball player was referred to our department from a nearby hospital 5 months after the onset of pain in the dorsal aspect of the right wrist, with an unknown cause. At the previous hospital, imaging findings led to a diagnosis of avascular necrosis of the capitate, and conservative treatment with a wrist brace did not improve the pain. At the initial visit to our department, the patient was noted to have a painful trigger wrist that was brought on by wrist flexion and extension. Preoperative imaging findings led to a diagnosis of trigger wrist caused by capitolunate instability secondary to avascular necrosis of the capitate. We performed a partial excision of the proximal capitate with tendon ball interposition. Two years after surgery, the patient's clinical outcome was favorable, with no recurrence of wrist pain or triggering. Both trigger wrist and avascular necrosis of the capitate are rare disorders. When a patient presents with painful triggering at the wrist, surgeons must bear in mind that avascular necrosis of the capitate may result in this phenomenon. We recommend partial excision of the proximal capitate with tendon ball interposition for the treatment of this lesion.

Acute retinal necrosis as a novel complication of chickenpox in adults.

PubMed Central

Matsuo, T; Koyama, M; Matsuo, N

1990-01-01

Three patients in their 20s suffered from chickenpox while in an immunocompromised state: one in pregnancy, one during a long course of corticosteroid for severe nephrotic syndrome, and the third with repeated upper airway infection due to bronchiectasis. They developed acute retinal necrosis about three weeks after the onset of chickenpox. Since acute retinal necrosis threatens sight, this unusual complication of chickenpox in adults needs serious consideration. Images PMID:2378860

Postoperative pneumatosis intestinalis (PI) and portal venous gas (PVG) may indicate bowel necrosis: a 52-case study.

PubMed

Higashizono, Kazuya; Yano, Hideaki; Miyake, Ouki; Yamasawa, Kunihiro; Hashimoto, Masanori

2016-07-08

The significance of pneumatosis intestinalis (PI) and portal venous gas (PVG) is controversial. This retrospective study evaluated the risk factors for bowel necrosis in patients with PI and/or PVG. Between 2002 and 2015, 52 patients were diagnosed with PI and/or PVG and were included in this study. The patients were classified according to the presence or absence of bowel necrosis in surgical findings or at autopsy. Patient characteristics and clinical findings related to bowel necrosis were investigated. Bowel necrosis was diagnosed in 17 (32.7 %) patients. Amongst these 17, 10 patients received salvage surgical intervention, and seven of those diagnosed with bowel necrosis survived after the operation. The remaining 35 patients received conservative treatment with or without exploratory laparotomy. Between patients with and without bowel necrosis, laboratory data revealed significant differences in the levels of C-reactive protein (P = 0.0038), creatinine (P = 0.0054), and lactate (P = 0.045); clinical findings showed differences in abdominal pain (P = 0.019) and peritoneal irritation signs (P = 0.016); computed tomography detected ascites (P = 0.011) and changes of bowel wall enhancement (P = 0.03) that were significantly higher in patients with bowel necrosis. The rate of PI and/or PVG detected in patients postoperatively was significantly higher in patients with bowel necrosis (P < 0.0001). Multivariate analysis showed that bowel necrosis was significantly more likely when PI or PVG was detected in postoperative patients than in patients who had not had surgery (P = 0.003). PI and/or PVG, alone, are not automatically indicative of bowel necrosis. However, when these conditions occur postoperatively, they indicate bowel necrosis requiring reoperation.

Subclinical myocardial necrosis and cardiovascular risk in stable patients undergoing elective cardiac evaluation.

PubMed

Tang, W H Wilson; Wu, Yuping; Nicholls, Stephen J; Brennan, Danielle M; Pepoy, Michael; Mann, Shirley; Pratt, Alan; Van Lente, Frederick; Hazen, Stanley L

2010-03-01

The presence of subclinical myocardial necrosis as a prodrome to longer-term adverse cardiac event risk has been debated. The debate has focused predominantly within patients with acute coronary syndrome, and on issues of troponin assay variability and accuracy of detection, rather than on the clinical significance of the presence of subclinical myocardial necrosis (ie, "troponin leak") within stable cardiac patients. Herein, we examine the relationship between different degrees of subclinical myocardial necrosis and long-term adverse clinical outcomes within a stable cardiac patient population with essentially normal renal function. Sequential consenting patients (N=3828; median creatinine clearance, 100 mL/min/1.73m(2)) undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (<0.03 ng/mL) were evaluated. The relationship of subclinical myocardial necrosis with incident major adverse cardiovascular events (defined as any death, myocardial infarction, or stroke) over 3-year follow-up was examined. "Probable" (cTnI 0.001-0.008 ng/mL) and "definite" (cTnI 0.009-0.029 ng/mL) subclinical myocardial necrosis were observed frequently within the cohort (34% and 18%, respectively). A linear relationship was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident major adverse cardiovascular events, particularly in those with cTnI 0.009 ng/mL or higher (hazard ratio, 3.00; 95% confidence interval, 2.4-3.8), even after adjustment for traditional risk factors, C-reactive protein, and creatinine clearance. The presence of subclinical myocardial necrosis was associated with elevations in acute phase proteins (C-reactive protein, ceruloplasmin; P<0.01 each) and reduction in systemic antioxidant enzyme activities (arylesterase; P<0.01) but showed no significant associations with multiple specific measures of oxidant stress, and showed borderline

Constraints on Horndeski theory using the observations of Nordtvedt effect, Shapiro time delay and binary pulsars

NASA Astrophysics Data System (ADS)

Hou, Shaoqi; Gong, Yungui

2018-03-01

Alternative theories of gravity not only modify the polarization contents of the gravitational wave, but also affect the motions of the stars and the energy radiated away via the gravitational radiation. These aspects leave imprints in the observational data, which enables the test of general relativity and its alternatives. In this work, the Nordtvedt effect and the Shapiro time delay are calculated in order to constrain Horndeski theory using the observations of lunar laser ranging experiments and Cassini time-delay data. The effective stress-energy tensor is also obtained using the method of Isaacson. Gravitational wave radiation of a binary system is calculated, and the change of the period of a binary system is deduced for the elliptical orbit. These results can be used to set constraints on Horndeski theory with the observations of binary systems, such as PSR J1738 + 0333. Constraints have been obtained for some subclasses of Horndeski theory, in particular, those satisfying the gravitational wave speed limits from GW170817 and GRB 170817A.

Channel catfish response to ultraviolet-B radiation

USGS Publications Warehouse

Ewing, M.S.; Blazer, V.S.; Fabacher, D.L.; Little, E.E.; Kocan, K.M.

1999-01-01

Fingerling channel catfish Ictalurus punctatus exposed to simulated ultraviolet-B radiation at an average daily dose of 2.9 J/cm2 were quite sensitive to the radiation. After a 24-h exposure, thinning of the most dorsal epidermis frequently was accompanied by edema. Compared with epidermis of unexposed fish, mucous cells in exposed fish were less superficial and club cells were less numerous both dorsally and high on the lateral surface of the body. Sunburn cells with pyknotic nuclei were evident in the epidermis of exposed fish. Among fish exposed for 48 h, focal necrosis and sloughing of the outer epidermal layer were widespread. A methanol-extractable skin substance that is associated with resistance to sunburn in other fish species was not detected in channel catfish.

Representing delayed force feedback as a combination of current and delayed states.

PubMed

Avraham, Guy; Mawase, Firas; Karniel, Amir; Shmuelof, Lior; Donchin, Opher; Mussa-Ivaldi, Ferdinando A; Nisky, Ilana

2017-10-01

To adapt to deterministic force perturbations that depend on the current state of the hand, internal representations are formed to capture the relationships between forces experienced and motion. However, information from multiple modalities travels at different rates, resulting in intermodal delays that require compensation for these internal representations to develop. To understand how these delays are represented by the brain, we presented participants with delayed velocity-dependent force fields, i.e., forces that depend on hand velocity either 70 or 100 ms beforehand. We probed the internal representation of these delayed forces by examining the forces the participants applied to cope with the perturbations. The findings showed that for both delayed forces, the best model of internal representation consisted of a delayed velocity and current position and velocity. We show that participants relied initially on the current state, but with adaptation, the contribution of the delayed representation to adaptation increased. After adaptation, when the participants were asked to make movements with a higher velocity for which they had not previously experienced with the delayed force field, they applied forces that were consistent with current position and velocity as well as delayed velocity representations. This suggests that the sensorimotor system represents delayed force feedback using current and delayed state information and that it uses this representation when generalizing to faster movements. NEW & NOTEWORTHY The brain compensates for forces in the body and the environment to control movements, but it is unclear how it does so given the inherent delays in information transmission and processing. We examined how participants cope with delayed forces that depend on their arm velocity 70 or 100 ms beforehand. After adaptation, participants applied opposing forces that revealed a partially correct representation of the perturbation using the current and the

Arsenic trioxide-induced osteo-necrosis treatment in a child: mini-review and case report.

PubMed

Marty, M; Noirrit-Esclassan, E; Diemer, F

2016-10-01

Arsenic oxide compounds were traditionally used as devitalizing agents. Due to its toxicity, leakage of such compounds into the periodontium can cause gingival and osteo-necrosis. Their use is forbidden in Europe and the USA for decades, however, some dentists seem to still use it. We report the case of a 14-year-old girl referred to the paediatric dentistry department of Toulouse University hospital, France, presenting a bone necrosis following the use of an arsenic trioxide product to accelerate pulp necrosis. The treatment included surgical removal of necrosis bone sequestrum, complete pulpectomy and an intermediate restoration of the tooth 27. After 1 week, the clinical conditions greatly improved. A restoration using a ceramic crown was performed after 2 months, and complete healing was observed after 1 year follow-up. Although arsenic trioxide is neither appropriate nor permitted for use in modern dentistry, especially in paediatric dentistry, some rare cases of arsenic-induced osteo-necrosis can still be encountered. A clearer message must be given to all dental practitioners against the use of arsenic trioxide in modern endodontic treatment.

Genetic inhibition of protein kinase Cε attenuates necrosis in experimental pancreatitis

PubMed Central

Liu, Yannan; Tan, Tanya; Jia, Wenzhuo; Lugea, Aurelia; Mareninova, Olga; Waldron, Richard T.; Pandol, Stephen J.

2014-01-01

Understanding the regulation of death pathways, necrosis and apoptosis, in pancreatitis is important for developing therapies directed to the molecular pathogenesis of the disease. Protein kinase Cε (PKCε) has been previously shown to regulate inflammatory responses and zymogen activation in pancreatitis. Furthermore, we demonstrated that ethanol specifically activated PKCε in pancreatic acinar cells and that PKCε mediated the sensitizing effects of ethanol on inflammatory response in pancreatitis. Here we investigated the role of PKCε in the regulation of death pathways in pancreatitis. We found that genetic deletion of PKCε resulted in decreased necrosis and severity in the in vivo cerulein-induced pancreatitis and that inhibition of PKCε protected the acinar cells from CCK-8 hyperstimulation-induced necrosis and ATP reduction. These findings were associated with upregulation of mitochondrial Bak and Bcl-2/Bcl-xL, proapoptotic and prosurvival members in the Bcl-2 family, respectively, as well as increased mitochondrial cytochrome c release, caspase activation, and apoptosis in pancreatitis in PKCε knockout mice. We further confirmed that cerulein pancreatitis induced a dramatic mitochondrial translocation of PKCε, suggesting that PKCε regulated necrosis in pancreatitis via mechanisms involving mitochondria. Finally, we showed that PKCε deletion downregulated inhibitors of apoptosis proteins, c-IAP2, survivin, and c-FLIPs while promoting cleavage/inactivation of receptor-interacting protein kinase (RIP). Taken together, our findings provide evidence that PKCε activation during pancreatitis promotes necrosis through mechanisms involving mitochondrial proapoptotic and prosurvival Bcl-2 family proteins and upregulation of nonmitochondrial pathways that inhibit caspase activation and RIP cleavage/inactivation. Thus PKCε is a potential target for prevention and/or treatment of acute pancreatitis. PMID:25035113

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

Prediction and measurement of thermally induced cambial tissue necrosis in tree stems

Treesearch

Joshua L. Jones; Brent W. Webb; Bret W. Butler; Matthew B. Dickinson; Daniel Jimenez; James Reardon; Anthony S. Bova

2006-01-01

A model for fire-induced heating in tree stems is linked to a recently reported model for tissue necrosis. The combined model produces cambial tissue necrosis predictions in a tree stem as a function of heating rate, heating time, tree species, and stem diameter. Model accuracy is evaluated by comparison with experimental measurements in two hardwood and two softwood...

Carbohydrate and ethane release with Erwinia carotovora subspecies betavasculorum--induced necrosis.

PubMed

Kuykendall, L David; Hunter, William J

2008-02-01

Erwinia carotovora subspecies betavasculorum, also known as E. betavasculorum and Pectobacterium betavasculorum, is a soil bacterium that has the capacity to cause root rot necrosis of sugarbeets. The qualitatively different pathogenicity exhibited by the virulent E. carotovora strain and two avirulent strains, a Citrobacter sp. and an Enterobacter cloacae, was examined using digital analysis of photographic evidence of necrosis as well as for carbohydrate, ethane, and ethylene release compared with uninoculated potato tuber slices. Visual scoring of necrosis was superior to digital analysis of photographs. The release of carbohydrates and ethane from potato tuber slices inoculated with the soft rot necrosis-causing Erwinia was significantly greater than that of potato tuber slices that had not been inoculated or that had been inoculated with the nonpathogenic E. cloacae and Citrobacter sp. strains. Interestingly, ethylene production from potato slices left uninoculated or inoculated with the nonpathogenic Citrobacter strain was 5- to 10-fold higher than with potato slices inoculated with the pathogenic Erwinia strain. These findings suggest that (1) carbohydrate release might be a useful measure of the degree of pathogenesis, or relative virulence; and that (2) bacterial suppression of ethylene formation may be a critical step in root rot disease formation.

Radiation-induced genomic instability: radiation quality and dose response

NASA Technical Reports Server (NTRS)

Smith, Leslie E.; Nagar, Shruti; Kim, Grace J.; Morgan, William F.

2003-01-01

Genomic instability is a term used to describe a phenomenon that results in the accumulation of multiple changes required to convert a stable genome of a normal cell to an unstable genome characteristic of a tumor. There has been considerable recent debate concerning the importance of genomic instability in human cancer and its temporal occurrence in the carcinogenic process. Radiation is capable of inducing genomic instability in mammalian cells and instability is thought to be the driving force responsible for radiation carcinogenesis. Genomic instability is characterized by a large collection of diverse endpoints that include large-scale chromosomal rearrangements and aberrations, amplification of genetic material, aneuploidy, micronucleus formation, microsatellite instability, and gene mutation. The capacity of radiation to induce genomic instability depends to a large extent on radiation quality or linear energy transfer (LET) and dose. There appears to be a low dose threshold effect with low LET, beyond which no additional genomic instability is induced. Low doses of both high and low LET radiation are capable of inducing this phenomenon. This report reviews data concerning dose rate effects of high and low LET radiation and their capacity to induce genomic instability assayed by chromosomal aberrations, delayed lethal mutations, micronuclei and apoptosis.

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 ...

Risk factors for pedicled flap necrosis in hand soft tissue reconstruction: a multivariate logistic regression analysis.

PubMed

Gong, Xu; Cui, Jianli; Jiang, Ziping; Lu, Laijin; Li, Xiucun

2018-03-01

Few clinical retrospective studies have reported the risk factors of pedicled flap necrosis in hand soft tissue reconstruction. The aim of this study was to identify non-technical risk factors associated with pedicled flap perioperative necrosis in hand soft tissue reconstruction via a multivariate logistic regression analysis. For patients with hand soft tissue reconstruction, we carefully reviewed hospital records and identified 163 patients who met the inclusion criteria. The characteristics of these patients, flap transfer procedures and postoperative complications were recorded. Eleven predictors were identified. The correlations between pedicled flap necrosis and risk factors were analysed using a logistic regression model. Of 163 skin flaps, 125 flaps survived completely without any complications. The pedicled flap necrosis rate in hands was 11.04%, which included partial flap necrosis (7.36%) and total flap necrosis (3.68%). Soft tissue defects in fingers were noted in 68.10% of all cases. The logistic regression analysis indicated that the soft tissue defect site (P = 0.046, odds ratio (OR) = 0.079, confidence interval (CI) (0.006, 0.959)), flap size (P = 0.020, OR = 1.024, CI (1.004, 1.045)) and postoperative wound infection (P < 0.001, OR = 17.407, CI (3.821, 79.303)) were statistically significant risk factors for pedicled flap necrosis of the hand. Soft tissue defect site, flap size and postoperative wound infection were risk factors associated with pedicled flap necrosis in hand soft tissue defect reconstruction. © 2017 Royal Australasian College of Surgeons.

Ionizing Radiation-Induced Immune and Inflammatory Reactions in the Brain

PubMed Central

Lumniczky, Katalin; Szatmári, Tünde; Sáfrány, Géza

2017-01-01

Radiation-induced late brain injury consisting of vascular abnormalities, demyelination, white matter necrosis, and cognitive impairment has been described in patients subjected to cranial radiotherapy for brain tumors. Accumulating evidence suggests that various degrees of cognitive deficit can develop after much lower doses of ionizing radiation, as well. The pathophysiological mechanisms underlying these alterations are not elucidated so far. A permanent deficit in neurogenesis, chronic microvascular alterations, and blood–brain barrier dysfunctionality are considered among the main causative factors. Chronic neuroinflammation and altered immune reactions in the brain, which are inherent complications of brain irradiation, have also been directly implicated in the development of cognitive decline after radiation. This review aims to give a comprehensive overview on radiation-induced immune alterations and inflammatory reactions in the brain and summarizes how these processes can influence cognitive performance. The available data on the risk of low-dose radiation exposure in the development of cognitive impairment and the underlying mechanisms are also discussed. PMID:28529513

An investigation of ear necrosis in pigs.

PubMed

Park, Jeonghwa; Friendship, Robert M; Poljak, Zvonimir; DeLay, Josepha; Slavic, Durda; Dewey, Catherine E

2013-05-01

Porcine ear necrosis was investigated in 23 conveniently chosen farms, consisting of 14 case farms and 9 control farms. Biopsies of lesions and oral swabs from pigs on 11 case farms were examined by histology and bacterial culture. All farms were visited for observations and a survey on management, housing, and the presence of other clinical signs or behavioral vices. Histological examination revealed that the lesions began on the surface and progressed to deeper layers, and that vascular damage did not appear to be the initiating cause. Spirochetes were only rarely observed in histological examination and were not cultured from biopsies and oral swabs. Staphylococcus aureus and Staphylococcus hyicus were cultured from 91% and 66% of samples, respectively. Ear biting and a humid environment were associated with ear necrosis. On some farms large numbers of pigs were affected and lesions were sometimes extensive. The condition appears to be an infectious disease beginning on the surface of the skin; contributing environmental and management factors are likely.

An investigation of ear necrosis in pigs

PubMed Central

Park, Jeonghwa; Friendship, Robert M.; Poljak, Zvonimir; DeLay, Josepha; Slavic, Durda; Dewey, Catherine E.

2013-01-01

Porcine ear necrosis was investigated in 23 conveniently chosen farms, consisting of 14 case farms and 9 control farms. Biopsies of lesions and oral swabs from pigs on 11 case farms were examined by histology and bacterial culture. All farms were visited for observations and a survey on management, housing, and the presence of other clinical signs or behavioral vices. Histological examination revealed that the lesions began on the surface and progressed to deeper layers, and that vascular damage did not appear to be the initiating cause. Spirochetes were only rarely observed in histological examination and were not cultured from biopsies and oral swabs. Staphylococcus aureus and Staphylococcus hyicus were cultured from 91% and 66% of samples, respectively. Ear biting and a humid environment were associated with ear necrosis. On some farms large numbers of pigs were affected and lesions were sometimes extensive. The condition appears to be an infectious disease beginning on the surface of the skin; contributing environmental and management factors are likely. PMID:24155434

Two types of bone necrosis in the Middle Triassic Pistosaurus longaevus bones: the results of integrated studies

NASA Astrophysics Data System (ADS)

Surmik, Dawid; Rothschild, Bruce M.; Dulski, Mateusz; Janiszewska, Katarzyna

2017-07-01

Avascular necrosis, diagnosed on the basis of either a specific pathological modification of the articular surfaces of bone or its radiologic appearance in vertebral centra, has been recognized in many Mesozoic marine reptiles as well as in present-day marine mammals. Its presence in the zoological and paleontologic record is usually associated with decompression syndrome, a disease that affects secondarily aquatic vertebrates that could dive. Bone necrosis can also be caused by infectious processes, but it differs in appearance from decompression syndrome-associated aseptic necrosis. Herein, we report evidence of septic necrosis in the proximal articular surface of the femur of a marine reptile, Pistosaurus longaevus, from the Middle Triassic of Poland and Germany. This is the oldest recognition of septic necrosis associated with septic arthritis in the fossil record so far, and the mineralogical composition of pathologically altered bone is described herein in detail. The occurrence of septic necrosis is contrasted with decompression syndrome-associated avascular necrosis, also described in Pistosaurus longaevus bone from Middle Triassic of Germany.

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.

Autologous Platelet Concentrates as Treatment for Avascular Necrosis of Femoral Head in a Dog.

PubMed

Parra, Estefanía; Vergara, Andrea; Silva, Raúl F

2017-03-01

Avascular necrosis of the femoral head is a developmental disturbance that generally affects young dogs of small breeds and produces ischemic necrosis of the femoral head resulting in an incongruous and malformed joint. The most common treatment is the excisional arthroplasty of the head and femoral neck. The aim of this study is to describe the treatment of avascular necrosis in a Yorkshire dog using intra-articular injections of autologous platelet concentrate. Evaluations were made at 0, 15, 30, 60, and 120 days of treatment, describing the following parameters: clinical gait analysis, perimetry, goniometry, and radiographic evaluations. The results obtained in this case suggest that the autologous platelet concentrate may be an alternative for the treatment of avascular necrosis of the femoral head in dogs. Copyright © 2017 Elsevier Inc. All rights reserved.

Submassive hepatic necrosis induced by dichloropropanol.

PubMed

Haratake, J; Furuta, A; Iwasa, T; Wakasugi, C; Imazu, K

1993-06-01

A hitherto undescribed industrial liver injury of fulminant form induced by dichloropropanol is reported. Two middle-aged men developed severe hepatic injury just after cleaning a dichloropropanol tank at a plant producing dichloropropanol. They died from hepatic failure 4 and 11 days respectively, after carrying out the work. Liver specimens taken at autopsy from one of the cases showed submassive hepatic necrosis. This accident prompted us to undertake an experimental study in rats of intraperitoneal one-shot injection of two isomeric substances of dichloropropanol, that is, 2,3-dichloro-1-propanol (DC1P) and 1,3-dichloro-2-propanol (DC2P). Saline was injected into the control rats. One, two, four, six, 24, 48, 72 h, and 1 week after the injection, rats in each group were sacrificed. Neither control nor DC1P-injected rats showed significant biochemical or histopathological abnormalities. DC2P-injected rats revealed elevations of transaminase from 6 h after the injections, and submassive necrosis of the liver was observed in many rats. It was concluded that the severe liver injuries in both the human cases and rats in our study were caused by DC2P.

Spontaneous and bilateral avascular necrosis of the navicula: Müller-Weiss disease.

PubMed

Aktaş, Erdem; Ayanoğlu, Tacettin; Hatipoğlu, Yasin; Kanatlı, Ulunay

2016-12-01

Although, trauma, foot deformity (pesplanovalgus), systemic diseases such as diabetes mellitus and lupus, drugs (steroids, antineoplastic) and excessive alcohol consumption have all been accused in the etiology of avascular necrosis of the tarsal bones, spontaneous avascular necrosis of the navicular bone, especially in adults, is a rare entity. In this article, we report a 50-year-old female patient with bilateral, spontaneous avascular necrosis of the navicular bone and related severe talonavicular arthrosis. Clinical and radiological findings were concordant with Müller-Weiss disease, which is a rare disease with complex idiopathic foot condition of the adult tarsal navicular bone characterized by progressive navicular fragmentation and talonavicular joint destruction. The patient was successfully treated with two-staged bilateral talonavicular arthrodesis.

[Novel Anticancer Strategy Targeting Switch Mechanisms in Two Types of Cell Death: Necrosis and Apoptosis].

PubMed

Sato, Akira

2017-01-01

 Two types of cell death, necrosis and apoptosis, are defined in terms of cell death morphological features. We have been studying the mechanisms by which cell death processes are switched during the treatment of mouse tumor FM3A with anticancer, 5-fluoro-2'-deoxyuridine (FUdR): it induces original clone F28-7 to necrosis, but its sub-clone F28-7-A to apoptosis. We identified several such switch regulators of cell death: heat shock protein 90 (HSP90), lamin-B1, cytokeratin-19, and activating transcription factor 3 (ATF3), by using transcriptomic, proteomic analyses and siRNA screening. For example, the inhibition of HSP90 by its inhibitor geldanamycin in F28-7 caused a shift from necrosis to apoptosis. We also observed that the knockdown of lamin-B1, cytokeratin-19, or ATF3 expression in F28-7 resulted in a shift from necrosis to apoptosis. Recently, we used microRNA (miRNA, miR) microarray analyses to investigate the miRNA expression profiles in these sister cells. The miR-351 and miR-743a were expressed at higher levels in F28-7-A than in F28-7. Higher expression of miR-351 or miR-743a in F28-7, induced by transfecting the miR mimics, resulted in a switch of cell death mode: necrosis to apoptosis. Furthermore, transfection of an miR-351 inhibitor into F28-7-A resulted in morphological changes, and mode of cell death from apoptosis to necrosis. These findings suggest that the identified cell death regulators may have key roles in switching cell death mode. Possible mechanisms involving cell death regulators in the switch of necrosis or apoptosis are discussed. We propose a novel anticancer strategy targeting the switch regulators of necrosis or apoptosis.

Radiation-induced transmissable chromosomal instability in haemopoietic stem cells

NASA Astrophysics Data System (ADS)

Kadhim, M. A.; Wright, E. G.

Heritable radiation-induced genetic alterations have long been assumed to be ``fixed'' within the first cell division. However, there is a growing body of evidence that a considerable fraction of cells surviving radiation exposure appear normal, but a variety of mutational changes arise in their progeny due to a transmissible genomic instability. In our investigations of G-banded metaphases, non-clonal cytogenetic aberrations, predominantly chromatid-type aberrations, have been observed in the clonal descendants of murine and human haemopoietic stem cells surviving low doses (~1 track per cell) of alpha-particle irradiations. The data are consistent with a transmissible genetic instability induced in a stem cell resulting in a diversity of chromosomal aberrations in its clonal progeny many cell divisions later. Recent studies have demonstrated that the instability phenotype persists in vivo and that the expression of chromosomal instability has a strong dependence on the genetic characteristics of the irradiated cell. At the time when cytogenetic aberrations are detected, an increased incidence of hprt mutations and apoptotic cells have been observed in the clonal descendants of alpha-irradiated murine haemopoietic stem cells. Thus, delayed chromosomal abnormalities, delayed cell death by apoptosis and late-arising specific gene mutations may reflect diverse consequences of radiation-induced genomic instability. The relationship, if any, between these effects is not established. Current studies suggest that expression of these delayed heritable effects is determined by the type of radiation exposure, type of cell and a variety of genetic factors.

Fat necrosis after abdominal surgery: A pitfall in interpretation of FDG-PET/CT.

PubMed

Davidson, Tima; Lotan, Eyal; Klang, Eyal; Nissan, Johnatan; Goldstein, Jeffrey; Goshen, Elinor; Ben-Haim, Simona; Apter, Sara; Chikman, Bar

2018-06-01

We describe FDG-PET/CT findings of postoperative fat necrosis in patients following abdominal surgery, and evaluate their changes in size and FDG uptake over time. FDG-PET/CT scans from January 2007-January 2016 containing the term 'fat necrosis' were reviewed. Lesions meeting radiological criteria of fat necrosis in patients with prior abdominal surgery were included. Forty-four patients, 30 males, mean age 68.4 ± 11.0 years. Surgeries: laparotomy (n=37; 84.1 %), laparoscopy (n=3; 6.8 %), unknown (n=4; 9.1 %). CTs of all lesions included hyperdense well-defined rims surrounding a heterogeneous fatty core. Sites: peritoneum (n=34; 77 %), omental fat (n=19; 43 %), subcutaneous fat (n=8; 18 %), retroperitoneum (n=2; 5 %). Mean lesion long axis: 33.6±24.9 mm (range: 13.0-140.0). Mean SUVmax: 2.6±1.1 (range: 0.6-5.1). On serial CTs (n=34), lesions decreased in size (p=0.022). Serial FDG-PET/CT (n=24) showed no significant change in FDG-avidity (p=0.110). Mean SUVmax did not correlate with time from surgery (p=0.558) or lesion size (p=0.259). Postsurgical fat necrosis demonstrated characteristic CT features and may demonstrate increased FDG uptake. However, follow-up of subsequent imaging scans showed no increases in size or FDG-avidity. Awareness of this entity is important to avoid misinterpretation of findings as recurrent cancer. • Postsurgical fat necrosis may mimic cancer in FDG-PET/CT. • Follow-up of fat necrosis showed no increase in FDG intensity. • CT follow-up showed a decrease in lesion size. • FDG uptake did not correlate with time lapsed from surgery.

Radiation and thyroid neoplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

McConahey, W.M.; Hayles, A.B.

1976-06-01

It is now generally accepted that an association exists between external radiation administered to the head, neck, and upper thorax of infants, children, and adolescents and the subsequent development of neoplastic changes in the thyroid gland. Until recent years, external radiation was frequently administered to shrink an enlarged thymus or for the treatment of tonsillitis, adenoiditis, hearing loss, hemangioma, acne, tinea capitis, and other conditions. During the course of these treatments, the thyroid gland was exposed to scatter radiation. The use of external radiation therapy was then accepted practice, and its value was attested by many. Concern about the adversemore » effects was not initially appreciated, primarily because of the long periods of time between the radiation and the recognition of changes in the thyroid. The availability and effectiveness of other therapeutic measures and the growing concern about the delayed effects of radiation therapy when administered to the young for relatively benign conditions has, in recent years, largely eliminated use of this form of therapy, except in a few unusual conditions.« less

Oxidative stress and cardiomyocyte necrosis with elevated serum troponins: pathophysiologic mechanisms.

PubMed

Robinson, Antwon D; Ramanathan, Kodangudi B; McGee, Jesse E; Newman, Kevin P; Weber, Karl T

2011-08-01

The progressive nature of heart failure is linked to multiple factors, including an ongoing loss of cardiomyocytes and necrosis. Necrotic cardiomyocytes leave behind several footprints: the spillage of their contents leading to elevations in serum troponins; and morphologic evidence of tissue repair with scarring. The pathophysiologic origins of cardiomyocyte necrosis relates to neurohormonal activation, including the adrenergic nervous system. Catecholamine-initiated excessive intracellular Ca accumulation and mitochondria Ca overloading in particular initiate a mitochondriocentric signal-transducer-effector pathway to necrosis and which includes the induction of oxidative stress and opening of their inner membrane permeability transition pore. Hypokalemia, ionized hypocalcemia and hypomagnesemia, where consequent elevations in parathyroid hormone further account for excessive intracellular Ca accumulation, hypozincemia and hyposelenemia each compromise metalloenzyme-based antioxidant defenses. The necrotic loss of cardiomyocytes and adverse structural remodeling of myocardium is related to the central role played by a mitochondriocentric pathway initiated by neurohormonal activation.

Radiation injury to the temporal bone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guida, R.A.; Finn, D.G.; Buchalter, I.H.

1990-01-01

Osteoradionecrosis of the temporal bone is an unusual sequela of radiation therapy to the head and neck. Symptoms occur many years after the radiation is administered, and progression of the disease is insidious. Hearing loss (sensorineural, conductive, or mixed), otalgia, otorrhea, and even gross tissue extrusion herald this condition. Later, intracranial complications such as meningitis, temporal lobe or cerebellar abscess, and cranial neuropathies may occur. Reported here are five cases of this rare malady representing varying degrees of the disease process. They include a case of radiation-induced necrosis of the tympanic ring with persistent squamous debris in the external auditorymore » canal and middle ear. Another case demonstrates the progression of radiation otitis media to mastoiditis with bony sequestration. Further progression of the disease process is seen in a third case that evolved into multiple cranial neuropathies from skull base destruction. Treatment includes systemic antibiotics, local wound care, and debridement in cases of localized tissue involvement. More extensive debridement with removal of sequestrations, abscess drainage, reconstruction with vascularized tissue from regional flaps, and mastoid obliteration may be warranted for severe cases. Hyperbaric oxygen therapy has provided limited benefit.« less

Thermal isotherms in PMMA and cell necrosis during total hip arthroplasty.

PubMed

Gundapaneni, Dinesh; Goswami, Tarun

2014-12-30

Polymethylmethacrylate (PMMA), also known as bone cement, is a commonly used adhesive material to fix implants in Total Hip Arthroplasty (THA). During implantation, bone cement undergoes a polymerization reaction which is an exothermic reaction and results in the release of heat to the surrounding bone tissue, which ultimately leads to thermal necrosis. Necrosis in the bony tissue results in early loosening of the implant, which causes pain and reduces the life of the implant. The main objective of the present study was to understand the thermal isotherms in PMMA and to determine the optimal cement mantle thickness to prevent cell necrosis during THA. In this study, the environment in the bony tissue during implantation was simulated by constructing 3D solid models to observe the temperature distribution in the bony tissue at different cement mantle thicknesses (1 mm, 3 mm and 5 mm), by applying the temperature conditions that exist during the surgery. Stems made with Co-Cr-Mo, 316L stainless steel and Ti6Al4V were used, which acted as heat sinks, and a thermal damage equation was used to measure the bone damage. FEA was conducted based on temperature conditions and thermal isotherms at different cement mantle thicknesses were obtained. Thermal isotherms derived with respect to distance in the bony tissue from the center of the cement mantle, and cell necrosis was determined at different mantle thicknesses. Based on the deduced results, cement mantle thickness of 1-5 mm does not cause thermal damage in the bony tissue. Considering the long term stability of the implant, cement mantle thickness range from 3 mm-5 mm was found to be optimal in THA to prevent cell necrosis.

[Programmed necrosis mediated by receptor-interacting protein 3: a new target for liver disease research].

PubMed

Zhang, J; Jing, Y; Li, Y N; Zhou, L; Wang, B M

2016-09-20

Hepatocyte death mainly includes apoptosis and necrosis and is a critical process in the pathophysiological mechanism of liver injury caused by various reasons. Recent studies have shown that key regulatory molecules in the inhibition of apoptosis such as caspase cannot be used as targets for inhibiting disease progression in clinical practice. In recent years, programmed necrosis mediated by receptor-interacting protein 3(RIP3)becomes a new hot research topic. It not only plays an important role in inducing inflammatory response, but also is closely regulated by intracellular signal factors, and it is a type of active cell death which can be interfered with. Compared with apoptosis, programmed necrosis is accompanied by the release of various inflammatory factors, which significantly affects local immune microenvironment. RIP3-mediated programmed necrosis has been taken seriously in many diseases. Although its mechanism of action in liver disease remains unclear, the results of recent studies confirmed its important role in the development of liver disease. This article reviews the research advances in the role of RIP3-mediated programmed necrosis signaling pathway in liver disease of various causes and investigates the possibility of RIP3-mediated programmed necrosis as a new target in the treatment of liver disease.

Spermidine rescues proximal tubular cells from oxidative stress and necrosis after ischemic acute kidney injury.

PubMed

Kim, Jinu

2017-10-01

Kidney ischemia and reperfusion injury (IRI) is associated with a high mortality rate, which is attributed to tubular oxidative stress and necrosis; however, an effective approach to limit IRI remains elusive. Spermidine, a naturally occurring polyamine, protects yeast cells against aging through the inhibition of oxidative stress and necrosis. In the present study, spermidine supplementation markedly attenuated increases in plasma creatinine concentration and tubular injury score after IRI. In addition, exogenous spermidine potently inhibited oxidative stress, especially lipid peroxidation after IRI in kidneys and exposure to hydrogen peroxide in kidney proximal tubular cells, suppressing plasma membrane disruption and necrosis. Consistent with spermidine supplementation, upregulation of ornithine decarboxylase (ODC) in human kidney proximal tubular cells significantly diminished lipid peroxidation and necrosis induced by hydrogen peroxide-induced injury. Conversely, ODC deficiency significantly enhanced lipid peroxidation and necrosis after exposure to hydrogen peroxide. Finally, small interfering RNA-mediated ODC inhibition induced functional and histological damage in kidneys as well as it increased lipid hydroperoxide levels after IRI. In conclusion, these data suggest that spermidine level determines kidney proximal tubular damage through oxidative stress and necrosis induced by IRI, and this finding provides a novel target for prevention of tubular damage induced by IRI.