Delayed diagnosis of an isolated posterolateral corner injury: a case report.

PubMed

Welsh, Patrick; DeGraauw, Christopher; Whitty, David

2016-12-01

Isolated injuries to the posterolateral corner of the knee are a rare and commonly missed injury associated with athletic trauma, motor vehicle accidents, and falls. Delayed or missed diagnoses can negatively impact patient prognosis, contributing to residual instability, chronic pain, and failure of surgical repair to other ligaments. A 44-year-old male CrossFit athlete presented with a history of two non-contact hyperextension injuries to his left knee while walking on ice. The only positive finding was the Dial Test at 30 degrees of knee flexion, indicative of an isolated posterolateral corner injury. After a delay in diagnosis, the patient underwent a reconstruction of the posterolateral corner and subsequent rehabilitation. Early recognition of this injury is important as this can affect the prognosis and activities of daily living of the patient. This case will discuss the clinical presentation, diagnostic procedures, and management of an isolated posterolateral corner injury and highlight the importance of early recognition and referrals from primary contact healthcare practitioners.

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.

Ghrelin as a Novel Therapy for Radiation Combined Injury

PubMed Central

Jacob, Asha; Shah, Kavin G; Wu, Rongqian; Wang, Ping

2010-01-01

The threat of nuclear terrorism has led to growing worldwide concern about exposure to radiation. Acute radiation syndrome, or radiation sickness, develops after whole-body or a partial-body irradiation with a high dose of radiation. In the terrorist radiation exposure scenario, however, radiation victims likely suffer from additional injuries such as trauma, burns, wounds or sepsis. Thus, high-dose radiation injuries and appropriate therapeutic interventions must be studied. Despite advances in our understanding of the pathophysiology of radiation injury, very little information is available on the therapeutic approaches to radiation combined injury. In this review, we describe briefly the pathological consequences of ionizing radiation and provide an overview of the animal models of radiation combined injury. We highlight the combined radiation and sepsis model we recently established and suggest the use of ghrelin, a novel gastrointestinal hormone, as a potential therapy for radiation combined injury. PMID:20101281

Gastrointestinal radiation injury: prevention and treatment.

PubMed

Shadad, Abobakr K; Sullivan, Frank J; Martin, Joseph D; Egan, Laurence J

2013-01-14

With the recent advances in detection and treatment of cancer, there is an increasing emphasis on the efficacy and safety aspects of cancer therapy. Radiation therapy is a common treatment for a wide variety of cancers, either alone or in combination with other treatments. Ionising radiation injury to the gastrointestinal tract is a frequent side effect of radiation therapy and a considerable proportion of patients suffer acute or chronic gastrointestinal symptoms as a result. These side effects often cause morbidity and may in some cases lower the efficacy of radiotherapy treatment. Radiation injury to the gastrointestinal tract can be minimised by either of two strategies: technical strategies which aim to physically shift radiation dose away from the normal intestinal tissues, and biological strategies which aim to modulate the normal tissue response to ionising radiation or to increase its resistance to it. Although considerable improvement in the safety of radiotherapy treatment has been achieved through the use of modern optimised planning and delivery techniques, biological techniques may offer additional further promise. Different agents have been used to prevent or minimize the severity of gastrointestinal injury induced by ionising radiation exposure, including biological, chemical and pharmacological agents. In this review we aim to discuss various technical strategies to prevent gastrointestinal injury during cancer radiotherapy, examine the different therapeutic options for acute and chronic gastrointestinal radiation injury and outline some examples of research directions and considerations for prevention at a pre-clinical level.

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

Delayed diagnosis of an isolated posterolateral corner injury: a case report

PubMed Central

Welsh, Patrick; DeGraauw, Christopher; Whitty, David

2016-01-01

Introduction: Isolated injuries to the posterolateral corner of the knee are a rare and commonly missed injury associated with athletic trauma, motor vehicle accidents, and falls. Delayed or missed diagnoses can negatively impact patient prognosis, contributing to residual instability, chronic pain, and failure of surgical repair to other ligaments. Case Presentation: A 44-year-old male CrossFit athlete presented with a history of two non-contact hyperextension injuries to his left knee while walking on ice. The only positive finding was the Dial Test at 30 degrees of knee flexion, indicative of an isolated posterolateral corner injury. After a delay in diagnosis, the patient underwent a reconstruction of the posterolateral corner and subsequent rehabilitation. Early recognition of this injury is important as this can affect the prognosis and activities of daily living of the patient. Summary: This case will discuss the clinical presentation, diagnostic procedures, and management of an isolated posterolateral corner injury and highlight the importance of early recognition and referrals from primary contact healthcare practitioners. PMID:28065990

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

Possible mechanisms for delayed neurological damage in lightning and electrical injury.

PubMed

Reisner, Andrew D

2013-01-01

This article provides and reviews hypotheses to help explain the poorly understood phenomenon of delayed neurological injury following lightning or electrical injury. A review of extant literature provides a starting point to integrate what is already known in an attempt to provide new hypotheses for this phenomenon, as well as to discuss existing hypotheses. The author proposes two theories which stem from the literature on the damaging effects of oxidative stress, and also reviews an existing hypothesis, the electroporation hypothesis. The former two theories can account for delayed damage which is either of vascular or nonvascular origin. The electroporation hypothesis can explain changes both in cases where there is cellular loss as well as cases where there only appears to be change in function after lightning or electrical injury. Although all theories discussed are speculative, the formation of hypotheses is always a starting point in the scientific process. In cases where there is delayed neurological damage with a vascular origin, it is possible that free radicals resulting from oxidative stress may gradually damage spinal vascular endothelial cells, cutting off blood supply, and ending in death of spinal neurons. When the delayed condition is demyelination without vascular damage, it is possible that the free radicals from oxidative stress are formed directly from the lipids found in abundance in myelin cells. The electroporation hypothesis, the formation of additional pores in neurons, may best explain immediate or progressive changes in structure and function after lightning or electrical injury.

RADIATION INJURY OF MYELOPOIESIS IN MONKEYS,

DTIC Science & Technology

RADIATION EFFECTS, *HEMATOPOIETIC SYSTEM, RADIATION INJURIES, GAMMA RAYS, LEUKOCYTES, BLOOD COUNTS, HEMOGLOBIN, MORTALITY RATE, BONE MARROW, LEUKEMIA, ANEMIAS , RADIATION SICKNESS, RADIATION DOSAGE, USSR.

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.

Chemical, Electrical, and Radiation Injuries.

PubMed

Friedstat, Jonathan; Brown, David A; Levi, Benjamin

2017-07-01

This article reviews the unique challenges presented by chemical, electrical, and radiation injuries. The authors discuss pathophysiology and diagnosis of these injuries and provide recommendations for management. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of ionizing radiation injuries and illnesses, part 1: physics, radiation protection, and radiation instrumentation.

PubMed

Christensen, Doran M; Jenkins, Mark S; Sugarman, Stephen L; Glassman, Erik S

2014-03-01

Ionizing radiation injuries and illnesses are exceedingly rare; therefore, most physicians have never managed such conditions. When confronted with a possible radiation injury or illness, most physicians must seek specialty consultation. Protection of responders, health care workers, and patients is an absolute priority for the delivery of medical care. Management of ionizing radiation injuries and illnesses, as well as radiation protection, requires a basic understanding of physics. Also, to provide a greater measure of safety when working with radioactive materials, instrumentation for detection and identification of radiation is needed. Because any health care professional could face a radiation emergency, it is imperative that all institutions have emergency response plans in place before an incident occurs. The present article is an introduction to basic physics, ionizing radiation, radiation protection, and radiation instrumentation, and it provides a basis for management of the consequences of a radiologic or nuclear incident.

Radiation Injury to the Brain

MedlinePlus

... healthy cells. The Merck Manual states the following: Radiation Injury to the Nervous System: The nervous system can be damaged by radiation therapy. Acute and subacute transient symptoms may develop early, but ...

Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

PubMed Central

Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

2015-01-01

Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

Longitudinal Assessment of Stereotypic, Proto-Injurious, and Self-Injurious Behavior Exhibited by Young Children with Developmental Delays

ERIC Educational Resources Information Center

Richman, David M.; Lindauer, Steven E.

2005-01-01

Twelve children (CA, 12 to 32 months) with developmental delay were observed in their homes during monthly analogue functional analysis probes to document patterns of emerging self-injurious behavior. Two patterns of emerging self-injury were observed for 5 participants: (a) The topography and functional analysis pattern remained the same, but the…

Peripheral Innervation in Children with Global Developmental Delay: Biomarker for Risk for Self-Injurious Behavior?

PubMed Central

Symons, Frank J.; Tervo, Raymond C.; Barney, Chantel C.; Damerow, John; Selim, Mona; McAdams, Brian; Foster, Shawn; Crabb, Gwen Wendelschafer; Kennedy, William

2015-01-01

The relation between somatosensory mechanisms and self-injury among children with neurological impairments associated with developmental delay is not well understood. We evaluated the feasibility of procuring skin biopsies to examine epidermal nerve fiber density and reported self-injury. Following informed parental consent, epidermal skin biopsies were obtained from a distal leg site with no pre-existing skin damage from 11 children with global developmental delay (55% male; mean age = 36.8 months, 17–63 mo.). Visual microscopic examination and quantitative analyses showed extremely high epidermal nerve fiber density values for some children. Children with reported self-injury (5/11) had significantly (p < 0.02) greater density values (138.8, sd = 45.5) than children without self-injury (80.5, sd = 17.5). Results from this novel immunohistological analysis of skin in very young children with neurodevelopmental delays suggests it may be a useful tool to study peripheral innervation as a possible sensory risk factor for self-injury. PMID:25918119

Peripheral Innervation in Children With Global Developmental Delay: Biomarker for Risk for Self-Injurious Behavior?

PubMed

Symons, Frank J; Tervo, Raymond C; Barney, Chantel C; Damerow, John; Selim, Mona; McAdams, Brian; Foster, Shawn; Wendelschafer Crabb, Gwen; Kennedy, William

2015-11-01

The relation between somatosensory mechanisms and self-injury among children with neurologic impairments associated with developmental delay is not well understood. We evaluated the feasibility of procuring skin biopsies to examine epidermal nerve fiber density and reported self-injury. Following informed parental consent, epidermal skin biopsies were obtained from a distal leg site with no pre-existing skin damage from 11 children with global developmental delay (55% male; mean age = 36.8 months, 17-63 months). Visual microscopic examination and quantitative analyses showed extremely high epidermal nerve fiber density values for some children. Children with reported self-injury (5/11) had significantly (P < .02) greater density values (138.8, standard deviation = 45.5) than children without self-injury (80.5, standard deviation = 17.5). Results from this novel immunohistologic analysis of skin in very young children with neurodevelopmental delays suggest it may be a useful tool to study peripheral innervation as a possible sensory risk factor for self-injury. © The Author(s) 2015.

The Evolving MCART Multimodal Imaging Core: Establishing a protocol for Computed Tomography and Echocardiography in the Rhesus macaque to perform longitudinal analysis of radiation-induced organ injury

PubMed Central

de Faria, Eduardo B.; Barrow, Kory R.; Ruehle, Bradley T.; Parker, Jordan T.; Swartz, Elisa; Taylor-Howell, Cheryl; Kieta, Kaitlyn M.; Lees, Cynthia J.; Sleeper, Meg M.; Dobbin, Travis; Baron, Adam D.; Mohindra, Pranshu; MacVittie, Thomas J.

2015-01-01

Computed Tomography (CT) and Echocardiography (EC) are two imaging modalities that produce critical longitudinal data that can be analyzed for radiation-induced organ-specific injury to the lung and heart. The Medical Countermeasures Against Radiological Threats (MCART) consortium has a well-established animal model research platform that includes nonhuman primate (NHP) models of the acute radiation syndrome and the delayed effects of acute radiation exposure. These models call for a definition of the latency, incidence, severity, duration, and resolution of different organ-specific radiation-induced subsyndromes. The pulmonary subsyndromes and cardiac effects are a pair of inter-dependent syndromes impacted by exposure to potentially lethal doses of radiation. Establishing a connection between these will reveal important information about their interaction and progression of injury and recovery. Herein, we demonstrate the use of CT and EC data in the rhesus macaque models to define delayed organ injury thereby establishing: a) consistent and reliable methodology to assess radiation-induced damage to the lung and heart, b) an extensive database in normal age-matched NHP for key primary and secondary endpoints, c) identified problematic variables in imaging techniques and proposed solutions to maintain data integrity and d) initiated longitudinal analysis of potentially lethal radiation-induced damage to the lung and heart. PMID:26425907

Activation of Protease Activated Receptor 2 by Exogenous Agonist Exacerbates Early Radiation Injury in Rat Intestine

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

Wang Junru; Boerma, Marjan; Kulkarni, Ashwini

2010-07-15

Purpose: Protease-activated receptor-2 (PAR{sub 2}) is highly expressed throughout the gut and regulates the inflammatory, mitogenic, fibroproliferative, and nociceptive responses to injury. PAR{sub 2} is strikingly upregulated and exhibits increased activation in response to intestinal irradiation. We examined the mechanistic significance of radiation enteropathy development by assessing the effect of exogenous PAR{sub 2} activation. Methods and Materials: Rat small bowel was exposed to localized single-dose radiation (16.5 Gy). The PAR{sub 2} agonist (2-furoyl-LIGRLO-NH{sub 2}) or vehicle was injected intraperitoneally daily for 3 days before irradiation (before), for 7 days after irradiation (after), or both 3 days before and 7 daysmore » after irradiation (before-after). Early and delayed radiation enteropathy was assessed at 2 and 26 weeks after irradiation using quantitative histologic examination, morphometry, and immunohistochemical analysis. Results: The PAR{sub 2} agonist did not elicit changes in the unirradiated (shielded) intestine. In contrast, in the irradiated intestine procured 2 weeks after irradiation, administration of the PAR{sub 2} agonist was associated with more severe mucosal injury and increased intestinal wall thickness in all three treatment groups (p <.05) compared with the vehicle-treated controls. The PAR{sub 2} agonist also exacerbated the radiation injury score, serosal thickening, and mucosal inflammation (p <.05) in the before and before-after groups. The short-term exogenous activation of PAR{sub 2} did not affect radiation-induced intestinal injury at 26 weeks. Conclusion: The results of the present study support a role for PAR{sub 2} activation in the pathogenesis of early radiation-induced intestinal injury. Pharmacologic PAR{sub 2} antagonists might have the potential to reduce the intestinal side effects of radiotherapy and/or as countermeasures in radiologic accidents or terrorism scenarios.« less

Delayed, post-injury treatment with aniracetam improves cognitive performance after traumatic brain injury in rats.

PubMed

Baranova, Anna I; Whiting, Mark D; Hamm, Robert J

2006-08-01

Chronic cognitive impairment is an enduring aspect of traumatic brain injury (TBI) in both humans and animals. Treating cognitive impairment in the post-traumatic stages of injury often involves the delivery of pharmacologic agents aimed at specific neurotransmitter systems. The current investigation examined the effects of the nootropoic drug aniracetam on cognitive recovery following TBI in rats. Three experiments were performed to determine (1) the optimal dose of aniracetam for treating cognitive impairment, (2) the effect of delaying drug treatment for a period of days following TBI, and (3) the effect of terminating drug treatment before cognitive assessment. In experiment 1, rats were administered moderate fluid percussion injury and treated with vehicle, 25, or 50 mg/kg aniracetam for 15 days. Both doses of aniracetam effectively reduced injury-induced deficits in the Morris water maze (MWM) as measured on postinjury days 11-15. In experiment 2, injured rats were treated with 50 mg/kg aniracetam or vehicle beginning on day 11 postinjury and continuing for 15 days. MWM performance, assessed on days 26-30, indicates that aniracetam-treated animals performed as well as sham-injured controls. In experiment 3, animals were injured and treated with aniracetam for 15 days. Drug treatment was terminated during MWM testing on postinjury days 16-20. In this experiment, aniracetam-treated rats did not perform better than vehicle-treated rats. The results of these experiments indicate that aniracetam is an effective treatment for cognitive impairment induced by TBI, even when treatment is delayed for a period of days following injury.

Delayed rearterialization unlikely leads to nonanastomotic stricture but causes temporary injury on bile duct after liver transplantation.

PubMed

Liu, Yang; Wang, Jiazhong; Yang, Peng; Lu, Hongwei; Lu, Le; Wang, Jinlong; Li, Hua; Duan, Yanxia; Wang, Jun; Li, Yiming

2015-03-01

Nonanastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure. Different delayed rearterialization times were compared using a porcine LT model. Morphological and functional changes in bile canaliculus were evaluated by transmission electron microscopy and real-time PCR. Immunohistochemistry and TUNEL were performed to validate intrahepatic bile duct injury. Three months after LT was performed, biliary duct stricture was determined by cholangiography; the tissue of common bile duct was detected by real-time PCR. Bile canaliculi were impaired in early postoperative stage and then exacerbated as delayed rearterialization time was prolonged. Nevertheless, damaged bile canaliculi could fully recover in subsequent months. TNF-α and TGF-β expressions and apoptosis cell ratio increased in the intrahepatic bile duct only during early postoperative period in a time-dependent manner. No abnormality was observed by cholangiography and common bile duct examination after 3 months. Delayed rearterialization caused temporary injury to bile canaliculi and intrahepatic bile duct in a time-dependent manner. Injury could be fully treated in succeeding months. Solo delayed rearterialization cannot induce NAS after LT. © 2014 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury

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

Li, Yonggang; Lein, Pamela J.; Liu, Cuimei

2012-07-15

Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylflurophosphate (DFP). Adult male Sprague–Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatmentmore » with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication. -- Highlights: ► NRG-1 blocked DFP induced neuronal injury. ► NRG-1 did not protect against seizures in rats exposed to DFP. ► NRG-1 blocked apoptosis and oxidative stress in the brains of DFP-intoxicated rats. ► Administration of NRG-1 at 1 h after DFP injection prevented delayed neuronal injury.« less

Delayed diaphragm injury and diaphragm force production.

PubMed

Jiang, T X; Reid, W D; Road, J D

1998-03-01

The present study was designed to examine the effect of delayed diaphragm injury produced by inspiratory resistive loading (IRL) on diaphragm force production. On Day 1, three groups of anesthetized and intubated NZW rabbits (n = 7 in each group) were subjected to moderate IRL (Pao approximately 30 cm H2O), high IRL (Pao approximately 45 cm H2O), or no load for 1.5 h. On Day 3, the baseline twitch transdiaphragmatic pressure (Pdi) and Pdi at 10 to 80 Hz were measured during bilateral phrenic stimulation and these measurements were repeated after another IRL (high level) in all three groups. Diaphragm injury was assessed by the point-counting technique. Marked diaphragm injury was observed in the high-IRL group (p < 0.01), but no significant diaphragm injury was observed in the moderate-IRL or control groups. The baseline twitch Pdi was maintained in both IRL groups, whereas the baseline Pdi-frequency values in the high-IRL group were significantly reduced at most frequencies (p < 0.05). The decreases in twitch and Pdi at different frequencies were more pronounced after the IRL on Day 3 in the high-IRL group compared with controls. Moderate IRL did not decrease diaphragm force either before or after the high IRL on Day 3. We conclude that the diaphragm injury induced by high IRL has a significant impact on diaphragm force production and the attendant force loss produced by IRL is dependent on the intensity of inspiratory loading.

Missed or Delayed Cervical Spine or Spinal Cord Injuries Treated at a Tertiary Referral Hospital in Rwanda.

PubMed

Nkusi, Agabe Emmy; Muneza, Sévérien; Hakizimana, David; Nshuti, Steven; Munyemana, Paulin

2016-03-01

This study was aimed at 1) reporting cases of missed cervical spine injuries treated at a tertiary-level hospital, King Faisal Hospital, Rwanda (KFH-R), and 2) identifying the causes of delaying the diagnosis. We prospectively collected data from patients with a missed or delayed cervical spine and/or cord injury treated at King Faisal Hospital, Kigali for a 12-month period (January 2012 to December 2012). The total number of cervical spine injury patients treated at our center was retrieved from the hospital admission registry. Forty-two patients with cervical spine or spinal cord injuries were treated at KFH-R in 2012, and 4 of them had a missed or delayed diagnosis. Clinical and radiologic findings of all 4 patients are presented, and the reasons for delaying diagnosis are identified. This study found that the cervical spine injuries were missed in 9.5% of the cervical spine trauma patients and resulted in a longer hospital stay for all 4 patients and severe disability in 1 patient (25%). The reasons for missed diagnoses in this study were 1) lack of cervical spine radiographic evaluation, 2) inadequate cervical spine radiographs to show the level of injury, 3) poor sensitivity of cervical spine plain radiography, 4) poor physical examination, 5) the presence of a distracting injury, and 6) poor sensitivity of radiographs and computed tomography scans for soft tissue injuries. Copyright © 2016 Elsevier Inc. All rights reserved.

Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice.

PubMed

Joo, Jin Deok; Kim, Mihwa; D'Agati, Vivette D; Lee, H Thomas

2006-11-01

Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.

Delayed repair of post-traumatic posterior urethral distraction injuries: long-term results.

PubMed

Tunc, H M; Tefekli, A H; Kaplancan, T; Esen, T

2000-06-01

There is still controversy regarding the treatment of post-traumatic posterior urethral distraction injuries. Initial suprapubic cystostomy and delayed perineal urethral reconstruction has been considered the reference standard. In this report, we review our experience with delayed perineal urethral reconstruction, with a focus on the long-term outcome and complications. A total of 77 men with posterior urethral distraction injury due to pelvic trauma underwent reconstruction with delayed perineal approach. In all cases, the area of fibrosis was aggressively excised, the corpus spongiosum was mobilized, and a tension-free, spatulated end-to-end anastomosis was achieved by splitting the corporeal bodies in 66.2% and by an additional perineally performed inferior pubectomy in 49.3% of the patients. The median time from injury to surgical repair was 12 months. The preoperative evaluation consisted of combined antegrade and retrograde cystourethrograms and cystourethrography. A detailed sexual history was obtained in 58 patients (75.3%). After a mean follow-up of 47 months (range 15 months to 14 years), the urethral continuity was adequate in 94. 8%; however, 2 patients required a perineal surgical revision (total of 79 operations). Postoperative incontinence was observed in 7 (9. 1%) of 77 patients. Postoperative erectile dysfunction was noted in 16.2% of patients who were known to be potent by history before surgery. Our results support the belief that delayed perineal reconstruction with extensive excision of fibrosis and a tension-free, spatulated end-to-end anastomosis is a successful treatment alternative for posterior urethral distraction defects, with acceptable morbidity.

Iatrogenic deep musculocutaneous radiation injury following percutaneous coronary intervention.

PubMed

Monaco, JoAn L; Bowen, Kanika; Tadros, Peter N; Witt, Peter D

2003-08-01

Radiation-induced skin injury has been reported for multiple fluoroscopic procedures. Previous studies have indicated that prolonged fluoroscopic exposure during even a single percutaneous coronary intervention (PCI) may lead to cutaneous radiation injury. We document a novel case of deep muscle damage requiring wide local debridement and muscle flap reconstruction in a 59-year-old man with a large radiation-induced wound to the lower thoracic region following 1 prolonged PCI procedure. The deep muscular iatrogenic injury described in this report may be the source of significant morbidity. Recommendations to reduce radiation-induced damage include careful examination of the skin site before each procedure, minimized fluoroscopy time, utilization of pulse fluoroscopy, employment of radiation filters, and collimator s and rotation of the location of the image intensifier.

Effect of early realignment on length and delayed repair of postpelvic fracture urethral injury.

PubMed

Koraitim, Mamdouh M

2012-04-01

To determine the effect of early realignment of posterior urethral injury on the length and delayed repair of ensuing urethral defect. We reviewed the medical records of 120 patients with a pelvic fracture urethral defect who were referred for delayed repair from elsewhere from 1995 to 2009. The review was focused on 5 variables: initial management of urethral injury, length of urethral defect, type of delayed repair, continence, and erectile function. Of the patients, 26 were excluded from the study and 94 were categorized as having been initially treated by realignment (42 patients, group 1) or suprapubic cystostomy (52 patients, group 2). Urethral defects ≤ 2 cm in length were found in 28 patients (67%) in group 1 versus 22 (42%) in group 2. Defects >2 cm were found in 14 patients (33%) in group 1 versus 30 (58%) in group 2. The repair was accomplished by a simple perineal operation in 32 (76%) and 30 (58%) patients in groups 1 and 2, respectively. An elaborated perineal or perineo-abdominal procedure was required in 10 (24%) and 22 (42%) patients in groups 1 and 2, respectively (all P < .05). Incontinence occurred in 1 patient in group 1. Impotence developed in 10 (28%) of 36 realigned adults and in 2 (5%) of 38 adults with suprapubic cystostomy. Early realignment of posterior urethral injury decreases the length of the ensuing urethral defect and facilitates its delayed repair. Incontinence and impotence appear to result from the injury itself and not the treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

PubMed

Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

2017-12-01

The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

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.

Penetrating Injury to Cauda Equina from a Missile Fragment, Completely Recovered after Delayed Surgical Removal of Ballistic Fragment

PubMed Central

Harsha, Kamble Jayaprakash; Thomas, Anu

2018-01-01

Penetrating injuries to cauda equina due to missile fragment are rare. The mechanism of injury may be more complex due to thermal effect of missile fragment, apart from mechanisms described in penetrating gunshot injuries or stab injuries. We report a case of a 42-year-old male with penetrating missile injury to cauda equina, improved completely after delayed surgical exploration and removal of ballistic fragment. Furthermore, his bowel and bladder dysfunction improved completely within 1 week of neurosurgical exploration. Although early neurosurgical intervention is recommended for penetrating injuries of the cauda equina, delayed intervention may also be beneficial in selected patients. Computed tomography (CT) scan and CT myelogram are extremely useful in surgical planning when magnetic resonance imaging contraindicated due to impregnated metal fragments. PMID:29682053

Penetrating Injury to Cauda Equina from a Missile Fragment, Completely Recovered after Delayed Surgical Removal of Ballistic Fragment.

PubMed

Harsha, Kamble Jayaprakash; Thomas, Anu

2018-01-01

Penetrating injuries to cauda equina due to missile fragment are rare. The mechanism of injury may be more complex due to thermal effect of missile fragment, apart from mechanisms described in penetrating gunshot injuries or stab injuries. We report a case of a 42-year-old male with penetrating missile injury to cauda equina, improved completely after delayed surgical exploration and removal of ballistic fragment. Furthermore, his bowel and bladder dysfunction improved completely within 1 week of neurosurgical exploration. Although early neurosurgical intervention is recommended for penetrating injuries of the cauda equina, delayed intervention may also be beneficial in selected patients. Computed tomography (CT) scan and CT myelogram are extremely useful in surgical planning when magnetic resonance imaging contraindicated due to impregnated metal fragments.

Delayed neuroprotection against cerebral ischemia reperfusion injury: putative role of BDNF and GSK-3β.

PubMed

Taliyan, Rajeev; Ramagiri, Sruthi

2016-08-01

Numerous studies have demonstrated the possible neuroprotective role of lithium treatment against neurological disorders. However, the role of lithium in delayed phase of neuronal death against focal ischemia has not been explored. Therefore, the present study was designed to investigate the effect and molecular mechanisms of post-lithium treatment against cerebral ischemic reperfusion (I/R) injury and associated cognitive deficits in rats. I/R injury was induced by right middle cerebral artery occlusion and lithium (40 and 60 mg/kg) were given intraperitoneally, 24 h after the insult and continued for 1 week with 24-h interval. Using Lasser Doppler, cerebral blood flow was monitored before, during and after MCAO induction. Besides behavioral, biochemical, and histological evaluation, levels of tumor necrosis factor alpha (TNF-α) and brain-derived neurotrophic factor (BDNF) were also estimated. I/R injury resulted in significant elevation of neurological deficits, oxidative stress, neuroinflammation, and cognitive impairments. We found that lithium injection, 24 h after I/R-injury continued for 1 week, dose dependently prevented behavioral abnormality and cognitive impairments. Moreover, lithium attenuated the levels of oxidative stress and pro-inflammatory-cytokines TNF-α level. Further, lithium treatments significantly reduced neuronal damage and augmented healthy neuronal count and improved neuronal density in hippocampus. These neuroprotective effects of delayed lithium treatment were associated with upregulation of neurotrophic factor BDNF levels. Delayed lithium treatment provides neuroprotection against cerebral I/R injury and associated cognitive deficits by upregulating BDNF expression that opens a new avenue to treat I/R injury even after active cell death.

Delayed diagnosis of injuries in pediatric trauma: the role of radiographic ordering practices.

PubMed

Willner, Emily L; Jackson, Hollie A; Nager, Alan L

2012-01-01

We sought to describe the use of radiographic studies in pediatric major trauma patients and determine the extent to which a selective, clinically guided use of imaging contributes to delayed diagnosis of injury (DDI). We conducted a retrospective chart review of 324 consecutive pediatric major trauma patients at our level 1 trauma center. One radiologist reviewed all imaging. Delayed diagnosis of injury was defined as detection after more than 12 hours. Equivalency testing was performed to compare radiology use in patients with and without DDI. Twenty-six (8%) of 324 patients had 36 DDI; 27 (75%) of 36 were orthopedic injuries. Median time to DDI detection was 20.5 hours (interquartile range, 15-60.5). During initial evaluation, DDI patients had similar numbers of plain radiographs (3.5 vs 3, P = .54) but more computed tomographic (CT) scans (4 vs 3, P = .03) compared with patients without DDI. Sixteen percent of all patients received CT thorax; 55%, CT cervical spine; and 56%, CT abdomen. Only 1 clinically important DDI was detected solely on the basis of a later CT scan (0.3%; 95% confidence interval, 0-1.5). No cervical spine, intrathoracic, or intraabdominal DDI was attributable to failure to obtain a CT during initial evaluation. Patients with DDI had higher injury severity scores, intubation rates, and pediatric intensive care unit admission rates than those without DDI. Patients with DDI had similar initial plain x-ray evaluations to patients without DDI, despite DDI patients being more severely injured. Delayed diagnosis of injury was not attributable to inadequate CT use. Most DDIs were orthopedic, highlighting the importance of a tertiary survey and a low threshold for skeletal radiographs. Copyright © 2012 Elsevier Inc. All rights reserved.

Primary closure versus delayed closure for non bite traumatic wounds within 24 hours post injury.

PubMed

Eliya-Masamba, Martha C; Banda, Grace W

2013-10-22

Acute traumatic wounds are one of the common reasons why people present to the emergency department. Primary closure has traditionally been reserved for traumatic wounds presenting within six hours of injury and considered 'clean' by the attending surgeon, with the rest undergoing delayed primary closure as a means of controlling wound infection. Primary closure has the potential benefit of rapid wound healing but poses the potential threat of increased wound infection. There is currently no evidence to guide clinical decision-making on the best timing for closure of traumatic wounds. To determine the effect on time to healing of primary closure versus delayed closure for non bite traumatic wounds presenting within 24 hours post injury. To explore the adverse effects of primary closure compared with delayed closure for non bite traumatic wounds presenting within 24 hours post injury. In May 2013, for this first update we searched the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions with respect to language, date of publication or study setting. Randomised controlled trials comparing primary closure with delayed closure of non bite traumatic wounds. Two review authors independently evaluated the results of the searches against the inclusion criteria. No studies met the inclusion criteria for this review. Since no studies met the inclusion criteria, neither a meta-analysis nor a narrative description of studies was possible. There is currently no systematic evidence to guide clinical decision-making regarding the timing for closure of traumatic wounds. There is a need for robust research to investigate the effect of primary closure compared with delayed closure for non bite traumatic wounds presenting within 24 hours of injury.

Outcomes of Iatrogenic Genitourinary Injuries During Colorectal Surgery.

PubMed

Eswara, Jairam R; Raup, Valary T; Potretzke, Aaron M; Hunt, Steven R; Brandes, Steven B

2015-12-01

To describe, categorize, and determine the outcomes of repairs of genitourinary (GU) injuries that occur during colorectal surgery. Presently, little is known regarding these injuries or the long-term outcomes of their repair. We performed a retrospective review of patients undergoing colorectal surgery between 2003 and 2013 who experienced iatrogenic GU injuries requiring surgical repair. GU repair failures were defined as development of urine leak, urinary fistula, or anastomotic stricture requiring secondary GU intervention. Possible risk factors associated with repair failures were examined and included age, American Society of Anesthesiology score, comorbidities, type of colorectal surgery, radiation, and chemotherapy. Of 42,570 colorectal surgeries performed, 75 GU injuries were identified (0.18%). Mean age was 57.5 years (range, 22-91), and median follow-up was 19.5 months (range, 1-128). Fifty-nine (59/75, 79%) patients required a single GU repair whereas 16 of 75 (21%) patients experienced repair failure requiring additional GU intervention. The most common GU injuries were cystotomy (26/75, 35%), incomplete ureteral transection (22/75, 29%), complete proximal and distal ureteral injuries (13/75, 17%; 11/75, 15%), urethral injury (2/75, 3%), and injury to a pre-existing ileal conduit (1/75, 1). Twenty-seven patients (36%) had prior radiation and 35 patients (47%) had prior chemotherapy. Preoperative radiation and chemotherapy were both associated with failure of the GU repair (P = .003; P = .013). Delayed repair of the GU injury was also associated with repair failure (P = .001). Iatrogenic GU injuries during colorectal surgery are rare, affecting only 0.18% of colorectal procedures. Preoperative external beam radiation therapy/chemotherapy and delayed GU repair are associated with worse outcomes of repairs of these injuries. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of A Novel Murine Model of Combined Radiation and Peripheral Tissue Trauma Injuries

PubMed Central

Antonic, Vlado; Jackson, Isabel L.; Ganga, Gurung; Shea-Donohue, Terez; Vujaskovic, Zeljko

2017-01-01

Detonation of a 10-kiloton nuclear bomb in an urban setting would result in >1 million casualties, the majority of which would present with combined injuries. Combined injuries, such as peripheral tissue trauma and radiation exposure, trigger inflammatory events that lead to multiple organ dysfunction (MOD) and death, with gastrointestinal (GI) and pulmonary involvement playing crucial roles. The objective of this study was to develop an animal model of combined injuries, peripheral tissue trauma (TBX animal model) combined with total body irradiation with 5% bone marrow shielding (TBI/BM5) to investigate if peripheral tissue trauma contributes to reduced survival. Male C57BL/6J mice were exposed to TBX10%, irradiation (TBI/BM5), or combined injuries (TBX10% + TBI/BM5). Experiments were conducted to evaluate mortality at day 7 after TBI/BM5. Serial euthanasia was performed at day 1, 3 and 6 or 7 after TBI/BM5 to evaluate the time course of pathophysiologic processes in combined injuries. Functional tests were performed to assess pulmonary function and GI motility. Postmortem samples of lungs and jejunum were collected to assess tissue damage. Results indicated higher lethality and shorter survival in the TBX10% +T BI/BM5 group than in the TBX10% or TBI/BM5 groups (day 1 vs. day 7 and 6, respectively). TBI/BM5 alone had no effects on the lungs but significantly impaired GI function at day 6. As expected, in the animals that received severe trauma (TBX10%), we observed impairment in lung function and delay in GI transit in the first 3 days, effects that decreased at later time points. Trauma combined with radiation (TBX10% + TBI/BM5) significantly augmented impairment of the lung and GI function in comparison to TBX10% and TBI/BM5 groups at 24 h. Histologic evaluation indicated that combined injuries caused greater tissue damage in the intestines in TBX10% + TBI/BM5 group when compared to other groups. We describe here the first combined tissue trauma/radiation

Neuregulin-1 is Neuroprotective in a Rat Model of Organophosphate-Induced Delayed Neuronal Injury

PubMed Central

Li, Yonggang; Lein, Pamela J.; Liu, Cuimei; Bruun, Donald A.; Giulivi, Cecilia; Ford, Gregory; Tewolde, Teclemichael; Ross-Inta, Catherine; Ford, Byron D.

2012-01-01

Current medical countermeasures against organophosphate (OP) nerve agents are effective in reducing mortality, but do not sufficiently protect the CNS from delayed brain damage and persistent neurological symptoms. In this study, we examined the efficacy of neuregulin-1 (NRG-1) in protecting against delayed neuronal cell death following acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague Dawley rats were pretreated with pyridostigmine (0.1 mg/kg BW, i.m.) and atropine methylnitrate (20 mg/kg BW, i.m.) prior to DFP (9 mg/kg BW, i.p.) intoxication to increase survival and reduce peripheral signs of cholinergic toxicity but not prevent DFP-induced seizures or delayed neuronal injury. Pretreatment with NRG-1 did not protect against seizures in rats exposed to DFP. However, neuronal injury was significantly reduced in most brain regions by pretreatment with NRG-1 isoforms NRG-EGF (3.2 μg/kg BW, i.a) or NRG-GGF2 (48 μg/kg BW, i.a.) as determined by FluroJade-B labeling in multiple brain regions at 24 h post-DFP injection. NRG-1 also blocked apoptosis and oxidative stress-mediated protein damage in the brains of DFP-intoxicated rats. Administration of NRG-1 at 1 h after DFP injection similarly provided significant neuroprotection against delayed neuronal injury. These findings identify NRG-1 as a promising adjuvant therapy to current medical countermeasures for enhancing neuroprotection against acute OP intoxication. PMID:22583949

Longitudinal assessment of stereotypic, proto-injurious, and self-injurious behavior exhibited by young children with developmental delays.

PubMed

Richman, David M; Lindauer, Steven E

2005-11-01

Twelve children (CA, 12 to 32 months) with developmental delay were observed in their homes during monthly analogue functional analysis probes to document patterns of emerging self-injurious behavior. Two patterns of emerging self-injury were observed for 5 participants: (a) The topography and functional analysis pattern remained the same, but the behavior eventually caused tissue damage; or (b) a new topography emerged that was similar to an established stereotypic motor behavior. Functional analysis results were inconclusive for the majority of target behaviors across participants due to undifferentiated responding across conditions. One participant exhibited two topographies that appeared to become sensitive to positive reinforcement over time. Results are discussed in terms of implications for future research on early intervention and prevention of self-injury.

Radiation-Induced Skin Injuries to Patients: What the Interventional Radiologist Needs to Know.

PubMed

Jaschke, Werner; Schmuth, Matthias; Trianni, Annalisa; Bartal, Gabriel

2017-08-01

For a long time, radiation-induced skin injuries were only encountered in patients undergoing radiation therapy. In diagnostic radiology, radiation exposures of patients causing skin injuries were extremely rare. The introduction of fast multislice CT scanners and fluoroscopically guided interventions (FGI) changed the situation. Both methods carry the risk of excessive high doses to the skin of patients resulting in skin injuries. In the early nineties, several reports of epilation and skin injuries following CT brain perfusion studies were published. During the same time, several papers reported skin injuries following FGI, especially after percutaneous coronary interventions and neuroembolisations. Thus, CT and FGI are of major concern regarding radiation safety since both methods can apply doses to patients exceeding 5 Gy (National Council on Radiation Protection and Measurements threshold for substantial radiation dose level). This paper reviews the problem of skin injuries observed after FGI. Also, some practical advices are given how to effectively avoid skin injuries. In addition, guidelines are discussed how to deal with patients who were exposed to a potentially dangerous radiation skin dose during medically justified interventional procedures.

Acute and delayed neuroinflammatory response following experimental penetrating ballistic brain injury in the rat

PubMed Central

Williams, Anthony J; Wei, Hans H; Dave, Jitendra R; Tortella, Frank C

2007-01-01

Background Neuroinflammation following acute brain trauma is considered to play a prominent role in both the pathological and reconstructive response of the brain to injury. Here we characterize and contrast both an acute and delayed phase of inflammation following experimental penetrating ballistic brain injury (PBBI) in rats out to 7 days post-injury. Methods Quantitative real time PCR (QRT-PCR) was used to evaluate changes in inflammatory gene expression from the brain tissue of rats exposed to a unilateral frontal PBBI. Brain histopathology was assessed using hematoxylin and eosin (H&E), silver staining, and immunoreactivity for astrocytes (GFAP), microglia (OX-18) and the inflammatory proteins IL-1β and ICAM-1. Results Time course analysis of gene expression levels using QRT-PCR indicated a peak increase during the acute phase of the injury between 3–6 h for the cytokines TNF-α (8–11 fold), IL-1β (11–13 fold), and IL-6 (40–74 fold) as well as the cellular adhesion molecules VCAM (2–3 fold), ICAM-1 (7–15 fold), and E-selectin (11–13 fold). Consistent with the upregulation of pro-inflammatory genes, peripheral blood cell infiltration was a prominent post-injury event with peak levels of infiltrating neutrophils (24 h) and macrophages (72 h) observed throughout the core lesion. In regions of the forebrain immediately surrounding the lesion, strong immunoreactivity for activated astrocytes (GFAP) was observed as early as 6 h post-injury followed by prominent microglial reactivity (OX-18) at 72 h and resolution of both cell types in cortical brain regions by day 7. Delayed thalamic inflammation (remote from the primary lesion) was also observed as indicated by both microglial and astrocyte reactivity (72 h to 7 days) concomitant with the presence of fiber degeneration (silver staining). Conclusion In summary, PBBI induces both an acute and delayed neuroinflammatory response occurring in distinct brain regions, which may provide useful diagnostic

Injury control in practice. Home radiator burns in inner-city children.

PubMed

Quinlan, K P

1996-09-01

To describe thermal burns from radiators in the homes of children in the inner city and an intervention to decrease the risk for this pediatric injury. Academic medical center in Chicago. Case series of 10 radiator-related burns. The burns described were found to be clustered in an area of a public housing project served by steam radiators. No burns were associated with hot water radiators. Just 14% of housing units with young children had adequate radiator covers and radiator pipe insulation. Radiator covers and insulation have now been replaced or repaired in all units of the 11 housing project buildings served by steam radiators. Steam radiators in the home represent a particular childhood burn hazard. Community-based clinicians are in a unique position to recognize local patterns of injury and work with other agencies in injury control efforts.

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

Radiation combined with thermal injury induces immature myeloid cells.

PubMed

Mendoza, April Elizabeth; Neely, Crystal Judith; Charles, Anthony G; Kartchner, Laurel Briane; Brickey, Willie June; Khoury, Amal Lina; Sempowski, Gregory D; Ting, Jenny P Y; Cairns, Bruce A; Maile, Robert

2012-11-01

The continued development of nuclear weapons and the potential for thermonuclear injury necessitates the further understanding of the immune consequences after radiation combined with injury (RCI). We hypothesized that sublethal ionization radiation exposure combined with a full-thickness thermal injury would result in the production of immature myeloid cells. Mice underwent either a full-thickness contact burn of 20% total body surface area or sham procedure followed by a single whole-body dose of 5-Gy radiation. Serum, spleen, and peripheral lymph nodes were harvested at 3 and 14 days after injury. Flow cytometry was performed to identify and characterize adaptive and innate cell compartments. Elevated proinflammatory and anti-inflammatory serum cytokines and profound leukopenia were observed after RCI. A population of cells with dual expression of the cell surface markers Gr-1 and CD11b were identified in all experimental groups, but were significantly elevated after burn alone and RCI at 14 days after injury. In contrast to the T-cell-suppressive nature of myeloid-derived suppressor cells found after trauma and sepsis, myeloid cells after RCI augmented T-cell proliferation and were associated with a weak but significant increase in interferon γ and a decrease in interleukin 10. This is consistent with previous work in burn injury indicating that a myeloid-derived suppressor cell-like population increases innate immunity. Radiation combined injury results in the increase in distinct populations of Gr-1CD11b cells within the secondary lymphoid organs, and we propose these immature inflammatory myeloid cells provide innate immunity to the severely injured and immunocompromised host.

Delayed coma in head injury: consider cerebral fat embolism.

PubMed

Metting, Zwany; Rödiger, Lars A; Regtien, Joost G; van der Naalt, Joukje

2009-09-01

To describe a case of a young man with delayed coma after mild head injury, suggestive of cerebral fat embolism (CFE). To underline the value of MR imaging in the differential diagnosis of secondary deterioration in mild head injury. A 21-year-old man admitted with mild head injury after a fall with facial fractures and long bone fractures. He was admitted to the intensive care unit and was mechanically ventilated. Weaning was not possible because of desaturations and pulmonary congestion. Low platelet count and anaemia developed. On several time points during his admission cerebral imaging data were obtained. Non-contrast CT on admission was normal while follow-up MRI showed extensive white matter abnormalities. These imaging abnormalities combined with the clinical presentation suggests cerebral fat embolism (CFE) as the most likely cause of secondary deterioration in our patient. In head injured patients with long bone fractures one should consider cerebral fat embolism. When the classical clinical syndrome is not present, MR imaging is warranted for diagnosis and to exclude other causes of secondary deterioration.

Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection

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

Oldfield, E.H.; Friedman, R.; Kinsella, T.

1990-05-01

To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the othermore » two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise unsafe doses of radiation in patients with CNS neoplasms.« less

Neuroprotective effects of Quercetin on radiation-induced brain injury in rats.

PubMed

Kale, Aydemir; Piskin, Özcan; Bas, Yilmaz; Aydin, Bengü Gülhan; Can, Murat; Elmas, Özlem; Büyükuysal, Çagatay

2018-04-24

Extensive research has been focused on radiation-induced brain injury. Animal and human studies have shown that flavonoids have remarkable toxicological profiles. This study aims to investigate the neuroprotective effects of quercetin in an experimental radiation-induced brain injury. A total of 32 adult male Wistar-Albino rats were randomly divided into four groups (control, quercetin, radiation, and radiation+quercetin groups, with eight rats in each group). Doses (50 mg/kg) of quercetin were administered to the animals in the quercetin and radiation+quercetin groups; radiation and radiation+quercetin groups were exposed to a dose of 20 Gy to the cranium region. Tissue samples, and biochemical levels of tissue injury markers in the four groups were compared. In all measured parameters of oxidative stress, administration of quercetin significantly demonstrated favorable effects. Both plasma and tissue levels of malondialdehyde and total antioxidant status significantly changed in favor of antioxidant activity. Histopathological evaluation of the tissues also demonstrated a significant decrease in cellular degeneration and infiltration parameters after quercetin administration. Quercetin demonstrated significant neuroprotection after radiation-induced brain injury. Further studies of neurological outcomes under different experimental settings are required in order to achieve conclusive results.

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...

Use of biomarkers for assessing radiation injury and efficacy of countermeasures

PubMed Central

Singh, Vijay K; Newman, Victoria L; Romaine, Patricia LP; Hauer-Jensen, Martin; Pollard, Harvey B

2016-01-01

Several candidate drugs for acute radiation syndrome (ARS) have been identified that have low toxicity and significant radioprotective and radiomitigative efficacy. Inasmuch as exposing healthy human volunteers to injurious levels of radiation is unethical, development and approval of new radiation countermeasures for ARS are therefore presently based on animal studies and Phase I safety study in healthy volunteers. The Animal Efficacy Rule, which underlies the Food and Drug Administration approval pathway, requires a sound understanding of the mechanisms of injury, drug efficacy, and efficacy biomarkers. In this context, it is important to identify biomarkers for radiation injury and drug efficacy that can extrapolate animal efficacy results, and can be used to convert drug doses deduced from animal studies to those that can be efficacious when used in humans. Here, we summarize the progress of studies to identify candidate biomarkers for the extent of radiation injury and for evaluation of countermeasure efficacy. PMID:26568096

Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.

PubMed

Yang, Lianhong; Yang, Jianhua; Li, Guoqian; Li, Yi; Wu, Rong; Cheng, Jinping; Tang, Yamei

2017-03-01

The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.

Neuroimmune interactions: potential target for mitigating or treating intestinal radiation injury.

PubMed

Wang, J; Hauer-Jensen, M

2007-09-01

Intestinal radiation injury is characterized by breakdown of the epithelial barrier and mucosal inflammation. In addition to replicative and apoptotic cell death, radiation also induces changes in cellular function, as well as alterations secondary to tissue injury. The recognition of these "non-cytocidal" radiation effects has enhanced the understanding of normal tissue radiation toxicity, thus allowing an integrated systems biology-based approach to modulating radiation responses and providing a mechanistic rationale for interventions to mitigate or treat radiation injuries. The enteric nervous system regulates intestinal motility, blood flow and enterocyte function. The enteric nervous system also plays a central role in maintaining the physiological state of the intestinal mucosa and in coordinating inflammatory and fibroproliferative processes. The afferent component of the enteric nervous system, in addition to relaying sensory information, also exerts important effector functions and contributes critically to preserving mucosal integrity. Interactions between afferent nerves, mast cells as well as other cells of the resident mucosal immune system serve to maintain mucosal homeostasis and to ensure an appropriate response to injury. Notably, enteric sensory neurons regulate the activation threshold of mast cells by secreting substance P, calcitonin gene-related peptide and other neuropeptides, whereas mast cells signal to enteric nerves by the release of histamine, nerve growth factor and other mediators. This article reviews how enteric neurons interact with mast cells and other immune cells to regulate the intestinal radiation response and how these interactions may be modified to mitigate intestinal radiation toxicity. These data are not only applicable to radiation therapy, but also to intestinal injury in a radiological terrorism scenario.

Clinical and dosimetric factors of radiation-induced esophageal injury: radiation-induced esophageal toxicity.

PubMed

Qiao, Wen-Bo; Zhao, Yan-Hui; Zhao, Yan-Bin; Wang, Rui-Zhi

2005-05-07

To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during three-dimensional conformal radiotherapy (3D-CRT). We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus > or =60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). Concurrent chemotherapy and the maximal esophageal point dose > or =60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT.

Delayed cerebral radiation necrosis following treatment for a plasmacytoma of the skull.

PubMed

Chambless, Lola B; Angel, Federica B; Abel, Ty W; Xia, Fen; Weaver, Kyle D

2010-10-25

Cerebral radiation necrosis is a relatively common complication of radiation therapy for intracranial malignancies which can also rarely be encountered after radiation of extracranial lesions of the head and neck. We present the first reported case of cerebral radiation necrosis in a patient who underwent radiation therapy for a plasmacytoma of the skull. A 68-year-old male with multiple myeloma presented with an enhancing right frontal mass, 8 years after receiving radiation therapy for a plasmacytoma of the left frontal skull. The patient underwent a diagnostic and therapeutic craniotomy for a presumed neoplastic lesion. The pathologic diagnosis made in this case was delayed radiation necrosis. The patient was followed for over a year during which this process continued to evolve before the ultimate resolution of his clinical symptoms and radiographic abnormality. This case highlights the importance of considering radiation necrosis in the differential diagnosis of any patient with an intracranial mass and a history of radiation for an extracranial head and neck malignancy, regardless of timing and laterality. This case also provides unique insights into the ongoing debate regarding the role of the aberrant immune response in the pathogenesis of delayed cerebral radiation necrosis.

Acute Cerebrovascular Radiation Syndrome: Radiation Neurotoxicity , mechanisms of CNS radiation injury, advanced countermeasures for Radiation Protection of Central Nervous System.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

Key words: Cerebrovascular Acute Radiation Syndrome (Cv ARS), Radiation Neurotoxins (RNT), Neurotransmitters, Radiation Countermeasures, Antiradiation Vaccine (ArV), Antiradiation Blocking Antibodies, Antiradiation Antidote. Psychoneuroimmunology, Neurotoxicity. ABSTRACT: To review the role of Radiation Neurotoxins in triggering, developing of radiation induced central nervous system injury. Radiation Neurotoxins - rapidly acting blood toxic lethal agent, which activated after irradiation and concentrated, circulated in interstitial fluid, lymph, blood with interactions with cell membranes, receptors and cell compartments. Radiation Neurotoxins - biological molecules with high enzymatic activity and/or specific lipids and activated or modified after irradiation. The Radiation Neurotoxins induce increased permeability of blood vessels, disruption of the blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier and developing severe disorder of blood macro- and micro-circulation. Principles of Radiation Psychoneuro-immunology and Psychoneuro-allergology were applied for determination of pathological processes developed after irradiation or selective administration of Radiation Neurotoxins to radiation naïve mammals. Effects of radiation and exposure to radiation can develop severe irreversible abnormalities of Central Nervous System, brain structures and functions. Antiradiation Vaccine - most effective, advanced methods of protection, prevention, mitigation and treatment and was used for of Acute Radiation Syndromes and elaboration of new technology for immune-prophylaxis and immune-protection against ϒ, Heavy Ion, Neutron irradiation. Results of experiments suggested that blocking, antitoxic, antiradiation antibodies can significantly reduce toxicity of Radiation Toxins. New advanced technology include active immune-prophylaxis with Antiradiation Vaccine and Antiradiation therapy that included specific blocking antibodies to Radiation Neurotoxins

Traumatic brain injury and delayed sequelae: a review--traumatic brain injury and mild traumatic brain injury (concussion) are precursors to later-onset brain disorders, including early-onset dementia.

PubMed

Kiraly, Michael; Kiraly, Stephen J

2007-11-12

Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI) and mild traumatic brain injury (MTBI). Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Objectives of this summary are, therefore, to instill appreciation regarding the importance of brain injury prevention, diagnosis, and treatment, and to increase awareness regarding the long-term delayed consequences following TBI.

Burden of road traffic injuries related to delays in implementing safety belt laws in low- and lower-middle-income countries.

PubMed

Martin, Aurélie; Lagarde, Emmanuel; Salmi, L Rachid

2018-02-28

Delayed implementation of effective road safety policies must be considered when quantifying the avoidable part of the fatal and nonfatal injuries burden. We sought to assess the avoidable part of disability-adjusted life years (DALYs) lost due to road traffic injuries related to delays in implementing road safety laws in low- and lower-middle-income countries. We chose one country for each of the regions of the World Health Organization (WHO) and World Bank (WB) country income levels. We used freely available data sets (WHO, International Traffic Safety Data and Analysis Group, the WB). Delays in implementation were calculated until 2013, from the year mandatory use of safety belts by motor vehicle front seat occupants was first introduced worldwide. We used life expectancy tables and age groups as social values in the DALY calculation model. From the estimated total burden, avoidable DALYs were calculated using estimates of the effectiveness of seat belt laws on fatal and nonfatal injuries combined, as extracted from published international reviews of evidence. From the reference year 1972, implementation delays varied from 27 years (Uzbekistan) to 41 years in Bolivia (no seat belt law as of 2013). During delays, total absolute numbers of DALYs lost due to road traffic injuries reached 8,462,099 in Nigeria, 7,203,570 in Morocco, 4,695,500 in Uzbekistan, 3,866,391 in Cambodia, 3,253,359 in Bolivia, and 3,128,721 in Sri Lanka. Using effectiveness estimates ranging from 3 to 20% reduction, the avoidable burden of road traffic injuries for car occupants was highest in Uzbekistan (avoidable part from 1.2 to 10.4%) and in Morocco (avoidable part from 1.5 to 12.3%). In countries where users of public transport and pedestrians were the most affected by the burden, the avoidable parts ranged from 0.5 to 4.4% (Nigeria) and from 0.5 to 3.4% (Bolivia). Burden of road traffic injuries mostly affected motorcyclists in Sri Lanka and Cambodia where the avoidable parts were

Exacerbation of lung radiation injury by viral infection: the role of Clara cells and Clara cell secretory protein.

PubMed

Manning, Casey M; Johnston, Carl J; Hernady, Eric; Miller, Jen-nie H; Reed, Christina K; Lawrence, B Paige; Williams, Jacqueline P; Finkelstein, Jacob N

2013-06-01

Viral infections have been associated with exacerbation of disease in human cases of idiopathic pulmonary fibrosis. Since pulmonary fibrosis is a common outcome after irradiation to the lung, we hypothesized that viral infection after radiation exposure would exacerbate radiation-induced lung injury. Epithelial injury, a frequent outcome after infection, has been hypothesized to contribute to the pathogenesis of pulmonary fibrosis and bronchiolar epithelial Clara cells participate in epithelial repair. Therefore, it was further hypothesized that altered responses after irradiation involve the bronchiolar epithelial Clara cells. C57BL/6J or CCSP(-/-) mice were irradiated with 0 (sham), 5, 10 or 15 Gy to the whole thorax. At ten weeks post-irradiation, animals were mock infected or infected with influenza A virus and body weight and survival were monitored. Pulmonary function was assessed by whole-body plethysmography. The Clara cell markers, CCSP and Cyp2f2, were measured in the lung by qRT-PCR, and protein expression was visualized in the lung by immunofluorescence. Following pulmonary function tests, mice were sacrificed and tissues were collected for pathological analysis. In 15 Gy irradiated animals infected with influenza A virus, accelerated respiratory rates, reduced pulmonary function, and exacerbated lung pathology occurred earlier post-irradiation than previously observed after irradiation alone, suggesting infection accelerates the development of radiation injury. After irradiation alone, CCSP and Cyp2f2 mRNA levels were reduced, correlating with reductions in the number of Clara cells lining the airways. When combined with infection, these markers further declined and an apparent delay in recovery of mRNA expression was observed, suggesting that radiation injury leads to a chronic reduction in the number of Clara cells that may potentiate the epithelial injury observed after influenza A virus infection. This novel finding may have considerable

The Urine Proteome as a Biomarker of Radiation Injury

PubMed Central

Sharma, Mukut; Halligan, Brian D.; Wakim, Bassam T.; Savin, Virginia J.; Cohen, Eric P.; Moulder, John E.

2009-01-01

Terrorist attacks or nuclear accidents could expose large numbers of people to ionizing radiation, and early biomarkers of radiation injury would be critical for triage, treatment and follow-up of such individuals. However, no such biomarkers have yet been proven to exist. We tested the potential of high throughput proteomics to identify protein biomarkers of radiation injury after total body X-ray irradiation in a rat model. Subtle functional changes in the kidney are suggested by an increased glomerular permeability for macromolecules measured within 24 hours after TBI. Ultrastructural changes in glomerular podocytes include partial loss of the interdigitating organization of foot processes. Analysis of urine by LC-MS/MS and 2D-GE showed significant changes in the urine proteome within 24 hours after TBI. Tissue kallikrein 1-related peptidase, cysteine proteinase inhibitor cystatin C and oxidized histidine were found to be increased while a number of proteinase inhibitors including kallikrein-binding protein and albumin were found to be decreased post-irradiation. Thus, TBI causes immediately detectable changes in renal structure and function and in the urinary protein profile. This suggests that both systemic and renal changes are induced by radiation and it may be possible to identify a set of biomarkers unique to radiation injury. PMID:19746194

Dietary Selenium for the Mitigation of Radiation Injury: Effects of Selenium Dose Escalation and Timing of Supplementation

PubMed Central

Sieber, Fritz; Muir, Sarah A.; Cohen, Eric P.; Fish, Brian L.; Mäder, Marylou; Schock, Ashley M.; Althouse, Bryan J.; Moulder, John E.

2011-01-01

We recently reported that daily dietary supplementation with 100 μg selenium (a dose exceeding a rat’s nutritional requirement by about 33-fold) initiated immediately after total-body irradiation (TBI) and maintained for 21 weeks mitigates radiation nephropathy in a rat model as indicated by blood urea nitrogen (BUN) levels and histopathological criteria (Radiat Res. 2009; 17:368–73). In this follow-up study, we explored the risks and benefits of delaying the onset of supplementation, shortening periods of supplementation, and escalating selenium supplementation beyond 100 μg/day. Supplementation with 200 μg selenium/day (as selenite or seleno-L-methionine) substantially improved the mitigation of radiation nephropathy by lowering BUN levels at 4 months after TBI from 115 to as low as 34 mg/dl and by proportionally lowering the incidence of histopathological abnormalities. Shortening the period of supplementation to 3 or 2 months did not compromise efficacy. Delaying the onset of supplementation for 1 week reduced but did not abrogate the mitigation of radiation nephropathy. Supplementation with 300 μg/day mitigated radiation nephropathy less effectively than 200 μg and was poorly tolerated. Rats that had been given 10 Gy of TBI were less tolerant of high-dose selenium than nonirradiated rats. This reduced tolerance of high-dose selenium would need to be taken into consideration when selenium is used for the mitigation of radiation injury in victims of nuclear accidents or acts of radiological terrorism. The high dose requirements, the pronounced threshold effect, and the superior performance of selenite suggest that the mitigation of radiation nephropathy involves mechanisms that go beyond the induction of selenoproteins. PMID:21867430

Delayed presentation of blunt duodenal injuries in children. Case report and review of literature

PubMed Central

TORBA, M.; GJATA, A.; BUCI, S.; TROCI, A.; SUBASHI, K.

2013-01-01

Summary: Background Duodenal injuries are rare in children and classically present following a fall over the handle bar. Retroperitoneal location of the duodenum may lead to delay in diagnosis, and missed injuries are associated with increased morbidity and mortality. Case report. A 5-year-old child was admitted to the National Trauma Center, in Tirana (Albania), 28 hours after a Motor Vehicle Crash (MVC), complaining of mild abdominal pain. He was febrile (39°C) and had a white blood cells count of 18,000 mm3. On physical exam he had mild tenderness. Plain abdominal X-rays and Focused Abdominal Sonography for Trauma (FAST) were negative for free air or free fluid. The CT scan of the abdomen demonstrated free air and fluid in the retroperitoneal space. At laparatomy, a perforation of the second portion of the duodenum was found. A single layer suture repair of the duodenum with wide drainage was performed. The patient was discharged from the hospital tolerating oral feeding 8 days later. Conclusion Duodenal injuries in children are rare. Most duodenal hematomas are managed non-operatively. This is a case of MCV with delayed presentation that was treated surgically for perforation successfully. PMID:23660164

Protective effect of inhalation of hydrogen gas on radiation-induced dermatitis and skin injury in rats

PubMed Central

Watanabe, Sadahiro; Fujita, Masanori; Ishihara, Masayuki; Tachibana, Shoichi; Yamamoto, Yoritsuna; Kaji, Tatsumi; Kawauchi, Toshio; Kanatani, Yasuhiro

2014-01-01

The effect of inhalation of hydrogen-containing gas (1.3% hydrogen + 20.8% oxygen + 77.9% nitrogen) (HCG) on radiation-induced dermatitis and on the healing of healing-impaired skin wounds in rats was examined using a rat model of radiation-induced skin injury. An X-ray dose of 20 Gy was irradiated onto the lower part of the back through two holes in a lead shield. Irradiation was performed before or after inhalation of HCG for 2 h. Inhalation of HCG significantly reduced the severity of radiodermatitis and accelerated healing-impaired wound repair. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) showed that the proportion of apoptotic keratinocytes and the level of staining in the X-irradiated skin of rats that pre-inhaled HCG were significantly lower than that of rats which did not pre-inhale HCG. Cutaneous full-thickness wounds were then created in the X-irradiated area to examine the time-course of wound healing. X-irradiation significantly increased the time required for wound healing, but the inhalation of HCG prior to the irradiation significantly decreased the delay in wound healing compared with the control and post-inhalation of HCG groups. Therefore, radiation-induced skin injury can potentially be alleviated by the pre-inhalation of HCG. PMID:25034733

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.

Delayed hydronephrosis due to retroperitoneal hematoma after a seatbelt injury

PubMed Central

Yumoto, Tetsuya; Kondo, Yoshitaka; Kumon, Kento; Masaoka, Yoshihisa; Hiraki, Takao; Yamada, Taihei; Naito, Hiromichi; Nakao, Atsunori

2018-01-01

Abstract Rationale: Hydronephrosis caused by retroperitoneal hematoma after a seatbelt injury is a unique clinical entity. Patient concerns: A 21-year-old man, who had been wearing a seatbelt, was brought to our hospital after a motor vehicle collision, complaining of abdominal pain. Computed tomography (CT) revealed retroperitoneal hematoma in the upper pelvic region. Since he was hemodynamically stable throughout admission, he was managed conservatively. Seventeen days after initial discharge, the patient revisited our emergency department due to right back pain. Diagnoses: CT scans indicated retroperitoneal hematoma growth resulting in hydronephrosis of the right kidney. Interventions: Laparoscopic drainage of the retroperitoneal hematoma was successfully performed. Outcomes: His symptoms resolved after the surgery. Follow-up CT scans three months later demonstrated complete resolution of the hydronephrosis and retroperitoneal hematoma. Lessons: Our case highlights a patient with delayed hydronephrosis because of retroperitoneal hematoma expansion after a seatbelt injury. PMID:29879068

Combined effects of radiation and trauma

NASA Astrophysics Data System (ADS)

Messerschmidt, Otfried

Injuries, caused by both whole-body irradiation and wounds or burns, have been relatively little studied. Possibly because many investigators think that these injuries are just modified radiation-induced diseases for which the same treatment principles are valid. Other authors had the impression that, for instance, the radiation burn trauma is a new kind of disease which differs significantly from either radiation syndrome alone or from burn disease. There are many experimental data on animals which suggest that the pathology of combined injuries differs significantly from that of radiation-induced disease or of thermal or mechanical traumas. Wounds or burns which, in general, do not cause septicaemia could become entrance ports for bacteria when animals are exposed to whole-body irradiation. Thrombocytopenia is the reason for hemorrhages in wounds. The susceptibility to shock is increased considerably in combined injuries and the formation of callus in the bone fractures is significantly delayed. The healing of wounds and burns in the initial phase of the radiation syndrome does not always differ from healing in the non-irradiated organism. However, a few days or weeks later very serious wound infections and hemorrhages can occur. The additional injuries almost always worsen the development and prognosis of radiation-induced disease. The recommended treatment for combined injuries will differ in many respects from the treatment of wounds and burns or the radiation syndrome.

[Delayed perforation of the cecum and sigmoid colon after blunt abdominal trauma in a patient with multiple injuries].

PubMed

Miranda, E; Arroyo, A; Ronda, J M; Muñoz, J L; Alonso, C; Martínez-Peñuelas, F; Martí-Viaño, J L

2007-01-01

Blunt abdominal trauma can damage the intestinal vasculature and may occasionally lead to delayed intestinal perforation, associated with a combined rate of morbidity and mortality of 25%. The diagnosis of such complications is hindered by sedation in critical patients, however, and morbimortality in this population is therefore higher. We report the case of a man with multiple injuries admitted to the intensive care unit, where delayed perforations of the sigmoid colon and cecum were diagnosed. The management of blunt abdominal trauma is reviewed and the possible causes, diagnostic approaches, and treatment options for colon injuries are discussed.

Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

PubMed

Jung, Enjae; Perrone, Erin E; Brahmamdan, Pavan; McDonough, Jacquelyn S; Leathersich, Ann M; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Hotchkiss, Richard S; Coopersmith, Craig M

2013-01-01

World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target.

Inhibition of Intestinal Epithelial Apoptosis Improves Survival in a Murine Model of Radiation Combined Injury

PubMed Central

Jung, Enjae; Perrone, Erin E.; Brahmamdan, Pavan; McDonough, Jacquelyn S.; Leathersich, Ann M.; Dominguez, Jessica A.; Clark, Andrew T.; Fox, Amy C.; Dunne, W. Michael; Hotchkiss, Richard S.; Coopersmith, Craig M.

2013-01-01

World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target. PMID:24204769

Rebamipide ameliorates radiation-induced intestinal injury in a mouse model.

PubMed

Shim, Sehwan; Jang, Hyo-Sun; Myung, Hyun-Wook; Myung, Jae Kyung; Kang, Jin-Kyu; Kim, Min-Jung; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Jin, Young-Woo; Lee, Seung-Sook; Park, Sunhoo

2017-08-15

Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. Radiation exposure produces an uncontrolled inflammatory cascade and epithelial cell loss leading to impaired epithelial barrier function. The goal of this study was to determine the effect of rebamipide on regeneration of the intestinal epithelia after radiation injury. The abdomens of C57BL/6 mice were exposed to 13Gy of irradiation (IR) and then the mice were treated with rebamipide. Upon IR, intestinal epithelia were destroyed structurally at the microscopic level and bacterial translocation was increased. The intestinal damage reached a maximum level on day 6 post-IR and intestinal regeneration occurred thereafter. We found that rebamipide significantly ameliorated radiation-induced intestinal injury. In mice treated with rebamipide after IR, intestinal barrier function recovered and expression of the tight junction components of the intestinal barrier were upregulated. Rebamipide administration reduced radiation-induced intestinal mucosal injury. The levels of proinflammatory cytokines and matrix metallopeptidase 9 (MMP9) were significantly reduced upon rebamipide administration. Intestinal cell proliferation and β-catenin expression also increased upon rebamipide administration. These data demonstrate that rebamipide reverses impairment of the intestinal barrier by increasing intestinal cell proliferation and attenuating the inflammatory response by inhibiting MMP9 and proinflammatory cytokine expression in a murine model of radiation-induced enteritis. Copyright © 2017 Elsevier Inc. All rights reserved.

Parecoxib Reduces Systemic Inflammation and Acute Lung Injury in Burned Animals with Delayed Fluid Resuscitation

PubMed Central

Chong, Si Jack; Wu, Jian; Lu, Jia; Moochhala, Shabbir M.

2014-01-01

Burn injuries result in the release of proinflammatory mediators causing both local and systemic inflammation. Multiple organ dysfunctions secondary to systemic inflammation after severe burn contribute to adverse outcome, with the lungs being the first organ to fail. In this study, we evaluate the anti-inflammatory effects of Parecoxib, a parenteral COX-2 inhibitor, in a delayed fluid resuscitation burned rat model. Anaesthetized Sprague Dawley rats were inflicted with 45% total body surface area full-thickness scald burns and subsequently subjected to delayed resuscitation with Hartmann's solution. Parecoxib (0.1, 1.0, and 10 mg/kg) was delivered intramuscularly 20 min after injury followed by 12 h interval and the rats were sacrificed at 6 h, 24 h, and 48 h. Burn rats developed elevated blood cytokines, transaminase, creatinine, and increased lung MPO levels. Animals treated with 1 mg/kg Parecoxib showed significantly reduced plasma level of CINC-1, IL-6, PGEM, and lung MPO. Treatment of 1 mg/kg Parecoxib is shown to mitigate systemic and lung inflammation without significantly affecting other organs. At present, no specific therapeutic agent is available to attenuate the systemic inflammatory response secondary to burn injury. The results suggest that Parecoxib may have the potential to be used both as an analgesic and ameliorate the effects of lung injury following burn. PMID:24579056

A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin

PubMed Central

Doctrow, Susan R.; Lopez, Argelia; Schock, Ashley M.; Duncan, Nathan E.; Jourdan, Megan M.; Olasz, Edit B.; Moulder, John E.; Fish, Brian L.; Mäder, Marylou; Lazar, Jozef; Lazarova, Zelmira

2012-01-01

In the event of a radionuclear attack or nuclear accident, the skin would be the first barrier exposed to radiation, though skin injury can progress over days to years following exposure. Chronic oxidative stress has been implicated as being a potential contributor to the progression of delayed radiation-induced injury to skin and other organs. To examine the causative role of oxidative stress in delayed radiation-induced skin injury, including impaired wound healing, we tested a synthetic superoxide dismutase (SOD)/catalase mimetic, EUK-207, in a rat model of combined skin irradiation and wound injury. Administered systemically, beginning 48 h after irradiation, EUK-207 mitigated radiation dermatitis, suppressed indicators of tissue oxidative stress, and enhanced wound healing. Evaluation of gene expression in irradiated skin at 30 days after exposure revealed a significant upregulation of several key genes involved in detoxication of reactive oxygen and nitrogen species. This gene expression pattern was primarily reversed by EUK-207 therapy. These results demonstrate that oxidative stress plays a critical role in the progression of radiation-induced skin injury, and that the injury can be mitigated by appropriate antioxidant compounds administered 48 h after exposure. PMID:23190879

Delayed urinary fistula from high velocity missile injury to the ureter.

PubMed Central

Cetti, N. E.

1983-01-01

Reports from the Vietnam War and from Northern Ireland describe the problem of delayed urinary fistula from a ureter seen to be 'intact' at previous laparotomy for high velocity missile injury to the abdomen. This is due to remote damage to the ureteric blood supply which is difficult to recognise or predict. A recent example of the problem from the Falklands Campaign is described. Prophylactic splintage at the initial exploration is suggested. Images Fig. 1 Fig. 2 Fig. 3 PMID:6614761

Intestinal Microbiota-Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

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

Ó Broin, Pilib; Department of Mathematical Sciences, Yeshiva University, New York, New York; Vaitheesvaran, Bhavapriya

2015-02-01

Purpose: Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials: Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative,more » untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results: We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusions: Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma.« less

Intestinal microbiota-derived metabolomic blood plasma markers for prior radiation injury.

PubMed

Ó Broin, Pilib; Vaitheesvaran, Bhavapriya; Saha, Subhrajit; Hartil, Kirsten; Chen, Emily I; Goldman, Devorah; Fleming, William Harv; Kurland, Irwin J; Guha, Chandan; Golden, Aaron

2015-02-01

Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative, untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma. Copyright © 2015 Elsevier Inc. All rights reserved.

Immediate and delayed hyperbaric oxygen therapy as a neuroprotective treatment for traumatic brain injury in mice.

PubMed

Baratz-Goldstein, Renana; Toussia-Cohen, Shlomi; Elpaz, Aviya; Rubovitch, Vardit; Pick, Chaim G

2017-09-01

Traumatic brain injury is the most common cause of death or chronic disability among people under-35-years-old. There is no effective pharmacological treatment currently existing for TBI. Hyperbaric oxygen therapy (HBOT) is defined as the inhalation of pure oxygen in a hyperbaric chamber that is pressurized higher than 1atm. HBOT offers physiological and mechanical effects by inducing a state of increased pressure and hyperoxia. HBOT has been proposed as an effective treatment for moderate traumatic brain injury (mTBI), yet the exact therapeutic window and mechanism that underlies this effect is not completely understood. HBOT was administrated for 4 consecutive days, post a mouse closed head weight drop moderate TBI (mTBI) in 2 different time lines: immediate treatment - initiated 3h post-injury and delayed treatment - initiated 7days post-injury. Behavioral cognitive tests and biochemical changes were assessed. The results were similar for both the immediate and the delayed treatments. mTBI mice exhibited impairment in learning abilities, whereas mTBI mice treated with HBO displayed significant improvement compared with the mTBI group, performing similar to the sham groups. mTBI mice had a decline in myelin basic protein, an increase in neuronal loss (NeuN staining), and an increase in the number of reactive astrocytes (GFAP). The HBO treated mice in both groups did not exhibit these changes and remained similar to the sham group. The delayed HBOT has a potential to serve as a neuroprotective treatment for mTBI with a long therapeutic window. Further research is needed for fully understanding the cellular changes. Copyright © 2017 Elsevier Inc. All rights reserved.

Photosynthetically active radiation (PAR) x ultraviolet radiation (UV) interact to initiate solar injury in apple

USDA-ARS?s Scientific Manuscript database

Sunburn or solar injury (SI) in apple is associated with high temperature, high visible light and ultraviolet radiation (UV). Fruit surface temperature (FST) thresholds for SI related disorders have been developed but there are no thresholds established for solar radiation. The objectives of the s...

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

Traumatic colon injury in damage control laparotomy-A multicenter trial: Is it safe to do a delayed anastomosis?

PubMed

Tatebe, Leah Carey; Jennings, Andrew; Tatebe, Ken; Handy, Alexandra; Prajapati, Purvi; Smith, Michael; Do, Tai; Ogola, Gerald O; Gandhi, Rajesh R; Duane, Therese M; Luk, Stephen; Petrey, Laura Bruce

2017-04-01

Delayed colonic anastomosis after damage control laparotomy (DCL) is an alternative to colostomies during a single laparotomy (SL) in high-risk patients. However, literature suggests increased colonic leak rates up to 27% with DCL, and various reported risk factors. We evaluated our regional experience to determine if delayed colonic anastomosis was associated with worse outcomes. A multicenter retrospective cohort study was performed across three Level I trauma centers encompassing traumatic colon injuries from January 2006 through June 2014. Patients with rectal injuries or mortality within 24 hours were excluded. Patient and injury characteristics, complications, and interventions were compared between SL and DCL groups. Regional readmission data were utilized to capture complications within 6 months of index trauma. Of 267 patients, 69% had penetrating injuries, 21% underwent DCL, and the mortality rate was 4.9%. Overall, 176 received primary repair (26 in DCL), 90 had resection and anastomosis (28 in DCL), and 26 had a stoma created (10 end colostomies and 2 loop ileostomies in DCL). Thirty-five of 56 DCL patients had definitive colonic repair subsequent to their index operation. DCL patients were more likely to be hypotensive; require more resuscitation; and suffer acute kidney injury, pneumonia, adult respiratory distress syndrome, and death. Five enteric leaks (1.9%) and three enterocutaneous fistulas (ECF, 1.1%) were identified, proportionately distributed between DCL and SL (p = 1.00, p = 0.51). No difference was seen in intraperitoneal abscesses (p = 0.13) or surgical site infections (SSI, p = 0.70) between cohorts. Among SL patients, pancreas injuries portended an increased risk of intraperitoneal abscesses (p = 0.0002), as did liver injuries in DCL patients (p = 0.06). DCL was not associated with increased enteric leaks, ECF, SSI, or intraperitoneal abscesses despite nearly two-thirds having delayed repair. Despite this being a multicenter study, it is

Genetic Modeling of Radiation Injury in Prostate Cancer Patients Treated with Radiotherapy

DTIC Science & Technology

2016-10-01

nucleotide polymorphisms, prostate cancer, radiation therapy, adverse effects, urinary morbidity, rectal injury, sexual dysfunction 16. SECURITY...prostate cancer, radiation therapy, adverse effects, urinary morbidity, rectal injury, sexual dysfunction 3. ACCOMPLISHMENTS: What were the...Significant results: As shown in Table 1A, the mean age of patients across the eight studies ranged from 65 to 72 years with some moderate variation

Delayed splenic vascular injury after nonoperative management of blunt splenic trauma.

PubMed

Furlan, Alessandro; Tublin, Mitchell E; Rees, Mitchell A; Nicholas, Dederia H; Sperry, Jason L; Alarcon, Louis H

2017-05-01

Delayed splenic vascular injury (DSVI) is traditionally considered a rare, often clinically occult, harbinger of splenic rupture in patients with splenic trauma that are managed conservatively. The purpose of our study was to assess the incidence of DSVI and associated features in patients admitted with blunt splenic trauma and managed nonoperatively. A retrospective analysis was conducted over a 4-y time. Patients admitted with blunt splenic trauma, managed no-operatively and with a follow-up contrast-enhanced computed tomography (CT) scan study during admission were included. The CT scans were reviewed for American Association for the Surgery of Trauma splenic injury score, amount of hemoperitoneum, and presence of DSVI. Logistic regression models were used to investigate the risk factors associated with DSVI. A total of 100 patients (60 men and 40 women) constituted the study group. Follow-up CT scan demonstrated a 23% incidence of DSVI. Splenic artery angiography validated DSVI in 15% of the total patient population. Most DSVIs were detected only on arterial phase CT scan imaging. The American Association for the Surgery of Trauma splenic injury score (odds ratio = 1.73; P = 0.045) and the amount of hemoperitoneum (odds ratio = 1.90; P = 0.023) on admission CT scan were associated with the development of DSVI on follow-up CT scan. DSVI on follow-up CT scan imaging of patients managed nonoperatively after splenic injury is common and associated with splenic injury score assessed on admission CT scan. Copyright © 2016 Elsevier Inc. All rights reserved.

Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

PubMed

Furuse, Motomasa; Nonoguchi, Naosuke; Kawabata, Shinji; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko

2015-12-01

Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

Stromal Progenitor Cells in Mitigation of Non-Hematopoietic Radiation Injuries

PubMed Central

Kulkarni, Shilpa; Wang, Timothy C.; Guha, Chandan

2016-01-01

Purpose of review Therapeutic exposure to high doses of radiation can severely impair organ function due to ablation of stem cells. Normal tissue injury is a dose-limiting toxicity for radiation therapy (RT). Although advances in the delivery of high precision conformal RT has increased normal tissue sparing, mitigating and therapeutic strategies that could alleviate early and chronic radiation effects are urgently needed in order to deliver curative doses of RT, especially in abdominal, pelvic and thoracic malignancies. Radiation-induced gastrointestinal injury is also a major cause of lethality from accidental or intentional exposure to whole body irradiation in the case of nuclear accidents or terrorism. This review examines the therapeutic options for mitigation of non-hematopoietic radiation injuries. Recent findings We have developed stem cell based therapies for the mitigation of acute radiation syndrome (ARS) and radiation-induced gastrointestinal syndrome (RIGS). This is a promising option because of the robustness of standardized isolation and transplantation of stromal cells protocols, and their ability to support and replace radiation-damaged stem cells and stem cell niche. Stromal progenitor cells (SPC) represent a unique multipotent and heterogeneous cell population with regenerative, immunosuppressive, anti-inflammatory, and wound healing properties. SPC are also known to secrete various key cytokines and growth factors such as platelet derived growth factors (PDGF), keratinocyte growth factor (KGF), R-spondins (Rspo), and may consequently exert their regenerative effects via paracrine function. Additionally, secretory vesicles such as exosomes or microparticles can potentially be a cell-free alternative replacing the cell transplant in some cases. Summary This review highlights the beneficial effects of SPC on tissue regeneration with their ability to (a) target the irradiated tissues, (b) recruit host stromal cells, (c) regenerate endothelium and

Radiation combined injury models to study the effects of interventions and wound biomechanics.

PubMed

Zawaski, Janice A; Yates, Charles R; Miller, Duane D; Kaffes, Caterina C; Sabek, Omaima M; Afshar, Solmaz F; Young, Daniel A; Yang, Yunzhi; Gaber, M Waleed

2014-12-01

In the event of a nuclear detonation, a considerable number of projected casualties will suffer from combined radiation exposure and burn and/or wound injury. Countermeasure assessment in the setting of radiation exposure combined with dermal injury is hampered by a lack of animal models in which the effects of interventions have been characterized. To address this need, we used two separate models to characterize wound closure. The first was an open wound model in mice to study the effect of wound size in combination with whole-body 6 Gy irradiation on the rate of wound closure, animal weight and survival (morbidity). In this model the addition of interventions, wound closure, subcutaneous vehicle injection, topical antiseptic and topical antibiotics were studied to measure their effect on healing and survival. The second was a rat closed wound model to study the biomechanical properties of a healed wound at 10 days postirradiation (irradiated with 6 or 7.5 Gy). In addition, complete blood counts were performed and wound pathology by staining with hematoxylin and eosin, trichrome, CD68 and Ki67. In the mouse open wound model, we found that wound size and morbidity were positively correlated, while wound size and survival were negatively correlated. Regardless of the wound size, the addition of radiation exposure delayed the healing of the wound by approximately 5-6 days. The addition of interventions caused, at a minimum, a 30% increase in survival and improved mean survival by ∼9 days. In the rat closed wound model we found that radiation exposure significantly decreased all wound biomechanical measurements as well as white blood cell, platelet and red blood cell counts at 10 days post wounding. Also, pathological changes showed a loss of dermal structure, thickening of dermis, loss of collagen/epithelial hyperplasia and an increased density of macrophages. In conclusion, we have characterized the effect of a changing wound size in combination with radiation

Combined Radiation and Thermal Injury after Nuclear Attack

DTIC Science & Technology

1990-01-01

0T’Fit f-copy Combined Radiation and Thermal Injury 04 After Nuclear Attack , (M) William K. Becker, Teresa M. Buescher, William G. Cioffi, William F...Chicago, 1979, pp. 5-61. 4. Reiss, E., Stirman, J. A., Artz, C . P., et al. Fluid and electrolyte balance in burns. JAMA 152:1309- 1313, 1953. 5...et al. Septicemia in burn injury. J Trauma 1:22-31,1961. 7. Moncrief , J. A., Lindberg, R. B., Switzer, W. E., et al. Use of topical antibacterial

Radiation-Induced Liver Injury in Three-Dimensional Conformal Radiation Therapy (3D-CRT) for Postoperative or Locoregional Recurrent Gastric Cancer: Risk Factors and Dose Limitations.

PubMed

Li, Guichao; Wang, Jiazhou; Hu, Weigang; Zhang, Zhen

2015-01-01

This study examined the status of radiation-induced liver injury in adjuvant or palliative gastric cancer radiation therapy (RT), identified risk factors of radiation-induced liver injury in gastric cancer RT, analysed the dose-volume effects of liver injury, and developed a liver dose limitation reference for gastric cancer RT. Data for 56 post-operative gastric cancer patients and 6 locoregional recurrent gastric cancer patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) from Sep 2007 to Sep 2009 were analysed. Forty patients (65%) were administered concurrent chemotherapy. Pre- and post-radiation chemotherapy were given to 61 patients and 43 patients, respectively. The radiation dose was 45-50.4 Gy in 25-28 fractions. Clinical parameters, including gender, age, hepatic B virus status, concurrent chemotherapy, and the total number of chemotherapy cycles, were included in the analysis. Univariate analyses with a non-parametric rank test (Mann-Whitney test) and logistic regression test and a multivariate analysis using a logistic regression test were completed. We also analysed the correlation between RT and the changes in serum chemistry parameters [including total bilirubin, (TB), direct bilirubin (D-TB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum albumin (ALB)] after RT. The Child-Pugh grade progressed from grade A to grade B after radiotherapy in 10 patients. A total of 16 cases of classic radiation-induced liver disease (RILD) were observed, and 2 patients had both Child-Pugh grade progression and classic RILD. No cases of non-classic radiation liver injury occurred in the study population. Among the tested clinical parameters, the total number of chemotherapy cycles correlated with liver function injury. V35 and ALP levels were significant predictive factors for radiation liver injury. In 3D-CRT for gastric cancer patients

Delayed inflammatory mRNA and protein expression after spinal cord injury

PubMed Central

2011-01-01

Background Spinal cord injury (SCI) induces secondary tissue damage that is associated with inflammation. We have previously demonstrated that inflammation-related gene expression after SCI occurs in two waves - an initial cluster that is acutely and transiently up-regulated within 24 hours, and a more delayed cluster that peaks between 72 hours and 7 days. Here we extend the microarray analysis of these gene clusters up to 6 months post-SCI. Methods Adult male rats were subjected to mild, moderate or severe spinal cord contusion injury at T9 using a well-characterized weight-drop model. Tissue from the lesion epicenter was obtained 4 hours, 24 hours, 7 days, 28 days, 3 months or 6 months post-injury and processed for microarray analysis and protein expression. Results Anchor gene analysis using C1qB revealed a cluster of genes that showed elevated expression through 6 months post-injury, including galectin-3, p22PHOX, gp91PHOX, CD53 and progranulin. The expression of these genes occurred primarily in microglia/macrophage cells and was confirmed at the protein level using both immunohistochemistry and western blotting. As p22PHOX and gp91PHOX are components of the NADPH oxidase enzyme, enzymatic activity and its role in SCI were assessed and NADPH oxidase activity was found to be significantly up-regulated through 6 months post-injury. Further, treating rats with the nonspecific, irreversible NADPH oxidase inhibitor diphenylene iodinium (DPI) reduced both lesion volume and expression of chronic gene cluster proteins one month after trauma. Conclusions These data demonstrate that inflammation-related genes are chronically up-regulated after SCI and may contribute to further tissue loss. PMID:21975064

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

Relatively short diagnostic delays (<8 hours) produce morbidity and mortality in blunt small bowel injury: an analysis of time to operative intervention in 198 patients from a multicenter experience.

PubMed

Fakhry, S M; Brownstein, M; Watts, D D; Baker, C C; Oller, D

2000-03-01

Blunt small bowel injury (SBI) is uncommon, and its timely diagnosis may be difficult. The impact of operative delays on morbidity and mortality has been unclear. The purpose of this study was to determine the relationship of diagnostic delays to morbidity and mortality in blunt SBI. Patients with blunt SBI with perforation were identified from the registries of eight trauma centers (1989-1997). Patients with duodenal injuries were excluded. Data were extracted by individual chart review. Patients were classified as multi-trauma (group 1) or near-isolated SBI (group 2 with Abbreviated Injury Scale score < 2 for other body areas). Time to operation and its impact on mortality and morbidity was determined for each patient. A total of 198 patients met inclusion criteria: 66.2% were male, mean age was 35.2 years (range, 1-90 years) and mean Injury Severity Score was 16.7 (range, 9-47). 100 patients had multiple injuries (group 1). There were 21 deaths (10.6%) with 9 (4.5%) attributable to delay in operation for SBI. In patients with near-isolated SBI, the incidence of mortality increased with time to operative intervention (within 8 hours: 2%; 8-16 hours: 9.1%; 16-24 hours: 16.7%; greater than 24 hours: 30.8%, p = 0.009) as did the incidence of complications. Delays as short as 8 hours 5 minutes and 11 hours 15 minutes were associated with mortality attributable to SBI. The rates of delay in diagnosis were not significantly associated with age, gender, intoxication, transfer status, or presence of associated injuries. Delays in the diagnosis of SBI are directly responsible for almost half the deaths in this series. Even relatively brief delays (as little as 8 hours) result in morbidity and mortality directly attributable to "missed" SBI. Further investigation into the prompt diagnosis of this injury is needed.

Mechanisms of motor recovery after subtotal spinal cord injury: insights from the study of mice carrying a mutation (WldS) that delays cellular responses to injury.

PubMed

Zhang, Z; Guth, L; Steward, O

1998-01-01

Partial lesions of the mammalian spinal cord result in an immediate motor impairment that recovers gradually over time; however, the cellular mechanisms responsible for the transient nature of this paralysis have not been defined. A unique opportunity to identify those injury-induced cellular responses that mediate the recovery of function has arisen from the discovery of a unique mutant strain of mice in which the onset of Wallerian degeneration is dramatically delayed. In this strain of mice (designated WldS for Wallerian degeneration, slow), many of the cellular responses to spinal cord injury are also delayed. We have used this experimental animal model to evaluate possible causal relationships between these delayed cellular responses and the onset of functional recovery. For this purpose, we have compared the time course of locomotor recovery in C57BL/6 (control) mice and in WldS (mutant) mice by hemisecting the spinal cord at T8 and evaluating locomotor function at daily postoperative intervals. The time course of locomotor recovery (as determined by the Tarlov open-field walking procedure) was substantially delayed in mice carrying the WldS mutation: C57BL/6 control mice began to stand and walk within 6 days (mean Tarlov score of 4), whereas mutant mice did not exhibit comparable locomotor function until 16 days postoperatively. (a) The rapid return of locomotor function in the C57BL/6 mice suggests that the recovery resulted from processes of functional plasticity rather than from regeneration or collateral sprouting of nerve fibers. (b) The marked delay in the return of locomotor function in WldS mice indicates that the processes of neuroplasticity are induced by degenerative changes in the damaged neurons. (c) These strains of mice can be effectively used in future studies to elucidate the specific biochemical and physiological alterations responsible for inducing functional plasticity and restoring locomotor function after spinal cord injury.

An uncommon clinical feature of IAN injury after third molar removal: a delayed paresthesia case series and literature review.

PubMed

Borgonovo, Andrea; Bianchi, Albino; Marchetti, Andrea; Censi, Rachele; Maiorana, Carlo

2012-05-01

After an inferior alveolar nerve (IAN) injury, the onset of altered sensation usually begins immediately after surgery. However, it sometimes begins after several days, which is referred to as delayed paresthesia. The authors considered three different etiologies that likely produce inflammation along the nerve trunk and cause delayed paresthesia: compression of the clot, fibrous reorganization of the clot, and nerve trauma caused by bone fragments during clot organization. The aim of this article was to evaluate the etiology of IAN delayed paresthesia, analyze the literature, present a case series related to three different causes of this pathology, and compare delayed paresthesia with the classic immediate symptomatic paresthesia.

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.

Effect of cell therapy on recovery of cognitive functions in rats during the delayed period after brain injury.

PubMed

Roshal, L M; Tzyb, A F; Pavlova, L N; Soushkevitch, G N; Semenova, J B; Javoronkov, L P; Kolganova, O I; Konoplyannikov, A G; Shevchuk, A S; Yujakov, V V; Karaseva, O V; Ivanova, T F; Chernyshova, T A; Konoplyannikova, O A; Bandurko, L N; Marey, M V; Sukhikh, G T

2009-07-01

We studied the effect of systemic transplantation of human stem cells from various tissues on cognitive functions of the brain in rats during the delayed period after experimental brain injury. Stem cells were shown to increase the efficacy of medical treatment with metabolic and symptomatic drugs for recovery of cognitive functions. They accelerated the formation of the conditioned defense response. Fetal neural stem cells had a stronger effect on some parameters of cognitive function 2 months after brain injury. The efficacy of bone marrow mesenchymal stem cells from adult humans or fetuses was higher 3 months after brain injury.

In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury

PubMed Central

Rannou, Emilie; François, Agnès; Toullec, Aurore; Guipaud, Olivier; Buard, Valérie; Tarlet, Georges; Mintet, Elodie; Jaillet, Cyprien; Iruela-Arispe, Maria Luisa; Benderitter, Marc; Sabourin, Jean-Christophe; Milliat, Fabien

2015-01-01

The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury. We created a mouse model with a specific deletion of PAI-1 in the endothelium (PAI-1KOendo) by a Cre-LoxP system. In a model of radiation enteropathy, survival and intestinal radiation injury were followed as well as intestinal gene transcriptional profile and inflammatory cells intestinal infiltration. Irradiated PAI-1KOendo mice exhibited increased survival, reduced acute enteritis severity and attenuated late fibrosis compared with irradiated PAI-1flx/flx mice. Double E-cadherin/TUNEL labeling confirmed a reduced epithelial cell apoptosis in irradiated PAI-1KOendo. High-throughput gene expression combined with bioinformatic analyses revealed a putative involvement of macrophages. We observed a decrease in CD68+cells in irradiated intestinal tissues from PAI-1KOendo mice as well as modifications associated with M1/M2 polarization. This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. PMID:26510580

[Occurrence of radiation-induced injury in vagina after radical radiotherapy of cervical cancer and its affecting factors].

PubMed

Zhang, K S; Liu, Z; Wang, T; Wang, J; Su, J; Shi, F; Wang, R H; Yuan, W; Li, Y

2018-04-25

Objective: To investigate the occurrence and degree of radiation-induced injury in vagina after radical radiotherapy of cervical cancer. Methods: A total of 282 cases of patients with cervical cancer were collected from November 2016 to September 2017. All of the above patients underwent radical radiotherapy from 2008 to 2017 in the First Affiliated Hospital of Xi ' an Jiaotong University. The patients' International Federation of Gynecology and Obstetrics (FIGO) staging (2009) , brachytherapy dose, whether receive synchronous chemotherapy or not, age and body mass index (BMI) for the occurrence and severity of vaginal radiation injury at different time periods were analyzed by cross-sectional survey method. The single factor would be analyzed by the method of Chi-square test and the multiple factors would be analyzed by logistic regression method to checkout. Results: Of the 282 patients, the incidence of radiation-injury in vaginal was 84.4% (238/282) , with the incidence rate of degree Ⅰ,Ⅱ and Ⅲ radiation injury were respectively 50.7% (143/282), 29.8% (84/282) and 3.9% (11/282; χ(2)=153.375, P< 0.05) , and there was no degree Ⅳ. Until the end of the follow-up time, the incidence of radiation-induced injury in vaginal after completing the treatment within 1 year, 1-2 years,>2-<5 years and ≥5 years were respectively 80.0% (24/30) , 87.2% (102/117) , 88.2% (60/68) and 77.6% (52/67; χ(2)=4.231, P= 0.238) . There were 30 cases be followed within 1 year after treatment, the incidence rate of degreeⅠ,Ⅱ and Ⅲ of radiation injury in vagina was 60.0% (18/30) , 20.0% (6/30) and 0, respectively (χ(2)=28.636, P< 0.05). There were 117 cases be followed between 1-2 years after treatment, the incidence rate of degreeⅠ,Ⅱ and Ⅲ vaginal radiation-induced injury were 54.7% (64/117) , 29.9% (35/117) and 2.6% (3/117) , respectively (χ(2)=77.198, P< 0.05) . There were 68 cases be followed between >2-<5 years after treatment, the incidence rate of degree �

Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice.

PubMed

Singh, Vijay K; Wise, Stephen Y; Fatanmi, Oluseyi O; Beattie, Lindsay A; Ducey, Elizabeth J; Seed, Thomas M

2014-01-01

The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5-12.5 Gy) of (60)Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans.

Delayed hydronephrosis due to retroperitoneal hematoma after a seatbelt injury: A case report.

PubMed

Yumoto, Tetsuya; Kondo, Yoshitaka; Kumon, Kento; Masaoka, Yoshihisa; Hiraki, Takao; Yamada, Taihei; Naito, Hiromichi; Nakao, Atsunori

2018-06-01

Hydronephrosis caused by retroperitoneal hematoma after a seatbelt injury is a unique clinical entity. A 21-year-old man, who had been wearing a seatbelt, was brought to our hospital after a motor vehicle collision, complaining of abdominal pain. Computed tomography (CT) revealed retroperitoneal hematoma in the upper pelvic region. Since he was hemodynamically stable throughout admission, he was managed conservatively. Seventeen days after initial discharge, the patient revisited our emergency department due to right back pain. CT scans indicated retroperitoneal hematoma growth resulting in hydronephrosis of the right kidney. Laparoscopic drainage of the retroperitoneal hematoma was successfully performed. His symptoms resolved after the surgery. Follow-up CT scans three months later demonstrated complete resolution of the hydronephrosis and retroperitoneal hematoma. Our case highlights a patient with delayed hydronephrosis because of retroperitoneal hematoma expansion after a seatbelt injury.

The burning issues of motor vehicle radiator scald injuries revisited - a fresh review and changing prevention strategies.

PubMed

Patel, J N; Tan, A; Frew, Q; Dziewulski, P

2016-12-31

A preventable subgroup of burn injuries is scalds sustained from motor vehicle radiators. This study was to determine changes in trends in epidemiology of such injuries and to discuss whether current and other prevention efforts proposed previously require reinforcement. We conducted a retrospective study (February 2007-August 2015) of all motor vehicle-related burn referrals to our regional burns service. 68 cases of motor vehicle radiator burns were identified. Male to female ratio was 65:3. Mean age was 35.1 (range = 9-71). Most cases occurred in the summer months (22/68 = 32.4%). 65 cases (95.6%) involved car radiators. 66% of injuries resulted from actively removing the pressure cap of an overheated radiator in the motor vehicle. Mean total burn surface area (%TBSA) was 2.1% (range = 0.5- 11%). The depths of burn injuries were mostly superficial partial thickness. Face, chest and upper limbs were the most common sites of injury. Mean healing time was 14.2 days (range = 4-60). Following the introduction of safety measures by vehicle manufacturers, motor vehicle radiator burns in this era are mostly minor injuries and can be potentially managed conservatively as an outpatient. This contrasts with findings from previous studies over a decade ago of larger, more significant injuries requiring admission and surgery. Whilst manufacturers have installed safety measures into the design of radiator caps, our findings suggest that re-educating the public to allow a period of cooling prior to opening caps should be reinforced.

Combined Therapy of Pegylated G-CSF and Alxn4100TPO Improves Survival and Mitigates Acute Radiation Syndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma.

PubMed

Kiang, Juliann G; Zhai, Min; Bolduc, David L; Smith, Joan T; Anderson, Marsha N; Ho, Connie; Lin, Bin; Jiang, Suping

2017-11-01

Exposure to ionizing radiation alone or combined with traumatic tissue injury is a crucial life-threatening factor in nuclear and radiological incidents. Radiation injuries occur at the molecular, cellular, tissue and systemic levels; their mechanisms, however, remain largely unclear. Exposure to radiation combined with skin wounding, bacterial infection or burns results in greater mortality than radiation exposure alone in dogs, pigs, rats, guinea pigs and mice. In the current study we observed that B6D2F1/J female mice exposed to 60 Co gamma-photon radiation followed by 15% total-body-surface-area skin wounds experienced an increment of 25% higher mortality over a 30-day observation period compared to those subjected to radiation alone. Radiation exposure delayed wound healing by approximately 14 days. On day 30 post-injury, bone marrow and ileum in animals from both groups (radiation alone or combined injury) still displayed low cellularity and structural damage. White blood cell counts, e.g., neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets, still remained very low in surviving irradiated alone animals, whereas only the lymphocyte count was low in surviving combined injury animals. Likewise, in surviving animals from radiation alone and combined injury groups, the RBCs, hemoglobin, hematocrit and platelets remained low. We observed, that animals treated with both pegylated G-CSF (a cytokine for neutrophil maturation and mobilization) and Alxn4100TPO (a thrombopoietin receptor agonist) at 4 h postirradiation, a 95% survival (vehicle: 60%) over the 30-day period, along with mitigated body-weight loss and significantly reduced acute radiation syndrome. In animals that received combined treatment of radiation and injury that received pegylated G-CSF and Alxn4100TPO, survival was increased from 35% to 55%, but did not accelerate wound healing. Hematopoiesis and ileum showed significant improvement in animals from both groups (irradiation

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

Correlates of self-injurious, aggressive and destructive behaviour in children under five who are at risk of developmental delay.

PubMed

Petty, J L; Bacarese-Hamilton, M; Davies, L E; Oliver, C

2014-01-01

Several behavioural correlates of self-injury, aggression and destructive behaviour have been identified in children and young adults with intellectual disabilities. This cross-sectional study aimed to further explore these correlates in very young children with developmental delay. Parents of 56 children (40 male) under the age of five years (mean age 2 years 10 months) completed a questionnaire about their child's behaviour and the presence of behavioural correlates, including repetitive, over-active or impulsive behaviour and more severe developmental delay. Parents reported very high prevalence of self-injurious, aggressive and destructive behaviour: 51%, 64% and 51%, respectively. A binary logistic regression revealed that a higher score on a measure of overactive and impulsive behaviour significantly predicted the presence of destructive behaviour. A multiple linear regression revealed that both repetitive behaviour and number of health problems approached significance as independent predictors of severe self-injurious behaviour. Despite the very small sample, several factors emerged as potential predictors of self-injurious, aggressive and destructive behaviour. These findings support the need for further investigation in a larger sample. Confirmation in this age group could help guide the development of targeted early intervention for these behaviours by identifying behavioural risk markers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optical cryoimaging for assessment of radiation-induced injury to rat kidney metabolic state

NASA Astrophysics Data System (ADS)

Mehrvar, Shima; Funding la Cour, Mette; Medhora, Meetha; Camara, Amadou K. S.; Ranji, Mahsa

2018-02-01

Objective: This study utilizes fluorescence cryoimaging to quantitatively assess the effect of a high dose of irradiation on rat renal metabolism through redox state. Introduction: Exposure to high doses of irradiation could lead to death, in part, due to renal dysfunction. The kidney is one of the most sensitive organs that exhibit delayed injuries in survivors of acute radiation syndrome. In this study, optical cryoimaging was utilized to examine the potential for renal mitochondrial dysfunction after partial-body irradiation (PBI) and the mitigating effect of lisinopril-treatment, an angiotensin converting enzyme inhibitor that is FDA-approved for other indications. Materials and methods: Rats were exposed to a single dose of 13 Gy leg-out partial body irradiation (PBI, by X-rays). Rats (n = 5/group) received no further treatment, or lisinopril started one week after irradiation and continued at 24 mg/m2 /day. The non-irradiated siblings were used as controls. After 150 days, the rats were sacrificed, and their kidneys harvested and snap frozen in liquid nitrogen for later cryoimaging. The 3D images of metabolic indices (NADH and FAD) were captured, and the redox ratio i.e. NADH/FAD was calculated. The mitochondrial redox state of three groups of rat kidneys were quantified by calculating the volumetric mean of redox ratio images (RR). Results: 3D cryoimaging revealed that in PBI only kidneys, the metabolic marker (RR) decreased significantly by 78% compared to non-irradiated controls. Treatment with lisinopril significantly improved the RR by 93% in groups exposed to PBI. Conclusion: This study aimed at quantifying the level of the mitochondrial redox state of irradiated rat kidneys compared to non-irradiated kidneys (controls) and the efficacy of lisinopril to preserve kidney metabolism after irradiation. PBI oxidized the metabolic state of kidneys and lisinopril mitigated the radiation-induced injury on renal mitochondria.

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.

Calreticulin attenuated microwave radiation-induced human microvascular endothelial cell injury through promoting actin acetylation and polymerization.

PubMed

Xu, Feifei; Wang, You; Tao, Tianqi; Song, Dandan; Liu, Xiuhua

2017-01-01

Recent work reveals that actin acetylation modification has been linked to different normal and disease processes and the effects associated with metabolic and environmental stressors. Herein, we highlight the effects of calreticulin on actin acetylation and cell injury induced by microwave radiation in human microvascular endothelial cell (HMEC). HMEC injury was induced by high-power microwave of different power density (10, 30, 60, 100 mW/cm 2 , for 6 min) with or without exogenous recombinant calreticulin. The cell injury was assessed by lactate dehydrogenase (LDH) activity and Cell Counting Kit-8 in culture medium, migration ability, intercellular junction, and cytoskeleton staining in HMEC. Western blotting analysis was used to detected calreticulin expression in cytosol and nucleus and acetylation of globular actin (G-actin). We found that HMEC injury was induced by microwave radiation in a dose-dependent manner. Pretreatment HMEC with calreticulin suppressed microwave radiation-induced LDH leakage and increased cell viability and improved microwave radiation-induced decrease in migration, intercellular junction, and cytoskeleton. Meanwhile, pretreatment HMEC with exogenous calreticulin upregulated the histone acetyltransferase activity and the acetylation level of G-actin and increased the fibrous actin (F-actin)/G-actin ratio. We conclude that exogenous calreticulin protects HMEC against microwave radiation-induced injury through promoting actin acetylation and polymerization.

Glycyrrhetinic acid alleviates radiation-induced lung injury in mice.

PubMed

Chen, Jinmei; Zhang, Weijian; Zhang, Lurong; Zhang, Jiemin; Chen, Xiuying; Yang, Meichun; Chen, Ting; Hong, Jinsheng

2017-01-01

Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-β1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-β1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-β1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-β1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-β1/Smads signaling pathway. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

The biological effect of prolonged radiation and ways of selecting new anti-radiation drugs effective in this kind of radiation injury

NASA Technical Reports Server (NTRS)

Rogozkin, V. D.; Chertkov, K. S.; Nikolov, I.

1974-01-01

The basic characteristics of prolonged radiation - increased tolerance of radiation injury - are attributed to cellular kinetics; as dose rate is reduced, the population rate is not disturbed, particularly that of stem cells which makes it possible for the organism to tolerate higher radiation loads. It is concluded that this effect makes approved radio protectors, whose effect contains an established cytostatic component, unsuitable for prolonged radiation. It is better to correct the stem pool formation process by either accelerating the proliferation of cells or limiting the effect of stimuli causing cells to lose colony forming properties.

C/EBPδ deficiency sensitizes mice to ionizing radiation-induced hematopoietic and intestinal injury.

PubMed

Pawar, Snehalata A; Shao, Lijian; Chang, Jianhui; Wang, Wenze; Pathak, Rupak; Zhu, Xiaoyan; Wang, Junru; Hendrickson, Howard; Boerma, Marjan; Sterneck, Esta; Zhou, Daohong; Hauer-Jensen, Martin

2014-01-01

Knowledge of the mechanisms involved in the radiation response is critical for developing interventions to mitigate radiation-induced injury to normal tissues. Exposure to radiation leads to increased oxidative stress, DNA-damage, genomic instability and inflammation. The transcription factor CCAAT/enhancer binding protein delta (Cebpd; C/EBPδ is implicated in regulation of these same processes, but its role in radiation response is not known. We investigated the role of C/EBPδ in radiation-induced hematopoietic and intestinal injury using a Cebpd knockout mouse model. Cebpd-/- mice showed increased lethality at 7.4 and 8.5 Gy total-body irradiation (TBI), compared to Cebpd+/+ mice. Two weeks after a 6 Gy dose of TBI, Cebpd-/- mice showed decreased recovery of white blood cells, neutrophils, platelets, myeloid cells and bone marrow mononuclear cells, decreased colony-forming ability of bone marrow progenitor cells, and increased apoptosis of hematopoietic progenitor and stem cells compared to Cebpd+/+ controls. Cebpd-/- mice exhibited a significant dose-dependent decrease in intestinal crypt survival and in plasma citrulline levels compared to Cebpd+/+ mice after exposure to radiation. This was accompanied by significantly decreased expression of γ-H2AX in Cebpd-/- intestinal crypts and villi at 1 h post-TBI, increased mitotic index at 24 h post-TBI, and increase in apoptosis in intestinal crypts and stromal cells of Cebpd-/- compared to Cebpd+/+ mice at 4 h post-irradiation. This study uncovers a novel biological function for C/EBPδ in promoting the response to radiation-induced DNA-damage and in protecting hematopoietic and intestinal tissues from radiation-induced injury.

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

Management of ionizing radiation injuries and illnesses, part 4: acute radiation syndrome.

PubMed

Christensen, Doran M; Iddins, Carol J; Parrillo, Steven J; Glassman, Erik S; Goans, Ronald E

2014-09-01

To provide proper medical care for patients after a radiation incident, it is necessary to make the correct diagnosis in a timely manner and to ascertain the relative magnitude of the incident. The present article addresses the clinical diagnosis and management of high-dose radiation injuries and illnesses in the first 24 to 72 hours after a radiologic or nuclear incident. To evaluate the magnitude of a high-dose incident, it is important for the health physicist, physician, and radiobiologist to work together and to assess many variables, including medical history and physical examination results; the timing of prodromal signs and symptoms (eg, nausea, vomiting, diarrhea, transient incapacitation, hypotension, and other signs and symptoms suggestive of high-level exposure); and the incident history, including system geometry, source-patient distance, and the suspected radiation dose distribution. © 2014 The American Osteopathic Association.

Radiation Injury After a Nuclear Detonation: Medical Consequences and the Need for Scarce Resources Allocation

PubMed Central

DiCarlo, Andrea L.; Maher, Carmen; Hick, John L.; Hanfling, Dan; Dainiak, Nicholas; Chao, Nelson; Bader, Judith L.; Coleman, C. Norman; Weinstock, David M.

2013-01-01

A 10-kiloton (kT) nuclear detonation within a US city could expose hundreds of thousands of people to radiation. The Scarce Resources for a Nuclear Detonation Project was undertaken to guide community planning and response in the aftermath of a nuclear detonation, when demand will greatly exceed available resources. This article reviews the pertinent literature on radiation injuries from human exposures and animal models to provide a foundation for the triage and management approaches outlined in this special issue. Whole-body doses >2 Gy can produce clinically significant acute radiation syndrome (ARS), which classically involves the hematologic, gastrointestinal, cutaneous, and cardiovascular/central nervous systems. The severity and presentation of ARS are affected by several factors, including radiation dose and dose rate, interindividual variability in radiation response, type of radiation (eg, gamma alone, gamma plus neutrons), partial-body shielding, and possibly age, sex, and certain preexisting medical conditions. The combination of radiation with trauma, burns, or both (ie, combined injury) confers a worse prognosis than the same dose of radiation alone. Supportive care measures, including fluid support, antibiotics, and possibly myeloid cytokines (eg, granulocyte colony-stimulating factor), can improve the prognosis for some irradiated casualties. Finally, expert guidance and surge capacity for casualties with ARS are available from the Radiation Emergency Medical Management Web site and the Radiation Injury Treatment Network. PMID:21402810

Radiation injury after a nuclear detonation: medical consequences and the need for scarce resources allocation.

PubMed

DiCarlo, Andrea L; Maher, Carmen; Hick, John L; Hanfling, Dan; Dainiak, Nicholas; Chao, Nelson; Bader, Judith L; Coleman, C Norman; Weinstock, David M

2011-03-01

A 10-kiloton (kT) nuclear detonation within a US city could expose hundreds of thousands of people to radiation. The Scarce Resources for a Nuclear Detonation Project was undertaken to guide community planning and response in the aftermath of a nuclear detonation, when demand will greatly exceed available resources. This article reviews the pertinent literature on radiation injuries from human exposures and animal models to provide a foundation for the triage and management approaches outlined in this special issue. Whole-body doses >2 Gy can produce clinically significant acute radiation syndrome (ARS), which classically involves the hematologic, gastrointestinal, cutaneous, and cardiovascular/central nervous systems. The severity and presentation of ARS are affected by several factors, including radiation dose and dose rate, interindividual variability in radiation response, type of radiation (eg, gamma alone, gamma plus neutrons), partial-body shielding, and possibly age, sex, and certain preexisting medical conditions. The combination of radiation with trauma, burns, or both (ie, combined injury) confers a worse prognosis than the same dose of radiation alone. Supportive care measures, including fluid support, antibiotics, and possibly myeloid cytokines (eg, granulocyte colony-stimulating factor), can improve the prognosis for some irradiated casualties. Finally, expert guidance and surge capacity for casualties with ARS are available from the Radiation Emergency Medical Management Web site and the Radiation Injury Treatment Network.

Delayed diagnosis of traumatic ventricular septal defect in penetrating chest injury: small evidence on echocardiography makes big difference.

PubMed

Jeon, Kihyun; Lim, Woo-Hyun; Kang, Si-Hyuck; Cho, Iksung; Kim, Kyung-Hee; Kim, Hyung-Kwan; Kim, Yong-Jin; Sohn, Dae-Won

2010-03-01

Cardiac trauma from penetrating chest injury is a life-threatening condition. It was reported that < 10% of patients arrives at the emergency department alive. Penetrating chest injury can cause serious damage in more than 1 cardiac structure, including myocardial lacerations, ventricular septal defect (VSD), fistula between aorta and right cardiac chamber and valves. The presence of pericardial effusion (even a small amount) on the initial echocardiography might be the only clue to serious cardiac damage in the absence of definite evidence of anatomical defect in heart. We here present a case, in which clear diagnosis of VSD and pseudoaneurysmal formation was delayed a few days after penetrating chest injury due to the lack of anatomical evidence of damage.

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

Early Versus Delayed Surgical Decompression of Spinal Cord after Traumatic Cervical Spinal Cord Injury: A Cost-Utility Analysis.

PubMed

Furlan, Julio C; Craven, B Catharine; Massicotte, Eric M; Fehlings, Michael G

2016-04-01

This cost-utility analysis was undertaken to compare early (≤24 hours since trauma) versus delayed surgical decompression of spinal cord to determine which approach is more cost effective in the management of patients with acute traumatic cervical spinal cord injury (SCI). This study includes the patients enrolled into the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) and admitted at Toronto Western Hospital. Cases were grouped into patients with motor complete SCI and individuals with motor incomplete SCI. A cost-utility analysis was performed for each group of patients by the use of data for the first 6 months after SCI. The perspective of a public health care insurer was adopted. Costs were estimated in 2014 U.S. dollars. Utilities were estimated from the STASCIS. The baseline analysis indicates early spinal decompression is more cost-effective approach compared with the delayed spinal decompression. When we considered the delayed spinal decompression as the baseline strategy, the incremental cost-effectiveness ratio analysis revealed a saving of US$ 58,368,024.12 per quality-adjusted life years gained for patients with complete SCI and a saving of US$ 536,217.33 per quality-adjusted life years gained in patients with incomplete SCI for the early spinal decompression. The probabilistic analysis confirmed the early-decompression strategy as more cost effective than the delayed-decompression approach, even though there is no clearly dominant strategy. The results of this economic analysis suggests that early decompression of spinal cord was more cost effective than delayed surgical decompression in the management of patients with motor complete and incomplete SCI, even though no strategy was clearly dominant. Copyright © 2016 Elsevier Inc. All rights reserved.

Rutin-Enriched Extract from Coriandrum sativum L. Ameliorates Ionizing Radiation-Induced Hematopoietic Injury

PubMed Central

Han, Xiaodan; Xue, Xiaolei; Zhao, Yu; Li, Yuan; Liu, Weili; Zhang, Junling; Fan, Saijun

2017-01-01

Hematopoietic injury is a major cause of mortality in radiation accidents and a primary side effect in patients undergoing radiotherapy. Ionizing radiation (IR)-induced myelosuppression is largely attributed to the injury of hematopoietic stem and progenitor cells (HSPCs). Coriander is a culinary herb with multiple pharmacological effects and has been widely used in traditional medicine. In this study, flavonoids were identified as the main component of coriander extract with rutin being the leading compound (rutin-enriched coriander extract; RE-CE). We evaluated the radioprotective effect of RE-CE against IR-induced HSPCs injury. Results showed that RE-CE treatment markedly improved survival, ameliorated organ injuries and myelosuppression, elevated HSPCs frequency, and promoted differentiation and proliferation of HSPCs in irradiated mice. The protective role of RE-CE in hematopoietic injury is probably attributed to its anti-apoptotic and anti-DNA damage effect in irradiated HSPCs. Moreover, these changes were associated with reduced reactive oxygen species (ROS) and enhanced antioxidant enzymatic activities in irradiated HSPCs. Collectively, these findings demonstrate that RE-CE is able to ameliorate IR-induced hematopoietic injury partly by reducing IR-induced oxidative stress. PMID:28468251

Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

PubMed Central

Balentova, Sona; Adamkov, Marian

2015-01-01

Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

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

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

PubMed Central

Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

2013-01-01

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage. PMID:23969972

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.

Delayed injury of hippocampal interneurons after neonatal hypoxia-ischemia and therapeutic hypothermia in a murine model.

PubMed

Chavez-Valdez, Raul; Emerson, Paul; Goffigan-Holmes, Janasha; Kirkwood, Alfredo; Martin, Lee J; Northington, Frances J

2018-05-21

Delayed hippocampal injury and memory impairments follow neonatal hypoxia-ischemia (HI) despite the use of therapeutic hypothermia (TH). Death of hippocampal pyramidal cells occurs acutely after HI, but characterization of delayed cell death and injury of interneurons (INs) is unknown. We hypothesize that injury of INs after HI is: i) asynchronous to that of pyramidal cells, ii) independent of injury severity, and iii) unresponsive to TH. HI was induced in C57BL6 mice at p10 with unilateral right carotid ligation and 45 min of hypoxia (FiO 2 =0.08). Mice were randomized to normothermia (36 0 C,NT) or TH (31 0 C) for 4h after HI and anesthesia-exposed shams were use as controls. Brains were studied at 24h (p11) or 8d (p18) after HI. Vglut1, GAD65/67, PSD95, parvalbumin (PV) and calbindin-1 (Calb1) were measured. Cell death was assessed using cresyl violet staining and TUNEL assay. Hippocampal atrophy and astroglyosis at p18 were used to assess injury severity and to correlate with number of PV+INs. VGlut1 level decreased by 30% at 24h after HI, while GAD65/67 level decreased by ∼50% in forebrain 8d after HI, a decrease localized in CA1 and CA3. PSD95 levels decreased in forebrain by 65% at 24h after HI and remained low 8 days after HI. PV+INs increased in numbers (per mm 2 ) and branching between p11 and p18 in sham mice but not in NT and TH mice, resulting in 21 to 52% fewer PV+INs in injured mice at p18. Calb1 protein and mRNA were also reduced in HI injured mice. At p18, somatodendritic attrition of INs was evident in all injured mice without evidence of cell death. Neither hippocampal atrophy nor astroglyosis correlated with the number of PV+INs at p18. Thus, HI exposure has long lasting effects in the hippocampus impairing the development of the GABAergic system with only partial protection by TH independent of the degree of hippocampal injury. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Space radiation-associated lung injury in a murine model.

PubMed

Christofidou-Solomidou, Melpo; Pietrofesa, Ralph A; Arguiri, Evguenia; Schweitzer, Kelly S; Berdyshev, Evgeny V; McCarthy, Maureen; Corbitt, Astrid; Alwood, Joshua S; Yu, Yongjia; Globus, Ruth K; Solomides, Charalambos C; Ullrich, Robert L; Petrache, Irina

2015-03-01

Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy (56)Fe or (28)Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions. Copyright © 2015 the American Physiological Society.

Clinical prediction rule for delayed hemothorax after minor thoracic injury: a multicentre derivation and validation study

PubMed Central

Émond, Marcel; Guimont, Chantal; Chauny, Jean-Marc; Daoust, Raoul; Bergeron, Éric; Vanier, Laurent; Moore, Lynne; Plourde, Miville; Kuimi, Batomen; Boucher, Valérie; Allain-Boulé, Nadine; Le Sage, Natalie

2017-01-01

Background: About 75% of patients with minor thoracic injury are discharged after an emergency department visit. However, complications such as delayed hemothorax can occur. We sought to derive and validate a clinical decision rule to predict hemothorax in patients discharged from the emergency department. Methods: We conducted a 6-year prospective cohort study in 4 university-affiliated emergency departments. Patients aged 16 years or older presenting with a minor thoracic injury were assessed at 5 time points (initial visit and 7, 14, 30 and 90 d after the injury). Radiologists' reports were reviewed for the presence of hemothorax. We used log-binomial regression models to identify predictors of hemothorax. Results: A total of 1382 patients were included: 830 in the derivation phase and 552 in the validation phase. Of these, 151 (10.9%) had hemothorax at the 14-day follow-up. Patients 65 years of age or older represented 25.3% (210/830) and 23.7% (131/552) of the derivation and validation cohorts, respectively. The final clinical decision rule included a combination of age (> 70 yr, 2 points; 45-70 yr, 1 point), fracture of any high to mid thorax rib (ribs 3-9, 2 points) and presence of 3 or more rib fractures (1 point). Twenty (30.8%) of the 65 high-risk patients (score ≥ 4) experienced hemothorax during the follow-up period. The clinical decision rule had a high specificity (90.7%, 95% confidence interval 87.7%-93.1%) in this high-risk group, thus guiding appropriate post-emergency care. Interpretation: One patient out of every 10 presented with delayed hemothorax after discharge from the emergency department. Implementation of this validated clinical decision rule for minor thoracic injury could guide emergency discharge plans. PMID:28611156

The burning issues of motor vehicle radiator scald injuries revisited – a fresh review and changing prevention strategies

PubMed Central

Patel, J.N.; Tan, A.; Frew, Q.; Dziewulski, P.

2016-01-01

Summary A preventable subgroup of burn injuries is scalds sustained from motor vehicle radiators. This study was to determine changes in trends in epidemiology of such injuries and to discuss whether current and other prevention efforts proposed previously require reinforcement. We conducted a retrospective study (February 2007-August 2015) of all motor vehicle-related burn referrals to our regional burns service. 68 cases of motor vehicle radiator burns were identified. Male to female ratio was 65:3. Mean age was 35.1 (range = 9-71). Most cases occurred in the summer months (22/68 = 32.4%). 65 cases (95.6%) involved car radiators. 66% of injuries resulted from actively removing the pressure cap of an overheated radiator in the motor vehicle. Mean total burn surface area (%TBSA) was 2.1% (range = 0.5- 11%). The depths of burn injuries were mostly superficial partial thickness. Face, chest and upper limbs were the most common sites of injury. Mean healing time was 14.2 days (range = 4-60). Following the introduction of safety measures by vehicle manufacturers, motor vehicle radiator burns in this era are mostly minor injuries and can be potentially managed conservatively as an outpatient. This contrasts with findings from previous studies over a decade ago of larger, more significant injuries requiring admission and surgery. Whilst manufacturers have installed safety measures into the design of radiator caps, our findings suggest that re-educating the public to allow a period of cooling prior to opening caps should be reinforced. PMID:28289357

An immunohistochemical panel to assess ultraviolet radiation-associated oxidative skin injury.

PubMed

Mamalis, A; Fiadorchanka, N; Adams, L; Serravallo, M; Heilman, E; Siegel, D; Brody, N; Jagdeo, J

2014-05-01

Ultraviolet (UV) radiation results in a significant loss in years of healthy life, approximately 1.5 million disability-adjusted life years (DALYs), and is associated with greater than 60,000 deaths annually worldwide that are attributed to melanoma and other skin cancers. Currently, there are no standardized biomarkers or assay panels to assess oxidative stress skin injury patterns in human skin exposed to ionizing radiation. Using biopsy specimens from chronic solar UV-exposed and UV-protected skin, we demonstrate that UV radiation-induced oxidative skin injury can be evaluated by an immunohistochemical panel that stains 8-hydroxydeoxyguanosine (8-OH-dG) to assess DNA adducts, 4-hydroxy-2-nonenal (HNE) to assess lipid peroxidation, and advanced glycation end products (AGEs) to assess protein damage. We believe this panel contains the necessary cellular biomarkers to evaluate topical agents, such as sunscreens and anti-oxidants that are designed to prevent oxidative skin damage and may reduce UV-associated skin aging, carcinogenesis, and inflammatory skin diseases. We envision that this panel will become an important tool for researchers developing topical agents to protect against UV radiation and other oxidants and ultimately lead to reductions in lost years of healthy life, DALYs, and annual deaths associated with UV radiation.

An ear punch model for studying the effect of radiation on wound healing.

PubMed

Deoliveira, Divino; Jiao, Yiqun; Ross, Joel R; Corbin, Kayla; Xiao, Qizhen; Toncheva, Greta; Anderson-Evans, Colin; Yoshizumi, Terry T; Chen, Benny J; Chao, Nelson J

2011-08-01

Radiation and wound combined injury represents a major clinical challenge because of the synergistic interactions that lead to higher morbidity and mortality than either insult would produce singly. The purpose of this study was to develop a mouse ear punch model to study the physiological mechanisms underlying radiation effects on healing wounds. Surgical wounds were induced by a 2 mm surgical punch in the ear pinnae of MRL/MpJ mice. Photographs of the wounds were taken and the sizes of the ear punch wounds were quantified by image analysis. Local radiation to the ear was delivered by orthovoltage X-ray irradiator using a specially constructed jig that shields the other parts of body. Using this model, we demonstrated that local radiation to the wound area significantly delayed the healing of ear punch wounds in a dose-dependent fashion. The addition of sublethal whole body irradiation (7 Gy) further delayed the healing of ear punch wounds. These results were replicated in C57BL/6 mice; however, wound healing in MRL/MpJ mice was accelerated. These data indicate that the mouse ear punch model is a valuable model to study radiation and wound combined injury.

Hepatic radiation injury mimicking metastasis in distal esophageal cancer.

PubMed

Demey, Karel; Van Veer, Hans; Nafteux, Philippe; Deroose, Christophe M; Haustermans, Karin; Coolen, Johan; Vandecaveye, Vincent; Coosemans, Willy; Van Cutsem, Eric

2017-08-01

A new hypermetabolic lesion on 18 FDG-PET/CT after neo-adjuvant chemoradiotherapy for distal esophageal cancer can be a hepatic metastasis and should be examined carefully before esophagectomy. We present a case of acute and nodular radiation-induced injury of the left liver after neo-adjuvant chemoradiotherapy for distal esophageal cancer, which resembles a hepatic metastasis on 18 FDG-PET/CT. Acute and nodular radiation hepatitis (RH) can be a potential cause of false-positive findings of malignancy and therefore exclude patients who could benefit from esophagectomy. 18 FDG-PET/CT images should therefore carefully be interpreted and compared with the radiation beams, dose distribution and eventually clarified by DW-MR imaging.

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.

Optical Spectroscopy and Multivariate Analysis for Biodosimetry and Monitoring of Radiation Injury to the Skin

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

Levitskaia, Tatiana G.; Bryan, Samuel A.; Creim, Jeffrey A.

2012-08-01

In the event of an intentional or accidental release of ionizing radiation in a densely populated area, timely assessment and triage of the general population for the radiation exposure is critical. In particular, a significant number of the victims may sustain cutaneous radiation injury, which increases the mortality and worsens the overall prognosis of the victims suffered from combined thermal/mechanical and radiation trauma. Diagnosis of the cutaneous radiation injury is challenging, and established methods largely rely on visual manifestations, presence of the skin contamination, and a high degree of recall by the victim. Availability of a high throughput non-invasive inmore » vivo biodosimetry tool for assessment of the radiation exposure of the skin is of particular importance for the timely diagnosis of the cutaneous injury. In the reported investigation, we have tested the potential of an optical reflectance spectroscopy for the evaluation of the radiation injury to the skin. This is technically attractive because optical spectroscopy relies on well-established and routinely used for various applications instrumentation, one example being pulse oximetry which uses selected wavelengths for the quantification of the blood oxygenation. Our method relies on a broad spectral region ranging from the locally absorbed, shallow-penetrating ultraviolet and visible (250 to 800 nm) to more deeply penetrating near-Infrared (800 – 1600 nm) light for the monitoring of multiple physiological changes in the skin upon irradiation. Chemometrics is a multivariate methodology that allows the information from entire spectral region to be used to generate predictive regression models. In this report we demonstrate that simple spectroscopic method, such as the optical reflectance spectroscopy, in combination with multivariate data analysis, offers the promise of rapid and non-invasive in vivo diagnosis and monitoring of the cutaneous radiation exposure, and is able accurately

Serum microRNAs are early indicators of survival after radiation-induced hematopoietic injury

PubMed Central

Acharya, Sanket S.; Fendler, Wojciech; Watson, Jacqueline; Hamilton, Abigail; Pan, Yunfeng; Gaudiano, Emily; Moskwa, Patryk; Bhanja, Payel; Saha, Subhrajit; Guha, Chandan; Parmar, Kalindi; Chowdhury, Dipanjan

2015-01-01

Accidental radiation exposure is a threat to human health that necessitates effective clinical planning and diagnosis. Minimally invasive biomarkers that can predict long-term radiation injury are urgently needed for optimal management after a radiation accident. We have identified serum microRNA (miRNA) signatures that indicate long-term impact of total body irradiation (TBI) in mice when measured within 24 hours of exposure. Impact of TBI on the hematopoietic system was systematically assessed to determine a correlation of residual hematopoietic stem cells (HSCs) with increasing doses of radiation. Serum miRNA signatures distinguished untreated mice from animals exposed to radiation and correlated with the impact of radiation on HSCs. Mice exposed to sublethal (6.5 Gy) and lethal (8 Gy) doses of radiation were indistinguishable for 3 to 4 weeks after exposure. A serum miRNA signature detectable 24 hours after radiation exposure consistently segregated these two cohorts. Furthermore, using either a radioprotective agent before, or radiation mitigation after, lethal radiation, we determined that the serum miRNA signature correlated with the impact of radiation on animal health rather than the radiation dose. Last, using humanized mice that had been engrafted with human CD34+ HSCs, we determined that the serum miRNA signature indicated radiation-induced injury to the human bone marrow cells. Our data suggest that serum miRNAs can serve as functional dosimeters of radiation, representing a potential breakthrough in early assessment of radiation-induced hematopoietic damage and timely use of medical countermeasures to mitigate the long-term impact of radiation. PMID:25972001

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.

Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

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

Dong, Lihua; Cui, Jingkun; Tang, Fengjiao

Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATMmore » polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries

[Mild head injury in children and adults: Diagnostic challenges in the emergency department].

PubMed

Leidel, B A; Lindner, T; Wolf, S; Bogner, V; Steinbeck, A; Börner, N; Peiser, C; Audebert, H J; Biberthaler, P; Kanz, K-G

2015-06-01

Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time.

[Mild head injury in children and adults. Diagnostic challenges in the emergency department].

PubMed

Leidel, B A; Lindner, T; Wolf, S; Bogner, V; Steinbeck, A; Börner, N; Peiser, C; Audebert, H J; Biberthaler, P; Kanz, K-G

2015-01-01

Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time.

Maternal Azithromycin Therapy for Ureaplasma Intra-Amniotic Infection Delays Preterm Delivery and Reduces Fetal Lung Injury in a Primate Model

PubMed Central

Grigsby, Peta L.; Novy, Miles J.; Sadowsky, Drew W.; Morgan, Terry K.; Long, Mary; Acosta, Ed; Duffy, Lynn B; Waites, Ken B.

2012-01-01

Objective We assessed the efficacy of a maternal multi–dose azithromycin (AZI) regimen, with and without anti–inflammatory agents to delay preterm birth and to mitigate fetal lung injury associated with Ureaplasma parvum intra–amniotic infection (IAI). Study Design Long–term catheterized rhesus monkeys (n=16) received intra–amniotic inoculation of U. parvum (107 CFU/ml, serovar 1). After contraction onset, rhesus monkeys received either no treatment (n=6); AZI (12.5mg/kg, q12h, IV for 10 days; n=5); or AZI plus dexamethasone (DEX) and indomethacin (INDO; n=5). Outcomes included amniotic fluid pro–inflammatory mediators, U. parvum cultures & PCR, AZI pharmacokinetics and the extent of fetal lung inflammation. Results Maternal AZI therapy eradicated U. parvum IAI from the amniotic fluid within 4 days. Placenta and fetal tissues were 90% culture negative at delivery. AZI therapy significantly delayed preterm delivery and prevented advanced fetal lung injury, although residual acute chorioamnionitis persisted. Conclusions Specific maternal antibiotic therapy can eradicate U. parvum from the amniotic fluid and key fetal organs, with subsequent prolongation of pregnancy which provides a therapeutic window of opportunity to effectively reduce the severity of fetal lung injury. PMID:23111115

An ear punch model for studying the effect of radiation on wound healing

PubMed Central

DeOLIVEIRA, DIVINO; JIAO, YIQUN; ROSS, JOEL R.; CORBIN, KAYLA; XIAO, QIZHEN; TONCHEVA, GRETA; ANDERSON-EVANS, COLIN; YOSHIZUMI, TERRY T.; CHEN, BENNY J.; CHAO, NELSON J.

2011-01-01

Purpose Radiation and wound combined injury represents a major clinical challenge because of the synergistic interactions that lead to higher morbidity and mortality than either insult would produce singly. The purpose of this study was to develop a mouse ear punch model to study the physiological mechanisms underlying radiation effects on healing wounds. Materials and methods Surgical wounds were induced by a 2 mm surgical punch in the ear pinnae of MRL/MpJ mice. Photographs of the wounds were taken and the sizes of the ear punch wounds were quantified by image analysis. Local radiation to the ear was delivered by orthovoltage X-ray irradiator using a specially constructed jig that shields the other parts of body. Results Using this model, we demonstrated that local radiation to the wound area significantly delayed the healing of ear punch wounds in a dose-dependent fashion. The addition of sublethal whole body irradiation (7 Gy) further delayed the healing of ear punch wounds. These results were replicated in C57BL/6 mice; however, wound healing in MRL/MpJ mice was accelerated. Conclusions These data indicate that the mouse ear punch model is a valuable model to study radiation and wound combined injury. PMID:21480768

Voiding and sexual dysfunctions after pelvic fracture urethral injuries treated with either initial cystostomy and delayed urethroplasty or immediate primary urethral realignment.

PubMed

Aşci, R; Sarikaya, S; Büyükalpelli, R; Saylik, A; Yilmaz, A F; Yildiz, S

1999-08-01

The aim of this study is to evaluate the effects of the different immediate treatment modalities on the sexual and voiding functions in pelvic fracture urethral injuries. The records of 38 male patients with traumatic posterior urethral injuries were reviewed, 18 of whom were treated by initial suprapubic cystostomy and delayed repair (Group 1), and 20 by primary urethral realignment (Group 2). Types of pelvic fractures and urethral injuries were classified according to surgical and radiological findings. Long-term voiding functions were determined by the patient questionnaire, residual urine and uroflow. Sexual functions were also determined by the patient questionnaire and a penile duplex ultrasound study. Mean follow-ups of Groups 1 and 2 were 37 and 39 months, respectively. Membranous urethral disruption extending to the urogenital diaphragm was the most frequent urethral injury (type 3), with incidences of 66.7% and 77.7%, respectively. There were no statistically significant differences in mean age, incidence of pelvic fracture types and urethral injury types between groups (p > 0.05). After the immediate treatments, 16.7% and 55% of the patients regained normal urination, and stricture developed in 83.3% and 45% of the patients, respectively. In 44.4% of the patients in Group 1 and 10% in Group 2, urethral strictures required open urethroplasty (p < 0.05). Erectile impotence before urethroplasty in 17.6% and 20%, anejaculation after urethroplasty in 17.6% and 15% and incontinence in 5.6% and 10% of the patients were found in Groups 1 and 2, respectively (p > 0.05). However, 88.8% and 90% of patients eventually achieved normal urination with complete continence. Sexual and voiding dysfunction after pelvic fracture posterior urethral injury seem to be the result of the injury itself, not of the immediate treatment modalities. In urethral disruption injuries, primary urethral realignment seems more favourable than suprapubic cystostomy and delayed repair.

Functional Impact of a Minor Thoracic Injury: An Investigation of Age, Delayed Hemothorax, and Rib Fracture Effects.

PubMed

Émond, Marcel; Sirois, Marie-Josée; Guimont, Chantal; Chauny, Jean-Marc; Daoust, Raoul; Bergeron, Éric; Vanier, Laurent; Camden, Stephanie; Le Sage, Natalie

2015-12-01

To investigate whether minor thoracic injuries (MTIs) relate to subsequent functional limitations. Approximately 75% of patients with an MTI are discharged after an emergency department (ED) visit, whereas significant functional limitations can occur in the weeks that follow. A 19 months' prospective cohort study with a 90-day follow-up was conducted at 4 university-affiliated EDs. Patients 16 years and older with an MTI were assessed at initial ED visit, 7, 14, 30, and 90 days after injury. Functional outcome was measured using the SF-12 scale. General linear model were used to assess outcome. A total of 482 patients were included, of whom 127 (26.3%) were 65 or older. Overall, 147 patients (30.5%) presented with at least 1 rib fracture and 59 subjects (12.2%) with delayed hemothorax. At 90 days, 22.8% of patients still had severe or moderate disabilities on global physical health score. Patients with solely delayed hemothorax and no rib fracture had the lowest global physical health score (46.4 vs 61.1, P < 0.01, effect size =  -2.60) than patients with simple MTI. Generally, functional limitations also increase with increments of number of rib fracture detected on radiograph. Outcomes were not different among patients 65 years or older when compared to their younger counterparts. In this prospective study of MTIs, severe to moderate disabilities were present in nearly 1 patient out of 5 at 90 days. The presence of delayed hemothorax and the number of rib fracture were associated with increased functional limitations after a MTI.

Effects of Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 in Radiation-Induced Intestinal Injury

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

Abderrahmani, Rym; Francois, Agnes; Buard, Valerie

2009-07-01

Purpose: To investigate effects of plasminogen activator inhibitor 1 (PAI-1) genetic deficiency and pharmacological PAI-1 inhibition with PAI-039 in a mouse model of radiation-induced enteropathy. Methods and Materials: Wild-type (Wt) and PAI-1{sup -/-} knockout mice received a single dose of 19 Gy to an exteriorized localized intestinal segment. Sham and irradiated Wt mice were treated orally with 1 mg/g of PAI-039. Histological modifications were quantified using a radiation injury score. Moreover, intestinal gene expression was monitored by real-time PCR. Results: At 3 days after irradiation, PAI-039 abolished the radiation-induced increase in the plasma active form of PAI-1 and limited themore » radiation-induced gene expression of transforming growth factor {beta}1 (TGF-{beta}1), CTGF, PAI-1, and COL1A2. Moreover, PAI-039 conferred temporary protection against early lethality. PAI-039 treatment limited the radiation-induced increase of CTGF and PAI-1 at 2 weeks after irradiation but had no effect at 6 weeks. Radiation injuries were less severe in PAI-1{sup -/-} mice than in Wt mice, and despite the beneficial effect, 3 days after irradiation, PAI-039 had no effects on microscopic radiation injuries compared to untreated Wt mice. Conclusions: A genetic deficiency of PAI-1 is associated with amelioration of late radiation enteropathy. Pharmacological inhibition of PAI-1 by PAI-039 positively impacts the early, acute phase increase in plasma PAI-1 and the associated radiation-induced gene expression of inflammatory/extracellular matrix proteins. Since PAI-039 has been shown to inhibit the active form of PAI-1, as opposed to the complete loss of PAI-1 in the knockout animals, these data suggest that a PAI-1 inhibitor could be beneficial in treating radiation-induced tissue injury in acute settings where PAI-1 is elevated.« less

Development of a guinea pig cutaneous radiation injury model using low penetrating X-rays.

PubMed

Rodgers, Kathleen E; Tan, Alick; Kim, Lila; Espinoza, Theresa; Meeks, Christopher; Johnston, William; Maulhardt, Holly; Donald, Melissa; Hill, Colin; diZerega, Gere S

2016-08-01

A guinea pig skin model was developed to determine the dose-dependent response to soft X-ray radiation into the dermis. X-ray exposure (50 kVp) was defined to a 4.0 × 4.0 cm area on the lateral surface of a guinea pig using lead shielding. Guinea pigs were exposed to a single fraction of X-ray irradiation ranging from 25-79 Gy via an XRAD320ix Biological Irradiator with the collimator removed. Gross skin changes were measured using clinical assessments defined by the Kumar scale. Skin contracture was assessed, as well as histological evaluations. Loss of dermal integrity was shown after a single dose of soft X-ray radiation at or above 32 Gy with the central 2.0 × 2.0 cm of the exposed site being the most affected. Hallmarks of the skin injury included moist desquamation, ulceration and wound contracture, as well as alterations in epithelium, dermis, muscle and adipose. Changes in the skin were time- and radiation dose-dependent. Full-thickness injury occurred without animal mortality or gross changes in the underlying organs. The guinea pig is an appropriate small animal model for the short-term screening of countermeasures for cutaneous radiation injury (CRI).

A Direct Comparison of Self-Injurious and Stereotyped Motor Behavior Between Preschool-Aged Children With and Without Developmental Delays

PubMed Central

Spofford, Lisa; Dimian, Adele; Tervo, Raymond; MacLean, William E.; Symons, Frank J.

2016-01-01

Objective To compare the prevalence of self-injurious behavior (SIB) and stereotyped motor behavior (STY) of preschool-aged children with developmental delays (DD group) and their peers without developmental delays (TD group) using a standardized caregiver report scale. Methods The Repetitive Behavior Scale-Revised was completed by caregivers of children with developmental delays and their peers without developmental delays. Frequency of occurrence and severity ratings for SIB and STY were compared between groups. Results SIB and STY were reported more often and at a greater level of severity in the DD group. Older chronological age was associated with more severe STY in the DD group but not the TD group. Gender was not related to STY or SIB for either group. Conclusions Differences in STY and SIB were evident between preschoolers with and without DD. Findings are discussed from developmental and behavioral psychology perspectives regarding the expression of repetitive behavior in developmentally at-risk pediatric populations. PMID:26514642

Application of Multivariate Modeling for Radiation Injury Assessment: A Proof of Concept

PubMed Central

Bolduc, David L.; Villa, Vilmar; Sandgren, David J.; Ledney, G. David; Blakely, William F.; Bünger, Rolf

2014-01-01

Multivariate radiation injury estimation algorithms were formulated for estimating severe hematopoietic acute radiation syndrome (H-ARS) injury (i.e., response category three or RC3) in a rhesus monkey total-body irradiation (TBI) model. Classical CBC and serum chemistry blood parameters were examined prior to irradiation (d 0) and on d 7, 10, 14, 21, and 25 after irradiation involving 24 nonhuman primates (NHP) (Macaca mulatta) given 6.5-Gy 60Co Υ-rays (0.4 Gy min−1) TBI. A correlation matrix was formulated with the RC3 severity level designated as the “dependent variable” and independent variables down selected based on their radioresponsiveness and relatively low multicollinearity using stepwise-linear regression analyses. Final candidate independent variables included CBC counts (absolute number of neutrophils, lymphocytes, and platelets) in formulating the “CBC” RC3 estimation algorithm. Additionally, the formulation of a diagnostic CBC and serum chemistry “CBC-SCHEM” RC3 algorithm expanded upon the CBC algorithm model with the addition of hematocrit and the serum enzyme levels of aspartate aminotransferase, creatine kinase, and lactate dehydrogenase. Both algorithms estimated RC3 with over 90% predictive power. Only the CBC-SCHEM RC3 algorithm, however, met the critical three assumptions of linear least squares demonstrating slightly greater precision for radiation injury estimation, but with significantly decreased prediction error indicating increased statistical robustness. PMID:25165485

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

Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury

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

Yoo, Hyun; Kang, Jeong Wook; Lee, Dong Won

Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a highmore » cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. - Highlights: • The effects of radiation on skin thickness in mice. • Next generation sequencing revealed that radiation inhibited pyruvate dehydrogenase kinase 2 expression. • PDK2 inhibited irradiation-induced cytokine gene expression. • Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness.« less

Dosimetric and clinical predictors for radiation-induced esophageal injury.

PubMed

Ahn, Sung-Ja; Kahn, Daniel; Zhou, Sumin; Yu, Xiaoli; Hollis, Donna; Shafman, Timothy D; Marks, Lawrence B

2005-02-01

To evaluate the clinical and three-dimensional dosimetric parameters associated with esophageal injury after radiotherapy (RT) for non-small-cell lung cancer. The records of 254 patients treated for non-small-cell lung cancer between 1992 and 2001 were reviewed. A variety of metrics describing the esophageal dose were extracted. The Radiation Therapy Oncology Group toxicity criteria for grading of esophageal injury were used. The median follow-up time for all patients was 43 months (range, 0.5-120 months). Logistic regression analysis, contingency table analyses, and Fisher's exact tests were used for statistical analysis. Acute toxicity occurred in 199 (78%) of 254 patients. For acute toxicity of Grade 2 or worse, twice-daily RT, age, nodal stage of N2 or worse, and most dosimetric parameters were predictive. Late toxicity occurred in 17 (7%) of 238 patients. The median and maximal time to the onset of late toxicity was 5 and 40 months after RT, respectively. Late toxicity occurred in 2%, 3%, 17%, 26%, and 100% of patients with acute Grade 0, 1, 2, 3, and 4 toxicity, respectively. For late toxicity, the severity of acute toxicity was most predictive. A variety of dosimetric parameters are predictive of acute and late esophageal injury. A strong correlation between the dosimetric parameters prevented a comparison between the predictive abilities of these metrics. The presence of acute injury was the most predictive factor for the development of late injury. Additional studies to define better the predictors of RT-induced esophageal injury are needed.

Biophysics and medical effects of enhanced radiation weapons.

PubMed

Reeves, Glen I

2012-08-01

Enhanced radiation weapons (ERW) are fission-fusion devices where the massive numbers of neutrons generated during the fusion process are intentionally allowed to escape rather than be confined to increase yield (and fallout products). As a result, the energy partition of the weapon output shifts from blast and thermal energies toward prompt radiation. The neutron/gamma output ratio is also increased. Neutrons emitted from ERW are of higher energy than the Eave of neutrons from fission weapons. These factors affect the patterns of injury distribution; delay wound healing in combined injuries; reduce the therapeutic efficacy of medical countermeasures; and increase the dose to radiation-only casualties, thus potentiating the likelihood of encountering radiation-induced incapacitation. The risk of radiation-induced carcinogenesis is also increased. Radiation exposure to first responders from activation products is increased over that expected from a fission weapon of similar yield. However, the zone of dangerous fallout is significantly reduced in area. At least four nations have developed the potential to produce such weapons. Although the probability of detonation of an ERW in the near future is very small, it is nonzero, and clinicians and medical planners should be aware of the medical effects of ERW.

Thrombopoietin Receptor Agonist Mitigates Hematopoietic Radiation Syndrome and Improves Survival after Whole-Body Ionizing Irradiation Followed by Wound Trauma

PubMed Central

Zhai, Min; Liao, Pei-Jun; Elliott, Thomas B.

2017-01-01

Ionizing radiation combined with trauma tissue injury (combined injury, CI) results in greater mortality and H-ARS than radiation alone (radiation injury, RI), which includes thrombocytopenia. The aim of this study was to determine whether increases in numbers of thrombocytes would improve survival and mitigate H-ARS after CI. We observed in mice that WBC and platelets remained very low in surviving RI animals that were given 9.5 Gy 60Co-γ-photon radiation, whereas only lymphocytes and basophils remained low in surviving CI mice that were irradiated and then given skin wounds. Numbers of RBC and platelets, hemoglobin concentrations, and hematocrit values remained low in surviving RI and CI mice. CI induced 30-day mortality higher than RI. Radiation delayed wound healing by approximately 14 days. Treatment with a thrombopoietin receptor agonist, Alxn4100TPO, after CI improved survival, mitigated body-weight loss, and reduced water consumption. Though this therapy delayed wound-healing rate more than in vehicle groups, it greatly increased numbers of platelets in sham, wounded, RI, and CI mice; it significantly mitigated decreases in WBC, spleen weights, and splenocytes in CI mice and decreases in RBC, hemoglobin, hematocrit values, and splenocytes and splenomegaly in RI mice. The results suggest that Alxn4100TPO is effective in mitigating CI. PMID:28408792

Delayed endovascular aortic repair is associated with reduced in-hospital mortality in patients with blunt thoracic aortic injury.

PubMed

Marcaccio, Christina L; Dumas, Ryan P; Huang, Yanlan; Yang, Wei; Wang, Grace J; Holena, Daniel N

2018-02-13

The traditional approach to stable blunt thoracic aortic injury (BTAI) endorsed by the Society for Vascular Surgery is early (<24 hours) thoracic endovascular aortic repair (TEVAR). Recently, some studies have shown improved mortality in stable BTAI patients repaired in a delayed manner (≥24 hours). However, the indications for use of delayed TEVAR for BTAI are not well characterized, and its overall impact on the patient's survival remains poorly understood. We sought to determine whether delayed TEVAR is associated with a decrease in mortality compared with early TEVAR in this population. We conducted a retrospective cohort study of adult patients with BTAI (International Classification of Diseases, Ninth Revision diagnosis code 901.0) who underwent TEVAR (International Classification of Diseases, Ninth Revision procedure code 39.73) from 2009 to 2013 using the National Sample Program data set. Missing physiologic data were imputed using chained multiple imputation. Patients were parsed into groups based on the timing of TEVAR (early, <24 hours, vs delayed, ≥24 hours). The χ 2 , Mann-Whitney, and Fisher exact tests were used to compare baseline characteristics and outcomes of interest between groups. Multivariable logistic regression for mortality was performed that included all variables significant at P ≤ .2 in univariate analyses. A total of 2045 adult patients with BTAI were identified, of whom 534 (26%) underwent TEVAR. Patients with missing data on TEVAR timing were excluded (n = 27), leaving a total of 507 patients for analysis (75% male; 69% white; median age, 40 years [interquartile range, 27-56 years]; median Injury Severity Score [ISS], 34 [interquartile range, 26-41]). Of these, 378 patients underwent early TEVAR and 129 underwent delayed TEVAR. The two groups were similar with regard to age, sex, race, ISS, and presenting physiology. Mortality was 11.9% in the early TEVAR group vs 5.4% in the delayed group, with the early group

Casualty Evacuation Delay and Outcomes

DTIC Science & Technology

2003-01-01

consequences of delay in therapy on wounded individuals. The contractor was charged with studying the effect of delay on evacuation on outcome of...process. 3 There are a remarkably small proportion of patient diagnoses and states in which time has an effect on outcome . This is because the vast...emphasis on estimating the effect of delayed evacuation on injury outcome and means to mitigating such effects . Since some of the Specific Aims were

Ophthalmologic survey of atomic bomb survivors in Japan, 1949. Atomic bomb radiation cataract case report with histopathologic study. Medical examination of Hiroshima patients with radiation cataracts (in Japanese and English)

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

Cogan, D.G.; Martin, S.F.; Kimura, S.J.

1959-01-01

This document contains 3 reports dealing with the delayed effects of radiation on the eyes of survivors of the atomic explosions in Hiroshima and Nagasaki. In the first study, 1000 persons who were listed as having been in the open and within two kilometers of the hypocenter at the time of the explosion were selected at random from the census files of the Atomic Bomb Casualty Commission for study. In addition, 231 others, comprising the total available number of surviving persons listed at present in the census files as having been within one kilometer of the hypocenter, were examined, asmore » were several hundred others who were contacted through newspaper publicity, referrals from local ophthalmologists, or through hearsay. The survey resulted in bringing in persons having, or having had, a variety of ocular conditions. Those connected with the atomic bomb included the following diagnoses; multiple injuries of eyes and eyelids; keratoconjunctivitis from ultraviolet and ionizing radiations; thermal burn of the cornea and of the retina; retinitis proliferans; and radiation cataracts. The cataracts were the only delayed manifestations of ocular injury from the atomic bomb. The second paper is a case report of a histopathologic study of atomic bomb radiation cataract. The third paper presents the results of medical examinations of survivors having radiation induced cataracts. 32 references, 8 figures. (DMC)« less

A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

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

Yannam, Govardhana Rao; Han, Bing; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi

Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevatedmore » alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.« less

A Direct Comparison of Self-Injurious and Stereotyped Motor Behavior Between Preschool-Aged Children With and Without Developmental Delays.

PubMed

Hoch, John; Spofford, Lisa; Dimian, Adele; Tervo, Raymond; MacLean, William E; Symons, Frank J

2016-06-01

To compare the prevalence of self-injurious behavior (SIB) and stereotyped motor behavior (STY) of preschool-aged children with developmental delays (DD group) and their peers without developmental delays (TD group) using a standardized caregiver report scale. The Repetitive Behavior Scale-Revised was completed by caregivers of children with developmental delays and their peers without developmental delays. Frequency of occurrence and severity ratings for SIB and STY were compared between groups. SIB and STY were reported more often and at a greater level of severity in the DD group. Older chronological age was associated with more severe STY in the DD group but not the TD group. Gender was not related to STY or SIB for either group. Differences in STY and SIB were evident between preschoolers with and without DD. Findings are discussed from developmental and behavioral psychology perspectives regarding the expression of repetitive behavior in developmentally at-risk pediatric populations. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

Radiological manifestations of radiation-induced injury to the normal upper gastrointestinal tract

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

Goldstein, H.M.; Rogers, L.F.; Fletcher, G.H.

1975-10-01

Radiation-induced injury to the normal esophagus, stomach, and duodenum in patients with advanced cervical carcinoma who received high para-aortic lymph- node irradiation to an average tumor dose of 5,000 rads is discussed. Radiation esophagitis is usually the result of mediastinal irradiation for bronchogenic carcinoma. The most consistent radiological finding is abnormal motility, with esophageal stricture and/or ulceration occurring less frequently. Radiation gastritis is usually present as pyloric ulceration or irregular contractions of the antrum, simulating gastric carcinoma. Postbulbar duodenal mucosal thickening, ulceration, and strictures may occur. Pertinent clinical features, pathogenesis, and pathological correlations are discussed. (auth)

Impact of associated injuries in the Floating knee: A retrospective study

PubMed Central

Rethnam, Ulfin; Yesupalan, Rajam S; Nair, Rajagopalan

2009-01-01

Background Floating knee injuries are usually associated with other significant injuries. Do these injuries have implications on the management of the floating knee and the final outcome of patients? Our study aims to assess the implications of associated injuries in the management and final outcome of floating knee. Methods 29 patients with floating knees were assessed in our institution. A retrospective analysis of medical records and radiographs were done and all associated injuries were identified. The impact of associated injuries on delay in initial surgical management, delay in rehabilitation & final outcome of the floating knee were assessed. Results 38 associated injuries were noted. 7 were associated with ipsilateral knee injuries. Lower limb injuries were most commonly associated with the floating knee. Patients with some associated injuries had a delay in surgical management and others a delay in post-operative rehabilitation. Knee ligament and vascular injuries were associated with poor outcome. Conclusion The associated injuries were quite frequent with the floating knee. Some of the associated injuries caused a delay in surgical management and post-operative rehabilitation. In assessment of the final outcome, patients with associated knee and vascular injuries had a poor prognosis. Majority of the patients with associated injuries had a good or excellent outcome. PMID:19144197

Differentiation of Recurrent Glioblastoma from Delayed Radiation Necrosis by Using Voxel-based Multiparametric Analysis of MR Imaging Data.

PubMed

Yoon, Ra Gyoung; Kim, Ho Sung; Koh, Myeong Ju; Shim, Woo Hyun; Jung, Seung Chai; Kim, Sang Joon; Kim, Jeong Hoon

2017-10-01

Purpose To assess a volume-weighted voxel-based multiparametric (MP) clustering method as an imaging biomarker to differentiate recurrent glioblastoma from delayed radiation necrosis. Materials and Methods The institutional review board approved this retrospective study and waived the informed consent requirement. Seventy-five patients with pathologic analysis-confirmed recurrent glioblastoma (n = 42) or radiation necrosis (n = 33) who presented with enlarged contrast material-enhanced lesions at magnetic resonance (MR) imaging after they completed concurrent chemotherapy and radiation therapy were enrolled. The diagnostic performance of the total MP cluster score was determined by using the area under the receiver operating characteristic curve (AUC) with cross-validation and compared with those of single parameter measurements (10% histogram cutoffs of apparent diffusion coefficient [ADC10] or 90% histogram cutoffs of normalized cerebral blood volume and initial time-signal intensity AUC). Results Receiver operating characteristic curve analysis showed that an AUC for differentiating recurrent glioblastoma from delayed radiation necrosis was highest in the total MP cluster score and lowest for ADC10 for both readers. The total MP cluster score had significantly better diagnostic accuracy than any single parameter (corrected P = .001-.039 for reader 1; corrected P = .005-.041 for reader 2). The total MP cluster score was the best predictor of recurrent glioblastoma (cross-validated AUCs, 0.942-0.946 for both readers), with a sensitivity of 95.2% for reader 1 and 97.6% for reader 2. Conclusion Quantitative analysis with volume-weighted voxel-based MP clustering appears to be superior to the use of single imaging parameters to differentiate recurrent glioblastoma from delayed radiation necrosis. © RSNA, 2017 Online supplemental material is available for this article.

Hematopoietic stem cell injury induced by ionizing radiation.

PubMed

Shao, Lijian; Luo, Yi; Zhou, Daohong

2014-03-20

Exposure to ionizing radiation (IR) as the result of nuclear accidents or terrorist attacks is a significant threat and a major medical concern. Hematopoietic stem cell (HSC) injury is the primary cause of death after accidental or intentional exposure to a moderate or high dose of IR. Protecting HSCs from IR should be a primary goal in the development of novel medical countermeasures against radiation. Significant progress has been made in our understanding of the mechanisms by which IR causes HSC damage. The mechanisms include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii) promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF-dependent differentiation checkpoint; (iii) induction of HSC senescence via the ROS-p38 pathway; and (iv) damage to the HSC niche. Induction of apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for IR-induced acute bone marrow (BM) injury. Long-term BM suppression caused by IR is mainly attributable to the induction of HSC senescence. However, the promotion of HSC differentiation and damage to the HSC niche can contribute to both the acute and long-term effects of IR on the hematopoietic system. In this review, we have summarized a number of recent findings that provide new insights into the mechanisms whereby IR damages HSCs. These findings will provide new opportunities for developing a mechanism-based strategy to prevent and/or mitigate IR-induced BM suppression. Antioxid.

ON THE MECHANISM OF INJURY OF FETUSES IN GRAVID ANIMALS WITH RADIATION SICKNESS (in Russian)

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

Kalinina, N.A.

1960-10-01

An assessment is made of the importance of the maternal organism in the mechanism of injury of the fetus during x-ray irradiation of gravid animals. A confrontation of the severity of radiation sickness in pregnant rats with the severity of injury of the fetuses divulged that in irradiation during the period before implantation in the mechanism of fetus injury of great importance are changes occurring in the irradiated organism of the mother; irradiation at the time of completed placentation produces a lesser deleterious effect on the state of the fetus than in earlier periods of gestation. Disturbance of lactation andmore » of the maternal instinct in the animals subjected to the action of ionizing radiation is one of the causes of postnatal death of the progeny of the irradiated rats. (auth)« less

A non-human primate model of human radiation-induced venocclusive liver disease and hepatocyte injury

PubMed Central

Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro; Roy-Chowdhury, Jayanta; Locker, Joseph; Abe, Michio; Enke, Charles A.; Baranowska-Kortylewicz, Janina; Solberg, Timothy D.; Guha, Chandan; Fox, Ira J.

2014-01-01

Background Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Since the characteristic venocclusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic venocclusive disease. Methods We performed a dose escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results At doses ≥40Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses where radiation-induced liver disease was mild or non-existent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions The cynomolgus monkey, as the first animal model of human venocclusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury. PMID:24315566

DTI and pathological changes in a rabbit model of radiation injury to the spinal cord after 125I radioactive seed implantation

PubMed Central

Cao, Xia; Fang, Le; Cui, Chuan-yu; Gao, Shi; Wang, Tian-wei

2018-01-01

Excessive radiation exposure may lead to edema of the spinal cord and deterioration of the nervous system. Magnetic resonance imaging can be used to judge and assess the extent of edema and to evaluate pathological changes and thus may be used for the evaluation of spinal cord injuries caused by radiation therapy. Radioactive 125I seeds to irradiate 90% of the spinal cord tissue at doses of 40–100 Gy (D90) were implanted in rabbits at T10 to induce radiation injury, and we evaluated their safety for use in the spinal cord. Diffusion tensor imaging showed that with increased D90, the apparent diffusion coefficient and fractional anisotropy values were increased. Moreover, pathological damage of neurons and microvessels in the gray matter and white matter was aggravated. At 2 months after implantation, obvious pathological injury was visible in the spinal cords of each group. Magnetic resonance diffusion tensor imaging revealed the radiation injury to the spinal cord, and we quantified the degree of spinal cord injury through apparent diffusion coefficient and fractional anisotropy. PMID:29623940

Delayed hemothorax superimposed on extrapleural hematoma after blunt chest injury: a case report.

PubMed

Masuda, Ryota; Ikoma, Yoichiro; Oiwa, Kana; Nakazato, Kenei; Takeichi, Haruka; Iwazaki, Masayuki

2013-09-20

We report a case showing delayed hemothorax superimposed on extrapleural hematoma after blunt chest injury. The patient was a 56-year-old man with a medical history of alcoholic hepatopathy who presented with a chief complaint of dyspnea on exertion. One month prior to presentation, he had sustained a fall that had resulted in left simple rib fracture. A chest radiograph taken at the time of injury showed notable reduction in the permeability of the left lung field along with high pulmonary collapse as well as rightward deviation of the shadow of the inferior mediastinum. Chest CT images showed a region of low absorption in the thoracic cavity with septi. Thoracic drainage was performed (1,300 mL total) and hemothorax was diagnosed. Thoracoscopic examination was then performed. When the inside of the thorax was observed, what had been presumed to be the septi of a multilocular fluid collection was found to be actually the parietal pleura, and a hematoma was confirmed inside the extrapleural cavity. The hematoma inside the extrapleural cavity was managed with lavage and drainage, and drainage tubes were placed inside both the thoracic cavity and extrapleural cavity at the end of the procedure. The patient's postoperative course was uneventful, and he was discharged on postoperative day 4.

Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

PubMed

Lorimore, S A; Wright, E G

2003-01-01

To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The

Medical Countermeasures for Radiation Exposure and Related Injuries: Characterization of Medicines, FDA-Approval Status and Inclusion into the Strategic National Stockpile

PubMed Central

Singh, Vijay K.; Romaine, Patricia L.P.; Seed, Thomas M.

2015-01-01

Abstract World events over the past decade have highlighted the threat of nuclear terrorism as well as an urgent need to develop radiation countermeasures for acute radiation exposures and subsequent bodily injuries. An increased probability of radiological or nuclear incidents due to detonation of nuclear weapons by terrorists, sabotage of nuclear facilities, dispersal and exposure to radioactive materials, and accidents provides the basis for such enhanced radiation exposure risks for civilian populations. Although the search for suitable radiation countermeasures for radiation-associated injuries was initiated more than half a century ago, no safe and effective radiation countermeasure for the most severe of these injuries, namely acute radiation syndrome (ARS), has been approved by the United States Food and Drug Administration (FDA). The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. In this communication, the authors have listed and reviewed the status of radiation countermeasures that are currently available for use, or those that might be used for exceptional nuclear/radiological contingencies, plus a limited few medicines that show early promise but still remain experimental in nature and unauthorized for human use by the FDA. PMID:25905522

Radiation-induced injury of the exocrine pancreas after chemoradiotherapy for gastric cancer.

PubMed

Wydmanski, Jerzy; Polanowski, Pawel; Tukiendorf, Andrzej; Maslyk, Barbara

2016-03-01

The pancreas is located almost entirely within the treatment area for radiotherapy of gastric cancer. The aim of this study was to analyze radiation-induced injury of the exocrine pancreas. The study included 127 gastric cancer patients, who underwent preoperative or postoperative chemoradiotherapy. A total dose of 45 Gy was given in 25 fractions. Concurrent chemotherapy was 5-fluorouracil-based. Lipase and α-amylase were assayed before, during and after treatment. Lipase and α-amylase deficiencies were found in 48.2% and 19.7% of patients, respectively. In the univariant analysis, age and pretreatment α-amylase and lipase activities influenced on risk of injury of the exocrine pancreas (p<0.05). Younger patients (<65 years) had a lower risk of hypoamylasemia than older patients. The probability of insufficiency was lower than 0.2 for patients with pretreatment α-amylase and lipase activities above 50 U/L and 55 U/L, respectively. The multivariate analyses of the time to hypolipasemia showed that only pretreatment lipase activity was significant. Gastric cancer patients have an increased risk of exocrine pancreatic insufficiency after chemoradiotherapy. Thus, the pancreas should be regarded as an OAR. Measuring lipase activity should be the standard for assessing radiation-induced pancreatic injury. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Loss of the Inducible Hsp70 Delays the Inflammatory Response to Skeletal Muscle Injury and Severely Impairs Muscle Regeneration

PubMed Central

Howard, Travis M.; Ahn, Bumsoo; Ferreira, Leonardo F.

2013-01-01

Skeletal muscle regeneration following injury is a highly coordinated process that involves transient muscle inflammation, removal of necrotic cellular debris and subsequent replacement of damaged myofibers through secondary myogenesis. However, the molecular mechanisms which coordinate these events are only beginning to be defined. In the current study we demonstrate that Heat shock protein 70 (Hsp70) is increased following muscle injury, and is necessary for the normal sequence of events following severe injury induced by cardiotoxin, and physiological injury induced by modified muscle use. Indeed, Hsp70 ablated mice showed a significantly delayed inflammatory response to muscle injury induced by cardiotoxin, with nearly undetected levels of both neutrophil and macrophage markers 24 hours post-injury. At later time points, Hsp70 ablated mice showed sustained muscle inflammation and necrosis, calcium deposition and impaired fiber regeneration that persisted several weeks post-injury. Through rescue experiments reintroducing Hsp70 intracellular expression plasmids into muscles of Hsp70 ablated mice either prior to injury or post-injury, we confirm that Hsp70 optimally promotes muscle regeneration when expressed during both the inflammatory phase that predominates in the first four days following severe injury and the regenerative phase that predominates thereafter. Additional rescue experiments reintroducing Hsp70 protein into the extracellular microenvironment of injured muscles at the onset of injury provides further evidence that Hsp70 released from damaged muscle may drive the early inflammatory response to injury. Importantly, following induction of physiological injury through muscle reloading following a period of muscle disuse, reduced inflammation in 3-day reloaded muscles of Hsp70 ablated mice was associated with preservation of myofibers, and increased muscle force production at later time points compared to WT. Collectively our findings indicate that

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.

Hematopoietic Stem Cell Injury Induced by Ionizing Radiation

PubMed Central

Shao, Lijian; Luo, Yi

2014-01-01

Abstract Significance: Exposure to ionizing radiation (IR) as the result of nuclear accidents or terrorist attacks is a significant threat and a major medical concern. Hematopoietic stem cell (HSC) injury is the primary cause of death after accidental or intentional exposure to a moderate or high dose of IR. Protecting HSCs from IR should be a primary goal in the development of novel medical countermeasures against radiation. Recent Advances: Significant progress has been made in our understanding of the mechanisms by which IR causes HSC damage. The mechanisms include (i) induction of HSC apoptosis via the p53-Puma pathway; (ii) promotion of HSC differentiation via the activation of the G-CSF/Stat3/BATF-dependent differentiation checkpoint; (iii) induction of HSC senescence via the ROS-p38 pathway; and (iv) damage to the HSC niche. Critical Issues: Induction of apoptosis in HSCs and hematopoietic progenitor cells is primarily responsible for IR-induced acute bone marrow (BM) injury. Long-term BM suppression caused by IR is mainly attributable to the induction of HSC senescence. However, the promotion of HSC differentiation and damage to the HSC niche can contribute to both the acute and long-term effects of IR on the hematopoietic system. Future Directions: In this review, we have summarized a number of recent findings that provide new insights into the mechanisms whereby IR damages HSCs. These findings will provide new opportunities for developing a mechanism-based strategy to prevent and/or mitigate IR-induced BM suppression. Antioxid. Redox Signal. 20, 1447–1462. PMID:24124731

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

PubMed Central

Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

2012-01-01

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

PubMed

Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

2015-10-22

Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

HDACi Valproic Acid (VPA) and Suberoylanilide Hydroxamic Acid (SAHA) Delay but Fail to Protect against Warm Hepatic Ischemia-Reperfusion Injury.

PubMed

Ruess, Dietrich A; Probst, Moriz; Marjanovic, Goran; Wittel, Uwe A; Hopt, Ulrich T; Keck, Tobias; Bausch, Dirk

2016-01-01

Histone deacetylases (HDAC) catalyze N-terminal deacetylation of lysine-residues on histones and multiple nuclear and cytoplasmic proteins. In various animal models, such as trauma/hemorrhagic shock, ischemic stroke or myocardial infarction, HDAC inhibitor (HDACi) application is cyto- and organoprotective and promotes survival. HDACi reduce stress signaling, cell death and inflammation. Hepatic ischemia-reperfusion (I/R) injury during major liver resection or transplantation increases morbidity and mortality. Assuming protective properties, the aim of this study was to investigate the effect of the HDACi VPA and SAHA on warm hepatic I/R. Male Wistar-Kyoto rats (age: 6-8 weeks) were randomized to VPA, SAHA, vehicle control (pre-) treatment or sham-groups and underwent partial no-flow liver ischemia for 90 minutes with subsequent reperfusion for 6, 12, 24 and 60 hours. Injury and regeneration was quantified by serum AST and ALT levels, by macroscopic aspect and (immuno-) histology. HDACi treatment efficiency, impact on MAPK/SAPK-activation and Hippo-YAP signaling was determined by Western blot. Treatment with HDACi significantly enhanced hyperacetylation of Histone H3-K9 during I/R, indicative of adequate treatment efficiency. Liver injury, as measured by macroscopic aspect, serum transaminases and histology, was delayed, but not alleviated in VPA and SAHA treated animals. Importantly, tissue destruction was significantly more pronounced with VPA. SAPK-activation (p38 and JNK) was reduced by VPA and SAHA in the early (6h) reperfusion phase, but augmented later on (JNK, 24h). Regeneration appeared enhanced in SAHA and VPA treated animals and was dependent on Hippo-YAP signaling. VPA and SAHA delay warm hepatic I/R injury at least in part through modulation of SAPK-activation. However, these HDACi fail to exert organoprotective effects, in this setting. For VPA, belated damage is even aggravated.

Protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury.

PubMed

Shi, Jing; Wang, Lan; Lu, Yan; Ji, Yue; Wang, Yaqing; Dong, Ke; Kong, Xiangqing; Sun, Wei

2017-01-01

Radiation-induced gastrointestinal syndrome, including nausea, diarrhea and dehydration, contributes to morbidity and mortality after medical or industrial radiation exposure. No safe and effective radiation countermeasure has been approved for clinical therapy. In this study, we aimed to investigate the potential protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury. C57/BL6 mice were orally administered seabuckthorn pulp oil, seed oil and control olive oil once per day for 7 days before exposure to total-body X-ray irradiation of 7.5 Gy. Terminal deoxynucleotidyl transferase dUTP nick end labeling, quantitative real-time polymerase chain reaction and western blotting were used for the measurement of apoptotic cells and proteins, inflammation factors and mitogen-activated protein (MAP) kinases. Seabuckthorn oil pretreatment increased the post-radiation survival rate and reduced the damage area of the small intestine villi. Both the pulp and seed oil treatment significantly decreased the apoptotic cell numbers and cleaved caspase 3 expression. Seabuckthorn oil downregulated the mRNA level of inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8. Both the pulp and seed oils elevated the level of phosphorylated extracellular-signal-regulated kinase and reduced the levels of phosphorylated c-Jun N-terminal kinase and p38. Palmitoleic acid (PLA) and alpha linolenic acid (ALA) are the predominant components of pulp oil and seed oil, respectively. Pretreatment with PLA and ALA increased the post-radiation survival time. In conclusion, seabuckthorn pulp and seed oils protect against mouse intestinal injury from high-dose radiation by reducing cell apoptosis and inflammation. ALA and PLA are promising natural radiation countermeasure candidates. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation

Radiation-induced ocular injury in the dog: a histological study.

PubMed

Ching, S V; Gillette, S M; Powers, B E; Roberts, S M; Gillette, E L; Withrow, S J

1990-08-01

Radiation-induced ocular injury secondary to treatment of nasal cancer occurs in humans and animals. Dogs with nasal carcinomas were randomized to receive 36 to 67.5 Gy in fractionated doses given in 4 weeks using a 6 MV linear accelerator. Ophthalmic examinations were performed according to a predetermined protocol and eyes were removed for histologic examination when dogs were euthanatized. The eye in the radiation field exhibited greater injury than the contralateral eye with nasal areas of the globe having more severe lesions than temporal areas. Lesions occurred in all dogs and at all doses. At 1 month or less postirradiation treatment, all dogs had blepharitis, keratoconjunctivitis and corneal epithelial atrophy. Surface lesions persisted in all eyes, becoming less severe and more chronic with time. At 3-6 months postirradiation treatment, degenerative angiopathy of retinal vessels appeared with multifocal retinal hemorrhage and mild diffuse retinal degeneration which affected outer layers first and progressed inwardly with time. At 6 months postirradiation treatment, there were cataracts, fibrosis of retinal vessel walls with loss of vascular smooth muscle, retinal hemorrhage, and mild to moderate retinal degeneration. At 1 year postirradiation treatment, retinal vessels remained sclerotic, retinal hemorrhage was less frequent, and there was moderate retinal degeneration with swelling and loss of ganglion cells. By 2 years or more postirradiation treatment, optic nerve axonal degeneration secondary to retinal changes had appeared. Tapetal and choroidal atrophy were inconsistently seen. Thus, ocular lesions at the doses received developed along a relatively predictable time course and recovery was not seen. Structures of the canine eye appear sufficiently sensitive that even relatively low total doses given in small doses per fraction cause significant long-term injury.

Mitigation of radiation-induced hematopoietic injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice

PubMed Central

Venkateswaran, Kavya; Shrivastava, Anju; Agrawala, Paban K.; Prasad, Ashok; Kalra, Namita; Pandey, Parvat R.; Manda, Kailash; Raj, Hanumantharao G.; Parmar, Virinder S.; Dwarakanath, Bilikere S.

2016-01-01

Protection of the hematopoietic system from radiation damage, and/or mitigation of hematopoietic injury are the two major strategies for developing medical countermeasure agents (MCM) to combat radiation-induced lethality. In the present study, we investigated the potential of 7, 8-diacetoxy-4-methylthiocoumarin (DAMTC) to ameliorate radiation-induced hematopoietic damage and the associated mortality following total body irradiation (TBI) in C57BL/6 mice. Administration of DAMTC 24 hours post TBI alleviated TBI-induced myelo-suppression and pancytopenia, by augmenting lymphocytes and WBCs in the peripheral blood of mice, while bone marrow (BM) cellularity was restored through enhanced proliferation of the stem cells. It stimulated multi-lineage expansion and differentiation of myeloid progenitors in the BM and induced proliferation of splenic progenitors thereby, facilitating hematopoietic re-population. DAMTC reduced the radiation-induced apoptotic and mitotic death in the hematopoietic compartment. Recruitment of pro-inflammatory M1 macrophages in spleen contributed to the immune-protection linked to the mitigation of hematopoietic injury. Recovery of the hematopoietic compartment correlated well with mitigation of mortality at a lethal dose of 9 Gy, leading to 80% animal survival. Present study establishes the potential of DAMTC to mitigate radiation-induced injury to the hematopoietic system by stimulating the re-population of stem cells from multiple lineages. PMID:27849061

Mitigation of radiation-induced lung injury with EUK-207 and genistein: effects in adolescent rats.

PubMed

Mahmood, J; Jelveh, S; Zaidi, A; Doctrow, S R; Hill, R P

2013-02-01

Exposure of civilian populations to radiation due to accident, war or terrorist act is an increasing concern. The lung is one of the more radiosensitive organs that may be affected in people receiving partial-body irradiation and radiation injury in lung is thought to be associated with the development of a prolonged inflammatory response. Here we examined how effectively damage to the lung can be mitigated by administration of drugs initiated at different times after radiation exposure and examined response in adolescent animals for comparison with the young adult animals that we had studied previously. We studied the mitigation efficacy of the isoflavone genistein (50 mg/kg) and the salen-Mn superoxide dismutase-catalase mimetic EUK-207 (8 mg/kg), both of which have been reported to scavenge reactive oxygen species and reduce activity of the NFkB pathway. The drugs were given by subcutaneous injection to 6- to 7-week-old Fisher rats daily starting either immediately or 2 weeks after irradiation with 12 Gy to the whole thorax. The treatment was stopped at 28 weeks post irradiation and the animals were assessed for levels of inflammatory cytokines, activated macrophages, oxidative damage and fibrosis at 48 weeks post irradiation. We demonstrated that both genistein and EUK-207 delayed and suppressed the increased breathing rate associated with pneumonitis. These agents also reduced levels of oxidative damage (50-100%), levels of TGF-β1 expression (75-100%), activated macrophages (20-60%) and fibrosis (60-80%). The adolescent rats developed pneumonitis earlier following irradiation of the lung than did the adult rats leading to greater severe morbidity requiring euthanasia (∼37% in adolescents vs. ∼10% in young adults) but the extent of the mitigation of the damage was similar or slightly greater.

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

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

The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

PubMed

MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

2012-10-01

The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

Cinnamon extract ameliorates ionizing radiation-induced cellular injury in rats.

PubMed

Azab, Khaled Sh; Mostafa, Abdel-Halem A; Ali, Ehab M M; Abdel-Aziz, Mohamed A S

2011-11-01

The present study aimed to investigate the protective role of cinnamon extract against inflammatory and oxidative injuries in gamma irradiated rats. Rats were subjected to fractionated doses of gamma radiation. Cinnamon extract were daily administrated before starting irradiation and continued after radiation exposure. The results obtained revealed that the administration of cinnamon extract to irradiated rats significantly ameliorated the changes induced in liver antioxidant system; catalase, superoxide dismutase and glutathione peroxidase activities as well as reduced glutathione concentration. The liver's lipid peroxidation and protein oxidation indices were significantly decreased when compared with their equivalent values in irradiated rats. Furthermore, the changes induces in xanthine oxidoreductase system were significantly diminished. In addition, the changes in liver nitric oxide contents, serum tumor necrosis factor alpha and C-reactive protein levels were markedly improved. In conclusion, the administration of cinnamon extract might provide substantial protection against radiation-induced oxidative and inflammatory damages. Copyright © 2011 Elsevier Inc. All rights reserved.

Immediate versus delayed primary nerve repair in the rabbit sciatic nerve

PubMed Central

Piskin, Ahmet; Altunkaynak, Berrin Zühal; Çιtlak, Atilla; Sezgin, Hicabi; Yazιcι, Ozgür; Kaplan, Süleyman

2013-01-01

It is well known that peripheral nerve injury should be treated immediately in the clinic, but in some instances, repair can be delayed. This study investigated the effects of immediate versus delayed (3 days after injury) neurorrhaphy on repair of transected sciatic nerve in New Zealand rabbits using stereological, histomorphological and biomechanical methods. At 8 weeks after immediate and delayed neurorrhaphy, axon number and area in the sciatic nerve, myelin sheath and epineurium thickness, Schwann cell morphology, and the mechanical property of nerve fibers did not differ obviously. These results indicate that delayed neurorrhaphy do not produce any deleterious effect on sciatic nerve repair. PMID:25206663

Factors associated with delay in trauma team activation and impact on patient outcomes.

PubMed

Connolly, Rory; Woo, Michael Y; Lampron, Jacinthe; Perry, Jeffrey J

2017-09-05

Trauma code activation is initiated by emergency physicians using physiological and anatomical criteria, mechanism of injury, and patient demographic factors. Our objective was to identify factors associated with delayed trauma team activation. We assessed consecutive cases from a regional trauma database from January 2008 to March 2014. We defined a delay in trauma code activation as a time greater than 30 minutes from the time of arrival. We conducted univariate analysis for factors potentially influencing trauma team activation, and we subsequently used multiple logistic regression analysis models for delayed activation in relation to mortality, length of stay, and time to operative management. Patients totalling 846 were included for our analysis; 4.1% (35/846) of trauma codes were activated after 30 minutes. Mean age was 40.8 years in the early group versus 49.2 in the delayed group (p=0.01). Patients were over age 70 years in 7.6% in the early activation group versus 17.1% in the delayed group (p=0.04). There was no significant difference in sex, type of injury, injury severity, or time from injury between the two groups. There was no significant difference in mortality, median length of stay, or median time to operative management. Delayed activation is linked with increasing age with no clear link to increased mortality. Given the severe injuries in the delayed cohort that required activation of the trauma team, further emphasis on the older trauma patient and interventions to recognize this vulnerable population should be made.

Capabilities for Clinical Management of Radiation Injuries of the Nikiforov Russian Center of Emergency and Radiation Medicine (EMERCOM of Russia).

PubMed

Aleksanin, S

2016-09-01

This article presents an overview of the capabilities for clinical management of radiation injuries available at the Nikiforov Russian Center of Emergency and Radiation Medicine (NRCERM) of the Ministry of the Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters (EMERCOM). NRCERM is a federal state budgetary institution and the Russian Federation's head organization for providing medical assistance for persons overexposed to ionizing radiation, responders to radiation emergencies and people evacuated from radiation contaminated areas. As the WHO Collaborating Center for Treatment and Rehabilitation of Accident Recovery Workers of Nuclear and Other Disasters and a member of the WHO Radiation Emergency Medical Preparedness and Assistance Network (REMPAN), NRCERM is prepared to provide assistance and technical support in case of a radiation accident. For this purpose, NRCERM hospitals are equipped with technologically advanced facilities and possess well-trained specialist staff. © World Health Organisation 2016. All rights reserved. The World Health Organization has granted Oxford University Press permission for the reproduction of this article.

Avoiding delayed diagnosis of significant blunt bowel and mesenteric injuries: Can a scoring tool make the difference? A 7-year retrospective cohort study.

PubMed

Zingg, Tobias; Agri, Fabio; Bourgeat, Mylène; Yersin, Bertrand; Romain, Benoît; Schmidt, Sabine; Keller, Nathalie; Demartines, Nicolas

2018-01-01

Significant blunt bowel and mesenteric injuries (sBBMI) are frequently missed despite the widespread use of computed tomography (CT). Early treatment improves the outcome related to these injuries. The aim of this study was to assess the prevalence of sBBMI, the incidence of delayed diagnosis and to test the performance of the Bowel Injury Prediction Score (BIPS), determined by the white blood cell (WBC) count, presence or absence of abdominal tenderness and CT grade of mesenteric injury. Single-centre, registry-based retrospective cohort study, screening all consecutive trauma patients admitted to Lausanne University Hospital Trauma Centre from 2008 to 2015 after a road traffic accident. All patients with reliable information about the presence or absence of sBBMI who underwent abdominal CT and for whom calculation of the BIPS was possible were included for analysis. The incidence of delayed (>24h after admission) diagnosis in the patient group with sBBMI was determined and the diagnostic performance of the BIPS for sBBMI was assessed. For analysis, 766 patients with reliable information about the presence or absence of sBBMI were included. The prevalence of sBBMI was 3.1% (24/766). In 24% (5/21) of stable trauma patients undergoing CT, a diagnostic delay of more than 24h occurred. Abdominal tenderness (p<0.0001) and CT grade ≥4 (p<0.0001) were associated with sBBMI, whereas CT grade 4 alone (p=0.93) and WBC count ≥17G/l (p=0.30) were not. A BIPS ≥2 had a sensitivity of 89% (95% CI, 67-99), specificity of 89% (95% CI, 86-91), positive likelihood ratio of 8 (95% CI, 6.1-10), negative likelihood ratio of 0.12 (95% CI, 0.03-0.44), positive predictive value (PPV) of 19% (95% CI, 15-24) and negative predictive value (NPV) of 99.7% (95% CI, 98.7-99.9). CT alone identified 79% (15/19) and the BIPS 89% (17/19) of patients with sBBMI (p=0.66). Diagnostic delays in patients with sBBMI are common (24%), despite the routine use of abdominal CT. Application of the BIPS

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

Targeted Metabolomics Identifies Pharmacodynamic Biomarkers for BIO 300 Mitigation of Radiation-Induced Lung Injury.

PubMed

Jones, Jace W; Jackson, Isabel L; Vujaskovic, Zeljko; Kaytor, Michael D; Kane, Maureen A

2017-12-01

Biomarkers serve a number of purposes during drug development including defining the natural history of injury/disease, serving as a secondary endpoint or trigger for intervention, and/or aiding in the selection of an effective dose in humans. BIO 300 is a patent-protected pharmaceutical formulation of nanoparticles of synthetic genistein being developed by Humanetics Corporation. The primary goal of this metabolomic discovery experiment was to identify biomarkers that correlate with radiation-induced lung injury and BIO 300 efficacy for mitigating tissue damage based upon the primary endpoint of survival. High-throughput targeted metabolomics of lung tissue from male C57L/J mice exposed to 12.5 Gy whole thorax lung irradiation, treated daily with 400 mg/kg BIO 300 for either 2 weeks or 6 weeks starting 24 h post radiation exposure, were assayed at 180 d post-radiation to identify potential biomarkers. A panel of lung metabolites that are responsive to radiation and able to distinguish an efficacious treatment schedule of BIO 300 from a non-efficacious treatment schedule in terms of 180 d survival were identified. These metabolites represent potential biomarkers that could be further validated for use in drug development of BIO 300 and in the translation of dose from animal to human.

Reducing rectal injury in men receiving prostate cancer radiation therapy: current perspectives

PubMed Central

Serrano, Nicholas A; Kalman, Noah S; Anscher, Mitchell S

2017-01-01

Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring. We also examine the use of intensity-modulated radiation therapy and how this compares to older radiation therapy techniques that allow for further sparing of the rectum during a radiation therapy course. We then review the literature on endorectal balloons and the effects of their daily use throughout a radiation therapy course. Tissue spacers are now being investigated in greater detail; these devices are injected into the rectoprostatic fascia to physically increase the distance between the prostate and the anterior rectal wall. Last, we review the use of systemic drugs, specifically statin medications and antihypertensives, as well as their impact on rectal toxicity. PMID:28814898

THE RELATION OF RADIATION INJURY TO NUTRITION IN MICE SUBMITTED TO WHOLE- BODY LD$sub 50$ X-RAY IRRADIATION

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

Hata, T.

1960-01-01

The relation of radiation injury to the qualitative and quantitative changes of nutrition was studied in mice. From the qualitative standpoint of nutrition, the high protein, high casein, and butter diet showed a degree of radiation protection in the changes of the peripheral blood, changes of body weight, and survival rate. The carbohydrate diet showed some effect in radiation protection and recovery. Quantitatively a low caloric diet was conducive to radiation injury and the high caloric diet showed protection and recovery effects in changes of the peripheral blood and body weight which is proportional to the number of calories. Themore » decrease of caloric intake after irradiation showed an undesirable effect on recovery. (Absts. Japan. Med., 1: No. 7, 1960.)« less

Injuries Associated with Specific Motor Vehicle Hazards: Radiators, Batteries, Power Windows, and Power Roofs

DOT National Transportation Integrated Search

1997-07-01

This report provides estimates of the numbers of persons injured as a result of : hazards involving four specific motor vehicle components: radiators, batteries, : power windows, and power roofs. The injury estimates are based upon data from : the Co...

Delayed evaluation of combat-related penetrating neck trauma.

PubMed

Fox, Charles J; Gillespie, David L; Weber, Michael A; Cox, Mitchell W; Hawksworth, Jason S; Cryer, Chad M; Rich, Norman M; O'Donnell, Sean D

2006-07-01

The approach to penetrating trauma of the head and neck has undergone significant evolution and offers unique challenges during wartime. Military munitions produce complex injury patterns that challenge conventional diagnosis and management. Mass casualties may not allow for routine exploration of all stable cervical blast injuries. The objective of this study was to review the delayed evaluation of combat-related penetrating neck trauma in patients after evacuation to the United States. From February 2003 through April 2005, a series of patients with military-associated penetrating cervical trauma were evacuated to a single institution, prospectively entered into a database, and retrospectively reviewed. Suspected vascular injury from penetrating neck trauma occurred in 63 patients. Injuries were to zone II in 33%, zone III in 33%, and zone I in 11%. The remaining injuries involved multiple zones, including the lower face or posterior neck. Explosive devices wounded 50 patients (79%), 13 (21%) had high-velocity gunshot wounds, and 19 (30%) had associated intracranial or cervical spine injury. Of the 39 patients (62%) who underwent emergent neck exploration in Iraq or Afghanistan, 21 had 24 injuries requiring ligation (18), vein interposition or primary repair (4), polytetrafluoroethylene (PTFE) graft interposition (1), or patch angioplasty (1). Injuries occurred to the carotid, vertebral, or innominate arteries, or the jugular vein. After evacuation to the United States, all patients underwent radiologic evaluation of the head and neck vasculature. Computed tomography angiography was performed in 45 patients (71%), including six zone II injuries without prior exploration. Forty (63%) underwent diagnostic arteriography that detected pseudoaneurysms (5) or occlusions (8) of the carotid and vertebral arteries. No occult venous injuries were noted. Delayed evaluation resulted in the detection of 12 additional occult injuries and one graft thrombosis in 11 patients

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

Pine polyphenols from Pinus koraiensis prevent injuries induced by gamma radiation in mice

PubMed Central

Li, Hui; Xu, Yier; Sun, Guicai

2016-01-01

Pine polyphenols (PPs) are bioactive dietary constituents that enhance health and help prevent diseases through antioxidants. Antioxidants reduce the level of oxidative damages caused by ionizing radiation (IR). The main purpose of this paper is to study the protective effect of PPs on peripheral blood, liver and spleen injuries in mice induced by IR. ICR (Institute of Cancer Research) male mice were administered orally with PPs (200 mg/kg b.wt.) once daily for 14 consecutive days prior to 7 Gy γ-radiations. PPs showed strong antioxidant activities. PPs significantly increased white blood cells, red blood cells and platelets counts. PPs also significantly reduced lipid peroxidation and increased the activities of superoxide dismutase, catalase and glutathione peroxidases, and the level of glutathione. PPs reduced the spleen morphologic injury. In addition, PPs inhibited mitochondria-dependent apoptosis pathways in splenocytes induced by IR. These results indicate that PPs are radioprotective promising reagents. PMID:27069807

Management of genitourinary injuries in patients with pelvic fractures.

PubMed Central

Weems, W L

1979-01-01

Associated injuries frequently occur in patients who sustain fractures of the pelvis. Hemorrhage from intrapelvic vessels, rupture of the urinary bladder and avulsion of the membranous urethra in males are among the integral risks in this trauma. Non-operative methods of managing hemorrhage have gained favor in recent experience. The case records of 282 male patients with pelvic fractures were reviewed to evaluate experience with lower genitourinary injuries. Early recognition is important in bladder injuries, and surgical repair is advised, except in selected patients who may be managed by catheter drainage alone. Delayed complications of bladder injury are rare. Membranous urethral injuries entail a high risk of chronic stricture disease and sexual impotence. The rationale of early repair versus delayed repair of these injuries is discussed. The results in this series show advantage for delayed repair. Images Fig. 2. Fig. 3. PMID:453943

Integrative Metabolic Signatures for Hepatic Radiation Injury

PubMed Central

Su, Gang; Meng, Fan; Liu, Laibin; Mohney, Robert; Kulkarni, Shilpa; Guha, Chandan

2015-01-01

Background Radiation-induced liver disease (RILD) is a dose-limiting factor in curative radiation therapy (RT) for liver cancers, making early detection of radiation-associated liver injury absolutely essential for medical intervention. A metabolomic approach was used to determine metabolic signatures that could serve as biomarkers for early detection of RILD in mice. Methods Anesthetized C57BL/6 mice received 0, 10 or 50 Gy Whole Liver Irradiation (WLI) and were contrasted to mice, which received 10 Gy whole body irradiation (WBI). Liver and plasma samples were collected at 24 hours after irradiation. The samples were processed using Gas Chromatography/Mass Spectrometry and Liquid Chromatography/Mass Spectrometry. Results Twenty four hours after WLI, 407 metabolites were detected in liver samples while 347 metabolites were detected in plasma. Plasma metabolites associated with 50 Gy WLI included several amino acids, purine and pyrimidine metabolites, microbial metabolites, and most prominently bradykinin and 3-indoxyl-sulfate. Liver metabolites associated with 50 Gy WLI included pentose phosphate, purine, and pyrimidine metabolites in liver. Plasma biomarkers in common between WLI and WBI were enriched in microbial metabolites such as 3 indoxyl sulfate, indole-3-lactic acid, phenyllactic acid, pipecolic acid, hippuric acid, and markers of DNA damage such as 2-deoxyuridine. Metabolites associated with tryptophan and indoles may reflect radiation-induced gut microbiome effects. Predominant liver biomarkers in common between WBI and WLI were amino acids, sugars, TCA metabolites (fumarate), fatty acids (lineolate, n-hexadecanoic acid) and DNA damage markers (uridine). Conclusions We identified a set of metabolomic markers that may prove useful as plasma biomarkers of RILD and WBI. Pathway analysis also suggested that the unique metabolic changes observed after liver irradiation was an integrative response of the intestine, liver and kidney. PMID:26046990

Radiation exposure prior to traumatic brain injury induces responses that differ as a function of animal age

PubMed Central

2014-01-01

Purpose: Uncontrolled radiation exposure due to radiological terrorism, industrial accidents or military circumstances is a continuing threat for the civilian population. Age plays a major role in the susceptibility to radiation; younger children are at higher risk of developing cognitive deterioration when compared to adults. Our objective was to determine if an exposure to radiation affected the vulnerability of the juvenile hippocampus to a subsequent moderate traumatic injury. Materials and methods: Three-week-old (juvenile) and eight-week-old young adult C57BL/J6 male mice received whole body cesium-137 (137Cs) irradiation with 4 gray (Gy). One month later, unilateral traumatic brain injury was induced using a controlled cortical impact system. Two months post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Morris water-maze. After cognitive testing, animals were euthanized and their brains frozen for immunohistochemical assessment of activated microglia and neurogenesis in the hippocampal dentate gyrus. Results: All animals were able to learn the water maze task; however, treatment effects were seen when spatial memory retention was assessed. Animals that received irradiation as juveniles followed by a moderate traumatic brain injury one month later did not show spatial memory retention, i.e., were cognitively impaired. In contrast, all groups of animals that were treated as adults showed spatial memory retention in the probe trials. Conclusion: Although the mechanisms involved are not clear, our results suggest that irradiation enhanced a young animal's vulnerability to develop cognitive injury following a subsequent traumatic injury. PMID:24164494

The protein PprI provides protection against radiation injury in human and mouse cells

PubMed Central

Shi, Yi; Wu, Wei; Qiao, Huiping; Yue, Ling; Ren, Lili; Zhang, Shuyu; Yang, Wei; Yang, Zhanshan

2016-01-01

Severe acute radiation injuries are both very lethal and exceptionally difficult to treat. Though the radioresistant bacterium D. radiodurans was first characterized in 1956, genes and proteins key to its radioprotection have not yet to be applied in radiation injury therapy for humans. In this work, we express the D. radiodurans protein PprI in Pichia pastoris yeast cells transfected with the designed vector plasmid pHBM905A-pprI. We then treat human umbilical endothelial vein cells and BALB/c mouse cells with the yeast-derived PprI and elucidate the radioprotective effects the protein provides upon gamma irradiation. We see that PprI significantly increases the survival rate, antioxidant viability, and DNA-repair capacity in irradiated cells and decreases concomitant apoptosis rates and counts of damage-indicative γH2AX foci. Furthermore, we find that PprI reduces mortality and enhances bone marrow cell clone formation and white blood cell and platelet counts in irradiated mice. PprI also seems to alleviate pathological injuries to multiple organs and improve antioxidant viability in some tissues. Our results thus suggest that PprI has crucial radioprotective effects on irradiated human and mouse cells. PMID:27222438

Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

PubMed

Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

2016-05-27

Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury.

Dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells of mice

PubMed Central

Luo, Lan; Yan, Chen; Urata, Yoshishige; Hasan, Al Shaimaa; Goto, Shinji; Guo, Chang-Ying; Zhang, Shouhua; Li, Tao-Sheng

2017-01-01

We evaluated the dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells (CDCs), a mixed cell population grown from heart tissues. Adult C57BL/6 mice were exposed to 0, 10, 50 and 250 mGy γ-rays for 7 days and atrial tissues were collected for experiments 24 hours after last exposure. The number of CDCs was significantly decreased by daily exposure to over 250 mGy. Interestingly, daily exposure to over 50 mGy significantly decreased the c-kit expression and telomerase activity, increased 53BP1 foci in the nuclei of CDCs. However, CD90 expression and growth factors production in CDCs were not significantly changed even after daily exposure to 250 mGy. We further evaluated the reversibility of radiation-induced injury in CDCs at 1 week and 3 weeks after a single exposure to 3 Gy γ-rays. The number and growth factors production of CDCs were soon recovered at 1 week. However, the increased expression of CD90 were retained at 1 week, but recovered at 3 weeks. Moreover, the decreased expression of c-kit, impaired telomerase activity, and increased 53BP1 foci were poorly recovered even at 3 weeks. These data may help us to find the most sensitive and reliable bio-parameter(s) for evaluating radiation-induced injury in CDCs. PMID:28098222

Delayed Consequences of Acute Kidney Injury

PubMed Central

Parr, Sharidan K; Siew, Edward D

2016-01-01

Acute kidney injury (AKI) is an increasingly common complication of hospitalization and acute illness. Experimental data indicate that AKI may cause permanent kidney damage through tubulointerstitial fibrosis and progressive nephron loss, while also lowering the threshold for subsequent injury. Furthermore, preclinical data suggest that AKI may also cause distant organ dysfunction. The extension of these findings to human studies suggests long-term consequences of AKI including, but not limited to recurrent AKI, progressive kidney disease, elevated blood pressure, cardiovascular events, and mortality. As the number of AKI survivors increases, the need to better understand the mechanisms driving these processes becomes paramount. Optimizing care for AKI survivors will require understanding the short- and long-term risks associated with AKI, identifying patients at highest risk for poor outcomes, and testing interventions that target modifiable risk factors. In this review, we examine the literature describing the association between AKI and long-term outcomes and highlight opportunities for further research and potential intervention. PMID:27113695

Scenario of a dirty bomb in an urban environment and acute management of radiation poisoning and injuries.

PubMed

Chin, F K C

2007-10-01

In the new security environment, there is a clear and present danger of terrorists using non-conventional weapons to inflict maximum psychological and economic damage on their targets. This article examines two scenarios of radiation contamination and injury, one accidental in nature leading to environmental contamination, and another of deliberate intent resulting in injury and death. This article also discusses the management of injury from radiological dispersion devices or dirty bombs, with emphasis on the immediate aftermath as well as strategy recommendations.

Trauma patients who present in a delayed fashion: a unique and challenging population.

PubMed

Kao, Mary J; Nunez, Hector; Monaghan, Sean F; Heffernan, Daithi S; Adams, Charles A; Lueckel, Stephanie N; Stephen, Andrew H

2017-02-01

A proportion of trauma patients present for evaluation in a delayed fashion after injury, likely due to a variety of medical and nonmedical reasons. There has been little investigation into the characteristics and outcomes of trauma patients who present delayed. We hypothesize that trauma patients who present in a delayed fashion are a unique population at risk of increased trauma-related complications. This was a retrospective review from 2010-2015 at a Level I trauma center. Patients were termed delayed if they presented >24 hours after injury. Patients admitted within 24 hours of their injury were the comparison group. Charts were reviewed for demographics, mechanism, comorbidities, complications and outcomes. A subgroup analysis was done on patients who suffered falls. During the 5-y period, 11,705 patients were admitted. A total of 588 patients (5%) presented >24 h after their injury. Patients in the delayed group were older (65 versus 55 y, P < 0.001) and more likely to have psychiatric comorbidities (33% vs. 24%, P = 0.0001) than the control group. They were also more likely to suffer substance withdrawal (8.9% vs. 4.1%, P < 0.001) but had toxicology testing for drugs and alcohol done at significantly lower rates. Patients that presented delayed after falls were similar in age and injury severity score (ISS) but more likely to suffer substance withdrawal when compared to those with falls that presented within 24 hours. Patients with falls that presented delayed had toxicology testing at significantly lower rates than the comparison group. Trauma patients that present to the hospital in a delayed fashion have unique characteristics and are more likely to suffer negative outcomes including substance withdrawal. Future goals will include exploring strategies for early intervention, such as automatic withdrawal monitoring and social work referral for all patients who present in a delayed fashion. Copyright © 2016 Elsevier Inc. All rights reserved.

Opportunity for Collaboration Between Radiation Injury Treatment Network Centers and Medical Toxicology Specialists.

PubMed

Davlantes, Elizabeth; Shartar, Samuel; Venero, Jennifer; Steck, Alaina; Langston, Amelia; Kazzi, Ziad N

2017-08-01

The Radiation Injury Treatment Network (RITN) comprises >50 centers across the United States that are poised to care for victims of a radiation emergency. The network is organized around bone marrow transplant centers because these facilities excel in both radiation medicine and the care of patients with severe bone marrow depression. A radiation emergency may cause not only irradiation from an external source but also internal contamination with radioactive material. Because medical toxicologists are trained in radiation injury management and have expertise in the management of internal contamination, RITN centers may benefit from partnerships with medical toxicology resources, which may be located at academic medical centers, hospital inpatient clinical services, outpatient clinics, or poison control centers. We determined the locations of existing RITN centers and assessed their proximity to various medical toxicology resources, including medical toxicology fellowship programs, inpatient toxicology services, outpatient toxicology clinics, and poison control centers. Data were derived from publicly available Internet sources in March 2015. The majority of RITN centers do not have a medical toxicology fellowship, an inpatient toxicology service, or an outpatient toxicology clinic within the same institution. Fifty-seven percent of RITN centers have at least one of these resources located in the same city, however, and 73% of centers have at least one of these resources or a poison control center within the same city. Ninety-five percent of RITN centers have at least one medical toxicology resource within the state. Most RITN centers are located in the same city as at least one medical toxicology resource. Establishing relationships between RITN centers and medical toxicologists needs to be explored further.

Ascending aortic injuries following blunt trauma.

PubMed

Sun, Xiumei; Hong, Jenny; Lowery, Robert; Goldstein, Steven; Wang, Zuyue; Lindsay, Joseph; Hill, Peter C; Corso, Paul J

2013-11-01

The diagnosis and the management of traumatic thoracic aortic injuries have undergone significant changes due to new technology and improved prehospital care. Most of the discussions have focused on descending aortic injuries. In this review, we discuss the recent management of ascending aortic injuries. We found 5 cohort studies on traumatic aortic injuries and 11 case reports describing ascending aortic injuries between 1998 to the present through Medline research. Among case reports, 78.9% of cases were caused by motor vehicle accidents (MVA). 42.1% of patients underwent emergent open repair and the operative mortality was 12.5%. 36.8% underwent delayed repair. Associated injuries occurred in 84.2% of patients. Aortic valve injury was concurrent in 26.3% of patients. The incidence of ascending aortic injury ranged 1.9-20% in cohort studies. Traumatic injuries to the ascending aorta are relatively uncommon among survivors following blunt trauma. Aortography has been replaced by computed tomography and echocardiography as a diagnostic tool. Open repair, either emergent or delayed, remains the treatment of choice. © 2013 Wiley Periodicals, Inc.

Urological injuries following trauma.

PubMed

Bent, C; Iyngkaran, T; Power, N; Matson, M; Hajdinjak, T; Buchholz, N; Fotheringham, T

2008-12-01

Blunt renal trauma is the third most common injury in abdominal trauma following splenic and hepatic injuries, respectively. In the majority, such injuries are associated with other abdominal organ injuries. As urological injuries are not usually life-threatening, and clinical signs and symptoms are non-specific, diagnosis is often delayed. We present a practical approach to the diagnosis and management of these injuries based on our experience in a busy inner city trauma hospital with a review of the current evidence-based practice. Diagnostic imaging signs are illustrated.

Imaging of Sports-Related Hip and Groin Injuries

PubMed Central

Lischuk, Andrew W.; Dorantes, Thomas M.; Wong, William; Haims, Andrew H.

2010-01-01

A normally functioning hip joint is imperative for athletes who use their lower extremities with running, jumping, or kicking activities. Sports-related injuries of the hip and groin are far less frequent than injuries to the more distal aspect of the extremity, accounting for less than 10% of lower extremity injuries. Despite the lower incidence, hip and groin injuries can lead to significant clinical and diagnostic challenges related to the complex anatomy and biomechanical considerations of this region. Loads up to 8 times normal body weight have been documented in the joint in common daily activities, such as jogging, with significantly greater force expected during competitive athletics. Additionally, treatment for hip and groin injuries can obviate the participation of medical and surgical specialties, with a multidisciplinary approach frequently required. Delay in diagnosis and triage of these injuries may cause loss of time from competition and, potentially, early onset of degenerative changes. Magnetic resonance imaging (MRI) of the hip has proven to be the gold standard for the diagnosis of sports-related hip and groin injuries in the setting of negative radiographs. With its exquisite soft tissue contrast, multiplanar capabilities, and lack of ionizing radiation, MRI is unmatched in the noninvasive diagnosis of intra-articular and extra-articular pathology, as well as intraosseous processes. This review focuses on MRI of common athletic injuries of the hip and groin, including acetabular labral tears, femoral acetabular impingement syndrome, muscle injuries around the hip and groin (including athletic pubalgia), and athletic osseous injuries. PMID:23015946

Imaging of sports-related hip and groin injuries.

PubMed

Lischuk, Andrew W; Dorantes, Thomas M; Wong, William; Haims, Andrew H

2010-05-01

A normally functioning hip joint is imperative for athletes who use their lower extremities with running, jumping, or kicking activities. Sports-related injuries of the hip and groin are far less frequent than injuries to the more distal aspect of the extremity, accounting for less than 10% of lower extremity injuries. Despite the lower incidence, hip and groin injuries can lead to significant clinical and diagnostic challenges related to the complex anatomy and biomechanical considerations of this region. Loads up to 8 times normal body weight have been documented in the joint in common daily activities, such as jogging, with significantly greater force expected during competitive athletics. Additionally, treatment for hip and groin injuries can obviate the participation of medical and surgical specialties, with a multidisciplinary approach frequently required. Delay in diagnosis and triage of these injuries may cause loss of time from competition and, potentially, early onset of degenerative changes. Magnetic resonance imaging (MRI) of the hip has proven to be the gold standard for the diagnosis of sports-related hip and groin injuries in the setting of negative radiographs. With its exquisite soft tissue contrast, multiplanar capabilities, and lack of ionizing radiation, MRI is unmatched in the noninvasive diagnosis of intra-articular and extra-articular pathology, as well as intraosseous processes. This review focuses on MRI of common athletic injuries of the hip and groin, including acetabular labral tears, femoral acetabular impingement syndrome, muscle injuries around the hip and groin (including athletic pubalgia), and athletic osseous injuries.

Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

PubMed Central

Azzam, Edouard I.; Jay-Gerin, Jean-Paul; Pain, Debkumar

2013-01-01

Cellular exposure to ionizing radiation leads to oxidizing events that alter atomic structure through direct interactions of radiation with target macromolecules or via products of water radiolysis. Further, the oxidative damage may spread from the targeted to neighboring, non-targeted bystander cells through redox-modulated intercellular communication mechanisms. To cope with the induced stress and the changes in the redox environment, organisms elicit transient responses at the molecular, cellular and tissue levels to counteract toxic effects of radiation. Metabolic pathways are induced during and shortly after the exposure. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Physiological levels of reactive oxygen and nitrogen species play critical roles in many cellular functions. In irradiated cells, levels of these reactive species may be increased due to perturbations in oxidative metabolism and chronic inflammatory responses, thereby contributing to the long-term effects of exposure to ionizing radiation on genomic stability. Here, in addition to immediate biological effects of water radiolysis on DNA damage, we also discuss the role of mitochondria in the delayed outcomes of ionization radiation. Defects in mitochondrial functions lead to accelerated aging and numerous pathological conditions. Different types of radiation vary in their linear energy transfer (LET) properties, and we discuss their effects on various aspects of mitochondrial physiology. These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes. PMID:22182453

Thermal effusivity: a promising imaging biomarker to predict radiation-induced skin injuries.

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

Chu, J. C. H.; Templeton, A.; Yao, R.

An effective screening technology is needed to triage individuals at the time of radiation incidents involving a large population. Three-dimensional thermal tomography is a relatively new development in active thermal imaging technology that produces cross-sectional images based on the subject's ability to transfer heat thermal effusivity at the voxel level. This noninvasive imaging modality has been used successfully in nondestructive examination of complex materials; also it has been shown to predict the severity of radiation-induced skin injuries several days before the manifestation of severe moist desquamations or blister formation symptoms in mice at 40 Gy. If these results are confirmedmore » at lower dose levels in human subjects, a thermal tomography imaging device may be an ideal screening tool in radiation emergencies. This imaging method is non-invasive, relatively simple, easily adaptable for field use, and when properly deployed, it will enhance public emergency preparedness for incidents involving unexpected radiation exposure.« less

Pathogenetic validation of the use of biological protective agents and early treatment in cases of radiation injury simulating radiation effects under space flight conditions

NASA Technical Reports Server (NTRS)

Rogozkin, V. D.; Varteres, V.; Sabo, L.; Groza, N.; Nikolov, I.

1974-01-01

In considering a radiation safety system for space flights, the various measures to protect man against radiation include drug prophylaxis. At the present time a great deal of experimental material has been accumulated on the prevention and treatment of radiation injuries. Antiradiation effectiveness has been established for sulfur- and nitrogen-containing substances, auxins, cyanides, polynucleotides, mucopolysaccharides, lipopolysaccharides, aminosaccharides, synthetic polymers, vitamins, hormones, amino acids and other compounds which can be divided into two basic groups - biological and chemical protective agents.

{sup 99m}Tc DTPA aerosol clearances in the assessment of radiation injury top the lung

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

Halkar, R.K.; Raghab, A.; Higazi, E.

1994-05-01

In a prospective study, 36 patients with inoperable lung Ca. (sq. cells-24, adeno-5, largecell-2, unknown-5) underwent pre and post radiation {sup 99m}Tc DTPA aerosol clearance studies. The aim was to evaluate the value of aerosol clearance in the prediction of radiation injury to the regions other than the radiation field. Aerosol study was done using a commercially available nebulizer, dynamic images were obtained (30 sec/frame) in the posterior projection for a duration of 45 min. ROIs were drawn on upper, mid and lower zones on either lung, and time activity curves were generated. Using a linear fit, clearance half timemore » (t{sub 1/2}) was calculated, for all six curves. The difference between pre and post radiation (t{sub 1/2}) was compared to the clinical follow up of each patient and a difference of more than 15 minutes was considered positive. Of the 36 patients 12 had a t{sub 1/2} difference of more than 15 minutes. Of these 5 patients had radiation pulmonlitis and the remaining 7 had respiratory failure due to infection and uremia. 24 patients had a t{sub 1/2} difference of less than 15 minutes and their clinical follow-up did not reveal any evidence of pulmonary radiation injury during this period. The results indicate that the clearance of Tc-99m DTPA aerosols is effective for excluding radiation pulmonlitis.« less

Cumulative effective radiation dose received by blunt trauma patients arriving to a military level I trauma center from point of injury and interhospital transfers.

PubMed

Van Arnem, Kerri A; Supinski, David P; Tucker, Jonathan E; Varney, Shawn

2016-12-01

Trauma patients sustaining blunt injuries are exposed to multiple radiologic studies. Evidence indicates that the risk of cancer from exposure to ionizing radiation rises in direct proportion to the cumulative effective dose (CED) received. The purpose of this study is to quantify the amount of ionizing radiation accumulated when arriving directly from point of injury to San Antonio Military Medical Center (SAMMC), a level I trauma center, compared with those transferred from other facilities. A retrospective record review was conducted from 1st January 2010 through 31st December 2012. The SAMMC trauma registry, electronic medical records, and the digital radiology imaging system were searched for possible candidates. The medical records were then analyzed for sex, age, mechanism of injury, received directly from point of injury (direct group), transfer from another medical facility (transfer group), computed tomographic scans received, dose-length product, CED of radiation, and injury severity score. A diagnostic imaging physicist then calculated the estimated CED each subject received based on the dose-length product of each computed tomographic scan. A total of 300 patients were analyzed, with 150 patients in the direct group and 150 patients in the transfer group. Both groups were similar in age and sex. Patients in the transfer group received a significantly greater CED of radiation compared with the direct group (mean, 37.6 mSv vs 28 mSv; P=.001). The radiation received in the direct group correlates with a lifetime attributable risk (LAR) of 1 in 357 compared with the transfer group with an increase in LAR to 1 in 266. Patients transferred to our facility received a 34% increase in ionizing radiation compared with patients brought directly from the injury scene. This increased dose of ionizing radiation contributes to the LAR of cancer and needs to be considered before repeating imaging studies. III. Published by Elsevier Inc.

Radiation-induced inflammatory markers of brain injury are modulated by PPARdelta activation in vitro and in vivo

NASA Astrophysics Data System (ADS)

Schnegg, Caroline Isabel

As a result of improvements in cancer therapy and health care, the population of long-term cancer survivors is growing. For these approximately 12 million long-term cancer survivors, brain metastases are a significant risk. Fractionated partial or whole-brain irradiation (fWBI) is often required to treat both primary and metastatic brain cancer. Radiation-induced normal tissue injury, including progressive cognitive impairment, however, can significantly affect the well-being of the approximately 200,000 patients who receive these treatments each year. Recent reports indicate that radiation-induced brain injury is associated with chronic inflammatory and oxidative stress responses, as well as increased microglial activation in the brain. Anti-inflammatory drugs may, therefore, be a beneficial therapy to mitigate radiation-induced brain injury. We hypothesized that activation of peroxisomal proliferator activated receptor delta (PPARō) would prevent or ameliorate radiation-induced brain injury, including cognitive impairment, in part, by alleviating inflammatory responses in microglia. For our in vitro studies, we hypothesized that PPARō activation would prevent the radiation-induced inflammatory response in microglia following irradiation. Incubating BV-2 murine microglial cells with the (PPAR)ō agonist, L-165041, prevented the radiation-induced increase in: i) intracellular ROS generation, ii) Cox-2 and MCP-1 expression, and iii) IL-1β and TNF-α message levels. This occured, in part, through PPARō-mediated modulation of stress activated kinases and proinflammatory transcription factors. PPARō inhibited NF-κB via transrepression by physically interacting with the p65 subunit, and prevented activation of the PKCα/MEK1/2/ERK1/2/AP-1 pathway by inhibiting the radiation-induced increase in intracellular ROS generation. These data support the hypothesis that PPARō activation can modulate the radiation-induced oxidative stress and inflammatory

Treatment of a delayed zipper injury.

PubMed

Mydlo, J H

2000-01-01

Penile zipper injuries have been reported occurring usually in the pediatric population, and occasionally in adults. Usually, the zipper can be dislodged with mineral oil or by breaking the median bar. When these attempts fail, a small elliptical incision may be used to remove the zipper and any devitalized tissue. Copyright 2000 S. Karger AG, Basel

Distinction Between Recurrent Glioma and Radiation Injury Using Magnetic Resonance Spectroscopy in Combination With Diffusion-Weighted Imaging

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

Zeng, Q.-S.; Li, C.-F.; Liu Hong

2007-05-01

Purpose: The aim of this study was to explore the diagnostic effectiveness of magnetic resonance (MR) spectroscopy with diffusion-weighted imaging on the evaluation of the recurrent contrast-enhancing areas at the site of treated gliomas. Methods and Materials: In 55 patients who had new contrast-enhancing lesions in the vicinity of the previously resected and irradiated high-grade gliomas, two-dimensional MR spectroscopy and diffusion-weighted imaging were performed. Spectral data for N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipid (Lip), and lactate (Lac) were analyzed in conjunction with the apparent diffusion coefficient (ADC) in all patients. Diagnosis of these lesions was assigned by means ofmore » follow-up or histopathology. Results: The Cho/NAA and Cho/Cr ratios were significantly higher in recurrent tumor than in regions of radiation injury (p < 0.01). The ADC value and ADC ratios (ADC of contrast-enhancing lesion to matching structure in the contralateral hemisphere) were significantly higher in radiation injury regions than in recurrent tumor (p < 0.01). With MR spectroscopic data, two variables (Cho/NAA and Cho/Cr ratios) were shown to differentiate recurrent glioma from radiation injury, and 85.5% of total subjects were correctly classified into groups. However, with discriminant analysis of MR spectroscopy imaging plus diffusion-weighted imaging, three variables (Cho/NAA, Cho/Cr, and ADC ratio) were identified and 96.4% of total subjects were correctly classified. There was a significant difference between the diagnostic accuracy of the two discriminant analyses (Chi-square = 3.96, p = 0.046). Conclusion: Using discriminant analysis, this study found that MR spectroscopy in combination with ADC ratio, rather than ADC value, can improve the ability to differentiate recurrent glioma and radiation injury.« less

Anterior cruciate ligament injury: A persistently difficult diagnosis.

PubMed

Parwaiz, Hammad; Teo, Alex Q A; Servant, Christopher

2016-01-01

Historically anterior cruciate ligament (ACL) injuries have been diagnosed poorly. A paper published in Injury in 1996 showed that less than 10% of patients with an ACL injury had the diagnosis made by the first physician to see them and that the average delay from first presentation to diagnosis was 21 months. The aim of our study was to investigate whether an improvement has been made over the last two decades in diagnosing ACL injuries. We identified 160 patients who had an ACL reconstruction performed by a single surgeon between October 2004 and December 2011 and for whom a complete data set was available. Data was extracted retrospectively from the hospital notes and a dedicated patient database. We performed a sub-group analysis comparing patients seen prior to the introduction of an acute knee injury clinic in April 2007 and patients seen after the introduction of the clinic. 75.1% (120/160) of patients presented first to an emergency department (ED) or to their general practitioner (GP), but only 14.4% (23/160) were diagnosed on initial presentation. The median number of healthcare professionals a patient saw prior to a diagnosis of ACL injury was 3. The median delay from injury to presentation was 0 weeks (range 0-885), injury to diagnosis 13 weeks (0-926), presentation to diagnosis 10 weeks (0-924), presentation to a specialist knee clinic 24 weeks (0-1006), and specialist knee clinic to surgery 13 weeks (0-102). The median total time from injury to surgery was 42 weeks (0-1047). Following the implementation of an acute knee injury clinic in 2007, the median delay from presentation to surgery dropped from 59 weeks to 36 weeks (p = 0.050) and there was a significant decrease in the median delay from specialist knee clinic to surgery from 23 to 11 weeks (p=0.002). Over the past two decades there appears to have been little improvement in the early diagnosis of ACL injuries, with only 14.4% of patients being diagnosed correctly at initial presentation. We

Glycyrrhetinic acid alleviates radiation-induced lung injury in mice

PubMed Central

Chen, Jinmei; Zhang, Weijian; Zhang, Lurong; Zhang, Jiemin; Chen, Xiuying; Yang, Meichun; Chen, Ting; Hong, Jinsheng

2017-01-01

Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-β1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-β1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-β1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-β1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-β1/Smads signaling pathway. PMID:27672101

[Studies on chemical protectors against radiation. XXXII. Protective effects of methanol extracts of various Taiwan crude drugs on radiation injuries].

PubMed

Wang, C M; Ohta, S; Shinoda, M

1990-11-01

This study is to investigate radioprotective effects of 23 Taiwan crude drugs on X-ray induced bone marrow death and skin injury in mice. Each methanol extract of these Taiwan crude drugs was injected intraperitoneally into ICR male mice at 6 weeks of age before irradiation. Mice were whole-body irradiated with a soft X-ray generator. Radiation factors of the two screening tests used were as follows: 70 kVp, 10 mA, 10 mm acrylate filter, 70R/min, 2100R for survival test, and 30 kVp, 10 mA, 190R/min, 1100R for protective test on skin injury. As a result of these studies, the survival effect was recognized in Solani Incani Herba and Orthosiphi Aristati Herba. On the other hand, Mimosae Herba, Canarii Radix, Bombacis Radix, Arecae Fructus, Hedyotidis Diffusae Herba and Cynomorii Caulis were shown to have significant protective potency on skin injury.

Evaluation of the preventive effect of dexpanthenol in radiation injury by lung perfusion scintigraphy: a preclinical experimental model of radiation injury.

PubMed

Koç, Zehra P; İn, Erdal; Karslioğlu, İhsan; Üçer, Özlem; Canpolat, Sinan

2015-12-01

The aim of this study was to show the preventative effects of dexpanthenol in radiation injuries caused by radiotherapy (RT) through the use of lung perfusion scintigraphy in the pre-RT and post-RT periods. Six male New Zealand rabbits (5-6 months of age and ∼2.5-3 kg in weight) were the used in this study. The animals were subjected to Tc-macroaggregated albumin lung perfusion scintigraphy in the pre-RT and post-RT (i.e. 2 weeks after treatment) periods. The scintigraphies were performed with the same dose by the same staff and the methodology used the same acquisition parameters. The rabbits were divided into two groups: group I (administered RT only) and group II (also administered intramuscular 500 mg dexpanthenol injections for 14 consecutive days after RT). Quantification was performed to compare the groups and the quantification variables were compared using a paired samples t-test, with P value less than 0.05 considered to be statistically significant. Histopathological analysis was also carried out. The post-RT scintigraphies indicated a decrease in the counts in both lungs, suggesting early post-RT injury. The difference between the counts obtained from both lungs in groups I and II was significantly different and favoured group II. Histopathological results confirmed the scintigraphy results. It is possible to estimate post-RT changes in the early period (in contrast to previous data) by lung perfusion scintigraphy. Dexpanthenol may also reduce the effects of RT to a degree. Although this is the first study to report the preventive effects of dexpanthenol on RT injuries, further studies are warranted in this area.

Transforming growth factor alpha is a critical mediator of radiation lung injury.

PubMed

Chung, Eun Joo; Hudak, Kathryn; Horton, Jason A; White, Ayla; Scroggins, Bradley T; Vaswani, Shiva; Citrin, Deborah

2014-09-01

Radiation fibrosis of the lung is a late toxicity of thoracic irradiation. Epidermal growth factor (EGF) signaling has previously been implicated in radiation lung injury. We hypothesized that TGF-α, an EGF receptor ligand, plays a key role in radiation-induced fibrosis in lung. Mice deficient in transforming growth factor (TGF-α(-/-)) and control C57Bl/6J (C57-WT) mice were exposed to thoracic irradiation in 5 daily fractions of 6 Gy. Cohorts of mice were followed for survival (n ≥ 5 per group) and tissue collection (n = 3 per strain and time point). Collagen accumulation in irradiated lungs was assessed by Masson's trichrome staining and analysis of hydroxyproline content. Cytokine levels in lung tissue were assessed with ELISA. The effects of TGF-α on pneumocyte and fibroblast proliferation and collagen production were analyzed in vitro. Lysyl oxidase (LOX) expression and activity were measured in vitro and in vivo. Irradiated C57-WT mice had a median survival of 24.4 weeks compared to 48.2 weeks for irradiated TGF-α(-/-) mice (P = 0.001). At 20 weeks after irradiation, hydroxyproline content was markedly increased in C57-WT mice exposed to radiation compared to TGF-α(-/-) mice exposed to radiation or unirradiated C57-WT mice (63.0, 30.5 and 37.6 μg/lung, respectively, P = 0.01). C57-WT mice exposed to radiation had dense foci of subpleural fibrosis at 20 weeks after exposure, whereas the lungs of irradiated TGF-α (-/-) mice were largely devoid of fibrotic foci. Lung tissue concentrations of IL-1β, IL-4, TNF-α, TGF-β and EGF at multiple time points after irradiation were similar in C57-WT and TGF-α(-/-) mice. TGF-α in lung tissue of C57-WT mice rose rapidly after irradiation and remained elevated through 20 weeks. TGF-α(-/-) mice had lower basal LOX expression than C57-WT mice. Both LOX expression and LOX activity were increased after irradiation in all mice but to a lesser degree in TGF-α(-/-) mice. Treatment of NIH-3T3 fibroblasts with TGF

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.

Expression of Angiotensin II and Aldosterone in Radiation-induced Lung Injury.

PubMed

Cao, Shuo; Wu, Rong

2012-12-01

Radiation-induced lung injury (RILI) is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILI was studied. Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-β1, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI.

The Urine Proteome as a Biomarker of Radiation Injury: Submitted to Proteomics- Clinical Applications Special Issue: "Renal and Urinary Proteomics (Thongboonkerd)"

PubMed

Sharma, Mukut; Halligan, Brian D; Wakim, Bassam T; Savin, Virginia J; Cohen, Eric P; Moulder, John E

2008-06-18

Terrorist attacks or nuclear accidents could expose large numbers of people to ionizing radiation, and early biomarkers of radiation injury would be critical for triage, treatment and follow-up of such individuals. However, no such biomarkers have yet been proven to exist. We tested the potential of high throughput proteomics to identify protein biomarkers of radiation injury after total body X-ray irradiation in a rat model. Subtle functional changes in the kidney are suggested by an increased glomerular permeability for macromolecules measured within 24 hours after TBI. Ultrastructural changes in glomerular podocytes include partial loss of the interdigitating organization of foot processes. Analysis of urine by LC-MS/MS and 2D-GE showed significant changes in the urine proteome within 24 hours after TBI. Tissue kallikrein 1-related peptidase, cysteine proteinase inhibitor cystatin C and oxidized histidine were found to be increased while a number of proteinase inhibitors including kallikrein-binding protein and albumin were found to be decreased post-irradiation. Thus, TBI causes immediately detectable changes in renal structure and function and in the urinary protein profile. This suggests that both systemic and renal changes are induced by radiation and it may be possible to identify a set of biomarkers unique to radiation injury.

Protective Effect of Lycium ruthenicum Murr. Against Radiation Injury in Mice

PubMed Central

Duan, Yabin; Chen, Fan; Yao, Xingchen; Zhu, Junbo; Wang, Cai; Zhang, Juanling; Li, Xiangyang

2015-01-01

The protective effect of Lycium ruthenicum Murr. against radiation injury was examined in mice. Kunming mice were randomly divided into a control group, model group, positive drug group and L. ruthenicum high dose (8 g/kg), L. ruthenicum middle dose (4 g/kg), L. ruthenicum low dose (2 g/kg) treatment groups, for which doses were administered the third day, seventh day and 14th day after irradiation. L. ruthenicum extract was administered orally to the mice in the three treatment groups and normal saline was administered orally to the mice in the control group and model group for 14 days. The positive group was treated with amifostine (WR-2721) at 30 min before irradiation. Except for the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body at one time. Body weight, hemogram, thymus and spleen index, DNA, caspase-3, caspase-6, and P53 contents were observed at the third day, seventh day, and 14th day after irradiation. L. ruthenicum could significantly increase the total red blood cell count, hemoglobin count and DNA contents (p < 0.05). The spleen index recovered significantly by the third day and 14th day after irradiation (p < 0.05). L. ruthenicum low dose group showed a significant reduction in caspase-3 and caspase-6 of serum in mice at the third day, seventh day, and 14th day after irradiation and L. ruthenicum middle dose group experienced a reduction in caspase-6 of serum in mice by the seventh day after irradiation. L. ruthenicum could decrease the expression of P53. The results showed that L. ruthenicum had protective effects against radiation injury in mice. PMID:26193298

Experimental evaluation of ileal patch in delayed primary repair of penetrating colon injuries: An animal study.

PubMed

Abbasi, Hamid Reza; Bolandparvaz, Shahram; Yarmohammadi, Hooman; Geramizadeh, Bita; Tanideh, Nader; Paydar, Shahram; Hosseini, Seyed Vahid

2006-10-01

Primary repair of traumatic colonic perforation is progressively gaining acceptance as the best method of management. However, when delayed, the risk of infection-related complications may increase. Here, we present a new method of repairing colon perforation in the presence of peritonitis. Acute colon injury was simulated in 22 German shepherd dogs. The dogs were randomly divided into two groups of 11 and after 24 hours they were operated on. The perforations were repaired by subserosal suture technique. In the first group (group A), ileal patch was used. In the other group (group B), the colon was closed by debridement and anastomosis. After 6 weeks, the repairs were assessed on the basis of survival, gross and histological assessments. Nine (82%) dogs in group A and six (56%) in group B survived. Ileal patch utilization significantly decreased the mortality rate (p < 0.05). The cause of death in two group A dogs and five group B dogs was peritonitis and intra-abdominal abscess formation. None of the surviving dogs showed evidence of anastomotic leakage or breakdown. Small bowel patch used in primary repair of colon injury in the presence of peritonitis may decrease the risk of postoperative infection-related complications and the mortality rate.

Intestinal injury mechanisms after blunt abdominal impact.

PubMed

Cripps, N P; Cooper, G J

1997-03-01

Intestinal injury is frequent after non-penetrating abdominal trauma, particularly after modern, high-energy transfer impacts. Under these circumstances, delay in the diagnosis of perforation is a major contributor to morbidity and mortality. This study establishes patterns of intestinal injury after blunt trauma by non-penetrating projectiles and examines relationships between injury distribution and abdominal wall motion. Projectile impacts of variable momentum were produced in 31 anaesthetised pigs to cause abdominal wall motion of varying magnitude and velocity. No small bowel injury was observed at initial impact velocity of less than 40 m/s despite gross abdominal compression. At higher velocity, injury to the small bowel was frequent, irrespective of the degree of abdominal compression (P = 0.00044). Large bowel injury was observed at all impact velocities and at all degrees of abdominal compression. This study confirms the potential for intestinal injury in high velocity, low momentum impacts which do not greatly compress the abdominal cavity and demonstrates apparent differences in injury mechanisms for the small bowel and colon. Familiarity with injury mechanisms may reduce delays in the diagnosis of intestinal perforation in both military and civilian situations.

Treatment of chronic radiation injury over the shoulder with a latissimus dorsi myocutaneous flap

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

Mendelson, B.C.; Masson, J.K.

1977-11-01

We report our experiences in treating chronic radiation injury about the shoulder, a complication of radiation after mastectomy. Left untreated, these can result in chronic infection and/or amputation. The coverage of a large shoulder area presents certain unique problems, which severely limit the usefulness of traditional procedures. We have found that the remarkable size and versatility of the latissimus dorsi myocutaneous flap enables one to use it with relative simplicity and safety. A further great advantage is that it brings new permanent blood supply into this ischemic area, thus favoring rapid healing and durable coverage.

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.

The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer.

PubMed

Son, Yeonghoon; Lee, Hae June; Rho, Jin Kyung; Chung, Soo Young; Lee, Chang Geun; Yang, Kwangmo; Kim, Sung Ho; Lee, Minyoung; Shin, In Sik; Kim, Joong Sun

2015-07-05

Silibinin has been known for its role in anti-cancer and radio-protective effect. Radiation therapy for treating lung cancer might lead to late-phase pulmonary inflammation and fibrosis. Thus, this study aimed to investigate the effects of silibinin in radiation-induced lung injury with a mouse model. In this study, we examined the ability of silibinin to mitigate lung injury in, and improve survival of, C57BL/6 mice given 13 Gy thoracic irradiation and silibinin treatments orally at 100 mg/kg/day for seven days after irradiation. In addition, Lewis lung cancer (LLC) cells were injected intravenously in C57BL/6 mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with lung radiation therapy at 13 Gy and with silibinin at a dose of 100 mg/day for seven days after irradiation. Silibinin was shown to increase mouse survival, to ameliorate radiation-induced hemorrhage, inflammation and fibrosis in lung tissue, to reduce the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and to reduce inflammatory cell infiltration in the respiratory tract. In LLC tumor injected mice, lung tissue from mice treated with both radiation and silibinin showed no differences compared to lung tissue from mice treated with radiation alone. Silibinin treatment mitigated the radiation-induced lung injury possibly by reducing inflammation and fibrosis, which might be related with the improved survival rate. Silibinin might be a useful agent for lung cancer patients as a non-toxic complementary approach to alleviate the side effects by thorax irradiation.

Mitigation of Radiation Injury by Selective Stimulation of the LPA2 Receptor

PubMed Central

Kiss, Gyöngyi N.; Lee, Sue-Chin; Fells, James; Liu, Jiangxiong; Valentine, William J.; Fujiwara, Yuko; Emmons-Thompson, Karin; Yates, Charles R.; Sümegi, Balázs; Tigyi, Gabor

2012-01-01

Due to its antiapoptotic action, derivatives of the lipid mediator lysophosphatidic acid (LPA) provide potential therapeutic utility in diseases associated with programmed cell death. Apoptosis is one of the major pathophysiological processes elicited by radiation injury to the organism. Consequently, therapeutic explorations applying compounds that mimic the antiapoptotic action of LPA have begun. Here we present a brief account of our decade-long drug discovery effort aimed at developing LPA mimics with a special focus on specific agonists of the LPA2 receptor subtype, which was found to be highly effective in protecting cells from apoptosis. We describe new evidence that 2-((3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)thio)benzoic acid (GRI977143), a prototypic nonlipid agonist specific to the LPA2 receptor subtype, rescues apoptotically condemned cells in vitro and in vivo from injury caused by high-dose γ-irradiation. GRI977143 shows the features of a radiomitigator because it is effective in rescuing the lives of mice from deadly levels of radiation when administered 24 h after radiation exposure. Our findings suggest that by specifically activating LPA2 receptors GRI977143 activates the ERK1/2 prosurvival pathway, effectively reduces Bax translocation to the mitochondrion, attenuates the activation of initiator and effector caspases, reduces DNA fragmentation, and inhibits PARP-1 cleavage associated with γ-irradiation-induced apoptosis. GRI977143 also inhibits bystander apoptosis elicited by soluble proapoptotic mediators produced by irradiated cells. Thus, GRI977143 can serve as a prototype scaffold for lead optimization paving the way to more potent analogs amenable for therapeutic exploration. PMID:23127512

Delayed pneumothorax complicating minor rib fracture after chest trauma.

PubMed

Lu, Ming-Shian; Huang, Yao-Kuang; Liu, Yun-Hen; Liu, Hui-Ping; Kao, Chiung-Lun

2008-06-01

Pneumothorax (PTX) after trauma is a preventable cause of death. Drainage procedures such as chest tube insertion have been traditionally advocated to prevent fatal tension PTX. We evaluated the safety of close observation in patients with delayed PTX complicating rib fracture after minor chest trauma. Adult patients (>18 years) with a diagnosis of chest trauma and 3 or fewer fractured ribs were reviewed. Case patients were divided according to age, location and number of fractured ribs, mechanism of trauma, and initial pulmonary complication after thoracic trauma for comparative analysis. There were 207 male (70.2%) and 88 female (29.8%) patients whose ages ranged from 18 to 93 years (median, 55 years). The mechanisms of trauma were a motor vehicle accident in 207 patients, falls in 66, pedestrian injury in 10, and assaults in 14. Ninety-five patients sustained 1 rib fracture, 95 had 2 rib fractures, and 105 suffered 3 rib fractures. Right-sided injury occurred in 164 cases, left-sided injury did in 127, and bilateral injury did in 4. The most frequent location of rib fractures was from the fourth rib to the ninth rib. The initial pulmonary complications after trauma were PTX in 16 patients, hemothorax in 43, pneumohemothorax in 14, lung contusion in 75, and isolated subcutaneous emphysema (SubcEmph) in 33. Thirty percent of the patients (n = 5/16) who presented with traumatic PTX were observed safely without drainage. Delayed PTX was recorded in 16 patients, occurring mostly during the first 2 days of their admission. Associated extrathoracic injury was recorded in 189 patients. The mean hospital stay of the patients was 7.66 days. Longer hospital stay was related to increasing number of fractured ribs, need for thoracic drainage, and the presence of associated extrathoracic injury. The mortality rate for the entire group was 2%. The presence of SubcEmph was the only risk factor associated with the development of delayed PTX. Patients sustaining blunt chest

Rapid Prediction of Hematologic Acute Radiation Syndrome in Radiation Injury Patients Using Peripheral Blood Cell Counts.

PubMed

Port, M; Pieper, B; Knie, T; Dörr, H; Ganser, A; Graessle, D; Meineke, V; Abend, M

2017-08-01

Rapid clinical triage of radiation injury patients is essential for determining appropriate diagnostic and therapeutic interventions. We examined the utility of blood cell counts (BCCs) in the first three days postirradiation to predict clinical outcome, specifically for hematologic acute radiation syndrome (HARS). We analyzed BCC test samples from radiation accident victims (n = 135) along with their clinical outcome HARS severity scores (H1-4) using the System for Evaluation and Archiving of Radiation Accidents based on Case Histories (SEARCH) database. Data from nonirradiated individuals (H0, n = 132) were collected from an outpatient facility. We created binary categories for severity scores, i.e., 1 (H0 vs. H1-4), 2 (H0-1 vs. H2-4) and 3 (H0-2 vs. H3-4), to assess the discrimination ability of BCCs using unconditional logistic regression analysis. The test sample contained 454 BCCs from 267 individuals. We validated the discrimination ability on a second independent group comprised of 275 BCCs from 252 individuals originating from SEARCH (HARS 1-4), an outpatient facility (H0) and hospitals (e.g., leukemia patients, H4). Individuals with a score of H0 were easily separated from exposed individuals based on developing lymphopenia and granulocytosis. The separation of H0 and H1-4 became more prominent with increasing hematologic severity scores and time. On day 1, lymphocyte counts were most predictive for discriminating binary categories, followed by granulocytes and thrombocytes. For days 2 and 3, an almost complete separation was achieved when BCCs from different days were combined, supporting the measurement of sequential BCC. We found an almost complete discrimination of H0 vs. irradiated individuals during model validation (negative predictive value, NPV > 94%) for all three days, while the correct prediction of exposed individuals increased from day 1 (positive predictive value, PPV 78-89%) to day 3 (PPV > 90%). The models were unable to provide

Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage.

PubMed

Glushakova, Olena Y; Johnson, Danny; Hayes, Ronald L

2014-07-01

Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. TBI in adult rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain pathology was assessed in white matter of the corpus callosum for 24 h to 3 months following injury using immunohistochemistry (IHC). TBI resulted in focal microbleeds that were related to the magnitude of injury. At the lower magnitude of injury, microbleeds gradually increased over the 3 month duration of the study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM-1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1 [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated inflammation (cluster of differentiation 68 [CD68]), all showing different temporal profiles. At chronic stages (up to 3 months), apparent myelin loss (Luxol fast blue) and scattered deposition of microbleeds were observed. Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased

A preclinical rodent model of acute radiation-induced lung injury after ablative focal irradiation reflecting clinical stereotactic body radiotherapy.

PubMed

Hong, Zhen-Yu; Lee, Hae-June; Choi, Won Hoon; Lee, Yoon-Jin; Eun, Sung Ho; Lee, Jung Il; Park, Kwangwoo; Lee, Ji Min; Cho, Jaeho

2014-07-01

In a previous study, we established an image-guided small-animal micro-irradiation system mimicking clinical stereotactic body radiotherapy (SBRT). The goal of this study was to develop a rodent model of acute phase lung injury after ablative irradiation. A radiation dose of 90 Gy was focally delivered to the left lung of C57BL/6 mice using a small animal stereotactic irradiator. At days 1, 3, 5, 7, 9, 11 and 14 after irradiation, the lungs were perfused with formalin for fixation and paraffin sections were stained with hematoxylin and eosin (H&E) and Masson's trichrome. At days 7 and 14 after irradiation, micro-computed tomography (CT) images of the lung were taken and lung functional measurements were performed with a flexiVent™ system. Gross morphological injury was evident 9 days after irradiation of normal lung tissues and dynamic sequential events occurring during the acute phase were validated by histopathological analysis. CT images of the mouse lungs indicated partial obstruction located in the peripheral area of the left lung. Significant alteration in inspiratory capacity and tissue damping were detected on day 14 after irradiation. An animal model of radiation-induced lung injury (RILI) in the acute phase reflecting clinical stereotactic body radiotherapy was established and validated with histopathological and functional analysis. This model enhances our understanding of the dynamic sequential events occurring in the acute phase of radiation-induced lung injury induced by ablative dose focal volume irradiation.

Manubriosternal dislocation with spinal fracture: A rare cause for delayed haemothorax.

PubMed

Kothari, Manish; Saini, Pramod; Shethna, Sunny; Dalvie, Samir

2015-01-01

Type 2 manubriosternal dislocations with concomitant spinal fracture are rare and may be associated with thoracic visceral injuries. The complication of delayed haemothorax has not been reported yet. We report a case of a young male who suffered manubriosternal dislocation with chance type thoracic spine fracture due to fall of a tree branch over his back. The haemothorax presented late on day three. The possible injury mechanism is discussed along with review of literature. We conclude that a lateral chest radiograph is indicated in spinal fracture patients complaining of midsternal pain. Computerized axial tomography scan of chest with contrast is indicated to rule out visceral injuries and a chest radiograph should be repeated before the patient is discharged to look for delayed haemothorax.

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.

Neurological complication after low-voltage electric injury: a case report.

PubMed

Kim, Ha Min; Ko, Yeong-A; Kim, Joon Sung; Lim, Seong Hoon; Hong, Bo Young

2014-04-01

Electrical shock can result in neurological complications, involving both peripheral and central nervous systems, which may present immediately or later on. However, delayed neurological complications caused by low-voltage electric shock are rarely reported. Here, a case of a man suffering from weakness and aphasia due to the delayed-onset of the peripheral nerve injury and ischemic stroke following an electrical shock is presented. Possible mechanisms underlying the neurological complications include thermal injury to perineural tissue, overactivity of the sympathetic nervous system, vascular injury, and histological or electrophysiological changes. Moreover, vasospasms caused by low-voltage alternating current may predispose individuals to ischemic stroke. Therefore, clinicians should consider the possibility of neurological complications, even if the onset of the symptoms is delayed, and should perform diagnostic tests, such as electrophysiology or imaging, when patients present with weakness following an electric injury.

In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy

PubMed Central

Jang, Won Hyuk; Shim, Sehwan; Wang, Taejun; Yoon, Yeoreum; Jang, Won-Suk; Myung, Jae Kyung; Park, Sunhoo; Kim, Ki Hean

2016-01-01

Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis. PMID:26755422

Lawn mower-related projectile injury.

PubMed

McNamara, William F; Yamout, Sani Z; Escobar, Mauricio A; Glick, Philip L

2009-07-01

Lawn mower injuries are a potentially devastating, yet preventable cause of morbidity and mortality in the pediatric population. The sequelae to these injuries can become even worse if the initial presentation goes unsuspected by medical staff, leading to a delay in treatment. The authors report the case of a lawn mower-related penetrating missile injury, where the extent of injury was not appreciated by the patient until signs and symptoms of a soft-tissue infection developed, prompting the patient to seek medical attention the next day.

Cognitive and motor abilities of young children and risk of injuries in the home.

PubMed

Ehrhardt, Jennifer; Xu, Yingying; Khoury, Jane; Yolton, Kimberly; Lanphear, Bruce; Phelan, Kieran

2017-02-01

Residential injury is a leading cause of morbidity and mortality in US children. Rates and types of injury vary by child age but little is known about injury risk based on child cognitive and motor abilities. The objective of this study was to determine whether cognitive or motor development in young children is associated with residential injury. We employed data from Health Outcomes and Measures of the Environment (HOME) Study. Parent report of medically attended injury was obtained at regular intervals from 0 to 42 months. Child development was assessed at 12, 24 and 36 months using Bayley Scales of Infant and Toddler Development, 2nd edition, which generates both mental developmental index (MDI) and a psychomotor developmental index (PDI). Injury risk was modelled using multivariable logistic regression as function of child's MDI or PDI. Effects of MDI and PDI on injury risk were examined separately and jointly, adjusting for important covariates. Children with cognitive delay (MDI <77) were at significantly higher risk of injury than children without cognitive delay (OR=3.7, 95% CI 1.4 to 10.5, p=0.012). There was no significant association of PDI with injury. There was, however, significant interaction of MDI and PDI (p=0.02); children with cognitive delay but normal motor development were at significantly higher risk of injury than children with normal cognitive and motor development (OR=9.6, 95% CI 2.6 to 35.8, p=0.001). Children with cognitive delays, especially those with normal motor development, are at elevated risk for residential injuries. Injury prevention efforts should target children with developmental delays. NCT00129324; post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

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

Ali, Haytham; Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University; Galal, Omima

Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days inmore » sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.« less

Pelvic-fracture urethral injury in children

PubMed Central

Hagedorn, Judith C.; Voelzke, Bryan B.

2015-01-01

Objective To review paediatric posterior urethral injuries and the current potential management options; because urethral injury due to pelvic fracture in children is rare and has a low incidence, the management of this type of trauma and its complications remains controversial. Methods We reviewed previous reports identified by searching the PubMed Medline electronic database for clinically relevant articles published in the past 25 years. The search was limited to the keywords ‘pediatric’, ‘pelvic fracture’, ‘urethral injury’, ‘stricture’, ‘trauma’ and ‘reconstruction’. Results Most paediatric urethral injuries are a result of pelvic fractures after high-impact blunt trauma. After the diagnosis, immediate bladder drainage via a suprapubic cystotomy, or urethral realignment, are the initial management options, except for a possible immediate primary repair in girls. The common complications of pelvic fracture-associated urethral injury include urethral stricture formation, incontinence and erectile dysfunction. Excellent results can be achieved with delayed urethroplasty for pelvic fracture-associated urethral injuries. Conclusion Traumatic injury to the paediatric urethra is rare and calls for an immediate diagnosis and management. These devastating injuries have a high complication rate and therefore a close follow-up is warranted to assure adequate delayed repair by a reconstructive urologist. PMID:26019977

Delayed splenic rupture presenting 70 days following blunt abdominal trauma.

PubMed

Resteghini, Nancy; Nielsen, Jonpaul; Hoimes, Matthew L; Karam, Adib R

2014-01-01

Delayed splenic rupture following conservative management of splenic injury is an extremely rare complication. We report a case of an adult patient who presented with delayed splenic rupture necessitating splenectomy, 2 months following blunt abdominal trauma. Imaging at the initial presentation demonstrated only minimal splenic contusion and the patient was discharge following 24 hours of observation. © 2014.

Mice lacking the extracellular matrix protein MAGP1 display delayed thrombotic occlusion following vessel injury

PubMed Central

Werneck, Claudio C.; Vicente, Cristina P.; Weinberg, Justin S.; Shifren, Adrian; Pierce, Richard A.; Broekelmann, Thomas J.; Tollefsen, Douglas M.

2008-01-01

Mice lacking the extracellular matrix protein microfibril-associated glycoprotein-1 (MAGP1) display delayed thrombotic occlusion of the carotid artery following injury as well as prolonged bleeding from a tail vein incision. Normal occlusion times were restored when recombinant MAGP1 was infused into deficient animals prior to vessel wounding. Blood coagulation was normal in these animals as assessed by activated partial thromboplastin time and prothrombin time. Platelet number was lower in MAGP1-deficient mice, but the platelets showed normal aggregation properties in response to various agonists. MAGP1 was not found in normal platelets or in the plasma of wild-type mice. In ligand blot assays, MAGP1 bound to fibronectin, fibrinogen, and von Willebrand factor, but von Willebrand factor was the only protein of the 3 that bound to MAGP1 in surface plasmon resonance studies. These findings show that MAGP1, a component of microfibrils and vascular elastic fibers, plays a role in hemostasis and thrombosis. PMID:18281502

Fructokinase activity mediates dehydration-induced renal injury.

PubMed

Roncal Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Rivard, Christopher J; Nakagawa, Takahiko; Ejaz, A Ahsan; Cicerchi, Christina; Inaba, Shinichiro; Le, MyPhuong; Miyazaki, Makoto; Glaser, Jason; Correa-Rotter, Ricardo; González, Marvin A; Aragón, Aurora; Wesseling, Catharina; Sánchez-Lozada, Laura G; Johnson, Richard J

2014-08-01

The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

The Role of Alveolar Epithelium in Radiation-Induced Lung Injury

PubMed Central

Almeida, Celine; Nagarajan, Devipriya; Tian, Jian; Leal, Sofia Walder; Wheeler, Kenneth; Munley, Michael; Blackstock, William; Zhao, Weiling

2013-01-01

Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11–13 Gy) and fractionated doses (24–36 Gy) of 137Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c+ cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis. PMID:23326473

Injury Characteristics of Low-Energy Lisfranc Injuries Compared With High-Energy Injuries.

PubMed

Renninger, Christopher H; Cochran, Grant; Tompane, Trevor; Bellamy, Joseph; Kuhn, Kevin

2017-09-01

Lisfranc injuries result from high- and low-energy mechanisms though the literature has been more focused on high-energy mechanisms. A comparison of high-energy (HE) and low-energy (LE) injury patterns is lacking. The objective of this study was to report injury patterns in LE Lisfranc joint injuries and compare them to HE injury patterns. Operative Lisfranc injuries were identified over a 5-year period. Patient demographics, mechanism of injury, injury pattern, associated injuries, missed diagnoses, clinical course, and imaging studies were reviewed and compared. HE mechanism was defined as motor vehicle crash, motorcycle crash, direct crush, and fall from greater than 4 feet and LE mechanism as athletic activity, ground level twisting, or fall from less than 4 feet. Thirty-two HE and 48 LE cases were identified with 19.3 months of average follow-up. There were no differences in demographics or missed diagnosis frequency (21% HE vs 18% LE). Time to seek care was not significantly different. HE injuries were more likely to have concomitant nonfoot fractures (37% vs 6%), concomitant foot fractures (78% vs 4%), cuboid fractures (31% vs 6%), metatarsal base fractures (84% vs 29%), displaced intra-articular fractures (59% vs 4%), and involvement of all 5 rays (23% vs 6%). LE injuries were more commonly ligamentous (68% vs 16%), with fewer rays involved (2.7 vs 4.1). LE mechanisms were a more common cause of Lisfranc joint injury in this cohort. These mechanisms generally resulted in an isolated, primarily ligamentous injury sparing the lateral column. Both types had high rates of missed injury that could result in delayed treatment. Differences in injury patterns could help direct future research to optimize treatment algorithms. Level III, comparative series.

Pancreatic injury: accidental or nonaccidental.

PubMed

Waseem, Muhammad; Perales, Orlando

2008-10-01

The diagnosis of abuse in a child with occult abdominal injuries is difficult. Not many patients with nonaccidental trauma present with a clear history of the injury. The absence of a reliable history in patients with nonaccidental trauma makes determination of an exact mechanism difficult. In most cases, patients present to the emergency department with inaccurate or misleading histories; some give no history of trauma, which may delay recognition of serious abdominal injuries. In addition, the child may have other injuries, such as neurologic or musculoskeletal, which divert attention from occult abdominal injuries. Pancreatic and duodenal injuries are considered specific for abuse. We report a child with pancreatic injury without an appropriate history of trauma, determined to be caused by nonaccidental trauma.

Intestinal tuft cells regulate the ATM mediated DNA Damage response via Dclk1 dependent mechanism for crypt restitution following radiation injury.

PubMed

Chandrakesan, Parthasarathy; May, Randal; Weygant, Nathaniel; Qu, Dongfeng; Berry, William L; Sureban, Sripathi M; Ali, Naushad; Rao, Chinthalapally; Huycke, Mark; Bronze, Michael S; Houchen, Courtney W

2016-11-23

Crypt epithelial survival and regeneration after injury require highly coordinated complex interplay between resident stem cells and diverse cell types. The function of Dclk1 expressing tuft cells regulating intestinal epithelial DNA damage response for cell survival/self-renewal after radiation-induced injury is unclear. Intestinal epithelial cells (IECs) were isolated and purified and utilized for experimental analysis. We found that small intestinal crypts of Villin Cre ;Dclk1 f/f mice were hypoplastic and more apoptotic 24 h post-total body irradiation, a time when stem cell survival is p53-independent. Injury-induced ATM mediated DNA damage response, pro-survival genes, stem cell markers, and self-renewal ability for survival and restitution were reduced in the isolated intestinal epithelial cells. An even greater reduction in these signaling pathways was observed 3.5 days post-TBI, when peak crypt regeneration occurs. We found that interaction with Dclk1 is critical for ATM and COX2 activation in response to injury. We determined that Dclk1 expressing tuft cells regulate the whole intestinal epithelial cells following injury through paracrine mechanism. These findings suggest that intestinal tuft cells play an important role in regulating the ATM mediated DNA damage response, for epithelial cell survival/self-renewal via a Dclk1 dependent mechanism, and these processes are indispensable for restitution and function after severe radiation-induced injury.

Delayed presentation of deep penetrating trauma to the subaxial cervical spine.

PubMed

Zaldivar-Jolissaint, Julien Francisco; Bobinski, Lukas; Van Dommelen, Yaelle; Levivier, Marc; Simon, Christian; Duff, John Michael

2015-05-01

To present a rare case of deep penetrating neck trauma in which a retained foreign body in the cervical spine (a broken knife blade) resulted in delayed radicular injury. We describe the surgical management using a retrojugular approach. Our patient sustained a stab wound to the supraclavicular triangle from a small pocketknife. He was initially managed in a local hospital by simple primary wound closure without any radiological examinations, and was discharged home. The patient re-consulted in a delayed fashion with mild local persistent neck pain. Subsequent radiological investigations revealed a foreign body (the broken blade of a pocket knife) embedded in the left neural foramen between the C6 and C7 vertebrae penetrating the disc space. The blade was lying between the left C7 nerve root and the ipsilateral vertebral artery (VA) at the transition of V1 and V2 segments. Initial neurological evaluation was normal. Some days later, the patient developed a delayed left C7 radicular deficit. We undertook urgent exploration along the wound corridor through a retrojugular, transforaminal approach with successful removal of the blade. To our knowledge, this is a unique case where a retained foreign body penetrated the soft tissues of the neck, embedding deep in the vertebral column without vascular, aerodigestive or significant primary neurological injury, while causing delayed neck pain and delayed onset radicular injury. We describe our surgical management for removal of the retained blade. The retrojugular approach gives excellent access to all of the important anatomical structures of the neck from an anterolateral approach.

Cellular Therapies for Treatment of Radiation Injury: Report from a NIH/NIAID and IRSN Workshop

PubMed Central

DiCarlo, Andrea L.; Tamarat, Radia; Rios, Carmen I.; Benderitter, Marc; Czarniecki, Christine W.; Allio, Theresa C.; Macchiarini, Francesca; Maidment, Bert W.; Jourdain, Jean-Rene

2017-01-01

In recent years, there has been increasing concern over the possibility of a radiological or nuclear incident occurring somewhere in the world. Intelligence agencies frequently report that terrorist groups and rogue nations are seeking to obtain radiological or nuclear weapons of mass destruction. In addition, there exists the real possibility that safety of nuclear power reactors could be compromised by natural (such as the tsunami and subsequent Fukushima accident in Japan in March, 2011) or accidental (Three Mile Island, 1979 and Chernobyl, 1986) events. Although progress has been made by governments around the world to prepare for these events, including the stockpiling of radiation countermeasures, there are still challenges concerning care of patients injured during a radiation incident. Because the deleterious and pathological effects of radiation are so broad, it is desirable to identify medical countermeasures that can have a beneficial impact on several tissues and organ systems. Cellular therapies have the potential to impact recovery and tissue/organ regeneration for both early and late complications of radiation exposure. These therapies, which could include stem or blood progenitor cells, mesenchymal stromal cells (MSCs) or cells derived from other tissues (e.g., endothelium or placenta), have shown great promise in treating other nonradiation injuries to and diseases of the bone marrow, skin, gastrointestinal tract, brain, lung and heart. To explore the potential use of these therapies in the treatment of victims after acute radiation exposure, the National Institute of Allergy and Infectious Diseases cosponsored an international workshop in July, 2015 in Paris, France with the Institut de Radioprotection et de Sûreté Nucléaire. The workshop included discussions of data available from testing in preclinical models of radiation injury to different organs, logistics associated with the practical use of cellular therapies for a mass casualty incident

[Prevention of Inonotus obliquus polysaccharides for high power microwave radiation induced testicular injury in rats: an experimental research].

PubMed

Zhao, Li-Wei; Zhong, Xiu-Hong; Sun, Yan-Mei; Yang, Shu-Yan; Shen, Nan; Zhang, Yi-Zhong; Yang, Ning-Jiang; Ren, Kuang; Lu, Shi-Jie

2014-07-01

To investigate the effect of Inonotus obliquus polysaccharides on testicular injury induced by exposure to high power microwave (HPM) in rats. A total of 30 male Wistar rats were randomly divided into 5 groups, i.e., the normal control group, the microwave radiation model group, the treatment group, the new microwave radiation model group, and the prevention group, 6 in each group. All rats, except those in the normal control group, were exposed to microwave at an average power density of 200 mW/cm2 for 6 min. Rats in the control group and the model group were administered with normal saline by gastrogavage, once a day. Rats in the treatment group and the prevention group were given with Inonotus obliquus polysaccharides by gastrogavage, 2 mL each time (400 mg/kg body weight), once a day. All rats were sacrificed on the 11th day.The sperm density and the rate of sperm deformity were determined. Pathological changes of testis were observed by light microscope and transmission electron microscope. Short-term HPM irradiation could significantly reduce the sperm density and increase the sperm deformity rate (P < 0.05). Meanwhile, obvious pathological changes of testes occurred. Compared with the two model groups, the sperm density increased and the sperm deformity rate decreased in the treatment group and the prevention group (P < 0.05). Under the light microscope, injuries of spermatogenic cells and stromal cells, as well as vascular dilatation and congestion were obviously alleviated in the treatment group and the prevention group. Mitochondrial swelling and endoplasmic reticulum expansion shown by ultrastructural observation were also significantly alleviated. Of them, injuries of spermatogenic cells and inflammation response were milder in the treatment group than in the prevention group. Inonotus obliquus polysaccharides had significant protective effect on microwave radiation induced testicular injury. Better effect was obtained by therapeutic medication than

Succinylcholine-induced hyperkalemia in the rat following radiation injury to muscle

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

Cairoli, V.J.; Ivankovich, A.D.; Vucicevic, D.

1982-02-01

During anesthetic preparation of a patient who had received routine radiation therapy for sarcoma of the leg, cardiac collapse occurred following succinylcholine (SCh) administration. Experiments were designed to test the hypothesis that radiation injury to muscle might cause increased sensitivity to SCh similar to that reported in patients with muscle trauma, severe burns, and lesions causing muscle denervation. Venous plasma potassium levels and arterial blood gas tensions were measured in rats after they were given SCh (3 mg/kg) at various times following /sup 60/Co irradiation of the hind legs. Nonirradiated rats responded to SCh with a slight but statistically significantmore » increase in plasma K+. Rats subjected to high levels of radiation (10,000 to 20,000 R) and given SCh 4 to 7 days later responded in the same way as the control rats. Plasma K+ levels in rats exposed to a fractionated irradiated dosage (2500 R given twice with a 1-week interval) followed by SCh 1 week later were similar to those in the control group, but when SCh was given 2 weeks later (3 weeks after initial irradiation) there was a marked elevation of plasma K+, from 3.6 to 7.7 meq/L, a statistically significant increase.« less

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

Early or delayed stabilization in severely injured patients with spinal fractures? Current surgical objectivity according to the Trauma Registry of DGU: treatment of spine injuries in polytrauma patients.

PubMed

Bliemel, Christopher; Lefering, Rolf; Buecking, Benjamin; Frink, Michael; Struewer, Johannes; Krueger, Antonio; Ruchholtz, Steffen; Frangen, Thomas Manfred

2014-02-01

Because of a lack of evidence, the appropriate timing of surgical stabilization of thoracic and lumbar spine injuries in severely injured patients is still controversial. Data of a large international trauma register were analyzed to investigate the medical care situation of unstable spinal column fractures in patients with multiple injuries, so as to examine the outcome related to timing of surgical stabilization. Data sets of the Trauma Registry of German Trauma Society (Deutsche Gesellschaft für Unfallchirurgie [DGU]) (1993-2010) were analyzed. The Trauma Registry of DGU is a prospective, multicenter register that provides information on severely injured patients. All patients with an Injury Severity Score (ISS) of 16 or greater caused by blunt trauma, subsequent treatment of 7 days or more, 16 years or older, and thoracic or lumbar spine injuries (spine Abbreviated Injury Scale [AIS] score ≥ 2) were included in our analysis. Patients with relevant spine injuries classified as having a spine AIS score of 3 or greater were further analyzed in terms of whether they got early (<72 hours) or late (>72 hours) surgical treatment due to unstable spinal column fractures. Of 24,974 patients, 8,994 (36.0%) had documented spinal injuries (spine AIS score ≥ 2). A total of 1,309 patients who sustained relevant thoracic spine injuries (spine AIS score ≥ 3) and 994 patients who experienced lumbar spine trauma and classified as having spine AIS score of 3 or greater were more precisely analyzed. Of these, 68.2% and 71.0%, respectively, received an early thoracic or lumbar spine fixation. With an increase in spinal injury severity, an increase in early stabilization in the thoracic and lumbar spine was seen. In the group of patients with early surgical stabilization, significantly shorter hospital stays, shorter intensive care unit stays, fewer days on mechanical ventilation, and lower rates of sepsis were seen. In the case that additional body regions were affected, for

Delayed repair of the peripheral nerve: a novel model in the rat sciatic nerve.

PubMed

Wu, Peng; Spinner, Robert J; Gu, Yudong; Yaszemski, Michael J; Windebank, Anthony J; Wang, Huan

2013-03-30

Peripheral nerve reconstruction is seldom done in the acute phase of nerve injury due to concomitant injuries and the uncertainty of the extent of nerve damage. A proper model that mimics true clinical scenarios is critical but lacking. The aim of this study is to develop a standardized, delayed sciatic nerve repair model in rats and validate the feasibility of direct secondary neurrorraphy after various delay intervals. Immediately or 1, 4, 6, 8 and 12 weeks after sciatic nerve transection, nerve repair was carried out. A successful tension-free direct neurorraphy (TFDN) was defined when the gap was shorter than 4.0 mm and the stumps could be reapproximated with 10-0 stitches without detachment. Compound muscle action potential (CMAP) was recorded postoperatively. Gaps between the two nerve stumps ranged from 0 to 9 mm, the average being 1.36, 2.85, 3.43, 3.83 and 6.4 mm in rats with 1, 4, 6, 8 and 12 week delay, respectively. The rate of successful TFDN was 78% overall. CMAP values of 1 and 4 week delay groups were not different from the immediate repair group, whereas CMAP amplitudes of 6, 8 and 12 week delay groups were significantly lower. A novel, standardized delayed nerve repair model is established. For this model to be sensitive, the interval between nerve injury and secondary repair should be at least over 4 weeks. Thereafter the longer the delay, the more challenging the model is for nerve regeneration. The choice of delay intervals can be tailored to meet specific requirements in future studies. Copyright © 2013 Elsevier B.V. All rights reserved.

Iatrogenic Hepatopancreaticobiliary Injuries: A Review

PubMed Central

Vachhani, Prasanti G.; Copelan, Alexander; Remer, Erick M.; Kapoor, Baljendra

2015-01-01

Iatrogenic hepatopancreaticobiliary injuries occur after various types of surgical and nonsurgical procedures. Symptomatically, these injuries may lead to a variety of clinical presentations, including tachycardia and hypotension from hemobilia or hemorrhage. Iatrogenic injuries may be identified during the intervention, immediately afterwards, or have a delayed presentation. These injuries are categorized into nonvascular and vascular injuries. Nonvascular injuries include biliary injuries such as biliary leak or stricture, pancreatic injury, and the development of fluid collections such as abscesses. Vascular injuries include pseudoaneurysms, arteriovenous fistulas, dissection, and perforation. Imaging studies such as ultrasound, computed tomography, magnetic resonance imaging, and digital subtraction angiography are critical for proper diagnosis of these conditions. In this article, we describe the clinical and imaging presentations of these iatrogenic injuries and the armamentarium of minimally invasive procedures (percutaneous drainage catheter placement, balloon dilatation, stenting, and coil embolization) that are useful in their management. PMID:26038625

Transcatheter Embolization for Delayed Hemorrhage Caused by Blunt Splenic Trauma

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

Krohmer, Steven J., E-mail: Steven.J.Krohmer@hitchcock.org; Hoffer, Eric K., E-mail: eric.k.hoffer@hitchcock.or; Burchard, Kenneth W., E-mail: Kenneth.W.Burchard@hitchcock.or

2010-08-15

Although the exact benefit of adjunctive splenic artery embolization (SAE) in the nonoperative management (NOM) of patients with blunt splenic trauma has been debated, the role of transcatheter embolization in delayed splenic hemorrhage is rarely addressed. The purpose of this study was to evaluate the effectiveness of SAE in the management of patients who presented at least 3 days after initial splenic trauma with delayed hemorrhage. During a 24-month period 4 patients (all male; ages 19-49 years) presented with acute onset of pain 5-70 days after blunt trauma to the left upper quadrant. Two had known splenic injuries that hadmore » been managed nonoperatively. All had computed axial tomography evidence of active splenic hemorrhage or false aneurysm on representation. All underwent successful SAE. Follow-up ranged from 28 to 370 days. These cases and a review of the literature indicate that SAE is safe and effective for NOM failure caused by delayed manifestations of splenic arterial injury.« less

[Delayed reconstructions of soft tissue defects of the face].

PubMed

Mest'ák, J

2007-06-01

The author describes a non-standard approach to the management of facial soft tissue defects. Significance of delayed reconstructions in defect face injuries and options for their employment in indicated cases are highlighted.

Laser eye injuries.

PubMed

Barkana, Y; Belkin, M

2000-01-01

Laser instruments are used in many spheres of human activity, including medicine, industry, laboratory research, entertainment, and, notably, the military. This widespread use of lasers has resulted in many accidental injuries. Injuries are almost always retinal, because of the concentration of visible and near-infrared radiation on the retina. The retina is therefore the body tissue most vulnerable to laser radiation. The nature and severity of this type of retinal injury is determined by multiple laser-related and eye-related factors, the most important being the duration and amount of energy delivered and the retinal location of the lesion. The clinical course of significant retinal laser injuries is characterized by sudden loss of vision, often followed by marked improvement over a few weeks, and occasionally severe late complications. Medical and surgical treatment is limited. Laser devices hazardous to the human eye are currently in widespread use by armed forces. Furthermore, lasers may be employed specifically for visual incapacitation on future battlefields. Adherence to safety practices effectively prevents accidental laser-induced ocular injuries. However, there is no practical way to prevent injuries that are maliciously inflicted, as expected from laser weapons.

Delayed diaphragmatic herniation masquerading as a complicated parapneumonic effusion.

PubMed

Tsang, J; Ryan, F

1999-01-01

Injury to the diaphragm following blunt or penetrating thoracoabdominal trauma is not uncommon. Recognition of this important complication of trauma continues to be a challenge because of the lack of specific clinical and plain radiographic features, the frequent presence of other serious injuries and the potential for delayed presentation. Delayed diaphragmatic herniation often presents with catastrophic bowel obstruction or strangulation. Early recognition of diaphragmatic injury is required to avoid this potentially lethal complication. The case of a 35-year-old man with a history of a knife wound to the left flank 15 years previously, who presented with unexplained acute hypoxemic respiratory failure and a unilateral exudative pleural effusion that was refractory to tube thoracostomy drainage, is reported. After admission to hospital, he developed gross dilation of his colon; emergency laparotomy revealed an incarcerated colonic herniation into the left hemithorax. Interesting clinical features of this patient's case included the patient's hobby of weightlifting, a persistently deviated mediastinum despite drainage of the pleural effusion and deceptive pleural fluid biochemical indices.

Not all intestinal traumatic injuries are the same: a comparison of surgically treated blunt vs. penetrating injuries.

PubMed

Adam, Nadir; Sorensen, Victor; Skinner, Ruby

2015-01-01

Traumatic intestinal injuries are less common with blunt compared to penetrating mechanisms of trauma and blunt injuries are often associated with diagnostic delays. The purpose of this study is to evaluate differences in the characteristics and outcomes between blunt and penetrating intestinal injuries to facilitate insight into optimal recognition and management. A retrospective analysis of trauma admissions from January 2009 to June 2011 was performed. Patient demographics, ISS, early shock, injury type, timing to OR, blood loss and transfusions, surgical management, infections, EC fistulas, enteric leaks, LOS and mortality were compared. Demographics - There was 3866 blunt admissions and 966 penetrating admissions to our level II trauma centre (Total n=4832) during this interval. The final study group comprised n=131 patients treated for intestinal injuries. Blunt n=54 (BI) vs. penetrating (PI) n=77. Age was similar between the groups: (BI 34 SD 12 vs. PI 30 SD 12). Comorbid conditions were similar as were ED hypotension and blood transfusions. Blunt mechanisms had higher ISS; BI (20 SD 14) vs. PI (16 SD 12), p=0.08 and organ specific injury scales were higher in blunt injuries. Operative Management - Time to operation was higher in BI: (500 SD 676min vs. PI 110 SD 153min, p=0.01). The use of an open abdomen technique was higher for BI: n=19 (35%) vs. PI: n=5 (6%), p=<0.001, as well as delayed intestinal repair in damage control cases. Outcomes - Anastomotic leaks were more prevalent in BI: n=4 (7%) vs. PI: n=2 (3%), p=0.38. Enteric fistulas were: (BI n=8 (15%), vs. PI n=2 (3%), p=0.02). Surgical site infections and other nosocomial infections were: (BI n=11 (20%) vs. PI n=4 (5%), p=0.02), (BI n=11 (20%) vs. PI n=2 (3%), p=0.002), respectively. Hospital and ICU LOS was: (BI=20 SD 14 vs. PI=11 SD 11, p=0.001), (BI=10 SD 10 vs. PI=5 SD 5, p=0.01) respectively. These differences were reflected in higher hospital charges in BI. Blunt and penetrating intestinal

Captopril and losartan for mitigation of renal injury caused by single-dose total-body irradiation.

PubMed

Moulder, John E; Cohen, Eric P; Fish, Brian L

2011-01-01

It is known that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can be used to mitigate radiation-induced renal injury. However, for a variety of reasons, these previous results are not directly applicable to the development of agents for the mitigation of injuries caused by terrorism-related radiation exposure. As part of an effort to develop an animal model that would fit the requirements of the U.S. Food and Drug Administration (FDA) "Animal Efficacy Rule", we designed new studies which used an FDA-approved ACEI (captopril) or an FDA-approved ARB (losartan, Cozaar®) started 10 days after a single total-body irradiation (TBI) at drug doses that are equivalent (on a g/m(2)/day basis) to the doses prescribed to humans. Captopril and losartan were equally effective as mitigators, with DMFs of 1.23 and 1.21, respectively, for delaying renal failure. These studies show that radiation nephropathy in a realistic rodent model can be mitigated with relevant doses of FDA-approved agents. This lays the necessary groundwork for pivotal rodent studies under the FDA Animal Efficacy Rule and provides an outline of how the FDA-required large-animal studies could be designed.

Captopril and Losartan for Mitigation of Renal Injury Caused by Single-Dose Total-Body Irradiation

PubMed Central

Moulder, John E.; Cohen, Eric P.; Fish, Brian L.

2011-01-01

It is known that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can be used to mitigate radiation-induced renal injury. However, for a variety of reasons, these previous results are not directly applicable to the development of agents for the mitigation of injuries caused by terrorism-related radiation exposure. As part of an effort to develop an animal model that would fit the requirements of the U.S. Food and Drug Administration (FDA) “Animal Efficacy Rule”, we designed new studies which used an FDA-approved ACEI (captopril) or an FDA-approved ARB (losartan, Cozaar®) started 10 days after a single total-body irradiation (TBI) at drug doses that are equivalent (on a g/m2/day basis) to the doses prescribed to humans. Captopril and losartan were equally effective as mitigators, with DMFs of 1.23 and 1.21, respectively, for delaying renal failure. These studies show that radiation nephropathy in a realistic rodent model can be mitigated with relevant doses of FDA-approved agents. This lays the necessary groundwork for pivotal rodent studies under the FDA Animal Efficacy Rule and provides an outline of how the FDA-required large-animal studies could be designed. PMID:21175344

Hypobaric Hypoxia Exacerbates the Neuroinflammatory Response to Traumatic Brain Injury

PubMed Central

Goodman, Michael D.; Makley, Amy T.; Huber, Nathan L.; Clarke, Callisia N.; Friend, Lou Ann W.; Schuster, Rebecca M.; Bailey, Stephanie R.; Barnes, Stephen L.; Dorlac, Warren C.; Johannigman, Jay A.; Lentsch, Alex B.; Pritts, Timothy A.

2015-01-01

Objective To determine the inflammatory effects of time-dependent exposure to the hypobaric environment of simulated aeromedical evacuation following traumatic brain injury (TBI). Methods Mice were subjected to a blunt TBI or sham injury. Righting reflex response (RRR) time was assessed as an indicator of neurologic recovery. Three or 24 h (Early and Delayed groups, respectively) after TBI, mice were exposed to hypobaric flight conditions (Fly) or ground-level control (No Fly) for 5 h. Arterial blood gas samples were obtained from all groups during simulated flight. Serum and cortical brain samples were analyzed for inflammatory cytokines after flight. Neuron specific enolase (NSE) was measured as a serum biomarker of TBI severity. Results TBI resulted in prolonged RRR time compared with sham injury. After TBI alone, serum levels of interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC) were increased by 6 h post-injury. Simulated flight significantly reduced arterial oxygen saturation levels in the Fly group. Post-injury altitude exposure increased cerebral levels of IL-6 and macrophage inflammatory protein-1α (MIP-1α), as well as serum NSE in the Early but not Delayed Flight group compared to ground-level controls. Conclusions The hypobaric environment of aero-medical evacuation results in significant hypoxia. Early, but not delayed, exposure to a hypobaric environment following TBI increases the neuroinflammatory response to injury and the severity of secondary brain injury. Optimization of the post-injury time to fly using serum cytokine and biomarker levels may reduce the potential secondary cerebral injury induced by aeromedical evacuation. PMID:20850781

Radiation-Induced Liver Injury Mimicking Metastatic Disease in a Patient With Esophageal Cancer: Correlation of Positron Emission Tomography/Computed Tomography With Magnetic Resonance Imaging and Literature Review.

PubMed

Rabe, Tiffany M; Yokoo, Takeshi; Meyer, Jeffrey; Kernstine, Kemp H; Wang, David; Khatri, Gaurav

2016-01-01

Post-radiation therapy evaluation of distal esophageal cancers with positron emission tomography/computed tomography can be problematic. Differentiation of recurrent neoplasm from postradiation changes is difficult in areas of fluorodeoxyglucose avidity in adjacent, incidentally irradiated organs. Few studies have described the magnetic resonance imaging appearance of radiation-induced hepatic injury. We report a case of focal radiation-induced liver injury with a new focus of fluorodeoxyglucose uptake on posttreatment positron emission tomography as well as masslike enhancement and signal abnormality on magnetic resonance imaging, thus mimicking new liver metastasis. Correlation with radiation planning images suggested the correct diagnosis, which was confirmed on follow-up imaging.

Pelvic fracture urethral injury in males-mechanisms of injury, management options and outcomes.

PubMed

Barratt, Rachel C; Bernard, Jason; Mundy, Anthony R; Greenwell, Tamsin J

2018-03-01

Pelvic fracture urethral injury (PFUI) management in male adults and children is controversial. The jury is still out on the best way to manage these injuries in the short and long-term to minimise complications and optimise outcomes. There is also little in the urological literature about pelvic fractures themselves, their causes, grading systems, associated injuries and the mechanism of PFUI. A review of pelvic fracture and male PFUI literature since 1757 was performed to determine pelvic fracture classification, associated injuries and, PFUI classification and management. The outcomes of; suprapubic catheter (SPC) insertion alone, primary open surgical repair (POSR), delayed primary open surgical repair (DPOSR), primary open realignment (POR), primary endoscopic realignment (PER), delayed endoscopic treatment (DET) and delayed urethroplasty (DU) in male adults and children in all major series have been reviewed and collated for rates of restricture (RS), erectile dysfunction (ED) and urinary incontinence (UI). For SPC, POSR, DPOSR, POR, PER, DET and DU; (I) mean RS rate was 97.9%, 53.9%, 18%, 58.3%, 62.0%, 80.2%, 14.4%; (II) mean ED rate was 25.6%, 22.5%, 71%, 37.2%, 23.6%, 31.9%, 12.7%; (III) mean UI rate was 6.7%, 13.6%, 0%, 14.5%, 4.1%, 4.1%, 6.8%; (IV) mean FU in months was 46.3, 29.4, 12, 61, 31.4, 31.8, 54.9. For males with PFUI restricture and new onset ED is lowest following DU whilst UI is lowest following DPOSR. On balance DU offers the best overall outcomes and should be the treatment of choice for PFUI.

Pelvic fracture urethral injury in males—mechanisms of injury, management options and outcomes

PubMed Central

Barratt, Rachel C.; Bernard, Jason; Mundy, Anthony R.

2018-01-01

Pelvic fracture urethral injury (PFUI) management in male adults and children is controversial. The jury is still out on the best way to manage these injuries in the short and long-term to minimise complications and optimise outcomes. There is also little in the urological literature about pelvic fractures themselves, their causes, grading systems, associated injuries and the mechanism of PFUI. A review of pelvic fracture and male PFUI literature since 1757 was performed to determine pelvic fracture classification, associated injuries and, PFUI classification and management. The outcomes of; suprapubic catheter (SPC) insertion alone, primary open surgical repair (POSR), delayed primary open surgical repair (DPOSR), primary open realignment (POR), primary endoscopic realignment (PER), delayed endoscopic treatment (DET) and delayed urethroplasty (DU) in male adults and children in all major series have been reviewed and collated for rates of restricture (RS), erectile dysfunction (ED) and urinary incontinence (UI). For SPC, POSR, DPOSR, POR, PER, DET and DU; (I) mean RS rate was 97.9%, 53.9%, 18%, 58.3%, 62.0%, 80.2%, 14.4%; (II) mean ED rate was 25.6%, 22.5%, 71%, 37.2%, 23.6%, 31.9%, 12.7%; (III) mean UI rate was 6.7%, 13.6%, 0%, 14.5%, 4.1%, 4.1%, 6.8%; (IV) mean FU in months was 46.3, 29.4, 12, 61, 31.4, 31.8, 54.9. For males with PFUI restricture and new onset ED is lowest following DU whilst UI is lowest following DPOSR. On balance DU offers the best overall outcomes and should be the treatment of choice for PFUI. PMID:29644168

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

New Approaches to Radiation Protection

PubMed Central

Rosen, Eliot M.; Day, Regina; Singh, Vijay K.

2015-01-01

Radioprotectors are compounds that protect against radiation injury when given prior to radiation exposure. Mitigators can protect against radiation injury when given after exposure but before symptoms appear. Radioprotectors and mitigators can potentially improve the outcomes of radiotherapy for cancer treatment by allowing higher doses of radiation and/or reduced damage to normal tissues. Such compounds can also potentially counteract the effects of accidental exposure to radiation or deliberate exposure (e.g., nuclear reactor meltdown, dirty bomb, or nuclear bomb explosion); hence they are called radiation countermeasures. Here, we will review the general principles of radiation injury and protection and describe selected examples of radioprotectors/mitigators ranging from small-molecules to proteins to cell-based treatments. We will emphasize agents that are in more advanced stages of development. PMID:25653923

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

Primary versus delayed repair for bile duct injuries sustained during cholecystectomy: results of a survey of the Association Francaise de Chirurgie

PubMed Central

Iannelli, Antonio; Paineau, Jacques; Hamy, Antoine; Schneck, Anne-Sophie; Schaaf, Caroline; Gugenheim, Jean

2013-01-01

Background Bile duct injuries (BDIs) sustained during a cholecystectomy still remain a major surgical problem, and it is still not clear whether the injury should be repaired immediately or a delayed repair is preferred. Methods A retrospective national French survey was conducted to compare the results of immediate (at time of cholecystectomy), early (within 45 days after a cholecystectomy) and late (beyond 45 days after a cholecystectomy) surgical repair for BDI sustained during a cholecystectomy. Results Forty-seven surgical centres provided 640 cases of bile duct injury sustained during a cholecystectomy of which 543 were analysed for the purpose of the present study. The timing of repair was immediate in 194 cases (35.7%), early in 216 cases (39.8%) and late in 133 cases (24.5%). The type of repair was a suture repair in 157 cases (81%), and a bilio-digestive reconstruction in 37 cases (19%) for immediate repair; a suture repair in 119 cases (55.1%) and a bilio-digestive anastomosis in 96 cases (44.9%) for the early repair; and a bilio-digestive reconstruction in 129 cases (97%) and a suture repair in 4 cases (3%) for late repair. A second procedure was required in 110 cases (56.7%) for immediate repair, 80 cases (40.7%) for early repair (P < 0.05) and in 9 cases (6.8%) for late repair (P < 0.001). Conclusion The timing of surgical repair for a bile duct injury sustained during a cholecystectomy influences significantly the rate of a second procedure and a late repair should be preferred option. PMID:23458568

Magnetic FB injuries: an old yet unresolved hazard.

PubMed

Gregori, Dario; Morra, Bruno; Gulati, Achal

2012-05-14

Among foreign bodies causing injuries in children, magnets have been reported to cause serious complications and being life-threatening. The aim of this study is to design a risk profile and an epidemiological figure of such injuries, for being used for prevention. Data on 366 injuries have been collected from public surveillance databases and from published scientific literature, and compared with the data of the Susy Safe registry, which is a pan-European registry of foreign bodies injuries co-funded by the European Commission. A median age of 48 months was observed, with a 63% prevalence of males is characterizing the injuries. Magnets have a median volume of 87.9 mm(3) vs the median volume of 41.86 mm(3) of the overall foreign bodies of the Susy Safe registry). Only 43% of the magnets were involving only on piece or objects, with a median number of two objects per injury, up to a maximum of 32 objects. Children are referred to the medical care system with a median delay of 3 days after onset of symptoms. Median length of stay in the hospital was 7 days with respect to 1 day as in the Susy Safe registry. Most of complications, and event the death of a child can be eventually re-conducted to either or both a delay in patient referral or appropriate diagnosis. Thus, it is an absolute priority that an information initiative is taken toward families and emergency doctors to avoid unnecessarily delays respectively in patient referral and in diagnosis. Copyright © 2012. Published by Elsevier Ireland Ltd.

Beneficial Biological Effects of Miso with Reference to Radiation Injury, Cancer and Hypertension

PubMed Central

Watanabe, Hiromitsu

2013-01-01

This review describes effects of miso with reference to prevention of radiation injury, cancer and hypertension with a twin focus on epidemiological and experimental evidence. Miso with a longer fermentation time increased crypt survival against radiation injury in mice. When evaluating different types of miso provided by different areas in Japan, miso fermented for a longer period increased the number of surviving crypts, and 180 days of fermentation was the most significant. Dietary administration of 180-day fermented miso inhibits the development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and rat colon cancers in F344 rats. Miso was also effective in suppression of lung tumors, breast tumors in rats and liver tumors in mice. The incidence of gastric tumors of groups of rats given NaCl was higher than those of the groups given miso fermented for longer periods. Moreover, the systolic blood pressure of the Dahl male rat on 2.3% NaCl was significantly increased but that of the SD rat was not. However, the blood pressures of the rats on a diet of miso or commercial control diet (MF) did not increase. Even though miso contains 2.3% NaCl, their blood pressures were as stable as those of rats fed commercial diet containing 0.3% salt. So we considered that sodium in miso might behave differently compared with NaCl alone. These biological effects might be caused by longer fermentation periods. PMID:23914051

Dynamics of wound healing signaling as a potential therapeutic target for radiation-induced tissue damage.

PubMed

Chung, Yih-Lin; Pui, Newman N M

2015-01-01

We hypothesized the histone deacetylase inhibitor phenylbutyrate (PB) has beneficial effects on radiation-induced injury by modulating the expression of DNA repair and wound healing genes. Hamsters received a radiosurgical dose of radiation (40 Gy) to the cheek and were treated with varying PB dosing regimens. Gross alteration of the irradiated cheeks, eating function, histological changes, and gene expression during the course of wound healing were compared between treatment groups. Pathological analysis showed decreased radiation-induced mucositis, facilitated epithelial cell growth, and preventing ulcerative wound formation, after short-term PB treatment, but not after vehicle or sustained PB. The radiation-induced wound healing gene expression profile exhibited a sequential transition from the inflammatory and DNA repair phases to the tissue remodeling phase in the vehicle group. Sustained PB treatment resulted in a prolonged wound healing gene expression profile and delayed the wound healing process. Short-term PB shortened the duration of inflammatory cytokine expression, triggered repeated pulsed expression of cell cycle and DNA repair-regulating genes, and promoted earlier oscillatory expression of tissue remodeling genes. Distinct gene expression patterns between sustained and short-term treatment suggest dynamic profiling of wound healing gene expression can be an important part of a biological therapeutic strategy to mitigate radiation-related tissue injury. © 2015 by the Wound Healing Society.

Delayed Anterior Cruciate Ligament Reconstruction in Young Patients With Previous Anterior Tibial Spine Fractures.

PubMed

Mitchell, Justin J; Mayo, Meredith H; Axibal, Derek P; Kasch, Anthony R; Fader, Ryan R; Chadayammuri, Vivek; Terhune, E Bailey; Georgopoulos, Gaia; Rhodes, Jason T; Vidal, Armando F

2016-08-01

Avulsion fractures of the anterior tibial spine in young athletes are injuries similar to anterior cruciate ligament (ACL) injuries in adults. Sparse data exist on the association between anterior tibial spine fractures (ATSFs) and later ligamentous laxity or injuries leading to ACL reconstruction. To better delineate the incidence of delayed instability or ACL ruptures requiring delayed ACL reconstruction in young patients with prior fractures of the tibial eminence. Case series; Level of evidence, 4. We identified 101 patients between January 1993 and January 2012 who sustained an ATSF and who met inclusion criteria for this study. All patients had been followed for at least 2 years after the initial injury and were included for analysis after completion of a questionnaire via direct contact, mail, and/or telephone. If patients underwent further surgical intervention and/or underwent later ACL reconstruction, clinical records and operative reports pertaining to these secondary interventions were obtained and reviewed. Differences between categorical variables were assessed using the Fisher exact test. The association between time to revision ACL surgery and fracture type was assessed by Kaplan-Meier plots. The association between need for revision ACL surgery and age, sex, and mechanism of surgery was assessed using logistic regression. Nineteen percent of all patients evaluated underwent delayed ACL reconstruction after a previous tibial spine fracture on the ipsilateral side. While there were a higher proportion of ACL reconstructions in type II fractures, there was not a statistically significant difference in the number of patients within each fracture group who went on to undergo later surgery (P = .29). Further, there was not a significant association between fracture type, sex, or mechanism of injury as it related to the progression to later ACL reconstruction. However, there was a significant association between age at the time of injury and progression

Seat-belt injuries of the spine in young children.

PubMed

Rumball, K; Jarvis, J

1992-07-01

Seat-belt fractures of the lumbar spine in adolescents and adults are well recognised but there are few reports of these injuries in young children. We reviewed all seat-belt injuries in skeletally immature patients (Risser 0), seen at a tertiary referral centre between 1974 and 1991. There were ten cases, eight girls and two boys, with an average age of 7.5 years (3 to 13). Four distinct patterns of injury were observed, most commonly at the L2 to L4 level. Paraplegia, which is thought to be uncommon, occurred in three of our ten cases. Four children had intra-abdominal injuries requiring laparotomy. There was a delay in diagnosis either of the spinal or of the intra-abdominal injury in five cases, although all had contusion of the abdominal wall, the 'seat-belt sign'. Treatment of the fractures was conservative, by bed rest and then hyperextension casts. The incidence of this potentially devastating injury can be reduced by the optimal use of restraints, but there is often a delay in diagnosis. Our classification system may aid in the early detection and evaluation of this injury.

Safety of Performing a Delayed Anastomosis During Damage Control Laparotomy in Patients with Destructive Colon Injuries

PubMed Central

Ordoñez, Carlos A; Pino, Luis F; Badiel, Marisol; Sánchez, Alvaro I; Loaiza, Jhon; Ballestas, Leonardo; Puyana, Juan Carlos

2011-01-01

Background Recent studies report the safety and feasibility of performing delayed anastomosis (DA) in patients undergoing damage control laparotomy (DCL) for destructive colon injuries (DCI). Despite accumulating experience in both civilian and military trauma, questions regarding how to best identify high risk patients and minimize the number of anastomosis-associated complications remain. Our current practice is to perform a definitive closure of the colon during DCL, unless there is persistent acidosis, bowel wall edema, or evidence of intra-abdominal abscess. In this study, we evaluated the safety of this approach by comparing outcomes of patients with DCI who underwent definitive closure of the colon during DCL versus patients managed with colostomy with or without DCL. Methods We performed a retrospective chart review of patients with penetrating DCI during 2003–2009. Severity of injury, surgical management, and clinical outcome were assessed. Results Sixty patients with severe gunshot wounds (GSW) and 3 patients with stab wounds were included in the analysis. DCL was required in 30 patients, all with GSW. Three patients died within the first 48 hours, 3 underwent colostomy, and 24 were managed with DA. Thirty-three patients were managed with standard laparotomy: 26 patients with primary anastomosis, and 7 with colostomy. Overall mortality rate was 9.5%. Three late deaths occurred in the DCL group, and only one death was associated with an anastomotic leak. Conclusions Performing a DA in DCI during DCL is a reliable and feasible approach as long as severe acidosis, bowel wall edema, and/or persistent intra-abdominal infections are not present. PMID:22182861

Safety of performing a delayed anastomosis during damage control laparotomy in patients with destructive colon injuries.

PubMed

Ordoñez, Carlos A; Pino, Luis F; Badiel, Marisol; Sánchez, Alvaro I; Loaiza, Jhon; Ballestas, Leonardo; Puyana, Juan Carlos

2011-12-01

Recent studies report the safety and feasibility of performing delayed anastomosis (DA) in patients undergoing damage control laparotomy (DCL) for destructive colon injuries (DCIs). Despite accumulating experience in both civilian and military trauma, questions regarding how to best identify high-risk patients and minimize the number of anastomosis-associated complications remain. Our current practice is to perform a definitive closure of the colon during DCL, unless there is persistent acidosis, bowel wall edema, or evidence of intra-abdominal abscess. In this study, we evaluated the safety of this approach by comparing outcomes of patients with DCI who underwent definitive closure of the colon during DCL versus patients managed with colostomy with or without DCL. We performed a retrospective chart review of patients with penetrating DCI during 2003 to 2009. Severity of injury, surgical management, and clinical outcome were assessed. Sixty patients with severe gunshot wounds and three patients with stab wounds were included in the analysis. DCL was required in 30 patients, all with gunshot wounds. Three patients died within the first 48 hours, three underwent colostomy, and 24 were managed with DA. Thirty-three patients were managed with standard laparotomy: 26 patients with primary anastomosis and 7 with colostomy. Overall mortality rate was 9.5%. Three late deaths occurred in the DCL group, and only one death was associated with an anastomotic leak. Performing a DA in DCI during DCL is a reliable and feasible approach as long as severe acidosis, bowel wall edema, and/or persistent intra-abdominal infections are not present.

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

Editorial Commentary: "Defer No Time, Delays Have Dangerous Ends" (Henry VI, Shakespeare): Delayed Anterior Cruciate Ligament Reconstruction Has Consequences.

PubMed

Siegel, Mark G

2018-06-01

There continues to be controversy over the timing of anterior cruciate ligament (ACL) surgery. Early or delayed intervention after ACL injury is a topic that has not been settled. The issue is whether ACL tears should have surgery performed in an expedient manner. Or is delay an option with no repercussions to the health of the knee? My associates in nonsurgical specialties wave the New England Journal of Medicine to support their view that surgery is not needed. I routinely espouse the literature confirming that delay of surgery may cause future damage. It is now established that a failure to intervene in a timely manner does cause additional damage. I stand vindicated and can affirm to my colleagues that I have found the answer. There is no longer any doubt or equivocation. Delay in reconstructing an unstable knee does cause damage. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

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

The Effects of Injury Magnitude on the Kinetics of the Acute Phase Response

PubMed Central

Bauzá, Graciela; Miller, Glenn; Kaseje, Neema; Wigner, Nathan A.; Wang, Zhongyan; Gerstenfeld, Louis C.; Burke, Peter A.

2013-01-01

Background The acute-phase response (APR) is critical to the body's ability to successfully respond to injury. A murine model of closed unilateral femur fractures and bilateral femur fracture were used to study the effect of injury magnitude on this response. Methods Standardized unilateral femur fracture and bilateral femur fracture in mice were performed. The femur fracture sites, livers, and serum were harvested over time after injury. Changes in mRNA expression of cytokines, hepatic acute-phase proteins, and serum cytokines overtime were measured. Results There was a rapid and short-lived hepatic APR to fracture injuries. The overall pattern in both models was similar. Both acute-phase proteins' mRNA (fibrinogen-γ and serum amyloid A-3) showed increased mRNA expression over baseline within the first 48 hours and their levels positively correlated with the extent of injury. However, increased severity of injury resulted in a delayed induction of the APR. A similar effect on the gene expression of cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) at the fracture site was seen. Serum IL-6 levels increased with increased injury and showed no delay between injury models. Conclusions Greater severity of injury resulted in a delayed induction of the liver's APR and a diminished expression of cytokines at the fracture site. Serum IL-6 levels were calibrated to the extent of the injury, and changes may represent mechanisms by which the local organ responses to injury are regulated by the injury magnitude. PMID:20693926

Associations between Deceased-Donor Urine Injury Biomarkers and Kidney Transplant Outcomes

PubMed Central

Reese, Peter P.; Hall, Isaac E.; Weng, Francis L.; Schröppel, Bernd; Doshi, Mona D.; Hasz, Rick D.; Thiessen-Philbrook, Heather; Ficek, Joseph; Rao, Veena; Murray, Patrick; Lin, Haiqun

2016-01-01

Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m2. In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant. PMID:26374609

High-Dose Selenium for the Mitigation of Radiation Injury: A Pilot Study in a Rat Model

PubMed Central

Sieber, Fritz; Muir, Sarah A.; Cohen, Eric P.; North, Paula E.; Fish, Brian L.; Irving, Amy A.; Mäder, Marylou; Moulder, John E.

2009-01-01

The purpose of this study was to evaluate in an animal model the safety and efficacy of dietary supplementation with high doses of selenium for the mitigation of the type of radiation injury that might be sustained during a nuclear accident or an act of radiological terrorism. Age-matched male rats were exposed to 10 Gy (single dose) of total-body irradiation (TBI) followed by a syngeneic bone marrow transplant, then randomized to standard drinking water or drinking water supplemented with sodium selenite or seleno-L-methionine. At 21 weeks after TBI, most rats on standard drinking water had severe renal failure with a mean blood urea nitrogen (BUN) level of 124 ± 29 mg/dl (geometric mean ± SE) whereas rats on selenium-supplemented drinking water (100 μg/day) had a mean BUN level of 67 ± 12 mg/dl. The mitigating effect of selenium was confirmed by histopathological analyses. None of the animals on high-dose selenium showed signs of selenium toxicity. Our results suggest that dietary supplementation with high-dose selenium may provide a safe, effective and practical way to mitigate radiation injury to kidneys. PMID:19267564

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

A standardized Hippophae extract (SBL-1) counters neuronal tissue injuries and changes in neurotransmitters: implications in radiation protection.

PubMed

Bala, Madhu; Gupta, Vanita; Prasad, Jagdish

2017-12-01

Effects of a radioprotective, standardized leaf extract (code SBL-1) from traditional medicinal plant, sea buckthorn [Hippophae rhamnoides L. (Elaeagnaceae)], on neurotransmitters and brain injuries in rats showing radiation-induced conditioned taste aversion (CTA), are not known. Understanding CTA in rats is important because its process is considered parallel to nausea and vomiting in humans. This study investigated the levels of neurotransmitters, antioxidant defences and histological changes in rats showing radiation CTA, and their modification by SBL-1. The inbred male Sprague-Dawley rats (age 65 days, weighing 190 ± 10 g) were used. Saccharin-preferring rats were selected using standard procedure and divided into groups. Group I (untreated control) was administered sterile water, group II was 60 Co-γ-irradiated (2 Gy), and group III was administered SBL-1 before irradiation. Observations were recorded up to day 5. Irradiation (2 Gy) caused (i) non-recoverable CTA (≥ 64.7 ± 5.0%); (ii) degenerative changes in cerebral cortex, amygdala and hippocampus; (iii) increases in brain dopamine (DA, 63.4%), norepinephrine (NE, 157%), epinephrine (E, 233%), plasma NE (103%) and E (160%); and (iv) decreases in brain superoxide dismutase (67%), catalase (60%) and glutathione (51%). SBL-1 treatment (12 mg/kg body weight) 30 min before irradiation (i) countered brain injuries, (ii) reduced CTA (38.7 ± 3.0%, day 1) and (iii) normalized brain DA, NE, E, superoxide dismutase, catalase and CTA from day 3 onwards. Radiation CTA was coupled with brain injuries, disturbances in neurotransmitters and antioxidant defences. SBL-1 pretreatment countered these disturbances, indicating neuroprotective action.

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

Emodin protects mice against radiation-induced mortality and intestinal injury via inhibition of apoptosis and modulation of p53.

PubMed

Wang, Jing; Zhang, Yue; Zhu, Qiuzhen; Liu, Yulan; Cheng, Hao; Zhang, Yuefan; Li, Tiejun

2016-09-01

The aim of this study was to explore the protective effect of emodin, a plant-derived anthraquinone, against gamma radiation-induced mortality and intestinal injury in mice, and to investigate the radioprotective molecular mechanism. C57BL/6 male mice were pre-treated with emodin for 7days via oral gavage before gamma radiation. We found that pretreatment with emodin prolonged mice survival time after 9Gy total body irradiation (TBI). Mice were sacrificed at 1 week after 7Gy TBI, we found that emodin attenuated intestinal morphological changes and increased villus height, crypt numbers, and reduced villus and crypt apoptosis as well as inhibited the expression of p53. MTT assay, flow cytometry, Hoechst 33258 staining, real-time PCR, and Western blotting indicated that emodin pretreatment can effectively increase human umbilical venous endothelial cells (HUVECs) viability and attenuate cell apoptosis; it also inhibited the expression of p53, Bax, and Caspase3 in HUVECs after irradiation. In summary, these results suggest the potential of emodin as an effective radioprotectant against radiation-induced intestinal injury. Copyright © 2016 Elsevier B.V. All rights reserved.

Delayed degeneration of the left fornical crus with verbal memory impairment in a patient with mild traumatic brain injury

PubMed Central

Jang, Sung Ho; Seo, Jeong Pyo

2017-01-01

Abstract Rationale: We report on a patient who showed delayed degeneration of the left fornical crus with verbal memory impairment following mild traumatic brain injury (TBI), which was demonstrated by diffusion tensor tractography (DTT). Patient concerns: fter flexion and hyperextension of her head to the opposite side, the patient experienced a dazed feeling for a while at the time of head trauma. The patient's Glasgow Coma Scale score was 15, and mini-mental state examination score was 30. Diagnoses: A 50-year-old right-handed female with 12 years of education suffered from head trauma resulting from a car accident. Interventions: A The patient showed normal memory function at one year after onset: the Memory Assessment Scale (global memory: 124 (95 percentile (%ile)), verbal memory: 111 (77%ile), and visual memory: 132 (98%ile) (A percentile is a measure used in statistics indicating the value below which a given percentage of observations in a group of observations fall). However, the patient began to experience decline of memory function such as forgetfulness at approximately 1.5 years after onset. On the 2-year evaluation, she showed decrement of memory function (global memory: 108 (70%ile), verbal memory: 86 (18%ile), and visual memory: 129 (97%ile). Outcomes: On 1-year DTT, the integrity of the fornix was well preserved between the fornical column and fornical crus. However, on 2-year DTT, a discontinuation was observed in the left fornical crus. Lessons: Delayed degeneration of the left fornical crus was demonstrated in a patient who showed delayed onset of verbal memory impairment following mild TBI. PMID:29390470

Effects of yak-activated protein on hematopoiesis and related cytokines in radiation-induced injury in mice.

PubMed

Duan, Yabin; Yao, Xingchen; Zhu, Junbo; Li, Yongping; Zhang, Juanling; Zhou, Xuejiao; Qiao, Yijie; Yang, Meng; Li, Xiangyang

2017-12-01

The aim of the present study was to investigate the protective effects of yak-activated protein on hematopoiesis and cytokine function in radiation-induced injury in mice. A total of 180 Kunming mice were randomly divided into three groups (A, B and C). Of these, 60 were randomly divided into a normal control group, a radiation model group, a positive control group and 3 yak-activated protein groups (high, medium and low dose groups; 10, 5 and 2.5 mg/kg, respectively). The other 120 mice were used for the subsequent experiments on days 7 and 14 following radiation. Yak-activated protein was administered orally to mice in the treatment groups and an equal volume of saline was administered orally to mice in the normal control and radiation model groups for 14 days. The positive control group received amifostine (150 mg/kg) via intraperitoneal injection. With the exception of the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body once. Changes in the peripheral hemogram, thymus and spleen indices, DNA content in the bone marrow, interleukin (IL)-2 and IL-6 levels, and the expression levels of B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) following irradiation were assessed. The low dose of yak-activated protein significantly increased Spleen indices in mice 14 days after irradiation and the high and middle dose of yak-activated protein significantly increased Thymus indices in mice 14 days after irradiation (P<0.05) compared with the control group. In addition, hemogram results increased gradually in the low-yak-activated protein dose group and were significantly higher 7 days after irradiation compared with the radiation model group (P<0.05). The DNA content in the bone marrow was markedly increased in the yak-activated protein groups, and increased significantly in the low dose group at 7 days post-irradiation compared with the radiation model group (P<0.05). The IL-2 content was significantly

Effects of yak-activated protein on hematopoiesis and related cytokines in radiation-induced injury in mice

PubMed Central

Duan, Yabin; Yao, Xingchen; Zhu, Junbo; Li, Yongping; Zhang, Juanling; Zhou, Xuejiao; Qiao, Yijie; Yang, Meng; Li, Xiangyang

2017-01-01

The aim of the present study was to investigate the protective effects of yak-activated protein on hematopoiesis and cytokine function in radiation-induced injury in mice. A total of 180 Kunming mice were randomly divided into three groups (A, B and C). Of these, 60 were randomly divided into a normal control group, a radiation model group, a positive control group and 3 yak-activated protein groups (high, medium and low dose groups; 10, 5 and 2.5 mg/kg, respectively). The other 120 mice were used for the subsequent experiments on days 7 and 14 following radiation. Yak-activated protein was administered orally to mice in the treatment groups and an equal volume of saline was administered orally to mice in the normal control and radiation model groups for 14 days. The positive control group received amifostine (150 mg/kg) via intraperitoneal injection. With the exception of the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body once. Changes in the peripheral hemogram, thymus and spleen indices, DNA content in the bone marrow, interleukin (IL)-2 and IL-6 levels, and the expression levels of B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) following irradiation were assessed. The low dose of yak-activated protein significantly increased Spleen indices in mice 14 days after irradiation and the high and middle dose of yak-activated protein significantly increased Thymus indices in mice 14 days after irradiation (P<0.05) compared with the control group. In addition, hemogram results increased gradually in the low-yak-activated protein dose group and were significantly higher 7 days after irradiation compared with the radiation model group (P<0.05). The DNA content in the bone marrow was markedly increased in the yak-activated protein groups, and increased significantly in the low dose group at 7 days post-irradiation compared with the radiation model group (P<0.05). The IL-2 content was significantly

Bicycle and motorcycle wheel spoke injury in children.

PubMed

Mak, C Y; Chang, J H T; Lui, T H; Ngai, W K

2015-04-01

To review bicycle and motorcycle wheel spoke injuries around the foot and ankle in 24 children. Medical records of 12 boys and 12 girls aged 2 to 11 (mean, 5.3) years who presented with an isolated posterior heel injury caused by wheel spokes of a motorcycle (n=9) or bicycle (n=15) were reviewed. All 9 motorcycle injury patients and 8 of 15 bicycle injury patients had lacerations. The remaining 7 bicycle injury patients had abrasions and developed skin necrosis and ulcerations, with 5 requiring debridement. The most common site of laceration was the posterolateral heel; 7 of these patients had deep soft tissue injury, and in 5 the Achilles tendon was partially cut or completely severed. The mean number of operations was 2.2 in the motorcycle group and 1.3 in the bicycle group. Seven patients with severe skin loss required skin grafting or flap surgery for wound coverage. The mean time from injury to definitive treatment was 8.2 days. The mean length of hospital stay was 18.4 days in the motorcycle group and 8.1 days in the bicycle group. Delayed definitive treatment was associated with more operations (r=0.499, p=0.013) and longer hospital stay (r=0.567, p=0.004). Wheel spoke injuries may result in severe soft tissue damage and bony trauma. Poor prognostic factors included high-energy injury, contamination and infection, and delayed treatment.

Age-Dependent Schwann Cell Phenotype Regulation Following Peripheral Nerve Injury.

PubMed

Chen, Wayne A; Luo, T David; Barnwell, Jonathan C; Smith, Thomas L; Li, Zhongyu

2017-12-01

Schwann cells are integral to the regenerative capacity of the peripheral nervous system, which declines after adolescence. The mechanisms underlying this decline are poorly understood. This study sought to compare the protein expression of Notch, c-Jun, and Krox-20 after nerve crush injury in adolescent and young adult rats. We hypothesized that these Schwann cell myelinating regulatory factors are down-regulated after nerve injury in an age-dependent fashion. Adolescent (2 months old) and young adult (12 months old) rats (n = 48) underwent sciatic nerve crush injury. Protein expression of Notch, c-Jun, and Krox-20 was quantified by Western blot analysis at 1, 3, and 7 days post-injury. Functional recovery was assessed in a separate group of animals (n = 8) by gait analysis (sciatic functional index) and electromyography (compound motor action potential) over an 8-week post-injury period. Young adult rats demonstrated a trend of delayed onset of the dedifferentiating regulatory factors, Notch and c-Jun, corresponding to the delayed functional recovery observed in young adult rats compared to adolescent rats. Compound motor action potential area was significantly greater in adolescent rats relative to young adult rats, while amplitude and velocity trended toward statistical significance. The process of Schwann cell dedifferentiation following peripheral nerve injury shows different trends with age. These trends of delayed onset of key regulatory factors responsible for Schwann cell myelination may be one of many possible factors mediating the significant differences in functional recovery between adolescent and young adult rats following peripheral nerve injury.

Intermittent catheterization with a hydrophilic-coated catheter delays urinary tract infections in acute spinal cord injury: a prospective, randomized, multicenter trial.

PubMed

Cardenas, Diana D; Moore, Katherine N; Dannels-McClure, Amy; Scelza, William M; Graves, Daniel E; Brooks, Monifa; Busch, Anna Karina

2011-05-01

To investigate whether intermittent catheterization (IC) with a hydrophilic-coated catheter delays the onset of the first symptomatic urinary tract infection (UTI) and reduces the number of symptomatic UTIs in patients with acute spinal cord injury (SCI) compared with IC with standard, uncoated catheters. A prospective, randomized, parallel-group trial. Fifteen North American SCI centers. Participants were followed up while in the hospital or rehabilitation unit (institutional period) and up to 3 months after institutional discharge (community period). The maximal study period was 6 months. A total of 224 subjects with traumatic SCI of less than 3 months' duration who use IC. The participants were randomized within 10 days of starting IC to either single-use hydrophilic-coated (SpeediCath) or polyvinyl chloride uncoated (Conveen) catheters. The time from the first catheterization to the first antibiotic-treated symptomatic UTI was measured as well as the total number of symptomatic UTIs during the study period. The time to the first antibiotic-treated symptomatic UTI was significantly delayed in the hydrophilic-coated catheter group compared with the uncoated catheter group. The delay corresponded to a 33% decrease in the daily risk of developing the first symptomatic UTI among participants who used the hydrophilic-coated catheter. In the institutional period, the incidence of antibiotic-treated symptomatic UTIs was reduced by 21% (P < .05) in the hydrophilic-coated catheter group. The use of a hydrophilic-coated catheter for IC is associated with a delay in the onset of the first antibiotic-treated symptomatic UTI and with a reduction in the incidence of symptomatic UTI in patients with acute SCI during the acute inpatient rehabilitation. Using a hydrophilic-coated catheter could minimize UTI-related complications, treatment costs, and rehabilitation delays in this group of patients, and reduce the emergence of antibiotic-resistant organisms. Copyright © 2011

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

PubMed Central

Akita, Sadanori; Akino, Kozo; Hirano, Akiyoshi; Ohtsuru, Akira; Yamashita, Shunichi

2010-01-01

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years. PMID:21151652

Delayed Gastric Emptying after Living Donor Hepatectomy for Liver Transplantation

PubMed Central

Griesemer, Adam D.; Parsons, Ronald F.; Graham, Jay A.; Emond, Jean C.; Samstein, Benjamin

2014-01-01

Delayed gastric emptying is a significant postoperative complication of living donor hepatectomy for liver transplantation and may require endoscopic or surgical intervention in severe cases. Although the mechanism of posthepatectomy delayed gastric emptying remains unknown, vagal nerve injury during intraoperative dissection and adhesion formation postoperatively between the stomach and cut liver surface are possible explanations. Here, we present the first reported case of delayed gastric emptying following fully laparoscopic hepatectomy for living donor liver transplantation. Additionally, we also present a case in which symptoms developed after open right hepatectomy, but for which dissection for left hepatectomy was first performed. Through our experience and these two specific cases, we favor a neurovascular etiology for delayed gastric emptying after hepatectomy. PMID:25610698

Bowel injury associated with pelvic radiotherapy

NASA Astrophysics Data System (ADS)

François, Agnès; Milliat, Fabien; Vozenin-Brotons, Marie-Catherine

2005-02-01

Radiation therapists have to deal with the difficulty to give an efficient radiation dose to the tumor without generating unacceptable normal tissue injury. Acute reactions are experienced in most of the patients and are characterized by diarrhea resulting from intestinal mucosal injury. In some cases, intestinal wall fibrosis may develop, with hazard of occlusion syndrome. The only therapeutic recourse consists of surgical resection of the injured bowel.

Current methods of diagnosis and management of ureteral injuries.

PubMed

Armenakas, N A

1999-04-01

A delay in diagnosis is the most important contributory factor in morbidity related to ureteral injury. The difficulty in making the diagnosis can be minimized by maintenance of a high index of suspicion and the timely performance of the appropriate radiographic and intraoperative evaluations. A decision on the timing of repair of the ureteral injury is based on the patient's overall condition, promptness of injury recognition, and proper injury staging. Ideally, when identified promptly, ureteral injuries should be repaired immediately. However, once there has been a delay in diagnosis or in the case of an unstable patient, temporizing measures can be used for urinary diversion. With the availability of simple, minimally invasive techniques to manage urinary extravasation and the absence of any risk of ureteral hemorrhage, ureteral reconstruction can be safely deferred until an opportune time during the recovery period. Successful surgical management requires familiarity with the broad reconstructive armamentarium and meticulous attention to the specific details of each procedure. Through adherence to the diagnostic and therapeutic principles outlined, complications can be minimized and renal preservation can be maximized in patients sustaining ureteral injuries.

Clinical Practice Guidelines for Prevention, Diagnosis and Management of Early and Delayed-onset Ocular Injuries Due to Mustard Gas Exposure

PubMed Central

Rajavi, Zhale; Safi, Sare; Javadi, Mohammad Ali; Jafarinasab, Mohammad Reza; Feizi, Sepehr; Moghadam, Mohammadreza Sedighi; Jadidi, Khosrow; Babaei, Mahmoud; Shirvani, Armin; Baradaran-Rafii, Alireza; Mohammad-Rabei, Hossein; Ziaei, Hossein; Ghassemi-Broumand, Mohammad; Baher, Siamak Delfaza; Naderi, Mostafa; Panahi-Bazaz, Mahmoodreza; Zarei-Ghanavati, Siamak; Hanjani, Shahriar; Ghasemi, Hassan; Salouti, Ramin; Pakbin, Mojgan; Kheiri, Bahareh

2017-01-01

Purpose: To develop clinical practice guidelines (CPGs) for prevention, diagnosis, treatment and follow-up of ocular injuries caused by exposure to mustard gas. Methods: The clinical questions were designed by the guideline team. Websites and databases including National Guidelines Clearinghouse, National Institute for Clinical Excellence, Cochrane, and PubMed were searched to find related CPGs and explore possible answers to the clinical questions. Since there were no relevant CPGs in the literature, related articles in Persian and English languages were extracted. Each article along with its level of evidence was summarized. Additionally, hand search was performed by looking the reference list of each article. Consequently, recommendations were developed considering the clinical benefits and side effects of each therapeutic modality. The recommendations were re-evaluated in terms of customization criteria. All recommendations along with the related evidence were scored from 1 to 9 by experts from all medical universities of Iran. The level of agreement among the experts was evaluated by analyzing the given scores. Results: The agreement was achieved for all recommendations. The experts suggested a number of minor modifications which were applied to the recommendations. Finally, CPGs were developed with 98 recommendations under three major domains including prevention of injury, diagnosis and management of the acute and delayed-onset mustard gas ocular injuries. Conclusion: Considering the lack of CPGs for the prevention, diagnosis, and management of mustard gas-induced keratitis, these recommendations would be useful to prevent the serious ocular complications of mustard gas and standardize eye care services to the affected individuals. PMID:28299009

Clinical Practice Guidelines for Prevention, Diagnosis and Management of Early and Delayed-onset Ocular Injuries Due to Mustard Gas Exposure.

PubMed

Rajavi, Zhale; Safi, Sare; Javadi, Mohammad Ali; Jafarinasab, Mohammad Reza; Feizi, Sepehr; Moghadam, Mohammadreza Sedighi; Jadidi, Khosrow; Babaei, Mahmoud; Shirvani, Armin; Baradaran-Rafii, Alireza; Mohammad-Rabei, Hossein; Ziaei, Hossein; Ghassemi-Broumand, Mohammad; Baher, Siamak Delfaza; Naderi, Mostafa; Panahi-Bazaz, Mahmoodreza; Zarei-Ghanavati, Siamak; Hanjani, Shahriar; Ghasemi, Hassan; Salouti, Ramin; Pakbin, Mojgan; Kheiri, Bahareh

2017-01-01

To develop clinical practice guidelines (CPGs) for prevention, diagnosis, treatment and follow-up of ocular injuries caused by exposure to mustard gas. The clinical questions were designed by the guideline team. Websites and databases including National Guidelines Clearinghouse, National Institute for Clinical Excellence, Cochrane, and PubMed were searched to find related CPGs and explore possible answers to the clinical questions. Since there were no relevant CPGs in the literature, related articles in Persian and English languages were extracted. Each article along with its level of evidence was summarized. Additionally, hand search was performed by looking the reference list of each article. Consequently, recommendations were developed considering the clinical benefits and side effects of each therapeutic modality. The recommendations were re-evaluated in terms of customization criteria. All recommendations along with the related evidence were scored from 1 to 9 by experts from all medical universities of Iran. The level of agreement among the experts was evaluated by analyzing the given scores. The agreement was achieved for all recommendations. The experts suggested a number of minor modifications which were applied to the recommendations. Finally, CPGs were developed with 98 recommendations under three major domains including prevention of injury, diagnosis and management of the acute and delayed-onset mustard gas ocular injuries. Considering the lack of CPGs for the prevention, diagnosis, and management of mustard gas-induced keratitis, these recommendations would be useful to prevent the serious ocular complications of mustard gas and standardize eye care services to the affected individuals.

Comparative proteomic profiling and possible toxicological mechanism of acute injury induced by carbon ion radiation in pubertal mice testes

NASA Astrophysics Data System (ADS)

Zhang, Hong

2016-07-01

We investigated potential mechanisms of acute injury in pubertal mice testes after exposure to carbon ion radiation (CIR). Serum testosterone was measured following whole-body irradiation with a 2Gy carbon ion beam. Comparative proteomic profiling and Western blotting were applied to identify potential biomarkers and measure protein expression, and terminal dUTP nick end-labeling (TUNEL) was performed to detect apoptotic cells. Immunohistochemistry and immunofluorescence were used to investigate protein localization. Serum testosterone was lowest at 24h after CIR, and 10 differentially expressed proteins were identified at this time point that included eIF4E, an important regulator of initiation that combines with mTOR and 4EBP1 to control protein synthesis via the mTOR signalling pathway during proliferation and apoptosis. Protein expression and localization studies confirmed their association with acute injury following exposure to CIR. These three proteins may be useful molecular markers for detecting abnormal spermatogenesis following exposure to environmental and cosmic radiation

Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase 18F-FET PET accuracy without dynamic scans.

PubMed

Lohmann, Philipp; Stoffels, Gabriele; Ceccon, Garry; Rapp, Marion; Sabel, Michael; Filss, Christian P; Kamp, Marcel A; Stegmayr, Carina; Neumaier, Bernd; Shah, Nadim J; Langen, Karl-Josef; Galldiks, Norbert

2017-07-01

We investigated the potential of textural feature analysis of O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET) PET to differentiate radiation injury from brain metastasis recurrence. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic 18 F-FET PET. Tumour-to-brain ratios (TBRs) of 18 F-FET uptake and 62 textural parameters were determined on summed images 20-40 min post-injection. Tracer uptake kinetics, i.e., time-to-peak (TTP) and patterns of time-activity curves (TAC) were evaluated on dynamic PET data from 0-50 min post-injection. Diagnostic accuracy of investigated parameters and combinations thereof to discriminate between brain metastasis recurrence and radiation injury was compared. Diagnostic accuracy increased from 81 % for TBR mean alone to 85 % when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBR max alone was 83 % and increased to 85 % after combination with the textural parameters Coarseness, Short-zone emphasis, or Correlation. Analysis of TACs resulted in an accuracy of 70 % for kinetic pattern alone and increased to 83 % when combined with TBR max . Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic 18 F-FET PET scans. • Textural feature analysis provides quantitative information about tumour heterogeneity • Textural features help improve discrimination between brain metastasis recurrence and radiation injury • Textural features might be helpful to further understand tumour heterogeneity • Analysis does not require a more time consuming dynamic PET acquisition.

STUDY ON THE CHEMICAL PROTECTION AGAINST RADIATION INJURIES. II. EFFECT OF VITAMINS B$sub 2$, B$sub 6$, H, C AND PANTOTHENIC ACID

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

Hashimoto, T.

Pure-bred mice were irradiated with a single exposure of 800 r (lethal dose) and 680 r (LD/sub 5//sub 0/) of x rays. No protective effect of vit. B/ sub 2/, B/sub 6/, or pantothenic acid against radiation injury was recognized. Only vit. B/sub 1/ was effective. These 2 results indicate that the protective effect of vit. B/sub 1/ is due to activation of SH base. Neither pantothenic acid nor pantothein had any radiation-protective effect, but the combined use of pantothenic acid with beta -mercaptoethylamine was effective. Probably the protection is due to some mechanism other than the SH group. Vit.more » H gave no protection, and there was some relationship between the dosage of vit. H and its toxity. Vit. C gave some protection against radiation injury, believed to be due to cooperation with glutathione in the oxidation-reduction system. This mechanism seems to be different from that of other types of radiation-protective agents. (Abstr. Japan Med., 1: No. 8, 1961)« less

The Pathogenesis and Therapy of Combined Radiation Injury

DTIC Science & Technology

2006-10-01

17 Table 7. Effects of Different Biological Respose Modifiers on Blood Cell Recovery After C o m b ined Inju ry...16 Table 7. Effects of Different Biological Respose Modifiers on Blood Cell Recovery After Combined Injury. Group 7 days 14 days 21 days 30 days...injury may become self -de- structive, and may be capable of explaining (in part) the more severe out- comes of combined injuries compared with acute

Biochemical metabolic changes assessed by 31P magnetic resonance spectroscopy after radiation-induced hepatic injury in rabbits

PubMed Central

Yu, Ri-Sheng; Hao, Liang; Dong, Fei; Mao, Jian-Shan; Sun, Jian-Zhong; Chen, Ying; Lin, Min; Wang, Zhi-Kang; Ding, Wen-Hong

2009-01-01

AIM: To compare the features of biochemical metabolic changes detected by hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) with the liver damage score (LDS) and pathologic changes in rabbits and to investigate the diagnostic value of 31P MRS in acute hepatic radiation injury. METHODS: A total of 30 rabbits received different radiation doses (ranging 5-20 Gy) to establish acute hepatic injury models. Blood biochemical tests, 31P MRS and pathological examinations were carried out 24 h after irradiation. The degree of injury was evaluated according to LDS and pathology. Ten healthy rabbits served as controls. The MR examination was performed on a 1.5 T imager using a 1H/31P surface coil by the 2D chemical shift imaging technique. The relative quantities of phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured. The data were statistically analyzed. RESULTS: (1) Relative quantification of phosphorus metabolites: (a) ATP: there were significant differences (P < 0.05) (LDS-groups: control group vs mild group vs moderate group vs severe group, 1.83 ± 0.33 vs 1.55 ± 0.24 vs 1.27 ± 0.09 vs 0.98 ± 0.18; pathological groups: control group vs mild group vs moderate group vs severe group, 1.83 ± 0.33 vs 1.58 ± 0.25 vs 1.32 ± 0.07 vs 1.02 ± 0.18) of ATP relative quantification among control group, mild injured group, moderate injured group, and severe injured group according to both LDS grading and pathological grading, respectively, and it decreased progressively with the increased degree of injury (r = -0.723, P = 0.000). (b) PME and Pi; the relative quantification of PME and Pi decreased significantly in the severe injured group, and the difference between the control group and severe injured group was significant (P < 0.05) (PME: LDS-control group vs LDS-severe group, 0.86 ± 0.23 vs 0.58 ± 0.22, P = 0.031; pathological control group vs pathological severe group, 0.86 ± 0.23 vs 0.60 �

Delayed versus immediate pushing in second stage of labor.

PubMed

Kelly, Mary; Johnson, Eileen; Lee, Vickie; Massey, Liz; Purser, Debbie; Ring, Karen; Sanderson, Stephanye; Styles, Juanita; Wood, Deb

2010-01-01

Comparison of two different methods for management of second stage of labor: immediate pushing at complete cervical dilation of 10 cm and delayed pushing 90 minutes after complete cervical dilation. This study was a randomized clinical trial in a labor and delivery unit of a not-for-profit community hospital. A sample of 44 nulliparous mothers with continuous epidural anesthesia were studied after random assignment to treatment groups. Subjects were managed with either immediate or delayed pushing during the second stage of labor at the time cervical dilation was complete. The primary outcome measure was the length of pushing during second stage of labor. Secondary outcomes included length of second stage of labor, maternal fatigue and perineal injuries, and fetal heart rate decelerations. Two-tailed, unpaired Student's t-tests and Chi-square analysis were used for data analysis. Level of significance was set at p < .01 following a Bonferroni correction for multiple t-tests. A total of 44 subjects received the study intervention (N = 28 immediate pushing; N = 16 delayed pushing). The delayed pushing group had significantly shorter amount of time spent in pushing compared with the immediate pushing group (38.9 +/- 6.9 vs. 78.7 +/- 7.9 minutes, respectively, p = .002). Maternal fatigue scores, perineal injuries, and fetal heart rate decelerations were similar for both groups. Delaying pushing for up to 90 minutes after complete cervical dilation resulted in a significant decrease in the time mothers spent pushing without a significant increase in total time in second stage of labor.In clinical practice, healthcare providers sometimes resist delaying the onset of pushing after second stage of labor has begun because of a belief it will increase labor time. This study's finding of a 51% reduction in pushing time when mothers delay pushing for up to 90 minutes, with no significant increase in overall time for second stage of labor, disputes that concern.

Ghrelin accelerates wound healing in combined radiation and wound injury in mice.

PubMed

Liu, Cong; Hao, Yuhui; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Li, Rong

2017-02-01

Impaired wound healing caused by radiation happens frequently in clinical practice, and the exact mechanisms remain partly unclear. Various countermeasures have been taken to tackle with this issue. Ghrelin was considered as a potent endogenous growth hormone-releasing peptide, and its role in enhancing wound repair and regeneration was firstly investigated in whole-body irradiated (γ-ray) mice in this study. Collagen deposition and neovascularization were mostly discussed. The results demonstrated that ghrelin administration promoted cutaneous wound healing in irradiated mice, followed with reduced average wound closure time, increased spleen index (SI) and improved haematopoiesis. After isolation and analysis of granulation tissues in combined radiation and wound injury (CRWI) mice treated with and without ghrelin, a phenomenon of increased DNA, hexosamine, nitrate and nitrite synthesis, elevated collagen content and enhanced neovascularization was observed after ghrelin treatment. Western blotting indicated that ghrelin also increased the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β), both responsible for wound healing. However, previous administration of growth hormone secretagogue receptor 1a (GHS-R1a) blocker blunted these therapeutic effects of ghrelin on CRWI mice. Our results identify ghrelin as a novel peptide that could be used for radiation-induced impaired wound healing. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Injuries to the duodenum and pancreas in 42 operated cases].

PubMed

Kiss, L; Remescu, A

2001-01-01

42 consecutive patients who sustained injuries to the duodenum or/and pancreas were admitted to our hospital. Over a twenty year period 32 blunt injuries and 10 penetrating injuries were encountered. Penetrating injuries were always suspected and treated by time: following blunt injury diagnostic delay was encountered in 14 patients and insufficient surgical procedure because of intra-operative misinterpretation in 2 patients. Most of the patients had associated intra-abdominal organ injuries. Adjusts to diagnosis such as abdominal roentgenograms, serum amylase levels and gastroduodenography was not helpful. CT scan and ultrasound allowed to confirm the suspected diagnosis in 3 cases only. Intraoperative diagnosis was also challenging. Complete mobilization of the strictures surrounding the duodenum and the pancreas to provide entire exposure was necessary in 12 patients treated first in a peripheral hospital, diagnosis of the injury have been missed at first laparotomy and reoperation was necessary in all of them. Suture closure of the duodenum and drainage of the pancreatic region wee the most common reparative techniques used. More complicated procedures with pancreatic and/or duodenal resection were performed in 12 patients. Overall mortality in patients surviving more than 24 hours was 14%. Suture live dehiscence after delayed operation (4) and 2 deaths due to brain injury.

Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury

PubMed Central

Long, Justin Alexander; Boggs, Robert Cole; Manga, Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q.

2016-01-01

Abstract Traumatic brain injury (TBI) remains a primary cause of death and disability in both civilian and military populations worldwide. There is a critical need for the development of neuroprotective agents that can circumvent damage and provide functional recovery. We previously showed that methylene blue (MB), a U.S. Food and Drug Administration–grandfathered drug with energy-enhancing and antioxidant properties, given 1 and 3 h post-TBI, had neuroprotective effects in rats. This study aimed to further investigate the neuroprotection of delayed MB treatment (24 h postinjury) post-TBI as measured by lesion volume and functional outcomes. Comparisons were made with vehicle and acute MB treatment. Multi-modal magnetic resonance imaging and behavioral studies were performed at 1 and 3 h and 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. We found that delaying MB treatment 24 h postinjury still minimized lesion volume and functional deficits, compared to vehicle-treated animals. The data further support the potential for MB as a neuroprotective treatment, especially when medical teatment is not readily available. MB has an excellent safety profile and is clinically approved for other indications. MB clinical trials on TBI can thus be readily explored. PMID:25961471

Targeted isometric force impulses in patients with traumatic brain injury reveal delayed motor programming and change of strategy.

PubMed

Cantagallo, Anna; Di Russo, Francesco; Favilla, Marco; Zoccolotti, Pierluigi

2015-04-15

The capability of quickly (as soon as possible) producing fast uncorrected and accurate isometric force impulses was examined to assess the motor efficiency of patients with moderate to severe traumatic brain injury (TBI) and good motor recovery at a clinical evaluation. Twenty male right-handed patients with moderate to severe TBI and 24 age-matched healthy male right-handed controls participated in the study. The experimental task required subjects to aim brief and uncorrected isometric force impulses to targets visually presented along with subjects' force displays. Both TBI patients and controls were able to produce force impulses whose mean peak amplitudes varied proportionally to the target load with no detectable group difference. Patients with TBI, however, were slower than controls in initiating their responses (reaction times [RTs] were longer by 125 msec) and were also slower during the execution of their motor responses, reaching the peak forces requested 23 msec later than controls (time to peak force: 35% delay). Further, their mean dF/dt (35 kg/sec) was slower than that of controls (53 kg/sec), again indicating a 34% impairment with respect to controls. Overall, patients with TBI showed accurate but delayed and slower isometric force impulses. Thus, an evaluation taking into account also response time features is more effective in picking up motor impairments than the standard clinical scales focusing on accuracy of movement only.

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.

Up-Regulation of Endothelin Type A Receptor in Human and Rat Radiation Proctitis: Preclinical Therapeutic Approach With Endothelin Receptor Blockade

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

Jullien, Nicolash; Blirando, Karl; Milliat, Fabien

2009-06-01

Purpose: Rectum radiation damage and fibrosis are often associated with radiation therapy of pelvic tumors. The endothelin (ET) system has been implicated in several fibrotic diseases but never studied in the context of gastrointestinal radiation damage. This study assessed modifications in ET type 1 (ET-1), ET type A receptor (ET{sub A}), and ET type B receptor (ET{sub B}) localization and/or expression in irradiated human rectal tissue and in a rat model of delayed colorectal injury. We also evaluated the therapeutic potential of long-term ET receptor blockade. Methods and Materials: Routine histological studies of sections of healthy and radiation-injured human rectummore » tissue were done; the sections were also immunostained for ET{sub A} and ET{sub B} receptors. The rat model involved the delivery of 27 Gy in a single dose to the colons and rectums of the animals. The ET-1/ET{sub A}/ET{sub B} expression and ET{sub A}/ET{sub B} localization were studied at 10 weeks postexposure. The abilities of bosentan and atrasentan to protect against delayed rectal injury were also investigated. Results: The immunolocalization of ET{sub A} and ET{sub B} in healthy human rectums was similar to that in rat rectums. However, strong ET{sub A} immunostaining was seen in the presence of human radiation proctitis, and increased ET{sub A} mRNA levels were seen in the rat following colorectal irradiation. Immunostaining for ET{sub A} was also strongly positive in rats in areas of radiation-induced mucosal ulceration, atypia, and fibroproliferation. However, neither bosentan nor atrasentan prevented radiation damage to the rectum when given long term. The only effect seen for atrasentan was an increased number of sclerotic vessel sections in injured tissues. Conclusions: As the result of the overexpression of ET{sub A}, radiation exposure deregulates the endothelin system through an 'ET{sub A} profile' in the human and rodent rectum. However, therapeutic interventions involving

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.

Succinylcholine-induced hyperkalemia in the rat following radiation injury to muscle. [60Co

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

Cairoli, V.J.; Ivankovich, A.D.; Vucicevic, D.

1982-02-01

During anesthetic preparation of a patient who had received routine radiation therapy of sarcoma of the leg, cardiac collapse occurred following succinylcholine (SCh) administration. Experiments were designed to test the hypothesis that radiation injury to muscle might cause increased sensitivity to SCh similar to that reported in patients with muscle trauma, severe burns, and lesions causing muscle denervation. Venous plasma potassium levels and arterial blood gas tensions were measured in rats after they were given SCh (3 mg/kg) at various times following 60Co irradiation of the hind legs. Nonirradiated rats responded to SCh with a slight but statistically significant increasemore » in plasma K+. Rats subjected to high levels of radiation (10,000 to 20,000 R) and given SCh 4 to 7 days later responded in the same way as the control rats. Plasma K+ levels in rats exposed to a fractionated irradiated dosage (25000 R given twice with a 1-week interval) followed by SCh 1 week later were similar to those in the control group, but when SCh was given 2 weeks later (3 weeks after initial irradiation) there was a marked elevation of plasma K+, from 3.6 to 7.7 meq/L, a statistically significant increase.« less

Brain injury and altered brain growth in preterm infants: predictors and prognosis.

PubMed

Kidokoro, Hiroyuki; Anderson, Peter J; Doyle, Lex W; Woodward, Lianne J; Neil, Jeffrey J; Inder, Terrie E

2014-08-01

To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes. MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW. At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. Copyright © 2014 by the American Academy of Pediatrics.

Factors affecting outcome of triceps motor branch transfer for isolated axillary nerve injury.

PubMed

Lee, Joo-Yup; Kircher, Michelle F; Spinner, Robert J; Bishop, Allen T; Shin, Alexander Y

2012-11-01

Triceps motor branch transfer has been used in upper brachial plexus injury and is potentially effective for isolated axillary nerve injury in lieu of sural nerve grafting. We evaluated the functional outcome of this procedure and determined factors that influenced the outcome. A retrospective chart review was performed of 21 patients (mean age, 38 y; range, 16-79 y) who underwent triceps motor branch transfer for the treatment of isolated axillary nerve injury. Deltoid muscle strength was evaluated using the modified British Medical Research Council grading at the last follow-up (mean, 21 mo; range, 12-41 mo). The following variables were analyzed to determine whether they affected the outcome of the nerve transfer: the age and sex of the patient, delay from injury to surgery, body mass index (BMI), severity of trauma, and presence of rotator cuff lesions. The Spearman correlation coefficient and multiple linear regression were performed for statistical analysis. The average Medical Research Council grade of deltoid muscle strength was 3.5 ± 1.1. Deltoid muscle strength correlated with the age of the patient, delay from injury to surgery, and BMI of the patient. Five patients failed to achieve more than M3 grade. Among them, 4 patients were older than 50 years and 1 was treated 14 months after injury. In the multiple linear regression model, the delay from injury to surgery, age of the patient, and BMI of the patient were the important factors, in that order, that affected the outcome of this procedure. Isolated axillary nerve injury can be treated successfully with triceps motor branch transfer. However, outstanding outcomes are not universal, with one fourth failing to achieve M3 strength. The outcome of this procedure is affected by the delay from injury to surgery and the age and BMI of the patient. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Impact of adaptive statistical iterative reconstruction on radiation dose in evaluation of trauma patients.

PubMed

Maxfield, Mark W; Schuster, Kevin M; McGillicuddy, Edward A; Young, Calvin J; Ghita, Monica; Bokhari, S A Jamal; Oliva, Isabel B; Brink, James A; Davis, Kimberly A

2012-12-01

A recent study showed that computed tomographic (CT) scans contributed 93% of radiation exposure of 177 patients admitted to our Level I trauma center. Adaptive statistical iterative reconstruction (ASIR) is an algorithm that reduces the noise level in reconstructed images and therefore allows the use of less ionizing radiation during CT scans without significantly affecting image quality. ASIR was instituted on all CT scans performed on trauma patients in June 2009. Our objective was to determine if implementation of ASIR reduced radiation dose without compromising patient outcomes. We identified 300 patients activating the trauma system before and after the implementation of ASIR imaging. After applying inclusion criteria, 245 charts were reviewed. Baseline demographics, presenting characteristics, number of delayed diagnoses, and missed injuries were recorded. The postexamination volume CT dose index (CTDIvol) and dose-length product (DLP) reported by the scanner for CT scans of the chest, abdomen, and pelvis and CT scans of the brain and cervical spine were recorded. Subjective image quality was compared between the two groups. For CT scans of the chest, abdomen, and pelvis, the mean CTDIvol (17.1 mGy vs. 14.2 mGy; p < 0.001) and DLP (1,165 mGy·cm vs. 1,004 mGy·cm; p < 0.001) was lower for studies performed with ASIR. For CT scans of the brain and cervical spine, the mean CTDIvol (61.7 mGy vs. 49.6 mGy; p < 0.001) and DLP (1,327 mGy·cm vs. 1,067 mGy·cm; p < 0.001) was lower for studies performed with ASIR. There was no subjective difference in image quality between ASIR and non-ASIR scans. All CT scans were deemed of good or excellent image quality. There were no delayed diagnoses or missed injuries related to CT scanning identified in either group. Implementation of ASIR imaging for CT scans performed on trauma patients led to a nearly 20% reduction in ionizing radiation without compromising outcomes or image quality. Therapeutic study, level IV.

Impact of adaptive statistical iterative reconstruction on radiation dose in evaluation of trauma patients

PubMed Central

Maxfield, Mark W.; Schuster, Kevin M.; McGillicuddy, Edward A.; Young, Calvin J.; Ghita, Monica; Bokhari, S.A. Jamal; Oliva, Isabel B.; Brink, James A.; Davis, Kimberly A.

2013-01-01

BACKGROUND A recent study showed that computed tomographic (CT) scans contributed 93% of radiation exposure of 177 patients admitted to our Level I trauma center. Adaptive statistical iterative reconstruction (ASIR) is an algorithm that reduces the noise level in reconstructed images and therefore allows the use of less ionizing radiation during CT scans without significantly affecting image quality. ASIR was instituted on all CT scans performed on trauma patients in June 2009. Our objective was to determine if implementation of ASIR reduced radiation dose without compromising patient outcomes. METHODS We identified 300 patients activating the trauma system before and after the implementation of ASIR imaging. After applying inclusion criteria, 245 charts were reviewed. Baseline demographics, presenting characteristics, number of delayed diagnoses, and missed injuries were recorded. The postexamination volume CT dose index (CTDIvol) and dose-length product (DLP)reported by the scanner for CT scans of the chest, abdomen, and pelvis and CT scans of the brain and cervical spine were recorded. Subjective image quality was compared between the two groups. RESULTS For CT scans of the chest, abdomen, and pelvis, the mean CTDIvol(17.1 mGy vs. 14.2 mGy; p < 0.001) and DLP (1,165 mGy·cm vs. 1,004 mGy·cm; p < 0.001) was lower for studies performed with ASIR. For CT scans of the brain and cervical spine, the mean CTDIvol(61.7 mGy vs. 49.6 mGy; p < 0.001) and DLP (1,327 mGy·cm vs. 1,067 mGy·cm; p < 0.001) was lower for studies performed with ASIR. There was no subjective difference in image quality between ASIR and non-ASIR scans. All CT scans were deemed of good or excellent image quality. There were no delayed diagnoses or missed injuries related to CT scanning identified in either group. CONCLUSION Implementation of ASIR imaging for CT scans performed on trauma patients led to a nearly 20% reduction in ionizing radiation without compromising outcomes or image quality

Crural artery traumatic injuries: treatment with embolization.

PubMed

Lopera, Jorge E; Suri, Rajeev; Cura, Marco; Kroma, Ghazwan; El-Merhi, Fadi

2008-01-01

The purpose of this paper is to report our experience with the endovascular treatment of crural arterial injuries using transcatheter and direct embolization techniques. A total of eight consecutive patients have been treated during a 7-year period. Six males and two females, mean age 32 years (range, 15-56 years), presented with penetrating trauma to the lower extremities. Mechanisms of injuries were stab wounds in six patients, gun shot wound in one patient, and iatrogenic injury in one patient. Five patients presented with acute trauma, while three patients presented with delayed injuries. Crural arterial injuries encountered included pseudoaneurysms with arteriovenous fistulas (n = 6), pseudoaneurysms with vessel transections (n = 2), and pseudoaneurysm (n = 1). Proximal and distal embolization with coils was used in three cases, proximal embolization with coils in three cases, percutaneous thrombin injection in one case, and liquid n-butyl cyanoacrylate in one case. Complete exclusion of the lesions was accomplished by sacrifice of one crural vessel in seven cases and of two crural vessels in one case. Two cases of delayed injuries required combined coil and liquid embolization techniques for lesion exclusion. A minor complication (groin hematoma) occurred in one patient, no distal ischemia was seen, and no amputations were required. Mean follow-up was 61 days (range, 1-180 days). One pseudoaneurysm treated with thrombin injection recurred and required surgical excision. We conclude that transcatheter embolization alone or in combination with different endovascular techniques is useful in the treatment of traumatic crural vessel injuries.

Crural Artery Traumatic Injuries: Treatment with Embolization

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

Lopera, Jorge E., E-mail: Lopera@uthscssa.edu; Suri, Rajeev; Cura, Marco

The purpose of this paper is to report our experience with the endovascular treatment of crural arterial injuries using transcatheter and direct embolization techniques. A total of eight consecutive patients have been treated during a 7-year period. Six males and two females, mean age 32 years (range, 15-56 years), presented with penetrating trauma to the lower extremities. Mechanisms of injuries were stab wounds in six patients, gun shot wound in one patient, and iatrogenic injury in one patient. Five patients presented with acute trauma, while three patients presented with delayed injuries. Crural arterial injuries encountered included pseudoaneurysms with arteriovenous fistulasmore » (n = 6), pseudoaneurysms with vessel transections (n = 2), and pseudoaneurysm (n = 1). Proximal and distal embolization with coils was used in three cases, proximal embolization with coils in three cases, percutaneous thrombin injection in one case, and liquid n-butyl cyanoacrylate in one case. Complete exclusion of the lesions was accomplished by sacrifice of one crural vessel in seven cases and of two crural vessels in one case. Two cases of delayed injuries required combined coil and liquid embolization techniques for lesion exclusion. A minor complication (groin hematoma) occurred in one patient, no distal ischemia was seen, and no amputations were required. Mean follow-up was 61 days (range, 1-180 days). One pseudoaneurysm treated with thrombin injection recurred and required surgical excision. We conclude that transcatheter embolization alone or in combination with different endovascular techniques is useful in the treatment of traumatic crural vessel injuries.« less

Delay to Reconstruction of the Adolescent Anterior Cruciate Ligament: The Socioeconomic Impact on Treatment.

PubMed

Newman, Justin T; Carry, Patrick M; Terhune, Elizabeth B; Spruiell, Murray; Heare, Austin; Mayo, Meredith; Vidal, Armando F

2014-08-01

A delay in pediatric and adolescent anterior cruciate ligament (ACL) reconstruction is associated with an increase in the number of concomitant meniscal and chondral injuries. Factors that contribute to this delay have not been well described. Socioeconomic and demographic factors are related to ACL surgery timing. Cohort study; Level of evidence, 3. All subjects who underwent primary ACL reconstruction at a single tertiary pediatric hospital between 2005 and 2012 were retrospectively reviewed. Variables included concomitant knee injuries (cartilage or meniscus injuries requiring additional operative treatment) and chronologic, demographic, and socioeconomic factors. Multivariable Cox proportional-hazards analyses were used to identify factors related to ACL surgery timing. The mean age of the 272 subjects was 15.2 ± 2.12 years. Time to surgery was significantly different among subjects who required multiple additional surgical procedures at time of ACL reconstruction (median, 3.3 months) compared with subjects with 1 (median, 2.0 months) or no additional injuries (median, 1.6 months). Subjects underwent ACL reconstruction significantly sooner if they were older at the time of injury (hazard ratio [HR], 1.2 per 1 year; 95% CI, 1.1-1.2; P < .0001) or were covered by a commercial insurance plan (HR, 2.0; 95% CI, 1.6-2.6; P < .0001). Median time to ACL surgery was 1.5 months (95% CI, 1.3-1.7) for subjects with commercial insurance plans compared with 3.0 months (95% CI, 2.3-3.3) for subjects with noncommercial insurance coverage. The risk of delayed ACL surgery was significantly higher among pediatric and adolescent subjects who were less affluent, who were covered by a noncommercial insurance plan, and who were younger. This study also confirms previous studies that have reported an association between a delay in ACL surgery and the presence of additional knee injuries requiring operative treatment, accentuating the importance of timely care. Access to care is a

Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

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

Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng

2013-11-01

Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays,more » were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.« less

Acute pain in an emergency clinic: latency of onset and descriptor patterns related to different injuries.

PubMed

Melzack, R; Wall, P D; Ty, T C

1982-09-01

Features of acute pain were examined in patients at an emergency clinic. Patients who had severe, life-threatening injuries or who were agitated, drunk, or 'in shock' were excluded from the study. Of 138 patients who were alert, rational and coherent, 51 (37%) stated that they did not feel pain at the time of injury. The majority of these patients reported onset of pain within an hour of injury, although the delays were as long as 9 h or more in some patients. The predominant emotions of the patients were embarrassment at appearing careless or worry about loss of wages. None expressed any pleasure or indicated any prospect of gain as a result of the injury. The occurrence of delays in pain onset was related to the nature of the injury. Of 46 patients whose injuries were limited to skin (lacerations, cuts, abrasions, burns), 53% had a pain-free period. Of 86 patients with deep-tissue injuries (fractures, sprains, bruises, amputation of a finger, stabs and crushes), only 28% had a pain-free period. The McGill Pain Questionnaire was administered to patients who felt pain immediately after injury or after a delay, and revealed a normal distribution of sensory scores but very low affective scores compared to patients with chronic pain. The results indicate that the relationship between injury and pain is highly variable and complex.

Neurodevelopmental delay with critical congenital heart disease is mainly from prenatal injury not infant cardiac surgery: current evidence based on a meta-analysis of functional magnetic resonance imaging.

PubMed

Li, Y; Yin, S; Fang, J; Hua, Y; Wang, C; Mu, D; Zhou, K

2015-06-01

No consensus has been reached regarding whether brain injury related to congenital heart disease (CHD) is caused by infant cardiac surgery and/or prenatal injury resulting from the CHD. We performed this meta-analysis to identify the likely cause of neurodevelopmental delay in CHD patients. We carried out a literature search without language restriction in December 2013, retrieving records from PubMed, EMBASE, the Cochrane Library and the World Health Organization trials center, to identify studies applying functional magnetic resonance imaging (fMRI) evaluation of brain function before surgery and, in some cases, after surgery (both immediate term and short term postoperatively). The preoperative and postoperative fMRI results were extracted, and meta-analysis was performed using Revman 5.1.1 and STATA 11.0, according to the guidelines from the Cochrane review and MOOSE groups. The electronic search yielded 937 citations. Full text was retrieved for 15 articles and eight articles (nine studies) were eligible for inclusion: six studies (n = 312 cases) with fMRI analysis before surgery and three (n = 36 cases) with complete perioperative fMRI analysis. The overall average diffusivity of CHD cases was significantly higher than that of controls, with a summarized standard (std) mean difference of 1.39 (95% CI, 0.70-2.08), and the fractional anisotropy was lower in CHD cases, with a summarized mean difference of -1.43 (95% CI, -1.95 to -0.91). N-acetylaspartate (NAA)/choline (Cho) for the whole brain was significantly lower in CHD cases compared with healthy ones, while lactate/Cho was significantly higher in CHD cases. Immediate term postoperatively, significant changes in NAA/creatine and NAA/Cho, relative to preoperative values, were found. However, the difference did not persist at the short-term follow-up. This meta-analysis suggests that the delay in neurological development in newborns with CHD is due mainly to prenatal injury, and cardiac surgery might

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

Mechanisms of Hypothermia, Delayed Hyperthermia and Fever Following CNS Injury

EPA Science Inventory

Central nervous system (CNS) damage is often associated with robust body temperature changes, such as hypothermia and delayed hyperthermia. Hypothermia is one of the most common body temperature changes to CNS insults in rodents and is often associated with improved outcome. Alth...

Experience with management of posterior urethral injury associated with pelvic fracture.

PubMed

Coffield, K S; Weems, W L

1977-06-01

Review of records from 205 patients with pelvic fracture and hematuria revealed that 121 underwent urologic and radiographic evaluation. Of these patients 20 had severe posterior urethral injuries documented by urethrography of voiding cystourethrography: 9 underwent primary repair and 11 had delayed scrotal-inlay urethroplasty after initial cystostomy alone. Patients who underwent primary repair had a 77 per cent incidence of stricture, a 22 per cent incidence of incontinence and a 33 per cent incidence of impotency. Patients who underwent delayed closure had no incidence of stricture, incontinence or impotence. Patients in both groups had urinary tract infections. Simple cystostomy followed by delayed scrotal-inlay urethroplasty appears superior to primary realignment in the management of patients with posterior urethral injuries.

Delayed presentation is no barrier to satisfactory outcome in the management of open tibial fractures.

PubMed

Ashford, Robert U; Mehta, Janak A; Cripps, Robin

2004-04-01

The management of open tibial fractures is a challenge to all orthopaedic trauma surgeons. The major goals are fracture union, uncomplicated soft tissue healing and return to pre-injury level of function. The geographical isolation and vastness of the Northern Territory of Australia complicates the management of these injuries by adding a significant delay to treatment. Forty-five patients sustained 48 open tibial fractures over the 30-month period of the study. Twelve received primary surgical treatment within 6h of injury but 33 were treated more than 6h after injury. The mean time to treatment in this latter group was 12h 15min (median 9h 45min, range 6-37h). The majority of injuries were high energy, with 23 patients having multiple injuries and 29 fractures (60%) being classified as AO C3 with 35 (73%) having Gustilo III soft tissue injuries. There was a mean time to union of 7.5 months and an overall complication rate of 42.2%. Thirteen patients (29%) required additional (late) surgical procedures subsequent to definitive fracture and soft tissue management. The zone of injury infection rate was 12.5%. The high incidence of open tibial fractures places a large financial burden on the state. However, despite the absence of a plastic surgical service and delays in presentation, satisfactory outcomes can be obtained by the application of the established surgical principles of thorough debridement, soft tissue management and fracture stabilisation.

Lithium stimulates the recovery of granulopoiesis following acute radiation injury.

PubMed

Gallicchio, V S; Chen, M G; Watts, T D; Gamba-Vitalo, C

1983-07-01

Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radiotherapy protocols. In this report, we have examined bone marrow and spleen cells for their recovery patterns of CFUS, CFUGM, CFUE, BFUE and 59Fe-incorporation, along with the usual peripheral blood indices (packed red cell volume, WBC and differential) from mice administered Li after receiving 200 rad whole body irradiation. Li increased granulopoietic recovery as measured by significant elevations in both marrow and spleen derived CFUGM compared to those values obtained from radiation controls. Significant elevation in the WBC, consisting mainly of neutrophils, was also observed. Bone marrow and splenic derived erythroid stem cells (CFUE, BFUE) and % 59Fe-incorporation measured from peripheral blood, femur and spleen were all slightly reduced, but not to a significant degree to alter the packed red cell volume. The CFUS populations from both irradiated groups (control and Li-treated) were depressed when compared to normal non-irr controls and this degree of suppression was greater in the Li-treated group. These results document the ability of Li to stimulate the recovery of granulopoiesis after radiation-induced hematopoietic injury and suggest Li may be useful in ameliorating the neutropenia that can often develop after routine radiotherapy protocols.

Sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells in mice

PubMed Central

Guo, Chang-Ying; Luo, Lan; Urata, Yoshishige; Goto, Shinji; Huang, Wen-Jing; Takamura, Syu; Hayashi, Fumiko; Doi, Hanako; Kitajima, Yuriko; Ono, Yusuke; Ogi, Tomoo; Li, Tao-Sheng

2015-01-01

We evaluated the sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells. Adult C57BL/6 mice were daily exposed to 0, 2, 10, 50, and 250 mGy γ-ray for 1 month in succession, respectively. The damage of hematopoietic stem/progenitor cells in bone marrow were investigated within 2 hours (acute phase) or at 3 months (chronic phase) after the last exposure. Daily exposure to over 10 mGy γ-ray significantly decreased the number and colony-forming capacity of hematopoietic stem/progenitor cells at acute phase, and did not completely recover at chronic phase with 250 mGy exposure. Interestingly, the daily exposure to 10 or 50 mGy γ-ray decreased the formation of mixed types of colonies at chronic phase, but the total number of colonies was comparable to control. Immunostaining analysis showed that the formation of 53BP1 foci in c-kit+ stem/progenitor cells was significantly increased with daily exposure to 50 and 250 mGy at acute phase, and 250 mGy at chronic phase. Many genes involved in toxicity responses were up- or down-regulated with the exposures to all doses. Our data have clearly shown the sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells of mice with daily exposures to 2 ~ 250 mGy γ-ray. PMID:25623887

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

Management of blunt duodenal injuries.

PubMed

Sriussadaporn, Suvit; Pak-art, Rattaplee; Sriussadaporn, Sukanya; Kritayakirana, Kritaya

2004-11-01

Blunt duodenal injuries are relatively rare. Diagnosis is usually delayed resulting in significant morbidity and mortality. Treatment of the injured duodenum varies according to severity of injury and duration before diagnosis. Duodenal fistulas are serious complications with potential mortality. The purpose of this study was to examine results of treatment of patients with blunt duodenal injuries at our institution. This is a retrospective study of patients who sustained blunt duodenal injuries and were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand from January 1990 to December 2003. During the study period, management of duodenal injuries at our institution depended largely on severity of injuries, timing of diagnosis and the presence of retroperitoneal infections. Intramural hematoma of the duodenum was treated conservatively. Uncomplicated wounds of the duodenum (grade II and grade III injury) with no obvious retroperitoneal infections were treated by simple duodenal repair. Pyloric exclusion was performed in cases of difficult duodenal repair and/or delayed diagnosis (> 24 hours after injury) with obvious evidence of retroperitoneal infections. Twenty six patients were entered into the study. Five patients (19.2%) had intramural hematoma of the duodenum, all were successfully treated by conservative treatment. Twenty one patients (80.8%) had transmural tear of the duodenal wall. Ten of them (47.6%) underwent simple repair, 10 (47.6%) underwent simple repair of the duodenal wounds combined with pyloric exclusion (2 of them underwent the operations elsewhere), and 1 (4.8%) underwent pancreaticoduodenectomy. Seven patients who had transmural tear of the duodenum developed complications (33.3%). Two patients had duodenal fistulas (9.5%); 1 in the simple repair group and 1 in the pyloric exclusion group. One patient who underwent pyloric exclusion had leakage of the gastrojejunostomy anastomosis with intact duodenal repair resulting in a

Isolated gallbladder injury in a case of blunt abdominal trauma.

PubMed

Birn, Jeffrey; Jung, Melissa; Dearing, Mark

2012-04-01

The diagnosis of blunt injury to the gallbladder may constitute a significant challenge to the diagnostician. There is often a delay in presentation with non-specific clinical symptoms. In the absence of reliable clinical symptoms, diagnostic imaging becomes an invaluable tool in the rapid identification of gallbladder injury. We present a case of isolated gallbladder injury following blunt abdominal trauma which was diagnosed by computed tomography and subsequently confirmed by cholecystectomy.

Xenon-delayed postconditioning attenuates spinal cord ischemia/reperfusion injury through activation AKT and ERK signaling pathways in rats.

PubMed

Liu, Shiyao; Yang, Yanwei; Jin, Mu; Hou, Siyu; Dong, Xiuhua; Lu, Jiakai; Cheng, Weiping

2016-09-15

Previous studies have shown that xenon-delayed postconditioning for up to 2h after reperfusion provides protection against spinal cord ischemia/reperfusion (I/R) injury in rats. This study was designed to determine the roles of phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection. The rats were randomly assigned to the following nine groups (n=16∗9): 1) I/R+N2 group, 2) I/R+Xe group, 3) I/R+PD98059+N2 group (ERK blocking agent), 4) I/R+wortmannin+N2 group (PI3K-Akt blocking agent), 5) I/R+PD98059+Xe group, 6) I/R+wortmannin+Xe group, 7) I/R+DMSO+Xe group (dimethyl sulfoxide, vehicle control), 8) I/R+DMSO+N2 group, and 9) sham group (no spinal cord ischemia and no xenon). Spinal cord ischemia was induced for 25min in male Sprague-Dawley rats. Neurological function was assessed using the Basso, Beattie, and Bresnahan (BBB) open-field locomotor scale at 6, 12, 24 and 48h after reperfusion. Histological examination of the lumbar spinal cord was performed using Nissl staining and TUNEL staining at 4 (n=8) and 48 (n=8)h after reperfusion. Western blotting was performed to evaluate p-Akt and p-ERK expression in the spinal cord at 4 (n=8) and 48 (n=8) h after reperfusion. Compared with the sham group, all rats in the I/R groups had lower BBB scores, fewer normal motor neurons, more apoptotic neurons and lower p-Akt and p-ERK levels at each time point (P<0.05). Compared with the I/R group, rats in the I/R+Xe group had higher neurological scores, more normal motor neurons, fewer apoptotic neurons and significantly higher levels of p-Akt and p-ERK at each time point (P<0.05). Compared with the I/R+Xe group, the I/R+PD98059+Xe and I/R+wortmannin+Xe groups showed worse neurological outcomes and less p-Akt and p-ERK at each time point (P<0.05). These results suggest that xenon-delayed postconditioning improves neurological outcomes to spinal cord I/R injury in rats through the activation of the AKT and ERK signaling

Management of Syndesmotic Ankle Injuries in Children and Adolescents.

PubMed

Shore, Benjamin J; Kramer, Dennis E

2016-06-01

Pediatric ankle injuries are common, especially in athletes; however, the incidence of syndesmosis injuries in children has been scarcely reported. Injuries to the ankle syndesmosis, termed "high ankle sprains," can affect high-level and recreational athletes and have been related to delayed return to play, persistent pain, and adult injuries have been associated with long-term disability. Syndesmotic injuries do occur in children, especially those who participate in sports that involve cutting and pivoting (football, soccer) or sports with rigid immobilization of the ankle (skiing, hockey). Unstable pediatric syndesmosis injuries requiring surgical fixation are often associated with concomitant fibular fracture in skeletally mature children. Physician vigilance and careful clinical examination coupled with appropriate radiographs can determine the extent of the injury in the majority of circumstances.

Neuromuscular dysfunction that may predict ACL injury risk: a case report.

PubMed

Saunders, Natalie; McLean, Scott G; Fox, Aaron S; Otago, Leonie

2014-06-01

This case report examined the neuromuscular function of a competitive female netball player six days prior to an incident where she sustained an acute anterior cruciate ligament injury during normal sports activity. Electromyography was used to examine activation onsets of four lower limb muscles (rectus femoris, biceps femoris, medial hamstrings and gluteus medius) relative to initial contact (IC) during netball-specific landings of varying complexity. The results of the injured participant were compared to the remaining participants in the study (n=8), and the injured participant's injured limb was compared to the contralateral limb. The injured participant was the only player to record delayed pre-injury muscle onsets after IC for all muscles tested in the injured limb, while her non-injured limb was comparable to the other participants tested. Furthermore, delayed muscle onset after IC occurred more frequently as landing complexity increased. This case report suggests that delayed muscle activity onset after IC during landing may be an important risk factor for ACL injury. Copyright © 2014 Elsevier B.V. All rights reserved.

Urethral injury in the multiple-injured patient.

PubMed

Cass, A S

1984-10-01

A total of 74 patients with urethral injury due to external trauma consisted of 48 posterior urethral injuries (25 complete rupture, 23 partial rupture) and 26 anterior urethral injuries (two complete rupture, 16 partial rupture, and eight contusion). The diagnosis was made by retrograde urethrography. All 48 patients with posterior urethral injury had associated injuries, including a fractured pelvis in 46, and a mortality rate of 33%. Only seven of the 26 patients with anterior urethral injury had associated injuries and a mortality rate of 14%. The management of posterior urethral injury is changing from primary realignment of the ruptured urethra to suprapubic cystostomy alone and followed later by urethral surgery for the resulting stricture. The impotence rate is significantly lower with management with suprapubic cystostomy alone. However, the type of pelvic fracture, the urethral injury itself disrupting neurovascular structures, and the surgical dissection (initial primary realignment or delayed urethroplasty) must be investigated before it can be determined whether the impotence associated with pelvic trauma is caused by the injury itself or by the surgical dissection undertaken to reconstruct the urethra.

Combined mitigation of the gastrointestinal and hematopoietic acute radiation syndromes by an LPA2 receptor-specific nonlipid agonist.

PubMed

Patil, Renukadevi; Szabó, Erzsébet; Fells, James I; Balogh, Andrea; Lim, Keng G; Fujiwara, Yuko; Norman, Derek D; Lee, Sue-Chin; Balazs, Louisa; Thomas, Fridtjof; Patil, Shivaputra; Emmons-Thompson, Karin; Boler, Alyssa; Strobos, Jur; McCool, Shannon W; Yates, C Ryan; Stabenow, Jennifer; Byrne, Gerrald I; Miller, Duane D; Tigyi, Gábor J

2015-02-19

Pharmacological mitigation of injuries caused by high-dose ionizing radiation is an unsolved medical problem. A specific nonlipid agonist of the type 2 G protein coupled receptor for lysophosphatidic acid (LPA2) 2-[4-(1,3-dioxo-1H,3H-benzoisoquinolin-2-yl)butylsulfamoyl]benzoic acid (DBIBB) when administered with a postirradiation delay of up to 72 hr reduced mortality of C57BL/6 mice but not LPA2 knockout mice. DBIBB mitigated the gastrointestinal radiation syndrome, increased intestinal crypt survival and enterocyte proliferation, and reduced apoptosis. DBIBB enhanced DNA repair by augmenting the resolution of γ-H2AX foci, increased clonogenic survival of irradiated IEC-6 cells, attenuated the radiation-induced death of human CD34(+) hematopoietic progenitors and enhanced the survival of the granulocyte/macrophage lineage. DBIBB also increased the survival of mice suffering from the hematopoietic acute radiation syndrome after total-body irradiation. DBIBB represents a drug candidate capable of mitigating acute radiation syndrome caused by high-dose γ-radiation to the hematopoietic and gastrointestinal system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Combat ocular trauma and systemic injury.

PubMed

Weichel, Eric D; Colyer, Marcus H

2008-11-01

To review the recent literature regarding combat ocular trauma during hostilities in Operations Iraqi Freedom and Enduring Freedom, describe the classification of combat ocular trauma, and offer strategies that may assist in the management of eye injuries. Several recent publications have highlighted features of combat ocular trauma from Operation Iraqi Freedom. The most common cause of today's combat ocular injuries is unconventional fragmentary munitions causing significant blast injuries. These explosive munitions cause high rates of concomitant nonocular injuries such as traumatic brain injury, amputation, and other organ injuries. The most frequent ocular injuries include open-globe and adnexal lacerations. The extreme severity of combat-related open-globe injuries leads to high rates of primary enucleation and retained intraocular foreign bodies. Visual outcomes of intraocular foreign body injuries are similar to other series despite delayed removal, and no cases of endophthalmitis have occurred. Despite these advances, however, significant vision loss persists in cases of perforating globe injuries as well as open and closed-globe trauma involving the posterior segment. This review summarizes the recent literature describing ocular and systemic injuries sustained during Operations Iraqi and Enduring Freedom. An emphasis on classification of ocular injuries as well as a discussion of main outcome measures and complications is discussed.

Missile vascular injuries: 19-year experience.

PubMed

Ahanger, Abdul Gani; Wani, Mohd Lateef; Lone, Reyaz Ahmad; Singh, Shyam; Hussain, Zahur; Mir, Ishtiyak A; Irshad, Ifat; Ashraf, Hakeem Zubair; Dar, Abdul Majeed; Lone, Ghulam Nabi; Bhat, Mohammad Akbar; Sharma, Mukand Lal

2010-03-01

Missile vascular injuries have reached an epidemic proportion in Kashmir valley since the eruption of militancy. The present study was undertaken to analyze the mode, pattern, presentation, and management of missile vascular injuries. A retrospective study of patients with missile vascular injury from January 1990 to October 2008 was undertaken. Five hundred eighty patients with missile vascular injury were studied. All patients with vascular injury due to causes other than missiles were excluded from the study. Most of the patients were treated by interpositional saphenous vein graft or end-to-end anastomosis. The most common complication was wound infection (22.7%) followed by graft occlusion (3.8%). The amputation rate was 3.3% and was higher in patients with a delay of >6 hours to revascularization and associated fractures. Missile vascular injury requires prompt resuscitation and revascularization. Preoperative angiography is seldom necessary. Doppler study may sometimes be needed to aid in the diagnosis.

Acute radiation enteritis caused by dose-dependent radiation exposure in dogs: experimental research.

PubMed

Xu, Wenda; Chen, Jiang; Xu, Liu; Li, Hongyu; Guo, Xiaozhong

2014-12-01

Accidental or intended radiation exposure in mass casualty settings presents a serious and on-going threat. The development of mitigating and treating agents requires appropriate animal models. Unfortunately, the majority of research on radiation enteritis in animals has lacked specific assessments and targeted therapy. Our study showed beagle dogs, treated by intensity-modulated radiation therapy (IMRT) for abdominal irradiation, were administered single X-ray doses of 8-30 Gy. The degree of intestinal tract injury for all of the animals after radiation exposure was evaluated with regard to clinical syndrome, endoscopic findings, histological features, and intestinal function. The range of single doses (8 Gy, 10-14 Gy, and 16-30 Gy) represented the degree of injury (mild, moderate, and severe, respectively). Acute radiation enteritis included clinical syndrome with fever, vomiting, diarrhea, hemafecia, and weight loss; typical endoscopic findings included edema, bleeding, mucosal abrasions, and ulcers; and intestinal biopsy results revealed mucosal necrosis, erosion, and loss, inflammatory cell infiltration, hemorrhage, and congestion. Changes in serum diamine oxides (DAOs) and d-xylose represented intestinal barrier function and absorption function, respectively, and correlated with the extent of damage (P < 0.05 and P < 0.05, respectively). We successfully developed a dog model of acute radiation enteritis, thus obtaining a relatively objective evaluation of intestinal tract injury based on clinical performance and laboratory examination. The method of assessment of the degree of intestinal tract injury after abdominal irradiation could be beneficial in the development of novel and effective therapeutic strategies for acute radiation enteritis. © 2014 by the Society for Experimental Biology and Medicine.

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.

Ankle injury manipulation before or after X-ray--does it influence success?

PubMed

Hastie, G R; Divecha, H; Javed, S; Zubairy, A

2014-03-01

Many acute, deformed ankle injuries are manipulated in the Emergency Department (ED) before X-rays are taken to confirm the nature of the injury. This often occurs in the absence of neurovascular or skin compromise without consideration of other possible injuries such as talar, subtalar or calcaneal injuries. We believe that an inappropriate manipulation of an unknown injury pattern may place the patient at increased risk. A balance needs to be struck between making the correct diagnosis and preventing any further neurovascular or skin compromise. We prospectively reviewed 197 patients admitted to the Royal Blackburn Hospital with acute ankle injuries. Their ED notes were reviewed, specifically assessing whether a manipulation was performed; if so, was it performed before X-rays and the documented reasons. A total of 90 ankle fractures were manipulated and 31 of these were performed before X-ray. One manipulation was performed for vascular compromise, one for nerve symptoms, three for critical skin and 25 for undocumented reasons. Outcomes (re-manipulation, delay to surgery and need for open reduction and internal fixation (ORIF)) were compared between injuries manipulated before or after X-ray. Re-manipulation was found to be significant (44% before X-ray vs. 18% after X-ray; chi-squared test: p=0.03; relative risk (RR)=2.72; 95% confidence interval (CI): 1.15-6.44). Delay to surgery and need for ORIF were not statistically different. We conclude that performing ankle injury X-rays before an attempt at manipulation, in the absence of neurovascular deficit or critical skin, may constitute best practice as it provides a better assessment of fracture configuration, guides initial reduction and significantly lowers the risk of re-manipulation and the potential risks associated with sedation without delaying surgery. Copyright © 2013 Elsevier Ltd. All rights reserved.

Radiation-induced pulmonary gene expression changes are attenuated by the CTGF antibody Pamrevlumab.

PubMed

Sternlicht, Mark D; Wirkner, Ute; Bickelhaupt, Sebastian; Lopez Perez, Ramon; Tietz, Alexandra; Lipson, Kenneth E; Seeley, Todd W; Huber, Peter E

2018-01-18

Fibrosis is a delayed side effect of radiation therapy (RT). Connective tissue growth factor (CTGF) promotes the development of fibrosis in multiple settings, including pulmonary radiation injury. To better understand the cellular interactions involved in RT-induced lung injury and the role of CTGF in these responses, microarray expression profiling was performed on lungs of irradiated and non-irradiated mice, including mice treated with the anti-CTGF antibody pamrevlumab (FG-3019). Between group comparisons (Welch's t-tests) and principal components analyses were performed in Genespring. At the mRNA level, the ability of pamrevlumab to prolong survival and ameliorate RT-induced radiologic, histologic and functional lung deficits was correlated with the reversal of a clear enrichment in mast cell, macrophage, dendritic cell and mesenchymal gene signatures. Cytokine, growth factor and matrix remodeling genes that are likely to contribute to RT pneumonitis and fibrosis were elevated by RT and attenuated by pamrevlumab, and likely contribute to the cross-talk between enriched cell-types in injured lung. CTGF inhibition had a normalizing effect on select cell-types, including immune cells not typically regarded as being regulated by CTGF. These results suggest that interactions between RT-recruited cell-types are critical to maintaining the injured state; that CTGF plays a key role in this process; and that pamrevlumab can ameliorate RT-induced lung injury in mice and may provide therapeutic benefit in other immune and fibrotic disorders.

Delayed surgery after acute traumatic central cord syndrome is associated with reduced mortality.

PubMed

Samuel, Andre M; Grant, Ryan A; Bohl, Daniel D; Basques, Bryce A; Webb, Matthew L; Lukasiewicz, Adam M; Diaz-Collado, Pablo J; Grauer, Jonathan N

2015-03-01

A retrospective study of surgically treated patients with acute traumatic central cord syndrome (ATCCS) from the National Trauma Data Bank Research Data Set. To determine the association of time to surgery, pre-existing comorbidities, and injury severity on mortality and adverse events in surgically treated patients with ATCCS. Although earlier surgery has been shown to be beneficial for other spinal cord injuries, the literature is mixed regarding the appropriate timing of surgery after ATCCS. Traditionally, this older population has been treated with delayed surgery because medical optimization is often indicated preoperatively. Surgically treated patients with ATCCS in the National Trauma Data Bank Research Data Set from 2011 and 2012 were identified. Time to surgery, Charlson Comorbidity Index, and injury severity scores were tested for association with mortality, serious adverse events, and minor adverse events using multivariate logistic regression. A total of 1060 patients with ATCCS met inclusion criteria. After controlling for pre-existing comorbidity and injury severity, delayed surgery was associated with a decreased odds of inpatient mortality (odds ratio = 0.81, P = 0.04), or a 19% decrease in odds of mortality with each 24-hour increase in time until surgery. The association of time to surgery with serious adverse events was not statistically significant (P = 0.09), whereas time to surgery was associated with increased odds of minor adverse events (odds ratio = 1.06, P < 0.001). Although the potential neurological effect of surgical timing for patients with ATCCS remains controversial, the decreased mortality with delayed surgery suggests that waiting to optimize general health and potentially allow for some spinal cord recovery in these patients may be advantageous. 3.

Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics

PubMed Central

Cheng, Cuilin; Baranenko, Denis; Wang, Jiaping; Li, Yongzhi; Lu, Weihong

2018-01-01

The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse. Therefore, there were higher pharmacokinetic parameters—AUC, MRT, and t1/2 of the two compounds in radiation-injured mouse, when compared with normal mouse. In order to investigate the intrinsic mechanism of AS on radiation injury, AS extract’s protective effects on brain, the main part of mouse that suffered from radiation, were explored. The function of AS extract in repressing expression changes of radiation response proteins in prefrontal cortex (PFC) of mouse brain included tubulin protein family (α-, β-tubulin subunits), dihydropyrimidinase-related protein 2 (CRMP2), γ-actin, 14-3-3 protein family (14-3-3ζ, ε), heat shock protein 90β (HSP90β), and enolase 2. The results demonstrated the AS extract had positive effects on nerve cells’ structure, adhesion, locomotion, fission, and phagocytosis, through regulating various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol 3 kinase/protein kinase B), Neurotrophin, Rap1 (Ras-related protein RAP-1A), gap junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1) signaling pathways to maintain normal mouse neurological activity. All of the results indicated that AS may be a promising alternative medicine for the treatment of radiation injury in mouse brain. It would be tested that whether the bioactive ingredients of AS could be

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.

Delayed Traumatic Intracranial Haemorrhage and Progressive Traumatic Brain Injury in a Major Referral Centre Based in a Developing Country

PubMed Central

Jeng, Toh Charng; Haspani, Mohd Saffari Mohd; Adnan, Johari Siregar; Naing, Nyi Nyi

2008-01-01

A repeat Computer Tomographic (CT) brain after 24–48 hours from the 1st scanning is usually practiced in most hospitals in South East Asia where intracranial pressure monitoring (ICP) is routinely not done. This interval for repeat CT would be shortened if there was a deterioration in Glasgow Coma Scale (GCS). Most of the time the prognosis of any intervention may be too late especially in hospitals with high patient-to-doctor ratio causing high mortality and morbidity. The purpose of this study was to determine the important predictors for early detection of Delayed Traumatic Intracranial Haemorrhage (DTICH) and Progressive Traumatic Brain Injury (PTBI) before deterioration of GCS occurred, as well as the most ideal timing of repeated CT brain for patients admitted in Malaysian hospitals. A total of 81 patients were included in this study over a period of six months. The CT scan brain was studied by comparing the first and second CT brain to diagnose the presence of DTICH/PTBI. The predictors tested were categorised into patient factors, CT brain findings and laboratory investigations. The mean age was 33.1 ± 15.7 years with a male preponderance of 6.36:1. Among them, 81.5% were patients from road traffic accidents with Glasgow Coma Scale ranging from 4 – 15 (median of 12) upon admission. The mean time interval delay between trauma and first CT brain was 179.8 ± 121.3 minutes for the PTBI group. The DTICH group, 9.9% of the patients were found to have new intracranial clots. Significant predictors detected were different referral hospitals (p=0.02), total GCS status (p=0.026), motor component of GCS (p=0.043), haemoglobin level (p<0.001), platelet count (p=0.011) and time interval between trauma and first CT brain (p=0.022). In the PTBI group, 42.0% of the patients were found to have new changes (new clot occurrence, old clot expansion and oedema) in the repeat CT brain. Univariate statistical analysis revealed that age (p=0.03), race (p=0.035), types of

Delayed rectifier potassium channels are involved in SO2 derivative-induced hippocampal neuronal injury.

PubMed

Li, Guangke; Sang, Nan

2009-01-01

Recent studies implicate the possible neurotoxicity of SO(2), however, its mechanisms remain unclear. In the present study, we investigated SO(2) derivative-induced effect on delayed rectifier potassium channels (I(K)) and cellular death/apoptosis in primary cultured hippocampal neurons. The results demonstrate that SO(2) derivatives (NaHSO(3) and Na(2)SO(3), 3:1M/M) effectively augmented I(K) and promoted the activation of delayed rectifier potassium channels. Also, SO(2) derivatives increased neuronal death percentage and contributed to the formation of DNA ladder in concentration-dependent manners. Interestingly, the neuronal death and DNA ladder formation, caused by SO(2) derivatives, could be attenuated by the delayed rectifier potassium channel blocker (tetraethylammonium, TEA), but not by the transient outward potassium channel blocker (4-aminopyridine, 4-AP). It implies that stimulating delayed rectifier potassium channels were involved in SO(2) derivative-caused hippocampal neuronal insults, and blocking these channels might be one of the possibly clinical treatment for SO(2)-caused neuronal dysfunction.

Agricultural injuries to the hand and upper extremity.

PubMed

Yaffe, Mark Aaron; Kaplan, F Thomas

2014-10-01

Agricultural injuries involving the hand and upper extremity are common, debilitating injuries that reflect the significant occupational hazards associated with the agricultural industry. Farm injuries occur in all age groups and are associated with significant resource utilization and treatment costs. Most of these injuries are associated with machinery, including tractors, power take-off devices, grain augers, hay balers, and combine harvesters. Each piece of machinery produces specific injury patterns and a spectrum of bone and soft-tissue injuries that are frequently characterized by the loss of a digit or limb, permanent disability, loss of function, and serious complications such as infection. Management of agricultural injuries includes expedient administration of antibiotic and tetanus prophylaxis, aggressive irrigation, serial débridement, consideration of delayed wound closure, and reconstruction or replantation of amputated digits and limbs, if feasible. Copyright 2014 by the American Academy of Orthopaedic Surgeons.

WE-D-BRE-01: A Sr-90 Irradiation Device for the Study of Cutaneous Radiation Injury

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

Dorand, JE; Bourland, JD; Burnett, LR

2014-06-15

Purpose: To determine dosimetric character for a custom-built Sr-90 beta irradiator designed for the study of Cutaneous Radiation Injury (CRI) in a porcine animal model. In the event of a radiological accident or terrorist event, Sr-90, a fission by-product, will likely be produced. CRI is a main concern due to the low energy and superficial penetration in tissue of beta particles from Sr-90. Seven 100 mCi plaque Sr-90 radiation sources within a custom-built irradiation device create a 40 mm diameter region of radiation-induced skin injury as part of a larger project to study the efficacy of a topical keratin-based productmore » in CRI healing. Methods: A custom-built mobile irradiation device was designed and implemented for in vivo irradiations. Gafchromic™ EBT3 radiochromic film and a PTW Markus chamber type 23343 were utilized for dosimetric characterization of the beta fluence at the surface produced by this device. Films were used to assess 2-dimensional dose distribution and percent depth dose characteristics of the radiation field. Ion chamber measurements provided dose rate data within the field. Results: The radiation field produced by the irradiation device is homogeneous with high uniformity (∼5%) and symmetry (∼3%) with a steep dose fall-off with depth from the surface. Dose rates were determined to be 3.8 Gy/min and 3.3 Gy/min for film and ion chamber measurements, respectively. A dose rate of 3.4 Gy/min was used to calculate irradiation times for in vivo irradiations. Conclusion: The custom-built irradiation device enables the use of seven Sr-90 beta sources in an array to deliver a 40 mm diameter area of homogeneous skin dose with a dose rate that is useful for research purposes and clinically relevant for the induction of CRI. Doses of 36 and 42 Gy successfully produce Grade III CRI and are used in the study of the efficacy of KeraStat™. This project has been funded in whole or in part with Federal funds from the Biomedical Advanced

Skin Response to Delayed Hypersensitivity Testing in Persons With Unilateral Stroke-related Paresis: Implications for People With Spinal Cord Injury

PubMed Central

Trautner, Barbara W; Zimmermann, Kuno P; Squyres, Sara A; Darouiche, Rabih O

2007-01-01

Background: Vaccination rates among individuals with spinal cord injury (SCI) could be improved if it can be shown that vaccination performed on insensate areas is effective. This would eliminate the the risk of discomfort and soreness at the injection site. Objective: To determine whether immune responsiveness varies between areas with intact and impaired innervation in patients with stroke-related paresis. Design: Prospective trial in which each subject served as his or her own control. Setting: Rehabilitation wards and long-term care units at a Veterans Affairs Medical Center. Patients: Individuals with a history of cerebrovascular accident (CVA) affecting 1 side of the body. Methods: The Multitest cell-mediated immunity (CMI) and purified protein derivative (PPD) of tuberculin were administered intradermally to each arm of each subject. Main Outcome Measures: Total millimeters of induration in response to either test and positive vs negative responses to either test were compared between the 2 arms of each subject. Results: Response to delayed hypersensitivity testing did not differ between the arms affected and unaffected by CVA in each subject, and the time since CVA also did not affect the magnitude of the skin response. Conclusions: Skin testing for delayed hypersensitivity can be effectively administered in the paretic arms of persons who have experienced CVA. Although this study was performed in patients with stroke-related impairment, it has implications for vaccine administration in individuals with SCI-related neurologic deficits. PMID:17853658

Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice

PubMed Central

2013-01-01

Background Radiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes. Methods Mouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred. Results Genistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group. Conclusion Genistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients. PMID:23672582

Outcomes of popliteal vascular injuries at Sri Lankan war-front military hospital: case series of 44 cases.

PubMed

Ratnayake, Amila; Samarasinghe, Bandula; Bala, Miklosh

2014-05-01

Traumatic injury to the popliteal vascular zone remains a challenging problem on the modern battlefield and is frequently associated with more complications than other vascular injuries. Limb salvage and morbidity (graft infection, thrombosis and delayed haemorrhage) were studied. All popliteal vascular injuries over an 8 month period admitted to the Military Base Hospital were analyzed. Local limb evaluation included confirmation of the presence of ischaemia, extent of soft tissue damage, muscle viability after calf fasciotomy, and neurological injury. Ischaemic time was recorded from the time of injury to definitive revascularization. If there was a prior attempt at reconstruction, the amputation was considered delayed. For a series of 44 patients with popliteal vascular injury average time to presentation was 390min, 46% were completely ischaemic. Of those 39 (89%) had popliteal artery injuries. There were 24 (62%) complete popliteal artery transections and associated venous (69%) and osseous (46%) injuries. The preferred technique of repair was inter-position venous graft (IPVG) (54%). Eleven immediate amputations were performed (28%). There were 13 wound infections (33%), 5 early graft thromboses (5 of 21 IPVG, 238%), 2 anastomotic disruptions (2 of 21 IPVG, 9%), which resulted in 4 delayed amputations. Mortality was 5% (2 patients). In this case series of popliteal artery injury early identification of limbs at risk, early four compartment fasciotomy, temporary intra-luminal shunting, definitive repair of concomitant venous injuries and aggressive treatment of haemodynamic instability were shown to be beneficial in achieving reasonable outcome in an austere environment with limited recourses. Copyright © 2014 Elsevier Ltd. All rights reserved.

Renal artery and vein injury following blunt trauma.

PubMed Central

Sturm, J T; Perry, J F; Cass, A S

1975-01-01

Blunt injuries of the renal vascular pedicle occur infrequently. The experience with fourteen cases of blunt renal vascular trauma is presented. Most patients were injured in motor vehicle accidents. The diagnosis was made immediately after admission in 6 patients, delayed in 5, and at autopsy in 3. Most patients presented with gross or microscopic hematuria. The diagnosis of renal vascular injury was suggested by IVP in most instances. Surgical management was used in the 6 patients in whom the immediate diagnosis of renal pedicle injury was made; primary vascular repair was carried out in 4 patients and nephrectomy in two. Conservative management was used in 4 of the 5 patients with delayed diagnosis, and nephrectomy was required in the fifth. Three patients received no treatment as two were dead on arrival and one die during laparotomy. Seven patients died (50%). One of the 7 survivors has a functioning kidney following repair of a renal vein laceration. Three patients with devascularized kidneys have been followed long term and have not developed hypertension. An IVP should be mandatory following severe blunt trauma, especially when hematuria is present. Renal arteriography is indicated with distortion of calyces, extravasation or nonfunction seen on IVP and allows a definitive diagnosis of renal vessel injury to be made. PMID:1190872

Ischemia and reperfusion injury in renal transplantation: hemodynamic and immunological paradigms

PubMed Central

Requião-Moura, Lúcio Roberto; Durão, Marcelino de Souza; de Matos, Ana Cristina Carvalho; Pacheco-Silva, Alvaro

2015-01-01

Ischemia and reperfusion injury is an inevitable event in renal transplantation. The most important consequences are delayed graft function, longer length of stay, higher hospital costs, high risk of acute rejection, and negative impact of long-term follow-up. Currently, many factors are involved in their pathophysiology and could be classified into two different paradigms for education purposes: hemodynamic and immune. The hemodynamic paradigm is described as the reduction of oxygen delivery due to blood flow interruption, involving many hormone systems, and oxygen-free radicals produced after reperfusion. The immune paradigm has been recently described and involves immune system cells, especially T cells, with a central role in this injury. According to these concepts, new strategies to prevent ischemia and reperfusion injury have been studied, particularly the more physiological forms of storing the kidney, such as the pump machine and the use of antilymphocyte antibody therapy before reperfusion. Pump machine perfusion reduces delayed graft function prevalence and length of stay at hospital, and increases long-term graft survival. The use of antilymphocyte antibody therapy before reperfusion, such as Thymoglobulin™, can reduce the prevalence of delayed graft function and chronic graft dysfunction. PMID:25993079

Nonoperative management of splenic injury in combat: 2002-2012.

PubMed

Mitchell, Thomas A; Wallum, Timothy E; Becker, Tyson E; Aden, James K; Bailey, Jeffrey A; Blackbourne, Lorne H; White, Christopher E

2015-03-01

Selective nonoperative management of combat-related blunt splenic injury (BSI) is controversial. We evaluated the impact of the November 2008 blunt abdominal trauma clinical practice guideline that permitted selective nonoperative management of some patients with radiological suggestion of hemoperitoneum on implementation of nonoperative management (NOM) of splenic injury in austere environments. Retrospective evaluation of patients with splenic injuries from November 2002 through January 2012 in Iraq and Afghanistan was performed. International Classification of Diseases, 9th Revision, Clinical Modification procedure codes identified patients as laparotomy with splenectomy, or NOM. Delayed operative management had no operative intervention at earlier North American Treaty Organization (NATO) medical treatment facilities (MTFs), and had a definitive intervention at a latter NATO MTFs. Intra-abdominal complications and overall mortality were juxtaposed. A total of 433 patients had splenic injuries from 2002 to 2012. Initial NOM of BSI from 2002 to 2008 compared to 2009-2012 was 44.1% and 47.2%, respectively (p=0.75). Delayed operative management and NOM completion had intra-abdominal complication and mortality rates of 38.1% and 9.1% (p<0.01), and 6.3% and 8.1% (p=0.77). Despite high-energy explosive injuries, NATO Role II MTFs radiological constraints and limited medical resources, hemodynamically normal patients with BSI and low abdominal abbreviated injury scores underwent NOM in austere environments. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Lung Cancer: Posttreatment Imaging: Radiation Therapy and Imaging Findings.

PubMed

Benveniste, Marcelo F; Welsh, James; Viswanathan, Chitra; Shroff, Girish S; Betancourt Cuellar, Sonia L; Carter, Brett W; Marom, Edith M

2018-05-01

In this review, we discuss the different radiation delivery techniques available to treat non-small cell lung cancer, typical radiologic manifestations of conventional radiotherapy, and different patterns of lung injury and temporal evolution of the newer radiotherapy techniques. More sophisticated techniques include intensity-modulated radiotherapy, stereotactic body radiotherapy, proton therapy, and respiration-correlated computed tomography or 4-dimensional computed tomography for radiotherapy planning. Knowledge of the radiation treatment plan and technique, the completion date of radiotherapy, and the temporal evolution of radiation-induced lung injury is important to identify expected manifestations of radiation-induced lung injury and differentiate them from tumor recurrence or infection. Published by Elsevier Inc.

Delayed Union of a Sacral Fracture: Percutaneous Navigated Autologous Cancellous Bone Grafting and Screw Fixation

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

Huegli, R. W.; Messmer, P.; Jacob, A. L.

2003-09-15

Delayed or non-union of a sacral fracture is a serious clinical condition that may include chronic pain, sitting discomfort, gait disturbances, neurological problems, and inability to work. It is also a difficult reconstruction problem. Late correction of the deformity is technically more demanding than the primary treatment of acute pelvic injuries. Open reduction, internal fixation (ORIF), excision of scar tissue, and bone grafting often in a multi-step approach are considered to be the treatment of choice in delayed unions of the pelvic ring. This procedure implies the risk of neurological and vascular injuries, infection, repeated failure of union, incomplete correctionmore » of the deformity, and incomplete pain relief as the most important complications. We report a new approach for minimally invasive treatment of a delayed union of the sacrum without vertical displacement. A patient who suffered a Malgaigne fracture (Tile C1.3) was initially treated with closed reduction and percutaneous screw fixation (CRPF) of the posterior pelvic ring under CT navigation and plating of the anterior pelvic ring. Three months after surgery he presented with increasing hip pain caused by a delayed union of the sacral fracture. The lesion was successfully treated percutaneously in a single step procedure using CT navigation for drilling of the delayed union, autologous bone grafting, and screw fixation.« less

CT imaging of blunt traumatic bowel and mesenteric injuries.

PubMed

LeBedis, Christina A; Anderson, Stephan W; Soto, Jorge A

2012-01-01

Delayed diagnosis of a bowel or mesenteric injury resulting in hollow viscus perforation leads to significant morbidity and mortality from hemorrhage, peritonitis, or abdominal sepsis. The timely diagnosis of bowel and mesenteric injuries requiring operative repair depends almost exclusively on their early detection by the radiologist on computed tomography examination, because the clinical signs and symptoms of these injuries are not specific and usually develop late. Therefore, the radiologist must be familiar with the often-subtle imaging findings of bowel and mesenteric injury that will allow for appropriate triage of a patient who has sustained blunt trauma to the abdomen or pelvis. 2012 Elsevier Inc. All rights reserved.

Radionuclide Imaging of Musculoskeletal Injuries in Athletes with Negative Radiographs.

PubMed

Nagle, C E; Freitas, J E

1987-06-01

In brief: Radionuclide bone scans can be useful in the diagnostic evaluation of musculoskeletal injuries in athletes. Bone scans can detect shinsplints, stress fractures, and muscle injuries before they are detectable on radiographs. Prognosis can be accurately assessed, allowing appropriate treatment to proceed without delay. The authors discuss the use of bone scans and identify musculoskeletal injuries that are associated with specific sports, such as stress fracture of the femur (soccer), tibia (running), scapula (gymnastics), and pars interarticularis (football or lacrosse).

HGF Gene Modification in Mesenchymal Stem Cells Reduces Radiation-Induced Intestinal Injury by Modulating Immunity.

PubMed

Wang, Hua; Sun, Rui-Ting; Li, Yang; Yang, Yue-Feng; Xiao, Feng-Jun; Zhang, Yi-Kun; Wang, Shao-Xia; Sun, Hui-Yan; Zhang, Qun-Wei; Wu, Chu-Tse; Wang, Li-Sheng

2015-01-01

Effective therapeutic strategies to address intestinal complications after radiation exposure are currently lacking. Mesenchymal stem cells (MSCs), which display the ability to repair the injured intestine, have been considered as delivery vehicles for repair genes. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF)-gene-modified MSCs on radiation-induced intestinal injury (RIII). Female 6- to 8-week-old mice were radiated locally at the abdomen with a single 13-Gy dose of radiation and then treated with saline control, Ad-HGF or Ad-Null-modified MSCs therapy. The transient engraftment of human MSCs was detected via real-time PCR and immunostaining. The therapeutic effects of non- and HGF-modified MSCs were evaluated via FACS to determine the lymphocyte immunophenotypes; via ELISA to measure cytokine expression; via immunostaining to determine tight junction protein expression; via PCNA staining to examine intestinal epithelial cell proliferation; and via TUNEL staining to detect intestinal epithelial cell apoptosis. The histopathological recovery of the radiation-injured intestine was significantly enhanced following non- or HGF-modified MSCs treatment. Importantly, the radiation-induced immunophenotypic disorders of the mesenteric lymph nodes and Peyer's patches were attenuated in both MSCs-treated groups. Treatment with HGF-modified MSCs reduced the expression and secretion of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ), increased the expression of the anti-inflammatory cytokine IL-10 and the tight junction protein ZO-1, and promoted the proliferation and reduced the apoptosis of intestinal epithelial cells. Treatment of RIII with HGF-gene-modified MSCs reduces local inflammation and promotes the recovery of small intestinal histopathology in a mouse model. These findings might provide an effective therapeutic strategy for RIII.

Delayed splenic rupture: dating the sub-capsular hemorrhage as a useful task to evaluate causal relationships with trauma.

PubMed

Riezzo, Irene; Di Battista, Benedetta; De Salvia, Alessandra; Cantatore, Santina; Neri, Margherita; Pomara, Cristoforo; Turillazzi, Emanuela; Fineschi, Vittorio

2014-01-01

The aim of the paper was to perform a chronological assessment of the phenomenon of delayed rupture of the spleen, to assess the phenomenological order about the sub-capsular hematoma transformation to determine the causal relationship with trauma as hypothetical cause of death. 80 cases of blunt trauma with splenic capsular hematoma and subsequent rupture of the spleen were evaluated: 38 had an acute rupture of the spleen, 42 presented a break in days or weeks after the traumatic injury. Time between the traumatic event and delayed rupture of the spleen is within a range of time from one day to more than one month. Data recorded included age, sex, type of trauma, injury severity score, grade of splenic injury, associated intra-abdominal injuries, pathologic specimen evaluation. Immunohistochemical investigation of perisplenic hematoma or laceration was performed utilizing polyclonal antibodies anti-fibrinogen, CD61 and CD68, and showed structural chronological differences of sub-capsular hematoma. Expression of modification and organization of erythrocytes, fibrinogen, platelets and macrophages provides an informative picture of the progression of reparative phenomena associated with sub-capsular hematoma and subsequent delayed splenic rupture. Sub-capsular splenic hematoma dating, which we divided into 4 phases, is representing a task in both clinical practice and forensic pathology. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Contribution of methylglyoxal to delayed healing of bone injury in diabetes.

PubMed

Aikawa, Takao; Matsubara, Hidenori; Ugaji, Shuhei; Shirakawa, Junichi; Nagai, Ryoji; Munesue, Seiichi; Harashima, Ai; Yamamoto, Yasuhiko; Tsuchiya, Hiroyuki

2017-07-01

Patients with diabetes are vulnerable to delayed bone fracture healing or pseudoarthrosis. Chronic sustained hyperglycemia, reactive intermediate derivatives of glucose metabolism, such as methylglyoxal (MGO), and advanced glycation end‑products (AGEs) are implicated in diabetic complications. In the present study, it was examined whether MGO is able to cause disturbed bone healing in diabetes. Diabetes was induced in male mice by injection of streptozotocin (50 mg/kg) for 5 days. A bone defect (1.0‑mm diameter) was created in the left distal femur, and bone repair was assessed from an examination of computed tomography scans. ST2 cells were exposed to MGO (0‑400 µM) to investigate osteoblastic differentiation, cell viability, and damage. Consequently, blood glucose and hemoglobin A1c levels in diabetic mice were determined to be 493±14.1 mg/dl and 8.0±0.05%, respectively. Compared with non‑diabetic control mice, diabetic mice exhibited markedly delayed bone healing, with increased levels of the MGO‑derived AGEs, Nε‑(carboxymethyl)‑lysine and Nδ‑(5‑hydro‑5‑methyl‑4‑imidazolone‑2‑yl)‑ornithine, in the sera and femurs. MGO inhibited the osteoblastic differentiation of ST2 cells in a dose‑dependent manner, and markedly decreased cell proliferation through cytotoxicity. In conclusion, MGO has been demonstrated to cause impaired osteoblastic differentiation and delayed bone repair in diabetes. Therefore, detoxification of MGO may be a potentially useful strategy against bone problems in patients with diabetes.

Injuries from non-retention in gillnet fisheries suppress reproductive maturation in escaped fish.

PubMed

Baker, Matthew R; Swanson, Penny; Young, Graham

2013-01-01

Exploitation of fisheries resources has unintended consequences, not only in the bycatch and discard of non-target organisms, but also in damage to targeted fish that are injured by gear but not landed (non-retention). Delayed mortality due to non-retention represents lost reproductive potential in exploited stocks, while not contributing to harvest. Our study examined the physiological mechanisms by which delayed mortality occurs and the extent to which injuries related to disentanglement from commercial gear compromise reproductive success in spawning stocks of Pacific salmon (Oncorhynchus spp.). We found evidence for elevated stress in fish injured via non-retention in gillnet fisheries. Plasma cortisol levels correlated with the severity of disentanglement injury and were elevated in fish that developed infections related to disentanglement injuries. We also analyzed sex steroid concentrations in females (estradiol-17β and 17,20β-dihydroxy-4-pregnen-3-one) to determine whether non-retention impairs reproductive potential in escaped individuals. We demonstrate evidence for delayed or inhibited maturation in fish with disentanglement injuries. These findings have important implications for effective conservation and management of exploited fish stocks and suggest means to improve spawning success in such stocks if retention in commercial fisheries is improved and incidental mortality reduced.

Injuries from Non-Retention in Gillnet Fisheries Suppress Reproductive Maturation in Escaped Fish

PubMed Central

Baker, Matthew R.; Swanson, Penny; Young, Graham

2013-01-01

Exploitation of fisheries resources has unintended consequences, not only in the bycatch and discard of non-target organisms, but also in damage to targeted fish that are injured by gear but not landed (non-retention). Delayed mortality due to non-retention represents lost reproductive potential in exploited stocks, while not contributing to harvest. Our study examined the physiological mechanisms by which delayed mortality occurs and the extent to which injuries related to disentanglement from commercial gear compromise reproductive success in spawning stocks of Pacific salmon (Oncorhynchus spp.). We found evidence for elevated stress in fish injured via non-retention in gillnet fisheries. Plasma cortisol levels correlated with the severity of disentanglement injury and were elevated in fish that developed infections related to disentanglement injuries. We also analyzed sex steroid concentrations in females (estradiol-17β and 17,20β-dihydroxy-4-pregnen-3-one) to determine whether non-retention impairs reproductive potential in escaped individuals. We demonstrate evidence for delayed or inhibited maturation in fish with disentanglement injuries. These findings have important implications for effective conservation and management of exploited fish stocks and suggest means to improve spawning success in such stocks if retention in commercial fisheries is improved and incidental mortality reduced. PMID:23894510

The contemporary management of penetrating splenic injury.

PubMed

Berg, Regan J; Inaba, Kenji; Okoye, Obi; Pasley, Jason; Teixeira, Pedro G; Esparza, Michael; Demetriades, Demetrios

2014-09-01

Selective non-operative management (NOM) is standard of care for clinically stable patients with blunt splenic trauma and expectant management approaches are increasingly utilised in penetrating abdominal trauma, including in the setting of solid organ injury. Despite this evolution of clinical practice, little is known about the safety and efficacy of NOM in penetrating splenic injury. Trauma registry and medical record review identified all consecutive patients presenting to LAC+USC Medical Center with penetrating splenic injury between January 2001 and December 2011. Associated injuries, incidence and nature of operative intervention, local and systemic complications and mortality were determined. During the study period, 225 patients experienced penetrating splenic trauma. The majority (187/225, 83%) underwent emergent laparotomy. Thirty-eight clinically stable patients underwent a deliberate trial of NOM and 24/38 (63%) were ultimately managed without laparotomy. Amongst patients failing NOM, 3/14 (21%) underwent splenectomy while an additional 6/14 (42%) had splenorrhaphy. Hollow viscus injury (HVI) occurred in 21% of all patients failing NOM. Forty percent of all NOM patients had diaphragmatic injury (DI). All patients undergoing delayed laparotomy for HVI or a splenic procedure presented symptomatically within 24h of the initial injury. No deaths occurred in patients undergoing NOM. Although the vast majority of penetrating splenic trauma requires urgent operative management, a group of patients does present without haemodynamic instability, peritonitis or radiologic evidence of hollow viscus injury. Management of these patients is complicated as over half may remain clinically stable and can avoid laparotomy, making them potential candidates for a trial of NOM. HVI is responsible for NOM failure in up to a fifth of these cases and typically presents within 24h of injury. Delayed laparotomy, within this limited time period, did not appear to increase

Hyperbaric oxygen for neurologic indications--action plan for multicenter trials in: stroke, traumatic brain injury, radiation encephalopathy & status migrainosus.

PubMed