Medical countermeasures for radiation combined injury: radiation with burn, blast, trauma and/or sepsis. report of an NIAID Workshop, March 26-27, 2007

Non-clinical human radiation exposure events such as the Hiroshima and Nagasaki bombings or the Chernobyl accident are often coupled with other forms of injury, such as wounds, burns, blunt trauma, and infection. Radiation combined injury would also be expected after a radiological or nuclear attack. Few animal models of radiation combined injury exist, and mechanisms underlying the high mortality associated with complex radiation injuries are poorly understood. Medical countermeasures are currently available for management of the non-radiation components of radiation combined injury, but it is not known whether treatments for other insults will be effective when the injury is combined with radiation exposure. Further research is needed to elucidate mechanisms behind the synergistic lethality of radiation combined injury and to identify targets for medical countermeasures. To address these issues, the National Institute of Allergy and Infectious Diseases convened a workshop to make recommendations on the development of animal models of radiation combined injury, possible mechanisms of radiation combined injury, and future directions for countermeasure research, including target identification and end points to evaluate treatment efficacy.     

Progress in research on radiation combined injury in China

The significant feature of radiation combined injury is the occurrence of a combined effect. For decades our institute has focused on studying the key complications of radiation-burn injury, including shock, suppression of hematopoiesis and immunity, gastrointestinal damage and local refractory wound healing. Here we summarize recent advancements in elucidating the mechanisms of and potential treatments for radiation combined injury. Concerning the suppression and regeneration of hematopoiesis in radiation combined injury, mechanisms of megakaryocyte damage have been elucidated and a new type of fusion protein stimulating thrombopoiesis has been developed and is being tested in animals. With regard to the damage and repair of intestinal epithelium, the important molecular mechanisms of radiation combined injury have been clarified, and new measures to prevent and treat gastrointestinal tract injury are proposed. With respect to the difficulties encountered in wound healing, the underlying causes of radiation combined injury have been proposed, and some potential methods to accelerate wound closure are under study. Systemic experiments have been done to determine the appropriate time for eschar excision and skin grafting, and the results provided significant insight into clinical treatment of the injury. In the search for early therapeutic regimens for severe burns and radiation combined injury to prevent deterioration of injuries and to improve survival, cervical sympathetic ganglion block was used for the treatment of animals with radiation combined injury and had significant benefits. These research advancements have potential for application in on-site emergency rescue and in-hospital treatment of radiation combined injury.     

Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries. Report of an NCI Workshop, December 3-4, 2003

To develop approaches to prophylaxis/protection, mitigation and treatment of radiation injuries, appropriate models are needed that integrate the complex events that occur in the radiation-exposed organism. While the spectrum of agents in clinical use or preclinical development is limited, new research findings promise improvements in survival after whole-body irradiation and reductions in the risk of adverse effects of radiotherapy. Approaches include agents that act on the initial radiochemical events, agents that prevent or reduce progression of radiation damage, and agents that facilitate recovery from radiation injuries. While the mechanisms of action for most of the agents with known efficacy are yet to be fully determined, many seem to be operating at the tissue, organ or whole animal level as well as the cellular level. Thus research on prophylaxis/protection, mitigation and treatment of radiation injuries will require studies in whole animal models. Discovery, development and delivery of effective radiation modulators will also require collaboration among researchers in diverse fields such as radiation biology, inflammation, physiology, toxicology, immunology, tissue injury, drug development and radiation oncology. Additional investment in training more scientists in radiation biology and in the research portfolio addressing radiological and nuclear terrorism would benefit the general population in case of a radiological terrorism event or a large-scale accidental event as well as benefit patients treated with radiation.     

Animal models for radiation injury, protection and therapy

Current events throughout the world underscore the growing threat of different forms of terrorism, including radiological or nuclear attack. Pharmaceutical products and other approaches are needed to protect the civilian population from radiation and to treat those with radiation-induced injuries. In the event of an attack, radiation exposures will be heterogeneous in terms of both dose and quality, depending on the type of device used and each victim's location relative to the radiation source. Therefore, methods are needed to protect against and treat a wide range of early and slowly developing radiation-induced injuries. Equally important is the development of rapid and accurate biodosimetry methods for estimating radiation doses to individuals and guiding clinical treatment decisions. Acute effects of high-dose radiation include hematopoietic cell loss, immune suppression, mucosal damage (gastrointestinal and oral), and potential injury to other sites such as the lung, kidney and central nervous system (CNS). Long-term effects, as a result of both high- and low-dose radiation, include dysfunction or fibrosis in a wide range of organs and tissues and cancer. The availability of appropriate types of animal models, as well as adequate numbers of animals, is likely to be a major bottleneck in the development of new or improved radioprotectors, mitigators and therapeutic agents to prevent or treat radiation injuries and of biodosimetry methods to measure radiation doses to individuals.     

Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection: report of a workshop at Bethesda,Maryland, December 17-18, 2001

Exposures to doses of radiation of 1-10 Gy, defined in this workshop as moderate-dose radiation, may occur during the course of radiation therapy or as the result of radiation accidents or nuclear/radiological terrorism alone or in conjunction with bioterrorism. The resulting radiation injuries would be due to a series of molecular, cellular, tissue and whole-animal processes. To address the status of research on these issues, a broad-based workshop was convened. The specific recommendations were: (1) Research: Identify the key molecular, cellular and tissue pathways that lead from the initial molecular lesions to immediate and delayed injury. The latter is a chronic progressive process for which postexposure treatment may be possible. (2) Technology: Develop high-throughput technology for studying gene, protein and other biochemical expression after radiation exposure, and cytogenetic markers of radiation exposure employing rapid and accurate techniques for analyzing multiple samples. (3) Treatment strategies: Identify additional biological targets and develop effective treatments for radiation injury. (4) Ensuring sufficient expertise: Recruit and train investigators from such fields as radiation biology, cancer biology, molecular biology, cellular biology and wound healing, and encourage collaboration on interdisciplinary research on the mechanisms and treatment of radiation injury. Communicate knowledge of the effects of radiation exposure to the general public and to investigators, policy makers and agencies involved in response to nuclear accidents/events and protection/treatment of the general public.     

入伍新训中膝关节损伤的特点与防治研究

目的：通过对某部新入伍官兵训练中膝关节损伤发生原因、特点进行流行性病学调查和分析,为合理训练,预防损伤发生和 治疗相关伤病提供指导依据。方法：对某部2013 年度450 名新入伍官兵的训练伤发病情况进行统计分析,重点分析膝关节损伤 发生率、伤病类型和致伤原因,并对其严重者进行关节镜治疗,观察和分析术后随访效果。结果：某部新兵的训练伤发生率为 20.0%。以关节急性扭伤最为多见,占81.1%。其中膝关节损伤共发生32 例,占训练伤发病率为7.1%,占训练伤发病率43.8%,其 中膝关节周围肌肉损伤20 例、交叉韧带损伤1 例、半月板损伤9 例、侧副韧带损伤2 例。致伤率最高的前3 位科目是5000 米负 重跑、跨越障碍训练、格斗训练,共27 例,占膝关节训练伤总数的84.4%。所有受伤患者中,12 例行手术治疗,20 例给予石膏、支具 固定、休息等保守治疗。经随访所有患者均得到较好的功能恢复。结论：对于新兵膝关节训练伤预防工作非常重要,避免致残;关 节镜手术技术的进步对于膝关节军事训练伤治疗有良好的效果。     

Human Ghrelin Mitigates Intestinal Injury and Mortality after Whole Body Irradiation in Rats

Widespread use of ionizing radiation has led to the realization of the danger associated with radiation exposure. Although studies in radiation countermeasures were initiated a half century ago, an effective therapy for a radiomitigator has not been identified. Ghrelin is a gastrointestinal hormone, and administration of ghrelin is protective in animal models of injuries including radiation combined injury. To test whether ghrelin can be protective in whole body irradiaton (WBI) alone, male Sprague Dawley (SD) rats were treated with human ghrelin (20 nmol/rat) daily for 6 days starting at either 24 h or 48 h after 10 Gray (Gy) WBI and survival outcome was examined. The 10 Gy WBI produced a LD^70/30 model in SD rats (30% survival in 30 days). The survival rate in rats treated with ghrelin starting at 24 h was significantly improved to 63% and when treatment was initiated at 48 h, the survival remained at 61%. At 7 days post WBI, plasma ghrelin was significantly reduced from the control value. Ghrelin treatment starting at 24 h after WBI daily for 6 days improved histological appearance of the intestine, reduced gut permeability, serum endotoxin levels and bacterial translocation to the liver by 38%, 42% and 61%, respectively at day 7 post WBI. Serum glucose and albumin were restored to near control levels with treatment. Ghrelin treatment also attenuated WBI-induced intestinal apoptosis by 62% as evidenced by TUNEL staining. The expression of anti-apoptotic cell regulator Bcl-xl was decreased by 38% in the vehicle and restored to 75% of the control with ghrelin treatment. Increased expression of intestinal CD73 and pAkt were observed with ghrelin treatment, indicating protection of the intestinal epithelium after WBI. These results indicate that human ghrelin attenuates intestinal injury and mortality after WBI. Thus, human ghrelin can be developed as a novel mitigator for radiation injury.     

Effects of dexamethasone on late radiation injury following partial-body and local organ exposures.

Dexamethasone was evaluated as a treatment for radiation-induced lung, kidney, liver, and spinal cord injuries in rats. One experimental group was partial-body-irradiated (22.5 Gy) with the head, femur, and exteriorized intestine shielded to prevent acute mortality. Other animals received local irradiation to the kidney (20 Gy), liver (25 Gy), or a 1-cm segment of cervical spinal cord (18 to 40 Gy). Following irradiation half of the animals in each radiation group were given drinking water containing 188 micrograms/liter of dexamethasone. Tests were done to assess kidney function (hematocrit, plasma urea nitrogen, ethylenediaminetetraacetic acid clearance), liver function (rose bengal clearance, plasma glutamic oxaloacetic acid transaminase), or spinal cord injury (paralysis). The effectiveness of dexamethasone in preventing radiation injury was tissue specific. Dexamethasone eliminated lethal pleural fluid accumulation after partial-body irradiation and delayed development of kidney dysfunction after local kidney irradiation. As a result, dexamethasone increased the median survival time from 63 to 150 days after partial-body irradiation and from 126 to 175 days after local kidney irradiation. After whole-liver irradiation, development of hepatic functional injury was retarded by dexamethasone treatment but without significantly changing survival time. Dexamethasone had no effect on spinal cord tolerance but significantly shortened the latent period between radiation and paralysis.     

急性脊髓损伤的药物治疗进展概况

脊髓损伤(spinal cord injury,SCI)是临床上常见的一种创伤性疾病。随着社会的发展呈现上升的趋势,其来源主要有交通事故,工伤,坠落伤,暴力伤,运动损伤,积累性损伤等。传统的手术治疗是围绕脊柱的骨性结构进行椎管减压、脊柱稳定性的重建,并不能解决瘫痪的主要原因-脊髓损伤问题,预后并不理想。近年来国内外学者都在对SCI进行深入研究,想要找到SCI的根本机制,从而能针对性的研究出能改变SCI患者预后的药物。本文就对脊髓损伤目前的常用治疗药物做一篇综述。     

远紫外辐射对紫杉幼苗针叶膜脂过氧化及内源保护系统的影响

实验室条件下用远紫外线(UV-BC)光源照射紫杉幼苗,随照射时间延长,针叶的离子渗出率、膜脂过氧化水平、组织自动氧化速率及H₂O₂含量显著增加,可溶性蛋白、抗坏血酸、类胡萝卜素和叶绿素含量下降,叶绿体光系统II电子传递活性显著下降,外源活性氧清除剂苯甲酸钠和抗坏血酸对针叶膜脂过氧化有抑制作用;甲基紫精和DDC对针叶膜脂过氧化有促进效果,远紫外线引起的紫杉伤害可能和针叶树的越冬光氧化伤害有类似之处.紫杉苗对紫外辐射的抗性远高于一般农作物.     

道路交通事故致胫腓骨骨折的特点及救治

目的：总结交通事故伤中胫腓骨骨折的流行病学分类、特点及救治注意事项。方法：对136例交通事故伤中胫腓骨骨折患者的临床资料进行回顾性分析。结果：交通事故致胫腓骨骨折以多发伤及复合伤多见,经早期彻底清创、恰当的骨折固定、抗生素应用等,治愈77例,截肢2例,伤口浅表感染6例,骨髓炎1例。结论：交通事故伤中胫腓骨骨折大多伤情严重,感染率高,且开放性居多,早期及时选择合适的治疗方法是取得良好预后的关键。     

The Management of Abdominal Injuries in the Presence of Head Injury

When head and blunt abdominal injuries are combined, the head injury is often afforded too much attention and the abdominal injury too little, especially when the patient is unconscious. If mismanaged, the abdominal injury is often the more serious threat to life. Except for extradural hemorrhage, neurosurgical intervention, when indicated, can be delayed until the patient has been thoroughly evaluated for the presence of extra cranial injuries with higher therapeutic priority.Abdominal examination of the unconscious or uncooperative patient is difficult. Tenderness as a sign of abdominal injury cannot be elicited. Abdominal rigidity (in the absence of rigid extremities), a silent abdomen, shock, and extreme restlessness may indicate intra-abdominal changes. Abdominal paracentesis is a valuable diagnostic aid, and the finding of blood, bile-stained fluid, intestinal contents or air is an indication for immediate laparotomy. Once all injuries are known, priorities for treatment can be assigned. Often head and abdominal injuries can be treated concomitantly.     

Epidemiology of training injuries in amateur taekwondo athletes: a retrospective cohort study

The objectives of this study were to estimate the incidence and describe the pattern and severity of training injuries in taekwondo, and to compare pattern and severity of training injuries with competition injuries. One hundred and fifty-two active Australian amateur taekwondo athletes, aged 12 years or over, completed an online survey comprising questions on training exposure and injury history over the preceding 12 months. The main outcome measures were: overall injury incidence rate per athlete-year; training injury incidence rate per athlete-year, per 1000 athlete-training-sessions, and per 1000 athlete-hours of training; injury severity; and injury proportions by anatomical region and by type of injury. Injury incidence rates were calculated with 95% confidence intervals using standard methods, while injury proportions were compared using Fisher''s exact test. The vast majority (81.5%) of taekwondo injuries in an average athlete-year occurred during training. The training injury incidence rate was estimated to be 1.6 (95% CI: 1.4, 1.9) per athlete-year, 11.8 (95% CI: 10.4, 13.4) per 1000 athlete-training-sessions, and 7.0 (95% CI: 6.1, 7.9) per 1000 athlete-hours of training. Among athletes with five or fewer injuries, the severity and injury pattern of training injuries were, by and large, the same as for competition injuries. Approximately sixty percent (60.3%) of training injuries required treatment by a health professional. Considering the burden of training injuries exceeds that of competition injuries, taekwondo governing bodies and stakeholders are encouraged to devote more efforts towards the identification of risk factors for, and prevention of, training injuries in the sport of taekwondo.     

Injuries to dancers: prevalence,treatment, and perceptions of causes.

A survey of injuries to dancers was commissioned by the National Organisation of Dance and Mime. Questionnaires asking about chronic and recent injuries were sent to 188 dancers and completed by 141 dancers from seven professional ballet and modern dance companies in the United Kingdom (75% response rate). It was found that of the 141 dancers, 67 (47%) had experienced a chronic injury and 59 (42%) an injury in the previous six months that had affected their dancing. A high proportion of injuries to the soft tissues had not responded to treatment. With correct treatment such injuries should usually heal completely. Dancers are aware of the high rate of injuries and also of procedures that might help to prevent injury--for example, dancing on floors that are sprung and in warmer studios; teachers'' and choreographers'' awareness of a dancer''s limitations and the need for rest and adequate treatment when an injury occurs.     

Surfactant sealing of membranes permeabilized by ionizing radiation

Acute tissue injury and subsequent inflammation, including tissue edema and erythema, can be caused by sufficiently high levels of exposure to gamma radiation. The mechanism of this tissue injury is related to the generation of reactive oxygen intermediates (ROI) which chemically alter biological molecules and cell physiology. Cell membrane lipids are vulnerable to ROI-mediated lipid peroxidation that then leads to many of the acute tissue effects. We hypothesize that increased cell membrane permeability leading to osmotic swelling and vascular transudation is one of these effects. Thus we used adult postmitotic rhabdomyocytes in culture and microscopic fluorescence techniques to quantify radiation-induced changes in cell membrane permeability. Based on time-resolved dye flux measurements, a characteristic lag time of 34 +/- 3 min was determined between exposure to 160 Gy of gamma radiation and the decrease in membrane permeability. Administration of 0.1 mM nonionic surfactant Poloxamer 188 added to the cell medium after irradiation completely inhibited the dye loss over the time course of 2 h. Thus a reproducible model was developed for studying the mechanism of acute radiation injury and the efficacy of membrane-sealing agents. As only supportive measures now exist for treating the acute, nonlethal injuries from high-dose radiation exposure, agents that can restore cell membrane function after radiation damage may offer an important tool for therapy.     

Epidemiology of Spinal Cord Injuries and Risk Factors for Complete Injuries in Guangdong,China: A Retrospective Study

Background

Spinal cord injuries are highly disabling and deadly injuries. Currently, few studies focus on non-traumatic spinal cord injuries, and there is little information regarding the risk factors for complete injuries. This study aims to describe the demographics and the injury characteristics for both traumatic and non-traumatic spinal cord injuries and to explore the risk factors for complete spinal cord injuries.

Methods

A retrospective study was performed by reviewing the medical records of 3,832 patients with spinal cord injuries who were first admitted to the sampled hospitals in Guangdong, China. The demographics and injury characteristics of the patients were described and compared between the different groups using the chi-square test. Logistic regression was conducted to analyze the risk factors for complete spinal cord injuries.

Results

The proportion of patients increased from 7.0% to 14.0% from 2003 to 2011. The male-to-female ratio was 3.0∶1. The major cause of spinal cord injuries was traffic accidents (21.7%). Many of the injured were workers (36.2%), peasants (22.8%), and unemployed people (13.9%); these occupations accounted for 72.9% of the total sample. A multivariate logistic regression model revealed that the OR (95% CI) for male gender compared to female gender was 1.25 (1.07–1.89), the OR (95%CI) for having a spinal fracture was 1.56 (1.35–2.60), the OR (95%CI) for having a thoracic injury was 1.23 (1.10–2.00), and the OR (95%CI) for having complications was 2.47 (1.96–3.13).

Conclusion

The proportion of males was higher than the proportion of females. Workers, peasants and the unemployed comprised the high-risk occupational categories. Male gender, having a spinal fracture, having a thoracic injury, and having complications were the major risk factors for a complete injury. We recommend that preventive measures should focus on high-risk populations, such as young males.     

Acute injuries in soccer,ice hockey,volleyball, basketball,judo, and karate: analysis of national registry data.

OBJECTIVE--To determine the acute injury profile in each of six sports and compare the injury rates between the sports. DESIGN--Analysis of national sports injury insurance registry data. SETTING--Finland during 1987-91. SUBJECTS--621,691 person years of exposure among participants in soccer, ice hockey, volleyball, basketball, judo, or karate. MAIN OUTCOME MEASURES--Acute sports injuries requiring medical treatment and reported to the insurance company on structured forms by the patients and their doctors. RESULTS--54,186 sports injuries were recorded. Injury rates were low in athletes aged under 15, while 20-24 year olds had the highest rates. Differences in injury rates between the sports were minor in this adult age group. Overall injury rates were higher in sports entailing more frequent and powerful body contact. Each sport had a specific injury profile. Fractures and dental injuries were most common in ice hockey and karate and least frequent in volleyball. Knee injuries were the most common cause of permanent disability. CONCLUSIONS--Based on the defined injury profiles in the different sports it is recommended that sports specific preventive measures should be employed to decrease the number of violent contacts between athletes, including improved game rules supported by careful refereeing. To prevent dental injuries the wearing of mouth guards should be encouraged, especially in ice hockey, karate, and basketball.     

Acute burns

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe the pathophysiology of burn injury. 2. Identify patient criteria for transfer to a burn center. 3. Calculate burn size and resuscitation requirements. 4. Treat inhalation injury in the acute setting. 5. Describe treatment options for burn injuries. 6. Describe preoperative selection, intraoperative procedures, and postoperative protocols for patients who require surgical care for their burn injuries. 7. Understand the survival and functional outcomes of burn injury. SUMMARY: The review article summarizes basic issues in the treatment of acute burn injury as practiced in 2008. The pathophysiology, treatment options, and expected outcomes for an acute burn are described and discussed. Special attention is directed to the nonoperative and surgical management of small to moderate-size burns that might be treated by the practicing plastic surgeon.     

Biomechanical assessment of the effects of significant hamstring injury: an isokinetic study

Soccer players may develop recurrent hamstring injuries. This may be due to inadequate rehabilitation or to recurrent injury. In addition, following injury, the hamstring muscular complex may be permanently damaged, resulting in decreased strength, and increased likelihood of recurrent injury. Fourteen professional soccer players were assessed by clinical examination and by isokinetic testing with a Cybex II machine. Seven had suffered moderate or major hamstring injuries in the past year. There were seven controls. None of the hamstring group were currently suffering from an acute hamstring injury. The results of the two groups were compared. There were no differences in the mean results. This pilot study suggests that no permanent functional damage occurs to the muscular complex after moderate or major hamstring injuries after correct treatment. However, further research is required to confirm this.