Learning From Biomarkers in Victims Accidentally Exposed to Ionizing Radiation

Biomarkers,such as chromosome aberration and micronuclei assays,prove to be reliable for facilitating clinical diagnosis in radiation accidents.In a radiation accident in India,chromosomal aberration,γ-H2AX,as well as other blood markers,were detected in accidentally exposed victims.This multi-parametric approach aided in confirming that individuals had been exposed by ionizing radiation.However,doses were impossible to estimate because of a 30-day delay in accident awareness.Exposure dose for victims was estimated using a dose-response curve previously established.Dose estimation,blood cell depletion kinetics,and no appearance of prodromal symptoms suggested that doses of exposure were low.Hematologic investigation,sampling time,and chromosome aberration scoring were all proposed according to data from the victims exposed to 60Co.Finally,knowledge regarding chromosome aberration analysis and the importance of international co-operation and assistance should be shared from this accident.     

What is risk management?

Medical accidents recently have become a social problem as a result of the old-fashioned hospital system in Japan. Therefore, risk management for medical procedures has been considered very important. In the field of radiotherapy, specific characteristics include the management of radiation and the triangular relationship between patients, referred doctors, and radiation oncologists. In future, the difference between incident and accident in radiotherapy should be clearly defined by the Society.     

放射外照射事故剂量重建中的蒙特卡罗模拟方法

目的 建立放射外照射事故剂量重建的计算机系统。方法 基于MIRD的人体及其器官的数学模型，采用蒙特卡罗(MC)方法，结合 放射事故的受照模式，建立放射外照射事故剂量重建的计算机系统。结果 成功研制了放射事故剂量重建的计算机系统。用这个系统计算了河南省^60Co放射事故危重病人的剂量，其计算结果与实验模拟测量和生物剂量检测结果十分一致。结论 本系统方便、快捷，它不但可估算事故受照人员的器官剂量和全身剂量，而且也能用于事故早期剂量的估计。     

南京“5.7”放射源丢失事故受照者照后医学随访观察

目的 通过开展2014年南京"5.7"¹⁹²Ir放射源事故患者受照后持续医学随访，探讨放射损伤的中远期效应，为电离辐射损伤的效应评估提供科学依据。方法 通过面访调查，询问受照患者康复治疗后至医学随访期间的新发疾病病史，进行体格和实验室检查，依据相关标准，系统评价其造血系统、免疫系统、内分泌系统、眼科、循环系统、消化系统、泌尿系统以及骨密度等生理生化指标。结果 患者无新发疾病，造血系统、免疫系统、内分泌系统各项指标趋于正常；循环系统、消化系统及泌尿系统出现退行性改变；眼科检查出现视力持续下降；骨密度检查提示骨量低下。结论 患者各项生理生化指标逐步恢复正常，未出现明显的放射性损伤症状，后续的医学随访观察仍需持续开展。     

Hematological aftermath of the radiation accident in Istanbul

Purpose: The effects of radiation exposure are long-lasting. Long-term monitoring is imperative to diagnose late effects and improve our far-sightedness about possible events in the future. A radiation accident occurred in Istanbul in 1998 that resulted in mild to moderate acute radiation syndrome (ARS). In this study we aimed to investigate the changes in hematological parameters at the long-term follow-up of ARS patients.

Methods: Ten adults were hospitalized after exposure to a 60Co source. Seven were diagnosed as having ARS and had severe and symptomatic pancytopenia. All of the exposed people recovered following intensive treatment. Treatment was supportive with transfusion, granulocyte-colony stimulating factor, and anti- infective management covering antifungal agents. Patients were closely monitored. Nine years after the accident, the initial and follow-up complete blood count examinations and peripheral blood smears (PBS) were comparatively evaluated by an experienced hematologist. The hematological laboratory values of the patients on admission, after treatment, and nine years after the accident were documented and compared.

Results: Biodosimetric analysis revealed that whole-body doses ranged from 1–1.9 Gy. All subjects have shown complete recovery of the hematological laboratory values after treatment. All but one of the subjects showed complete blood cell recovery. The improvement of the blood cell count of the excepted patient stalled at a mildly reduced level and his bone marrow was still hypocellular nine years after the accident; however, no malignant changes were detected. Values at admission were significantly different compared with post treatment and present values of all patients. Post treatment and follow-up values were similar. One of the patients died of lung cancer. None of the patients developed hematological malignancy.

Conclusions: In this study, the recovery from ARS was complete after treatment. The small population, short follow-up period, and the relatively small doses resulted in no long-term adverse effects, as would be predicted.     

急性核辐射对人的远期效应

内容仅涉及事故性急性核辐射的远期效应:1.日本原爆幸存者(包括宫内受照者约2800名)的流行病学调查结果,归纳为强关联、弱关联和无关联的远期效应。在第8～15孕周阶段接受1Gy照射的胎儿,约有43%会发生智力发育延迟,为受照0.01Gy以下的对比组危险度的50倍以上。对原爆人群各部位癌症的相对、绝对和归因危险作了介绍。对原爆幸存者受照射后怀孕所生子女(1946年5月以后出生),用(1)不利的妊娠结果、(2)死亡事件、(3)携带有性染色体异常儿童的频率、(4)携有由于基因突变引起的血液蛋白电泳变异体儿童的频率等遗传学指标提示,近爆心(<2000m)幸存者(>1Gy)所生儿童与远离爆心组(0.01～0.09Gy)相比,仅仅是预期趋势上有差别,实际上未发现有统计学意义的差异。即使如此,这两组儿童间的差异用上述4个指标中的前3个观察结果,估计了加倍剂量,平均数是1.56Sv,但是有争议。2.马绍尔群岛放射性落下灰受照居民医学随访近况,甲状腺疾病发病率高,而在日本原爆幸存者中则未见类似情况,估计与马绍尔群岛居民甲状腺因摄入放射性碘而照射量较大有关。3.日本福隆丸号渔民受落下灰照射后远后效应资料。4.美国Y-12工厂共8名受照者的远后效应:4例有放射性白内障,1998年时仅活存3例。5.前苏联切尔诺贝利核电站事故中急性放射病(ARS)病人远后效应:2例Ⅲ度ARS病人分别于照后第6年和第9年发生骨髓增生异常综合征(MDS)引起死亡,1例Ⅰ度ARS病人也于照后第9年诊断为MDS,另一例Ⅱ度ARS病人照后第11年发生急性单核细胞白血病。6.巴西137Cs事故5年后远期效应。     

河南“4.26”~(60)Co源辐射事故患者早期分类诊断及医学处理

目的　总结 1999年 4月 2 6日河南发生的6 0 Co源辐射事故中 7名受照者的早期分类诊断和医学处理 ,探讨类似辐射事故的医学应急处理。方法　根据生物剂量和物理剂量的估算、受照者照后初期的临床症状和体征、照后外周血白细胞和淋巴细胞的变化做出初步诊断 ,并采取相应的救治措施。结果　 7例受照者的初期诊断与临床诊断一致 ,正确的早期分类诊断和医学处理有利于制定救治方案、判断预后 ,使患者顺利度过极期。结论　早期分类诊断应综合分析患者照后出现的症状、体征、外周血白细胞和淋巴细胞的变化 ;初期症状的发生尤其是呕吐开始的时间和严重程度不但与受照剂量有关 ,也受剂量率、受照部位、不均匀程度和个体差异等因素的影响 ;生物剂量和物理剂量的估算是早期分类诊断的基础 ,发生事故后应尽早开始。     

Dosimetry in leakage of <Superscript>188</Superscript>Re-DTPA during intracoronary balloon brachytherapy

Rhenium-188 is reported to be one of the best radionuclides for intracoronary balloon brachytherapy. Among several preparations of ¹⁸⁸Re available for brachytherapy, ¹⁸⁸Re-diethylene triamine penta-acetic acid (DTPA) and ¹⁸⁸Re-mercaptoacetyltriglycine (MAG3) are recommended owing to their rapid excretion via the renal system and the absence of accumulation in the thyroid. The aim of this study was to calculate the dose of radiation exposure in a real human accident. During a 4-year clinical trial of ¹⁸⁸Re-DTPA balloon brachytherapy in 242 patients, there was one accident involving balloon leakage. Dosimetry was performed by both image-based and biological analysis. The radiation exposure to the whole body was calculated as 113 mGy by image-based analysis and 83 or 88 mGy by biological analysis, which was approximately half the reported dose in the case of ¹⁸⁸Re-perrhenate. The radiation exposures to other vital organs were also within the tolerated ranges. We conclude that ¹⁸⁸Re-DTPA has better clinical feasibility and safety for intracoronary balloon brachytherapy than ¹⁸⁸Re-perrhenate.     

用蒙特卡罗方法估算~(60)Co辐射源事故患者的辐射剂量

目的　计算河南6 0 Co放射源事故中事故患者“梅”受到的辐射剂量。方法　基于MIRD的成人数学模型用蒙特卡罗随机模型方法计算事故患者的辐射剂量 ,并编制了一个用于此计算实用计算机程序。结果　模拟事故患者的具体情况 ,计算了人体主要器官剂量和全身剂量。结论　这种理论模拟的方法与用体模的实验模拟测量结果较为一致 ,说明用这种算法算出的各个器官剂量和全身剂量 ,对于临床治疗有参考价值 ,而且模拟方便 ,快速 ,适用于核事故医学应急中的患者器官剂量估算。     

南京“5.7”192Ir源放射事故患者造血系统的改变

目的 通过对南京¹⁹²Ir源放射事故中患者的血液系统进行观察研究,探讨造血系统损伤规律,为核与辐射事故医学应急的救治和随访提供临床资料和积累经验。方法 应用血细胞分析仪动态观察患者的白细胞计数、淋巴细胞计数、血小板计数及血红蛋白值的变化,取其双侧髂骨骨髓涂片观察骨髓象的改变,采用PCR-以测序为基础的分型技术(PCR-SBT)方法检测融合基因突变情况;分别采用流式细胞术和放射免疫分析法测定T淋巴细胞亚群百分率和血清免疫球蛋白(IgA、IgG、IgM)、补体(C3、C4)含量,评价细胞免疫和体液免疫功能。结果 患者骨髓造血轻度障碍,予以粒细胞集落刺激因子(G-CSF)治疗后,短时间内恢复正常,受照后约40 d进入恢复期;受照侧骨髓增生低下;融合基因检测未检测到突变;局部感染导致淋巴细胞计数及免疫功能下降。结论 轻度骨髓型急性放射病造血系统损伤较小,病程分期不明显,造血功能恢复较快,尚未造成免疫抑制,但局部感染可导致免疫功能下降。临床医生需注意全身治疗与局部治疗的统一。     

Evaluation of radiation injury by 1H and 31P NMR of human urine

¹H and ³¹P NMR techniques were applied to study the changes in metabolite profiles in human urine resulting from radiation exposure following the Chemobyl reactor accident. In cases of acute leukemia and different accumulated doses of external radiation (from 0.20 to 4.00 Sv), the proton spectra were classified on the basis of the peaks due to N-trimethyl groups, creatinine, citrate, glycine, and hippurate. Unidentified resonances were observed between 15.9 and 21.4 ppm in six phosphorus spectra of patients with preleukemia and acute leukemia. Characteristic spectral changes were similar for external radiation and Incorporation-induced internal irradiation. The spectral patterns described may serve as a criterion of radiation injury.     

“6.25”60Co源辐射事故病人照后2.5年远后效应随访观察

探讨“６．２５”６０Ｃｏ源辐射事故所致５名骨髓型急性放射病患者的远后效应。方法照后２．５年对患者临床表现、造血功能、免疫功能、神经系统、生殖功能、眼晶体及某些癌基因进行检查。结果发现患者在上述诸方面存在不同程度辐射损伤。结论研究结果不仅为患者的医疗保健提供了依据，而且为急性放射病远后效应积累宝贵资料     

骨髓细胞染色体畸变在山东济宁事故受照人员剂量估算中的应用

目的对山东济宁“10．21”辐射事故受照者进行染色体畸变（CA）分析，并估算受照剂量。方法对2例患者（A和B）的外周血和骨髓样本进行常规CA分析，根据双着丝粒（dic）和环（r）畸变频率估算受照剂量。结果2例患者的外周血未见中期分裂细胞。骨髓获得了可供分析的细胞。2例患者的dic＋r畸变频率超过了剂量效应方程所能估计的上限剂量相对应的数值。用直接比较法估算2例患者受到比较均匀的大剂量照射，与用物理方法、微核法和ESR法所估剂量接近，与临床表现基本一致。结论用骨髓CA估算辐射事故患者的受照剂量在国内尚属首次。对肠型放射病患者A的剂量估算是迄今采用骨髓进行常规CA分析估计事故病人受照剂量的最高记录。     

Initial medical management of patients severely irradiated in the Tokai-mura criticality accident

A nuclear criticality accident occurred in Japan on September 30, 1999, which resulted in severe exposure of three victims to mixed flux of neutrons and gamma-rays. Estimated average doses for the three victims were 5.4 Gy of neutrons and 8.5 Gy of gamma-rays for Patient A, 2.9 Gy of neutrons and 4.5 Gy of gamma-rays for Patient B, and 0.81 Gy of neutrons and 1.3 Gy of gamma-rays for Patient C. They then suffered the consequences of the effects of ionizing radiation resulting in acute radiation syndrome. In Patients A and B, bone marrow failure was so severe that they received haematopoietic stem cell transplantation. The graft initially took successfully in both patients, although in Patient B it was later taken over by his own haematopoietic cells. They also suffered from severe skin lesions, later exhibited gastrointestinal bleeding and eventually died of multiple organ failure 82 and 210 days after the accident, respectively. The survival of these patients beyond the period of agranulocytosis means that bone marrow failure per se caused by exposure to ionizing radiation may now be overcome. Patient C also developed bone marrow failure and was treated with granulocyte colony-stimulating factor as well as supportive care. He recovered without major complications and is now under periodical follow-up. Remarkably, during the prodromal phase, all the patients exhibited hypoxaemia, two of whom also showed interstitial oedema of the lungs. In Patient C these manifestations improved within a week. The circumstances of the accident and the initial medical treatment of the victims are described.     

河南“4.26”60Co源辐射事故患者早期分类诊断及医学处理

目的：总结1999年4月26日河南发生的^60Co源辐射事故中7名受照者的早期分类诊断和医学处理,探讨类拟辐射事故的医学急处理,方法：根据生物剂量和物理剂量的估算,受照者照后初期的临床症状和体征,照后外周血白细胞和淋巴细胞的变化做出初步诊断,并采用相应的救治措施,结果：7例受照者的初期诊断与诊床诊断一致,正确的早期分类诊断和医学处理有利于制定救治方案,判断预后,使患者顺利度过极期,结论：早期分类诊断应综合分析患者照后出现的症状,体征,外周血白细胞和淋巴细胞的变化,初期症状的发生尤其是哎吐开始的时间和严重程度不但与受照剂量有关,也受剂量率,受照部位,不均匀程度和个体差异等因素的影响,生物剂量和物理剂量的估算是早期分类诊断的基础,发生事故后应尽早开始。     

极重度骨髓型和肠型急性放射病合并真菌感染的临床治疗

目的研究探讨极重度骨髓型放射病和肠型放射病合并真菌感染的诊治经验。方法2004年10月24日收治极重度骨髓型放射病和肠型放射病两例患者，行HIA相合及半相合造血干细胞移植成功并顺利恢复造血。病程中2例均反复并发严重的多部位、多种类真菌感染。结果采用联合抗真菌治疗及对症支持，病例A效果不好，病例B真菌明显控制，但2例最终死于急性放射病、严重感染及多脏器衰竭。结论真菌感染是放射病严重的合并症，多药联合抗真菌治疗放射病合并严重真菌感染，治疗有效，未见明显毒性增加，值得借鉴。     

四例骨髓型急性放射病患者受照后12年医学随访观察

目的 通过对1999年河南省发生的“4.26”60Co源辐射事故所致的4名骨髓型急性放射病患者受照后12年医学随访观察,探讨电离辐射远后效应,为核事故医学应急的救治和随访提供临床资料和积累经验.方法 采用“一对一”和“多对一”的方式采集病史,观察和记录“梅”、“旺”、“天”、“民”4名患者的临床症状和体征.实验室及器械检查包括血细胞分析、肝肾功能、甲状腺功能、体液免疫、性激素水平、肿瘤标志物及眼科检查、甲状腺彩超、腹部B超、心电图及胸部X片检查,评价其全身情况.辐射遗传学分析包括外周血淋巴细胞染色体畸变分析和微核分析.应用实时荧光定量PCR法,检测其外周血GADD45和nm23-H1基因的mRNA表达,与健康对照人群相比较.采用卡特尔16种个性因素测验(16PF)、抑郁自评量表(SDS)、焦虑自评量表(SAS),对4名患者实施心理测评.结果 4名患者受照后12年造血免疫功能基本恢复正常.“天”乙肝两对半的检查结果中,表面抗原(HBsAg)及核心抗体(HBcAb)为阳性,乙肝病毒复制转为慢性期,传染性弱.4人眼晶状体均有不同程度的混浊性改变,“梅”受照后3年即发生放射性白内障.“梅”、“天”、“民”性激素水平仍有异常.外周血淋巴细胞染色体畸变分析可见少许断片和双着丝粒,但易位率仍较高.分子生物标志物外周血GADD45和nm23-H1基因mRNA定量分析较正常对照组差异无统计学意义.心理测评发现,“梅”重度抑郁、焦虑,其余3人存在紧张、焦虑、恐慌情绪.结论 对4名骨髓型急性放射病患者进行了较为系统的医学随访观察和心理测评,为类似病例的临床救治和随访提供资料.     

用蒙特卡罗方法估算60Co辐射源事故患者的辐射剂量

目的：计算河南^60Co放射源事故中事故患者“梅”受到的辐射剂量,方法：基于MIRD的成人数学模型蒙特卡罗随机模型方法计算故忠患者的辐射剂量,并编制了一个用用此计算实用计算机程序,结果：模拟事故患者的具体情况,计算了人体主要器官剂量和全身剂量,结论：这种理论模拟的方法与用模的实验模拟测量结果较为一致,说明用这种算法算出的各个器官剂量和全身剂量,对于临床治疗有参考价值,而且模拟方便,快速,适用于核事故医学应急中的患者器官剂量估算。     

核事故剂量的顺磁分析方法研究与应用

目的建立电离辐射事故剂量的实际测量方法。方法用电子自旋共振（ＥＳＲ）技术，在人体骨髓型急性放射病阈剂量以上范围，对人体生物样品及可能的随身佩带材料的剂量响应特性，信号稳定性，本底均一性，可测剂量下限及辐射条件和环境影响因素等基本剂量学特性进行了实验研究。结果建立了多项适于实际事故剂量测量的顺磁剂量测量指标和方法，并在包括切尔诺贝利事故在内的三起辐射事故剂量评估中得到了成功的应用。结论这项工作进一步证实了ＥＳＲ在事故剂量评估中的重要作用。     

Dynamische kontrastverst?rkte Computertomographie

Technical innovations in multislice computed tomography (CT) allow for larger volume coverage in ever shorter scan times. This progress has stimulated the clinical application of dynamic contrast-enhanced (DCE) CT techniques, which offer the possibility to noninvasively characterize tissue microcirculation in terms of well-defined physiological quantities. This educational review imparts to radiologists the essential physiological terms and definitions as well as the basic tracer kinetic concepts required for the analysis of DCE-CT data. In particular, four different approaches are presented and exemplified by the analysis of representative DCE data: the steepest-gradient method, model-free algebraic deconvolution in combination with the indicator-dilution theory, two-compartment modelling and the so-called adiabatic approximation to the homogeneity model. Even though DCE-CT offers substantial methodological and practical advantages as compared to DCE-MRI (magnetic resonance imaging), there are also two serious and interconnected shortcomings: the low contrast enhancement in relation to the noise level and the high exposure of patients to ionizing radiation. These limiting aspects are considered in detail from a radiation hygienic point of view, emphasizing the basic principles of justification and optimization. Clinically established as well as potential future applications of DCE-CT will be presented in a subsequent paper.