高Z纳米介质放射增敏的宏观剂量效应评价及其局限

目的：建立高Z纳米介质对X—γ射线和质子／重离子的宏观剂量增强效应模型,讨论其评价高Z纳米介质放射增敏效应的局限性。方法：基于宏观剂量学的质能吸收系数、质量阻止本领、电子阻止本领以及传能线密度（LET）概念,推导组织内均匀分布的高Z纳米介质对X-γ光子、质子或重离子的宏观剂量增强比;分析剂量增强比随射线能量、纳米介质原子序数和组织内含量的变化规律;对比放射增敏比实验研究结果,讨论宏观剂量学模型评价高Z纳米介质放射增敏效应的局限性。结果：宏观剂量学分析表明高Z纳米介质可以对X-γ射线和质子／重离子产生宏观剂量增强效应,但基于多重均匀化假设的宏观剂量增强比计算结果对实际放射增敏效应有明显低估。结论：高Z纳米介质放射增敏的准确量效关系需建立严格的微观剂量学模型评价,微观剂量学模型需要考虑四方面因素：（1）次级电子局域剂量分布;（2）纳米颗粒非均匀团聚分布;（31纳米颗粒亚细胞分布：（4）局域剂量的自由基效应。     

质子和其他放射治疗肿瘤的比较

质子加速器是目前世界上最先进的放射治疗设备。本文对质子和目前各国常用的常规射线(兆伏特级的光子和电子),在肿瘤的放射治疗方面进行了比较。并复习了世界各国用质子治疗肿瘤的经验,介绍质子治疗肿瘤的优点、发展历史以及发展前景。质子束进入人体组织时,其大量的能量集中在接近射程终点,称为Bragg峰。放射治疗医生可以通过调节质子加速器能量的方式,使高能量区集中在病人体内一定的区域;在此高量区的后方,放射剂量骤降为零。因此,医生可以使放射线的高剂量区集中在靶区(肿瘤区),避免周围正常组织部受到照射。而用常规射线照射时,周围正常组织仍受到较高量的照射。用目前先进的三维适形放射治疗和调强放射治疗技术,只需用少数的照射野,即可达到非常满意的放射剂量分布。到2004年2月,世界上已有11个国家正在开展质子治疗工作;已用质子治疗病人35838例。所治疗的肿瘤有眼葡萄膜黑色素瘤、中枢神经系统肿瘤、颅底肿瘤、前列腺癌、非小细胞肺癌、胃肠道肿瘤、鼻咽癌、乳腺癌和官颈癌等,均取得较好的效果。目前已引起世界各国放射治疗学界的重视。     

211 At标记单克隆抗体肿瘤放射免疫治疗的研究进展(文献综述)

将放射性核素标记到单抗(Monoclonal antibody, McAb)上,利用单抗的肿瘤导向作用和放射性核素的细胞毒作用进行肿瘤的放射免疫治疗,是当今肿瘤核医学的主要研究方向之一.建立有效的放射免疫治疗方法首先考虑的是放射性核素的选择以及核素的辐射特性要与肿瘤的靶特征相适应.目前治疗常用核素多是β射线辐射体如90Y等,β射线是低LET,对细胞的杀伤力较弱,β射线在生物组织中射程为1～10mm,对于微小病灶和非实体瘤,因β射线的射程远大于病灶或细胞的直径,所以β粒子的主要能量不能释放在病灶或肿瘤细胞内,不能有效地杀死病变细胞.同时β粒子的大量能量被释放在周围正常组织,造成的毒性作用非常明显,严重限制其应用.而选择发射短射程、高LET射线的核素用于导向治疗则可提高治疗效率,降低毒副作用[1,2].因此,选用发射α射线的核素标记抗肿瘤单抗,用于肿瘤的放射免疫治疗很有潜力.本文就211At标记单抗及其片段在肿瘤导向治疗中的应用研究进展作一简要综述.     

利用蒙特卡罗模拟评估空气间隙对点扫描质子治疗的剂量影响

目的:利用蒙特卡罗模拟探究空气间隙对点扫描质子治疗的剂量影响。方法:利用通用蒙特卡罗程序Geant4平台构建使用射程移位器的治疗头末端的点扫描质子束流模型,并进行验证。模拟计算不同能量、不同射程移位器、不同束斑尺寸、不同束斑数目在不同空气间隙条件下的质子束流在水模体中的剂量沉积,并通过获得的积分深度剂量生成剂量修正因子对剂量的差异进行比较。结果:不同空气间隙会造成剂量损失,随空气间隙增大而增大,随水模体中深度增加而减小。对于能量更高的射束和使用水等效厚度更薄的射程移位器,剂量损失越大。束斑尺寸改变和束斑数目增加较少时造成的剂量损失与同条件下单一束流无显著差别。结论:当使用射程移位器、肿瘤位置较浅、空气间隙较大时,建议建立剂量修正因子数据库应用于治疗计划系统对剂量进行修正。     

高能电子束的物理特点及其临床应用注意事项

1高能电子束的物理特点 高能电子束在水中或组织中的剂量学特点不同于X射线,其特点归纳如下: (1)加速器产生的电子束在临床上可以看成是单能射线,在水或组织中具有射程概念.在射程内,它与物质的原子作用,通过碰撞与辐射两种方式损失其全部能量而被物质吸收.电子束的射程并不是指电子在物质中所经过的全部路经,它定义为入射电子沿其入射方向从入射物质表面到电子被物质吸收的最大直线距离.电子束的能量越高,其射程越大.射程以外不存在电子线的剂量贡献.根据高能电子束的百分深度剂量特性曲线,大致可划分为四个区段,即剂量建成区、高剂量坪区、剂量跌落区和X射线污染区.     

质子治疗技术的发展及其挑战

质子治疗有显著的剂量学优势,布拉格峰的迅速跌落可保证肿瘤在接受相同照射剂量的同时,大大减少肿瘤周围正常组织受照射剂量,降低放疗并发症。但是质子剂量学优势能否充分转化为临床患者的获益仍然存在一定的争议。本文综述了质子治疗的历史、基础原理及其技术发展历程,并分析了质子治疗的优势和面临的挑战。     

质子放疗

质子放射治疗近年来有了较快的发展,世界上作为研究用的很多家质子治疗机构早就在运行,作为商业产品的质子放疗机也已经有多台设备在世界各地安装和运行.质子束对于肿瘤治疗比其它放疗模式优越的地方主要在于利用质子束的Bragg峰,更好地适形包络肿瘤的不同形状,其包络的边界比X和γ-射线更锐.质子放疗之所以能够商业化,得益于质子加速器技术和质子剂量学的进步,以及包括核心部件在内的整套设备的可靠性大大提高.但是质子放疗在运动靶区和实时的影像监督方面也还有很多问题仍然需要进一步完善.以山东淄博万杰医院为代表,国内也已经开始质子放疗的临床工作,还有医院正在筹建.作为处于商业化初级阶段的质子放疗,由于设备的复杂性和价格,在中国还缺乏合格的医学物理师和维护工程师的情况下,这类放疗设备不宜大量发展.     

质子治疗的疗效与适应症分析

通过对医学文献进行分析后发现,质子治疗的适应症与常规X(γ)射线放疗相似,由于具有物理剂量学的特性,因而在治疗某些关键器官或临近关键器官的病变时具有显著优势。然而尚需进行大量临床研究,特别是前瞻性随机分组试验,以明确这种治疗的优越性。     

放射生物LQ线性二次模型的数理基础及临床意义

目的：本文拟从对LQ模型提出的数学、物理、数理统计、放射生物学模型的研究分析LQ模型的数理基础和理论背景，系统阐述LQ模型的理论基础，为更好理解并应用放射生物LO模型提供理论基础，为临床放疗方案改变作参考。方法：从LQ模型的数学公式研究入手，充分发掘LQ模型计算公式得出的数理依据和放射生物学实验结果，分别从LQ模型的N无穷次贝努力实验的泊松概率模型、低LET射线和高LET射线对DNA双链造成击打原理和模型、笛卡尔坐标系和半对数坐标系的应用、细胞存活曲线的计算和表达等几个方面系统阐述LQ模型的理论基础。并研究了α损伤和卢的不同数学背景，从射线和细胞作用过程分析人手重新阐述了α、β值的放射生物学意义，同时研究了早晚反正组织中损伤等效剂量计算公式的应用范围。结果：通过对L0模型分析得到α损伤其实代表了高LET射线与细胞中靶DNA的作用模式，作用概率和辐射场粒子存在一次正相关关系，口是低LET射线与细胞中靶DNA作用的结果，和辐射场中粒子通量存在二次方正相关关系；早晚反应组织等效剂量除了需要满足f〉√βl/βN。外还需要满足本文（18）式提出的条件。结论：放射生物学LO模型不单是一个放射生物学模型，其模型得意提出和应用和辐射剂量学、分析数学、数理统计学、生物物理学等学科息息相关，只有深刻理解以上学科在该模型中意义才能正确理解和应用LO模型。     

扫描治疗头的蒙特卡罗模型研究

目的:评估质子治疗中扫描治疗头对束流品质的影响。方法:通过扫描治疗头的蒙特卡罗模型研究深度剂量曲线的变化,计算射程移位器对束斑截面的影响以及分析扫描磁场对单质子束的偏转情况。结果:随着能量的增加,质子在水中的射程增加,同时散射也越严重,最终布拉格峰变宽,尾端变胖。相比于直接入射水模,通过治疗头后质子在水中的射程缩短了约0.6 cm,但布拉格峰形基本保持不变;将4 cm厚度聚乙烯射程移位器放置于距离水模表面0、10、20、30、40和50 cm分别进行独立计算,发现与水模距离越远,质子的散射越大,因此治疗过程中射程移位器应尽量靠近患者;当扫描磁铁加载磁场后,束斑将偏离束流中心。设置纵向扫描磁场Bx=0.1 T,横向扫描磁场By=0.3 T,180 MeV质子束在Y方向偏离了2.693 cm,横向扫描磁场使质子在-X方向上偏离了8.427 cm。当束流有偏转的时候,要求射程移位器横截面足够大以满足宽扫描场的需要。结论:扫描治疗头的蒙特卡罗模型将有助于理解质子治疗这一新兴的放疗方法以及熟悉扫描治疗的束流特性,在调试和质量保证中提供参考。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.