超声二次谐波声面声学造影评价冠脉的微血管血流灌注

目的：本文获取冠状动脉血流变化所致的心肌灌注类型,以了解冠脉的微血管血流灌注变化。方法：36人先后完成冠状动脉影,静脉注射声学造影剂利声显（Levovist),通过超声二次谐波技术获取心肌灌注图像,按心肌灌注积分指数将病人分为三组。结果：三组病人的冠状动脉狭窄程度、心肌灌注积分指数明显差异（P＜0．001）,冠状动脉狭窄波＜75％者,病人心肌灌注多为正常,随着冠状动脉狭窄程度加重,出现不同程度的心肌灌注异常。8例完全阻塞的冠状动脉有不同的冠状动脉侧支循环表现为不同的心肌灌注类型。结论：静脉心肌声学造影是反映心肌灌注的有效方法,能够反应冠状动脉血流的改变及微循环结构的完整性变化,从而弥补冠状动脉造影仅能显示心外膜下的冠状动脉而无法观察毛细血管水平的心肌灌注之缺限。当心肌灌注不良时,MCE能提示冠状动脉病变的存在,及其严重性,但要注意侧支循环对心肌灌注之影响,可影响对冠脉病变程度判断的精确性。冠状动脉造影确定某支冠脉病变时,MCE心机灌注有助于评价侧支循环状态。     

狭窄几何参数评估稳定型冠心病心肌灌注效能的指导价值

目的 探讨狭窄病变严重程度和病变累及长度等狭窄形态特征对稳定型冠心病心肌灌注效能的评估价值,提出一项定性定量描述冠心病局域心肌灌注效能的预测指标.方法 将54例稳定型冠心病患者纳入统计研究,对其行冠状动脉造影及FFR检查测量,对反映心肌灌注效能的狭窄病变严重程度和病变累及长度等狭窄形态几何参数进行量化分析,包括α值(反映病变严重程度,α=Dmin/Dnormal)、β值(反映病变累及长度)、α×β值(反映局部心肌血流供需关系).结果 纳入分析的54组病变数据中,未发生心肌灌注不良者(FFR≥0.8)43例,心肌灌注不良者(FFR<0.8)11例,心肌灌注不良组α值、β值与未发生心肌灌注不良组间无显著相关性(P>0.05),但心肌灌注不良组的α×β明显大于未发生心肌灌注不良组(P<0.05).ROC曲线分析显示,通过α×β值评估病变对于心肌灌注影响的曲线下面积为0.783(95％CI:0.603～0.964),敏感度为63.6％,特异度为93.0％,阳性预测值为70.0％,阴性预测值为90.9％,评估准确度为92.6％.结论 α×β值较大组别对应的临床FFR值更小,该项指标与心肌灌注效能之间具有较强敏感性,这与临床现象一致.提示α×β这一指标可定性定量描述冠心病心肌灌注效能,为辅助评价狭窄血管是否发生局域心肌灌注不足提供理论支持.     

99Tcm-替曲膦心肌灌注显像在冠心病诊断的应用及治疗决策的作用

目的 评价99Tcm-替曲膦(99Tcm-Tetrofosmin)心肌灌注显像在冠心病诊断的应用及治疗决策的作用.方法 73例临床初步诊断冠心病患者行99Tcm-替曲膦心肌灌注显像,第一日行99Tcm-替曲膦静息心肌灌注显像,次日行99Tcm-替曲膦负荷(运动负荷或药物负荷)心肌灌注显像,一周内行冠状动脉造影(Coronary arteriongraphy,CAG).对99Tcm-替曲膦心肌灌注显像阴性者36例、99Tcm-替曲膦心肌灌注显像心肌灌注显像阳性者37例与其CAG结果对比,得出99Tcm-替曲膦心肌灌注显像对胸闷、胸痛等不同症状患者心肌缺血程度的初步评测及其在治疗决策中的作用.结果 99Tcm-替曲膦心肌灌注显像提示未见缺血的36例患者中,在其CAG结果中发现冠状动脉病变2支以上者3例(狭窄程度最大值不超过75％,狭窄程度均值为71.42％±3.78％),单支病变者8例(狭窄程度最大值不超过75％,狭窄程度均值为63.75％±6.94％),25例患者CAG提示冠状动脉未见狭窄,予以对症药物治疗或临床密切观察.99Tcm-替曲膦心肌灌注显像提示明显心肌缺血26例,在其CAG结果中发现冠状动脉病变2支以上者8例(狭窄程度均值为78.75％±11.34％),单支病变者14例(狭窄程度均值为78.93％±5.94％),上述22例患者均进一步行球囊扩张术和(或)支架植入术;4例患者CAG提示未见明显狭窄.99Tcm-替曲膦心肌灌注显像提示轻度心肌缺血者11例,对应其CAG结果发现冠状动脉病变2支以上者5例(狭窄程度最大值不超过80％,均值为70.91％ ±8.31％),单支病变者5例(狭窄程度最大值不超过80％,狭窄程度均值为68.00％±8.36％),1例患者CAG提示冠状动脉未见狭窄,均进行药物治疗.结论 99Tcm-替曲膦心肌灌注显像对冠心病进行诊断、治疗方案的选择有重要的临床应用价值.     

非创伤缺血预处理对大鼠缺血再灌注心肌的作用

目的:确定非创伤性缺血预处理对大鼠缺血/再灌注(I/R)心肌损伤是否具有对抗作用,以扩展缺血预处理的实际应用.方法:采用非创伤性下肢缺血预处理及经典缺血预处理的动物模型,比较两种处理方法对I/R心肌损伤的效应.实验动物分4组:正常对照组(NC,n=8),开胸旷置50 min;缺血/再灌注组(I/R,n=12),结扎冠脉30 min,再灌注20、180 min;经典缺血预处理组(C-IPC,n=12),按经典Murry法复制;非创伤性下肢缺血预处理组(N-WIPC,n=12),捆绑双下肢5 min,松开5 min,反复4次后,阻断冠脉30 min,再灌20、180 min.以左室功能,心肌梗塞范围,血清肌酸激酶(CK)及心肌组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性为观察指标.结果:与I/R组相比,N-WIPC组与C-IPC组均显著缩小I/R后的心肌梗塞范围(P＜0.01);明显恢复I/R后的左室功能(P＜0.05,0.01);减轻自由基对心肌的损害:血清CK,心肌MDA含量显著降低(P＜0.01).N-WIPC组还使心肌SOD活性增高(P＜0.05).结论:非创伤性下肢缺血预处理与经典缺血预处理可诱发同等强度的心肌预处理效应.     

冠脉介入治疗后心肌梗死区灌注程度及存活对左室重构及功能的影响

评价冠脉介入治疗（PCI）后核素显像心肌梗死区灌注程度及存活对左室重构及功能的影响。选取20例急性前壁心肌梗死患者,男18例,女2例。梗死后20h内,梗死相关血管已接受冠状动脉介入治疗,冠脉血流正常。所有患者PCI术后10天内接受静息状态下双核素心肌显像（心肌灌注及心肌代谢显像）。根据基线梗死区灌注减低程度和心肌有无存活,分为两组,通过超声心动观察不同组患者12个月后左室舒张末直径（LVEDD）及左室收缩功能（LVEF）的变化,观察梗死区心肌存活状态及灌注情况对于左室重构的影响,间接反映其对自身心肌干细胞修复功能的影响。结果表明,梗死心肌有存活的患者（n=10）与无存活组（n=10）相比,两组12个月后LVEDD都无明显变化。梗死心肌有存活的患者LVEF有所改善,43.6±7.83 vs.46.79±12.68,无存活组LVEF轻度下降,39.10±8.71 vs.37.70±7.57,P〉0.05。梗死区灌注减低程度不同的两组患者PCI术后12个月,LVEDD都无明显变化。LAD PER%〈50%组（n=9）LVEF值有所改善,39.89±10.19%vs.42.22±13.54%,但变化不具有显著性,P〉0.05;LAD PER%〉50%组（n=11）LVEF值无改善,并可见轻度下降,42.55±6.86%vs.41.20±8.32%。LAD PER%〈50%且同时梗死区有存活心肌的患者（n=5）LVEF改善明显,上升了4.8%,与LAD PER%〉50%且同时梗死区无存活心肌的患者（n=6）相比具有统计学意义,P=0.029。结论：急性前壁心肌梗死并行PCI治疗的患者,心肌灌注程度不同与梗死区心肌是否有存活都对患者的左室重构改善无明显影响,但心肌灌注程度较好的患者和有心肌存活的患者左室收缩功能都有轻度改善;尤其值得注意的是,在心肌灌注程度较好,并且有存活心肌存在的情况下,心功能改善明显。而相对梗死区灌注差且无心肌存活的患者,12个月后,心功能减低,左室重构更加明显。     

大鼠在体心脏缺血后处理模型的建立与优化

目的建立并优化大鼠在体心脏缺血后处理(I-postC)模型。方法采用冠状动脉左前降支垫扎球囊法建立在体心脏I-postC模型,健康雄性SD大鼠随机分为7组(n=8):缺血/再灌注(I/R)组(冠状动脉左前降支缺血45min/再灌注2h)、缺血预处理(IPC)组(I/R前先行3轮缺血5min/再灌注5min处理)、I-postC组(包括4个亚组,于冠脉缺血45min后先进行3或4轮再灌注30s/缺血30s或再灌注60s/缺血60s后处理后再进行冠脉再灌注)以及假手术(sham)组。氯化三苯四氮唑(TTC)法测定心肌梗死面积,试剂盒检测血浆乳酸脱氢酶(LDH)和心肌组织超氧化物歧化酶(SOD)活性。结果I/R引起明显的心肌梗死和组织损伤,采用冠状动脉左前降支垫扎球囊法进行I-postC可以显著减少I/R后心肌梗死面积,尤以3或4轮再灌注30s/缺血30s组保护作用明显,其梗死区占缺血区百分比分别比I/R组下降30.26%和58.81%(P分别<0.05),与IPC保护效果相近。结论I-postC可以减轻心肌I/R损伤,其中4轮再灌注30s/缺血30s诱导的I-postC在限制心肌梗死面积方面作用最明显,是理想的大鼠在体心脏I-postC模型。     

核素TID比值诊断非梗阻性冠心病心肌缺血

目的 利用核素门控运动/静息心肌灌注显像半定量指标左心腔一过性缺血性扩张(TID)比值来诊断非梗阻性冠心病患者心内膜下心肌缺血.方法 非梗阻性冠心病32例(冠状动脉造影或冠脉CTA狭窄小于50％),有心绞痛症状;健康对照组30例,无高血压、无肥胖、无糖尿病.分别行运动/静息状态下核素门控心肌灌注显像.采用Siemens Ecam双探头SPECT仪器心脏软件对数据进行处理分析,计算出TID比值.结果 非梗阻性冠心病组:运动/静息TID比值为1.31±0.27,总灌注缺损率(TPD)65.6％;健康对照组:运动/静息TID比值为0.94±0.20,总灌注缺损率(TPD)3.3％.结论核素TID比值是诊断非梗阻性冠心病心内膜下心肌缺血的有效且无创的较佳指标.     

冠心病患者血清胱抑素C、一氧化氮、超氧化物歧化酶及超敏C反应蛋白水平变化及与冠脉狭窄程度的相关性

目的:分析血清胱抑素C(CysC)、一氧化氮(NO)、超氧化物歧化酶(SOD)及超敏C反应蛋白(hs-CRP)水平与冠状动脉狭窄程度的关系及其临床意义。方法:162例心血管病患者依据冠脉造影结果分为对照组(冠脉狭窄50%,n=40);单支病变组(一支冠脉狭窄≥50%,n=44);双支病变组(两支冠脉狭窄≥50%,n=43);多支病变组(两支以上冠脉狭窄≥50%,n=35)。对四组患者进行冠脉狭窄Gensini积分及血清CysC、NO、SOD及hs-CRP水平检测,分析冠心病患者各指标变化及其与Gensini积分的相关性。结果:单支病变组、双支病变组、多支病变组的CysC和hs-CRP水平均高于对照组(P0.05),并依次递增;单支病变组、双支病变组、多支病变组的NO及SOD水平均低于对照组(P0.05),并依次递减。冠心病患者Gensini积分与血清CysC和hs-CRP水平呈正相关,相关系数分别为0.473,0.429(P0.05);与NO和SOD水平呈负相关,相关系数分别为-0.356,-0.384(P0.05)。结论:冠心病患者冠脉狭窄程度的增加与CysC、hs-CRP水平升高及NO、SOD水平降低有明显相关性。     

心肌血流储备分数在冠状动脉临界病变中的应用

目的:探讨心肌血流储备分数(FFR)在冠状动脉临界病变处理中的意义。方法:经冠状动脉造影(CAG)证实单支血管病变程度介于50%～70%的临界病变心脏病患者24例,对狭窄血管行FFR测定,测量值FFR<0.75的患者行支架植入,FFR≥0.75的患者行药物治疗,8个月后比较两组患者的冠状动脉狭窄程度、FFR及心绞痛发生情况。结果:FFR<0.75组植入支架前后冠脉狭窄程度由(68.00±10.00)%下降到(8.00±2.00)%(P<0.01),FFR值由(0.70±0.03)%提高到(0.92±0.03)%(P<0.01),心绞痛发生例数由10例减少为0例(P<0.01)。FFR≥0.75组药物治疗前后各指标比较无明显差异(P>0.05)。组间治疗后比较,FFR<0.75组冠脉狭窄程度较FFR≥0.75组显著降低,FFR值升高,心绞痛发生例数减少为0(P均<0.01)。结论:在冠状动脉临界病变中测量FFR值能有效评估心肌供血情况,为临床是否行支架植入提供参考。     

犬急性心肌梗死模型的多层螺旋CT心肌灌注和冠状动脉造影

目的 :研究急性心肌缺血和梗死的多层螺旋CT(MSCT)心肌灌注特点 ,探索MSCT冠状动脉造影对冠状动脉阻断的显示情况。方法 :犬左冠状动脉前降支结扎前、后不同时期分别进行MSCT心肌灌注扫描 ,分析其特点 ,并与病理检查相对照 ;同时做MSCT冠状动脉造影观察冠状动脉阻断的情况。结果 :犬心肌正常灌注量为 ( 69.3±1 3 .9)ml·1 0 0g- 1·min- 1、达峰值时间 ( 1 2 .8± 2 .1 )sec。左冠状动脉前降支结扎 3 0min后MSCT心肌灌注表现为灌注量减低 ,时间密度曲线低平 ,延迟 1 0min扫描局部心肌密度无显著改变。结扎 4h后 ,局部心肌呈明显延迟增强。MSCT冠状动脉造影显示冠状动脉前降支中断。结论 :MSCT心肌灌注结合冠状动脉造影可以判断心肌缺血和梗死 ,同时显示冠状动脉的阻塞状况     

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.     

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.     

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.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

'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.     

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.