多房性胸腺囊肿合并胸腺瘤6例临床病理分析

目的探讨多房性胸腺囊肿(multilocular thymic cyst, MTC)合并胸腺瘤的临床病理学特征及发病机制。方法回顾性分析6例MTC合并胸腺瘤的临床资料、病理学特征,并复习相关文献。结果 74例胸腺瘤中伴MTC者6例,发病率为8.1%。其中男性5例,女性1例,年龄39～66岁,平均57.5岁。病变组织呈囊实性结构,囊性区域为多房性囊腔,衬覆单层扁平或立方上皮或鳞状上皮,或无上皮衬覆,囊壁内可见多量急慢性炎细胞浸润;实性成分为胸腺瘤,组织学亚型为AB型2例,B2型3例,B3型1例。免疫表型:囊性区域上皮CK和EMA均阳性,p40弱阳性。结论 MTC相对少见,合并胸腺瘤则更为罕见,需充分取材,并对囊壁进行形态学观察,以免漏诊。MTC合并胸腺瘤患者的预后,有可能比单纯性胸腺瘤预后好。     

多发性肌炎/皮肌炎合并淋巴瘤的临床特点分析

目的 探讨多发性肌炎(PM)/皮肌炎(DM)合并淋巴瘤的临床特点。方法 回顾性分析2000至2015年北京协和医院收治的PM/DM合并淋巴瘤患者的资料,分析临床特点和预后,并以“多发性肌炎、皮肌炎、淋巴瘤”为关键词在Pub Med检索并文献复习。结果 PM/DM合并胸腺瘤住院患者共10例,女性6例,男性4例。PM/DM的平均确诊年龄44.5岁,淋巴瘤的平均确诊年龄44.9岁。PM/DM进展至胸腺瘤的平均病程为4.7月。10例患者中6例为皮肌炎,4例为多发性肌炎,3例有肺间质病变,2例有关节炎,抗Jo-1抗体均阴性。合并淋巴瘤时前3位表现:淋巴结肿大(9例)、发热(8例)和脾大(5例)。淋巴瘤的病理确诊前3位组织来源:淋巴结(4例)、皮肤活检(2例)和局部肿物(2例)。10例患者均为非霍奇金淋巴瘤,其中T细胞来源4例,B细胞来源2例,4例分型不清。临床分期为:IIIB期4例,IVB期6例。10例患者在确诊后均使用免疫抑制治疗,确诊淋巴瘤后随访,5例死亡,4例化疗,1例失访。结论 PM/DM可以合并淋巴瘤,病程较短,病死率高,值得引起临床医师重视。     

胸腺上皮性肿瘤52例的临床病理分析

目的 探讨胸腺上皮性肿瘤的临床病理学特点,评价2004年WHO胸腺肿瘤分类的可重复性及其临床意义.方法 收集2001年1月至2009年6月间52例胸腺七皮性肿瘤的资料,对其形态学特征和免疫表型进行回顾性复习,按照2004年WHO胸腺肿瘤分类进行组织学分型,并对临床资料加以分析和总结.结果 胸腺瘤45例,胸腺癌7例.胸腺瘤中以AB型最多见,占33.3%(15/45),其次为B2型和B3型,均为20.0%(9/45).A型和B1型相对少见,分别占13.4%(6/45)和8.9%(4/45).另有2例化生性胸腺瘤(4.4%).7例胸腺癌中6例为鳞状细胞癌分化,1例为神经内分泌癌.临床上,多数患者因咳嗽或胸痛就诊,部分病例为体检中偶然发现.胸腺瘤中13例伴有重症肌无力(25.0%).影像学上,49例(94.2%)位于前纵隔,其中A、AB、B1和多数B2型胸腺瘤表现为边缘光整、密度均匀的肿块,少数B2型、多数B3型胸腺瘤和胸腺癌表现为边界欠清、外形不规则和密度不均的肿块.48例手术Masaoka分期为:Ⅰ期20例(41.7%),Ⅱ期15例(31.3%),Ⅲ期11例(22.9%),Ⅳ期2例(4.1%).分析显示,组织学分型与临床分期有显著相关性(χ~2=32.5,P＜0.01).结论 基于细胞形态、功能和遗传学的2004年WHO胸腺肿瘤分类具有较高的可重复性,并在一定程度上反映胸腺瘤各亚型的生物学行为,对临床治疗和预后判断有指导意义.     

胸腺癌与B3型胸腺瘤的临床病理研究

目的探讨胸腺肿瘤的临床病理特征。方法复习9例胸腺癌和21例B3型胸腺瘤，全部临床病史、影像学、实验室资料和肿瘤分期。标本常规病理制片、光镜观察和免疫组化标记。结果男17例，女13例，年龄28～70岁(中位43岁)，病程平均7．4个月。19例伴重症肌无力；9／22例纵隔X线检查未见异常；20／22例CT诊断胸腺瘤；肿瘤临床分期Ⅱ期1例，Ⅲ期22例，Ⅳ期7例，全部肿瘤呈浸润性生长，包括肺(22例)、心包(15例)、无名静脉(10例)和主动脉(5例)等，27例肿瘤完全切除。组织学表现低分化鳞状细胞癌(4例)，梭形细胞型鳞癌(2例)，大细胞未分化癌(2例)，基底细胞样癌(1例)和B3型胸腺瘤(21例)。肿瘤细胞以实性、索状浸润生长为其主要特征，缺乏核分裂象，部分肿瘤伴B1和B2型胸腺瘤成分；标记显示梭形细胞型鳞状细胞癌缺乏神经内分泌分化。结论胸腺癌和B3型胸腺瘤好发于40岁后中年人，肿瘤完全浸润性生长，术前多数患者系肿瘤的临床Ⅲ期，CT检查是诊断该病的主要手段，90％患者可行外科治疗，确诊依赖于病理组织学检查。     

胸腺瘤手术治疗体会（附23例分析）

胸腺瘤在纵隔肿瘤中最为常见,均起源于胸腺上皮细胞,在各种治疗方案中,以手术治疗为首选。自1992年5月至1998年12月,我们共收治胸腺瘤病人23例,其中手术治疗21例,另2例自动离院。合并重症肌无力5例,占21.7％与文献报告10～30％相符。现结合文献学习将手术治疗体会报告如下。 一、临床资料 本组23例中,男11例,女12例,年龄19～64岁。其中合并重症肌无力者:男2例,女3例。手术前病程3个月至4年。所有病人均经胸部拍片或CT检查发现前上纵隔内肿瘤影,2例     

胸腔镜下扩大胸腺切除治疗重症肌无力48例分析

目的 探讨胸腔镜下扩大胸腺切除活疗重症肌无力手术方法及疗效.方法 48例胸腺瘤或胸腺增生合并重症肌无力患者行胸腔镜手术治疗.其中男28例,女20例,年龄18～65岁,平均(38.7±3.2)岁.全组病例均于胸腔镜下行胸腺瘤或胸腺组织切除加纵隔脂肪组织清扫术.结果 所有手术胸腔镜下均顺利完成,无中转开胸者.全组患者手术时间40～120 min,术中出血量10～120ml,无手术死亡患者.全组术后无肌危象发生,留置胸引管2～5 d,住院时间3～8d.所有患者近期效果良好,获1年以上随访39例,随访率为81.25％.39例中15例完全缓解,占38.46％;16例改善,占41.03％;7例无变化,占17.95％;1例恶化,占2.56％.结论 胸腔镜下全胸腺及纵膈脂肪切除术治疗重症肌无力是一种安全可行的有效方法,具有创伤小、手术时间短、并发症少、恢复快等优点,符合外科微创化的发展方向,值得临床推广.     

胸骨异位胸腺瘤1例报告并文献复习

目的：探讨胸骨异位胸腺瘤的临床和病理特征,以提高临床诊断和治疗水平。方法和结果：复习异位胸腺瘤相关的临床和病理文献。手术治疗并经术后病理确诊胸骨异位胸腺瘤1例,术后随访30个月,无局部复发和转移。结论：异位胸腺瘤发生于胸骨非常罕见,目前国内外尚未见有文献报道;一旦确诊即应手术切除,预后取决于病理分型和分期。     

胸腺肿瘤108例的病理组织学分型和预后相关性研究

目的 研究胸腺肿瘤组织学分型与预后多因素的相关性.方法 回顾性研究108例胸腺肿瘤患者的临床病理资料,按2004年WHO胸腺肿瘤分型标准重新对肿瘤分型,根据临床和随访结果,对其预后与Masaoka临床分期、胸腺肿瘤的组织学分型、肿瘤完整切除与否、患者年龄、性别、肿瘤大小及是否伴有重症肌无力多因素进行相关性研究.结果 组织学分型:A型7例(6.5%),AB型19例(17.6%),B1型23例(21.3%),B2型19例(17.6%),B3型27例(25.0%),C型13例(12.0%).临床分期:Ⅰ期36例(33.3%),Ⅱ期34例(31.5%),Ⅲ期27例(25.0%),Ⅳa期11例(10.2%).临床分期与组织学分型存在显著相关性(P=0.000).A型、AB型、B1型、B2型、B3型胸腺瘤的5年生存率分别为100%、100%、93%、83%、43%;10年生存率分别为100%、100%、81%、70%、33%.C型胸腺瘤中位生存时间62.5个月.B2、B3型胸腺瘤患者的预后介于C型胸腺瘤和A、AB、B1型胸腺瘤之间(P=0.000).临床Ⅰ、Ⅱ、Ⅲ期胸腺肿瘤切除术后5年生存率分别为100%、77%、54%;10年生存率分别为100%、70%、27%.Ⅳa期患者中位生存时间14.0个月.在多因素统计分析中,Masaoka临床分期足胸腺瘤患者最重要的独立预后指标(P=0.000).胸腺肿瘤组织学分型和肿瘤完整切除与否是影响预后的重要决定因素.结论 Masaoka临床分期是影响胸腺瘤患者生存的最重要的预后参数,WHO组织学分型和肿瘤是否完整切除是影响胸腺瘤患者术后生存的决定因素.WHO组织学分型能反映胸腺瘤各亚型的临床生物学行为,A、AB和B1型胸腺瘤为潜在恶性的肿瘤,而B2和B3型胸腺瘤为中度恶性肿瘤,C型胸腺瘤预后差,属于高度恶性肿瘤.     

胸腺上皮性肿瘤中PD-L1的表达及意义

目的探讨PD-L1在胸腺上皮性肿瘤(thymic epithelial tumors,TETs)中的表达及与其临床病理特征的关系。方法收集南京市胸科医院2012～2017年手术切除的胸腺瘤上皮性肿瘤标本124例,根据WHO(2015)将TETs分成A、AB、B1、B2、B3型胸腺瘤和胸腺癌。采用免疫组化En Vision两步法检测PD-L1蛋白表达。结果 124例TETs中,39例PD-L1阳性:A型胸腺瘤1例,AB型胸腺瘤2例,B1型胸腺瘤7例,B2型胸腺瘤9例,B3型胸腺瘤10例,胸腺癌10例。PD-L1蛋白在B2、B3型胸腺瘤及胸腺癌中的表达高于A、AB、B1型胸腺瘤(P 0. 001),在Masaoka临床分期Ⅲ+Ⅳ期中的表达高于Ⅰ+Ⅱ期(P 0. 05),与患者性别、年龄等临床特征均无统计学意义(P 0. 05)。结论 PD-L1表达与TETs组织学类型有关,随着胸腺肿瘤上皮细胞增多,病理分级的增高,表达也增高,因此抗PD-1/PD-L1免疫治疗药物在有些胸腺瘤及胸腺癌中可能会有一定帮助。     

全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤30例

目的：探讨全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤的临床价值。方法：回顾性分析30例经全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤患者的临床资料,总结其手术方法、分期、病理学类型、后续治疗、并发症、随访结果等。结果：30例患者全部经右侧胸腔镜完成胸腺切除术,其中男性12例、女性18例,无中转开胸,无围手术期死亡和严重并发症;手术时间40—200min,平均（91．7±38．1）min,出血量30～300ml,平均（106±75）ml;术后住院时间5—7d,平均（5．1±0．8）d。术后临床分期,I期17例（56．7％）、II期13例（43．3％）。病理学类型,A型14例、AB型10例、B1型5例、B2型1例。Ⅱ期患者术后均接受辅助放疗。患者全部随访,随访时间6—72个月,中位随访时间44个月。随访期内无一例复发或死亡,总生存率（OS）为（70．2±1．7）个月（95％CI：66．8—73．6）。结论：全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤安全、有效,而且更加微创,值得临床推广应用。     

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.     

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.     

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.     

'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.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.