Open, Double-Blind and Long-Term Study of Vigabatrin in Chronic Epilepsy

We performed an open, double-blind, and long-term study of vigabatrin (gamma-vinyl-GABA, GVG) in patients with treatment-resistant epilepsy who were receiving only one or at most two standard antiepileptic drugs (AEDs). The novel design included a parallel, double-blind, placebo-controlled phase that minimized the number of patients receiving placebo and allowed determination of the optimum dose of GVG for each patient before initiation of the double-blind phase. The study was divided into four phases. The first phase was a 6-week period of baseline observation. In the second phase, GVG was added openly to previous AEDs for 8 weeks. During the first 2 weeks of this phase, the dose of GVG was increased weekly and then, in the absence of adverse effects, was held constant for the next 6 weeks. At the end of this open phase, seizure frequency during the 6 weeks of constant treatment was compared with the baseline seizure frequency for each patient. Patients who experienced reduction greater than 50% in the frequency of any seizure type during the open phase were defined as responders. These responders were then entered into the third and double-blind phase, in which they were randomly allocated wither to continue active GVG treatment or placebo for 8 weeks. Thirty-three patients entered the study; 31 of 33 patients completed the initial open phase. Twenty patients achieved a reduction greater than or equal to 50% in the frequency of one or more seizure types and were eligible for the double-blind phase; 10 were randomized to continue GVG and 10 were randomized to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic GVHD in minor salivary glands and oral mucosa: histopathological and immunohistochemical evaluation of 25 patients

BACKGROUND: Graft-vs.-host disease (GVHD) is the major cause of morbidity and mortality in patients undergoing allogeneic Bone Marrow Transplantation (BMT). The aim of our study was to identify the most relevant histological features for diagnosis of chronic Graft-vs.-Host Disease (cGVHD) in oral mucosa and minor salivary glands of 25 patients, as well as to evaluate the immunophenotype of the inflammatory cells. METHODS: Sixteen patients that were submitted to allogeneic BMT but did not present cGVHD were selected as a control group. The sections were studied on H & E and CD68, CD45, CD4, CD8, CD20 staining. RESULTS: The most frequent histologic findings in oral mucosa at the day of diagnosis of cGVHD were: hydropic degeneration of the basal layer of the epithelium, apoptotic bodies, lymphocytic infiltration, and focal or total cleavage between the epithelial and connective tissue. In the labial salivary glands (LSG), lymphocytic infiltration, acinar loss and fibrosis were the main alterations. Cytotoxic CD8-T cells and macrophages were predominant both in the epithelium and connective tissue, as well as in minor salivary glands. CONCLUSIONS: Histological features were useful in the diagnosis of oral cGVHD. It is suggested that CD8-T cells and macrophages play important role in the pathogenesis of the disease.     

Acute Cellular Rejection with CD20-Positive Lymphoid Clusters in Kidney Transplant Patients Following Lymphocyte Depletion

Lymphoid clusters (LC) containing CD20-positive B cells in kidney allografts undergoing acute cellular rejection (ACR) have been identified in small studies as a prognostic factor for glucocorticoid resistance and graft loss. Allograft biopsies obtained during the first episode of ACR in 120 recipients were evaluated for LC, immunostained with CD20 antibody, and correlated with conventional histopathologic criteria, response to treatment and outcome. LC were found in 71 (59%) of the 120 biopsies. All contained CD20 positive B cells that accounted for 5-90% of the LC leukocyte content. The incidence of LC was highest in the patients who had no lymphoid depletion or had been treated with Thymoglobulin preconditioning (79% vs. 75%, respectively) compared to 37% in patients pretreated with Campath (p = 0.0001). Banff 1a/1b ACR were more frequent in the LC-positive than the LC-negative group (96% vs. 80%, respectively; p = 0.0051). With a posttransplant follow-up of 953 +/- 430 days, no significant differences were detected between LC-postitive and LC-negative groups in time to ACR, steroid resistance, serum creatinine and graft loss. CD20+LC did not portend glucocorticoid resistance or worse short to medium term outcomes. CD20+LC may represent a heterogenous collection in which there may be a small still to be fully defined unfavorable subgroup.     

三种实验性IgA肾病模型的比较

目的探讨建立一种理想的IgA肾病（IgAN）动物模型方法。方法分别采用葡聚糖G200、大肠杆菌外膜蛋白和金葡菌的细胞膜20肽抗原决定簇诱导小鼠IgA肾病模型。用分子生物学和病理学方法对3组IgAN模型小鼠进行鉴定和比较。结果（1）葡聚糖组尿蛋白增高，伴有血尿；免疫荧光显示部分肾小球大量IgA沉积；光镜下肾小球系膜细胞增多，肝和脾可见弥漫性的粉染物质沉积；电镜下肾小球系膜区少量低电子密度的致密沉积物，肝和脾可见淀粉丝样物质沉积。（2）大肠杆菌外膜蛋白组尿蛋白增高，伴有血尿；免疫荧光显示肾小球有少量IgA沉积；光镜下肾小球系膜细胞轻度增多，间质炎细胞浸润明显；电镜下肾小球系膜区无电子致密沉积物。（3）金葡菌细胞膜20肽抗原决定簇组尿蛋白增高，伴有血尿；免疫荧光显示多数肾小球均可见大量IgA沉积；光镜下肾小球系膜细胞增多，伴系膜基质轻度增生；电镜下肾小球系膜区和基底膜的内皮细胞下可见高电子密度的致密沉积物。结论金葡菌细胞膜20肽抗原决定簇组诱导的IgAN模型从临床表现和病理学变化与人IgAN极其相似，是3种IgAN模型中最理想的IgAN模型。     

锌指蛋白A20 RNAi载体的构建及筛选

目的我们前期的实验结果显示A20 mRNA和蛋白在人脑胶质瘤组织及细胞系（U251、U87、BT325）中高表达，本研究拟构建A20RNAi载体，并检测其对U251细胞A20表达的抑制作用。方法构建三种针对人A20基因的真核干涉表达载体，以脂质体法将其分别转染人脑胶质瘤细胞系U251，以RT-PCR、蛋白印迹法检测各干涉载体对U251细胞中A20mRNA和蛋白表达的抑制作用。结果成功构建三种针对A20基因的RNAi载体，经RT-PCR、蛋白印迹检测筛选出对A20基因干涉效果最佳的载体，命名为pSilencer3．1-A20R1。结论成功构建A20基因干涉载体，为进一步探讨A20与脑胶质瘤恶性增殖、血管形成以及抗凋亡的关系奠定实验基础。     

Cytokeratin 7 and 20 as immunohistochemical markers in identification of primary tumors in craniospinal metastases: Do they have a significant role?

Cytokeratin (CK)7 and CK20, the low molecular weight cytokeratins, have been found to have a benefit in the differential diagnosis of some epithelial neoplasms. In the present study, the actual role of these markers in the search of primary tumors in 32 patients with craniospinal metastasis of an unknown primary site at presentation, is evaluated. A series of 36 patients with a known primary tumor were presented for comparison. In the first group, two CK7 and CK20 expression profiles were observed; 87% of metastatic tumors were CK7+/CK20‐ and 13% CK7‐/CK20‐. The lung was the major source (82%) of CK7+/CK20‐ metastatic tumors, whereas it represented only 38% of primary tumor in the second group of a known primary site (P = 0.006). Given the fact that metastatic tumors to the craniospinal axis of an unknown primary site are frequently CK7+/CK20‐, and they have commonly metastasized from the lung, it is doubtful that immunohistochemistry is really helpful. However, CT scan and MRI of the chest still play an important role. Many patients in the present study had to undertake these imaging studies, regardless of the CK7/CK20 result. The immunostains may be useful in cases with other expression profiles, but such examples constituted only a minority in the present study.     

Sonoanatomy of the foot

Summary To show the possibilities of imaging diagnostic procedures using high and extremely high resolution ultrasonic probes we investigated the anatomic structures of the foot. We examinated 10 cadaver foots of the anatomic institute and in a clinical trial 20 healthy patients with 10 to 20-MHz-probes and could identify correctly single tendons and ligaments even in the toe region. Especially the possibility of dynamic examination had to be mentioned beside the other advantages of ultrasound diagnostic (saving of expenses, lack of radiation, side-to-side comparison).      

雷公藤生物碱的分离鉴定

我们从雷公藤（ＴｒｉｐｔｅｒｙｇｉｕｍＷｉｌｆｏｒｄｉｉＨｏｏｋ．ｆ．）中按常法分离得到总碱后经ＨＰＬＣ分析出现８个峰，经硅胶柱层析及硅胶ＲＰ－１８反相中压柱层析分离得到５个生物碱，由化学方法和光谱分析证明为雷公藤吉碱（Ｗｉｌｆｏｒｇｉｎｅ２０）．雷公藤次碱（Ｗｉｌｆｏｒｉｎｅ２１），雷公藤春碱（Ｗｉｌｆｏｒｔｒｉｎｅ２２），雷公藤碱戊（Ｗｉｌｆｏｒｉｄｉｎｅ２３），呋喃南蛇碱（Ｃｅｌａｆｕｒｉｎｅ１６）。ＨＰＬＣ分析指出含量最高为雷公藤吉碱，其次为呋喃南蛇碱。     

直肠癌肠系膜静脉血CK20 mRNA的检测及其临床意义

目的　检测直肠癌肠系膜静脉血细胞角蛋白 2 0 (CK2 0 )mRNA ,并探讨其临床意义。方法　以RT -PCR方法检测 4 2例直肠癌术中肠系膜静脉血CK2 0mRNA。结果　 4 2例中 2 2例CK2 0mRNA阳性 ,阳性率 5 2 .4 %。随着病理分期的进展 ,肠系膜静脉血CK2 0mRNA阳性率升高 :DukesC +D期CK2 0mRNA阳性率高于DukesA +B期(P <0 .0 1)。随访发现 ,肠系膜静脉血阳性者远处转移率增高 (18.2 % )。结论　肠系膜静脉血CK2 0mRNA的检测可提高直肠癌临床分期的准确性 ;CK2 0mRNA阳性者 ,远处转移的可能性大。