Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes.

PURPOSE: This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. EXPERIMENTAL DESIGN: In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. RESULTS: In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. CONCLUSIONS: On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.     

Prognostic Value of PCNA and Mutant p53 Expression in Laryngeal Squamous Cell Carcinoma

The objective of this study was to investigate the prognostic significance of p53, and proliferative cell nuclear antigen (PCNA) in laryngeal squamous cell carcinoma (LSCC). Sixty pathologic specimens from the patients with LSCC were examined for the expression of the p53 and PCNA, with complete follow-up data. Sixty-three percent of the cases displayed nuclear p53 overexpression. There was a correlation between p53 overexpression and histological grades (p = 0.03), and localization site (p = 0.05). Median of PCNA index was 42.2 (range 5.9 to 85.2). There was no difference between the p53 overexpression group and the normal group in proliferative activity determined by PCNA (p = 0.73). In univariate analyses, localization site, grade, stage, invasion pattern, lymph node status, were significant factors in estimating disease free survival (DFS). Grade was the most important factor affecting recurrence (p = 0.002). In multivariate analyses, grade was the only significant predictor for DFS (p = 0.001). Grade (p = 0.001) and invasion pattern (p = 0.03) were found to be significant predictors of overall survival. In conclusion, the histological grade was the most reliable important prognostic factor. Further studies are necessary to facilitate understanding of the mechanisms of laryngeal carcinogenesis.     

HLA-G upregulation in pre-malignant and malignant lesions of the gastrointestinal tract

HLA-G belongs to the nonclassical MHC class Ib group of molecules and has been implicated in mediating immune-responsiveness in various cancerous and non-cancerous cell types. We have examined HLA-G expression in a number of human gastrointestinal malignancies, including pancreatic ductal adenocarcinoma, ampullary cancer, biliary cancer, and colorectal cancer by immunolabeling analysis. We used indices of <5% (negative), 6–25%, 26–50%, 51–75%, and >75% (diffuse) to subclassify lesions based on percentage of positive cell labeling. Across all cancer subtypes, 52–79% of lesions demonstrated expression of HLA-G, with up to 33% of lesions demonstrating diffuse (>75%) expression. In addition, we utilized the neoplastic progression model of colorectal cancer to evaluate HLA-G protein expression in normal colon, tubulovillous adenomas, invasive cancer, and liver metastases arising from colorectal cancer. Focal HLA-G expression was detected in regions of normal colon adjacent to sites of adenomatous and cancerous lesions, as well as in all stages of cancer progression. Overall, the percentage of diffusely (>75%) labeled lesions appeared increased in preneoplastic and neoplastic conditions, as compared to normal colon. Specifically, tubulovillous adnenomas demonstrated pronounced diffuse labeling in 58% of lesions examined. No correlation with HLA-G expression and CD4+ or CD8+ T cells was identified. We propose that HLA-G expression is upregulated in a large percentage of gastrointestinal lesions and may serve to mediate immuneresponsiveness in certain instances.     

葛根素注射液对急性脑缺血模型大鼠脑细胞损伤后Fas蛋白表达的影响

目的:探讨葛根素注射液对急性脑缺血模型大鼠脑细胞损伤后Fas表达的影响.方法:采用闭夹大脑中动脉造成大鼠局部急性脑缺血模型,用免疫组化SP法测定Fas表达情况,光镜观察脑组织损伤程度.结果:葛根素组死亡细胞数显著少于对照组(P＜0.01),葛根素组与对照组比较Fas阳性细胞数差异无显著意义(P＞0.05),各组Fas阳性细胞数与死亡细胞数间无明显相关性(P＞0.05).结论:葛根素对急性脑缺血模型大鼠脑细胞损伤具有保护作用,其机制可能主要通过上调HSP70蛋白的表达而实现,而与Fas蛋白的表达及细胞凋亡等相关不强.     

前列腺增生并高血压患者术前后的观察及护理

目的 探讨前列腺增生合并高血压患者术前后的观察及护理.方法 对40例前列腺增生合并高血压患者加强心理护理,进行生活方式干预,密切观察血压情况,术后加强病情观察、管道护理,严防并发症发生,给予康复指导.结果 40例患者血压控制在140/90mmHg左右,手术成功无并发症发生,术后排尿顺畅.结论 加强对前列腺增生合并高血压患者术前后的心理护理,进行生活干预,稳定血压,加强术后病情观察及管道护理,适当给予健康指导是前列腺增生合并高血压患者手术成功的保证.     

PAX2在肾小管上皮细胞转分化中的作用

目的 揭示核转录因子（PAX2）在肾小管上皮细胞转分化过程中的可能作用。方法 38例病例组肾组织按间质病变程度分为轻、中、重3组,其中轻度病变15例,中度病变11例,重度病变12例;对照组为5例外伤后肾切除组织。采用免疫组化法评定肾组织PAX2的表达率和肾小管上皮细胞转分化率。对肾间质病变轻、中、重3组组内肾小管上皮细胞转分化率、PAX2表达率作方差分析,对PAX2表达量与肾小管上皮细胞转分化率作相关分析。结果 正常对照组肾小管上皮细胞只表达角蛋白（CK）,不表达平滑肌肌动蛋白（α-SMA）及PAX2。病例组肾间质病变轻、中、重3组肾小管上皮细胞均不同程度表达α-SMA及PAX2;不同肾间质病变组,肾小管上皮细胞转分化率及PAX2表达量差异均有统计学意义。相关分析表明,PAX2表达量和肾小管上皮细胞转分化率呈正相关（r=0．886,P〈0．05）。结论 PAX2回归表达可能导致肾小管上皮细胞转分化。     

血浆置换对重型乙型病毒性肝炎HBV DNA含量的影响及与预后的关系

探讨经血浆置换（PE）治疗重型乙型病毒性肝炎后,患者血清中HBV DNA含量的变化对预后的影响。随机选取60例乙型肝炎病毒标志物阳性患者,20例为对照组,40例在内科治疗的基础上加PE治疗。观察治疗前后血清HBV DNA含量变化。40例经PE治疗的患者血清HBV DNA含量下降,PE治疗有效组比PE治疗无效组和对照组降低更明显,且肝功能指标改善也更明显。PE治疗可以有效的去除重型肝炎患者血清HBV DNA,改善肝功能及预后,提高患者的存活率。     

膝骨关节病性髁间窝撞击症的镜下诊断与治疗

目的 探讨膝骨性关节炎合并股骨髁间窝撞击症的诊断和治疗方法.方法 关节镜下确诊合并股骨髁间窝撞击症的膝骨性关节炎患者37例43膝.采用镜下清理骨赘、股骨髁间窝扩大成形术治疗.结果 43膝均获随访,时间6～24个月.术前Lysholm评分平均61分(41～80分) ,术后平均85分(75～100分),关节功能均获明显改善(P＜0.05).结论 关节镜检查及镜下微创手术对膝骨关节病性髁间窝撞击症的诊断和治疗有着重要的价值,镜下股骨髁间窝扩大成形术是治疗该病的有效方法.     

梗阻性黄疸18F-FDG PET/MR成像中国专家共识

梗阻性黄疸病因复杂,定性和定位诊断具有挑战性。一体化正电子发射计算机断层成像/磁共振（positron emission tomography/magnetic resonance, PET/MR）检查,通过PET与MR在梗阻性黄疸诊断中的优势互补,形成整合优势。在满足诊断需求的前提下,如何缩短PET/MR扫描时长、选择适宜的个性化扫描协议是临床关注的焦点。本文在文献复习和大量临床应用积累基础上,基于病灶是否具有显像剂聚集,建立简繁不同的PET/MR成像协议和报告,并形成专家共识。     

216例自杀案法医学分析

目的 研究自杀案件的规律性,为自杀案件的鉴定提供帮助.方法 对辖区内216例自杀案件中死者的基本情况、自杀原因、自杀方式、时间分布进行统计分析.结果 自杀原因以家庭隔阂为最常见;自杀方式中服毒、自缢和溺水分别列前3位;自杀时间分布也有一定规律性.结论 自杀案件具有其特殊规律性.