Young age at first pregnancy does protect against early onset breast cancer in <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> mutation carriers

Purpose

Previous research assessing the impact of pregnancy and age at first pregnancy on breast cancer risk in BRCA1 and BRCA2 mutation carriers has produced conflicting results, with some studies showing an increased risk following early first pregnancy in contrast to the reduced risk in the general population of women. The present study addresses these inconsistencies.

Methods

Female BRCA1 and BRCA2 carriers from North West England were assessed for breast cancer incidence prior to 50 years of age comparing those with an early first full-term pregnancy (< 21 years) to those without a full-term pregnancy. Breast cancer incidence per decade from 20 years and Kaplan–Meier analyses were performed.

Results

2424 female mutation carriers (1278 BRCA1; 1146 BRCA2) developed 990 breast cancers under the age of 50 years. Women who had their first term pregnancy prior to age 21 (n = 441) had a lower cancer incidence especially between age 30–39 years. Kaplan–Meier analysis showed an odds ratio of 0.78 for BRCA1 (p = 0.005) and 0.73 for BRCA2 (p = 0.002).

Conclusions

The present study demonstrates a clear protective effect of early first pregnancy on breast cancer risk in both BRCA1 and BRCA2 mutation carriers.

     

脑外伤患者发生院内肺部感染的危险因素及预防研究

目的探讨脑外伤患者发生院内肺部感染的危险因素,以针对危险因素加强临床预防措施。方法回顾性分析保定市第一医院2010年6月-2011年6月收治的97例脑外伤患者的临床资料,统计院内肺部感染的发生率并分析发生的危险因素。结果脑外伤患者院内肺部感染发生率为18．6％（18／97）,其发生与患者性别、体重、置尿管无明显关系（P〉0．05）,而受到患者年龄、格拉斯哥评分、激素应用、机械通气、气管切开、抗生素联用、置胃管的影响（P〈0．05）。结论临床上应注意脑外伤患者发生院内肺部感染的危险因素并采取针对性的预防措施,降低院内肺部感染发生率,促进患者的康复。     

熔融高速搅拌法制备氢氯噻嗪缓释微丸

通过对处方和工艺进行优化和筛选 ,采用熔融高速搅拌法制备了利尿药氢氯噻嗪的缓释微丸。结果表明 :以固体石蜡和单硬脂酸甘油酯为粘合剂 ,在 6 4℃、70 0r/min条件下操作 ,成粒子后再加入少量固体石蜡和钙盐 ,继续搅拌 ,降温整粒 8min可得圆整的缓释微丸。验证了应用熔融高速搅拌法制备氢氯噻嗪缓释微丸的适用性和技术特殊性 ,为工业生产奠定了基础。     

Cadherin-Catenin复合体在胃癌中的表达及生物学意义

目的:探讨Cadherin-Catenin复合体在胃癌癌变过程中的表达及生物学意义。方法:建立组织芯片技术平台,应用该技术和免疫组化sp法检测2种蛋白在胃癌石蜡标本中的表达。结果:126例标本的组织芯片制备成功。其中E-cad在4组中的阳性率分别为86.7%,80.7%,55%和53.8%,胃癌组与正常胃和胃炎组比较有统计学意义(P<0.05和P<0.05)。而β-cat的阳性率分别为93.3%,57.7%,55%和49.2%,其中胃癌组,胃上皮非典型增生,胃炎组与正常组比较均有统计学意义(P<0.01,P<0.05和P<0.05)。两种蛋白的表达与胃癌的组织分化和淋巴结转移显著相关,但与年龄、临床分期等无明显相关。结论:建立了组织芯片技术平台,本研究中E-cad、β-cat的表达下调指示二者与胃癌发生密切相关,且均与胃癌组织分化和淋巴结转移密切相关,联合检测E-cad、β-cat可作为预测胃癌发生和发展的肿瘤标志物。     

IgA肾病血尿误诊为尿路感染血尿三例分析

目的 探讨IgA肾病的病理特点,提高诊断合格率.方法 回顾性分析3例有血尿症状的IgA肾病患者被误诊为尿路感染血尿的经过和原因.结果 3例患者均为系膜增生性IgA肾病患者,HaasⅠ级2例、HaasⅡ级1例,均于发病前出现过尿路感染,确诊后均已治愈.结论 IgA肾病的复杂性和隐匿性使其易被误诊,临床诊断要全面掌握IgA肾病的临床与病理特点,不能局限于表面症状的诊断.     

绝经前后女性冠心病患者HDL及LDL颗粒与冠状动脉病变程度的相关性研究

目的探讨绝经前后女性冠心病患者高密度脂蛋白(HDL)颗粒及低密度脂蛋白(LDL)颗粒与冠状动脉病变程度的关系。方法收集经冠状动脉造影确诊的女性冠心病患者79例,根据是否绝经分为绝经前组(n=37)和绝经后组(n=42)。Lipoprint脂蛋白分析仪对HDL颗粒及LDL颗粒进行检测分析,探讨两种脂蛋白颗粒与冠状动脉病变程度的关系。结果与绝经前组比较,绝经后组大颗粒HDL浓度(102.6±45.2 mg/L比143.8±49.7 mg/L,P0.05)及所占比例(23.34%±8.26%比31.15%±7.98%,P0.05)、LDL颗粒平均直径(259.5±8.1比265.7±3.7,P0.05)均降低,小颗粒HDL浓度(124.0±76.8 mg/L比87.0±34.9 mg/L,P0.05)及所占比例(27.26%±12.34%比18.62%±6.53%,P0.05)、LDL B型比例(73.8%比48.6%,P0.05)、Gensini积分(50.88±26.46比30.43±18.54,P0.05)均增高。绝经前组及绝经后组多支病变患者大颗粒HDL浓度、LDL颗粒平均直径均低于单支病变患者,Gensini积分高于单支病变患者;绝经后组大颗粒HDL浓度、LDL颗粒平均直径均低于绝经前组,小颗粒HDL所占比例及Gensini积分高于绝经前组。绝经前组和绝经后组LDL颗粒大小及大颗粒HDL浓度均与Gensini积分呈负相关。结论与绝经前组相比,绝经后组大颗粒HDL浓度较低,小颗粒HDL浓度较高,LDL颗粒平均直径较小,冠状动脉病变程度较严重;大颗粒HDL浓度及LDL平均直径与冠状动脉病变严重程度明显相关。     

Hypermethylation of the 5' region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies

An abnormal increase in numbers of CCGG sites methylated in the 5' region of the human calcitonin (CT) gene occurred in tumor cell DNA samples from 90% (17 of 19) of patients with non-Hodgkin's T and B cell lymphoid neoplasms and in 95% (21 of 22) of tumor cell DNA samples from patients with acute nonlymphocytic leukemia (ANLL). The changes were not seen in patients with chronic myelogenous leukemia (0 of 9). The abnormal methylation patterns appear to be a property only of transformed or malignant cells since they were not found in DNA from nonneoplastic adult tissues including sperm, early myeloid progenitor cells, benign lymphoid hyperplasia, peripheral lymphocytes stimulated to divide, or early myeloid progenitor cells (obtained by immunoaffinity using anti-My-10 antibody), but they did appear after Epstein-Barr virus transformation of lymphocytes. Moreover, during the course of therapy in patients with ANLL, the hypermethylation pattern reflects the presence of the leukemic clone even in normal-appearing granulocytes derived from this clone. The increased methylation of the CT gene may then provide an important molecular marker for biologic events in human cell transformation or tumor progression and may prove clinically useful in monitoring patients with lymphoid and acute myelogenous neoplasms.     

Heterogeneity of the T-cell receptor delta gene indicating subclone formation in acute precursor B-cell leukemias

Precursor B-cell acute lymphoblastic leukemias (B-ALLs) have been shown to be oligoclonal at the Ig heavy-chain (IgH) gene level in up to 40% of cases by Southern blot hybridization. In contrast, oligoclonality as deduced from diversity of T-cell receptor (TcR)-delta gene rearrangements of the immature types (ie, V delta 2-D delta 3, D delta 2-D delta 3) has not been reported, so far. We detected oligoclonality characterized by the coexistence of different junctional regions of identical V delta 2-D delta 3 rearrangements in four childhood precursor B-ALLs. No variation was found in the IgH gene status. Therefore, we define these populations as subclones. Two leukemias displayed the variants in an unequal proportion. In the other two leukemias, for which similar quantities of the coexisting rearrangements were detected, single cell-nuclei polymerase chain reaction (PCR) showed two separate leukemic populations. Subclone formation could not be demonstrated by Southern blot hybridization, but was detectable after PCR amplification of the V delta 2-D delta 3 rearrangement and separation by polyacrylamide gel electrophoresis. The variants arose independently from each other, as deduced from their individual sequences. Using subclone-specific oligonucleotides for hybridization to amplified DNA obtained at diagnosis and during follow- up from bone marrow samples, we demonstrate, (1) specificity of all subclone-deduced probes, (2) that one residual leukemic cell can be detected in 10(4) to 10(5) normal mononuclear cells in a semiquantitative assay, and (3) that none of the subclones persisted after induction therapy. We propose that in a leukemic cell population, TcR-delta gene diversity arises after rearrangements of the IgH genes resulting in apparent clonality at the IgH gene level. However, cells are oligoclonal, if the TcR-delta gene rearrangements are considered. As various subclones may respond differently to chemotherapy, they may hamper the detection of minimal residual disease. Therefore, we use all subclone-specific oligonucleotides for hybridization to amplified DNA from follow-up samples.