幽门螺杆菌感染对胃黏膜病理变化的影响

背景：幽门螺杆菌(H．pylori)感染已被公认为慢性胃炎和消化性溃疡的重要危险因素，根除H．pylori能加速消化性溃疡的愈合，但其对胃黏膜病理变化的影响尚有待进一步探索。目的：了解根除H．pylori对慢性胃炎胃黏膜病理变化和癌前状态的影响。方法：采用多中心随机对照临床试验和回顾性队列研究，样本选自胃癌高发区：上海郊区的金山区和奉贤区。共纳入360例经内镜检查证实有H．pylori感染的慢性胃炎伴或不伴十二指肠溃疡患者，随机分为两组。治疗组用三联疗法(质子泵抑制剂或Hz受体阻滞剂加两种抗生素)治疗，对照组单纯慢性胃炎患者予西沙必利、十二指肠溃疡患者予西米替丁治疗。在第1年和第4年末随访胃镜，根据H．pylori是否根除将患者分为两组：H．pylori阳性组和H．pylori阴性组。所有胃黏膜活检标本由两位病理科医师统一复读。结果：至第4年末，有120例患者完成全部随访，其中H．pylori持续根除组54例，阳转组5例；H．pylori持续未根除组45例，阴转组16例。持续根除组第1年随访时，活动性炎症比例减少(P＜O．05)；第4年随访时，慢性炎症和肠化程度以及活动性炎症比例减少(P＜O．05)。持续未根除组第1年随访时，慢性炎症程度增加(P＜O．05)；第4年随访时，慢性炎症和肠化程度以及活动性炎症比例增加(P＜O．05)，萎缩程度较第1年随访时增加(P＜O．05)。结论：根除H．pylori可以减轻慢性胃炎的炎症程度，防止肠化的发生和发展。     

CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer

BACKGROUND/AIMS: Colorectal cancer is the third leading cause of cancer-related mortality in Taiwan. We became interested in searching for the factors predictive of survival. Serum CA19-9 (carbohydrate antigen 19-9) level has been reported as a factor predictive of survival in patients with colorectal cancer. A few articles have reported that patients with metastatic colorectal cancer who have normal (< or = 37 U/mL) serum CA19-9 levels survived significantly longer than those with higher serum CA19-9 levels. However, these reports are contradictory and lack definite conclusions. This study was carried out in an effort to evaluate the prognostic significance of serum CA19-9 levels in patients with metastatic colorectal cancer in Taiwan. METHODOLOGY: Between 1991 and 1994, a total of 128 patients with histologically confirmed metastatic colorectal cancers were evaluated retrospectively at Veterans General Hospital-Taipei. All patients had measurable metastatic lesions and life expectancies of more than 3 months. 5-Fluorouracil-based chemotherapy, either in a weekly bolus regimen or a monthly 5-day bolus schedule, were administered to all of them. Data on age, sex, performance status, location of primary tumor, extent of metastases, site of metastases, histological differentiation, serum CEA (carcinoembryonic antigen) and CA19-9 levels were analyzed before chemotherapy to determine their association with survival. Blood samples for CEA and CA19-9 measurement were analyzed using the radioimmunoassay method. Multivariate analysis by the Cox's proportional hazards regression model was performed to determine independent prognostic factors among all of the possible variables. RESULTS: By univariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.022) were identified as prognostic factors, while age, sex, location of primary tumor, site of metastasis, histological differentiation, and pre-treatment serum CEA levels were not considered significant. By multivariate analysis, serum CA19-9 levels (P < 0.001) and performance status of the patients (P = 0.014) were still found as independent prognostic factors of these patients. CONCLUSIONS: The data from our study indicate that serum CA19-9 level is the most significant prognostic indicator of patients with metastatic colorectal cancer. It is recommended that stratification for further clinical trials for patients with metastatic colorectal cancer should be carried out according to serum CA19-9 levels.     

Heterogeneity in the response of vascular smooth muscle to heparin: altered signaling in heparin-resistant cells

OBJECTIVE: Vascular smooth muscle cells show phenotypic heterogeneity in vivo that affects the extent to which they respond to the antimitogenic effects of heparin. In vitro, heparin-resistant cells are readily selected. This study was undertaken to determine whether differences in the antiproliferative response to heparin involve differences in activity of heparin-sensitive signal transduction pathways. METHODS: Rat thoracic aorta smooth muscle cells (ASMC) at early passage together with two established vascular smooth muscle lines, PAC-1 and A10, were examined before and after selection for growth in the presence of heparin (10 micrograms/ml). Cells were rendered quiescent and then stimulated with serum. RESULTS: The three cell types showed different sensitivities to the antimitogenic effects of heparin. With respect to [3H]thymidine incorporation, A10 cells were insensitive to 1 microgram/ml heparin whereas PAC-1 cells responded down to 0.05 microgram/ml and ASMC were of intermediate sensitivity. ASMC and PAC-1 cells but not A10 showed a decrease in c-fos mRNA in response to 1 microgram/ml heparin, and a decrease in the c-Fos content of AP-1 DNA binding activity. None of the cells had decreased c-jun mRNA in the presence of heparin. Although induction of c-fos by serum is thought to signal through the Erk mitogen activated protein kinase family, Erk activity was decreased more by 1 microgram/ml heparin in A10 cells than in PAC-1 or ASMC. When cells were selected by growth in the presence of 10 micrograms/ml heparin, A10 cells were unaffected but PAC-1 and ASMC showed a blunted effect of heparin on serum stimulation. In contrast to A10 and their controls not exposed to continuous heparin, heparin-selected PAC-1 and ASMC showed a diminished ability to induce c-fos in response to serum. CONCLUSIONS: Smooth muscle cell lines show different responses to the antimitogenic effects of heparin that correlate with the heparin sensitivity of c-Fos/c-Jun expression. Although Erk is implicated in c-fos induction, cells comparatively resistant to heparin still show heparin-dependent inhibition of Erk activation, suggesting that other pathways may be more important for heparin resistance. Furthermore, cells selected for heparin resistance may develop c-fos-independent pathways for proliferation.     

老年高血压心肌肥厚患者的年龄与心率变异指数

目的了解老年高血压心肌肥厚患者的年龄与心率变异性指数（ＨＲＶＩ）的关系。方法１７１例老年及老年前期高血压心肌肥厚患者经超声心动图和２４小时动态心电图测定左室质量指数（ＬＶＭＩ）、左室射血分数（ＬＶＥＦ）、ＨＲＶＩ，并采用多元逐步回归法分析了年龄与ＨＲＶＩ的关系。结果ＨＲＶＩ减低的发生率和平均ＨＲＶＩ在４５～５９岁组（４５例）为５７．８％，２４．７±９．１；在６０～７４岁组（７０例），为６７．１％，２２．９±１０．３；在≥７５岁组（５６例）为７６．８％，２０．９±８．７（Ｐ＜０．０５）。多元逐步回归分析显示，ＨＲＶＩ的变化与年龄（ｒ＝－０．２７４６，Ｐ＝０．０００１２）和ＬＶＭＩ（ｒ＝－０．４０１５，Ｐ＝０．０００２１）呈负相关关系，而与ＬＶＥＦ呈正相关关系（ｒ＝０．４２８３，Ｐ＝０．００００９）。结论老年高血压左心室肥厚患者随年龄增长ＨＲＶＩ逐渐减低。     

Familial breast cancer in southern Taiwan

The purpose of this study is to evaluate whether there are pathobiologic differences and differences in overall rates survival between familial and non-familial breast cancer patients in Taiwan. A retrospective study was performed evaluating 76 familial breast cancer patients in 69 families, which included two BRCA1 related cases and six BRCA2 related cases. Patients were compared with 425 non-familial sporadic cases. Familial breast cancer patients had similar ages and stages as non-familial patients (mean, 46.6 years vs 48.9 years, p = 0.306). However, the familial breast cancer patients with BRCA1 and BRCA2 related cases presented at lower stages (p = 0.034) and younger ages than non-familial patients (mean, 45.1 years vs 48.9 years P = 0.042). The occurrence of infiltrating ductal carcinoma and lobular carcinoma in situ was not significantly different in the two groups. Mucinous carcinoma was represented with 6.7% (4/76) and 1.3% (1/76) medullary carcinoma. The overall grade of familial breast cancer, including BRCA1 and BRCA2 related cases in 8 infiltrating ductal carcinoma, was significantly higher than that of controls. The mean follow up was 4.5 years for familial breast cancers. Five- and 10-year overall survival rates were 69% and 61% for those with a family history, compared with 86% and 64% for those in the control group (p = 0.644). There were no statistically significant differences in disease-free survival rates between the two groups at 5 or 10 years (69% vs 78% in 5 years; 48% vs 58% in 10 years) (p = 0.862). Despite the younger ages and earlier stages at presentation in familial breast cancer patients with BRCA1 and BRCA2 related cases, the familial breast cancer patients had higher grade patholobiologic characteristics, but similar prognoses when compared with sporadic breast cancer patients. Owing to the limited number of familial cases in this study, more cases and longer follow up are needed.     

血管紧张素转换酶和血管紧张素Ⅱ-1型受体基因多态性与冠心病的相关性分析

目的研究血管紧张素转换酶（ACE）基因I／D多态性和血管紧张素Ⅱ-Ⅰ型受体（AT1R）基因A1166／C多态性与冠心病（CHD）的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）技术检测130例CHD组和90例对照组ACE和AT1R基因多态性。结果ACE—DD基因型频率在CHD组显著高于对照组（38．5％，14．4％，P〈0．001）。AT1R—AC基因型在两组间差异无显著性（13．1％，10％，P〉0．05），但合并AC基因型的DD型患者发生CHD和MI的OR值（5．836和3．985）明显高于合并AA型（3．102和2．979）。结论ACE基因I／D多态性中DD基因型是冠心病发病的独立危险因素之一，AT1R—C等位基因增加ACE—DD型发生CHD和MI的危险，二者具有协同作用。     

乙型、丙型肝炎DNA疫苗单次联合接种后小鼠的免疫应答

目的：观察由编码ＨＢｓＡｇ与ＨＣＶ－ＣＥ２抗原的两种重组真核细胞表达质粒制备的ＤＮＡ疫苗联合接种ＢＡＬＢ／ｃ小鼠后,其施生行异性免疫应答的规律和相互影响。方法：应用上述２种ＤＮＡ疫苗单次联合免疫小鼠,动态观察血中特生抗体水平;并完成稳定转染,表达相应抗原的ＳＰ２／０骨髓瘤细胞的建株,采用ＣＴＬ杀伤活性体内诱生实验的方法建立观察ＤＮＡ疫苗免疫保护与治疗泊动物模型。结果：两种ＤＮＡ疫苗单次联合免疫小鼠     

Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes

OBJECTIVE: In a follow-up study, we determined the prevalence, incidence, and natural course of positive antithyroperoxidase antibodies (TPOAbs) and antithyroglobulin antibodies (TgAbs) in the general population and examined the influences of iodine intake. DESIGN: The study was conducted in Panshan, Zhangwu, and Huanghua, regions with mildly deficient, more than adequate, and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 3018 participated in the 5-yr follow-up study. Serum TSH, TPOAb, and TgAb levels were measured. RESULTS: Among subjects in Panshan, Zhangwu, and Huanghua, the prevalence of positive TPOAbs was 11.23, 11.83 and 12.02%, respectively, whereas 11.23, 11.17, and 11.26% of subjects were TgAb positive, respectively. In the older population (> or =45 yr), TgAb-positive individuals were more frequent in Huanghua than Panshan and Zhangwu (P < 0.05). The 5-yr cumulative incidence of positive TPOAb was 2.08, 3.84, and 2.84% in Panshan, Zhangwu, and Huanghua, respectively, whereas 2.91, 3.64, and 5.07% of subjects were TgAb positive, respectively (P < 0.05), corresponding to the increase in iodine intake. Subjects who were TPOAb and/or TgAb positive at baseline developed thyroid dysfunctions more frequently than those without antibodies (14.44 vs. 3.31%, P < 0.01); their incidence of elevated TSH levels was 1.32, 8.46, and 15.38% in Panshan, Zhangwu, and Huanghua, respectively (P < 0.05). CONCLUSIONS: Subjects who were TPOAb and TgAb positive at baseline developed thyroid dysfunctions more frequently than seronegative subjects. High iodine intake was a risk factor for developing hypothyroidism in antibody-positive subjects. A constant exposure to excessive iodine intake increased the incidence of positive TgAb.     

异基因外周血干细胞移植后淋巴细胞和粒细胞嵌合体的动态改变

目的：探讨异基因外周血干细胞移植(allo-PBSCT)后T细胞、粒细胞嵌合体的动态改变及临床价值。方法：将多重PCR扩增短串联重复序列(STR—PCR)的法医试剂进行条件优化，间隔短时间抽取9例恶性血液病患者(5例清髓性PBSCT，4例非清髓性PBSCT)的外周血样，STR—PCR定量分析T细胞和粒细胞的嵌合体，并观察其对移植后应用免疫抑制剂的指导作用。结果：STR—PCR定量分析嵌合体的敏感性为5％，并具高度可重复性。清髓性PBSCT后10d( 10d)，5／5例患者的粒细胞迅速演变为完全供者嵌合体(CDC)， 14d，4，／5例患者的T细胞获得CDC。非清髓性PBSCT， 7～ 14d，供者T细胞信号的植入速度快于粒细胞；随后，供者粒细胞的比例突然增加，并迅速获得CDC，T细胞的植入却渐缓慢，最后，T细胞取得CDC的时间迟于粒细胞。依据供者T细胞信号的植入程度，及时调整非清髓性PBSCT后环孢素A(CsA)的用量，移植早期T细胞即获CDC，随访2～16个月，T细胞和粒细胞均呈稳定的供者植入状态。结论：供者T细胞的完全植入迟于粒细胞．动态监测T细胞嵌合体，可能有助于免疫抑制剂的调整。