HER2-targeted therapy reduces incidence and progression of midlife mammary tumors in female murine mammary tumor virus huHER2-transgenic mice.

PURPOSE: This study examined the effectiveness of early and prolonged mu4D5 (the murine form of trastuzumab/Herceptin) treatment in transgenic mice that overexpress human HER2 (huHER2), under the murine mammary tumor virus promoter, as a model of huHER2-overexpressing breast cancer. EXPERIMENTAL DESIGN: Mice were randomly assigned to one of three treatment groups and received i.p. injections from 17 weeks of age until either 52 weeks of age or morbidity. Fourteen mice received 100 mg/kg mu4D5, 14 mice received 100 mg/kg antiherpes simplex virus glycoprotein D control antibody, and 11 mice received a diluent control. RESULTS: High levels of huHER2 expression were detectable in mammary glands of young virgin founder mice. Mammary adenocarcinomas were frequently found in female founders and progeny at an average age of 28 weeks, with some progressing to metastatic disease. The incidence of mammary tumors was significantly reduced, and tumor growth inhibition was observed in mice receiving mu4D5 compared with control mice. In addition, Harderian gland neoplasms, highly associated with overexpression of huHER2 in this transgenic line, were entirely absent in the mu4D5 treatment group, indicating down-regulation of huHER2 in vivo activity. CONCLUSIONS: Early intervention with mu4D5 was of benefit in our transgenic mice at high risk for developing huHER2-overexpressing breast cancer. This study suggests a potential benefit of early treatment with Herceptin in HER2-positive primary breast cancer.     

beta-Catenin and ras oncogenes detect most human colorectal cancer.

PURPOSE AND STUDY DESIGN: Recent studies have shown that beta-catenin translocated into the cell nucleus functions like an oncogene. Accumulating evidence suggests that activation of the beta-catenin oncogenic signaling cascade along with its twin, the K-ras cascade, may exert syngeneic or synergistic effects on tumor development and progression. In the study reported here, we analyzed oncogenic beta-catenin activation on the basis of its nuclear accumulation (NA) and compared the results with those of mutational activation of K-ras in 74 patients with colorectal cancer to determine whether the two oncogene-mediated signaling cascades interact. RESULTS: We found two distinct patterns of beta-catenin activation, i.e., diffuse NA in 20 cases (27%) and selective NA at the tumor invasion front (NAinv) in 19 cases (26%). The presence of the NAinv pattern was significantly correlated with advanced Dukes' stage tumor (P = 0.0005) and the presence of distant metastases (P = 0.0064). K-ras proto-oncogene was mutated in the tumors of 31 cases (42%). Activated beta-catenin or K-ras was detected in most (78%) colorectal cancers analyzed, although a weak inverse correlation was found between the activities of the two oncogenes in the tumors. Importantly, most (7 of 8) patients with tumor showing both K-ras activation and the NAinv pattern of beta-catenin activation were in Dukes' stage C at surgery, and half of them developed distant metastases to the liver and lungs. CONCLUSION: The results suggest that although oncogenic activation of beta-catenin and K-ras is independent in the process of clinical cancer development, combined analysis of the two major oncogenes can detect most colorectal cancers and identify a subset of patients with poorer outcomes. Consequently, activation of either or both of these oncogenes may serve as a genetic marker for molecular diagnosis.     

Irinotecan as second-line treatment for unresectable liver metastases of colon cancer

A 53-year-old woman had shown repeated, partial responses to chemotherapy for large, multiple liver metastases of sigmoid colon cancer. After a partial response to 5-fluorouracil plus leucovorin therapy, an 89.7% reduction of the 5-fluorouracil-resistant metastatic tumor was achieved by giving CPT-11 (irinotecan) at a dose of 100 mg/body per week. We suggest that CPT-11 should be recommended as an effective second-line treatment for unresectable liver metastases of colon cancer, after 5-fluorouracil-based chemotherapy.     

湖南省学生生长发育长期变化趋势分析

目的了解湖南省儿童青少年生长发育长期变化趋势,为开展学校卫生保健工作提供资料.方法分析2000年湖南省7～22岁学生体质调研资料,并与1985年进行比较.结果城市男女生、农村男女生身高分别平均增长了2.9 cm,2.4 cm,2.3 cm和1.5 cm,体重分别平均增长了4.7 kg,2.6 kg,1.8 kg和0.6 kg.城市男女学生胸围分别平均增长了1.1 cm和2.6 cm,农村男生胸围平均减少0.9 cm,农村7～9岁女生胸围下降明显.城乡各年龄组男女学生肺活量指数均显著下降(P＜0.01).农村学生形态指标发育高峰年龄明显提前.结论湖南省学生身高、体重发育呈现出长期增长趋势,其增长值小于同期全国平均水平.应加强学生体育锻炼,注意改善农村学生营养,青春期卫生教育应始于小学高年级.     

儿童频繁性眨眼101例的矫治效果

目的:观察分析综合疗法矫治儿童频繁眨眼的疗效。方法:采用心理疗法、药物、手术等去除病因后,均给以针灸等综合疗法,治疗频繁眨眼患儿101例(202眼)。结果:在去除病因后均在心理治疗的诱导下,针刺新明II、攒竹、四白穴,针刺2次频繁眨眼症状消失者68例(67.3%),5次治愈者31例(30.6%),10次治愈者2例(1.4%)。结论:综合疗法是矫治儿童频繁眨眼的有效方法。     

临床瞳孔检查新进展

瞳孔每时每刻处于动态的变化之中,因此瞳孔的检查也是一个较为复杂的过程。随着对屈光手术质量要求的日益提高,特别是暗适应下瞳孔的大小往往在一定程度上可能决定着术后质量的好坏,因此暗适应下瞳孔的精确测量变得尤为重要。现对近年来涌现的瞳孔检查新技术作一简要概括。     

上斜肌前部前徙术治疗上斜肌麻痹的外旋斜的研究

目的 观察术中可调整缝线的上斜肌前部前徙术治疗上斜肌麻痹的外旋斜的效果。方法 对6例(9眼)外旋斜患者(其中双眼外旋斜和单眼外旋斜各3例)行此术式，在术前、术中、术后1周分别行双马多氏杆检查第一眼位的主观旋转斜。分析旋转斜度与手术量的关系及治疗效果。结果 6例患者术前都存在正前方及下方双眼复视症状，第一眼位的外旋斜5～15。，平均10．5。。术毕双马多氏杆检查第一眼位为0^o～内旋斜5^o,平均内旋斜3．7^o。术后所有患者正前方及向下看复视症状消失，术后1周为外旋2^o～内旋4^o,平均内旋1．4^o。其中2例患者术后7个月复诊，一例外旋斜3^o；另一例为旋转斜0^o，都未出现明显复视症状。结论 术中可调整缝线的上斜肌前部前徙术是一种安全可靠的矫正上斜肌麻痹的外旋斜的手术方式，常需要过矫至内旋5^o左右来代偿术后出现的回退。     

Clinical Features and Surgical Treatment of A-pattern Exotropia

IntroductionAnA鄄patternexotropiashowssignificantlymoreexodeviationindowngazeversusupgaze,inwhichthechangeofbinocularalignmentresemblesthealphaberA.Accordingtopublishedreports[1～4],A鄄patternexotropiaisviewedastheleasttypeofAandVpatterns.However,thepr鄄evalenceofA鄄patternexotropiaratherincreasedinourclinicalstudies[5],inwhichparticularattentionwaspaidtoobservethedeviationindownwardgazeandassesssuperiorobliquefunction.Accordingly,clinicalcharacteristics,surgicaltreatmentandtreatmentoutcome…     

Leptin and asthma in overweight children at 12 years of age

Obesity is suggested as a risk factor for asthma, but the mechanisms are unclear. The relationship between obesity and asthma has not been considered in children born with very low-birth weight (VLBW). We hypothesized that overweight was a contributing factor for asthma in VLBW children, and that leptin and leptin-associated cytokines might play roles in overweight-related asthma. Seventy-four VLBW and 64 normal birth weight (NBW) children participated in a 12-yr follow up study assessing asthma and allergy. Twenty-seven (12 VLBW) of the 138 children were overweight according to the proposed international definition. The diagnosis of current asthma was made by a pediatrician. Serum levels of leptin and interferon (IFN)-gamma were analyzed by enzyme-linked immunosorbent assay (ELISA). Leptin levels were considerably higher in the overweight than in the non-overweight children (median value: 18.1 vs. 2.8 ng/ml, p < 0.001). In the overweight children, current asthmatics had twice as high levels of leptin as children without current asthma (median value: 30.8 vs. 14.3 ng/ml, p = 0.14), but this was not the case in the non-overweight children. IFN-gamma was more often detected in the overweight than in the non-overweight children (61% vs. 12%, p < 0.001), and there was a positive correlation between the levels of leptin and the levels of IFN-gamma (Rho = 0.40, p < 0.001). In the VLBW group, the overweight children had a significantly increased risk for current asthma compared with the non-overweight children after adjustment for the neonatal risk factors [adjusted odds ratio (OR) 5.8, 95% confidence interval (CI): 1.2-27]. Thus, overweight was associated with asthma in the VLBW children. Our hypothesis remained that leptin might be involved in the pathogenesis of asthma in the overweight children, and IFN-gamma might be a pathway in the process of leptin-induced inflammation.     

葡萄糖酸依诺沙星溶液的稳定性研究

目的考察葡萄糖酸依诺沙星溶液的稳定性。方法采用紫外分光光度法测定溶液中葡萄糖酸依诺沙星含量,HPLC法测定有关物质含量,考察了不同pH值的葡萄糖酸依诺沙星溶液在光照及高温条件下的质量变化。结果葡萄糖酸依诺沙星溶液在光照下易变色pH值5.5～6.0溶液在高温、光照5d后即出现结晶。pH值3.0～4.0溶液在光照条件下含量下降较多,有关物质增加较多。pH在4.0～5.5之间的葡萄糖酸依诺沙星溶液稳定性较好。结论本品应遮光保存,液体制剂的pH值范围确定在4.0～5.5之间较好。