Molecular determinants of cetuximab efficacy.

PURPOSE: To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. PATIENTS AND METHODS: Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. RESULTS: There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. CONCLUSION: This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.     

The influence of some non-steroidal anti-inflammatory drugs on the retraction of collagen lattices.

The effects of some antirheumatics on the formation and retraction of collagen lattices seeded with fibroblasts have been studied. Among the antirheumatics, diclofenac was the most active inhibitor of lattice retraction, then tropesin and to a lesser extent indomethacin. Ibuprofen which is known as a very slight inhibitor of protein synthesis was able to significantly enhance lattice retraction when 10 micrograms/ml (48.5 microM) and 50 micrograms/ml (242 microM) were used.     

宫腔镜在辅助生殖技术中的应用

目的：探讨宫腔镜检查术在辅助生殖技术中应用的重要性。方法：对150例拟行辅助生殖技术的不育妇女行常规宫腔镜检查。结果：宫腔镜150例中47例（31％）有镜下异常，其中：子宫内膜息肉或息肉样增生18例（12％），子宫内膜单纯性增生17例（11％），子宫畸形7例（5％），宫腔粘连狭窄3例（2％），子宫内膜结核1例（0．7％），子宫黏膜下肌瘤或腺肌瘤1例（0．7％）。以宫腔镜诊断为标准，阴道超声诊断敏感性、特异性、阳性预测值、阴性预测值、准确率分别为66％（31／47）、98％（101／103）、94％（31／33）、86％（101／117）、88％（132／150），子宫造影分别为26％（12／47）、100％（95／95）、100％（12／12）、73％（95／130）、75％（107／142）。结论：宫腔镜检查术具有良好的可接受性和准确性，应作为辅助生殖技术前的常规检查。     

切开复位内固定治疗骨盆桶柄样Tilt骨折

目的探讨骨盆桶柄样Tilt骨折手术治疗方法。方法切开复位内固定治疗52例骨盆桶柄样Tilt骨折。前骨盆经Plan—nenstiel入路固定9例，Pfannenstiel入路结合部分髂腹般沟入路固定43例。37例行骨盆重建钢板固定，骨盆重建钢板固定结合耻骨上支髓内螺钉固定9例，6例2块骨盆重建钢板固定。后环37例经患侧髂嵴入路以骨盆重建钢板固定。8例骶骨骨折行骶髂关节螺钉固定。7例未行后骨盆固定。结果平均随访18个月。全部骨性愈合，无下肢不等长，骨盆畸形基本纠正。按Majeed疗效评定标准优良率为93．8％。结论通过前后联合入路，切开复位治疗骨盆桶柄样Tilt骨折疗效满意，并可防止远近期并发症的发生。     

Characteristics of antibody responses in tick-borne encephalitis vaccination breakthroughs

Tick-borne encephalitis (TBE) virus is an important human pathogenic flavivirus that is endemic in Europe and Asia. The disease can be effectively prevented by inactivated vaccines and vaccination breakthroughs (VBTs) are rare. We investigated the characteristics of antibody responses in such VBTs in comparison to those in unvaccinated TBE patients. In contrast to the unvaccinated controls, most of the VBTs displayed a delayed IgM antibody response and had high avidity and strongly neutralizing antibodies already in the first sample taken upon hospitalization. The antibody profile of these patients therefore had the characteristics of an anamnestic immune response. In the VBTs analyzed, immunological priming and memory were apparently not sufficient or fast enough to prevent the disease.     

Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein of mumps virus vaccine strain Urabe AM9 is not a requirement for neurovirulence

The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence.     

案例教学法在护理伦理学中的应用分析

目的分析案例式教学在护理伦理学教学中应用的效果，以探讨适合护理伦理学的教学方法。方法采用传统教学法与案例教学法相对照进行护理伦理学的授课，对528名授课学生进行问卷调查并收集资料。结果92．4％的学生认为案例教学法能激发学习兴趣，87．2％的学生认为能调动学习的积极性，82．6％的学生认为有利于对知识的理解，72．1％的学生认为能培养思维和决策能力，68．0％的学生认为能增进师生互动。结论案例教学法可提高教学效果。培养学生的批判性思维能力。