The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies.

To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy.     

Newly developed hybrid suture without lubricant: noninvasive in vivo assessment of biocompatibility with multiparametric MR imaging.

Magnetic resonance imaging (MRI) and magnetic resonance (MR) relaxometry were used to assess noninvasively the tissue response of a new uncoated hybrid braided suture made from a combination of ultra-high-molecular-weight polyethylene (UHMWPE) and polyester (polyethylene terephthalate) (PET) yarns in comparison to a silicone impregnated braided 100% polyester (PET) control suture (Ticron). Both biomaterials were monitored for a period of 30 days following implantation in both incised and nonincised paravertebral rabbit muscles. In all cases, MR images and relaxometry demonstrated that the hybrid suture elicited either a milder or a similar tissue and cellular response compared to the control suture. These findings were confirmed by conventional histological analysis of the surrounding tissues. They also demonstrated that the hybrid suture promoted faster healing in terms of collagen infiltration between the yarns and individual filaments. This milder inflammatory reaction and improved biocompatibility represent a real advantage in the healing performance of sutures for cardiac and vascular surgery, and support the need for continued research and development of hybrid structures. This study also demonstrated the ability of MRI techniques to noninvasively evaluate the biocompatibility of biomaterials. By extending the capacity of MR diagnostic tools from patients to experimental animals, it is now possible to validate the healing performance of foreign materials with statistical reliability and fewer animals.     

Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts.

Osteogenesis is synergistically enhanced by the combined effect of complimentary factors. This study showed that Nell-1 and BMP-2 synergistically enhanced osteogenic differentiation of myoblasts and phosphorylated the JNK MAPK pathway. The findings are important because of the osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of coordinated BMP-2 and Nell-1 delivery. INTRODUCTION: BMPs play an important role in the migration and proliferation of mesenchymal cells and have a unique ability to alter the differentiation of mesenchymal cells toward chondrogenic and osteogenic lineages. Signaling upstream of Cbfa1/Runx2, BMPs effects are not limited to cells of the osteoblast lineage. Thus, additional osteoblast-specific factors that could synergize with BMP-2 would be advantageous for bone regeneration procedures. NELL-1 (NEL-like molecule-1; NEL [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]) is a novel growth factor believed to preferentially target cells committed to the osteochondral lineage. MATERIALS AND METHODS: C2C12 myoblasts were transduced with AdLacZ, AdNell-1, AdBMP-2, or AdNell-1+AdBMP-2 overexpression viruses. Effects were studied by cell morphology, alkaline phosphatase activity, osteopontin production, and MAPK signaling. Additionally, in a nude mouse model, viruses were injected into leg muscles, and new bone formation was examined after 2 and 8 wk. RESULTS: C2C12 myoblasts co-transduced with AdNell-1+AdBMP-2 showed a synergistic effect on osteogenic differentiation as detected by alkaline phosphatase activity and osteopontin production. Nell-1 stimulation on AdNell-1 + AdBMP-2 preconditioned C2C12 cells revealed significant activation of the non-BMP-2 associated c-Jun N-terminal kinase (JNK) MAPK signaling pathway, but not the p38 or extracellular signal-regulated kinase (ERK1/2) MAPK pathways. Importantly Nell-1 alone did not induce osteogenic differentiation of myoblasts. In a nude mouse model, injection of AdNell-1 alone stimulated no bone formation within muscle; however, injection of AdNell-1+AdBMP-2 stimulated a synergistic increase in bone formation compared with AdBMP-2 alone. CONCLUSIONS: These findings are important because of the confirmed osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of enhanced BMP-2 action with coordinated Nell-1 delivery.     

Onset, progression, and plateau of skeletal lesions in fibrous dysplasia and the relationship to functional outcome.

Most lesions in FD and their attendant functional disability occur within the first decade; 90% of lesions are present by 15 years, and the median age when assistive devices are needed is 7 years. These findings have implications for prognosis and determining the timing and type of therapy. INTRODUCTION: Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder in which normal bone is replaced by abnormal fibro-osseous tissue. Variable amounts of skeletal involvement and disability occur. The age at which lesions are established, the pace at which the disease progresses, if (or when) the disease plateaus, and how these parameters relate to the onset of disability are unknown. To answer these questions, we performed a retrospective analysis of a group of subjects with FD. MATERIALS AND METHODS: One hundred nine subjects with a spectrum of FD were studied for up to 32 years. Disease progression was assessed in serial (99)Tc-MDP bone scans by determining the location and extent of FD lesions using a validated bone scan scoring tool. Physical function and the need for ambulatory aids were assessed. RESULTS: Ninety percent of the total body disease skeletal burden was established by age 15. Disease was established in a region-specific pattern; in the craniofacial region, 90% of the lesions were present by 3.4 yr, in the extremities, 90% were present by 13.7 yr, and in the axial skeleton, 90% were present by 15.5 yr. Twenty-five of 103 subjects eventually needed ambulatory aids. The median age at which assistance was needed was 7 yr (range, 1-43 yr). The median bone scan score for subjects needing assistance was 64.3 (range, 18.6-75) compared with 23.1 (range, 0.5-63.5) in the unassisted subjects (p < 0.0001). Among subjects needing assistance with ambulation, 92% showed this need by 17 yr. CONCLUSIONS: The majority of skeletal lesions and the associated functional disability occur within the first decade of life. The implication is that the window of time for preventative therapies is narrow. Likewise, therapeutic interventions must be tailored to where the patient is in the natural history of the disease (i.e., progressive disease [young] versus established disease [older subjects]). These findings have implications for prognosis, the timing and type of therapy, and the development of trials of new therapies and their interpretation.     

浙江省某乡村慢性肾脏病的流行病学研究

目的 研究我国南方某农村人群中慢性肾脏病（CKD）的患病率及相关因素。方法 对浙江省东阳市某乡村18岁以上的常住居民慢性肾脏病情况及相关因素进行调查和检测。结果 获得完整资料的居民占该村18岁以上自然人口的76．2％。将该村自然人口按年龄性别构成校正后，白蛋白尿发生率为10．4％；肾小球滤过率〈60ml·min^-1·（1．73m^2）^-1的发生率为3．0％；血尿发生率为1．4％。本研究中40岁以上调查对象与北京市某社区及NHANESⅢ中40岁以上调查对象相比，高血压及糖尿病的患病率较低，白蛋白尿和肾功能下降的发生率介于2者之间。多因素Logistic回归提示，年龄增加10岁、糖代谢异常及收缩压水平与白蛋白尿的发生独立相关；女性、年龄增加10岁、高尿酸血症与肾功能下降独立相关；年龄增加10岁及吸烟与血尿独立相关。结论 在该经济快速发展的南方乡村，CKD的疾病谱和相关因素已经与我国大城市和发达国家类似。此外，该人群可能另有导致CKD高发的特殊原因，需进一步研究。     

泰勒宁片和科洛曲片用于隆乳术后镇痛的比较

目的:评价泰勒宁片和科洛曲片对隆乳手术后疼痛的疗效和不良反应。方法:采用随机开放平行对照试验。共完成60例,其中A组30例予泰勒宁片,单次1片;B组30例予科洛曲片,单次1片。结果:泰勒宁片对隆乳手术后引起的中度或重度疼痛总有效率可达96.7%,科洛曲片的总有效率可达83.3%。服药后泰勒宁片组的疼痛强度差均高于科洛曲组,经统计学处理,有显著性差异(P<0.05)。不良反应发生率较科洛曲片组高。结论:泰勒宁片为中强度镇痛药,对于隆乳手术后引起的中重度疼痛有良好的镇痛效果。     

Neurilemmoma of tongue

Neurilemmoma is usually soimry, benign tumour derived from schwan cells of the Sheaths of peripheral cranial or autonomie nerves. In thehead and neck region it occurs most commonly in association with acoustic nerve within the skuil and is rely fottnd in the oral cavity (1,2). We report here two cases of the iongue diagnosed on histopathohgy.     

三叶草钢板治疗肱骨近端3、4部分骨折

我院于2003-2006年运用三叶草钢板对32例肱骨近端3、4部分骨折进行手术治疗取得满意结果,现报告如下。1临床资料32例肱骨近端骨折,男21例,女11例;年龄25~82岁,平均54·4岁。根据Neer分型[1],其中Ⅳ型3部分11例,4部分4例;Ⅴ型3部分12例,4部分3例;Ⅵ型3部分1例,4部分1例。病程1~10 d,平均4·5 d。损伤原因:跌伤22例,交通伤7例,高处坠落伤3例。2治疗方法选用臂丛麻醉或全麻,患者取“沙滩椅”位,采用改良Thompson切口。将上臂外展以利切口暴露,以肱二头肌肌间沟作为解剖标记。如有肱骨头脱位应先复位,将钢板根据肱骨外形塑形,精确匹配肱骨近端…     

尿石症住院患者1100例分析

目的了解近年来尿石症住院患者情况的变化。方法对1998年~2003年间的尿石症住院患者1100例进行分析。结果本组中,肾结石251例(22.8%)、输尿管结石742例(67.5%)、膀胱结石97例(8.8%)、尿道结石10例(0.9%)。上、下尿路结石的比例为9.28∶1。高钙尿患者27例(13.0%)、高钙血症91例(9.1%)、高尿酸血症167例(17.8%)。结石成分分析结果:草酸钙168例(62.7%);磷酸钙59例(22.0%);尿酸及尿酸盐25例(9.3%);磷酸镁铵10例(3.7%);碳酸盐5例(1.7%);胱氨酸1例(0.4%)。治疗:ESWL658例(59.8%)、肾切开取石术35例、肾切除术6例、输尿管切开取石术92例(占8.4%)、输尿管镜加气压弹道碎石52例(4.7%)、膀胱切开取石53例(其中前列腺摘除术加膀胱切开取石术26例);膀胱镜加气压弹道碎石20例;前列腺电切术加气压弹道碎石7例;膀胱镜加大力钳碎石术9例。尿道切开取石术1例;经尿道镜取石术2例;尿道镜加气压弹道碎石3例。结论本组尿石症患者以上尿路结石为主,含钙结石占绝大多数。尽管微创手术的普遍开展,ESWL仍不失为一种创伤小、效果好的治疗方法。