APPswe/Aβ regulation of osteoclast activation and RAGE expression in an age‐dependent manner

Alzheimer's disease (AD), one of the most dreaded neurodegenerative disorders, is characterized by cortical and cerebrovascular amyloid β peptide (Aβ) deposits, neurofibrillary tangles, chronic inflammation, and neuronal loss. Increased bone fracture rates and reduced bone density are commonly observed in patients with AD, suggesting one or more common denominators between both disorders. However, very few studies are available that have addressed this issue. Here, we present evidence for a function of amyloid precursor protein (APP) and Aβ in regulating osteoclast (OC) differentiation in vitro and in vivo. Tg2576 mice, which express the Swedish mutation of APP (APPswe) under the control of a prion promoter, 1 exhibit biphasic effects on OC activation, with an increase of OCs in younger mice (< 4 months old), but a decrease in older Tg2576 mice (> 4 months old). The increase of OCs in young Tg2576 mice appears to be mediated by Aβ oligomers and receptor for advanced glycation end products (RAGE) expression in bone marrow macrophages (BMMs). However, the decrease of OC formation and activity in older Tg2576 mice may be due to the increase of soluble rage (sRAGE) in aged Tg2576 mice, an inhibitor of RANKL‐induced osteoclastogenesis. These results suggest an unexpected function of APPswe/Aβ, reveal a mechanism underlying altered bone remodeling in AD patients, and implicate APP/Aβ and RAGE as common denominators for both AD and osteoporosis. © 2011 American Society for Bone and Mineral Research.     

Genetic evidence points to an osteocalcin‐independent influence of osteoblasts on energy metabolism

The skeleton has been shown recently to regulate glucose metabolism through an osteoblast‐specific hormone, osteocalcin, which favors β‐cell proliferation, insulin secretion, insulin sensitivity, and energy expenditure. An implication of this finding is that a decrease in osteoblast numbers would compromise glucose metabolism in an osteocalcin‐dependent manner. To test this hypothesis, osteoblasts were inducibly ablated by cross‐breeding transgenic mice expressing a tamoxifen‐regulated Cre under the control of the osteocalcin promoter with mice in which an inactive form of the diphtheria toxin A chain was introduced into a ubiquitously expressed locus. Ablation of osteoblasts in adult mice profoundly affected glucose metabolism. In a manner similar to what is seen in the case of osteocalcin deficiency, a partial ablation of this cell population resulted in hypoinsulinemia, hyperglycemia, glucose intolerance, and decreased insulin sensitivity. However, and unlike what is seen in osteocalcin‐deficient mice, osteoblast ablation also decreased gonadal fat and increased energy expenditure and the expression of resistin, an adipokine proposed to mediate insulin resistance. While administration of osteocalcin reversed (fully) the glucose intolerance and reinstated normal blood glucose and insulin levels, it only partially restored insulin sensitivity and did not affect the improved gonadal fat weight and energy expenditure in osteoblast‐depleted mice. These observations not only strengthen the notion that osteoblasts are necessary for glucose homeostasis and energy expenditure but also suggest that in addition to osteocalcin, other osteoblast‐derived hormones may contribute to the emerging function of the skeleton as a regulator of energy metabolism. © 2011 American Society for Bone and Mineral Research     

Documenting the location of prostate biopsies with image fusion

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? Currently, systematic prostate biopsies are obtained with minimal information about their actual location. This study demonstrates that a electromagnetically tracked ultrasound probe can be used to guide biopsies into specific areas of the prostate. By registering the ultrasound to an MRI scan of the prostate, obtained prior to biopsy, it is possible to accurately map the location of biopsies. Thus, if a patient requires a repeat biopsy, or there is a question about whether a specific area of the prostate was sampled, this system can be used to more accurately guide biopsies in the future. OBJECTIVE To develop a system that documents the location of transrectal ultrasonography (TRUS)‐guided prostate biopsies by fusing them to MRI scans obtained prior to biopsy, as the actual location of prostate biopsies is rarely known. PATIENTS AND METHODS Fifty patients (median age 61) with a median prostate‐specific antigen (PSA) of 5.8 ng/ml underwent 3T endorectal coil MRI prior to biopsy. 3D TRUS images were obtained just prior to standard TRUS‐guided 12‐core sextant biopsies wherein an electromagnetic positioning device was attached to the needle guide and TRUS probe in order to track the position of each needle pass. The 3D‐TRUS image documenting the location of each biopsy was fused electronically to the T2‐weighted MRI. Each biopsy needle track was marked on the TRUS images and these were then transposed onto the MRI. Each biopsy site was classified pathologically as positive or negative for cancer and the Gleason score was determined. RESULTS The location of all (n= 605) needle biopsy tracks was successfully documented on the T2‐weighted (T2W) MRI. Among 50 patients, 20 had 56 positive cores. At the sites of biopsy, T2W signal was considered ‘positive’ for cancer (i.e. low in signal intensity) in 34 of 56 sites. CONCLUSION It is feasible to document the location of TRUS‐guided prostate biopsies on pre‐procedure MRI by fusing the pre‐procedure TRUS to an endorectal coil MRI using electromagnetic needle tracking. This procedure may be useful in documenting the location of prior biopsies, improving quality control and thereby avoiding under‐sampling of the prostate as well as directing subsequent biopsies to regions of the prostate not previously sampled.     

Oncological outcome of T1 rectal cancer undergoing standard resection and local excision

Aim We studied the outcome and prognostic factors for T1 rectal cancer patients undergoing standard resection or transanal excision. Method One hundred and twenty‐four patients with T1 rectal cancer were included in the study, of whom 66 (53.2%) underwent standard resection and 58 (46.8%) underwent transanal excision. Survival analysis was performed to compare the outcome. Results The 5‐year local recurrence rate was 11.0% in the transanal excision group versus 1.6% in the standard resection group (P = 0.031) but the 5‐year disease‐free survival and overall survival rates were not significantly different between the two groups. Multivariate analysis suggested that a high tumour grade and perineural or lymphovascular invasion were independent risk factors for local recurrence and recurrence‐free survival. For high‐risk patients (with at least one of the above risk factors), the 5‐year local recurrence and 10‐year recurrence‐free survival rates were 21.2% and 74.5%, versus 1.2% and 92.0% in low‐risk patients (P = 0.00003 and P = 0.003). In patients undergoing transanal excision, none in the low‐risk group had local recurrence during follow up, while 40% (6 of 15) of patients in the high‐risk group developed local recurrence within 5 years after surgery. The 5‐year local recurrence rate was 45.0%. Conclusion Transanal excision in T1 rectal cancer may result in a high rate of local failure for patients with a high‐grade tumour, or perineural or lymphovascular invasion. Local excision should be avoided as a curative treatment in high‐risk patients.     

Pedicle screw instrumentation plus augmentation vertebroplasty using calcium sulfate for thoracolumbar burst fractures without neurologic deficits

Objective: To evaluate the efficacy of posterior instrumentation plus vertebroplasty and posterolateral fusion using calcium sulfate for thoracolumbar burst fractures without neurologic deficits. Methods: Between July 2005 and January 2008, a total of 45 patients who had been diagnosed as having thoracolumbar burst fractures without neurologic deficits were treated with pedicle screw instrumentation plus vertebroplasty using calcium sulfate in our unit. The Cobb angles and loss rates of anterior‐middle columns height at different time intervals were measured on lateral radiographs, and the preoperative and postoperative functional outcomes were evaluated using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI). Results: The Cobb angles and loss rates of anterior‐middle columns height postoperatively period were restored significantly compared with those noted preoperatively. The angles and heights were well maintained for at least two years using this technique. The mean postoperative VAS (back pain) score was 2.1 ± 0.8, which was significantly better (P < 0.001) than the mean preoperative VAS score 7.9 ± 1.1. The average preoperative ODI was 66.6 ± 8.1% and this had improved significantly to 15.5 ± 4.5% by the latest follow‐up (P < 0.001). No instrumentation failure was detected in this study. The calcium sulfate had been absorbed completely by 3–6 months postoperatively. Conclusion: Pedicle screw instrumentation plus augmentation vertebroplasty with calcium sulfate is an economic, efficient and reliable technique for treating unstable thoracolumbar fractures without neurologic deficits.     

Macroscopic Serosal Classification Predicts Peritoneal Recurrence for Patients with Gastric Cancer Underwent Potentially Curative Surgery

Background

Previous studies revealed serosal invasion as one of the most important predictors of peritoneal micrometastasis. However, even for cancers with serosal invasion, the macroscopic serosal appearance is highly heterogeneous. The aim of the present study was to propose a macroscopic serosal classification (MSC) and to investigate the validity of this classification as a predictor of peritoneal recurrence.

Materials and Methods

Clinicopathologic features including MSC of 1528 patients with pT3/pT4a stage gastric cancers who underwent potentially radical surgery were retrospectively reviewed. MSC was classified as reactive type, nodular type, tendonoid type, and color-diffused type according to the macroscopic serosal appearance.

Results

There were significant differences in tumor size, location, Bormann type, Lauren grade, lymphatic and/or blood vessels invasion (LBVI), width of serosa changes, depth of invasion, number of nodes metastasis, lymph node metastasis ratio, pN stage, and peritoneal cytology between patients with different types of serosa. Multivariate analysis revealed MSC, as well as depth of invasion, Lauren grade, and pN stage, significantly predicted the presence of peritoneal-free cancer cells. Both MSC and peritoneal cytology significantly correlated with patient survival. However, only MSC significantly predicted peritoneal recurrence on multivariate analysis, but peritoneal cytology did not, indicating MSC was more sensitive than cytologic examination. Further investigation suggested MSC and pN stage were also independent predictors of peritoneal recurrence for patients with negative peritoneal cytology.

Conclusions

The MSC sensitively predicts the presence of peritoneal micrometastasis for pT3/pT4a-stage gastric cancer patients who underwent potentially radical surgery. Consequently, it might be considered a good indicator to guide perioperative adjuvant therapy for patients with high risk of peritoneal recurrence.     

Phrenic nerve end-to-side neurotization in treating brachial plexus avulsion: an experimental study in rats

The aim of this study was to extend the clinical application of phrenic nerve neurotization in treating brachial plexus avulsion injury, reducing the possible damage on the diaphragm function. Fifty-one male Sprague-Dawley rats and 9 transgenic rats were used in this study. Evaluations including behavioral observation, histology, and electrophysiology study were performed postoperatively. The functional recovery of rats with the end-to-side neurorrhaphy reached 80% of those with end-to-end neurorrhaphy, and the function of diaphragm was preserved. The fluorescence study revealed abundant collateral sprouting of the phrenic nerve axons through the coaptation site in all the experimental groups. The study showed that the end-to-side neurorrhaphy in a helicoid manner and the standard end-to-side neurorrhaphy were effective in the treatment of brachial plexus root avulsion injury with little harm to the function of diaphragm. This will extend the clinical application of phrenic nerve neurotization in treating brachial plexus avulsion injury.     

46例肘关节镜手术并发症的分析——10年269例肘关节镜手术回顾

目的探讨肘关节镜手术并发症发生情况及其原因。方法回顾研究1998年6月-2008年11月269例肘关节镜中46例（17.1％）并发症的发生、处理及预后。男32例,女14例,年龄（32．9±15．1）岁（13-6l岁）。其中骨关节炎20例,关节粘连8例,肱骨外上髁炎4例,类风湿关节炎4例,急性创伤5例,肱骨内上髁炎1例,剥脱性骨软骨炎2例,色素绒毛结节性滑膜炎1例,肘关节不稳1例。最多见为一过性神经损伤36例,其中累及桡神经7例,尺神经7例,腋神经1例,肢体远端末梢神经感觉障碍21例;迟发性尺神经炎5例;伤口术后渗液1例,皮下血肿1例;残留游离体5例。2例肘关节发生了2种并发症。结果36例一过性神经损伤患者中的32例在术后1—7天内缓解,最迟1例桡神经深支损伤术后8个月好转。3例迟发性尺神经炎行尺神经前移术,1例伤口血肿行血肿清除术,2例游离体残留行游离体二次取出术,余保守治疗,均治愈。结论肘关节镜的并发症以一过性神经损伤最多见,还有迟发性尺神经炎、伤口并发症、游离体残留。这些并发症绝大多数都是轻微可逆的,故肘关节镜是一种安全有效的技术。     

小儿心脏手术麻醉期间空气混合氧(Fi020.5)改善气体交换

目的:100%O2常规用于麻醉前预先吸氧和麻醉诱导.吸高氧浓度更快地发生肺不张,一个重要的原因是全麻期间损害肺气体交换.我们用气管插管后0.5 FiO2混合空气和100%O2的通气效果,评价损害气体交换的发展过程.方法:102名年龄1月～15岁,先天性心脏病(非紫绀型)手术病人,均100%O2麻醉前预先吸氧3min和(麻醉诱导时)面罩通气2min,接下来气管插管.这些病人随机分为两组:Ⅰ组49例0.5FIO2和空气混合通气,Ⅱ组53例100%O2通气.分别于预先吸氧前和气管插管后30min、入ICU、拔管后30min、术后前三天做动脉血气分析,做记录接着计算PaO2/FiO2比值.结果用t检验和单相方差分析.P值＜或=0.05结果相差显著.结果:PCO2值入ICU(C)时CO2交换Ⅰ组明显优于Ⅱ组,PaO2术后在入ICU(C)60%FiO2、拔管后30min(D)1.5L/min FIO2面罩吸氧两个时间点动脉血氧Ⅰ组明显高于Ⅱ组,PaO2/FiO2值在插管后30min(B)、入ICU(C)60%FiO2、拔管后30min(D)Ⅰ组明显高于Ⅱ组(P值＜0.03).结论:先天性心脏病(非紫绀型)手术患儿全麻时,0.5 FiO2混合空气通气较100%O2通气能够显著的改善肺的气体交换功能.     

迷走神经电刺激后处理对大鼠心肌缺血再灌注损伤的影响

目的 评价迷走神经电刺激后处理对大鼠心肌缺血再灌注损伤的影响.方法 雄性SD大鼠60只,体重250～350 g,采用随机数字表法,将其随机分为3组(n＝20):假手术组(S组)、缺血再灌注组(I/R组)和迷走神经电刺激后处理组(POES组).I/R组和POES组采用结扎左冠状动脉前降支30 min和再灌注120 min的方法制备心肌缺血再灌注损伤模型,S组仅穿线.POES组在心肌缺血15 min时对右侧迷走神经干实施电刺激30 min,电刺激参数:波宽2ms,频率10 Hz,电流强度随大鼠HR进行调整,以保持HR较刺激前降低10％.于缺血前(基础状态)、缺血1、10 min和再灌注30、60、120 min时记录HR和MAP,计算HR和MAP的乘积(RPP).各组随机取10只大鼠,于再灌注120 min时,采集颈动脉血样,采用ELISA法检测血清cTnI、CK-MB、TNF-α、高迁移率族蛋白1(HMGB1)、细胞间粘附分子1(ICAM-1)、IL-1、IL-6和IL-10的浓度;颈动脉采血后,采用伊文蓝和TTC双重染色法测定心肌梗死体积.再灌注120 min时,各组随机处死10只大鼠,取缺血区和非缺血区心肌组织,采用ELISA法检测TNF-α、HMGB1、ICAM-1、IL-1、IL-6和IL-10的含量.结果 与S组比较,I/R组缺血10 min和再灌注30 min时HR增快,缺血1min时MAP和RPP降低,心肌梗死体积、血清cTnI、CK-MB、TNF-α、HMGB1、ICAM-1、IL-1和IL-6的浓度、缺血区和非缺血区心肌组织TNF-α、HMGB1、ICAM-1、IL-1、IL-6和IL-10的含量升高;POES组缺血10 min时HR增快,血清TNF-α浓度降低,心肌梗死体积、血清cTnI、CK-MB、ICAM-1和IL-10的浓度、缺血区心肌组织ICAM-1、IL-1、IL-6和IL- 10的含量、非缺血区心肌组织HMGB1、ICAM-1、IL-1、IL-6和IL-10的含量升高(P<0.05);与I/R组比较,POES组HR、MAP和RPP差异无统计学意义(P＞0.05),心肌梗死体积、血清cTnI、CK-MB、TNF-α、HMGB1、ICAM-1、IL-1和IL-6的浓度、缺血区和非缺血区心肌组织TNF-α、HMGB1、ICAM-1、IL-1和IL-6的含量降低,IL- 10含量升高(P<0.05).结论 迷走神经电刺激后处理可减轻大鼠心肌缺血再灌注损伤,其机制与抑制局部和全身炎性反应有关.