The utility of repeated computed tomography to track a foreign body penetrating the esophagus to the level of the thyroid gland

Objective

Foreign body (FB) ingestion is a common problem in otolaryngology. One uncommon complication of FB ingestion is penetration to the level of the thyroid gland. To our knowledge, only 21 such cases have been reported in the literature. Here, we report a case of an esophageal FB penetrating to the level of the right thyroid gland.

Case report

The patient was a 38-year-old woman in whom an esophageal FB penetrated to the level of the right thyroid gland. We traced the path to the thyroid gland using repeated computed tomography (CT) scans and demonstrated the importance of multiplanar reconstruction in locating the FB and formulating a precise surgical plan.

Conclusions

To our knowledge, this is the first report of repeat CT scans being used to demonstrate the migratory route, over time, of a FB penetrating through the esophagus to the level of the thyroid gland. Our results suggest that multiplanar reconstruction may play a key role in the precise diagnosis of a FB at the level of the thyroid gland and may help surgeons choose the best approach for removal.     

Biomechanical evaluation of maxillary Lefort Ι fracture with bioabsorbable osteosynthesis internal fixation

The aim of this study was to apply biomechanical analysis model to evaluate the effects of bioabsorbable internal fixation devices on maxillary Lefort Ι fracture. CT scan technology and the finite element software (ansys ) were used to establish three‐dimensional finite element models of five resorbable internal fixation devices in maxillary Lefort Ι fractures. We used the model to calculate the stress of the upper jaw and internal fixation. We further analyzed the stability of fixation under four occlusions. The fixation using two bioabsorbable plates was not stable. The zygomaticomaxillary pillars fixation is more stable than other fixations. The stability of fracture fixation was influenced with the molar occlusion. The current study developed a functional three‐dimensional finite element model of bioabsorbable internal fixation and compared the stability of five fixation methods for maxillary Lefort Ι fractures. The results would facilitate the application of bioabsorbable materials in dental clinic.     

Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal

Directed migration of diverse cell types plays a critical role in biological processes ranging from development and morphogenesis to immune response, wound healing, and regeneration. However, techniques to direct, manipulate, and study cell migration in vitro and in vivo in a specific and facile manner are currently limited. We conceived of a strategy to achieve direct control over cell migration to arbitrary user-defined locations, independent of native chemotaxis receptors. Here, we show that genetic modification of cells with an engineered G protein-coupled receptor allows us to redirect their migration to a bioinert drug-like small molecule, clozapine-N-oxide (CNO). The engineered receptor and small-molecule ligand form an orthogonal pair: The receptor does not respond to native ligands, and the inert drug does not bind to native cells. CNO-responsive migration can be engineered into a variety of cell types, including neutrophils, T lymphocytes, keratinocytes, and endothelial cells. The engineered cells migrate up a gradient of the drug CNO and transmigrate through endothelial monolayers. Finally, we demonstrate that T lymphocytes modified with the engineered receptor can specifically migrate in vivo to CNO-releasing beads implanted in a live mouse. This technology provides a generalizable genetic tool to systematically perturb and control cell migration both in vitro and in vivo. In the future, this type of migration control could be a valuable module for engineering therapeutic cellular devices.The ability of many cell types to migrate long distances within the body and specifically localize to target sites of action is critical for their proper function. For example, immune cells rapidly home to sites of infection, concentrating their powerful cytotoxic and proinflammatory activities for maximum efficacy while limiting damage to healthy tissue. In morphogenesis, cells undergo a complex stereotyped process involving migration as well as proliferation, differentiation, and programmed cell death to produce fully developed multicellular structures. In wound healing and regenerative processes, stem and progenitor cells home to injured tissues from nearby sites—as well as from distant locations including the bone marrow—to provide a stream of new cells to replenish and provide trophic support to old and damaged cells.Cell migration is also an important factor to consider in the use of cells as therapeutic agents. The use of cells for the treatment of a growing array of diseases including cancer, autoimmunity, and chronic wounds is currently being explored (1–6). The appropriate and efficient localization of therapeutic cells to sites of disease has been identified as an important factor for successful cell-based therapy (7–17). However, preclinical studies and clinical trials to date have shown that the homing to sites of disease of many cell types commonly used as therapeutics is frequently impaired or limited, especially after ex vivo expansion of cells in culture (7, 12, 18, 19).The ability to redirect the migration of cells to any user-specified location in the body would be a powerful enabling technology for basic research as well as for future applications, but there are currently few easily generalizable strategies to accomplish this goal. We conceived of an approach to direct cellular homing to small molecules by expressing, in motile cells, engineered G protein-coupled receptors (GPCRs) called receptors activated solely by a synthetic ligand (RASSLs) (20, 21).RASSLs are engineered to be unresponsive to endogenous ligands but can be activated by pharmacologically inert orthogonal small molecules (Fig. 1A). Versions of these receptors exist for the three major GPCR signaling pathways (Gαs-, Gαi-, and Gαq-coupled receptors), and the design of a new arrestin-biased variant has recently been reported (21, 22). Because GPCRs control many important physiological functions, including cell migration, we hypothesized that, by expressing these engineered receptors in motile cells, we could develop a general strategy for establishing user control over cell homing (Fig. 1B). Here, we use a family of second-generation RASSLs, known as designer receptors exclusively activated by a designer drug (DREADDs), that are activated only by the small molecule clozapine-N-oxide (CNO), an inert metabolite of the FDA-approved antipsychotic drug clozapine (Fig. S1) (20). CNO is highly bioavailable in rodents and humans, lacks affinity for any known receptors, channels, and transporters, and does not cause any appreciable physiological effects when systemically administered in normal mice (20, 23, 24).Open in a separate windowFig. 1.Engineered Gαi-coupled GPCRs Di3 and Di mediate cytoskeletal changes and chemotaxis of HL-60 neutrophils in response to CNO. (A) RASSLs are engineered GPCRs that interact orthogonally with a bioinert small-molecule drug. Natural ligands do not interact with the engineered receptors, and the bioinert drug that activates the engineered receptors does not interact with native receptors. (B) We tested whether certain second-generation RASSLs known as DREADDs could mediate cell motility. (C) Changes in electrical impedance that result from cell spreading in response to drug or ligand are detected by an electrode array. HL-60 neutrophils transiently transfected to express engineered GPCRs were plated on fibronectin-coated impedance assay plates and stimulated with vehicle control, 100 nM fMLP (positive control chemoattractant) or 100 nM CNO. All cells responded to fMLP whereas only Di3- or Di-expressing cells responded to CNO. Mean ± SEM for n = 3 replicates is shown. (D) Cell migration of HL-60 neutrophils transiently transfected with engineered GPCRs was quantitated in a porous transwell Boyden-chamber assay. All cells migrated in response to fMLP whereas only Di3- or Di-expressing cells migrated in response to CNO. Drug concentrations used: 100 nM CNO, 100 nM fMLP. Mean ± SEM for n = 3 replicates is shown. (E) Polarization and cell migration in neutrophils involves Rac and PI3K activation. Di-expressing HL-60 neutrophils were treated with 100 nM fMLP or 100 nM CNO before immunoblotting for phosphorylated Akt and phosphorylated PAK as readouts for PI3K and Rac activity, respectively. Peak levels of phospho-Akt and phospho-PAK are shown for each condition. Both were increased by CNO stimulation in Di cells but not in control cells (P < 0.01 by Student t test). Stimulation with fMLP increased phospho-Akt and phospho-PAK levels in both Di and control cells (P < 0.01 by Student t test), but Di cells showed higher peak levels of phospho-Akt than did control cells (P < 0.01 by Student t test). Three (for CNO) or four (for fMLP) independent experiments were performed and mean ± SEM are shown.     

CD40／CD40配体结合产生共刺激信号对干细胞及B细胞增殖分化的影响

目的：探讨CD40／CD40配体结合产生的共刺激信号对干细胞、B细胞增殖分化的影响及CD40配体抗白血病的作用。 资料来源：检索Pubmed和Springer数据库1995—01／2005-12与CD40／CD40配体、白血病干细胞及白血病相关文献，检索词为“CD40，CD40L，Leukemia，Leukemic stem cell”，限定文献语种为英语。 资料选择：对资料进行初审，选取实验包括实验组和对照组的文献，排除明显不随机实验和临床研究及重复性研究。 资料提炼：共收集到30篇关于CD40／CD40配体结合产生的共刺激信号对干细胞、B细胞增殖分化的影响及CD40配体抗白血病作用的实验文章，23篇符合纳入标准，排除的7篇均为同一研究。 资料综合：综合23个实验包括CD40／CD40配体对白细胞干细胞、B细胞增殖分化的影响，对白血病患者预后的影响及CD40配体对白血病患者的治疗作用，并对CD40／CD40配体对白细胞干细胞、B细胞及白血病患者的影响、作用进行分析。 结论：CD40／CD40L结合所产生的共刺激信号可促进白血病干细胞和B细胞的增殖分化，与白血病的发生、发展和预后有密切关系。CD40／CD40L在免疫应答中起关键作用，广泛应用于白血病的免疫治疗。     

Effectiveness and safety of endoscopic versus open carpal tunnel decompression

Purpose

To evaluate the effectiveness and safety of endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR) using a meta-analysis of data from randomized controlled trials.

Materials and methods

Electronic searches of the Cochrane Register of Controlled Trials (CENTRAL, Issue 11 of 12, Nov 2012), PUBMED (1980 to Dec 2012), and EMBASE (1980 to Dec 2012) were used to identify randomized controlled trials that evaluated endoscopic vs open methods for treatment of carpal tunnel syndrome. Studies to be used were independently identified by two researchers. The methodological quality of the studies was assessed by the Cochrane Collaboration tool for assessing risk of bias.

Results

Fifteen randomized controlled trials involving 1,596 hands were included. Based on the Cochrane Collaboration tool for assessing risk of bias, four studies were rated as high quality, five studies were rated as moderate quality, and six were rated as low quality. Our meta-analysis indicated that ECTR resulted in better recovery of pinch strength, earlier time of return to work, but a higher rate of reversible nerve problems (including neurapraxia and numbness) than OCTR. ECTR also resulted in a lower rate of irreversible nerve damage (P > 0.05), wound problems (including wound infection, wound hematoma and wound dehiscence) and reflex sympathetic dystrophy (P > 0.05) compared with OCTR. Our meta-analysis revealed no obvious statistical differences in relief of symptoms (pain and paraesthesia), recovery of grip strength and reoperation rate.

Conclusion

Our meta-analysis of available randomized controlled trials demonstrated that ECTR and OCTR were similar in relief of symptoms, but ECTR resulted in better recovery of function and earlier return to work and was safer than OCTR.     

The effects of non-calcium-based phosphate binders versus calcium-based phosphate binders on cardiovascular calcification and bone remodeling among dialysis patients: a meta-analysis of randomized trials

Background: Vascular calcification significantly increases the rates of cardiovascular mortality in hemodialysis (HD) patients. Abnormalities in mineral metabolism may play a role in the pathogenesis of arterial calcification. Whether patients treated with non-calcium-based phosphate binders had reduced aortic vascular calcification compared to those treated with calcium-based phosphate binders is still unclear. Methods: We searched multiple databases for studies published through August 2013 that evaluated the effects of non-calcium-based phosphate binders (NCBP) versus calcium-based phosphate binders (CBP) on cardiovascular calcification and bone remodeling among dialysis patients. We summarized test performance characteristics with the use of forest plots, fixed and random effects models, and Egger regression test. Results: Eighteen eligible randomized controlled trials totaling 3676 patients were included. Meta-analysis results showed NCBP could significantly attenuate the progression of coronary artery calcification than CBP (WMD: ?144.62, 95% CI: ?285.62 to ?3.63). The serum calcium levels significant lower in NCPB group than in CPB groups (WMD: ?0.26, 95% CI: ?0.37 to ?0.14), but the serum iPTH levels were significantly higher in NCPB groups (WMD: 57.1, 95% CI: 13.42 to 100.78). The osteoid volume and osteoblast numbers were significant higher in NCPB group than in CPB group (WMD: 1.75, 95% CI: 0.78 to 2.73 for osteoid volume; WMD: 4.49, 95% CI: 1.83 to 7.15 for osteoblast numbers). The Egger regression test also showed no potential publication bias (p?=?0.725). Conclusions: Based on available data, NCBPs have equally effective with CBPs for serum phosphate control. But there was significantly lower incidence of coronary artery calcification and a significant higher bone formatting rate in NCBP groups than in CBP groups. So we recommend NCBPs as phosphate binders for HD patients.     

三氧化二砷及其不同浓度对角膜基质细胞增殖和移行的影响

目的:观察不同浓度三氧化二砷对体外培养的兔角膜基质细胞增殖和移行的影响。方法:实验于2004-11/2005-04在哈尔滨医科大学肿瘤研究所完成。实验动物为健康日本大耳白兔2只,取其角膜用组织块培养法培养原代及传代得兔角膜基质细胞,将传至2～3代的兔角膜基质细胞用于实验。向实验细胞中分别加入含不同浓度(100,50,25,12.5,10,6.25,5,2.5,1.25,0.625μmol/L)的三氧化二砷培养液,同时以加入不含三氧化二砷的培养液作为阴性对照,以加入含0.0025%丝裂霉素的培养液作为阳性对照。用细胞计数法和四甲基偶氮唑盐法检测三氧化二砷对角膜基质细胞增殖的影响,用缺损闭合法观察三氧化二砷对角膜基质细胞移行的影响。结果:实验纳入大耳白兔2只,取其4只角膜培养传至二三代的角膜基质细胞均无污染,细胞数量足够实验所需。①细胞计数法观察不同浓度的三氧化二砷对角膜基质细胞增殖的影响:低浓度的三氧化二砷(<12.5μmol/L)对角膜基质细胞增殖无明显抑制作用,而高浓度的三氧化二砷(≥12.5μmol/L)对角膜基质细胞的增殖具有明显的抑制作用,抑制率均在50%以上,且抑制作用随浓度的增加而增强。台盼兰染色显示各组细胞存活率均在90%以上,未见细胞毒性。②四甲基偶氮唑盐法观察不同浓度的三氧化二砷对角膜基质细胞增殖的影响:四甲基偶氮唑盐法检测结果与细胞计数法基本一致,三氧化二砷对角膜基质细胞增殖的抑制率随浓度的增加逐渐增强。与阳性对照比较,给予25,50,100μmol/L三氧化二砷的角膜基质细胞在加药后6d其增殖抑制率明显降低(56.4%,45.4%,50.2%,55.4%,P<0.05)。③三氧化二砷对角膜基质细胞移行的影响:给予低浓度的三氧化二砷(<25μmol/L)及阴性对照药的角膜基质细胞在用药后48h已有较多的细胞长入,4d后完全闭合,而给予高浓度三氧化二砷的角膜基质细胞在用药后48h只有极少数细胞长入缺损区,8d后仍未见缺损闭合,缺损闭合的时间明显延长。结论:三氧化二砷对角膜基质细胞增殖的抑制率随浓度的增加逐渐增强,高浓度的三氧化二砷具有抑制兔角膜基质细胞增殖和移行的作用,而低浓度的三氧化二砷此种作用不明显。三氧化二砷的浓度在100μmol/L以下时,对角膜基质细胞无明显的毒性反应。     

颈动脉体瘤的MR诊断

目的:探讨MR诊断颈动脉体瘤(CBT)的价值。材料与方法:4例经手术病理证实的CBT进行MRI和MRA检查。结果:4例CBT MR检查均显示颈总动脉分叉(common cartid artery bifurcation,CCAB)处类圆形或椭圆形肿瘤,包绕颈内、外动脉,T_1WI呈等或略高信号,T_2WI呈高信号;包膜完整。T_1WI、T_2WI均呈低信号。肿瘤中见多发蜿蜓纡曲的肿瘤小血管。MRA均示CCAB角杯状扩大及肿瘤血管丛。结论:MR不仅能直接显示肿瘤部位、形态、大小及颈动脉关系,也能显示肿瘤血管及CCAB角扩大,是CBT诊断与鉴别的理想方法。     

Collision malignant melanoma and medullary carcinoma of the thyroid

This report presents the case of a 54‐year‐old woman with a collision tumour of malignant melanoma and medullary thyroid carcinoma in the thyroid. Twenty four of 25 neck lymph nodes contained metastatic melanoma, with the rest having both metastatic melanoma and medullary carcinoma. Systemic chemotherapy was administered for the malignant melanoma, and a complete response was thus obtained. However, just after having the chemotherapy, multiple lung and brain metastases emerged. The simultaneous occurrence of malignant melanoma and medullary carcinoma in the same thyroid has not been previously reported in the literature. Collision tumour of malignant melanoma and medullary carcinoma of the thyroid might imply bad prognosis.