Tumor cell‐associated neuropilin‐1 and vascular endothelial growth factor expression as determinants of tumor growth in neuroblastoma

We sought to characterize the expression of vascular endothelial growth factor (VEGF) and its receptors in neuroblastoma (NBL) and to correlate the results with N‐myc (MYCN) expression and in vivo growth of these tumors. Two representative human‐derived NBL cell lines, SK‐N‐AS (AS) with low and SK‐N‐DZ (DZ) with a high MYCN copy number, were used for the study. We examined their proliferation, VEGF and VEGF receptor expression in vitro and xenograft tumor growth in vivo. In parallel, human NBL specimens were analyzed for expression of VEGF and neuropilin‐1 (NRP‐1). DZ cells exhibited a 4‐fold higher proliferation rate than AS. In contrast, VEGF protein expression was significantly higher in AS cells. NRP‐1 was the only VEGF receptor produced in AS and DZ cells in vitro and in vivo. Both AS and DZ cells formed tumors in athymic mice but AS tumors grew 3.5 times larger than DZ tumors and had larger diameter tumor vessels. VEGF and NRP‐1 expression was also demonstrated in human NBL specimens. Our studies indicate that VEGF and VEGF receptor expression in NBL tumor cells are associated with tumor growth and that angiogenic factors may serve as a biological marker together with already established MYCN amplification.     

Regression of aggressive corneal vascularization after photodynamic therapy,subconjunctival Avastin injections and topical cyclosporin-A 1% drops: A case report

We describe a case of significant regression of aggressive, deep and superficial corneal vascularization using photodynamic therapy (PDT) with verteporfin, repeated subconjunctival injections of Avastin®, plus topical cyclosporin-A 1% drops.The area of the corneal vascularization was treated with PDT with verteporfin. The subconjunctival space – next to the area of vascularization – was injected with Avastin® (1.25 mg/0.05 ml), immediately after PDT, and then for two more times during the follow-up period. The patient was kept on topical cyclosporin and prednisolone acetate. The outcome was evaluated clinically and photographically for 13 months. Corneal vascularization regressed significantly. No adverse effects were observed, neither locally or systemically. PDT with verteporfin, repeated subconjunctival injections of Avastin®, and topical cyclosporin-A drops appear to be safe and effective in treating aggressive corneal vascularization.     

First-trimester serum analytes, biophysical tests and the association with pathological morphometry in the placenta of pregnancies with preeclampsia and fetal growth restriction

Objective

We test the hypothesis that first-trimester serum analytes, 4-D power Doppler placental vascular indices and uterine artery Doppler (UAD) predicts abnormal placental morphometry in pregnancies with preeclampsia (PE) and fetal growth restriction (FGR).

Study design

Maternal serum analytes (PAPP-A, hCG, ADAM12s, and PP13), bilateral UADs, and placental vascular indices were measured at 11-14 weeks in a nested-case control study within a prospective cohort of women followed from the first-trimester to delivery. Vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were obtained from 4-D power Doppler histograms. Serum analytes were measured using immunofluorometric assays and values converted to multiples of the median (MoM) for gestational age. Morphometric analysis was performed on placentas from pregnancies complicated by PE (n = 13), gestational hypertension (HBP, n = 7) and FGR (defined as fetal weight <10th percentile with abnormal umbilical artery Doppler: n = 7); and 20 uncomplicated pregnancies. Two pregnancies had both FGR and PE. Each placenta was weighed and random samples taken, and fixed in formalin within 1 h of delivery. Hematoxylin & Eosin stained slides were analyzed by design-based stereology to quantify linear dimensions, surface areas and volumes of placental components. Paired t-test and ANOVA with adjustments for multiple comparisons were used.

Results

The surface areas of terminal and intermediate villi as well as the volume of terminal villi were significantly smaller in placentas from pregnancies complicated by FGR and PE. Compared with the control group the mean PAPP-A (MoM) was lower in the pregnancies with abnormal placenta morphometry (1.1 ± 0.5 versus 0.7 ± 0.5, P = 0.03). The morphometric indices were lower in those pregnancies with low PAPP-A and IUGR compared with preeclampsia.

Conclusion

First-trimester PAPP-A levels are associated with abnormal placental morphometry at delivery in pregnancies with PE and IUGR. These findings may explain the association between adverse pregnancy outcomes and first-trimester PAPP-A.     

以化学去细胞法处理同种异体神经与周围静脉伴行修复面神经缺损

背景：有研究表明化学去细胞法处理的同种异体神经修复面神经缺损可以取得较好的修复效果。 目的：在化学去细胞法处理同种异体神经的基础上探索一种修复面神经缺损更有效的修复方式。  方法：将新西兰大白兔随机分为2组,实验组制备面神经颊支缺损动物模型,采用经化学去细胞的同种异体腓肠神经进行移植,且与伴行静脉行外膜缝合;对照组在同样位置的远近端分别切断面神经,但不破坏被切断神经与周围组织的正常解剖关系,再切断处行外膜缝合桥接。 结果与结论：修复后3个月两组兔均存活,面部表情基本对称,胡须活动正常,神经移植处未见明显瘢痕及神经瘤形成。电镜观察结果显示,实验组与对照组右侧面神经颊支传导速度,移植体远端吻合口附近5.0 mm段有髓神经纤维数量,靶肌肉运动终板计数均差异无显著性意义(P > 0.05)。结果证实,化学去细胞同种异体神经与周围静脉伴行修复家兔面神经缺损的方法可以达到与自体面神经原位移植相似的修复效果。     

组织工程骨预制及其血管化的研究进展

组织工程化骨预制技术是目前骨组织工程领域的研究热点。从组织工程骨的预制、血管化及预制骨骨缺损修复作用三个方面对组织工程化骨预制技术研究的现状和发展趋势进行了回顾和展望。旨在分析当前的研究成果与组织工程化骨预制技术的最终广泛临床应用之间存在的差距,并为尽快缩短这一距离提供合理的设想。     

Lateral arm flap: analysis of its anatomy and modification using a vascularized fragment of the distal humerus

Soft tissue injuries with associated bone defects are difficult to manage and often require prolonged treatment with repeated interventions. Frequently, a free flap is applied as a first step and bone grafting is carried out in a second procedure. Ideally, these two procedures are combined in one operation, utilizing a soft tissue flap with an attached vascularized bone fragment. The lateral arm flap can provide such an osteoseptocutaneous flap and has been utilized clinically with success; however, the vascular anatomy of the flap, especially the humeral fragment, has not been described in detail previously, and there is broad disagreement concerning its innervation. In this study, the arteries and nerves of 24 fresh cadaver arms were dissected after injection of colored latex. The levels of origin of the periosteal arteries of the humerus were also documented. The lateral arm flap has a consistent arterial supply from three septocutaneous perforating branches that are arranged in a predictable pattern. The lateral supracondylar ridge of the humerus is vascularized by direct branches of the posterior branch of the radial collateral artery and by arteries that arise from muscular branches supplying adjacent muscles. The innervation of the lateral arm flap is by the inferior lateral cutaneous nerve of the arm. Knowledge of the consistent vascular anatomy of the lateral humerus and soft tissue of the donor site allows an osteoseptocutaneous flap to be raised safely with an appropriate technique. We recommend use of the lateral arm flap with a humeral fragment for the treatment of combined soft tissue and bone defects when a single step surgical solution is indicated.     

Transvaginal colour Doppler in patients with ovarian endometriomas and pelvic pain

BACKGROUND: The aim of this investigation was to correlate ovarian endometrioma vascularization with the presence of pelvic pain. METHODS: The presence of blood flow, peak systolic velocity (PSV, cm/s) and lowest pulsatility index (PI), assessed by transvaginal colour Doppler ultrasonography and CA-125 plasma concentrations, were retrospectively analysed in 74 patients who had undergone operations for cystic ovarian endometriosis. Fifty-two patients were asymptomatic (group A) and 22 presented with pelvic pain (group B). There were 56 endometriomas in group A and 26 in group B. RESULTS: Blood flow was found in 66.1 and 88.5% of endometriomas in groups A and B respectively (P = 0.036). PI was significantly lower (P = 0.009) and CA-125 concentration higher (P = 0.0004) in group B. There were no differences in PSV. CONCLUSIONS: We conclude that vascularization of ovarian endometriomas in patients presenting with pelvic pain is higher than in asymptomatic patients. This could be an indicator of endometriosis activity.