Fenestrations of Intracranial Arteries

BACKGROUND AND PURPOSE:Few data are available on the frequency and location distribution of fenestrations of intracranial arteries. We used 3D rotational angiography of all intracranial arteries in a cohort of 179 patients with suspected intracranial aneurysms to assess the prevalence and location of fenestrations and the relation of fenestrations to aneurysms.MATERIALS AND METHODS:Of 179 patients with subarachnoid hemorrhage admitted between March 2013 and June 2014, 140 had 3D rotational angiography of all cerebral vessels. The presence and location of aneurysms and fenestrations were assessed. In patients with both aneurysms and fenestrations, we classified the relation of the location of the aneurysm as remote from the fenestration or on the fenestration.RESULTS:In 140 patients, 210 aneurysms were present. In 33 of 140 patients (24%; 95% confidence interval, 17.2%–31.3%), 45 fenestrations were detected with the following locations: anterior communicating artery in 31 (69%), A1 segment of the anterior cerebral artery in 4 (9%), middle cerebral artery in 4 (9%), basilar artery in 4 (9%), vertebral artery in 1 (2%), and anterior inferior cerebellar artery in 1 (2%). Of 56 patients with anterior communicating artery aneurysms, 14 had a fenestration on the anterior communicating artery complex. The remaining 31 fenestrations had no anatomic relation to aneurysms. In 140 patients with 210 aneurysms, 14 aneurysms (7%) were located on a fenestration and 196 were not.CONCLUSIONS:In patients with a suspected ruptured aneurysm, fenestrations of intracranial arteries were detected in 24% (33 of 140). Most fenestrations were located on the anterior communicating artery. Of 45 fenestrations, 14 (31%) were related to an aneurysm.

Fenestrations of intracranial arteries are segmental duplications of the lumen into 2 distinct channels, each comprising endothelial and muscular layers with or without a shared adventitia. Fenestrations are anatomic variants and can range from a small focus of divided tissue to duplication of a long vessel segment.^1,2Fenestrations result from partial failure of fusion of paired primitive embryologic vessels or from incomplete obliteration of anastomosis in a primitive vascular network.²The association of fenestrations with aneurysms and other neurovascular disorders has been noted. Some suggest that altered flow dynamics in the presence of fenestrations may promote aneurysm development, though the exact relationship is not well-defined.Surgical and anatomic studies suggest that fenestrations are common in intracranial arteries with the highest prevalence in the anterior communicating artery (AcomA) complex.^3–5 Demonstration of fenestrations with imaging is uncommon.^6,7 Most fenestrations are only visible from a specific viewing angle that is often not provided by conventional angiography or reconstructed cross-sectional imaging. With 3D imaging, especially 3D rotational angiography, the detection rate of fenestrations has improved.⁸ Scant data are available on the frequency and location distribution of fenestrations of intracranial arteries, to our knowledge. We used 3D rotational angiography of all intracranial arteries in a cohort of 179 patients with suspected intracranial aneurysms to assess the prevalence and location of fenestrations and the relation of fenestrations with aneurysms.     

Platelet adhesion to fibronectin in flow: the importance of von Willebrand factor and glycoprotein Ib

We describe glycoprotein (GP) Ib as a mediator of adhesion to fibronectin, specifically in flow. A monoclonal antibody (MoAb) directed to the von Willebrand factor (vWF)-binding site on this receptor or the absence of this receptor on the platelet membrane, in the case of a patient with the Bernard-Soulier syndrome, reduced platelet coverage to fibronectin to approximately 30% of the control value. A MoAb directed to the GP Ib-binding site on vWF showed a similar effect. With washed platelets in the absence of plasma vWF, the inhibitory effect of the anti-GP Ib antibody was the same as with whole blood. No inhibition with the anti-GP Ib antibody was observed when we used blood from patients with severe von Willebrand disease (vWD) or from a patient with vWD type I (platelet low). Addition of vWF to vWD blood resulted in restoration of adhesion. Immunoelectron microscopy on platelets adhering to fibronectin showed that GP Ib was homogeneously distributed over the entire surface of the platelet. vWF was present at the central zone and the edges of the platelet and at the basal interface between the platelet and the fibronectin surface. No direct binding of vWF to fibronectin could be demonstrated. These data indicate that GP Ib-mediated adhesion to fibronectin fully depends on vWF and that normal levels of plasma or platelet vWF are sufficient for optimal adhesion to fibronectin. The data suggest that the presence of platelets during perfusion is a prerequisite for vWF to support platelet adhesion to fibronectin.     

Effects of fresh-frozen plasma and its cryosupernatant fraction on von Willebrand factor multimeric forms in chronic relapsing thrombotic thrombocytopenic purpura

Remission plasma samples of some patients with chronic relapsing thrombotic thrombocytopenic purpura (TTP) contain unusually large von Willebrand factor (vWF) multimers similar to those produced by normal human endothelial cells in culture. The infusion of the cryosupernatant fraction of normal plasma is as effective as normal fresh-frozen plasma (FFP) in the treatment or prevention of TTP episodes in patients with the chronic relapsing form of TTP. Three patients with chronic relapsing TTP during remission have unusually large vWF multimers present in their plasma. Two of the patients were transfused once with FFP, one of the two received cryosupernatant on three occasions, and the third patient was studied before and immediately after plasma exchange. Unusually large vWF multimers decreased or disappeared from patient plasma samples within 1/2 to 1 1/2 hours following the transfusion of FFP (on two occasions) or cryosupernatant (on two of three occasions), and immediately after plasma exchange (on one occasion). The patient who received cryosupernatant was studied serially after the infusions. Unusually large vWF multimers returned to her plasma within ten to 24 hours and persisted thereafter. Unusually large vWF multimers did not disappear from patient remission plasma samples, or from the culture medium removed from normal human endothelial cells, when these fluids were incubated in vitro with either normal FFP or cryosupernatant. We conclude that an activity in FFP, and its cryosupernatant fraction, promoted the rapid in vivo disappearance of unusually large vWF multimers from the plasma of two patients with chronic relapsing TTP in remission, and plasma exchange reversed the abnormality in a third patient who was in partial remission. Neither FFP nor cryosupernatant directly converted unusually large multimers to smaller vWF forms in vitro in the fluid phase. These results indicate that an activity in the cryosupernatant fraction of normal plasma is involved in vivo in controlling the metabolism of unusually large vWF multimers, and that this process is defective in some chronic relapsing TTP patients.     

Frequency and prognostic significance of HRX rearrangements in infant acute lymphoblastic leukemia: a Pediatric Oncology Group study

Chromosome band 11q23, the location of the HRX gene, is a site of recurrent translocations in human malignancies. Infants with acute lymphoblastic leukemia (ALL) commonly have 11q23 translocations and have an especially poor prognosis despite intensive chemotherapy. We analyzed 96 cases of infant ALL treated on three consecutive Pediatric Oncology Group protocols to determine the frequency and prognostic significance of molecular rearrangements of HRX. Overall, 78 cases (81%) had HRX rearrangements detected by Southern blot analysis performed with a single HRX cDNA probe, whereas 18 cases (19%) had germline HRX. Of the 78 cases with HRX rearrangements, only 50 had abnormalities of 11q23 detected cytogenetically. Molecular abnormalities of HRX were associated with early treatment failure and a very poor outcome. Estimated event-free survival for patients with HRX rearrangements was 19% (SE, 7%) at 3 years, compared with 46% (SE, 17%) for patients with germline HRX (P = .033 by the two-sided logrank test). Therefore, infants with ALL and molecular abnormalities of HRX represent a group with an extremely high rate of failure who clearly need innovative or experimental treatment. Furthermore, cytogenetic analysis alone failed to detected 36% of HRX rearrangements, suggesting that molecular analysis be performed on all infants with ALL to identify this group of high-risk patients.     

人工全膝关节置换术中关节周围注射镇痛药物对术后痛的效果

目的:关节周围注射混合镇痛药物是比较新颖的术后镇痛方法。运用随机对照的前瞻性方法观察人工全膝关节置换术中膝关节周围注射布比卡因、吗啡、肾上腺素等混合药物的止痛效果。方法:①实验对象:于2006-09/2007-05上海市第六人民医院关节外科病房选取60例择期、单侧人工全膝关节置换患者,患者知情同意参加本实验,随机分为研究组30例和对照组30例。②实验方法:研究组患者术中关节周围注射镇痛药物(0.5%布比卡因30mL,肾上腺素1:200000,吗啡10mg,生理盐水30mL),对照组患者没有运用镇痛药物。所有患者术后都运用镇痛泵(曲马多500mg,氯诺昔康16mg,稀释到100mL,2mL/h),持续运用48h。③实验评估:术前、术后分别记录静止和活动视觉模拟疼痛评分和膝关节活动度。结果:60例患者均进入结果分析。①视觉模拟疼痛评分:研究组术后6,12,24h静止视觉模拟疼痛评分低于对照组(P均<0.01),研究组术后6,12,24h运动视觉模拟疼痛评分也低于对照组(P均<0.01)。两组术后36,48,72h静止和运动视觉模拟疼痛评分比较差异无显著性(P>0.05)。②手术前后镇痛药物使用情况:研究组术后有6例需长期服用奇曼丁(曲马多),对照组术后有18例需长期服用奇曼丁,两组相比有统计学差异。同时,对照组术后有5例需肌注吗啡(10g/L)。③膝关节活动度:研究组术后第1,2,3天膝关节活动度高于对照组(P均<0.01)。两组术后第1,2周膝关节活动度比较差异无显著性。④并发症:没有任何因为注射而引起的伤口并发症、心脏或中枢神经系统的毒性被发现。结论:人工全膝关节置换术中应用关节周围注射镇痛药物可以在术后早期减少静止和活动状态疼痛评分并且减少术后镇痛药的使用、改善术后早期关节活动度。     

体外实验观察小分子干扰RNA对胶质瘤U251细胞血管内皮生长因子表达的影响

目的:血管内皮生长因子能促进血管内皮细胞增生和血管形成,而RNA干扰技术可高效特异地导致转录后基因沉默现象。实验针对人血管内皮生长因子基因化学合成小分子干扰RNA,观察其对胶质瘤U251细胞的体外干扰效应。方法:实验于2006-09/2007-02在中国科学院上海生物化学研究所分子生物学国家重点实验室完成。①实验材料:人类U251胶质母细胞瘤细胞株由上海市肿瘤研究所朱景德教授惠赠。非特异性小分子干扰RNA,绿色荧光标记的FAMnegativecontrolsiRNA(上海吉玛公司)。②实验方法:选择基因序列号为NM0033761的血管内皮生长因子基因cDNA序列上的3个位点设计3条不同序列的小分子干扰RNA,并应用BLAST技术排除其他同源基因。采用脂质体法转染U251细胞,以200nmol/L进行转染,以转染非特异性小分子干扰RNA作为阴性对照组,以未加入小分子干扰RNA作为空白对照组。48h后RT-PCR筛选最佳小分子干扰RNA,将抑制率最高的小分子干扰RNA再分别按50,100,200,300nmol/L进行转染。③实验评估:荧光显微镜及流式细胞仪检测转染效率,RT-PCR法半定量检测浓度梯度下小分子干扰RNA对U251细胞血管内皮生长因子mRNA表达的抑制效果。结果:①荧光显微镜及流式细胞术检测转染效率:镜下可见胞质内的绿色荧光,同一视野下细胞核呈蓝染,转染效率达95%以上。②RT-PCR检测血管内皮生长因子mRNA的表达水平:不同序列的小分子干扰RNA以200nmol/L转染细胞后血管内皮生长因子mRNA的表达水平均有所下调,以小分子干扰RNA1转染组最为明显(P<0.01),抑制率大于70%,选为最佳特异性小分子干扰RNA。U251细胞转染50,100,200,300nmol/L的小分子干扰RNA148h后,随着转染浓度的升高,小分子干扰RNA1的抑制效果逐渐增强,各浓度转染组血管内皮生长因子mRNA的表达水平可下调16%～73%。结论:以血管内皮生长因子为靶基因、化学修饰合成的特异性小分子干扰RNA,在体外可有效抑制目的基因mRNA的表达。     

应用细胞培养、流式细胞技术和Western Blot检测氮杂糖化合物SZL在体外抑制人宫颈癌HeLa细胞增殖与诱导凋亡的效应

目的:存在于细胞表面的糖复合物参与细胞的通讯、增殖、迁移、分化等生理过程,在机体中具有复杂的生物学调控作用。探讨氮杂糖化合物SZL在体外对人宫颈癌HeLa细胞生长、DNA损伤、线粒体膜电位以及细胞凋亡的干预。方法:实验于2004-12/2006-12在北京大学医学部细胞生物学系完成。①实验材料:人子宫颈癌HeLa细胞株由北京大学医学部细胞生物学系杜晓娟副教授提供。SZL由北京大学天然药物及仿生药物重点实验室叶新山教授合成。②实验方法:取对数生长期HeLa细胞,消化后制成细胞悬液,按1.5×103/孔的密度接种,培养24h细胞完全贴壁后,SZL组加入5,10,25,50,100μmol/L的SZL,空白对照组加入DMEM培养液。③实验评估:SZL作用24,48,72h后,采用酸性磷酸酶法检测细胞生长抑制情况,瑞氏染色镜下观察细胞形态;AnnexinV-PI染色后,流式细胞仪检测细胞凋亡率;Rhodamine123标记活细胞后,流式细胞仪检测线粒体膜电位的变化;WesternBlot法检测SZL作用后凋亡相关蛋白的表达;单细胞凝胶电泳检测SZL作用后细胞DNA损伤情况。结果:①细胞生长抑制:5,10,25,50,100μmol/LSZL作用24,48,72h后的半数抑制浓度分别为73.6,43.2,33.6μmol/L,显著抑制Hela细胞的增殖。镜下空白对照组HeLa细胞分布均匀,胞质透明清亮,呈铺展状态生长;50μmol/LSZL作用24h后,HeLa细胞密度变稀,体积变小,胞核染色质呈聚集状态。②细胞凋亡:50,100μmol/LSZL作用24h后细胞凋亡率分别为(3.51±0.41)%,(58.46±8.45)%;在24～48h过程中,凋亡的细胞逐渐坏死,SZL作用48h后细胞凋亡率分别为(10.51±2.20)%,(17.29±7.52)%。空白对照组24,48h后细胞凋亡率均为1%。③线粒体跨膜电位的变化:50μmol/LSZL作用24,48h后,HeLa细胞的线粒体膜电位平均荧光强度均明显低于空白对照组(P<0.01)。④凋亡相关蛋白的表达:25,50,100μmol/LSZL作用HeLa细胞48h后,凋亡相关蛋白pro-caspase3、Bcl-2表达降低,细胞色素c含量升高。⑤细胞DNA损伤:50μmol/LSZL作用24h后,受损细胞DNA在电场中迁出,呈现彗星状拖尾。结论:氮杂糖类化合物SZL能够抑制HeLa细胞的增殖,诱导细胞发生DNA损伤,通过干预线粒体途径实现细胞凋亡。     

Prevalence of markers for human immunodeficiency virus types 1 and 2, human T-lymphotropic virus type I, cytomegalovirus, and hepatitis B and C virus in multiply transfused thalassemia patients. The French Study Group On Thalassaemia

The prevalence of markers for human immunodeficiency virus types 1 and 2 (HIV-1, HIV-2), human T-lymphotropic virus type I (HTLV-I), hepatitis B virus (HBV) and hepatitis C virus (HCV), and cytomegalovirus (CMV) was evaluated in a population of 305 multiply transfused thalassemia patients in Belgium, France, and Italy (Sicily). No patients were found positive for HIV-2 antibodies. Two French patients were seropositive for HIV-1, having been infected before systematic blood screening. Antibodies to HTLV-I were found in two Sicilian patients. A positive anti-HCV enzyme-linked immunosorbent assay was found in one-third of the patients and a positive CMV IgG test in two-thirds. Twenty-two percent of the patients in the three countries were uninfected by HBV and were not vaccinated. With the exception of HIV-1, HIV-2, HTLV-I, and anti-hepatitis B surface antigen assays, all markers were encountered more frequently in Sicilian patients than in French or Belgian patients. This study emphasizes the need to improve HBV vaccination coverage in the three countries. At present, data indicate that the introduction of routine screening for HTLV-I should be considered, particularly in Sicily.     

大鼠卵巢组织中早期卵泡发育及卵母细胞凋亡与白藜芦醇的影响

目的:观察白藜芦醇对大鼠卵巢组织中早期卵泡发育及凋亡的影响。方法:实验于2006-07/12在汕头大学医学院细胞衰老实验室完成。成年SD大鼠合笼,所生的新生雌鼠分为3组:①对照组:正常出生者,不干预。②腹腔注射组:正常出生后12h内开始腹腔注射白藜芦醇25mg/(kg·d),1次/d。③母鼠灌胃组:正常怀孕的母鼠在孕12d(以发现阴道栓为怀孕0.5d)开始进行白藜芦醇25mg/(kg·d)灌胃,1次/d,直至分娩后生下的雌鼠。各组大鼠分别在出生2,4d处死取卵巢,应用苏木精-伊红染色观察大鼠早期卵泡发育情况(计算卵母细胞巢中卵母细胞及原始卵泡和发育卵泡的比率),应用TUNEL染色观察卵母细胞凋亡的情况。结果:①腹腔注射组和母鼠灌胃组大鼠卵母细胞巢内卵母细胞比例高于对照组[2d龄:(39.78±9.22)%,(53.20±5.08)%,(15.76±6.68)%;4d龄:(9.39±1.82)%,(5.39±2.12)%,(2.62±1.18)%;P均<0.05];2d龄母鼠灌胃组和腹腔注射组大鼠原始卵泡和发育卵泡比例低于对照组[原始卵泡:(57.64±7.23)%,(46.40±5.20)%,(74.57±9.36)%;发育卵泡:(2.58±2.41)%,(4.51±4.60)%,(9.67±4.70)%;P均<0.05]。②生后第2天是大鼠卵母细胞凋亡的高峰期,母鼠灌胃组和腹腔注射组卵泡凋亡率高于对照组,但差异不显著[(9.88±3.30)%,(12.95±3.34)%,(8.50±4.13)%,P>0.05]。结论:白藜芦醇可以延缓大鼠卵巢组织中卵母细胞巢破裂,抑制原始卵泡的发育启动;但是对于卵母细胞的凋亡没有明显影响。