Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients

Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.     

Compliance, attitudes and barriers to post-operative colorectal cancer follow-up

Rationale Meta‐analyses demonstrate that surveillance following curative‐intent colorectal cancer (CRC) surgery can improve survival. Our multidisciplinary team adopted a stringent CRC follow‐up (FU) guideline in 2000. The purpose of this study was to assess adherence and barriers to FU for CRC. Methods Patients with primary CRC aged 19–75 years, treated with curative intent surgery from July 2000 to December 2002 were identified from a prospective database. Compliance with FU was assessed primarily by chart review. We also surveyed patients and providers to explore attitudes and barriers to surveillance adherence using tenets of the Health Belief Model. Results 96 patients met inclusion criteria and were appropriate for FU. Median FU was 34 months. Guideline targets were met for 70% of clinic visits; 49% of carcinoembryonic antigen (CEA) determinations; and 62% of abdominal imaging studies. Post‐operative colonoscopy did not occur in 6/93 patients. Seventy per cent of health care providers and 55% of patients completed a survey. Access to testing and confusion about which provider orders investigations were identified as important barriers to FU. Conclusion Patterns of CRC FU were widely variable despite implementation of a guideline. Despite patient and provider agreement with the principles of CRC FU, adoption was inhibited by confusion among multiple providers regarding investigation coordination.     

Effects of SR 48968 on the neuropeptide gamma-induced contraction of the human isolated bronchus

Summary— Neuropeptide gamma (NPγ) induced a contractile response of the human isolated bronchus which was potentiated by the neutral endopeptidase inhibitor, phosphoramidon, but was not modified by atropine and indomethacin. NPγ was 3.31-fold more potent than NKA. Contractile response curves to NPγ were shifted to the right and maximal responses reduced by the non-peptide NK₂-receptor antagonist, SR 48968. The pK_B of SR 48968 (8.94 ± 0.18, n = 15), calculated according to Kenakin (1987) was very close to that reported for [Nle¹⁰]-NKA (4–10), a specific agonist of neurokinin NK₂-receptors (8.86 ± 0.13, n = 13), suggesting that the contractile effects of NPγ on the human isolated bronchus were mediated through NK_2A-receptors.     

何首乌丸加味干预后衰老模型大鼠睾丸生精细胞p53基因表达的变化

目的:观察中药何首乌丸加味对衰老模型大鼠睾丸生精细胞凋亡、血清睾酮含量和抗氧化能力的影响。方法:实验于2004-04/07在承德医学院基础医学研究所完成。①选用40只雄性SD大鼠,随机分为正常组、模型组、何首乌丸加味组和阴性对照组,每组均为10只。模型组、何首乌丸加味组和阴性对照组均采用D-半乳糖200mg/(kg·d)连续腹腔注射40d制作亚急性衰老大鼠模型。模型组大鼠于造模成功后不再作任何处理;何首乌丸加味用药组大鼠于造模成功后用何首乌丸加味(由何首乌15g,怀牛膝15g,肉苁蓉10g,淫羊藿10g,丹参25g,茯苓15g组成,每副含生药90g,按传统方法加水煎成溶液)8.1g/kg灌胃给药,1次/d,共30d;阴性对照组大鼠于造模成功后每天灌胃同等剂量的生理盐水,时间同何首乌丸加味用药组。正常组大鼠自由摄食、饮水,未加任何干预措施。②所有大鼠经内眦取血2mL,采用酶联免疫吸附法检测各组大鼠血清睾酮含量、黄嘌呤氧化酶法检测血清超氧化物歧化酶的活性;大鼠处死后取睾丸组织、常规石蜡包埋,SP免疫组化法检测睾丸生精细胞p53基因的表达。结果:大鼠40只全部进入结果分析。①血清睾酮含量:模型组明显低于正常组,分别为(0.52±0.14),(1.26±0.32)μg/L(t=3.004,P<0.05);何首乌丸加味组为(1.16±0.32)μg/L,高于模型组(t=2.321,P<0.05)。②血清超氧化物歧化酶活性:模型组明显低于正常组,分别为(106.22±9.63),(148.73±12.93)kNU/L(t=13.339,P<0.01);何首乌丸加味组为(140.05±15.57)kNU/L,高于模型组(t=9.970,P<0.01)。③p53阳性细胞率:模型组明显高于正常组,分别为(59.13±10.53)%和(36.99±9.45)%,(χ2=9.696,P<0.01);何首乌丸加味组为(43.03±12.65)%,低于模型组(χ2=5.122,P<0.05)。结论:何首乌丸加味可通过提高睾酮含量、增强抗氧化能力、降低生精细胞的凋亡改善衰老大鼠睾丸的功能,起到延缓衰老的作用。     

心肌梗死大鼠血管内皮功能及心功能变化与培哚普利的干预效应

目的:观察心肌梗死后心力衰竭大鼠血管内皮功能和心功能的变化与血管紧张素转换酶抑制剂培哚普利的干预关系。方法:实验于2004-12/2006-03于中山大学附属第二医院医学实验中心完成。实验动物:成年雄性SD大鼠75只,体质量250～300g。实验分组:取60只大鼠结扎冠状动脉左前降支建立心肌梗死大鼠模型,另取15只为假手术组做对照。实验方法:术后1周行超声心动图检查,以centerline方法判断心肌梗死面积。术后第2周,心肌梗死大鼠中30只给予培哚普利灌胃,另30只为对照组给予盐水灌胃。评估标准:10周后测定左室血流动力学参数,循环血液中一氧化氮,内皮素-1和C-反应蛋白的水平,并观察离体胸主动脉环对内皮依赖性扩血管物质乙酰胆碱的舒张反应。结果:75只大鼠进入结果分析:①血浆内皮素-1和血清一氧化氮、C-反应蛋白含量的变化:与假手术组相比,心肌梗死盐水组血浆内皮素-1水平上升,血清一氧化氮含量下降,血清C-反应蛋白水平升高(P均<0.05);与心肌梗死盐水组相比,培哚普利治疗组血浆内皮素-1水平下降,血清一氧化氮含量上升,血清C-反应蛋白水平下降(P均<0.05)。②各组大鼠胸主动脉环对乙酰胆碱的反应性测定:心肌梗死盐水组胸主动脉环对乙酰胆碱介导的最大舒张反应显著小于假手术组和培哚普利治疗组(39.5±6.38,79.4±7.59,67.9±6.92,P均<0.05);与假手术组相比,心肌梗死盐水组胸主动脉环对各个浓度的乙酰胆碱介导的舒张反应显著减弱(P均<0.05);与心肌梗死盐水组相比,培哚普利治疗组显著改善各个浓度乙酰胆碱介导的舒张反应(P均<0.05)。③各组大鼠血流动力学指标改变:与假手术组相比,心肌梗死盐水组大鼠出现明显的心力衰竭,表现为左室内收缩压降低,左室舒张末期压升高,室内压最大上升/下降速率降低(P均<0.05);与心肌梗死盐水组相比培哚普利治疗组大鼠的心功能显著改善(P均<0.05)。④各组大鼠存活率:10周后培哚普利治疗组存活率显著高于心肌梗死盐水组(67%,43%,P<0.05)。结论:心肌梗死大鼠血管内皮功能和心功能在长期应用培哚普利治疗后得到改善,其机制可能与抑制炎症反应有关。     

图形翻转视觉诱发电位在视神经管减压后视神经损伤不同时期的变化特征

目的:观察视神经损伤动物模型在损伤后和不同时期视神经管减压后视觉诱发电位的变化,了解创伤性视神经损伤的手术时机与疗效的关系。方法:实验于2005-03/05在解放军南京军区南京总医院动物实验中心完成。①实验分组:30只新西兰白兔随机分为正常对照组、术后2d减压组、术后7d减压组、术后14d减压组、术后不减压组,每组6只。②造模:除正常对照组外,其余各组在视神经孔中塞入一细端为2mm直径的圆锥软硅胶,阻塞视神经孔,造成视神经的挤压伤。③指标检测:采用图形翻转视觉诱发电位检测损伤前、损伤后1h、减压前1h、减压后2周视功能变化,记录NPN曲线主波(P波)的绝对潜伏期、绝对波幅。正常对照组仅采集一组数据作为对照。结果:30只实验动物均进入结果分析。①正常对照组家兔图形翻转视觉诱发电位检查均引出典型NPN波型曲线,视神经挤压伤后1hNPN波形低阔扁平,P波潜伏期延长,波幅降低。②P波潜伏期:术后2d减压组减压后短于减压前[(71.25±8.51),(86.47±14.28)ms,P<0.05];术后7d减压组减压前后比较差异无显著性(P>0.05);术后14d减压组减压后明显长于减压前[(158.73±15.16),(116.35±17.13)ms,P<0.05]。术后2d减压组和术后7d减压组短于术后不减压组(P<0.01)。术后7,14d减压组和术后不减压组明显长于正常对照组(P<0.01)。③P波波幅:术后2d减压组减压后高于减压前[(5.25±0.78),(4.42±0.42)μV,P<0.05]。术后2d减压组减压后低于术后7d减压组、术后14d减压组(P<0.01),术后14d减压组低于术后7d减压组(P<0.05);术后7d减压组、术后14d减压组、术后不减压组低于正常对照组(P<0.01)。结论:神经元继发性损伤是视功能进行性下降的重要原因,视神经减压术有利于减轻视神经间接损伤,较早期(损伤后48h以内)减压可阻止轴突继发性损伤,避免视功能进一步下降,并在一定程度上逆转视功能的损害。     

三维CT评估发育性髋关节脱位的骨性形态学特征

目的:通过使用CT三维测量髋臼发育情况及髋臼对股骨头覆盖率对比性观察,整体反映髋臼发育情况。方法:①观察对象:选择2003-06/2005-04对41例发育性髋关节脱位患者55个髋关节。其中男12例,女29例;年龄18个月～6岁。患髋右侧23例,左侧32例,其中双侧12例。健康侧27髋。患儿家属均知情同意。②实验方法:所有患儿使用PQ6000型多层螺旋CT扫描,扫描数据进行骨组织三维重建。将测量数据制成图表,显示三维的髋臼发育情况,并量化表示髋臼的缺损情况。③实验评估:计算不同截面正常侧髋臼指数、中心边缘角(假设符合正态分布)的均数、标准差、分布范围及95%可信区间。观察发育性髋关节脱位术前术后骨骼形态学变化。分别在术前、术后测量患者患侧髋臼指数、中心边缘角和前倾角,测量值均分别与正常值进行对比。结果:患侧55个髋,健康侧27髋,均进入结果分析。①发育性髋关节脱位术前术后骨骼形态学变化:术前55侧发育性髋关节脱位髋关节脱位程度为,参照T"nnis分类方法,Ⅰ度5髋(9.1%),Ⅱ度11髋(20%),Ⅲ度32髋(58.2%),Ⅳ度7髋(12.7%)。术后患者均表现髋臼α角均>90°,头臼呈同心圆对位,Shenton线连续,股骨头较术前明显发育,原先未出现头骺的患者,出现头骺,但较正常仍偏小;髋臼口呈类圆形,髋臼边缘欠光滑,髋臼整体呈一定程度前倾。②术前术后髋臼指数、中心边缘角和前倾角变化对比:术后患者的髋臼指数和前倾角与正常对照组之间差异无显著性(P>0.05),术后患者的中心边缘角大于正常对照组[(33.4±2.6)°(29.1±2.0)°,P<0.01],术后患者的髋臼指数和前倾角测量值均小于术前(P<0.01)。结论:介绍了一种对髋臼形态测量的新方法,它能够全面反映髋臼的发育情况,不但增加了对中心边缘髋臼病理改变的认识程度,还为手术提供了精确的可信度较高的矫形设计方案。