Central drive and ventilatory failure in late-onset Pompe disease: At the gates of a new phenotype

Subjects with late-onset Pompe disease (LOPD) typically present as slowly progressive proximal muscle weakness. Respiratory muscle weakness and diaphragmatic paralysis are common features, and may be the initial manifestation of the disease. There is often a poor correlation between the severity of limb and respiratory muscle weakness. Early clinical observations about disproportionate hypercapnia to the respiratory muscular weakness in late-onset Pompe disease were recognized and will be discussed with special reference to blunted respiratory drive, and the connections between early clinical observations, respiratory functional studies and anatomical findings. According to new evidence about blunted respiratory drive in Pompe disease, it is necessary to rethink what is meant by “asymptomatic Pompe disease” and propose a new phenotype with its therapeutic implications. The conceptual model of the mechanisms leading to respiratory failure in this disease could be considered according to these new findings. It may broaden the diagnostic spectrum of the adult forms and warrants a closer interaction between neurologists and pulmonologists. The recognition of this new phenotype of predominant central alveolar hypoventilation in Pompe disease will improve the understanding of the underlying mechanisms of ventilatory failure and could lead to improved future therapeutic strategies.     

EGFR、p53在db/db自发性糖尿病小鼠颌下腺的表达

目的 观察表皮生长因子受体（EGFR）、p53在糖尿病小鼠颌下腺中的表达。方法 选取3、4、6、8、10月龄db／db糖尿病小鼠及相应月龄的db／＋m正常小鼠颌下腺。应用HE染色及免疫组织化学方法染色后进行图像分析，统计EGFR、p53在颌下腺组织内表达的细胞阳性率。结果 随着糖尿病的发展，颌下腺组织出现腺叶萎缩及实质细胞排列不整齐，堆集呈簇。纤维及血管增多；EGFR、p53在对 照组及糖尿病组颌下腺中均有表达。其细胞阳性率随月龄增大均呈增高趋势。且糖尿病组显著高于对照组。结论 ①db／db糖尿病可导致颌下腺组织萎缩及实质细胞形态学改变。②EGFR、p53表达增多。说明糖尿病时EGFR作为多效应受体，可能被激活从而诱导了颌下腺的细胞凋亡；p53表达的上升。提示随着糖尿病发展，颌下腺实质细胞有凋亡趋势。     

Meta-analysis of retrojugular versus antejugular approach for carotid endarterectomy

Introduction

The retrojugular approach for carotid endarterectomy (CEA) has been reported to have the advantages of shorter operative time and ease of dissection, especially in high carotid lesions. Controversial opinion exists with regard to its safety and benefits over the conventional antejugular approach.

Methods

A systematic review of electronic information sources was conducted to identify studies comparing outcomes of CEA performed with the retrojugular and antejugular approach. Synthesis of summary statistics was undertaken and fixed or random effects models were applied to combine outcome data.

Findings

A total of 6 studies reporting on a total of 740 CEAs (retrojugular approach: 333 patients; antejugular approach: 407 patients) entered our meta-analysis models. The retrojugular approach was found to be associated with a higher incidence of laryngeal nerve damage (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 1.46–7.07). No significant differences in the incidence of hypoglossal or accessory nerve damage were identified between the retrojugular and antejugular approach groups (OR: 1.09 and 11.51, 95% CI: 0.31–3.80 and 0.59–225.43). Cranial nerve damage persisting during the follow-up period was similar between the groups (OR: 2.96, 95% CI: 0.79–11.13). Perioperative stroke and mortality rates did not differ in patients treated with the retrojugular or antejugular approach (OR: 1.26 and 1.28, 95% CI: 0.31–5.21 and 0.25–6.50).

Conclusions

Currently, there is no conclusive evidence to favour one approach over the other. Proof from a well designed randomised trial would help determine the role and benefits of the retrojugular approach in CEA.     

转染癌基因的骨髓基质干细胞体外分化特征

目的:观察转染癌基因的骨髓基质干细胞在体外分化情况,为肝细胞癌的细胞源研究提供实验依据。方法:实验于2003-05/2004-06在南方医科大学药理教研室实验室完成。①两步法获取大鼠肝细胞,梯度离心法分离大鼠骨髓基质干细胞。②单基因转染是单独将c-myc或K-ras癌基因瞬时转染大鼠骨髓基质干细胞,6孔培养板中培养,24h后荧光显微镜下观察骨髓基质干细胞转染结果。双基因转染步骤相同,只是将c-myc和K-ras癌基因同时转染大鼠骨髓基质干细胞。③c-myc癌基因转染组、K-ras癌基因转染组、双癌基因转染组常规培养,加入含体积分数为0.1胎牛血清的DMEM培养基,于37℃、体积分数为0.05的CO2孵箱培养,每24h半量更换培养液。④c-myc癌基因转染 肝细胞组、K-ras癌基因转染 肝细胞组、双癌基因转染 肝细胞组将已转染癌基因的骨髓基质干细胞,置于叠加的培养板半透膜的上方(细胞密度均为1×105个/cm2),再将肝细胞置于半透膜的下方(每孔细胞密度为3×105/cm2)进行共培养,其余步骤同常规培养。⑤通过反转录聚合酶式反应和细胞免疫组化检测骨髓基质干细胞分化情况。结果:①癌基因转染24h骨髓基质干细胞检测结果:单独转染c-myc或K-ras癌基因的细胞,其绿色荧光蛋白呈均匀一致分布;双基因转染的细胞,绿色荧光蛋白呈点片状分布。②各组骨髓基质干细胞向肿瘤细胞分化检测结果:c-myc癌基因转染组、K-ras癌基因转染组、双癌基因转染组的骨髓基质干细胞,均未向肿瘤细胞分化;c-myc癌基因转染 肝细胞组、K-ras癌基因转染 肝细胞组、双癌基因转染 肝细胞组的骨髓基质干细胞,均向肝细胞癌发展;空白对照组骨髓基质干细胞细胞均为阴性。此外,双癌基因转染 肝细胞组的骨髓基质干细胞分化增殖迅速,反转录聚合酶式反应和免疫组化检测发现,培养第7天出现甲胎蛋白表达,并迅速增加,而第7天出现的白蛋白和细胞角蛋白18表达迅速减弱,第14天消失。结论:转染癌基因的骨髓基质干细胞,在向肝细胞诱导的条件下,部分癌基因可以使干细胞分化为肝癌细胞;多癌基因转染时,更易于使干细胞分化为肝癌细胞。     

Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis

Apoptosis, or programmed cell death, is a general mechanism for removal of unwanted cells from the immune system. It is characterized by chromatin condensation, a reduction in cell volume, and endonuclease cleavage of DNA into oligonucleosomal length fragments. Apoptosis is also accompanied by a loss of membrane phospholipid asymmetry, resulting in the exposure of phosphatidylserine at the surface of the cell. Expression of phosphatidylserine at the cell surface plays an important role in the recognition and removal of apoptotic cells by macrophages. Here we describe a new method for the detection of apoptotic cells by flow cytometry, using the binding of fluorescein isothiocyanate-labeled annexin V to phosphatidylserine. When Burkitt lymphoma cell lines and freshly isolated germinal center B cells are cultured under apoptosis inducing conditions, all cells showing chromatin condensation strongly stain with annexin V, whereas normal cells are annexin V negative. Moreover, DNA fragmentation is only found in the annexin V-positive cells. The nonvital dye ethidium bromide was found to stain a subpopulation of the annexin V-positive apoptotic cells, increasing with time. Our results indicate that the phase in apoptosis that is characterized by chromatin condensation coincides with phosphatidylserine exposure. Importantly, it precedes membrane damage that might lead to release from the cells of enzymes that are harmful to the surrounding tissues. Annexin V may prove important in further unravelling the regulation of apoptosis.     

急性有机磷杀虫药中毒中间综合征的临床分析

目的探讨急性有机磷杀虫药中毒中间综合征（intermediate syndrome,IMS）的诊断治疗。方法回顾性分析10例IMS患者临床表现和治疗方法。结果有机磷中毒中间综合征的10例患者均出现不同程度呼吸肌麻痹症,及时建立人工气道及机械通气和乙酰胆碱酯酶（AchE）复能剂应用,治愈8例,死亡2例。结论 IMS应早期识别,建立人工气道与机械通气是抢救成功的重要方法。