Extrapontine myelinolysis in a 4 year old with diabetic ketoacidosis

Extrapontine and central pontine myelinolysis (EPM/CPM) are rare events in pediatric neurology but can have devastating consequences. They are most commonly associated with rapid correction of hyponatremia but have been reported in other situations as well. This condition is relatively more common in adult neurology, not surprisingly, as alcoholism and associated malnutrition are often predisposing conditions. There have been few case reports in children with regards to this. We describe a 4-year old who presented with focal neurological deficits in the setting of diabetic ketoacidosis and the ensuing underlying osmotic imbalances. The patient made a remarkable recovery with no deficits of note-cognitive or motor. To our knowledge this is the youngest case reported so far of EPM in a child with diabetic ketoacidosis. The history of the condition, early animal experiments, clinicopathologic correlates, previous case reports and other scenarios in which this unusual event can occur are discussed--though the exact pathogenesis of this condition still remains unclear. We hope to bring to the attention of clinicians caring for children in the acute care setting, the importance of gradual correction of serum osmolality to reduce morbidity and mortality.     

Recombinant α2(IV)NC1 domain of type IV collagen is an effective regulator of retinal capillary endothelial cell proliferation and inhibits pre-retinal neovascularisation

Background A recombinant form of the α2(IV)NC1 domain of type IV collagen has been shown to have potent anti-angiogenic activity although this peptide has not been studied in the context of proliferative retinopathies. In the current investigation we examined the potential for α2(IV)NC1 to regulate retinal microvascular endothelial cell function using a range of in vitro and in vivo assay systems. Materials and methods α2(IV)NC1 at concentrations between 0.1 and 1 μg/ml was added to retinal microvascular endothelial cells (RMECs) followed by assessment of cell attachment, proliferation and survival. This agent was also tested within a novel in vitro three-dimensional retinal angiogenesis assay and the number of angiogenic sprouts quantified. α2(IV)NC1 was also delivered intra-vitreally to mice with oxygen-induced proliferative retinopathy (OIR) and neovascularisation evaluated in comparison with vehicle-treated controls. Results RMECs treated with α2(IV)NC1 (0.1, 0.5 and 1 μg/ml) showed delayed attachment at 3 h post-seeding, although this deficit had been restored at the 6-h time point. BrdU assay of DNA replication revealed that confluent RMECs treated with α2(IV)NC1 showed no measurable response in comparison with vehicle-treated controls. By contrast, proliferation of sub-confluent RMECs was significantly reduced by α2(IV)NC1 at 0.5 μg/ml (P<0.01). α2(IV)NC1 also induced apoptosis in RMECs and inhibited angiogenesis of pre-existing retinal vascular networks in vitro (P<0.001). Intra-vitreal injection of α2(IV)NC1 in the OIR model significantly inhibited pre-retinal neovascularisation compared with vehicle-treated controls (P<0.001). Conclusion α2(IV)NC1 inhibits angiogenesis in the retinal microvasculature. This recombinant protein has potential for the treatment of neovascularisation in proliferative retinopathies. BioStratum Inc. did not sponsor this research in any way. None of the authors are paid consultants with this company.     

高糖对大鼠系膜细胞肝细胞生长因子受体表达的影响及其机制研究

目的 观察高糖作用下大鼠系膜细胞(MsC)肝细胞生长因子（HGF）受体c-Met的表达，并探讨其机制和意义。 方法 用RT-PCR和Western 印迹方法检测高糖作用大鼠MsC的不同时间点（0、12、24、48、96 h）c-Met的表达。分别用光辉霉素A（mithramycin A）和SU11274抑制转录因子Sp1的DNA结合活性和阻断c-Met。用电泳迁移率改变实验(EMSA)观察Sp1与c-Met基因启动子的结合活性。以荧光探剂二氯双氢荧光素二乙酸酯(DCFH-DA)捕获细胞内活性氧。 结果 大鼠MsC的c-Met表达在高糖作用12、24和48 h都明显上升，96 h开始下降。光辉霉素A呈浓度依赖性抑制高糖作用下大鼠MsC的c-Met表达上调。大鼠MsC内Sp1与c-Met基因启动子的结合活性在高糖作用下明显增强。HGF及c-Met显著抑制高糖诱导的大鼠MsC内活性氧的增多。 结论 高糖作用下大鼠MsC的c-Met表达增强，其机制可能是通过Sp1介导。HGF-c-Met信号通路激活能抑制高糖所致大鼠MsC内的氧化应激反应。     

尿视黄醇结合蛋白在2型糖尿病肾病早期诊断中的意义

目的　探讨检测尿视黄醇结合蛋白 (RBP)在糖尿病肾病 (DN)早期诊断中的临床意义。方法　分别对 4 2例 2型糖尿病患者及 36例健康对照者用酶联免疫法 (ELISA)测定尿RBP ,用放射免疫法测定尿α1 微球蛋白 (α1 M )、β2 微球蛋白 (β2 M)。结果　糖尿病组三种尿微量蛋白排泄量明显高于健康对照组 ,且以尿RBP敏感性最高。结论　尿RBP的检测可敏感反映早期糖尿病患者肾小管损伤。     

白细胞对早期糖尿病视网膜病变作用的研究

目的探讨白细胞在早期糖尿病大鼠视网膜毛细血管中粘附、堆积及其与视网膜微血管形态学变化的关系。方法健康成年雄性Wistar大鼠90只，随机分成正常对照组和链脲佐菌素（streptozotocin, STZ）诱导的糖尿病组各45只（3、7、14 d组各5只，30、90、180 d组各10只）。取大鼠右眼制备视网膜消化铺片，进行形态学观察及白细胞共有抗原（leukocyte common antigen, CD45）单克隆抗体免疫组织化学研究。结果正常对照组视网膜毛细血管中有少许CD45阳性细胞；糖尿病发生3 d后，CD45的表达明显增加，病程第14 d达高峰，以后基本稳定。病程90 d时，视网膜毛细血管已出现节段性膨大、囊样扩张及闭锁等形态学改变；病程180 d时，上述病变进一步加重。结论白细胞粘附发生在糖尿病视网膜病变（diabetic retinopathy, DR）的早期阶段，是DR在微血管水平病理变化的开端。白细胞粘附可能作为视网膜微血管形态学改变的基础，在DR的发生发展中起着重要作用。(中华眼底病杂志,2003,19:344-347)     

Effects of STA-MCA anastomosis for ischaemic oculopathy due to occlusion of the internal carotid artery

Summary Effects of STA-MCA anastomosis on two patients with neovascular glaucoma due to occlusion of the internal carotid artery are presented. Both patients improved in visual acuity and central retinal artery pressure as well as in signs of transient ischaemic attack. Postoperative angiography showed a marked decrease in collateral flow through the ophthalmic artery, which is reversed from the normal direction, with the development of blood flow through the anastomosis. Discussion is offered indicating that the lack of collateral flow through both the anterior and posterior communicating arteries is important in addition to occlusion of the internal carotid artery in order to produce full-blown ischaemic oculopathy such as venous stasis retinopathy, neovascular glaucoma or rubeosis iridis. It is stressed that EC-IC bypass surgery should be performed soon after the appearance of ischaemia and before the development of neovascular glaucoma or rubeosis iridis in order to obtain normal vision. In ischaemic oculopathy the results of EC-IC bypass can be evaluated objectively and quantitatively by many noninvasive neuro-ophthalmological tests which are important in discussing the efficacy of the bypass surgery.     

Diabetes mellitus and hearing loss

A prospective hearing survey was performed in a sample of 102 diabetic patients. The hearing data were compared with the hearing thresholds of three control population groups. A significant difference was found in the average hearing thresholds between the diabetic patients and all of the three control populations. Diabetic patients have worse hearing threshold levels especially at low and mid frequencies (P < 0.001). There was also a correlation between the duration of diabetes and hearing loss. No significant correlation was found between the different stages of diabetic retinopathy and the degree of hearing loss.     

Approved indications of lipo-PGE1 in Japan

For its peripheral vascular dilating effect and platelet agglutination inhibitory activity, prostaglandin E₁ is used in the treatment of diseases which are likely to cause peripheral circulatory failure or thrombus. In Japan, lipo-PGE₁, which was developed to give it a target-directed nature by modifying the conventional PGE₁, has been used and found to be useful in clinical practice. In this report, we attempt to describe the clinical benefits of lipo-PGE₁ focusing on the diseases which have been approved for its indications.     

Treatment of diabetic polyneuropathy with the neurotrophic peptide ORG 2766

The efficacy of the neurotrophic peptide ORG 2766 in diabetic patients with polyneuropathy was evaluated in a double-blind, placebo-controlled, multicentre trial. One hundred and twenty four patients were randomised in five groups to receive 0.1, 0.4, 2 or 5 mg ORG 2766 or placebo, once daily, administered subcutaneously 52 weeks. Thermal discrimination thresholds (TDT) and vibration perception thresholds (VPT), motor and sensory nerve conduction velocity, Hoffmann reflex, heart rate variation during deep breathing and heart rate response after standing up, neurological examination score and neuropathic symptom score were determined at baseline and after 17, 34 and 52 weeks of treatment. Of the nerve function indices studied, at week 52 the TDT_warmth of the hand in the ORG 2766 0.1, 0.4 and 5 mg groups and the TDT_cold of the foot in the ORG 2766 0.1 and 0.4 mg groups significantly improved compared with placebo. Further significant improvement as compared with placebo was observed in the paraesthesia score at week 34 and week 52 in the ORG 2766 2 mg group. Only at week 34 had both the heartbeat variation during deep breathing and the VPT of the foot in the ORG 2766 0.1 mg group improved significantly, compared with placebo. No further statistically significant differences were observed at time for the other measures. No adverse reactions were observed. The only recorded drug-induced side effect was pain at the injection site. Taking all measures of efficacy into account, the statistically significant results observed did not show consistency within each measure. Therefore, it is concluded that ORG 2766, in contrast to earlier reports, is not effective in treating diabetic polyneuropathy.