Phenotype of dent disease in a cohort of Indian children

Objective

To describe the clinical and genotypic features of Dent disease in children diagnosed at our center over a period of 10 years.

Design

Case series.

Setting

Pediatric Nephrology Clinic at a referral center in Northern India.

Methods

The medical records of patients with Dent disease diagnosed and followed up at this hospital from June 2005 to April 2015 were reviewed. The diagnosis of Dent disease was based on presence of all three of the following: (i) low molecular weight proteinuria, (ii) hypercalciuria and (iii) one of the following: nephrolithiasis, hematuria, hypophosphatemia or renal insufficiency, with or without mutation in CLCN5 or OCRL1 genes.

Results

The phenotype in 18 patients diagnosed with Dent disease during this period was characterized by early age at onset (median 1.8 y), and polyuria, polydipsia, salt craving, hypophosphatemic rickets and night blindness. Rickets was associated with severe deformities, fractures or loss of ambulation in six patients. Nephrocalcinosis was present in three patients, while none had nephrolithiasis. Generalized aminoaciduria was seen in 13 patients, two had glucosuria alone, and one had features of Fanconi syndrome. Over a median follow up of 2.7 years, one patient developed renal failure. Genetic testing (n=15) revealed 5 missense mutations and 3 nonsense mutations in CLCN5 in 13 patients. Five of these variations (p.Met504Lys, p.Trp58Cys, p.Leu729X, p.Glu527Gln and p.Gly57Arg) have not been reported outside the Indian subcontinent.

Conclusion

Our findings suggest a severe phenotype in a cohort of Indian patients with Dent disease.

     

A randomised controlled trial of a personalised lifestyle coaching application in modifying periconceptional behaviours in women suffering from reproductive failures (iPLAN trial)

Background

Lifestyle, in particular obesity and smoking has significant impacts on fertility and an important focus for the treatment of reproductive failures is the optimisation of periconceptional lifestyle behaviours. The preimplantation intrauterine environment within the uterus is also key for embryo development and early programming. Although the benefits a healthy periconceptional lifestyle are well described, there remains a paucity of data demonstrating the efficacy of interventions designed to optimise preconceptional lifestyle behaviours and choices.

Methods

This study is a prospective randomised controlled trial which aims to address the question of whether an online personalised lifestyle coaching application is an effective means of delivering periconceptional advice in women suffering from reproductive failures. Women suffering from subfertility or recurrent miscarriages attending the outpatient clinic will be randomised into either the intervention arm (personalised online lifestyle coaching application) or the control arm (standard periconceptional advice including information from NHS websites). Both groups will be asked to complete a validated lifestyle questionnaire at baseline, and 6, 12, 18 and 24?weeks after randomisation. The primary outcome is the composite dietary and lifestyle risk score at 12?weeks. The secondary outcomes will include compliance with the program, proportion achieving spontaneous conception during the study period and the dietary and lifestyle risk score at 24?weeks.

Discussion

With this study, we aim to clarify whether a personalised online based lifestyle coaching application is more effective at improving behaviours than standard advice offered by National Health Service (NHS) resources. A personalised lifestyle coaching application may represent an empowering and cost effective means of delivering periconceptional advice in women with subfertility or recurrent miscarriages.

Trial registration

The iPLAN trial was retrospectively registered (ISRCTN 89523555).

     

血管内皮生长因子与运动的相关性

目的:血管内皮生长因子是一种广泛存在于机体组织的细胞因子,与运动密切相关,是近来运动人体科学界和运动医学界研究的焦点。对近来血管内皮生长因子与运动的相关研究进行综述,以能够找到提高训练质量乃至运动水平的方法。资料来源:应用计算机检索Medscape.net1996-01/2006-12的相关文章,并根据相关的参考文献检索了部分文章,检索词“vascular endothelial growth factor,exercise”,限定语言种类为English;同时计算机检索中国知识资源总库1996-01/2006-12的相关文献,限定语言种类为中文,检索词“血管内皮生长因子,运动”。资料选择:纳入条件:①随机对照试验研究。②试验包括对照组和干预组。同时排除综述和重复的研究。资料提炼:共找到相关研究47篇,排除17篇,30篇符合标准。通过30个实验对运动中血管内皮生长因子在机体中的表达、作用及含量和动态变化进行了相关的分析和研究。资料综合:①血管内皮生长因子与运动的关系密切相关,现在仍然是运动医学界的研究焦点之一,研究的方向为运动对机体血管内皮生长因子的影响,目的是发现运动对机体的影响。②不同的运动方式对机体的血管内皮生长因子的表达不同,目前采用的训练方式多为极限运动或运动与其他因素相结合,如低压强 运动。③观察部位多集中在大脑、肌肉、心血管、血液等,不同部位的表达不同。④运动对血管内皮生长因子表达有动态变化的规律。结论:血管内皮生长因子与运动的关系密切相关,不同的运动方式会造成血管内皮生长因子在机体不同部位不同表达。运动对血管内皮生长因子表达的影响呈现出规律性。     

A Necessary Step Toward Kidney Donor Safety: The Transition From Locking Polymer Clips to Transfixion Techniques in Laparoscopic Donor Nephrectomy

Donor safety is of paramount importance in addressing end-stage renal failure through living kidney transplantation. The United States Food and Drug Administration (FDA) issued a Class II recall on the use of Hem-o-lok (Teleflex, Limerick, Pennsylvania, United States) polymer clips on the renal artery in laparoscopic donor nephrectomy (LDN) in June 2006 following 3 reported cases of donor deaths secondary to slipped ligature. The National University Hospital of Singapore made the transition regarding hilar control in minimally invasive donor nephrectomy, from using polymer and titanium clips to transfixion techniques (pure or hand-assisted laparoscopic) via laparoscopic staples or intracorporeal suturing, respectively. This study assessed safety during the transition in arterial transfixion techniques in minimally invasive donor nephrectomy for both donors and recipients. Forty-five consecutive kidney donors underwent donor nephrectomy over a 2-year period starting from June 2010. A total of 37 donors who underwent LDN (pure laparoscopic or hand-assisted laparoscopic) were included in the analysis. Of the 37 patients, 23 kidney donors had renal arterial control using Hem-o-lok while 14 patients from November 2011 onward underwent transfixion of the renal artery. The 2 groups of donor who underwent renal arterial control by either clips ligature or transfixion technique were comparable. The outcomes for the recipients in each group were similar with no statistical difference between postoperative creatinine level, incidence of delayed graft function, or graft survival at 1 year. We conclude that the transition in renal arterial control technique to transfixion techniques in LDN in line with FDA recommendation is feasible and affords equivalent donor and recipient outcomes.     

巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

Treatment of high-risk acute myelogenous leukaemia by myeloablative chemoradiotherapy followed by co-infusion of T cell-depleted haematopoietic stem cells and culture-expanded marrow mesenchymal stem cells from a related donor with one fully mismatched human leucocyte antigen haplotype

A 20-year-old woman with high-risk acute myelogenous leukaemia was transplanted with granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood CD34+ haematopoietic stem cells and bone-marrow-derived mesenchymal stem cells (MSC) from her human leucocyte antigen haplotype-mismatched father after myeloablative conditioning therapy. The patient engrafted rapidly and had no acute or chronic graft-versus-host disease. Since transplantation, the patient has shown an enduring trilineage haematological complete response without any evidence of leukaemia relapse at 31 months. We suggest that MSC can be used effectively for genetically haploidentical haematopoietic stem cell transplantation for acute leukaemia.