Catalase Overexpression Prevents Nuclear Factor Erythroid 2–Related Factor 2 Stimulation of Renal Angiotensinogen Gene Expression,Hypertension, and Kidney Injury in Diabetic Mice

This study investigated the impact of catalase (Cat) overexpression in renal proximal tubule cells (RPTCs) on nuclear factor erythroid 2–related factor 2 (Nrf2) stimulation of angiotensinogen (Agt) gene expression and the development of hypertension and renal injury in diabetic Akita transgenic mice. Additionally, adult male mice were treated with the Nrf2 activator oltipraz with or without the inhibitor trigonelline. Rat RPTCs, stably transfected with plasmid containing either rat Agt or Nrf2 gene promoter, were also studied. Cat overexpression normalized systolic BP, attenuated renal injury, and inhibited RPTC Nrf2, Agt, and heme oxygenase-1 (HO-1) gene expression in Akita Cat transgenic mice compared with Akita mice. In vitro, high glucose level, hydrogen peroxide, and oltipraz stimulated Nrf2 and Agt gene expression; these changes were blocked by trigonelline, small interfering RNAs of Nrf2, antioxidants, or pharmacological inhibitors of nuclear factor-κB and p38 mitogen-activated protein kinase. The deletion of Nrf2-responsive elements in the rat Agt gene promoter abolished the stimulatory effect of oltipraz. Oltipraz administration also augmented Agt, HO-1, and Nrf2 gene expression in mouse RPTCs and was reversed by trigonelline. These data identify a novel mechanism, Nrf2-mediated stimulation of intrarenal Agt gene expression and activation of the renin-angiotensin system, by which hyperglycemia induces hypertension and renal injury in diabetic mice.     

ACS national surgical quality improvement program: Targeting quality improvement in Canadian pediatric surgery

Purpose

The pediatric NSQIP program is in the early stages of facilitated surgical quality improvement for children. The objective of this study is to describe the initial experience of the first Canadian Children’s Hospital participant in this program.

Method

Randomly sampled surgical cases from the “included” case list were abstracted into the ACS-NSQIP database. These surgical procedure-specific data incorporate patient risk factors, intraoperative details, and 30 day outcomes to generate annual reports which provide hierarchical ranking of participant hospitals according to their risk-adjusted outcomes.

Results

Our first risk-adjusted report identified local improvement opportunities based on our rates of surgical site infection (SSI) and urinary tract infection (UTI). We developed and implemented an engagement strategy for our stakeholders, performed literature reviews to identify practice variation, and conducted case control studies to understand local risk factors for our SSI/UTI occurrences. We have begun quality improvement activities targeting reduction in rates of SSI and UTI with our general surgery division and ward nurses, respectively.

Conclusions

The NSQIP pediatric program provides high quality outcome data that can be used in support of quality improvement. This process requires multidisciplinary teamwork, systematic stakeholder engagement, clinical research methods and process improvement through engagement and culture change.     

Mesh Migration Into Urinary Bladder After Open Ventral Herniorrhaphy With Mesh: A Case Report

Ventral hernia repair with mesh products is of increasing popularity. The long-term results of mesh repair of ventral hernia are superior to primary suture repair. However, occasional complications may still present. We report on a 77-year-old man who underwent ventral hernia repair with a mesh 5 years ago with complication of mesh migration into the urinary bladder and enterovesical fistula. The patient presented with lower urinary tract symptoms initially. By urinalysis, persistent hematuria and pyuria were found after antibiotic treatment. For further investigation of hematuria, intravenous urography was performed, which revealed a faint radio-opaque patch at the right pelvis. To obtain a more precise relationship between the lesion and the adjacent organs, computed tomography and cystoscopy were arranged. They confirmed a mesh with stone formation in the urinary bladder. To remove the mesh, segmental resection of the ileum and cystorrhaphy were performed.Key words: Incisional hernia, Surgical mesh, Complications, Urinary Bladder CalculiPrimary repair of ventral hernia with component separation is still the major repair method. There is increasing popularity of ventral hernia repair with mesh products. The long-term results of mesh repair of ventral hernia are superior to primary suture repair.^1,2 However, occasional complications may still occur. Mesh migration to adjacent organs is one of the complications. It has been reported in some patients with a surgical history of either open or laparoscopic herniorrhaphy with mesh.^3–8 In this case report, a 77-year-old man, who underwent ventral hernia repair with mesh before, had the complication of mesh migration into the urinary bladder and enterovesical fistula with the initial presentation of lower urinary tract symptoms.     

干扰素β-1b对多发性硬化患者生活质量影响的1年随访

目的观察干扰素β-1b(IFNβ-1b)治疗复发缓解型多发性硬化(MS)患者的疗效并进行生活质量评估,进一步探索生活质量的相关因素。方法选择接受IFNB-1b治疗的MS患者13例,并于治疗后第1个月、3个月、6个月、9个月、12个月对患者进行随访,评估包括扩展的功能缺损状况(EDSS)评分、多发性硬化患者生活质量量表(MSQOL-54)及汉密尔顿焦虑抑郁量表(HAMA、HAMD)评分。结果经IFNB1b治疗的MS患者在第1、3、6、9、12个月随访时生活质量、EDSS、HAMA、HAMD评分与治疗前比较均无明显变化(P0.05)。治疗前生活质量中躯体功能、性功能及对性生活满意度与EDSS评分呈负相关(P值均0.05);情绪致角色受限、疼痛与病程呈正相关(P值均0.05);躯体功能、情绪状况、社会功能、性功能及对性生活满意度与HAMA评分呈负相关(P值均0.05);认知、应激与HAMD评分均呈负相关(P值均0.05)。躯体致角色受限、精力、健康认知、总体生活质量及健康变化与病程、EDSS、HAMA、HAMD各项无相关性,年龄与MSQOL-54无关(P值均0.05)。结论 IFNB-1b短期内可能对MS患者生活质量无明显影响,生活质量与患者的EDSS评分、焦虑抑郁症状相关。     

Spinal root avulsion: an excellent model for studying motoneuron degeneration and regeneration after severe axonal injury简

<正>Spinal root avulsion is an excellent model for studying the response of motoneurons to severe injury to their axons(Koliatsos et al.,1994).In this model(‘Avulsion Model’),spinal roots are torn off from spinal cord without removing the vertebra at     

Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or Familial Parkinson's Disease

MethodsWe performed a gene-dosage analysis of PARK2 using real-time polymerase chain reaction for 189 patients with early-onset PD or familial PD, and 191 control individuals. In the case of PD patients with heterozygous gene-dosage mutation, we performed a sequencing analysis to exclude compound heterozygous mutations. The association between heterozygous mutation of PARK2 and PD was tested.ResultsWe identified 22 PD patients with PARK2 mutations (11.6%). Five patients (2.6%) had compound heterozygous mutations, and 13 patients (6.9%) had a heterozygous mutation. The phase could not be determined in one patient. Three small sequence variations were found in 30 mutated alleles (10.0%). Gene-dosage mutation accounted for 90% of all of the mutations found. The frequency of a heterozygous PARK2 gene-dosage mutation was higher in PD patients than in the controls.ConclusionsHeterozygous gene-dosage mutation of PARK2 is a genetic risk factor for patients with early-onset or familial PD in Koreans.     

Left atrial appendage occlusion: Initial experience with the Amplatzer™ Amulet™

Background

The Amplatzer™ Amulet™ (Amulet) is the evolution of the Amplatzer™ Cardiac Plug, a dedicated device for percutaneous left atrial appendage (LAA) occlusion. The new device has been designed to facilitate the implantation process, improve the sealing performance and further reduce the risk of complications. The objective of the study was to describe the initial experience with the Amplatzer Amulet for percutaneous LAA occlusion.

Methods

This was a prospective single-center study of patients undergoing percutaneous LAA occlusion. The indication for LAA closure was a formal contraindication for oral anticoagulation or previous history of stroke due to INR lability. All procedures were done under general anesthesia and transesophageal echocardiography (TEE) guidance. Transthoracic echocardiography was performed 24 h after the procedure in order to rule out procedural complications before discharge. Further follow-up was done with a clinical visit and TEE at 1–3 months.

Results

Between July-2012 and June-2013, 25 patients with a mean CHA₂DS₂-VASC of 4.3 ± 1.7 underwent LAA occlusion with the Amplatzer Amulet. The device was successfully implanted in 24 patients (96%) without any procedural stroke, pericardial effusion or device embolization. None of the patients presented any clinical event at follow-up. Follow-up TEE showed complete LAA sealing in all patients with no residual leaks > 3 mm and no device embolization. One patient (4.1%) presented a device thrombosis at follow-up without clinical expression.

Conclusion

In this initial series of patients, the Amulet showed a remarkable acute and short-term performance in terms of feasibility and safety as depicted by the high successful implantation rate and the low incidence of complications.