Influence of antipsychotic, antiemetic, and Ca(2+) channel blocker drugs on the cellular accumulation of the anticancer drug daunorubicin: P-glycoprotein modulation

We investigated the effect of antiemetic, antipsychotic, and Ca(2+) blocker drugs on the function of P-glycoprotein (Pgp) in vitro and compared inhibitory concentrations with therapeutic blood levels. Human colon adenocarcinoma (Caco-2) and human blood-brain barrier endothelial cells were transfected or transduced to express Pgp, and the uptake of rhodamine123, calcein AM, or daunorubicin was measured by flow cytometry in the presence of the drugs. NIH3T3/MDR1 cells were used for reference testing. Results of the flow cytometric studies were supported by cell proliferation and monolayer permeability studies. Thirty-five drugs are included in this study, of which 13 modulate the function of Pgp at the therapeutic blood concentration and 8 at a concentration 2 to 4 times higher. Two drugs, which block the function of Pgp only partially at therapeutic blood concentrations, blocked the function of Pgp completely if used concomitantly. Based on these in vitro experiments, we conclude that administration of several drugs that modulate the function of Pgp simultaneously may adversely affect the natural function of this efflux pump and may cause drug-induced side effects in patients.     

Laparoscopic Nissen Fundoplication Plus Mid-gastric Plication for Treatment of Obese Patients with Gastroesophageal Reflux Disease

Background

Gastroesophageal reflux disease (GERD) is commonly associated with obesity, and its surgical management is debatable.

Objective

The objective of this study was to prove the safety and feasibility of laparoscopic Nissen’s fundoplication (LNF) combined with mid-gastric plication (MGP) for treatment of obese patients with GERD.

Methods

LNF combined with MGP was done for 18 patients. All interventions were performed under general anesthesia. The follow-up protocol included body mass index (BMI), percentage of excess weight loss (%EWL), percentage of excess BMI loss (%EBMIL), and clinical assessment using the Gastro-esophageal Reflux Health-Related Quality-of-Life (GERD-HRQOL) scale at 6 and 12 months.

Results

The period of follow-up ranged from 12 to 33 months with a mean of 17.74 ± 3.73 months. The operation time was 1.40 ± 0.27 h. No serious procedure-related complications occurred. GERD-related symptoms resolved in all patients (p < 0.001). There was a significant improvment in endoscopic findings at 6 months compared to properatively (p = 0.001). There was a significant patient satisfaction score using GERD-HRQOL at 6 and 12 months (p = 0.000). The 1-year follow-up excess weight was significantly less than the baseline excess weight (p < 0.001). The average BMI decreased from 37.59 ± 1.89 kg/m² at baseline to 30.61 ± 1.57 kg/m² at 1 year (p < 0.001).

Conclusions

LNF combined with MGP for treatment of obese patients with GERD is technically safe, feasible, and promising with no serious procedure-related complications. The technique is effective in terms of weight loss and cure of GERD. However, future larger studies are required to demonstrate the safety, effectiveness, and long-term durability of the procedure.

     

Comparison Between Stable Line Reinforcement by Barbed Suture and Non-reinforcement in Sleeve Gastrectomy: a Randomized Prospective Controlled Study

Introduction

Laparoscopic sleeve gastrectomy (LSG) is now a popular bariatric procedure worldwide with rising prevalence over the last decade. Staple line leak and bleeding are the most dangerous complications of LSG. Staple line reinforcement (SLR) by oversewing the staple line was suggested to reduce the incidence of leak and bleeding. We designed a randomized controlled prospective study to investigate the value of SLR by invaginating the whole staple line using unidirectional absorbable 3/0 V-Loc 180 sutures (Covidien, Mansfield, MA, USA) to no SLR in LSG.

Patients and Methods

Nine hundred and twenty patients undergoing LSG between March 2016 and March 2017 were included in the study; they were prospectively randomized into two groups: A and B, each of 460 patients. In group A, the entire staple line was invaginated with continuous seromuscular suturing using 3/0 V-Loc 180 suture (Covidien, Mansfield, MA, USA), and in group B, no reinforcement was done. The patients were selected according to National Institute of Health (NIH) guidelines. All procedures were performed by the same team of experienced bariatric surgeons. Patients were followed up for 6 weeks after surgery for occurrence of complications.

Results

The two groups were matched considering the demographic data. Operative time was significantly longer in group A (P?=?0.001), with mean operative time in group A was 69 min, while that in Group B was 50.8 min. Leak occurred in eight cases (1.7%) in group B and none (0%) in group A; leak was significantly lower in group A (P?=?0.008). Bleeding occurred in two patients (0.4%) in group A and in seven (1.5%) in group B (P?=?0.178), with no statistically significant difference between both groups as regards bleeding.

Conclusion

Comparing SLR by invaginating the whole staple line using unidirectional absorbable 3/0 V-Loc 180 sutures (Covidien, Mansfield, MA, USA) to no SLR in a relatively large cohort of patients undergoing LSG, in a randomized controlled prospective study, has proved statistically significant value for SLR by invaginating sutures.

     

延边地区汉族和朝鲜族居民脂肪分布与代谢异常的关系

目的:了解延边地区朝鲜族和汉族居民的脂肪分布特征及其与血压、血脂及血糖的关系。方法:于2006-08-8/17在延边地区九龙和翁声社区随机选择40～60岁朝鲜族和汉族常住居民2378名进行内脏脂肪率和体脂肪率以及血压、血脂、血糖等生化指标的检测。调查以健康体检形式进行,①内脏脂肪和体脂肪率测定采用日本TANITA株式会社生产的BC-600型体成分计测定,并且按其判定标准确定超过标准者[内脏脂肪率≥15%(男)、≥10%(女),体脂肪率(40～59岁)≥23%(男)、≥36%(女),体脂肪率(≥60岁)≥25%(男)、≥37%(女)]。②取清晨空腹(禁食12h)静脉血,采用日立-7600-010全自动生化分析仪测量血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇、空腹血糖等指标。③高血压的诊断标准:收缩压≥140mmHg(1mmHg=0.133kPa)及或舒张压≥90mmHg。④血脂异常的诊断标准:总胆固醇≥5.72mmol/L,三酰甘油≥1.7mmol/L,高密度脂蛋白胆固醇<0.90mmol/L(男)、<1.0mmol/L(女)。⑤高血糖的诊断标准:空腹血糖≥6.1mmol/L。结果:①汉族男性的内脏脂肪率和体脂肪率均值分别为(10.51±3.66)%和(22.70±4.85)%,朝鲜族男性分别为(9.16±3.81)%和(20.28±5.02)%,汉族均高于朝鲜族(P<0.01);汉族女性的内脏脂肪率和体脂肪率分别为(6.22±2.27)%和(35.31±5.65)%,朝鲜族女性分别为(5.88±2.19)%和(34.00±5.72)%,汉族均高于朝鲜族(P<0.01)。②汉族男性的内脏脂肪率和体脂肪率超标率分别为12.1%和45.8%,朝鲜族男性分别为7.8%和28.6%,汉族均高于朝鲜族(P<0.05);汉族女性的内脏脂肪率和体脂肪率超标率分别为6.7%和47.9%,朝鲜族女性分别为3.8%和37.3%,汉族均高于朝鲜族(P<0.05)。③Logistic逐步回归分析结果表明,内脏脂肪率与民族、性别、年龄、高血压、高三酰甘油血症和高血糖有密切关系;体脂肪率与民族、性别、高血压、高三酰甘油血症、低高密度脂蛋白血症和高血糖有密切的关系。结论:①延边地区汉族居民内脏脂肪率和体脂肪率平均水平及其超标率明显高于朝鲜族。②内脏脂肪率和体脂肪率均与民族、性别、年龄(体脂肪率除外)、高血压、高三酰甘油血症和高血糖相关。     

Laparoscopic anterior and posterior native tissue repair: a new pelvic floor approach

Introduction: Traditionally, a cystocele caused by a midline defect of the pelvic fascia is treated by vaginal fascia duplication, also known as anterior colporraphy. The rectocele is managed by suturing the posterior fascia and, frequently, the levator ani muscles. We developed the approach of laparoscopic anterior and posterior fascia repair by native tissue.

Material and methods: The methods were based on anterior and posterior exposure of pelvic fascia similar to the preparation of an extended sacral colpopexy. The fascia was compressed and narrowed by absorbable woven sutures, size 1. Twenty-seven patients were followed up for 6–13?months. All patients received additional apical fixation by pectopexy.

Results: In the examination group, 13 patients underwent anterior laparoscopic fascia repair and 23 had posterior repair. We detected one apical and one posterior relapse, and also one in the anterior repair group. The patient with the apical relapse reported pain and de novo urgency. Anatomical reconstruction was achieved in all other patients.

Summary: Laparoscopic anterior and posterior native tissue repair appears to be a feasible method for the treatment of midline cystocele and rectocele. No new risks were observed. The technique leaves no scar in the vagina and is well accepted.

Abbreviations: POPQ: Pelvic Organ Prolapse Quantification System; FDA: Food and Drug Association; US: United States; Fig: Figure; ICIQ: International Consultation on Incontinence Questionnaire     

Novel inhalational murine model of invasive pulmonary aspergillosis

We developed a novel model of invasive aspergillosis (IA) that recapitulates human disease. Mice were immunosuppressed with cyclophosphamide and cortisone acetate and then infected in an aerosol chamber. This procedure reproducibly delivered 1 x 10(3) to 3 x 10(3) conidia to the lungs. Lethal pulmonary IA developed over 2 weeks and was prevented by amphotericin B.     

认知矫正治疗对慢性精神分裂症患者临床症状和社会功能的影响

目的:观察认知矫正治疗对慢性精神分裂症患者临床症状和社会功能的改善作用。方法:选择2003-01/08在北京回龙观医院住院的慢性精神分裂症患者104例。均符合CCMD-Ⅲ及DSM-Ⅳ关于精神分裂症诊断标准;年龄25～55岁;病程≥2年;病情稳定,处于迁延、残留或部分缓解状态;药物治疗状况稳定,近期无换药打算;纳入对象或家属同意入组并签署知情同意书。应用随机数字表法将患者分认知矫正治疗组和对照组,每组52例。在相近药物治疗的基础上,认知矫正治疗组以Ann Delahunty和Rodney Morice等制定的神经认知矫正手册(汉化)为治疗工具,在治疗师的指导下进行认知作业练习,内容包括认知灵活性、工作记忆、计划执行功能3大功能模块。对照组予以相同时间的工娱治疗,主要包括有治疗师指导的操作性音乐治疗和舞蹈治疗。治疗前后两组患者分别进行PANSS、住院精神患者社会功能缺陷量表和护士观察量表的评定。结果:实验共纳入慢性精神分裂症患者104例,认知矫正治疗组44例,对照组46例进入结果分析,14例脱落。①治疗前后两组患者PANSS量表总分以及阴性症状量表、复合量表、一般精神病理量表、反应缺乏量表4个分量表的评分均有下降,组内比较差异有显著性意义(t=2.12～4.59,P<0.05);减分情况在两组间差异不明显(P>0.05)。②两组患者的社会功能缺陷量表总分在治疗后均有下降,与治疗前比较,差异有显著性意义(t=3.89,2.04,P<0.05);两组间比较,差异无显著性意义(P>0.05)。认知矫正治疗组治疗后护士观察量表的总病情以及总消极、迟滞2个分量表评分下降,与治疗前比较差异有显著性意义(t=1.49,1.19,2.81,P<0.05);其中迟滞项的减分在两组间比较,差异具有显著性意义(F=4.97,P<0.05)。③社会功能量表的改善与词语流畅性的改善呈正相关(R2=0.36,P<0.05),护士观察量表中总病情与积极两项评分的改善也与言语流畅性测验的改善正相关(R2=0.37,0.34,P<0.05)。结论:认知矫正治疗能在一定程度上改善精神分裂症患者的社会功能,并与部分认知功能的改善相关,但对临床症状无明显改善作用。