A novel technique for vas deferens transection repairs

The purpose of this study is to describe a technique, that is as successful as microsurgery in terms of patency rates and histopathologic assessments, and can be performed even by untrained hands in microsurgery, for repairing vas deferens injuries that can be perceived during inguinal herniorrhaphy. Thirty male Wistar-Albino rats were randomly allocated to five groups. In control group, the vas deferens was harvested without any surgical intervention (Group 1) and in sham group the vas was harvested after a limited dissection (Group 2). Three suture approximation technique was carried out in Group 3, and a novel vasovasostomy technique was carried out by using a hypodermal needle in Groups 4 and 5, with polypropylene and polyglactin 910 (rapid vicryl), respectively. Results were evaluated in terms of operative time, patency and flow rates, inflammation and sperm granuloma. The mean operative times for hypodermal needle assisted approximation of Groups 4 and 5 were found significantly less than Group 3. The compared results of the groups in terms of patency, flow rate, inflammation and spermatic granuloma indicated Group 4 to be superior to the other groups. We have found the hypodermal needle assisted approximation technique to be easier, less time consuming and cost effective. With these promising results, this modus operandi can be described as an appropriate technique for vas deferens transection repairs.     

Diffuse and segmental variants of cutaneous leiomyomatosis: novel mutations in the fumarate hydratase gene and review of the literature

Multiple cutaneous and uterine leiomyomatosis (MCUL; OMIM 150800) is an autosomal dominantly inherited disease characterized by leiomyomas of the skin and uterine leiomyomas. Recently, association of MCUL with different forms of renal cancer has been described. This syndrome is referred to as hereditary leiomyomatosis and renal cell cancer (OMIM 605839). Both disorders result from heterozygous germline mutations in the fumarate hydratase (FH) gene that may function as a tumor suppressor. Interestingly, cutaneous leiomyomas do not only manifest in a diffuse and symmetric fashion. Rather frequently, a segmental or band-like manifestation pattern can be observed, usually following the lines of Blaschko. Here, we sought to elucidate the molecular basis of diffuse and segmental cutaneous leiomyomatosis in six unrelated Dutch and Spanish patients and their families. We identified six novel FH mutations, including one missense and one nonsense mutation, two deletions and two splice-site mutations. The segmental phenotype that was observed in various patients with FH mutations most likely reflects a type 2 segmental manifestation of cutaneous leiomyomatosis as previously also described for other autosomal dominantly inherited skin diseases. The results presented here extend the current data on the molecular basis of familial cutaneous leiomyomatosis and comprise, to the best of our knowledge, the first genetic study in Dutch and Spanish patients with this disorder. In addition, we review the clinical and molecular aspects of the disease.     

Comparison of quetiapine and risperidone in Chinese Han patients with schizophrenia: results of a single-blind,randomized study

Abstract

Objective:

To evaluate the efficacy and safety of 750?mg/day quetiapine fumarate (Seroquel) in the treatment of Chinese Han patients with schizophrenia.     

布地奈德/福莫特罗干粉联合吸入治疗儿童支气管哮喘临床疗效观察

目的：探讨布地奈德/福莫特罗干粉联合吸入治疗儿童支气管哮喘临床疗效.方法：将40例确诊为支气管哮喘的患儿采用信必可都保治疗.治疗8周.在治疗过程中,观察哮喘、咳嗽、咳痰、肺部哮鸣音等临床症状和体征,FEV1、FEV1占预计值百分比、PEF、PEF占预计值百分比、PEF昼夜波动率等肺功能指标,肝、肾功能以及不良反应.结果：患儿在治疗8周后,临床疗效总有效率达87.5％,患儿的临床症状和肺功能指标得到很大的改善,肺功能指标治疗前后比较差异有统计学意义（P＜0.05）.在治疗的过程中患儿未出现肝、肾功能损害以及严重的不良反应.结论：布地奈德/福莫特罗干粉联合吸入治疗儿童支气管哮喘临床疗效好,值得临床推广应用.     

A safety evaluation of dimethyl fumarate in moderate-to-severe psoriasis

ABSTRACT

Introduction: Psoriasis is a chronic inflammatory disorder affecting skin, nails and joints. Systemic therapy of psoriasis is based upon several drugs which include fumaric acid esters (FAEs), initially introduced in 1959. Since 2017, one of the key substances among FAE spectrum (dimethyl fumarate; DMF) was registered by the European Medicines Agency (EMA) for the treatment of moderate-to-severe psoriasis vulgaris.

Areas covered: This article covers the basic concepts underlying usefulness of DMF in psoriasis and extensively reviews the studies, which included its use in monotherapy of this dermatosis, with a particular emphasis on safety aspects and adverse events (AEs).

Expert opinion: DMF monotherapy is a valuable systemic modality in the management of moderate-to-severe psoriasis as proved by a recent phase III study. AEs associated with DMF therapy are frequent, usually of mild severity, with a dose-independent manner. Occasionally they are burdensome and require drug discontinuation. The most common AEs comprise gastrointestinal symptoms, flushing and white blood cell count abnormalities. The latter require strict monitoring to prevent serious complications. Acknowledging the possibility of AEs, the use of DMF in moderate-to-severe psoriasis is encouraged while the need of further studies still remains.     

聚丙烯输液瓶中抗氧剂含量及迁移量的测定研究

目的研究聚丙烯输液瓶中抗氧剂含量及迁移量的测定。方法采用高效液相色谱法对聚丙烯输液瓶中抗氧剂1010、330、168进行含量测定,以及3种抗氧剂在0.9%氯化钠注射液和5%葡萄糖注射液中的迁移量测定,色谱柱:Agilent ZORBAX-C 18(4.6×150mm×5μm);流动相:乙腈-四氢呋喃-水(63∶30∶7);流速:0.80mL·min^-1;柱温:35℃;检测波长:280nm;进样量:10μL。结果抗氧剂1010、330、168分别在0.016~4.85μg(r=1.0000)、0.014~4.83μg(r=1.0000)、0.0097~4.88μg(r=0.9999)线性良好;含量测定的平均回收率在90.15%~100.24%范围内,RSD均小于4.0%;迁移量测定的平均回收率在91.49%~100.10%,RSD均小于4.0%。结论本方法专属性强,灵敏度高,重现性好,可用于聚丙烯输液瓶质量及相容性评价。     

Dimethyl fumarate and curcumin attenuate hepatic ischemia/reperfusion injury via Nrf2/HO-1 activation and anti-inflammatory properties

BackgroundHepatic ischemia/reperfusion (I/R) injury occurs in different clinical settings as hepatic transplantation, and different types of shock. I/R injury is the main cause of hepatic damage and failure due to the production of reactive oxygen species (ROS) and inflammatory cytokines. Dimethyl fumarate (DMF), an immunomodulatory drug, activates cellular antioxidant signaling pathways exerting cytoprotective properties. Curcumin (CUR), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties.MethodTo study potential protective effects of DMF with CUR against hepatic I/R injury in rats, animals were randomly allocated into seven groups as follows: (1) Sham; (2) DMF (25 mg/Kg, p.o); (3) CUR (400 mg/Kg, p.o.); (4) I/R; (5) DMF + I/R; (6) CUR + I/R; and combination (COM) therapy + I/R. Drugs were given for 14 days before I/R.ResultsCompared with I/R group, COM group showed the best amelioration in hepatic injury induced by I/R insult. This was confirmed by a significant reduction in serum ALT and AST activity with improved histopathological results when compared to every single treatment. Hepatic protection afforded by DMF was mediated by activating Nrf2/HO-1 signaling and increasing GSH and TAC contents. CUR treatment improved the inflammatory markers (TNF-α, IL-1β, Il-6 and iNOS) as well as neutrophilic infiltration assessed as MPO. Moreover, CUR potentiated Nrf2/HO-1 signaling induced by DMF with significant suppression in lipid peroxidation.ConclusionWe concluded that combining DMF and CUR has more efficient hepatoprotective effects against hepatic-induced IRI via potentiating antioxidant and anti-inflammatory properties mediated by Nrf2/HO-1 pathway.     

Comparative effectiveness using a matching-adjusted indirect comparison between delayed-release dimethyl fumarate and fingolimod for the treatment of multiple sclerosis

Objective: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) and fingolimod are approved oral disease-modifying treatments for relapsing–remitting multiple sclerosis. In phase 3 trials, DMF (DEFINE/CONFIRM) and fingolimod (FREEDOMS/FREEDOMS II) resulted in significant reductions in clinical and magnetic resonance imaging activity, with acceptable safety profiles. Direct comparisons of these treatments are not possible due to a lack of head-to-head trials. We compared 2 year efficacy of DMF versus fingolimod at the approved dosage using a matching-adjusted indirect approach.

Research design and methods: Individual patient data from DEFINE and CONFIRM, and aggregate data from FREEDOMS and FREEDOMS II, were pooled and compared using the matching-adjusted in-direct method. To account for cross-trial differences, data from trials with available individual patient data were adjusted to match aggregate data (i.e. average patient characteristics) from trials without patient-level data. Data from DMF-treated patients were weighted such that average baseline characteristics matched those of fingolimod-treated patients. After matching, weighted treatment outcomes for DMF-treated patients (240?mg twice daily) were compared with summary outcomes for fingolimod-treated patients (0.5?mg once daily). All comparison results of DMF versus fingolimod used fingolimod as the reference.

Results: After matching, baseline characteristics were balanced between DMF and fingolimod. At year 2, the efficacy of DMF was similar to that of fingolimod for annualized relapse rate (rate ratio [95% confidence interval (CI)]: 1.11 [0.88, 1.40]), 12 week confirmed disability progression (hazard ratio [95% CI]: 0.90 [0.63, 1.29]), and Multiple Sclerosis Functional Composite (mean difference [95% CI]: 0.04 [?0.05, 0.13]). For patient-reported outcomes (EuroQoL 5-Dimensions questionnaire), the mean differences (95% CI) were 0.05 (0.01, 0.08) for utility score and 3.22 (0.58, 5.86) for visual analog scale score, significantly favoring DMF. There was no significant difference in the percentage of patients with no evidence of disease activity (NEDA) for DMF versus fingolimod among matching-adjusted patients with complete NEDA data: rate ratio (95% CI): 0.92 (0.51, 1.64).

Conclusions: Using the matching-adjusted indirect comparison approach, the efficacy of DMF and fingolimod were similar on all clinical outcomes, while patient-reported outcomes showed greater benefit with DMF. Study limitations include possible confounding from unobserved/unknown differences between trials, and trial length may have been insufficient to detect significant differences on disability progression.

Clinical trial registration: NCT00420212 (DEFINE); NCT00451451 (CONFIRM); NCT00289978 (FREEDOMS); NCT00355134 (FREEDOMS II).     

富马酸奎硫平与氟哌啶醇对精神分裂症抑郁症状影响的对照研究

目的:对照比较富马酸奎硫平与氟哌啶醇对精神分裂症患者抑郁症状的作用。方法:70例精神分裂症偏执型患者随机分为两组,分别予以富马酸奎硫平及氟哌啶醇治疗4周,于入组前、用药第1、14天及第28天以中文版卡尔加里精神分裂症抑郁量表(CDSS-C)、阳性和阴性症状量表(PANSS)及治疗中出现的症状量表(TESS)进行评定,并体格检查及实验室检查,记录不良事件的发生,以量表分值的变化来判断治疗效果及药物不良反应。结果:①70例患者中有21例患者CDSS-C评分≥6分,抑郁发生率为30%;②富马酸奎硫平组与氟哌啶醇组患者在抑郁症状疗效上差异有统计学意义(有效率分别为90.9%和37.5%,P=0.000),在精神病性症状改善方面无统计学差异(有效率分别为44.4%和54.9%,P=0.481);③氟哌啶醇组药物不良反应严重程度及不良反应所引起的痛苦均要明显高于奎硫平组,且对血泌乳素水平影响较大,多个研究时点TESS评分两组差异均有统计学意义(P=0.000～0.002)。结论:富马酸奎硫平相对于氟哌啶醇对精神分裂症的抑郁症状有较好的疗效和较小的不良反应。