Non-clinical single- and repeated-dose toxicity studies of ET-26 hydrochloride in rats

ET-26 hydrochloride (ET-26HCl), a novel analog of etomidate, induces as effective sedation, with good cardiac and respiratory stability, as etomidate but with mild adrenocortical suppression. The objective of this study was to evaluate the potential adverse effects of ET-26HCl in rats. In a single-dose toxicity study, abnormal urine color (red) was observed in all groups: control (100%), 8 mg/kg (10%), 16 mg/kg (50%), and 20 mg/kg (70%) ET-26HCl, which returned to normal on the day of dosing. There were no mortalities or serious toxicological signs; the maximum tolerable dose of ET-26HCl was 20 mg/kg. In the repeated-dose toxicity study, deaths occurred in the 12- (13.33% of males) and 16-mg/kg/day (20% of males and 3.33% of females) groups. Abnormal urine color (red or brown) was detected in the control group (10%) and all treatment groups (30%, 46.67%, and 40% at 8, 12 and 16 mg/kg/day, respectively), at a frequency of 1.43% in the control group, 4.76% in 8 mg/kg/day, 7.62% in 12 mg/kg/day, and 4.29% in 16 mg/kg/day. Increases in neutrophils and plasma fibrinogen were temporary and recoverable effects. Macroscopic and histopathologic changes were found only at the injection sites: abnormal skin color, scabbing, thrombus, ulceration, and inflammation. During the recovery period, there was evidence of reversibility, including fibroblast proliferation and vessel recanalization. The no-observed-adverse-effect level of ET-26HCl was 8 mg/kg/day. Toxicokinetic variables of ET-26HCl, except the calculated initial concentration in females on Day 1, showed a dose-dependent increase to exposure, with no gender difference and no evidence of accumulation.     

加拿大药品特别准入计划对我国同情用药制度的启示

目的在新型冠状病毒肺炎患者没有特效药可治的背景下,为完善我国同情用药制度提供国外经验借鉴。方法通过文献研究等方法对加拿大的特别准入计划的具体内容进行研究。结果 加拿大具有相对完善的制度体系,值得我国借鉴。结论 结合我国具体国情,从医生、政府、企业三个维度进行同情用药制度的完善。     

儿童霍奇金淋巴瘤83例临床研究

目的 探讨儿童霍奇金淋巴瘤(HL)的病理及临床特点,初步分析患者EB病毒感染状态,总结根据危险度分层治疗即化疗联合低剂量受累野放疗的疗效及相关不良反应.方法 回顾性分析2003年1月至2013年3月接受规范化治疗的83例HL患儿的临床资料.全部行活组织检查病理形态及免疫组织化学检查,参照世界卫生组织(WHO)2001病理分型标准诊断,按HL Ann Arbor分期标准分期.根据不同的危险因素及对治疗的反应,将患儿分成低危、中危、高危3个治疗组.结果 83例患儿中,男性69例,女性14例;Ⅲ～Ⅳ期59例(71.1％).1例为结节性淋巴细胞为主型,其余82例均为经典型HL,其中64例(77.1％)为经典混合细胞型.侵犯部位广泛,巨大瘤块34例(41.0％),大于4个淋巴结区受累26例,有B组症状35例.70例行EB病毒感染指标[潜伏膜蛋白(LMP)和(或)EB病毒编码RNA(EBER)染色]检测,65例(92.9％)阳性.随访时间(72±32)个月.低危组3例,中危组27例,高危组53例.总体生存率97.5％,5年无事件生存率92.8％.结论 儿童HL男性多于女性,与EB病毒相关,病理以混合细胞型居多,预后相对较好.根据疾病危险度进行联合化疗及低剂量受累野放疗的近期疗效可靠,但随访时间尚短,需进一步观察远期不良反应.     

Advances in chemical pharmacotherapy for the treatment of pediatric immune thrombocytopenia

Introduction: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder of heterogeneous pathophysiological mechanisms. Treatment endpoints include elevation of platelets and reduction of bleeding risk, elevation of quality of life, reduction of concomitant therapies and prevention from bleeding. Persistent and chronic ITP is more common in adults but occurs in children. Standard therapies include corticosteroids and immunoglobulins, both associated with side effects. There are new treatments, such as thrombopoietin-receptor agonists and promising investigational drugs.

Areas covered: Experience from the management of adults is valuable for children with persistent and chronic symptomatic ITP. In this review first- and second-line therapies, but also investigational drugs for children with ITP are discussed.

Expert opinion: Although time-consuming and based on experience, children with no or mild bleeding can be safely managed with a watch and wait strategy. Chronic symptomatic immune thrombocytopenia is an area of second-line treatments based on a highly individualized approach. Furthermore, there are investigational drugs, which may also be of benefit for children with chronic symptomatic ITP.     

Rates and risks of transmission of smallpox and mechanisms of prevention

In 1980, the World Health Organization declared smallpox eradicated from the world; the last known natural case had occurred in Somalia in 1977, and the United States had stopped routinely vaccinating its citizens in 1972. However, with increasing concerns regarding domestic and international terrorism, smallpox has resurfaced as a potential threat to global health. We review the direct and indirect modes of smallpox transmission and how patterns of transmission vary substantially, depending on the severity of circulating disease, vaccination status, environmental and socioeconomic factors, and the setting of an outbreak. We examine mechanisms for controlling outbreaks of disease and preventing further transmission in the event of an outbreak, with an emphasis on smallpox vaccination.     

Safety and immunogenicity of a primary series of Sabin-IPV with and without aluminum hydroxide in infants

Background

An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and middle-income countries in the context of the global polio eradication initiative.

Method

Safety and immunogenicity of Sabin-IPV (sIPV) was evaluated in a double-blind, randomized, controlled, dose-escalation trial in the target population. Healthy infants (n = 20/group) aged 56–63 days, received a primary series of three intramuscular injections with low-, middle- or high-dose sIPV with or without aluminum hydroxide or with the conventional IPV based on wild poliovirus strains (wIPV). Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after three vaccinations.

Results

The incidence of local and systemic reactions was comparable with the wIPV. Seroconversion rates after three vaccinations were 100% for type 2 and type 3 polioviruses (both Sabin and wild strains) and 95–100% for type 1 polioviruses. Median titers were high in all groups. Titers were well above the log₂(titer) correlated with protection (=3) for all groups. Median titers for Sabin-2 were 9.3 (range 6.8–11.5) in the low-dose sIPV group, 9.2 (range 6.8–10.2) in the low-dose adjuvanted sIPV group and 9.8 (range 5.5–15.0) in the wIPV group, Median titers against MEF-1 (wild poliovirus type 2) were 8.2 (range 4.8–10.8) in the low-dose sIPV group, 7.3 (range 4.5–10.2) in the low-dose adjuvanted Sabin-IPV group and 10.3 (range 8.5–17.0) in the wIPV group. For all poliovirus types the median titers increased with increasing dose levels.

Conclusion

sIPV and sIPV adjuvanted with aluminum hydroxide were immunogenic and safe at all dose levels, and comparable with the wIPV.EudraCTnr: 2011-003792-11, NCT01709071.     

不同时机行连续性肾替代治疗对重症急性胰腺炎疗效的影响

目的：探讨连续性肾替代治疗（ CRRT）时机对重症急性胰腺炎（ SAP）患者疗效的影响。方法回顾性分析38例重症急性胰腺炎患者的临床资料,按开始CRRT时机分为两组,早期组（21例）为重症急性胰腺炎发病后48 h内行连续性肾替代治疗,晚期组（17例）为48 h以后行连续性肾替代治疗,比较两组APACHEⅡ评分、ICU住院时间、28 d病死率。结果与早期组比较,晚期组第1、2天时APACHEⅡ评分均明显升高（ t＝2．231、2．304,均P＜0．05）;与早期组比较,晚期组入院时、CRRT开始时APACHEⅡ评分差异均无统计学意义（均P＞0．05）;与早期组比较,晚期组ICU住院时间、28 d病死率均明显升高（ t＝2．156,χ2＝4.293,均P＜0．05）;两组入院时年龄、性别、APACHE Ⅱ评分等差异均无统计学意义（均P＞0．05）。结论早期行CRRT治疗,可以降低SAP患者病死率,减少住院时间。     

韦氏颈椎手法配合中药烫疗治疗神经根型颈椎病的临床研究

目的：观察韦氏颈椎手法配合中药烫疗治疗神经根型颈椎病的临床疗效.方法：将264例神经根型颈椎病患者随机分为治疗组133例和对照组131例.治疗组采用韦氏颈椎手法配合中药烫疗治疗,对照组采用颈椎牵引配合中药烫疗治疗.治疗结束后3个月分别采用Boeden测量法、Northwick Park颈痛量表及《中医病证诊断疗效标准》中的颈椎病疗效标准评定并比较2组患者的颈椎生理曲度、颈椎症状体征功能评分及总体疗效.结果：①颈椎生理曲度.治疗前2组患者颈椎生理曲度比较,差异无统计学意义[（3.67±2.32） mm,（3.15±2.14） mm,t=-1.194,P=0.234];治疗结束后3个月2组患者颈椎生理曲度均改善[（7.79±3.74）mm,（5.98 ±3.56）mm],治疗组改善更明显[（4.12±2.34）mm,（2.83±1.18）mm,t=5.221,P=0.000].②颈椎症状体征功能评分.治疗前2组患者颈椎症状体征功能评分比较,差异无统计学意义[（38.77±12.25）分,（38.36±8.79）分,t=0.311,P=0.756];治疗结束后3个月2组患者的颈椎症状体征功能评分均降低[（17.65±5.94）分,（20.50±8.79）分],治疗组降低更明显[（21.12±10.64）分,（17.86±8.93）分,t=2.310,P=0.022].③总体疗效.治疗组治愈32例,显效81例,有效15例,未愈5例;对照组治愈12例,显效85例,有效17例,未愈17例.治疗组总体疗效优于对照组,差异有统计学意义（Z=-3.569,P=0.000）.结论：采用韦氏颈椎手法配合中药烫疗治疗神经根型颈椎病,能有效改善患者的临床症状与体征,以及颈椎生理曲度和颈椎功能,疗效优于颈椎牵引配合中药烫疗,值得临床推广应用.     

张力带别针结合钢缆内固定与空心钉结合钢丝张力带内固定治疗髌骨横形骨折的比较研究

目的：比较张力带别针结合钢缆内固定和空心钉结合钢丝张力带内固定治疗髌骨横形骨折的临床疗效与安全性.方法：回顾性分析67例髌骨横形骨折患者的病例资料,其中采用张力带别针结合钢缆内固定33例（观察组）,采用空心钉结合钢丝张力带内固定34例（对照组）;横断骨折32例,上极骨折16例,下极骨折11例,粉碎性骨折8例.比较2组患者的手术时间、骨折愈合时间、术后并发症的发生情况及患者满意度情况.参照B（o）stman髌骨骨折疗效评分标准评定2组患者的临床疗效.结果：①一般指标.观察组患者的手术时间小于对照组[（40.80±27.50） min,（42.50±23.30） min,t=7.151,P=0.042];2组患者骨折愈合时间比较,差异无统计学意义[（12.09±1.77）min,（12.51±1.21） min,t=6.823,P=0.062].②临床疗效与患者满意度.观察组优28例、良4例、可1例,对照组29例、良3例、可2例.2组患者临床疗效比较,差异无统计学意义（Z=0.000,P=1.000）.观察组患者满意27例、基本满意4例、不满意2例,对照组患者满意25例、基本满意5例、不满意4例.2组患者满意度比较,差异无统计学意义（Z=-0.853,P=0.394）.结论：对于闭合性髌骨横形骨折患者而言,虽然张力带别针结合钢缆内固定与空心钉结合钢丝张力带内固定在骨折愈合时间、临床疗效、患者满意度及安全性方面无明显差异,但张力带别针结合钢缆内固定具有操作简单、手术时间短的优点,是治疗髌骨横形骨折的一种较理想的方法,值得临床推广应用.