rhIL-1Ra对恒河猴肾脏毒性的病理组织学观察

目的 观察重组人白介素-1受体拮抗剂(rhIL-1Ra)的毒性靶器官及毒性的严重程度.方法 32只成年恒河猴分为rhIL-1Ra 2mg/(kg·d)(n=6)、10mg/(kg·d)(n=6)和50mg/(kg·d)(n=6)连续给药90天组,10mg/(kg·d)(n=4)连续给药30天组,正常对照组(n=5)和溶剂对照组(n=5).rhIL-1Ra为皮下注射给药,每日1次.观察指标包括一般药物反应、尿八项、心电图、眼底检查、外周血细胞计数及白细胞分类、凝血时间、血清生化、外周血T细胞亚群和猴抗rhIL-1Ra抗体测定、脏器重量和脏器系数、常规病理组织学检查.结果 给药后30天各给药组动物血清非特异性抗体明显升高.rhIL-1Ra 2mg/(kg·d)组其他检测指标均未见明显地改变.rhIL-1Ra 10mg/(kg·d)组给药后90天肾小球毛细血管基底膜明显增厚,但此剂量给药时间为30天时未见任何异常.rhIL-1Ra 50mg/(kg·d)组肾小球及肾小管中蛋白性液体量多,小球毛细血管基底膜增厚更为严重,且停药30天后基底膜增厚程度仍未见明显减轻或改善.结论 rhIL-1Ra的主要毒性靶器官为肾脏,2mg/(kg·d)为安全剂量,10mg/(kg·d)给药30天时为安全剂量,给药90天为恒河猴中毒性剂量,而50mg/(kg·d)为明显的毒性反应剂量,可产生难以恢复的肾脏纤维化.     

复方磷酸萘酚喹对疟原虫DNA含量及溶酶体pH值的影响

目的 :探讨磷酸萘酚喹及其复方的抗疟作用机制。方法 :采用流式细胞术 (FCM)分析了磷酸萘酚喹、青蒿素及两者组成的复方对鼠伯氏疟原虫K173株DNA含量及溶酶体pH值的影响。结果 :复方磷酸萘酚喹和青蒿素均可以使原虫寄生率迅速下降 ,但两者对原虫DNA含量的影响均不明显。磷酸萘酚喹单药给药后 1h疟原虫溶酶体pH值开始升高 ,药后 2h升至最高 ,到 4h基本恢复至药前水平 ;青蒿素对疟原虫溶酶体pH值的影响是先降后升 ;复方磷酸萘酚喹给药后溶酶体pH值变化类似青蒿素 ,但作用较弱。结论 :复方磷酸萘酚喹和青蒿素的杀虫机制与其对疟原虫DNA及疟原虫溶酶体pH值的影响不相关     

速效抗晕胶囊口服对Beagle犬长期毒性的研究

目的 观察速效抗晕胶囊对Beagle犬的长期毒性.方法 速效抗晕胶囊以17.5 mg/kg、35.0 mg/kg、87.5 mg/kg剂量,连续给Beagle犬灌胃90 d,停药30 d,观察一般状况,称体质量,测肛温、心电图、血液学指标、血液生化指标、并做尿液检查、骨髓检查和病理组织学检查.结果 与对照组相比,给药组动物服药后,随着剂量增加而更兴奋,体质量随剂量增加而下降,其余一般状况与对照组相比无明显变化;心电图、血液学指标、血液生化指标、尿液检查、骨髓检杳均未见明显差异;病理组织学检查未见与药物毒性相关的主要脏器组织形态学改变;停药后给药组体质量和精神恢复正常,也未见药物延迟性毒性反应.结论 速效抗晕胶囊犬长期毒性试验安全剂量为17.5 mg/kg.     

3种抗疟药物对马里维和任务区恶性疟疾治疗效果比较

目的 比较3种抗疟药物治疗马里维和任务区恶性疟疾的临床效果。方法 回顾性分析自2014年1月至2018年12月马里维和任务区收治的108例恶性疟疾患者的临床资料。根据治疗方法将患者分为蒿甲醚组(n=45)、复方磷酸萘酚喹片组(n=31)及复方双氢青蒿素片组(n=32)。主要观察指标包括患者的发热持续时间、症状持续时间及住院时间。次要观察指标为肝、肾功能的检验结果,肝功能指标包括谷丙转氨酶(ALT)、谷草转氨酶(AST);肾功能指标包括尿素氮、肌酐。结果 3组患者发热持续时间比较,差异无统计学意义(P>0.05)。复方双氢青蒿素片组治疗后患者的症状持续时间明显短于篙甲醚组,组间比较,差异有统计学意义(P<0.05)。复方磷酸萘酚喹片组和复方双氢青蒿素片组患者的住院时间明显短于蒿甲醚组,差异均有统计学意义(P<0.05);而复方磷酸萘酚喹片组与复方双氢青蒿素片组比较,差异无统计学意义(P>0.05)。复方磷酸萘酚喹片组治疗1～2 d及3 d时的ALT均高于治疗后5～6 d,差异均有统计学意义(P<0.05);复方磷酸萘酚喹片组治疗1～2 d时的AST高于治疗后...     

前药dl-PHPB在Beagle犬中反复给药毒性及伴随毒代动力学研究

目的评价I类抗脑缺血新药2-（α-羟基戊基）苯甲酸钾（dl-PHPB）在Beagle犬中反复给药30d的毒性及伴随毒代动力学。方法 Beagle犬反复给药30d,给药剂量分别为6、18、54mg/kg（分别相当于临床人体用量的3.6、10.8和32.4倍）并设溶剂对照组,停药后恢复期观察3周。同时采用HPLC-UV方法测定不同剂量下首次和末次给药的血清药物浓度。结果 54mg/kg剂量组的主要毒性反应为部分动物给药过程中出现头部颤抖,给药结束时可见血尿素氮（BUN）、肌酐（Cr）和尿pH值有所增加,相关脏器病理组织学检查未见异常;恢复期结束时上述指标均恢复正常。在6、18、54mg/kg剂量下,药后1h内dl-PHPB即完全转化为丁基苯酞（dl-NBP）。首次给药后,其活性代谢物dl-NBP的AUC0-∞分别为2.8、7.2、32.5μg·h^-1·ml^-1,末次给药dl-NBP的AUC0-∞分别为2.9、8.1、38.7μg·h^-1·ml^-1。其转化为dl-NBP的暴露比（AUC30th/AUC1st）分别为1.02、1.12和1.17。结论 Beagle犬静脉滴注dl-PHPB30d连续给药非毒性反应剂量为18mg/kg。伴随毒代动力学研究显示dl-PHPB的毒性反应与其快速转化为dl-NBP密切相关。     

两种抗疟药治疗恶性疟疾临床疗效观察

目的：观察双氢青蒿素哌喹片和复方磷酸萘酚喹片治疗恶性疟疾的临床疗效及不良反应。方法：将驻利比里亚中国维和二级医院收治的轻型恶性疟66例,随机分为观察组和对照组各33例。观察组采用双氢青蒿素哌喹片治疗,对照组采用复方磷酸萘酚喹片治疗。比较两组治愈率、复燃率、平均原虫转阴时间和平均退热时间及不良反应。结果：两组治愈率与复燃率均为97．0％和3．0％;平均原虫转阴时间分别为（45．2±17．7）h和（48．3±19．1）h;平均退热时间分别为（25．5±8．7）h及（27．9±7．8）h;两组比较,均差异不显著（P〉0．05）。两组不良反应发生率分别为12．1％和21．2％,两组比较,差异显著（P〈0．05）。但不良反应均较轻微,停药后均自行缓解。结论：双氢青蒿素哌喹片和复方磷酸萘酚喹片治疗恶性疟治愈率高,复燃率低,均可作为治疗轻型恶性疟的一线药物,但双氢青蒿素哌喹片不良反应较少。     

中剂量丙种球蛋白治疗特发性血小板减少性紫癜近期疗效观察

目的　观察中剂量丙种球蛋白治疗特发性血小板减少性紫癜 (ITP)的近期疗效。方法　将确诊的 74例ITP患者 ,随机分为中剂量丙种球蛋白治疗组 39例 ,丙种球蛋白 0 .2g·kg·d-1,iv ,连续给药 4d ,治疗完成后用肾上腺皮质激素维持 ;大剂量丙种球蛋白为对照组 35例 ,丙种球蛋白 0 .4g·kg·d-1,iv ,连续给药 4d ,维持药物同治疗组。结果　治疗组 39例 ,显效 17例 ,总有效率 92 .31% ;对照组 35例 ,显效 16例 ,总有效率 94 .2 8%。两组比较无显著差异 (P >0 .0 5 ) ,治疗组未发现不良反应。结论　中剂量丙种球蛋白对ITP的近期治疗 ,疗效确切 ,无不良反应 ,且降低费用。     

萘酚喹衍生物的合成及体内抗疟活性评价

目的通过对萘酚喹进行改造,以发现活性更高的抗疟药。方法用3-羟基丙胺、4-羟基丁胺、N-(2-氨基乙基)吗啉、3,5-二甲基哌啶、3,5-二甲基哌嗪替代萘酚喹特丁氨基,采用曼尼希反应与关键中间体7缩合,得到目标化合物,结构经1H-NMR和ESI-MS验证。采用4日抑制法对衍生物进行体内抗疟活性评价,计算ED50。结果合成的5个萘酚喹衍生物为新化合物,均未见报道。体内活性结果显示化合物8、9、11具有抗疟活性,其中化合物9的抗疟活性较好。结论萘酚喹的特丁氨基被不同的含氮六元环取代会影响化合物的体内抗疟活性。     

rhIL-11+rhG-CSF对中子急性放射病狗的治疗作用

目的　探讨rhIL-11与rhG-CSF联用对中子急性放射病(ARS)的治疗作用。方法　18只雄性成年比格狗,随机分为照 射对照组、对症治疗组和两因子+对症联合治疗组。所有动物均接受90%中子照射,吸收剂量为2.0Gy。联合治疗组动物于照射后 即刻开始皮下注射rhG-CSF10μg/(kg·d)和rhIL-1150μg/(kg·d),给药时间分别为14天和21天,观察照射后动物外周血象及骨髓 有核细胞形成CFU-GM能力的变化。结果　对症治疗组和联合治疗组动物全部存活,而照射对照组动物30天存活率为57.1%。照 射后联合治疗组各检测点外周血白细胞数及恢复期血小板和红细胞数均明显高于照射对照组及对症治疗组。照射后1天,联合治疗 组骨髓CFU-GM数量是两个对照组的6倍(P<0.01),33天分别是照射对照组、对症治疗组的1.75和1.46倍(P<0.01)。结论　 rhIL-11与rhG-CSF联合给药可以升高2.0Gy裂变中子照射狗的外周血白细胞、血小板数的最低值,缩短白细胞最低值持续的时间, 加速骨髓造血功能的恢复,对2.0Gy中子照射狗有明显的治疗作用。     

重组人血管内皮细胞抑制因子对犬的长期毒性研究

目的 评价重组人血管内皮细胞抑制因子(endostatin)注射液的长期毒性作用,为临床试验提供安全性依据.方法 将24只纯种Beagle犬随机分为4组,每组6只,雌雄各半,其中一组为空白对照组,另3组分别按1.6mg/kg、6.3mg/kg和25.0mg/kg静脉注射endostatin注射液,每天注射1次,连续3个月,观察犬的一般毒性反应、体重、心电图、血液学、血清生化学、尿常规及病理组织学等指标.结果 在给药早期见高剂量组一犬出现食欲减退、轻度腹泻等症状.这些症状持续4天左右自行消失.各剂量组犬的体重增长正常,心电图导联Ⅱ、血液学、血清生化学、尿常规等指标均在正常范围内.病理组织学检查见低剂量组和空白对照组各有一犬的肝、肾组织有不同程度的病理改变,分析这些病理改变为犬的自发性病变,与该药物的使用、剂量无关.结论 在此试验条件下,endostatin注射液静脉注射给药3个月对Beagle犬的无毒剂量为6.3mg/kg.     

Knee injury and Osteoarthritis Outcome Score (KOOS) - validation of a Swedish version

The Knee injury and Osteoarthritis Outcome Score (KOOS) is a self-administered instrument measuring outcome after knee injury at impairment, disability, and handicap level in five subscales. Reliability, validity, and responsiveness of a Swedish version was assessed in 142 patients who underwent arthroscopy because of injury to the menisci, anterior cruciate ligament, or cartilage of the knee. The clinimetric properties were found to be good and comparable to the American version of the KOOS. Comparison to the Short Form-36 and the Lysholm knee scoring scale revealed expected correlations and construct validity. Item by item, symptoms and functional limitations were compared between diagnostic groups. High responsiveness was found three months after arthroscopic partial meniscectomy for all subscales but Activities of Daily Living.     

The acutely limping child

Acute limping may be the result of multiple pathologies in children. The differential diagnosis varies based on the age of the child. Irrespective of age, the initial imaging work-up includes AP and frog leg radiographs of the pelvis and ultrasound; MRI may sometimes be helpful. In children less than 3 years, infections and trauma are most frequent. MRI is the imaging modality of choice when osteomyelitis is clinically suspected. Between the ages of 3 and 10 years, transient synovitis of the hip and Legg-Calvé-Perthes disease are main considerations but infection, inflammation and focal bony lesions are also considered. In children over 10 years, slipped capital femoral epiphysis also is considered.     

Do Balance Board Training Programs Reduce the Risk of Ankle Sprains in Athletes?

Introduction Ankle sprains are the most common musculo-skeletal injury that occurs in athletes,particularly in sports that require jumping and landing on one foot such as soccer,and basketball(1-4).These injuries often result in significant time loss from participation,long-term disability,and have a major impact on health care costs and resources(5-8).     

High Intensity Interval Training:New Insights

KEY POINTS ·High-intensity interval training(HIT)is characterized by repeated sessions of relatively brief，intermittent exercise.often performed with an“a11 out”effort or at an intensity close to that which elicits peak oxygen uptake(i.e.，≥90%of VO2 peak).     

Endovascular management of carotid-cavernous fistulas

Objective To investigate endovascular treatment of traumatic direct carotid-cavernous fistulas （CCF） and their complications such as pseudoaneurysms. Methods： Over a five-year period, 22 patients with traumatic direct CCFs were treated endovascularly in our institution. Thirteen patients were treated once with the result of CCF occluded, 8 twice and 1 three times. Treatment modalities included balloon occlusion of the CCF, sacrifice of the ipsilateral internal carotid artery with detachable balloon, coll embolization of the cavernous sinus and secondary pseudoaneurysms, and covered-stem management of the pseudoaneurysms. Results All the direct CCFs were successfully managed endovascularly. Four patients developed a pseudoaneurysm after the occlusion of the CCF with an incidence of pseudoaneurysm formation of 18.2% （4/22）. A total number of 8 patients experienced permanent occlusion of the ICA with a rate of ICA occlusion reaching 36.4% （8/22）. Followed up through telephone consultation from 6 months to 5 years, all did well with no recurrence of CCF symptoms and signs. Conclusion Traumatic direct CCFs can be successfully managed with endovascular means. The pseudoaneurysms secondary to the occlusion of the CCFs can be occluded with stent-assisted coiling and implantation of covered stents.     

Developmental validation of the PowerPlex(®) ESI 16 and PowerPlex(®) ESI 17 Systems: STR multiplexes for the new European standard

In response to the ENFSI and EDNAP groups’ call for new STR multiplexes for Europe, Promega^® developed a suite of four new DNA profiling kits. This paper describes the developmental validation study performed on the PowerPlex^® ESI 16 (European Standard Investigator 16) and the PowerPlex^® ESI 17 Systems. The PowerPlex^® ESI 16 System combines the 11 loci compatible with the UK National DNA Database^®, contained within the AmpFlSTR^® SGM Plus^® PCR Amplification Kit, with five additional loci: D2S441, D10S1248, D22S1045, D1S1656 and D12S391. The multiplex was designed to reduce the amplicon size of the loci found in the AmpFlSTR^® SGM Plus^® kit. This design facilitates increased robustness and amplification success for the loci used in the national DNA databases created in many countries, when analyzing degraded DNA samples. The PowerPlex^® ESI 17 System amplifies the same loci as the PowerPlex^® ESI 16 System, but with the addition of a primer pair for the SE33 locus. Tests were designed to address the developmental validation guidelines issued by the Scientific Working Group on DNA Analysis Methods (SWGDAM), and those of the DNA Advisory Board (DAB). Samples processed include DNA mixtures, PCR reactions spiked with inhibitors, a sensitivity series, and 306 United Kingdom donor samples to determine concordance with data generated with the AmpFlSTR^® SGM Plus^® kit. Allele frequencies from 242 white Caucasian samples collected in the United Kingdom are also presented. The PowerPlex^® ESI 16 and ESI 17 Systems are robust and sensitive tools, suitable for the analysis of forensic DNA samples. Full profiles were routinely observed with 62.5 pg of a fully heterozygous single source DNA template. This high level of sensitivity was found to impact on mixture analyses, where 54–86% of unique minor contributor alleles were routinely observed in a 1:19 mixture ratio. Improved sensitivity combined with the robustness afforded by smaller amplicons has substantially improved the quantity of data obtained from degraded samples, and the improved chemistry confers exceptional tolerance to high levels of laboratory prepared inhibitors.     

Bronchial stump fistula :treatment with covered retrievable hinged metallic stents-preliminary clinical experience

Objective To evaluate the preliminaily clinical efficacy and retrievability of a retrievable hinged covered metallic stent in the treatment of the bronchial stump fistula （BSF）. Methods Between April 2003 and March 2005, 8 patients with bronchial stump fistula after pneumonectomy or lobectomy were treated with two types （A and B） of retrievable hinged covered metallic stents. Type A stent was placed in 6 patients and type B in 2 under fluoroscopic guidance. The stent was removed with a retrieval set when BSF was healed or complications occurred. Results Stent placement in the bronchial tree was technically successful in all patients, without procedure-related complications. Immediate closure of the BSF was achieved in all patients after the procedure. Stents were removed from all patients but one. Removal of the stents was difficult in two patients due to tissue hyperplasia. Patients were followed up for 6 - 21 months. Placement of the stents remained stable in all patients except one due to severe cough. Permanent closure of BSF was achieved in 7 （87.5%） of 8 patients. Conclusion Use of a retrievable hinged covered expandable metallic stent is a simple, safe, and effective procedure for closure of the BSF. Retrieval of the stent seems to be feasible. （J Intervent Radiol, 2007, 16： 253-257）     

Prevalence and severity of hip and groin pain in sub‐elite male football: a cross‐sectional cohort study of 695 players

The purpose of this study was twofold: (a) to investigate the prevalence of hip and groin pain in sub‐elite male adult football in Denmark and (b) to explore the association between prevalence and duration of hip and groin pain in the previous season with the Copenhagen Hip and Groin Outcome Score (HAGOS) in the beginning of the new season. In total 695 respondents from 40 teams (Division 1–4) were included. Players completed in the beginning of the new season (July–Sept 2011) a self‐reported paper questionnaire on hip and/or groin pain during the previous season and HAGOS. In total 49% (95% CI: 45–52%) reported hip and/or groin pain during the previous season. Of these, 31% (95% CI: 26–36%) reported pain for >6 weeks. Players with the longest duration of pain during the previous season had the lowest HAGOS scores, when assessed at the beginning of the new season, P < 0.001. This study documents that half of sub‐elite male adult football players report pain in the hip and/or groin during a football season. The football players with the longest duration of pain in previous season displayed the lowest HAGOS scores in the beginning of the new season.