Is dose modification or discontinuation of nilotinib necessary in nilotinib-induced hyperbilirubinemia?

Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first- or second-line treatment in imatinib-resistant chronic myelogenous leukemia (CML) patients. Hepatotoxicity due to nilotinib is a commonly reported side effect; however, abnormal liver function test (LFT) results have been reported in asymptomatic cases. When alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are more than five-fold the upper limit of the normal (ULN) or when the serum total bilirubin level is more than three-fold the ULN, dose modification or discontinuation of nilotinib is recommended, resulting in decreased levels of hematological indicators in certain patients with CML. Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels. Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver. The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity. Therefore, nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia, and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings, physicians should consider maintaining nilotinib dose intensity without modifications.     

Arthroscopy of the knee in children and adolescents

A retrospective review was done of 69 children and adolescents (7-17 years old) who underwent 75 arthroscopies of the knee during a 5-year period. Girls were overrepresented (71%). Thirty-eight were children under the age of 16. Of 46 injuries, 34 (74%) happened during sports. Children and adolescents were divided into two age groups based on their presumed state of skeletal maturity (boys 9–15 and girls 7–14 in group I and boys 16–17 and girls 15–17 in group II); meniscal lesions were equally common in the two groups, whereas anterior cruciate ligament tears were more common in older children (NS). Eleven of 17 (65%) anterior cruciate ligament lesions were combined with other intra-articular pathology, most often meniscal tears (9/11). As in other studies, half of the prearthroscopic diagnoses were incorrect. A high frequency of incorrect prearthroscopic diagnoses and of combined lesions justifies arthroscopy as an important diagnostic tool in children and adolescents with a history of twisting knee injury or chronic nonspecific knee problems. Girls practising ball games seem to be especially prone to knee injuries leading to arthroscopy.     

Functional anatomy and biomechanics of the meniscus

The meniscus is no longer considered the evolutionary remnant in the knee joint.Rather, it is now well established as an important structure that is integral to the complex biomechanics and proper functioning of the knee. The medial and lateral menisci form two crescent-shaped wedges of fibrocartilage between the femoral condyles and tibial plateaus.The knee joint biomechanics are based on a complex interaction of these intra-articular structures. The functions ascribed to the menisci include load transmission, shock absorption, stability, proprioception, joint lubrication, and joint nutrition. Load transmission generally is accepted as one of its primary functions. The menisci transmit a portion of the axial forces across the knee joint by converting this load into “hoop stresses.” This is accomplished by their unique shape, composition, and anatomic attachments. The menisci are relatively mobile structures and their motion during knee flexion also is determined by their shape and soft tissue attachments/constraints. Preservation of the meniscal functions is essential, and the authors review the basic anatomic and biomechanical concepts necessary to understand techniques for repair and restoration of these functions.     

美国处理医疗损伤责任纠纷的法律程序

不论是一般的民事或刑事案件,还是医疗损伤责任案件,法律的具体实施程序实际上都是一个个独立的决策过程。本文介绍了美国医疗损伤责任纠纷的法庭外解决方式、医疗损伤责任纠纷的法庭诉讼程序和其他与医疗损伤责任纠纷相关的法律。     

代谢综合征患者血管内皮损伤标志物、C反应蛋白与胰岛素抵抗的关系

目的:观察代谢综合征(MS)患者血管内皮损伤标志物血管性假性血友病因子抗原(vWF:Ag)、凝血酶调节蛋白(TM)及超敏C反应蛋白(Hs-CRP)的水平变化及其与胰岛素抵抗的关系。方法:测定67例MS患者(其中合并冠心病31例)及35例健康对照组TM、vWF:Ag、Hs-CRP、空腹胰岛素(Fins)水平,计算胰岛素抵抗指数(IR)。结果:单纯MS组(B组)TM、vWF:Ag、Hs-CRP水平明显高于对照组(A组),P<0.05;MS合并冠心病组(C组)TM、vWF:Ag、Hs-CRP水平均高于A组和B组,差异有显著性统计学意义(P<0.05)。单因素直线相关分析表明TM、vWF:Ag、Hs-CRP与IR显著正相关(r分别为0.32、0.36、0.38)。结论:MS患者血管内皮损伤标志物、CRP水平升高,且与IR抵抗有关。     

脊髓损伤后bFGF和GFAP的变化及其意义

目的：研究脊髓损伤后碱性成纤维细胞因子和胶质纤维酸性蛋白的变化及其两者的相关性,探讨脊髓损伤后脊髓的自身保护机制以及星形胶质细胞在脊髓损伤中的作用。方法：用免疫组织化学,组织学染色和图像分析的方法检测损伤脊髓碱性成纤维细胞及胶质纤维酸性蛋白表达的动态变化。结果：脊髓损伤后1d损伤脊髓中碱性成纤维细胞的表达明显增高,7d达到高峰,14d末回落,而胶质纤维酸性蛋白表达则在1－14d内呈进行性增高趋势,两指标相关性显著（r=0.777,P=0.001),结论：脊髓损伤后反应性星形细胞胶质化对脊髓的再生和自身修复起着重要作用,提示脊髓本身存在自身保护机制。     

急性颅脑损伤病人免感染营养支持的分析

目的了解国内外急性颅脑损伤病人的营养支持,并就如何做到避免、减少感染并发症的发生作适当分析.资料与方法所借助的专业数据库Medline、万方数据库数字化期刊、清华同方CHKD期刊全文库.在比较、归纳有关内容的基础上进行分析.结果共搜索到论著6篇,专题研究5篇,专题讲座8篇,相关报道13篇.急性颅脑损伤患者的营养支持途径主要为经胃肠外营养(PN)、全肠外营养(TPN)和胃肠内营养(EN).在急性颅脑损伤早期进行营养支持已达成共识,但如何安排肠外营养与肠内营养的使用,一直有不同的主张.结论肠内营养支持比肠外营养支持更可以避免、减少本类病人因营养支持导致感染并发症的发生;对于本类病人进行营养支持可分为两阶段第一阶段肠外营养支持与肠内营养支持同时进行,待脑损伤病情稳定后过渡到第二阶段全胃肠内营养支持.     

关节镜下治疗膝关节半月板损伤7例分析

目的 探讨关节镜下膝关节半月板损伤治疗方法。方法 自2001年12月至2003年5月对7例膝关节半月板损伤进行关节镜下检查及治疗。7例中，右侧5例，左侧2例；内侧半月板损伤3例，外侧半月板4例。O‘Connor关节镜下损伤类型：斜形撕裂2例，水平撕裂1例，纵形撕裂1例，瓣状撕裂2例，复合撕裂1例；半月板部分切除术3例，半月板次全切除术4例。结果 7例均经随访，随访时间12～30个月，平均20个月。7例患者均于次日进行股四头肌等长训练，第3天膝关节开始屈伸活动，第7天下地行走，2周基本恢复正常膝关节活动功能，未发生关节镜器械折断在关节腔现象，无骨关节炎表现。结论 关节镜技术治疗膝关节半月板损伤具有损伤小、恢复快等优点。     

三氯生亚急性经口毒性的研究

目的研究三氯生大鼠亚急性毒性作用。方法选用80只健康Wistar大鼠随机分为40、158、632mg/kg三氯生剂量组及对照组,每组20只,雌、雄各半,经口染毒30d。观察大鼠生长情况、体重、食物利用率、脏体比、血液学指标、生化指标及病理学指标。结果雄性3个剂量组及雌性中、高剂量组体重和食物利用率均低于对照组(P<0·01);高剂量组体重、增重、脾体比低于对照组(P<0·01);高剂量组肝体比及雄性肾体比高于对照组(P<0·01);高剂量组血清丙氨酸转氨酶、尿素氮和肌酐均高于对照组(P<0·05);中剂量组肌酐高于对照组(P<0·05);高剂量组病理组织学检查可见肝肾损害。结论长期大剂量接触三氯生能引起肝脏和肾脏毒性,并可能对免疫系统造成一定影响。     

关节镜治疗半月板囊肿

目的介绍半月板囊肿的发病情况、临床表现、诊断及关节镜治疗方法。方法6例患者均使用关节镜进行探查和治疗，囊肿行刨吸，半月板酌情行全切、次全切或半月板修复术。结果6例患者随访3～14个月，均无膝关节不适主诉。结论半月板囊肿是一种少见的膝关节疾息，MRI检查是诊断的主要依据，关节镜治疗是较好的治疗方法。