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.     

全国著名骨伤专家梁铁民教授学术思想和正骨经验

总结了全国著名骨伤专家梁铁民教授的学术思想和正骨经验,简述了梁老生平。梁老学术思想表现在突出整体观念,主张辨证施术;注重调理气血,强调药物接续;重视望问切触量法五诊结合等三个方面。对于梁老正骨经验先进行了综合论述,进一步佐证其学术思想;后分别从小儿桡骨头半脱位、颈椎错位、胸腰椎小关节错位、肋骨骨折等梁老研究较深入和比较擅长的几个方面进行了阐述。特别是颈椎错位这种高难度高风险的手法操作,体现出梁老高超的手法技艺。     

The role of cardiopulmonary exercise testing in evaluating children with exercise induced dyspnoea

Exercise induced dyspnoea (EID) is a common manifestation in children and adolescents. Although EID is commonly attributed to exercise induced bronchoconstriction, several conditions other than asthma can cause EID in otherwise healthy children and adolescents. Cardiopulmonary exercise testing (CPET) offers a non-invasive comprehensive assessment of the cardiovascular, ventilatory and metabolic responses to exercise and is a powerful diagnostic and prognostic tool. CPET is a reproducible, non-invasive form of testing that allows for comparison against age- and gender-specific norms. CPET can assess the child’s exercise capacity, determine the limiting factors associated with this, and be used to prescribe individualised interventions. EID can occur due to asthma, exercise induced laryngeal obstruction, breathing pattern disorders, chest wall restriction and cardiovascular pathology among other causes. Differentiating between these varied causes is important if effective therapy is to be initiated and quality of life improved in subjects with EID.     

High-magnitude mechanical strain inhibits the differentiation of bone-forming rat calvarial progenitor cells

Purpose: Orthodontic tooth movement occurs during the bone remodeling induced by therapeutic mechanical strain. It is important to investigate the relation between the strength of mechanical stress and bone formation activity. The aim of this study was to determine the effect of high-magnitude mechanical strain on bone formation in detail.

Materials and methods: Osteoblast-like cells isolated from fetal rat calvariae were loaded with 18% cyclic tension force (TF) for 48?h. To phenotypically investigate the effect of TF, we measured the number and the size of bone nodules stained by von Kossa technique on day 21 after cell seeding and determined the calcium content of bone nodules on day 14. Furthermore, we examined the gene expression of BMP-2, Runx2 and Msx2, which are important factors for bone nodule formation, on days 1, 4 and 7 after TF loading.

Results: The maximum bone nodule size in the control group was 1620 and 719?μm in the TF group. Furthermore, the mean number of bone nodules sized over 360?μm in the TF group was significantly decreased compared to the control group. The calcium content was also significantly decreased to 42% by TF loading. The mRNA expression of BMP-2, Runx2 and Msx2 was decreased 1 and 4 days after TF loading.

Conclusion: The differentiation of bone forming progenitor cells into bone nodule forming cells was inhibited by TF due to the decreased expression of bone formation related factors such as BMP-2, Runx2 and Msx2.     

γ-干扰素对大鼠胚胎基底前脑及隔区核团胆碱能神经元分化的影响

为了研究γ-干扰素(IFNγ)对大鼠胚胎基底前脑及隔区核团胆碱能神经元分化的作用,采用免疫组织化学方法对胆碱能神经元的特异性标记酶-胆碱乙酰基转移酶(ChAT)进行染色,ChAT阳性细胞的数量反映了胆碱能神经元的数量,并用14C-乙酰CoA作底物来检测ChAT活性。结果显示,IFNγ处理过的实验组,ChAT阳性细胞数量显著增加,ChAT活性也增加,这种增加被大鼠抗小鼠IFNγ单克隆抗体(Ab-IFNγ)完全拮抗。采用流式细胞术对细胞周期进行分析,细胞周期及细胞百分率无明显改变。用MAP2标记神经细胞,神经细胞数基本未增加。以上结果提示:IFNγ不能促进基底前脑和隔区神经元增殖,胆碱能神经元表达增加不是因为神经元数目增加而是分化的结果。     

Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy

Osteoclastogenesis inhibitory factor (OCIF) is a novel secreted protein that inhibits osteoclastogenesis both in vitro and in vivo. In this study, we examined the effects of OCIF on serum calcium (Ca) concentrations in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. In normal mice, a single intraperitoneal injection of OCIF reduced serum Ca levels in a dose-dependent manner. Significant decrease in serum Ca (by 1.6 ± 0.3 mg/dL, n = 5) was observed 2 h after the injection of OCIF at 20 mg/kg and the hypocalcemic effect continued for up to 12 h. Serum phosphate (Pi) concentrations also decreased in response to OCIF. Urinary excretion of Ca, Pi, and creatinine did not change significantly after injection of OCIF or vehicle. In hypercalcemic, tumor-bearing nude mice, a single intraperitoneal injection of OCIF at 20 mg/kg resulted in a dramatic decrease in serum Ca (maximal decrease 2.8 ± 0.37 mg/dL, n = 11), which continued for up to 24 h. The results suggest that OCIF decreased serum Ca through its inhibitory effect on bone resorption. Furthermore, it is suggested that OCIF has therapeutic potential for the treatment of hypercalcemic conditions such as malignancy-associated hypercalcemia.     

9-顺式维甲酸体外诱导神经母细胞瘤细胞分化的研究

目的：为设计维甲酸治疗神经母细胞瘤可能的有效方案，本文对9-顺式维甲酸（9-cis retinoic acid,9-cisRA)体外诱导分化神经母细胞瘤细胞（SK-N-SH）作用进行了研究。方法：SK-N-SH细胞经9-cisRA处理后，采用相差显微镜，神经纤维银染法，透射电镜观察等手段。观察9-cisRA对细胞生长的影响。结果：9-cisRA作用SK-N-SH细胞7d后，细胞形态发生变化；12d时出现神经原性表型，多个细胞形成“神经节”，节间形成粗而长的类神经纤维；尼氏小体和银染法亦证明细胞产生显著分化，透射电镜观察结果表明，9-cisRA对该细胞有分化作用。却无明显凋亡诱导作用。结论：9-cisRA对神经母细胞瘤细胞体外能产生明显诱导分化作用。     

Cytokeratin expression in a congenital multipotential primitive neuroectodermal tumor

A case of an uncommon congenital primitive neuroectodermal cerebellar tumor (PNET) in a 5-month-old child is reported. After subtotal surgical resection, the residual tumor did not respond to radiation and chemotherapy. Histologically, the tumor was composed of small, round, undifferentiated cells and several other patterns like astrocytomatous, oligodendrogliomatous, and ependymomatous structures. Immunostaining was positive for most of the cells for vimentin and S 100, fewer were positive for glial fibrillary acid protein (GFAP) and neuron-specific enolase, and only a few for synaptophysin. Surprisingly, the tumor showed strong expression of several monoclonal cytokeratins (CK) with different molecular weights, together with epithelial membrane antigen. Furthermore, we found a coexpression of the tumor cells for CK and vimentin, while CK-GFAP and CK-S 100 were negative. Ultrastructurally, intracyto-plasmic intermediate filaments could be observed corresponding to immunohistochemical CK expression. The very strong CK and vimentin expression in this case was interpreted as a sign of the embryonic nature of the tumor.     

李松林副主任医师治疗肾小球肾炎的经验

李松林副主任医师将肾小球肾炎的病机概括为湿、热、毒、瘀、虚等方面，在中医辨证的基础上，结合现代医学对其病因和发病机理的认识及中草药药理作用，针对不同的病理机制和临床表现，提出清热解毒法，活血化瘀法，调补脾肾法，扶正固本法，并视症有机结合，恰当治疗，疗效显著。     

良性前列腺增生中医证型与尿动力学参数相关性研究

目的:探讨良性前列腺增生(BPH)中医证型与尿动力学参数的相关性。方法:152例BPH患者,中医辨证分为肾阴不足、肾阳虚弱、瘀阻水道、脾气虚弱、肺热气郁、湿热下注、痰浊郁结七型,均进行尿动力学检查。结果:152例BPH患者中,肾阳虚弱型71例(46.71%),瘀阻水道型40例(26.31%),肾阴不足型14例(9.21%)。膀胱出口梗阻为III～VI度肾阳虚弱型有58例,瘀阻水道型有38例,其中严重梗阻(V～VI)26例。膀胱逼尿肌收缩功能极弱中(n=12),肾阳虚弱型4例,占33.33%(4/12),瘀阻水道型7例,占58.33%(7/12);膀胱逼尿肌收缩功能弱者中(n=48),肾阳虚弱型为27例,占56.25%(27/48),瘀阻水道型17例,占35.42%(17/48)。结论:BPH中医各辨证分型与膀胱出口梗阻和膀胱逼尿肌收缩力有一定的相关性,从而为中医证型的量化和客观化提供相应的证据。