A case of drug-induced hematotoxicity: from in vivo to in vitro assessment

As part of the early preclinical development of a new antipsychotic compound, Wistar rats of both sexes were dosed orally for upto 7 days. At high doses, expected changes in appearance and behavior, decreases in bodyweight gain and feed intake but also a fluid and pale bone marrow (BM) were observed. Blood cell counts were normal as were clinical chemical values. BM sections showed a red cell hypoplasia. Circulating reticulocytes and erythroblasts on BM smears were decreased suggesting that the compound might have a selective toxicity for the erythroid lineage. In a mechanistic experiment, rats were dosed for 9 days and phlebotomized after 7 days of exposure to stimulate erythroid regeneration. Red-blood cell mass, reticulocytes and erythropoietin (EPO) levels were monitored before and upto 48 h after bleeding. Results showed that an EPO-mediated pathogenesis could be excluded. The effect of the drug on the formation of Colony-forming units (CFU)-E and CFU-GM was then quantitatively measured in vitro after direct exposure to the compound. In two successive assays, rat or human BM cells were incubated with the drug dissolved in the collection medium at final concentrations of 0.3×10^–7 –3×10^–5 M. In the presence of adequate growth factors, CFU-E and CFU-GM were cultured and cell proliferation was compared between treated and control groups. Our results showed an expected inhibition by the drug of the growth of erythroid progenitors associated to a similar effect on myeloid progenitors. The CFU-E and CFU-GM of both human and rat sources were totally inhibited from the concentration of 3×10^–5 M. The IC₅₀ values were consistent with rat peak plasma levels reached in vivo by the drug. Therefore, the short-term cloning assays performed on rat BM cells were sensitive indicators of the hematotoxicity of the compound and were considered as predictive for human toxicity.     

经结膜下穹隆至上颌窦插管术治疗泪道阻塞的临床研究

采用经结膜囊下穹隆至上颌窦插管的术式引流泪液，治疗泪道阻塞引起的溢泪症，获得较为满意的效果。手术的主要步骤是：局麻后于结膜囊下穹隆内1／3区作一4mm长的结膜切口，自筋膜下分离至眶线下5mm。从切口伸入上颌窦骨钻钻通上颌窦顶壁，插入长短适度的义管，并向管内注入生理盐水，证实有液体流入鼻咽部后，固定义管。术后定期冲洗，无需拆线，应用这种术式治疗泪道阻塞引起的溢泪症218眼，其中溢泪完全消失151眼占82．1％，溢泪减轻的27眼占14．6％，总效率96．7％。     

牙根发育不良疾病的研究进展

牙根发育不良疾病是牙齿根部生理性发育出现障碍的疾病。其发病率为1%~10%,乳、恒牙列均可发生,其结果可导致牙根缺如或短根,严重者可造成牙齿过早脱落。国外学者将该疾病统称为短根异常疾病。其发病因素有遗传性疾病、全身性疾病、外源性因素和医源性因素等。     

唇腭裂患者上颌骨牵引成骨术后发音方式的变化

目的:通过对行颅外支架式上颌骨牵引成骨术(rigidexternaldistraction,RED)唇腭裂患者治疗前后的错误发音数量变化、不同发音部位、不同发音方法以及不同类型错误发音发生特点及其变化评价,分析上颌骨RED对患者发音方式的影响。方法:1999年至2001年行上颌骨RED的唇腭裂术后上颌发育不足患者21例,其中男性13例,女性8例,平均年龄15.05岁。所有患者RED前后进行语音测听并分类。治疗前后错误发音的差异性用非参数检验。结果:RED术后42.9%患者错误发音数较RED前增加,19.0%减少,38.1%无变化。从发音部位,舌尖前音错误发音发生率最高,其次为舌面音。从发音方法,错误发音多发于塞擦音。错误发音类型以咽喉摩擦/爆破音为主,其次为腭化构音和声门爆破音。上颌骨RED后腭化构音累及音节数减少,但咽喉摩擦/爆破音和声门爆破音反而增加,尤其是咽喉摩擦/爆破音。结论:唇腭裂患者经RED前移上颌骨后,会对患者发音方式产生影响,在行语音治疗前需考虑全面。     

上颌第一磨牙近中颊根第二根管的治疗体会

目的 探讨在临床上上颌第一磨牙近中颊根第二根管（MB2）的发现及扩通。方法 在25例需要进行根管治疗的上颌第一磨牙上寻找MB2，若无法找到，使用超声根管异物清除工作尖10P清理髓底及慢速圆钻去除预计位置部分牙本质，再次寻找。找到后通畅根管，若无法扩通，使用慢速圆钻在MB2根管口处向根方去除少量牙本质。结合使用EDTA再次通畅根管。结果 25颗治疗齿中有13颗找到MB2（52％），其中2颗是在超声根管锉清理髓室底后发现的，4颗在进一步去除MB2根管口位置的牙本质后发现。8颗治疗齿的MB2通畅（32％），其中3颗自然扩通，5颗在去除MB2根管口处部分矛本质并使用EDTA后通畅。结论 临床上上颌第一磨牙MB2发现率为52％。扩通率为32％。掌握MB2的解剖位置，使用超声方法以及EDTA可提高MB2的发现率和扩通率。     

兔实验性上颌窦炎模型的制备和扩大上颌窦自然开口的疗效

目的 探讨实验性上颌窦炎动物模型的制备方法，并在此基础上讨论扩大兔上颌窦自然开口对慢性上颌窦炎的治疗效果。方法 40只新西兰大白兔分为6组；空白对照组(5侧)，假手术对照组(10侧)、窦口阻塞组(13侧)，仅注入细菌组(10侧)窦口阻塞加注入金黄色葡萄球菌组(20侧)，窦口阻塞加注入肺炎链球菌组(22侧)；将鼻窦炎模型再分为窦口开放和窦口扩大两组，观察术后不同时间的窦腔脓性分泌物和细菌培养情况。结果 对照组(空白对照组 假手术对照组)细菌培养阳性率为13．3％(2／15侧)，窦口阻塞组为84．6％(1l／13侧)，仅注入细菌组为10．0％(1／10侧)，窦口阻塞加注入金黄色葡萄球菌和肺炎链球菌组均为100．0％(20／20侧，22／22侧)。扩大上颌窦自然开口对实验性上颌窦炎的有效率达80.8％(21／26侧)，开放上颌窦窦口对实验性上颌窦炎的有效率达50．0％(8／16侧)。结论 窦口阻塞加注入细菌的方法可成功制造实验性上颌窦炎模型，窦口扩大术对实验性上颌窦炎的疗效较窦口开放术好。     

Pathology of the lung in the fetus and neonate, with particular reference to problems of growth and maturation

The major forms of lung pathology in the perinatal period are reviewed with emphasis on disturbances of growth and maturation. Lung hypoplasia results from impairment in the physiological control of lung growth during the fetal period. It is more common than organogenetic defects which are discussed only briefly. Hyaline membrane disease is now seldom seen in a pure form due to improvements in perinatal care. However, its complications and sequelae such as interstitial emphysema, pneumothorax and bronchopulmonary dysplasia are encountered more frequently. In addition, a wide variety of pathological processes may localize to, or be expressed in, the lung of the newborn, notably asphyxial changes, persistent pulmonary hypertension, haemorrhage and infection.     

釉质发育不全乳牙的超微形态研究

目的：观察不同类型乳牙釉质发育不全的超微表面形态，分析其在分类、致病机制、龋齿易感性中的意义。方法：将发育不全的乳牙固定脱水，临界点干燥，喷金镀膜，日立S－450扫描电子显微镜观察，加速电压20kV。结果：发育不全釉质中存在不同程度形态缺损，病报部位还存在矿化不良。结论：釉质发育不全不仅有釉质量的减少，而且有质的改变，因而可能提高了发育不全釉质对龋齿的易感性。