Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors.

PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.     

精子冷冻环无保护剂玻璃化冷冻方法的初步研究

目的探讨精子冷冻环无保护剂玻璃化冷冻方法的可行性。方法正常精液标本上游处理后,进行常规冷冻和冷冻环无保护剂的玻璃化冷冻,复苏后分别从活力参数及电镜下超微结构等指标比较两种冷冻方法的效果。结果两种方法冷冻后精子存活率、活动率之间差异无显著性(48%∶48%;44.5%∶43.5%,P>0.05),但均较未冷冻的89%和88.5%明显下降(P<0.001)。超微结构亦较未冷冻时发生了一定的改变,但核结构基本保持完整。结论精子冷冻环无保护剂的玻璃化冷冻是一种简单、方便而行之有效的冷冻方法。     

暴发流行的肺炎衣原体肺炎影像学表现分析

目的研究肺炎衣原体肺炎暴发流行的胸部影像学特征表现。方法对经过痰和咽试子标本,PCR,MIF检测证实的15例暴发流行的肺炎衣原体肺炎住院患者胸部X线和高分辨CT表现进行分析。结果本组暴发流行的肺炎衣原体肺炎患者均有发热,头痛,全身肌肉酸痛,干咳,声音嘶哑,咽痛等症状。肺部呼吸音减低或细湿啰音4例(26.7%),出现明显肺部影像学表现10例(66.7%)。10例暴发流行的肺炎衣原体肺炎常表现为多发或单发以小叶为中心阴影和腺泡状结节影(100%),病变以两中、下肺叶,外、中带分布;以小叶分布的气腔实变和磨玻璃样阴影(分别为100%和40%)和支气管血管束增厚(90%)。无肺门或纵隔淋巴结增大和胸腔积液。结论暴发流行的肺炎衣原体肺炎具有群体发病,临床和影像学表现有相似的特征,早期CT检查更能真实地反映病变大小、多少和分布范围。     

急性肺栓塞时心肌血流灌注的变化

目的观察急性肺栓塞（APE）后冠状动脉血流量及心脏肌钙蛋白T（cTnT）与肌红蛋白（Mb）含量变化，探讨心肌血流灌注在急性肺栓塞继发心肌损伤机制中的作用。方法通过介入方法经导管注入自体血栓选择性栓塞肺动脉，建立不同栓塞面积的急性肺栓塞动物模型。监测栓前、栓后5、30min，1、2h冠状动脉血流量变化及栓后4h血清cTnT与Mb含量。结果急性肺栓塞后血清cTnT与Mb含量升高。急性肺栓塞导致冠状动脉血流量显著下降，肺血管栓塞后15～30min降至最低值，30min后趋于平稳。右冠血流量下降程度与肺栓塞面积有显著相关性。结论冠状动脉血流量减少及血清心肌结构蛋白含量升高为急性肺栓塞继发心肌缺血改变提供了直接证据。急性心肌缺血严重影响急性肺栓塞的预后。     

肾移植术后并发尿路上皮肿瘤的临床分析

目的 分析肾移植患者并发尿路上皮肿瘤的特点，探讨其诊治方法。方法 自1998～2003年肾移植患者1293例，术后发生尿路上皮恶性肿瘤21例（1．6％）。男4例，女17例。17例原发病为慢性问质性肾炎。发生尿路上皮肿瘤距肾移植6～62个月，平均26个月。其中膀胱癌6例，单侧肾盂或输尿管癌6例，单侧肾盂或输尿管、膀胱癌8例，双侧肾盂输尿管癌1例。10例上尿路肿瘤发生部位与移植肾同侧，4例发生于移植肾对侧。临床症状以无痛性肉服血尿和反复泌尿系感染为主。19例行手术治疗，术后所有患者免疫抑制剂用量减少1／3并辅以局部灌注化疗。结果 2例行姑息性治疗的晚期肿瘤患者分别于发现肿瘤5、8个月死亡。余19例现已随访2～5年。13例肿瘤复发，复发部位为膀胱或对侧原。肾、输尿管。所有患者在免疫抑制剂减量期间均未出现急性排斥。2例因切除移植肾恢复透析，17例肾功能正常。结论 慢性间质性。肾炎导致。肾功能衰竭的。肾移植患者和女性肾移植患者易发生移植后尿路上皮肿瘤；移植肾同侧上尿路较对侧好发肿瘤；对移植肾对侧为首发的上尿路发生肿瘤者可预防性行双侧上尿路根治性切除。     

Recombinant AAV-mediated HSVtk gene transfer with direct intratumoral injections and Tet-On regulation for implanted human breast cancer

Background  

HSVtk/ganciclovir (GCV) gene therapy has been extensively studied in tumors and relies largely on the gene expression of HSVtk. Most studies, however, have failed to demonstrate any significant benefit of a controlled gene expression strategy in cancer treatment. The Tet-On system is commonly used to regulate gene expression following Dox induction. We have evaluated the antitumor effect of HSVtk/ganciclovir gene therapy under Tet-On regulation by means of adeno-associated virus-2 (AAV-2)-mediated HSVtk gene transfer with direct intratumoral injections in mice bearing breast cancer tumors.