Intra-arterial administration of carboplatin and the blood brain barrier permeabilizing agent,RMP-7: A toxicologic evaluation in swine

RMP-7 is a bradykinin B2 receptor agonist shown to permeabilize the blood-brain barrier, especially that associated with brain tumors, when administered via both intracarotid and intravenous routes. Both routes of administration are currently being tested in human trials in combination with the chemotherapeutic agent carboplatin as therapy for gliomas. As an essential prerequisite to the initial intracarotid clinical trials, the potential neurotoxicity of intra-arterial administration of RMP-7 (at a high or low dose), alone and in combination with carboplatin, was assessed in anesthetized Red Duroc swine. Five treatment groups were evaluated with each pig receiving a series of alternating, intra-arterial infusions of RMP-7 (or saline) followed by carboplatin (or saline), as follows: (1) vehicle control: saline/saline; (2) carboplatin only control: saline/carboplatin (50 mg total); (3) RMP-7 only control: RMP-7 (750 ng/kg)/saline; (4) low dose combination: RMP-7 (75 ng/kg)/carboplatin (50 mg total); and (5) high dose combination: RMP-7 (750 ng/kg)/carboplatin (50 mg total). For each subject, one of the alternating dosing sequences (above) was repeated four times during a single dosing session which lasted approximately 40 minutes. Assessments during the in-life phase of the study in the pre- and post-treatment periods consisted of heart rate, arterial blood pressure (systolic, diastolic, and mean), blood gases, body weight, general clinical observations (including evaluation for neurological deficit) and clinical pathology (including a comprehensive battery of standard blood coagulation, hematological and serum chemistry tests). In addition, during the time of treatment, heart rate and arterial blood pressure were monitored. The animals were terminated two weeks after dosing and the brain and rete mirabile (distal to site of infusion) were evaluated for gross and histopathological abnormalities. The histopathology analysis included a reader-blinded analysis using low and high power light microscopic examination of both H&E and Kluver-Berrera stained sections through several key cortical and subcortical brain regions. Transient decreases in arterial blood pressure (mean of 10–25 mmHg) were observed in both groups receiving the high dose of RMP-7 (i.e., 750 ng/kg). No other side effects attributable to RMP-7 and/or carboplatin were observed, and clinical observations revealed no evidence of neurologic deficits. Post-mortem examination revealed no evidence of CNS or cerebral vascular pathology attributable to carboplatin and RMP-7. This study demonstrates that intracarotid administration of the maximum tolerated dose of RMP-7 (750 ng/kg) alone, or in combination with carboplatin (50 mg) is not accompanied by any serious adverse effect, apparent cerebrovascular abnormality or neuropathologic consequence and offers further evidence for the safety of this novel therapeutic approach for enhancing delivery of chemotherapeutics to brain tumors.     

Blood-brain barrier and blood volume imaging of cerebral glioma using functional CT: A pictorial review

Five cases of cerebral glioma are presented here that illustrate the benefit of functional CT imaging of blood-brain barrier permeability and cerebral blood volume. Functional CT uses Patlak analysis of a single location dynamic sequence to extract physiological information that is useful clinically in the assessment of cerebral gliomas. Functional CT offers distinct advantages over other functional modalities including clearer delineation of tumour, tumour grading, measurement of tumour activity and monitoring response to therapy.     

乌龙丹治疗急性脑梗塞及对下丘脑—垂体—甲状腺轴内分泌激素变化的影响

目的 :通过对 66例急性脑梗塞住院患者进行了较系统的临床观察和有关下丘脑—垂体—甲状腺轴内分泌激素水平的检测 ,以探讨中药复方乌龙丹的临床疗效和有关机制。方法 :临床疗效评定采用计分法 ,治疗组 (3 5例 )用低分子右旋糖酐静脉滴注加乌龙丹口服。对照组 (3 1例 )用低分子右旋糖酐静脉滴注加尼莫通口服 ,疗程均为 4周 ,治疗前后采血用放免法检查 :三碘甲状腺原氨酸 (T3)、甲状腺素 (T4)、游离三碘甲状腺原氨酸 (FT3)、游离甲状腺素(FT4)、促甲状腺素 (TSH)。结果 :治疗组疗效优于对照组 ,疗效评分值增加 ;经 4周治疗用药后 ,治疗组的T3、FT3和TSH由治疗前的较低水平升高至正常范围 ,两组用药前后各指标变化差值比较 ,在T3、FT3、TSH有显著性差异 (P <0 0 1 )。结论 :本研究表明了中药乌龙丹在低分子右旋糖酐改善微循环作用的基础上发挥了更有效的治疗作用 ,对脑梗塞急性期下丘脑—垂体—靶腺轴功能紊乱、激素分泌异常有一定的调节作用 ,从而有助于维持内环境的相对稳定。     

急性脑梗塞患者血管内皮细胞活性因子的变化和活血化瘀对其影响的临床观察

为探讨急性脑梗塞中医不同证型与血管内皮细胞的关系，以及活血化阏对其影响。方法对２０名健康得及６６例ＡＣＩ偏虚证和偏实证患者检测了血浆纤缩溶解系统，前列环素系统以及第Ⅷ因子相关抗原等的水平。     

川芎嗪抗缺氧致脑细胞损伤作用的实验研究

目的:观察川芎嗪对缺氧状态下离体大脑皮层细胞脂质过氧化物(LRO)含量及超氧化物歧化酶(SOD)活性的影响。方法:将4～5日龄 Wistar 大鼠大脑皮层分离并制成细胞悬液(5×10~6个细胞/ml),在 CO_2培养箱内孵育2h 之后观测单纯缺氧1h(细胞悬液通以95％N_2加5％CO_2),以及预先向细胞悬液加入磷酸川芎嗪(分10~(-5)、10~(-4)和10~(-3)mol/L3个剂量组),再缺氧1h 细胞 LPO 含量与 SOD 活性的改变。结果:缺氧可使 LPO 显著增加、SOD 活性明显降低;预先加入川芎嗪能有效防止缺氧所致的 LPO 升高和 SOD 活性降低。结论:川芎嗪对缺氧致细胞脂质过氧化损伤具有保护作用,其机制可能是通过增强内源性 SOD 活性、清除氧自由基,进而降低了细胞脂质过氧化程度。     

大肠癌巨─微血管构筑的临床研究

为了探讨大肠癌和其间质血管的关系，我们研究了48例大肠癌标本不同部位的巨─-微血管构筑。方法：用癌瘤标本造影摄X线片、立体显微镜和微机图象定量分析。结果显示：癌中心血管稀疏或为无血管的坏死区及血管破坏；癌远近端瘤组织内血管增多增粗，畸形及紊乱；其血管定量参数与癌中心和癌远近端肠粘膜相比有显著差异（P＜O．05，P＜0．01）。结论：①大肠癌的发生发展依赖于血管形成和细胞增殖。②在理论上解释了大肠癌的临床病理过程。③大肠癌的恶性程度与其血管密度间似有负相关的趋势。④探讨了其临床应用价值。     

三氧化二砷诱导血管平滑肌细胞凋亡的实验研究

目的：探讨三氧化二砷（Ａｓ２Ｏ３）诱导大鼠血管平滑肌细胞（ＶＳＭＣｓ）调亡的作用。方法：建立大鼠ＶＳＭＣｓ增生模型。用四甲基偶氮唑蓝还原反应（ＭＴＴ法）、透射电镜、琼脂糖凝胶电泳、流式细胞术等方法观察Ａｓ２Ｏ３诱导ＶＳＭＣｓ凋亡的作用。结果：经Ａｓ２Ｏ３作用后ＶＳＭＣｓ出现典型的凋亡变化,透射电镜下可风细胞核仁消失,染色质浓缩聚集于核膜下。ＤＡ琼脂糖凝胶电泳出现凋亡特征性梯形电泳条带。汉式细胞术检     

合肥市蜀山镇2～13岁儿童脑性瘫痪现况研究

目的 了解合肥市界山镇小儿脑瘫的流行现况。方法 于１９９８年对蜀山镇７３８８名２～１３岁的儿童进行脑瘫现患调查。结果 共发现脑瘫患儿１１例,总患病率为１．４９‰,其中男性６例（１．５１‰）,女性５例（１．４７‰）。２～５岁组儿童脑瘫的患经为０．５４‰,６～９岁组为２．０６％,１０～１３岁组为１．５３‰。脑瘫患儿中痉挛型６例,肌张力低下率为１．４９‰,男女性别患病率无差异（Ｐ〉０．０５）;各年龄组之     

前列地尔治疗急性中重型脑梗死的疗效观察

目的观察前列地尔注射液对超过治疗时间窗的急性中重型脑梗死的疗效和安全性。方法采用随机对照方法,将发病2～7d的30例大脑中动脉区中重型脑梗死按1∶2比例分配,对照组10例应用对症治疗的中性疗法,治疗组20例则加用前列地尔注射液治疗。均治疗14d。结果治疗组神经功能缺损减分率、ADL评分、治疗有效率均优于对照组,有显著性差异(P<0.025,P<0.0005,P<0.005);在治疗中未发现明显不良反应。结论前列地尔注射液对急性中重型脑梗死有明显疗效,药物安全性能良好,有一定临床推广应用价值。     

Malignant vascular lesions of bone: radiologic and pathologic features

The malignant vascular tumors of bone represent an uncommon diverse group of tumors with widely variable clinical and radiographic presentations. Although the radiographic imaging features of the lytic osseous lesions typically seen with this group of tumors are relatively nonspecific, the propensity to develop multifocal disease in an anatomic region is a feature that can be helpful in suggesting the diagnosis of a vascular tumor. The differential diagnosis varies according to the age of the patient and presence of solitary or multifocal disease. The histologic features are variable and range from tumors with vasoformative features to those that mimic mesenchymal neoplasm or metastatic carcinoma. Familiarity with the radiographic and pathologic spectrum of disease is essential for making an accurate diagnosis in this diverse group of neoplasms. This paper will provide a review of the nomenclature for the malignant vascular tumors of bone and discuss the radiographic and pathologic differential diagnosis. Received: 17 December 1999 Revision requested: 8 February 2000 Revision received: 19 May 2000 Accepted: 9 June 2000