新型重组人肿瘤坏死因子药代动力学的实验方法

目的 为探讨新型重组人肿瘤坏死因子（nrTNF α）药代动力学而建立生物样品中nrhTNFα的检测方法。方法 （1）方法Ⅰ（RA）：动物肌注^125 Ⅰ标记的nrhTNFα后，测定各生物样品中的总放射活性；（2）方法Ⅱ（HPLC－RA）；上述生物样品无经HPLC分离后，收集并测定其中^125Ⅰ－nrhTNFα部分的放射活性；（3）方法 ⅢELISA法。结果 RA，HPLC－RA法检测的nrhTNFα质量浓度与放射性呈直线相关（RA，r=0.999HPLC－RA,r=0.999)。ELISA法证明nrhTNFα的酶联免疫检测药盒适用于nrhTNFα的检测，nrhTNFα的标准曲线与nrhTNFα的标准曲线显正相关，r=0.994,这一检测系统与其他细胞因子包括IFNα，TNFβ，IL－2和IL－6无交叉反应。结论 RA，HPLC－RA和ELISA法均可作为nrhTNFα的药代动力学实验方法。     

双支撑骨柱移植术治疗股骨头坏死的远期疗效分析

目的分析双支撑骨柱移植术治疗股骨头坏死的远期疗效。方法从1988年3月以来,采用双支撑骨柱移植术治疗成人股骨头坏死366例466髋,获5年以上随访者186例206髋,平均年龄32.2(20~60)岁。按病因分类:激素性者60例68髋,酒精性者86例96髋,激素加酒精者30例32髋,外伤性者10例10髋。ARCOⅡB、ⅡC、ⅢA、ⅢB、ⅢC、Ⅳ期患者分别为36、30、40、40、32、28髋。参照百分法进行疗效评价。结果术后所有患者的髋关节疼痛均获得明显缓解或消失,股骨头高度有不同程度增加,关节活动度有改善。平均随访时间10.5(5~16)年,手术前与随访时临床评价(疼痛、功能、关节活动度)、X线评价、总分数比较,差异均有统计学意义(P<0.01)。结果显示ⅡB~Ⅳ期优良率分别为83.3%、80.0%、75.0%、65.0%、40.6%、28.6%,总优良率为63.6%。Ⅱ期效果好(81.8%),Ⅲ期早期(ⅢA、ⅢB)效果较好(70%),ⅢC、Ⅳ期者效果差(35%)。期别间疗效依次降低,差异有统计学意义(P=0.0001)。30岁以内患者术后股骨头内植骨愈合较快,平均为3.2(2.9~3.5)个月。50~60岁患者植骨愈合需时较长,平均为5.5(4.4~6.4)个月。结论该术式治疗股骨头坏死的远期疗效良好,治疗效果与股骨头坏死期别有关,尤其适用于股骨头坏死Ⅱ期和Ⅲ期的早期病例。     

Are cytokines possible mediators of cancer cachexia?

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.This work was supported by a grant from the Japan-Sweden Foundation in 1991.     

Kinetics of soluble TNF-receptors and soluble adhesion molecules ICAM-1, E-selectin and VCAM-1 under systemic rhTNFα therapy

Cytostatic as well as cytotoxic effects of tumour necrosis factor alpha (TNF-α) therapy have been shown in vitro and in experimental in vivo models. Nevertheless, the mechanism of anti-tumour activity in humans in vivo remains unclear. To determine the role of the vascular lining endothelial cells as important mediators of several immunological interactions, we investigated changes in the levels of the soluble endothelial cell adhesion molecules intercellular adhesion molecule 1, E-selectin and vascular cell adhesion molecule 1 as well as of soluble TNF receptors I and II during systemic therapy with recombinant human rhTNF-α (rhTNF-α). All tests were performed by enzyme-linked immunosorbent assays (ELISAs). The clinical efficacy of the intravenous rhTNF-α therapy was poor. Only one patient with isolated intra-arterial limb perfusion had a delayed, marked, but only temporary necrosis of tumour cells. In contrast, we found a marked, significant and (during therapy) undulating augmented increase in the levels of soluble adhesion molecules as well as of the soluble TNF receptors. Taken together, these data support the hypothesis that a sufficient tumour-specific cellular immunity is required to achieve a clinically apparent efficacy of systemic rhTNF-α therapy in addition to cytokine-dependent inducible activation mechanisms. In this context, the vascular lining endothelial cells might play an important role as mediators of the complex immunological antitumoral activity.     

Contribution of tumor necrosis factor to the lethality of mice with endotoxin shock presensitized by serum from tumor-bearing mice

Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 115, No. 1, pp. 57–59, January, 1993.     

核素动态显像因子分析诊断股骨头缺血性坏死的应用初探

本文介绍了的核素动态显像因子分析成象原理与方法，并对１０例正常人和２８例成人股骨头缺血性坏死（ＡＦＨＩＮ）病人进行了放射性核素显像因子分析，结果表明：ＡＦＨＩＮ病人病变股骨的骨因子图像表现为明显浓聚，随病情加重股骨头头影像增大，且逐渐增浓。Ⅰ、Ⅱ期ＡＦＨＩＮ病人软组织因子图像无异常，Ⅲ期以上者的软组织因子图像可见髋关节处有明显浓聚。因此，核素动态显像因子分析不但可以早期诊断ＡＦＨＩＮ，而且对该病的分期判定也有重要的临床应用价值。     

肿瘤坏死因子刺激牛脑微血管内皮细胞释放内皮素-1及粉防己碱的拮抗作用

目的:观察肿瘤坏死因子（TNF）对培养的牛脑微血管内皮细胞释放内皮素-1（ET－1）的刺激作用及粉防己碱（Tet）对ET－1释放的抑制作用。方法：放免测定法。结果：TNF在（l～100μg·L(-1)）之间能剂量依赖性的促进牛脑微血管内皮细胞释放ET-1，Tet（10(－6)～10(－4)mol·L(－1)）能拮抗TNF诱导的ET－1释放并呈量效关系。     

鼠脾细胞肿瘤坏死因子的诱生和检测

本文报道采用Ｅ．ｃｏｌｉ ＬＰＳ刺激ＡＬＢ／Ｃ小鼠脾细胞诱生ＴＮＦ的最适条件，并用人ＴＮＦ ＥＬＩＳＡ方法检测小鼠ＴＮＦ。结果显示：脾细胞经ＬＰＳ刺激２ｈ就可在上清液中测出ＴＮＦ，１２ｈ达高峰，ＬＰＳ最适刺激浓度为１０＾－２μｇ／ｍｌ，ＴＮＦ产量依赖于脾细胞的浓度。     

Secondary hyperparathyroidism and acute tubular necrosis following renal transplantation

In the present study we investigated the relationship betweensecondary hyperparathyroidism in renal graft recipients andpost-transplantation acute tubular necrosis (ATN). Patientswere divided into two groups according to graft function: groupA consisted of 28 patients who had an uneventful postoperativeperiod and did not require haemodialysis. Group B comprised26 patients with primary non-function of the graft due to biopsy-provenATN who required continued haemodialysis for the first postoperativeweek or longer (mean 14.2 ±8.7 days). Both groups hadcomparable donor characteristics, HLA-matching and ischaemiatimes. All patients were given cyclospo-rin and low-dose prednisolonefor immunosuppression. Pretransplant levels of intact PTH weresignificantly greater in group B than in group A (203.5 ±193.1pg/ml versus 81.7±45.2 pg/ml, P<0.01). Group B patientshad more transplant biopsies (50 versus 7) and a longer hospitalizationtime (33.4 ± 10.9 days versus 21.9 ± 11.9 days,P<0.01), although serum creatinine on the day of dischargewas higher in group B (1.77 ± 0.51 mg/dl versus 1.5±0.45mg/dl, P<0.05). We conclude that patients with secondaryhyperparathyroidism as assessed by measuring circulating levelsof intact PTH have an increased incidence of ATN.     

腕部电烧伤肢体远端继发性坏死原因分型及治疗

１９８５年１月至１９９４年５月，我科共收治腕部电烧伤５４例、共７８个腕部受损。其中肢体远端原发性坏死者２５例，肢体远端继发性坏死及有继发性坏死倾向者１６例，占腕部电烧伤２０．５％（１６／７８）。继发性坏死者８例，有继发性坏死倾向经积极抢救治疗保住肢体者８例。在临床实践中，我们观察到腕部电烧伤远端肢体继发性坏死可分为三种类型：供血不足型，以动脉阻塞为主；血液瘀滞型，以静脉阻塞为主；血液粘滞度升高型，表现为微血管阻塞。并针对三种类型采用扩血管药物和抗血小板药物等不同预防治疗方法，临床上降低了截肢率，取得较为满意的效果。