Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation

Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical, radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary complications of the graft. Received for publication on March 8, 1999; accepted on April 30, 1999     

Cellular distribution of the NMDA receptor subunit NMDAR1 in fetal ventral mesencephalon transplants in the dopamine-depleted striatum of a rat

Immunohistochemistry was performed to demonstrate the cellular distribution of N-methyl-D-aspartate (NMDA) receptor subunit NMDAR1 in the intrastriatal grafts of a rat model of Parkinson's disease. Unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal pathway were produced in young adult female rats. Neural transplantation was performed with fetal ventral mesencephalon (VM) tissue (at embryonic day 15) 3 weeks after the 6-OHDA lesions. In the fetal VM in which the tyrosine hydroxylase (TH) immunoreactivity was intensely observed, no NMDAR1 subunit immunoreactivity was detected. Immunopositive cells of NMDAR1 were densely distributed in the intact SNc contralateral to the lesions, in which intense immunoreactivity for TH was observed. In contrast, the cells positive for NMDAR1 in the SNr were scattered. The immunoreactivity for NMDAR1 was markedly decreased in the SNc, but not in the SNr on the lesioned side. Double immunostaining revealed that most TH-positive cells in the SNc showed moderate NMDAR1 immunoreactivity. Within the intrastriatal fetal VM grafts containing TH-positive cells, NMDAR1-positive cells tended to locate homogeneously within the grafts. These were composed of various cell sizes and shapes, but they were mainly medium-sized and aspiny cells. Double immunostaining revealed that a part of the TH-positive cells in the grafts was also immunopositive for NMDAR1. Taken together with our previous studies, it is suggested that both dopaminergic neurons and nondopaminergic neurons in the VM transplants appear to be modified functionally by glutamatergic afferents via various glutamate receptors, including NMDAR1.     

The effect of microglia on embryonic dopaminergic neuronal survival in vitro: diffusible signals from neurons and glia change microglia from neurotoxic to neuroprotective

When embryonic dopaminergic neurons are transplanted into the adult brain, approximately 95% die within a few days. To assess whether microglia activated during transplantation might be responsible for this rapid death, we examined the effect of microglia on rat embryonic dopaminergic neurons in vitro. Conditioned medium from 7-day-old microglia was found to decrease the number of dopamine neurons surviving in primary culture, but activation of the microglia with N-formyl-methionyl-leucyl-phenylalanine (FMLP) or Zymosan A did not increase the toxicity of the conditioned medium. We next tested the effect of coculturing microglia and dopaminergic neurons by placing microglia in semipermeable well inserts over the neuronal cultures. The presence of microglia now increased dopaminergic neuronal survival, microglial activation again having no effect. To increase yet further the possible interactions between microglia and neurons, the mesencephalic cells and microglia were mixed together and placed as a tissue in three-dimensional culture, and here again the presence of microglia increased dopaminergic neuronal survival with no effect of activation. Contact of microglia with the mesencephalic cells therefore converted them from being toxic to dopaminergic neurons to promoting their survival. The change in microglial effect from toxic to protective was caused by soluble molecules secreted by cells in the neuronal cultures, as conditioned medium derived from microglia-neuronal cocultures also had a dopaminergic neuron survival effect, indicating that microglia in cocultures behave differently from microglia removed from neuronal and glial influence. Microglia cocultured with either neurons or astrocytes downregulated inducible nitric oxide synthase (iNOS), indicating a decrease in the production of nitric oxide and possibly other toxic molecules. These findings indicate that in their natural environment, microglia are likely to be beneficial for the survival of embryonic dopaminergic grafts.     

Perioperative blood transfusions after allogenic renal transplantation

Summary The requirement of blood transfusions was evaluated in a two compartment (retrospective/prospective) study in our renal transplantation program. Between July 1st, 1993 and December 31st, 1994 (observation period I) we retrospectively investigated 110 patients with end stage renal disease and anemia undergoing kidney transplantation. Between January 1st, 1995 and December 31st, 1996 (observation period II) the requirement of blood transfusions was followed prospectively in 134 patients after allogenic renal transplantation. The amount of blood drawn for preoperative diagnostic investigations was in observation period I significantly higher (280 ml) than in observation period II (150 ml) (p = 0.02). For postoperative diagnostic tests in observation period II significantly less blood (240 ml) was needed than in observation period I (510 ml) (p = 0.01). The intraoperative bloodloss was similar in both periods (170 ml vs. 190 ml; p = 0.6). The need for closer graft observation was the reason for significantly increased amount of blood transfusions in patients with delayed graft function. The number of blood transfusions was significant lower in patients with primary graft function (p = 0.0001). There was no correlation between blood transfusions and the use of ATG/OKT3, surgical complications and reoperations. With an improved management of blood drawing for diagnostic tests after allogenic kidney transplantation the number of perioperative blood transfusions can be reduced significantly.      

游离骨膜与复合rhBMP2的异种骨联合移植修复骨缺损的实验研究

目的 探讨复合基因重组人ＢＭＰ２（ｒｈＢＭＰ２）的异种骨与游离骨膜（ＦＰ）联合移植修复节段性骨缺损的效果。方法 将ｒｈＢＭＰ２与去抗原牛松质骨载体（ＢＣＢ）复合,制成ｒｈＢＭＰ２／ＢＣＢ;选用新西兰大耳白兔２８只,制成烧骨干１５ｍｍ缺损动物模型,分别行ＦＰ和ｒｈＢＭＰ２／ＢＣＢ复合移植（ｎ＝６）、ｒｈＢＭ２／ＢＣＢ移植（ｎ＝６）和单纯ＢＣＢ移植（ｎ＝２）;术后４、８、１２、１６周取材,通过Ｘ线、生     

老年患者肾移植（附10例报告）

为探讨老年患者肾移植的临床疗效,分析自１９９０年６月至１９９７年６月期间１０例６０ｙ以上肾移植受者的临床资料。结果表明：术后发生急性排斥反应２例。发生各种并发症７例。４例死亡,分别死于肺部感染、脑出血、脑梗死和急性坏死性胰腺炎。术后１、３、５ａ的人／肾存活率分别为９０％／９０％、８０％／８０％、６０％／６０％。认为年龄已不再是老年尿毒症患者选择手术的障碍,老年患者同样可以安全地接受肾移植并获得满意的疗效。并发症所致的患者带肾死亡是移植失败的主要原因。严格选择手术适应证,移植前原发疾病和合并症的积极治疗,免疫抑制剂的合理应用以及术后并发症的积极防治对提高老年肾移植的长期存活率具有重要的意义。     

Endothelial cell transplantation and growth behavior of the human corneal endothelium

Background: The human corneal endothelium has a limited proliferative capacity in vivo. Until now it has only been possible to replace damaged endothelium by transplantation of a donor cornea. After establishing methods for the isolation and in vitro cultivation of human corneal endothelial cells, transplantation of these cells my be an alternative therapeutic option. Materials and methods: In this review methods for the in vitro cultivation of human corneal endothelial cells and their transplantation on the Descemet membrane of donor corneas are described. Results: In vitro proliferation of human adult corneal endothelial cells was achieved by the development of defined cell culture conditions, including supplementation of culture medium with specified growth factors and substances. Dependent on the culture conditions, as well as independent of them, in vitro cultured endothelial cells showed phenotypic changes and different proliferative behavior. Thus, molecular biological examinations revealed a different expression pattern of growth factor receptors in fibroblast-like endothelial cells (dedifferentiated) compared to typical endothelial cells (differentiated). Moreover, the proliferative capacity of the cells differed, dependent on their corneal location. Cells isolated from the peripheral part of donor corneas have a higher proliferative capacity than cells obtained from the central part. The propagation of corneal endothelial cells in vitro offered the possibility of their transplantation on donor corneas in an in vitro model. After transplantation, these cells formed a monolayer whose morphology and cell density depended on the differentiation of the cells. DNA synthesis was predominantly detectable in cells of the corneal periphery. Conclusions: Our findings are the basis of the following hypothesis: the periphery of the cornea represents a regenerative zone of the corneal endothelium. The fact that early after transplantation corneal endothelial cells form a monolayer on the natural extracellular matrix (ECM), which shows contact inhibition, suggests that inhibitory factors are released by the Descemet membrane that influence the proliferation of the cells. Further studies on the regulation of the proliferation and differentiation of human corneal endothelial cells in vitro and after transplantation might offer the possibility to establish a selective procedure for the treatment of corneal endothelial cell loss in the near future.      

自体角膜缘移植治疗翼状胬肉的临床观察

目的 探讨自体角膜移植治疗翼状胬肉的疗效。方法 对４２例（４８只眼）初发性和复发性翼状胬肉行自体角膜缘移植术,术后随访３６例（４２只眼）,随访时间４个月～２年,平均９个月。结果 上皮愈合良好、稳定,无新生血管及结产生,角膜光滑,未见复发。结论 自体角膜缘移植可通过提供新的干细胞来源,提高翼状胬肉手术的成功率,降低术后的复发率,是一种有推广价值的手术方法。     

角膜缘干细胞与结膜移植治疗翼状胬肉

目的:观察角膜缘干细胞与结膜移植治疗翼状胬肉的疗效。方法:采用自体角膜缘干细胞与结膜移植术,对38例43眼初发和复发性翼状胬肉患者进行治疗,术后随访3～30月,平均10月。结果:38例43眼中34例38眼上皮愈合稳定,角膜恢复正常光滑、透明,胬肉无复发。4例5眼失访。结论:自体角膜缘上皮移植为病变区角膜和结膜提供新的干细胞来源,是治疗翼状胬肉的理想方法。眼科学报1999;15:89—90。