Unsere Erfahrungen mit der Infektionsprophylaxe und -therapie nach 53 Lebertransplantationen

Summary An attempt was made to reduce the risk of infection following liver transplantation by means of selective bowel decontamination with tobramycin, polymyxin E and amphotericin B, as well as short-term systemic antibiotics with cephotaxim and tobramycin. After 53 consecutive orthotopec hepatic transplants performed in 51 patients between 1985 and 1987, a total of eight pneumonias occurred as the clinically most significant infection. Two pneumonias were caused by cytomegalovirus, one by Pneumocystis carinii, one by Candida and the remaining four by various bacteria. In 6 patients, bacteria were cultured from the blood, but only in one case was an indwelling catheter identified as the source of the septicemia. Taking all samples together, Streptococcus faecalis was the bacterium most frequently cultured, which was not covered by the prophylactic antimicrobial regime applied. Pseudomonas, however, and gram-negative bacteria were demonstrated much less frequently. Vaginal and oral Candida infections, as well as oral and genital herpes simplex infections, responded well to topical therapy with fungicide and aciclovir, respectively. Three patients developed cytomegalovirus (CMV) hepatitis. All five CMV infections were successfully treated with ganciclovir and hyperimmunoglobulin, as well as reduction of prophylactic immunosuppression. Out of 15 patients transplanted for posthepatitic cirrhosis, 7 developed a recurrence of the infection (5 hepatitis B virus) 2 hepatitis C virus) in the graft. Two died of the cirrhosis, three are still alive with cirrhosis but sufficient graft function, and one patient is suffering from chronic active hepatitis. One patient grafted for acute hepatic failure was able to clear the delta virus within 1 year post-transplant. During the perioperative phase, however, we never lost a single patient to infectious complications. Therefore, bowel decontamination and antibiotic prophylaxis, including Streptococcus faecalis, are recommended.

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Unsere Erfahrungen mit der Infektionsprophylaxe und -therapie nach 53 Lebertransplantationen

Zusammenfassung Durch selektive Darmdekontamination mit Tobramycin, Polymyxin E and Amphotericin B über 8 Tage and kurzzeitige Antibiotikatherapie mit Cefotaxim und Tobramycin wurde versucht, die hohe Infektionsrate nach Lebertransplantation zu reduzieren. Nach 53 konsekutiven orthotopen Leberverpflanzungen bei 51 Patienten zwischen 1985 and 1987 traten als klinisch bedeutsamste Infekte 8 Pneumonien auf. Bei 4 Patienten waren these bakterieller Natur, 2 durch Cytomegalovirus verursacht, 1 durch Pneumocystis carnii and 1 durch Candida. 6 Patienten hatten eine Septikämie, wobei nur in 1 Fall ein Venenkatheter als Ausgangspunkt identifiziert werden konnte. Alle Proben zusammengenommen wurde am häufigsten Streptokokkus faecalis kultiviert, ein Keim, der durch das angewendete antimikrobielle Regime nicht erfaßt wird. Pseudomonaden hingegen und gramnegative Stäbchen wurden in einem wesentlich geringeren Prozentsatz nachgewiesen. Vaginale and orale Candidainfektionen erlangten ebenso wie orale and genitale Herpes simplex-Infektionen kaum Krankheitswert und wurden jeweils topisch mit einem Antimykotikum bzw. Acyclovir behandelt. Neben den 2 CMV-Pneumonien wurden auch 3 durch CMV verursachte Hepatitiden beobachtet. Alle CMV-Infekte konnten mit Gancyclovir und Hyperimmunglobulin bei gleichzeitiger Reduktion der Basisimmunosuppression beherrscht werden. Von 15 Patienten, die wegen posthepatitischer Zirrhose transplantiert wurden waren, entwickelten 7 eine Reinfektion des Transplantates (5 HBV, 2 HCV), wovon 2 an der Zirrhose verstarben, 3 mit einer Zirrhose and noch ausreichender Transplantatfunktion leben, wie auch der Patient, der eine chronisch aktive Hepatitis entwickelt hatte. Eine im akuten Leberversagen transplantierte Patientin hat das Deltavirus innerhalb eines Jahres eliminiert. In der perioperativen Phase wurde jedoch kein einziger Patient an einer infektiösen Komplikation verloren, so da auch bei fehlender Kontrollgruppe die Darmdekontamination sowie die antibiotische Kurzzeitprophylaxe empfohlen werden können.

     

Prevention and suppression of autoimmune pancreatic Beta-cell destruction in BB rats by syngeneic lymphocytes obtained from long-term normoglycaemic donors

Summary To prove whether a cell-mediated mechanism is responsible for maintaining long-term normoglycaemia in BB/OK rats with a proved immune attack (insulitis, reduced Beta-cell volume), we transferred lymphocytes obtained from those rats into normoglycaemic diabetes-prone BB/OK rats or into diabetic BB/OK rats receiving a simultaneous syngeneic islet graft. Our results show the presence of a lymphocyte population in the long-term normoglycaemic BB/OK rats, which is able to arrest pancreatic Beta-cell destruction in diabetes-prone BB/OK rats detected by a decreased diabetes incidence following single lymphocyte transfusion. Syngeneic islets were destroyed by recurrence of the autoimmune process when transplanted into diabetic BB/OK rats. Lymphocytes obtained from long-term normoglycaemic BB/OK rats were able to protect the syngeneic BB/OK islet graft from autoimmune destruction in diabetic BB/OK rats, whereas allogeneic islet destruction was not prevented. The phenotype of the effective lymphocyte population is not yet clear, but it is negative for RT6. We conclude that the mechanism responsible for maintaining normoglycaemia in long-term normoglycaemic BB/OK rats is cell mediated, because this property can be transferred to prevent autoimmune destruction of pancreatic Beta cells.     

Sequential electrodiagnostic evaluation of diabetic neuropathy after combined pancreatic and renal transplantation

To asses the long-term evolution of diabetic polyneuropathy after a combined kidney-pancreas transplant, an electrophysiological study was performed in 20 diabetic patients before transplant, and 1 (n=18), 2 (n=16), 3 (n=10) and 4 years (n=5) at a later date. Motor and sensory scores were calculated for conduction velocity and amplitude to determine the physiopathological process. During evolution the scores were not found to be decreasing. Motor and sensory velocity scores were significantly improved (p<0.05) 1=" and=" 2=" years=" after=" the=" graft,=" when=" score=" values=" tended=" to=" stabilize.=" motor=" and=" sensory=" amplitude=" scores,=" which=" are=" more=" sensitive=" for=" axonal=" loss=" assessment=" were=" slightly=" but=" not=" significantly=">     

Characterization of rat hyperplastic bile ductular epithelial cells in culture andin vivo

A novel intrahepatic biliary cell culture/in vivo transplantation system has been developed with an essentially pure population of bile ductular epithelial cells isolated from rat liver 6–12 weeks after bile duct ligation. In primary culture, these cells retain staining strongly for -glutamyltranspeptidase and glutathione S-transferase P. The cytoplasm of cultured bile ductular cells reacts with an anti-laminin antibody, but loses immunoreactivity with a monoclonal anti-cytokeratin 19 antibody. Semiconservative DNA synthesis in the cultured cells was dependent upon the continued presence of 10% fetal calf serum in the medium. Replicating bile ductular cells could be subcultured for a finite number of passages. In addition, freshly isolated bile ductular epithelial cells gave rise to well differentiated bile ductular structures when transplanted into the interscapular fat pads of syngeneic recipient rats.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.This work was supported by USPHS Grant RO1 CA39225 to Dr. Sirica by the National Cancer Institute, Department of Health and Human Services.     

同胞脐血移植治疗儿童急性白血病

脐血移植可以根治白血病、再生障碍性贫血、血红蛋白病及先天性免疫缺陷等疾病，尤其适合于儿童患者。临床资料表明同胞脐血移植的效果优于无关供者的脐血移植。对12例白血病或重症再障患儿进行了脐血HLA配型，结果配型完全相合4例，进行脐血移植3例，均成功植活，体重最大50kg。可以在胎儿出生时留取脐血配型，同时将脐血进行低温保存。提示剖宫产和自然分娩、体内采集脐血和体外采集脐血对脐血的采集体积无明显影响。单份同胞脐血可以重建几乎全部儿童患者的造血功能。对同胞脐血移植的病例，主张在分娩时留取脐血进行HLA配型，减少产前穿刺对孕妇及胎儿的损伤，同时脐血进行冷冻，若配型相合再进行脐血移植。     

小儿非骨化性纤维瘤的临床特点及诊治

目的：探讨小儿非骨化性纤维瘤的临床特点及治疗方法。方法：回顾性分析我院收治的小儿非骨化性纤维瘤20例。其中男12例，女8例，年龄1．5～14岁，平均8．5岁。病灶均在下肢长管状骨，其中股骨远端10例，股骨颈1例，胫骨近端7例，远端1例，腓骨1例。全部病例均经手术治疗，术式包括单纯病灶切除、病灶切除加自体髂骨或加异体骨移植术。结果：全部病例均经病理证实为非骨化性纤维瘤。术后随访1～5年，平均3．2年，无一例复发。结论：非骨化性纤维瘤的病因和发病机制不清。根据其临床特点，典型的X线片表现，诊断并不困难。但应与骨纤维异样增殖症、骨囊肿及骨巨细胞瘤相鉴别。因本病可引起疼痛及病理性骨折，确诊后应早期手术治疗。术式以病灶切除植骨术为主。     

病灶清除椎间植骨治疗胸腰椎结核15例报告

目的 观察病灶清除椎间植骨治疗胸腰椎结核的疗效。方法 全组15例，病灶涉及2节椎体10例，3节椎体5例。术前后凸畸形成角13℃～45℃，平均30℃。手术采用瘸灶清除椎体间植骨融合，使用自体肋骨5例，髂骨10例。植骨加前路钢板固定2例。结果 平均随访4年，优良率92％，植骨融合率97％。术后后凸畸形成角5℃～20℃，平均14℃。结论 胸腰椎结核病灶清除椎间植骨融合，能恢复脊柱的稳定性，骨融合率高，可纠正脊柱后凸畸形，减少晚期腰背痛的发生。     

调整免疫抑制方案改善移植肾功能

目的：探讨调整免疫抑制药的使用方案能否改善肾移植后慢性移植物肾病患者的肾功能。方法：对32例(A组)慢性移植物肾病早期肾功不全的患者在1～2周内将其神经钙蛋白阻滞药(环孢素A或他克莫司)减少至原剂量的1／3或完全停用，同时适当增加硫唑嘌呤或霉酚酸酯(MMF)的用量，与同期内环孢素A或他克莫司未作大幅度减量、仅适当增加硫唑嘌呤或霉酚酸酯用量的26例(B组)慢性移植物肾病患者进行对比，随访比较两组的移植肾功能，观察急性排斥反应情况。结果：1年后A组有21例(65．6％)患者移植肾功能得以好转或不再继续恶化，而B组除3例(11．5％)移植肾功能维持在原有水平外，其他患者肾功能均进行性恶化。两组急性排斥反应发生率无显著差异。结论：大幅度减少甚至停用神经钙蛋白阻滞药可使部分肾移植后慢性移植物肾病患者的肾功能得以改善或者防止其进行性恶化。这种药物调整是安全的。     

免疫抑制活性物质335A对小鼠免疫功能的影响

对链霉菌 335产生的代谢产物 335 A的体外、体内免疫反应的作用进行了研究。结果表明 ,335 A体外对小鼠脾细胞的增殖反应及混合淋巴细胞反应均呈强烈的抑制作用 ,半数抑制浓度 (IC50 )分别为 2 .2和10 ng/ ml,且是一种特异的 T细胞抑制剂。以上作用并不是非特异性细胞毒作用所致。通过不同时间加入335 A,显示其作用在 T淋巴细胞活化的早期。 335 A对三种实验动物模型的免疫抑制作用的研究表明 ,4 mg/ kg的 335 A对小鼠抗绵羊红细胞抗体产生的抑制率为 98.7% ,并对绵羊红细胞诱导的 DTH反应有明显的抑制作用 ;8mg/ kg的 335 A使小鼠移植心肌的存活时间由 (8.71± 0 .4 8) d延长至 (13.0± 0 .1) d。初步的作用机制研究表明它主要抑制 Th细胞分泌淋巴因子及其受体表达。     

年轻宫颈癌患者卵巢移位临床效果初步分析

目的　探讨宫颈癌患者卵巢移位术的临床意义。方法　收集 1 999年 9月～ 2 0 0 2年 1月间北京大学人民医院妇科收治的 1 4例绝经前患者在手术治疗的同时行卵巢移位术的临床资料 ,分析术后患者的更年期症状 ,并与临床特征进行比较。结果　① 1 4例患者均为绝经前 ,平均年龄 37 36岁 (2 7～ 4 3岁 ) ,宫颈原位癌累腺 2例、Ia 3例、Ib7例、Ⅱa2例 ;② 1 4例患者中 ,双侧卵巢移位术 6例 ,随访 8 3个月 ,5例未出现更年期症状 ;单侧卵巢移位 8例 ,4例无更年期症状 ;③术后辅助治疗 6例 ,均为宫颈浸润癌术后辅助放疗和 /或化疗 ,其中 5例分别于术后 6～ 1 8个月出现更年期症状 ,术后未辅助治疗 8例 ,其中 1例 (4 3岁 )于术后 6个月出现更年期症状。结论　宫颈癌患者术中行卵巢移位术 ,可保留卵巢的功能 ,但术后辅助放疗仍直接影响卵巢的功能 ,卵巢移位术的临床价值 ,有待进一步探讨