本文選題：腎移植 + 聚乙二醇干擾素α-2b　； 參考：《華中科技大學(xué)》2014年博士論文

【摘要】：目的探討聚乙二醇干擾素a-2b聯(lián)合利巴韋林治療腎移植術(shù)后丙型肝炎的療效及安全性。 方法對(duì)9例腎移植術(shù)后1年以上、血肌酐穩(wěn)定在正常范圍的丙型肝炎患者,采用聚乙二醇干擾素α-2b(佩樂(lè)能)50μg皮下注射,每周1次；同時(shí)口服利巴韋林400-600mg/d治療。每月檢測(cè)HCV-RNA, HCV-RNA轉(zhuǎn)陰后繼續(xù)鞏固治療3-9月。觀測(cè)病毒學(xué)應(yīng)答情況,同時(shí)觀察肝腎功能、血常規(guī)變化以及治療過(guò)程中出現(xiàn)的不良反應(yīng)。 結(jié)果9例患者的總療程為4-20月,其中6例(66.7%)獲得滿意的持續(xù)病毒學(xué)應(yīng)答(SVR),觀查至停止干擾素治療后6月未出現(xiàn)復(fù)發(fā)；2例在獲得快速病毒學(xué)應(yīng)答后,于鞏固治療3月停止治療后復(fù)發(fā)；1例在治療8個(gè)月的過(guò)程中未見明顯病毒學(xué)應(yīng)答。治療中所有患者血肌酐均在正常范圍內(nèi)波動(dòng),未見急性排斥反應(yīng)跡象。治療過(guò)程中的主要不良反應(yīng)包括流感樣癥候群(發(fā)熱、肌肉酸痛、食欲不振等)、一過(guò)性骨髓抑制以及貧血等。所有不良反應(yīng)未經(jīng)處理或經(jīng)對(duì)癥處理后均可緩解或耐受。 結(jié)論聚乙二醇干擾素α-2b聯(lián)合利巴韋林治療移植腎功能穩(wěn)定的丙型肝炎患者有確切療效,對(duì)移植腎功能無(wú)明顯影響,無(wú)嚴(yán)重不良反應(yīng),較為安全。 目的探討腎移植術(shù)后間質(zhì)性肺炎的臨床病程規(guī)律、治療原則及影響轉(zhuǎn)歸的主要因素。 方法回顧性分析2006年11月至2013年12月診治的30例同種異體腎移植術(shù)后早期間質(zhì)性肺炎患者的臨床資料,對(duì)其臨床表現(xiàn)、病程進(jìn)展規(guī)律、治療措施及臨床轉(zhuǎn)歸進(jìn)行分析。 結(jié)果30例患者中29例于腎移植術(shù)后2-6月內(nèi)發(fā)病,其病程進(jìn)展具有較一致的規(guī)律性,整個(gè)病程時(shí)間平均34.9±7.5天,通過(guò)每周肺部CT檢查,發(fā)現(xiàn)起病到病程高峰平均14.8±1.9天,病程達(dá)到高峰后一般維持7.3±3.6天,即會(huì)出現(xiàn)明顯的病程好轉(zhuǎn)。若病程高峰時(shí)的肺部CT表現(xiàn)嚴(yán)重,且維持時(shí)間長(zhǎng)而未出現(xiàn)病程好轉(zhuǎn),則往往預(yù)后較差。病程恢復(fù)期平均13.1±3.7天。治療上通過(guò)對(duì)激素、抗生素、抗真菌藥物的使用進(jìn)行優(yōu)化調(diào)整,結(jié)合營(yíng)養(yǎng)支持、提高免疫力以及大幅減量或停用免疫抑制劑等措施,病程高峰期胸部CT表現(xiàn)程度為較輕及中度的23例患者均治愈出院,胸部CT表現(xiàn)較重的7例患者中3例治愈,4例死亡。 結(jié)論腎移植術(shù)后早期間質(zhì)性肺炎具有比較規(guī)律的病程進(jìn)展特點(diǎn)。對(duì)目前的大多數(shù)文獻(xiàn)報(bào)道的治療方案,包括甲基強(qiáng)的松龍的使用、抗生素的使用、抗真菌藥物的使用、營(yíng)養(yǎng)支持和免疫抑制劑的使用等方面進(jìn)行進(jìn)一步的優(yōu)化調(diào)整,在避免過(guò)度醫(yī)療的情況下取得了良好的治療效果。 目的探討和比較相同濃度下即復(fù)寧和ATG-F殺傷淋巴細(xì)胞的效價(jià)。 方法將相同濃度的即復(fù)寧和ATG-F倍比稀釋,對(duì)正常受試者外周血淋巴細(xì)胞進(jìn)行淋巴細(xì)胞毒試驗(yàn)(CDC),用流式細(xì)胞儀進(jìn)行相關(guān)檢測(cè)。 結(jié)果1.體外淋巴毒試驗(yàn)中即復(fù)寧和ATG-F對(duì)6名健康志愿者外周血淋巴細(xì)胞的殺傷作用隨著稀釋滴度的增加逐漸下降。即復(fù)寧滴度為1：1時(shí)殺傷淋巴細(xì)胞比率最高,54.06%-82.49%(66.24±10.35),在1：128時(shí)殺傷比率10%(5.59±2.59)。ATG-F滴度為1：1時(shí)殺傷效果最強(qiáng),38.06%-70.38%(59.8±11.8),在1：64時(shí)殺傷比率10%(6.31±4.80)。2.即復(fù)寧對(duì)外周血T淋巴細(xì)胞殺傷比率平均為51.23%,ATG-F為49.84%。即復(fù)寧對(duì)B淋巴細(xì)胞殺傷比率平均為30.45%,ATG-F則為24.31%(P=0.0002)。 結(jié)論即復(fù)寧和ATG-F均可顯著清除正常人外周血淋巴細(xì)胞。相同濃度下,即復(fù)寧的效價(jià)大約是ATG-F的2倍。此外,即復(fù)寧比ATG-F有更強(qiáng)的清除B細(xì)胞的作用。 目的探討腎移植受者長(zhǎng)期服用五酯膠囊提高他克莫司(Tac)血藥濃度的安全性和適應(yīng)癥。 方法在Tac谷濃度相當(dāng)?shù)囊浦材I功能穩(wěn)定受者中根據(jù)是否長(zhǎng)期服用五酯膠囊分為五酯組10例和對(duì)照組10例,比較兩組間的Tac藥代學(xué)參數(shù),并比較五酯膠囊對(duì)不同CYP3A5基因型受者服用Tac劑量的影響。 結(jié)果五酯組服用五酯膠囊平均31月,Tac平均谷濃度6.3μg/L；對(duì)照組Tac平均谷濃度5.9μg/L。五酯組Tac的平均峰濃度和曲線下面積均略高于對(duì)照組,達(dá)峰時(shí)間稍延遲,但總體差異無(wú)統(tǒng)計(jì)學(xué)意義。CYP3A5*1/*3型在二組都占60%,而五酯組受者的平均Tac劑量比對(duì)照組下降約36%(p0.01)。*1/*1型受者在五酯組占30%,其服用五酯膠囊后Tac的平均劑量比*1/*3型受者減少更明顯,幾乎達(dá)到平均服藥量最低的對(duì)照組*3/*3型受者的Tac服藥量。 結(jié)論腎移植后長(zhǎng)期服用五酯膠囊提升Tac濃度的方法對(duì)大部分CYP3A5*1基因型受者安全有效,尤其對(duì)CYP3A5*1/*1型受者。
[Abstract]:Objective to evaluate the efficacy and safety of peginterferon a-2b combined with Leigh Bhave Lin in the treatment of hepatitis C after renal transplantation.
Methods 1 years after renal transplantation, 9 patients with normal blood creatinine in the normal range of hepatitis C were subcutaneously injected with peginterferon alpha -2b (Pepe -2b), 1 times a week, and 1 times a week. At the same time, Leigh Bhave Lin 400-600mg/d was taken orally. HCV-RNA was detected each month and HCV-RNA was further consolidated after 3-9 months. The response of Virology was observed. At the same time, liver and kidney function, blood routine changes and adverse reactions during treatment were observed.
Results the total course of treatment for 9 patients was 4-20 months, of which 6 cases (66.7%) received a satisfactory sustained virological response (SVR), and no recurrence occurred in June after the observation of cessation of interferon therapy. After the rapid virology response was obtained, the relapse after the consolidation therapy was stopped in March, and the 1 cases had no obvious virological response during the treatment of 8 months. Blood creatinine in all patients fluctuated in the normal range, and no signs of acute rejection were found. The major adverse reactions during the treatment included influenza like syndrome (fever, muscle soreness, loss of appetite, etc.), an excessive myelosuppression and anemia. All adverse reactions were relieved or tolerated after untreated or symptomatic treatment.
Conclusion peginterferon alpha -2b combined with Leigh Bhave Lin is effective in the treatment of hepatitis C patients with stable renal function, and has no obvious effect on renal transplantation, no serious adverse reaction and safe.
Objective to investigate the clinical course, principles and main factors affecting the prognosis of interstitial pneumonia after renal transplantation.
Methods the clinical data of 30 patients with early interstitial pneumonia after the allograft kidney transplantation were analyzed retrospectively. The clinical manifestations, the progress of the course of the disease, the treatment measures and the clinical outcome were analyzed.
Results of the 30 patients, 29 were found within 2-6 months after renal transplantation. The course of the disease progresses with a consistent regularity. The average duration of the disease was 34.9 + 7.5 days. Through the weekly lung CT examination, the average duration of the onset was 14.8 + 1.9 days, and the duration of the disease was generally 7.3 + 3.6 days after the course reached the peak. When Cheng Gaofeng had a severe CT performance in the lungs and maintained a long duration without a improvement in the course of the disease, the prognosis was poor. The average duration of the course was 13.1 + 3.7 days. The treatment of hormone, antibiotics and antifungal drugs was optimized, combined with nutritional support, improvement of immunity, significant reduction or stop use of immunosuppressants. At the peak of the disease, 23 cases of mild and moderate CT were cured and discharged. 3 of the 7 patients with severe chest CT were cured and 4 died.
Conclusion early interstitial pneumonia after renal transplantation has a relatively regular course of progression. Most of the present treatment schemes, including the use of methylprednisolone, the use of antibiotics, the use of antifungal drugs, nutritional support and the use of immunosuppressive agents, are further optimized and avoided. Under the condition of excessive medical treatment, good therapeutic effect has been achieved.
Objective to investigate and compare the titers of the killing lymphocytes of Fu Ning and ATG-F at the same concentration.
Methods the lymphocyte toxicity test (CDC) was carried out on peripheral blood lymphocytes of normal subjects, and the flow cytometry was used to detect the same concentration of the peripheral blood lymphocytes of the normal subjects.
Results 1. in the 1. in vitro lymphatic test, the killing effect of tannin and ATG-F on the peripheral blood lymphocytes of 6 healthy volunteers gradually decreased with the increase of the dilution titer. That is, the ratio of the killer lymphocyte was the highest when the tannin titer was 1:1, 54.06%-82.49% (66.24 + 10.35), and the killing ratio of 10% (5.59 + 2.59).ATG-F titer at 1:1 at 1:1. The injury effect was the strongest, 38.06%-70.38% (59.8 + 11.8), the killing ratio at 1:64 was 10% (6.31 + 4.80).2., that was, the average killing ratio of T lymphocyte in the peripheral blood of the Ningxia was 51.23%, ATG-F was 49.84%., the average of B lymphocyte killing ratio was 30.45%, and ATG-F was 24.31% (P= 0.0002).
It is concluded that tannin and ATG-F can clear the peripheral blood lymphocytes of normal people. Under the same concentration, the titer of tannin is about 2 times that of ATG-F. In addition, the effect of tannin is stronger than that of ATG-F.
Objective to investigate the safety and indications of long-term use of five ester capsules in improving the plasma concentration of tacrolimus (Tac) in renal transplant recipients.
Methods the Tac pharmacokinetic parameters between the two groups were compared and the effects of the five ester capsules on the dose of Tac were compared between the two groups according to whether the five ester capsules were divided into five esters in 10 cases and the control group were divided into 10 cases and the control group.
Results the average concentration of Tac in the five ester group was 31 months and the average Valley concentration was 6.3 g/L, and the average peak concentration of Tac in the control group was slightly higher than that of the control group, and the area under the curve was slightly higher than that of the control group. The peak time was slightly delayed, but the overall difference was not statistically significant in the two groups of the two groups and 60%, while the average Tac of the five ester group was Tac. The dosage of the dose compared to the control group was about 36% (P0.01) and the group.*1/*1 was 30% in the five ester group. The average dose of Tac after taking five ester capsules was more obvious than that of the *1/*3 type, and it almost reached the Tac dosage of the *3/*3 type recipient in the control group with the lowest average dosage.
Conclusion long term use of five ester capsules to enhance Tac concentration after renal transplantation is safe and effective for most CYP3A5*1 genotype recipients, especially for CYP3A5*1/*1 type recipients.

【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R699.2

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