地尔硫卓对肾移植受者他克莫司血浓度的影响及临床意义

目的观察钙通道阻滞剂地尔硫卓对免疫抑制剂他克莫司(FK506)血浓度的影响及临床意义。方法将13例术后服用他克莫司的肾移植受者分为实验组(6例)和对照组(7例),分别检测其FK506血浓度,比较实验组服用钙拮抗剂地尔硫卓后其FK506血浓度与对照组的差异、量化关系及不良反应。结果与对照组相比,实验组患者服用地尔硫卓后FK506的血药浓度提高了49.77%,减少术后FK506的服用量达27.44%,肝肾功能都有明显改善。结论地尔硫卓能提高肾移植受者FK506的血药浓度、减少术后FK506的服用量,改善肝肾毒性,具有较大的临床应用价值及社会经济效益。     

FK506对异体神经移植的影响

周围神经损伤后,异体神经移植对神经大段缺损的修复起着至关重要的作用。但免疫排斥反应仍是影响异体神经移植成败的关键所在,迄今为止已经有很多免疫抑制剂应用于临床。免疫抑制剂FK506能有效地抑制周围神经同种异体移植中的排斥反应。本综述从免疫抑制剂FK506的理化性质和作用机制及其对异体神经移植的影响因素入手,阐述免疫抑制剂FK506对神经恢复的促进作用,为FK506进一步的深入研究和临床应用提供理论依据。     

FK506对异体神经移植的影响

周围神经损伤后,异体神经移植对神经大段缺损的修复起着至关重要的作用。但免疫排斥反应仍是影响异体神经移植成败的关键所在,迄今为止已经有很多免疫抑制剂应用于临床。免疫抑制剂FK506能有效地抑制周围神经同种异体移植中的排斥反应。本综述从免疫抑制剂FK506的理化性质和作用机制及其对异体神经移植的影响因素入手,阐述免疫抑制剂FK506对神经恢复的促进作用,为FK506进一步的深入研究和临床应用提供理论依据。     

抗生素和免疫抑制剂的个体化用药对肝移植受体术后感染的影响

目的评价采用抗生素和免疫抑制剂的个体化治疗方案对肝移植受体术后感染的影响。方法回顾性分析采用抗生素和免疫抑制剂的个体化用药对31例肝移植受体术后的感染发生率、病原菌谱以及病死率的影响。结果住院期间发生感染15例次,常见病原菌为阴沟肠杆菌、铜绿假单胞菌、肺炎克雷伯菌、鲍曼不动杆菌、表皮葡萄球菌等,根据药敏试验,主要以泰能、他格适或特治星进行治疗。通过控制免疫抑制剂的血药浓度,术后感染率(48.4%)显著低于2003年之前移植病例的感染率(86.7%),P<0.05。细菌和真菌感染率明显减少(P<0.05),巨细胞病毒(CMV)感染率差异无统计学意义(P>0.05)。结论抗生素和免疫抑制剂的个体化应用,可以明显减少肝移植受体术后发生感染和其他并发症的风险。     

尿液转铁蛋白与他克莫司血药浓度的相关研究

目的分析肾移植患者尿液转铁蛋白(TRU)浓度检验指标与他克莫司(FK506)血药浓度之间的相关关系,以甄别TRU是否可以作为及时准确反映FK506浓度和肾功能损伤关系的检测指标。方法选取2011-2017年在天津市职业病防治院收治的30例肾移植受者进行回顾性分析,收集所有肾移植患者FK506血药浓度数据及血药浓度测定当天的尿液特定蛋白浓度化验检测结果。将患者根据FK506血药浓度分为四组(Ⅰ组≤5 ng/ml,5 ng/mlⅡ组≤10 ng/ml,10 ng/mlⅢ组≤15 ng/ml,15 ng/mlⅣ组),对四组数据中的尿液特定蛋白检测指标进行统计分析。结果相比其他四种尿液特定蛋白(尿微量白蛋白、尿液α1微球蛋白、尿液β2微球蛋白、尿液免疫球蛋白G),TRU含量与FK506血药浓度相关程度较低。结论不建议将检测TRU含量作为监测FK506对肾脏损伤的灵敏指标。     

异基因造血干细胞移植后巨细胞病毒及多瘤病毒感染相关临床特征

目的探讨异基因造血干细胞移植(allo-HSCT)术后人巨细胞病毒(HCMV)和多瘤病毒(BKV和JCV)感染相关临床特征。方法收集2016年6月—2017年12月共53例行allo-HSCT的恶性血液病患者临床资料。移植当天开始监测患者外周血与尿的HCMV、BKV和JCV核酸载量,每周一次至100 d。分析病毒感染的发生率、发生时间、相关临床表现及危险因素。结果 51例患者发生病毒感染,感染率为96.23%。其中,HCMV感染率为54.72%(29/53)、BKV感染率为77.36%(41/53)、JCV感染率为28.30%(15/53)。肺部感染、急性移植物抗宿主病(aGVHD)和出血性膀胱炎(HC)的发生率分别为54.72%、58.49%和20.75%。危险因素分析显示:发生aGVHD(OR=24.61,95%CI:2.30～46.24)、预处理采用全身照射(OR=33.39,95%CI:1.57～79.13)及使用ATG(OR=24.77,95%CI:1.16～52.58)是影响HCMV血症的独立危险因素,HLA全相合(OR=0.003,95%CI:0.00～0.10)可降低发生HCMV血症的风险;预处理采用全身照射(OR=15.10,95%CI:1.14～39.27)是影响BKV尿症的独立危险因素,供受者血型相合(OR=0.07,95%CI:0.01～0.64)可降低发生BKV尿症的风险。结论移植术后应尽早监测受者血及尿中HCMV及多瘤病毒感染情况,以期及时预防及减少并发症的发生。     

抗生素和免疫抑制剂的个体化用药对肝移植受体术后感染的影响

目的评价采用抗生素和免疫抑制剂的个体化治疗方案对肝移植受体术后感染的影响。方法回顾性分析采用抗生素和免疫抑制剂的个体化用药对31例肝移植受体术后的感染发生率、病原菌谱以及病死率的影响。结果住院期间发生感染15例次，常见病原菌为阴沟肠杆菌、铜绿假单胞菌、肺炎克雷伯菌、鲍曼不动杆菌、表皮葡萄球菌等，根据药敏试验，主要以泰能、他格适或特治星进行治疗。通过控制免疫抑制剂的血药浓度，术后感染率（48．4％）显著低于2003年之前移植病例的感染率（86．7％），P〈0．05。细菌和真菌感染率明显减少（P〈0．05），巨细胞病毒（CMV）感染率差异无统计学意义（P〉0．05）。结论抗生素和免疫抑制剂的个体化应用，可以明显减少肝移植受体术后发生感染和其他并发症的风险。     

山东1035例孕前妇女TORCH感染情况调查分析

目的探讨山东地区孕前妇女TORCH感染情况,为本地区孕前妇女保健提供参考依据,降低不良妊娠发生率。方法收集1035例孕前妇女外周血标本,利用化学发光免疫分析法(CLIA)对弓形虫(TOX)、巨细胞病毒(CMV)、风疹(RV)、单纯疱疹(HSV)的Ig G以及Ig M抗体进行检测,分析感染率。结果 Ig G抗体检测结果:TOX阳性率为1. 64%(17/1035),CMV阳性率为89. 47%(926/1035),RV阳性率为87. 73%(908/1035),HSV阳性率为94. 98%(983/1035)。Ig M抗体检测结果:TOX阳性率为0. 97%(10/1035),CMV阳性率为2. 80%(29/1035),RV阳性率为5. 12%(53/1035),HSV阳性率为15. 75%(163/1035)。HSV、CMV、RV感染模式均以Ig M-/Ig G+为主,而TOX感染模式则以Ig M-/Ig G-为主。结论山东地区孕前妇女TORCH的感染较普遍,急性感染以HSV为主,且HSV、CMV、RV既往感染率或疫苗接种率较高,人群存在一定免疫力,而对TOX抵抗力相对较差,需加强疫苗接种。     

套式PCR检测骨髓移植人巨细胞病毒感染的研究

骨髓移植受体由于免疫抑制或免疫缺陷诱发人巨细胞病毒感染常常造成移植失败。应用套式ＰＣＲ对骨髓移植３３例受体和９８例供体检测发现，受体人巨细胞病毒的感染率（７５．８％，２５／３３）明显高于普通正常人（５７％，５６／９８），移植后４０天可达９３．９％（３１／３３），呈感染上升趋势。结果提示有必要在ＢＭＴ时对供受体进行人巨细胞病毒感染检测，便于ＢＭＴ术前选择和术后治疗，以提高移植的成功率。     

巨细胞病毒感染与炎症性肠病患者糖皮质激素剂量、 CD_4~+T淋巴细胞数量的相关性

目的 探讨巨细胞病毒(CMV)感染与炎症性肠病(IBD)患者糖皮质激素剂量、CD_4⁺T淋巴细胞数量的相关性。方法 选取2017年6月-2020年6月南通市中医院门诊诊治的IBD患者240例，依据IBD患者是否合并CMV感染分为CMV感染组、非CMV感染组。收集患者临床资料，采用流式细胞仪检测外周血中CD_4+T淋巴细胞数量的相关性。方法 选取2017年6月-2020年6月南通市中医院门诊诊治的IBD患者240例，依据IBD患者是否合并CMV感染分为CMV感染组、非CMV感染组。收集患者临床资料，采用流式细胞仪检测外周血中CD_4⁺T淋巴细胞数量。结果 240例IBD患者检出CMV感染50例，CMV感染率为20.83%。CMV感染组患者病程≥24个月、发热症状、并发症、既往用药史为糖皮质激素类药物及免疫抑制剂、结肠镜表现为深大溃疡的占比均高于非CMV感染组，ALB、Hb水平均低于非CMV感染组(P<0.05)。CMV感染组应用糖皮质激素剂量高于非CMV感染组，CD_4+T淋巴细胞数量。结果 240例IBD患者检出CMV感染50例，CMV感染率为20.83%。CMV感染组患者病程≥24个月、发热症状、并发症、既往用药史为糖皮质激素类药物及免疫抑制剂、结肠镜表现为深大溃疡的占比均高于非CMV感染组，ALB、Hb水平均低于非CMV感染组(P<0.05)。CMV感染组应用糖皮质激素剂量高于非CMV感染组，CD_4⁺T淋巴细胞数量低于非CMV感染组(P<0.05)。病程、Hb、ALB水平、糖皮质激素剂量、CD_4+T淋巴细胞数量低于非CMV感染组(P<0.05)。病程、Hb、ALB水平、糖皮质激素剂量、CD_4⁺T淋巴细胞数量为IBD患者合并CMV感染的影响因素(P<0.05)。受试者工作特征曲线(ROC)分析显示糖皮质激素剂量、CD_4+T淋巴细胞数量为IBD患者合并CMV感染的影响因素(P<0.05)。受试者工作特征曲线(ROC)分析显示糖皮质激素剂量、CD_4⁺T淋巴细胞数量联合检测预测IBD患者CMV感染的曲线下面积为0.887。结论 病程长、血清Hb和ALB水平降低、糖皮质激素剂量高和CD_4+T淋巴细胞数量联合检测预测IBD患者CMV感染的曲线下面积为0.887。结论 病程长、血清Hb和ALB水平降低、糖皮质激素剂量高和CD_4⁺T淋巴细胞数量降低，是IBD患者CMV感染风险升高的影响因素，糖皮质激素剂量、CD_4+T淋巴细胞数量降低，是IBD患者CMV感染风险升高的影响因素，糖皮质激素剂量、CD_4⁺T淋巴细胞数量检测对IBD患者CMV感染有较高预测价值。     

Co-detection and discrimination of JCV and BKV DNA by duplex nested-PCR in renal transplant recipients

AIM: Several studies have disclosed a correlation between human polyomavirus BK (BKV) and interstitial nephritis in renal transplant recipients. It has recently been hypothesized that some cases of nephropathy may be associated with human polyomavirus JC (JCV). METHODS: In this paper we describe the development of duplex nested-PCR assay which allows the simultaneous detection and discrimination of genomic sequences of JCV and BKV 'large T antigen', resulting in amplicons of 150 bp and 278 bp, respectively. Thus, the presence of JCV and BKV DNA in urine and serum samples from 51 renal transplant recipients and 29 healthy controls was investigated and related to immunosuppressive regimens and renal function. RESULTS: The comparison between the incidence of the of BKV and/or JCV infections (detected by viruria and/or viraemia) in renal transplant recipients and the control group revealed a highly significant increase of the incidence of BKV infection in immunosuppressed patients vs healthy subjects (62.7% vs 27.6%; p=0.005). In particular, we found a significant increase of BKV-DNA viruria in renal transplant recipients vs healthy subjects (49% vs 17.2%; p=0.01), in agreement with the BKV urinary shedding in renal transplant recipients of the literature (5-45%). CONCLUSION: The nested-PCR technique is a valid diagnostic tool to detect viral presence in urine and its systemic diffusion. Our assay links the high sensitivity of nested amplification with the simultaneous detection and discrimination of genomic sequences of JC and BK polyomaviruses and thus provides a handy, rapid and sensitive means for DNA analysis of large numbers of samples.     

肾移植受者巨细胞病毒感染检测的临床意义

目的　比较肾移植受者采用不同方法检测巨细胞病毒 (CMV)感染的意义。方法　比较肾移植受者和健康供肾者外周血中的CMV -IgM ,CMV -IgG和CMV抗原 (CMV -Ag)的阳性率及其与CMV病的关系。结果　 167例肾移植受者CMV -IgM阳性率为 1 8% ,CMV -IgG阳性率为 98 8% ,CMV -Ag阳性率为47 2 % ,平均阳性抗原指数 3 2个 /5万白细胞 ;对照组 13例CMV -IgM均阴性 ,CMV -IgG均阳性。观察组3 6例CMV肺炎中CMV -IgG均阳性 ,CMV -IgM5 6%阳性 ,CMV -Ag91 7%阳性 ,平均阳性抗原指数 3 6个 /5万白细胞。结论　肾移植受者以CMV -Ag检测诊断CMV活动性感染及CMV病敏感性及特异性优于CMV -IgM及CMV -IgG。     

Rapid shell vial culture for the detection of respiratory viruses from bronchoalveolar lavage in immunocompromised patients

AIM: Viral lower respiratory tract infections (LRTI) are an important cause of morbidity in immunocompromised patients. The aim of this study was to evaluate the clinical impact of rapid shell vial cultures from bronchoalveolar lavage (BAL). METHODS: Sixty-seven BAL samples from 46 patients have been retrospectively examined: 51 from 31 transplant recipients and 16 from 15 immunocompromised patients. BAL were inoculated on human embryonic lung fibroblasts and VERO cells to isolate the following viruses: cytomegalovirus (CMV), herpesviruses, varicella-zoster virus, respiratory syncytial virus, adenovirus, Influenza viruses A and B and Parainfluenza viruses. Clinical, microbiological, laboratory, and radiological data were collected. RESULTS: A LRTI was present in 56.7% of cases: viral 40.3%, bacterial and/or fungal 23.9%, and mixed 7.5%. CMV accounted for 92.6% of viral LRTI. The prevalence of viral infections did not differ between symptomatic and asymptomatic patients; only bacterial and/or fungal infections were significantly more prevalent in symptomatic patients. No clinical, radiological or laboratory feature was significantly associated with the presence of a viral LRTI. In lung transplant recipients the rate of CMV infection was 50%. The result of BAL suggested commencement of antiviral chemotherapy in 25/67 episodes. CONCLUSION: Rapid shell vial culture and immunofluorescence techniques from BAL could play an important role in the clinical management of immunocompromised subjects.     

Sex differences in renal transplantation in Canada

To determine if a patient's sex influences access to renal transplantation in Canada, transplant recipient data for first cadaveric unrelated renal transplants were obtained from the Canadian Organ Replacement Register (CORR) for the period 1985-1992. There were 4683 first unrelated cadaveric transplant recipients during this time. Differences in the proportion of men and women registered with CORR who received a renal transplant were analyzed. In Canada between 1985 and 1992, 25% of males 40 years and older on dialysis received renal transplants compared with 18% of females (p < 0.0001, RR 1.54, 95% CI 1.40-1.67). There was no difference in the rates of transplants in males and females who were under 40 years of age. Adjusting for panel-reactive antibody data did not change the significance of the difference in transplant rates between the sexes. In Canada from 1985 to 1992, male patients with end-stage renal disease received proportionately more transplants than females.     

他克莫司对肾移植术后患者血钙水平的远期影响

目的探讨他克莫司对肾移植术后患者血钙水平的远期影响。方法将我院2002-2004年接受肾移植手术的124例患者,按免疫抑制方案不同随机分两组:观察组(他克莫司 MMF 强的松,n=58);对照组(环孢素A MMF 强的松,n=66)。比较两组患者肾移植2年后的血钙水平及高钙血症发生率。结果FK506治疗组和环孢素A组肾移植术后高钙血症发生率分别为5.17%和13.63%,两组比较具有显著性差异(P<0.01)。结论肾移植患者术后应用他克莫司比环孢素A可有效降低高钙血症的发生率。     

肾移植患者巨细胞病毒感染并发急性呼吸窘迫综合征

目的 探索肾移植患者巨细胞病毒(CMV)感染的诱因和治疗措施。方法 对4例CMV感染并发急性呼吸窘迫综合征(ARDS)的病例进行回顾性分析。结果 CMV感染并发ARDS死亡率高，75％病例死亡。结论 治疗CMV感染并发ARDS的关键是早期诊断、尽早治疗、适当调整免疫抑制剂。     

肾移植术后肺部感染的临床探讨

目的：探讨肾移植术后肺部感染的防治。方法：对1123例肾移植术后并发肺部感染的110例患者的临床资料进行回顾性分析。结果：101例肺部感染临床治愈，11例ARDS中抢救成功2例，死亡9例。病原菌分布：细菌感染69例（63％），巨细胞病毒（CMV）感染20例（18％），真菌感染16例（15％），结核菌感染8例（7％），病原菌不明9例（8％）。结论：细菌是肾移植术后肺部感染的主要致病菌；早期作出病原学诊断是治疗肾移植术后肺部感染的关键。     

CMV-specific polymeric and monomeric IgA antibodies in serum of renal transplant patients.

CMV-specific IgA, IgM and IgG antibodies were detected by ELISA in sera from 81 renal transplant patients. Twenty-seven patients were followed from transplantation; 6 patients who underwent on transplantation before the beginning of the study were followed during admissions for graft failure or acute illness; 48 outpatients were periodically monitored. One of the patient followed from transplantation experienced a primary CMV infection, serologically demonstrated by the appearance of specific IgM and IgG. Specific IgA appeared at the same time as IgM and lasted for about six months. A specific IgA response was observed in all but five recurrent CMV infections too, even when specific IgM were not present. In all outpatients periodically monitored for CMV serology specific IgA were not found. About specific IgA polimerization, a transient marked polymeric IgA (p-IgA) response was observed in only the primary infection whereas in all the other IgA positive patients, specific IgA were represented by monomers (m-IgA).     

Nosocomial infections in renal transplant patients: risk factors and treatment implications associated with urinary tract and surgical site infections

A prospective cohort study was conducted from January 2000 to December 2001 to determine the rate of bacterial nosocomial infections in renal transplant recipients. The patients were divided into two groups according to the origin of the allograft, namely deceased or living related donors. One hundred and sixty-three renal transplant recipients were reviewed during hospitalization; 110 (67.5%) kidneys were from deceased donors and 53 (32.5%) kidneys were from living related donors. The median length of hospitalization was 12 days for transplants from living related donors and 26 days for transplants from deceased donors (P<0.0001). Twenty-one (39.6%) recipients of kidneys from living related donors and 68 (61.8%) recipients of kidneys from deceased donors had bacterial nosocomial infectious episodes (P=0.019). The post-transplant nosocomial infections diagnosed during hospitalization included urinary tract infections (UTIs) (44.8%), surgical site infections (SSIs) (11%), pneumonia (6.1%), catheter-related bloodstream infections (4.2%) and others (1.8%). Risk factors for UTI included: recipient of kidney from a deceased donor, substitution of the initial immunosuppressive regimen, duration of urinary bladder catheterization, and length of hospitalization before the infection. Six Enterobacter cloacae strains with multiple resistances to antibiotics were identified in UTIs, and hospital dissemination was documented using molecular typing. UTI was the single most important hospital infection and was significantly higher in recipients of kidneys from deceased donors (P=0.001).     

CMC and EBV infections in children

CMV and EBV infections are common in humans. In immunocompetent persons those infections are usually asymptomatic but in immunocompromised can manifest as a severe disease. CMV is a common cause of congenital infections. It is also a frequent complication in transplant recipients. The aim of this study was to assess the prevalence of CMV and EBV infections among hospitalized children. Specific antibodies against CMV and EBV were detected in serum by ELISA test. Presence of CMV DNA was determined in leucocytes by Murex Hybrid Capture System. CMV and EBV infections were defined as the presence in serum IgM-class specific antibodies. Obtained results indicate that CMV and EBV infections are frequent in immunocompromised patients. Among patients with CMV or EBV infection, 40% have been diagnosed with cancer, most of whom with hematologic malignancies: leukemia or lymphoma. CMV and EBV coinfection was detected in 14% of infected children. Of all patients with CMV, 50% were neonates and infants. Congenital infection was diagnosed only in one case. The remaining infections were acquired during perinatal period or later.