人细小病毒B19生物学特性研究进展

细小病毒B19是目前细小病毒家族中除人博卡病毒(HBoV)和新型细小病毒PARV4(Humanparvovirus 4)以外唯一可以引起人类疾病的病毒。它可能是多种疾病的致病因子,感染儿童可引起传染性红斑,感染成人可引起多发性关节病综合征,而对一些有免疫病,血液病的患者,B19感染可以引起严重的疾病,如慢性红细胞贫血,暂时性再障危象。病毒感染后对细胞的毒性是引起暂时性障碍危象和纯红细胞再障的直接原因。血液病患者中,B19病毒感染是引起暂时性障碍危象的主要病因,持续B19病毒感染会导致免疫缺损患者     

再生障碍性贫血中医药防治研究进展

再生障碍性贫血是由多种原因引起的骨髓造血功能衰竭,以全血细胞减少为特征的一种综合病症。目前普遍认为其发病机理与免疫因素介导的造血干细胞受损导致造血微环境异常相关。近年来,中医药以其独特的理论体系和治疗方法,在再生障碍性贫血的病因病机及防治防等研究方面取得了较大进展。中医药防治再生障碍性贫血一般从肾精亏虚、毒损髓络、生血乏源入手,以补肾填精、生血解毒为治疗法则,采用中药方剂或/和联合西药,可提高治疗有效率,降低西药的毒副作用,并可以调控T淋巴细胞的分化及相关细胞因子的表达。中药治疗可以改善骨髓造血微环境、不同程度的恢复骨髓的造血功能,提高患者的生存质量。现就中医药对此病的相关研究作一综述。     

经支气管镜局部灌注两性霉素B联合氩气刀治疗肺根霉病1例CSCD

报道1例经支气管镜局部灌注两性霉素B联合氩气刀技术治疗造血干细胞移植术后肺部小孢根霉感染。患者,男,13岁,诊断为肝炎相关性重症再生障碍性贫血,行外周血干细胞移植后出现高热、咳嗽、咳痰、气促,影像学表现为双肺感染性病变、部分实变,伴双侧胸腔积液,双下肺部分膨胀不全。经病理及二代基因测序证实为小孢根霉感染,通过支气管镜于右主支气管、右下基底段精准灌注两性霉素B治疗共16次,成功治愈。     

环孢霉素A治疗儿童再生障碍性贫血的临床疗效研究

目的:探讨环孢霉素A治疗儿童再生障碍性贫血患者的临床疗效。方法:选择在我院就诊或住院治疗的50例儿童再生障碍性贫血患者,随机分为实验组和对照组,每组25例。对照组患者给予司坦唑醇治疗,实验组患者在对照组基础上给予环孢素治疗。治疗结束后,检测并比较两组患者的血清雌二醇、睾酮水平、网织红细胞计数以及临床疗效。结果:与治疗前相比,两组患者治疗后的血清雌二醇水平均显著下降(P0.05),血清睾酮水平以及网织红细胞计数水平均明显升高(P0.05);与对照组相比,实验组患者的血清雌二醇水平较低(P0.05),血清睾酮水平以及网织红细胞计数水平较高(P0.05)。此外,实验组的临床治疗总有效率较对照组明显升高(P0.05)。结论:环孢霉素A可提高儿童AA患者的疗效,可能与其降低血清雌二醇水平,升高血清睾酮水平以及网织红细胞计数水平有关。     

疑难全血细胞减少症的免疫学变化及病因分析

目的:研究疑难全血细胞减少症的免疫学指标改变,探讨其病因构成及预后.并研究骨髓Coombs试验在疑难全血细胞减少症病因诊断中的意义.方法:对36例疑难全血细胞减少症患者的免疫指标,T细胞亚群,骨髓Coombs试验结果进行分析,根据免疫指标的变化,给予部分患者试验性用药,出院后随访一年.另以25例再生障碍性贫血患者为再障对照组,以22例健康成人为健康对照组,比较骨髓Coombs试验阳性率的差异,X2检验P＜0.05有统计学意义.结果:36位患者,18例诊断明确:5例为再生障碍性贫血,6例为免疫相关性全血细胞减少症,3例为系统性红斑狼疮,1例骨髓纤维化,1例肝癌,2例与妊娠相关的全血细胞减少;18例诊断不明确:8例患者于试验性升血治疗后血象好转,2例好转不明显,8例失访.骨髓Coombs试验阳性率在研究组与对照组的比较:疑难全血细胞减少症组(16.7％)高于再障对照组(X2=4.621,P＜0.05),也高于正常对照组(x2□4.09,P＜0.05)差异有统计学意义.结论:1对疑难全血细胞减少症患者进行试验性激素治疗及长期随访,有利于疾病的最终诊断.2免疫指标的检查及动态监测对明确疑难全血细胞减少症的病因十分重要.3骨髓Coombs试验对明确疑难全血细胞减少症病因有重要意义.     

人微小病毒B19感染的研究进展

近年来人微小病毒B19(human parvovirus B19)作为人类疾病的重要病原已愈来愈广泛受到重视。大量研究成果不但揭示了B19病毒的致病机理,Th-1介导的细胞免疫应答,而且发展了B19感染的诊断和B19污染血制品的筛查技术,并且为疫苗的研制奠定了基础。这里对人类B19病毒的病原学特征、致病机理、临床症状及实验室诊断方法和技术进行了较全面的综述。     

49例全血细胞减少的鉴别诊断

全血细胞减少是指周围血液中红细胞、白细胞、血小板计数均低于正常范围 ,它不是疾病的诊断 ,而是引起血液有形成分减少的某些疾病的共同临床现象。因此了解全血细胞减少的原因、诊断 ,对治疗措施的实施及预后评价十分重要。我院自1 989年 1月至 1 998年 8月共收治全血细胞减少病人 49例 ,现结合这组病人就其病因分类、诊断步骤及鉴别要点分析报告如下。1　临床资料1 .1　一般资料　 49例患者中 ,男 2 3例 ,女 2 6例 ,年龄 1 3～ 69岁 ,平均年龄 3 8岁。再生障碍性贫血2 5例 ,急性再生障碍性贫血 2例 ,慢性再生障碍性贫血 2 3例 ;急性白血病…     

肝肾移植术后患者隐球菌感染的临床特征分析

目的研究肝、肾移植术后患者隐球菌感染的临床特征。方法选取2010年1月到2015年7月来浙江大学医学院附属第一医院就诊的肝、肾移植术后并确诊为隐球菌感染的患者,对其临床特征进行回顾性分析。结果研究周期内有23例患者符合入组要求,其中肾移植术后21例、肝移植术后2例。对23例患者进行分析,发现单纯隐球菌肺炎6例(占26.0%)、单纯隐球菌性脑膜炎6例(占26.0%)、隐球菌性脑膜炎合并隐球菌肺炎8例(占34.7%)、隐球菌败血症2例(占8.6%),皮肤隐球菌感染1例(占4.3%)。所有隐球菌肺炎均经肺穿刺病理确诊,临床表现以发热,咳嗽咳痰,气急症状居多。胸部CT表现为结节、空洞、肿块、渗出等。所有隐球菌脑膜炎患者中9例经脑脊液培养出新生隐球菌、7例脑脊液墨汁染色见隐球菌,其中3例培养及涂片均为阳性。临床表现以头痛、发热、呕吐症状居多,1例并发癫痫,1例并发意识障碍。所有患者分别给予氟康唑、两性霉素B、氟胞嘧啶针、伏立康唑等抗真菌治疗,其中3例隐球菌脑膜炎患者予两性霉素B鞘内注射。经1~6个月治疗后,总体预后情况良好(好转22例,死亡1例)。结论肝、肾移植术后患者因免疫抑制剂的长期使用,隐球菌感染值得重视,其临床症状不典型,易误诊及漏诊,通过对其主要症状及影像学特点判断,结合肺穿刺活检、脑脊液检查、血培养等检查手段,可明显提高隐球菌感染的检出率,从而做到早诊断,早治疗,降低病死率。     

环孢霉素A治疗再生障碍性贫血临床观察

单用雄激素治疗再生障碍性贫血 ,完全缓解率3 5 %～ 5 3 %。我们于 1 995年 1月～ 1 999年 4月应用环孢霉素 A、雄激素治疗再生障碍性贫血 2 0例 ,取得较好效果 ,现报告如下。1　临床资料1 .1　一般资料　 2 0例中 ,男 1 2例 ,女 8例 ,年龄1 1～ 46岁 ,平均 3 3岁。治疗前病程 1～ 48个月。诊断标准参照 1 987年第四届再障学术会议修订的标准 ,其中慢性再障 1 3例 ,重型再障 I型 5例 ,重型再障 型 2例 ;慢性再生障碍性贫血患者在应用环孢霉素 A治疗前均使用过康力龙、丙酸宰丸酮、左旋咪唑、一叶秋碱、再障生血片、泼尼松、输注脐血或胎…     

再障红细胞的膜化学组成改变与代谢障碍机理

再生障碍性贫血（AA）严重危害人类健康．为阐明患者造血干细胞与骨髓微环境受损的病理生化机理,多年来从多条途径进行了探索．1986～2001年,研究组从临床生化与实验血液学的角度,较系统地研究了AA患者与AA大、小鼠模型红细胞的膜化学组成改变与代谢障碍．现就所获结果扼要作一综述．     

Clinically Evident,Non-terminal Infections with Herpesviruses and the Wart Virus in Immunosuppressed Renal Allograft Recipients

The clinical incidence of herpes simplex lesions, herpes zoster, cytomegalovirus infection, and warts has been determined in a group of renal allograft recipients. Herpes simplex lesions appeared to be no more common after transplantation than before in those patients subject to recurrent attacks. Among 74 patients there were seven cases of herpes zoster and seven serologically proved cases of cytomegalovirus infection with clinical manifestations. The incidence of warts increased with length of time after transplantation, 42% of patients being affected more than one year after transplantation. All of the viral infections studied behaved as in healthy adults, and serious illness, dissemination, wide-spread lesions, and complications were not seen. No factors other than immunosuppression and steroid therapy could be identified with certainty as predisposing to these infections.     

CMV infections in bone marrow transplanted patients--evaluation of prophylaxis with Cytotect (CMV hyperimmuneglobulin)

Cytomegalovirus (CMV) infection is a frequent and clinically important infection following bone marrow transplantation. Candidates for this study were patients admitted for transplantation: 22 patients received bone marrow from a HLA-identical, MCR-nonreactive sibling, in 9 patients an autologous BMT was performed. The anti-CMV IgG (Cytotect) was administered at a dosage of 1 ml/kg on days -7, 13, 33, 53, 73 and 93 after BMT. 5 patients in the very beginning of our BMT program did not receive Cytotect. Patients were given random blood products from the bloodbank not tested for CMV positivity. Active CMV infection or seroconversion in our patients was defined as a rise in IgG titer against the late antigen of fourfold or more or an IgM increase. In the allogeneic BMT group the pretransplant serological status was in 6 cases negative in recipients and donor, in 7 patients positive in recipients and negative in donors, and in 4 patients positive in recipients and donors. Of the 6 patients seronegative in recipients and donors, 3 developed active infection and of the 7 patients pretransplant positive with seronegative donors 3 developed active infection and 4 latent infections during the period from 2 to 100 days following grafting. 1 patient out of the group transplanted in third partial remission of AML developed interstitial pneumonia and died on day +30.4 of the 4 cases with seropositivity of recipients and donors developed active CMV infection. Of 9 patients with autologous transplantation 6 patients were pretransplant seropositive. 3 of these 6 developed active infection and 2 latent infection 30 to 180 days after grafting.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous immunoglobulin treatment of four patients with juvenile polyarticular arthritis associated with persistent parvovirus B19 infection and antiphospholipid antibodies

Children with rheumatic oligoarthritis and polyarthritis frequently establish persistent parvovirus B19 infections that may be associated with the production of antiphospholipid antibodies (anti-PL IgG). In this study we analysed the influence of high-dose intravenous immunoglobulin (IVIG) therapy on virus load, on the level of anti-PL IgG and its potential capacity to improve the patients' clinical status. Four juvenile patients with long-lasting polyarticular rheumatic diseases and persistent parvovirus B19 infection, associated in three cases with the presence of antibodies against beta2-glycoprotein I (anti-beta2GPI IgG), were treated with two cycles of IVIG on five successive days (0.4 g/kg per day). Clinical parameters including scores of disease activity, virus load and anti-PL IgG levels were determined before, during and after treatment. Two patients showed a complete remission that has lasted 15 months. During that period they showed neither clinical nor laboratory signs of inflammation. Viral DNA was not detectable in serum, and a decrease in anti-beta2GPI IgG was observed. As assessed by the Childhood Health Assessment Questionnaire and the Health-related Quality of Life Questionnaire for Children, both patients were no longer restricted in their activities of daily living and no impact on the health-related quality of life was observed. In one patient the therapy failed: there was no improvement of symptoms and no decrease in virus load or inflammatory parameters. In the fourth patient, clinical and laboratory parameters did not improve despite a decrease in both viral load and anti-PL IgG. Our results show that the use of IVIG to treat parvovirus B19-triggered polyarticular rheumatic disease of childhood might offer an opportunity to improve this disabling condition.     

Cutaneous and Bone Marrow Histoplasmosis After 18 Years of Renal Allograft Transplant

The frequency of histoplasmosis among solid organ transplant (SOT) recipients appears to be low where there are only a few case series, mostly among renal and liver transplant recipients. Herein we report a case of a 44-year-old woman who underwent a living-related renal transplant 18 years prior to evaluation, developed a nodule after followed by ulceration upon her posterior right leg and a second one upon her left leg 3 months and 2 months before her hospitalisation, respectively. The biopsy of lesion revealed the presence of Histoplasma spp. Bone marrow aspiration was performed and also revealed the same organism. She had initially received itraconazole without improvement of lesions, while a new lesion appeared on her left arm. Healing of all lesions could be observed after 40 days of liposomal amphotericin B when she was submitted to skin grafts on the legs and a surgical treatment on the arms, and the myelosuppression improved simultaneously. Histoplasmosis seems to be very uncommon among patients who underwent to organ solid transplantation. Most cases occur within 12–18 months after transplantation, although unusual cases have been presented many years post-transplant. There are cases reported in the literature, occurring from 84 days to 18 years after organ transplantation, but without cutaneous involvement. Our patient developed lesions on limbs and myelosuppression after 18 years of chronic immunosuppression medication. This case suggests that besides cutaneous histoplasmosis is an uncommon infection following iatrogenic immunosuppression and even rarer over a long period after the transplantation. Clinicians who care SOT recipient patients must bear in mind histoplasmosis infection as differential diagnosis in any case of cutaneous injury with prolonged fever and try to use as many tools as possible to make the diagnosis, once this disease presents a good prognosis if it is diagnosed and treated promptly.     

Quantitative competitive-PCR assay to measure human parvovirus B19-DNA load in serum samples

The B19 virus can persist in immunocompromised patients for several months and sometimes even years because of impaired immune response. Viremia in persistent and recurrent infection may range from very low to high titers and may be associated with chronic clinical manifestations, such as chronic anemia. Several recently developed techniques that quantify B19-DNA have improved laboratory diagnosis of the infection and can help guide the choice of treatment in persistent infections (i.e., intravenous immunoglobulin (IVIG) treatment vs immunosuppression reduction). Here we describe the development of a reliable internally controlled quantitative competitive (QC)-polymerase chain reaction (PCR) assay that measures B19-DNA load in serum samples by densitometric analysis of the amplification products for monitoring B19 infection in high-risk patients. A retrospective quantification of B19-DNA in the serum samples from 48 anemic transplanted patients by the QC-PCR assay we developed in our laboratory confirmed the presence of B19-DNA in 11 of 48 samples and showed a viral DNA load between 10³ and 10⁸ B19-DNA copies/mL depending on the patients' serostatus (the highest viral load was found in IgM-positive/IgG-negative patients that is, in patients with active B19 infection at onset). The assay also confirmed B19-DNA negative patients. Our QC-PCR assay may be easily relation between active B19 infection and occurrence of anemia and to assess the efficacy of IVIG therapy or immunosuppression reduction in clearing the virus in high-risk patients.     

Long-term immunologic induction of donor-specific tolerance to skin allografts by bone marrow transplant in rabbits

The induction of donor-specific tolerance to skin allografts was investigated in rabbits using bone marrow transplantation techniques reported to be effective in mice. Various routes of bone marrow transplantation (i.e., intravenous, portal venous, or intraosseous) were also examined. In regimen A, the animals were treated with portal venous injection of bone marrow cells from the donor on day 0 and intravenous injection of bone marrow cells from the same donor on posttransplant day 5. In regimen B, the animals were treated with portal venous and intraosseous injections of donor bone marrow cells on day 0 and intravenous injection of bone marrow cells from the same donor on posttransplant day 5. In regimen C, the animals were given intraosseous injection of donor bone marrow cells on day 0 and intravenous injection of bone marrow cells from the same donor on posttransplant day 5. It was found that regimens B and C were more effective than regimen A in prolonging allograft survival. The results demonstrate that induction of allograft tolerance can be achieved by bone marrow transplantation in a rabbit model. This protocol deserves further study in other large animal models.     

Factors associated with efficacy of pegylated interferon-α plus ribavirin for chronic hepatitis C after renal transplantation

Hepatitis C virus (HCV) infection is the major cause of chronic liver disease after renal transplantation (RT), which reduces both graft and patient survival. After RT, the most widely used approach is interferon (IFN)-based therapy of hepatitis C which may be unsatisfactory with both poor efficacy and an increasing risk of allograft rejection. Thus, it is not recommended unless patients develop fibrosing cholestatic hepatitis. Several recent studies, however, suggest that treatment was possible with preservation of both renal and liver functions. From the limited studies on HCV infection after RT, several factors have been identified as important tools for the management of therapy in these patients. Infection with HCV genotypes 2 and 3, low baseline viral load and absence of advanced fibrosis/cirrhosis in the liver are associated with a sustained virologic response (SVR). After initiation of treatment, initial viral decline with undetectable HCV-RNA at week 4 of therapy (RVR) is the best predictor of SVR independent of HCV genotype. Furthermore, some factors must be taken into consideration in order to avoid allograft rejection, such as the time between transplantation and therapy for HCV, the dose and duration of regimen and renal function. Careful evaluation of predictions of stable renal function and SVR for those patients helps to reduce inefficient treatment regimes and to increase the cure rate in addition to reducing the possible risk. In this review, the latest information was collected and we focus on the discussion of the factors influencing the attainment of SVR after RT.     

Obesity and adiponectin after kidney transplantation

Obesity and hyperlipidaemia are found very frequently after kidney transplantation (Tx) and may represent independent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored, a total of 68 obese transplant patients [body mass index (BMI) > 30 kg/m2] with dyslipidaemia over a period of 24 months. We compared the findings of a new therapeutic regimen 1 year (start of the study) and 2 years after renal transplantation. Based on a Subjective Global Assessment Scoring Sheet, we started at the end of the first year with an individualized hypoenergic-hypolipidaemic diet (IHHD). Subsequently, after corticoid withdrawal, IHHD was supplemented regularly with statins (atorvastatin 10-20 mg/day)) and followed-up for 2 years. All patients were on a regimen of cyclosporin A or tacrolimus and mycophenolate mofetil. During the study period, there was a significant decrease in BMI (p < 0.025) and an increase of the adiponectin level (p < 0.01). Long-term therapy was associated with a significant decrease in serum leptin (p < 0.01) and lipid metabolism parameters (p < 0.01). Inulin clearance, mean systolic and diastolic blood pressure, proteinuria, lipoprotein(a) and apo-lipoprotein E isoforms did not differ significantly. Based on our results, we assume that obesity and hyperlipidaemia after renal transplantation can be treated effectively by modified immunosuppression (corticosteroid withdrawal), statins and long-term diet (IHHD). The increased level of adiponectin may be a marker of reducing atherosclerotic and chronic allograft nephropathy processes.     

Clinical outcome following nerve allograft transplantation

The clinical outcome of seven patients who underwent reconstruction of long upper- and lower-extremity peripheral nerve gaps with interposition peripheral nerve allografts is reported. Patients were selected for transplantation when the nerve gaps exceeded the length that could be reconstructed with available autograft tissue. Before transplantation, cadaveric allografts were harvested and preserved for 7 days in University of Wisconsin Cold Storage Solution at 5 degrees C. In the interim, patients were started on an immunosuppressive regimen consisting of either cyclosporin A or tacrolimus (FK506), azathioprine, and prednisone. Immunosuppression was discontinued 6 months after regeneration across the allograft(s) was evident. Six patients demonstrated return of motor function and sensation in the affected limb, and one patient experienced rejection of the allograft secondary to subtherapeutic immunosuppression. In addition to providing the ability to restore nerve continuity in severe extremity injuries, successful nerve allografting protocols have direct applicability to composite tissue transplantation.     

Intravenous immunoglobulin treatment of four patients with juvenile polyarticular arthritis associated with persistent parvovirus B19 infection and antiphospholipid antibodies

Children with rheumatic oligoarthritis and polyarthritis frequently establish persistent parvovirus B19 infections that may be associated with the production of antiphospholipid antibodies (anti-PL IgG). In this study we analysed the influence of high-dose intravenous immunoglobulin (IVIG) therapy on virus load, on the level of anti-PL IgG and its potential capacity to improve the patients' clinical status. Four juvenile patients with long-lasting polyarticular rheumatic diseases and persistent parvovirus B19 infection, associated in three cases with the presence of antibodies against β₂-glycoprotein I (anti-β₂GPI IgG), were treated with two cycles of IVIG on five successive days (0.4 g/kg per day). Clinical parameters including scores of disease activity, virus load and anti-PL IgG levels were determined before, during and after treatment. Two patients showed a complete remission that has lasted 15 months. During that period they showed neither clinical nor laboratory signs of inflammation. Viral DNA was not detectable in serum, and a decrease in anti-β₂GPI IgG was observed. As assessed by the Childhood Health Assessment Questionnaire and the Health-related Quality of Life Questionnaire for Children, both patients were no longer restricted in their activities of daily living and no impact on the health-related quality of life was observed. In one patient the therapy failed: there was no improvement of symptoms and no decrease in virus load or inflammatory parameters. In the fourth patient, clinical and laboratory parameters did not improve despite a decrease in both viral load and anti-PL IgG. Our results show that the use of IVIG to treat parvovirus B19-triggered polyarticular rheumatic disease of childhood might offer an opportunity to improve this disabling condition.