呼出气一氧化氮在儿童哮喘缓解期的应用价值

目的：探讨呼出气一氧化氮检测用于评估临床缓解期哮喘儿童病情的价值。方法选取214例处于临床缓解期哮喘儿童,按照有无进行规范化治疗分为治疗组和对照组。同时记录FeNO及PC20 FEV1数值。结果治疗组与对照组平均FeNO值分别为22．63×10－9 ppb和39．67×10－9 ppb ,差异有统计学意义（ P＜0．01）。治疗组与对照组平均 PC20 FEV1数值分别为（7．43±6．16）和（6．78±5．83）,差异无统计学意义（P＞0．05）。FeNO与PC20 FEV1呈负相关性（r＝－0．372,P＜0．01）,直线回归方程为Y＝35．883－1．074X（X表示PC20 FEV1,Y 表示FeNO）。结论 FeNO数值可以作为哮喘患儿非特异性气道炎症控制状况的可靠指标。呼出气一氧化氮检测与支气管激发试验联合,可显著提高临床缓解期哮喘患儿的诊断率。     

Predicting long-term outcomes after cardiac arrest by using serum neutrophil gelatinase-associated lipocalin

Objectives

Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by various tissues in pathologic states. Previous studies reported that post-cardiac arrest serum NGAL levels correlate with short-term neurologic outcomes and survival. The aim of this study was to examine the associations between NGAL levels post-cardiac arrest and long-term outcomes and survival.

Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases

Vision is the sense that we use to navigate the world around us. Thus it is not surprising that blindness is one of people's most feared maladies. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through drug therapy, gene augmentation or a cell-based transplantation approach. In this review we will discuss the use of the induced pluripotent stem cell technology to model and develop various treatment modalities for the treatment of inherited retinal degenerative disease. We will focus on the use of iPSCs for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell transplantation and replacement.     

布地奈德联合沙丁胺醇雾化吸入对急性哮喘发作患儿诱导痰液炎性细胞和细胞因子的影响

目的 布地奈德（普米克令舒）联合沙丁胺醇雾化吸入治疗儿童哮喘急性发作前后气道炎性细胞、白介素6（IL-6）、IL-8、肿瘤坏死因子α（TNF-α）的变化，探讨其影响机制。方法 对急性哮喘发作患儿采用上述联合治疗1周，共对34例急性发作期、24例缓解期患儿和15例正常儿童的诱导痰液进行炎性细胞计数和分类，测定其中IL-6、IL-8、TNF-α水平。结果 急性组的总白细胞数，嗜酸粒细胞、中性粒细胞单核细胞比例及IL-6、IL-8、TNF-α水平均高于正常对照组。缓解组除嗜酸粒细胞及淋巴细胞比例明显高于正常对照组外，其余上述炎性细胞比例及细胞因子水平均降至正常。结论 普米克令舒联合沙丁胺醇雾化吸入可显著降低急性哮喘发作患儿气道分泌物内嗜酸粒细胞、中性粒细胞和单核细胞数量及IL-6、IL-8、TNF-α水平。     

可诱导表达BMP4的正常来源及隐睾特异性iPSCs的建立及分化研究

目的建立可诱导表达骨形态发生蛋白质4(bone morphogenetic protein 4,BMP4)的正常来源及隐睾特异性诱导多能干细胞(induced pluripotent stem cells,iPSCs),比较两者体外定向分化的差异,为研究部分隐睾患儿成年后不育的原因提供具有人类遗传背景的体外研究模型。方法①建立可诱导表达BMP4的正常来源及隐睾特异性iPSCs,将正常来源iPSCs作为对照组,隐睾特异性iPSCs作为隐睾组;利用多西环素(doxycycline,Dox)进行诱导,筛选出BMP4表达量最高的细胞株;②将外源性添加BMP4的正常来源iPSCs作为外源性添加BMP4组(外源组),将Dox内源诱导BMP4表达的正常来源iPSCs作为Dox内源诱导BMP4表达组(内源组),此两组共同作为实验组;在细胞形态和基因表达水平比较实验组两组间BMP4因子诱导效果的差异;③通过Dox诱导BMP4的表达、双氢睾酮(dihydrotestosterone,DHT)、全反式维甲酸(all trans retinoid acid,ATRA)组成的三步法诱导分化方案,逐步诱导人的正常来源及隐睾特异性iPSCs向生精细胞方向分化,在基因及蛋白水平进行检测,比较两株细胞在分化过程中的差异。结果①经Dox诱导后,在正常来源及隐睾特异性iPSCs两株细胞中均可检测到BMP4表达明显升高、同时多能性基因OCT4的表达均呈明显下降趋势,与d0相比差异具有统计学意义,其中对照组的3#细胞株与隐睾组的5#细胞株在Dox诱导后BMP4表达量最高;②与外源组相比,内源组的细胞株形态变化更为均一、同步,BMP4的基因表达量更高,两组间的差异具有统计学意义;③在向生精细胞诱导分化过程中,对照组及隐睾组细胞的DAZL和PRDM1的表达量在两组之间的差异均无统计学意义;隐睾组的VASA、SYCP3、ACROSIN和TEKT1的表达量于诱导d14和d21时均明显低于对照组,两组之间的差异具有统计学意义。免疫染色结果显示:DAZL的阳性率在对照组和隐睾组细胞间的差异无统计学意义;隐睾组的VASA和SYCP3的阳性率于诱导d14和d21时均明显低于对照组,ACROSIN的阳性率于诱导d21时明显低于对照组,差异均具有统计学意义。结论本研究为部分隐睾患儿成年后不育的原因提供了具有人类遗传背景的体外研究模型,为未来的进一步研究奠定了良好基础。     

TREATMENT OF HAIRY CELL LEUKEMIA WITH INCREASING DOSES OF RECOMBINANT ALPHA A INTERFERON

:Since July 1984, eight patients with advanced hairy cell leukemia have received treatment with recombinant alpha A interferon. At commencement of interferon, seven patients had progressive cytopenia, and one was in leukemic phase (>20times10⁹/L circulating hairy cells). All patients had had previous splenectomy. Interferon was administered subcutaneously. The initial dose was 3times10⁶ U/day, continued until peripheral counts stabilised. Subsequently, patients received 6times10⁶ U/day, 9times10⁶ U/day, and finally 12 times 10⁶ U/day. The dose increases proceeded every 8–12 weeks, as tolerated. Seven patients had an objective response. There were four complete remissions, two partial remissions, and one minor response. Complete remission was documented only in patients on at least 6 times 10⁶ U/day for 12 weeks. The median time to complete remission was 40 weeks (range 35–53). Normalisation of peripheral blood counts preceded histologic marrow improvement. The median times for response (platelets ≤ 100 times 10⁹L, hemaglobin > 12 gm/dL, neutrophils < 1.5 times 10⁹/L), were six to eight and 17 weeks, respectively. Toxicity included myelosuppression during the first four weeks of therapy. With increasing doses of interferon, myelosuppression did not recur. A transient, mild, flu-like syndrome affected all patients. Two patients developed asymptomatic transaminitis at doses >6 times 10⁶ U/day. This resolved with dose reduction. In one case impotence was reported during the first four weeks of each interferon level. One patient discontinued after two weeks due to an exacerbation of systemic vasculitis. The median duration of treatment for the seven responding patients is 78 weeks (range 30–156). All remain on interferon without disease progression. This report confirms a high remission rate, which may reflect a dose-response phenomenon for long-term treatment with alpha interferon in hairy cell leukemia. (Aust NZ J Med 1988; 18: 557–562).     

Double cancer (lung and colon cancer) that showed complete remission with irinotecan and cisplatin combined chemotherapy

We report a rare case of double (colon and lung) cancer which showed complete remission with chemotherapy with irinotecan (CPT-11) and cisplatin (CDDP). The patient was a 67-year-old man who was diagnosed as having double cancer (stage IIIb pulmonary adenocarcinoma and stage 0 [or 1] well-differentiated adenocarcinoma of the ascending colon). Two courses of chemotherapy (CPT-11, 60 mg/m², days 1 and 8; CDDP, 30 mg/m², days 1 and 8) were performed. The combination therapy of CPT-11 and CDDP was very effective. In Japan, there have been few published reports describing the use of CPT-11 for the treatment of gastrointestinal cancer. We think that the use of CPT-11 in gastrointestinal cancer is promising. Received: August 18, 1999 / Accepted: March 24, 2000     

Ida-FLAG plus imatinib mesylate-induced molecular remission in a patient with chemoresistant Ph1+ acute myeloid leukemia

Imatinib mesylate is a potent, selective inhibitor of the tyrosine kinase activity of bcr-abl,which is now established as the state-of-the-art treatment for chronic, accelerated or even blastic phase of Philadelphia-positive [Ph(1)(+)] chronic myelogenous leukemia. It is also active in Ph(1)(+) acute lymphoblastic leukemia, but its role in Ph(1)(+) acute myeloid leukemia (AML) is less well investigated. We report here a patient with chemoresistant Ph(1)(+) AML, who responded promptly to one cycle of Ida-FLAG second-line chemotherapy by achieving complete morphologic, immunophenotypic, and cytogenetic remission but not a molecular one. The addition of imatinib mesylate led to a molecular remission, which is sustained for 10 months so far.