中性粒细胞缺乏期感染的综合防治

目的：探讨接受联合化疗的恶性肿瘤患者在中性粒细胞缺乏期感染的发生情况及相关因素。方法：１０４ 例接受联合化疗患者在中性粒细胞缺乏期分别采用综合措施，即层流室隔离，预防性应用抗生素、ＧＭ－ＣＳＦ激活骨髓等，单用抗生素防治，两组病例均为５２ 例。结果：综合组中性粒细胞恢复快，粒细胞缺乏期明显缩短，仍有８ 例发生感染，感染率１５．４％ ，但程度轻，预后好，无霉菌感染；单用抗生素组１４ 例发生感染，感染率２６．９％ ， Ｐ＞ ０．０５，差异无显著性，２ 例合并霉菌感染，死亡２例。结论：综合措施防治联合化疗中性粒细胞缺乏期感染是有效的。     

Safety of a low-dosage Filgrastim (rhG-CSF) treatment in non-neutropenic surgical intensive care patients with an inflammatory process

Objective: To evaluate the effect and safety of a low dose Filgrastim treatment in surgical intensive care patients. Design: Prospective, clinical study. Setting: Surgical intensive care unit (ICU) in a university hospital. Patients: Ten patients with the systemic inflammatory response syndrome (SIRS) and ten patients with sepsis were included in the study. Interventions: Filgrastim was given intravenously at 1.0 μg/kg for 3 days, followed by 0.5 μg/kg for 4 days. Measurements and results: Filgrastim treatment increased leukocyte counts and plasma levels of G-CSF. Cytokine levels (IL-6 and IL-8) decreased in the first 3 days of treatment. None of the SIRS patients developed sepsis or multiple organ failure and none of the patients died. In the sepsis group four patients died. No adverse side effects were observed, especially no attenuation of lung injury. Conclusions: Low-dosage Filgrastim treatment in ICU patients is safe. Whether the observed changes of the inflammatory response can be attributed to Filgrastim has to be clarified in further randomized trials. Received: 12 April 1996 Accepted: 15 September 1996     

中剂量环磷酰胺或增大环磷酰胺剂量的常规化疗联合G-CSF动员恶性肿瘤患者外周血造血祖细胞

目的　多中心临床研究糖基化的G CSF联合中剂量环磷酰胺 (Cy)或增大针对性联合化疗中Cy剂量动员自体外周血造血祖细胞的效果。方法　北京地区 4所医院 30例患者纳入方案。其中非霍奇金淋巴瘤 (NHL) 2 1例 ,霍奇金病 (HD) 1例 ,乳腺癌 7例及卵巢癌 1例。采用中剂量Cy或以增大Cy剂量为基础的针对性化疗联合G CSF动员自体外周血造血祖细胞 (APBPC)。在化疗后白细胞计数达最低值时开始应用G CSF。当白细胞升至 5 .0× 10 9 L以上时 ,用血细胞分离机采集。结果　Cy平均实际使用剂量为 3.95g(2 .3g m2 ) ;G CSF的剂量分别为 2 5 0 μg d(2 9例 ) ,5 0 0 μg d(1例 ) ,实际剂量3 1～ 6 .4 μg·kg- 1 ·d- 1 。 30例患者平均采集 2 .7次 ,其中 13例采集 2次 ,14例采集 3次 ,3例采集 4次。达到目标采集量单个核细胞≥ 6× 10 8 kg为 2 1例 (70 .0 % ) ,CD34 + 细胞≥ 2× 10 6 kg为 30例 (10 0 % ) ,CFU GM≥ 2× 10 5 kg为 2 4例中 15例 (6 2 .5 % )。 1次采集后 2 7例 (90 .0 % )、2次采集后 2 9例 (96 .7% )患者达到了CD34+ 细胞数目标采集量。结论　G CSF 2 5 0 μg d联合中剂量Cy或以增大Cy剂量为基础的针对性化疗可采集到足够数量的APBPC。     

胸、腹水中测定G-CSF的意义

目的观察胸、腹水中G—CH的水平及意义。方法应用中国医学科学院生产的粒细胞集落刺激因子（G—CSF）酶联免疫检测试剂盒对140例胸、腹水标本中G－CSF水平进行检测。结果漏出液组60例，G－CSF阳性检出度为3．3％，渗出液组80例，G－CH阳性检出率为77．5％，经x2检验具有显著性差异，且渗出液阳性标本WBC＞2．0X109／L，以中性粒细胞为主，提示感染性胸、腹水，渗出液18例阴性标本中，WBC计数在0．5—1.2X109／L之间，分类以淋巴细胞为主，提示非感染性渗出液。结论检测胸、腹水中的G－CSF可以鉴别渗出液和漏出液，且可作为诊断感染性渗出浓的重要依据。     

经粒细胞集落刺激因子动员的正常供者自发性脾破裂一例——附文献复习

目的讨论异基因外周血造血干细胞移植过程中粒细胞集落刺激因子（G—CSF）的不良反应及其动员的正常供者的安全问题。方法报道国内第1例经G—CSF动员的正常供者自发性脾破裂，并进行相关文献复习。结果本文供者和3例文献报道的供者，在G—CSF动员后脾脏均增大并发生自发性脾破裂；1例文献报道的供者，在G—CSF动员后脾脏未增大，但也出现自发性脾破裂。结论供者在G—CSF动员、采集过程中、采集后出现腹痛、头昏时应警惕脾破裂的发生。     

Long-Term Safety of Short-Term Administration of Filgrastim (rhG-CSF) and Leukophresis Procedure in Healthy Children: Application of Peripheral Blood Stem Cell Collection in Pediatric Donors

Administration of filgrastim (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) (Neupogen) in healthy donors to mobilize hematopoietic stem cells (HSCs) is a widespread practice in adults. Application of peripheral blood stem cell (PBSC) collection in normal pediatric donors is scarce due to ethical issues. Hence, there are insufficient data on the long-term impact of PBSC procedure in healthy children. This retrospective study aimed to evaluate the early and late adverse effects of PBSC donation in pediatric donors. Bone marrow and PBSC procedures and known adverse events of each technique were completely explained to parents and when applicable to children and written informed consent was obtained. rhG-CSF was administered for 4 days. HSCs were collected on the fifth day through continuous-flow apheresis and donors were followed for 30 days. Manual chart review was performed to collect short-term complications. Donors' health status was assessed via a questionnaire. A total of 145 healthy pediatric donors with a median age of 10 years at the time of donation (2 to 15 years) were followed for a median of 4.8 years (range, 1.2 to 14.2 years). The most frequent symptoms of rhG-CSF administration were fatigue (5%) and headache (3%). Thirty-five (24%) donors experienced hypocalcaemia during apheresis procedure that quickly responded to treatment. Two pregnancies occurred after rhG-CSF administration that resulted in normal births. We did not encounter any serious adverse events, including neoplastic disorders and death in this study. rhG-CSF and leukophresis procedure were well-tolerated in this study and all children completed the donation process without interruption or reduction of rhG-CSF dosage. Our results suggest that rhG-CSF is a safe drug in healthy children for the purpose of HSC mobilization.     

粒—巨噬细胞集落刺激因子对Vp16诱导白血病细胞凋亡的调控作用

目的：探讨粒－巨噬细胞集落刺激因子（ＧＭ－ＣＳＦ）对Ｖｐ１６诱导白血病细胞凋亡的调控作用，指导白血病临床治疗中正确使用ＧＭ－ＣＳＦ。方法：在构建高效表达ＧＭ－ＣＳＦ的逆转录载体Ｎ２Ａ／ＣＭＶ／ＧＭ－ＣＳＦ表达系统的基础上，对转ＧＭ－ＣＳＦ基因和未转ＧＭ－ＣＳＦ基因的白血病ＨＬ－６０细胞进行研究。结果：未转ＧＭ－ＣＳＦ基因及转空载体Ｎ２Ａ的ＨＬ－６０细胞经Ｖｐ１６处理后均出现凋亡的特征性表现：ＤＮＡ电泳呈梯状；流式细胞仪ＤＮＡ直方图上呈现特征性的亚二倍体（亚Ｇ１）峰；透射电镜观察细胞形态可见凋亡的特征性改变。结论：Ｖｐ１６具有诱导白血病细胞发生凋亡的作用，而ＧＭ－ＣＳＦ能够抑制Ｖｐ１６诱导的细胞凋亡。以上结果表明，白血病临床治疗中为预防和改善化疗所致骨髓抑制而应用ＧＭ－ＣＳＦ时，应谨慎地选择时机，在化疗前和化疗期间不宜使用，以避免白血病细胞对抗癌药物诱导的凋亡产生抵抗而导致耐药。     

超声心动图评价粒细胞集落刺激因子动员自身骨髓干细胞对心肌梗死后左心室重构及心功能的影响

目的　运用超声心动图评价粒细胞集落刺激因子(granulocyte colonystimulatingfactor,G CSF)动员自体骨髓干细胞对大鼠心肌梗死(心梗)后左室重构及心功能的影响。方法　40只雄性SD大鼠 随机分成G CSF治疗组(16只)、对照组(16只)和假手术组(8只)。治疗组及对照组结扎大鼠冠状动脉左 前降支,造成大鼠急性前壁心梗。假手术组仅单纯开胸。心梗后6h起治疗组给予皮下注射G CSF150 μg·kg-1·d-1共5d,其余两组给予生理盐水。心梗前、心梗后1d、2周及6周运用超声心动图评价左室 形态及心功能变化。心梗后6周处死大鼠,取出心脏,测量并比较治疗组及对照组的心肌瘢痕指数。结果 心肌梗死后6周,与对照组相比,治疗组的左室舒张末期内径(LVDd)和左室收缩末期内径(LVDs)明显减 小[LVDd(0.72±0.03)cm对(0.83±0.02)cm,P=0.006;LVDs(0.34±0.03)cm对(0.55±0.03)cm, P<0.001];左室射血分数(LVEF)、缩短分数(FS)则显著增高[LVEF(87.6±2.9)%对(62.5±2.5)%; FS(52.7±2.4)%对(30.6±2.0)%,P均<0.001];Tei指数则明显降低(0.23±0.06对0.44±0.05,P =0.009)。心梗后6周治疗组的瘢痕指数亦较对照组明显降低[(37.3±11.0)%对(51.9±11.5)%,P< 0.05]。结论　G CSF动员自身骨髓干细胞减轻左室重构,改善心功能。超声心动图可     

Interferon-α suppressed granulocyte colony stimulating factor production is reversed by CL097, a TLR7/8 agonist

Background and Aim: Neutropenia, a major side‐effect of interferon‐α (IFN‐α) therapy can be effectively treated by the recombinant form of granulocyte colony stimulating factor (G‐CSF), an important growth factor for neutrophils. We hypothesized that IFN‐α might suppress G‐CSF production by peripheral blood mononuclear cells (PBMCs), contributing to the development of neutropenia, and that a toll‐like receptor (TLR) agonist might overcome this suppression. Methods: Fifty‐five patients who were receiving IFN‐α/ribavirin combination therapy for chronic hepatitis C virus (HCV) infection were recruited. Absolute neutrophil counts (ANC), monocyte counts and treatment outcome data were recorded. G‐CSF levels in the supernatants of PBMCs isolated from the patients and healthy controls were assessed by enzyme‐linked immunosorbent assay following 18 h of culture in the absence or presence of IFN‐ α or the TLR7/8 agonist, CL097. Results: Therapeutic IFN‐α caused a significant reduction in neutrophil counts in all patients, with 15 patients requiring therapeutic G‐CSF. The reduction in ANC over the course of IFN‐α treatment was paralleled by a decrease in the ability of PBMCs to produce G‐CSF. In vitro G‐CSF production by PBMCs was suppressed in the presence of IFN‐α; however, co‐incubation with a TLR7/8 agonist significantly enhanced G‐CSF secretion by cells obtained both from HCV patients and healthy controls. Conclusions: Suppressed G‐CSF production in the presence of IFN‐α may contribute to IFN‐α‐induced neutropenia. However, a TLR7/8 agonist elicits G‐CSF secretion even in the presence of IFN‐α, suggesting a possible therapeutic role for TLR agonists in treatment of IFN‐α‐induced neutropenia.     

粒细胞集落刺激因子在抗甲状腺药物诱发的粒细胞缺乏症治疗中的应用

粒细胞缺乏是抗甲状腺药物最严重的不良反应,缺乏特异性的治疗。研究发现粒细胞集落刺激因子(G-CSF)用于抗甲状腺药物诱发的粒细胞缺乏有良好效果,现从机制、疗效、具体应用方法、安全性等方面进行阐述。