低体质量儿童外周血干细胞的动员和采集

目的通过评价环磷酰胺+吡柔比星+长春新碱(CDV)、吡柔比星+长春新碱+环磷酰胺+顺铂(AVCP)、卡铂+替尼泊苷+长春新碱(CTV)动员方案对低体质量儿童神经母细胞瘤和原始神经外胚层肿瘤/横纹肌肉瘤/视网膜母细胞瘤自体外周血造血干细胞移植动员采集的临床效果,探讨安全有效地动员和采集低体质量儿童(体质量<20 kg)外周血干细胞的方法。方法在采用CDV/AVCP/CTV方案化疗+粒细胞集落刺激因子(G-CSF)动员后使用CS-3000 Plus血细胞分离机(美国Baxter公司),专用SVSC分离槽和SVCC收集槽,并选择儿童单个核细胞收集程序进行外周血干细胞采集。结果20例(神经母细胞瘤13例,视网膜母细胞瘤3例,横纹肌肉瘤2例,原始神经外胚层肿瘤2例)体质量小于20 kg患儿采用CDV/AVCP/CTV方案动员,化疗第4-9天(平均6 d)WBC<2×109L-1,应用G-CSF第6-15天(平均9 d)开始采集外周血造血干细胞,20例均采集到足够的单个核细胞数(MNC)和CD34+细胞,采集次数1~4次,平均2.1次,MNC:(6.1±1.2)×108kg-1,CD34+细胞为(3.9±0.8)×106...     

肿瘤患儿外周血单个核细胞采集及其对受体造血恢复的影响

目的回顾分析26例白血病和实体瘤患儿外周血干细胞采集效果及其对受体造血恢复影响,筛选可能与采集效率提高和受体造血恢复相关的因素。方法总结26例供体的49次粒系集落刺激因子(G-CSF)动员后的外周血采集过程,统计分析供体动员剂量、采集时外周血白细胞、收获的单个核细胞(MNC)和CD34 细胞数、受体造血恢复三者间的相关性。结果26例供体均能很好耐受动员和采集过程。采集物MNC和CD34 细胞中位数分别为4.5×108/kg和1.9×106/kg。动员剂量与采集物中MNC数呈正相关,与采集物CD34 细胞数无相关。采集当天供体外周血白细胞总数对采集细胞量无影响,而MNC水平与CD34 细胞采量正相关。结论受体的造血恢复与采集物中的CD34 细胞数可能存在相关性。因此这类患儿的采集时有必要动态监测其动员时的外周血CD34 细胞水平,确定最佳采集时间,以获取足够的CD34 细胞采量。     

HD-A+VM_(26)+rhG-CSF动员白血病患儿外周血造血干细胞的初步研究

目的 　评价HD -A +VM2 6+rhG -CSF动员白血病患儿外周血造血干细胞的效果。方法 　 5例高危急性白血病患儿 ,其中急性淋巴细胞白血病 (HR -ALL) 4例 ,急性杂合细胞白血病 (AHL) 1例。年龄 9～ 1 3岁。 5例患儿均采用HD -A +VM2 6+rhG -CSF方案进行动员。在化疗后第 9天应用rhG -CSF ,当白细胞升至 5× 1 0 9/L以上时 ,使用CS - 30 0 0血细胞分离机采集PBSC。结果 　 4例采集 1次 ,1例采集 2次。全部患儿均能耐受该动员方案治疗。MNC值为 5 96 5( 5 0 2～ 7 2 )× 1 0 8/kg。CD3 4+ 细胞量为 4 372 ( 3 95～ 5 6 2 )× 1 0 6/kg。结论 　G -CSF联合大剂量Ara -C和VM2 6的化疗可采集到足够数量的自体外周血干细胞。     

CD34+细胞自身移植治疗儿童难治性系统性红斑狼疮

目的　探讨CD34+ 细胞分选的自身干细胞移植在儿童难治性系统性红斑狼疮 (SLE)中的治疗效果。方法　 2例病程分别为 5年和 7年、狼疮肾 III级和IV级、主要表现为持续性血小板减少、蛋白尿和胸腔积液的患儿 ,首先经重组人粒细胞集落刺激因子动员、CS 30 0 0血细胞分离机采集外周血 ,获取单个核细胞 ,通过CliniMACSCD34+ 细胞分选仪分别得到了 1 7× 1 0 6 /kg及 1 0× 1 0 6 /kgCD34+ 细胞 ,采集物中分别尚存 2× 1 0 5/kg及 1× 1 0 4 /kg的CD3+ 细胞。然后给予患儿环磷酰胺[50mg/ (kg·d)× 4d]和抗胸腺细胞球蛋白 [5mg/ (kg·d)× 3d]预处理 ,48h后回输冻存的CD34+ 细胞。结果　两患儿分别于移植后 9和 7天即获粒细胞重建 ,自 1 5天起血小板一直维持在正常水平。因停用皮质激素 ,移植 3个月后患儿库欣征完全消退 ,1例患儿还获得了自患病 7年来的首次身高增长 (半年内身高增长了 5cm)。现已分别随访 1 3个月和 6个月 ,原发病症状完全消失、自身免疫相关抗体全部转阴 ,但细胞免疫功能仍未恢复 ,CD4仍处于低水平。结论　CD34+ 细胞自身干细胞移植治疗儿童难治性系统性红斑狼疮近期疗效满意     

肿瘤

05 1 8 48　 HD-A+VM2 6+rh G-CSF动员白血病患儿外周血造血干细胞的初步研究 /竺晓凡…∥中国小儿血液 .-2 0 0 4,9(3 ) .-1 2 5～ 1 2 75例高危急性白血病患儿 ,其中急性淋巴细胞白血病(AL L) 4例 ,急性杂合细胞 (AHL) 1例。年龄 9～ 1 3岁。 5例均采用 HD-A+VM2 6+rh G-CSF方案进行动员。4例采集 1次 ,1例采集 2次。全部患儿均能耐受该动员方案治疗。 MNC值为 5 .965 (5 .0 2× 1 0 8～ 7.2× 1 0 8/ Kg)。 CD3 4 +细胞量为 4.3 72 (3 .95× 1 0 6～ 5 .62× 1 0 6/ Kg)。此结果提示 ,G-GSF联合大剂量 Ara-C和 VM2 6的化…     

造血干细胞动员不佳的4例儿童患者应用普乐沙福经验分享

目的 分析造血干细胞动员不佳儿童应用普乐沙福的疗效和安全性。方法 回顾性分析4例造血干细胞动员不佳儿童应用普乐沙福的动员效果和安全性,并结合相关文献复习。结果 4例患儿均为男性,中位年龄为7.5(2～10)岁,诊断松果体混合型生殖细胞瘤1例,髓母细胞瘤1例,神经母细胞瘤2例。4例患儿既往动员效果不佳,3例患儿在使用普乐沙福后CD34+细胞采集量>2.0×10⁶/kg,中位CD34+细胞采集量为2.54(1.41～4.01)×10⁶/kg,中位采集天数为1.5(1～2)d,无不良反应。使用普乐沙福前后外周血CD34+细胞中位数分别为11.5cells/μL和28.2cells/μL,中位增长倍数为2.8。4例患儿均进行自体造血干细胞移植治疗,白细胞和血小板的中位植入中位时间分别为12d和16.5d。结论 普乐沙福对于造血干细胞动员不佳的儿童患者具有显著的疗效且安全性良好。     

含氟达拉滨的预处理方案在脐血移植治疗重型β地中海贫血的疗效观察

目的　观察在“Bu+Cy+ATG”典型预处理中加入氟达拉滨 (Flu)对脐血造血干细胞移植 (UCBT)治疗重型β地中海贫血(地贫)的植入和移植物抗宿主病(GVHD)的影响。方法　2000年 6月至 2004年 6月中山大学附属二院儿科对 22例行脐血干细胞移植的地贫患儿,按预处理方案是否含Flu分为无Flu组 (8例 )和Flu组(14例)。无Flu组:Bu,Cy和马抗人胸腺细胞球蛋白 (ATG);Flu组在此基础上加Flu。观察两组植入率,急、慢性GVHD(aGVHD、cGVHD)的发生率及其程度。结果　无Flu组 8例患儿HLA全相合 5例,不全相合 3例,接受单个核细胞(MNC)为 7 03×107 /kg[ (4 7 ~12 7 )×107 /kg],其中CD34+数为 4 0×105 /kg[ ( 0 6 ~11 7 )×105 /kg], 6例植入,中性粒细胞绝对计数 (ANC)≥0 5×109 /L时间平均为 18d,血小板 (BPC)≥20×109 /L时间平均为 36 5d, 4例发生aGVHD, 1例发生cGVHD;Flu组 14例,HLA全相合 6例,不全相合 8例,平均输入供者MNC为 7 53×107 /kg[ (3 4~10)×107 /kg],其中CD34+数为 5 01×105 /kg[ (0 6~11 7)×105 /kg], 4例植入,ANC≥0 5×109 /L时间平均为 16d,BPC≥20×109 /L时间平均为 72d, 2例发生aGVHD, 3例发生cGVHD;两组植入率、aGVHD及cGVHD发生率无明显差异。Flu组的HLA不全相合病例多于非Flu组。结论　allo H     

CD34+CXCR4+与非亲缘脐血移植后粒细胞和血小板重建关系的研究

目的　研究回输CD34+CXCR4 +的输入量在非亲缘脐血移植治疗儿童急性白血病中对中性粒细胞(ANC)和血小板 (BPC)恢复时间的影响。方法　用流式细胞术分析回输CD34+CXCR4 +细胞数 ,并对 2 3例儿童急性白血病在非亲缘脐血移植后的ANC和BPC恢复时间等临床资料进行测定。结果　 2 3例患儿中 ,CD34+CXCR4 +输入量为 (2 1～ 198 6 )× 10 4/kg(中位数 19 9× 10 4/kg)。在 2 1例植入成功患儿中 ,ANC >0 5× 10 9/L的时间为 11～ 4 1d(中位数 2 0d) ;而在 2 0例获得统计资料的患儿中 ,BPC >2 0× 10 9/L的时间为 12～ 12 0d(中位数4 4 5d)。CD34+细胞输入量与ANC、BPC恢复时间的r值分别为 - 0 35 4 (P =0 116 )、- 0 4 30 (P =0 0 5 8) ,CD34+CXCR4 +细胞输入量与ANC、BPC恢复时间的r值分别为 - 0 5 2 7(P =0 0 17)、- 0 6 2 9(P =0 0 0 4 )。结论　CD34+CXCR4 +输入量与非亲缘脐血移植后的造血重建有关。     

外周血CD34+造血干细胞加适量T细胞输注进行HLA半相合的异体移植

对1例Ph+染色体的急淋患儿进行母子间HLA半相合的异体外周血造血干细胞移植 ,为避免由于HLA不相合所产生的由T细胞介导的严重移植物抗宿主病(GVHD) ,采用了CD34+细胞正性分离去除淋巴细胞 ;同时为避免由于T细胞过度去除而引起宿主抗移植物反应(HVG)导致植入失败 ,在移植次日又加入部分T细胞 ,使病儿接受CD34 +细胞6×106/kg 和CD3 +细胞1.05×107/kg。结果 :随访1年来 ,红系、粒系和巨核系均恢复正常 ,临床上仅出现一过性的IIOaGVHD以及轻微的局限于口唇粘膜的cGVHD。STR位点DNA检验以及染色体检查 :移植后 +180天受体已从供体型嵌合体转为完全供体型 ,病儿获得植入成功。结果表明 ,常规剂量的CD34 +细胞移植加以适量CD3 +T细胞 ,可克服HLA部分不相配的难点 ,减轻GVHD ,同时也可避免由于过度的T细胞去除而出现的HVG。     

儿童自体外周血干细胞动员和采集的临床研究

目的　评价环磷酰胺、长春新碱、依托泊苷、泼尼松 (COEP) /吡柔比星、长春新碱、依托泊苷、泼尼松(DOEP)动员方案对儿童急性淋巴细胞白血病和淋巴瘤自体外周血造血干细胞移植动员采集的临床效果。方法　以COEP方案和DOEP方案为动员化疗方案 ,观察采集干细胞效果。结果　 13例 (6例非霍奇金淋巴瘤和 7例急性淋巴细胞白血病 )儿童采用COEP/DOEP方案动员 (8例用COEP方案 ,5例用DOEP方案 ) ,化疗后第 4～10d(平均 6d)白细胞数 <2× 10 9/L ,用粒细胞集落刺激因子后第 4～ 19d(平均 8d)开始采集外周血造血干细胞 ,采集单个核细胞数 (4 19～ 9 96 )× 10 8/kg(平均 6 78× 10 8/kg) ,CD34+细胞数 (2 90～ 12 78)× 10 6/kg(平均 8 90× 10 6/kg) ,粒单造血祖细胞数 (3 4 9～ 4 1 72 )× 10 4/kg(平均 15 5 7× 10 4/kg)。动员的并发症较轻 ,患儿均能耐受。自体外周血干细胞移植后均获快速造血功能重建 ,白细胞开始回升 (中性粒细胞绝对值 >0 5× 10 9/L)的时间为移植后 10～ 2 2d(平均 14d) ,血红蛋白恢复 (>80 g/L)的时间为移植后 10～ 2 8d(平均 17d) ,血小板恢复 (>2 0× 10 9/L)的时间为移植后 10～ 2 0d(平均 19d)。结论　COEP/DOEP方案可以安全高效地完成儿童白血病和淋巴瘤自体外周血干细胞的动     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

A profile of respiratory symptoms in urban and rural South Australian school children

This report describes the cross-sectional analyses of data from the first year of a longitudinal study using questionnaire and respiratory function data over a 5 year period from a sample of rural South Australian school children. The cumulative or lifetime prevalences of respiratory symptoms were estimated in 825 rural and 1261 urban school children aged between 5 and 15 years in order to determine if the prevalence rates differed between rural and urban school children. The study found the overall cumulative prevalence of asthma and/or wheezy breathing (AWB) to be 24.1% in the rural school children compared to 27.6% in the urban school children. Most children developed AWB symptoms before the age of 7 years, with 20% reporting moderately severe symptoms and 10% having more than one attack per fortnight. The cumulative prevalence of bronchitis, loose/rattly cough (BLRC) differed significantly between the rural school children (34.1%) and urban school children (47.9%). The BLRC symptoms preceded the development of AWB in many cases. Urban school children also reported a higher prevalence of atopic conditions.     

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Hauttemperaturen verschiedener Körperoberflächenareale des Rumpfes bei Säuglingen

Summary In two groups of infants (3–53 weeks old) skin temperatures were controlled in different areas of the trunk—i.e.: regions of sternum, lungs, heart, liver, spleen, kidneys—at different room-temperatures (group I: 21–25°C; group II: 29–32°C). Rectal temperatures of some probands in both groups also had been controlled simultaneously. A definite change in the reaction to heat was proofed in different periods of the first year of life. In higher environmental temperatures the skin temperature was almost constant at every controll-point of the skin, even in older infants. In lower environmental temperatures the skin temperatures lowered continuously with age till 7. to 9. moth. From 10. to 12. month the lowering of skin temperature discontinued. The rectal temperatures were relatively constant in all infants. Only in infants from 7. to 12. month, whose skin temperatures were controlled in lower as well as in higher environmental temperatures, a tendency to higher rectal temperatures was proofed in warmer environmental temperatures.The significance of these results is discussed.

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Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.