慢性病贫血患儿肿瘤坏死因子α、白介素6与红细胞生成素的关系

目的　探讨小儿慢性病贫血 (ACD)血清红细胞生成素 (EPO)水平与肿瘤坏死因子α(TNF α)、白介素 6 (IL 6 )的关系以及体外重组TNF α(rhTNF α)对EPO产生的影响。方法　住院患儿6 0例 ,其中ACD组 2 0例 ,慢性病无贫血组 (NA) 19例 ,缺铁性贫血组 (IDA) 2 1例。TNF α、IL 6采用ELISA方法检测 ,EPO应用化学发光法测定 ,对人肝癌细胞株HepG2进行体外培养 ,应用逆转录 聚合酶链反应 (RT PCR)半定量方法 ,探讨rhTNF α对EPO生成的影响。结果　三组患儿血清EPO水平差异有显著性 (F =4 4 6 8,P <0 0 1) ,ACD患儿血清EPO水平高于NA患儿 ,但在相同Hb值时 ,ACD患儿EPO低于IDA患儿。三组患儿血清TNF α水平差异有显著性 (F =2 5 12 ,P <0 0 1) ,血清TNF α水平 ,ACD组高于NA组和IDA组 ;三组患儿血清IL 6水平差异有显著性 (F =13 2 6 ,P <0 0 1) ,血清IL 6水平ACD组高于NA组和IDA组。ACD患儿血清TNF α及血清IL 6与EPO无相关性 (r=- 0 35 ,P >0 0 5 ;r=- 0 0 5 ,P >0 0 5 )。体外实验中 ,rhTNF α抑制低氧状态下EPOmRNA的表达 ,且随着rhTNF α剂量的增大而对EPO抑制作用增强 (F =6 4 2 0 ,P <0 0 1)。结论　ACD患儿EPO虽存在代偿性增高但代偿生成不足 ,是小儿ACD的发病原因之一 ;血清TNF α、IL 6与EPO     

重组人促红细胞生成素预治早产儿贫血的临床研究

为探讨重组人促红细胞生成素 (r HuEPO)防治早产儿贫血的疗效 ,将 5 2例早产儿按入院顺序随机分成治疗组 2 7例 ,对照组 2 5例。治疗组于生后 1周内给予rHu EPO 2 0 0IU/(kg·w) ,一周两次 ,皮下注射 ,共 6周 ;对照组未予rHu EPO。两组早产儿均给予口服铁剂 ,元素铁 3mg/(kg·d) ,每周增加 2mg/(kg·d) ,维生素E 2 5mg/d。必要时输血 ,共观察 7周。结果显示 :两组早产儿生后其血红蛋白值 (Hb)均逐渐下降 ,但程度不同。治疗组程度较轻 ,于第 6周时降至最低点 (118 0 4± 9 5 6g/L) ,第 7周时开始上升 ;治疗结束时二者差异显著 (P <0 0 0 1)。治疗组与第 2周开始网织红细胞计数 (Ret)较对照组明显升高 (P <0 0 0 1) ,于第 3周达到峰值 ,治疗结束时两组Ret无明显差异 (P >0 0 5 )。治疗组血清铁 (SI)第 2周时较对照组明显降低(P <0 0 0 1) ,第 4周时降至最低 (8 76± 1 84umol L) ,治疗结束时两组SI无明显差异(P >0 0 5 )。治疗组输血率 (7 4% )较对照组 (3 6% )明显减少 (P <0 0 5 )。两组早产儿治疗结束时体重无明显差异 (P >0 0 5 )。观察期间未发现明显副作用。结论 ,早期应用 (生后 1周以内 )rHu EPO能有效地减轻早产儿的贫血程度 ,并减少输血次数。     

促红细胞生成素对缺氧缺血新生鼠脑损伤学习记忆能力的影响

目的 研究促红细胞生成素(EPO)对缺氧缺血性脑损伤(HIBD) 新生大鼠海马的近期病理改变和远期学习记忆功能的影响.方法 新生7 d大鼠随机分3组假手术组、HIBD模型组和HIBD+EPO组.HIBD术后72 h观察脑组织病理改变、海马CA1区凋亡抑制蛋白Bcl-2的表达,术后28 d评估海马学习记忆功能.结果 EPO治疗能显著减轻缺氧缺血侧大脑半球水肿、梗死和出血等病理学改变.免疫组化结果显示HIBD后72 h缺血侧海马CA1区Bcl-2蛋白表达量均为HIBD+EPO组＞HIBD组＞假手术组,3者间比较差异有统计学意义.Morris水迷宫定位航行实验结果显示,5 d总平均逃逸潜伏期HIBD组(67.93±7.29) s, HIBD+EPO组(42.95±7.29) s, 假手术组(29.67±6.95) s,平均逃逸潜伏期在不同时段和不同实验组之间的差异有统计学意义;空间探索实验示HIBD组站台周边区域I搜索时间和搜索路程与HIBD+EPO组、假手术组间差异均有统计学意义,而HIBD+EPO组和假手术组间差异无统计学意义,提示HIBD鼠学习记忆能力下降, EPO干预能减轻HIBD对海马学习记忆功能的损害.结论 EPO对新生鼠缺氧缺血性脑损伤具有近期病理和远期功能保护作用,其机制与抑制细胞凋亡的发生有关.     

急性白血病患儿血清促红细胞生成素水平检测

目的　探讨小儿急性白血病 (AL)血清促红细胞生成素 (sEPO)的变化及其临床意义。方法　EPO测定采用放射免疫分析法。结果　 1.sEPO :初治组ALL( 2 4例 )为 42 .47± 2 6.47mIU/ml,AML( 11例 )为 2 4.3 0± 13 .0 6mIU/ml,正常对照组为 10 .3 3± 2 .62mIU/ml。ALL、AML显著高于正常对照组 (P <0 .0 5 ) ,而ALL显著高于AML(P <0 .0 5 ) ;4周化疗完全缓解 (CR)组ALL( 14例 )为 2 2 .5 9± 13 .3 3mIU/ml,AML( 5例 )为 2 2 .85± 12 .66mIU/ml,仍高于正常对照组 ( P <0 .0 5 ) ;ALL组低于初治时水平 ( P <0 .0 5 ) ,AML与初治时无差异 (P >0 .0 5 ) ;长期缓解组ALL( 13例 )为 12 .77± 4.3 3mIU/ml,低于第 4周缓解组 (P <0 .0 5 ) ,与正常对照组无差异 (P >0 .0 5 )。 2 .sEPO与血红蛋白 (Hb)间呈显著负相关关系 (P <0 .0 1)。结论　AL时EPO生成和代偿正常 ,因而AL患儿贫血不是EPO缺乏导致 ,用EPO治疗效果可能有限     

益髓生血灵对β-珠蛋白生成障碍性贫血患儿促红细胞生成素的影响

目的　探讨益髓生血灵对 β 珠蛋白生成障碍性贫血 (β 地贫 )患儿促红细胞生成素 (EPO)的影响。方法　应用酶联法检测 8例重型 β 地贫和 17例中间型β 地贫患者采用益髓生血灵治疗 3个月前后血清EPO含量。结果　重型和中间型 β 地贫组患者治疗后血红蛋白 (Hb)、红细胞 (RBC)、胎儿血红蛋白 (HbF)和网织红细胞 (Ret) 4项指标均较治疗前明显提高 ,差异有显著意义 (P <0 .0 0 1) ;而重型和中间型 β 地贫组患者治疗后EPO含量较治疗前有所下降 ,其中重型 β 地贫组 (91.5 3± 3.19/ 89.14± 3.76 )pg/ml差异无统计学意义 (P >0 .0 5 ) ,中间型 β 地贫组 (82 .5 3± 11.6 3/ 79.85± 10 .82 ) pg/ml差异有统计学意义 (P <0 .0 5 )。 结论　益髓生血灵治疗β 地贫不是通过刺激EPO分泌来改善贫血 ,对 β 地贫红系造血可能有综合调控作用     

大剂量静脉注射免疫球蛋白对新生儿肺炎T、B淋巴细胞功能的抑制作用

目的　观察两种剂量静脉注射免疫球蛋白（intravenous immunoglobulin，IVIG）对新生儿肺炎患儿的疗效及其免疫抑制作用，为IVIG在新生儿肺炎的应用提供依据。方法　随机选取41例新生儿肺炎患儿，分为对照组、500～700mg/kgIVIG组及1000～1200mg/kgIVIG组，后两组分别于病程第1～4天接受IVIG治疗，其余治疗三组相同。观察疗效并检测治疗前后患儿血清IgG、IgA、IgM和IgG亚类，T、B淋巴细胞增殖反应，外周血单个核细胞产生IgG亚类、IL-2、IL-4及IL-6能力。结果　两种剂量IVIG组患儿临床恢复情况与对照组相比差异无显著性。与对照组比较，大剂量IVIG组治疗后血清IgG及IgG亚类水平明显升高，但其T淋巴细胞增殖反应（40062±13274)～(24476±8241)cpm,B淋巴细胞增殖反应（1751±677)～(996±423）cpm,PBMC产生IL-2（472±201)～(185±83）ng/L及IgG     

促红细胞生成素治疗早产儿贫血的疗效评定

为了验证人基因重组促红细胞生成素注射剂(EPO)对早产儿贫血的治疗效果,将53例早产儿贫血患儿随机分为EPO治疗组(31例)和对照组(22例),治疗组予以EPO 200IU/kg皮下注射,每周2次,8周后两组间外周血血红蛋白、红细胞、红细胞压积出现显著性差异(P＜0.001),治疗组上述指标均显著高于对照组,且无明显副作用,说明EPO治疗早产儿贫血安全有效.     

过敏性紫癜患儿血清白细胞介素—6、肿瘤坏死因子—α、白细胞介素—10的变化

目的　探讨过敏性紫癜 (HSP)的免疫作用机制。方法　采用双抗体夹心酶联免疫吸附试验(ELISA) ,对 5 0例HSP患儿进行血清白细胞介素 6(IL 6)、肿瘤坏死因子 α(TNF α)、IL 10的测定 ,并与 3 0例正常对照组比较。结果　HSP组血清IL 6( 0 .0 72± 0 .0 2 6)ng/ml,对照组 ( 0 .0 42± 0 .0 15 )ng/ml;TNF α( 0 .92 7± 0 .3 80 )ng/ml,对照组 ( 0 .5 92± 0 .3 2 0 )ng/ml;IL 10 ( 0 .0 67± 0 .0 3 1)ng/ml,对照组 ( 0 .0 40± 0 .0 19)ng/ml;IgE( 12 .0 3± 2 .45 ) g/L ,对照组 ( 4.60± 3 .70 )g/L ;IgA( 1.75± 0 .3 5 ) g/L ,对照组 ( 1.0 0± 0 .5 0 ) g/L ;IL 6、IL 10、TNF α、IgA、IgE均明显高于对照组 ( P <0 .0 1) ,经相关分析发现IL 6、IL 10与IgA呈显著正相关 (r=0 .798,0 .82 9　P <0 .0 1)。结论　过敏性紫癜存在细胞免疫功能紊乱 ,其参与了HSP的发病过程     

重组人促红细胞生成素对早产儿贫血和细胞免疫功能的影响

目的　观察重组人促红细胞生成素 (rHu Epo)对早产儿贫血的预防和细胞免疫功能的影响。 方法　将 6 0例早产儿随机分为治疗组和对照组各 30例 ,治疗组用rHu Epo 6 0 0IU/kg ,隔日一次× 6周 ,加常规治疗[速力菲 8mg/ (kg·d) ,VitC 0 .1Bid ;VitE 10mg ,qd],对照组仅用常规治疗。两组同时监测红细胞计数 (RBC)、血红蛋白 (Hb)、网织红细胞 (Ret) )、血清铁和细胞免疫功能的变化。结果　疗程结束后治疗组Ret 2 .0 7% ,对照组 0 .80 9% ,两组Ret相差 10个百分点左右。治疗组血清铁 13μmol/L ,对照组 2 2 .13μmol/L ,P<0 .0 1。治疗组贫血发生率 3.3% ,对照组 6 3.4% ,P <0 .0 1,两组贫血症状有明显差异。结论　rHu Epo能预防早产儿贫血     

高浓度氧对早产鼠肺一氧化氮合酶基因表达的影响

目的　探讨高浓度氧 (简称高氧 )对早产鼠肺一氧化氮合酶 (NOS)分布及基因表达的影响。方法　将 2 1d孕早产鼠随机分为高氧暴露组 (简称高氧组 )和空气对照组 (对照组 ) ,分别置于常压高氧仓中 (氧体积分数 >0 95 )和正常空气中暴露 7d ,采用逆转录 聚合酶链反应 (RT PCR)、免疫蛋白分析和免疫组织化学染色观察NOS分布及基因表达。此外对肺组织干 /湿重比值 ,支气管肺泡灌洗液 (BALF)成份和肺病理组织变化也进行了对比分析。结果　高氧组与对照组比较 ,早产鼠肺组织有明显水肿、出血和炎症 ;高氧组支气管肺泡灌洗液中蛋白含量 (中位数为 1 4 9g/L)、细胞数 (中位数为 139 70× 10 7/L)和肺组织干 /湿重比值 (5 5 7± 0 2 9)较对照组 (分别为 :0 32g/L、16 30× 10 7/L、5 2 9± 0 2 5 )均明显增加 (t=2 8、2 1、2 2 9,P均 <0 0 5 ) ;高氧组肺组织内皮细胞型一氧化氮合酶 (eNOS)mRNA、eNOS和诱导型一氧化氮合酶 (iNOS)蛋白表达 (分别为 :1 0 2± 0 0 6、8 77± 0 75、4 6 1± 0 6 5 )较对照组 (分别为 :0 70± 0 12、4 5 2± 1 0 2、3 2 4± 0 5 5 )明显增加 (t =6 36、8 14、3 2 1,P <0 0 1、P <0 0 1、P <0 0 5 )。iNOSmRNA也显示有增加的趋势 ,但差异无统计学意义 ,同时免疫组织化     

Effect of high doses of human recombinant erythropoietin on the need for blood transfusions in preterm infants.

To determine whether prophylactic treatment with recombinant human erythropoietin (rHuEPO) and iron would reduce the need for blood transfusions, we randomly assigned 22 premature infants with gestational ages less than or equal to 32 weeks and birth weights less than or equal to 1.75 kg to receive rHuEPO, 400 IU/kg three times a week, plus iron, 20 mg/wk intravenously, from the second day of life (11 infants), or no rHuEPO and no iron (11 infants). The two groups had similar birth weights and clinical variables. The treated infants required fewer blood transfusions (0.8 +/- 1.5 vs 3.1 +/- 2.1; p = 0.01) and less volume of packed erythrocytes (14.2 +/- 25.9 vs 48.4 +/- 34.0 ml/kg; p = 0.02). The amounts of blood sampled were not different (19.5 +/- 21.1 vs 27.8 +/- 19.1 ml/kg; p = 0.35). Reticulocyte and hematocrit values were higher in the treated group (4.46% +/- 0.8% vs 1.49% +/- 1.1% (p = 0.0001) and 48.1% +/- 7.3% vs 43.8% +/- 4.7% (p = 0.004), respectively). No side effects of either rHuEPO or intravenously administered iron were noted. These data indicate that rHuEPO, in combination with iron supplementation, is effective in reducing the need for blood transfusions in the premature infant. More information is needed on dosage, timing, and iron and vitamin supplementation.     

Avoidance of red blood cell transfusion in an extremely preterm infant given recombinant human erythropoietin therapy

To avoid red blood cell (RBC) transfusions, recombinant human erythropoietin (rHuEPO) was given to an infant born at a gestation of 26 weeks and a birthweight of 830 g to parents who were Jehovah's Witnesses. The infant had hyaline membrane disease and required 52 days of assisted ventilation and 19 days of oxygen therapy. He received theophylline therapy for 61 days for recurrent apnoea and bradycardia. He developed bilateral intraventricular haemorrhage (IVH) and left-sided periventricular leucomalacia (PVL). Intravenous rHuEPO was started on day 1 at 200 U/kg per day for 1 month followed by subcutaneous rHuEPO 400 U/kg three times a week for 6 more weeks, supplemented with Vitamin E, folic acid and iron. Blood sampling was kept to a minimum and non-invasive blood-gas monitoring was used consistently. Consequently, the estimated cumulative volume of blood loss from sampling was only 21 mL during his hospital stay. His haemoglobin (Hb) was 150 g / L at birth and this fell to below 100 g / L from day 25 onwards. His lowest leucocyte count was 3.6x10⁹/L. He was discharged on day 83 with a Hb of 95 g/L, Hct of 29%, reticulocyte count of 2.8% and weight of 2400 g. At a postnatal age of 3 months, he had a Hb of 113 g/L. At 6 months, investigations showed: Hb 121 g/L, haematocrit 33%, reticulocyte 1% and a weight of 4.4 kg. He was readmitted to hospital once for an episode of vomiting and follow up to date showed developmental delay. Concerns remained whether the withholding of RBC transfusion in the infant was related to his IVH, PVL, prolonged recurrent apnoea and bradycardia and poor weight gain. Although rHuEPO therapy shows promise in reducing the need for RBC transfusions, its overall efficacy and safety remain to be proven and its routine use in preterm infants has to be weighed up against the potential benefits and risks of RBC transfusions.     

Is epoetin alfa a treatment option for chemotherapy-related anemia in children?

BACKGROUND: The efficacy and safety of epoetin alfa in ameliorating cancer- or chemotherapy-related anemia and reducing red blood cell (RBC) transfusion requirements have been demonstrated in numerous trials in adult patients. However, limited information is available about recombinant human erythropoietin (rHuEPO, epoetin alfa) as a treatment option in pediatric cancer patients. PROCEDURE: To gain more information about the efficacy and safety of epoetin alfa in the treatment of chemotherapy-induced anemia in children with solid tumors receiving either platinum- or nonplatinum-containing chemotherapy, an 8-week randomized trial was conducted. Epoetin alfa 150 IU/kg was given 3 times a week for 8 weeks to 17 patients; 17 control patients received standard of care. RESULTS: Transfusions, administered if the hemoglobin (Hb) level dropped to below 6 g/dL, were necessary for only one patient in the epoetin alfa group, as compared with eight patients in the control group (change in Hb from 8.5-10.21 g/dL in the epoetin alfa group vs. 8.48-8.41 g/dL in the control group). CONCLUSIONS: The data from this study suggest that this dosing regimen of epoetin alfa is effective and safe in pediatric cancer patients with chemotherapy-related anemia. Further studies with epoetin alfa in more children with different chemotherapy regimens are needed.     

重组人类促红细胞生成素治疗极低出生体重早产儿贫血的近期疗效观察

目的:应用重组人类促红细胞生成素(rhu-EPO)治疗极低出生体重早产儿贫血并随访至出生后4个月,观察其疗效。方法：将56例极低出生体重早产儿按随机抽样原则分为对照组(26例)、治疗组(30例)。治疗组于生后第8天即予rhu-EPO,每次300 IU/kg,皮下注射,每周2次,共4周;第3周开始口服铁剂(每日5～10 mg/kg)。两组均于生后7 d内口服维生素E(每日5 mg/kg)、叶酸片(5 mg/d)。随访至出生后4个月。结果：随年龄增大两组血红蛋白、红细胞数、红细胞压积均逐渐下降,在7 d, 14 d, 21 d,28 d,35 d时,治疗组上述指标均较对照组高,差异有显著性意义(P<0.01或0.05);治疗结束后,两组的血清铁蛋白［(103±25 μmol/L vs (123±24) μmol/L)差异有显著性(P<0.01);治疗组较对照组出现贫血率低(43% vs 89%),两组比较差异有显著性(P<0.01)。结论：早期大剂量rhu-EPO能减轻早产儿贫血的程度,可减少甚至替代输血。     

抗癫癎药妥泰对幼鼠肝毒性的实验研究

目的：目的妥泰（TPM）以其多重的药理作用，在儿童癫癎治疗中表现出明显的治疗效果，然而上市后少数病例报道出现肝功能衰竭、肝炎等不良反应，引起医学界的关注。该研究从血清生化、氧化应激指标和肝脏形态学方面探讨TPM单药高、低剂量及与丙戊酸钠（VPA）合用对幼鼠肝脏的毒性作用，为临床合理用药提供实验室依据。方法：将3周龄雄性Wistar大鼠60只，随机分为5组，每组12只。实验组（分别为A，B，C 3组），每日1次经口灌胃给予TPM 40 mg/kg，TPM 80 mg/kg和TPM 40 mg/kg＋VPA 300 mg/kg；阴性对照组（D组）给予等量的蒸馏水；阳性对照组（E组）经皮下注射10％四氯化碳橄榄油溶液5 mL/kg，每周2次。连续用药3个月后观察体重改变及肝脏形态学变化，检测与肝脏毒性有关的血清生化指标、氧化应激指标。结果：①实验组的3组大鼠，体重均显著低于阴性对照组。②实验组血清丙氨酸氨基转移酶、碱性磷酸酶和肝组织丙二醛含量、超氧化物歧化酶活性与阴性对照组相比没有显著变化，TPM高剂量组和合用药组肝组织谷胱甘肽含量较阴性对照组、TPM低剂量组明显降低，分别为29.85±1.62 mg/g蛋白和29.63±4.47 mg/g蛋白，差异有显著性(均P＜0.05)。③病理组织学检查，光镜下阳性对照组可见广泛的肝细胞脂肪变性和弥漫性点状坏死灶；TPM低剂量组可见少数肝细胞浊肿变性；TPM高剂量组可见少数肝细胞点状坏死；TPM＋VPA组可见部分肝细胞浊肿变性和脂肪变性，视野内还可见少数肝细胞点状坏死。结论：长期服用TPM可引起机体抗氧化能力降低，肝脏病理组织学检查可见轻微病理改变，TPM高剂量及合用药组影响大于TPM低剂量组。［中国当代儿科杂志，2007，9（1）：54-58］     

地塞米松和氨基胍及氨力农对内毒素休克兔氧代谢的影响

目的　探讨地塞米松、氨力农和氨基胍三种不同作用机理的药物对内毒素休克兔氧代谢的影响。方法　将 35只兔随机均分成 5组 ,即手术对照组、内毒素组、地塞米松组、氨力农组和氨基胍组。各组分别于术后 30min(T0 )、注射内毒素 (40 0 μg/kg)后达到休克诊断标准时 (T)、用药治疗后 1～ 6h (T1 ～T6 )取动脉、混合静脉血作血气分析 ,记录心输出量。计算氧运输量 (DO2 ) ,氧消耗量(VO2 )和氧摄取率 (ERO2 )。结果　T0 点所有指标组间差异无显著性。内毒素组DO2 与VO2 逐渐下降 ,试验结束时DO2 为 (8 1± 2 4)ml/ (kg·min) ,VO2 为 (2 7± 1 0 )ml/ (kg·min)。地塞米松组DO2 和VO2 于治疗后保持稳定 ,T6 时分别为 (1 2 4± 3 1 )和 (5 1± 1 6)ml/ (kg·min) ,均显著高于内毒素组 (P分别 <0 0 1 ,<0 0 5)。氨基胍组T1 、T2 点DO2 分别为 (1 7 0± 2 8)、(1 7 2± 2 5)ml/ (kg·min) ,明显高于内毒素组的 (1 2 2± 2 6)和 (1 4 1± 3 8)ml/ (kg·min) ,P均 <0 0 5 ,但试验结束时DO2 为 (1 1 2± 1 7)ml/ (kg·min)与内毒素组差异无显著性 (P >0 0 5)。用药后VO2 缓慢升高。试验结束时VO2 与内毒素组差异有显著性 (P <0 0 1 )。氨力农组仅T3、T4 点VO2 较内毒素组显著升高。T6 时DO2 为 (     

促红细胞生成素在小儿普外科中的应用

目的初步评价重组人促红细胞生成素(rHuEPO)在小儿普外科围手术期应用的临床意义和安全性。方法 22例择期手术患儿随机分成两组,即治疗组10例,对照组12例。治疗组于术前第7天单次使用重组人促红细胞生成素皮下注射,剂量100 U/kg,对照组不给予rHuEPO注射。观察rHuEPO应用后对异体输血量的影响及其安全性。结果治疗组在异体输血量方面明显低于对照组,其中异体输血量绝对值(即每个患儿异体输血量)治疗组为(77.0±26.6)mL,对照组(200.0±42.6)mL,P值0.05;输血量相对值(即每个患儿异体输血量/体重)治疗组为(8.5±3.0)mL、对照组为(22.4±4.6)mL、P值0.05,未发现有高血压、高血钾、血小板升高及其他副作用。结论 rHuEPO术前应用可有效减少择期手术患儿围手术期异体输血量,安全性较高。     

Cholesterol synthesis and de novo lipogenesis in premature infants determined by mass isotopomer distribution analysis

Premature infants change from placental supply of mainly carbohydrates to an enteral supply of mainly lipids earlier in their development than term infants. The metabolic consequences hereof are not known but might have long-lasting health effects. In fact, knowledge of lipid metabolism in premature infants is very limited. We have quantified de novo lipogenesis and cholesterogenesis on d 3 of life in seven premature infants (birth weight, 1319 +/- 417 g; gestational age, 30 +/- 2 wk). For comparison, five healthy adult subjects were also studied. All subjects received a 12-h [1-(13)C] acetate infusion, followed by mass isotopomer distribution analysis (MIDA) on lipoprotein-palmitate and plasma unesterified cholesterol. The fraction of lipoprotein-palmitate synthesized at the end of the infusion period was 5.4 +/- 3.9% in infants, which was in the same range as found in adult subjects on a normal diet, suggesting that hepatic de novo lipogenesis is not a major contributor to fat accumulation in these premature neonates. The fractional contribution of newly synthesized cholesterol to plasma unesterified cholesterol was 7.4 +/- 1.3% after a 12-h infusion. The calculated rate of endogenous cholesterol synthesis was 31 +/- 7 mg/kg/d, a value approximately three times higher than that found in adult subjects (10 +/- 6 mg/kg/d). These results indicate that the cholesterol-synthesizing machinery is well developed in premature infants.     

Effects of ciclosporin A, tacrolimus and sirolimus on cytokine production in neonatal immune cells

BACKGROUND: It was the aim of this study to evaluate the effects of the well-known immunosuppressive drugs ciclosporin A (CsA), tacrolimus and sirolimus on the intracytoplasmic cytokine expression of neonatal immune cells. METHODS: Immunosuppressive drugs were added to whole blood cultures of neonatal cord blood samples (n = 17) and peripheral blood samples of adults (n = 17) in vitro prior to stimulation of lymphocytes with phorbol 12-myristate 13-acetate (PMA)/ionomycin or monocytes. RESULTS: Upon exposure to ciclosporin A (500 ng/mL) or tacrolimus (25 ng/mL) the number of cytokine expressing T cells was almost completely blocked in neonatal T cells while sirolimus (10 ng/mL) only inhibited intracytoplasmatic tumour necrosis factor alpha (TNF-alpha) expression (mean% positive cells; 4.0 +/- 2.1% vs. 1.09 +/- 0.6%, p = 0.003), but mildly stimulated the intracellular expression of interleukin (IL)-2 (24.4 +/- 6.5% vs. 28.1 +/- 7.1%, p = 0.041). In cord blood lymphocytes, the inhibitory effect of ciclosporin A and tacrolimus was dose-dependent (e.g. IL-2: control, 12.3 +/- 5.33%, ciclosporin A 5 ng/mL, 10.1 +/- 5.5%; 50 ng/mL, 7.1 +/- 4.7%; 500 ng/mL, 1.2 +/- 0.3%; tacrolimus 0.25 ng/mL, 9.3 +/- 4.9%; 2.5 ng/mL, 6.1 +/- 3.3%; 25 ng/mL, 1.0 +/- 0.6%), while the function of adult lymphocytes was only impaired at high doses of both compounds. In contrast, the number of cytokine expressing monocytes was not influenced by ciclosporin A and tacrolimus except for a minor decrease of TNF-alpha producing neonatal monocytes after addition of tacrolimus (17.9% vs. 13.9%, p = 0.031). Interestingly, sirolimus was shown to inhibit intracellular IL-6 production in adults (63.1 +/- 12.7% vs. 52.0 +/- 16.0%, p = 0.005), but in neonatal monocytes intracellular IL-6 expression was stimulated (53.5 +/- 22.0% vs. 64.7 +/- 19.1%, p = 0.041). CONCLUSIONS: The potent dose-dependent inhibitory effect of ciclosporin A and tacrolimus in cord blood lymphocytes provides the basis for further studies on functional immaturity of the neonatal immune system and for future strategies to optimize umbilical cord blood transplantion. Sirolimus was demonstrated to have a distinct effect on neonatal immune cells as shown by increased expression of IL-2 in lymphocytes and IL-6 in monocytes, while only lymphocytic TNF-alpha expression was inhibited.     

Radiant heat loss versus radiant heat gain in premature neonates under radiant warmers

Premature infants nursed on open radiant warmer beds are exposed to short-wavelength infrared power density distributed evenly over the bed surface. Additionally, infants' sides are exposed to relatively cooler nursery walls, and to the radiant warmer bed platform which may heat and reradiate to the baby. Therefore, infants may not only gain heat from the warmer (Q radiant warmer) but lose or gain radiant heat to the sides as well (+/- Q radiant loss). In order to quantitate these parameters, ten premature newborn infants nursed under radiant warmers servocontrolled to 36.5 degrees C skin temperature (weight 1.27 +/- 0.24 SD kg, gestation 31 +/- 3 weeks) were investigated, and partitional calorimetry previously reported. In the present study, calculation of net rate of radiant heat transfer (Q net radiant) was made from these data (-2.63 +/- -1.52 kcal/kg/h), and compared to direct measurements of Q radiant warmer (-2.49 +/- -0.90 kcal/kg/h). The present report further partitions net radiant heat transfer to evaluate Q radiant loss: -0.13 +/- 1.82 kcal/kg/h (range -3.16 to 1.93). From these calculations mean radiant temperature of this environment was estimated (45.3 +/- 4.3 degrees C) and compared to the radiant warmer temperature received (45.0 +/- 2.9 degrees C). This information suggests other strategies to reduce radiant heat loss as well as convective and evaporative losses in premature neonates nursed on open radiant warmer beds.