Alpha1-antitrypsin and alpha2-macroglobulin in newborn infants

The levels of alpha₁-antitrypsin and alpha₂-macroglobulin in the plasma of 129 newborns were determined. The infants were divided into 3 groups according to their perinatal history.In healthy newborns with an uneventful perinatal history the normal values for alpha₁-antitrypsin were 1.97±0.44 g/l, and for alpha₂-macroglobulin 3.11±0.69 g/l. No changes in these levels were found during the first week of life. The levels of alpha₁-antitrypsin and alpha₂-macroglobulin showed significant correlation to each other.In healthy newborns with different complications in the obstetric history the levels of alpha₁-antitrypsin were not influenced, whereas alpha₂-macroglobulin decreased slightly during the first week of life. The levels of alpha₁-antitrypsin and of alpha₂-macroglobulin showed no further correlation to each other.In sick term and preterm newborns (n=18) alpha₁-antitrypsin was increased in 5 of 7 babies suffering from bacterial infections and lowered in 4 of 9 cases with respiratory disturbances. Alpha₂-macroglobulin was lowered in 15 babies. These results indicate different kinetics of the two antiproteases in vivo.With support of the Landesamt für Forschung des Landes Nordrhein-Westfalen     

Airway eicosanoids in acute severe respiratory syncytial virus bronchiolitis

We prospectively studied the levels of eicosanoids in intubated patients with severe bronchiolitis and compared them to electively intubated non-infected infants. LeukotrieneE(4) (LTE(4)), leukotrieneB(4) (LTB(4)), and prostaglandinE(2) (PGE(2)) levels were significantly increased (P <.01) from endotracheal (ET) aspirates of infants with bronchiolitis compared with controls, as were urinary LTE(4) levels (P <.001). We conclude that eicosanoids are increased in the tracheal aspirates and urine of children with bronchiolitis.     

Rate of synthesis of haemoglobin A2 in thalassaemia

The relative rate of haemoglobins A and A₂ synthesis by red cell precursors of normal and thalassaemia major subjects has been investigated.Biosynthetic studies have been performed in vitro by using reticulocytes incubated with uniformly labeled ¹⁴C-aminoacids (algal hydrolysate). Haemoglobins have been purified by column chromatography method and the specific activity of each concentrated haemoglobin fraction has been assayed in a liquid scintillation counting system.It is demonstrated that the rate of synthesis of Hb A and Hb A₂ in thalassaemia major is not similar to that in non-thalassaemic disorders. The ratio Hb A/A₂ is less than unity in thalassaemia major in the first minutes of incubation but the subsequent increase of the ratio over unity did not reach the high values of the results obtained in non-thalassaemic disorders.Research supported by a grant from C.N.R., Italia     

Haemoglobin A2 in newborn infants of different maturity

From 70 infants born after gestation periods of 28–41 weeks Hb F and Hb A₂ were determined in the cord blood; Hb A was calculated from the two values. Hb F decreased with maturity, Hb A and Hb A₂ increased. The percentage of Hb A₂ calculated from the sum of Hb A+Hb A₂ (non-fetal Hb) increased from 0.57% to 0.83% with maturity. These values are much lower than those in adult controls (1.83%). The results show that during development the synthesis of the δ-globin chains lags behind that of the β-globin chains. This is remarkable considering the location of the δ-globin gene within the β-globin like gene cluster.     

No reduction of high density lipoprotein2 during weight reduction in obese children and adolescents

The effects of a 3 week weight reduction regimen on lipids and lipoproteins, in particular high density lipoprotein (HDL)-subfractions in 61 grossly obese children and adolescents (37 females and 26 males) aged 11–15 years were studied. Dietary treatment resulted in a significant weight reduction of initial body weight of 9.6±2.1%, a highly significant decrease in cholesterol, low density lipoprotein cholesterol (LDL-C) and HDL-C (P<0.001), as well as a significant reduction in triglycerides, HDL₃ and Apolipoprotein B concentrations (P<0.01). HDL₂ concentrations remained almost constant. It is concluded that HDL reduction during a weight reducing regimen in adolescents does not result in a decrease of the antiatherogenic HDL₂ subfraction.     

Atlanto-axial instability in children with Down syndrome

One hundred fifty-eight patients with Down syndrome underwent roentgenologic examinations of the cervical spine in neutral position, in hyperflexion, and in hyperextension. Fifteen children with Down syndrome were found to have a distance between the joint surfaces of 5 mm and more. The majority of these children were asymptomatic, one child displayed hyperactive deep tendon reflexes and two children were symptomatic and underwent surgery.     

Energy expenditure in neonates with Down syndrome

Resting energy expenditure was measured in term neonates with Down syndrome during the first week of life and compared with healthy neonates. Infants with Down syndrome expended 14% fewer calories than did healthy infants of the same age.     

MORPHOLOGICAL AND BIOCHEMICAL CHANGES INDUCED BY ARSENIC TRIOXIDE IN NEUROBLASTOMA CELL LINES

Arsenic trioxide has recently been shown to inhibit growth and induce apoptosis in a variety of hematologic malignancies, but very little is known about its effects on solid tumors and especially on neuroblastoma cells that have self-differentiating characteristics. To demonstrate the growth inhibition induced in neuroblastoma cells (the SH-SY5Y and SK-N-AS cell line) and acute promyelocytic leukemia cells (HL-60) by arsenic trioxide (As₂O₃), the viable cell numbers were counted after trypan blue staining. Apoptosis was assessed by the cell morphology, by flow cytometry with annexin-V staining, and by Western blot analysis for the apoptosis-related proteins (bcl-2 and PARP). To decide the dose for the clinical application of As₂O₃, normal peripheral blood lymphocytes were also examined. The growth and survival of the SH-SY5Y and SK-N-AS cells were markedly inhibited by As₂O₃ treatment at a 3 μM concentration before the changes of the normal lymphocytes were observed. The apoptotic cells showed a shrunken cell nucleus, and an increase in the number and balloon-like swelling of the mitochondria at 72 h after the As₂O₃ was added. Apoptosis of the annexin-V-positive cell proportion in the neuroblastoma cell lines was increased with increasing the exposure time and the concentration of As₂O₃, just like the HL-60 cells. Bcl-2 downregulation and PARP degradation were also noted all the cell lines, but these changes were not statistically significant among the 3 cell lines. Taken together, these results indicate that As₂O₃ is an excellent candidate as a therapeutic agent for the treatment of neuroblastoma.     

Oxygen saturation in healthy infants immediately after birth

OBJECTIVE: Because the optimal concentration of oxygen (FiO2) required for stabilization of the newly born infant has not been established, the FiO2 is commonly adjusted according to the infant's oxygen saturation (SpO2). We aimed to determine the range of pre-ductal SpO2 in the first minutes of life in healthy newborn infants. STUDY DESIGN: We applied an oximetry sensor to the infant's right palm or wrist of term and preterm deliveries immediately after birth. Infants who received any resuscitation or supplemental oxygen were excluded. SpO2 was recorded at 60 second intervals for at least 5 minutes and until the SpO2 was >90%. RESULTS: A total of 205 deliveries were monitored; 30 infants were excluded from the study. SpO2 readings were obtained within 60 seconds of age from 92 of 175 infants (53%). The median (interquartile range) SpO2 at 1 minute was 63% (53%-68%). There was a gradual rise in SpO2 with time, with a median SpO2 at 5 minutes of 90% (79%-91%). CONCLUSION: Many newborns have an SpO2 <90% during the first 5 minutes of life. This should be considered when choosing SpO2 targets for infants treated with supplemental oxygen in the delivery room.     

幼兔胎粪吸入性肺损伤后肺组织血栓素B_2 6-酮前列环素1α水平及其意义

目的了解幼兔胎粪吸入后肺组织中血栓素B2(TXB2)和6-酮前列环素1α (6-keto-PGF-1α)的动态变化。方法将动物分为轻度胎粪吸入组(16 h,24 h,48 h,72 h)、重度胎粪吸入组和对照组,通过气管内灌入胎粪0.6 ml/kg和4 ml/kg建立轻、重度幼兔胎粪吸入模型;应用右心室穿刺法经压力传感器与日本光电公司生产RM-6000型多道生理记录仪相连,测定右心室收缩压;应用放射免疫法检测肺组织中TXB2和6-keto-PGF-1α含量。结果轻度胎粪吸入组右心室收缩压从胎粪吸入后16 h升高(2.57±0.10 kPa),24 h达高峰(3.57±0.14 kPa),72 h恢复正常(1.89±0.14 kPa)。重度胎粪吸入组右心室收缩压(4.36±0.14 kPa)明显高于轻度胎粪吸入组和对照组(1.85±0.05 kPa);轻度幼兔胎粪吸入16 h肺组织TXB2(153.80±15.37 pg/ml)和6-keto-PGF-1α(117.40±22.88 pg/ml)水平开始增高,24 h达高峰(369.00±28.80 pg/ml;207.20±28.59 pg/ml),至72 h开始降低(103.20±11.95 pg/ml;83.62±8.76 pg/ml),重度胎粪吸入肺组织TXB2(500.60±24.58 pg/ml)和6-keto-PGF-1α(300.00±20.31 pg/ml)增加更明显。TXB2和6-Keto-PGF1α分别与右心室压作相关分析,均具有明显相关性(r=0.95;0.96, P<0.01)。结论随着胎粪吸入性肺损伤加重,TXB2和6-Keto-PGF1α增加更明显,表明TXB2和6-keto-DGF-1α参与胎粪吸入性肺损伤发生发展。     

Iatrogenic IgG2 deficiency in a leukaemic child

A girl with acute non-lymphoblastic leukaemia was treated with immunosuppressive chemotherapy. After cessation of therapy she had three consecutive episodes of infection due toStreptococcus pneumoniae from which she recovered and was shown to have developed a combined deficiency of both IgG₂ and IgG₄. The patient eventually relapsed and died 3 years after the initial diagnosis. The importance of measuring IgG subclasses in patients treated with immunosuppressive chemotherapy is discussed.     

Relationship of the ventilatory response to hypoxia with neonatal apnea in preterm infants

OBJECTIVE: Correlate the ventilatory response of preterm infants to hypoxic exposure with incidence of neonatal apnea.Study design Seventeen stable convalescing premature infants underwent bedside cardiorespiratory monitoring of respiration using respiratory inductance plethysmography, heart rate, and oxygen saturation (SaO(2)) for a 12-hour period. These studies were scored for number of apneas > or =15 and > or =20 seconds. Infants then underwent a 3-minute hypoxic exposure. Minute ventilation (V(E)) was calculated for 30-second epochs from the time inspired oxygen reached 15%. Linear regression analysis was used to correlate the change in V(E) normalized for decrease in SaO(2) (DeltaV(E)/DeltaSaO(2)) during the first and third minutes of hypoxic exposure with the number of apneic episodes during the 12-hour study. RESULTS: The majority of infants exhibited an anticipated biphasic ventilatory response to hypoxia. There was a significant positive correlation between DeltaV(E)/DeltaSaO(2) during the first and third minutes of hypoxic exposure and number of apneic episodes > or =15 and > or =20 seconds during the preceding 12 hours. CONCLUSIONS: Preterm infants with a greater number of apneic episodes exhibit an increased ventilatory response to hypoxic exposure, suggesting that apnea of prematurity may be associated with enhanced peripheral chemoreceptor activity.     

Exposure to carbon dioxide and helium reduces in vitro proliferation of pediatric tumor cells

Background: Minimally invasive techniques are increasingly applied to children with malignant tumors. We showed previously that CO₂ used for pneumoperitoneum modulates the function of macrophages and polymorphonuclear cells via direct effects and via acidification. Numerous in vitro and small animal model studies also confirmed an alteration of the behavior of several types of adult tumor cells by CO₂. The impact of CO₂ and other gases used for pneumoperitoneum on the behavior of various pediatric tumors has not yet been determined. Methods: Cell lines of neuroblastoma (IMR 32, SK-N-SH, Sy5y), lymphoma (Daudi), hepatoblastoma (Huh 6), hepatocellular carcinoma (Hep G2), and rhabdomyosarcoma (Te 671) were incubated for 2 h. Incubation was performed with 100% CO₂, 100% helium, and 5% CO₂ as control. Cell proliferation was determined by the MTT-assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] by actively growing cells to produce a blue formazan product. The MTT-assay was performed before, directly after incubation, and daily for 4 days. Vitality of the cells was determined by trypan blue. The extracellular pH during incubation was measured during gas exposition every 10 min using Bayer Rapid Lab 855. Results: CO₂ for 2 h significantly decreased the proliferation of neuroblastoma, lymphoma, hepatoblastoma, and hepatocellular carcinoma cells. This decrease persisted over 4 days in neuroblastoma, lymphoma, and hepatocellular carcinoma cells. The CO₂ had no impact on hepatoblastoma and rhabdomyosarcoma cells. Helium had a similar effect on neuroblastoma cells. After 4 days, a significant decrease of cell activity was found in two neuroblastoma cell lines and in hepatoblastoma cells. Helium had no effect on lymphoma and hepatocellular carcinoma cells. The extracellular pH was 6.2 during incubation with CO₂, and 7.6 during incubation with helium. Conclusion: CO₂ and helium may affect the proliferation of some pediatric tumor cell lines in vitro. However, some of these effects and the impact on the extracellular pH are differential. The role of pH modulation, hypoxia and direct effects of gases remain to be investigated before a general recommendation on the use of minimally invasive techniques in pediatric oncology can be given.     

1,25-(OH)2D3抑制脂多糖诱导的脐血CD4+T细胞IL-13和IL-17的表达

目的 本研究旨在探讨生命早期脂多糖(LPS)对脐血CD4+T细胞白介素-13(IL-13)和白介素-17(IL-17)表达的影响及1,25-(OH)2D3对其表达的干预作用,为维生素D的临床合理应用及其对哮喘等变态反应性疾病的防治提供理论依据。方法 选取顺产的足月新生儿12例,断脐后立即取胎盘端脐静脉血50 mL,采用密度梯度离心法分离脐血单个核细胞(CBMCs),磁珠分选CD4+T细胞后依据不同的处理方法分为空白刺激组、LPS(10 μg/mL)单独刺激组和LPS(10 μg/mL)+1,25-(OH)2D3(10-8 mmol/L)共刺激组。培养72 h后采用双抗夹心酶联免疫吸附试验(ELISA)和Real-Time PCR分别检测培养上清液中IL-13和IL-17水平及CD4+T细胞中IL-13和IL-17 mRNA表达。结果 与空白刺激组相比,LPS单独刺激组培养上清液中IL-13和IL-17水平及CD4+T细胞中IL-13和IL-17 mRNA表达水平明显升高(均P<0.01),而1,25-(OH)2D3处理可降低其表达水平(均P<0.05),但仍高于空白刺激组(均P<0.01)。结论 LPS可促进脐血CD4+T细胞IL-13和IL-17的表达;1,25-(OH)2D3对于LPS诱导的脐血CD4+T细胞IL-13和IL-17表达具有抑制作用,提示1,25-(OH)2D3可能在变应原致敏的早期发挥一定保护作用。     

1,25-（OH）2D3对哮喘小鼠肺内高迁移率族蛋白B1及Toll样受体4表达的影响

目的 观察1,25-（OH）2D3 对哮喘小鼠气道重塑、肺组织高迁移率族蛋白B1（HMGB1）及Toll样受体4（TLR4）表达的影响。方法 30 只雌性BALB/c 小鼠随机分为对照组、哮喘组和1,25-（OH）2D3 干预组。采用卵清蛋白腹腔注射致敏联合雾化吸入激发建立哮喘小鼠模型,干预组于每次激发前0.5 h 给予腹腔内注射1,25-（OH）2D3,对照组以生理盐水代替。苏木精-伊红染色观察小鼠气道结构变化;采用RT-PCR 法从mRNA水平及免疫组化法从蛋白质水平检测HMGB1 及TLR4 表达的变化;同时对相关变量进行Pearson 相关分析。结果 哮喘组气道壁厚度较对照组明显增厚,干预组较哮喘组气道壁增厚程度明显减轻（P<0.05）。哮喘组HMGB1、TLR4 的mRNA 和蛋白表达水平均较对照组增高（均P<0.05）;而干预组HMGB1、TLR4 的mRNA 和蛋白表达水平均较哮喘组降低,但仍高于对照组（均P<0.05）。肺组织内HMGB1 蛋白与TLR4 蛋白的表达呈正相关（P<0.01）,HMGB1 mRNA 及TLR4 mRNA 的表达亦呈正相关（P<0.01）。结论 在哮喘气道重塑模型中,HMGB1 及TLR4 可能参与哮喘气道重塑过程;1,25-（OH）2D3 可改善哮喘小鼠气道重塑,其机制可能与降低哮喘小鼠肺内HMGB1 及TLR4 的表达有关。     

A physiological mode of puberty induction in hypogonadal girls by low dose transdermal 17β-oestradiol

Transdermal 17-oestradiol administration (17-E₂), used mainly in menopausal women, allows a continuous 17-E₂ delivery through the skin into the systemic circulation, avoiding intestinal and hepatic passage. In order to explore whether transdermal 17-E₂ could be used for the induction of puberty, 17-E₂ patches with low dose delivery were administered in nine prepubertal girls with Turner syndrome (bone age >10.5 years) for a mean period of 2.2 years. Treatment schedule: 5 g/day for 6–9 months, 10 g/day for 6–9 months, 25 g/day for long-term substitution; addition of cyclic gestagen p.o. after 18–24 months. Breast development started within 3 months of therapy and menstruation occurred after 2 years. Growth rate increased from 3.2 to 5.0 cm/year during the 1st year of therapy, height prediction did not change. Serum oestradiol (E₂) and urinary E₂ conjugates increased proportionally with 17-E₂ doses, serum oestrone (E₁) rose much less. The possibility to imitate time course, clinical events and hormonal changes of normal puberty, the absence of adverse drug reactions and the excellent acceptance and easy mode of application suggest that transdermal 17-E₂ is optimally suited for hormonal substitution in girls with hypogonadism.Presented in part at the Annual Meeting of the European Society for Paediatric Endocrinology and the LWSPE, Jerusalem November 1989