Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an iv bolus injection of growth hormone releasing hormone 1–29, 1 μg/kg, significantly enhanced the growth hormone response to the neuropeptidc, confirming the results of previous studies which used the iv route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.     

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an iv bolus injection of growth hormone releasing hormone 1–29, 1 μg/kg, significantly enhanced the growth hormone response to the neuropeptidc, confirming the results of previous studies which used the iv route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.     

Diastolic flow velocity of the left pulmonary artery of patent ductus arteriosus in preterm infants

BACKGROUND: The usefulness of diastolic pulmonary flow velocity determined by echocardiography in the assessment of symptomatic patent ductus arteriosus (sPDA) in preterm infants has not been confirmed. METHODS: Echocardiography was performed daily in infants ranging from 23 to 31 gestational weeks of age, and diastolic flow velocity of the left pulmonary artery (DFLPA) was measured. The DFLPA data before indomethacin administration for sPDA were compared with data obtained after indomethacin administration. The normal range of DFLPA was also determined from serial measurements performed in infants who did not develop sPDA during the first 7 days of life. Then, this range was compared with data from infants who did develop sPDA during this time. RESULTS: In infants who underwent indomethacin treatment, DFLPA increased with the development of sPDA and decreased when the symptoms of sPDA disappeared. On the basis of results from serial DFLPA measurement, the sensitivity and specificity of DFLPA for assessing sPDA was found to be 0.82 and 0.83, respectively. CONCLUSIONS: Measurement of DFLPA by echocardiography is a useful method for assessing sPDA in preterm infants.     

Relation between infusion rate of indomethacin and cerebral blood flow velocity

Background: Indomethacin is a very effective drug for patent ductus arteriosus (PDA). Decrease of cerebral blood flow, however, is an adverse effect of this drug. Differences in cerebral blood flow velocity (CBFV) with the different administration periods and the relation between CBFV and plasma drug level were investigated with the aim of establishing an administration protocol. Methods: The subjects were 14 neonates with PDA in the Neonatal Intensive Care Unit of Ehime Prefectural Central Hospital who received indomethacin. They were divided into two groups: 10 min drug infusion (n= 8) and 120 min drug infusion (n= 6). CBFV and blood concentration of indomethacin were measured. Results: CBFV in the10 min group was decreased significantly at 15 min and remained low until 120 min, but no significant change was seen in the 120 min group. The highest plasma levels in the 10 min group and 120 min group were 1257 ± 360 ng/mL and 819 ± 146 ng/mL, respectively. A comparison showed that the plasma level was significantly higher in the 10 min group, which had significantly lower CBFV. Changes in the plasma levels in the beta phase in the two groups were found to be almost the same. Ductus closure was confirmed in 13 of 14 neonates given indomethacin (10 min group, 7/8; 120 min group, 6/6). Conclusion: Slow administration of indomethacin >2 h is thought to be safer from the perspective of CBFV even though the clinical effect was unchanged.     

The effect of phototherapy on cerebral blood flow velocity in preterm infants

Cerebral blood flow velocity was studied with two-dimensional/pulsed Doppler ultrasound before, during and after discontinuation of phototherapy in 22 preterm infants (gestational age ≤32 weeks), who were treated for a minimum of 12h with blue-light phototherapy for non-haemolytic hyperbilirubinaemia. Before the cerebral blood flow velocity measurements, patency of the ductus arteriosus was diagnosed by Doppler echocardiography. All infants had normal brain ultrasound scans. Mean cerebral blood flow velocity increased significantly after initiation of phototherapy in all infants. Only in “healthy” (non-ventilated) infants did cerebral blood flow velocity return to pre-phototherapy values (baseline) after discontinuation of phototherapy, whereas in “unhealthy” (ventilated) infants cerebral blood flow velocity did not return to baseline. In 10 infants the ductus arteriosus reopened during phototherapy. In those infants, mean cerebral blood flow velocity returned to pre-phototherapy values after 2h of phototherapy prior to its discontinuation.     

促性腺激素释放激素激动剂治疗女童性早熟的不良反应探析

促性腺激素释放激素激动剂(gonadotropin releasing hormone agonist,GnRHa)是目前临床广泛应用的相对安全的性早熟治疗药物.患儿在停药后可以正常月经来潮、怀孕、生育.GnRHa不会降低青春期后的子宫体积,停药后的黄体生成素、卵泡刺激素及性激素水平可恢复至接近或超过停药前水平.研究提示促性腺激素释放激素拟似物可能会增加罹患雄激素过多症及多囊卵巢综合征的风险,但尚缺乏较高等级的证据.现有的研究不能提供充分证据表明GnRHa对骨矿物质密度有显著和不可逆的负面影响.GnRHa可能具有增加体质量指数(BMI)的不良反应,亦有研究表明GnRHa有助于降低BMI,或不会增加BMI.     

Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

We evaluated the response of preterm fetuses to maternal intravenous injection of 400 micrograms of thyrotropin releasing hormone (TRH) between 30 minutes and 5 hours before delivery (n = 12). An additional seven mothers received saline solution and served as control subjects. There were no statistically significant differences in gestational age, birth weight, or Apgar scores between groups. At delivery, concentrations of maternal thyrotropin were elevated in the TRH group compared with the control group (12.0 +/- 1.6 vs 5.6 +/- 0.5 mU/L; p less than 0.005); however, maternal triiodothyronine (T3) values remained unchanged. Significant elevations of fetal thyrotropin and T3 were observed after maternal administration of TRH compared with control subjects (45.8 +/- 7.7 vs 8.4 +/- 0.9 mU/L (p less than 0.002) and 1.3 +/- 0.07 vs 0.7 +/- 0.04 nmol/L or 87 +/- 5 vs 49 +/- 3 ng/dl (p less than 0.001), respectively). Fetal thyroxine (T4) and prolactin values were also elevated after exposure to TRH (135 +/- 5 vs 86 +/- 10 nmol/L or 10.5 +/- 0.4 vs 6.7 +/- 0.8 micrograms/dl (p less than 0.001) and 212 +/- 31 vs 105 +/- 28 micrograms/L (p less than 0.05), respectively). Two hours after birth, a significant increase in T3 but not T4 levels was observed in both groups of infants. These data indicate that fetal exposure to a single dose of TRH via maternal administration of this hormone results in marked stimulation of the preterm fetal pituitary-thyroid axis, as in the fetus at term, and that this treatment does not inhibit the early postnatal surge of T3.     

促性腺激素释放激素类似物联合重组人生长激素对中枢性性早熟女童身高的影响

目的 研究促性腺激素释放激素类似物（GnRHa）与重组人生长激素（rhGh）联合治疗以及GnRHa单用对骨龄≥10岁的特发性中枢性性早熟（ICPP）女童成年身高的改善情况。方法 将6个医学中心确诊为ICPP符合研究条件的80例女童（年龄9.0±0.7岁,骨龄≥10岁）根据治疗方法分为GnRHa与rhGh联合治疗组（31例）及GnRHa单用组（49例）。观察治疗前后的预测成年身高、接近成年身高和身高净获等各项指标的变化。结果 两组在治疗后按骨龄的身高标准差分值均较治疗前有显著改善（P<0.01）,其中GnRHa与rhGh联合治疗组明显优于GnRHa单用组（P<0.01）。联合用药组接近成年身高（157±6 cm vs 157±4 cm）、身高净获（4.68 cm vs 3.89 cm）、停药时预测成年身高（161±5 cm vs 158±5 cm）、接近成年身高与遗传靶身高差值等指标均略高于GnRHa单用组,但差异无统计学意义（均P >0.05）。结论 GnRHa与rhGh联合治疗或GnRHa单用组均能改善骨龄≥10岁ICCP女童的成年身高,但两药联用优势不明显。对ICPP患儿预测成年身高的评估需要慎重,停药时的预测值偏高。     

The influence of behavioural states on cerebral blood flow velocity patterns in stable preterm infants

Previous Doppler ultrasound studies assessing cerebral blood flow velocities in the anterior cerebral artery (ACA) among healthy term and preterm infants, showed a widespread range for the calculated flow indices. However, only one of these studies accounted for the infant's behavioural state.

In the present study a stable pattern of the cerebral blood flow velocity tracings and of the Pulsatility Index (PI) was observed during state 1, whereas marked fluctuations in cerebral blood flow velocity and PI were found during state 4 or active wakefulness. During state 2, minor variations of cerebral blood flow velocity and PI occurred though tended to be less pronounced than during active wakefulness. Thus at the time of Doppler assessment the cerebral blood flow velocity pattern and its variability will be better understood by taking into account the behavioural state of the infant.     

Effects of repeated indomethacin administration on cerebral oxygenation and haemodynamics in preterm infants: Combined near infrared spectrophotometry and Doppler ultrasound study

The objectives of this study were to evaluate the effect of repeated indomethacin administration on cerebral oxygenation in relation to changes in cerebral blood flow velocity (CBFV) and other relevant physiological variables. Fourteen preterm infants with patent ductus arteriosus were studied during three subsequent indomethacin bolus administrations with intervals of 12 and 24 h. Changes in concentration of oxyhaemoglobin (cO₂Hb), deoxyhaemoglobin (cHHb) and oxidized cytochrome aa₃ (cCyt.aa₃) in cerebral tissue and changes in cerebral blood volume (CBV) were measured by near infrared spectrophotometry; changes in mean CBFV in the internal carotid artery were measured by pulsed Doppler ultrasound. Simultaneously heart rate, transcutaneouspO₂ andpCO₂, arterial O₂ saturation and blood pressure were measured. All variables were continuously recorded until 60 min after indomethacin administration. Within 5 min after each indomethacin administration, significant decreases in CBFV, CBV and cO₂Hb and cCyt.aa₃ were observed which persisted for at least 60 min, while cHHb increased or did not change at all. There were no changes in the other variables recorded. These data demonstrate that indomethacin administration is accompanied by a reduction in cerebral tissue oxygenation due to decreased cerebral blood flow. Therefore, low arterial oxygen content, either caused by low arterial O₂ saturation or by low haemoglobin concentration, may be a contraindication for indomethacin treatment in preterm infants.     

Predictive factors for the effect of gonadotrophin releasing hormone analogue therapy on the height of girls with idiopathic central precocious puberty

The factors influencing the final height of central precocious puberty patients treated with gonadotrophin releasing hormone (GnRH) analogues remain a critical issue. This study compares the predicted final height before and after GnRH analogue therapy to identify predictive factors for final height. Fourteen girls with idiopathic central precocious puberty were treated with a GnRH analogue. All had an active non-regressive form before therapy, full and permanent suppression of oestrogenic activity during therapy (duration >2 years, 3.1±0.3 years, mean ±SEM), and the pubertal pituitary-ovarian axis had normalized in all of them 1 year after the cessation of therapy. The mean predicted final height increased from 152±1.8 cm before therapy to 162.2±1.2 cm (P<0.01) at the last evaluation performed 4.5±0.3 years after the onset of therapy. The mean gain in predicted final height between the onset of therapy and the last evaluation was 10.2±1.1 cm. It was correlated with the following data recorded at the onset of therapy: bone age advance over chronological age (r=0.66,P<0.02), predicted final height at the onset of therapy (r=–0.76,P<0.001), and the difference between the target height and the predicted height at onset of therapy (r=0.76,P<0.001). We conclude that GnRH analogue therapy is more likely to improve final height prognosis in girls who initially present with a markedly advanced bone age and a great difference between their target and predicted heights. Both these parameters reflect the severity of the disease at diagnosis.This work was presented in part at the international symposium on GnRH analogues in cancer and human reproduction, Geneva, November 1990. Abstract, Gynecol Endocrinol 4 [Suppl 2]:101 (1990)     

肿瘤坏死因子-α在宫内急性缺氧缺血后胎鼠肾脏炎性反应发生中的作用

目的：探讨宫内急性缺氧缺血后肿瘤坏死因子α（TNF－α）在胎鼠肾脏炎性反应发生中的作用。方法：通过钳夹孕21日龄大鼠供应子宫的血管，制备胎鼠宫内不同程度缺氧缺血（HI）模型和再灌注不同时间模型；利用酶联免疫分析方法和化学方法测定胎肾组织匀浆中TNF－α和髓过氧化物酶（MPO）的变化；同时观察肾组织形态学改变。结果：1．宫内HI后胎肾TNF－α水平上升，在缺血35－45min时明显（P＜0．05），缺血15min后再灌注1h胎肾TNF－α水平即开始显著升高（P＜0．01），8h达高峰，30h接近假手术组。2．胎肾MPO活力随缺血程度加重而略渐升高，缺血45min时明显（P＜0．05），缺血15min再灌注4h时胎肾TNF－α水平即明显升高（P＜0．05），15h达高峰（P＜0．01），30h仍高于假手术组（P＜0．05），3．组织学改变，缺血15min再灌注15h病理改变最明显，肾组织普遍充血和渗出，可见中性粒细胞浸润，肾小管普遍空泡变性，伴细胞核模糊，细胞崩解，基底膜阶段性断裂，尤以近端小管明显。结论：宫内急性缺血和再灌注后胎肾存在炎症反应，TNF－α可能是启动该反应的重要媒介，而MPO可反映炎症反应程序。αα     

Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis

Growth hormone-insulin-like growth factor-I status and response to growth hormone therapy (0.6 IU/kg/week sc, six times a week for 12 months) were evaluated in 12 girls (chronological age 9.4 ± 1.6 years) suffering from central precocious puberty with growth velocity less than 4 cm/year and no substantial increase or decrease in predicted adult height during gonadotropin releasing hormone (Gn-RH) analogue treatment (D-Trp⁶-LH-RH, 60 μg/kg im/28 days). At baseline, large variations were observed in nocturnal growth hormone (GH) means (pathological values (< 3.6μg/l) 33.3%), stimulated levodopa GH peaks (pathological values (<10.0 μg/I) 28.6%) and serum insulin-like growth factor-I (IGF-I) levels. Neither GH nor IGF-I levels were correlated with growth velocity. During recombinant GH therapy, growth velocity increased significantly (baseline 3.0 ± 0.9 cm/year; 6 months 6.4 ± 1.9cm/year, p < 0.001 versus baseline; 12 months 6.0 ± 1.3cm/year, p < 0.001 versus baseline). There was a significant increase in height SDS for bone age (baseline –1.6 ±0.5 SDS; 12 months -1.04 ± 0.6SDS; p < 0.002) and in predicted adult height (baseline 152.0 ± 3.6cm; 12 months 155.9 ± 3.4cm; p < 0.002). Our results suggest that combined therapy with Gn-RH analogues and recombinant GH can improve growth velocity and predicted adult height in girls with central precocious puberty and impaired height prognosis during Gn-RH analogue treatment.