基因重组生长激素治疗青春期前特发性矮小疗效观察

目的探讨基因重组人生长激素（rhGH）对青春期前特发性矮小（ISS）的疗效。方法观察27例青春期前特发性矮小患儿,平均年龄（8.9±2.0）岁,身高（118.0±10.6）cm。治疗组13例,男10例,女3例,均接受基因重组人生长激素治疗,剂量（0.12±0.01）IU/kg,睡前皮下注射,疗程6个月至1年;对照组14例,男6例,女8例。结果治疗组患儿生长速率（GV）由治疗前（4.28±0.86）cm/a提高到（9.38±1.77）cm/a,P〈0.01;年龄身高标准差积分（HtSDSCA）由-2.28±0.48增至-1.72±0.62（P〈0.01）;骨龄身高标准差积分（HtS-DSBA）由-0.24±1.02增至0.27±0.99（P〈0.05）;与对照组比较,GV、HtSDS（CA）和HtSDS（BA）差异均有统计学意义（P均〈0.05）;两组△BA/△CA比较差异无统计学意义（P均〉0.05）。结论GH治疗能改善ISS儿童的GV及HtSDS（CA）、HtSDS（BA）,而骨龄（BA）加速不明显,疗效肯定。     

中药辅助托吡酯治疗Tourette综合征

目的探讨托吡酯联合中药治疗对Tourette综合征患儿的疗效。方法将42例确诊为Tourette综合征的患儿随机分为研究组22例及对照组20例。对照组仅予口服托吡酯治疗,初始剂量0.5 mg/kg,1次/d,逐渐增加剂量,直到症状减轻或控制,最大量不超过5.0 mg/（kg.d）。研究组在此基础上经中医辨证后加服中药止抽汤治疗,治疗第12周末评价疗效。治疗前后使用耶鲁抽动症整体严重度量表（YGTSS）及治疗中需处理的不良反应症状量表（TESS）评估其疗效及不良反应。采用SPSS 11.5软件进行统计学分析。结果治疗前2组YGTSS总分无统计学差异[研究组（48.20±10.42）分vs对照组（52.04±10.21）分P〉0.05]。治疗第12周末,研究组YGTSS总分低于对照组[（27.88±14.24）分vs（36.53±17.45）分P〈0.05],研究组减分率高于对照组[（43.12±18.42）%vs（33.49±14.38）%P〈0.05]。治疗第12周末研究组TESS分值低于对照组[（2.16±2.25）vs（4.78±3.75）P〈0.05]。结论托吡酯联合中药治疗能有效改善儿童Tourette综合征的抽动症状,不良反应相对较小。     

小剂量单药托吡酯治疗抽动障碍的效果

目的探讨小剂量单药托吡酯治疗抽动障碍的临床效果。方法随机选择在儿科门诊就诊、明确诊断抽动障碍、未曾用药53例（第一组）和经治疗药物效果不佳者32例（第二组）患儿,采用小剂量托吡酯单药治疗,初始剂量1.0mg/（kg·d）,1周后症状无好转可每周递增0.5mg/（kg·d）,症状控制后,有效剂量巩固维持观察3个月无复发,再减量停药。结果第一组38例服药至第2周1.5mg/（kg·d）时,抽动消失;15例服至第3周2.0mg/（kg·d）时,抽动消失。第二组19例托吡酯服至第2周1.5mg/（kg·d）时,抽动完全控制;13例托吡酯服至2.0mg/（kg·d）,第3周抽动完全控制。85例患儿有效剂量巩固维持治疗,观察3个月均无复发。3例服至2mg/（kg·d）时有食欲不振和少汗,余82例未发现不良反应。结论小剂量单药托吡酯治疗抽动障碍患儿效果好,有效控制量只需1.5～2.0mg/（kg·d）,不良反应少。     

肺炎患儿血清一氧化氮和锌水平变化及其相关性

目的探讨肺炎患儿血清一氧化氮（NO）与锌水平的变化及临床意义。方法2005年10月-2006年5月本院儿科住院的符合肺炎诊断标准的患儿48例。其中有充血性心力衰竭的重症肺炎17例,轻症肺炎31例。本院儿科门诊同期健康体检者20例为健康对照组。抽取2组儿童晨起空腹静脉血3mL,其中26例肺炎患儿采集恢复期血液。应用UV-2100分光光度计545nm对肺炎患儿（包括恢复期）及健康对照组血清采用比色法测血清NO水平,采用原子吸收分光光度分析法用P-E503型原子吸收分光光度计直接测出肺炎患儿（包括恢复期）及健康对照组血清锌水平,分析血清NO与锌水平相关性,统计学处理采用SPSS10.0软件进行处理。结果肺炎患儿急性期肺炎血清NO水平[（57.76±19.41）μmol/L]较健康对照组[（25.09±5.51）μmol/L]、肺炎恢复期[（30.08±8.05）μmol/L]明显升高（Pa〈0.01）;重症组[（80.26±11.72）μmol/L]较轻症组[（45.77±12.58）μmol/L]明显升高（P〈0.01）;急性期患儿血清锌水平[（77.61±10.95）μmol/L]较对照组[（115.18±12.66）μmol/L]、肺炎恢复期患儿[（88.08±9.82）μmol/L]显著降低（Pa〈0.01）,重症组[（70.38±6.61）μmol/L]较轻症组[（81.47±10.90）μmol/L]显著降低（P〈0.01）。肺炎患儿急性期NO与锌水平呈显著负相关（r=-0.327P〈0.01）。结论血清NO、锌水平变化与肺炎的发生发展和病情严重程度有关,在肺炎治疗过程中,阻断NO的过多分泌、及时补锌有一定临床意义。     

极化液治疗危重病患儿应激性高血糖的效果

目的探讨极化液治疗儿童应激性高血糖的疗效。方法应激性高血糖患儿30例随机分成极化液治疗组和对照组,每组各15例。在综合治疗基础上,治疗组予极化液降糖,对照组仅将葡萄糖输入量严格控制在4mg/（kg·min）以下。监测二组患儿治疗前、入院8～12h、第2、3天血糖。同时应用简化小儿危重病例评分法进行病情评估。结果入院时、入院8～12h、第2、3天血糖值,治疗组分别为（20.7±5.02）、（11.98±3.13）、（7.55±1.94）、（5.12±1.04）mmol/L,对照组分别为（19.16±4.49）、（14.89±3.42）、（10.7±2.63）、（5.95±1.33）mmol/L。与入院时血糖比较,治疗组血糖下降较快;8～12h及第2天二组血糖下降比较差异有显著性意义（Pa〈0.01）;第3天,二组血糖下降比较差异无显著性意义（P〉0.05）。二组入院时危重状态及极危重状态各分别为7和8例;第2天,治疗组3例仍为危重状态,其余转为非危重,转安率为80%;对照组尚有7例危重,2例极危重,转安率为40%,二组转安率比较差异有显著性意义（P〈0.05）。第3天,治疗组均转为非危重,对照组尚有2例危重状态、1例极危重状态。二组转安率分别为100%、80%,二组比较差异无显著性意义（P〉0.05）。结论应用极化液治疗儿童应激性高血糖安全有效,经济简便,利于疾病恢复。     

流行性乙型脑炎患儿脑脊液和血清S100β蛋白水平的变化及其意义

目的探讨流行性乙型脑炎（乙脑）患儿脑脊液和血清S100β蛋白水平的变化及其意义。方法乙脑患儿45例,分别在极期和恢复期空腹采静脉血2mL,极期采脑脊液1mL,ELISA法测定其脑脊液和血清S100β蛋白水平。20例拟行非心脏外科手术治疗的行腰麻的患儿采取肘静脉血2mL和脑脊液1mL作为对照。采用ELISA法检测S100β蛋白水平。结果轻型、普通型、重型乙脑患儿极期脑脊液S100β蛋白分别为（0.35±0.12）、（0.76±0.15）、（1.29±0.22）μg/L,血清S100β蛋白分别为（0.08±0.04）、（0.14±0.07）、（0.22±0.12）μg/L;对照组脑脊液S100β蛋白为（0.05±0.03）μg/L,血清S100β蛋白为（0.03±0.02）μg/L。乙脑患儿极期脑脊液和血清S100β蛋白水平均显著高于对照组（Pa〈0.01）,且随临床分型加重而增高。乙脑患儿恢复期血清S100β蛋白为（0.08±0.03）μg/L,较极期[（0.24±0.13）μg/L]显著下降（P〈0.01）。结论乙脑患儿脑脊液和血清S100β蛋白水平与临床分型相关,检测乙脑患儿脑脊液和血清S100β蛋白水平的变化,有助于判定脑组织受损的严重程度及评估患儿的预后。     

急性病毒性心肌炎患儿血清肿瘤坏死因子-α、白细胞介素-6水平变化的意义

目的探讨急性病毒性心肌炎（AVM）患儿血清肿瘤坏死因子-α（TNF-α）及白细胞介素-6（IL-6）水平变化的意义。方法应用放射免疫法（RIA）和酶联免疫吸附法（ELISA）检测53例AVM患儿及20例健康儿童血清TNF-α及IL-6水平,分析TNF-α及IL-6血清水平与儿童AVM发生的关系。结果AVM组急性期血清TNF-α和IL-6水平分别为（526.7±32.9）和（3.23±0.53）mg/L,健康对照组分别为（383.1±27.5）和（1.63±0.22）mg/L,二组比较均有显著性差异（Pa〈0.05）;临床治愈后,AVM组TNF-α及IL-6分别降至（407.3±34.4）和（1.97±0.29）mg/L,与健康对照组比较均无显著性差异（Pa〉0.05）。结论AVM患儿急性期血清TNF-α和IL-6明显增高,心肌炎治愈后降至正常,检测TNF-α及IL-6血清水平及变化有助于判断AVM患儿病情及心肌损害程度。     

川崎病患儿血清可溶性血管细胞黏附分子-1、肿瘤坏死因子-α水平变化的意义

目的探讨可溶性血管细胞黏附分子-1（sVCAM-1）与肿瘤坏死因子-α（TNF-α）在川崎病（KD）发病中的意义。方法采用双抗体夹心酶联免疫法（ELISA）分别测定确诊为KD34例患儿急性期血清sVCAM-1、TNF-α水平,测定其中32例恢复期患儿血清sVCAM-1、TNF-α水平,26例健康儿童为健康对照组。结果KD组血清急性期sVCAM-1、TNF-α[（97.8±35.6）、（73.9±21.7）μg/L]均高于健康对照组[（41.2±8.9）、（2.7±1.8）μg/L],差异有显著性（Pa〈0.01）;KD患儿恢复期血清sVCAM-1、TNF-α水平[（46.9±16.8）、（4.3±2.9）μg/L]下降显著与急性期比较差异有显著性（Pa〈0.01）;而KD恢复期患儿与健康对照组无显著差异（P〉0.05）,且sVCAM-1与TNF-α呈正相关（r=0.798P〈0.001）。结论sVCAM-1、TNF-α可能参与KD发病的病理过程,血清sVCAM-1、TNF-α检测有助于对KD病情发展作出判断。     

毛细支气管炎患儿血清MCP-4、MDC和IL-4水平及临床意义

目的研究毛细支气管炎患儿外周血中单核细胞趋化蛋白4（MCP-4）、巨噬细胞衍生趋化因子（MDC）和白介素4（IL-4）水平的变化,探讨其临床意义。方法采用酶联免疫吸附法（ELISA）分别测定31例毛细支气管炎患儿（毛支组）和30例健康儿童（正常对照组）血清MCP-4、MDC和IL-4水平,并进行比较。结果毛支组患儿急性期血清MCP-4、MDC和IL-4水平为（103.56±27.31,692.67±107.22,19.48±7.40）pg/ml,明显高于正常对照组（86.34±14.50,242.12±27.40,9.22±4.10）pg/ml（P均〈0.01）。MCP-4、IL-4的升高程度与病情严重程度相关,且两者之间呈正相关。结论MCP-4、MDC参与调节毛细支气管炎Th2细胞因子IL-4的募集、释放,参与毛细支气管炎的发病;监测血清MCP-4水平可反映毛细支气管炎的病情严重程度,具有重要的临床价值。     

用尿脱氧吡啶啉及羟脯氨酸排泄率评价肾病综合征患儿骨吸收功能状况

目的　观察糖皮质激素（激素）对肾病综合征(肾病)患儿骨吸收功能的影响。方法　采用酶联免疫竞争法和分光光度比色法,对68例泼尼松治疗不同阶段的肾病患儿及同龄健康儿童16例尿脱氧吡啶啉（DPD）及羟脯氨酸（HOP）进行检测。结果　（1）激素足量治疗组DPD/肌酐(Cr)为（30±17）nmol/mmol,较正常对照组［（21±5）nmol/mmol］、初发激素治疗前组［(20±8)nmol/mmol］及激素减量治疗组［(20±11)nmol/mmol］均有升高（P均<0.05);（2）与DPD/Cr值变化趋势一致,激素足量治疗组HOP/Cr为［(5.3±2.7)mg/mmol］,与正常对照组［(3.2±1.2)mg/mmol］、初发激素治疗前组［(3.5±0.9)mg/mmol］及激素减量治疗组［(3.7±1.7)mg/mmol］比较差异均有显著意义(P＜0.05,<0.01,<0.05);（3）DPD/Cr与HOP/Cr两指标在正常对照组及肾病各组均呈明显正相关(r=0.64、0.65、0.76、0.78,P均<0.01)。结论　超生理剂量的泼尼松治疗能使肾病患儿骨吸收功能增强,易导致骨质疏松。     

Comparison of growth hormone releasing hormone therapy and growth hormone therapy in growth hormone deficiency

Seven children with growth hormone deficiency of hypothalamic origin responded to an i.v. bolus of growth hormone releasing hormone (GHRH) (1–29)-NH2 with a mean serum increase of 10.7 ng/ml growth hormone (GH) (range 2.5–29.3 ng/ml). Continuous s.c. administration of GHRH of 4–6 g/kg twice daily for at least 6 months did not improve the growth rate in five of the patients. One patient increased his growth rate from 1.9 to 3.8 cm/year and another from 3.5 to 8.2 cm/year; however, the growth rate of the latter patient then decreased to 5.4 cm/year. When treatment was changed to recombinant human growth hormone (rhGH) in a dose of 2 U/m² daily, given s.c. at bedtime, the growth rate improved in all patients to a mean of 8.5 cm/year (range: 6.2 to 14.6). Presently GHRH cannot be recommended for the routine therapy of children with growth hormone deficiency since a single daily dose of rhGH produced catch-up growth which GHRH therapy did not.Abbreviations GH growth hormone - GHD growth hormone deficiency - GHRH growth hormone releasing hormone - hGH human growth hormone - rhGH recombinant human growth hormone - SM C/IGF I somatomedin C/insulin-like growth factor I On the occasion of the 85th birthday of Prof. Dr.Dr.h.c. mult. Adolf Butenandt     

Circulating immunoreactive growth hormone releasing hormone concentrations and growth hormone response to growth hormone releasing hormone in short children

To study the role of peripheral immunoreactive growth hormone releasing hormone (ir-GHRH) concentrations and the GHRH test in the evaluation of growth hormone (GH) secretion in short stature, 46 children with a mean age of 9.4 years (range 1.6–16.3 years) and a mean relative height score of –3.2 SD (range –5.0–2.1 SD) were investigated. The children were divided into prepubertal (n=35) and pubertal (n=11) and the prepubertal children further into three groups based on their maximal GH responses to insulin-induced hypoglycaemia (IIH) and clonidine: (1) GH deficient subjects (maximal GH<10 g/l in both test); (2) discordant responders (maximal GH<10 g/l in one test and 10 g/l in the other); and (3) normal responders (maximal GH10 g/l in both test). Peripheral ir-GHRH concentrations were measured during the IIH test by radioimmunoassay after purification of plasma samples on Sep-pak cartridges. Among the prepubertal children 10 fell into group 1, 16 into group 2 and 9 into group 3. Children in group 1 were older, than those in group 3. There were no significant differences in relative heights and weights or absolute and relative growth velocities between the groups. Subjects in groups 1 and 2 had lower maximal GH responses to GHRH than those in group 3. There were no significant differences in the basal plasma ir-GHRH concentrations between the groups. Nine children (19.6%) had somatotrophs with a poor response to a single dose of exogenous GHRH (maximal GH<10 g/l). These subjects had increased basal plasma ir-GHRH concentrations. All of them had a decreased GH response to IIH and/or clonidine. Pubertal children had higher circulating ir-GHRH levels than the prepubertal subjects. There was an inverse correlation (r=–0.46;P<0.001) between the maximal GH response to GHRH and calendar age in the whole series. These observations suggest that: (1) a substantial proportion of short children have a heterogenous GH response to pharmacological stimuli necessitating complementary evaluation of their spontaneous GH secretion; (2) a poor response to exogenous GHRH is associated with increased ir-GHRH levels in the peripheral circulation; (3) all children with normal GH responses in pharmacological tests respond normally to GHRH and (4) the pituitary sensitivity to GHRH decreases with increasing age. Peripheral ir-GHRH concentrations do not differentiate between short children with growth hormone deficiency (GHD) and those with undefined short stature. The GHRH test is of limited value in the diagnosis of GHD, since a normal GH response does not exclude GHD, although a subnormal response appears to reflect dysfunctional GH secretion.     

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.     

Changes with growth hormone treatment in growth hormone deficient children

A total of 54 previously untreated patients (15 girls, 39 boys) with poor growth due to idiopathic growth hormone deficiency (IGHD) were treated with human growth hormone (hGH), continuously up to 4 years. All of the patients had a peak hGH level which was below 10 ng/mL after at least two pharmacological tests and/or blunted physiologic hGH secretion, and their height was below ?2.5 s.d. for age and gender. After the 1st year of therapy, height velocity (HV) increased significantly when compared with baseline (from 3.18 ±0.76 cm/year to 9.17±1.03 cm/year; P <0.001), declined during the 2nd year and then remained significantly higher than pretreatment HV. When considering improvement in height expressed by height standard deviation score (SDS), during the therapy all of the patients showed a significant gain ± 1.72±1.09 (from ?4.11±0.61 to ?2.21±0.48). The height values were significantly higher than pretreatment, but remained below ?2 s.d. after 4 years of hGH therapy in our patients. Increased height velocity has been sustained, but height improvement after therapy was inversely correlated to height SDS for chronological age of patients at the start of therapy. In conclusion post-treatment height has been shown to be related to height deficit at the beginning of therapy. Therapy was well tolerated with no local or systemic adverse effects or acceleration of bone age.     

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.     

Effects of long-term growth hormone releasing hormone 1 -29 in significantly short children

Seven children with significant idiopathic short stature (SISS) whose heights were significantly below the third percentile (SD score for height —2.5 to —3.5) and who had normal levels of growth hormone (GH) were treated with growth hormone releasing hormone (GH-RH) in a dose of 30 /μg/kg/day. Therapy was discontinued if patients failed to increase their rates of growth by more than 2.0 cm/year over their pre-therapy growth rate. Treatment was discontinued in two of the patients after 12 months but was continued in the other five for 24 months. These data demonstrate that some patients with SISS grow well during the first 2 years of treatment with GH-RH.     

Diagnostic value of growth hormone-releasing hormone test in children and adolescents with idiopathic growth hormone deficiency

Average growth hormone (GH) peaks following an i.v. growth hormone releasing hormone (GHRH) 1–29 stimulation test were significantly lower in 48 children and adolescents with GH deficiency (GHD) than in 20 age-matched controls (15.2+12.7 vs 37.5+28.1 ng/ml, 2P<0.001). Twelve patients exhibited a low GH peak (<5 ng/ml), 27 demonstrated a normal response (>10 ng/ml) and 9 showed an intermediate rise in plasma GH (5–10 ng/ml). Six of the 12 patients with low GH response to the first GHRH stimulation failed to respond to two other tests immediately before and after a 1 week priming with s.c. GHRH. These subjects with subnormal GH increase at repeat testing had total GHD (TGHD) and multiple pituitary hormone deficiency (MPHD) and had suffered from perinatal distress. On the contrary, 26 of 27 patients with normal GH response to the first test had isolated GHD and only a minority (8/27) had signs of perinatal distress. It is concluded that perinatal injuries primarily damage pituitary structures and that a pituitary defect more probably underlies more severe forms (TGHD and MPHD) of GHD.Presented in part at the 7th Meeting of the Italian Society for Paediatric Endocrinology (Milan, 20–21 October 1989)     

Malignant thymoma in a patient with growth hormone deficiency during growth hormone therapy

Malignant thymoma was found in an 8-year-old Japanese boy with growth hormone (GH) deficiency who had received GH therapy for 3 years and 5 months. There may be a possible relationship between the occurrence of malignant thymoma and GH therapy.     

重组人生长激素治疗生长激素缺乏症疗效观察

目的 观察基因重组人生长激素(rhGH)对生长激素缺乏症(GHD)患儿的疗效。方法 对15例GHD患儿应用rhGH治疗,每晚睡前皮下注射0.1 IU/kg,疗程6个月。结果 患儿身高由治疗前109.3±9.9cm增加到115.5±11.3 cm;年身高生长速度由治疗前2.8±0.6cm/年增加到11.6±3.5cm/年。治疗期间除少数患儿出现亚临床甲状腺功能低下,注射部位有轻度反应外,未发现明显副作用。结论 皮下注射rhGH是治疗儿童GHD的一种安全有效的方法。     

Growth hormone therapy

Growth hormone (GH) therapy has revolutionized treatment of children with growth hormone deficiency (GHD). Improved height outcome with final height in the target height range has been achieved in these children. Identification of Creutzfeldt-Jakob disease, a deadly prion mediated disorder, in recipients of pituitary GH accelerated the transition from pituitary derived GH to recombinant GH. Once daily subcutaneous administration of the freeze-dried preparation at evening is the recommended mode of GH therapy. Studies have led to use of higher dose of GH for improving height outcome (0.33 mg/kg/week or 0.14 IU/kg/day) albeit at a significantly high cost. Growth velocity increases from 3–4 cm/year before therapy to 10–12 cm/year during the first two years of therapy and is maintained at 7–8 cm/year after a period of two years. Close follow-up with regular clinical and laboratory monitoring is essential for achieving a desirable height outcome. A theoretical unlimited supply has led to wide spread use of GH in a variety of disorders other than GHD. Initially started in children with Turner syndrome, GH has now been used in chronic renal failure, idiopathic short stature and intrauterine growth restriction besides a wide array of newly emerging indications.