Therapeutic efficacy and adverse effects of adrenocorticotropic hormone therapy in west syndrome: differences in dosage of adrenocorticotropic hormone, onset of age, and cause

OBJECTIVES: To determine the dosage and factors influencing efficacy of adrenocorticotropic hormone (ACTH) for West syndrome. STUDY DESIGN: A retrospective study of 135 patients receiving ACTH therapy with a synthetic analogue for initial effect, seizure outcome 1 year after therapy, and adverse effects. Efficacy and adverse effects were compared among the groups divided by clinical factors: dosage, treatment lag, onset age, and cause. RESULTS: One hundred thirteen patients had seizure control with ACTH. For more than 1 year after ACTH, 59 remained seizure free. Adverse effects were observed in 57, and ACTH therapy was discontinued in 23. The lowest dosage group (0.0125 mg/kg/d) had fewer episodes of discontinuation (P<.05), whereas differences in efficacy between different dosages were insignificant. None of the clinical factors correlated with initial effect. The earlier-onset group (<4 months) showed unfavorable seizure outcome 1 year after ACTH (P<.01). The cryptogenic patients showed better seizure outcome (P<.05) compared with the symptomatic. CONCLUSION: Synthetic ACTH therapy at a lower dosage is as effective as natural ACTH therapy at a higher dosage. Considering the adverse effects and the benefits for seizure control, the ACTH dosage of 0.0125 mg/kg/d (synthetic analogue) is more favorable than larger dosage.     

促肾上腺皮质激素应用于原发性肾病综合征频复发及激素依赖患儿疗效及安全性初探

目的 探讨促肾上腺皮质激素（ACTH）治疗原发性肾病综合征（PNS）频复发或激素依赖患儿的疗效和安全性。方法 以符合PNS频复发或激素依赖患儿为ACTH组,每月给予ACTH缓慢静滴 3~5 d,并逐渐激素减量至停药;以激素维持治疗PNS患儿为对照组。观察治疗前与治疗后3、6和12个月两组激素剂量、复发次数、肾上腺皮质功能及不良反应。结果 2010年9~12月ACTH组纳入14例,对照组纳入6例。①ACTH组12/14例均能顺利将激素减量至停药,无复发;2例因感染尿蛋白波动,感染控制后尿蛋白仍阳性,激素加量至尿蛋白转阴后减量,继续ACTH冲击,其中1例因感染后再次复发,停用ACTH改用他克莫司。ACTH组13例进入分析。②ACTH组治疗后3、6和12个月激素剂量与治疗前差异有统计学意义（P<0.05）;对照组治疗后3、6和12个月激素剂量与治疗前差异无统计学意义（P>0.05）;ACTH组与对照组治疗后6、12个月激素剂量差异有统计学意义（P<0.05）。③治疗前ACTH组和对照组均存在肾上腺皮质功能低下,ACTH组13例在治疗3、6和12个月分别有9、11和13例肾上腺皮质功能恢复正常;对照组6例12个月治疗期间均表现为肾上腺皮质功能低下。④ACTH组观察到腰部皮疹和心率加快各1例。⑤ACTH组治疗后6、12个月身高与治疗前差异有统计学意义,对照组治疗前后身高差异无统计学意义（P＞0.05）。ACTH组治疗前后体重差异无统计学意义,对照组治疗后6、12个月体重与治疗前差异有统计学意义（P<0.05）。⑥ACTH组和对照组治疗前后骨密度差异均无统计学意义（P＞0.05）。结论 ACTH治疗PNS频复发或激素依赖患儿有一定疗效,可避免长期激素治疗的不良反应,值得进一步探讨。     

常规剂量与小剂量促肾上腺皮质激素治疗婴儿痉挛的对照研究

目的：比较常规剂量与小剂量促肾上腺皮质激素（ACTH）治疗婴儿痉挛（West syndrome,WS）疗效及副作用的差异,寻找ACTH的最小有效剂量。方法：采用前瞻性随机对照研究,将30例WS（8例隐原性,22例症状性）随机分为常规剂量组（n=15）或小剂量组（n=15）。常规剂量组ACTH 50 IU/d×2周,随后2周减量至停药;小剂量组每日0.4 IU/kg×2周,若痉挛发作停止,随后2周减量至停药,若未完全控制或无效,加量至每日1 IU/kg 再用2周,随后用2周的时间逐渐减量至停药。比较ACTH两种不同剂量治疗WS的疗效及副作用。结果：常规剂量与小剂量治疗WS的近期疗效相似,有效率分别为53%及60%（P>0.05）,治疗后脑电图变化、痉挛复发及复发时间两组间差异无显著性（P>0.05）。8例完成12个月以上随诊,长期疗效两组间也无差异。ACTH对隐原性WS的有效率及脑电图高峰失律消失例数均高于症状性组（P<0.05）。常规剂量组副作用发生率(93%,14/15)明显高于小剂量组(20%,3/15),常规剂量组中1例出现轻度脑萎缩。结论：ACTH 50 IU/d与每日0.4 IU/kg两种剂量治疗WS的近期及远期疗效相似,对隐原性WS的疗效优于症状性,为避免副作用的发生,ACTH的使用应从小剂量（每日 0.4 IU/kg）开始。［中国当代儿科杂志,2009,11（6）：445-448］     

Quality of life after growth hormone therapy and induced puberty in women with Turner syndrome

OBJECTIVE: To evaluate health-related quality of life (HRQoL) in young women with Turner syndrome (TS) after long-term growth hormone (GH) therapy and induced puberty and to analyze whether HRQoL was influenced by auxologic parameters, pubertal development, or subjective parameters. STUDY DESIGN: The study group comprised 49 women with TS, mean (standard deviation) age 19.6 (+/-3.0) years, all former participants of 2 GH studies, > or =6 months after GH discontinuation. Puberty was induced by estrogen treatment, at mean age 12.9 (+/-1.1) years. HRQoL was measured by self-reports of the 2 generic questionnaires, SF36 and TAAQOL. As an additional source of information on HRQoL, we applied parental proxy reports. RESULTS: HRQoL of the women with TS was normal. Remarkably, the women with TS had higher HRQoL scores on some of the scales, including "social functioning" and "role-emotional." Satisfaction with height and breast development had a positive influence on several HRQoL scales. CONCLUSIONS: The young women with TS who reached normal height and had age-appropriate pubertal development reported normal HRQoL. The relatively high scores on some of the HRQoL scales can be explained by an estrogen effect or by a possible response shift, indicating a different internal reference in women with TS. We hypothesize that GH and estrogen treatment positively influenced HRQoL in young women with TS.     

The effect of human growth hormone therapy on L-(Methyl-2H3)-leucine turnover and urinary pseudouridine concentration in patients with Ullrich-turner syndrome

Abstract The effect of daily human growth hormone (hGH) injections (3 I.U./m²/day) on tissue anabolism was determined in six patients with Ullrich-Turner syndrome (XO) (8.7–19 years of age) using novel techniques such as whole body leucine kinetics during continuous infusion of L-(Methyl-²H₃)-leucine and urinary pseudouridine (5-ribosyluracil) excretion on the one hand and traditional methods like serum urea and amino acid concentrations on the other. Pseudouridine is only found in ribonucleic acid (RNA) and is neither reincorporated nor catabolically broken down and is therefore considered an ideal index of whole body RNA turnover. The mean L-(Methyl-²H₃)-leucine turnover of the six XO patients before hGH was 1.90±0.15 moles/kg per minute. After 3 months of hGH-treatment it had increased in three patients, whereas it had decreased in the other three. The results obtained with the stable isotope technique were correlated with the urinary pseudouridine concentrations (r=0.68;P<0.01). The growth rates were positively correlated with leucine turnover (r=0.63;P<0.02) and urinary pseudouridine concentration (r=0.73;P<0.006) as well as negatively correlated with the serum urea concentrationsr=–0.62;P<0.03). The decrease in the individual serum urea concentrations were tightly correlated with the hGH induced change in growth rate (r=0.90;P<0.01). The individual bone ages were negatively correlated with the hGH induced changes in leucine turnover (r=–0.77;P<0.003) as well as with the urinary pseudouridine concentrations (r=–0.87P<0.0002). The hGH effect on leucine and RNA turnover, showing effectiveness only until a developmental age between 11 and 12 years, leads the discussion of the ideal moment of oestrogen supplementation when girls with Ullrich-Turner syndrome are treated with hGH in early adolescence.Conclusion The protein metabolism of patients with Ullrich-Turner syndrome is influenced by hGH in an age dependent manner. In a clinical setting, pseudouridine, an easily determined derivative of ribonucleic acids, may be able to replace the tedious work with expensive stable isotopes when questions related to tissue anabolism are to be answered.     

Evaluation of long-term safety,tolerability, and behavioral outcomes with adjunctive rufinamide in pediatric patients (≥1 to <4 years old) with Lennox-Gastaut syndrome: Final results from randomized study 303

Objective

Evaluate the long-term safety, tolerability, and behavioral effects of adjunctive rufinamide in pediatric patients (≥1 to <4 years old) with inadequately controlled seizures associated with Lennox-Gastaut syndrome (LGS).

不同病因矮身材儿童TW2-R、C、T骨龄评分特征研究

目的　探讨不同病因矮身材儿童TW2-R、C、T骨龄评分特征, 为矮身材的病因诊断提供参考。方法　以363例未经治疗的矮身材儿童为研究对象, 根据病因分为4组：生长激素缺乏症(GHD, 27例)、特发性矮小(ISS, 280例)、小于胎龄儿(SGA, 41例)、Turner综合征(TS, 15例)。拍摄左手腕骨骨龄片, 应用TW-2骨龄评分法对各组患儿R骨龄、C骨龄及T骨龄进行评分, 将各序列骨龄与年龄对比分析。结果　GHD组男、女儿童表现为R骨龄、C骨龄及T骨龄均较年龄落后2岁以上。ISS组男童R骨龄、C骨龄及T骨龄较年龄落后约1岁; ISS组女童各序列骨龄与年龄比较无显著差异。SGA组男女儿童各序列骨龄与年龄比较无显著差异。TS组R骨龄及T骨龄较年龄显著落后, C骨龄与年龄比较无显著差异。结论 不同病因所致的矮身材儿童具有不同的TW-2 R、C、T各序列骨龄特点。TW-2 R、C、T各序列骨龄的评估对于矮身材儿童病因的诊断具有辅助作用。     

Effect of maternal CD4 cell count, acquired immunodeficiency syndrome, and viral load on disease progression in infants with perinatally acquired human immunodeficiency virus type 1 infection

Among a cohort of 152 infants perinatally infected with human immunodeficiency virus type 1, and their mothers, we correlated infant outcome with maternal CD4 ⁺ lymphocyte count and the presence of maternal acquired immunodeficiency syndrome near delivery. In a subset of 50 mother-infant pairs, we also correlated infant outcome with maternal quantitative viral burden as measured by the nucleic acid sequence based amplification system. We found that low maternal CD4 ⁺ cell count and high viral burden were associated with decreased time to category C disease or death in infants infected with human immunodeficiency virus type 1. In a multivariate analysis, high maternal viral load and maternal acquired immunodeficiency syndrome were independently associated with shorter time to category C disease or death in infants with human immunodeficiency virus type 1 infection. High viral load in pregnant women, independent of the presence of advanced maternal disease, appears to increase the risk of rapidly progressive disease in their infected offspring. (J Pediatr 1997;130:830-7)