曲普瑞林治疗女童特发性中枢性性早熟52例

目的观察曲普瑞林治疗女童特发性中枢性性早熟(ICPP)的疗效。方法采用曲普瑞林治疗医院收治的ICPP女童52例,治疗24个月,观察其第二性征、骨龄(BA)、黄体生成素释放激素(LHRH)激发试验和生长速率变化。结果与治疗前比较,乳房分期(2.7,1.5)差异有统计学意义(P<0.05);治疗前后BA(9.7,11.6)、预测成人身高(151.7,158.5)、促黄体生成素(21.7,1.5)、卵泡刺激素(12.7,3.1)峰值比较,差异有统计学意义(P<0.05或P<0.01);治疗前后7～12个月、13～18个月、19～24个月生长速率比较,差异有统计学意义(P<0.05)。结论曲普瑞林治疗ICPP可有效改善患儿第二性征、骨龄、预测成人身高及抑制性激素分泌。     

曲普瑞林治疗特发性中枢性性早熟女童的效果

目的 观察曲普瑞林治疗特发性中枢性性早熟(ICPP)女童的临床效果。方法 纳入2018年4月—2020年1月南华大学衡阳医学院附属第二医院收治的ICPP女童180例,所有患儿均应用曲普瑞林治疗,依据患儿治疗效果调整用药剂量,比较治疗前后盆腔脏器发育情况、生长指标及性激素水平。结果 治疗12个月后,患儿第二性征均出现不同程度改善;患儿双侧卵巢容积、子宫容积、双侧卵巢长径、子宫长径、宫颈长径小于治疗前,骨龄指数、促黄体生成素(LH)、促卵泡激素(FSH)与雌二醇(E2)水平均低于治疗前,体质指数、预测成年身高均高于治疗前,差异均有统计学意义(P <0.01)。结论 曲普瑞林治疗ICPP女童的效果好,可显著抑制患儿第二性征,改善性征发育,延缓骨龄生长,对增加患儿成年身高具有重要意义。     

不同疗程GnRHa治疗中枢性性早熟25例疗效比较

目的探讨促性腺激素释放激素类似物(GnRHa)治疗特发性中枢性性早熟(ICPP)的适宜疗程。方法厦门市第一医院儿科于2002年3月至2006年3月收治25例ICPP女童,随机分为两组,A组15例,年龄9.2±0.5岁,骨龄11.6±0.7岁,每4周肌肉注射曲普瑞林60～120μg/kg,疗程1年;B组10例,年龄8.7±0.9岁,骨龄11.2±0.5岁,每4周肌肉注射曲普瑞林60～120μg/kg,疗程2年。治疗过程中每月测量身高、体重、性征变化,每三个月监测骨龄(BA)、B超、预测身高(PAH)。结果经治疗骨龄增速减慢,A、B组骨龄变化与实际年龄变化的比值ΔBA/ΔCA分别由治疗前的1.23±0.07、1.29±0.12降低为0.62±0.25、0.53±0.06;两组患儿随疗程进展ΔBA/ΔCA比值均逐渐下降,治疗后BA的增长低于CA的增长。两组患儿治疗后预测成年身高在治疗6个月时即较治疗前有所改善,在治疗6个月及治疗1年时,两组差异无统计学意义;治疗后预测成年身高的增长值(ΔPAH),在治疗结束时B组比A组高(P<0.001)。结论GnRHa治疗中枢性性早熟疗程至少需6个月,治疗2年对终身高的改善更好。     

曲普瑞林治疗女童特发性中枢性性早熟的疗效观察

目的:观察促性腺激素释放激素类似物曲普瑞林治疗女童特发性中枢性性早熟(ICPP)的临床疗效。方法:选取某院2008—2012年确诊的68例ICPP女童,予曲普瑞林治疗1~2年,观察治疗前后乳房、子宫容积、卵巢容积、促黄体生成素峰值(P-LH)、促卵泡刺激素峰值(P-FSH)、血清雌二醇(E2)与随疗程进行的体质量指数(BMI)、骨龄(BA)、骨龄与生活年龄比值(BA/CA)、预测成年身高(PAH)、身高年龄对骨龄的追赶(HtSDSBA)、生长速率(GV)的动态变化及药物不良反应。同时选取52例未经治疗的ICPP患儿作为对照组,随访1~2年,测量各阶段乳房、子宫容积、卵巢容积、P-LH、P-FSH、E2以及BMI、BA等指标并进行比较。结果:治疗后患儿乳房、子宫、卵巢容积均有缩小,P-LH、P-FSH、E2均显著降低,骨龄成熟延迟,BA/CA值下降,身高年龄对骨龄的追赶、PAH治疗后较治疗前有改善,差异具有统计学意义(P<0.05);而未经治疗的对照组ICPP患儿乳房、子宫、卵巢容积有不同程度的增大,骨龄进展,BA/CA升高。结论:曲普瑞林治疗ICPP能有效抑制下丘脑-垂体-性腺轴及性征发育,延缓BA成熟,改善成年终身高。     

促性腺素释放素类似物治疗特发性中枢性性早熟18例

目的 :观察促性腺素释放素类似物 (GnRH A)治疗特发性中枢性性早熟 (ICPP)的临床疗效。方法 :用GnRH A缓释剂治疗 18例 (男性 1例 ,女性 17例 )ICPP病人 ,疗程为 6～ 12mo ,观察第二性征变化 ,男性睾丸 ,女性乳房、子宫、卵巢容积 ,骨龄 ,生长速率 ,促黄体素释放素 (LHRH)激发试验。结果 :经治疗男性睾丸、女性卵巢、子宫容积及乳房均缩小 ,子宫容积和乳房分期治疗 6mo与治疗前比较分别为 [(2 .4±s 0 .3)cm3vs (5 .9± 0 .9)cm3,P <0 .0 1]和 [(1.8± 0 .7)vs (2 .80± 0 .10 ) ],P <0 .0 1]。骨龄延缓 ,BA /CA值随疗程而缩小。治疗后身高、骨龄及实际年龄三者间的差距逐步改善 ,治疗 12mo预测成人终身高 (PAH)从 (15 4.7± 1.7)cm提高到 (15 8± 3)cm。结论 :GnRH A缓释剂治疗ICPP可有效抑制性征发育 ,延缓骨龄成熟 ,并随疗程延长而改善成人终身高     

曲普瑞林治疗特发性中枢性性早熟女童的临床效果分析

目的探讨曲普瑞林治疗特发性中枢性性早熟女童的临床效果。方法选择我院2006年8月至2010年8月特发性中枢性性早熟女童共28例,本组患儿均给予曲普瑞林治疗,起初剂量为80～100μg/kg,肌肉注射,每隔30d注射一次,在治疗过程中根据患儿性腺抑制情况及身高增加情况调整剂量。在性腺抑制的前提下逐渐减量,维持生长速度>4cm/年。本组患儿连续治疗2年。观察本组患儿治疗前后骨龄指数、身高年龄对骨龄的追赶(HtSDSBA)、体质量指数、预测成年身高。结果本组患儿治疗后骨龄指数、身高年龄对骨龄的追赶(HtSDSBA)、体质量指数、预测成年身高分别与治疗前比较,差异有统计学意义(P<0.05)。结论曲普瑞林能够抑制特发性中枢性性早熟女童性腺轴及第二性征发育,有助于延缓骨龄成熟,疗效显著。     

醋酸曲普瑞林治疗特发性中枢性性早熟女童的短期疗效评估

目的：观察促性腺素释放激素类似物醋酸曲普瑞林对患有特发性中枢性性早熟（ICPP）女童治疗3个月后的疗效。方法采用醋酸曲普瑞林治疗30例 ICPP 女童,治疗3个月后,观察其第二性征变化;比较治疗前后血清雌二醇浓度和促性腺激素释放激素（LHRH）激发试验以及子宫、卵巢体积的变化,并观察醋酸曲普瑞林的副作用。结果治疗3个月后所有患儿乳房回缩,既往有月经初潮的患儿月经停止;子宫、卵巢容积均有不同程度缩小,与治疗前相比差异有统计学意义（t＝5．792,P ＜0．01;t＝4．268,P ＜0．01）;发育卵泡减少或消失,与治疗前相比差异有统计学意义（χ2＝40．000,P ＜0．01）;治疗后所有患者 LHRH 激发试验均回到青春期前水平,LH／FSH明显减小（t＝4．950,P ＜0．01）;患儿血清雌二醇水平显著下降,达到青春期前水平（t＝7．408,P ＜0．01）。结论醋酸曲普瑞林治疗 ICPP 3个月后即可有效抑制性征发育。     

基因重组人生长激素治疗小胎龄身材矮小的临床观察

目的观察分析用基因重组人生长激素治疗前后,小胎龄身材矮小儿(smallforgestationalage,SGA)身高生长速率及骨龄变化及成年身高预测,以了解GH对SGA在促进生长的同时对骨龄及成年身高的影响。方法确诊为SGA12例,男8例,女4例,年龄8.2±3.4岁,用rhGH0.15Iu/(kg.d)治疗,疗程1年,于治疗前、治疗后6个月及1年观察生长指标变化(身高、生长速度、身高年龄、骨龄)及进行骨龄评价和成年身高预测。结果多数患儿用药后食欲有所增加,睡眠状况良好,身高等各项指标较治疗前明显增加,而以治疗前半年增长最快,同时骨龄增长也最快,P<0.01,但△HA/△BA的比值均<1,身高增长与骨龄增长呈平衡,为1﹕1比例。用药治疗后预测成年身高也有增加,能改善终身高。结论SGA儿用rhGH在促进身高增长同时促进骨龄增长,两者呈平行线关系,GH治疗对SGA儿身高及骨龄增长呈正性影响,实现生长与成熟的平衡,并能改善成年终身高。     

司坦唑醇对特发性中枢性性早熟患儿预测成人终身高及性腺发育的影响

目的 探讨司坦唑醇联合常规治疗方案对特发性中枢性性早熟(idiopathic central precocious puberty,ICPP)患儿预测成人终身高(predicted adult height,PAH)及性腺发育的影响。方法 选取2018年6月至2020年6月于我院就诊的ICPP患儿80例,随机分为对照组(常规方案)和观察组(常规方案+司坦唑醇),每组40例,比较两组患儿PAH及性腺发育情况。结果 治疗后,观察组生长速度、PAH均高于对照组(P <0.05);Tanner分期及阴毛分期优于对照组(P <0.05);左右卵巢容积小于对照组(P <0.05)。观察组中,大骨龄(11～14岁)患儿达成PAH的效果优于小骨龄(8～11岁)者（P <0.05）。两组患儿治疗期间均未出现严重药物相关不良反应。结论 司坦唑醇对儿童ICPP疗效显著,能明显提高PAH,改善症状,抑制性腺发育,且安全性良好,尤其对大骨龄患儿促生长作用更佳。     

曲普瑞林对特发性中枢性性早熟女童体质量指数及终身高的影响

目的：观察促性腺激素类似物（ GnRHa）曲谱瑞林对特发性中枢性性早熟（ ICPP）女童体质量指数（BMI）及最终成年身高（FAH）的影响。方法总结及追踪回访120例ICPP女童。62例ICPP女童接受曲普瑞林治疗（治疗组）,观察治疗后6、12、18、24、36个月的骨龄（BA）、生长速率（GV）、BMI、预测身高（PAH）,终身高及达终身高时的BMI。未治疗组（对照组）也观察相关的指标如BMI及终身高。结果曲普瑞林治疗后骨龄的增长低于年龄的增长,预测身高随着治疗疗程的增长有所提升。治疗后12、18、24、36个月PAH分别为（153．4＆#177;7．1）cm、（154．6＆#177;6．2）cm、（155．7＆#177;4．7）cm、（156．9＆#177;5．9）cm,与对照组比较差异均有统计学意义（t＝2．23、2．67、3．01、2．88,均P ＜0．01）;BMI 分别为（16．37＆#177;1．41） kg／m2、（16．99＆#177;1．21） kg／m2、（17.17＆#177;1．38）kg／m2、（17.02＆#177;1．42）kg／m2,与对照组比较差异均无统计学意义（t＝0．69、1．28、0．89、1．11,均P＞0．05）。治疗组和对照组终身高分别为（158．2＆#177;3．9） cm、（153．7＆#177;2．8） cm,两组差异有统计学意义（t＝3．04,P＜0．01）。达终身高时两组BMI分别为（19．1＆#177;1．9）kg／m2、（18．7＆#177;1．8）kg／m2,两组差异无统计学意义（ t＝0．35,P＞0．05）。结论曲普瑞林能有效抑制ICPP的性征发育、骨龄增长、改善成年终身高,对BMI无明显影响。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.