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作者：易文刘建华张星星何小解吴小川党西强何庆南中南大学湘雅二医院

1997年1月1日～2000年12月31日，由湖南省自然科学基金资助进行研究。小儿肾病综合征(NS)是儿科泌尿系统的一种常见、多发病，生长障碍是小儿NS的并发症之一，多见于持续进展、久治不愈的病例。随着小儿NS临床疗效的提高，在NS治疗中... 详细信息

标准号: 0401170073

1997年1月1日～2000年12月31日，由湖南省自然科学基金资助进行研究。小儿肾病综合征(NS)是儿科泌尿系统的一种常见、多发病，生长障碍是小儿NS的并发症之一，多见于持续进展、久治不愈的病例。随着小儿NS临床疗效的提高，在NS治疗中既需有效地控制临床症状，又要提高患儿的生存质量，使患儿正常生长发育，为此探讨了小儿NS引起生长障碍的发生机制。一、方法 (一)按全国儿科肾脏病协作组制定的小儿肾病综合征的诊断标准收集未用糖皮质激素治疗的初发病例。 (二)24只雄性SD大鼠随机分为正常组、食物对照组、阿霉素(5mg/kg)肾病组和地塞米松18mg/kg /d治疗肾病组。二、结果 (一)NS患儿在其生长尚未出现明显障碍时，其体内调节体格生长的生化环境，即已经存在血清生长激素浓度-血清胰岛素样生长因子-血清胰岛素样生长因子结合蛋白(GH-IGF-IGFBP)轴的功能紊乱，当疾病持续进展时即可发生明显生长障碍，影响患儿的生存质量。提出防治NS患儿生长障碍，应在NS发病的早期就采取有效对策。 (二)患儿和动物实验证实，肾病患儿和肾病鼠血清GH 浓度并无明显下降，其生长障碍发生的主要机制是机体存在GH抵抗现象。由此对防治小儿肾病的生长障碍提出了新的思路，即应采用非生长激素药物或使用介导GH效应的药物。 (三)除证实肾病时的营养不良和糖皮质激素治疗是其发生生长障碍的原因外，还系统证实了肾病本身时存在的GH抵抗和IGF-IGFBP功能紊乱是其发生生长障碍的重要机制。1.证实了肾病本身所致的生长障碍与肝脏生长激素受体(GHR)表达下降引发的GH抵抗有关，糖皮质激素治疗可使GHR表达量进一步下降而加重对GH 的抵抗，进一步加重生长障碍。2.证实肾病本身所致血清IGFBP-2浓度增高是其发生生长障碍的重要因素之一，而肾病时继发性营养不良和糖皮质激素治疗所致生长障碍是血清IGF-1和IGFBP-3浓度下降所致。3.证实了肾病时血清IGFBP-3浓度下降的重要原因是其肾小管分泌的IGFBP-3蛋白酶降解活性增强。 (四)证实甲状腺激素水平降低是NS时血清IGF-1水平和活性下降及IGFBPs自分泌/旁分泌紊乱进而引发生长障碍的机制之一。三、推广应用研究成果多次在全国及国际的学术会议上进行了交流，有的论文被编入日本、美国的专著。

关键词：肾变病综合征/并发症生长障碍/病因学

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Growth and endocrine disorders in multisystem Langerhans' cell histiocytosis

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CLINICAL ENDOCRINOLOGY 2000年第4期53卷 509-515页

作者： Nanduri, VR Bareille, P Pritchard, J Stanhope, R Great Ormond St Hosp Sick Children Dept Endocrinol London WC1N 3JH England Great Ormond St Hosp Sick Children Dept Haematol Oncol London WC1N 3JH England Inst Child Hlth Dept Surg London England

INTRODUCTION Langerhans' cell histiocytosis is a rare disorder, with diabetes insipidus occurring in up to half of patients. Causes of growth failure include the illness itself, treatments used and growth hormone insufficiency. PATIENTS AND METHODS We identified all patients with an endocrinopathy secondary to Langerhans' cell histiocytosis (LCH). Growth data were analysed from all patients with multisystem involvement. RESULTS Of 144 patients with multisystem LCH, 50 had an endocrinopathy, 49 of whom had diabetes insipidus. Growth hormone insufficiency (GHI) was present in 21 patients, seven of whom had other anterior pituitary deficiencies as well (gonadotrophin deficiency + GHI n = 2, gonadotrophin deficiency + TSH deficiency + GHI n = 2, panhypopituitarism n = 3). GH insufficiency, the development of which appeared to be independent of pituitary radiation, occurred at a median age of 8.3 years (4.7-18 years) and at a median interval of 3.5 years (0-11.8 years) after diagnosis of LCH. The median height SDS at diagnosis of growth hormone insufficiency was -2.9. Thirteen of the patients with growth hormone insufficiency attained final height with a median height SDS of -1.2. The final height SDS of 15 patients without GH insufficiency was closer to target height SDS, but not statistically different from that of the GH insufficient group. CONCLUSIONS GH therapy significantly improves growth in GH insufficient patients with Langerhans' cell histiocytosis. Early institution of GH therapy may further improve height outcome. However, most children with Langerhans' cell histiocytosis regardless of endocrine function, failed to reach target height.

关键词：尿崩症/诊断尿崩症/病因学促性腺素类垂体/缺乏生长障碍/诊断生长障碍/药物疗法生长障碍/病因学生长激素/缺乏生长激素/治疗应用组织细胞增多症郎格尔汉斯细胞/并发症组织细胞增多症郎格尔汉斯细胞/诊断组织细胞增多症郎格尔汉斯细胞/药物疗法磁共振成像垂体功能试验垂体/病理学垂体照射统计学非参数促甲状腺素/缺乏青少年儿童儿童学龄前女(雌)性人类

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SOME ASPECTS OF CHILDHOOD MALNUTRITION - CLASSIFICATION, LONG-TERM EFFECTS, EXPERIMENTAL ANALOGIES

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AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE 1975年第2期5卷 87-96页

作者： WATERLOW, JC LONDON SCH HYGIENE & TROP MED DEPT HUMAN NUTRLONDON WC1E 7HTENGLAND

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PRODUCTION OF WEANLING RAT DORSOMEDIAL HYPOTHALAMIC SYNDROME BY CATHODAL ELECTROLYTIC LESION CURRENT

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JOURNAL OF NEUROSCIENCE RESEARCH 1976年第4期2卷 291-298页

作者： BERNARDIS, LL GOLDMAN, JK SUNY BUFFALO DEPT SURGBUFFALONY 14214 SUNY BUFFALO DEPT PATHOLBUFFALONY 14214 SUNY BUFFALO DEPT MEDBUFFALONY 14214 VET ADM HOSP BUFFALONY 14215

Weanling male Sprague-Dawley rats received bilateral electrolytic lesions in the dorsomedial hypothalamic area by means of a direct cathodal current. Sham-operated rats served as controls. Ponderal and linear growth, obesity index, food intake, and several indices of intermediary metabolism of adipose tissue and muscle were measured. Cathodal lesions, as did anodal lesions reported on previously resulted in retardation of body weight, length, and food intake, while the obesity index remained in the normal range. Similarly, the metabolic data in adipose tissue and muscle are comparable to those from experiments in which dorsomedial lesions were placed by anodal current: incorporation of glucose into CO2 lipid, and glycogen of muscle tissue (diaphragm) were similar in DMN-lesioned rats and controls. The difference between anodal and cathodal lesions in this hypothalamic syndrome is a delay in the onset of hypophagia until about 30 days after the hypothalamic operation. The data support the concept that lesions in the hypothalamus, in general, exert their effect by destruction of neuronal assemblies, i.e., nerve cells and/or fiber tracts passing through the lesioned area.

关键词：脂肪组织/药物作用脂肪组织/代谢动物新生体重二氧化碳/代谢膈摄食行为葡萄糖/代谢糖原/代谢生长障碍/病因学下丘脑/生理学下丘脑中/生理学胰岛素/药理学脂类代谢肌/药物作用肌/代谢蛋白质类/代谢综合征动物男(雄)性大鼠

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FETAL GROWTH RETARDATION IN RELATION TO MATERNAL SMOKING AND WEIGHT-GAIN IN PREGNANCY

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AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY 1976年第1期125卷 55-60页

作者： MILLER, HC HASSANEIN, K HENSLEIGH, PA UNIV KANSAS COLL HLTH SCI MED CTR DEPT PEDIAT KANSAS CITY KS 66103 USA UNIV KANSAS COLL HLTH SCI MED CTR DEPT BIOMETRY KANSAS CITY KS 66103 USA UNIV KANSAS COLL HLTH SCI MED CTR DEPT OBSTET & GYNECOL KANSAS CITY KS 66103 USA UNIV KANSAS HOSP KANSAS CITY KS USA

Two types of fetal growth retardation were recognized in term infants. One type was characterized by an abnormally low ponderal index (defined as birth weight in grams .times. 100 .div. crown-heel length in cubic centimeters). The other type of growth-retarded infants had abnormally short crown-heel lengths for fetal age. Both types were observed under all conditions studied. Mothers who smoked cigarettes during pregnancy were more likely to have infants with short body lengths for dates, whereas mothers who had low weight gain in pregnancy were more likely to have infants with low ponderal indices. Social group, prepregnancy weight, parity, marital status, and fetal sex were less determinant of fetal growth than were maternal weight gain and smoking habits.

关键词：出生体重身高体重胎儿疾病/病因学胎儿/生理学生长生长障碍/病因学吸烟/并发症社会阶级女(雌)性人类婴儿新生妊娠

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Impact of anatomic closure on somatic growth among small, asymptomatic children with secundum atrial septal defect

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第12期85卷 1472-1475页

作者： Rhee, EK Evangelista, JK Nigrin, DJ Erickson, LC Childrens Hosp Dept Cariol Boston MA 02115 USA Harvard Univ Sch Med Dept Pediat Boston MA USA Childrens Hosp Div Endocrinol Boston MA 02115 USA Harvard Univ Sch Med Dept Pediat Boston MA USA

We retrospectively identified 92 children aged less than or equal to 9 years with isolated secundum atrial septal defect (ASD) with preoperative height or weight z score less than or equal to 1.0 (16th percentile), respectively Children with additional cardiac malformations, chromosomal abnormalities, recognized syndromes, pulmonary hypertension, heart failure, prematurity (<34 weeks' gestation), or use of cardiac medications were excluded from further analysis. After exclusion, 24 low-weight and 25 low-height children were compared with 48 and 50 age-, gender-, and size-matched normal controls, respectively. Univariate and multivariate analyses were performed separately for height and weight groups for achieving an end point of improvement in height or weight z score by +0.5 after repair. There were no significant preoperative demographic differences. After repair, 50% of low-weight patients improved +0.5 SD in weight within 2.6 years versus 5.6 years for controls (p = 0.02). Similarly, 50% of low-height patients improved +0.5 SD in height within 1.7 years versus 11.6 years for controls (p < 0.001). Multivariate analysis also indicated a benefit of repair with relative risks of 2.35 (95% confidence interval 1.20 to 4.62;p = 0.01) and 5.11 (95% confidence interval 2.45 to 10.65;p < 0.0001), respectively, for improving height or weight by +0.5 SD in patients with ASD relative to controls. Furthermore, children heavier at repair were less likely to improve in weight (relative risk 0.56 [0.34, 0.92] per 1.0 z [p = 0.02]). Likewise, children older at repair were less likely to improve in height (relative risk 0.77 [0.64, 0.92] per year of age [p = 0.003]). We conclude that undersized children with ASD exhibit improved growth after repair. Poor growth should be considered a relative indication for early ASD repair. (C) 2000 by Excerpta Medica, Inc.

关键词：身高体重生长生长障碍/病因学房间隔缺损/并发症房间隔缺损/病理生理学房间隔缺损/外科学多元分析回归分析回顾性研究儿童学龄前女(雌)性人类男(雄)性

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Role of intrauterine growth retardation on physical growth of Pakistani squatter children from birth to 2 years of age

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JOURNAL OF TROPICAL PEDIATRICS 1999年第6期45卷 338-344页

作者： Fikree, FF Rahbar, MH Berendes, HW Aga Khan Univ Dept Community Hlth Sci Karachi 74800 Pakistan NICHHD Div Epidemiol Stat & Prevent Res NIH Bethesda MD USA

A birth cohort of 727 squatter children from Karachi was followed to study growth patterns by measuring anthropometric parameters at specific ages during the first 2 years of life, The mean weight and length of the intrauterine growth retarded and appropriate for gestational age children fell below the 10th percentile of the NCHS standards after 9 months and further deteriorated in the subsequent study period. However, the intrauterine growth retarded children showed slightly higher growth velocities compared to appropriate for gestational age children in the first few months for all four measurements, but subsequently these differences in growth velocities diminished. Our results suggest that nutrition intervention strategies should begin in early pregnancy.

关键词：人体测量术出生体重儿童发育队列研究胎儿生长迟缓孕龄生长障碍/病因学营养需要巴基斯坦贫困妊娠并发症/预防和控制儿童学龄前女(雌)性人类婴儿婴儿新生男(雄)性妊娠

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Effect of prenatal gamma irradiation during the late fetal period on the postnatal development of the mouse

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TERATOLOGY 1999年第3期59卷 133-138页

作者： Hossain, M Devi, PU Bisht, KS Kasturba Med Coll Dept Radiobiol Manipal 576119 Karnataka India

Pregnant Swiss albino mice were exposed to 0.3, 0.5, 1.0, or 1.5 Gy of gamma radiation on day 17 of gestation. Sham-exposed controls were examined for comparison;Exposed mice as well as controls were left to complete gestation and parturition. Pups were observed up to age 6 weeks;appearance of physiological markers (pinna detachment, eye opening, fur development, vaginal opening, and testes descent), postnatal mortality, body weight, body length, head length, head width, and tail length were recorded. A significant delay in fur development was observed at 0.3 Gy and in other physiological markers at doses above 0.3 Gy, while a significant increase in mortality and growth retardation occurred only at 1.0 and 1.5 Gy. Although congenital anomalies such as syndactyly and bent tail were observed at doses of 0.5-1.5 Gy, only syndactyly showed a statistically significant increase in frequency. A statistically significant lower body weight was observed during the first week of postnatal life, but body weights increased to normal levels by the second week in animals exposed to doses less than 1.0 Gy. At higher doses, low body weight persisted throughout the postnatal period. Head length and tail length showed a significant decrease from controls at 0.5-1.5 Gy, and the effect was evident from birth to age 6 weeks. But a similar effect on body length and head width was noticed only at 1.0 and 1.5 Gy. These studies indicate that even in the absence of any major morphological changes, normal development of physiological landmarks and postnatal growth can be impaired by fetal irradiation at 17 days p.c. (post coitus). Morphological changes appear to have a threshold between 0.3-0.5 Gy, while physiological marker effects may occur with a lower threshold. (C) 1999 Wiley-Liss, Inc.

关键词：畸形辐射性/病因学剂量效应关系辐射胚胎和胎儿发育/辐射效应 γ射线孕龄生长障碍/病因学小鼠/生长和发育产前暴露迟发效应动物女(雌)性妊娠

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Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2000年第12期97卷 6868-6873页

作者： Ueki, I Ooi, GT Tremblay, ML Hurst, KR Bach, LA Boisclair, YR Cornell Univ Dept Anim Sci Ithaca NY 14853 USA Prince Henrys Inst Med Res Clayton Vic 3168 Australia Univ Melbourne Austin & Repatriat Med Ctr Dept Med Heidelberg Vic 3084 Australia McGill Univ Dept Biochem Montreal PQ H3G 1Y6 Canada

Insulin-like growth factors (IGFs) I and II are important regulators of cell proliferation and differentiation. After birth, plasma IGFs, representing mostly liver-derived IGFs, circulate in ternary complexes of 150 kDa consisting of one molecule each of ICF, IGF-binding protein (IGFBP) 3, and an acid labile subunit (ALS). Onset of ALS synthesis after birth is the primary factor driving the formation of ternary complexes. Capture of IGFs by ALS is thought to allow the development of a plasma reservoir without negative effects such as hypoglycemia and cell proliferation. To evaluate the importance of ALS and ternary complexes, we have created mice in which the ALS gene has been inactivated. The mutation was inherited in a Mendelian manner, without any effects on survival rates and birth weights. A growth deficit was observed in null mice after 3 weeks of life and reached 13% by 10 weeks. This modest phenotype was observed despite reductions of 62 and 88% in the concentrations of plasma IGF-I and IGFBP-3, respectively. Increased turnover accounted for these reductions because indices of synthesis in liver and kidney were not decreased. Surprisingly, absence of ALS did not affect glucose and insulin homeostasis. Therefore, ALS is required for postnatal accumulation of IGF-l and IGFBP-3 but, consistent with findings supporting a predominant role for locally produced ICF-I. is not critical for growth. This model should be useful to determine whether presence of ALS is needed for other actions of liver-derived ICF-I and for maintenance of homeostasis in presence of high circulating levels of IGF-II.

关键词：碳水化合物代谢生长障碍/病因学胰岛素样生长因子结合蛋白质3/生物合成胰岛素样生长因子结合蛋白质3/血液胰岛素样生长因子Ⅰ/分析胰岛素样生长因子Ⅰ/生物合成肝/代谢小鼠近交BALBC RNA 信使/分析生长调节素类/遗传学生长调节素类/生理学动物女(雌)性小鼠

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Growth and pubertal development in transfusion-dependent children and adolescents with thalassaemia major and sickle cell disease: A comparative study

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JOURNAL OF TROPICAL PEDIATRICS 1999年第1期45卷 23-30页

作者： Soliman, AT ElZalabany, M Amer, M Ansari, BM Univ Alexandria Childrens Hosp Dept Paediat Alexandria Egypt Univ Glamorgan Sch Appl Sci Pontypridd CF37 1DL M Glam Wales E Glamorgan Gen Hosp Dept Paediat Pontypridd M Glam Wales

Despite regular blood transfusion and desferrioxamine treatment, growth impairment and pubertal delay are commonly seen in children and adolescents with transfusion-dependent thalassaemia and sickle cell disease (SCD). We evaluated growth parameters and sexual maturation in a large cohort of children and adolescents with SCD (n = 110) and thalassaemia (n = 72) receiving nearly the same protocol of transfusion and chelation, and compared them with those for 200 normal age-matched children, 30 children with constitutional delay of growth (CSS), and 25 children with growth hormone deficiency (GHD). Before transfusion, haemoglobin concentration had not been less than 9g/dl in the past 7 years;desferrioxamine was administered for 7-10 years, including by the intramuscular and subcutaneous routes, three times or more per week. The height standard deviation score (HtSDS), growth velocity (GV) (cm/yr), and growth velocity standard deviation score (GVDSD) of children and adolescents with thalassaemia and SCD were significantly decreased compared to normal children (p less-than 0.01). Forty-nine percent of thalassaemic patients and 27 percent of patients with SCD had HtSDS less than -2, and 83 percent of thalassaemic patients and 67 per cent of SCD patients had HtSDS less than -1. Fifty-six percent of thalassaemic children and 51 percent of children with SCD had GVSDS less than -1. The GV, of thalassaemic children was significantly slower than that for children with SCD. Children with thalassaemia and SCD had HtSDS and GVSDS comparable to those for children with CSS but higher than those for patients with GHD. Serum ferritin concentration was correlated significantly with the linear GV in all patients (r = 0.45, p less-than 0.001). The bone age delay did not differ among the three groups with thalassaemia, SCD and CSS, but the delay was significant in the group with GHD. The mid-arm circumference was significantly smaller in children with thalassaemia and SCD than in normal c

关键词：方差分析贫血镰状细胞性/并发症贫血镰状细胞性/流行病学横断面研究埃及/流行病学生长障碍/病因学线性模型纵向研究青春期延迟/病因学 β地中海贫血/并发症 β地中海贫血/流行病学青少年儿童儿童学龄前女(雌)性人类男(雄)性

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