Influence of dietary lipids on the erythrocyte antioxidant status of hypercholesterolaemic children

The aim of this work was to examine the effect of dietary lipid intakes on the biomarkers of red cell antioxidant status in hypercholesterolaemic children. The study population included 34 children (18 boys and 16 girls) with cholesterol levels ≥5.2 mmol/l and 16 normolipidaemic children (9 boys and 7 girls) between 6 and 12 years of age. The status of the erythrocyte antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and reduced glutathione (GSH) were estimated spectrophotometrically. Dietary intake was assessed by 24-h recall and seven-day records. The hypercholesterolaemic children showed a decreased activity of antioxidant enzymes in relation to the control group. There was a negative correlation between energy intake and the activity of antioxidant enzymes (SOD and CAT) and GSH levels. Cholesterol intake was inversely correlated with CAT and GPx activity and GSH levels. The intake of polyunsaturated fat was positively correlated with the GPx activity. A decrease in the fat content of the diet for 6 months was proposed and 15 children followed the diet strictly. The activities of antioxidant enzymes in these children were significantly higher after the low-fat diet; the greatest increment was noted in the activity of GPx (91% with respect to the initial values), SOD was increased by 44% and CAT by 70%. We conclude that the intake of dietary lipids can modulate the antioxidant defence system, and an excess of energy and cholesterol has a negative influence on the antioxidant enzymes.     

Insulin secretion in children with growth retardation

The effect of tolbutamide administration on insulin secretion was studied in 69 children with growth retardation. Diminished insulin secretion was found in all the patients, compared to the control group. This insulin deficit was most evident in patients with isolated, total GH deficiency and least evident in children with idiopathic short stature. Intermediate values were found in dwarfism due to isolated, partial GH deficiency.These results favour the hypothesis that hypoinsulinism contributes to the somatotropin deficiency in causing growth retardation.Abbreviations PD pituitary dwarfism - FSS familial short stature - GR growth retardation - GH growth hormone - ISS idiopathic short stature - tbt tolbutamide - GHtd isolated, total GH deficiency - GHpd isolated, partial GH deficiency     

营养不良性生长迟缓生长追赶的相关因素分析

目的　了解营养不良性生长迟缓儿生长追赶的影响因素。方法　观察２８ 例营养不良性生长迟缓儿,在调整营养供应后至少４ 个月的身高体重增长与基础体格指标、骨龄和遗传因素的关系。结果　身高Ｚ评分增长与身高别体重Ｚ评分增长正相关（ Ｐ＜ ０－０１） ,与基础身高别体重Ｚ评分负相关（ Ｐ＜ ０－０１） ,与基础骨龄正相关（ Ｐ＜ ０－０５）;与年龄及遗传身高Ｚ评分不相关。体重Ｚ评分增长与基础身高别体重Ｚ评分负相关（ Ｐ＜ ０－０１） ,与骨龄正相关（ Ｐ＜０－０１）。身高增长速度可超过其年龄应有生长能力。部分患儿恢复期仍有高生长激素血症（ 营养不良所致促生长素轴代谢代偿重整状态的持续）。结论　对营养不良性生长迟缓应尽早供给足够热量和蛋白,以充分利用促生长素轴的代谢代偿转为促生长效应,获得最大追赶。     

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.     

Rheumatoid arthritis and growth retardation in children: Treatment with human growth hormone

Twenty patients with rheumatoid arthritis or Still's disease associated with growth failure were treated with human growth hormone, 7.5 to 17 U/m² body surface per week.Five patients did not respond with better growth. In the remainder the mean growth rate increased from 1.9 cm/year (range: 0 to 3.3) to 6.2 cm/year (range: 3.6 to 12) over 5 to 7 months. Twelve patients treated for longer periods increased their mean growth rate from 2.3 cm/year (range: 0.7 to 5.7) to 6.3 cm/year (range: 2.4 to 9.7) and continued to grow during a second year of treatment. Growth velocity decreased in 6 patients when the hGH therapy was discontinued.The causes for this improvement in growth are possibly multifactorial: the growth rate is depressed by the severity of the disease and high-dose glucocorticoid therapy. Increases of growth rate occured during improvements in the disease, reduction of steroid medication, as a result of therapy with human growth hormone, and because of puberty in some patients.Human growth hormone seemed to improve the underlying condition of four of the patients but had no influence on the disease in the remaining children.On the occasion of the 75th birthday of Prof. Dr. Dr. h. c. Adolf Butenandt     

Effect of two consecutive administrations of GHRH in children with constitutional growth delay

It has been suggested that children with constitutional growth delay might have a transient immaturity of the neurotransmitter pathways necessary for the control of growth hormone releasing hormone (GHRH) secretion. In this study we evaluated the effects of two consecutive GHRH boluses (1 g/kg, i.v.) in nine prepubertal boys with constitutional growth delay. Growth hormone (GH) responses to GHRH administration were similar to that observed in normal children (first GHRH bolus, GH net incremental area under the curve (nAUC) ±SE: 788±244 vs 984±242 ng/ml per hour; second bolus, GHnAUC: 657±122 vs 541±129 ng/ml per hour, respectively). These data suggest that no relevant abnormalities in the mechanisms determining the somatotroph sensitivity to GHRH are present in children with constitutional growth delay.     

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目的探讨生长激素-胰岛素样生长因子(GH-IGF)轴在先天性心脏病患儿中的变化。方法2004年1~10月在广西医科大学一附院经超声心动图或手术确诊的先天性心脏病患儿50例,应用ELISA方法检测50例患儿及20名健康小儿血中生长激素结合蛋白(GHBP),应用免疫放射分析检测血中胰岛素样生长因子-1(IGF-1)及胰岛素样生长因子结合蛋白-3(IGFBP-3)。结果先天性心脏病患儿血清IGF-1、IGFBP-3质量浓度下降,有紫绀及心衰者下降更为显著;GHBP浓度在有紫绀及心功能不全的患儿中下降。结论先天性心脏病患儿GH-IGF轴发生紊乱,存在生长激素抵抗或不敏感。GHR下调可能是生长激素抵抗或不敏感的分子机制之一。     

Early recognition of growth abnormalities permitting early intervention

Normal growth is a sign of good health. Monitoring for growth disturbances is fundamental to children's health care. Early detection and diagnosis of the causes of short stature allows management of underlying medical conditions, optimizing attainment of good health and normal adult height.

Conclusion

This review summarizes currently available information on monitoring for short stature in children and conditions usually associated with short stature and summarizes the authors’ conclusions on the early recognition of growth disorders.     

Effect on growth of children with cardiac dysrhythmias treated with amiodarone

Summary We report the results of treatment with amiodarone in nine children with dysrhythmias resistant to conventional drugs, namely, one with ventricular tachycardia, two with atrial tachycardia, one with junctional tachycardia, three with reciprocal rhythm tachycardia, and two with Wolff-Parkinson-White syndrome. The initial dose was 800 mg/1.73 m², administered for two weeks, followed by half the dose for five days a week. The duration of the treatment varied from nine months to 19 months (mean duration, 13 months). Patients were followed up for a period ranging between nine and 33 months (mean period, 17 months). A complete remission was obtained in 56% of patients and partial success in 46%. The following side effects were detected: photosensitization in two; effect on weight, height, growth velocity, and thyroid hormones in three, six, five, and six, respectively; and acceleration in bone age in three. These effects were observed from two to nine months after the beginning of treatment. They persisted for 5–18 months after treatment had been suspended. The main side effect of amiodarone in children is presumably initial hypothyroidism, followed by a biological hyperthyroid reaction. For these reasons we suggest that amiodarone should be restricted as an alternative drug for resistant critical dysrhythmias and be used only for a limited period of two years.     

Influence of recombinant interferon alpha on nutritional status and growth pattern in children with chronic viral hepatitis

Anorexia and weight loss are frequently reported as adverse effects during recombinant interferon α (rIFN-α) treatment. The aim of the present study was to assess both nutritional status and growth of children and adolescents treated with rIFN-α for chronic viral hepatitis. Eleven patients aged 4–16 years with histologically proven chronic active hepatitis (hepatitis B, n = 9; hepatitis C, n = 2) receiving rIFN-α subcutaneously thrice a week for 6 months were studied. Weight and height increments were assessed during the 6 months before starting rIFN-α. Weight and height were measured every 3 months (M0, M3, M6) during the 6 months of rIFN-α treatment, then every 6 months during the follow up period (6–36 months). Weight decreased in every child during rIFN-α treatment (weight loss varies from 0.5 to 2.6 kg after 3 months of treatment). Weight/age Z-score decreased from 0.12 at M0 to –0.69 at M3 (P < 0.01), then increased between M3 and M6 (–0.33) (P < 0.01), but normalized (0.02) only 6 months after completion of treatment. Nutritional status was significantly impaired during treatment (Z-score for weight/height decreased from 0.18 at M0 to –0.74 at M3, P < 0.01) and recovered progressively thereafter. Height and height velocity were not modified by rIFN-α treatment. A reduction of the caloric intake observed between M0 and M3 might explain these features. Conclusion Significant but transient abnormalities of the nutritional status are encountered constantly at the beginning of rIFN-α therapy without any deleterious effect on growth. Information of the families and nutritional intervention during treatment should be required, in order to limit the importance of weight loss. Received: 12 March 1996 Accepted: 28 May 1996     

Craniofacial and acral growth responses in growth hormone-deficient children treated with growth hormone

OBJECTIVES: To investigate the effects of growth hormone (GH) therapy on craniofacial growth and body proportions in growth hormone deficient children. STUDY DESIGN: By using a cross-sectional study design, we investigated GH effects on craniofacial growth with photographic facial morphometrics, head circumference, and hand and foot size in 52 children with GH deficiency (GHD) treated with GH (0.27 mg/kg/wk) for 0.19 to 15.5 years, compared with untreated children with GHD and normal first-degree relatives. To detect disproportion and to correct for stature, age and height age (HA) SD scores were analyzed. RESULTS: Untreated subjects with GHD had retarded facial height and width (P values=.001) compared with normal controls; small head circumference for age and HA (P=.001); small hands for age (P<.001) that were large for HA (P=.003); and small feet for age (P<.001) that were normal for HA. When compared with normal controls, GH-treated subjects had proportional facial heights but narrower facial widths. Head circumference, however, increased disproportionately to height (P=.001), becoming large for stature, and increasing with duration of therapy and cumulative GH dose (P<.001). Hands and feet grew proportionately to height. CONCLUSION: Growth hormone treatment with conventional doses partially corrects craniofacial deficits and does not adversely affect hand and foot growth but appears to result in excessive head circumference growth.     

Left ventricular volume and mass in children on growth hormone therapy compared with untreated children

The myotropic effects of growth hormone (GH) have long been known. An excess of GH as in acromegaly, causes various problems within the circulatory system including cardiac hypertrophy. Although the latter has not been reported as a complication of GH therapy in children, we assessed this possibility in 54 children. Ninety-six echocardiographic studies were performed, in which bisectional images were analysed by Simpson's rule to determine left ventricular volume and mass. Of special interest were 47 results obtained from girls with Ullrich-Turner-syndrome (UTS) treated with supraphysiological doses of GH. Our results showed a significant increase of the myocardial mass in children on GH therapy compared with untreated children, as well as a dose related effect of GH on cardiac mass in girls and cardiac volume in boys. No cardiac hypertrophy, however, could be observed; the increase in muscular mass merely amounting to a normalization of previously low values.     

Correlation between pituitary growth hormone reserve and degree of growth failure in children with short stature

The correlation between a releasable pituitary growth hormone (GH) pool and degree of growth failure was examined in 30 children with GH deficiency (group I) and 19 children with normal short stature (group II). Based on the responsiveness of GH to GH-releasing hormone (GHRH), group I, with low GH responses (below 7 ng/ml) to both insulin and arginine, was classified into three subgroups; I_a (peak value less than 10 ng/ml, n=19), I_b (10–20 ng/ml, n=5) and I_c (above 20 ng/ml, n=6). Group II, with a GH response above 10 ng/ml to either insulin or arginine, was also divided into II_a (below 20 ng/ml, n=5) and II_b (above 20 ng/ml, n=14). Body length and growth velocity in I_a and I_b were significantly reduced vs I_c; bone age in I_a was retarded vs I_c; plasma somatomedin C (Sm-C) levels in I_a and I_b were decreased vs I_c, who had almost normal levels (0.90±0.55 U/ml). The incidence of other combined pituitary hormone deficiencies and previous perinatal distress was definitely high in I_a and I_b, but zero in I_c. In group II also, body length and growth velocity were significantly decreased in II_a vs II_b (P<0.01). These results indicate that [1] the pituitary reserve of GH estimated by GHRH is a good reflection of the degree of growth failure in GH-deficient children as well as in those of normal short stature, [2] hypothalamic GHRH deficiency tends to have a milder effect on growth retardation than pituitary GH deficiency, and [3] normal short children with a diminished GH reserve may be potential candidates for the GH treatment.Abbreviations ACTH adrenocorticotropin - LH luteinizing hormone - LH-RH luteinizing hormone-releasing hormone - GH growth hormone - GHRH growth hormone-releasing hormone - Sm-C somatomedin C - TRH thyrotropin-releasing hormone - TSH thyrotropin     

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)     

The effect of human growth hormone therapy on skinfold thickness in growth hormone-deficient children

Skinfold thickness (ST) was measured in 43 children with various forms of growth hormone (GH) deficiency during the first year of GH therapy. The average (and SEM) initial ST, expressed as standard deviation score (SDS) was 1.17 (0.25) for subscapular, 0.63 (0.18) for triceps, and 0.40 (0.21) for biceps ST. During therapy the average decrease is 1 SD. Children in the pubertal age group and those with partial GH deficiency showed smaller decreases. A larger decrease of triceps ST was associated with lower GH and insulin peaks, and lower age, bone age and initial weight-for-height. Some correlations between ST decrease and growth response in the first year were significant, but still too low to allow of reliable predictions. The same was true for other clinical parameters. These data indicate that a chronic lack of GH leads to unequal fat distribution, possibly due to different sensitivities to GH in the trunk and extremities. The variability of ST responses to GH therapy limits clinical applications.Abbreviations GH growth hormone - hGH human growth hormone - SDS standard deviation score - SDS_BA standard deviation score for bone age - SDS_CA standard deviation score for chronological age - SEM standard error of the mean - ST skin fold thickness - ST-SDS skinfold thickness, expressed as a standard deviation score - ST-log skinfold thickness, expressed as 100.log₁₀ (reading in 0.1 mm-18) - TSH thyroid stimulating hormone     

Impact of availability of oral hydrocortisone on growth of children with CAH

Objectives: 1. To compare growth parameters of patients with Congenital Adrenal Hyperplasia (CAH) managed on Prednisolone (PR) before and on Hydrocortisone (HC) after its availability in India. 2. To compare growth parameters of patients with CAH who have been on treatment with HC since diagnosis with patients managed on PR.Methods: Growth parameters of twelve children (8 m, 4f) with congenital adrenal hyperplasia were retrospectively studied while on treatment with prednisolone (PR) earlier and then hydrocortisone (HC) after it became freely available in India.Results: Patients treated with PR had height Z score of -0.42, weight Z score of -0.45, and height velocity Z score of -2.06. On HC these scores were -0.27, +0.16 and + 2.27. Patients treated with HC from the begining had a height Z Score of + 0.08, weight Z score of +0.22, and height velocity Z score of +0.68.Conclusion : Hydrocortisone has a less growth effect than prednisolone and patients treated with HC from the beginning showed near normal growth     

rhGH替代治疗对生长激素缺乏儿童糖代谢的影响

目的探讨重组人生长激素(rhGH)替代治疗对生长激素缺乏症(GHD)儿童糖和胰岛素代谢的影响以及 GH 与糖代谢平衡之间的关系。方法对44例(男28例,女16例)4.5～16.5(10.4±2.6)岁 GHD 患儿在接受 rhGH 治疗前及治疗后每3个月检测体重指数、胰岛素样生长因子-1(IGF-1)、行口服葡萄糖耐量试验,计算稳态模型胰岛素抵抗指数。结果 (1)空腹血糖和 IGF-1在治疗3个月时即显著提高,一直持续较高水平,每个随访时间点与治疗前比较,差异均有统计学意义(F=6.81,7.31,P 均<0.01);稳态模型胰岛素抵抗指数和空腹胰岛素分别在治疗3和9个月时提高(P<0.01和 P<0.05),1年后下降,治疗1年半时与治疗前比较,差异已无统计学意义(均 P>0.05)。(2)相关分析发现,稳态模型胰岛素抵抗指数与体重指数、IGF-1和治疗持续时间显著相关(r=0.251,0.437,0.281,P 均<0.001)。二次方程曲线回归分析发现,稳态模型胰岛素抵抗指数与治疗持续时间呈近似抛物线量变关系。(3)发现2例暂时性高血糖,分别在停用 rhGH 治疗后1个月和5d 血糖恢复正常,再注射 rh GH 后,行口服葡萄糖耐量试验正常。结论 GHD 儿童接受 rhGH 治疗(尤第1年内)可增加胰岛素抵抗,极少数引起短暂糖代谢紊乱。循环 IGF-1可能参与控制胰岛素的敏感性,在 GH 与胰岛素平衡间起重要作用。有必要对所有接受 rhGH 治疗者定期监测糖代谢指标和 IGF-1水平。     

Final height in Swedish children with idiopathic growth hormone deficiency enrolled in KIGS treated optimally with growth hormone

Aim: To assess final height in children with growth hormone deficiency (GHD) treated with human recombinant growth hormone (GH). Methods: Final height data for 401 Swedish children with idiopathic GHD and treated with GH, included in KIGS (Pfizer International Growth Database) between 1987 and spring 2006, were analysed retrospectively. Data were grouped according to sex, age and severity of GHD. Height at entry into KIGS, at the onset of puberty and near final height were analysed between groups. Results: Groups were heterogeneous for GHD, which ranged from partial to severe. For all groups, mean final height corrected for mid‐parental height was within the normal Swedish height range. In patients with severe GHD, mean final height was almost identical to mean normal Swedish height. About 16% of patients showed disproportionality (short legs) at final height and were significantly shorter than other patients. The parents of these children also demonstrated short stature. Conclusion: Children with idiopathic GHD receiving GH replacement therapy can achieve a final height that as a group is within the normal range and all achieve a height within their genetic potential.     

Treatment with probucol of children with familial hypercholesterolaemia

Nine children with familial hypercholesterolaemia, age range 2 to 12 years, were treated with a low cholesterol diet and probucol (10 mg/kg/day). The year before, the children received, as only treatment, a low fat-cholesterol diet. During this period their mean plasma total cholesterol level fell from 8.2 +/- 1.45 mmol/l to 7.17 +/- 0.84 mmol/l (12.6%). This level was further reduced to 5.92 +/- 0.63 mmol/l (17.1%) after the addition of probucol. Plasma high density lipoprotein cholesterol levels were lowered in absolute terms but not in relation to total cholesterol. No apparent side effects were observed. However, the use of probucol should be restricted for the moment to severe cases of hypercholesterolaemia as the long-term excretion of the drug in children is not yet known.     

Sudden death in growth hormone-treated children with Prader-Willi syndrome

A 4-year-old boy with Prader-Willi syndrome died suddenly while asleep on day 67 of growth hormone treatment. During treatment, snoring had worsened. Autopsy showed multifocal bronchopneumonia. This case and two others recently published suggest that growth hormone may be associated with obstructive apnea, respiratory infection, and sudden death in this condition.