Follow up study on children with dyslipidaemia detected by mass screening at 18 months of age: effect of 12 months dietary treatment

The present study was done to evaluate the effect of short-term dietary therapy on 148 dyslipidaemic children (24 familial hypercholesterolaemia, 105 non-familial hypercholesterolaemia and 19 hypertriglyceridaemia), detected by mass screening in children at 18 months of age. In the model diet used for treatment, 15% of the total calories were obtained from protein, 27% from fat and 57% from carbohydrate. Cholesterol intake was set at <200 mg/day and the ratio of polyunsaturated to saturated fatty acid (P/S ratio) was 1.2. When compared to the composition of the diet ingested by the dyslipidaemic children, only the P/S ratio changed from 0.7 to 1.2. During 12 months treatment, levels of total cholesterol, low density lipoproteins cholesterol and apoB decreased by 10%–15% in children with familial and non-familial hypercholesterolaemia. There was no significant change in the levels of high density lipoproteins. In 19 children with hypertriglyceridaemia, the intake of carbohydrate was limited to 55% of the total calories consumed and after 12 months of treatment, triglyceride levels reverted to normal. Throughout the study period, apprimately 70% of the children on this dietary therapy were seen in our clinics every 3–6 months and physical development was within normal ranges. These results, taken together, indicate that dietary therapy can be effective for correcting dyslipidaemia, even in young children.     

Management of familial hypercholesterolaemia in children and adolescents

Familial hypercholesterolaemia is a disorder of low-density lipoprotein (LDL) cholesterol metabolism, which is associated with the onset of vascular changes associated with coronary heart disease in childhood. This disorder has co-dominant transmission with a prevalence of one in 500 in the general population. Cascade screening is the most effective method of identifying children. Children in the at-risk group should have their cholesterol levels checked between the age of 2 and 10 years. Children with LDL cholesterol levels ≥ 3.4 mmol/L are likely to suffer from this disorder, although at this level there is a significant false positive rate. Molecular genetic testing is available for the LDL receptor gene, APOB gene and the PCSK9 gene. This is the most specific test for familial hypercholesterolaemia but has a false negative rate of 20-50%. Once diagnosed, treatment should be considered in children with an LDL cholesterol level ≥ 4.9 mmol/L. If the child has two other risk factors or a positive family history, this threshold should be lowered to ≥4.1 mmol/L. Guidelines recommend that treatment should be commenced by the age of 10 years, although some advise waiting until menarche in females. Statin therapy is currently recommended as first line treatment. Randomised placebo trials have shown that statin therapy reduces LDL cholesterol levels by 25% and is not associated with increased risk of adverse events. These are short-term studies, and longer follow-up will be required to definitively prove efficacy and safety.     

Quality of life, anxiety and concerns among statin-treated children with familial hypercholesterolaemia and their parents

AIM: To assess the quality of life, anxiety and concerns among statin-treated children with familial hypercholesterolaemia (FH) and their parents. METHODS: 69 FH children on statin therapy and 87 parents (51 families) participated in this study. Quality of life of the children, and anxiety levels of both the children and their parents, were investigated using self-report questionnaires. In addition, a questionnaire was designed to evaluate FH-specific concerns of these children and their parents on six different topics: 1, knowledge about FH; 2, experience of the disease; 3, family communication; 4, screening; 5, diet; and 6, experience of medication therapy. RESULTS: FH children and their parents reported no problems with regard to quality of life and anxiety. In contrast, the FH survey showed specific FH-related concerns. One-third of the children thought that FH can be cured, and 44% of the children suffered from the fact they have FH, but taking medication makes them feel safer (62%). The majority of the children kept a low cholesterol diet and more than 50% took care not to eat too much fat. Almost 38% of the parents experienced FH as a burden to their family and 79% suffered because their child had FH. CONCLUSION: These findings show that statin-treated children with FH and their parents did not report affected psychosocial functioning, but did show specific FH-related concerns.     

Efficacy and safety of fluvastatin in children and adolescents with heterozygous familial hypercholesterolaemia

AIM: To assess whether early initiation of statin therapy for heterozygous familial hypercholesterolaemia favourably affects lipid profiles or vascular morphological changes. METHODS: Children and adolescents aged 10-16 y with heterozygous familial hypercholesterolaemia were administered fluvastatin (80 mg/d) for 2 y in a single-arm two-centre study. Carotid B-mode intima-media thickness (IMT) and M-mode arterial wall stiffness (beta) were recorded. Eighty of the 85 enrolled subjects completed the trial. RESULTS: The median decrease in low-density lipoprotein (LDL) cholesterol from baseline at last study visit was 33.9%; median decreases in total cholesterol, triglycerides and apolipoprotein B were 27.1%, 5.3% and 24.2%, respectively; the median increase in high-density lipoprotein (HDL) cholesterol was 5.3%. Changes in carotid arterial wall thickness and stiffness versus baseline were fractional and statistically non-significant (delta IMT -0.005 mm, 95% CI -0.018 to +0.007 mm, n=83; and delta beta = 0.017, 95% CI -0.219 to +0.253, n=79). Adverse events, all non-serious, were reported by 58 subjects (68.2%); four were suspected to be drug-related. Change in hormone levels and sexual maturation were appropriate for this age group. CONCLUSION: Fluvastatin lowered LDL cholesterol, total cholesterol and apolipoprotein B levels effectively over a prolonged period in children and adolescents with heterozygous familial hypercholesterolaemia. Carotid IMT and wall stiffness remained largely unchanged.     

The effect of oral calcium carbonate administration on serum lipoproteins of children with familial hypercholesterolaemia (type II-A)

The effect of oral calcium carbonate on serum lipoprotein concentrations was tested in 50 children with familial hypercholesterolemia (type II-A) consuming a low cholesterol high polyunsaturated fat diet, using a cross-over design versus a placebo. Cholesterol was measured in serum and in the individual lipoprotein density classes. Serum apolipoprotein B (the protein moiety of low density lipoprotein) and apolipoprotein A-I (the main protein of high density lipoprotein) were measured by specific immunoassays. Calcium carbonate treatment induced only a slight increase in serum apolipoprotein A-I (+4%) and a slight decrease in low density lipoprotein cholesterol (-4%), both changes being significant at the P=0.05 level.     

Colestipol tablets in adolescents with familial hypercholesterolaemia

The objective of this study was to examine palatability and side effects of the new tablet formulation of colestipol. A clinical series of 23 boys and 4 girls aged 10-16 years with heterozygous familial hypercholesterolaemia were given 2-12 g colestipol daily for 6 months in an open study. There were no serious side effects. The median reduction in low density lipoprotein cholesterol level was 20%. All preferred the tablets to resin granules they had tried previously. We conclude that low-dose colestipol tablets appear to be safe and effective, and are preferred by adolescents.     

Sonography in the detection of achilles tendon xanthomata in children with familial hypercholesterolaemia

Patients with heterozygous familial hypercholesterolaemia (FH) are at high risk for the development of coronary artery disease. Achilles tendon xanthomata are often the first clinical manifestation of FH, but are seldom palpable earlier than during the third decade. Twenty-one FH children aged 3–18 years underwent high-frequency ultrasound examination of the achilles tendon. Hypoechoic infiltration of the normal tendon structure was demonstrated in 8 of 21 (38%) of the FH children. The findings were similar in boys and girls. Control subjects (n = 68) aged 1–25 years had no sonographically detectable tendon abnormalities. The thickness of the achilles tendon of the FH children was (mean ±SD) 7.1 ± 1.5 mm (range 5–10 mm). The respective values for the controls were 5.8 ± 1.0 mm (3–7 mm. We conclude that ultrasound examination sensitively detects cholesterol accumulation in the achilles tendon of FH children before tendon xanthomata are clinically evident.     

Low-density lipoprotein plasmaphaeresis with and without lovastatin in the treatment of the homozygous form of familial hypercholesterolaemia

A 7-year-old girl with homozygous familial hypercholesterolaemia and plasma low-density lipoprotein (LDL)-cholesterol levels of 820 mg/dl (21.2 mmol/l) and progressive xanthomata was treated with heparin extracorporeal low-density lipoprotein precipitation (HELP) to lower her plasma LDL. On weekly HELP treatment she maintained her pre-HELP treatment LDL-cholesterol levels at 409 mg/dl (10.6 mmol/l). The long-term HELP treatment was well tolerated and led to regression of her xanthomata. Subsequently, lovastatin [Mevacor; Merck Sharp & Dohme, Westpoint, Pa., USA (20 mg/day)] was added to the regimen, causing a further 20% decrease in her pre-HELP treatment plasma LDL-cholesterol levels. Lovastatin alone did not sufficiently lower her plasma LDL and could not replace the weekly HELP therapy. Our data show that lovastatin is an effective adjunctive therapy for lowering plasma LDL-cholesterol in a homozygous patient, once plasma LDL levels have already been lowered by regular HELP treatment.This work is dedicated to Professor Fritz Scheler, Department of Internal Medicine, University of Göttingen, on his 65th birthday     

小儿顺铂腹腔热灌注化疗的可行性研究

目的探讨小儿顺铂(DDP)腹腔热灌注化疗的可行性.方法①兔的模拟顺铂腹腔热灌注化疗实验,了解其药代动力学特点、实施方法和可能的副作用;②5例小儿腹部恶性肿瘤术中肿瘤切除后行腹腔热灌注化疗,观察临床症状和血象、肝肾功能改变.结果动物实验表明腹腔热灌注化疗后腹腔液DDP浓度明显高于血浆浓度、也高于静脉用药后的腹腔液浓度(均为P＜0.01),而肾组织DDP浓度较低(P＜0.05).灌注温度＞43℃可能导致腹腔脏器坏死.41～42℃、速度逐渐加快至100ml/min,灌注60min腹腔脏器无明显损害.临床应用5例均无明显并发症,血象和肝肾功能均在正常值范围内.结论DDP腹腔热灌注化疗可明显提高腹腔液药浓度和生物利用度,减少肾毒性.在适当温度下可安全用于小儿.     

Use of cholestyramine in treatment of children with familial hypercholesterolaemia

19 children with heterozygous familial hypercholesterolaemia have been treated with cholestyramine administered twice daily in a total dosage of 8 to 24 g/day (0·3 to 1·1 g/kg body weight per day). Serum cholesterol concentration was reduced by a mean of 36% (range 27 to 47%). The therapeutic effect was similar whether or not dietary fat was restricted, and the reduction in serum cholesterol has been maintained for periods of up to 20 months.Side effects of cholestyramine have been confined to the gastrointestinal tract. Absorption of fat was impaired in some patients, but has not been associated with diarrhoea. Serum folate levels have decreased in all patients, and 6 out of 12 tested have had subnormal red blood cell folate. There has been no evidence of malabsorption of other vitamins or of minerals. Growth rate has been normal in all children.     

氨己烯酸治疗难治性癫痫25例临床分析

为探讨氨己烯酸对小儿难治性癫痫的治疗价值，采用增药试验的方法，观察了该药对２５例患儿的疗效及安全性。服药后２个月，总有效率６８．０％。服药≥４个月者共２４例，总有效率７０．８％（２１／２４）。服用氨己烯酸后，苯巴比妥血浓度低于用药前水平。血清丙氨酸转氨酶水平较服药前降低。２２例未见毒副作用；２例于服药后早期分别出现轻度头晕和困倦，均自行缓解；１例出现严重的躁动不安而终止治疗。观察结果表明，氨己烯酸对于小儿难治性癫痫有较好的疗效，患儿对其有较好的耐受性。     

法布里病患儿临床特点及酶替代治疗四例初探

目的分析法布里病患儿的临床特点及使用酶替代药物治疗基本情况。方法对2014年1月至2020年7月间浙江大学医学院附属儿童医院确诊的4例法布里病患儿的临床资料、实验室检查、基因变异及治疗进行回顾性分析。临床观察其酶替代药物阿加糖酶β治疗的效果。结果 4例患儿(男2例、女2例)年龄12.4(6.0~16.8)岁,临床表现各异,其中肢端疼痛1例、少汗2例、尿崩1例,均有左心室肥厚和尿检异常,但均未发现典型皮疹及听力异常。4例患儿均结合临床症状、体征、家族史,通过α-半乳糖苷酶A酶活性、基因检测结果明确诊断。共检出3个GLA基因错义变异 c.424T>C(p.C142R)、c.335G>A(p.R112H)和c.644A>G(p.N215S)。其中前2个变异为经典型法布里病患者变异位点,后者多表现为迟发型但亦有经典型的报道。例1使用阿加糖酶β用量为每次1 mg/kg静脉泵注,每2周用药1次。患儿诉用药后疼痛强度有缓解,少汗症状得到改善。患儿在最初的2个月输注阿加糖酶β过程中未发生严重不良反应,在输注阿加糖酶β 3次后24 h尿蛋白升至1 015.6 mg,未予处理,1周后复查降至正常。结论法布里病在儿童期临床表现多样,需要多学科联合协同诊断并探讨酶替代治疗的时机,阿加糖酶β治疗患儿短期严重不良反应少见。     

Paraoesophageal hernia in children: familial occurrence and review of the literature

Paraoesophageal hernia (PH) in children is a rare entity, and most reported cases refer to adult patients. Its etiology is not precisely known, but the hypothesis of its congenital origin is widely accepted. Similarly to other congenital diaphragmatic defects, PH follows a sporadic pattern of incidence in most cases. Familial occurrence of sliding hiatal herniae has been reported in more than 20 cases, but only one family with two members affected by PH was described in the literature. We present two pairs of siblings with the paraoesophageal type of hiatus hernia and discuss the clinical presentation of this anomaly in children. Accepted: 15 September 1998     

注意缺陷多动障碍患儿药物治疗前后microRNA表达量与临床症状的关系

目的 探讨注意缺陷多动障碍（ADHD）儿童药物治疗前后microRNA表达量与临床症状的关系。方法 选取2017年5月至2018年10月初诊为ADHD儿童80例为研究对象,将愿意接受药物治疗的儿童随机分为盐酸哌甲酯治疗组（n=31）和盐酸托莫西汀治疗组（n=33）,不愿接受治疗的作为未治疗组（n=16）,随访中盐酸哌甲酯组脱落10例,盐酸托莫西汀组脱落13例。另随机选取同时期行健康体检儿童60例作为健康对照组。ADHD儿童在首诊、随访3个月、6个月时进行SNAP-V评分,并采集ADHD及健康对照组儿童血清样本以荧光定量PCR法检测miR-4655-3p和miR-7641的相对表达量。结果 重复测量方差分析结果显示,注意力不足症状SNAP-V评分在两治疗组和未治疗组中,以及两种miRNA相对表达量在两治疗组和健康对照组中均存在分组与时间因素差异,且分组与时间因素均存在交互作用（P < 0.05）。多动冲动症状SNAP-V评分在两治疗组和未治疗组中存在时间因素差异（P < 0.05）,而分组因素差异无统计学意义,且时间因素与分组因素无交互作用（P > 0.05）。经药物治疗的ADHD儿童注意力不足症状SNAP-V评分与miRNA-4655-3p和miRNA-7641相对表达量均呈负相关（分别r=-0.314、-0.495,P < 0.05）。结论 药物治疗可显著改善ADHD儿童的临床症状;血清中miR-4655-3p和miR-7641的表达水平可能作为ADHD的诊断及疗效评估的分子指标。     

儿童急性淋巴细胞白血病化疗后血流感染的病原体分布与耐药变迁分析北大核心CSCD

目的研究儿童急性淋巴细胞白血病化疗后血流感染病原体分布变化及耐药变迁趋势。方法收集2015年1月至2020年12月郑州大学第一附属医院收治的急性淋巴细胞白血病化疗后血流感染患儿的临床资料,并按送检时间分为前3年组和后3年组,分析病原体分布及耐药性的差异。结果共检出病原体235株,其中革兰阴性菌159株(67.7%),以大肠埃希菌和肺炎克雷伯菌为主;革兰阳性菌61株(26.0%),以表皮葡萄球菌为主;真菌15株(6.4%),以白色念珠菌为主。前3年组和后3年组革兰阴性菌(68.8%vs 66.9%)、革兰阳性菌(29.2%vs 23.7%)比例差异无统计学意义(P>0.05),后3年组缓症链球菌(5.8%vs 0.0%)和真菌(9.4%vs 2.1%)比例较前3年组增高(P<0.05),两组间革兰阴性菌和革兰阳性菌的耐药率差异无统计学意义(P>0.05)。结论急性淋巴细胞白血病患儿化疗后血流感染病原体以肠杆菌科细菌为主,而缓症链球菌和真菌检出呈增多趋势,临床需重视。