Brain magnetic resonance imaging in children with optimally controlled hyperphenylalaninaemia

Summary This study was undertaken to investigate whether the white-matter changes on MRI and the EEG abnormalities detectable in treated adolescents and adults with hyperphenylalaninaemia (HPA) can be detected in younger children on an optimally controlled diet. The study included 17 children, 7–12 years of age, with HPA. The MRI of five healthy children were included in the blind evaluation of the MR images. According to mutation genotype and dietary tolerance of phenylalanine, 9 patients have severe HPA and 8 have moderate HPA, all requiring dietary treatment. Mild white-matter hyperintensity was detected in 1 of the 5 healthy children and in 10 of 17 patients. EEG was abnormal in 2 patients. This group of children was compared with a previously reported group of adolescents with HPA who had been treated according to the same dietary regimen. MRI changes and EEG abnormalities were significantly less frequent in the group of children than in the group of adolescents. It is suggested that the more frequent MRI changes and EEG abnormalities seen in adolescents are related to the fact that a relaxation of the dietary treatment after the age of 8 years is often accepted.     

青少年儿童肠易激综合征的流行病学调查

目的分析青少年儿童肠易激综合征(IBS)的患病率、分布特征(包括区域、学龄段、性别分布等)及其致病的相关危险因素。方法采用多级整群随机抽样方法,对黑龙江省与上海市共9所学校中5403名中小学生进行流行病学问卷调查,估算符合罗马Ⅱ诊断标准IBS的期间患病率,对其致病的相关危险因素进行单因素与多因素分析。结果推测被调查的两地中小学生符合罗马Ⅱ诊断标准的IBS患病率为13.25%,男女患病率差异无统计学意义(P>0.05)。区域性分层研究表明,患病率在黑龙江省(14.02%)和上海市(11.72%)之间差异有统计学意义(P<0.05)。学龄段分层研究表明,高中生患病率(17.80%)明显高于其他学龄段(P<0.01)。多因素回归分析表明,饮酒、吸烟、辛辣食物、痢疾史、腹部手术史、服用大量抗生素史、受凉、疲劳、心情焦虑、心情压抑及内向性格11个因素为最具可能性的危险因素,其OR值分别为1.25、1.44、1.13、1.37、1.63、1.93、2.83、1.10、1.07、1.13及1.05。结论IBS是青少年儿童人群的常见病和多发病。青少年儿童IBS患病率存在区域性与学龄段差异。心理因素、食物、不良外界环境因素及家庭环境因素等可能是诱发青少年儿童IBS致病的相关危险因素。     

全国城市中小学生肠易激综合征现况调查

目的分析我国城市中小学生肠易激综合征（IBS）的患病率及分布特征。方法采用多级整群随机抽样方法,对我国六个省及两个直辖市中51956名中小学生进行流行病学问卷调查。结果全国符合Manning及罗马Ⅱ诊断标准IBS期间患病率分别为53．5％及20．2％,以高中生居多,男女患病率差异无统计学意义（P〉0．05）;南方地区患病率分别为53．3％及19．6％;北方地区患病率分别为51．2％及18．9％;西部地区患病率分别为58．0％及23．4％。结论IBS是城市中小学生的常见病及多发病,患病率随着年龄的增长而上升。     

Lysosomal protein degradation in experimental hyperphenylalaninaemia

The influence of -methylphenylalanine-induced hyperphenylalaninaemia (HYP) on the lysosomal protein degradation system in brain and liver of suckling rats was investigated. In both tissues cathepsind andl activities, measured at 5, 10 and 15 days post partum (p.p.), exhibited no differences between experimental and control animals.N-Acetyl--d-glucosaminidase (NAGase) activity in brain, measured at 10 and 15 days p.p., was not affected by HYP either. The release of valine and lysine from liver and brain homogenates respectively, serving as a measure for the lysosomal content of degradable proteins, was not influenced by HYP. Lysosomal integrity during incubation of homogenate was monitored by the recovery of NAGase activity in the cytosolic supernatant, and by the relative NAGase activity in total homogenates in the absence of the lysosome disrupting detergent Triton X-100. In conclusion, experimental HYP appears unlikely to influence the lysosomal protein degradation system in brain and liver of suckling rats.     

Hepatic phenylalanine hydroxylase activity in hyperphenylalaninaemia

Phenylalanine tolerancein vivo has been compared with the phenylalanine hydroxylase activity of liver biopsy specimens in 14 newly detected cases of hyperphenylalaninaemia. Hepatic phenylalanine hydroxylase activity does not predict the degree of dietary restriction that will be required.     

福建省青少年肠易激综合征的流行病学调查

目的分析城市中小学生肠易激综合征(IBS)的患病率、分布特征、致病的相关危险因素及焦虑性情绪障碍状况。方法采用多级整群随机抽样方法,对福建省两个地级市中4826名中小学生进行流行病学问卷调查。结果①校正后符合Manning及罗马Ⅱ诊断标准IBS的期间患病率分别是52．16％及17．10％,以高中生居多,男女患病率差异无统计学意义(P>0．05)。②Logistic回归分析揭示,年级、喜食辛辣或生冷食物、胃肠道感染、经常服用抗生素、遗传、经常因IBS症状而就诊、进食时吞咽困难、经常采用吞气来帮助终止打嗝、纳差、心情压抑11种因素为最具可能性的危险因素,其OR值均> 1。③4826名学生中有焦虑性情绪障碍倾向者占22．53％,男性17．84％,女性26．45％,两者差异有统计学意义(P<0．01)。④在儿童焦虑性情绪障碍筛查表(SCARED量表)5个领域的分值比较中,IBS学生高于非IBS学生,IBS就诊学生高于未就诊学生。结论①IBS是城市中小学生的常见病及多发病,患病率随年龄增长而上升;②不良饮食习惯、胃肠道感染、滥用抗生素、遗传及精神心理因素等可能是诱发城市中小学生IBS致病的相关危险因素;③焦虑性情绪障碍倾向发生率随年龄增长而上升。     

Disturbances of amino acid transport in rats with experimental hyperphenylalaninaemia

Liver and brain cortex slices from rats made hyperphenylalaninaemic withp-chlorophenylalanine showed decreased leucine uptake but increased uptake of tryptophan and glycine.     

Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin

Aim: Canagliflozin is a sodium‐glucose co‐transporter 2 (SGLT2) inhibitor that is being investigated for the treatment of type 2 diabetes mellitus (T2DM). Methods: This was a randomized, double‐blind, placebo‐controlled, parallel‐group, 28‐day study conducted at two sites, in 29 subjects with T2DM not optimally controlled on insulin and up to one oral antihyperglycaemic agent. Subjects were treated with canagliflozin 100 mg QD or 300 mg twice daily (BID) or placebo. Safety, tolerability, pharmacokinetic characteristics and pharmacodynamic effects of canagliflozin were examined. Glucose malabsorption following a 75‐g oral glucose challenge was also examined. Results: Canagliflozin pharmacokinetics were dose‐dependent, and the elimination half‐life ranged from 12 to 15 h. After 28 days, the renal threshold for glucose excretion was reduced; urinary glucose excretion was increased; and A1C, fasting plasma glucose and body weight decreased in subjects administered canagliflozin (A1C reductions: 0.19% with placebo, 0.73% with 100 mg QD, 0.92% with 300 mg BID; body weight changes: 0.03 kg increase with placebo, 0.73 kg reduction with 100 mg QD, 1.19 kg reduction with 300 mg BID). Glucose malabsorption was not observed with canagliflozin treatment. There were no deaths, serious adverse events or severe hypoglycaemic episodes. The incidence of adverse events was similar across groups. There were no clinically meaningful changes in routine laboratory safety tests, vital signs or electrocardiograms. Conclusion: In subjects receiving insulin and oral antihyperglycaemic therapy, canagliflozin was well tolerated without evidence for glucose malabsorption, had pharmacokinetic characteristics consistent with once‐daily dosing, and improved glycaemic control.     

Transient hyperphenylalaninaemia with a high neopterin to biopterin ratio in urine

A case of transient hyperphenylalaninaemia with a maturational delay of dihydropteridine synthesis is described. With the Guthrie test, the patient showed a blood phenylalanine level of 38 mg dl^–1, which had fallen to a normal value without a phenylalanine restricted diet by 3 months of age. The neopterin level and the neopterin to biopterin ratio in the patient's urine were very high at 19 days of age. The blood phenylalanine level did not decrease when tetrahydrobiopterin (2.5 mg kg^–1) was administered at 19 days of age, while administration of tetrahydrobiopterin (7.5 mg kg^–1) at 20 days of age had decreased the blood phenylalanine level to 50% of the preloading level after 24 h. The oral phenylalanine loading test showed the pattern of classic phenylketonuria (PKU) at 15 days of age, but it showed the normal pattern at 1 year 8 months of age.     

Hepatic phenylalanine hydroxylase activity in hyperphenylalaninaemia

Phenylalanine tolerance in vivo has been compared with the phenylalanine hydroxylase activity of liver biopsy specimens in 14 newly detected cases of hyperphenylalaninaemia. Hepatic phenylalanine hydroxylase activity does not predict the degree of dietary restriction that will be required.     

High nocturnal melatonin in adolescents with chronic fatigue syndrome

Decreased quality of sleep is frequently reported by chronic fatigue syndrome (CFS) patients. The pineal hormone melatonin is involved in regulation of sleep. We analyzed the nocturnal rise in melatonin in 13 adolescent CFS patients and 15 healthy age-matched controls. Saliva samples were collected at hourly intervals between 1700 and 0200 h. Nocturnal saliva melatonin levels were significantly higher in CFS patients, compared with controls, at midnight, 0100 h, and 0200 h (P < 0.001). No differences were observed in timing of melatonin increase in saliva between patients and controls. Time of sleep onset and duration of sleep did not differ significantly between patients and controls. However, all CFS patients and only one of the controls in our study group reported unrefreshing sleep. Our data demonstrate that sleep problems in adolescents with CFS are associated with increased melatonin levels during the first part of the night. Based on these data, we suggest that there is no indication for melatonin supplementation in adolescents with CFS.