苯丙酮尿症48例

目的探讨泰安地区新生儿苯丙酮尿症(PKU)的发病率及致病基因携带率。方法应用Guthrie细菌抑制法,对苯丙氨酸(phe)水平>20 mg/L的患儿进一步复查,作四氢生物蝶呤(BH4)负荷实验、尿蝶呤分析、二氢蝶啶还原酶活性检测,以此鉴别四氢生物蝶呤缺乏症(BH4D)。免费给予低phe饮食和药物治疗,定期检测血phe水平及体格和智能发育。结果共筛查355 615例新生儿,确诊PKU 48例,PKU在泰安地区发病率为1/7408,致病基因携带者为1/48。PKU患儿体能和智能发育各项指标与正常儿童均无显著性差异(P均>0.05)。结论新生儿PKU的筛查及早期治疗,是减少出生缺陷、提高人口素质的重要措施之一。     

治疗延迟的苯丙酮尿症患儿脑髓鞘发育延迟与智力发育的研究

目的　应用磁共振成像(MRI)观察苯丙酮尿症(PKU)治疗延迟患儿治疗前后脑髓鞘发育延迟与智商的关系。方法　2 0 0 2～2 0 0 3年中日友好医院确诊经典型治疗延迟PKU患儿1 7例,治疗前后分别进行头颅MRI及智商检查,脑髓鞘发育按Staudt标准对不同年龄阶段患儿1 0个脑区域进行量化评估。智商检测采用Gesell发育量表测定。结果　治疗前所有病例存在脑髓鞘发育延迟,在1 0个脑区域脑髓鞘发育延迟平均发生率为44 . 7% ,主要部位在脑叶和胼胝体,并存在不同程度的智力发育落后,平均智商为44 .2 ;经低苯丙氨酸饮食治疗1年后,1 0个脑区域髓鞘发育延迟平均发生率为3 0 . 6% ,平均智商为60 . 6;治疗前、后脑髓鞘延迟改善有显著性(P <0. 0 1 ) ,平均智商改善有统计学意义(P <0. 0 5) ,且智商改善率与髓鞘延迟改善率间可见部分相关性。结论　治疗延迟的PKU患儿的脑髓鞘发育延迟及智力发育落后发生率较高,经低苯丙氨酸饮食治疗可使其在一定程度有所改善,但不能达到完全正常,提示脑髓鞘发育延迟可能是导致PKU患儿智力发育落后的原因之一。     

误诊为脑性瘫痪的苯丙酮尿症

目的分析苯丙酮尿症(PKU)患儿的临床误诊情况。方法对2003年1月~2006年10月本院门诊首诊为脑性瘫痪的72例PKU患儿进行回顾性分析,包括家族史、现病史、体格检查、脑电图和CT摄片、末梢血苯丙氨酸(phe)水平。结果临床表现为癫17例,运动障碍19例,语言障碍64例,湿疹25例,情绪暴躁43例,尿液、汗液有明显异味70例。采用Guthrie's法测定患儿血phe水平,并采用四氢生物喋呤负荷实验对72例患儿进行诊断,其中71例确诊为经典型PKU,1例确诊为四氢生物喋呤缺乏症。结论PKU引起的智能落后较常见,临床上易被忽视,导致漏诊和误诊。     

中山市先天性甲状腺功能减低症筛查及治疗效果分析

目的总结先天性甲状腺功能减低症(CH)筛查状况,并分析替代治疗疗效。方法采用时间分辨荧光免疫法测定新生儿滤纸干血片标本的促甲状腺激素(TSH)水平,阳性者召回并采用化学发光法检测静脉血TSH、游离甲状腺素以确诊。选取经确诊CH并规范治疗2年的永久性CH患儿54例(CH组)及正常健康儿童120例(对照组),两组均长期监测体格发育,并于6月龄、24月龄时采用Gesell婴幼儿发育量表及儿童气质量表分别评估神经运动发育水平及气质特征。结果共筛查新生儿285242例,确诊140例,CH发病率1/2037。CH组及对照组的年龄别身高Z评分(LAZ)及年龄别体质量Z评分(WAZ)差异无统计学意义(P均0.05);6月龄、24月龄时CH组Gesell总发育商与对照组差异无统计学意义(P均0.05),但大运动发育商均落后于对照组,差异有统计学意义(P均0.05);6月龄、24月龄时,CH组和对照组气质类型的分布差异有统计学意义(P均0.05);相比对照组,CH组中难养型及中间偏难养型的比例较高。CH组与对照组在活动水平、适应性、反应强度及坚持性四个维度的得分差异有统计学意义(P均0.05)。结论 CH患儿经早期替代治疗后体格生长及神经运动发育基本正常,但尚需关注其心理行为问题。     

肠内营养粉剂(AA-PKU1)对0～1岁苯丙酮尿症患儿治疗的有效性和安全性

目的 评价肠内营养粉剂(AA-PKU1)对0～1岁苯丙酮尿症(PKU)患儿治疗的有效性和安全性.方法 采用前瞻、开放、自身前后对照、多中心临床研究方法,对2009年4月至2011年2月收治的39例0～4个月PKU患儿进行评估,评估基线、治疗8周及32周后患儿血苯丙氨酸(PHE)水平、发育商测定(Gesell法)、身高、体质量、头围、营养学指标以及血、尿常规、肝肾功能的变化情况和不良事件发生情况.结果 治疗8周后脱落病例3例,36例进入符合方案集进行有效性统计分析,39例进入安全性统计分析;治疗32周后脱落病例5例,34例进入符合方案集进行有效性统计分析,39例进入安全性统计分析.治疗8周和32周时患儿血PHE平均水平分别为196.0 μmol/L、191.1 μmol/L,与基线水平(649.5μmol/L)比较,患儿血PHE水平显著下降,差异有统计学意义(P ＜0.000 1),血PHE水平控制在360 μmol/L以内的控制率分别为88.89％、88.24％;治疗8周和32周时发育商水平与基线比较,差异无统计学意义;治疗8周和32周时的身高、体质量、头围与基线比较,差异均有统计学意义(P均＜0.000 1);治疗32周时的血浆总蛋白、清蛋白、前清蛋白、总胆固醇、三酰甘油、低密度脂蛋白水平与基线比较,差异无统计学意义.安全性方面,不良反应发生例次14次,发生例数10例,均为轻中度胃肠道反应如腹泻、呕吐,可自行缓解或对症处理后缓解和消失.结论 AA-PKU1能有效控制0～1岁患儿的血PHE水平在360 μmol/L以内,通过有效控制患儿血PHE水平,可避免患儿发育商水平进一步下降;AA-PKU1能满足0～1岁患儿正常生长发育的需要并能满足患儿的营养需求及改善患儿的营养状况;临床应用安全、耐受性好.     

深圳地区先天性甲状腺功能减退症的治疗及远期随访

目的 探讨先天性甲状腺功能减退症(CH)患儿早期治疗效果和对生长发育的影响.方法 对2005年9月-2006年12月深圳市出生的新生儿进行足底血片促甲状腺激素(TSH)筛查,筛查阳性儿童召回,行血清促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)检测.确诊CH 68例.平均27.1 d开始治疗,口服左旋甲状腺素钠片.定期检测患儿TSH、FT3、FT4,并根据临床表现调整药物剂量使FT4维持在正常高值水平.监测患儿体格发育如头围、身高和体质量.采用贝利婴幼儿发育量表方法进行智力发育评价.采用SPSS 12.0软件进行数据分析.结果 确诊患儿治疗1个月后临床症状完全消失,TSH、FT4维持正常水平.身高、体质量、头围等体格发育指标均在正常范围,均值50%,贝利婴幼儿发育量表测试中运动发育指数测定均在冲等水平,智力发育指数测定均基本达到同龄健康儿童.结论 早期诊治CH能明显改善预后,降低脑损害、智力低下的发生率.新生儿筛查是早期诊断CH的有效方法.     

早期替代治疗对先天性甲状腺功能减退症患儿智能发育的影响

目的 分析先天性甲状腺功能减退症(CH)患儿的智能发育,探讨治疗前后甲状腺功能与智能发育水平的关系.方法 采用Gesell方法对坚持进行左旋甲状腺素替代治疗的30例经南京市妇幼保健院新生儿筛查中心确诊的CH患儿(CH组)以及30例健康儿童(健康对照组)进行智能测定.2组年龄、性别相匹配.应用荧光法测定患儿治疗前后的甲状腺功能.结果 CH组患儿智能均达基本正常(>70),但各能区发育商(DQ值)和总分平均值均显著低于健康对照组(t=-7.02、-3.87、-4.75、-5.77、-6.77、-7.82 Pa<0.01).各能区DQ值与起始治疗天数呈显著负相关,精细动作、个人社交2个能区的DQ值与治疗前游离甲状腺素水平呈显著正相关(Pa<0.05).结论 早期替代治疗后CH患儿的智能发育基本正常,但仍稍落后于健康儿童.建议在尽早治疗的同时,及时评估,并加强对患儿精细动作和社交能力的训练,将有助于其智能发育,改善预后.     

苯丙酮尿症患儿治疗前后脑白质病变的观察

目的：该研究应用MRI观察晚治苯丙酮尿症(PKU)患者治疗前后脑白质病变。方法：确诊为经典型PKU患者19例,进行低苯丙氨酸(PHE)饮食治疗随诊8～16月,治疗前后分别进行了头颅MRI及智商检查。头颅MRI采用常规矢状面、轴面T1W和轴面T2W扫描,对脑白质T2高信号病变按Thompson6级分级法进行分级并评分。观察比较治疗前后脑白质病变的改变。结果：9例晚治PKU患者头颅MRI均存在脑白质病变,其病变主要表现为侧脑室周围及三角区白质等区域存在孤立性斑片状异常T2高信号,治疗前后的平均MRI脑白质T2高信号分级分别为2.59和1.76,治疗前后MRI分级按分数计算,差异有显著性(P<0.01),治疗后T2高信号等级改善。19例均存在不同程度的智力发育落后,在智商改善与T2高信号等级改善可见部分一致关系。血PHE浓度与脑白质病变间有关。结论：晚治PKU患者脑白质病变及智力发育落后具高发生率,低苯丙氨酸饮食治疗降低血苯丙氨酸浓度后脑白质病变及智商均有部分改善,提示PKU患者脑白质病变及智力损害是部分可逆的,PKU患者脑白质改变可能是导致晚治PKU患者智能发育障碍的原因之一。     

新生儿先天性甲状腺功能低下症的筛查与治疗评估

目的探讨先天性甲状腺功能低下症(甲低)的筛查、治疗方法和随访及疗效评估。方法采用时间分辨荧光免疫法检测滤纸血斑中促甲状腺素(TSH)水平;对召回的可疑患儿,采用化学发光免疫法检测血清甲状腺功能,确诊后予以左甲状腺素钠治疗,正规治疗2~3年后,停药观察,结合甲状腺核素扫描或超声检查、智力测定、骨龄检测及体格检查,进行疗效评估。结果筛查新生儿557 193例,检出甲低339例,发病率1/1644。其中治疗满18个月以上221例(治疗18个月~2年34例、2~3年112例、>3年75例)。甲状腺核素扫描100例,超声检查150例(2项均检查29例):甲状腺异常48例(缺如、异位各8例,发育不良32例);正常173例。发育商>85者98.6%,平均106.5;骨龄发育正常75%,稍落后25%;身高与体质量均达正常。治疗评估:48例确诊为原发性甲低,予终身治疗;173例暂时性甲低,其中86例停药观察,可终止治疗69例,确诊为暂时性甲低;重新恢复治疗9例,确诊为亚临床甲低;继续随访8例。结论开展新生儿疾病筛查,结合安全有效的治疗和规范的随访,完全能预防智残疾病发生和保障儿童体格和智能正常发育。     

肠内营养粉剂AA-PKU2治疗1~8岁苯丙酮尿症患儿的有效性和安全性研究

目的 评价肠内营养粉剂AA-PKU2对1~8岁苯丙酮尿症（PKU）患儿治疗的有效性和安全性。方法 2009年7月至2011年5月采用前瞻、开放、自身前后对照、多中心临床研究方法,共入组1岁至7岁4个月PKU患儿121例,评估肠内营养粉剂AA-PKU2治疗前、治疗8周及32周后患儿血苯丙氨酸（PHE）浓度、智能发育（1~4岁Gesell法,>4岁WPPSI或WISR-R法）、身高、体重、头围、血常规、尿常规、肝肾功能、血脂和蛋白水平等血清营养学指标的变化以及不良事件发生情况。结果 AA-PKU2治疗8周和32周后患儿血PHE浓度平均水平分别为353±253、361±280 μmol/L,与治疗前 （487±327 μmol/L）相比,差异有统计学意义（P<0.01）;治疗8周和32周后血PHE浓度≤360 μmol/L的控制率分别为65.5%、66.7%。在Gesell法评估的患儿中,AA-PKU2治疗8周和32周后总发育商与治疗前比较差异无统计学意义,但显示了智能改善的趋势;在WPPSI或WISR-R法评估的患儿中,AA-PKU2治疗8周和32周后总智商比治疗前明显增加（P<0.01）。AA-PKU2治疗8周和32周后患儿的身高、体重、头围与治疗前比较均显著增加（P<0.01）,与同年龄段正常儿童的指标相当。治疗8周和32周后患儿血浆总蛋白、白蛋白、前白蛋白、总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白平均水平与治疗前的平均水平基本相当,均在正常范围内。与AA-PKU2治疗相关的不良事件发生率为2.5%（3例）,均为轻度腹泻,未特殊处理而好转。结论 肠内营养粉剂AA-PKU2能有效控制1~8岁患儿的血PHE浓度在360 μmol/L以内;通过有效控制患儿血PHE浓度,可改善患儿的智力发育,满足患儿正常生长发育的需要,且临床应用安全、耐受性好。     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.     

Understanding infant formula

The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and healthcare professionals) will experiment with the infant formula available and then attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.