先天性症状性巨细胞病毒感染脑脊液病毒载量与听力损伤相关性

目的 探讨症状性先天性巨细胞病毒(cytomegalovirus,CMV)感染新生儿脑脊液(cerebrospinal fluid,CSF) CMV DNA载量与感音性听力损伤(sensorineural hearing loss,SNHL)的相关性.方法 36例先天性症状性CMV感染患儿,PCR法检测CSF CMV DNA载量,并于出生1个月内、生后6个月及1年左右行脑干听觉诱发电位检测.结果 (1)36例患儿,其中CSF CMV DNA阳性15例,阳性率41.2％,SNHL17例,SNHL发生率47.2％.(2) CSF CMV DNA阳性组SNHL发生率60.0％(9/15);阴性组SNHL发生率38.1％ (8/21),两组发生率比较差异无统计学意义(P =0.194).(3)CSFCMVDNA阳性组中,SNHL组与听力正常组CSF CMV DNA载量为3.35 ±0.68和3.17±0.56,两组载量比较,差异无统计学意义(P=0.36).结论 先天性症状性CMV感染患儿CSF CMV DNA是否阳性及其载量不是预测SNHL的指标.     

Concomitant cytomegalovirus infection and congenital toxoplasmosis in a newborn

We report what we believe to be the first case of simultaneous infection by Toxoplasma gondii and cytomegalovirus in a newbornAbbreviations CMV cytomegalovirus - CSF cerebrospinal fluid     

Clinical findings and adverse outcome in neonates with symptomatic congenital cytomegalovirus (SCCMV) infection

Introduction Congenital cytomegalovirus (CCMV) infection is a common neonatal infection affecting 1% of all live births, 10% of which are symptomatic. Many of these infants have long-term sequelae. The objective is to document the clinical presentation of SCCMV infection in neonates, the frequency of sequelae and severity of adverse neurologic outcomes and risk factors.Methods A review and analysis of all symptomatic infants diagnosed with SCCMV infection are given. SCCMV was defined as a diagnosis of CCMV infection in the first three weeks of life in the presence of any clinical manifestations. Outcome data from 2 years of age and later are analyzed.Results There were 104 patients identified as having SCCMV infection and of these 42 cases had definite infection. The common findings at presentation were hepatosplenomegaly 19/42 (45%), thrombocytopenia 21/42 (50%), elevated transaminases 21/42(50%), abnormal cranial US scan 24/41(56%), abnormal head CT scan 29/41(71%) and abnormal brain MRI 17/19(89%). The risk factors for an adverse outcome including death or deafness or blindness or moderate to severe neurological deficits included an abnormal cranial US scan (OR 8.5), abnormal head CT scan (OR 21) and abnormal brainstem auditory evoked responses (BAER) (OR 8.7).Conclusions There was only three (7%) patients without any deficits and severely affected infants have been identified with a diverse clinical presentation, reinforcing the importance of CMV as a major public health problem.     

Cerebrospinal fluid 309-1309-1309-1in neonates with central nervous system infections

Beta₂-microglobulin (₂m) determination in CSF of 72 neonates who underwent a spinal tap as part of a sepsis or meningo-encephalitis workup was performed to evaluate the usefulness of this test in the diagnosis of CNS infections. ₂m was measured by enzyme immunoassay. Sixty neonates had sterile culture and normal neurological status at discharge. Twelve infants had CNS infections: 8 bacterial meningitis, 3 TORCH infections (T=toxoplasmosis, O=others, R=rubella, C=cytomegalovirus and H=herpes simplex) and 1 viral meningitis. Neonates with CNS infection exhibited significantly higher CSF ₂m levels compared to neonates with sterile culture (6.24±2.66 vs 1.74±0.5 mg/l;P<0.0001). CSF ₂m levels did not correlate with the white cell count, total protein concentration or glucose level in CSF. When serum and CSF levels were measured simultaneously, the CSF ₂m level was significantly higher than the corresponding serum level in patients with CNS infection (6.98±2.5 vs 3.2±0.25 mg/l;P<0.01). Sensitivity, specificity, and predictive values were estimated for different cut-off points. The best operational diagnostic cut-off value was 2.25 mg/l. Receiver operating characteristic curve analysis showed an appropriate trade-off between specificity and sensitivity and indicated that CSF ₂m was accurate in distinguishing between neonates with and without CNS infection.Conclusion CSF ₂m may be a useful ancillary tool in neonates when CNS infection is suspected.Presented in part at the European Society for Paediatric Research Meeting, Edinburgh, September 1993     

Increased total-Tau levels in cerebrospinal fluid of pediatric hydrocephalus and brain tumor patients

Total Tau (t-Tau), hyperphosphorylated Tau (p-Tau(181P)) and beta-amyloid(1-42) in cerebrospinal fluid (CSF) have shown to be markers of neuronal and axonal degeneration in various neurological and neurodegenerative diseases. The aim of this study was to evaluate the influence of the presence of a brain tumor and hydrocephalus on t-Tau, p-Tau(181P) and beta-amyloid(1-42) levels in CSF of pediatric patients. t-Tau, p-Tau(181P) and beta-amyloid(1-42) levels were simultaneously quantified by xMAP technology in 22 lumbar and 15 ventricular CSF samples from newly diagnosed pediatric brain tumor patients and 39 lumbar and 12 ventricular CSF samples from pediatric patients without a brain tumor. t-Tau, p-Tau(181P) and beta-amyloid(1-42) levels in both lumbar and ventricular CSF were not significantly correlated with age. t-Tau levels in lumbar CSF were elevated in brain tumor patients, being especially high in medulloblastoma patients. Lumbar CSF p-Tau(181P) levels were lower in brain tumor patients compared to normal controls. Ventricular levels of t-Tau, p-Tau(181P) and beta-amyloid(1-42) were not significantly different between the brain tumor patients and non-tumor patients, but t-Tau levels were significantly increased in patients with radiological signs of hydrocephalus. Two patients with an infected ventriculo-peritoneal drain also had high CSF t-Tau levels. In conclusion, high t-Tau levels in CSF are found in pediatric patients with a brain tumor, patients with hydrocephalus and patients with a serious CNS infection, reflecting neuronal and axonal damage. Ongoing studies should determine whether these neurodegenerative markers in CSF can be used to monitor neuronal and axonal degeneration in these patients during therapy and long-term follow up.     

中枢神经系统感染患儿脑脊液中IGF-Ⅰ与NSE变化的相关性探讨

目的探讨中枢神经系统(CNS)感染患儿脑脊液(CSF)中胰岛素样生长因子I(IGF-I)及神经元特异性烯醇化酶(NSE)变化的相关性。方法选择90例患儿,其中化脓性脑膜炎30例,病毒性脑膜炎30例,对照30例。所有受试者均于入院后24~48h做腰椎穿刺,采集CSF0·5~1ml,采用FJ-2008PSγ免疫计数器检测IGF-I及NSE含量。结果观察组CSF中IGF-I与NSE含量与对照组比较均差异显著(P<0·01);两观察组间比较,差异无显著性(P>0·05);两观察组间IGF-I与NSE测定值无相关性,但15例意识障碍患儿IGF-I及NSE两值间呈正相关。结论CNS感染时,CSF中IGF-I与NSE均明显增高,较重患儿的CSF中IGF-I和NSE值呈正相关,推测IGF-I在CNS损伤的保护和修复中发挥一定作用。     

A novel mutation in the monocarboxylate transporter 8 gene in a boy with putamen lesions and low free T4 levels in cerebrospinal fluid

We describe brain lesions in a patient with a monocarboxylate transporter 8 mutation. Imaging showed a high T2 lesion in the left putamen at age 3 and a right putamen lesion at age 6. Cerebrospinal fluid free thyroxine concentrations were low, with normal 3,3',5-triiodothyronine concentrations.     

Comparison of cerebrospinal fluid in newborns and in infants ≤2 months old with or without meningitis

Background: The aim of the present study was to evaluate the characteristics and accuracy of cerebrospinal fluid (CSF) parameters for neonatal meningitis, by comparing CSF data in newborns and in infants ≤2 months of age, with or without meningitis. Methods: This case–control study was performed on 120 newborns and infants ≤2 months old. 60 patients with meningitis were considered as the case group and 60 ill patients without meningitis were defined as the control group. Each of the two groups was divided into 0–1 months and 1–2 months old. CSF characteristics were compared in newborns in the case and control groups; in infants ≤2 months old in the case and control groups; and in healthy newborns and healthy infants ≤2 months old. Results: The mortality rate was 16.7% in the case group. The differences of CSF parameters in the case and control groups were mostly not significant, except for CSF glucose only in term newborns <7 days old (P= 0.04), and white cell count (WBC) only in 0–7‐day‐old term and preterm neonates (P= 0.04 and P= 0.01, respectively). Polymorphonuclear leukocyte (PMNL) level in the case group was significantly higher than in the control group (P= 0.02). CSF characteristics in healthy newborns were nearly the same as in healthy infants ≤2 months old. Prevalence of positive CSF culture was 31.7% in the case group. The most common pathogen was Neisseria meningitidis in the two age groups. The concomitant positive blood culture in the case group was 26.3%. Conclusion: In the case of meningitis with negative CSF culture and Gram stain, diagnosis can be made on CSF parameters, clinical and laboratory findings and suspicion of meningitis. Therefore, a clinical prediction rule to classify risk for bacterial meningitis on evaluation of CSF parameters in any region should be established. More regional trials are needed to enhance the probability of diagnosis according to CSF parameters.     

Alpha1-antitrypsin and alpha2-macroglobulin in newborn infants

The levels of alpha₁-antitrypsin and alpha₂-macroglobulin in the plasma of 129 newborns were determined. The infants were divided into 3 groups according to their perinatal history.In healthy newborns with an uneventful perinatal history the normal values for alpha₁-antitrypsin were 1.97±0.44 g/l, and for alpha₂-macroglobulin 3.11±0.69 g/l. No changes in these levels were found during the first week of life. The levels of alpha₁-antitrypsin and alpha₂-macroglobulin showed significant correlation to each other.In healthy newborns with different complications in the obstetric history the levels of alpha₁-antitrypsin were not influenced, whereas alpha₂-macroglobulin decreased slightly during the first week of life. The levels of alpha₁-antitrypsin and of alpha₂-macroglobulin showed no further correlation to each other.In sick term and preterm newborns (n=18) alpha₁-antitrypsin was increased in 5 of 7 babies suffering from bacterial infections and lowered in 4 of 9 cases with respiratory disturbances. Alpha₂-macroglobulin was lowered in 15 babies. These results indicate different kinetics of the two antiproteases in vivo.With support of the Landesamt für Forschung des Landes Nordrhein-Westfalen     

Prostaglandin E2 administration in infants with ductus-dependent cyanotic congenital heart disease

Prostaglandin E₂ was administered to 22 newborns with ductus-dependent cyanotic congenital heart disease. Twelve patients had pulmonary atresia and ten simple dextrotransposition of the great arteries. Patients were classified into two groups: group 1 (n=11) received prostaglandin E₂ by the intravenous route (dose: 0.01–0.05 g/kg per min); group 2 (n=11) received prostaglandin E₂ by the oral route (dose: 35–65 g/kg per 1–4 h). Treatment lasted for 1–90 days. All infants except one of group 2 showed a significant (>10 Torr) increase in PaO₂ following PGE₂ administration. The mean increase in PaO₂ was higher (P<0.01) in group 1 (21.8±1.7, Torr) than in group 2 (15.8±1.5, Torr). PaO₂ fell significantly (P<0.01) in five patients of group 1 who continued treatment orally with satisfactory (>30 Torr) levels in four of them. Severe side effects were observed only in group 1. The data show that similarly to prostaglandin E₁ infusions, prostaglandin E₂, given i.v. or orally, is useful in the management of infants with ductus-dependent cyanotic congenital heart disease. Oral prostaglandin E₂, administration is less effective than i.v. infusions, but can be used for long-term, therapy being more convenient and causing minimal morbidity.Presented at the IX European Congress of Perinatal Medicine, Dublin, Ireland, 1984     

Atypical vitamin B12-unresponsive methylmalonic aciduria in a sibship with severe progressive encephalomyelopathy: A new genetic disease?

We report on two siblings, a girl of 7 years and a boy of 2 years, who presented in infancy with hypotonia, athetoid movements, myopathy and severe developmental delay. The progressive clinical course was characterized by ophthalmoplegia, pyramidal tract signs, loss of visual contanct and failure to thrive. The older sister died at the age of 7 years. The younger brother followed an almost identical clinical course. MRI of the brain revealed bilateral hypodensities and atrophy of the putamen. Neurophysiological investigations were consistent with peripheral neuropathy. Investigations for neurometabolic disorders in urine, plasma and CSF of both patients revealed a consistent increase of methylmalonic acid in urine, plasma and CSF as well as borderline low free GABA in CSF. Except for an inconstant elevation of lactate in the boy, metabolic acidosis, hypoglycaemia, episodic ketoacidosis, or hyperammonaemia, the usual concomitants of organoacidopathies, were absent in both children. Homocystinuria was excluded. Methylmalonic aciduria did not respond to antibiotic treatment, vitamin B₁₂ therapy nor dietary protein restriction. Incorporation of [¹⁴C]propionate into protein in cultured fibroblasts was pathologically but inconsistently decreased. Both patients' cell lines showed only minimal response to hydroxocobalamin and normal methylmalonyl-CoA mutase activity.Conclusion Even though the definitive undorlying enzymatic defect in this sibship remains obscure our results suggest a new genetic disorder. This report illustrates that hitherto undescribed metabolic disorders remain to be elucidated even in long investigated areas of intermediary metabolism such as methylmalonic aciduria.     

下呼吸道感染患儿支气管肺泡灌洗液的病原学研究

目的 研究下呼吸道感染患儿病原体特点,为临床医生合理使用抗生素提供依据。方法 选取2017年1月至2018年6月因下呼吸道感染住院且接受纤维支气管镜治疗的108例患儿为研究对象,收集其支气管肺泡灌洗液,通过多重实时荧光PCR检测其病原体。结果 在108例患儿中,检测出病原体85例（78.7%）,其中单一病原体感染检出52例（48.1%）,多重病原体感染检出33例（30.6%）。肺炎支原体检出率最高,共检出38例（35.2%）,其中36~ < 72月龄患儿检出率最高;其次为肺炎链球菌及流感嗜血杆菌,各检出29例（26.9%）,其中肺炎链球菌主要集中于24月龄以下患儿。检出率较低的为鲍曼不动杆菌、白色念珠菌及肺炎克雷伯杆菌,各检出3例（2.8%）。在31例支气管肺炎患儿中,流感嗜血杆菌检出率最高（9例,29%）。在34例大叶性肺炎患儿中,肺炎支原体检出率最高（22例,65%）。在22例支气管异物合并支气管肺炎患儿中,肺炎链球菌检出率最高（10例,45%）。结论 在下呼吸道感染患儿中,肺炎支原体检出率最高,其次为肺炎链球菌及流感嗜血杆菌。不同年龄、不同类型下呼吸道感染患儿的病原体检出率存在差异。     

先天性甲状腺功能减退症患儿DUOX2基因突变的研究

目的 研究先天性甲状腺功能减退症(congenital hypothyroidism, CH)患儿DUOX2 基因突变类型和特点,并初步探讨基因型- 表现型的关系,为CH 患儿的基因诊断和基因治疗提供理论依据.方法 从10例CH 伴甲状腺肿大患儿外周血白细胞中提取基因组DNA,采用PCR 扩增和直接测序的方法对DUOX2 全部外显子进行基因突变检测.结果 在1 例患儿中发现DUOX2 基因第28 外显子cDNA 的3632 位点发生了G>A 的突变(c.G3632A),导致第1 211 密码子的精氨酸变为组氨酸(p.R1211H).在3 例患儿中发现DUOX2 基因第17 外显子cDNA 的2 033 位点发生了T>C 的突变(c.T2033C),导致第678 密码子的组氨酸变为精氨酸(p.H678R).此两种突变均为杂合型的错义突变.结论 CH 患儿存在DUOX2 基因杂合突变,该杂合突变可能引起蛋白质功能的改变从而导致CH;基因型与表现型的关系尚不明确,需要进一步的研究.     

White matter abnormalities in patients with treated hyperphenylalaninaemia: Magnetic resonance relaxometry and proton spectroscopy findings

In order to further clarify the pathogenesis and clinical significance of MRI white matter abnormalities in treated hyperphenylalaninaemia (HPA), ten patients (seven type I HPA, two type II and one type III) underwent T₂ relaxometry (n=8) and/or¹H spectroscopy (n=7) in addition to conventional MR spin-echo imaging at 1.5 T. Two patients with severe MRI abnormalities had repeat examinations during and after a 6-to 8-month period of strict diet control. The clinical evaluation included a detailed neurological examination. In nine out of ten patients visual evoked potentials (VEP) were obtained parallel to the MR examination. MR imaging demonstrated typical symmetrical areas of prolonged T₂ relaxation time predominantly in the posterior periventricular white matter in all but one of type I and II patients. There was no consistent relationship between MRI findings and time of diagnosis/initiation of therapy, IQ or visual evoked potential changes. MRI abnormalities tended to be more severe in patients with poor dietary control and high current plasma phenylalanine levels, whereas a normal MRI was found only in patients with plasma phenylalanine levels continuously below 0.36 mmol/l. There was marked regression of MRI abnormalities already after 3 months of strict diet control. T₂ relaxometry showed a bi-exponential behaviour of T₂ in the affected white matter, with a slow component of about 200–450 ms, indicating an increase in free (extracellular) water.¹H spectroscopy revealed no signs of severe neuronal damage. We conclude, that the observed white matter changes in treated HPA probably represent reversible structural myelin changes rather than permanent demyelination.     

Transcutaneous PO2 monitoring in infants with cyanotic congenital heart disease treated with prostaglandin E1

Summary Transcutaneous PO₂ (tcPO₂) has been shown to closely approximate arterial PO₂ (PaO₂) in infants with normal oxygenation (PaO₂ 60–100 mm Hg). During hypoxemia (PaO₂<60 mm Hg), or administration of vasoactive drugs, such as tolazoline, correlation is frequently so poor that tcPO₂ monitoring is of little value. We examined the relationship of tcPO₂ to PaO₂ among 6 infants with cyanotic congenital heart disease who were receiving prostaglandin E₁ (PGE₁). Close, linear correlation was found, even during hypoxemia. We conclude that tcPO₂ monitoring has potential clinical value in such patients.Supported by a grant (RR-81) from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health.     

Decreased levels of alpha2 HS-glycoprotein in children with protein-energy-malnutrition

Serum levels of alpha₂ HS-glycoprotein were determined in ten marasmic children without infections and 14 non-infected children with kwashiorkor. The results obtained were compared with those of 16 non-infected well-nourished children of the same age and sex. No significant difference could be found between the two groups of children with protein-energy-malnutrition (PEM). Well-nourished children however had significantly higher levels than the PEM children. The reduced serum levels of this glycoprotein in PEM children could indicate disturbance of bone minerilisation, leading to stunted growth, and contribute to impairment of defence ability in these children.Abbreviations PEM protein-energy-malnutrition     

中枢神经系统感染儿脑脊液内皮素、血栓烷及前列环素的意义

目的探讨内皮素(ET1)、血栓烷(TXA2)和前列环素(PGI2)在小儿中枢神经系统感染(FCNS)中的意义。方法采用放射免疫方法检测FCNS儿脑脊液(CSF)中ET1及TXA2和PGI2的稳定代谢产物TXB2和6-k-PGF1α,非感染手术儿CSF为对照。结果FCNS儿CSF、ET1、TXB2及TXB2／6-k-PGF1α(T／K)比值升高,昏迷儿CSF、ET1、TXB2高于非昏迷儿,恢复期CSF、ET1、TXB2／6-k-PGF1α。比值较急性期下降。结论FCNS时神经系统ET1和TXA2生成增加,CSF中ET1、TXD2和6-k-PGF1。改变可反映脑实质损伤程度,有助于临床病情判断。