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The human neonate is at a higher risk for hypoglycemia-induced neuronal injury than other pediatric and adult patients. Repetitive and profound neonatal hypoglycemia can result in severe neurologic sequelae, of which the mechanisms was not elucidated by hitherto. Moreover, no reliable animal model of brain injury induced by neonatal hypoglycemia is available in order to carry out more research. Therefore, we tried to induce neonatal hypoglycemia in newborn rats by fasting and insulin injection, and then examined the neuronal degeneration after repetitive hypoglycemic insults by Fluoro-Jade B (FJB) staining. Experimental animals were randomly divided into four groups: insulin-treated rats with short hypoglycemia, insulin-treated rats with prolonged hypoglycemia, fasted rats, and control rats. Insulin injection and fasting both could induce consistent hypoglycemia in newborn rats. But from FJB staining results, only in insulin-treated rats with prolonged hypoglycemia could extensive neurodegeneration be detected. We can conclude that FJB staining is a useful method of marking neuronal degeneration in neonatal rats following hypoglycemic brain damage. Repetitive and profound neonatal hypoglycemia can result in extensive neurodegeneration, and it seems that neurons of the cortex, dentate gyrus of the hippocampus, the thalamus, and the hypothalamus are more vulnerable to hypoglycemic insult in newborn rats. Repetitive and profound insulin-induced hypoglycemia in newborn rats can establish a reliable animal model of brain injury resulting from neonatal hypoglycemia. [ABSTRACT FROM AUTHOR]

GB virus C (GBV-C) is a blood-borne flavivirus. The prevalence of GBV-C viremia among healthy adults is 0.5% to 4% and, to date, no disease has been definitely associated with GBV-C infection. We conducted a cross-sectional study to evaluate GBV-C viremia prevalence in a group of 327 healthy children with normal alanine amino transferase (ALT) levels (Group A) and elevated ALT levels (Group B) of unknown origin, and among 38 pediatric patients with mother-to-child-transmitted hepatitis C virus (HCV) infection (Group C). No statistically significant differences were observed between prevalences in Groups A and B (2.2% vs 6.7%, p = 0.06). None of the children in Groups A or B who tested positive for GBV-C RNA showed any clinical symptoms. The prevalence of GBV-C viremia in Group A was lower than for patients in Group C (2.2% vs 13.2%, p = 0.007); no differences were observed in HCV infection characteristics between those patients who were co-infected with GBV-C and those who were not. In conclusion, while GBV-C viremia is more frequent among HCV-infected pediatric patients, it is neither associated with liver disease nor has any influence on HCV-related chronic hepatitis. [ABSTRACT FROM AUTHOR]

Alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome; OMIM 203550) is a very rare genetic disorder with distinct features. To our knowledge, there have been four cases documented to date. In addition, another three patients, previously described as having IFAP syndrome (OMIM %308205), may also have ACD syndrome. We report on one patient with short stature, total alopecia, ichthyosis, photophobia, seizures, ectrodactyly, vertebral anomalies, scoliosis, multiple contractures, mental retardation, and striking facial and other features (e.g. microdolichocephaly, missing eyebrows and eyelashes, long nose, large ears) consistent with ACD syndrome. Results of laboratory testing in the literature case reports were normal, although in none of them, array-CGH (microarray-based comparative genomic hybridization) analysis was performed. In conclusion, the combination of specific features, including total alopecia, ichthyosis, mental retardation, and skeletal anomalies are suggestive of ACD syndrome. We propose that children with this syndrome undergo a certain social pediatric protocol including EEG diagnostics, ophthalmological investigation, psychological testing, management of dermatologic and orthopedic problems, and genetic counseling. [ABSTRACT FROM AUTHOR]

Fecal incontinence is a common disorder in children. Many children with fecal incontinence have psychosocial co-morbidity. In this study, the effect of psychosocial co-morbidity on the treatment outcome of children with fecal incontinence was evaluated. One hundred and fifty children with fecal incontinence were treated in a multidisciplinary program. All children had been treated unsuccessfully for at least one year before entering the program. The treatment consisted of laxative treatment, psychosocial interventions, and biofeedback training. Psychosocial co-morbidity was classified according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). One hundred and forty-one children were completely analyzed (102 boys, mean age 9.6 (range 6.5-16.5) years). Of these, 31 (22%) children had fecal incontinence without constipation and 110 (78%) children had fecal incontinence associated with constipation. In 95% of children, at least one psychosocial co-morbidity was present. Treatment was successful at 12 months in 69% of patients. Treatment was less successful in children with attention deficit hyperactivity disorder (ADHD), in children with parent-child relational problems, and in mentally retarded children. The results indicate that the early assessment and treatment of psychosocial co-morbidity might improve treatment response in children with fecal incontinence. Children with fecal incontinence are treated less successfully in the first year if they have ADHD, parent-child relational problems, or mental retardation. Psychosocial evaluation and the early assessment and treatment of psychosocial co-morbidity is indicated in order to improve response rate. Family counseling--aimed at improving parent-child relations--should be an integral part of a multidisciplinary treatment program for fecal incontinence. [ABSTRACT FROM AUTHOR]

This study was an investigation of a possible correlation between either the gestational age (GA) and type of brain injury or between the gestational age and type, distribution and severity of cerebral palsy (CP). Four hundred sixty-one children with a birthweight > or = 1250 g and GA > or = 30 weeks with a complicated neonatal period and/or brain injury on serial cerebral ultrasound were selectively followed at the regional Center for Developmental Disorders. The children were divided into a preterm and term group. There were 40 children with cerebral palsy in the preterm group and 38 children with cerebral palsy in the term group. Various types of brain injury diagnosed by echography were nosologically classified. The type, distribution and severity of cerebral palsy were also registered. The type of brain injury most frequently occurring in the term group was hypoxic-ischemic injury to the basal ganglia (39%), focal ischemia (18%), subcortical hemorrhage (13%) and parasagittal cerebral injury (10%). In the preterm group 39% of the children with cerebral palsy had periventricular leukomalacia, 24% intraventricular hemorrhage and 18% persistent flares. There was a significant correlation between the GA and type of brain injury (P < 0.001; Cramer's V = 0.76) and between the GA and type (P = 0.004; Cramer's V = 0.47) and distribution (P < 0.001; Cramer's V = 0.55) of CP. There was no significant correlation between the GA and severity of CP. The type of brain injury detected by serial ultrasound during the neonatal period, as well as the type and location of CP detected during later childhood, are all GA-dependent in at-risk newborn infants with a birthweight of > or = 1,250 g and GA > or = 30 weeks. [ABSTRACT FROM AUTHOR]

A new human parvovirus, human bocavirus, has recently been identified in respiratory secretions, feces and serum. It is associated with lower and most likely also upper respiratory tract infections. Most commonly reported symptoms are cough, rhinorrhea, expiratory wheezing and fever, and the virus is preferentially detected in young children. We report three children with acute lymphoblastic leukemia who had acute febrile episodes with concomitant detection of human bocavirus in their respiratory secretions. One of them had five consecutive febrile episodes during 6 months, all associated with the presence of human bocavirus at varying viral loads, suggesting prolonged shedding or reactivation of the virus. [ABSTRACT FROM AUTHOR]

Mycoplasma pneumoniae is an important pathogen which causes nervous system disorders during or after the course of a respiratory tract infection. The exact pathogenic mechanism which causes neurological disorders still remains unknown. Although meningoencephalitis and acute disseminated encephalomyelitis are common complications, there are few cases of acute transverse myelitis and isolated abducens nerve palsy associated with M. pneumoniae infection in childhood. The association between ocular myasthenia gravis and M. pneumoniae infection has not been described before. Here, we describe five patients with different nervous system complications associated with M. pneumoniae infection and discuss the pathological features of central nervous system involvement. [ABSTRACT FROM AUTHOR]

Pendred syndrome is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by mutations in the PDS/SLC26A4 gene (OMIM 605646) encoding for pendrin. Hypothyroidism in Pendred syndrome can be--although rarely--present from birth and therefore diagnosed by neonatal screening. The aim of our study was to identify patients with Pendred syndrome among a historical cohort of patients with congenital hypothyroidism (CH) identified by neonatal screening, and to find their mutations in the PDS/SLC26A4 gene. We investigated 197 Czech Caucasian children with CH detected by the neonatal screening between the years 1985 and 2005. The clinical diagnosis of Pendred syndrome was based on the laboratory and sonographic signs of thyroid dyshormonogenesis in association with sensorineural hearing loss. In subjects clinically diagnosed with Pendred syndrome, we sequenced all exons and exon-intron boundaries of the PDS/SLC26A4 gene. Hearing loss was present in 10/197 children with screening-detected CH. Of these, three fulfilled the diagnostic criteria of Pendred syndrome. Two patients were compound heterozygotes for PDS/SLC26A4 mutations: patient 1 carried c.2089+1G>A / c.3G>C and patient 2 carried p.Tyr530His / p.Val422Asp. Two of the four identified mutations were novel (c.3G>C in patient 1 and p.Val422Asp in patient 2). The third patient was free of mutations in the PDS/SLC26A4 gene, representing a phenocopy. In conclusion, our results indicate the rarity of Pendred syndrome as a cause of CH. The identification of two novel mutations expands the spectrum of mutations in the PDS/SLC26A4 gene and emphasizes their marked allelic heterogeneity. [ABSTRACT FROM AUTHOR]

A 6-week-old child presented with hypotonia, myopathy, and a rapidly worsening dilated cardiomyopathy with severe atrial and ventricular arrhythmias and pulmonary hypertension, which proved fatal at age 3 months. Biochemical analysis showed a combined deficiency of the enzymatic activities of complexes I and IV and molecular studies identified a T14709C mutation in the mitochondrial tRNA glutamic acid gene. A review of symptomatology in patients with this mutation shows that it mainly presents in childhood or young adults with mild myopathy and diabetes mellitus. Infants with a high, nearly homoplasmic mutant load can present with more severe symptoms including cardiomyopathy. Families with this mitochondrial DNA mutation should be aware that increased mutant load in a subsequent generation may result in severe and often fatal cardiac symptoms. [ABSTRACT FROM AUTHOR]

Background: Findings have been inconsistent regarding the effect of T1DM (type 1 diabetes) on age at menarche.Objective: The purpose was to investigate in young German women with T1DM menarcheal age and factors potentially affecting menarche, including glycemic control, BMI (body mass index), relative T1DM duration (proportion of life with diabetes), insulin dose, and insulin therapy intensity. Initiated in 1990, the DPV program is an ongoing, prospective long-term longitudinal follow-up study to benchmark the quality of care provided to pediatric and, more recently, adult diabetes patients. Two hundered two German diabetes centers participated in nationwide data collection. Based on ethnicity and the availability of menarche and T1DM onset data as the main inclusion criteria, 643 young German women were selected from 11,629 female T1DM patients aged <20 years, recruited by referral, clinic or hospital ascertainment, or self report. Mean age at menarche (+/-SD) was 13.22 +/- 1.31 years, representing a delay of 0.52 years (p < 0.001) relative to the general population. Significant delay (p < 0.05) was also found for relative T1DM duration, BMI SD score, insulin dose, and HbA1c level, with a 1% increase in HbA1c resulting in a delay in menarche by 0.07 years.Conclusions: Age at menarche is delayed in type 1 diabetes mellitus. The delay increases with relative T1DM duration and poor quality of glycemic control. [ABSTRACT FROM AUTHOR]

Our aim was to compare intrapleural streptokinase (SK) treatment and simple tube drainage in the treatment of children with complicated parapneumonic pleural effusion. A retrospective review of medical records included patient demographics, clinical presentation, biochemical and microbial studies of pleural effusion, radiographic evaluation of chest tube drainage, use of fibrinolytic agents and type of surgical intervention. During the 2.5-year period (1999-2002), 53 children (29 M, 24 F) with complicated parapneumonic effusions or empyema were identified. Closed tube drainage and antibiotic treatment were administered to patients with a diagnosis of complicated parapneumonic effusion (n = 24) until October 2000; after that time point, intrapleural streptokinase was added to this regimen (n = 29). The median age at the time of presentation was 2.5 years (range: 5 months-14.6 years). There were no significant differences in terms of clinical outcomes between the two groups. The average length of hospital stay was 19.1 +/- 5.5 and 21.9 +/- 11.2 days for the drainage and streptokinase groups, respectively; the time to afebrile state after admission was 5.8 +/- 4.1 and 7.6 +/- 7.5 days. The percentage of patients who eventually required surgical intervention was 8.3% for the drainage group and 20.6% for the streptokinase group. In conclusion, in the treatment of complicated parapneumonic effusions or empyema, the adjunctive treatment with intrapleural SK does not significantly reduce durations of fever, chest tube drainage and hospital stay, and the need for surgery, regardless of the stage of the disease, compared to simple closed tube drainage. [ABSTRACT FROM AUTHOR]

Opisthotonus is a relatively rare, but challenging neurological symptom of spasticity or dystonia that most often results from a dramatic event such as near-drowning. The classic treatment option for opisthotonus is the oral administration of medication such as benzodiazepines and baclofen. However, results with these medications are usually not very beneficial. Numerous studies however have shown that intrathecal treatment with baclofen (ITB) is an efficient and safe treatment for generalized therapy-resistant spasticity, even in children. In this retrospective study, we describe 11 children (mean age 9 years) with pronounced opisthotonus and quadriplegia caused by different types of acquired lesions who were treated with intrathecal baclofen. Results show that in addition to an expected decrease in muscle tonus, there was also a clear improvement in patient comfort and nursing. A remarkable weight gain was observed in most patients, even when calorie intake did not change. This increase in weight might be due to a reduction in energy expenditure as a result of the decrease in spasticity. Intrathecal treatment with baclofen should be considered in every child with opisthotonus. [ABSTRACT FROM AUTHOR]

There are conflicting reports regarding the association of Helicobacter pylori ( H. pylori) infection with growth failure. We evaluated the role of H. pylori infection on malnutrition and growth failure in dyspeptic children. The study cases included 108 dyspeptic children and were evaluated by endoscopic gastric biopsy, while 50 healthy children constituted the control group. The study cases were grouped as H. pylori [+] ( n = 57) and H. pylori [−] ( n = 51) by the presence or absence of microorganism in gastric tissue, respectively. Age, gender, height for age (H/A), weight for height (W/H), body mass index (BMI), weight and height z scores and the daily calorie intake of the children were recorded. Malnutrition and growth failure were evaluated by the Waterlow criteria and height z score, respectively. Then, the H. pylori [+], H. pylori [−] and control groups were compared in relation to the variables defined above. All groups were similar with respect to gender and age. The daily calorie intake was lower in dyspeptic children. Although anthropometric variables were similar in the H. pylori [+] and [−] groups, the control cases had higher W/H compared to both H. pylori [+] ( p = 0.030) and H. pylori [−] ( p = 0.000) cases, and higher BMI ( p = 0.001) and weight z scores ( p = 0.014) than those in the H. pylori [−] group. The malnutrition rate was similar in the H. pylori [+] and [−] groups. However, mild acute ( p = 0.033) and general malnutrition rates ( p = 0.000) were lower in the control cases compared to the study cases. The short stature rate was not different significantly in all three groups. In conclusion, the results of this study do not support the data that H. pylori infection plays an extra role in malnutrition and growth failure in children presenting with dyspeptic complaints. However, as a major cause of dyspepsia, H. pylori infection might be considered to cause malnutrition secondary to decreased calorie intake associated with dyspepsia. [ABSTRACT FROM AUTHOR]

Aplasia cutis congenita, congenital absence of a localized area of skin, usually on the vertex of the scalp, occurs as an isolated defect, or with one or more other congenital anomalies as part of a syndrome, sequence or association. To date, more than 500 cases have been reported. A more severe and extensive form, almost complete absence of skin and subcutaneous tissue, was reported by Park et al. in 1998 [J Med Genet 35:609-611]. Until now, no other such lethal case has been reported. Here, we report the second case of systemic aplasia cutis congenita. The female was born without any skin at all, and with hypoplastic lungs, syndactyly, skull defect, esophageal atresia, intestinal malrotation, and calcifications of the hepatic capsule, as well as with other anomalies. She died about 12 hours after birth probably due to dehydration. On microscopic examination, the external surface of the body showed complete absence of the epidermis. Muscle fibers were thin. There was no evidence of skin appendages. The present case gives strong support to the suggestion that systemic aplasia cutis congenita is a newly recognized syndrome. More cases will have to be reported and studied in order to understand the etiology and establish diagnostic criteria. Thus, it is our conclusion that systemic aplasia cutis congenita might be a newly recognized syndrome. [ABSTRACT FROM AUTHOR]

Unlabelled: Hypertrophic osteoarthropathy (HOA) is characterized by clubbing, periosteal new bone formation and polyarthritis. The pathogenesis of clubbing involves an increased expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) from the digitally lodged platelet clumps, which bypass the pulmonary capillary network as a result of various systemic disorders. Intrathoracic neoplasms are rare causes of HOA in children. We report here a 14-year-old boy with digital clubbing, who eventually received the diagnosis of intrathoracic Hodgkin lymphoma (HL) and HOA. Eight cases previously reported with these two diagnoses are reviewed to emphasize the prognostic significance of HOA in childhood HL.Conclusion: Given the pathogenesis of clubbing and the prognostic significance of HOA, intrathoracic disease should be considered when HOA is detected in a child with a known or suspected malignant disease, and the occurrence of HOA during follow-up should alert the physicians for possible recurrence of the neoplastic disease or intrathoracic involvement. [ABSTRACT FROM AUTHOR]

It is difficult to prevent hyperammonaemia in patients with urea cycle disorders that present in the newborn period. This is true, even if treatment is started prospectively because of an affected relative. We propose several additional measures that could be used in conjunction with conventional therapy to improve the metabolic control. Catabolism could be reduced by delivering the babies by elective caesarean section, by starting intravenous glucose immediately after delivery and, possibly, by using beta-blockers or octreotide and insulin. The effectiveness of sodium benzoate and sodium phenylbutyrate might be increased by giving phenobarbital to the mother before delivery and subsequently to the baby to induce the enzymes for conjugation. We would expect the proposed measures to reduce the risk of hyperammonaemia and to improve the outcome for these patients. They have not, however, previously been used in this context, so families would need to be counselled carefully and controlled studies should be undertaken. [ABSTRACT FROM AUTHOR]

Anomalous left coronary artery from pulmonary artery (ALCAPA) is a rare congenital cardiac malformation. It presents predominantly in infancy with features of myocardial ischaemia or cardiac failure and may be mistaken for common paediatric conditions such as colic, reflux or bronchiolitis. With early surgical correction the prognosis is good, but awareness of this condition is essential for prompt diagnosis and referral to a tertiary cardiac centre. In this report we review the five cases that presented during our 5-year study period and discuss the incidence and clinical presentation of ALCAPA among infants. Our observed incidence of 1 in 4243 live births--0.023%--is higher than previously reported. ALCAPA may be more common than previously recognised, and there should be a high index of awareness among paediatricians, paediatric trainees and general practitioners to enable early surgical intervention and improved prognosis for these children. [ABSTRACT FROM AUTHOR]

Gomez-Lopez-Hernandez syndrome is a very rare genetic disorder with a distinct phenotype (OMIM 601853). To our knowledge there have been seven cases documented to date. We report on an additional male patient now aged 15 8/12 years with synostosis of the lambdoid suture, partial scalp alopecia, corneal opacity, mental retardation and striking phenotypic features (e.g., brachyturricephaly, hypertelorism, midface hypoplasia and low-set ears) consistent with Gomez-Lopez-Hernandez syndrome. In early childhood the patient demonstrated aggressive behavior and raging periods. He also had seizures that were adequately controlled by medication. Magnetic resonance imaging (MRI) revealed rhombencephalosynapsis, i.e., a rare fusion of the cerebellar hemispheres, also consistent with Gomez-Lopez-Hernandez syndrome. In addition a lipoma of the quadrigeminal plate was observed, a feature not previously described in the seven patients reported in the literature. Cytogenetic and subtelomere analyses were inconspicuous. Microarray-based comparative genomic hybridization (array-CGH) testing revealed five aberrations (partial deletions of 1p21.1, 8q24.23, 10q11.2, Xq26.3 and partial duplication of 19p13.2), which, however, have been classified as normal variants. Array-CGH has not been published in the previously reported children. The combination of certain craniofacial features, including partial alopecia, and the presence of rhombencephalosynapsis in the MRI are suggestive of Gomez-Lopez-Hernandez syndrome. Children with this syndrome should undergo a certain social pediatric protocol including EEG diagnostics, ophthalmological investingation, psychological testing, management of behavioral problems and genetic counseling. [ABSTRACT FROM AUTHOR]

Unlabelled: Successful therapy of vasodilatory shock in adults and children with arginine-vasopressin (AVP) has been reported previously. Data on the use of vasopressin in neonates is limited. This retrospective study reports the effects of AVP-treatment in neonates with catecholamine-resistant systemic vasodilatation after cardiopulmonary bypass. From March 2003 through December 2005, 172 neonates underwent open-heart surgery, 17 developed vasopressor-resistant hypotension and were treated with AVP. Thirteen patients had a stage I palliation of single ventricle, two had a Ross-operation and two had an arterial switch operation. All patients received multiple traditional inotropes and vasopressors prior to administration of AVP. AVP was started at median 0.0001 U x kg(-1) x min(-1) (range 0.00005-0.0002) and titrated up to a maximum of median 0.0003 U x kg(-1) x min(-1) (range 0.0001-0.001). AVP led to a significant increase in blood pressure (from 49+/-8 mmHg to 69+/-7 mmHg) and the requirement of traditional vasopressors decreased significantly. No peripheral vasoconstriction or ischemia was observed. Four of 13 patients, all with single ventricle palliation, died. In two patients death occurred due to additional complications 6 days after AVP was discontinued. One patient, who was still on AVP, died 42 hours postoperatively after prolonged hypoxemia not responding to inhaled nitric oxide. One patient arrested on the third postoperative day when AVP was almost weaned.Conclusion: In neonates with vasodilatory shock after cardiopulmonary bypass AVP is a potent agent to increase blood pressure when traditional vasopressors are failing. [ABSTRACT FROM AUTHOR]

The article describes the case of a now 5 1/2 year old girl who was diagnosed with Schimke immunoosseous dysplasia complicated by pulmonary embolism at the age of 3 1/2 years. At the age of 5 1/2 years, the patient developed fulminant respiratory insufficiency within a day and died with signs of pulmonary edema. Pulmonary embolism in the girl might be caused by the combination of vascular affection and hypercoagulopathy of nephrotic syndrome in Schimke immunoosseous dysplasia.

Hypopituitarism has been increasingly recognised following traumatic brain injury. We report four children involved in motor vehicle accidents who had traumatic brain injury-mediated hypopituitarism. Various hormone defects are described. Growth hormone was the most commonly affected pituitary hormone. The time interval between the injury and diagnosis of pituitary hormone deficiency was between 2.5 weeks to 1.5 years. Hormone replacement therapy permitted normal completion of growth and development. Awareness among physicians treating children with traumatic brain injury of the risk of hypopituitarism is necessary to optimise the outcome. [ABSTRACT FROM AUTHOR]

Analysis of the recovery period following physical exercise has gained importance in evaluating cardiopulmonary capacity, not only in athletes but also in patients with proven or suspected heart failure. The purpose of this study was to apply these methods to long-term survivors of acute lymphoblastic leukemia (ALL) in childhood, who are at risk of developing anthracycline-induced cardiomyopathy. Nine children (mean age 12 years) and 10 adults (mean age 24 years) were included in the study after treatment for childhood ALL. Recovery of oxygen uptake and heart rate following maximal spiroergometric exercise was compared to that in 29 trained and untrained age-matched controls. The change in oxygen uptake (DeltaVO2) and heart rate (DeltaHR) between maximal effort and 60 s of recovery did not differ significantly, either between children after oncological therapy (DeltaVO2: 14.95 ml/kg, DeltaHR: 35 bpm) and healthy children (DeltaVO2: 15.85 ml/kg, DeltaHR: 37 bpm), or between adult former oncological patients (DeltaVO2: 13.1 ml/kg, DeltaHR: 27 bpm) and untrained adults (DeltaVO2: 15.7 ml/kg, DeltaHR: 31 bpm). There was, however, a significant difference in DeltaVO2 between trained adults (DeltaVO2: 24.5 ml/kg) and both untrained adult controls (DeltaVO2: 15.7 ml/kg, p=0.004) and adult patients (DeltaVO2: 13.1 ml/kg, p=0.0002). This difference was not detected for heart rate. In conclusion, the recovery period did not reveal a discernible difference in cardiopulmonary capacity between former ALL patients and untrained age-matched controls. We did confirm that heart rate and oxygen uptake recovery serve as indicators of physical fitness. [ABSTRACT FROM AUTHOR]

Patients with phagocytic, cellular, combined and other primary immunodeficiencies exhibit immune deficits that confer increased susceptibility to fungal infections. A number of yeasts and moulds, most commonly Candida and Aspergillus but also Cryptococcus, Histoplasma, Paecilomyces, Scedosporium, Trichosporon, Penicillium and other, rarely isolated, fungal organisms, have been variably implicated in causing disease in patients with chronic granulomatous disease, severe combined immunodeficiency, chronic mucocutaneous candidiasis, hyper-IgE syndrome, myeloperoxidase deficiency, leukocyte adhesion deficiency, defects in the interferon-gamma/interleukin-12 axis, DiGeorge syndrome, X-linked hyper-IgM syndrome, Wiskott-Aldrich syndrome and common variable immunodeficiency. Differences in the spectrum of fungal pathogens as well as in the incidence and clinical presentation of the infections may be observed among patients, depending upon different immune disorders. Fungal infections in these individuals may occasionally be the presenting clinical manifestation of a primary immunodeficiency and can cause significant morbidity and potentially fatal outcome if misdiagnosed or mistreated. A high degree of suspicion is needed and establishment of diagnosis should actively be pursued using appropriate imaging, mycological and histological studies. A number of antifungal agents introduced over the last fifteen years, such as the lipid formulations of amphotericin B, the second-generation triazoles, and the echinocandins, increase the options for medical management of these infections. Surgery may also be needed in some cases, while the role of adjunctive immunotherapy has not been systematically evaluated. The low incidence of primary immunodeficiencies in the general population complicates single-center prospective or retrospective clinical studies aiming to address diagnostic or therapeutic issues pertaining to fungal infections in these patients. [ABSTRACT FROM AUTHOR]

Background: Besides profound hypoglycemia with hyperlacticemia, glycogen storage disease type Ia (GSD Ia) presents hypertriglyceridemia that is often resistant to dietary treatment with cornstarch. The present study aimed to evaluate the effects of medium-chain triglycerides (MCT)--which are absorbed via the portal vein without being incorporated into chylomicrons--on hypertriglyceridemia and to explore otherwise metabolic changes in children with GSD Ia.Patients and Methods: A 13-year-old boy with GSD Ia who received a dietary treatment with MCT milk after cornstarch administration and two infants also with GSD Ia, ages 6 and 7 months, who received MCT milk after carbohydrate-rich, lipid-poor milk were enrolled. In addition to serum glucose and lactate levels, serum levels of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol were serially determined. Simultaneously, serum levels of total carnitine, free carnitine, acylcarnitine, and ketone bodies were determined to evaluate fatty acid beta-oxidation.Results: Mean glucose level (mmol/l) of patient 1 remained stable, the value being around 4.5, while those of patients 2 and 3 increased to this level from 4.00 and 3.72, respectively. Lactate levels were significantly decreased in all patients. Mean triglyceride levels (mM) of patient 1 decreased from 3.00 to 2.05. Also, triglyceride levels of patients 2 and 3 decreased from 2.74 and 3.15 to 2.13 and 2.70, respectively. HDL cholesterol, acylcarnitine, and ketone body levels increased in all patients after MCT administration, while total and free carnitine levels decreased.Conclusion: We describe here the beneficial effects on lipid and carbohydrate metabolisms in three Japanese children with GSD Ia. In light of the unfavorable influence of lipid restriction on growth and development in infancy, dietary treatment with MCT milk may be a better treatment for infants with GSD Ia. Further investigation should be required to confirm the efficacy of MCT milk in GSD Ia. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a disorder with unclear etiology and pathogenesis characterized by abnormal clonal proliferation and accumulation of antigen presenting Langerhans' cells at various tissues and organs. Almost all organs or systems may be involved, and the prognosis depends on the involved sites and the presence of organ dysfunction. Thyroid tissue is a rarely affected site in children, and without histopathological evaluation it may be difficult to distinguish from other thyroid disorders because of the similar physical examination, laboratory and imaging findings. Here we report on two patients with histopathologically proven thyroid involvement of LCH. Additionally, the differential diagnosis of diffusely enlarged or multinodular thyroid glands in children is discussed, and a review of the literature of thyroid involvement in LCH is given. In the differential diagnosis of enlarged thyroid glands, especially in the presence of other endocrinological manifestations, LCH must be taken into consideration. [ABSTRACT FROM AUTHOR]

We report on a 6-year-old boy with chronic granulomatous disease (CGD) complicated by chronic inflammatory reactions with formation of large pulmonary granuloma as well as intracerebral lesions. Bone marrow transplantation (BMT) from an unrelated donor led to stable reconstitution, to rapid resolution of pulmonary granuloma, and to rapid resolution of intracerebral lesions. [ABSTRACT FROM AUTHOR]

Despite its incidence, there are still few reports in literature relating to tinnitus in children. Almost all data were collected by means of questionnaires or in a limited population of children. In order to collect data in a homogeneous way and directly from the patients, the protocol of study proposed by Savastano has been applied to 1,100 children. The results showed tinnitus as present in 374 children but only 6.5% of the cases complained spontaneously about it. In all, 76.4% of the children demonstrated normal hearing, whereas 64.5% reported being bothered by their tinnitus. Tinnitus measurements were obtained and are reproducible in all patients older than 8 years of age. The loudness level was <10 dB in 48.6% of cases, which was higher than 10 dB in 51.4%. As for the frequency distribution, in most cases it appears to be between 0 and 1,000 Hz. There is a correspondence between the loudness level and masking level. A total inhibition of <60 s for most children with lower loudness was obtained. The present study demonstrates that the application in the infancy of a specific protocol of study allows the presence of tinnitus to be discovered, giving specific and detailed information about it so as to minimize its damage to be obtained. Moreover, for the first time, data regarding the measurement of tinnitus in childhood has been gathered. [ABSTRACT FROM AUTHOR]

Despite being one of the most common congenital defects in boys, the etiology of hypospadias remains largely unknown. In this case-referent study, we evaluated a wide spectrum of potential risk factors for hypospadias. Cases were identified from the hospital information system, and referents were recruited through the parents of the cases. Both parents of cases and referents completed written questionnaires that they received through the mail. Logistic regression analyses were used to assess the independent contribution of different factors to the risk of hypospadias. The final database included 583 cases and 251 referents. Hypospadias more often occurred in children whose father had hypospadias (OR=9.7; 95%CI: 1.3-74.0) and in children with a low birth weight (OR=2.3; 95%CI: 1.2-4.2). Indications for elevated risks were found when mothers were DES-daughters (OR=3.5; 95%CI: 0.8-15.6), fathers were subfertile (OR=1.8; 95%CI: 0.7-4.5), the parents had undergone fertility treatment (OR=2.3; 95%CI: 0.9-5.8), and in twin or triplet pregnancies (OR=2.0; 95%CI: 0.8-5.1). Maternal use of iron supplements (OR=2.2; 95%CI: 0.8-6.0), maternal smoking (OR=1.5; 95%CI: 1.0-2.4), paternal prescriptive drug use (OR=2.6; 95%CI: 1.1-6.6), and paternal exposure to pesticides (OR=2.1; 95%CI: 0.6-7.1) during the 3 months immediately prior to conception or in the first trimester of pregnancy also appeared to increase the risk of hypospadias. The associations found in this study support the hypothesis that genetic predisposition, placental insufficiency, and substances that interfere with natural hormones play a role in the etiology of hypospadias. [ABSTRACT FROM AUTHOR]

An association between early-onset neonatal Group B streptococcal (GBS) sepsis and subsequent diagnosis of late-onset diaphragmatic hernia has been reported. We report one such case and review the literature. The index case involved a male preterm neonate in whom late-onset right diaphragmatic was diagnosed on day 21 following early-onset GBS sepsis. Our literature review identified 40 cases of such an association. The typical description involves near term male neonates, who improved from an early-onset GBS sepsis only to have a secondary respiratory deterioration leading to the diagnosis of late-onset right diaphragmatic hernia. With surgical repair, this condition has an excellent survival rate. In conclusion, the pathophysiological mechanisms underlying the association remain to be elucidated. Awareness of the associated pleural effusion is important to avoid inadvertent organ injury due to chest drains. [ABSTRACT FROM AUTHOR]

The intentions of our investigation were (1) to search for atherogenic risk factors and signs of incipient atherosclerosis in children and adolescents with type 1 diabetes (T1DM) in comparison to well-matched control subjects, (2) to evaluate risk factor associations with carotid intima media thickness (cIMT) in diabetic patients and control subjects, and (3) to acquire a better knowledge of early atherogenesis in children and adolescents with and without T1DM. 94 diabetic children (age median 12.3 years, HbA1c median 7.7%) and 40 non-diabetic controls (age median 12.3 years) were investigated. Mean cIMT was determined using high-resolution B-mode ultrasound with an automated contour identification procedure. Compared to controls, subjects with diabetes had significantly elevated cIMT (p = 0.041) and systolic BP (p = 0.007) but showed a less atherogenic lipid profile. Most markers of inflammation, endothelial function and fibrinolytic activity were higher in diabetic subjects than in controls. Multiple linear regression analysis revealed a significant relationship (r = 0.53, p = 0.036) between bilateral mean cIMT and diverse risk factors in patients with T1DM. Spearman rank correlation showed that diabetes duration (rho = 0.32, p = 0.029), systolic BP (rho = 0.32, p = 0.004), weight (rho = 0.257, p = 0.022), and height (rho = 0.265, p = 0.018) significantly correlated with bilateral mean cIMT in the 94 diabetic patients. In conclusion, in well-controlled type 1 diabetic children systolic BP may be of greater importance than dyslipidaemia in early atherogenesis. BMI, markers of sustained inflammation, endothelial dysfunction and fibrinolytic activity are increased in diabetic versus non-diabetic children but none of them correlates significantly with cIMT. Their prognostic value remains to be determined. [ABSTRACT FROM AUTHOR]

Recent improvements in perinatal management have improved the prognosis in patients with severe congenital diaphragmatic hernia (CDH). However, in surviving patients with severe CDH, hearing loss has sometimes been reported to occur during the follow-up period. Although some of the risk factors for developing sensorineural hearing loss (SNHL) have been reported in CDH, no definitive risk factors have yet been reported. We, therefore, investigated the risk factors regarding postnatal management in patients with severe CDH. In 16 surviving patients with severe CDH, which had all been detected antenatally, and whose lung-to-thoracic ratio was less than 0.2, four patients demonstrated late onset SNHL, which occurred between 1.5 and 5 years of age. The risk factors for SNHL regarding the postnatal treatment for CDH were analyzed between the four patients with SNHL and the remaining 12 patients without SNHL, regarding such factors as the use of ototoxic drugs, neuromuscular blocking agents, high-frequency oscillation (HFO), and inhaled nitric oxide, the duration of hypocapnia, hypoxia, severe acidosis, severe alkalosis, and mechanical ventilation. In addition, the types of neuromuscular blocking agents were also analyzed, including the administration of pancuronium bromide (PB) and vecuronium bromide (VB). The patients with SNHL were found to have a significantly higher risk than the patients without SNHL regarding the duration of loop diuretics usage and the duration of usage of both mechanical ventilation and HFO. Furthermore, all four patients with SNHL used PB. In contrast, none of the five patients using VB developed SNHL The duration and cumulative dose of PB used in the patients with severe CDH showed a significant correlation to the occurrence of SNHL. Although this study was retrospective, based on our data, the prolonged use of PB, in addition to the duration of treatment by loop diuretics, mechanical ventilation, and HFO usage, might, thus, be suggested to be a possible risk factor for late onset SNHL in patients with severe CDH. [ABSTRACT FROM AUTHOR]

X-linked lymphoproliferative disease is a rare T and NK cell immune deficiency which most frequently presents as fulminant infectious mononucleosis following infection with the Epstein-Barr virus (EBV). We report the case of a 4-year-old boy from a Spanish family presenting with severe infectious mononucleosis. In the course of the disease he developed hepatic failure, pancytopenia and neurologic impairment, leading to death after less than 2 months. The results of bone marrow biopsy and autopsy indicated a histological diagnosis of both high-grade B-cell lymphoma and virus-associated haemophagocytic syndrome, thereby confirming the simultaneous presence of two different manifestations of X-linked lymphoproliferative disease (XLP) in this patient. The family history revealed four close male relatives dying under similar circumstances, one of whom died following a vaccination against measles. Molecular genetic studies identified a novel mutation in the SH2D1A gene in several members of the family, establishing the diagnosis of XLP. Fatal EBV infection in male infants is highly indicative of XLP. Virus-associated haemophagocytic syndrome and B-cell lymphoma can occur concomitantly and may be difficult to distinguish due to their similar histological pictures. [ABSTRACT FROM AUTHOR]

A single, 2 g/kg dose of immune globulin (IG), denoted 2 g-intravenous (IV)IG, has become a standard regimen for treating Kawasaki disease (KD) because of its highly preventive effect on coronary arterial lesions (CAL). However, IG is obtained from blood specimens, a drawback to many patients, and is also very expensive. This randomized prospective study reported here was carried out with the aim of developing a treatment regimen that would reduce the total dose of IG. The study tested two protocols (A: 2 g-IVIG; B: 1 g-IVIG) that included the strategy of administering additional IVIG to IVIG-resistant patients based on the criteria we described previously. In protocol A, an additional 2 g-IVIG was administered only once; in protocol B, the first additional IVIG was 1 g-IVIG and the second was 2 g-IVIG. One hundred and nine patients who were admitted before the seventh day of illness and had no CAL at the time of admission were enrolled in the study (protocol A: 54 patients; B: 55 patients). In the protocol A group, 7.4% (4/54) of the patients received 4 g/kg IG. In protocol B, 41.8% (23/55) were treated only with 1 g/kg IG, and 10.9% (6/55) received 4 g/kg IG. No significant differences were observed between the patients of the two subgroups receiving 4 g/kg IG in each protocol group. Discriminate analysis also suggested that 52.4% of the patients in the protocol A group could be treated only with 1 g/kg IG. On the other hand, no significant difference was observed in the incidence of aneurysms between patients in the protocol A group (1/54) and those in the protocol B group (4/55). Our protocol based on 1 g-IVIG, including additional IVIG, was assessed to be an effective treatment and to provide a considerably useful means to reduce the total dose of IG. [ABSTRACT FROM AUTHOR]

Introduction: Otitis media with effusion is one of the most frequent diseases in children, and its management requires the attention of general practitioners, pediatricians and ear, nose and throat (ENT) surgeons. The main complications associated with tympanostomy tube insertion, are: (1) purulent otorrhea (10-26% of cases), in which local otic preparations might be effective, and biofilm-resistant tubes may decrease this complication in the future; (2) myringosclerosis (39-65% of operated ears), with usually no serious sequelae; (3) segmental atrophy (16-75% of cases); (4) atrophic scars and pars flaccida retraction pockets (28 and 21% of operated ears, respectively); (5) tympanic membrane perforations (3% of cases, although with T-tubes, the incidence may be as high as 24%); (6) cholesteatoma (1% of cases), although tympanostomy tubes may sometimes prevent, rather than contribute to its development; (7) granulation tissue (5-40% of instances), when the duration of tube retention is prolonged.Conclusion: It would appear that the complications associated with tympanostomy tube insertion are more frequent than anticipated, reaching 80% of operated ears under specific circumstances and in certain subgroups of children. These complications may resolve with conservative management, but in persistent cases surgical removal of the tubes is mandatory. [ABSTRACT FROM AUTHOR]

Brachytelephalangic chondrodysplasia punctata (CDPX1, OMIM: #302950) is a rare congenital skeletal dysplasia caused by arylsulfatase E deficiency (OMIM: #300180). Although the symptoms are usually mild, severe spinal cord compression by dysplastic vertebras may develop. We report four new cases with severe cervical spinal canal narrowing documented by radiography, magnetic resonance imaging (MRI), and autopsy. In all, nine cases of CDPX1 with severe cervical spinal cord compression have now been described. Because these cases account for a large proportion of all reported CDPX1 cases, we believe that an antenatal suspicion of CDPX1 should lead to genetic counseling and to investigations for spinal cord compression. After birth, this complication must be routinely anticipated, and we suggest spinal MRI in all CDPX1 infants. Unless spinal cord compression is confidently ruled out, we recommend that these newborns receive the same care as trauma patients suspected of craniocervical junction disruption. [ABSTRACT FROM AUTHOR]

Opsoclonus-myoclonus syndrome (OMS) in children is a rare neurological condition with opsoclonus, myoclonus, ataxia and irritability in the first 2 years of life. It can be idiopathic, parainfectious, or paraneoplastic with tumours of the neural crest. Few studies of long-term follow-up after OMS have been published. We investigated the motor, cognitive and behavioural outcome of ten patients (eight girls and two boys) seen between 1987 and 2002. We reviewed the records and reassessed the patients. A ganglioneuroma was found in one patient and a neuroblastoma in another. Tumour resection did not influence the OMS. The age at diagnosis was 10-24 months and the follow-up period 1-17 years (average 6.5 years). The interval between the first signs and symptoms and starting treatment was 2-12 weeks: treatment consisted of different immunosupressants. Remission was achieved within 5 months in seven, and relapses were present in seven of ten. At follow-up, only one child had mild ataxia. IQ testing was performed in nine with scores below 75 in four and above 85 in four. Attention deficit and visuomotor difficulties led to school problems with special needs, also in those three children with normal IQs. Only two children were attending regular schools. Behavioural problems were reported in seven, and speech difficulties were present in five. In conclusion, the long-term outcome in our patients with OMS was dominated by cognitive and behavioural problems and not by ataxia. Compared with previous reports, our patients were treated earlier. Larger studies and uniform treatment protocols are needed to demonstrate whether early and prolonged immunosupressant therapy has a favourable influence on outcome. [ABSTRACT FROM AUTHOR]

Introduction: Tufting enteropathy (intestinal epithelial dysplasia), a rare congenital enteropathy, presents in the first few months of life with chronic watery diarrhoea and impaired growth. The molecular basis for this condition is not known. We report our experience with a case of tufting enteropathy that developed an unusual skeletal dysplasia with an abnormal blood picture. After extensive investigations including repeated gastrointestinal endoscopies and biopsies, the diagnosis of tufting enteropathy was made. During the third year of her life, the patient's height was static. A full skeletal survey was performed and demonstrated features of generalised skeletal dysplasia, some of them consistent with those of parastremmatic dwarfism. At the age of five years, she developed Coomb's positive haemolytic anaemia and thrombocytopenia with a negative auto-antibody screen including anti-enterocyte antibodies.Conclusion: There might be generalised matrix (including cartilage matrix protein), basement membrane abnormalities or both. A secondary protein leak might occur in the intestine with autosensitisation and development of autoimmune phenomena. More molecular research is needed to identify a possible link. [ABSTRACT FROM AUTHOR]

Cochlear dysplasia is a rare congenital anomaly. However, early detection of this anomaly can prevent serious consequences. We describe three cases of cochlear dysplasia that presented with recurrent meningitis and cerebro-spinal fluid (CSF) leak in children in which early diagnosis prevented further complications. [ABSTRACT FROM AUTHOR]

Failure to thrive, feeding difficulties, variable forms of infantile epilepsy or psychomotor developmental delay and hypotonia were the most frequent clinical disease presentations in eight children with combined oxidative phosphorylation enzyme complex deficiencies carrying mutations in the polymerase gamma (POLG1) gene. Five out of eight patients developed severe liver dysfunction during the course of the disease. Three of these patients fulfilled the disease criteria for Alpers syndrome. Most children showed deficiencies of respiratory chain enzyme complexes I and III, in combination with complex II, complex IV and/or PDHc in muscle, whereas in fibroblasts normal enzyme activities were measured. All children carried homozygous or compound heterozygous mutations in the POLG1 gene, including two novel mutations in association with mtDNA depletion. Conclusion We suggest performing POLG1 mutation analysis in children with combined oxidative phosphorylation deficiencies in muscle, even if the clinical picture is not Alpers syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Nephrotic children are prone to develop thromboembolic complications secondary to an acquired hypercoagulable state. Cerebral sinovenous thrombosis (CSVT) is increasingly recognised in this population, but clinical characteristics and outcome are not well documented.Patients and Methods: The database of the Canadian Pediatric Ischemic Stroke Registry (Toronto Site) containing prospectively enrolled children from 1992-2004 with CSVT identified four children with NS. A pooled literature analysis retrieved 17 additional cases reports.Results: CSVT presented in the majority of cases during the first flare or within 6 months after the onset of NS and was found to occur more often in SSNS/SDNS (n=13) than in SRNS (n=4). Clinical manifestations were non-specific and consisted primarily of seizures (n=8) and signs of raised intracranial pressure (n=16). Imaging studies revealed a predilection for superior sagittal sinus involvement (n=21) and rare parenchymal lesions (n=4). The most consistent biological risk factors were a severe hypoalbuminaemia (n=14) and, to a lesser extent, decreased antithrombin (AT) levels (n=9/16). Deficiency of other coagulation inhibitors (protein S, protein C) was not identified. Inherited thrombophilia was documented in a single case, suggesting that acquired, more than genetic, coagulation factors are involved. Anticoagulation was safe, and the outcome was good in most patients, and no recurrence of thrombotic event was reported.Discussion: In conclusion, CSVT is now a well-described complication of NS with potential morbidity. A high index of suspicion is required, especially in young children with NS presenting neurological symptoms. Reliable biological predictors of CSVT are lacking. [ABSTRACT FROM AUTHOR]

Introduction: We performed a prospective, multicentre study in children with Guillain-Barré syndrome (GBS), diagnosed according to international criteria, to investigate the frequency and aetiology of antecedent diseases. All infections and vaccinations occurring within a 6-week period prior to the onset of GBS were documented.Materials and Methods: Stool cultures, standardised serological investigations and PCR analyses for 24 different infective agents were performed. Serological findings were regarded as significant if specific immunoglobulin (Ig)M or IgA antibodies were detected, if the IgM enzyme immunoassay or immunfluorescence assay findings were confirmed by immunoblot, if complement fixation test titres rose fourfold or if geometric titres were more than threefold higher than in uninfected control persons. Ninety-five children with GBS were included in the study over a 40-month period. Preceding events were reported in 82%.Results: Microbiological studies carried out on 84 patients resulted in a probable diagnosis in 46 (55%). Coxsackieviruses (15%), Chlamydia pneumoniae (8%), cytomegalovirus (7%) and Mycoplasma pneumoniae (7%) were the most frequently involved agents. Serological evidence of a Campylobacter jejuni infection was found in six patients (7%). Eight children had been vaccinated during the 6 weeks preceding the onset of GBS; in six of these children concomitant infectious diseases were reported, and in one child the time between vaccination and GBS was extremely short.Conclusion: We conclude that, in contrast to adults, Campylobacter spp. does not seem to play a major role in childhood GBS in German-speaking countries. The aetiology of antecedent diseases is distributed over a wide spectrum of paediatric infectious diseases. Most of the children who had been vaccinated showed concomitant infectious diseases, thus obscuring the causative role for GBS. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the effects of arginine on nutrition, growth and urea cycle function in boys with late-onset ornithine transcarbamylase deficiency (OTCD). Seven Japanese boys with late-onset OTCD enrolled in this study resumed arginine treatment after the cessation of this therapy for a few years. Clinical presentations such as vomiting and unconsciousness, plasma amino acids and urinary orotate excretion were followed chronologically to evaluate urea cycle function and protein synthesis with and without this therapy. In addition to height and body weight, blood levels of proteins, lipids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein -3 (IGFBP-3) were monitored.Results: The frequency of hyperammonemic attacks and urinary orotate excretion decreased significantly following the resumption of arginine treatment. Despite showing no marked change in body weight, height increased gradually. Extremely low plasma arginine increased to normal levels, while plasma glutamine and alanine levels decreased considerably. Except for a slight increase in high-density lipoprotein cholesterol level, blood levels of markers for nutrition did not change. In contrast, low serum IGF-I and IGFBP-3 levels increased to age-matched control levels, and normal urinary GH secretion became greater than the level observed in the controls.Conclusion: Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth. [ABSTRACT FROM AUTHOR]

Overview: In newborns with symptomatic congenital cytomegalovirus (CMV) infection, neuroimaging is the best available predictor of neurodevelopmental outcome. Cerebrospinal fluid (CSF) findings in congenital CMV infection have seldom been described. Neonates with central nervous system infections present high CSF Beta(2)-microglobulin (beta(2)-m) levels.Objectives: The objectives of this study were: (1) to determine whether CSF beta(2)-m is increased in newborns with symptomatic congenital CMV infection, and (2) to examine its correlation with neuroimaging findings.Materials and Methods: Fourteen newborns with symptomatic congenital CMV infection admitted to La Paz Hospital from 1990 through 2004 underwent determination of CSF beta(2)-m. Ninety-three newborns, constituting the comparison group, underwent CSF beta(2)-m determination as part of a sepsis or meningo/encephalitis work-up, and at discharge had sterile cultures and normal neurological status. Neuroimaging findings were scored according to a semiquantitative system: (0) no abnormalities; (1) single punctate periventricular (PV) calcification and/or hyperechogenic areas in the thalamus and basal ganglia; (2) multiple discrete PV calcifications and/or ventriculomegaly; and (3) extensive PV calcifications and/or brain atrophy.Discussion and Conclusion: CSF beta(2)-m was increased in newborns with CMV infection (median 6.21 mg/L) compared with controls (1.68 mg/L) (P<.001). beta(2)-m showed a correlation with neuroimaging scores (r (s)=0.753, P=.002). beta(2)-m was higher in patients who scored 2-3 (12.83 mg/L) than in patients who scored 0-1 (5.52 mg/L) (P=.028). CSF beta(2)-m is increased in newborns with symptomatic congenital CMV infection and correlates with neuroimaging abnormalities. beta(2)-m appears to be an indicator of the severity of brain involvement in congenital CMV infection. [ABSTRACT FROM AUTHOR]

Introduction: We report three cases of sinus histiocytosis, a rare disease of unknown aetiology with massive lymphadenopathy (SHML), also known as Rosai-Dorfman (RD) disease, in a paediatric population. This proliferative histiocytic disorder is defined by histological and immunohistochemical (IHC) characteristics and can manifest as nodal involvement with variable enlargement of the lymph nodes (two cases) and extranodal manifestations involving skin and larynx involvement (one case). One patient had hypergammaglobulinemia. The morphological investigation revealed that all lymph nodes showed hyperplasia of sinuses with abundant histiocytic cell with intracytoplasmic lymphocytes. Skin and larynx biopsies showed a histiocyte and lymphocyte infiltrate with similar characteristics. An ultrastructural study was carried out on material from one patient. In the IHC study, SHML cells expressed phagocytic markers such as CD68 and S100, but markers for Langerhan's (CD1a) or dendritic cells (DRC, CD23 and CNA42) were absent. Two patients had a complete remission after surgical excision and no other treatment, but the third patient was treated with radiotherapy after a relapse with obstruction of the upper airway.Conclusion: This disorder must be considered in the differential diagnosis of young patients who exhibit massive or multiple lymphadenopathies, especially when involvement of the cervical area occurs. Due to the good outcome of the disease, a conservative approach is justified. [ABSTRACT FROM AUTHOR]

Two unrelated children presenting with episodic isolated peripheral weakness were found to have pyruvate dehydrogenase (PDH) deficiency (OMIM 312170) due to previously undescribed mutations (Pro250Thr, Arg88Cys) in the gene for the E1alpha subunit (PDHA1). Taken in context with the literature, these patients suggest that acute weakness initially resembling Guillain-Barré syndrome is a potentially reversible and probably underdiagnosed manifestation of PDH deficiency and that peripheral nerve function should be evaluated in PDH-deficient patients. [ABSTRACT FROM AUTHOR]

A 12-year-old Turkish girl suffered from abdominal pain located in the right lower abdomen for 3 weeks. Ultrasound revealed palisade-like swelling of the mucosa in the ileum. Gastrointestinal biopsy showed incipient granulomas in the stomach and moderate fibrosis of the terminal ileum. Subsequently, bilateral hilar adenopathy and an abnormal level of serum angiotensin-converting enzyme were detected. The relevance of paediatric sarcoidosis mimicking Crohn's disease is discussed. [ABSTRACT FROM AUTHOR]

We carried out a 4-year study of 159 children (ages 1 month-14 years) with pneumococcal meningitis. The study was divided into two periods: the retrospective period (1998-2000: 107 patients), and the prospective period (2001-2002: 52 patients). About 2/3 of the children were under 2 years of age: 72 (45%) were under 1 year of age and 38 (24%) had meningitis during the second year of life. One-third of the patients had signs of otitis media; convulsions were more frequent in patients under 1 year compared with older patients (34.7 vs. 14.9%; P=0.004); 13/159 children (8.2%) died; 93/159 (58.5%) recovered completely, 12.6% had motor sequelae, 6.9% hydrocephalus, 29.8% sensorineural hearing loss; 140/159 (88%) were treated with third generation cephalosporins, yet only 8.7% of the pneumococci identified were completely penicillin-resistant (> or =1 microg/ml); 119/159 were treated with dexamethasone. Four patients had received an injection of heptavalent vaccine. Antibiotics for 1 week prior to admission, shock, abnormal pupils, leukocytes count <6,000 mm(3), and CSF glucose < or =8.5 mg/dl were significantly associated with poor outcome and/or death in the univariate analysis. No patient with leukocytosis >16,000/mm(3) died. Conclusion. Sequelae are very common in pneumococcal meningitis. Poor outcome was associated with pupillary abnormality and a leukocyte count <6,000/mm(3) on admission. Leukocytosis was protective against poor outcome. [ABSTRACT FROM AUTHOR]

Unlabelled: We report two children with renovascular hypertension and fibromuscular dysplasia. They initially presented with severe hyponatremia, hypokalemia, polyuria, and transient proteinuria. This combination of symptoms is known to occur in patients with renovascular and malignant hypertension, and is known as hyponatremic-hypertensive syndrome (HHS), although it is considered rare in children. Since in both of our patients, the renal arterial stenosis was very severely or almost totally occlusive, we could not perform percutaneous transluminal renal artery angioplasty, and therefore nephrectomy was the only option. A histological study showed partial or complete occlusion with intimal hyperplasia and medial fibroplasia of intrarenal arteries such as the interlobular arteries.Conclusion: Both patients showed rapidly progressive renovascular hypertension and loss of function of the affected kidney. In order to preserve renal function in such cases, early invasive intervention appears to be necessary. [ABSTRACT FROM AUTHOR]

We summarize the treatment of 20 patients with Crigler-Najjar disease (CND) managed at one center from 1989 to 2005 (200 patient-years). Diagnosis was confirmed by sequencing the UGTA1A gene. Nineteen patients had a severe (type 1) phenotype. Major treatment goals were to maintain the bilirubin to albumin concentration ratio at <0.5 in neonates and <0.7 in older children and adults, to avoid drugs known to displace bilirubin from albumin, and to manage temporary exacerbations of hyperbilirubinemia caused by illness or gallstones. A variety of phototherapy systems provided high irradiance over a large body surface. Mean total bilirubin for the group was 16+/-5 mg/dl and increased with age by approximately 0.8 mg/dl per year. The molar ratio of bilirubin to albumin ranged from 0.17 to 0.75 (mean: 0.44). The overall non-surgical hospitalization rate was 0.12 hospitalizations per patient per year; one-half of these were for neonatal hyperbilirubinemia and the remainder were for infectious illnesses. Ten patients (50%) underwent elective laproscopic cholecystectomy for cholelithiasis. No patient required invasive bilirubin removal or developed bilirubin-induced neurological damage under our care. Visual acuity and color discrimination did not differ between CND patients and age-matched sibling controls. Four patients treated with orthotopic liver transplantation were effectively cured of CND, although one suffered significant transplant-related complications.Conclusions. While patients await liver transplantation for CND, hyperbilirubinemia can be managed safely and effectively to prevent kernicterus. Lessons learned from CND can be applied to screening and therapy of non-hemolytic jaundice in otherwise healthy newborns. [ABSTRACT FROM AUTHOR]

Muscles and bones of patients with congenital heart disease (CHD) are subject to various potentially deleterious influences during growth. The aim of the present study was to analyse the outcome of bone and muscle parameters in adolescents and young adults with a spectrum of CHD. Bone and muscle parameters of the forearm were examined at two standard sites, 4% and 65%, in 29 adolescents and young adults with CHD, aged 14-24 years, by quantitative computed tomography. For the entire study population, bone and muscle parameters did not deviate significantly from the reference values except for age- and gender-corrected body height (ASDS-height: -0.6+/-1.2, p=0.01). Both age- and gender- and height- and gender-corrected (HSDS) abnormal bone mass (BMC) was found at the distal radius in patients with Fontan repair (ASDS-BMC4%: -1.5+/-0.9, p=0.008; HSDS-BMC4%: -1.2+/-1.0, p=0.05) and in those in NYHA class III (ASDS-BMC4%: -1.3+/-0.4, p=0.001; HSDS-BMC4%: -1.4+/-0.5, p=0.004). There was minimal overlap between Fontan patients (n=6) and NYHA class III (5 Fontan patients were in NYHA class I or II). In conclusion, most patients with CHD show a normal muscle and bone development in proportion to their reduced body height. Further follow-up is required to determine whether patients in a worse clinical status (NYHA III) and those with single ventricle physiology are at increased risk of osteoporosis and fractures. [ABSTRACT FROM AUTHOR]