A new life, a new journal

Zheng-Yan Zhao

Pediatric gastroenterology and nutrition:

present and future

Ying-Kit Leung

Hong Kong, China

Author Affiliations: Department of Pediatrics, University at Buffalo, State University of New York, Buffalo, NY, USA; the Hong Kong Society of Pediatric Gastroenterology, Hepatology and Nutrition, Hong Kong, China (Leung YK)

Background: Although the frequency of associated malformation is high, the incidence of inheritable syndromes is widely underestimated in children with anorectal malformation (ARM).

Data sources: OMIM database, patient records and charts of the Department of Pediatric Surgery, Johannes Gutenberg-University, Mainz, Germany.

Methods: We analyzed all associations, sequences and syndromes listed in the OMIM database that can be accompanied by ARM. A large cohort of children born with ARM was then retrospectively investigated as to the type of ARM, presence of additional malformations and possible categorization as a syndrome, sequence or association. For this process a syndrome finder was developed and employed. This simplistic tool allows for a rapid first check of possible syndromes before a more complex analysis is started using the OMIM database and consulting specialists.

Results: Among 317 children with ARM, associated malformations were present in 77.7% of 127 children with high ARM, in 68.7% of 32 with intermediate ARM, and in 25.3% of 158 with a low type ARM. Three or more organ systems were involved in 29.1% children with high type ARM and 25% with intermediate ARM and 8.2% with a low type ARM. An association of the vertebral anal tracheo-esophageal renal (VATER) and vertebral anal cardiac tracheo-esophageal renal limb (VACTERL) type was found in a total of 35 patients. Before analysis, 11 syndromes and 35 associations which were not clear previously in this patient cohort were described. In other 17 patients, 14 syndromes and 3 associations were identified.

Conclusions: The high number of only retrospectively identified syndromes suggests that a routine search is necessary in every patient with ARM and additional malformations.

Key words: anorectal malformation; associated malformation; association; syndrome; VACTERL/VATER

The dynamic nature of pulmonary vascular resistance (PVR) in the neonate makes it difficult to maintain a Qp/Qs approximating 1. The reactive pulmonary vasculature is unpredictable and may result in poor systemic perfusion with pulmonary edema or inadequate oxygenation and elimination of carbon dioxide. The increase of pulmonary blood flow is at the expense of perfusion of the body and perfusion of the body at the expense of oxygenation and removal of carbon dioxide. The mortality is high if PVR is not managed properly and, therefore, an understanding of the physiology and treatment options is important to lowering the morbidity and mortality of unequal Qp/Qs. This article reviews the normal changes in PVR at birth, discusses various dynamic parameters of PVR, outlines accepted treatment options to maintain a Qp/Qs close to 1 in patients with reactive pulmonary vasculature, and discusses a new therapy for pulmonary hypertension that is being evaluated in the basic science laboratory.

Key words: pulmonary vascular resistance; nitric oxide; prostacyclin; milrinone; prostaglandin E1; eiconasoids

Background: Childhood obesity, a disorder that is increasing in prevalence globally, is associated with medical complications that were primarily seen in adults, and is challenging to manage clinically. The challenges of childhood obesity are not limited to one country, but confront most nations around the world. This review article addresses the following issues concerning pediatric overweight and obesity: global prevalence trends, assessment of fat mass in growing children, medical comorbidities and Type 2 diabetes, and the efficacy of obesity treatment.

Data sources and study selection: We analyze trends and prevalence around the world and present research and clinical setting measures of body composition. Comorbidities and Type 2 diabetes are discussed in light of increasing prevalence globally. Intervention as well as prevention data are summarized in order to offer a complete view of the possibilities available for daily clinical practice. We outline directions for prevention research, one of the most pressing needs in biomedical research.

Conclusions: We conclude by outlining efforts to manage and prevent childhood obesity that involves education, research and intervention. Education and research can inform prevention efforts and assist with the development of public policy to manage the problem. Further research exploring the health risks associated with childhood obesity is needed to guide treatment efforts.

Background: Although hepatitis B vaccine has been highly effective and passive-active immunoprophylaxis has been used, 20%-30% babies whose mothers are hepatitis B virus (HBV) carriers may fail with vaccination against HBV. Since intrauterine HBV infection is responsible for most failures of immunoprophylaxis, this study was focused on combined antepartum and postpartum immunoprophylaxis for interruption of HBV transmission from mothers with both positive HBsAg and HBeAg to their infants.

Methods: One hundred and four pregnant women were HBsAg carriers with HBeAg positive. They were randomly divided into HBV specific immunoglobulin (HBIG) group and control group after informed consent was obtained and the study design was approved by the institutional ethics committee. The HBIG group received 400 IU HBIG at months 3, 2, 1 before delivery, whereas the control group did not. A total of 105 neonates (including twins) in the two groups were given a dose of 200 IU HBIG at birth and 2 weeks after birth, followed by 3 doses of Hepatitis B vaccine at 1, 2 and 7 months of age. A series of blood specimens obtained from the neonates at birth and 1, 2, and 7 months of age were tested for HBsAg, HBeAg, HBV-DNA, and anti-HBs.

Results: In the HBIG group, 3 of 51 neonates were infected by HBV at birth, which was found to be persistent for one year. The average titers of anti-HBs in 47 neonates at 1 month and 48 neonates at 12 months were 46±9.7 and 36±15.1, respectively. In the control group, 12 of 54 neonates were infected by HBV at birth. Ten of the 12 HBV infected neonates were found to be persistent for 4 months and 9 for 12 months. The average titers of anti-HBs in 42 neonates at 1 month and 45 neonates at 12 months were 41±8.2 and 35±12.9, respectively.

Conclusions: The rates of intrauterine HBV infection in the HBIG group and control group were 5.9% and 18.5% respectively (χ2=3.86, P<0.05). The average values of anti-HBs at one month of age in the 2 groups were 46±9.7 and 41±8.2 (t=2.609, P<0.05). More than 94% high-risk infants at one year of age can be protected by the combined antepartum and postpartum immunoprophylaxis by significantly interrupting the transmission of HBV from mothers with both HBsAg and HBeAg positive to their infants.

Background: There are few reports on the relationship of anti-β2-glycoprotein-I antibodies and anti-cardiolipin antibodies in children with systemic lupus erythematosus (SLE). This study was undertaken to compare the serum levels of anti-β2-glycoprotein I (β2-GPI) antibodies with those of anticardiolipin (aCL) antibodies in SLE patients with secondary anti-phospholipid syndrome (SAPS) and without SAPS (WSAPS).

Methods: Forty-two SLE patients with SAPS and 68 without SAPS were studied. Serum aCL antibodies and anti-β2-glycoprotein I antibodies were measured by ELISA.

Results: The serum level of anti-β2-GPI antibodies in 57.1% (24/42) of the patients in the SAPS-SLE group was higher than that in the control group, whereas it was only 1.5% (1/68) in the WSAPS-SLE group (P<0.01). The serum level of aCL antibodies was higher in 6.68% (28/42) of the patients in the SAPS-SLE group and in 42% (29/68) in the WSAPS-SLE group (P<0.01).

Conclusions: Anti-β2-glycoprotein I (β2-GPI) antibodies are not only strongly associated with SAPS in children with SLE but also highly specific in predicting SAPS-SLE in comparison with aCL antibodies.

Key words: anti-β2-glycoprotein I; platelet; anticardiolipin antibodies; thrombopeny; hemolysis; children; SLE

Background: Streptococcus pneumoniae (S. pneumoniae) is one of the most clinically significant pathogens with emerging antibiotic resistance, and most of the highly resistant strains to penicillin were clone related all over the world. This study was undertaken to investigate the antibiotic-resistant pattern and the genetic background of S. pneumoniae isolated from children in Hangzhou, China.

Methods: The sensitivities of 323 strains of S. pneumoniae to 9 different antibiotics were determined in vitro with the Kirby-Bauer diffusion method. Minimal inhibitory concentrations (MICs) of penicillin, cefotaxime and erythromycin were determined with the E-test method. Genetic types were analyzed with BOX-PCR.

Results: Among the 323 strains isolated from children between August 2001 and July 2002, 136 strains (42.1%) were sensitive to penicillin, while 57 strains (17.7%) were penicillin-resistant isolates. MICs for penicillin ranged from 0.012 μg/ml to 4.0 μg/ml. Three hundred and sixteen (97.8%) isolates were sensitive to cefotaxime with the MICs ranging from 0.008 μg/ml to 1.0 μg/ml. Seven isolates (2.2%) showed intermediate MICs with 2.0 μg/ml. Remarkably high levels of resistance were observed in 90.7% and 87.6% of the strains being resistant to erythromycin and tetracycline, respectively. Resistance to trimethoprim-sulfamethoxazole and choloromycetin was found in 48.6% and 14.9% of the strains. One hundred and ninety-seven strains (61.0%) were multi-resistant pneumococci, and most of them were cross-resistant to trimethoprim-sulfamethoxazole, erythromycin and tetracycline. Two strains (0.6%) were resistant to rifampin, and none was resistant to vacomycin and ofloxacin. On the basis of BOX-PCR typing of penicillin resistant Streptococcus pneumonia, no dominant fingerprinting pattern could be identified among clinical isolates, whereas the banding patterns were always similar to or identical among the isolates from healthy individuals or from the same specimen / patient at different times.

Conclusions: The antibiotic-resistance of pneumococci has been found to be high in Hangzhou, but third-generation cephalosporins are still the first option against penicillin-resistant Streptococcus pneumonia. The penicillin-resistant pneumococci might be one of geographic origins in the Hangzhou region, and one child could be infected or colonized by more than one pneumococci clone at the same time or at different times.

Background: SARS is an acute infectious pulmonary disease caused by a so-called coronavirus. The aim of this study was to assess the characteristics of clinical images of severe acute respiratory syndrome (SARS) in children for further understanding of the disease.

Methods: Clinical data and radiographic findings in 38 patients with clinically confirmed SARS in the period of January 2003-April 2003 were retrospectively analyzed. Chest radiography was performed in all the patients, and additional chest HRCT was given in a few of these patients.

Results: The radiological features of SARS in these patients were divided into three patterns: 1) massive consolidation (n=27, 71.1%) marked by patchy and segment air-space consolidations; 2) pulmonary interstitial infiltration (n=8, 21.0%) shown by coarse lung markings, and enhanced or inordinated reticular and drop shadows; 3) mixed pattern (n=3, 7.9%) characterized by marked lung markings with patchy opacity and reticular shadows. Radiographically the foci of lesions appeared early, progressed rapidly and were absorbed slowly. They could be grouped into early, progressive and convalescent stages, in which the median days were 4, 6 and 9 respectively.

Conclusions: The lung lesions of pediatric SARS patients appear early, and present bilateral or unilateral single or multiple patchy shadows predominantly. It is necessary to differentiate SARS from other pulmonary diseases through combined use of clinical and laboratory examinations.

Background: Thrombopoietin (TPO), the major hormone controlling platelet production, and transforming growth factor-beta1 (TGF-β1), a kind of growth suppressor acting on megakaryopoiesis, have been measured in thrombocytopenias with discordant results. The aim of this study was to explore the relationship between TPO, TGF-β1 and idiopathic thrombocytopenic purpura (ITP) in children.

Methods: TPO and TGF-β1 levels in the serum and bone marrow of 45 children with ITP were measured using the enzyme-linked immunosorbent assay (ELISA) method. Twelve healthy children were enrolled as controls.

Results: The serum level of TPO was higher in ITP children than in the controls, but no significant difference was observed between them (P>0.05). The serum level of TGF-β1 was significantly higher in ITP children than in the controls (P<0.01). The serum level of TPO after therapy was lower than that before treatment, but there was no significant difference between them. Some ITP children having a poor response to steroids had a significantly higher serum TPO level than those having good response and the controls. The bone marrow level of TPO was higher in ITP children than in the controls and also higher than the serum level. There was a positive correlation between the serum level and bone marrow level of TPO (r=0.99, P<0.01). The bone marrow level of TGF-β1 was higher than the normal serum level. There was a positive relation between serum level and bone marrow level of TGF-β1 (r=0.80, P<0.01). Before treatment, ITP children had a low platelet count but a high level of TPO. After treatment, when the platelet count increased, the level of TPO reduced. There was a negative correlation between TPO and platelet count (r=-0.649, P<0.05) and between TPO and megakaryocyte count (r=-0.519, P<0.05).

Conclusions: In the pathogenesis of ITP, TGF-β1 is a feedback regulating factor. The levels of TPO and TGF-β1 in serum and bone marrow could help evaluate ITP children’s conditions, estimate prognosis, and enact treatment regimens.

Key words: children; thrombocytopenia; thrombopoietin; transforming growth factor-beta1; eneyme-linked immunosorbent assay; relativity

Background: Acute leukemia (AL) is a heterogeneous group of malignancies with varying clinical, morphologic, immunologic, and molecular characteristics. Many distinct types are known to carry predictable prognoses and warrant specific therapy. Hence the distinction between lymphoid and myeloid leukemia, most often made by flow cytometry (FCM), is crucially important. This study was undertaken to evaluate the value of multi-color flow cytometry in the immunophenotyping of acute leukemia in children.

Methods: Three- or four-color flow cytometry and CD45/SSC gating were used to analyze the surface and cytoplasmic antigen expressions from 222 children with acute leukemia.

Results: Cells from the 222 children were analyzed. Based on the diagnostic criteria proposed by EGIL, four categories of the cells could be identified: undifferentiated type, 2 patients (0.9%); acute myeloid leukemia (AML), 78 (35.1%); acute lymphoblastic leukemia (ALL), 124 (55.9%); and mixed lineage AL, 18 (8.1%). Of the 124 patients with ALL, 94 (75.8%) were classified as having B lineage and 30 (24.2%) T lineage ALL. Antigen aberrant expressions were found in 19 (24.4%) of 78 patients with AML, 34 (36.2%) of 94 with B lineage ALL and 9 (30.0%) of 30 with T lineage ALL. The most commonly expressed lymphoid antigen in 78 patients with AML was CD7, 10 patients (12.8%), followed by CD19, 5 (6.4%), and CD2, 4 (5.1%). The most commonly expressed myeloid antigen in 124 patients with ALL was CD13, 23 patients (18.5%), followed by CD15, 14 (11.3%), CD11b, 8 (6.5%) and CD33, 4 (3.2%). CD117 and CD56 were present in 55 (73.3%) and 27 (38.6%) of the 75 patients and 71 patients with AML, respectively, but were generally absent in blast cells of ALL. Cytoplasmic (Cy) CD22, CyCD3 and CyMPO were specifically expressed in B lineage, T lineage and myeloid lineage leukemia, respectively, and the first two could be more sensitively detected than they were on the cell membrane surface.

Conclusions: Multi-color flow cytometry is a reliable technique in the diagnosis, differential diagnosis and classification of acute leukemia in children.

Background: The perinatal brain shows both an increased tolerance to hypoxic ischemic injury and a faster and more complete recovery than the adult one. It is, therefore, important to understand the sequence of events following hypoxia and ischemia in young animals. This study aims to clarify the time-course of μ-calpain activation, and expressions of c-fos protein (c-Fos), c-jun protein (c-Jun), HSP70 and HSP27 during hypoxic-ischemic brain injury (HIBI) in neonatal rats.

Methods: The model of HIBI was made in 7-day-old SD rats by left carotid arterial ligation and hypoxia (8% oxygen). The protein concentration was determined using a modified Bradford assay. μ-calpain activation, and expressions of c-Fos, c-Jun, HSP70 and HSP27 were observed by Western blot in cortical and hippocampal samples at 0, 1, 2, 4, 12 and 24 hours after the development of lesion.

Results: The cleavage of cytosolic μ-calpain was demonstrated in both cortical and hippocampal samples in neonatal rats after hypoxic-ischemia (HI). The ratio of 76/80 kD of μ-calpain was increased significantly after HI and reached a maximum at 24 hours after HI. Compared with that observed in the control group, the expression of nuclear c-Fos and c-Jun in cortical and hippocampal samples increased significantly at 1, 2, 4, 12 and 24 hours after HI (P<0.05). But significant expressions of cytosolic HSP70 and HSP27 could only be seen at 12 or 24 hours after HI (P<0.05). The significant differences between the cerebral cortex and the hippocampus were observed in c-Fos expression at 2 and 4 hours, and in HSP70 and HSP27 expressions at 24 hours after HI (P<0.05).

Conclusion: The early activation of μ-calpain and increased expressions of c-Fos, c-Jun, HSP27 or HSP70 following HI may contribute to neuronal apoptosis as well as induction of a significant brain neuroprotection in neonatal hypoxic-ischemic rat brain.

Background: The mechanism of asthma has not been clearly elucidated. This study was undertaken to explore the effect of IL-13 gene polymorphism on the levels of serum IL-13 and total IgE and to better understand the role of IL-13 gene polymorphism in the mechanism of pediatric asthma.

Methods: Restriction fragment length polymorphism (RFLP) method was used to detect +1923 site polymorphism of the IL-13 gene in intron 13 region and ELISA was used to detect the levels of serum IL-13 and total IgE.

Results: TT and TC gene frequencies were significantly higher in asthma group than in control group. CC type frequency was higher in the control group than in the asthma group. Serum IL-13 and total IgE levels were significantly higher in TT and TC gene types in the asthma group than in CC gene type in both groups.

Conclusion: IL-13 gene polymorphism may play an important role in the mechanism of asthma in children.

Background: Infants with congenital heart diseases undergoing open-hear surgery require mechanical ventilation. Failed extubation (FE) is statistically associated with prolonged mechanical ventilation. This study was undertaken to investigate the risk factors of FE after cardiac surgery in infants.

Mothods: A total of 227 infants of less than 1 year old who had undergone congenital heart surgery (CHS) were enrolled in this study. Logistic regression analysis was used to assess the risk factors of FE. Odds ratio was used to assess the degree of relationship between FE and risk factors.

Results: Out of the 227 infants undergoing CHS, 30 (13.22%) failed at the extubation. Risk factors for failed extubation included postoperative duration of mechanical ventilation (EOR=12.0; 95%CI=4.04-35.71; P=0.009), postoperative pneumonia (EOR=5.33, 95%CI=1.81-15.68, P=0.002), and preoperative pulmonary hypertension (EOR=2.80, 95%CI=1.21-10.45, P=0.041). Postoperative pneumonia and preoperative pulmonary hypertension were the 2 independent risk factors for FE (P<0.05).

Conclusions: Postoperative pneumonia and preoperative pulmonary hypertension are the major risk factors for FE after CHS in infants. The prevention and treatment of postoperative pneumonia and pulmonary hypertensive crises are beneficial to the successful extubation.

Ulf Kessler, Mathias Nelle, Zacharias Zachariou and Otwin Linderkamp

Bern, Switzerland and Heidelberg, Germany

Author Affiliations: Department of Surgical Pediatrics, Inselspital, Bern, Switzerland (Kessler U and Zachariou Z); Division of Neonatology, Department of Pediatrics, Inselspital, Bern, Switzerland (Nelle M); and Division of Neonatology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany (Kessler U and Linderkamp O)