Shanghai, China

Author Affiliations: Division of Pediatric Hematology-Oncology, Xinhua Hospital, Shanghai Children's Medical Center, Shanghai Second Medical University, Shanghai 200127, China (Wang YP)

Recently, there has been increasing awareness of adrenal exhaustion/immuno-endocrine derangements in the chronically ill patients receiving intensive care. Hypotension refractory to the administration of fluid and vasopressors is frequently encountered. In low gestation newborns, the administration of hydrocortisone has been associated with improved hemodynamic stability. To gain an insight into the underlying mechanism of this phenomenon, the relevant literature from a combined search through MEDLINE and EMBASE was examined. Available evidence suggests that adrenal insufficiency/exhaustion in low gestation newborns may be a principal underlying factor for persistent ductus arteriosus and low systemic blood pressure that is unresponsive to vasopressor treatment. It is hypothesized that early postnatal hydrocortisone supplement would facilitate immuno-endocrine homeostasis and the attainment of hemodynamic stability, thereby minimizing the morbidity and mortality associated with inadequate perfusion in this extremely vulnerable population.

Background: Dyskinetic cerebral palsy results from extrapyramidal damage, often with high handicap in movement and hard to treat. In this article, we discuss the classification of epidemiology and etiology, neuroimaging findings, treatment and prognosis of dyskinetic cerebral palsy in children.

Data sources: The literature about dyskinetic cerebral palsy was reviewed.

Results: Dyskinesia accounts for approximately 20 percent in all types of cerebral palsy.  The primary semiological features of dyskinetic cerebral palsy are voluntary motion disorders with increased involuntary movements which may show various combined symptoms such as torsion spasm, dystonia, chorea, athetosis and so on. Dyskinesia due to hypoxic ischemic brain injury and bilirubin encephalopathy may have different clinical and pathophysiological basis. The magnetic resonance imaging (MRI) findings of dyskinesia are characteristic. In general, the handicaps relating to dystonia belong to moderate and severe disabilities, which are almost hard to ambulate, while pure athetosis are mild disabilities with good prognosis.

Conclusions: The symptoms and neuroimaging findings are dependent on the period, etiology, spot of brain lesions. MRI should be considered as the optimal selection for the diagnosis and etiological research of dyskinetic cerebral palsy.     

Insulin-like growth factors (IGF) are key players in regulating growth and development of pre- and postnatal tissues. In addition, insulin-like growth factor-1 (IGF-1) known to be a key stimulus of placental substrate uptake inhibits fetal placental catabolism and reduces placental lactate production. Insulin-like growth factor-1 receptor (IGF-1) deletions cause intrauterine failure to thrive. IGF-1R gene knockout experiments have revealed a mild pre- and postnatal growth deficit in heterozygous IGF-1R+/- mice. A gene dosage effect of the IGF-1R gene on embryonic and postnatal growth, and also on postnatal growth of tissues and organs has been investigated in clonal mice strains with a wide spectrum of IGF-1R deficiency. Approximately 10% of infants with intrauterine growth retardation (IUGR) remain small, but the causes remain unknown. Recently, monoallelic loss of chromosome 15q, mutations of the IGF-1 receptor gene, and loss of one copy of the IGF-1 receptor gene again owing to deletions of the distal long arm of chromosome 15 have been found in patients with intrauterine growth retardation and postnatal growth deficit. Binding of IGF-1 to erythrocytes in short children with IUGR has shown to be lower than in children with normal height. The number of IGF-1 receptor copies on human fibroblasts seems to be predictive of their proliferative response to IGF-1. Hemizygosity for IGF-1R can cause primary IGF-1 resistance despite normal or even elevated GH and/or IGF-1 serum concentrations. At present IGF-dependent growth in prenatal life seems to be largely independent of GH, except for a small effect just before birth, while IGF-dependent growth after birth and particularly during puberty is strongly related to growth hormone (GH) action. In conclusion, mutations and deletions of the IGF-1 receptor gene lead to abnormalities in the function and/or number of IGF-1 receptors. Alterations of the IGF-1 receptor signaling pathway seem to retard intrauterine and postnatal growth in humans. In the future, expression of such mutations in cells in vitro provides an opportunity to define the role of IGF-1 receptor in human growth and growth disorders.

Background: The raising prevalence of childhood obesity is becoming a major public health concern in many countries, but little is known about the prevalence of childhood obesity in China. This study was undertaken to establish a screening standard for body mass index (BMI) in Chinese school children and adolescents on the basis of data obtained from different geographic regions and populations.

Methods: The data were obtained from 228 250 students aged 6 to 18 years who had participated in the 2000 National Surveillance Program on Students' Health and Physical Fitness, China. Analysis was made between groups of students from different geographic regions, from urban and rural areas, and from regions with different socioeconomic development. The percentiles of 5%, 50% and 95% were calculated and compared.

Results: Differences in BMI between the various groups were seen in the percentile of 95%. The BMI on the percentile of 95% for 13-year-old boys was 25.7 in the group from large and developed cities, compared with 21.1 for peers living in underdeveloped rural areas. The corresponding figures for girls were 22.8 in urban and 20.8 in rural areas. Significant geographical north-south differences were found, particularly during the adolescent growth spurt. Among 11-year-old girls, the average BMI was 22.3 in north and 21.0 in south China, whereas in 14-year-old boys the average BMI was 25.4 in the north and 23.5 in the south. The results of this study showed clearly that obesity is particularly prevalent in the metropolitan areas and in north China. Significant differences in BMI between developed and developing areas are already visible in primary school children. Differences in BMI on the percentile of 5% were less pronounced, showing that malnutrition and underweight are still prevalent in all subgroups.

Conclusions: As the national criteria for obesity screening in China, a reference group from developed metropolitan areas may best reflect the current situation and may also represent the general tendency of develop-ment. However, significant rural-urban and north-south differences exist along with gross inequalities in terms of material living standards, which should be taken into consideration.

Background: Body mass index as a measure for overweight and obesity is widely accepted. There are no references of BMI for Shanghai adolescents and children.This study was undertaken to construct percentile curves of body mass index (BMI) and cut off points for overweight and obesity of children in Shanghai.

Methods: The data on birthday, height and weight of the 96 104 children from Shanghai (48 790 boys and 47 314 girls) were measured during 1999 to 2002. The BMI percentile curves for Shanghai children aged 0-18 years were constructed by the LMS method. Based on the recommendations of the International Obesity Task Force (IOTF) and the Working Group on Obesity in China (WGOC), the percentile curves passing through 25 and 30 kg/m2 or 24 and 28 kg/m2 at age of 18 were established as overweight and obesity cut off points for Shanghai children.

Results: The age and sex specific BMI percentile curves of Shanghai children were constructed. The BMI in childhood changes substantially with age. The medians at birth are 13.7 and 13.4 kg/m2 for boys and girls, respectively, and increase to 18.3 and 17.8 kg/m2at age of 6 months. They decrease to 15.7 kg/m2 at age of 5.5 years for boys, and 15.4 kg/m2 at age of 6 years for girls, and then increase to 21.4 and 20.1 kg/m2 at age of 18 years for boys and girls respectively. The percentile curves passing through 24 and 28 kg/m2 at age of 18 years are P75.5 and P93.3 for boys, and P89.1 and P98.2 for girls, whereas those passing through 25 and 30 kg/m2 at age of 18 are P82.0 and P96.5 for boys and P93.0 and P99.2 for girls.

Conclusions: Based on the recommendations of the IOTF and WGOC, the BMI cut off points for overweight and obesity for Shanghai children aged 2-18 years have been constructed for the first time in China.

Key words: BMI percentiles; LMS method; children; cut off point

Background: The plasma concentrations of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) can reflect cardiac function and therefore can be used for the diagnosis of congestive heart failure (CHF) and the evaluation of cardiac function. However, few studies focused on BNP and NT-proBNP in pediatric patients with congenital heart defects. The aim of this study was to assess the value of NT-proBNP in the diagnosis of patients with ventricular septal defect (VSD) and congestive heart failure.

Methods: Fifty-one children with VSD aged from 2 months to 2 years (mean 7.9 months) were enrolled in this study. According to the modified Ross Score, they were divided into 3 groups: 20 patients without CHF (score 0-2), 18 patients with mild CHF (score 3-6), and 13 patients with moderate to severe CHF (score 7-12). A group of 15 age-matched healthy children served as controls. The levels of plasma NT-proBNP were determined with an enzyme immunoassay. All participants were subjected to complete echocardiographic examination for measuring left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic wall stress (LVESWS), heart rate-corrected mean velocity of circumferential fibre shortening (mVcFc), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and contractility index (Con). The correlation of plasma NT-proBNP with the modified Ross Score and functional indices measured echocardiographically was analyzed. The sensitivity, specificity and the receiver operating characteristic (ROC) curve for NT-proBNP as a diagnostic marker of CHF were calculated.

Results: The levels of plasma NT-proBNP were positively correlated with the modified Ross Score (r=0.75, P<0.01). The levels were significantly higher in patients with moderate to severe CHF (2061±908 fmol/ml) than in those with mild CHF (810±335 fmol/ml), but in the latter the levels were significantly higher than in patients without CHF (309±68 fmol/ml). In 97% of the patients without CHF and healthy controls, the plasma levels were below 400 fmol/ml. In 83% of the patients with mild CHF, the levels ranged from 400 to 1400 fmol/ml, whereas in 85% of the patients with moderate to severe CHF the levels of plasma NT-proBNP were above 1400 fmol/ml. Plasma NT-proBNP was positively correlated with LVEDVI and LVESWS, but it was not correlated with mVcFc, LVEF, LVFS and Con. When plasma NT-proBNP ≥400 fmol/ml was used as cut-off point for diagnosing CHF, the sensitivity was 89.3%, the specificity was 91.2%, and the area under the ROC curve was 0.944.

Conclusion: Plasma NT-proBNP can be used to evaluate cardiac function and diagnose CHF in pediatric patients with VSD.

Background: There has been a persistent debate in pediatricians on whether or not patients with congenital heart disease with large left-to-right shunt and pulmonary hypertension (PH). The severity of pulmonary hypertension has a strong impact on the effectiveness of operative treatment and prognosis. Invasive assessment with cardiac catheterization has been used to obtain more accurate data on pre- and post-operative hemodynamic change in order to study the relationship between the age at operation and prognosis in children with severe pulmonary hypertension.

Methods: Forty children with severe PH (increased total pulmonary circulation resistance) caused by ventricular septal defect (VSD) were divided into two groups according to their age at operation. Group I were younger than 2 years old and group II older than 2 years old. The ratios of pulmonary arterial pressure to systemic arterial pressure (Pp/Ps), pulmonary resistance to systemic resistance (Rp/Rs), and the levels of pulmonary vascular resistance (PVR) to small pulmonary arterial resistance (PAR) were measured before surgery, 1 week after surgery, and 5-7 years after surgery.

Results: No differences in Pp/Ps, Rp/Rs, PVR and PAR before surgery were observed between group I and group II (P>0.05) in contrast to significant differences in Pp/Ps, Rp/Rs, PVR and PAR 1 week and 5-7 years after surgery (P<0.01). In group I a week after surgery, Pp/Ps was 0.32±0.05, Rp/Rs 0.24±0.06, PVR 235.49±71.64 mmHg, and PAR 194.29±46.54 mmHg; 5-7 years after surgery, Pp/Ps was 0.24±0.03, Rp/Rs 0.19±0.05, PVR 158.26±36.51 mmHg, and PAR 119.70±32.48 mmHg. In group II a week after surgery, Pp/Ps was 0.50±0.15, Rp/Rs 0.42±0.14, PVR 381.23±35.96 mmHg, and PAR 347.07±87.52 mmHg; 5-7 years after surgery, Pp/Ps was 0.34±0.08, Rp/Rs 0.26±0.08, PVR 328.18±32.65 mmHg, and PAR 274.89±68.57 mmHg. During follow-up in group I, all the hemodynamic parameters were normal, whereas in group II, only Pp/Ps and Rp/Rs were close to normal and the other 6 parameters were still abnormal.

Conclusions: Early operation would be the only way to gain optimal long-term result and decrease the incidence of pulmonary vascular disease in children with PH due to VSD.

Background: Antimicrobial resistance in Helicobacter pylori (H. pylori) is an increasing serious problem, and the development of methods for detecting the resistance and the constant surveillance of both prevalence and evolution of H. pylori resistance in children would greatly improve the selection of antibiotics used to treat gastroduodenal infection with this organism. This study was designed to investigate the prevalence of H. pylori resistance to clarithromycin, metronidazole and amoxicillin isolated from pediatric patients in China.

Methods: A total of 44 H. pylori isolates from pediatric patients with gastritis and peptic ulcer undergoing endoscopy were cultured during the period of October 2002 to November 2003 at Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China. The susceptibilities of the 44 H. pylori isolated strains to clarithromycin, metronidazole and amoxicillin were tested by the agar dilution test to determine the minimum inhibitory concentration (MIC).

Results: The range of MIC was as follows: clarithromycin 0.125-64 μg/ml; metronidazole <0.125-128 μg/ml; and amoxicillin <0.125-64 μg/ml. The rate of H. pylori resistant to clarithromycin, metronidazole and amoxicillin in the children was 18.2% (8 strains), 31.8% (14 strains) and 9.1% (4 strains), respectively. Three strains (6.8%) were simultaneously resistant to the 3 antibiotics.

Conclusions: The prevalence of H. pylori resistance to metronidazole is high in children, and the rate of resistance to clarithromycin is higher than that in adults. Amoxicillin-resistant strains are found, and multi-drug-resistant strains of H. pylori to clarithromycin, metronidazole and amoxicillin are also found.

Background: SLE is treated currently by multiple immunosuppression, but side-effects are obvious after long time administration. This study was to observe changes in T, B cells, NK cells and IL12 in patients with systemic lupus erythematosus (SLE) before and after treatment of eliminating intermittent white blood cells and to probe the mechanism of this treatment.

Methods: In 23 patients with SLE, 5 were male and 18 female, with an average age of 15.78±5.40 years. These patients accepted treatment of eliminating intermittent white blood cells. The expressions of CD19+, CD3+, CD4+CD8+, CD4+/CD8+, CD(15+56)+ were tested by flow cytometry before and after the treatment. The amounts of immunoglobulins, IgM, IgG, IgA in periphery blood were measured separately by immunoradiometric analysis before and after the treatment. The level of IL12 was detected by ELISA. Twenty volunteers served as controls.

Results: The expression of CD19+ in the patients increased markedly before the treatment. Statistical significance was noted in the control group and the patient group after the treatment (P<0.01 or P<0.001). The expression of IgM and IgG increased markedly before the treatment. Statistical significance was seen between the control group and the patient group after the treatment (P<0.01 or P<0.001). The expressions of activated CD3+ and CD8+ increased markedly in the patients with SLE before the treatment (P<0.05) (P<0.01 or 0.001) respectively. The expressions of CD3+ and CD4+ decreased markedly (P<0.01 or P<0.05) (P<0.001) respectively. The ratio of CD4+ to CD8+ decreased markedly (P<0.01). The expression of CD3+ after the treatment decreased more remarkably in the patients with SLE than in the control group (P<0.05). The changes in the expression of CD(15+56)+ suggested that the expression of CD(15+56)+ increased markedly before the treatment. Significant statistical difference was observed in the patient group and the control group after the treatment (P<0.05 or P<0.001). The expression of IL12 in the patients with SLE decreased, but it decreased more significantly than in the control group before the treatment (P<0.05 or P<0.01).

Background: This study was designed to explore the possible use of the bladder submucosa acellular matrix (BSAM) as a cell deliverer in tissue engineering.

Methods: Smooth muscle cells (SMCs) were isolat-ed from bladder tissues by collagenase digestion and cultured and passaged in DMEM supplemented with 10% fetal bovine serum. Bladder submucosa was extracted from bladder by microdissection and washed thoroughly with 0.5% SDS and dH₂O. Smooth muscle cells were seeded onto the matrix at a density of 5.0×10⁶ cells per cm². The cell-matrix complex was harvested at 1, 2, 3 and 4 weeks. The growth of SMCs was evaluated by HE staining and electronic microscopy.

Results: SMCs adhered to the BSAM. One week later they located on the limited surface areas of the matrix or penetrated into the surfaces. After cell seeding for 2 and 3 weeks, the quantity of the cells increased markedly and most of them reached the inner side of the matrix. Four weeks after seeding, however, the number of the cells in the cell-matrix complex decreased.

Conclusions: The BSAM as a well biocompatible material in vitro can be used as a cell deliverer in tissue engineering research. The BSAM seeded with cells should be placed back to the host within 3 weeks after cell seeding.

Background: Despite it is recognized that high level of nitrotyrosine formation may play a role in acute lung injury (ALI), few studies have assessed protein nitration in ALI after meconium aspiration. This study was undertaken to observe the expression of inducible nitric oxide synthase (iNOS) and formation of nitrotyrosine in ALI after meconium aspiration and evaluate the contribution of iNOS and nitrotyrosine to tissue injury.

Methods: Sixteen healthy male Sprage-Dawley rats were divided randomly into control group and meconium group, which were administrated intratracheally 1 ml/kg saline or 20% human newborn meconium suspension respectively. The animals were sacrificed 24 hours after treatment. Bronchoalveolar lavage fluid (BALF) cell count, BALF protein, pulmonary myeloperoxidase (MPO) activity, malondialdehide (MDA), and nitrate/nitrite levels were measured. Western blot was used to determine the expression of pulmonary nitrotyrosine, a specific "footprint" of peroxynitrite and iNOS. Lung injury score was also evaluated.

Results: Compared with the control group, the rats in the meconium group showed an increase in cell count (mean±SD 4.04±1.01 vs 0.53±0.19×10⁶/ml, P<0.01), BALF protein (mean±SD 2.54±0.74 vs 0.67±0.26 mg/L, P<0.01), pulmonary MPO activity (mean±SD 1.49±0.22 vs 0.62±0.16 U/g wet lung, P<0.01), MDA level (mean±SD 3.30±0.85 vs 1.40±0.35 nmol/mg protein, P<0.01), nitrate/nitrite level (mean±SD 12.77±5.00 vs 4.89±1.32 µmol/mg protein, P<0.01), and lung injury score (9.88±1.36 vs 2.25±1.04, P<0.01). Western blot examination demonstrated increased expression of nitrotyrosine and iNOS in the meconium group (mean±SD 0.46±0.19 vs 0.11±0.08 and 1.49±0.60 vs 0.13±0.11, respectively, P<0.01).

Conclusions: Meconium causes increased expression of pulmonary iNOS, leading to over production of NO and nitrotyrosine, which may be of pathogenic importance in ALI after meconium aspiration.

We describe a case of renal osteodystrophy presenting as an unresolved musculoskeletal injury. The injury from playing soccer had been treated unsuccessfully with conservative rehabilitation. Although the patient presented in a subtle way, his persistent symptoms high-lighted the need to search for other systemic problems. Once evident that he had a complex agglomeration of skeletal and radiologic abnormalities a diagnosis of chronic renal failure was made. The patient was subjected to immediate evaluation by a specialist in this hospital. Earlier diagnosis of children with renal osteodystrophy will result in more timely management of the associated metabolic and bony complications of this condition.

Background: The clinical features of ring chromo-some 14 and its possible relationship with severe growth retardation were studied.

Methods: Chromosome high-resolution G banding analysis on cultures at 550 band level of skin biopsy specimen and peripheral blood lymphocytes in patients with mental retardation at this hospital revealed a case of mosaicism of ring chromosome 14 (p11.2; q32.3), chromosome monosomy 14. The reported cases of ring 14 were analyzed.

Results: Ring chromosome 14 was detected in a 18-month-old female infant with severe growth retardation, seizure and minor abnormal craniofacial features including scaphocephaly and microcephalic, low-set ears, elongated face, short palpebral fissures, prominent nasal bridge, micrognathia, high palate, and short neck. Cells from skin fibroblasts showed that 50% cell line with 46, XX, r(14) and 50% with 45, XX, -14, had a 46, XX, r(14) (p11.2-q32.2)/45, XX, -14 karyotype.

Conclusions: Patients with ring 14 are characterized by mental retardation, seizures, microcephaly, low set ears, short palpebral fissure, depressed nasal bridge, shot neck, and retinal pigmentation. The seizure was a unique feature of ring chromosome 14; mental retardation, severe seizure, and abnormal facial features should be evaluated cytogenetically to rule out the appearance of ring chromosome 14. The amount of genetic material can be deleted from chromosome 14. The ring instability leading to aneusomy and the position effect of a telomere on ring chromosome determine the physical abnormalities and manifestations of ring chromosome 14. The structural and behavioral instability of a ring chromosome give rise to high proportion of secondary aneuploid, resulting in more severe growth retardation.