cnAbstractObjectiveTo probe into the correlation between P-gp170 expression level of peripheral blood mononuclear cells(PBMC) and intracellular dexamethasone(Dex) concentration by testing P -gp170 expression and intracellular Dex concentration at different time point, in order to analyze the role P-gp170 may play in SRNS and the mechanism involved.Methods24 children with NS without any glucocorticoid treatment before admission were chosen as subjects, namely SSNS and SRNS, and 10 healthy children serving as control. High performance liquid chromatography was used to test intracellular Dex concentration at different time, namely 0,12,24 and 36 h, and Western blotting assay was adopted to test P-gp170 expression level of peripheral blood mononuclear cell membranes, and correlation analysis of Dex concentration and expression of P-gp170, then regression analysis on those having correlations were performed.ResultsIntracellular Dex concentration of children with SSNS varied with different time, the longer the period of time cells cultured, the higher the Dex concentration, and a significant difference was found between each time point according to statistics(P<0.05), and there was also notable difference between SSNS group and control group(P<0.05), and intracellular Dex concentration of children with SRNS varied with different time as well, but there was no significant difference between each time point statistically(P>0.05); No change was found in P-gp170 expression level of PBMC of healthy blank control at different time, thus no significant difference was found between groups according to statistics(P>0.05)；P- gp170 expression level of PBMC of Dex groups in SSNS decreased by and by, with a significant difference between different time point statistically(P<0.01)；P-gp170 expression level of PBMC of Dex groups decreased with time passing by, and with a significant difference between different time point statistically(P<0.05)；there was significant P-gp170 expression level of each time point(P<0.05)；No change was found in P-gp170 expression level of PBMC of children with SSNS at different time (P>0.05); P-gp170 expression level of PBMC of SSNS Dex groups decreased with time passing by, with a significant difference between different times statistically(P<0.05)；P-gp170 expression levels of different time points were all higher compared with healthy Dex control(P>0.05)； P-gp170 expression levels of PBMC of SSNS Dex groups were all higher than those of SSNS blank control(P<0.05)；No change was found in P-gp170 expression level of PBMC of children with SRNS at different time (P>0.05)；and there was a significant difference of P-gp170 expression level compared with healthy blank control statistically(P<0.05)；No change was found in P-gp170 expression level of PBMC of children with SRNS Dex group at different time(P>0.05)；and statistically there was a significant difference of P-gp170 expression level compared with SRNS(P<0.05)； P-gp170 expression levels of different time points were all lower compared with SRNS blank control(P>0.05) and P-gp170 expression levels in Dex group of different time points were all lower, a significant difference were found between groups according to statistics(P>0.05), No change of P-gp170 expression level of peripheral blood mononuclear cells of children with SRNS in Dex group were found at different time compared with SRNS bank control(P>0.05)；A negative correlation was found between intracellular Dex concentration and expression of P-gp170 of Dex groups in healthy control，r was -0.852，-0.794，- 0.847 ，respectively(P<0.05)；and the same was between those of SSNS, r was -0.728，-0.785，-0.842，respectively(P<0.05); No correlation was found between those of SRNS according to statisticas(P>0.05).Conclusions①Expression of P-gp170 was found both in children with NS and control with the later higher than the former, thus P-gp170 may play different roles physiologically and pathologically in NS children. ②Mechanisms in some children with SRNS may attribute to up-regulating the expression of P-gp170 primarily, while others developing SRNS may resulting from a large amount of GC administration during a long period, which was the mechanism of second GC resistant, GC administration may lead to higher expression of P-gp170 in cell membrane, a large amount of GC administration during a long period clinically may result in GC resistance by way of up- regulating the expression of P-gp170, consequently an inhibition of GC from outside into inside of the cells.③Up-regulating the expression of P-gp170 was one of the markers of GC resistance in NS children.
cnAbstractObjectiveUsing meta-analysis method, to assess the efficacy and safety of combined therapy with deferiprone and deferoxamine in thalassemia major patients.MethodsThe Cochrane library, PubMed, EMBASE, Ovid, Springer, CBMdis,CNKI and VIP were searched from January 1,1985 to May 31,2008 by using the terms deferipron and deferoxamine and thalassemia for human clinical trails. Two reviewers independently performed data extraction and assessed the quality of included studies.Serum ferritin(SF),liver iron concentrae(LIC), myocardial iron, drug adverse reaction, total iron excretion and cardiac function were chosen as evaluation index to evaluate the combined WMD or SMD or RR value and 95% confidence interval(CI). Extracted data were input and analyzed by software of Review Manager 4.3.2, recommended by Cochrane Collaboration.ResultsFive randomized controlled studies involving 230 patients were included. Only one of the five trails used double-blind. Combined therapy group (deferiprone applied 5-7 d/w plus twice weekly deferoxamine) was compared to control group (deferoxamine monotherapy applied 5-7 d/w), Meta-analysis based on included studies showed: the changes of SF and LIC before and after therapy were (SMD=-0.04, 95%CI：-0.48-0.41),(SMD＝-0.1，95%CI: - 0.47-0.27) respectively, the total iron excretion (WMD=0.18,95%CI:0-0.37),there were no significant differences between the two groups. The improvement of left ventricular ejection fraction (WMD=3.40, 95%CI：0.97-5.82)was higher in combined therapy group than in control group. The incidence of gastrointestinal symptoms (RR =2.77, 95%CI：1.41-5.42)were higher in combined therapy group, but there were no significant differences between the arthrosis side effect (RR =1.45, 95%CI：0.59-3.52),the incidence of neutropenia(RR=0.85, 95%CI：0.27-2.68) and the reactions at the infusion site (RR=0.57, 95%CI：0.20-1.65). The evidence was not strong enough to judge whether the combined chelation therapy was superior to deferoxamine monotherapy due to only one RCT study evaluating myocardial iron by MRI T2* was enrolled.ConclusionsAvailable evidence showed combined chelation therapy (deferiprone applied 5-7 d/week plus twice weekly deferoxamine) was as effective as deferoxamine monotherapy(applied 5-7 d/week) and may be superior to deferoxamine monotherapy in improving myocardial siderosis and heart function, the common side effect was gastrointestinal symptoms. Combined chelation therapy was not only effective but also could reduce the pain from long-term deferoxamine infusion, and this should be translated into improved survival and compliance.
cnAbstractObjectiveTo analyze the efficacy of protocol B-NHL2001 for B cell non-Hodgkin′s lymphoma (B-NHL) and anaplastic large cell lymphoma(ALCL).MethodsDepending on the reports from developed country and the results of our former protocol NHL-CCCG-97, the protocol B-NHL 2001 revised the eligibility, grouping criteria, intensity of chemotherapy and time of treatment. Patients were divided into low, middle and high risk groups (R1,R2,R3) based on staging and the level of lactate dehydrogenase (LDH), and given 3, 5, and 6 courses of chemotherapy respectively. All the patients from 2001 to June 2007 were enrolled. The software of SPSS 11.0 was used and the event free survival was generated by Kaplan-Meier.ResultsThere were 45 patients in total, 35 males and 10 females. The average age was 7.1 years (ranged from 10 months to 15.5 years), medium age was 6.3 years. Two patients were in stage Ⅰ, 17 in stageⅡ, 18 in stageⅢ and 8 in stageⅣ. The original tumor was found in abdomen for 23 patients, nose-pharynges for 7, periephel lymph- nodes for 7, cutaneous for 1, mediastinum for 1, bone for 2,mumps for 2 , chest wall for 1 and extensive infiltration in chest and abdomen for 1. They were pathologically sub-classified as Burkitt′s for 14 cases，large B cell for 13,anaplastic large cell for 3 and B-NHL(non-lymphoblastic, no further sub-classification) for 15.Two patients were allocated into low risk group (R1), 14 into middle risk group(R2) and 29 into high risk group (R3). Three were ruled off the analysis because of abandoning treatment by parents after 1 course therapy without progressive disease (1 of stage Ⅰ, 2 of stage Ⅲ ). Forty-one of 45 patients reached complete response(CR) after 2 courses of chemotherapy. Another 3 received second look surgery because of residual disease after 3 courses therapy, 2 of them were proved CR (no tumor cells in residual mass) by pathology, 1 with alive tumor cells. In total, 43 of 45 reached CR (95.5%), one of stage Ⅲ and one of stage Ⅳ never reached CR. To Dec 2007, 40 of them kept in CR(88.9%) with 6 to 77 months follow-up, average 26.9 months, medium 19 months. Three cases relapsed at original place, bone marrow and in cranial (2 of stage Ⅲ and 1 of stage Ⅳ) which occurred in 5,6 and 8 months. The estimated 5-year event free survival (EFS)was 88.3%.ConclusionsThe estimated 5-year event free survival indicated that B-NHL 2001 was reasonable for both B-NHL and ALCL and worth to enroll more patients.
cnAbstractObjectiveThis paper is to analyze the feasibility of morning urine copper/zinc (Cu/Zn ratio instead of the 24 h urinary copper quantification in the diagnosis of Wilson′s disease(WD).MethodsClinical data, samples of morning and 24 h urine were collected from all the patients who were over three years old, and hospitalized for the liver disease in Children′s hospital of Fundan university from July 2005 to June 2007. We scored each patient based on the Score of Diagnosis of Wilson′s disease,and categorized them into two groups: WD and non -WD. We measured the concentration of Cu and Zn with Inductively Coupled Plasma Mass Spectrometry(ICP-MS) and calculated the Cu/Zn ratio of each sample and the excretion of copper and zinc in 24 h urine. Statistical analysis was performed using the SPSS 13.0 statistical package. Descriptive statistics were used for demographic and baseline data and summarized as mean/median or percentage. To evaluate the correlation between the morning urine Cu/Zn ratio and 24 h urinary copper excretion, a simple linear regression with calculation of Pearson′s correlation coefficient (r) was used for all cases. The accuracy of a morning urine Cu/Zn ratio for detection of WD was compared with the 24 h urinary copper excretion by using comprehensive clinical diagnosis as a gold standard. Sensitivity, specificity and predictive values of the morning urine Cu/Zn ratio were measured by using different cut-off values.ResultsThe number of patients in WD, non-WD groups was 24, 64 respectively. The morning urine Cu/Zn ratio and the 24 h urinary Cu excretion had good correlation coefficient (r=0.840, P =0.000). The median of the Cu/Zn ratio in morning urine, the Cu/Zn ratio in 24 h urine, the Cu excretion in 24 h urine, and the Zn excretion in 24 h urine in the WD group were 0.370, 0.394, 87.1 and 398.7, while those in the non-WD group were 0.051, 0.061, 24.2 and 358.9. Between the above mentioned two groups, the Cu/Zn ratio in morning urine, the Cu/Zn ratio in 24 h urine and the Cu excretion in 24 h urine had significant difference (the z-values were -6.502, -6.020 and -6.208 respectively, P values were all 0.000). ROC analysis indicated that the diagnostic cutoff value of morning urine copper/zinc ratio, 24 h urine copper/zinc ratio and 24 h copper excretion were 0.17, 0.12 and 50.8. The areas under curve were 0.953（95 ％CI: 0.909～0.998）, 0.911 (95%CI: 0.834～0.987) , 0.934（95％CI：0.867～1.001）respectively. By using cutoff values of 0.17, 0.12, 50.8, the sensitivity and specificity were 86.4% and 92.2%, 86.4% and 85.9%, 90.9% and 93.7%respectively. ConclusionsMorning urine Cu/Zn ratio has good correlation with 24 h urinary Cu excretion, with high sensitivity and specificity in diagnosing WD children. It is possible to replace the 24 h Cu excretion method with morning urine Cu/Zn ratio method to diagnose WD.
cnAbstractObjectiveTo evaluate the growth of preterm (gestational age <34 weeks)or low birth weight(birth weight < 2 000 g) infants fed with preterm or term formula during early postnatal stage and give the recommendation of preterm infant formula selection.MethodsThree neonatal intensive care units participated in this study in Shanghai. Neonates were involved if they were born less than 34 weeks of gestational age or birth weight less than 2 000 g. All neonates were randomly divided into preterm (group Ⅰ) or term formula (group Ⅱ) group. Independent investigators collected the data. Independent analysis accomplished all the statistical analysis using SPSS 10.0. The formula was supplied by Synutra International Inc. and all investigators were blinded except trial designer. ResultsThe rates of weight gain, linear growth and head growth were all higher in group Ⅰ as compared to group Ⅱ neonates. During the whole trial, the average weight gain was 12.6 g·kg-1·d-1 and 10.6 g·kg-1·d-1 in group Ⅰ and group Ⅱ respectively（P＜ 0.001）.The increase of head circumference was 0.86 cm per week and 0.80 cm per week（P＜0.05）and linear growth was 0.73 cm per week and 0.67 cm per week（P＜0.05）in group Ⅰ and Ⅱ respectively. If all these data were recalculated after regaining their birth weight, there was still statistical significance between two groups. The average weight gain was 16.2 g·kg-1·d -1 in group Ⅰ and 14.1 g·kg-1·d-1 in group Ⅱ（P＜0.001）.The increase of linear growth was 1.08 cm per week in group Ⅰ and 0.99 cm per week in group Ⅱ（P＜0.05）.The rate of head growth was 0.96 cm per week in group Ⅰ and 0.89 cm per week in group Ⅱ（P＜0.05）.Group Ⅰ also had lower incidence of EUGR（57.3％） than group Ⅱ (72.5％） (P＜0.05).ConclusionsPreterm infants fed with preterm formula had better growth than fed with term formula. The rates of weight gain, linear growth and head growth in infants fed with preterm formula could reach intrauterine growth rates. The incidence of EUGR was also significantly decreased in infants fed with preterm formula.
Objective High-risk neuroblastoma （NB） is a childhood malignancy with a poor prognosis. Gradual improvements in survival have correlated with therapeutic intensity, and the ability to harvest, process and store autologous hematopoietic stem cells has allowed for dose intensification beyond marrow tolerance. The aims of this study were to evaluate the prognosis of children with advanced NB and to compare the outcomes of unpurged autologous hematopoietic stem-cell (ASCT) and CD34＋ selected stem-cell transplantation with traditional chemotherapy alone in stage Ⅲ and Ⅳ NB.MethodsA retrospective analysis of stage Ⅲ and Ⅳ NB children from Jun 2000 to Apr 2007 was performed. A sensitive FQ-PCR method to test the expression of tyrosine hydroxylase was used to monitor minimal residual disease (MRD) and to evaluate the purity of CD34+ selected transplantation.ResultsTotally 55 NB patients finished chemotherapy and were enrolled in this study with 14 in stage Ⅲ and 41 in stage Ⅳ. In stage Ⅲ: 9/14 NB patients didn′t receive transplant (chemotherapy group) and 5/14 receive ASCT (transplant group). In stage Ⅳ: 18/41 NB patients were in chemotherapy group and 23/41 were in transplant group. In stage Ⅳ transplant group: 13/23 NB patients received CliniMACS based CD34＋ selected stem cells transplantation while 10/23 received unpurged autologous transplant. For ASCT: all NB patients received the conditioning regimen including carboplatin 300 mg·m-2·d-1×4 d + etoposide (VP16) 160 mg·m-2·d-1×4 d + melphalan 180－210 mg·m-2. The mean number of total nuclear cells and CD34+ cells from autograft was （7.1±2.5）×108· kg-1 and （4.0±1.5）×106·kg-1. The mean time for the neutrophile recovering over 0.5 ×109·L-1 was (10.5±5.7) days and for the platelet recovering over 2.0 ×109·L-1 was (16.8±9.4) days with average 2 units of packed red blood cells and 4 units of platelet were transfused during the process of transplantation. None of our patients died of transplant related disease. The survival time and relapse rate were evaluated：①for patients with stage Ⅲ NB: 3 of 9 patients in chemotherapy group (median follow up, 33.5 months) and 1 of 5 patients in transplant group relapsed (median follow up, 37 months). The median survival time was (37.0±15.7) and (18.0±29.9) months respectively and there was no significant difference between these two groups (P=0.446). ②for patients with stage Ⅳ NB: 13 of 18 patients(72%) in chemotherapy group (median follow up, 20 months) and 14 of 23 patients(61%) in transplant group relapsed (median follow up, 29 months). The median survival time was (24.0±5.5) and (36.0±2.8) months respectively and there was a significant difference between these two groups (P=0.006). ③for CD34＋cells selected transplant: 7/13 patients(54%) received CD34＋ purged (median follow up, 30 months) and 7/10 patients(70%) received unpurged ASCT relapsed (median follow up, 27.8 months). The median survival time was (34.0±11.8) and (36.0±5.1) months respectively and there was no significant difference between these two groups (P=0.722). 8 samples (4 before CD34+ selection and 4 after CD34+ selection) were tested by RT-PCR for the expression of tyrosine hydroxylase. Among these 4 contrasted samples after CD34+ selection all the 2 original MRD positive samples became MRD negative.ConclusionsASCT could obviously prolong the life of patients with stage Ⅳ NB, but it didn′t benefit for stage Ⅲ NB. The process of CD34＋ selected transplant was as safe as unmanipulated transplant. But it didn′t show any clinical predominance within these limited cases.
Objective Coronary artery lesions are critical in the long-term follow up of children with Kawasaki disease. Echocardiography is the most general imaging method and it is important to recognize the limitations of echocardiography in the evaluation of distal coronary artery aneurysm, thrombus and coronary artery stenosis. Recent years, technical advances of 64-slice computed tomography coronary angiography (64SCTCA) in evaluating coronary artery abnormalities and minimally invasive characteristics have led to the application in Kawasaki disease and got attention gradually. This study was to understand circumstances about the evolution and regression of coronary artery lesions and explore the value of 64SCTCA and echocardiography in clinical diagnosis and follow-up of coronary artery aneurysms caused by Kawasaki disease.MethodsFifteen patients with coronary artery aneurysms caused by Kawasaki disease followed in Beijing Children′s Hospital during Dec 2006 to May 2007 were selected. Diagnostic criteria of coronary artery aneurysm were defined coronary arteries as those with a lumen diameter >4 mm and 1.5 times the size of an adjacent segment. Fifteen patients underwent a regular follow-up after the onset of Kawasaki disease. They received an overall examination in hospital every half a year or one year, including the changes of clinical symptoms and physical signs and the results of electrocardiogram, echocardiography, treadmill exercises test, etc. In this study, all 15 patients underwent 64SCTCA and echocardiography examination. Then the examination findings were described and analyzed.ResultsEchocardiography in acute stage showed coronary artery lesions in 48 of 60 arteries(80%). Coronary aneurysms showed regression during follow-up in 75% arteries (2.8±2.0) years（9 months to 8.6 years）after the onset of Kawasaki disease. Further dilation or no changing of the arteries occurred in 25% arteries. Last studies showed coronary artery lesions in 34 of 60 arteries (56.7%). Echocardiography detected thrombi in 2 arteries. No stenosis and calcification were identified in follow-up period. 64SCTCA showed coronary artery lesions in 30 of 60 arteries (50%). The lesions mainly involved right coronary arteries (RCA) and left anterior descending arteries (LAD). 64SCTCA identified similar sites of coronary lesion as compared to echocardiography. A statistically significant correlation was observed between maximal diameter of coronary artery aneurysms by 64SCTCA and echocardiography (Pearson coefficient r =0.837, P<0.001). 64SCTCA detected thrombi at 4 sites, calcification at 5 sites and stenosis at 3 sites.Conclusions64SCTCA and echocardiography had respective application value in long-term follow-up of coronary artery aneurysms resulting from Kawasaki disease. Combined application of two diagnostic methods could increase the detectable rate of pathological changes.
Objective To investigate the association of chromosome karyotype abnormalities with congenital heart diseases.MethodsA total of 4 046 cases were recruited in the study, who underwent chromosome examination during Jan 1990 to Dec 2006 in Children′s Hospital of Fudan University. Ages were ranged from 1 day to 17 years old. Retrospective analysis was used to analyze the karyotype of chromosome and the types of congenital heart diseases. The method to analyze karyotype was G-band, and Philips/SONOS 7500,HP/SONOS 5500 or HP/SONOS 2500 ultrasonic system were used to diagnose congenital heart disease.ResultsAmong 4 046 cases, there were 660 cases with abnormal chromosome karyotypes.In autosome abnormal cases,21-trisomy was the most common one, which included 458 cases. In sex chromosome abnormal cases, Turner syndrome was the most common one, which included 105 cases. There were 391 cases with congenital heart diseases, and 185 of whom showed abnormal chromosome kayotypes.There were 157 cases with both 21-trisomy and congenital heart diseases.The mainly abnormal structure of heart in 21-trisomy was septal defects,totally 133 cases. There were 4 cases with both Turner syndrome,but 2 cases′ heart structure showed coarctation of the aorta. The rate of abnormal karyotype in congenital heart diseases was significantly higher than that in non-congenital heart diseases (P<0.05). However, 105 cases of 391 congenital heart disease cases had conotruncal defects. Only 16 out of 105 cases of conotruncal defects had abnormal chromosome karyotypes . The rate of abnormal karyotype in conotruncal defects was significantly lower than that in non-conotruncal defects cases(P<0.05). In 206 cases with normal karyotype but with congenital heart diseases, the rate of conotruncal defects was almost as same as non-conotruncal defects .ConclusionsOur study showed that there were close relationship between chromosome abnormalities and congenital heart disease. Patients with chromosome karyotype abnormalities had higher incidence of congenital heart disease, while some types of congenital heart diseases had higher incidence of abnormal chromosome karyotype.The results suggested that heart examinations should be undertaken in those patients who had chromosome abnormalities.On the other hand, some congenital heart diseases had been detected with normal chromosome karyotype,and we should find proper technique to increase the detectable rate.
We report one neonate with the neonatal type of nonketotic hyperglycinemia. Pathogenesis,clinical symptoms,diagnosis and treatment are discussed in this article.
