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Vol 1, No 2
Vol 1, No 2 October 2005 ISSN 1708-8569
Review articles
Original articles
Case report
Prevention and treatment of childhood asthma in China
  Yu-Zhi Chen

Yu-Zhi Chen

Beijing, China

Author Affiliations: Center for Asthma Prevention, Capital Institute of Pediatrics, Beijing 100020, China (Chen YZ)

Corresponding Author: Yu-Zhi Chen, MD, Center for Asthma Prevention, Capital Institute of Pediatrics, Beijing 100020, China (Tel: 86-10-85634298; Fax: 86-10-85235323; Email: chenyuzh@publica.bj.cninfo.net; acecbc@public3.bta.net.cn)
  [Abstract] [Full Text] [PDF]  
Review articles:
Ethical and moral dilemmas in neonates
  Victor Yu

Background: Among the many neonatal ethical problems, the one which neonatologists are faced with on a regular basis involves the issue of selective non-treatment, that is, clinical decisions made after the birth of a liveborn infant to either withhold or withdraw treatment in certain clinical situations.

Data sources: Original data from national surveys performed in Australia and the Neonatal Intensive Care Unit (NICU) at Monash Medical Centre (MMC) were reported. The policy underlying clinical practice of selective non-treatment at MMC was reviewed and compared to that reported from other NICUs in both developed and developing countries.

Results: If doctors believe that the infant has little prospect for intact survival, their management would be suboptimal and they create a self-fulfilling prophecy. A policy establishing criteria for initiating life-sustaining treatment must be developed with proper consideration of the cultural, social and economic factors operating in the developed or developing country. There are infants whose subsequent clinical course after initiation of neonatal intensive care will indicate that further curative efforts are futile or lack compensating benefit. A policy establishing criteria for withdrawing lifesustaining treatment must also be developed to allow the appropriate use of palliative care in these instances. The clinical situations in which selective non-treatment is taking place in the neonatal intensive care unit are: (1) when death is considered to be inevitable whatever treatment is provided; (2) even when death is not inevitable, there is a significantly high risk of severe physical and mental disability should the infant survive; and (3) when survival with moderate disability is possible, but the infant is likely to experience ongoing pain and suffering, repeated hospitalization and invasive treatment, and early death in childhood.

Conclusions: The principles underlining clinical practice should be the same for developed and developing countries. However, compared to developed countries, communications between the medical and nursing staff and the parents are less adequate in developing countries. Less medical paternalism and more informed parental involvement are encouraged in developing countries in addressing ethical and moral dilemmas in neonates.

Key words: newborn infants; neonatal intensive care;bioethics; healthcare policy; moral-ethical dilemma
  [Abstract] [Full Text] [PDF]  
Thyroid cancer in children
  Diana Diesen and Michael A. Skinner

Background: Thyroid cancer is an uncommon childhood malignancy usually related to radiation exposure and/or genetic predisposition, such as MEN syndromes. This review article will discuss the etiology and genetic factors contributing to carcinoma of the thyroid in children as well as the literature on appropriate surgical treatment of these patients.

Data resources: The surgical literature was reviewed in regard to the management of children with thyroid cancer.

Results: Children most often present with a thyroid mass and diagnosis is made via fine needle aspiration or surgical excision. Treatment consists primarily of surgical resection though there is controversy over the extent of excision necessary for proper oncologic treatment. An emerging consensus is developing that outcome is improved with radioiodine treatment after surgery.

Conclusions: Early aggressive treatment and frequent long-term follow up is essential in the management of these children with thyroid cancer, and most patients can be successfully cured of their disease.

Key words: thyroid cancer; RET gene; thyroidectomy
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Original articles:
Early physical intervention of premature infants to reduce incidence of cerebral palsy
  National Cooperative Group for Lowering Incidence of Cerebral Palsy of Premature Infants through Early Intervention

Background: Preterm infants are more likely to suffer from cerebral palsy than term infants. The aim of this study was to evaluate the effect of early physiotherapy on the incidence of cerebral palsy in premature infants.

Methods: A total of 2684 infants born at less than 37-week gestation, excluding those with congenital deformity and hereditary metabolic diseases, and treated at 29 collaborative units in China from March 2001 to December 2004 were included in this study. The premature infants were classified into 2 groups: intervention group (1390 infants) whose family members actively participated in the early intervention after the initiation of this investigation; routine group (1294 infants) including the premature infants born within 1 year before this investigation, and the premature infants born after the investigation and who did not receive early intervention because of lack of support from family members. The infants of the intervention group received massage, exercise and motor training on the basis of early education at home after discharge from hospitals. All infants with abnormal motor manifestations were given appropriate rehabilitation training. The infants in the routine care group received only conventional baby care.

Results: In the 2 groups, no significant differences were found in complications of pregnant mothers, average gestational age and birth weight, proportion of small for gestational age (SGA) and appropriate gestational age (AGA), proportion of single and multiple births, fetal stress, postnatal asphyxia, Apgar Score, incidence of neonatal hypoxic ischemic encephalopathy (HIE) and intracranial hemorrhage (P>0.05). The findings indicate that the two groups were comparable. At 1 year of age, cerebral palsy occurred in 13 (9.4‰) of the intervention group vs 46 (35.5‰) of the routine care group (P<0.001).

Conclusions: The instructions for the parents to carry out physical intervention for their premature infants can reduce the incidence of cerebral palsy.

Key words: premature infants; early physical intervention; cerebral palsy
  [Abstract] [Full Text] [PDF]  
Incidences of type 1 diabetes in children in the Beijing area in the period of 1988-1996 and 1997-2000
  Chun-Xiu Gong, Cheng Zhu, Chun Yan, Jian-Ping Liang, Gui-Chen Ni, Jie Gao, Yu-Chuan Li, Min Liu, Xiao-Xia Peng and Ze Yang

Background: This study was undertaken to acquire the incidences of type 1 diabetes among children in the Beijing area in the period of 1997-2000 and to compare these data with those in the period of 1988-1996.

Methods: According to the WHO capture-recapture protocol, we collected data from children under 15 years who had been diagnosed as having type 1 diabetes in the Beijing area in the period of 1997 and 2000. The incidence of the disease was calculated from the demographic data and the age-adjusted incidence from the data from the Chinese population of 2000. Confidence intervals of 95% were established with the Poisson distribution, and statistical significance of differences was tested with the chi-square test.

Results: In the period of 1997-2000, the incidence of type 1 diabetes ranged from 0.759 cases per 100 000 to 1.215 cases per 100 000 with an average annual incidence of 1.014/100 000 (95% confidence interval 0.98/100 000 to 1.16/100 000). No significant difference was found in the incidence in this period as compared with the period of 1988-1996, nor in age adjusted incidence (age-adjusted incidence 0.83/100 000 for 1988-1996 vs 0.86/100 000 for 1997-2000). The incidence of the disease was significantly higher in 10- to 14-year-old children than in younger groups (P=0.002). No gender-specific differences were found.

Conclusions: The study did not reveal any statistical difference when comparing the two periods of 1988-1996 and 1997-2000 in the age-adjusted incidence of type 1 diabetes in children in the Beijing area. The results were not consistent with those reported from other countries. Although the economic and social conditions in Beijing changed considerably in the periods of our study, we did not find their influence on the incidence of type 1 diabetes in the pediatric population. Immigration of people from other parts of China to the Beijing area was an intervening factor in this study.

Key words: diabetes mellitus; insulin-dependent; incidence; Beijing; child
  [Abstract] [Full Text] [PDF]  
Clinical characteristics and acetylcholine receptor antibodies in juvenile myasthenia gravis
  Wen-Hui Li, Shui-Zhen Zhou and Dao-Kai Sun

Background: Anti-acetylcholine receptor antibody (AchRab) plays an important role in the pathogenesis of myasthenia gravis (MG). The purpose of this study was to evaluate the clinical characteristics and long-term changes of anti-acetylcholine receptor antibodies in patients with juvenile MG.

Methods: The data from 77 patients with juvenile MG, aged from 3 months to 16 years (45 were female and 32 male with a female to male ratio of 1.4:1) treated at Children’s Hospital, Fudan University from 1992 to 2002 were reviewed retrospectively. All the patients were confirmed clinically and by the neostigmine test. Information about mode of MG presentation, myasthenia, ocular and systemic involvement, AchRab level, therapy and outcome was collected and evaluated. The serological test was done during follow-up.

Results: The onset of MG occurred at age below 3 years. The extraocular muscles were most frequently involved. According to the modified Osserman’s criteria, 54 patients (70%) were classified into type I, 21 (27%) type II, and 2 (3%) type III. Of 52 patients, 18 (35%) were positive for AchRab and 16 (31%) were positive for acetylcholine premembrane receptor antibodies. The clinical state of the patients was not clearly correlated with the levels of the antibodies. No significant difference was observed between clinical type and AchRab positive among the 3 groups. Two (11%) of 18 patients were positive for thymona associated antibody (Titinab). Serological test during follow-up showed that 6 (60%) of 10 AchRab seronegative patients turned to be AchRab seropositive. In 85% of the patients, cluster of differentiation (CD) cells were abnormal, most of them showed reduced levels of CD4+ or CD3+ and CD8+. Thymus proliferation was found in 22 patients (42%) by CT and thymoma was confirmed operatively in 2 (4%). In 50% of the patients, electromyography (EMG) showed nothing abnormal. After administration of anticholinesterase drugs and steroids, the prognosis of the patients with MG was fairly good.

Conclusions: The age of onset of MG is younger, and the incidence of type II MG is increased. AchRab seronegative patients could turn to be positive. Serological monitoring is helpful to find more AchRab seropositive cases. Steroids have been proven effective and safe in treatment of juvenile MG. Methylprednisolone may produce less side-effects than oral predisone after steroid therapy.

Key words: childhood; juvenile myasthenia gravis
  [Abstract] [Full Text] [PDF]  
Association of asthma and transforming growth factor-β1 polymorphism in children
  Wen-Dong Liu, Ji-Rong Lu, Wen-Bin Liu, Kai-Shu Zhao, Cai-Xia Wang and Hong Yu

Background: There are few reports on the relationship of transforming growth factor-β1 (TGF-β1) and asthma. This study was undertaken to explore the association of TGF-β1 gene polymorphism with asthma in children.

Mothods: Ninety-eight children with asthma and 52 normal children were enrolled. The TGF-β1 gene -509C/T polymorphism in the 5’-flanking region was detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The total serum IgE level was examined by the sandwich ELISA method.

Results: No significant differences were found in genotype distribution and allele frequencies between asthmatic individuals and normal controls. But significant differences were seen among severe asthma, mild asthma and normal controls. The serum IgE levels of TT genotype in asthmatic individuals were higher than those of CC or CT genetype.

Conclusions: TGF-β1-509C/T gene mutation is not a high risk factor of asthma, but it is closely correlated with asthma severity, and could be one of candidate genes in severe asthma. The level of serum total IgE is related to TGF-β1-509C/T gene mutation homozygotes.

Key words: bronchial asthma; TGF-β1 gene; polymorphism PCR-RFLP; children
  [Abstract] [Full Text] [PDF]  
Clinical epidemiological investigation of acute lung injury and acute respiratory distress syndrome in children
  Lu-Qi Zhu and Xia Chen

Background: Few epidemiological studies on pediatric acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) have been published. This investigation aimed to understand clinical epidemiological situation of ALI and ARDS in China.

Methods: A series of 64 patients with ALI hospitalized at the pediatric intensive care unit (PICU) of our hospital from February 1996 to January 2001 was analyzed by case-control study. Six death risk factors were studied by single-factor relative risk analysis.

Results: All 64 patients accounted for 0.084% of total hospital admissions and 3.77% of critically ill patients at the PICU during the same period, with an increased morbidity and a mortality of 34.38%. In primary intra-pulmonary diseases, pneumonia was predominant, followed by inhalation. Extra-pulmonary diseases were mainly due to sepsis and heat-stroke syndrome. The order of 6 death risk factors included systemic inflammatory response syndrome (SIRS), extra-pulmonary organ dysfunction, PaO2/FiO2≤200, sepsis, critically ill score ≤70, and pneumonia.

Conclusions: The morbidity of ALI/ARDS is increasing because of improved recognition and diagnosis of the disease. The mortality remains high, while SIRS developing into multiple organ dysfunction syndrome is a high-risk factor causing death.

Key words: pediatrics; acute lung injury; acute respiratory distress syndrome; epidemiology
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Value of 16S rRNA microarray detection in early diagnosis of neonatal septicemia
  Mei-Qin Tong, Shi-Qiang Shang, Yi-Dong Wu and Zheng-Yan Zhao

Background: Neonatal septicemia is a serious life-threatening infectious disease. Early diagnosis will improve the effectiveness of intervention, prognosis, and will reduce complications. This study was undertaken to explore the value of 16S rRNA oligonucleotide microarray in the early diagnosis of neonatal septicemia.

Methods: Primers and oligonucleotide probe against the 16S rRNA gene were designed, then the probe was fixed on a specially designed glass slide to make a microarray. Venous blood was drawn from 285 neonates who were suspected of bacterial infection for blood culture and gene analysis of bacterial 16S rRNA, respectively. The DNA extracted from blood sample and cerebrospinal fluid was amplified by PCR, and the positive products were applied to the microarray for hybridization. Finally, the chip was scanned with laser, and the results were analyzed.

Results: The positive rate of PCR detection was 5.96% (17/285), significantly higher than that of blood culture (2.81%, 8/285) (P<0.01). In contrast to the confirmed diagnosis of septicemia in these patients, the sensitivity, specificity and correct diagnosis index of PCR were 100%, 96.75%, and 0.968, respectively. Microarray hybridization was carried out for the 17 samples of PCR-positive reaction. Positive results were detected in all samples by universal probes: G+ probe in 12 samples, and G- probe in 5 samples. In the 8 samples with positive results shown by PCR and blood culture, the results of microarray hybridization were consistent with those of blood culture in detecting bacterial species.

Conclusions: Microarray technique can be used to rapidly diagnose neonatal septicemia by specially detecting the 16S rRNA gene in clinical samples. The sensitivity and specificity of this technique are much higher than those of blood culture, PCR, and other methods. It also can quickly identify the pathogen of the disease.

Key words: septicemia; ribonucleic acid; bacteria; polymerase chain reaction; microarray
  [Abstract] [Full Text] [PDF]  
Clinical characteristics and treatment of chronic graft versus host disease in pediatric patients
  Ke Huang, Yang Li, Shao-Liang Huang, Jian-Pei Fang, Dun-Hua Zhou and Chun Chen

Background: Chronic graft versus host disease (cGVHD) is an important complication and a cause of mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, new immunosuppressants such as tacrolimus (FK506) and mycophenolate mofetil (MMF) have been available and shown positive curative effects in cGVHD patients. This study was undertaken to analyze the clinical characteristics and risk factors of cGVHD after allogeneic hematopoietic stem cell transplantation and to assess the therapeutic effectiveness of methylprednisolone (MP) and MMF in combination with FK506 or cyclosporine A (CSA) in the immunosuppressive treatment of pediatric cGVHD.

Methods: In 40 patients who received allo-HSCT and engrafted, 25 were treated with umbilical cord blood transplantation (UCBT) and the remaining 15 with peripheral stem cell transplantation (PBSCT). GVHD prophylaxis employed CSA, MP and MMF. Treatment regimen consisted of MP, MMF and FK506 in one group, and MMF and CSA in the other.

Results: Eleven of the 40 engrafted patients (27.5%) developed cGVHD. The cGVHD morbidity was 20% among UCBT patients (5 of 25) and 40% among PBSCT patients (6 of 15). Eight patients presented the continuation of acute GVHD. One patient fully recovered after combined use of CSA and MMF, and 10 patients were given 1 “triple therapy” including MP, MMF and FK506, with an overall response rate of 100%. Three patients died of cytomegalovirus (CMV)-induced interstitial pneumonia, septicemia, and fungi pneumonia, respectively, giving a mortality rate of 27.3%. Seven patients showed an even-free survival (EFS) of more than 3 years, another patient has so far been surviving 29 months at writing. Hepatotoxicity, nephrotoxicity, hypertension, articular capsulitis and cardiac arrhythmia were side-effects most frequently observed. Infection was identified as the main complication and the major cause of death.

Conclusions: The incidence of cGVHD is higher after PBSCT than after UCBT, and the presence of acute GVHD is an important risk factor for subsequent cGVHD. A combination of MP, MMF and FK506 or CSA is safe and effective in the treatment of cGVHD in pediatric patients.

Key words: chronic graft versus host disease; methylprednisolone; mycophenolate mofetil; tacrolimus
  [Abstract] [Full Text] [PDF]  
Strategy for surgical treatment of infective endocarditis in children
  Wen-Dong Wang, Kai-Lun Zhang and Zhi-Wei Hu

Background: The mortality of infective endocarditis (IE) in children is high and it is controversial over timing of surgery for this disease. This study was undertaken to explore the strategy of surgical treatment for IE in children.

Methods: Of 43 patients with IE, 38 had underlying heart diseases, including congenital heart disease (30 patients), rheumatic heart disease (6), hypertrophic cardiomyopathy (1), and postoperative Falot’s tetrology (1). In these patients, 28 underwent surgery, and 10 were treated by medication. In the remaining 5 patients who did not have any underlying heart diseases, 4 showed post-IE valve lesions, and 1 valve lesion. Three of the 5 patients were subjected to surgical treatment but the remaining 2 were treated by medication.

Results: All the 31 patients who had undergone surgical treatment recovered. Two of the 12 patients who had received medication died. Twenty-seven patients undergoing surgical treatment were followed up, and no death or recurrent endocarditis occurred. The life quality of the patients was improved markedly.

Conclusions: Similar clinical characteristics and echocardiographic manifestations of IE were noted in children and adults. Surgery is effective in the treatment of infective endocarditis, and the timing of surgery is crucial. Most children with IE have abnormalities of the heart or congenital heart disease. Hence, these patients should be treated early to avoid the occurrence of IE.

Key words: endocarditis, bacterial; surgical procedure, operative; heart disease, congenital
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Preoperative chemotherapy combined with TACE in treatment of inoperable Wilms’ tumor
  Min-Ju Li, Yong Huang, Da-Xing Tang, Yin-Bao Zhou, Hong-Feng Tang and Jian-Feng Liang

Background: Wilms’ tumor is the most common malignant renal tumor in children. Nephrectomy has played a central role in the treatment of Wilms’ tumor, but some advanced Wilms’ tumors could not be resected immediately because of massive tumor size, involvement of vital structures, inferior vena cava invasion or distal metastasis. To improve the prognosis of patients with these inoperable Wilms’ tumors, we used preoperative chemotherapy and transcatheter arterial chemoembolization (TACE) before surgery. The aim of this study was to investigate the effectiveness of preoperative therapy and to compare it with the strategy of immediate surgery.

Methods: Sixty-two patients with histologically confirmed advanced Wilms’ tumor aged from 5 months to 10 years (mean 3.2 years) were identified from case records during the period from January 1993 to December 2002. The inclusion criteria included a volume of more than 550 ml or the mass extending beyond the midline, involvement of vital structures, inferior vena cava invasion, distal metastasis or bilateral Wilms’ tumor judged by imaging studies. The patients were treated with the following 3 methods separatelly: (1) TACE with epirubicin (EPI)-lipiodol emulsion and two-week systemic chemotherapy with vincristine (VCR) and actinomycin D (ACTD) before surgery (group TACE) (31 patients); (2) conventional systemic preoperative chemotherapy with VCR, ACTD plus EPI for 4-5 weeks (group PC) (20); and (3) initial surgery (group IS) (11). In the three groups, stage II-III was present in 22 (71%), 16 (80%) and 9 (82%) patients; stage III in 5 (16%), 4 (20%) and 2 (18%); stage IV in 3 (10%), 0 and 0; and stage V in 1 (3%), 0 and 0, respectively. Unfavorable histology was found in 2, 1 and 1 patients in the three groups, respectively. Postoperative treatment for all patients was based on the postoperative stage and histology of tumors. Tumor shrinkage before operation, cases of total tumor necrosis, rate of no tumor rupture during operation, and 2-year and 4-year survival rates were compared among the 3 groups.

Results: In the patients treated with TACE, no drug-induced complications including cardiotoxicity, nephrotoxicity, hepatic dysfunction or bone marrow suppression were observed except for mild fever caused by tumor necrosis. Pulmonary metastases on CT disappeared in 2 of 3 patients after TACE with short-term systemic chemotherapy. The percentages of tumor size shrinkage were 32.4% and 20.3% in group TACE and group PC, respectively. No perioperative death occurred in group TACE and group PC, but two in group IS. In group TACE, only 6.5% patients experienced tumor rupture during operation in comparison with 20.0% in group PC and 45.5% in group IS. Complete surgical removal of the tumor was achieved in 27 patients (87.1%) in group TACE, significantly higher in comparison with 14 (70.0%) in group PC and 2 (18.2%) in group IS. Event-free survival (EFS) at 2 and 4 years were 87.1% (27/31) and 84.5% (11/13) in group TACE, 60.0% (12/20) and 56.3% (9/16) in group PC, 18.2% (2/11) and 18.2% (2/11) in group IS, respectively.

Conclusions: This study has shown that both preoperative TACE and conventional preoperative chemotherapy can be applied to properly selected patients with inoperable Wilms’ tumor who are not candidates for immediate surgery. The survival rate is significantly increased in the patients undergoing preoperative TACE and short-term systemic chemotherapy compared with conventional preoperative chemotherapy and initial surgery in the same period. TACE is an effective, safe, and useful method for the initial treatment of inoperable Wilms’ tumor.

Key words: Wilms’ tumor; preoperative chemotherapy; transcatheter arterial chemoembolization
  [Abstract] [Full Text] [PDF]  
Treatment of congenital clubfoot and study of calf muscle histopathology
  Li Zhao, Wei Lei, Long-Shun Xu and Yao-Tian Huang

Background: Congenital clubfoot (talipes equinovarus) is a common condition in pediatric orthopedic surgery. However, there is still disagreement over the best surgical approaches and age indications.

Methods: Surgical treatment was carried out by early operation, achieving dynamic muscle balance in 926 congenital clubfeet of 644 patients who had been followed up for 6 months to 33 years, with reference to unsuccessful treatment because of failure to achieve dynamic muscle balance. Muscle biopsy specimens were taken from the calf muscles in patients with congenital clubfoot for histochemical studies.

Results: Excellent and good results were achieved in 90.9% of the involved feet. Histochemical studies of calf muscle biopsy specimens showed hypertrophy and predominance of type I fibres, grouping of fibre types, and loss of fibre direction in the posteromedial muscles, but no evidence of active denervation and degeneration in the involved calf muscles.

Conclusions: Our findings support the theory of muscle imbalance in the etiology of congenital clubfoot. It is advocated that surgical treatment of congenital clubfoot be carried out immediately after 6 months of age by an operation achieving dynamic muscle balance for the maintenance of satisfactory correction and the 3rd cuneiform be the most appropriate site for a new insertion of transferred tendon.

Key words: congenital clubfoot; clinical follow-up; histopathology
  [Abstract] [Full Text] [PDF]  
Case report:
Anesthetic management of a premature infant weighing 1100 g undergoing ligation of the patent ductus arteriosus
  Yao-Qin Hu, Dong-Pi Wang, Jian Kang and Qiang Shu

Hangzhou, China

Author Affiliations: Department of Anesthesiology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Hu YQ, Wang DP, Kang J and Shu Q)

Corresponding Author: Yao-Qin Hu, MD, Department of Anesthesiology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Tel: 86-571-87061007 ext 60317; Fax: 86-571-87078641; Email: huyaoqin@sina.com)

  [Abstract] [Full Text] [PDF]  
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