Abstract:
BACKGROUND/PURPOSE:Since the discovery of the cystic fibrosis transmembrane regulator (CFTR) gene, cystic fibrosis has been an attractive target for gene therapy. Postnatal gene transfer in the respiratory epithelium has been difficult and particularly inefficient in the submucosal gland cells, the target cells for CFTR gene transfer. The authors hypothesized that during development, there is a favorable environment for fetal gene therapy with fewer physical barriers to efficient gene transfer and more accessible epithelial and submucosal gland precursor cells. The authors tested this hypothesis in a novel human fetal tracheal organ culture system using a serotype 2 recombinant AAV that contains an enhanced green fluorescent protein (eGFP) reporter gene (AAV-CMV-eGFP). METHODS:Human fetal tracheas at between 16 and 20 weeks' gestation age were used in this study. The distal end of each trachea was ligated and secured in an upright position with the open proximal end facing up. Only the ante-lumenal surface was exposed to culture media. 5 x 10(9) particles of AAV-CMV-eGFP were administered intratracheally through the open end. Fetal tracheas were maintained in tracheal organ culture media and harvested at either 2 weeks (n = 3) or 4 weeks (n = 7) after injection. The fetal tracheas were processed for routine H&E, standard electron microscopy (EM), and fluorescence microscopy for analysis of eGFP transgene expression. RESULTS:Histology confirmed the preservation of structural integrity out to 4 weeks of fetal tracheal organ culture. EM showed intact tight junctions of the apical respiratory epithelium. At 2 weeks after AAV-CMV-eGFP injection, there was minimal transgene expression. However, at 4 weeks there was extensive transgene expression in not only the respiratory surface epithelium but also the submucosal gland cells of the human fetal tracheal organ culture. Transgene expression was seen in nearly all cells in the submucosal glands. CONCLUSIONS:AAV-mediated gene transfer in human fetal tracheal organ culture was highly efficient with excellent transgene expression at 4 weeks in both respiratory surface epithelium and submucosal gland cells. This highly efficient gene transfer may result from fewer physical barriers and more accessible target precursor cells. These results are consistent with more efficient gene transfer in fetal tracheobronchial epithelium and show the potential for fetal gene therapy using AAV for the treatment of congenital airway disease such as cystic fibrosis.
journal_name
J Pediatr Surgjournal_title
Journal of pediatric surgeryauthors
Lim FY,Martin BG,Sena-Esteves M,Radu A,Crombleholme TMdoi
10.1053/jpsu.2002.33843subject
Has Abstractpub_date
2002-07-01 00:00:00pages
1051-7; discussion 1051-7issue
7eissn
0022-3468issn
1531-5037pii
S0022346802000246journal_volume
37pub_type
杂志文章abstract::Children with anal atresia often have compromised function. This is especially common with the anatomic "high lesion." Twenty-five patients have been studied using clinical evaluation, computed tomography (CT), and manometry to make an objective evaluation. The patients were an average of 9.6 years old; the male-to-fe...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/s0022-3468(05)80274-x
更新日期:1993-02-01 00:00:00
abstract:BACKGROUND:Care of infants with gastroschisis is centralized in Canada and noncentralized in the United States. We conducted an outcomes comparison between the two countries and analyzed the determinants of such outcomes. METHODS:Inpatient mortality and hospital stay of gastroschisis patients from the Canadian Pediatr...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2016.02.046
更新日期:2016-06-01 00:00:00
abstract::Most babies born with congenital diaphragmatic hernia (CDH) die after birth. The natural course of CDH in the human fetus is not known. We found 94 cases of fetal CDH in the records of surgeons and obstetricians surveyed in the United States and Canada. We found the following: (1) prenatal diagnosis of CDH is accurate...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/s0022-3468(85)80219-0
更新日期:1985-08-01 00:00:00
abstract:AIM OF THE STUDY:Management of isolated intestinal perforation (IIP) poses a challenge for the pediatric surgeon. Intestinal resection and primary anastomosis is considered to be as good as the classical approach, namely, intestinal diversion by ileostomy. However, few reports compare primary anastomosis and ileostomy ...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2016.02.086
更新日期:2016-08-01 00:00:00
abstract::In infants and children requiring prolonged and multiple central venous catheterizations, conventional cannulation sites may become thrombosed or stenotic, making inability to gain vascular access a life-threatening problem. The technique we use for the percutaneous placement of inferior vena caval tunneled silastic c...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/0022-3468(90)90341-6
更新日期:1990-06-01 00:00:00
abstract:BACKGROUND/PURPOSE:Diaphragmatic agenesis (DA) is a distinct clinical entity with poorer survival rate compared with patients with posterolateral diaphragmatic hernia. The large defect in DA is repaired frequently with a synthetic patch in the neonatal period. Well-known, long-term complications include recurrent herni...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1053/jpsu.2001.27937
更新日期:2001-11-01 00:00:00
abstract:BACKGROUND/PURPOSE:Inguinal hernia repair and orchidopexy are among the most common operations in boys. The impact on future fertility has not been conclusively defined. This study evaluates sperm quality after previous inguinal surgery. METHODS:Spermiograms of men with a desire to conceive children were analyzed. His...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2018.10.012
更新日期:2019-01-01 00:00:00
abstract::A rare case of VACTEL syndrome with antenatally diagnosed duodenal atresia is reported. We performed one-staged radial surgery for the esophageal atresia with tracheoesophageal fistula and duodenal atresia. The prognosis of VACTEL syndrome with duodenal atresia is very poor. This is the first reported case cured opera...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/s0022-3468(89)80104-6
更新日期:1989-11-01 00:00:00
abstract::A 10-month-old boy was noted to have hepatomegaly, and hepatic angiography showed a huge tumor of the medial segment of the left lobe, located close to the hepatic hilum and involving the anterior segment of the right lobe in contiguity. We considered at first that resection would not be possible, but at operation the...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/s0022-3468(89)80109-5
更新日期:1989-11-01 00:00:00
abstract::The authors report on a male infant aged 4(1/2) weeks who underwent a pyloromyotomy for hypertrophic pyloric stenosis. After an uncomplicated postoperative course with normal feeding and weight gain, projectile vomiting reoccurred. The boy underwent a repyloromyotomy for recurrent hypertrophic pyloric stenosis. The un...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1053/jpsu.2002.36213
更新日期:2002-11-01 00:00:00
abstract:PURPOSE:We adopted antibiotic (Ab) protocols for managing surgical site infections in children and assessed their effectiveness. METHODS:We used our protocols on 1313 children between 2004 and 2005. All wounds were monitored for 30 days and classified as clean, clean-contaminated, contaminated, or dirty-infected. Infe...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2007.01.034
更新日期:2007-06-01 00:00:00
abstract::Enterocolitis (EC) remains the most serious complication of Hirschsprung's disease (HD). The aetiology of EC is uncertain. Ischemic and bacterial causes, and recently rotavirus infection, have been suggested to explain the occurrence of EC. The gut has an abundance of neuroendocrine (NE) cells which modulate gut funct...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/0022-3468(93)90520-u
更新日期:1993-08-01 00:00:00
abstract::The benefit of extracorporeal membrane oxygenation (ECMO) in cases of high-risk congenital diaphragmatic hernia (CDH) was studied by comparing pre-ECMO (1987-1990) and post-ECMO (1991-1994) 3-month survival statistics. Fifty-five CDH patients who presented in respiratory distress within 6 hours after birth were referr...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/0022-3468(95)90408-5
更新日期:1995-10-01 00:00:00
abstract::An infant presented with abdominal distension and failure to thrive. This patient was a 3.5-month-old, ex-26-week premature infant at the time of presentation who required supplemental parenteral nutrition until day 9 of life. Workup found ascites and a complex cystic mass in the porta hepatis. A perforated gallbladde...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1053/jpsu.2002.35029
更新日期:2002-09-01 00:00:00
abstract:PURPOSE:We established a vitamin A-deficient (VAD) model of pregnant rats to evaluate the effect of vitamin A deficiency in maternal rats on tumor formation in filial rats. METHODS:Ten pregnant Wistar rats were divided into 2 groups: (1) VAD group, 6 rats were given nonvitamin A diet from 2 weeks before mating till de...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2008.07.008
更新日期:2009-03-01 00:00:00
abstract::Is gastroschisis embryologically distinct from omphalocele or simply a ruptured small omphalocele (hernia of the umbilical cord)? Serial sonographic imaging of a fetus with a small omphalocele at 27 weeks gestation has now provided the "missing link" in the pathogenesis of gastroschisis by documenting in utero rupture...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/s0022-3468(85)80229-3
更新日期:1985-08-01 00:00:00
abstract:INTRODUCTION:Bacterial intestinal translocation plays an important role in neonatal sepsis. We aimed to elucidate the importance of such translocation in causing central line associated blood stream infection (CLABSI) in patients undergoing gastrointestinal surgery (GIS). METHODS:Using a database of pediatric patients...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2020.02.012
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to identify the risk of respiratory disease for developing inguinal hernia (IH). STUDY DESIGN:A retrospective case-control study reviewed medical records of 100 outborn infant males, gestational age (GA) less than 35 weeks, admitted between July 1999 and November 2002 to our lev...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2006.06.007
更新日期:2006-11-01 00:00:00
abstract:AIM:The objective of this study is to compare laparoscopy-assisted pull-through (LPT) and open pull-through (OPT) for Hirschsprung's disease with special reference to postoperative fecal continence. METHODS:Thirteen OPT patients (1991-1996) were reviewed retrospectively, and 22 LPT (1997-2002) were reviewed prospectiv...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2007.08.033
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:Elective preterm delivery of the fetus with gastroschisis may help to limit injury to the extruded fetal gut and thus promote faster recovery of neonatal gut function and earlier hospital discharge. This hypothesis has not previously been tested in a prospective randomized controlled trial. METHODS:Between ...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jpedsurg.2005.07.047
更新日期:2005-11-01 00:00:00
abstract::The endoparasitic twin is the most common form of asymmetric fetal duplication (heteropagus). A 2-month-old girl who had a parasitic right lower limb with axial skeleton, vertebral column, uterus, fallopian tube, ovary, and bladder implanted in the sternum region is described as another example of exoparasitic twin, t...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/s0022-3468(97)90573-x
更新日期:1997-10-01 00:00:00
abstract::In adults, small bowel diaphragm disease is a rare complication of small bowel enteropathy secondary to the use of nonsteroidal antiinflammatory drugs. The main clinical manifestations are gastrointestinal bleeding and subacute obstruction, and management can be challenging. We present a case of a 5-year-old girl with...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2012.05.003
更新日期:2012-08-01 00:00:00
abstract::We herein report a rare case of a newborn girl with a right-sided congenital diaphragmatic hernia where a herniated liver had an abnormal vessel communication with the right lung. A surgical repair was initially attempted through a thoracic approach at 4 days of age where only a plication of the hernia capsule was per...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2005.12.032
更新日期:2006-03-01 00:00:00
abstract::Emergency pneumonostomy was curative in a critically ill child with acute lung abscess. This procedure may be indicated for the rare acute lung abscess which fails to respond to medical therapy. ...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/s0022-3468(83)80377-7
更新日期:1983-10-01 00:00:00
abstract:PURPOSE:The aim of this study was to determine the risk of central line associated blood-stream infections (CLABSI) in neonatal gastroschisis patients, risk factors, outcomes, and financial implications. METHODS:The 2016 Healthcare Cost and Utilization Project (HCUP)'s kid's inpatient database (KID), a national databa...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2019.10.028
更新日期:2020-02-01 00:00:00
abstract::Anomalies of the biliary system are rare. Anomalies of the gallbladder and anomalies of the bile ducts are distinguished. We observed a newborn with a gallbladder in an extraabdominal malposition, an anomaly that has not been previously described. Ultrasonography revealed a cystic structure with a ductlike connection ...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2008.07.016
更新日期:2008-11-01 00:00:00
abstract::This study was undertaken to search for a rational basis for the use of anal dilatation and internal sphincterotomy as the treatment for chronic intractable constipation in children. Sixteen children, age 5 months to 13 years, who had constipation resistant to conservative treatment were compared with 39 age-matched c...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/s0022-3468(97)90395-x
更新日期:1997-07-01 00:00:00
abstract:PURPOSE:The aim of this study was to review the surgical complications of pancreatectomy for persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI). METHODS:A retrospective review was conducted of patients undergoing pancreatectomy for PHHI in one institution over the past 13 years. RESULTS:The records of 48 pa...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1053/jpsu.2003.50001
更新日期:2003-01-01 00:00:00
abstract::Controversy exists over the best method and technique of repair of oesophageal atresia and diaphragmatic hernia. Open surgical repairs have a long established history of over 60 years of experience. Set against this has been a series of successful thoracoscopic repairs of both congenital anomalies reported over the pa...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章,评审
doi:10.1016/j.jpedsurg.2014.11.008
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:We have previously reported that rejected allografts show dysmotility, which can be detected by real-time monitoring in swine. We examined the correlation between the motility and the mucosal histology to detect rejection at an early stage by real-time monitoring. METHODS:Intestinal transplantation was perf...
journal_title:Journal of pediatric surgery
pub_type: 杂志文章
doi:10.1016/j.jpedsurg.2007.03.038
更新日期:2007-08-01 00:00:00