• Journal of the korean academy of Pediatric Dentistry
• /
• v.30 no.2
• /
• pp.217-228
• /
• 2003

Co-ordinate growth of the brain and skull is achieved through a series of tissue interactions between the developing brain, the growing bones of the skull and the sutures that unite the bones. Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of these interactions. Bmp2, one of bone morphogenetic proteins (Bmps), is involved in the regulation of the shapes of individual bones and the relative proportions of the skeleton. Mutations in the homeobox gene Msx2, known as a downstream gene of Bmp, cause Boston-type human craniosynostosis. The phenotype of Dlx5 homozygote mutant mouse presents craniofacial abnormalities including a delayed ossification of calvarial bone. These facts suggest important roles of Bmp2, Msx2 and Dlx5 genes in the cranial bone growth and suture morphogenesis. To elucidate the function of these molecules in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of Bmp2(E15-18), Msx2 and Dlx5 genes in the developing sagittal suture of calvaria during the embryonic stage. Bmp2 mRNA was intensely expressed in the osteogenic fronts and also at the low level in the periosteum of parietal bones during embryonic stage, Msx2 mRNA was intensely expressed in the sutural mesenchyme and mildly expressed in the dura mater during the embryonic stage. Dlx5 mRNA was intensely expressed osteogenic fronts and parietal bones. To further examine the role of Bmp signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of Bmp2-soaked beads onto the osteogenic fronts after 48 hours organ culture resulted in the increase of the tissue thickness and cell number around Bmp2 beads, compared to BSA control beads. In addition Bmp2 induced etopic expressions of Msx2 and Dlx5 genes. On the other hand, overexpression of FGF2 did not induce the expression of Msx2 and Dlx5. Taken together, these data indicate that Bmp2 signaling molecule has a important role in regulating the cranial bone growth and early morphogenesis of cranial suture. We also suggest that Bmp signaling is involved in all the stages of osteogenesis of cranial bones and the maintenance of cranial suture by regulating Msx2 and Dlx5 genes, and that Msx2 and Dlx5 genes are specific transcription factors of Bmp signaling pathway.

• Advances in pediatric surgery
• /
• v.12 no.2
• /
• pp.155-166
• /
• 2006

Inguinal hernia is the most common disease treated by the pediatric surgeon. There are several controversial aspects of management 1)the optimal timing of surgical repair, especially for preterm babies, 2)contralateral groin exploration during repair of a clinically unilateral hernia, 3)use of laparoscope in contralateral groin exploration, 4)timing of surgical repair of cord hydrocele, 5)perioperative pain control, 6)perioperative management of anemia. In this survey, we attempted to determine the approach of members of KAPS to these aspects of hernia treatment. A questionnaire by e-mail or FAX was sent to all members. The content of the questionnaire were adapted from the "American Academy of Pediatrics (AAP) Section on Surgery hernia survey revisited (J Pediatr Surg 40, 1009-1014, 2005)". For full-term male baby, most surgeons (85.7 %) perform an elective operation as soon as diagnosis was made. For reducible hernia found in ex-preterm infants already discharged from the neonatal intensive care unit (NICU), 76.2 % of surgeons performed an elective repair under general anesthesia (85.8 %). 42.9 % of the surgeons performed the repair just before discharge. For same-day surgery for the ex-premature baby, the opinion was evenly divided. For an inguinal hernia with a contralateral undescended testis in a preterm baby, 61.9 % of surgeons choose to 'wait and see' until 12 month of age. The most important consideration in deciding the timing of surgery of inguinal hernia in preterm baby was the existence of bronchopulmonary dysplasia (82.4 %), episode of apnea/bradycardia on home monitoring (70.6 %). Most surgeons do not explore the contralateral groin during unilateral hernia repair. Laparoscope has not been tried. Most surgeons do not give perioperative analgesics or blood transfusion.

• Neonatal Medicine
• /
• v.18 no.1
• /
• pp.70-75
• /
• 2011

Purpose: Recently, the incidence of preterm and low birth weight infants (LBWI) is increasing, even though the birth rate is continuously low in Korea. Despite that change, there continues to be a deficit of beds in the neonatal intensive care unit (NICU). This study is based on the 2009 Korean Statistical Information Service that examined the development of a Korean NICU service and the survival rate of preterm infants by regionally analyzing the rate of total live births, preterm infants, LBWI, and NICU beds in Korea. Methods: Data were obtained from the Korean Health Insurance Review and Assessment Service and Korean Statistical Information Service. We confirmed the regional total live birth rate, number of LBWI, and preterm infants and NICU numbers, and all of the results were compared to the average value to determine deficient areas of NICU beds. Results: There were 25,374 (5.7%) preterm infants and 21,954 (4.9%) LBWI in the total number of live births (444,849) in 2009, and regions of high proportion compared to the mean value were Busan, Daegu, and Ulsan. Total NICU beds totaled 1,284, and regions of high rates preterm infants and LBWI per 1 NICU bed compared to the mean value were Incheon, Daegu, Ulsan, etc. The NICU holding rate was 87.5% (1,284/1,468), which was increased from 2005. However, there were still shortages of 184 NICU beds (12.5%), especially in Gyeonggi-do, which lacked 157 beds. Conclusion: High risk neonates difficult to transfer, and they need immediate and continuous treatment. As a result, a foundation of well-balanced, national NICU regionalization is necessary. This study suggested that more NICU facilities must be implemented, and clinicians should realize the continuing deficiency of NICU beds in cities and provinces.

• Neonatal Medicine
• /
• v.18 no.1
• /
• pp.42-48
• /
• 2011

Purpose: Several factors including prolonged inflammatory response are thought to contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). The clinical findings can be explained by an increased production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-$\alpha$ ). We investigated the relationship between susceptibility to BPD and TNF-$\alpha$ promoter polymorphisms to identify genetic factors of the disease. Methods: Thirty-eight preterm infants who had developed BPD and 55 controlled infants with a birth weight <1,500 g were analyzed for TNF-$\alpha$ genotypes. The alleles of five promoter sites (-1031/-863/-857/-308/-238) of TNF-$\alpha$ gene were determined using $Taqman^{(R)}$-based allelic discrimination assays. Results: Gestational age ($27^{+5}{\pm}2^{+0}$ wk vs. $29^{+2}{\pm}1^{+4}$ wk, P<0.0001) and birth weight (990${\pm}$270 g vs. 1,220${\pm}$230 g, P<0.0001) were lower in the BPD group compared to the control group. The incidence of respiratory distress syndrome (71.1% vs. 49.1%, P=0.035) and patent ductus arteriosus (71.1% vs. 50.9%, P=0.052) was higher in the BPD group compared to the control group. The frequencies of the alleles and genotypes of five promoter sites (-1031/-863/-857/-308/-238) of TNF-$\alpha$ gene did not show differences between the BPD group and the control group. Conclusion: TNF-$\alpha$ promoter polymorphisms are not associated with susceptibility to BPD in Korean preterm infants.

• Neonatal Medicine
• /
• v.18 no.1
• /
• pp.96-103
• /
• 2011

Purpose: Although infants with bronchopulmonary dysplasia (BPD) are at risk of developing secondary pulmonary hypertension (PH), which is associated with significant morbidity and mortality, little has been reported about the incidence, clinical course and prognosis of PH secondary to BPD in premature infants. This study was done to investigate the incidence, risk factors, clinical course, and the ultimate prognosis of PH developed secondary to BPD in very low birth weight infants (<1,500 g). Methods: Medical records of very low birth weight infant (VLBWI) admitted to Samsung Medical Center NICU from January 2000 to July 2007 were reviewed retrospectively. BPD was defined by Jobe's classification. The diagnosis of pulmonary hypertension was established as velocity of tricuspid valve regurgitation (TR) ${\geq}$3 m/s and a flattening of the intraventricular septum by conducting Doppler echocardiography. Results: The incidence of pulmonary hypertension was 6% in VLBWI with BPD and it developed in moderate to severe BPD. The diagnosis of pulmonary hypertension was made on postnatal 133 days (range 40-224 days) and the risk factors related to developing pulmonary hypertension were severe BPD, small for gestational age and outborn infants. The mortality rate was 57% and especially higher in severe BPD (70%). The time to recovery spent 3 months (range 1-10 months) in survived patients. Conclusion: Based on the results of this research, pulmonary hypertension secondary to BPD in VLBWI related to severity of BPD and had a poor prognosis. We expect that regular long-term echocardiography may be helpful in treating reversible in VLBWI with moderate to severe BPD.

• Clinical and Experimental Pediatrics
• /
• v.51 no.8
• /
• pp.874-878
• /
• 2008

Purpose : This study was undertaken to develop an animal model of periventricular leukomalacia (PVL) induced by in utero clamping of pregnant rat aorta in fetal rats. Methods : A timed pregnanct Sprague-Dawley rat on embryonic day 21 just prior to delivery was sedated and anesthetized, and a Harvard ventilator for small animals was applied. Following laparotomy, the maternal aorta was clamped reversibly for 40 minutes using a surgical clip. The fetal rats were then delivered by Cesarean section, resuscitated if necessary, and reared by a surrogate mother rat until postnatal day 21 to obtain the brain specimen. After systemic perfusion and fixation, $10{\mu}m$ thick serial brain sections were obtained and stained for pathologic examination and assessment of ventriculomegaly. Ventriculomegaly was assessed by the measured ventricle to total brain volume ratio. Results : Eight out of eleven fetal rats (73%) survived in the ischemia group after induction of in utero ischemia by clamping maternal rat aorta, and all ten survived in the control group. Body and brain weights measured at postnatal day 21 were significantly lower in the ischemia group compared to the control group. In pathologic findings, significant ventriculomagaly ($3.67{\pm}1.21%$ vs. $0.23{\pm}0.06%$) was observed in the ischemia group compared to the control group; although cystic lesion was not observed, mild (n=6) and moderate (n=2) rerefaction of the brain tissue was observed. Conclusion : A fetal rat model of PVL induced by in utero clamping of pregnant rat aorta was developed.

• Journal of Korean Neurosurgical Society
• /
• v.29 no.12
• /
• pp.1555-1562
• /
• 2000

Objects : Surgical management of the distal anterior cerebral artery(DACA) aneurysms presents several unique problems to surgeons, such as difficulty in early identification of parent arteries, high incidence of rebleeding and premature rupture, and requirement of unfamiliar approach other than conventional frontotemporal craniotomy. Therefore, preoperative anatomical knowledge of anterior interhemispheric fissure and entry point of dissection is prerequisite. Authors utilized a frontobasal approach for DACA aneurysms by using consistent external landmark for guidance to the deep structure. Materials and Methods : From Nov. 1995 to Jun. 1999, a surgical clipping of DACA aneurysms was carried out in 9 patients among a total 131 patients with intracranial aneurysms. In each case, the clinical and aneurysmal features were carefully reviewed through the angiograms, medical records, and intraoperative findings. Results : The incidence of DACA aneurysms was 6.9% from our series. All cases were arisen from juxtacallosal por-tion ; 6 cases from pericallosal-callosomarginal(PC-CM) junction and 3 from pericallosal-frontopolar(PC-FP) junction. Associated vascular anomalies were noted in 3 cases and multiple aneurysms in 3 cases, respectively. The preoperative clinical grades were generally poor. An early surgery was performed in 7 cases and frontobasal interhemispheric approaches in 7 cases. Postoperatively, two patients died of complications ; one delayed ischemic vasospasm and one aspiration pneumonia but remaining patients recovered well. Conclusion : The frontobasal interhemispheric approach was useful for DACA aneurysms in early surgery. Division of superior sagittal sinus(SSS) enabled a minimal retraction of brain on both sides, and prevention of intraoperative rupture was possible. Authors suggest the frontopolar(first frontal bridging) vein as a constant external landmark for approaching the genu of the corpus callosum and juxtacallosal DACA aneurysms.

• Clinical and Experimental Pediatrics
• /
• v.50 no.3
• /
• pp.268-271
• /
• 2007

Purpose : Premature narrowing of the foramen ovale is rare but serious clinical entity. Prenatal narrowing or obstruction of the foramen ovale shows symptoms such as right heart failure, fetal hydrops, triscupid regurgitation, left heart obstructive disease, and supraventricular tachycardia. This study aimed to assess the prenatal diagnosis and postnatal clinical course of restrictive foramen ovale in utero in otherwise normal heart. Methods : The subjects were five patients diagnosed with restrictive foramen ovale in utero from January 2001 to June 2005 at Chungnam National University Hospital. The diagnostic criteria was defined when the maximum diameter in a 4-chamber view is less than 2.5 mm and there is a continuous doppler velocity at the foramen ovale of more than 0.6m/s. Results : At the time of diagnosis of restrictive foramen ovale, gestation age was 34~37 wks, and chief complaints were fetal arrhythmia(2 cases), pericardial effusion, Ebstein anomaly and subaortic stenosis. Two cases which were diagnosed fetal hydrops and supraventricular tachycardia delivered by emergent cesarian section. Five cases were found to have right heart dilatation on echocardiogram after birth, but right heart dilatation became normalized at day 7 after birth and the clinical courses were not eventful. Conclusion : Identifying an obstructed foramen ovale in the fetus warrants the further search for additional cardiac and extracardiac anomalies, which may alter the prognosis. Delivery should be induced if possible in cases of foramen ovale obstruction with signs of cardiac decompensation.

• Reproductive and Developmental Biology
• /
• v.32 no.1
• /
• pp.51-58
• /
• 2008

This study was performed to investigate the relation between birth weight and survivability on the production of cloned Hanwoo calves. The 580 cloned embryos were transferred into the 293 recipients. The pregnancy rate of the cloned embryos was 72.3% at 50 days after embryo transfer, and then the rate was dramatically decreased. The mean gestation lengths were 287 days in both clone (range of$279{\sim}295$ days) and artificial insemination (AI, range of $255{\sim}293$ days) calves, respectively. The mean birth weight of cloned calves (30.3kg) was significantly higher compared to that of AI calves (23.7kg) (p<0.05). Among the cloned calves, the birth weight was not different in both normal delivery (n=17, 29.9kg) and caesarean section (n=14, 32.3kg). The weight, however, was significantly higher in the clones (n=18, 32.8kg) dead within 175 days than that of the clones (n=11, 28.3kg) alive more than 175 days after birth (p<0.05). Interestingly, all cloned calves weighed <15kg (n=5) or >35kg (n=9) at birth have been dead within 175 days from the date of birth. The causes of death in the cloned calves were premature birth (n=2, 10.0%), abnormal function of lung and liver (n=2, 10.0%), abnormal function of lung (n=4, 20.0%), malformation (n=4, 20.0%), unknown (n=4, 20.0%), and sudden death syndrome (n=4, 20.0%), respectively. Our findings suggest that normal birth weight is one of the most important factors to survive more than 6 months in cloned calves.

• Pediatric Infection and Vaccine
• /
• v.11 no.1
• /
• pp.112-120
• /
• 2004

Purpose : Methicillin Resistant-Coagulase Negative Staphylococcus(MR-CNS) infection has become an increasingly important cause of morbidity in NICU infants. We investigated the c linical characteristics of MR-CNS sepsis. Methods : This study included 40 neonates with MR-CNS sepsis who were admitted to the neonatal intensive care unit of Kangnam Sacred Heart Hospital, Hallym University from January 1998 to July 2002. MR-CNS sepsis was defined as MR-CNS recovery from blood with clinical symptoms and signs of infection. Retrospective analyses of the medical records of patients with MR-CNS sepsis were performed. The analyses included demographic findings, clinical features, hospital courses, risk factors for infection including invasive procedures and mortality. Results : From 1998 to 2002, there were 40 cases of MR-CNS sepsis, comprising 17.7% of late onset infections in NICU of Kangnam Sacred Heart Hospital. The male/female ratio was 1.5 : 1. The mean gestational age of infected babies was $32.4{\pm}4.3$ weeks at birth. And the first positive MR-CNS culture was done in the day $10.6{\pm}9.3$ after birth. Clinical symptoms such as fever, dyspnea, cyanosis, grunting, bradycardia, vomiting and diarrhea were frequent in MR-CNS. Mechanical ventilation was applied in 12 cases and catheter was inserted in 11 cases. The mortality(12.5%) directly attributable to MR-CNS sepsis was similar to other late onset infections. Conclusion : MR-CNS is a pathogen responsible for most late onset and nosocomial infections. And it will be life-threatening in high-risk neonate. Awareness of increasing infections due to MR-CNS in NICU is important not only for infection control but also placing a great limit in use of antibiotics and invasive procedures, especially in premature infants.