• Toxicological Research
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• v.26 no.4
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• pp.275-283
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• 2010

Placenta transfer study in non-human primate (NHP) is one of the crucial components in the assessment of developmental toxicity because of the similarity between NHP and humans. To establish the method to determine placenta transfer in non-human primate, toxicokinetics of valproic acid (VPA), a drug used to treat epilepsy in pregnant women, were determined in pregnant cynomolgus monkeys. After mating, pregnancy-proven females were daily administered with VPA at dose levels of 0, 20, 60 and 180 mg/kg by oral route during the organogenesis period from gestation day (GD) 20 to 50. Concentrations of VPA and its metabolite, 4-ene-VPA, in maternal plasma on GDs 20 and 50, and concentrations of VPA and 4-ene-VPA in placenta, amniotic fluid and fetus on GD 50 were analyzed using LC/MS/MS. Following single oral administration of VPA to pregnant monkeys, concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma from all treatment groups up to 4-24 hours post-dose, demonstrating that VPA was absorbed and the monkeys were systemically exposed to VPA and 4-ene-VPA. After repeated administration of VPA to the monkeys, VPA was detected in amniotic fluid, placenta and fetus from all treatment groups, demonstrating that VPA was transferred via placenta and the fetus was exposed to VPA, and the exposures were increased with increasing dose. Concentrations of 4-ene-VPA in amniotic fluid and fetus were below the limit of quantification, but small amount of 4-ene-VPA was detected in placenta. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at dose levels of 20, 60 and 180 mg/kg during the organogenesis period. VPA was transferred via placenta and the fetus was exposed to VPA with dose-dependent exposure. The metabolite, 4-ene VPA, was not detected in both amniotic fluid and fetus, but small amount of 4-ene-VPA was detected in placenta. These results demonstrated that proper procedures to investigate placenta transfer in NHP, such as mating and diagnosis of pregnancy via examining gestational sac with ultrasonography, collection of amniotic fluid, placenta and fetus after Caesarean section followed by adequate bioanalysis and toxicokinetic analysis, were established in this study using cynomolugus monkeys.

• Pediatric Infection and Vaccine
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• v.7 no.1
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• pp.113-119
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• 2000

Purpose : Rotavirus is a most common etiologic agent of pediatric gastroenteritis. The standard method to diagnose rotavirus infection was the detection of viral particles in specimens through electron microscopy. But it was complex. Enzyme immunoassay and latex agglutinin are preferred because they are relatively handy, inexpensive and take a short time, in comparison with electron microscopy. However, several reports have shown that the use of ELISA to diagnose rotavirus infection in neonates can result in false positive reactions. The main purpose of this study is to compare ELISA and RT-PCR in the diagnosis of neonatal rotavirus infection. Methods : Data presented in this study were obtained form 123 newborn babies in the nursery of the Fatima Hospital, Masan, Korea, form Jury to December, 1997. We obtained two samples of stool from each of the newborn babies and then performed the Rotazyme test and the RT-PCR. In the Rotazyme test, the results were interpreted according to visual findings. The samples were used for the RT-PCR test after at stock $-30^{\circ}C$ to identify rotavirus group A. The result of the two tests were compared. Results : The informations are divided into 73 males and females. Out of the total informations 15 were transferred from other hospitals. Their average gestational age was $38.5{\pm}1.6$ weeks. The average birth weight was $3134.8{\pm}539gm$. In the Rotazyme test, 75 samples turned out to be positive. Out of them, 55 samples(75.3%) were positive and 18 samples(24.7%) were negative in the RT-PCR. On the other hand, in the Rotazyme test, 50 samples turned out be negative. Out of them, 27 samples(54%) were positive and 23 samples(46%) were negative in the RT-PCR. Conclusion : Rotavirus infection in uncommon in neonates. The diagnosis based on visual findings using Rotazyme test has a disadvantage in the sense that it can result in false positive reactions and false negative reactions in the diagnosis of neonatal rotavirus infection.

• Neonatal Medicine
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• v.15 no.2
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• pp.160-165
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• 2008

Purpose : Cephalhematomas rarely lead to serious complications, such as skull fractures and intracranial hematomas, so CT and/or MRI scans are indicated only in cases in which depressed fractures are suspected or neurologic symptoms develop. Nevertheless, we have experienced several cases of cephalhematomas associated with intracranial hematomas in the absence of remarkable neurologic symptoms. The aim of this study was to evaluate the correlation between cephalhematomas and intracranial hematomas and determine the need for neuroimaging in infants with cephalhematomas. Methods : Infants who were admitted to the NICU with cephalhematomas and underwent neuroimaging (CT and/or MRI) between January 2002 and July 2006 were evaluated. Neuroimaging was done when the symptoms suggested the development of an intracranial hematoma. Results : Among 54 infants with cephalhematomas, 18 infants underwent neuroimaging. Six of 18 infants (33.3%) had intracranial hematomas, 4 infants had epidural hematomas, and 2 infants had subdural hematomas. Four of these 6 infants had neurologic symptoms or depressed skull fractures; 2 infants had no neurologic symptoms or depressed skull fractures. The neuroimaging was done to evaluate the cause of an excessive elevation of serum bilirubin and unexplained anemia. There were no remarkable differences between the infants with and without intracranial hematomas with respect to gestational age, birth weight, head circumference, diameter of the cephalhematoma, neurologic symptoms, and other clinical signs and symptoms. Conclusion : Based on this study, intracranial hematomas are common complications of cephalhematomas, thus more careful inspection and neuroimaging may be needed in cases of cephalhematomas in newborns.

• Development and Reproduction
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• v.16 no.2
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• pp.95-100
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• 2012

Bisphenol A (BPA), a chemical with weak estrogenic activity is reported to affect preimplantation embryos, fetuses and alter their postnatal development. This study amied to determine the relation between the levels of BPA in the amniotic fluid and pregnancy outcomes. ELISA was used to measure amniotic fluid BPA in 120 pregnant women who underwent genetic amniocentesis at 15~20 weeks gestation. The most common indication for amniocentesis was advanced maternal age (35 yrs or older). BPA was detected in all amniotic fluid. The range of amniotic fluid BPA concentrations was from 0.89 ng/mL to 37.13 ng/mL with a mean level of 7.24 ng/mL. We compared the means of amniotic fluid BPA concentrations according to maternal age (${\geq}35$ vs. <35 yrs), fetal sex (male vs. female), gestational age at birth (${\geq}37$ vs. <37 weeks), and infant birth weight (${\geq}2.5$ vs. <2.5 kg). No significant differences were found in these outcomes. This is the first report of amniotic fluid BPA levels in Korean pregnant women. Our findings suggest that BPA may not affect the pregnancy outcomes such as fetal sex, preterm delivery and low birth weight. Whether prenatal exposure to BPA can have teratogenic effect on developing embryo needs to be studied.

• Toxicological Research
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• v.24 no.4
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• pp.263-271
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• 2008

Recently we reported that 2-bromopropane (2-BP) has maternal toxicity, embryotoxicity, and teratogenicity in Sprague-Dawley rats. The aims of this study are to examine the potential effects of 2-BP administration on pregnant dams and embryo-fetal development, and to investigate the effects of metabolic activation induced by phenobarbital (PB) on developmental toxicities of 2-BP. Pregnant rats received 1000 mg/kg/day subcutaneous 2-BP injections on gestational days (GD) 6 through 10 (Group II and Group IIII) or 11 through 15 (Group IV). Pregnant rats in Group III received an intraperitoneal PB injection once daily at 80 mg/kg/day on GD 3 through 5 for induction of the liver metabolic enzyme system. Control rats received vehicle injections only on GD 6 through 15. All dams underwent caesarean sections on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. Significant adverse effects on pregnant dams and embryo-fetal development were observed in all the treatment groups, and the maternal and embryo-fetal effects of 2-BP observed in Group II were higher than those seen in Group IV. Conversely, maternal and embryo-fetal developmental toxicities observed in Group III were comparable to those seen in Group II. These results suggest that the potential effects of 2-BP on pregnant dams and embryo-fetal development are more likely in the first half of organogenesis (days $6{\sim}10$ of pregnancy) than in the second half and that the metabolic activation induced by PB pre-treatment did not modify the developmental toxic effects of 2-BP in rats.

• Toxicological Research
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• v.24 no.4
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• pp.307-314
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• 2008

The present study was carried out to investigate the potential adverse effects of 1,3-dichloro-2-propanol on pregnant dams after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The tested chemical was administered orally to pregnant rats at dose levels of 0, 10, 30, or 90 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights, and Caesarean section findings were examined. In the 90 mg/kg group, decreases in the body weight gain and food consumption, and increases in the weights of liver and adrenal glands were observed. Serum biochemical investigations revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol (CHO), triglyceride (TG), alkaline phosphatase (ALP), and bilirubin (BIL) and decreases in glucose (GLU), albumin (ALB) and total protein (TP). In the 30 mg/kg group, a decrease in the food consumption and an increase in the liver weight were observed. Serum biochemical investigation also showed increases in CHO and TG and a decrease in glucose. Since there were no signs of maternal toxicity in the 10 mg/kg group, it is considered to be the no-observed-adverse-effect level (NOAEL) of 1,3-dichloro-2-propanol. It is concluded that successive oral administration of 1,3-dichloro- 2-propanol to pregnant rats for 14 days may cause significant toxicities in body weight and liver at a dose rate ${\geq}$ 30 mg/kg/day.

• Journal of Veterinary Clinics
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• v.25 no.2
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• pp.79-84
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• 2008

For estimating the ovulation time in Miniature Schnauzer dogs during the estrous cycle, radioimmunoassay of plasma estradiol-$17{\beta}$ and progesterone concentrations was conducted on blood samples in 21 pregnant and 13 non pregnant dogs. When Day 0 was that plasma progesterone concentrations exceeded 4.0 ng/ml, on Day 64, parturition day, progesterone declined below 1.0 ng/ml with $0.92\;{\pm}\;0.29\;ng/ml$ and when Day 0 was that plasma progesterone concentrations declined below 1.0 ng/ml, on Day -64, progesterone increased above 4.0 ng/ml with $4.56\;{\pm}\;0.87\;ng/ml$. Gestational length was $63.71\;{\pm}\;1.35$ (Mean${\pm}$S.D.) days from plasma progesterone concentrations exceeded 4.0 ng/ml and was $66.29\;{\pm}\;1.98$ days from first male acceptance. The plasma estradiol-$17{\beta}$ concentrations reached maximum value with $28.20\;{\pm}\;2.86\;pg/ml$ on Day .2, and plasma progesterone concentrations reached $5.90\;{\pm}\;0.36 ng/ml, 5.18\;{\pm}\;0.32 ng/ml on Day 0, and the maximum of 61.58\;{\pm}\;10.47 ng/ml on Day 19 and 56.05\;{\pm}\;8.86\;ng/ml$ on Day 16 in pregnant and non pregnant dogs, respectively. Afterward, plasma progesterone concentrations declined below 1.0 ng/ml on Day 64 with $0.92\;{\pm}\;0.29\;ng/ml$ in pregnant cycles and on Day 58 with $0.95\;{\pm}\;0.63\;ng/ml$ in non pregnant dogs. No difference were found pregnant and non pregnant dogs in plasma estradiol-$17{\beta}$ and progesterone concentrations (p<0.01). Based on first male acceptance (Day 0), the maximum of plasma estradiol-$17{\beta}$ concentrations ($29.31\;{\pm}\;3.61\;pg/ml$) occurred on Day -1 and plasma progesterone concentrations exceeded 4.0 ng/ml on Day 2 in pregnant ($5.37\;{\pm}\;0.76\;ng/ml$) and non pregnant ($4.25\;{\pm}\;0.80\;ng/ml$) dogs. These results suggest that in Miniature Schnauzers, the ovulation occurred when plasma progesterone concentrations exceeded 4.0 ng/ml, 3 days after plasma estradiol-$17{\beta}$ peak and 2 days after first male acceptance.

• Advances in pediatric surgery
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• v.12 no.2
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• pp.167-174
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• 2006

Central venous catheter (CVC) for long-term venous access is indispensable for various reasons including hyperalimentation, frequent blood sampling, frequent IV drug use in pediatric patients. We report clinical experience of surgical neonates in whom CVC was inserted primarily via great saphenous vein into suprarenal inferior vena cava. From March 2004 to March 2006, we performed CVC insertion via saphenous vein - contralateral side to main wound - into suprarenal inferior vena cava in surgeries of neonates. 2.7Fr or 4.2Fr, single lumen, tunneled Broviac catheters (Bard Access system, Inc, Salt Lake City, Utah) were used. Skin exit site of tunneled catheter was located in ipsilateral flank area just below edge lower rib. At the end of the procedure, location of the catheter tip was confirmed by plain radiography of abdomen. We retrospectively reviewed the admission records of the patients including nursing staff charts. Nine (50.0 %) patients were male and nine (50.0%) were female. Median gestational age was 38 weeks (range, 29-42 weeks) and median birth weight was 3,105 gm (range, 1,040-3,720 gm). Median age at catheter insertion was 38.5 days (range, 1-236 days). The purpose of CVC insertion was short-and long-term hyperalimentation in nine (50.0 %) patients. CVC insertion was performed in operation room under general anesthesia in sixteen (88.9 %) patients (in these cases, CVC insertion was performed just prior to concurrent operation) and neonatal intensive care unit (NICU) under local anesthesia with adequate sedation in two (11.2%). During the admission period (total catheter-indwelling time: 553 days), CVC functioned well without any significant side effects. Transient swelling of the ipsilateral leg (n=1, 5.6 %) and transient migration of catheter tip (n=1, 5.6 %) were noted, which did not affect function of the indwelled CVC. Mean catheter-indwelling time was 30.7days (range, 3-72 days). All catheters were removed electively except two mortality case. Complications, such as thrombosis, infection, kinking or extravasation of drugs, were not observed in our study period. Tunneled trans-great saphenous vein inferior vena cava catheters are not only comparable to cervical CVCs in terms of function and complication rates, but also very beneficial in selected patients, especially those in whom cervical approach is technically impossible or contraindicated.

• Advances in pediatric surgery
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• v.17 no.1
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• pp.15-22
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• 2011

Meconium obstruction (MO) in neonates arises from highly viscid meconium and the poor motility of the premature gut. Recently the incidence of the MO in neonates has been Increasing, but, the diagnosis and treatment of this disease have not yet been clarified. Between March 2004 and April 2010, 24 neonates were treated for MO at Severance Children's Hospital. Their clinical characteristics and treatment were reviewed retrospectively. Twenty neonates were diagnosed with MO and 4 neonates were diagnosed with Hirschsprung's disease (HD). The mean birth weight and gestational age of the 20 neonates with MO were $1.45{\pm}0.90kg$ and $31.1{\pm}4.6$ weeks, respectively. Thirteen neonates (65 %) diagnosed with MO weighed less than 1.5 kg and 10 neonates (50 %) weighed less than 1 kg. Half of the neonates with MO were treated by non-operative methods and the other half were treated by operative methods. Compared with the group that weighed over 1.5 kg, the group that weighed less than 1.5 kg were more frequently operated upon (61.5% vs. 28.5%), and contrast enemas were performed later and more frequently. Also the group that weighed less than 1.5 kg had a higher mortality rate (15.4% vs. 0%). Three of the four neonates with HD were diagnosed with long-segment aganglionosis. In conclusion, MO occurred in very low birth weight neonates more often and must be differentiated from HD. Also, MO in very low birth weight neonates should be treated with special attention due to more a complicated clinical course.

• Journal of Yeungnam Medical Science
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• v.11 no.1
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• pp.35-41
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• 1994

Newborns with ileal atresia freqently present with abdominal distension, bilious vomiting. and failure to pass meconium. Diagnosis is usually established on plain x-ray of the abdomen by the findings of distended small bowel loops and air-fluid levels. In the period of October 1988 to February 1994, 8 patients with congenital ileal atresia were operated and the following results were obtained. 1. Eight patients were comprised of 4 males and 4 females, the ratio of male and female was 1 : 1. 2. Six patients(75%) had been admittted to our hospital during three days of life. 3. Congenital ileal atresia was in 8 cases : Type I in two(25%), Type II in two(25%), Type IIIa in three(37.5%), Type IIIb in one(12.5%). 4. There was one premature patient who was small for gestational age. 5. Overall, abdominal distension and bilious vomiting occurring in seven patients, were frequent presenting complaints. 6. Diagnosis was possible with clinical symptom and simple abdomen. 7. Operative treatment was undertaken as soon as the diagnosis was made. In seven cases a primary end-to-end anastomosis was performed after resection of dilated proximal loop. 8. A total of four associated congenital anomalies were found in one patient. 9. Postoperative complications occurred in three cases(37.5%).