Low levels of tissue inhibitor of metalloproteinase-2 at birth may be associated with subsequent development of bronchopulmonary dysplasia in preterm infants / 소아과

PURPOSE: Bronchopulmonary dysplasia (BPD) is characterized by inflammation with proteolytic damage to the lung extracellular matrix. The results from previous studies are inconsistent regarding the role of proteinases and antiproteinases in the development of BPD. The aim of the present study was to investigate whether matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, and TIMP-1 levels in the serum of preterm infants at birth are related to the development of BPD. METHODS: Serum was collected from 62 preterm infants at birth and analyzed for MMP-8, MMP-9, TIMP-2, and TIMP-1 by using enzyme-linked immunosorbent assay. MMPs and TIMPs were compared in BPD (n=24) and no BPD groups (n=38). Clinical predictors of BPD (sex, birth weight, gestational age, etc.) were assessed for both groups. The association between predictors and outcome, BPD, was assessed by using multivariate logistic regression. RESULTS: Sex, birth weight, and mean gestational age were similar between the groups. BPD preterm infants had significantly lower TIMP-2 levels at birth compared with no BPD preterm infants (138.1+/-23.0 ng/mL vs. 171.8+/-44.1 ng/mL, P=0.027). No significant difference was observed in MMP-8, MMP-9, and TIMP-1 levels between the two groups. Multivariate logistic regression analysis indicated that the TIMP-2 levels were predictive of BPD after adjusting for sex, birth weight, gestational age, proteinuric preeclampsia, and intraventricular hemorrhage (beta=-0.063, P=0.041). CONCLUSION: Low TIMP-2 serum levels at birth may be associated with the subsequent development of BPD in preterm infants.

Two Cases of Congenital Diaphragmatic Hernia Manifestated with Atypical Symptoms in Newborn Infants / 대한주산의학회잡지

Most of the congenital diaphragmatic hernia (CDH) cases are diagnosed at prenatal period or immediately after birth with severe respiratory symptom. The classic triad, which is respiratory distress, apparent dextrocardia and a scaphoid abdomen, is usually seen in this period. Several case reports have described older infants and children with a wide spectrum of symptoms of CDH, whereas extremely few cases were reported in neonatal period except classic triad such as straungulation of the bowel. These atypical manifestations can lead physician to delayed diagnosis. We report two cases of CDH newborns. First case was diagnosed with pneumoperitoneum following tension pneumothorax, transient diaphragm eventration on 5 days after birth. The other case was diagnosed with failure to thrive and mediastinal mass on 30 days after birth. These cases suggest physicians to consider CDH in late newborn period with pneumoperitoneum following tension pneumothorax, transient diaphragm eventration, failure to thrive, and mediastinal mass.

Admission of Term Infants to Neonatal Intensive Care Unit from Nursery / 대한주산의학회잡지

PURPOSE: We evaluated the clinical characteristics of term infants admitted to the neonatal intensive care unit (NICU) from nursery. METHODS: This is a study of NICU-admitted infants who were born > or =37 weeks of gestation at the Bungdang CHA Hospital between January 2012 and August 2013 (n=161). The infants were divided into 3 groups. The "nursery room (NR) group" (n=97) comprised admissions from the nursery following a late deterioration in condition. The "delivery room (DR) group" (n=64) comprised infants who required admission to the NICU immediately after delivery. In addition, healthy term infants who were selected as the "Term group" (n=95). RESULTS: The NR group had a higher incidence of respiratory distress syndrome than DR group (28.9% vs. 14.1%, P=0.029). Compared with the Term group, the NR group had increased incidence of prolonged (>18 h) premature rupture of membranes (PROM) (6.2% vs. 0.0%, P=0.029). By logistic regression analysis, comparing NR group and Term group, a 1 min Apgar score < or =7 points {odds ratio (OR) and 95% confidence intervals (CI) 3.1 (1.0-9.1)}, a requirement of O2 at birth 2.6 (1.2-5.9) and abnormalities detected on an antenatal sonogram 3.3 (1.4-7.8) were associated with an increased risk of admission to NICU. CONCLUSION: Risk factors for NICU admission from nursery in term infants included prolonged PROM, a 1 min Apgar score of < or =7 points, a requirement of O2 at birth, and abnormalities on antenatal sonograms. Term infants with these risk factors should be carefully observed in the early neonatal period.

Advanced Maternal Age and Weight at Birth in Newborn Infants: Distribution and Clinical Characteristics / 대한주산의학회잡지

PURPOSE: This study aimed to compare the neonatal outcome by quantifying the effect of maternal age on low birth weight (LBW). METHODS: We reviewed the medical records of 12,742 newborn infants born at CHA Bundang Medical Center from January 2009 to December 2013. Infants were compared after being categorized by the following 4 maternal age groups - or =40 years (N=640). Statistical analysis included use of logistic regression models with likelihood ratio tests for interaction effects. RESULTS: Incidence of perinatal complications tended to increase significantly with maternal age - gestational diabetes mellitus (GDM; P or =40 years (OR=0.841, 95% CI 0.671-1.056, P=0.136) for LBW. After adjusted by gestational age, incidence of in vitro fertilization (IVF), and perinatal complications, maternal age was not found to be an independent risk factor for LBW (OR=0.847, 95% CI 0.730-0.982, P=0.028 for 35-39 years, and OR=0.652, 95% CI 0.481-0.884, P=0.006 for > or =40 years). CONCLUSION: Although incidence of perinatal complications tends to increase with age, neonatal outcome of age group of > or =35 years measured by incidence of LBW infants was not unfavorable compared to the reference group. The result suggests that the thorough prenatal care may be more important than the maternal age itself.

A Case of Systemic Mastocytosis Associated with Acute Myeloid Leukemia Terminating as Aleukemic Mast Cell Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

In up to 40% of systemic mastocytosis (SM) cases, an associated clonal hematological non-mast cell lineage disease such as AML is diagnosed before, simultaneously with, or after the diagnosis of SM. A 40-yr-old man was diagnosed with AML with t(8;21)(q22;q22). Mast cells were not noted at diagnosis, but appeared as immature forms at relapse. After allogeneic hematopoietic stem cell transplantation (HSCT), leukemic myeloblasts were not observed; however, neoplastic metachromatic blasts strikingly proliferated during the state of bone marrow aplasia, and finally, aleukemic mast cell leukemia developed. As the disease progressed, we observed serial morphologic changes from immature mast cells with myeloblasts to only metachromatic blasts and atypical mast cells as mast cell leukemia; FISH analysis showed that the neoplastic mast cells originated from the same clone as the leukemic myeloblasts of AML.

Association of Interleukin-1alpha-889, beta-31, beta-511 Polymorphism with Risk of Bronchopulmonary Dysplasia

PURPOSE: Although improvements in neonatal care techniques have increased the survival rate of preterm infants, bronchopulmonary dysplasia (BPD) remains an important factor in neonatal mortality and morbidity. BPD is a multifactorial disease associated with genetic and clinical risk factors related to lung development and perinatal inflammation. Interleukin-1 (IL-1) is a crucial cytokine in the early stages of inflammation. In the present study, we aimed to determine the association between the IL-1 polymorphisms, clinical risk factors, and BPD in preterm infants. METHODS: The study was performed who consented infants born at less than 34 weeks' gestation. The alleles of the 3 sites of the IL-1 gene (IL-1alpha-889, IL-1beta-31, and IL-1beta-511) were determined using Taqman(R)-based allelic discrimination assays. Clinical data were reviewed from the medical records. RESULTS: A total of 31 infants with BPD and 73 control infants were enrolled in the study. The gestational age (P=0.001) and birth weight (P=0.001) were lower in the BPD group compared to those in the control group. The incidence of respiratory distress syndrome (RDS; P=0.002), patent ductus arteriosus (P=0.01), and retinopathy of prematurity (P<0.001) was higher in the BPD group compared to that in the control group. The frequency of IL-1alpha-889TT was higher in the BPD group (6.5% vs. 0.0%, P=0.028) compared to that in the control group. The frequencies of IL-1alpha-889T, IL-1beta-31T, and IL-1beta-511T did not differ between the BPD and control groups. In logistic regression analysis, gestational age and RDS were found to be associated with BPD. CONCLUSION: IL-1alpha-889, IL-1beta-31, and IL-1beta-511 polymorphisms are not associated with the development of BPD in preterm infants.

Insulin pump therapy in transient neonatal diabetes mellitus

Neonatal diabetes mellitus (NDM) is a rare disease requiring insulin treatment. Its treatment is primarily focused on maintaining adequate glycemic control and avoiding hypoglycemia. Although insulin pump therapy is frequently administered to adults and children, there is no consensus on the use of insulin pumps in NDM. A 10 day-old female infant was referred to us with intrauterine growth retardation and poor weight gain. Hyperglycemia was noted, and continuous intravenous insulin infusion was initiated. However, the patient's serum glucose levels fluctuated widely, and maintaining the intravenous route became difficult within the following weeks. Continuous subcutaneous insulin infusion with an insulin pump was introduced on the twenty-fifth day of life, and good glycemic control was achieved without any notable adverse effects including hypoglycemia. We suggest that the insulin pump is a safe and effective mode for treating NDM and its early adoption may shorten the length of hospital stays in patients with NDM.

Perinatal Outcomes of In Vitro Fertilized Twins in Women of Advanced Age

PURPOSE: The purpose of this study is to compare perinatal outcomes between in vitro fertilization (IVF) twins and naturally conceived twins born to women aged 35 years or older and to provide basic information for taking care of IVF twins born to women aged 35 years or older. METHODS: We reviewed the records of perinatal and neonatal outcomes in 288 IVF twins and 220 naturally conceived twins born to women aged 35 years or older between January 2001 and December 2010 at CHA Bundang Medical Center. RESULTS: No difference was observed in the maternal ages of mothers giving birth to IVF twins and those giving birth to naturally conceived twins. Gestational ages and birth weights of IVF twins were not different from those of naturally conceived twins. Various perinatal outcomes, including gestational diabetes mellitus, pregnancy-induced hypertension, placenta previa, premature amniotic membrane rupture, and need for a Cesarean section did not differ between the 2 groups. However, the 1-min and 5-min Apgar scores (P=0.019 and P=0.045, respectively) were different between the 2 groups. The incidence of early-onset sepsis was lower in the IVF twins than in the naturally conceived twins (P=0.02). However, the 2 groups did not show any difference in the incidence of respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, and other congenital anomalies. CONCLUSION: The perinatal outcomes in IVF twins born to women aged 35 years or older were not significantly different from those of naturally conceived twins.

Association between Ureaplasma urealyticum Colonization and Adverse Outcomes in Premature Infants

PURPOSE:Present evidences suggest that Ureaplasma urealyticum is a cause of pneumonia, septicemia, and bronchopulmonary dysplasia (BPD) in newborn infants, particularly those born prematurely. The purpose of this work was to examine the relationship between Ureaplasma urealyticum in the tracheal aspirates and adverse outcomes, such as BPD and early onset neonatal sepsis in premature infants. METHODS:A polymerase chain reaction (PCR) was performed on tracheal aspirates collected within 24 hour after birth in 176 premature infants less than 35 weeks of gestation and admitted to the neonatal intensive care unit of Bundang CHA Hospital. RESULTS:U. urealyticum was detected in 37 of 176 preterm infants (21.0%). Gestational age (29+5+/-2+5 wk vs. 30+6+/-2+5 wk, P=0.013) and birth weight (1.39+/-0.44 kg vs. 1.59+/-0.55 kg, P=0.037) were lower in the U. urealyticum-positive group compared to the control group. The incidence of early onset neonatal sepsis (16.2% vs. 6.5%, P=0.045) and BPD (45.9% vs. 29.5%, P=0.047) was higher in the U. urealyticum-positive group compared to the control group, but the severity of BPD was not different between two groups. However, multiple logistic regression analysis revealed that the presence of U. urealyticum was not independently related to the development of early onset neonatal sepsis and BPD. CONCLUSION:The results suggest that colonization of the lower respiratory tract by U. urealyticum might not be related to the development of neonatal sepsis and BPD directly in preterm infants.

A case of submucosal gastric lymphoepithelioma-like carcinoma / 대한내과학회지

Gastric lymphoepithelioma-like carcinoma (LELC) is a rare disease with a good prognosis. Submucosal LELC is very rare and difficult to diagnose by endoscopic biopsy. Endoscopic ultrasonography is the best modality for diagnosing submucosal tumors. Submucosal LELC can be confused with benign submucosal tumors. Here, we report a case of a submucosal gastric lymphoepithelioma-like carcinoma.

A case of cytomegalovirus esophagitis associated with upper gastrointestinal bleeding / 대한내과학회지

Cytomegalovirus (CMV) infections are common in immunocompromised patients, although they may occur occasionally in immunocompetent patients. The majority of CMV infections in immunocompetent adults are asymptomatic or associated with mild mononucleosis-like syndrome. CMV involvement of the colon is the most common site of infection in the gastrointestinal tract and is more commonly a cause of massive gastrointestinal bleeding compared to CMV involvement of the upper gastrointestinal tract and small intestine. However, although rarely, CMV esophagitis can be the source of upper gastrointestinal bleeding. We report an immunocompetent patient with cytomegalovirus esophagitis and massive upper gastrointestinal bleeding who had undergone left lobectomy and cholecystectomy for intrahepatic duct stones and gallstones.

Two cases of gallbladder cancer diagnosed by detection of hemobilia / 대한내과학회지

Hemobilia is a hemorrhage into the biliary tract and is a relatively rare cause of bleeding in the digestive tract. Gallbladder cancer is the most common tumor in the biliary tract. Gastrointestinal bleeding including hemobilia is reported in only 3% of cases of gallbladder cancer. Here, we report two rare cases of gallbladder cancer diagnosed by the detection of hemobilia. One case was an anemic patient with no abnormal endoscopic findings; capsule endoscopy showed blood in the duodenum and repeat gastroendoscopy revealed hemorrhage from the ampulla of Vater. The diagnosis of early gallbladder cancer was made and the patient underwent surgery and was followed-up. The other case presented with a symptom triad including hemobilia, and endoscopic retrograded cholangiopancreatography (ERCP) revealed hemobilia and a filling defect in the gallbladder. This patient also underwent radical cholecystectomy with the diagnosis of gallbladder cancer.

Clinical Overview of Acute Lower Gastrointestinal Bleeding / 대한소화기내시경학회지

BACKGROUND/AIMS: Acute lower gastrointestinal bleeding (LGIB) is a common disorder that requires hospitalization. Colonoscopy is considered as the procedure of choice for diagnosing acute LGIB. The aim of this study was to analyze the clinical characteristics, endoscopic diagnosis and clinical course of acute LGIB. METHODS: From January 2000 to August 2007, 117 patients with hematochezia, who visited Yeungnam University hospital emergency center and underwent colonoscopy or sigmoidoscopy, were reviewed retrospectively. The male to female ratio was 2.25 (81:36). The mean age was 59.1+/-16.9 years. RESULTS: The mean time from presentation to endoscopy was 12.6 hours. The cause of bleeding was identified in 88.9% of the cases after endoscopy. The causes of the acute LGIB were colitis: 26 cases, post polypectomy bleeding: 17 cases, colon ulcer: 16 cases, diverticular bleeding: 13 cases, colon cancer: 9 cases, angiodysplasia: 7 cases and hemorrhoid: 6 cases. Thirty six patients were treated by the endoscopic method; the mean duration of admission was 10.6+/-10.0 days and the mean amount of transfusion was 3.0+/-1.9 U. Those numbers showed statistically significant differences according to the diagnosis. CONCLUSIONS: The most common cause of acute LGIB was colitis and the causes of bleeding were a significant factor that affects the severity of bleeding and the duration of admission.

Early stress hyperglycemia as independent predictor of increased mortality in preterm infants / 소아과

Purpose: Stress hyperglycemia is common in critically ill adult patients. It is known as a predictor of increased mortality, and intensive insulin therapy has been shown to improve the prognosis in such patients. We have investigated the relationship between early stress hyperglycemia and clinical outcomes in preterm infants. Methods: In this study, 141 preterm infants with a gestational age of less than 30 weeks were enrolled. The hyperglycemic group was defined as that having maximum glucose of more than 150 mg/dL (n=61) during the first 48 h of life, and the non-hyperglycemic group was defined as that having maximum glucose of less than 150 mg/dL (n=80). Perinatal history, severity of illness using the Clinical Risk Index for Babies (CRIB) score, clinical outcomes, and mortality of the two groups were compared. Results: There was no significant difference in the gestational age between the two groups, but the birth weight (P<0.001) was significantly lower, and the CRIB score (P<0.001) was significantly higher in the hyperglycemic group. Disseminated intravascular coagulation (P<0.001) and clinically suspected sepsis (P=0.046) were more common in the hyperglycemic group. Mortality was markedly higher in the hyperglycemic group (11.3% vs. 41.0%, P<0.001). On performing a stepwise multiple logistic regression analysis, hyperglycemia (OR 3.787; 95% CI 1.324 to 10.829), the CRIB score (OR 1.252; 95% CI 1.047 to 1.496) and birth weight (OR 0.997; 95% CI 0.994 to 1.000) was independently associated with higher mortality. Conclusion: Stress hyperglycemia within the first 48 h of life is independently related to increased morbidity and mortality in preterm infants.

A Solitary Colonic Neurofibroma in a Patient without Neurofibromatosis / 대한소화기내시경학회지

Neurofibromas are usually manifestations of neurofibromatosis type 1 (Nf1). There are usually multiple lesions on presentation. Solitary neurofibromas of the colon are extremely rare. A 34-year-old Asian male came to our hospital for non-specific findings, except for a complaint of loose stools for 2 months. A colonoscopy was performed. A sessile polyp 0.4 cm in diameter was detected at the sigmoid colon. Microscopically, a biopsy from the polyp showed proliferation of spindle cells in the mucosa, myxoid changes and infiltration of inflammatory cells. Immunohistochemical staining was positive for S-100 protein. The above morphological and immunohistochemical characteristics were consistent with a diagnosis of a neurofibroma. Only 13 cases of isolated colonic neurofibromatosis without Nf1 have been documented in the literature. We report this case as an isolated neurofibroma of the colon is even a rarer manifestation, and only three cases have been published in the clinical literature.

A pilot study of neuroprotection with umbilical cord blood cell transplantation for preterm very low birth weight infants / 소아과

PURPOSE: Preterm very low birth weight infant have high rate of adverse neurodevelopmental sequale. Recently, there have been lots of reports that human umbilical cord blood transplantation ameliorates functional deficits in animal models as hypoxic ischemic injury. This pilot study was undertaken to determine the clinical efficacy and safety of autologous umbilical cord blood cell transplantation for preventing neurodevelopmental sequale in perterm VLBW. METHODS: Subjects were 26 preterm infants whose birth weight are less than 1,500 g and delivered under the intrauterine period 34 weeks. Autologous umbilical mononuclear cells (about 5.87x10(7)/kg) were injected to neonate via the umbilical vein on the postnatal 24-48 hour. The therapeutic efficacy was assessed by numbers of nucleated RBC, urinary uric acid/creatinine ratio, concentration of neuron specific enolase (NSE), interleukin 6 (IL6), interleukin-1beta (IL-1beta), and glial cell derived neurotrophic factor (GDNF) in serum and cerebrospinal fluid on day 1 and 7. RESULTS: There were no significant differences in the numbers of the nucleated RBC, urinary uric acid/creatinine ratio, concentration of creatine kinase between the transplanted infants and controls. But the nucleated RBC is more likely to be rapidly discharged in the transplanted group. In the transplanted group, the concentrations of IL6, IL-1beta, and GDNF were no significant difference between day 1 and 7, although GDNF seemed to be elevated. Serum NSE concentration was significantly elevated after transplantation, but not in CSF. CONCLUSION: It is suggested that autologous umbilical cord blood transplantation in preterm very low birth weight infant is safe to apply clinical practice. Long term follow up study should be needed to evaluate the potential therapeutic effect of umbilical cord blood transplantation for neuroprotection.

Hematologic and Clinical Features of 3q21q26 Syndrome: Extremely Poor Prognosis and Association with Central Diabetes Insipidus / 대한진단검사의학회지

BACKGROUND: 3q21q26 syndrome includes chromosomal abnormalities of inv(3)(q21q26), t(3;3) (q21;q26), and ins(3;3)(q26;q21q26). It causes hematological diseases by the leukemogenic mechanism that the enhancer of ribophorin I gene in 3q21 induces the transcription of ecotropic viral integration site-1 gene in 3q26. Recently, it has been proposed that the 3q21q26 syndrome may be preceded by diabetes insipidus (DI), particularly when combined with monosomy 7, and is a unique disease entity. METHODS: From May 2001 to June 2006, a total of 5 patients with hematologic malignancy were found to have 3q21q26 syndrome and monosomy 7. Laboratory findings, clinical data, and association with DI were investigated. RESULTS: The rearrangement type of 3q21q26 was inv(3)(q21q26) in four patients and t(3;3)(q21; q26) in one. These patients' French American British types were AML M1, M2, M4 and M7, showing evident dysmegakaryopoiesis. Aberrant antigenic expressions of CD7 and CD56 were observed. The platelet count was relatively high as AML. All the five patients were refractory or in early relapse. Patient 5 was diagnosed with AML M7 20 days after being diagnosed with DI. While DI was well controlled with oral desmopressin, leukemia was refractory to chemotherapy. CONCLUSIONS: This study supports the recent opinion that 3q21q26 syndrome with monosomy 7 combined with DI is a disease of unique characteristics. In the relation between DI and monosomy 7 or 3q21q26 syndrome, there has been no explanation about how acquired abnormality of hematopoietic cells affects production of DDAVP by neurohormonal cells in hypothalamus. The mechanism needs further study, and this research should contribute to the understanding of genetic roles in leukemia appearing in different forms.

Successful Treatment of Aortic Thrombosis after Umbilical Catheterization with Low-Molecular-Weight Heparin

Aortic thrombosis is one of the common complications caused by umblical cord catheterization. There are three treatment options for aortic thrombosis:anticoagulation, thrombolysis, surgery. Low-molecular-weight heparin has several advantages over unfractionized heparin in the treatment of thrombosis. However, there is limited experience on using low-molecular-weight heparin in children, especially in the newborns. We experienced a case of aortic thrombosis caused by umbilical cord catheterization, which was successfully treated with low-molecular-weight heparin.

A Case of Goldenhar's Syndrome with Vesicoureteral Reflux / 대한주산의학회잡지

Goldenhar's syndrome is a kind of congenital anomaly with epibulbar dermoid, preauricular skin tag, blind-ended fistula and vertebral anomaly. The primary cause is unknown but thought to be a structural developmental abnormalities of the 1st, and 2nd branchial arch. In this syndrome, we can observe characteristic anomalies of the face, ear, vertebrae, heart, and the nervous system. Treatment is surgical correction, removal of epibulbar dermoid, prevention of hearing loss through early hearing test. The consultations of ophthalmologist, otorhinolaryngologist, orthopedist and dentist are necessary for this syndrome. We report a case of Goldenhar's syndrome with hemifacial hypoplasia, preauricular skin tags, blind-ended fistulas, hemivertebrae and vesicoureteral reflux.

A Case of Goldenhar's Syndrome with Vesicoureteral Reflux / 대한주산의학회잡지

Goldenhar's syndrome is a kind of congenital anomaly with epibulbar dermoid, preauricular skin tag, blind-ended fistula and vertebral anomaly. The primary cause is unknown but thought to be a structural developmental abnormalities of the 1st, and 2nd branchial arch. In this syndrome, we can observe characteristic anomalies of the face, ear, vertebrae, heart, and the nervous system. Treatment is surgical correction, removal of epibulbar dermoid, prevention of hearing loss through early hearing test. The consultations of ophthalmologist, otorhinolaryngologist, orthopedist and dentist are necessary for this syndrome. We report a case of Goldenhar's syndrome with hemifacial hypoplasia, preauricular skin tags, blind-ended fistulas, hemivertebrae and vesicoureteral reflux.