OBJECTIVE: Several lines of evidence have shown that neuronal injury might represent a possible pathway to mood disorders. The present study was performed to examine the possibility that the neuroprotective effects of R(-)- and S(+)-citalopram depend on types of neuronal cell death. METHODS: Free radical neurotoxicity was induced in mixed cortical cell cultures by continuous exposure to 30 micrometer Fe++ for 24 hours, which produced hydroxyl radicals via a Fenton reaction. Cultures measuring excitotoxicity were exposed for 24 hours to 50 micrometer NMDA. Neuronal apoptosis was induced by 100 nM staurosporine exposure for 24 hours. Neuronal death was analyzed 24 hours later by measuring the efflux of lactate dehydrogenase (LDH) into the bathing medium or by counting viable neurons after staining with trypan blue. RESULTS: Co-treatment with R(-)-or S(+)-citalopram prevented staurosporine-induced apoptosis of cultured cortical cells, as well as activation of caspase-3. In contrast to the differences between enantiomers found in serotonin uptake inhibition and in the in vivo behavioral depression model, both enantiomers in this study showed similar protective effects on staurosporine-induced apoptosis. Mixed cortical cell cultures exhibited marked swelling of the neuronal cell bodies accompanied by widespread neuronal death during the 24 hours following exposure to 30 micrometer Fe++ or 50 micrometer NMDA that was not sensitive to either the R(-)-or S(+)-enantiomers of citalopram. CONCLUSION: These features suggest that the neuroprotective effect of citalopram depend on type of neuronal injury.
Apoptosis ; Baths ; Caspase 3 ; Cell Culture Techniques ; Cell Death ; Citalopram ; Depression ; Diminazene ; L-Lactate Dehydrogenase ; Mood Disorders ; N-Methylaspartate ; Necrosis ; Neurons ; Neuroprotective Agents ; Serotonin ; Staurosporine ; Trypan Blue

PURPOSE: There has been no exact answer to the question of when to discontinue antiepileptic drugs(AEDs) in children with well-controlled epilepsy for a long period. This study is about the risk factors of relapse after withdrawal of AEDs in seizure(Sz)-free patients to show a guideline for discontinuation of AEDs. METHODS: One hundred and sixty-nine children were diagnosed as epileptic at the Pediatric Dept.of Kyung-Hee Univ. between 1993 to 1998, in whom AEDs had been withdrawn after at least two years of Sz-free period. Univariate analysis using Kaplan-Meier survival analysis and multivariate analysis using Cox-proportional hazard model were performed for sixteen risk factors. RESULTS: Forty-nine of the 169 patients(28.9%) had recurrence of Szs. The mean follow-up after withdrawal of AEDs was 4.1 years, mean treatment period was 4.1 years, and the mean Sz-free period was 3.3 years. Factors associated with an increased risk of relapse were young age at onset, symptomatic Sz, Sz type in West and Lennox-Gastaut syndrome, neurologic deficit, longer Sz-controlling period, shorter total treatment period, number of AEDs used(more than one drug), age at withdrawal of AEDs, and Sz-free period less than two years in univariate analysis using Kaplan-Meier mothod. From multivariate analysis, the factors indicating a significantly higher relapse risk were pre-treatment period after first Sz attack, Sz-controlling period, Sz-free period, number of AEDs used, neurologic abnormalities. CONCLUSIONS: For epileptic children who were Sz-free for more than two years, and were more than six-years-old, the discontinuation of AEDs should be considered positively, according to age of onset, Sz type, age at withdrawal of AEDs, total treatment period, Sz-controlling period, number of AEDs used, etiology, neurologic deficit, and the wishes of the patients and the their parents.
Age of Onset ; Anticonvulsants ; Child* ; Drug Therapy* ; Epilepsy* ; Follow-Up Studies* ; Humans ; Multivariate Analysis ; Neurologic Manifestations ; Parents ; Proportional Hazards Models ; Recurrence* ; Risk Factors

PURPOSE: To identify the characteristic ultrasonographic findings of the normal appendix in children in order to detect it more easily and so to exclude acute appendicitis from a diagnosis with more confidence. MATERIALS AND METHODS: Among 64 patients presenting with right lower quadrant pain, 44 patients, excluding 15 patients diagnosed as acute appendicitis and 5 patients with non-visualization of the appendix due to severe ileus and obesity, were evaluated for the point of incidence, the thickness and the presence of folding of the inner hypoechoic band of the normal appendix. The age of the patients ranged from 3 to 15 years with a mean age of 6.5 years. Two patients were operated on and we correlated the preoperative ultrasonographic findings with the histologic findings. RESULTS: In all the cases of the 44 patients with normal appendix, the inner hypoechoic band was discovered, which was seen as a linear structure without folding along the whole length of appendix. This measured as 0.75 mm (0.3-1.5 mm) for the mean thickness. The inner hypoechoic band corresponded to the mucosal layer that had abundant lymphoid tissue on the histologic examination. CONCLUSION:For the pediatric normal appendix, the inner hypoechoic band without folding is present, and this corresponds to the mucosal layer with abundant lymphoid tissue.
Appendicitis ; Appendix* ; Child* ; Diagnosis ; Humans ; Ileus ; Incidence ; Lymphoid Tissue ; Obesity ; Ultrasonography*

BACKGROUND: A tumor must continuously stimulate the growth of new capillary blood vessels for the tumor itself to grow and metastasize. Vascular endothelial growth factor (VEGF) promotes vascular permeability and endothelial cell growth. A hepatocellular carcinoma (HCC) is a typical hypervascular tumor. METHODS: We evaluated the expression of VEGF in 36 cases of HCC by using immunohistochemical staining in order to define its prognostic value. RESULTS: The expression rate of VEGF was 44.4% (16/36) in tumor cells and 0% (0/36) in non- tumorous liver parenchyme. VEGF expression did not correlate with any clinicopathological characteristics. And patients with expression of VEGF in tumor cells had no survival difference in comparison to those without VEGF expression. CONCLUSIONS: These results suggest that the expression of VEGF in HCC cells by itself may not be a significant factor in the prognosis of HCC.
Blood Vessels ; Capillaries ; Capillary Permeability ; Carcinoma, Hepatocellular* ; Endothelial Cells ; Humans ; Liver ; Prognosis ; Vascular Endothelial Growth Factor A*

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare hematological malignancy in children that is characterized by bruise-like skin lesions, with or without bone marrow involvement. Because the clinical course of BPDCN is highly aggressive and fatal in adults, allogeneic hematopoietic stem cell transplantation (HSCT) is recommended as the optimal treatment. Due to its rarity, the pediatric experience with BPDCN is limited and standard treatment has so far not been defined. We report a case of a 14-year-old boy with BPDCN involving the skin, bone marrow and lymph nodes. The patient was treated with high-risk group acute lymphoblastic leukemia protocol. He achieved a complete remission after induction chemotherapy and still maintains clinical remission without HSCT for 17 months after initial diagnosis.
Adolescent ; Adult ; Bone Marrow ; Child ; Dendritic Cells ; Diagnosis ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Lymph Nodes ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Skin

BACKGROUND: Currently, data on the role of tacrolimus and mini-dose methotrexate (MTX) in pediatric unrelated hematopoietic stem cell transplantation (HSCT) is limited. We report the outcomes of unrelated hematopoietic stem cell recipients, evaluating engraftment status, incidence of acute and chronic graft-versus-host disease (GVHD) and toxicities after use of tacrolimus and mini-dose MTX for GVHD prophylaxis.METHODS: Thirty-five children who received tacrolimus and mini-dose MTX as prophylaxis from January 2004 to December 2013 were reviewed. All patients received tacrolimus beginning the day prior to transplant at a dose of 0.03 mg/kg/day by continuous intravenous infusion. MTX was administered at a dose of 5 mg/m2 IV on days 1, 3, 6 and 11.RESULTS: Median age at transplantation was 8.42 years (range 0.75-18.9 years). Seventeen patients received human leukocyte antigen (HLA) fully matched donor transplants and 18 received partially mismatched transplants. All but two patients who received unrelated cord blood transplants showed successful engraftment. The median time to ANC recovery was 12 days. The incidence of acute GVHD was 33.3% including 15.1% grade III-IV GVHD. Localized chronic GVHD developed in only 2 of 27 (7.4%) evaluable patients. Lower tacrolimus levels during days 1-21 were associated with a higher incidence of acute GVHD (P=0.033). The estimated 4-year event free survival and overall survival of the patients were 71.2% and 80.0%.CONCLUSION: Overall, the combination of tacrolimus and mini-dose MTX could be effectively administered in the setting of pediatric unrelated HSCT.
Child ; Disease-Free Survival ; Fetal Blood ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Incidence ; Infusions, Intravenous ; Korea ; Leukocytes ; Methotrexate ; Tacrolimus ; Tissue Donors

BACKGROUND: Immune thrombocytopenic purpura (ITP) in children less than one year of age is less well characterized compared to ITP in toddlers and school-age children. Since children of different ages may have differing clinical courses, better delineation of the natural history of ITP in infants is needed. METHODS: We retrospectively reviewed the admission records of 248 consecutive pediatric patients between 1 month and 15 years of age who were admitted and treated for acute ITP at Pusan National University Children's Hospital from 2009 through 2017. All patients less than 1 year of age were identified and enrolled in this study. We investigated their demographics, clinical features, laboratory examinations, response to treatment, and long-term outcomes and made a comparison to those of children aged 1 to 10 years of age. RESULTS: Ninety nine infants were identified. Male to female ratio was highest in infants and decreased with age. Seventy nine (79.8%) of the 99 infant were found to be under 6 months old. The median platelet counts at diagnosis was 6×10⁹/L. Minor bleeding (bleeding score 0–2) was significantly dominant in infant compared to older subjects. Eighty two (96.5%) out of 85 patients achieved complete remission after initial intravenous immunoglobulin (IVIG) treatment. The relapse rate after initial CR was significantly lower than older ages (P=0.003). The platelet count after IVIG treatment in infant showed more rapid response compared to older subjects (P=0.04). Follow up information at 12 months was available for 70 infants. Chronic ITP at 12 month was seen less frequently in infants than in children 1 to 10 years of age (1.4% vs. 20.2%, P<0.001). CONCLUSION: Infants with acute ITP respond more favorably to IVIG treatment and are less likely to develop chronic ITP compared to children 1 to 10 years of age.
Busan ; Child ; Demography ; Diagnosis ; Female ; Follow-Up Studies ; Hemorrhage ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Infant ; Male ; Natural History ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Recurrence ; Retrospective Studies

A 28-year-old primi gravida visited our department at 20 weeks gestation. The ultrasound screening revealed twin gestation, and follow up screening revealed a bilobed large fetal neck mass in the 1st twin. We measured thyroid volume with ultrasound which was 5.072 cm3. Other fetal organs appeared normal. Cordocentesis was performed for fetal thyroid function and congenital hypothyroidism was confirmed. In addition, maternal thyroid hormones were checked. The other fetus was normal. Thyroid stimulating hormone (TSH) in the maternal serum was increased, but thyroxine (T3) was (within normal range). Two weeks later, we checked TSH and free T4 in amniotic fluid and administered intra-amniotic thyroxine (200 ?g). We repeated the procedures 2 more times in two consecutive weeks. After 3 intra-amniotic thyroxine injection, follow-up cordocentesis revealed euthyroid status of the fetus. Although the thyroid gland had decreased in size and volume, it was still goitrous. At 36 weeks of gestation, the patient was admitted for preterm premature rupture of the membranes and the twin was delivered vaginally. The 1st twin was proved as an euthyroid status and antithyroid antibody was not detected. During the 3 years follow up, the baby had no considerable developmental problem. The intrauterine recognition and treatment of congenital goitrous hypothyroidism may not only reduce the obstetric complications associated with large goiters, but possibly improve the prognosis for normal growth and mental development of affected fetuses.
Adult ; Amniotic Fluid ; Congenital Hypothyroidism ; Cordocentesis ; Female ; Fetal Membranes, Premature Rupture ; Fetus ; Follow-Up Studies ; Goiter ; Humans ; Hypothyroidism ; Mass Screening ; Membranes ; Neck ; Pregnancy ; Prognosis ; Rupture ; Thyroid Gland ; Thyroid Hormones ; Thyrotropin ; Thyroxine ; Twins

Umbilical cord blood is an attractive source of hematopoietic stem cells in allogeneic hematopoietic stem cell transplantation. Umbilical cord blood transplantation has merits of rapid availability and low risk of severe acute graft versus host disease. Umbilical cord blood should be an important source of stem cell transplantation for patients who have no suitable human leukocyte antigen-matched bone marrow, or peripheral stem cell donor. Transplantation of umbilical cord blood is limited by insufficient cell doses. This had led to the alternative concept of attempting to increase the number of cell doses using two cord blood units from different donor. We report a case of double-unit cord blood transplantation for 55-year-old male with primary refractory acute myeloid leukemia.
Bone Marrow ; Fetal Blood* ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukemia, Myeloid, Acute* ; Leukocytes ; Male ; Middle Aged ; Stem Cell Transplantation ; Stem Cells ; Tissue Donors

We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.
Autoantibodies ; Female ; Glucose ; Graves Disease ; HLA-DRB1 Chains ; Humans ; Hypoglycemia ; Hypoglycemic Agents ; Insulin ; Insulinoma ; Methimazole