Clinical Characteristics of Gynecologic Problems During Childhood in the Korean Population.

BACKGROUND: This study analyzed common gynecologic problems among Korean patients younger than ten years. METHODS: We performed a retrospective analysis of medical records of patients younger than ten years who visited the Pediatric and Adolescent Gynecology Clinic at Samsung Medical Center between 1995 and 2020. RESULTS: Among the 6,605 patients who visited the Pediatric and Adolescent Gynecology Clinic, data from 642 patients younger than ten years were analyzed in this study. The most common chief complaint was genital anomalies, followed by increased vaginal discharge and abnormal findings on clinical examinations. The most common disease entity was agglutination of the labia minora, which was commonly discovered incidentally during routine screenings. Vulvovaginitis, the second most common disease, was identified by symptoms of vaginal discharge, pruritus, and vaginal spotting. Neoplasm, issues with vaginal bleeding, and "other causes" were additional categories of gynecologic problems. 245 patients (38.2%) were referred from primary care sources, 175 patients (27.4%) sought care directly at the clinic, 169 patients (26.3%) were referrals from the institution's pediatric department, and the remainder were referrals from other departments. CONCLUSION: This study provides information about the gynecologic problems most frequently encountered in pediatric patients. The study provides helpful insight for primary care physicians into the proper management and timing of referrals for these gynecologic problems of pediatric patients.

Research Trends in C-Terminal Domain Nuclear Envelope Phosphatase 1.

C-terminal domain nuclear envelope phosphatase 1 (CTDNEP1, formerly Dullard) is a member of the newly emerging protein phosphatases and has been recognized in neuronal cell tissues in amphibians. It contains the phosphatase domain in the C-terminal, and the sequences are conserved in various taxa of organisms. CTDNEP1 has several roles in novel biological activities such as neural tube development in embryos, nuclear membrane biogenesis, regulation of bone morphogenetic protein signaling, and suppression of aggressive medulloblastoma. The three-dimensional structure of CTDNEP1 and the detailed action mechanisms of CTDNEP1's functions have yet to be determined for several reasons. Therefore, CTDNEP1 is a protein phosphatase of interest due to recent exciting and essential works. In this short review, we summarize the presented biological roles, possible substrates, interacting proteins, and research prospects of CTDNEP1.

Rates and subsequent clinical course of fetal congenital anomalies detected by prenatal targeted ultrasonography of 137 cases over 5 years in a single institute: a retrospective observational study.

BACKGROUND: With the establishment of international guidelines and changes in insurance policies in Korea, the role of targeted ultrasonography has increased. This study aimed to identify the rates and clinical course of anomalies detected using prenatal targeted ultrasonography. METHODS: This study was a retrospective analysis of all pregnancies with targeted ultrasonography performed in a single secondary medical center over 5 years. RESULTS: Fetal anomalies were detected by targeted ultrasonography in 137 of the 8,147 cases (1.7%). The rates of anomalies were significantly higher in female fetuses (2.0% vs. 1.3%). In cases of female fetuses, the rate of anomalies was significantly higher in the advanced maternal age group (2.4% vs. 1.2%). In cases of male fetuses, the rate of anomalies was significantly higher in nulliparous (2.4% vs. 1.5%) and twin (5.7% vs. 1.9%) pregnancies. Pulmonary anomalies were significantly more common in the multiparity group (17.6% vs. 5.8%). Among the 137 cases, 17.5% terminated the pregnancy, 16.8% were diagnosed as normal after birth, and 42.3% were diagnosed with anomalies after birth or required follow-up. CONCLUSION: Through the first study on the rates and clinical course of anomalies detected by targeted ultrasonography at a single secondary center in Korea, we found that artificial abortions were performed at a high rate, even for relatively mild anomalies or anomalies with good prognosis. We suggest the necessity of a nationwide study to establish clinical guidelines based on actual incidences or prognoses.

Uterine alveolar rhabdomyosarcoma in an elderly patient manifesting extremely poor prognosis; a rare subtype of rhabdomyosarcoma.

Alveolar rhabdomyosarcoma (ARMS) arising in the corpus uteri is an extremely rare condition with exceptionally rapid progression and poor prognosis. Furthermore, ARMS is primarily diagnosed in the pediatric population. Due to rarity of the disease, there are no standard treatment guidelines. A 90-year-old woman was presented with a huge pelvic mass causing dyspnea and abdominal distension. The patient underwent debulking surgery and was diagnosed with uterine ARMS by fresh specimen biopsy. Despite intensive postoperative care, the patient died on the eighth postoperative day. Here, we report a case of uterine ARMS that will add to our understanding of this exceptionally rare type of tumor.

Relationship Between Aggravation of Seizures and Methylphenidate Treatment in Subjects with Attention-Deficit/Hyperactivity Disorder and Epilepsy.

OBJECTIVES: We aimed to investigate the effectiveness and safety of methylphenidate (MPH), and especially its influence on seizures, in subjects with attention-deficit/hyperactivity disorder (ADHD) and epilepsy through a retrospective chart review of subjects treated with MPH in a clinical setting. We also evaluated factors that could affect seizure aggravation during MPH treatment. METHODS: From April 2004 to July 2011, MPH was prescribed to 105 subjects with ADHD and epilepsy. The demographic characteristics, psychiatric and medical history, and electroencephalography (EEG) results were reviewed. Two pediatric neurologists reviewed seizure type, epilepsy diagnosis, changes in seizure frequency, and EEG parameters during MPH treatment. Pediatric neurologists and psychiatrists determined the temporal relationship between seizure aggravation and MPH treatment. RESULTS: The mean age of the subjects was 14.8 ± 3.4 years (range: 7-24 years). Sixty-five (61.9%) of the subjects were male. The mean duration of MPH treatment was 22 months (range: 2 weeks to 89 months) and the mean dose of MPH was 0.84 mg/kg/day. MPH was effective in controlling ADHD symptoms in both the seizure aggravation and nonaggravation groups. However, 21 (20%) subjects had aggravated seizures and 32 (32.3%) subjects had worsened EEG findings. Subjects with uncontrolled seizure or anxiety disorders at baseline were more likely to show aggravated seizures. Subjects who had epileptiform discharges, anxiety disorders, or were free of antiepileptic drug use at baseline experienced EEG worsening more frequently. The median duration of MPH treatment was significantly longer in subjects who did not show seizure aggravation than in those who did (p < 0.001). CONCLUSIONS: MPH treatment may be related to aggravation of seizures or significant worsening of EEG findings in subjects with ADHD and epilepsy. Thus, clinicians should closely monitor seizure aggravation after MPH administration, especially for high-risk subjects with uncontrolled seizures or anxiety disorders at baseline.

Preparation of fluoride-loaded microcapsules for anticariogenic bacterial growth using a coaxial ultrasonic atomizer.

A new method to deliver fluoride using biodegradable poly(lactic-co-glycolic acid) microcapsules to suppress cariogenic bacterial growth during orthodontic treatment was investigated. A coaxial ultrasonic atomizer was used to encapsulate KF solution into microcapsules. The orthodontic adhesive resin disk containing fluoride loaded microcapsules (DFLM) was prepared by LED light curing. The microstructure of microcapsules, successful loading of KF, fracture strength, and shear bonding strength were assessed by FE-SEM, confocal laser scanning microscope, and general purpose testing machine, respectively. Fluoride release from the DFLM in phosphate buffered saline and pH changes were measured after different periods of soaking time. Antibacterial activity of the DFLM was assessed in tryptic soy broth containing mutant streptococci. The starting inoculum and the orthodontic resin disk containing microcapsules not loaded with KF were used as negative and positive controls, respectively. As results, the cumulative amount of KF after 49 days was about 85% of the initial amount of fluoride contained in the microcapsules. The fracture and shear bonding strengths of the orthodontic resin disks with and without the microcapsules were similar to each other. The DFLM showed lower bacterial growth than the control groups, whereas no statistically significant differences were found between the negative and positive controls. It can be concluded that the microcapsules loaded with fluoride prepared by a coaxial ultrasonic atomizer have good potential for application as an antibacterial agent due to their excellent cariogenic antibacterial activity when incorporated into orthodontic adhesive resin. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 31-39, 2018.

Evaluation of the safety and efficiency of novel metallic implant scaler tips manufactured by the powder injection molding technique.

BACKGROUND: Although many studies have compared the properties of ultrasonic scaling instruments, it remains controversial as to which is most suitable for implant scaling. This study evaluated the safety and efficiency of novel metallic ultrasonic scaler tips made by the powder injection molding (PIM) technique on titanium surfaces. METHODS: Mechanical instrumentation was carried out using four types of metal scaler tips consisting of copper (CU), bronze (BR), 316 L stainless steel (316 L), and conventional stainless steel (SS) tips. The instrumented surface alteration image of samples was viewed with scanning electron microscope (SEM) and surface profile of the each sample was investigated with confocal laser scanning microscopy (CLSM). Arithmetic mean roughness (Ra) and maximum height roughness (Rmax) of titanium samples were measured and dissipated power of the scaler tip was estimated for scaling efficiency. RESULTS: The average Ra values caused by the 316 L and SS tip were about two times higher than those of the CU and BR tips (p < 0.05). The Rmax value showed similar results. The efficiency of the SS tip was about 3 times higher than that of CU tip, the 316 L tip is about 2.7 times higher than that of CU tip, and the BR tip is about 1.2 times higher than that of CU tip. CONCLUSIONS: Novel metallic bronze alloy ultrasonic scaler tip minimally damages titanium surfaces, similar to copper alloy tip. Therefore, this bronze alloy scaler tip may be promising instrument for implant maintenance therapy.

Two cases of familial cerebral cavernous malformation caused by mutations in the CCM1 gene.

Cerebral cavernous malformation (CCM) is a vascular malformation characterized by abnormally enlarged capillary cavities without any intervening neural tissue. We report 2 cases of familial CCMs diagnosed with the CCM1 mutation by using a genetic assay. A 5-year-old boy presented with headache, vomiting, and seizure-like movements. Brain magnetic resonance imaging (MRI) revealed multiple CCM lesions in the cerebral hemispheres. Subsequent mutation analysis of his father and other family members revealed c.940_943 del (p.Val314 Asn315delinsThrfsX3) mutations of the CCM1 gene. A 10-month-old boy who presented with seizure-like movements was reported to have had no perinatal event. His aunt was diagnosed with cerebral angioma. Brain and spine MRI revealed multiple angiomas in the cerebral hemisphere and thoracic spinal cord. Mutation analysis of his father was normal, although that of the patient and his mother revealed c.535C>T (p.Arg179X) mutations of the CCM1 gene. Based on these studies, we suggest that when a child with a familial history of CCMs exhibits neurological symptoms, the physician should suspect familial CCMs and consider brain imaging or a genetic assay.

Causes and outcomes of asymptomatic gross haematuria in children.

AIM: Although asymptomatic gross haematuria (GHU) is relatively common in children, its causes and clinical outcomes are not clearly defined. METHODS: Children with asymptomatic GHU were examined and work-up was performed. Patients with recurrent GHU with proteinuria, or significant proteinuria, were considered for renal biopsy. RESULTS: The male : female ratio of all patients was 190:75, and the median age at onset of GHU was 6.4 years. Patients were grouped according to abnormalities on initial evaluation as follows: idiopathic (50%), proteinuria (21%), hypercalciuria (14%), sonographic abnormality (7%), hypocomplementaemia (4%), familial (3%), and bleeding tendency (2%). Of patients with idiopathic GHU, 38% had a single episode, and of these, 34% had persistent microscopic haematuria, which resolved on follow-up. Late onset proteinuria was accompanied in 11% of patients with recurrent GHU. Nutcracker syndrome was diagnosed in one patient with recurrent idiopathic GHU. Of patients with recurrent GHU, 89% had no proteinuria on follow-up, and GHU and microscopic haematuria resolved in 97% and 89%, respectively. CONCLUSIONS: Our work-up protocol was useful for diagnosis and follow-up planning. Asymptomatic GHU in children was most commonly the idiopathic form. Overall, long-term prognosis appears to be benign; however, careful follow-up is essential.

Risk factors for neurological complications and their correlation with survival following pediatric liver transplantation.

Despite the improved outcomes of LT, post-operative NCs remain a significant cause of morbidity and mortality. The aim of the study was to identify the incidence of and risk factors for NCs in children who underwent LT. The medical records of pediatric patients who underwent LT at Asan Medical Center Children's Hospital between January 1994 and December 2010 were retrospectively analyzed. The onset and types of NC and pretransplant variables associated with NC were evaluated. We identified 190 children (85 boys [44.7%], 105 girls [55.3%]) of mean age 4.1 ± 4.7 yr, who underwent LT. Forty-six NCs occurred in 41 (21.6%) patients after LT, the most common being seizures (n = 13, 28.3%) and encephalopathy (n = 10, 21.7%). Of the 46 NCs, 24 (52.2%) occurred within three months after LT. Multivariate analysis showed that primary liver disease, preoperative neurological problems, preoperatively higher serum creatinine concentration, and graft failure were significant risk factors for NCs. The survival rate was significantly lower for patients with NCs than for those without (p < 0.001). NCs after pediatric LTs were common and associated with a higher mortality rate in our study. Close monitoring and appropriate risk management may improve the long-term outcomes of pediatric patients who undergo LT.

Determinants of intelligence in childhood-onset epilepsy: a single-center study.

The purpose of this study was to quantify the intelligence of children with epilepsy and to determine the clinical factors associated with intellectual impairment. The medical records of patients diagnosed with childhood-onset epilepsy at a single tertiary medical center in Korea between 2006 and 2011 were retrospectively reviewed. The Korean Education Development Institute-Wechsler Intelligence Scale for Children or Korean Wechsler Intelligence Scale for adults was used to quantify the level of intelligence. Age at seizure onset, etiology, epilepsy duration, number of seizures in the last year, use of antiepileptic drugs, EEG/MRI findings, and epilepsy classification were recorded. The association between clinical factors and the intelligence was determined using logistic regression. Three hundred and twenty-two patients were included in the analysis. One hundred and seventy-six (54.7%) patients had low intelligence (intelligence quotient [IQ]<80) with 18 (5.6%) defined as borderline mental retardation (IQ 70-79), 47 (14.6%) as mild mental retardation (IQ 60-69), and 111 (34.5%) as moderate-to-severe mental retardation (IQ<60). Epilepsy duration, number of seizures in the last year, and epilepsy classification were significantly associated with low intelligence in multivariate logistic regression (p<0.05). However, when analyzed according to etiology, these factors were not associated with low intelligence in children with idiopathic epilepsy. The most important factors associated with low intelligence in childhood-onset epilepsy are the underlying etiology and, in cryptogenic and symptomatic epilepsy, seizure burden. The results of this study underscore the importance of seizure control to alleviate the harmful impact of epilepsy on cognition.

Long-term use of clobazam in Lennox-Gastaut syndrome: experience in a single tertiary epilepsy center.

OBJECTIVE: Clobazam (CLB) is a 1,5-benzodiazepine, which is known to be effective for treating refractory partial epilepsy. We have evaluated the long-term efficacy and tolerability of CLB as an add-on therapy in patients with Lennox-Gastaut syndrome (LGS). METHODS: Forty-six patients with LGS who had received CLB add-on therapy were enrolled in this study. We retrospectively reviewed their clinical characteristics, including type of seizures, use of CLB, efficacy, adverse events, and retention rate. RESULTS: The mean±SD dose of CLB was 0.70±0.37 mg/kg per day (range, 0.16-1.60 mg/kg per day). After 1 month on CLB, 15 patients (32.6%) became seizure-free and 10 patients (21.7%) had 50% or greater seizure reduction. Response to CLB was not significantly associated with age, sex, or etiology (symptomatic or not). Five (10.8%) of 46 patients maintained seizure remission for more than 12 months. Tolerance developed in 48.0% of initial responders, and the 3-year retention rate by the Kaplan-Meier method was 76.6%. Seven patients (15.2%) reported adverse events, including somnolence and behavioral change, but only one discontinued CLB. CONCLUSIONS: Clobazam add-on therapy was effective and very tolerable in patients with LGS.

Magnetic resonance imaging and spectroscopic analysis in 5 cases of Pelizaeus-Merzbacher disease: metabolic abnormalities as diagnostic tools.

Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive disorder characterized by dysmyelination in the central nervous system. PMD results from deletion, mutation, or duplication of the proteolipid protein gene (PLP1) located at Xq22, leading to the failure of axon myelination by oligodendrocytes in the central nervous system. PMD may be suspected when there are clinical manifestations such as nystagmus, developmental delays, and spasticity, and genetic analysis can confirm the diagnosis. Further diagnostic manifestations of the disease include a lack of myelination on brain magnetic resonance (MR) imaging and aberrant N-acetyl aspartate (NAA) and choline concentrations that reflect axonal and myelination abnormalities on phroton MR spectroscopy. We report 5 cases of PMD (in 1 girl and 4 boys). PLP1 duplication was detected in 2 patients. Brain MR analyses and MR spectroscopy were performed for all the patients. The brain MR images showed white matter abnormalities typical of PMD, and the MR spectroscopic images showed diverse patterns of NAA, creatinine, and choline concentrations. We propose that MR spectroscopic analysis of metabolic alterations can aid the PMD diagnosis and can contribute to a better understanding of the pathogenesis of the disease.

A Novel Frameshift Mutation of the ALDOB Gene in a Korean Girl Presenting with Recurrent Hepatitis Diagnosed as Hereditary Fructose Intolerance.

Hereditary fructose intolerance is an autosomal recessive disorder that is caused by a deficiency in fructose-1-phosphate aldolase (Aldolase B). Children can present with hypoglycemia, jaundice, elevated liver enzymes and hepatomegaly after intake of dietary fructose. Long-term intake of fructose in undiagnosed patients can result in hepatic failure or renal failure. We experienced a case of hereditary fructose intolerance presenting as recurrent hepatitis-like episodes. Detailed evaluation of her dietary habits revealed her avoidance of sweetened foods and fruits. Genetic analysis of ALDOB revealed that she is a homozygote for a novel frameshifting mutation c[758_759insT]+[758_759insT] (p.[val25 3fsX24]+[val253fsX24]). This report is the first of a Korean patient diagnosed with hereditary fructose intolerance using only molecular testing without undergoing intravenous fructose tolerance test or enzyme assay.

Central nervous system (CNS) involvement is a critical prognostic factor for hemophagocytic lymphohistiocytosis.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder that frequently involves the central nervous system (CNS). We compared the clinical characteristics, treatment, and prognosis of patients with HLH according to the degree of CNS involvement. METHODS: The clinical manifestations, initial laboratory data, treatment, and outcomes for 50 patients diagnosed with HLH and treated at Asan Medical Center between January 1995 and August 2011 were retrospectively reviewed and analyzed. CNS involvement was defined as the presence of neurological symptoms or an elevated white blood cell (WBC) count in the cerebrospinal fluid (CSF). RESULTS: Among these 50 patients, 23 (46%) developed CNS disease. Among patients with CNS disease, 19 had neurological symptoms, including seizures, altered consciousness, facial palsy, dysarthria, and dysphagia. Four patients had elevated CSF WBC counts without neurological symptoms. Twelve patients had abnormal brain imaging results, including high signal intensity lesions on T2-weighted magnetic resonance imaging (MRI) findings, ventriculomegaly, hemorrhage, atrophy, and leptomeningeal enhancement. Patients with CNS disease had lower ferritin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels as well as reduced 5-year survival as compared to those without CNS disease. CONCLUSION: CNS involvement is common among patients with HLH. Overall, patients with CNS disease achieve poorer outcomes than patients without CNS involvement. To improve outcomes, physicians must carefully monitor the neurological manifestations in patients with HLH and administer the appropriate course of intensified chemotherapy to patients with CNS disease.

Determination of the effective gas diffusivity of a porous composite medium from the three-dimensional reconstruction of its microstructure.

The present work describes a procedure to calculate the effective diffusivity of a porous composite medium from the three-dimensional reconstruction of its microstructure. We perform Monte Carlo simulations based on the mean-square displacement method on numerical models of composite materials microstructures. First, computations of the effective diffusivity in the bulk diffusion regime account for the effect of the tortuosity of the geometry on gas diffusion. The Bruggeman equation, which is often used in the literature to relate the effective diffusivity to the porosity of the structure, appears to be inaccurate for porosities ε<0.40. A more accurate correlation for this range of porosities is provided based on the results of our simulations. Second, the Bosanquet equation, which accounts for the effect of pore confinement on gas diffusion, is validated provided that the definition of the Knudsen number is based on the appropriate characteristic length. The procedure to calculate this characteristic length is demonstrated for analytical geometries. However, in practice, geometries obtained from experimental measurements are discrete. For discrete geometries, we show the effect of the resolution of the geometry on the accuracy of the calculation of the effective diffusivity and other properties of the porous material. In addition, the tesselation of solid surfaces affects the calculation of the chord-length distribution regardless of the resolution. This hinders the accurate estimation of the characteristic length necessary to compute the Knudsen number and the effective diffusivity.