BACKGROUND: Rituximab (RTX) can be used as a rescue therapy for steroid-dependent nephrotic syndrome (SDNS). However, the efficacy and safety of long-term, repeated use of RTX are not established. This study was conducted to assess the efficacy and safety of long-term, repeated RTX treatment in children. METHODS: Eighteen consecutive child patients with SDNS who were treated with three or more cycles of RTX for one year or longer were recruited, and their medical records were retrospectively reviewed. RESULTS: The patients were followed for 4.7 ± 1.9 years and received 5.2 ± 2.3 cycles of RTX over 2.8 ± 1.1 years. Approximately 70% of the additional RTX cycles were administered due to recovery of B-cells without relapse. The relapse rate decreased from 3.4 ± 2.0 per year initially to 0.4 ± 0.8 per year at the third year after RTX treatment. Approximately 10% of the RTX infusions were accompanied by mild infusion reactions. Eight patients showed sustained remission without any oral medication after the last cycle of RTX, while 10 patients had one or more episodes of relapse after the last cycle of RTX. The relapse rate in the latter group decreased from 2.8 ± 1.5 per year before RTX treatment to 1.3 ± 0.8 per year after cessation of RTX treatment. No significant differences in clinical parameters were found between the two groups. CONCLUSION: This retrospective study showed that pre-emptive and long-term, repeated RTX treatment is relatively effective and safe in children with SDNS. However, well-designed prospective studies are needed to confirm these findings.
B-Lymphocytes ; Child ; Humans ; Medical Records ; Nephrotic Syndrome* ; Prospective Studies ; Recurrence ; Retrospective Studies ; Rituximab*

PURPOSE: Breast cancer is one of the most frequent malignant tumors in Korea. The major tumor suppressor genes (TSGs) such as p16, Rb, E-cadherin and p53 may play important roles in cell cycle regulation, apoptosis and the regulation of the expression of other genes as well as tumor suppression. Microsatellite alteration such as loss of heterozygosity (LOH) have been reported to be a novel mechanism of carcinogenesis and a useful prognostic factor for many malignant tumors. Also, LOH is also known to be related with allelic loss of various TSGs. This study evaluated LOH of 4 TSGs in invasive ductal carcinomas (IDCs) and we correlated these results with the clinicopathological factors. METHODS: LOH analysis was carried out using a polymerase chain reaction with 12 polymorphic microsatellite markers of 4 TSGs in 50 surgically resected tumors and their non-tumorous counterparts. RESULTS: There was no detectable LOH in the normal tissue. LOH was detected in 86% of the 50 cases of IDCs. LOH was detected on all chromosomes and this showed a statistical difference between benign tumor and malignant tumor. LOH of p16, Rb, E-cadherin and p53 TSGs was detected in 36%, 26%, 54% and 60% of the tumors, respectively. LOH of the p16 and Rb genes was inversely correlated with tumor grade 1. The low rate of detecting LOH on the E-cadherin gene was noted in T1 tumor and stage I disease. LOH of the p53 gene correlated well with the tumor size and stage. The LOH-High results correlate well with the tumor size and stage and the LOH-High results are similar to those of the p53 gene LOH. CONCLUSION: These results suggest that LOH of the 4 major TSGs may contribute to the development and invasion of IDCs. Also, the combined use of various LOH markers may help in deciding the prognosis of IDCs.
Apoptosis ; Breast Neoplasms ; Cadherins ; Carcinogenesis ; Carcinoma, Ductal* ; Cell Cycle ; Genes, p53 ; Genes, Retinoblastoma ; Genes, Tumor Suppressor* ; Korea ; Loss of Heterozygosity* ; Microsatellite Repeats ; Polymerase Chain Reaction ; Prognosis

BACKGROUND: This study investigates the perception of the general public regarding the concentration to metropolitan, hospitals of cardiac and cerebrovascular surgeries, and the perceived public need for government policies to resolve this issue. METHODS: A total of 800 participants were recruited for our telephone interview survey. Quota sampling was performed, adjusting for age and sex, to select by various geographic regions. Sampling with random digit dialing was performed; we called the randomly generated telephone numbers and made three attempts for non-responders before moving on to a different telephone number. RESULTS: Our sample population was 818 participants, 401 men (49.0%) and 417 women (51.0%). Our data showed that 85.5% of participants thought that cardiac surgery and neurosurgery patients are concentrated in large hospitals in Seoul. The principle reason for regional patients to want to receive surgery at major hospitals in Seoul was because of poor medical standards associated with regional hospitals (87.7%). We found that a vast majority of participants (97.5%) felt that government policies are needed to even out the clustering of cardiac surgery and neurosurgery patients, and that this clustering may be alleviated if policies that can specifically enhance the quality and the capacity of regional hospitals to carry out surgeries are adopted (98.3%). CONCLUSION: Government policy making must reflect public desiderata, and we suggest that these public health needs may be partially resolved through government-designated cardiac and neurosurgery specialist hospitals in regional areas.
Cardiovascular Diseases ; Cerebrovascular Disorders ; Female ; Hospitals, Urban* ; Humans ; Interviews as Topic ; Male ; Neurosurgery ; Policy Making ; Public Health ; Seoul ; Specialization ; Surgical Procedures, Operative ; Telephone ; Thoracic Surgery

The most common type of refractory hypertension found in children is secondary hypertension, which is a potentially curable disease. Reninoma, a renin-secreting juxtaglomerular cell tumor, is a rare cause of severe hypertension that is usually diagnosed in adolescents and young adults. Surgical resection of the tumor completely cures the hypertension of patients with reninoma. The typical clinical presentation of reninoma includes hypokalemia, metabolic alkalosis, and features secondary to the increased activation of the renin-angiotensin system without renal artery stenosis. We report a case of reninoma in a female adolescent with a typical clinical presentation, in which surgical removal of the tumor completely cured hypertension. We discuss here the clinical features, imaging studies, and immunohistochemical examination of the tumor used to establish the diagnosis of reninoma and for the management of the condition.
Adolescent ; Alkalosis ; Child ; Diagnosis ; Humans ; Hypertension ; Hypertension, Renal ; Hypokalemia ; Juxtaglomerular Apparatus ; Renal Artery Obstruction ; Renin ; Renin-Angiotensin System ; Young Adult

Cardiovascular manifestations in hyperthyroidism occur frequently with various phenotypes. An association between hyperthyroidism and pulmonary arterial hypertension has been reported. In previously reported cases, the hemodynamic and symptomatic recovery of pulmonary arterial hypertension is usually concomitant with achievement of euthyroidism. We report a patient who had pulmonary arterial hypertension associated with Graves' disease, which persisted after euthyroidism was obtained.
Achievement ; Graves Disease ; Hemodynamics ; Humans ; Hypertension ; Hypertension, Pulmonary ; Hyperthyroidism ; Phenotype

PURPOSE: To analyze the MR findings of chondroblastoma and peritumoral bone marrow, focussing on the enhancement pattern. MATERIALS AND METHODS: Enhanced MR images obtained from 23 patients with pathologically proven chondroblastoma were retrospectively reviewed by three radiologists. The enhancement pattern was classified as one of three types: homogeneous, heterogeneous, or peripheral rim, while peritumoral bone marrow enhancement was assigned one of four grades. Correlation between the enhancement pattern and T2 signal intensity of a tumor was analyzed by Fisher's exact test. RESULTS: The enhancement pattern was homogeneous in ten cases, heterogeneous in six, and involved the peripheral rim in seven. In 11 cases, peritumoral bone marrow enhancement was observed. Among the ten instances of homogeneous enhancement the signal intensity seen at T2WI was homogeneously iso or low in six cases, homogeneously high in two, and heterogeneous in two. Among the seven cases in which there was peripheral rim enhancement, the signal intensity observed at T2WI was homogeneously high in three, fluid-fluid level in three, and homogeneously iso or low in one. CONCLUSION: At MR imaging, chondroblastoma shows variable signal intensities and enhancement patterns. The peripheral rim enhancement observed at T2WI correlated with homogeneously high signal intensity or fluid-fluid levels.
Bone Marrow ; Chondroblastoma* ; Humans ; Magnetic Resonance Imaging ; Retrospective Studies

Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor (NF)-kappaB, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.
Aripiprazole ; Apoptosis ; Bipolar Disorder ; Brain ; Caspase 3 ; Cell Survival ; Glioma ; Liver ; Macrophages ; Nitric Oxide ; Schizophrenia ; Toll-Like Receptor 4

Nephronophthisis-related ciliopathy (NPHP-RC) is a common genetic cause of end-stage renal failure during childhood and adolescence and exhibits an autosomal recessive pattern of inheritance. Genetic diagnosis is quite limited owing to genetic heterogeneity in NPHP-RC. We designed a novel approach involving the step-wise screening of Sanger sequencing and targeted exome sequencing for the genetic diagnosis of 55 patients with NPHP-RC. First, five NPHP-RC genes were analyzed by Sanger sequencing in phenotypically classified patients. Known pathogenic mutations were identified in 12 patients (21.8%); homozygous deletions of NPHP1 in 4 juvenile nephronophthisis patients, IQCB1/NPHP5 mutations in 3 Senior–Løken syndrome patients, a CEP290/NPHP6 mutation in 1 Joubert syndrome patient, and TMEM67/MKS3 mutations in 4 Joubert syndrome patients with liver involvement. In the remaining undiagnosed patients, we applied targeted exome sequencing of 34 ciliopathy-related genes to detect known pathogenic mutations in 7 (16.3%) of 43 patients. Another 18 likely damaging heterozygous variants were identified in 13 NPHP-RC genes in 18 patients. In this study, we report a variety of pathogenic and candidate mutations identified in 55 patients with NPHP-RC in Korea using a step-wise application of two genetic tests. These results support the clinical utility of targeted exome sequencing to resolve the issue of allelic and genetic heterogeneity in NPHP-RC.
Adolescent ; Diagnosis* ; Exome* ; Genetic Heterogeneity* ; Humans ; Kidney Failure, Chronic ; Korea ; Liver ; Mass Screening ; Wills

Purpose: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria. Methods: This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks. Results: In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period. Conclusions Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. ClinicalTrials.gov trial registration (NCT0223277)