Clinical Features of and Antibiotic Resistance in Recurrent Urinary Tract Infection in Children with Vesicoureteral Reflux

Purpose@#This study aimed to investigate the clinical features of recurrent urinary tract infection (UTI) in children with vesicoureteral reflux (VUR) and to compare the causative uropathogen and antibiotic susceptibility between the first and recurrent UTI episodes. @*Methods@#We retrospectively reviewed the medical records of children with VUR who had recurrent UTI. Group 1 included patients in whom the same pathogen caused the first and recurrent UTI episodes. Group 2 included patients in whom different pathogens caused the first and recurrent UTI episodes. @*Results@#During a 13-year study period (2005–2018), 77 children with VUR experienced at least one episode of UTI. Among these, 47 patients (61.0%) had recurrent UTI. Of the children with recurrent UTI, 19 (40.4%) were in group 1 and 28 (59.6%) were in group 2. Escherichia coli was the most commonly isolated uropathogen (n=37; 39.4%) in both episodes of recurrent UTIs, followed by Klebsiella pneumoniae (n=18; 19.1%), Enterococcus faecalis (n=14; 14.9%), and Enterobacter aerogenes (n=7; 7.4%). Although the difference was not significant, the rate of resistance to the antibiotics ceftazidime, piperacillin/tazobactam, and trimethoprim-sulfamethoxazole increased in patients with the second episode of E. coli recurrence in group 1, and that to cefotaxime, ceftazidime, piperacillin/tazobactam, and meropenem increased in children with the second episode of E. aerogenes recurrence in group 1. @*Conclusions@#When selecting empirical antibiotics for recurrent UTI in children with VUR, it is important to consider that the pathogen and antimicrobial susceptibility of the previous UTI are not always the same in recurrent UTIs.

Range of Eye Movement in a Normal Population and Its Relationship to Age

PURPOSE: The purpose of this study is to measure the range of normal eye movement and to evaluate the effect of age on the range of ocular movement in a normal population. METHODS: We conducted a prospective observational study of 85 subjects aged between 5 and 91 years. Photographs were taken of the cardinal position, and these images were analyzed using an image analysis software (Adobe Photoshop 6.0, Adobe, San Jose, CA, USA). To measure the range of eye movement, the preprocessed images were analyzed using the Image J program. The range of movement of the eyeball was quantitatively measured using corneal limbal analysis. Specifically, the ranges of ocular movement according to adduction, abduction, elevation, and depression were measured. RESULTS: The normal movement ranges were 44.4 ± 6.9° in adduction, 44.8 ± 5.5° in abduction, 27.7 ± 7.6° in elevation, and 46.7 ± 8.4° in depression. Adduction, abduction, and elevation were negatively correlated with age (R² = 0.220, R² = 0.126, and R² = 0.304, respectively, all p < 0.001). However, there was no significant correlation between age and depression (R² = 0.030, p = 0.113). CONCLUSIONS: For all ages, the range of normal ocular movement in the horizontal direction was symmetric, while the range of ocular movement in elevation was smaller than that of depression. As age increased, the range of ocular movement decreased in all directions except depression, but depression did not decrease with age. When assessing eye movement, it is necessary to consider the range of ocular movements relative to both the movement direction and changes in the ocular movement range according to age.

Relationship between serum sodium level and coronary artery abnormality in Kawasaki disease / 소아과

PURPOSE: Kawasaki disease (KD) is an immune-related multisystemic vasculitis that occurs in children, especially ensuing from a coronary artery abnormality. Sodium level is known to be related to vascular injury, which could affect the progress of KD. The purpose of this study was to determine the serum sodium levels that could predict the occurrence of cardiac and coronary artery events in KD. METHODS: We conducted a retrospective review of medical records for 104 patients with KD from January 2015 to December 2015. Patients with serum Na levels of <135 mEq/L at the time of initial diagnosis were assigned to the hyponatremia group. Laboratory findings and echocardiographic data were analyzed for various aspects. RESULTS: Among the 104 patients with KD, 91 were included in the study, of whom 48 (52.7%) had hyponatremia. The degree of fever, white blood cell count, percentage of neutrophils, percentage of lymphocytes, total bilirubin level, brain natriuretic peptide level, erythrocyte sedimentation rate, and C-reactive protein level were higher in the patients with hyponatremia. They also demonstrated a trend of larger coronary artery diameters based on Z scores. CONCLUSION: The severity of vascular inflammation in acute KD with hyponatremia might worsen the prognosis of coronary vasculature. Although no statistically significant correlation was found between the initial serum sodium levels and coronary arteriopathy in the patients with KD in this study, a long-term follow-up study with a larger number of enrolled patients should be designed in the future to elucidate the relationship between serum sodium level and coronary arteriopathy in patients with KD.

Therapeutic Plasma Exchange in Pediatric Kidney Disease: 23-year Experience at the Severance Children's Hospital in Korea

PURPOSE: The American Society for Apheresis provides clinical guidelines for therapeutic apheresis in adults, but there are no guidelines for children. This study aimed to analyze the effect of therapeutic plasma exchange (TPE) in pediatric patients with various kidney diseases in Korea. METHODS: We retrospectively reviewed the data of 16 children (up to 18 years of age) who were admitted to Severance Children's Hospital with refractory kidney disease. All patients received TPE between 1994 and 2016. Clinical and laboratory characteristics such as age, weight, sex, change in blood urea nitrogen (BUN), and creatinine level before and after TPE, and complications after TPE were analyzed. RESULTS: The mean age and weight of the 16 patients at the time of TPE was 11.3±4.0 years and 34.6±17.5 kg, respectively. The BUN level was 35.4 mg/dL before TPE and significantly decreased to 21.5 mg/dL (P=0.025) at 1 week and 20.5 mg/dL (P=0.01) at 1 month after TPE. The creatinine level significantly decreased from 1.20 mg/dL before TPE to 0.90 mg/dL (P=0.02) at 1 week after TPE. Four complications (hypovolemia, anemia, hypocalcemia, and thrombocytopenia) were reported, but were not fatal. CONCLUSION: Our findings suggest that TPE is an effective therapeutic modality in children with refractory kidney disease and can be indicated for the treatment of various kidney diseases.

Therapeutic Plasma Exchange in Pediatric Kidney Disease: 23-year Experience at the Severance Children's Hospital in Korea

PURPOSE: The American Society for Apheresis provides clinical guidelines for therapeutic apheresis in adults, but there are no guidelines for children. This study aimed to analyze the effect of therapeutic plasma exchange (TPE) in pediatric patients with various kidney diseases in Korea. METHODS: We retrospectively reviewed the data of 16 children (up to 18 years of age) who were admitted to Severance Children's Hospital with refractory kidney disease. All patients received TPE between 1994 and 2016. Clinical and laboratory characteristics such as age, weight, sex, change in blood urea nitrogen (BUN), and creatinine level before and after TPE, and complications after TPE were analyzed. RESULTS: The mean age and weight of the 16 patients at the time of TPE was 11.3±4.0 years and 34.6±17.5 kg, respectively. The BUN level was 35.4 mg/dL before TPE and significantly decreased to 21.5 mg/dL (P=0.025) at 1 week and 20.5 mg/dL (P=0.01) at 1 month after TPE. The creatinine level significantly decreased from 1.20 mg/dL before TPE to 0.90 mg/dL (P=0.02) at 1 week after TPE. Four complications (hypovolemia, anemia, hypocalcemia, and thrombocytopenia) were reported, but were not fatal. CONCLUSION: Our findings suggest that TPE is an effective therapeutic modality in children with refractory kidney disease and can be indicated for the treatment of various kidney diseases.

Clinical Significance of Extended-spectrum β-lactamase-producing Bacteria in First Pediatric Febrile Urinary Tract Infections and Differences between Age Groups

PURPOSE: Extended-spectrum β-lactamase-producing bacteria-induced urinary tract infections are increasing and require more potent antibiotics such as carbapenems. We evaluated the clinical significance of extended-spectrum β-lactamase urinary tract infection in children younger than 5 years to select proper antibiotics and determine prognostic factors. Differences were compared between age groups. METHODS: We retrospectively studied 288 patients with their first febrile urinary tract infection when they were younger than 5 years. Patients were divided into extended-spectrum β-lactamase-positive and extended-spectrum β-lactamase-negative urinary tract infection groups. Clinical characteristics and outcomes were compared between the groups; an infant group was separately analyzed (onset age younger than 3 months). RESULTS: Extended-spectrum β-lactamase urinary tract infection occurred in 11% patients who had more frequent previous hospitalization (P=0.02) and higher recurrence rate (P=0.045). During the antimicrobial susceptibility test, the extendedspectrum β-lactamase-positive urinary tract infection group showed resistance to third-generation cephalosporins; however, 98% patients responded clinically. In the infant group, extended-spectrum β-lactamase-positive urinary tract infection occurred in 13% patients and was associated with a longer pre-onset hospitalization history (P=0.002), higher C-reactive protein level (P=0.04), and higher recurrence rate (P=0.02) than that in the older group. CONCLUSION: Extended-spectrum β-lactamase urinary tract infection requires more attention because of its higher recurrence rate. The antimicrobial susceptibility test demonstrated resistance to third-generation cephalosporins, but they can be used as first-line empirical antibiotics because of their high clinical response rate. Aminoglycosides can be second-line antibiotics before starting carbapenems when third-generation cephalosporins do not show bactericidal effects for extended-spectrum β-lactamase urinary tract infection.

Clinical Significance of Extended-spectrum β-lactamase-producing Bacteria in First Pediatric Febrile Urinary Tract Infections and Differences between Age Groups

PURPOSE: Extended-spectrum β-lactamase-producing bacteria-induced urinary tract infections are increasing and require more potent antibiotics such as carbapenems. We evaluated the clinical significance of extended-spectrum β-lactamase urinary tract infection in children younger than 5 years to select proper antibiotics and determine prognostic factors. Differences were compared between age groups. METHODS: We retrospectively studied 288 patients with their first febrile urinary tract infection when they were younger than 5 years. Patients were divided into extended-spectrum β-lactamase-positive and extended-spectrum β-lactamase-negative urinary tract infection groups. Clinical characteristics and outcomes were compared between the groups; an infant group was separately analyzed (onset age younger than 3 months). RESULTS: Extended-spectrum β-lactamase urinary tract infection occurred in 11% patients who had more frequent previous hospitalization (P=0.02) and higher recurrence rate (P=0.045). During the antimicrobial susceptibility test, the extendedspectrum β-lactamase-positive urinary tract infection group showed resistance to third-generation cephalosporins; however, 98% patients responded clinically. In the infant group, extended-spectrum β-lactamase-positive urinary tract infection occurred in 13% patients and was associated with a longer pre-onset hospitalization history (P=0.002), higher C-reactive protein level (P=0.04), and higher recurrence rate (P=0.02) than that in the older group. CONCLUSION: Extended-spectrum β-lactamase urinary tract infection requires more attention because of its higher recurrence rate. The antimicrobial susceptibility test demonstrated resistance to third-generation cephalosporins, but they can be used as first-line empirical antibiotics because of their high clinical response rate. Aminoglycosides can be second-line antibiotics before starting carbapenems when third-generation cephalosporins do not show bactericidal effects for extended-spectrum β-lactamase urinary tract infection.

Successful treatment of tubulointerstitial nephritis and uveitis with steroid and azathioprine in a 12-year-old boy / 소아과

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, often underdiagnosed or misdiagnosed in children. We describe the case of a 12-year-old boy who presented to Severance Hospital with a 1-month history of bilateral conjunctival injection. He was first evaluated by an Ophthalmologist in another hospital and diagnosed with panuveitis. Laboratory tests indicated renal failure, and a renal biopsy confirmed the diagnosis of acute tubulointerstitial nephritis. An extensive exclusion of all possible causes allowed a diagnosis of TINU syndrome. The patient was treated with a systemic corticosteroid (initially prednisolone, 2 mg/kg and later deflazacort 1 mg/kg) and topical steroid drops for 1 month. Azathioprine was later added to the treatment regimen and the systemic steroid was slowly tapered. The final outcome of renal-ocular disease was favorable in the patient. However, long-term follow-up is necessary to properly manage frequent relapses and incomplete renal recovery. TINU should be considered as a differential diagnosis in children with uveitis or acute renal failure.

Usefulness of neutrophil-lymphocyte ratio in young children with febrile urinary tract infection / 소아과

PURPOSE: Acute pyelonephritis (APN) is a serious bacterial infection that can cause renal scarring in children. Early identification of APN is critical to improve treatment outcomes. The neutrophil-lymphocyte ratio (NLR) is a prognostic marker of many diseases, but it has not yet been established in urinary tract infection (UTI). The aim of this study was to determine whether NLR is a useful marker to predict APN or vesicoureteral reflux (VUR). METHODS: We retrospectively evaluated 298 pediatric patients (age≤36 months) with febrile UTI from January 2010 to December 2014. Conventional infection markers (white blood cell [WBC] count, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and NLR were measured. RESULTS: WBC, CRP, ESR, and NLR were higher in APN than in lower UTI (P<0.001). Multiple logistic regression analyses showed that NLR was a predictive factor for positive dimercaptosuccinic acid (DMSA) defects (P<0.001). The area under the receiver operating characteristic (ROC) curve was high for NLR (P<0.001) as well as CRP (P<0.001) for prediction of DMSA defects. NLR showed the highest area under the ROC curve for diagnosis of VUR (P<0.001). CONCLUSION: NLR can be used as a diagnostic marker of APN with DMSA defect, showing better results than those of conventional markers for VUR prediction.

Usefulness of neutrophil-lymphocyte ratio in young children with febrile urinary tract infection / 소아과

PURPOSE: Acute pyelonephritis (APN) is a serious bacterial infection that can cause renal scarring in children. Early identification of APN is critical to improve treatment outcomes. The neutrophil-lymphocyte ratio (NLR) is a prognostic marker of many diseases, but it has not yet been established in urinary tract infection (UTI). The aim of this study was to determine whether NLR is a useful marker to predict APN or vesicoureteral reflux (VUR). METHODS: We retrospectively evaluated 298 pediatric patients (age≤36 months) with febrile UTI from January 2010 to December 2014. Conventional infection markers (white blood cell [WBC] count, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and NLR were measured. RESULTS: WBC, CRP, ESR, and NLR were higher in APN than in lower UTI (P<0.001). Multiple logistic regression analyses showed that NLR was a predictive factor for positive dimercaptosuccinic acid (DMSA) defects (P<0.001). The area under the receiver operating characteristic (ROC) curve was high for NLR (P<0.001) as well as CRP (P<0.001) for prediction of DMSA defects. NLR showed the highest area under the ROC curve for diagnosis of VUR (P<0.001). CONCLUSION: NLR can be used as a diagnostic marker of APN with DMSA defect, showing better results than those of conventional markers for VUR prediction.

Outcomes of Hemodialysis in Children: A 35-Year Experience at Severance Hospital

PURPOSE: The aim of this study was to analyze the results of children treated with hemodialysis (HD) at Severance Hospital over 35 years in terms of incidence, etiologies, characteristics, complications, and clinical outcomes. MATERIALS AND METHODS: We analyzed 46 children admitted to Severance Hospital who had undergone HD between January 1979 and December 2013. RESULTS: The main etiologies of the 23 end-stage renal disease (ESRD) patients who had received HD were chronic glomerulonephritis (7 patients, 30.4%) and congenital anomalies of the kidney and urinary tract (7 patients, 30.4%), whereas the etiology of the 23 acute kidney injury (AKI) patients was hemolytic uremic syndrome (6 patients, 26.1%). Compared with ESRD patients, hemocatheter placement in the femoral vein was preferred over the subclavian or internal jugular vein in the AKI patients (p=0.012). The most common complication was catheter related complication (10 patients, 21.7%). The site of hemocatheter insertion was not related to the frequency of oozing. Placing the hemocatheter in the femoral vein resulted in significantly more events of catheter obstruction than insertion in the internal jugular vein or the subclavian vein (p=0.001). Disequilibrium syndrome occurred more frequently in older patients (p=0.004), as well as patients with a greater body weight (p=0.008) and a higher systolic and diastolic blood pressure before HD (systolic: p=0.021; diastolic: p=0.040). CONCLUSION: Based on the 35 years of experience in our center, HD can be sufficiently and safely carried out even in children without significant complications.

Noninfectious Complications of Peritoneal Dialysis in Korean Children: A 26-Year Single-Center Study

PURPOSE: The aim of this study was to investigate noninfectious complications of peritoneal dialysis (PD), including mechanical and metabolic complications, at a single center in Korea. MATERIALS AND METHODS: We analyzed data from 60 PD patients aged < or =18 years (40 boys and 20 girls) during the period between 1986 and 2012. The collected data included gender, age, causes of PD, incidence of noninfectious complications, and treatment for the complications. RESULTS: The mean duration of PD therapy was 28.7+/-42.1 months (range 1-240 months). The most common cause of end-stage renal disease was glomerular disease (43.3%). There were no statistically significant differences between patients with and without mechanical complications regarding gender, age at the start of PD, and total duration of PD. Outflow failure was the most common catheter-related complication (14.3%), followed by leakage (10.0%) and hernia (8.6%). Metabolic complications, such as hyperglycemia and hypokalemia, were observed in three of 16 patients. The frequency of noninfectious complications of PD in our study was comparable with those in previous pediatric studies. PD was switched to hemodialysis (HD) in only three patients. CONCLUSION: Our results indicate that noninfectious complications of PD are common, though they hardly lead to catheter removal or HD in pediatric patients on PD.

The Clinical Efficacy of an Individualized Pulmonary Rehabilitation Program in Patients with Coal-worker Pneumoconiosis / 대한내과학회지

BACKGROUND/AIMS: It is unknown whether pulmonary rehabilitation (PR) is an effective intervention to manage coal-worker pneumoconiosis (CWP). We evaluated the efficacy and safety of an individualized PR program in 53 patients with CWP hospitalized in two medical institutions. METHODS: The PR program consisted of upper and lower extremity exercises to improve exercise endurance and skeletal musculoskeletal strength. All subjects performed treadmill and ergometer exercise with steady loading weights three times/week for 12 weeks. The following tests were performed before and after the study to investigate the efficacy of the PR program: modified Borg scale, pulmonary function test, mid-thigh circumference, maximum muscular strength, 6-min walk distance (6MWD), and the St. George's Respiratory Questionnaire (SGRQ), Korean version. RESULTS: Forty patients (75.5%) completed their PR programs. They improved significantly on the modified Borg scale, mid-thigh circumference, maximum muscular strength, 6MWD (all p < 0.000), and SGRQ (p = 0.007); however, no significant improvement was observed on the pulmonary function test. A significant improvement in dyspnea (p = 0.004) and 6MWD (p = 0.002) was observed in 12 patients with forced expiratory volume in 1 sec < 60%. The PR program with smoking cessation resulted in significantly more improvement on the 6MWD (p < 0.0001) and the SGRQ score (p = 0.002), as compared to those of patients who did not quit smoking. CONCLUSIONS: Our results show that an individualized 12-week PR program improves exercise capacity and quality of life for patients with CWP.

A Nationwide Epidemiological Study of Nocturnal Enuresis in Korean Adolescents and Adults: Population Based Cross Sectional Study

We performed a nationwide epidemiological study to evaluate the prevalence and characteristics of nocturnal enuresis (NE) in Korean adolescents and adults. A questionnaire was sent via e-mail to 51,073 people aged 16-40 yr by stratified sampling according to age, sex, and region among a 200,000 internet survey panel pool. The questionnaire included following information; presence or absence of NE, frequency of NE, possible risk factors for NE, self-esteem scale score and depression score results, and measures for the treatment of NE. Among the 2,117 responders, 54 (2.6%) had NE (> or =1 enuretic episode within 6 months). Of 54 bedwetters, 9.3% wet > or =1 night per week and 20.5% wet > or =1 per month. The prevalence rates remained relatively stable with no apparent trend of reduction with age. The presence of sleep disturbance, family history, urgency, or urge incontinence increased the probability of NE episode significantly. The self-esteem score was lower (P=0.053) and the depression scale score was higher (P=0.003) in bedwetters compared with non-bedwetters. Overall 2.6% of Korean aged 16-40 yr have NE. The higher rate of urgency and urge incontinence in adolescent and adult enuretics suggests that bladder function has an important role in adolescent and adult NE.

Risk Factors for Treatment Failure in Benign Paroxysmal Positional Vertigo / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Particular repositioning maneuver (PRM) have been recommended as a treatment of benign paroxysmal positional vertigo (BPPV). Some patients require multiple treatments for remission, although most of the patients are treated at the first trial of single maneuver. The purpose of this study was to evaluate risk factors for the treatment failure in patients with posterior canal BPPV (p-BPPV) and horizontal canal BPPV (h-BPPV). SUBJECTS AND METHOD: Retrospective review was performed for the 287 patients diagnosed as BPPV visiting the dizziness clinic between February 2011 and August 2012. The diagnostic criteria for BPPV were met by following the guidelines provided by the American Academy of Otolaryngology-Head and Neck Surgery. Patients were classified into two groups: Group 1 (treatment success) that requires only 1 PRM and Group 2 (treatment failure) that requires more than 2 PRMs. We analyzed the relationship between treatment failure and the clinical characteristics, and studied the etiology of BPPV. RESULTS: The study included 183 patients with p-BPPV, 54 patients with h-BPPV (geotropic type), and 50 patients with h-BPPV (apogeotropic type). The type of BPPV and average numbers of PRM required for remission were significantly related with treatment failure by statistical analysis (p<0.05, respectively). Statistically significant correlation was demonstrated between the history of ipsilateral inner ear viral infection (acute vestibular neuritis, sudden sensorineural hearing loss) and treatment failure (p<0.05). CONCLUSION: Multiple PRMs may be required in patients with h-BPPV (apogeotropic type) or with secondary BPPV caused by ipsilateral inner ear viral disease. Clinically, this information may be used to provide helpful information for clinicians performing PRM to treat BPPV.

Outcomes of Peritonitis in Children on Peritoneal Dialysis: A 25-Year Experience at Severance Hospital

PURPOSE: Relatively little is known on the microbiology, risk factors and outcomes of peritoneal dialysis (PD)-associated peritonitis in Korean children. We performed this study in order to evaluate the incidence, treatment and clinical outcomes of peritonitis in pediatric PD patients at Severance Hospital. MATERIALS AND METHODS: We analyzed data from 57 PD patients younger than 18 years during the period between June 1, 1986 and December 31, 2011. The collected data included gender, age at commencement of PD, age at peritonitis, incidence of peritonitis, underlying causes of end stage renal disease, microbiology of peritonitis episodes, antibiotics sensitivity, modality and outcomes of PD. RESULTS: We found 56 episodes of peritonitis in 23 of the 57 PD patients (0.43 episodes/patient-year). Gram-positive bacteria were the most commonly isolated organisms (40 episodes, 71.4%). Peritonitis developed in 17 patients during the first 6 months following initiation of PD (73.9%). Peritonitis episodes rarely resulted in relapse or the need for permanent hemodialysis and no patient deaths were directly attributable to peritonitis. Antibiotic regimens included cefazolin+tobramycin from the years of 1986 to 2000 and cefazolin+ceftazidime from the years of 2001 to 2011. While antibiotic therapy was successful in 48 episodes (85.7%), the treatment was ineffective in 8 episodes (14.3%). The rate of continuous ambulatory PD (CAPD) peritonitis was statistically higher than that of automated PD (APD) (p=0.025). CONCLUSION: Peritonitis was an important complication of PD therapy and we observed a higher incidence of PD peritonitis in patients with CAPD when compared to APD.

Validation of Tissue Microarrays for the Study of Immunosuppressive Agent-induced Nephrotoxicity / 대한이식학회지

BACKGROUND: Tissue microarray analysis (TMA) is a high-throughput method for histologic evaluation, immunohistochemistry, and in situ hybridization using paraffin embedded tissue. Despite its high efficiency as an experimental tool, TMA is limited because it only contains a very small tissue fragment from each case. Therefore, the purpose of this study was to evaluate the validity of TMA in a study of nephrotoxicity caused by immunosuppressants. METHODS: Male Sprague-Dawley rats were treated with vehicle (n=16), cyclosporine (n=23), and cyclosporine plus losartan (n=13) for a maximum of 7 weeks. After animal sacrifice, renal tissues were embedded in paraffin and processed into slides for microscopic examination using conventional methods and the TMA technique. Acute tubular injury, vascular hyaline change, and interstitial fibrosis were scored in both conventional and TMA slides. The number of interstitial macrophages was counted after ED-1 immunohistochemistry and the results also compared between conventional and TMA slides. RESULTS: The degree of acute tubular injury and interstitial fibrosis showed a significant agreement between conventional and TMA methods (kappa value, 0.79 and 1.00, respectively). The number of interstitial macrophages counted in conventional and TMA slides showed a significant correlation as well (r=0.934, P<0.001). However, the degree of vascular hyaline changes showed less agreement between conventional and TMA methods (kappa value, 0.40). CONCLUSIONS: TMA is a useful and reliable method for the study of nephrotoxicity induced by immunosuppressive agents. TMA also reflects the findings of conventional methods, especially for acute and chronic tubular and interstitial changes.

Risk Factors for Neurologic Complications of Hand, Foot and Mouth Disease in the Republic of Korea, 2009

In 2009, the first outbreak of hand, foot and mouth disease (HFMD) or herpangina (HP) caused by enterovirus 71 occurred in the Republic of Korea. This study inquired into risk factors associated with complications of HFMD or HP. A retrospective medical records review was conducted on HFMD or HP patients for whom etiologic viruses had been verified in 2009. One hundred sixty-eight patients were examined for this investigation. Eighty patients were without complications while 88 were accompanied by complications, and 2 had expired. Enterovirus 71 subgenotype C4a was the most prevalent in number with 67 cases (54.9%). In the univariate analysis, the disease patterns of HFMD rather than HP, fever longer than 4 days, peak body temperature over 39degrees C, vomiting, headache, neurologic signs, serum glucose over 100 mg/dL, and having an enterovirus 71 as a causative virus were significant risk factors of the complications. After multiple logistic analysis, headache (Odds ratio [OR], 10.75; P < 0.001) and neurologic signs (OR, 42.76; P < 0.001) were found to be the most significant factors. Early detection and proper management of patients with aforementioned risk factors would be necessary in order to attain a better clinical outcome.

Effect of Combining Multiple CNV Defining Algorithms on the Reliability of CNV Calls from SNP Genotyping Data

In addition to single-nucleotide polymorphisms (SNP), copy number variation (CNV) is a major component of human genetic diversity. Among many whole-genome analysis platforms, SNP arrays have been commonly used for genomewide CNV discovery. Recently, a number of CNV defining algorithms from SNP genotyping data have been developed; however, due to the fundamental limitation of SNP genotyping data for the measurement of signal intensity, there are still concerns regarding the possibility of false discovery or low sensitivity for detecting CNVs. In this study, we aimed to verify the effect of combining multiple CNV calling algorithms and set up the most reliable pipeline for CNV calling with Affymetrix Genomewide SNP 5.0 data. For this purpose, we selected the 3 most commonly used algorithms for CNV segmentation from SNP genotyping data, PennCNV, QuantiSNP; and BirdSuite. After defining the CNV loci using the 3 different algorithms, we assessed how many of them overlapped with each other, and we also validated the CNVs by genomic quantitative PCR. Through this analysis, we proposed that for reliable CNV-based genomewide association study using SNP array data, CNV calls must be performed with at least 3 different algorithms and that the CNVs consistently called from more than 2 algorithms must be used for association analysis, because they are more reliable than the CNVs called from a single algorithm. Our result will be helpful to set up the CNV analysis protocols for Affymetrix Genomewide SNP 5.0 genotyping data.

Cerebral Salt Wasting Treated with Fludrocortisone in a 17-Year-Old Boy

Cerebral salt wasting is characterized by inappropriate natriuresis and volume contraction with associated cerebral pathology. It is distinct from the syndrome of inappropriate antidiuretic hormone secretion, which is characterized by inappropriate retention of free water. We report a patient with a porencephalic cyst who developed cerebral salt wasting. His initial treatment was supplementation of water and salt, which did not improve natriuresis or volume contraction. Fludrocortisone administration effectively managed the cerebral salt wasting.