Clinical and molecular characterization of Korean children with infantile and late-onset Pompe disease: 10 years of experience with enzyme replacement therapy at a single center / 소아과

PURPOSE: Pompe disease (PD) is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase resulting from pathogenic GAA variants. This study describes the clinical features, genotypes, changes before and after enzyme replacement therapy (ERT), and long-term outcomes in patients with infantile-onset PD (IOPD) and late-onset PD (LOPD) at a tertiary medical center. METHODS: The medical records of 5 Korean patients (2 male, 3 female patients) diagnosed with PD between 2002 and 2013 at Samsung Medical Center in Seoul, Republic of Korea were retrospectively reviewed for data, including clinical and genetic characteristics at diagnosis and clinical course after ERT. RESULTS: Common initial symptoms included hypotonia, cyanosis, and tachycardia in patients with IOPD and limb girdle weakness in patients with LOPD. Electrocardiography at diagnosis revealed hypertrophic cardiomyopathy in all patients with IOPD who showed a stable disease course during a median follow-up period of 10 years. Patients with LOPD showed improved hepatomegaly and liver transaminase level after ERT. CONCLUSION: As ERT is effective for treatment of PD, early identification of this disease is very important. Thus, patients with IOPD should be considered candidates for clinical trials of new drugs in the future.

Relationship of Nurses' Perception of the Joint Commission International Hospital Accreditation, Nursing Performance, Self-concept and Retention Intention / 간호행정학회지

PURPOSE: This study was done to identify the relationships of perception of JCI (Joint Commission International) hospital accreditation, nursing performance, self-concept and retention intention in nurses. METHODS: Self-administered questionnaires were used to collect data from 199 JCI-accredited nurses in general hospitals located in Gyeonggi Province. Data collection was done in May 2015 and analyzed using t-test, ANOVA, Scheffé's test, and Pearson correlation coefficients. RESULTS: The scores for perception, and nursing performance were (on a five-point Likert scale) 3.34, 3.78 respectively, and self-concept and retention intention were (on a eight-point Likert scale) 5.40 and 5.21 respectively. Nurses' perception, nursing performance, self-concept, and retention intention showed significant differences depending on age, marital status, education, department, work experience, position, Korean accreditation, and JCI accreditation. A positive correlation was observed between perception, nursing performance, self-concept, and retention intention. CONCLUSION: The results of this study indicate that enhancing positive perception and good nursing performance can produce good self-concept and retention intention.

Factors Influencing Use of Medical Alert Identification in Diabetic Patients Using Insulin / 임상간호연구

PURPOSE: The aim of this study was to identify perception, use status and factors influencing use of medical alert identification (ID) in diabetic patients who are on insulin. METHODS: A survey was conducted from December 2013 to April 2014 with 198 people who were asked to participate in the survey. RESULTS: The medical alert ID perception score was 3.54 on a 5-point scale. Most of respondents (82.8%) knew about the medical alert ID, but only 23.2% of respondents wore a medical alert ID and only 43.5% of respondents always wore a medical alert ID. Perception and frequency of possession were positively correlated (r=.41, p<.001). The most influential factor for the possession of a medical alert ID was the perception of the medical alert ID (β=.41, p<.001). The perception of the medical alert ID explained 17% of variance in possession of a medical alert ID. CONCLUSION: Most of diabetic patients who take insulin received education about hypoglycemia and knew about the medical alert ID, but only few of them wore a medical alert ID. Findings from this study indicate that perception is an important variable related to possession of a medical alert ID in this population.

Impact of Enzyme Replacement Therapy on Linear Growth in Korean Patients with Mucopolysaccharidosis Type II (Hunter Syndrome)

Hunter syndrome (or mucopolysaccharidosis type II [MPS II]) arises because of a deficiency in the lysosomal enzyme iduronate-2-sulfatase. Short stature is a prominent and consistent feature in MPS II. Enzyme replacement therapy (ERT) with idursulfase (Elaprase(R)) or idursulfase beta (Hunterase(R)) have been developed for these patients. The effect of ERT on the growth of Korean patients with Hunter syndrome was evaluated at a single center. This study comprised 32 patients, who had received ERT for at least 2 yr; they were divided into three groups according to their ages at the start of ERT: group 1 (<6 yr, n=14), group 2 (6-10 yr, n=11), and group 3 (10-20 yr, n=7). The patients showed marked growth retardation as they got older. ERT may have less effect on the growth of patients with the severe form of Hunter syndrome. The height z-scores in groups 2 and 3 revealed a significant change (the estimated slopes before and after the treatment were -0.047 and -0.007, respectively: difference in the slope, 0.04; P<0.001). Growth in response to ERT could be an important treatment outcome or an endpoint for future studies.

A study of the relationship between clinical phenotypes and plasma iduronate-2-sulfatase enzyme activities in Hunter syndrome patients / 소아과

PURPOSE: Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS activity, which is measured in leukocyte pellets or fibroblasts, was reported to be related to clinical phenotype by Sukegawa-Hayasaka et al. Measurement of residual plasma IDS activity using a fluorometric assay is simpler than conventional measurements using skin fibroblasts or peripheral blood mononuclear cells. This is the first study to describe the relationship between plasma IDS activity and clinical phenotype of MPS II. METHODS: We hypothesized that residual plasma IDS activity is related to clinical phenotype. We classified 43 Hunter syndrome patients as having attenuated or severe disease types based on clinical characteristics, especially intellectual and cognitive status. There were 27 patients with the severe type and 16 with the attenuated type. Plasma IDS activity was measured by a fluorometric enzyme assay using 4-methylumbelliferyl-alpha-iduronate 2-sulphate. RESULTS: Plasma IDS activity in patients with the severe type was significantly lower than that in patients with the attenuated type (P=0.006). The optimal cut-off value of plasma IDS activity for distinguishing the severe type from the attenuated type was 0.63 nmol.4 hr-1.mL-1. This value had 88.2% sensitivity, 65.4% specificity, and an area under receiver-operator characteristics (ROC) curve of 0.768 (ROC curve analysis; P=0.003). CONCLUSION: These results show that the mild phenotype may be related to residual lysosomal enzyme activity.

A study of the relationship between clinical phenotypes and plasma iduronate-2-sulfatase enzyme activities in Hunter syndrome patients / 소아과

PURPOSE: Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS activity, which is measured in leukocyte pellets or fibroblasts, was reported to be related to clinical phenotype by Sukegawa-Hayasaka et al. Measurement of residual plasma IDS activity using a fluorometric assay is simpler than conventional measurements using skin fibroblasts or peripheral blood mononuclear cells. This is the first study to describe the relationship between plasma IDS activity and clinical phenotype of MPS II. METHODS: We hypothesized that residual plasma IDS activity is related to clinical phenotype. We classified 43 Hunter syndrome patients as having attenuated or severe disease types based on clinical characteristics, especially intellectual and cognitive status. There were 27 patients with the severe type and 16 with the attenuated type. Plasma IDS activity was measured by a fluorometric enzyme assay using 4-methylumbelliferyl-alpha-iduronate 2-sulphate. RESULTS: Plasma IDS activity in patients with the severe type was significantly lower than that in patients with the attenuated type (P=0.006). The optimal cut-off value of plasma IDS activity for distinguishing the severe type from the attenuated type was 0.63 nmol.4 hr-1.mL-1. This value had 88.2% sensitivity, 65.4% specificity, and an area under receiver-operator characteristics (ROC) curve of 0.768 (ROC curve analysis; P=0.003). CONCLUSION: These results show that the mild phenotype may be related to residual lysosomal enzyme activity.

The Determinants of Job Satisfaction of Nurses: Focused on Work Rewards

PURPOSE: The purpose of this study was to investigate the determinants of job satisfaction of hospital nurses. The focus was on work rewards. A causal model of job satisfaction of hospital nurses was constructed based on situational perspectives. METHODS: The sample for this study consisted of 505 nurses from 2 general hospitals located in Seoul and Kyeonggi Province, Korea. Data were collected with self-administrated questionnaires and analyzed by hierarchical multiple regression. RESULTS: All variables except workload were positively correlated with job satisfaction. It was found that three task reward variables (workload, meaning, and participation), two organizational reward variables (security and promotional chances) and one social reward variable (family support) had significant influence on nurses' job satisfaction. The explained variance for job satisfaction was 41.4%. The data further indicate that task rewards were the most significant determinants of nurse job satisfaction. CONCLUSION: Theses findings provide strong empirical evidence for importance of task, organizational and social reward variables in explaining job satisfaction of nurses. The model used for this study will be useful for predicting nurse job satisfaction.

Apoptosis and Expression of AQP5 and TGF-beta in the Irradiated Rat Submandibular Gland / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the effect of X-ray irradiation on apoptosis and change of expression of aquaporin 5 (AQP5) and transforming growth factor-beta(TGF-beta) in the rat submandibular gland (SMG). MATERIALS AND METHODS: SMGs of 120 male Sprague-Dawley rats were irradiated with a single X-ray dose (3, 10, 20, or 30 Gy). At the early and late post-irradiation phase, apoptosis was measured by the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method, and expression of AQP5 and TGF-beta was determined by immunohistochemical staining. RESULTS: At the late post-irradiation phase, increased apoptosis was evident and marked decreases of expression of AQP5 expression by acinar cells and TGF-beta expression by ductal cells were evident. CONCLUSION: Apoptosis after X-ray irradiation develops relatively late in rat SMG. Irradiation reduces AQP5 and TGF-beta expression in different SMG cell types.

Effects and adverse-effects of growth hormone therapy in children with Prader-Willi syndrome: A two year study / 소아과

PURPOSE: The objective of this study was to evaluate the effects and adverse side-effects of growth hormone (GH) therapy in children with Prader-Willi syndrome (PWS). METHODS: Forty-one patients who had been treated with GH for more than two years (24 boys and 17 girls, mean age 7.3+/-3.3 years during treatment initiation) were enrolled for this study. RESULTS: After 2 years of GH therapy, the height and weight standard deviation scores (SDS) increased significantly (- 1.19+/-1.37 vs. - 0.02+/-1.45, and 1.02+/-2.42 vs. 1.63+/-2.22, P<0.002); however the percentage body fat decreased (44.6+/-9.9% vs. 38.1+/-10.5%, P<0.001). Further, no change was observed in the thyroid and serum glucose levels, but the total cholesterol level decreased. GH therapy did not impact glucose control in the patients with diabetes. The most common adverse effects of GH therapy were the progression of scoliosis and adenoid hypertrophy. CONCLUSION: GH therapy improved the height SDS and body composition in patients with PWS. However, GH should be used with caution in patients with scoliosis and adenoid hypertrophy.

Peptide YY, Cholecystokinin, Insulin and Ghrelin Response to Meal did not Change, but Mean Serum Levels of Insulin is Reduced in Children with Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.

Marked Suppression of Ghrelin Concentration by Insulin in Prader-Willi Syndrome

The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86+/-0.15 to 0.58+/-0.12 ng/mL in the controls, and from 2.38+/-0.76 to 1.12+/-0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82+/-44.4 vs. -10.41+/-2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS.

Effect of Flavopiridol on Radiation-induced Apoptosis of Human Laryngeal and Lung Cancer Cells / 대한방사선종양학회지

PURPOSE: To investigate the flavopiridol effect on radiation-induced apoptosis and expression of apoptosis- related genes of human laryngeal and lung cancer cells. MATERIALS AND METHODS: A human laryngeal cancer cell line, AMC-HN3 and a human lung cancer cell line, NCI-H460, were used in the study. The cells were divided into four groups according to the type of treatment: 1) control groups; 2) cells that were only irradiated; 3) cells treated only with flavopiridol; 4) cells treated with flavopiridol and radiation simultaneously. The cells were irradiated with 10 Gy of X-rays using a 4 MV linear accelerator. Flavopiridol was administered to the media at a concentration of 100 nM for 24 hours. We compared the fraction of apoptotic cells of each group 24 hours after the initiation of treatment. The fraction of apoptotic cells was detected by measurement of the sub-G1 fractions from a flow cytometric analysis. The expression of apoptosis-regulating genes, including cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), p53, p21, cyclin D1, and phosphorylated Akt (protein kinase B) were analyzed by Western blotting. RESULTS: The sub-G1 fraction of cells was significantly increased in the combination treatment group, as compared to cells exposed to radiation alone or flavopiridol alone. Western blotting also showed an increased expression of cleaved caspase-3 and cleaved PARP expression in cells of the combination treatment group, as compared with cells exposed to radiation alone or flavopiridol alone. Treatment with flavopiridol down regulated cyclin D1 expression of both cell lines but its effect on p53 and p21 expression was different according to each individual cell line. Flavopiridol did not affect the expression of phophorylated Akt in both cell lines. CONCLUSION: Treatment with flavopiridol increased radiation-induced apoptosis of both the human laryngeal and lung cancer cell lines. Flavopiridol effects on p53 and p21 expression were different according to the individual cell line and it did not affect Akt activation of both cell lines.

Clinical Characteristics and Genetic Analysis of Prader-Willi Syndrome

PURPOSE: Prader-Willi syndrome(PWS) is a complex disorder affecting multisystems with characteristic clinical features. Its genetic basis is an expression defect in the paternally derived chromosome 15q11-q13. We analyzed the clinical features and genetic basis of PWS patients for early detection and treatment. METHODS: We retrospectively studied 24 patients with PWS in Department of Pediatrics, Samsung Medical Center, from September 1997 to September 2001. We performed cytogenetic and molecular genetic techniques using high resolution GTG banding techniques, fluorescent in situ hybridization and methylation-specific PCR for CpG island of SNRPN gene region. RESULTS: The average birth weight of PWS patients was 2.67+/-0.47 kg and median age at diagnosis was 1.3 years. The average height and weight of PWS patients under one year at diagnostic time were located in a 3-10 percentile relatively, and a rapid weight gain was seen between two and six years. Feeding problems in infancy and neonatal hypotonia were the two most consistently positive major criteria in over 95% of the patients. In 18 of the 24 cases(75%), deletion of chromosome 15q11-q13 was demonstrated and one case among 18 had an unbalanced 14;15 translocation. In four cases without any cytogenetic abnormality, it may be considered as maternal uniparental disomy and the rest showed another findings. CONCLUSION: We suggest diagnostic testing for PWS in all infants/neonates with unexplained feeding problems and hypotonia. It is necessary for clinically suspicious patients to undergo an early genetic test. As the genetic basis of PWS was heterogenous and complex, further study is required.