Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy

Background@#Ceramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes.Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy. @*Methods@#We used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control- or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes. @*Results@#OLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination [GFA]) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity. @*Conclusion@#We showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production.Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease.

Oncologic Outcomes of Postoperative Chemoradiotherapy Versus Chemotherapy Alone in Stage II and III Upper Rectal Cancer

PURPOSE: The aim of this study was to assess oncological outcomes of postoperative radiotherapy plus chemotherapy (CRT) versus chemotherapy alone (CTx) in stage II or III upper rectal cancer patients who underwent curative surgery. METHODS: We retrospectively reviewed 263 consecutive patients with pathologic stage II or III upper rectal cancer who underwent primary curative resection with postoperative CRT or CTx from January 2008 to December 2014 at Chonnam National University Hwasun Hospital. Multivariate and propensity score matching analyses were used to reduce selection bias. RESULTS: Median follow-up was 48.1 months for the entire cohort and 53.5 months for the matched cohort. In subgroup analysis of the propensity score matched cohort, the 3-year local recurrence-free survival was 94.1% (95% confidence interval [CI], 87.8%–100%) in the CRT group and 90.1% (95% CI, 82.8%–97.9%) in the CTx group (P = 0.370). No significant difference in disease-free survival was observed according to treatment type. On multivariate analysis, circumferential resection margin involvement (hazard ratio [HR], 2.386; 95% CI, 1.190–7.599; P = 0.032), N stage (HR, 6.262; 95% CI, 1.843–21.278, P = 0.003), and T stage (HR, 5.896, 95% CI, 1.298–6.780, P = 0.021) were identified as independent risk factors for local recurrence of tumors of the upper rectum. CONCLUSION: Omission of radiotherapy in an adjuvant treatment setting may not jeopardize oncologic outcomes in stages II and III upper rectal cancer.

Changes of the Airway Space and the Position of Hyoid Bone after Mandibular Set Back Surgery Using Bilateral Sagittal Split Ramus Osteotomy Technique / 대한악안면성형재건외과학회지

PURPOSE: Although there have been several studies of reduced airway space after mandibular setback surgery using the sagittal split ramus osteotomy technique, research on the risk factors for changes of the airway space is lacking. Therefore, this study was performed to examine airway changes and the position of the hyoid bone after orthognathic surgery, and to assess possible risk factors. METHODS: In this retrospective study, 50 patients who underwent posterior displacement of the mandible by the bilateral sagittal split ramus osteotomy technique were included. Changes of the position of the hyoid bone and the airway space were analyzed over various follow-up periods, using cephalometric radiography taken preoperatively, immediately after surgery, eight weeks after surgery, six months after surgery, and one year after surgery. To identify risk factors, multiple regression analysis of age, gender, body mass index (BMI), posterior mandibular movement, and the presence of genioplasty was performed. RESULTS: Inferor and posterior movement of the hyoid bone was observed postoperatively, but subsequent observations showed regression towards the anterosuperior aspect. The airway space also significantly decreased after surgery (P<0.05), and increased slightly up until six months after surgery. The airway space significantly decreased (beta=0.47, P<0.01) as the amount of mandibular setback increased. However, age, sex, BMI, and presence of genioplasty were not associated with airway reduction. CONCLUSION: The amount of mandibular set back was significantly associated with postoperative reduction of airway space. It is necessary to establish a treatment plan considering this factor.

Effect of volunteerism as exercise instructor on physical and cognitive function in community-dwelling elderly women / 体力科学

The purpose of this study was to examine whether volunteering as exercise instructors over a continuous period of time affected the physical and cognitive functions of community-dwelling, elderly women. Longitudinal analysis was conducted on data from 18 volunteer leaders (Leader group) aged 65-79 years (69.6 ± 3.9 years) and 18 age-matched survey participants (Control group). We evaluated physical function using 8 physical performance tests along with their standardized total score, and we evaluated cognitive function using the Five Cognitive Function Test. We used two-way ANOVA to examine the effectiveness of engaging in a yearlong volunteer activity and Cohen's d for effect size. There were significant interactions in timed up and go, hand working with pegboard, standardized score of performance tests and the Five Cognitive Function Test score (<i>P</i> < 0.05). The Leader group improved significantly in sit and reach (d = 0.55), 5-repetition sit-to-stand (d = 0.77), timed up and go (d = 0.77), 5-m habitual walk (d = 0.88), 4-way choice reaction time (d = 0.86), standardized score of performance tests (d = 0.96) and the Five Cognitive Function Test score (d = 0.93). Although the Control group also improved significantly in some tests, the effect size tended to be lower: sit and reach (d = 0.49), hand working with pegboard (d = 0.57), standardized score of performance tests (d = 0.38) and the Five Cognitive Function Test score (d = 0.54). These results suggest that volunteering as an exercise instructor improves volunteers' physical and cognitive functions.

Antibiotic susceptibility and imaging findings of the causative microorganisms responsible for acute urinary tract infection in children: a five-year single center study / 소아과

PURPOSE: We studied the differences in the antibiotic susceptibilities of the microorganisms that causeing urinary tract infections (UTI) in children to obtain useful information on appropriate drug selection for childhood UTI. METHODS: We retrospectively analyzed the antibiotic susceptibilities of 429 microorganisms isolated from 900 patients diagnosed with UTI in the Department of Pediatrics, Chungbuk National University Hospital, from 2003 to 2008. RESULTS: The most common causative microorganisms for UTI were Escherichia coli (81.4%), Klebsiella pneumoniae (8.4%), Enterobacter spp. (1.7%), and Proteus spp. (0.4%). E. coli showed relatively high susceptibility as compared to imipenem (100%), amikacin (97.7%), aztreonam (97.9%), cefepime (97.7%), and ceftriaxone (97.1%), while it showed relatively low susceptibility to gentamicin (GM) (79.0%), trimethoprim/sulfamethoxazole (TMP/SMX) (68.7%), ampicillin/sulbactam (33.0%), and ampicillin (AMP) (28.6%). There were no significant differences in the image findings for causative microorganisms. CONCLUSION: Gram-negative organisms showed high susceptibility to amikacin and third-generation cephalosporins, and low susceptibility to AMP, GM, and TMP/SMX. Therefore, the use of AMP or TMP/SMX as the first choice in empirical and prophylactic treatment of childhood UTI in Korea should be reconsidered and investigated further.

A Case of Congenital Laryngeal Atresia with Diaphragmatic Hernia / 대한주산의학회잡지

Congenital laryngeal atresia is a rare cause of airway obstruction that is almost always lethal within short period of time after birth unless diagnosed prenatally and emergency tracheostomy was performed. Other life-threatening anomalies such as tracheoesophageal fistula, gastrointestinal or urinary anomalies, and VATER syndrome are often associated with laryngeal atresia. Recently, we experienced a case of congenital laryngeal atresia with diaphragmatic hernia, ear and skull anomalies, not diagnosed prenatally, died of asphyxia due to intubation failure, and confirmed by autopsy. We report this case with a brief review of the literatures.

Clinical study of urinary tract infection, natural courses, and prenatal ultrasonographic results according to the grades of hydronephrosis / 소아과

PURPOSE: Although renal ultrasonography (USG) has improved the detection rate of hydronephrosis (HN), its clinical courses and postnatal management remains controversial. Here, we reviewed the clinical features of patients with HN according to the grades. METHODS: We retrospectively studied 207 patients who were regularly followed-up among 367 patients with HN detected by renal USG postnatally between April 1998 and December 2007. These patients were grouped into four groups, grades 1-4, according to renal pelvic diameter (RPD). For analysis, each group was merged into two categories (mild: grade 1, 2; severe: grade 3, 4). RESULTS: During follow-up, 128 episodes of urinary tract infection (UTI) occurred in 91 patients. According to grades from 1 to 4, 35/89 (39.3%), 41/88 (46.5%), 11/22 (50%), and 4/8 (50%), respectively, had UTI, without any significance between the mild and severe groups. However, the severe group presented a higher risk in cumulative episodes of UTI per year (P=0.041). The spontaneous resolution of HN was observed in 103 (58.8%) of the 175 mild group patients and in 3 (10.7%) of the 28 severe group patients (P<0.001). Furthermore, the detection rate of prenatal HN by prenatal USG was much higher in patients with severe RPD (P<0.001). CONCLUSION: We found that the severer the grade of HN, the lower was the rate of spontaneous resolution and higher was the frequency of UTI. Therefore, the establishment of guidelines for managing treatments such as antibiotic prophylaxis for patients with HN is needed to improve renal prognosis.

Effects of soy-based formula on infants' growth and blood laboratory values spanning 3 years after birth / 소아과

PURPOSE: We compared body growth, blood cell counts, and chemistry among infants receiving soy-based formula (SF), breast milk (BM), and casein-based formula (CF). METHODS: Full-term neonates delivered at our hospital from June 2001 to August 2003 were recruited and divided into 3 feeding groups (BM=20, SF=19, CF=12) according to the parents wishes. Breast feeding or artificial formulae were given during the initial 3 months of age; thereafter, weaning foods were added freely. Height, weight, head circumference, skin-fold thickness, and mid-arm circumference were measured at birth and 1, 2, 4, 5, 12, and 36 months of age. Cell counts and blood chemistry were analyzed at 5, 12, and 36 months of age. RESULT: At 5 months of age, body weight was the lowest in the SF group; the height was similar among all groups. Thereafter, there were no differences in height or weight among the groups until 36 months of age. Hemoglobin was the lowest in the BM group at 5 and 12 months of age (P<0.05). At 5 months of age, serum cholesterol, BUN, phosphates, and K+ were significantly lower in the SF group; thereafter, all chemical parameters were similar until 36 months of age. CONCLUSION: Infants fed with SF showed normal growth during the first 3 years of life as compared to infants fed with BM and CF. Low values of serum phosphates and K+ at 5 months of age in the SF group, despite the high mineral content, suggest that further investigation is needed for effective mineral absorption.

A Case of Diabetic Nephropathy Progressed to End-Stage Renal Disease in an Adolescent with Type 1 Diabetes

Type 1 diabetes mellitus (T1DM) commonly occurs in childhood and adolescence and diabetic nephropathy is a serious metabolic complication of T1DM that leads to serious morbidity. With poor glycemic control prepubertal diabetes duration contributes to the risk of long-term microvascular complications, however, the younger age at onset or longer prepubertal diabetes duration seems to prolong the time to development of microalbuminuria or later end-stage renal disease (ESRD). Therefore, there have been a few cases of diabetic nephropathy in prepubertal patients and therefore the ESRD cases developed during adolescence in T1DM children were very rare. Here we report an adolescent with T1DM who had poor glycemic control and was diagnosed as diabetic nephropathy in a prepubertal period and leading to end-stage renal disease during adolescence.

Atypical presentation of Kawasaki disease resembling a retropharyngeal abscess / 소아과

Kawasaki disease is an acute systemic inflammatory disorder, the etiology of which has not yet been established. The clinical manifestations are non-specific and are common to many pediatric infectious and immunologic diseases. In 2 cases presenting fever, cervical lymphadenopathy, and retropharyngeal abscess-like lesions on the neck shown in a computerized tomography (CT) scan, the diagnosis of Kawasaki disease was delayed. The patients were not responsive to antibiotic therapy, and fluid collection was not found during retropharyngeal aspiration. They showed typical Kawasaki manifestations over time and atrioventricular valve regurgitation in the echocardiogram. A diagnosis of Kawasaki disease should be considered in similar cases of fever and cervical lymphadenopathy. A CT scan that shows a retropharyngeal abscess-like lesion on the neck can be a false positive finding, and other laboratory exams, including echocardiography, should be performed as early as possible to avoid unnecessary medical and surgical procedures.

A Case of Gastritis Cystica Profunda with a Long Stalk Presenting with Upper Gastrointestinal Bleeding / 대한소화기내시경학회지

Gastritis cystica profunda (GCP) is a rare disease in which hyperplastic and cystic dilatation of the gastric mucous glands extend into the tissues beneath the submucosa. GCP is mainly observed at the site of a gastroenterostomy; however, it may occur in the stomach without a previous history of surgery. GCP may present not only as a submucosal tumor or as solitary or diffuse polyps but also rarely as a giant gastric mucosal fold. In a patient without a previous history of surgery, GCP presents mainly as a sessile polypoid protrusion or as a submucosal tumor. In addition, GCP presents with non-specific symptoms and is most commonly found incidentally. We present a case of GCP that developed upper gastrointestinal bleeding and showed a long stalk and a focal ulcerative lesion on the surface of a polyp that developed in the stomach without a history of previous surgery. This lesion was removed by the use of an endoscopic polypectomy and was histologically diagnosed as GCP.

Estimation of heritability attributable to single-locus effects with a regression of offspring on mid-parent (ROMP) method for cardiovascular risk factors / 한국역학회지

PURPOSE: The objective of this study was to estimate the heritability attributable to single-locus effects with a regression of offspring on mid-parent (ROMP) method for cardiovascular risk factors. METHODS: The regression of offspring on mid-parent is determined with and without the inclusion of a single-locus effect, and the difference between the slopes of these two regression is an estimate of the heritability attributable to the single-locus effect. The study population included 1,550 family members of 295 patients, derived from cardiovascular genome center. The risk factors considered were total serum cholesterol, triglyceride, LDL cholesterol, apoAI and apoB. Heritability was estimated from the slope of the linear regression of offspring on mid-parents. RESULTS: Estimated heritability was 35 to 46% for total cholesterol with 6.2% attributable to polymorphism S128R. For triglyceride, the estimated heritability was 47.6% with 2% attributable to polymorphism G-217A. The heritability was 36-46% for LDL-cholesterol. For LDL cholesterol, S128R specific effect was 8.7%. Estimated heritability was 62.2% for apoAI with 3.2% attributable to polymorphism G-217A and 58 to 75% for apoB with 5.4% attributable to polymorphism S128R. CONCLUSIONS: These traits were significantly associated with polymorphism S128R. These results highlight the importance of considering genetic factors in studies of cardiovascular risk factors. Unlike traditional population-based tests of association, ROMP appears to be robust with respect to population stratification.

Test-retest Reliability of a Self-Administered Smoking Questionnaire for Middle and High School Students / 한국역학회지

PURPOSE: Since 1988, the annual or biannual survey was conducted by Korean Association of Smoking and Health (KASH) to examine the smoking rate, knowledge and attitude on smoking of students attending middle and high school in Korea. The objective of this study was to investigate the test-retest reliability of self-administered smoking questionnaire for Korean middle and high school students. METHODS: For the test-retest study, we sampled 30 school among 106 schools which participated in annual survey on June of 2002. Among 30 schools, 26 schools (86.7%) were responded for this study. RESULTS: 1) For the subjects of 1st and 2nd surveys, there were no difference on smoking related variable including attitude, knowledge, perceived health status, father's smoking status, friend's smoking status, willingness to smoke, and readiness to quit smoking 2) For middle school students among male, current smoking rates were 3.5% for 1st survey and 3.0% for 2nd survey, which was statistically no significant. For high school students, however, current smoking rate of 1st survey was higher (21.1%) than that of 2nd (18.2%), although the rate was not significantly differed. 3) For middle school students among female, current smoking rates were 1.1% for 1st survey and 3.3% for 2nd survey, which was statistically no significant. Corresponding rate for high school students were 9.8% and 11.4%, respectively. CONCLUSION: The results indicated that smoking questionnaire has been conducted by KASH is reliable for use in estimation for prevalence of smoking for middle and high school students.