Analysis of Pediatric Surgery Using the National Healthcare Insurance Service Database in Korea: How Many Pediatric Surgeons Do We Need in Korea?

Background@#In the past, general surgeons (GSs) without a pediatric surgical subspecialty often performed surgery on children and, even now, GSs are performing many pediatric surgeries. We aimed to investigate the involvement of pediatric surgeons (PSs) and GSs in pediatric surgery, compare the outcomes of surgery in the neonatal intensive care unit (NICU), and estimate the appropriate PS workforce in Korea. @*Methods@#We used surgical data from the National Health Insurance Service database that was collected from patients under the age of 19 years in hospitals nationwide from January 2002 to December 2017. In this database, we found 37 hospitals where PSs worked by using the index operation (congenital diaphragmatic hernia, esophageal atresia, hypertrophic pyloric stenosis, Hirschsprung's disease, abdominal wall defect, jejunoileal atresia, malrotation, anorectal malformation, and biliary atresia). It was assumed that the surgery in the 37 hospitals was performed by PS and that the surgery in other hospitals was performed by GS. Mortality was analyzed to compare the outcomes of acute abdominal surgery in the NICU. We estimated the number of PS currently needed in Korea for each situation under the assumption that PS would perform all operations for the index operation, main pediatric diseases (index operation + gastroesophageal reflux disease, choledochal cyst, inguinal hernia, and appendicitis), acute abdominal surgery in the NICU, and all pediatric surgeries.Additionally, we estimated the appropriate number of PS required for more advanced pediatric surgery in the future. @*Results@#The number of pediatric surgeries from 2002 to 2017 increased by 124%.Approximately 10.25% of the total pediatric surgeries were performed by PSs, and the percentage of the surgery performed by PSs increased from 8.32% in 2002 to 15.92% in 2017. The percentage of index operations performed by PSs annually was 62.44% in average. It was only 47.81% in 2002, and increased to 88.79% in 2017. During the last 5 years of the study period, the average annual number of surgeries for main pediatric diseases was approximately 33,228. The ratio of the number of surgeries performed by PS vs. GS steadily increased in main pediatric diseases, however, the ratio of the number of surgery performed by PS for inguinal hernia and appendicitis remained low in the most recent years. The percentage of the number of acute abdominal surgery performed by PS in the NICU was 44% in 2002, but it had recently risen to 89.7%. After 30 days of birth, mortality was significantly lower in all groups that were operated on by PS, rather than GS, during the last 5 years. In 2019, 49 PSs who were under the age of 65 years were actively working in Korea. Assuming that all pediatric surgeries of the patients under the age of 19 years should be performed by PS, the minimum number of PS currently required was about 63 if they perform all of the index operations, the main pediatric surgery was about 209, the NICU operation was about 63, and the all pediatric surgeries was about 366. Additionally, it was determined that approximately 165 to 206 PS will be appropriate for Korea to implement more advanced pediatric surgery in the future. @*Conclusion@#The proportion of the pediatric surgery performed by PS rather than GS is increasing in Korea, but it is still widely performed by GS. PSs have better operative outcomes for acute abdominal surgery in the NICU than GSs. We believe that at least the index operation or the NICU operation should be performed by PS for better outcome, and that a minimum of 63 PSs are needed in Korea to do so. In addition, approximately 200 PSs will be required in Korea in order to manage main pediatric diseases and to achieve more advanced pediatric surgery in the future.

Analysis of Pediatric Surgery Using the National Healthcare Insurance Service Database in Korea: How Many Pediatric Surgeons Do We Need in Korea?

Background@#In the past, general surgeons (GSs) without a pediatric surgical subspecialty often performed surgery on children and, even now, GSs are performing many pediatric surgeries. We aimed to investigate the involvement of pediatric surgeons (PSs) and GSs in pediatric surgery, compare the outcomes of surgery in the neonatal intensive care unit (NICU), and estimate the appropriate PS workforce in Korea. @*Methods@#We used surgical data from the National Health Insurance Service database that was collected from patients under the age of 19 years in hospitals nationwide from January 2002 to December 2017. In this database, we found 37 hospitals where PSs worked by using the index operation (congenital diaphragmatic hernia, esophageal atresia, hypertrophic pyloric stenosis, Hirschsprung's disease, abdominal wall defect, jejunoileal atresia, malrotation, anorectal malformation, and biliary atresia). It was assumed that the surgery in the 37 hospitals was performed by PS and that the surgery in other hospitals was performed by GS. Mortality was analyzed to compare the outcomes of acute abdominal surgery in the NICU. We estimated the number of PS currently needed in Korea for each situation under the assumption that PS would perform all operations for the index operation, main pediatric diseases (index operation + gastroesophageal reflux disease, choledochal cyst, inguinal hernia, and appendicitis), acute abdominal surgery in the NICU, and all pediatric surgeries.Additionally, we estimated the appropriate number of PS required for more advanced pediatric surgery in the future. @*Results@#The number of pediatric surgeries from 2002 to 2017 increased by 124%.Approximately 10.25% of the total pediatric surgeries were performed by PSs, and the percentage of the surgery performed by PSs increased from 8.32% in 2002 to 15.92% in 2017. The percentage of index operations performed by PSs annually was 62.44% in average. It was only 47.81% in 2002, and increased to 88.79% in 2017. During the last 5 years of the study period, the average annual number of surgeries for main pediatric diseases was approximately 33,228. The ratio of the number of surgeries performed by PS vs. GS steadily increased in main pediatric diseases, however, the ratio of the number of surgery performed by PS for inguinal hernia and appendicitis remained low in the most recent years. The percentage of the number of acute abdominal surgery performed by PS in the NICU was 44% in 2002, but it had recently risen to 89.7%. After 30 days of birth, mortality was significantly lower in all groups that were operated on by PS, rather than GS, during the last 5 years. In 2019, 49 PSs who were under the age of 65 years were actively working in Korea. Assuming that all pediatric surgeries of the patients under the age of 19 years should be performed by PS, the minimum number of PS currently required was about 63 if they perform all of the index operations, the main pediatric surgery was about 209, the NICU operation was about 63, and the all pediatric surgeries was about 366. Additionally, it was determined that approximately 165 to 206 PS will be appropriate for Korea to implement more advanced pediatric surgery in the future. @*Conclusion@#The proportion of the pediatric surgery performed by PS rather than GS is increasing in Korea, but it is still widely performed by GS. PSs have better operative outcomes for acute abdominal surgery in the NICU than GSs. We believe that at least the index operation or the NICU operation should be performed by PS for better outcome, and that a minimum of 63 PSs are needed in Korea to do so. In addition, approximately 200 PSs will be required in Korea in order to manage main pediatric diseases and to achieve more advanced pediatric surgery in the future.

Laparoscopic Pediatric Inguinal Hernia Repair; Intracorporeal Purse-String Suture Using Needlescopic 2-mm Instruments

Purpose@#Two-millimeter needlescopic instruments induce minimal damage to the abdominal wall and have excellent cosmetic benefits. We aimed to evaluate the feasibility of a laparoscopic intracorporeal suture using 2-mm instruments for pediatric inguinal hernia. @*Methods@#We retrospectively reviewed 131 patients who underwent laparoscopic repair between March 2011 and February 2017. Three trocars were used: a 5-mm umbilical trocar for a needle holder and two 2-mm trocars for a camera and a grasper. The internal ring was closed with an intracorporeal purse-string suture. A telephone interview was conducted to confirm recurrence. @*Results@#In the 131 patients, 169 procedures were successfully performed. The ages ranged from 2 months to 14 years (mean, 52.5 months), and the mean body weight was 18.0 kg (range, 6.7~49 kg). The mean operating time was 42 minutes for the unilateral cases and 46 minutes for the bilateral inguinal hernia repairs. All the cases were completed laparoscopically without intraoperative complications. Herniotomy was not performed in all the patients except nine. A contralateral patent processus vaginalis was present in 27.3% (35/128) of the patients. During the mean follow-up period of 54.6 months, 3 recurrences (2.3%) were observed. Two recurrences were treated using laparoscopy and one using open herniorrhaphy. Hydrocele occurred in one male patient. No wound complications or umbilical hernias developed. No testicular atrophy was observed. @*Conclusion@#This study showed that laparoscopic intracorporeal internal ring suture using 2-mm instruments for pediatric inguinal hernia was technically feasible and safe, with excellent cosmetic results.

Percutaneous Internal Ring Suturing for Indirect Inguinal Hernia in Pediatric Patients

Many laparoscopic techniques have been developed to repair inguinal hernia in children using either an intraperitoneal or extraperitoneal approach. Percutaneous internal ring suturing (PIRS) is one of the extracorporeal suture techniques. It could be performed with comparable surgical complication or recurrence rates and excellent cosmetic results. To minimize the perioperative complications, surgical procedures of PIRS can be performed carefully with technical refinements for inguinal hernia repair in children.

Feasibility of Laparoscopic Surgery for Intussusception in Pediatric Patients and Risk of Bowel Resection

No abstract available.

Cyclooxygenase-2 Inhibitor Reduces Hepatic Stiffness in Pediatric Chronic Liver Disease Patients Following Kasai Portoenterostomy

PURPOSE: The purpose of this study was to define the role of cyclooxygenase-2 inhibitors (COX-2i) in reducing hepatic fibrosis in pediatric patients with chronic liver disease. MATERIALS AND METHODS: From September 2009 to September 2010, patients over 2 years old who visited our outpatient clinic for follow-up to manage their chronic liver disease after Kasai portoenterostomy for biliary atresia, were included in this study. Volunteers were assigned to the study or control groups, according to their preference. A COX-2i was given to only the study group after obtaining consent. The degree of hepatic fibrosis (liver stiffness score, LSS) was prospectively measured using FibroScan, and liver function was examined using serum analysis before and after treatment. After 1 year, changes in LSSs and liver function were compared between the two groups. RESULTS: Twenty-five patients (18 females and 7 males) were enrolled in the study group. The control group included 44 patients (26 females and 18 males). After 1 year, the least square mean values for the LSSs were significantly decreased by 3.91±0.98 kPa (p=0.004) only in the study group. Serum total bilirubin did not decrease significantly in either group. CONCLUSION: COX-2i treatment improved the LSS in patients with chronic liver disease after Kasai portoenterostomy for biliary atresia.

Clinical Characteristics and Management of Benign Transient Non-Organic Ileus of Neonates: A Single-Center Experience

PURPOSE: The term benign transient non-organic ileus of neonates (BTNIN) is applied to neonates who present symptoms and plain radiographic findings of Hirschsprung's disease, but do not have aganglionic bowel and are managed well by conservative treatment. It can often be difficult to diagnose BTNIN because its initial symptoms are similar to those of Hirschsprung's disease. The aim of this study is to evaluate the clinical characteristics and proper treatment of BTNIN. MATERIALS AND METHODS: A retrospective review was made on the clinical data of 19 neonates who were treated for BTNIN between January 2008 and December 2011 at a single facility. RESULTS: Abdominal distension occurred in every patient (19/19). Other common symptoms included emesis (5/19), explosive defecation (5/19), and constipation (4/19). The vast majority of patients (15/19) experienced the onset of symptoms between 2 and 4 weeks of age. Radiograph findings from all of the patients were similar to Hirschsprung's disease. A barium study showed a transition zone in 33.4% (6/18) of the patients. However, rectal biopsy revealed ganglion cells in the distal rectum in 88.2% (15/17) of the patients, and anorectal manometry showed a normal rectoanal inhibitory reflex in 90% (9/10). All patients responded well to conservative treatment. Symptoms disappeared at the mean age of 4.9+/-1.0 months, and the abdominal radiographs normalized. CONCLUSION: BTNIN had an excellent outcome with conservative treatment, and must be differentiated from Hirschsprung's disease. A rectal biopsy and anorectal manometry were useful diagnostic tools in the differential diagnosis.

Feasibility of a Laparoscopic Approach for Generalized Peritonitis from Perforated Appendicitis in Children

PURPOSE: This study evaluated the feasibility of a laparoscopic approach in children with generalized peritonitis secondary to perforated appendicitis. MATERIALS AND METHODS: We retrospectively analyzed the medical records of patients who underwent laparoscopic appendectomy with drainage for generalized peritonitis secondary to perforated appendicitis at our hospital between September 2001 and April 2012. Laparoscopic outcomes were compared with outcomes of an open method for perforated appendicitis. RESULTS: Ninety-nine patients underwent laparoscopic appendectomy (LA) for generalized peritonitis from perforated appendicitis, and 87 patients underwent open appendectomy (OA) for perforated appendicitis. Wound infection was more common in the OA group (12.6%) than in the LA group (4.0%; p=0.032). The incidence of intestinal obstruction during long-term follow-up was significantly higher in the OA group (4.6% vs. 0.0% in the LA group; p=0.046). LA was possible in most patients for whom LA was attempted, with a conversion rate of 10.8%. Conversion to OA was affected by the preoperative duration of symptoms and the occurrence of intraoperative complications. CONCLUSION: LA is feasible for use in children with generalized peritonitis from perforated appendicitis, with reasonable open conversion and perioperative complication rates comparable to those of the OA group.

Minimally invasive surgery in infants with congenital diaphragmatic hernia: outcome and selection criteria / 대한외과학회지

PURPOSE: The aim of the study was to determine clinical indications for performing minimally invasive surgery (MIS) with acceptable results by reviewing our experience in congenital diaphragmatic hernia (CDH) repair and comparing outcomes of MIS with open surgery. METHODS: Medical records of patients who underwent CDH repair were reviewed retrospectively between January 2008 and December 2012, and outcomes were compared between MIS and open repair of CDH. RESULTS: From 2008 to 2012, 35 patients were operated on for CDH. Among these patients, 20 patients underwent open surgery, and 15 patients underwent MIS. Patients with delayed presentations (60.0% [9/15] in the MIS group vs. 20.0% [4/20] in the open surgery group; P = 0.015) and small diaphragmatic defect less than 3 cm (80.0% [12/15] in the MIS group vs. 0.0% [0/20] in the open surgery group; P < 0.001) were more frequently in the MIS group than the open surgery group. All 10 patients who also had other anomalies underwent open surgery (P = 0.002). Moreover, nine patients who needed a patch for repair underwent open surgery (P = 0.003). Patients in the MIS group showed earlier enteral feeding and shorter hospital stays. There was no recurrence in either group. CONCLUSION: CDH repair with MIS can be suggested as the treatment of choice for patients with a small sized diaphragmatic defect, in neonates with stable hemodynamics and without additional anomalies, or in infants with delayed presen tation of CDH, resulting in excellent outcomes.

Second Serial Transverse Enteroplasty Procedure in an Infant with Extreme Short Bowel Syndrome

The serial transverse enteroplasty (STEP) procedure is a novel technique to lengthen and taper the bowel in patients with short bowel syndrome. The advantages of STEP include not only technical ease and simplicity, but also the ability to repeat the procedure. Herein, we report a case of extreme short bowel syndrome that was successfully treated by the second STEP procedure. A 3-day old newborn girl underwent STEP because of jejunal atresia with the small bowel length of 15 cm, but her bowel elongation was not enough to escape from short bowel syndrome. At the age of 6 months, she underwent a second STEP procedure. The bowel lengthening by the second STEP made her tolerable to enteral feeding with body weight gain and rescued her from short bowel syndrome. This case showed that second STEP is very helpful in treatment of extreme short bowel syndrome.

Clinical characteristics and treatment of esophageal atresia: a single institutional experience / 대한외과학회지

PURPOSE: Treatment for esophageal atresia has advanced over several decades due to improvements in surgical techniques and neonatal intensive care. Subsequent to increased survival, postoperative morbidity has become an important issue in this disease. The aim of our study was to analyze our experience regarding the treatment of esophageal atresia. METHODS: We reviewed and analyzed the clinical data of patients who underwent surgery for esophageal atresia at Severance Children's Hospital from 1995 to 2010 regarding demographics, surgical procedures, and postoperative outcomes. RESULTS: Seventy-two patients had surgery for esophageal atresia. The most common gross type was C (81.9%), followed by type A (15.3%). Primary repair was performed in 52 patients. Staged operation was performed in 17 patients. Postoperative esophageal strictures developed in 43.1% of patients. Anastomotic leakages occurred in 23.6% of patients, and recurrence of tracheoesophageal fistula was reported in 8.3% of patients. Esophageal stricture was significantly associated with long-gap (> or =3 cm or three vertebral bodies) atresia (P = 0.042). The overall mortality rate was 15.3%. The mortality in patients weighing less than 2.5 kg was higher than in patients weighing at least 2.5 kg (P = 0.001). During the later period of this study, anastomotic leakage and mortality both significantly decreased compared to the earlier study period (P = 0.009 and 0.023, respectively). CONCLUSION: The survival of patients with esophageal atresia has improved over the years and the rate of anastomotic leakage has been significantly reduced. However, overall morbidities related to surgical treatment of esophageal atresia still exists with high incidence.

Initial Experience of Robot-assisted Resection of Choledochal Cyst in Children

Although laparoscopic surgery for hepatobiliary disease in children is possible, it is technically challenging. In an attempt to overcome these difficulties, the da Vinci Robotic Surgical System(R) was used to facilitate the minimally invasive treatment of choledochal cyst in six children. In early consecutive three cases, we experienced three complications; a case of laparotomy conversion, a case of late stenosis of the hepaticojejunostomy, and a case of leakage from a hepaticojejunostomy. However, in the last three cases the complete resection of the choledochal cyst and Roux-en-Y hepaticojejunostomy were performed using the robotic surgical system without complication. We think robot-assisted choledochal cyst resection in children appears safe and feasible, and may increase the variety of complex procedures in pediatric surgical fields.

High Incidence of Hiatal Hernia in Esophageal Atresia and Its Etiologic Factors

Hiatal hernia is a very rare disease in the pediatric population. However information from our esophageal atresia postoperative follow-up program has hypotheses; "Hiatal hernia may more frequently occur in postoperative esophageal atresia patients (EA group) than in the general pediatric population (GP group)" and "The tension on the esophagus after esophageal anastomosis may be an important etiologic factor of hiatal hernia in EA group". To prove the first hypotheses, we compared the incidence of hiatal hernia in the GP group with the incidence in the EA group. The Incidence in the GP group was obtained from national statistic data from Statistics Korea and Health Insurance Review and Assessment Service of Korea. The incidence in the EA group was obtained from the medical record and the imaging studies of our esophageal atresia postoperative follow-up program. To prove the second hypothesis, the presumptive risk factors for the development of hiatal hernia in EA group, such as the type of esophageal atresia, degree of esophageal gap, the stage operation and the redo-operation with resection and re-anastomosis of esophagus were analyzed statistically. The total number of patients in the EA group was ninety-nine and there were 5 hiatus hernias. The incidence of EA group (5 %) is significantly higher than incidence of GP group (0.024 %). (p=0.0001) The statistical analysis of the presumptive risk factors for hiatal hernia development in EA group failed to show any evidence of correlation between postoperative esophageal tension and the hiatal hernia. This study shows that the postoperative patients with esophageal atresia have high occurrence of hiatal hernia and should be followed up carefully to detect hiatal hernia.

Home intravenous antibiotic treatment for intractable cholangitis in patients with biliary atresia following Kasai portoenterostomies / 대한외과학회지

PURPOSE: Patients with biliary atresia (BA) treated with Kasai portoenterostomy may later develop intractable cholangitis (IC) that is unresponsive to routine conservative treatment. It may cause biliary cirrhosis and eventually hepatic failure with portal hypertension. Control of IC requires prolonged hospitalization for the administration of intravenous antibiotics. To reduce the hospitalization period, we designed a home intravenous antibiotic treatment (HIVA) which can be administered after initial inpatient treatment. In this study, we reviewed the effects of this treatment. METHODS: We reviewed medical records of 10 patients treated with HIVA for IC after successful Kasai portoenterostomies performed for BA between July 1997 and June 2009. RESULTS: The duration of HIVA ranged from 8 to 39 months (median, 13.5 months). The median length of hospital stay was 5.7 days per month for conventional treatments to manage IC before HIVA and, 1.5 days per month (P = 0.012) after HIVA. The median amount of medical expenses per month was reduced by about one tenth with HIVA. One patient underwent liver transplantation due to uncontrolled esophageal variceal bleeding, but the other nine patients had acceptable hepatic function with native livers. CONCLUSION: HIVA may be an effective primary treatment for IC after Kasai portoenterostomies for BA, and reduce length of hospital stay and medical expense.

Meconium Obstruction in Neonates-Clinical Characteristics and Treatment

Meconium obstruction (MO) in neonates arises from highly viscid meconium and the poor motility of the premature gut. Recently the incidence of the MO in neonates has been increasing, but, the diagnosis and treatment of this disease have not yet been clarified. Between March 2004 and April 2010, 24 neonates were treated for MO at Severance Children's Hospital. Their clinical characteristics and treatment were reviewed retrospectively. Twenty neonates were diagnosed with MO and 4 neonates were diagnosed with Hirschsprung's disease (HD). The mean birth weight and gestational age of the 20 neonates with MO were 1.45+/-0.90kg and 31.1+/-4.6 weeks, respectively. Thirteen neonates (65%) diagnosed with MO weighed less than 1.5kg and 10 neonates (50%) weighed less than 1kg. Half of the neonates with MO were treated by non-operative methods and the other half were treated by operative methods. Compared with the group that weighed over 1.5kg, the group that weighed less than 1.5kg were more frequently operated upon (61.5% vs. 28.5%), and contrast enemas were performed later and more frequently. Also the group that weighed less than 1.5kg had a higher mortality rate (15.4% vs. 0%). Three of the four neonates with HD were diagnosed with long-segment aganglionosis. In conclusion, MO occurred in very low birth weight neonates more often and must be differentiated from HD. Also, MO in very low birth weight neonates should be treated with special attention due to more a complicated clinical course.

Reliability and Validity of Short Form, Parental Version of the Korean Swanson, Nolan and Pelham-IV (SNAP-IV) / 신경정신의학

OBJECTIVES: This study was conducted to investigate the reliability and validity of the short form, parental version of the Korean SNAP-IV. METHODS: The Korean SNAP-IV, SNAP, CPRS were applied to the groups of 605 control and 94 ADHD children, aged 6-12 years. Test-retest reliability, internal consistency and split half reliability were performed as a reliability test and criterion validity, factor analysis and discriminant validity were also performed as a validity test. RESULTS: The Coefficient of test-retest reliability and split half reliability were 0.84/0.86 and 0.73/0.78 for both inattention and hyperactivity/impulsivity subscales. The Internal consistency was also excellent. The Criterion validity and discriminant validity rates were between 0.59 and 0.82. Three factors were identified in factor analysis. CONCLUSION: This study demonstrates that the short form, parental version of the Korean SNAP-IV is a reliable and valid instrument in the evaluation and screening of ADHD-related behaviors in children.

Ethyl Pyruvate Ameliorates Renal Ischemia- reperfusion Injury

PURPOSE: Reactive oxygen species (ROS) significantly contribute to ischemia-reperfusion injury, and are also associated with the gradual loss of renal function and renal failure following renal transplantation. Pyruvate is an endogenous antioxidant, but its use as a therapeutic agent for treating conditions mediated by oxidative stress is limited due to its poor stability in solution. However, ethyl pyruvate (EP), a soluble pyruvate derivative, has far greater stability than pyruvate; thus, may serve as a practical pyruvate precursor. Therefore, the ability of EP in the prevention of renal ischemia-reperfusion injury was assessed. METHODS: Sprague-Dawley rats (n=54) were subjected to 40 minutes of renal warm ischemia. The animals were divided into three groups: the sham group without warm ischemia (n=18), the EP group (n=18, EP given before ischemia), and the ischemic control (n=18). The serum levels of creatinine and TNF-alpha were measured 1, 3 and 5 days after induction of ischemia. The expression of high mobility group box-1 (HMGB-1), a delayed inflammatory mediator, was also assessed by Western blot of renal specimens. RESULTS: In the EP group, late improvements in the serum levels of creatinine and TNF-alpha were observed in comparison with the ischemic control. Based on this delayed effect, the expression of HMGB-1 was assessed in renal tissue. The HMGB-1 expression increased over time during the ischemia process, but EP suppressed this expression 3 and 5 days after renal ischemia-reperfusion injury. CONCLUSION: These results have demonstrated, for the first time, that EP ameliorates renal ischemia-reperfusion injury. EP attenuates the renal ischemia-reperfusion injury, at least in part, by suppressing the expression of HMGB-1, a late mediator of delayed inflammation.

Effects of Inosine Monophosphate Dehydrogenase Inhibition on Platelet-derived Growth Factor- Induced Fibronectin Secretion and Cellular Reactive Oxygen Species in Mouse Mesangial Cells / 대한이식학회지

PURPOSE: Mesangial cell extracellular matrix (ECM) synthesis plays an important role in various renal diseases. Mycophenolic acid (MPA), which is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), inhibits mesangial cell proliferation and ECM synthesis. However, the exact mechanism of MPA has not been clearly elucidated in mesangial cells. To examine the relative importance of IMPDH on the inhibitory action of MPA, we compared the effects of MPA or IMPDH2 siRNA on platelet-derived growth factor (PDGF)-induced fibronectin secretion and cellular reactive oxygen species (ROS) in mouse mesangial cells (MMC). METHODS: MMC were stimulated with PDGF 10 ng/ml with or without MPA 0.1~10micrometer, IMPDH2 siRNA 10~50 nM, or N-acetylcystein (NAC). IMPDH2 siRNA was transiently transfected by lipofectamine for 24 hours. MPA 0.1~10micrometer, ribavirin 10~100micrometer, and NAC 5 mM were administered 1 hour before the stimulation. Cell viability was measured by methylthiazoletetrazolium (MTT) assay, fibronectin secretion by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS by flow cytometry. RESULTS: PDGF 10 ng/ml effectively increased fibronectin secretion and cellular ROS in MMC. MPA and NAC at concentration without affecting basal level of fibronectin and cellular ROS ameliorated PDGF-induced fibronectin secretion and cellular ROS. However, IMPDH2 siRNA only partially reduced PDGF- induced fibronectin secretion and cellular ROS in MMC. CONCLUSION: These results suggest that MPA may inhibit PDGF-induced fibronectin secretion partly through IMPDH2 or cellular ROS in MMC, and there may be other mechanisms on the inhibitory action of MPA in mesenchymal cells.

The Efficacy of the Affinity Column-mediated Immunoassay Method in Cyclosporine Concentration Assay Compared with the Microparticle Enzyme Immunoassay Method / 대한이식학회지

PURPOSE: Cyclosporine is a potent immunosuppressive drug used in organ transplantation. Because of its substantial toxic effect, narrow therapeutic index, and the inter-individual variability of pharmacokinetics, therapeutic drug monitoring of the whole blood cyclosporine concentration has been recommended. We have investigated the comparability of the results of two immunoassay systems, the affinity column- mediated immunoassay (ACMIA) and the microparticle enzyme immunoassay (MEIA), and compared the differences in the cyclosporine concentrations between the two methods in relation to the hematologic and biochemical values. METHODS: One hundred twenty-one blood samples from kidney recipients were used. We used Dimension? RxL HM with a CSA Flex? reagent cartilage for the ACMIA method and AXSYM? Cyclosporine for the MEIA method. RESULTS: Cyclosporine concentrations measured by the ACMIA method (n=121) were closely correlated with those measured by the MEIA method (r=0.948, P<0.0001). The Bland-Altman plot using concentration differences between the two methods and the average of the two methods also showed no specific trends (R2=0.02, P=0.125). Except hematocrit, other hematologic and biochemical value (albumin, total bilirubin) didn't affect to both cyclosporine level by MEIA and ACMIC method. Both cyclosporine levels determined by the MEIA method and the ACMIA method were positively correlated with hematocrit (P<0.05). CONCLUSION: The ACMIA method used for a cyclosporine assay is precise and has advantages, including the lack of a required pretreatment procedure, and shows same influence by hematocrit compared with the MEIA.

Pre-transplant Serum Soluble CD30 Level; Correlation with Panel Reactive Antibodies and Lymphocyte Cross Matching / 대한이식학회지

PURPOSE: Serum level of soluble form CD30 (sCD30), a marker for T helper 2-type cytokine-producing T cells, is used as a marker of immunologic status of pre-transplant recipient that can predict graft rejection and graft survival. This study compared pre-transplant serum sCD30 levels with conventional pre-transplant immunologic parameter, such as panel- reactive antibodies (PRA) and lymphocyte cross matching (LCM). METHODS: Adult seventy two patients were enrolled this study. The blood for tests was sampled simultaneously. Measurement of serum sCD30 level was performed using enzyme-linked immunosorbent assay kit (Bender MedSystems, Co. CA, USA). We tested PRA using a commercial ELISA kit (Lambda Cell Tray Lymphocytotoxicity assay)(One Lambda Inc. CA, USA). We established LCM tests for T cells by Modified NIH (National institute center of health)/Johnson's Method/AHG (Anti human globulin), and for B cells by warm test. RESULTS: Mean score of sCD30 was 90.3+/-6.4 U/mL, ranged from 12.2 to 244.4 U/mL. There was no significant correlation between patient's age or sex and sCD30 level. The correlation between sCD30 and mode or duration of dialysis was not statistically significant clinical situation. The result of LCM didn't show significant correlation with sCD30 level (87.3+/-55.7 U/mL in LCM positive group versus 91.9+/-1.3 U/mL in LCM negative group, P=0.696). And sCD30 level equal to or more than 86 U/mL could not predict the positive result of LCM. The positive and negative predictive value of sCD30 to LCM was merely 27.8% and 58.3% (P=0.322). Also the correlation between sCD30 level and PRA was not significant (P=1.0). CONCLUCION: There was no significant correlation between serum sCD30 level and conventional immunologic parameter such as PRA or LCM. That means the pre-transplant monitoring of the sCD30 level can be used as an independent immunologic parameter.