Activated phosphoinositide 3-kinase δ syndrome (APDS)1 is caused by gain-of-function mutations in PIK3CD, which encodes the catalytic p110δ subunit of phosphoinositide 3 kinase. We describe three patients with APDS1, the first thereof in Korea. Therein, we investigated clinical manifestations of APDS1 and collected data on the efficacy and safety profile of sirolimus, a mammalian target of rapamycin inhibitor and pathway-specific targeted medicine. The same heterozygous PIK3CD mutation was detected in all three patients (E1021K). After genetic diagnosis, all patients received sirolimus and experienced an excellent response, including amelioration of lymphoproliferation and improvement of nodular mucosal lymphoid hyperplasia in the gastrointestinal tract. The median trough level of sirolimus was 5.5 ng/mL (range, 2.8–7.5) at a dose of 2.6–3.6 mg/m2. Two patients who needed highdose, short-interval, immunoglobulin-replacement treatment (IGRT) had a reduced requirement for IGRT after initiating sirolimus, and the dosing interval was extended from 2 and 3 weeks to 4 weeks. The IgG trough level after sirolimus treatment (median, 594 mg/dL; range, 332–799 mg/dL) was significantly higher than that before sirolimus treatment (median, 290 mg/dL; range, 163–346 mg/dL) (p<0.001). One episode of elevated serum creatinine with a surge of sirolimus (Patient 2) and episodes of neutropenia and oral stomatitis (Patient 1) were observed. We diagnosed the first three patients with APDS1 in Korea. Low-dose sirolimus may alleviate clinical manifestations thereof, including hypogammaglobulinemia.

PURPOSE: Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run procedures of the KROG 17-06 study. MATERIALS AND METHODS: Two steps tested hippocampus contouring variability and radiation therapy planning compliance. In the first step, the variation of the hippocampus delineation was investigated for two representative cases using the Dice similarity coefficients. In the second step, the participating institutions were requested to generate a HS-WBRT with SIB treatment plan for another representative case. The compliance of the treatment plans to the planning protocol was evaluated. RESULTS: In the first step, the median Dice similarity coefficients of the hippocampus contours for two other dummy run cases changed from 0.669 (range, 0.073 to 0.712) to 0.690 (range, 0.522 to 0.750) and from 0.291 (range, 0.219 to 0.522) to 0.412 (range, 0.264 to 0.598) after providing the hippocampus contouring feedback. In the second step, with providing additional plan priority and extended dose constraints to the target volumes and normal structures, we observed the improved compliance of the treatment plans to the planning protocol. CONCLUSION: The dummy run studies demonstrated the notable inter-institutional variability in delineating the hippocampus and treatment plan generation, which could be decreased through feedback from the trial center.
Brain ; Carcinoma, Non-Small-Cell Lung ; Compliance ; Hippocampus ; Lung Neoplasms ; Neoplasm Metastasis ; Prospective Studies ; Radiation Oncology ; Radiotherapy

OBJECTIVE: Accumulation of advanced glycation end-products (AGE) and mitochondrial glycation is importantly implicated in the pathological changes of the brain associated with diabetic complications, Alzheimer disease, and aging. The present study was undertaken to determine whether sildenafil, a type 5 phosphodiesterase type (PDE-5) inhibitor, has beneficial effect on neuronal cells challenged with AGE-induced oxidative stress to preserve their mitochondrial functional integrity. METHODS: HT-22 hippocampal neuronal cells were exposed to AGE and changes in the mitochondrial functional parameters were determined. Pretreatment of cells with sildenafil effectively ameliorated these AGE-induced deterioration of mitochondrial functional integrity. RESULTS: AGE-treated cells lost their mitochondrial functional integrity which was estimated by their MTT reduction ability and intracellular ATP concentration. These cells exhibited stimulated generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, induction of mitochondrial permeability transition, and release of the cytochrome C, activation of the caspase-3 accompanied by apoptosis. Western blot analyses and qRT-PCR demonstrated that sildenafil increased the expression level of the heme oxygenase-1 (HO-1). CoPP and bilirubin, an inducer of HO-1 and a metabolic product of HO-1, respectively, provided a similar protective effects. On the contrary, the HO-1 inhibitor ZnPP IX blocked the effect of sildenafil. Transfection with HO-1 siRNA significantly reduced the protective effect of sildenafil on the loss of MTT reduction ability and MPT induction in AGE-treated cells. CONCLUSION: Taken together, our results suggested that sildenafil provides beneficial effect to protect the HT-22 hippocampal neuronal cells against AGE-induced deterioration of mitochondrial integrity, and upregulation of HO-1 is involved in the underlying mechanism.
Adenosine Triphosphate ; Aging ; Alzheimer Disease ; Apoptosis ; Bilirubin ; Blotting, Western ; Brain ; Caspase 3 ; Cytochromes c ; Diabetes Complications ; Glycosylation End Products, Advanced ; Heme Oxygenase-1 ; Hippocampus ; Membrane Potential, Mitochondrial ; Mitochondria ; Neurons* ; Oxidative Stress ; Permeability ; Reactive Oxygen Species ; RNA, Small Interfering ; Transfection ; Up-Regulation ; Sildenafil Citrate

OBJECTIVE: To compare the diagnostic accuracy of ultrasonographic endometrial thickness with that of hysteroscopy, it is to establish the most appropriate method for the diagnosis of endometrial cancer and other endometrial diseases in postmenopausal women with abnormal uterine bleeding (AUB). METHODS: This retrospective study was conducted in 105 consecutive postmenopausal patients with AUB, who underwent ultrasonographic evaluation of endometrial thickness, hysteroscopy and endometrial biopsy. Evaluation of sensitivity and specificity was performed. RESULTS: Histologic findings for <4 mm level revealed that atrophy was present in 30 (71.4%) and in 1 case (2.4%) endometrial cancer was found; for > or =4 mm values polyps and myomas were present in 31 (49.2%) and there were 3 (4.8%) in endometrial cancer. Sensitivity and specificity for trans-vaginal ultrasound, with a cut-off value > or =4 mm, was 75% and 40.6%. CONCLUSIONS: Generally speaking, obstetrics & gynecologists know that endometrial aspiration biopsy is the routine method in postmenopausal women with AUB. However transvaginal ultrasound remains the first line diagnostic procedure in postmenopausal women without AUB. In case of endometrial thickness less than 4 mm, it is likely to miss the early stage endometrial cancer but trans-vaginal ultrasound remains the first line diagnostic procedure in postmenopausal women, because it is not invasive and has high sensitivity for detecting endometrial cancer and other endometrial disease; According to our experience, hysteroscopy with biopsy is mandatory in all postmenopausal women with AUB.
Atrophy ; Biopsy ; Biopsy, Needle ; Diagnosis ; Endometrial Neoplasms ; Female ; Hemorrhage* ; Humans ; Hysteroscopy* ; Myoma ; Obstetrics ; Polyps ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography ; Uterine Diseases ; Uterine Hemorrhage

BACKGROUND:Staphylococcu S. aureus (S. aureus) is one of the most important etiologic agents of CAPD-associated infection and the nasal carriage of S. aureus increases the risk of CAPD-associated infection. We evaluated the nasal carriage status of S. aureus in CAPD patients and the association between nasal carriage of S. aureus and CAPD-associated infection. METHODS:We did a retrospective study about 167 patients on CAPD who regularly visited outpatient department at Seoul National University Hospital, Seoul National University Boramae Hospital, Seoul National University Bundang Hospital. Nasal swab cultures for S. aureus were taken once between September of 2005 and February of 2006. RESULTS:Nasal swab culture showed that S. aureus nasal carriage rate was 22.2%. S. aureus nasal carrier group showed that increased incidence of exit site infection and peritonitis caused by S. aureus and all other causes of exit site infection, but these were statistically insignificant. In diabetic patients, S. aureus nasal carriage rate was 21.6%. The observation of these patients also showed that S. aureus nasal carriage insignificantly increased the incidence of exit site infection and peritonitis caused by S. aureus and all oth er causes of exit site infection. CONCLUSION:In our study, the S. aureus nasal carriers did not show significantly higher risk for development of exit site infection and peritonitis by S. aureus or all other causes of exit site infection.
Humans ; Incidence ; Outpatients ; Peritoneal Dialysis, Continuous Ambulatory ; Peritonitis ; Prevalence* ; Retrospective Studies ; Seoul ; Staphylococcus aureus* ; Staphylococcus*

BACKGROUND: Nuss procedure used in pectus excavatum repair is preferred, because of its excellent effect from the cosmetic point of view and improved pulmonary function, but it cause severe pain due to thoracic expansion after the operation. This study was designed to evaluate effective fentanyl dose using an intravenous patient-controlled analgesia (IV-PCA) pump for pain control following pectus excavatum repair in pediatric patients. METHODS: Sixty patients undergoing elective thoracic surgery were randomly assigned to received fentanyl 0.5microgram/kg/hr (Group I, n = 20), 0.7microgram/kg/hr (Group II, n = 20), and 1.0microgram/kg/hr (Group III, n = 20) via an IV-PCA pump (basal, 1 ml/h; bolus, 0.5 ml; lock out interval, 30 min) after operation. A blind observer evaluated each patient using the Children's Hospital of Eastern Ontario pain scale (CHEOPS) and the faces scale (FS). Incidences of side effects and pain control satisfaction were assessed at postoperative 48 hrs. RESULTS: There were no significant differences in CHEOPS or FS score between the groups the postoperative 48 hrs period. CHEOPS and FS scores at 4 and 8 hrs in groups II and III were significantly lower than in group I (P<0.05), but all groups showed lower CHEOPS and FS scores during the first postoperative 48 hrs. Satisfaction of pain control assessment by mothers was significantly higher in groups II and III than in group I (P<0.05). CHEOPS and FS scores were highly correlated with each other (P<0.001). CONCLUSIONS: We conclude that infusion of fentanyl at 0.5microgram/kg/hr using an IV-PCA pump is effective for pain control of 5 years of age or older after Nuss procedure.
Analgesia, Patient-Controlled* ; Fentanyl* ; Funnel Chest* ; Humans ; Incidence ; Mothers ; Ontario ; Thoracic Surgery

BACKGROUND/AIMS: Lymph node (LN) metastasis occurs in approximately 10% of patients with submucosally invasive colorectal carcinoma. This study was performed to determine the role of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) production and microvessel formation on the LN metastasis in submucosally invasive colorectal carcinoma. METHODS: A total of forty-one subjects with surgically resected submucosally invasive colorectal carcinoma were included in this study. Immunohistochemical staining of MMP-2, MMP-9, TIMP-1, TIMP-2, and urokinase-type plasminogen activator were performed. Angiogenesis was evaluated by counting the number of microvessels in each pathologic specimen as identified by CD34 immunohistochemical staining. RESULTS: The depth of submucosal invasion was not significantly correlated with the expression of MMP-2, MMP-9, TIMP-1, TIMP-2, or urokinase-type plasminogen activator, but the microvessel count was significantly correlated with the absolute depth of invasion (r=0.312, p<0.05). Upregulation of TIMP-2 was positively correlated with adjacent lymphatic invasion (p<0.05) and increased TIMP-2 expression was correlated with LN metastasis in submucosally invasive colorectal carcinoma (p=0.088). CONCLUSIONS: These results suggest that the expression of TIMP-2 and the microvessel count may be useful parameters for considering additional surgery after endoscopic treatment of submucosally invasive colorectal carcinoma.
Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms/blood supply/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Matrix Metalloproteinases/*metabolism ; Middle Aged ; Neoplasm Invasiveness ; Neovascularization, Pathologic/*pathology ; Tissue Inhibitor of Metalloproteinases/*metabolism

Carcinoid tumors arise from enterochromaffin cells of neural crest origin. Rectal carcinoid tumors make up 1 to 2% of all rectal tumors. Approximately 50% of rectal carcinoid tumors are found incidentally on routine endoscopy, and they are asymtomatic. Rectal carcinoid is easily diagnosed by the characteristic submucosal tumor with yellowish color. There have been, however, some rare cases where the rectal carcinoid tumor was not easily diagnosed because of its atypical feature. We report a case of atypical rectal carcinoid tumor misdiagnosed as rectal cancer on endoscopic finding: this atypical gross morphology on endoscopy may be due to atypical histopathologic findings.
Carcinoid Tumor* ; Colonoscopy ; Endoscopy ; Enterochromaffin Cells ; Neural Crest ; Rectal Neoplasms ; Rectum

BACKGROUND: Chlamydia pneumoniae is one of common causes in upper and lower respiratory infections. Isolating C. pneumoniae from clinical specimens is very difficult due to the characteristics of the organism. Recently, we succeeded in isolating C. pneumoniae from a Korean patient, who suffered from acute pharyngitis. This is the first isolate from a clinical specimen in Korea. METHOD: We attained a nasopharyngeal swab from a 22-year-old female patient, and inoculated it on a monolayer of the Hep-2 cell line. After 8 passages, we found the inclusion bodies of C. pneumoniae by an immunofluorescence(IF) test. The species-specific monoclonal antibody IF staining and species-specific PCR were done to confirm the species of the isolate, and electron microscopy was used to characterize the morphology. RESULT: The isolate was confirmed to be C. pneumoniae by species-specific IF and PCR, and the strain was named LKK-1. The shape of the elementary body was round and with a narrow periplasmic space, as shown by electron microscopy, which is similar to the Japanese strain, but not the Western strain. CONCLUSION: We succeeded in isolating C. pneumoniae from a 22-year-old patient with acute pharyngitis, which is the first isolate in Korea. In the future, this Korean strain will be useful to the study of C. pneumoniae.
Female ; Humans

PURPOSE: To better understand the extent to which chemokines participate in the mucosal inflammatory response in patients with ulcerative colitis (UC), we assessed the expression of an array of chemokines in the colonic mucosa of UC patients. METHODS: Colonic mucosal biopsy specimens were obtained from 15 patients with UC and 12 normal controls. Messenger RNA (mRNA) levels for 10 chemokines were quantitated by reverse-transcription PCR using synthetic standard RNAs. The biopsy specimens were also cultured, and secreted chemokines in culture supernatants were assayed by ELISA. RESULTS: The mRNA expression of C-X-C (IL-8, GROalpha, GRObeta, GROgamma, ENA-78, and IP-10) and C-C (MCP-1, MIP-1beta, and RANTES), but not C (lymphotactin) chemokines was significantly higher in the affected mucosa of UC patients than in the unaffected mucosa of UC patients or in the normal mucosa of normal controls. The degree of increased expression was more prominent in the C-X-C than in the C-C chemokines. Further, the secretion of IL-8, GROalpha, ENA-78, and MCP-1 was higher in UC patients than in normal controls. Secretions of MIP-1beta and RANTES also showed a trend toward an increase in UC, but it did not reach statistical significance. CONCLUSION: The increased expression of a variety of chemokines in UC suggest that chemokines may play an important role in the immunopathogenesis of UC.
Biopsy ; Chemokine CCL4 ; Chemokine CCL5 ; Chemokines* ; Chemokines, CC ; Colitis, Ulcerative* ; Colon* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-8 ; Mucous Membrane* ; Polymerase Chain Reaction ; RNA ; RNA, Messenger ; Ulcer*