Background: Calcineurin inhibitor (CNI) toxicity is a significant cause of graft dysfunction in kidney transplant recipients, yet distinguishing it from acute rejection (AR) and acute tubular necrosis (ATN) remains challenging. This study investigated the use of urinary mRNA biomarkers as a noninvasive tool for identifying CNI toxicity. Methods: We retrospectively enrolled 110 kidney transplant recipients and classified them into four groups based on pathological findings: stable graft function (n=35), CNI toxicity (n=25), AR (n=30), and ATN (n=20). Candidate biomarkers were selected using the GEO database. Urinary mRNA was extracted from cell pellets, reverse-transcribed, and quantified by real-time polymerase chain reaction. Results: Estimated glomerular filtration rates were comparable among the CNI toxicity, AR, and ATN groups. Four transcripts (LTF, NNMT, WFDC2, and HIF1A) were identified as candidate biomarkers. Urinary mRNA levels of LTF, NNMT, and HIF1A were significantly lower in the CNI toxicity group than the AR group. NNMT and HIF1A levels were also significantly lower than those observed in the ATN group. In contrast, WFDC2 levels did not differ significantly across groups. A three-gene signature (LTF, NNMT, and HIF1A) effectively differentiated CNI toxicity from AR and ATN (area under the curve [AUC], 0.867;95% confidence interval [CI], 0.787–0.947) and significantly enhanced the diagnostic performance of the clinical variable-based model (AUC increased from 0.776; 95% CI, 0.660–0.892, to 0.934; 95% CI, 0.881–0.986). Conclusions Urinary mRNA levels of LTF, NNMT, and HIF1A may serve as useful biomarkers for identifying CNI toxicity in kidney transplant recipients with graft dysfunction.

BACKGROUND/AIMS: Few studies have addressed whether there are differences in clinical efficacy between intravenous methylprednisolone (methyl-Pd) and intravenous immunoglobulin (IVIg) use. METHODS: We retrospectively compared platelet responses and toxicities associated with these two treatments in adult patients with immune thrombocytopenia. Patients received intravenous methyl-Pd therapy followed by oral prednisolone (Pd) from 1993 to 2002 and IVIg together with oral Pd from 2003 to 2008. RESULTS: Early response and maintenance of the response were assessed at 7 days and 6 months after treatment, respectively. Of the 87 patients enrolled, 77 (88.5%) were eligible for analysis. Early responses occurred in 30 of 39 patients (76.9%) receiving methyl-Pd versus 33 of 38 patients (86.6%) receiving IVIg (p = 0.187). The response was maintained in 28 patients (71.8%) in the methyl-Pd arm and in 23 patients (60.5%) in the IVIg arm (p = 0.187). The time to a complete response in the IVIg arm (6 days; range, 1 to 35) was shorter than that in the methyl-Pd arm (13.5 days; range, 2 to 29) (p = 0.002). Side effects were mild and tolerable in both arms. Five years after initiating treatment, 7 of 18 patients (38.9%) and five of 14 patients (35.7%) were still maintaining a response in the methyl-Pd and IVIg arms, respectively. CONCLUSIONS These results indicate that neither the early response rate nor the long-term outcome differed between the methyl-Pd and IVIg treatments. However, IVIg induced a complete response more rapidly than did methyl-Pd.

Operational tolerance (OT), defined as maintaining stable graft function without immunosuppression after transplant surgery, is an ideal goal for kidney transplant recipients (KTRs). Recent investigations have demonstrated the distinctive features of B cells, T cells, and dendritic cell-related gene signatures and the distributions of circulating lymphocytes in these patients; nonetheless, substantial heterogeneities exist across studies. This study was conducted to determine whether previously reported candidate gene biomarkers and the profiles of lymphocyte subsets of OT could be applied in Korean KTRs. Peripheral blood samples were collected from 153 patients, including 7 operationally tolerant patients. Quantitative real-time PCR and flow cytometry were performed to evaluate gene expression and lymphocyte subsets, respectively. Patients with OT showed significantly higher levels of B cell-related gene signatures (IGKV1D-13 and IGKV4-1), while T cell-related genes (TOAG-1) and dendritic cell-related genes (BNC2, KLF6, and CYP1B1) were not differentially expressed across groups. Lymphocyte subset analyses also revealed a higher proportion of immature B cells in this group. In contrast, the distributions of CD4⁺ T cells, CD8⁺ T cells, mature B cells, and memory B cells showed no differences across diagnostic groups. An OT signature, generated by the integration of IGKV1D-13, IGKV4-1, and immature B cells, effectively discriminated patients with OT from those in other diagnostic groups. Finally, the OT signature was observed among 5.6% of patients who had stable graft function for more than 10 years while on immunosuppression. In conclusion, we validated an association of B cells and their related signature with OT in Korean KTRs.
B-Lymphocytes ; Biomarkers ; Flow Cytometry ; Gene Expression ; Humans ; Immunosuppression ; Kidney Transplantation ; Kidney* ; Lymphocyte Subsets ; Lymphocytes ; Memory ; Precursor Cells, B-Lymphoid ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; T-Lymphocytes ; Transplant Recipients* ; Transplants

PURPOSE: To evaluate the treatment outcome and prognostic factor after postoperative radiotherapy in retroperitoneal sarcoma. MATERIALS AND METHODS: Forty patients were treated with surgical resection and postoperative radiotherapy for retroperitoneal sarcoma from August 1990 to August 2008. Treatment volume was judged by the location of initial tumor and surgical field, and 45-50 Gy of radiation was basically delivered and additional dose was considered to the high-risk area. RESULTS: The median follow-up period was 41.4 months (range, 3.9 to 140.6 months). The 5-year overall survival (OS) was 51.8% and disease free survival was 31.5%. The 5-year locoregional recurrence free survival was 61.9% and distant metastasis free survival was 50.6%. In univariate analysis, histologic type (p = 0.006) was the strongest prognostic factor for the OS and histologic grade (p = 0.044) or resection margin (p = 0.032) had also effect on the OS. Histologic type (p = 0.004) was unique significant prognostic factor for the actuarial local control. CONCLUSION: Retroperitoneal sarcoma still remains as a poor prognostic disease despite the combined modality treatment including surgery and postoperative radiotherapy. Selective dose-escalation of radiotherapy or combination of effective chemotherapeutic agent must be considered to improve the treatment result especially for the histopathologic type showing poor prognosis.
Disease-Free Survival ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Sarcoma ; Treatment Outcome

PURPOSE: Total knee replacement is one of the most painful orthopedic procedures, and effective pain relief is essential for early mobility and discharge from hospital. The aim of this study was to evaluate whether addition of single-injection femoral nerve block to epidural analgesia would provide better postoperative pain control, compared to epidural analgesia alone, after total knee replacement. MATERIALS AND METHODS: Thirty-eight patients received a single-injection femoral nerve block with 0.25% levobupivacaine (30 mL) combined with epidural analgesia (femoral nerve block group) and 40 patients received epidural analgesia alone (control group). Pain intensity and volume of patient-controlled epidural analgesia medication and rescue analgesic requirements were measured in the first 48 hours after surgery at three time periods; 0-6 hours, 6-24 hours, and 24-48 hours. Also, side effects such as nausea, vomiting, and pruritus were evaluated. RESULTS: Median visual analog scale at rest and movement was significantly lower until 48 hours in the femoral nerve block group. Patient-controlled epidural analgesia volume was significantly lower throughout the study period, however, rescue analgesia requirements were significantly lower only up to 6 hours in the femoral nerve block group. The incidences of nausea and vomiting and rescue antiemetic requirement were significantly lower in the femoral nerve block group up to 6 hours. CONCLUSION: The combination of femoral nerve block with epidural analgesia is an effective pain management regimen in patients undergoing unilateral total knee replacement.
Aged ; Analgesia, Epidural/*methods ; Analgesia, Patient-Controlled/*methods ; Anesthetics, Local/administration & dosage/therapeutic use ; Arthroplasty, Replacement, Knee/*methods ; Bupivacaine/administration & dosage/analogs & derivatives/therapeutic use ; Female ; Femoral Nerve/*drug effects ; Humans ; Injections ; Male ; Middle Aged ; Nerve Block/*methods

BACKGROUND/AIMS: Neuroendocrine tumors (NET) of the pancreas are rare. Its prognosis is better than pancreas adenocarcinoma due to the slow growth, however, malignant NET of the pancreas are observed. The purposes of this study were to evaluate the clinical characteristics and to find the predictive factors of NET which are associated with malignancy and survival. METHODS: We retrospectively evaluated the clinical outcomes of 122 patients with NET of the pancreas who were pathologically diagnosed at Asan Medical Center between 1990 and 2006. RESULTS: Mean age of the patients was 48.9+/-14.0 years and there was no gender predilection. The major clinical manifestations were abdominal pain (44.0%) in non-functional tumor, neuroglycopenic symptoms (100%) in insulinoma and diarrhea (60%) in gastrinoma. Tumor size ranged from 4 to 140 mm (average 29.8+/-23.22). Ninety cases (73.8%) were classified as benign tumors and 32 cases (26.2%) as malignant. In multivariate analysis of clinical characteristics, large sized tumor (>20 mm, p=0.001) was confirmed as sole independent factor to predict malignant NET. Surgical resection was performed in 114 patients. All patients with benign NET are still alive without recurrence. Six out of 32 patients with malignant NET died at an average 40.3 months after diagnosis. The factors indicating favorable outcome were small size of tumors (p=0.046), resection of primary tumor (p=0.000), absence of lymph node invasion (p=0.0116) and distant metastasis (p=0.0005). CONCLUSIONS: Large NET of the pancreas, regardless of their functioning status, were more likely to be associated with malignancy and predictor of worse survival.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Neuroendocrine Tumors/*diagnosis/mortality/pathology ; Pancreatectomy ; Pancreatic Neoplasms/*diagnosis/mortality/pathology ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Survival Analysis

PURPOSE: Pathophysiological causes of the development and progression of diabetic nephropathy are not well known, but the angiotensin-converting enzyme (ACE) gene polymorphism has been proposed to be involved in its development. To clarify risk factors for the development of microalbuminuria in Korean type 2 diabetes patients, a retrospective study on the last 10 years was conducted on outpatients with type 2 diabetes. METHODS: The impact of insertion/deletion (I/D) genotypes on the progression of diabetic nephropathy in 105 Korean type 2 diabetes patients with normoalbuminuria at diagnosis was investigated by retrospective review of clinical data. Polymorphisms of the ACE gene were examined. RESULTS: During the follow up over the last 10 years, 23 of 105 patients developed Microalbuminuria (21.9%). ACE genotypes were D/D 19.5%, D/I 41.5%, I/I 39% in microalbuminuria group, as compared with D/D 17.4%, I/D 26.1%, I/I 56.5% in normoalbuminuria group. Higher levels of mean HbA1c and mean triglyceride were noted in microalbuminuira group, as compared with those in normoalbuminuria group. Kaplan-Meier survival curve showed that higher HbA1c and higher triglyceride level were significant predictors to the development of Microalbuminuria, but I/D genotype of ACE gene did not affect. Cox regression model also showed that higher HbA1c and triglyceride were independent variables. CONCLUSION: The control of blood glucose or lipid, rather than the genetic factors such as ACE polymorphism, was considered to be more influential factor on the development of microalbuminuria in Korean patients with type 2 diabetes mellitus.
Blood Glucose ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Follow-Up Studies ; Genotype ; Humans ; Outpatients ; Peptidyl-Dipeptidase A ; Polymorphism, Genetic ; Retrospective Studies ; Risk Factors

This study is to compare the effect of wound healing using three different types of chitin, which include the shapes of sponge, velvet, thick non-woven fabrics, and thin non-woven fabrics. The sponge type had more capacity to absorb the first discharge of a wound than the velvet type and the two non-woven fabrics types. Instead of absorbing the discharge effectively, the velvet type showed a difficulty to take off the dressing stuff from a wound since it was solidly stuck to the wound. The sponge type showed less infiltration of inflammatory cells, producing angiogenesis and fibroblast faster than any other types. Next, the thick non-woven fabrics type was a little more effective than the thin non-woven fabrics type: However, there was no difference between two types. The velvet type sustained the infiltration of inflammatory cells for the longest duration, producing slower angiogenesis and fibroblast. In wound contraction and wound healing, the sponge type was most effective with statistical significance than any other types(p<0.05). The two types of non-woven fabrics did not present any statistical significance in wound contraction, wound epithelization and wound healing(p>0.05). In conclusion, the sponge type showed the best effectiveness to absorb the early discharge, facilitating the progress of inflammatory phase to increase the healing rate. It induced an early healing of wound caused by wound contraction rather than by wound epithelization.
Bandages ; Chitin ; Chitosan* ; Fibroblasts ; Porifera ; Wound Healing* ; Wounds and Injuries*

We present a case of recurrent extraventricular neurocytoma with malignant glial differentiation in left temporoparietal area. A 37-year-old man with presentation of generalized seizure had undergone biopsy of brain tumor in left parietal area in 1987, which revealed extraventricular neurocytoma and radiotherapy was followed. Postoperative course was uneventful until eleven years after biopsy, when he became gradually aphasic and right hemiplegic. Brain CT and MRI revealed enlargement of tumor with peritumoral edema and calcifications. He underwent subtotal tumor removal in 1998. Microscopic examination of second biopsy specimen revealed presence of large areas composed of anaplastic glial cells with frequent mitosis, nuclear pleomorphism, large eosinophilic cytoplasm and eccentric nuclei, resembling gemistocytes, which were strongly immunoreactive to glial fibrillary acidic protein(GFAP) but not to synaptophysin(SNP). Also focal areas of neuronal cells were found, which were immunoreactive to SNP but not to GFAP. These histologic findings imply that this recurred tumor was a high grade, mixed tumor with divergent differentiation of neuronal and astrocyte lineage. We report a rare case of extraventricular cerebral neurocytoma with malignant glial differentiation with review of the literature.
Adult ; Astrocytes ; Biopsy ; Brain ; Brain Neoplasms ; Cytoplasm ; Edema ; Eosinophils ; Glial Fibrillary Acidic Protein ; Humans ; Magnetic Resonance Imaging ; Mitosis ; Neurocytoma* ; Neuroglia ; Neurons ; Rabeprazole ; Radiotherapy ; Seizures ; Synaptophysin

Primary papillary serous carcinoma of the peritoneum(PPSCP) is vere rare. It has been suggested that PPSCP derives from embryonal coelomic epithelium with m llerian ducts potential. PPSCP can develop from a single or multicentric focus. The clinical and histologic disease entities are similar to those of primary papillary serous carcinoma of the ovary, but PPSCP involves the ovarian surface only minimally(microscopic disease) or spares the ovaries entirely. We have experienced a case of primary papillary serous carcinoma of the peritoneum and report this case with brief review of the concerned literature.
Epithelium ; Female ; Ovary ; Peritoneum*