Significance of elevated SCC-Ag level on tumor recurrence and patient survival in patients with squamous-cell carcinoma of uterine cervix following definitive chemoradiotherapy: a multi-institutional analysis / 부인종양

OBJECTIVE: There is no definitive guideline for the significance and cut-off value of squamous-cell carcinoma antigen (SCC-Ag) in cervical cancer. Thus, we analyzed the significance and optimal cut-off value of SCC-Ag for predicting tumor recurrence and patient survival in squamous-cell carcinoma of uterine cervix. METHODS: From January 2010 to October 2016, we enrolled 304 cervical cancer patients with squamous-cell carcinoma staging International Federation of Gynecology and Obstetrics (FIGO) Ib–IVa and treated with definitive chemoradiotherapy (CRT) followed by intra-cavitary radiotherapy (ICR). The cut-off value of SCC-Ag level for tumor recurrence was calculated using the receiver operating characteristic (ROC) curve. The recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan-Meier method to estimate the significance of SCC-Ag level. RESULTS: The optimal cut-off value of SCC-Ag level for predicting tumor recurrence was calculated and set at 4.0 ng/mL in the ROC curve. After a median follow-up period of 36.5 months, the 3-year RFS (56.6% vs. 80.2%, p < 0.001) and OS (72.1% vs. 86.8%, p=0.005) were significantly lower in SCC-Ag ≥4 ng/mL arm than in < 4 ng/mL arm. The 3-year locoregional recurrence (17.6% vs. 7.0%, p=0.012), distant metastasis (20.4% vs. 6.9%, p=0.002), and para-aortic recurrence (9.4% vs. 2.1%, p=0.012) rates were significantly higher in SCC-Ag ≥4 ng/mL arm than in SCC-Ag < 4 ng/mL arm. CONCLUSION: Pre-treatment SCC-Ag level higher than 4 ng/mL may be a useful predictor of tumor recurrence in patients with squamous-cell carcinoma of uterine cervix treated with definitive CRT and ICR.

Retrospective analysis of intensity-modulated radiotherapy and three-dimensional conformal radiotherapy of postoperative treatment for biliary tract cancer

PURPOSE: This study was conducted to compare the outcome of three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for the postoperative treatment of biliary tract cancer.MATERIALS AND METHODS: From February 2008 to June 2016, 57 patients of biliary tract cancer treated with curative surgery followed by postoperative 3D-CRT (n = 27) or IMRT (n = 30) were retrospectively enrolled.RESULTS: Median follow-up time was 23.6 months (range, 5.2 to 97.6 months) for all patients and 38.4 months (range, 27.0 to 89.2 months) for survivors. Two-year recurrence-free survival is higher in IMRT arm than 3D-CRT arm with a marginal significance (25.9% vs. 47.4%; p = 0.088). Locoregional recurrence-free survival (64.3% vs. 81.7%; p = 0.122) and distant metastasis-free survival (40.3% vs. 55.8%; p = 0.234) at two years did not show any statistical difference between two radiation modalities. In the multivariate analysis, extrahepatic cholangiocarcinoma, poorly-differentiated histologic grade, and higher stage were significant poor prognostic factors for survival. Severe treatment-related toxicity was not significantly different between two arms.CONCLUSIONS: IMRT showed comparable results with 3D-CRT in terms of recurrence, and survival, and radiotherapy toxicity for the postoperative treatment of biliary tract cancer.

Physicians' perceptions of asymptomatic hyperuricemia in patients with chronic kidney disease: A questionnaire survey

BACKGROUND: Hyperuricemia is associated with the development and progression of chronic kidney disease (CKD) as well as cardiovascular diseases. However, there is no consistent recommendation regarding the treatment of asymptomatic hyperuricemia (AHU) in CKD patients. Here, we surveyed Korean physicians’ perceptions regarding the diagnosis and management of AHU in CKD patients. METHODS: Questionnaires on the management of AHU in CKD patients were emailed to regular members registered with the Korean Society of Nephrology. RESULTS: A total of 158 members answered the questionnaire. Among the respondents, 49.4%/41.1% were considered hyperuricemic in male CKD patients whereas 36.7%/20.9% were considered hyperuricemic in female CKD patients when defined by serum uric acid level over 7.0/8.0 mg/dL, respectively. A total of 80.4% reported treating AHU in CKD patients. The most important reasons to treat AHU in CKD patients were renal function preservation followed by cerebro-cardiac protection. Majority of respondents (59.5%) thought that uric acid-lowering agents (ULAs) were the most effective method for controlling serum uric acid levels. Approximately 80% chose febuxostat as the preferred medication. A total of 32.3% and 31.0%, respectively, initiated ULA treatment if the serum uric acid level was more than 8.0 or 9.0 mg/dL, respectively. In addition, 39.2% and 30.4% answered that target serum uric acid levels of less than 6.0 or 7.0 mg/dL, respectively, were appropriate. The two major hurdles to prescribing ULAs were concerns of adverse reactions and the existing lack of evidence (i.e., the absence of Korean guidelines). CONCLUSION: Most Korean physicians treat AHU in CKD patients to prevent CKD progression and cerebro-cardiovascular complications.

AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis

PURPOSE: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. MATERIALS AND METHODS: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. RESULTS: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. CONCLUSION: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.

Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal mesothelial cells

BACKGROUND: Peritoneal fibrosis is one of the major causes of technical failure in patients on peritoneal dialysis. Epithelial-to-mesenchymal transition (EMT) of the peritoneum is an early and reversible mechanism of peritoneal fibrosis. Human peritoneal mesothelial cells (HPMCs) have their own renin-angiotensin-aldosterone system (RAAS), however, it has not been investigated whether aldosterone, an end-product of the RAAS, induces EMT in HPMCs, and which mechanisms are responsible for aldosterone-induced EMT. METHODS: EMT of HPMCs was evaluated by comparing the expression of epithelial cell marker, E-cadherin, and mesenchymal cell marker, alpha-smooth muscle actin after stimulation with aldosterone (1-100nM) or spironolactone. Activation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) were assessed by western blotting and 2',7'-dichlorofluororescein diacetate staining, respectively. The effects of MAPK inhibitors or antioxidants (N-acetyl cysteine, apocynin, and rotenone) on aldosterone-induced EMT were evaluated. RESULTS: Aldosterone induced EMT in cultured HPMCs, and spironolactone blocked aldosterone-induced EMT. Aldosterone induced activation of both ERK1/2 and p38 MAPK from 1 hour. Either PD98059, an inhibitor of ERK1/2, or SB20358, an inhibitor of p38 MAPK, attenuated aldosterone-induced EMT. Aldosterone induced ROS in HPMCs from 5 minutes, and antioxidant treatment ameliorated aldosterone-induced EMT. N-acetyl cysteine and apocynin alleviated activation of ERK and p38 MAPK. CONCLUSION: Aldosterone induced EMT in HPMCs by acting through the mineralocorticoid receptor. Aldosterone-induced generation of ROS followed by activation of ERK, and p38 MAPK served as one of the mechanisms of aldosterone-induced EMT of HPMCs.

Dosimetric evaluation of Tomotherapy and four-box field conformal radiotherapy in locally advanced rectal cancer

PURPOSE: To report the results of dosimetric comparison between intensity-modulated radiotherapy (IMRT) using Tomotherapy and four-box field conformal radiotherapy (CRT) for pelvic irradiation of locally advanced rectal cancer. MATERIALS AND METHODS: Twelve patients with locally advanced rectal cancer who received a short course preoperative chemoradiotherapy (25 Gy in 5 fractions) on the pelvis using Tomotherapy, between July 2010 and December 2010, were selected. Using their simulation computed tomography scans, Tomotherapy and four-box field CRT plans with the same dose schedule were evaluated, and dosimetric parameters of the two plans were compared. For the comparison of target coverage, we analyzed the mean dose, V(n Gy), D(min), D(max), radical dose homogeneity index (rDHI), and radiation conformity index (RCI). For the comparison of organs at risk (OAR), we analyzed the mean dose. RESULTS: Tomotherapy showed a significantly higher mean target dose than four-box field CRT (p = 0.001). But, V(26.25 Gy) and V(27.5 Gy) were not significantly different between the two modalities. Tomotherapy showed higher D(max) and lower D(min). The Tomotherapy plan had a lower rDHI than four-box field CRT (p = 0.000). Tomotherapy showed better RCI than four-box field CRT (p = 0.007). For OAR, the mean irradiated dose was significantly lower in Tomotherapy than four-box field CRT. CONCLUSION: In locally advanced rectal cancer, Tomotherapy delivers a higher conformal radiation dose to the target and reduces the irradiated dose to OAR than four-box field CRT.

Treatment outcome in patients with vulvar cancer: comparison of concurrent radiotherapy to postoperative radiotherapy

PURPOSE: To evaluate outcome and morbidity in patients with vulvar cancer treated with radiotherapy, concurrent chemoradiotherapy or postoperative radiotherapy. MATERIALS AND METHODS: The records of 24 patients treated with radiotherapy for vulvar cancer between July 1993 and September 2009 were retrospectively reviewed. All patients received once daily 1.8-4 Gy fractions external beam radiotherapy to median 51.2 Gy (range, 19.8 to 81.6 Gy) on pelvis and inguinal nodes. Seven patients were treated with primary concurrent chemoradiotherapy, one patient was treated with primary radiotherapy alone, four patients received palliative radiotherapy, and twelve patients were treated with postoperative radiotherapy. RESULTS: Twenty patients were eligible for response evaluation. Response rate was 55% (11/20). The 5-year disease free survival was 42.2% and 5-year overall survival was 46.2%, respectively. Fifty percent (12/24) experienced with acute skin complications of grade III or more during radiotherapy. Late complications were found in 8 patients. 50% (6/12) of patients treated with lymph node dissection experienced severe late complications. One patient died of sepsis from lymphedema. However, only 16.6% (2/12) of patients treated with primary radiotherapy developed late complications. CONCLUSION: Outcome of patients with vulvar cancer treated with radiotherapy showed relatively good local control and low recurrence. Severe late toxicities remained higher in patients treated with both node dissection and radiotherapy.

Radiation-induced brain injury: retrospective analysis of twelve pathologically proven cases

PURPOSE: This study was designed to determine the influencing factors and clinical course of pathologically proven cases of radiation-induced brain injury (RIBI). MATERIALS AND METHODS: The pathologic records of twelve patients were reviewed; these patients underwent surgery following radiotherapy due to disease progression found by follow-up imaging. However, they were finally diagnosed with RIBI. All patients had been treated with 3-dimensional conventional fractionated radiotherapy and/or radiosurgery for primary or metastatic brain tumors with or without chemotherapy. The histological distribution was as follows: two falx meningioma, six glioblastoma multiform (GBM), two anaplastic oligodendroglioma, one low grade oligodendroglioma, and one small cell lung cancer with brain metastasis. RESULTS: Radiation necrosis was noted in eight patients and the remaining four were diagnosed with radiation change. Gender (p = 0.061) and biologically equivalent dose (BED)3 (p = 0.084) were the only marginally influencing factors of radiation necrosis. Median time to RIBI was 7.3 months (range, 0.5 to 61 months). Three prolonged survivors with GBM were observed. In the subgroup analysis of high grade gliomas, RIBI that developed or =6 months (p = 0.085). CONCLUSION: Our study demonstrated that RIBI could occur in early periods after conventional fractionated brain radiotherapy within normal tolerable dose ranges. Studies with a larger number of patients are required to identify the strong influencing factors for RIBI development.

Hydration Status in Elderly Hemodialysis Patients: Bioimpedance Analysis / 대한신장학회지

PURPOSE: This study was aimed to compare hydration status between young and elderly end-stage renal disease (ESRD) patients on hemodialysis (HD) and to analyze factors related to overhydration. METHODS: We measured fluid status before a mid-week HD session in clinically stable 47 patients on maintenance HD using bioimpedance spectroscopy (BIS) device. In addition, weight and blood pressure (BP) were recorded during the treatment. RESULTS: Participants were divided into young ( or =65 years, n=15) patients. In elderly patients, pre-HD diastolic BP, intracellular water (ICW), and lean tissue index (LTI) were significantly lower and extracellular water (ECW)/total body water (TBW) was significantly higher than in young patients. However, there were no differences in pre-HD body mass index (BMI), ultrafiltration volume, pre-HD systolic BP, TBW, ECW, and fat tissue index between the two groups. ECW/TBW ratio and LTI were significantly correlated with age. In a multivariate regression analysis, age and pre-HD pulse pressure were significantly associated with ECW/TBW. CONCLUSION: Although BMI and TBW of elderly ESRD patients were similar to those of young patients, ICW and LTI were lower and ECW/TBW was higher in elderly patients than in young patients. Therefore, clinical manifestations related to overhydration may develop more frequently in elderly patients compared with young patients.

Non-Dipper Status and Left Ventricular Hypertrophy as Predictors of Incident Chronic Kidney Disease

We have hypothesized that non-dipper status and left ventricular hypertrophy (LVH) are associated with the development of chronic kidney disease (CKD) in non-diabetic hypertensive patients. This study included 102 patients with an estimated glomerular filtration rate (eGFR) > or = 60 mL/min/1.73 m2. Ambulatory blood pressure monitoring and echocardiography were performed at the beginning of the study, and the serum creatinine levels were followed. During the average follow-up period of 51 months, CKD developed in 11 patients. There was a significant difference in the incidence of CKD between dippers and non-dippers (5.0% vs 19.0%, P < 0.05). Compared to patients without CKD, patients with incident CKD had a higher urine albumin/creatinine ratio (52.3 +/- 58.6 mg/g vs 17.8 +/- 29.3 mg/g, P < 0.01), non-dipper status (72.7% vs 37.4%, P < 0.05), the presence of LVH (27.3% vs 5.5%, P < 0.05), and a lower serum HDL-cholesterol level (41.7 +/- 8.3 mg/dL vs 50.4 +/- 12.4 mg/dL, P < 0.05). Based on multivariate Cox regression analysis, non-dipper status and the presence of LVH were independent predictors of incident CKD. These findings suggest that non-dipper status and LVH may be the therapeutic targets for preventing the development of CKD in non-diabetic hypertensive patients.

A More Appropriate Cardiac Troponin T Level That Can Predict Outcomes in End-Stage Renal Disease Patients with Acute Coronary Syndrome

PURPOSE: Cardiac troponin T (cTnT), a useful marker for diagnosing acute myocardial infarction (AMI) in the general population, is significantly higher than the usual cut-off value in many end-stage renal disease (ESRD) patients without clinically apparent evidence of AMI. The aim of this study was to evaluate the clinical usefulness of cTnT in ESRD patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: Two hundred eighty-four ESRD patients with ACS were enrolled between March 2002 and February 2008. These patients were followed until death or June 2009. Medical records were reviewed retrospectively. The cut-off value of cTnT for AMI was evaluated using a receiver operating characteristic (ROC) curve. We calculated Kaplan-Meier survival curves, and potential outcome predictors were determined by Cox proportional hazard analysis. RESULTS: AMIs were diagnosed in 40 patients (14.1%). The area under the curve was 0.98 in the ROC curve (p or =0.35 ng/mL compared to the other groups. Initial serum cTnT concentration was an independent predictor for mortality. CONCLUSION: Because ESRD patients with an initial cTnT concentration > or =0.35 ng/mL have a poor prognosis, it is suggested that urgent diagnosis and treatment be indicated in dialysis patients with ACS when the initial cTnT levels are > or =0.35 ng/mL.

The Effect of Monocyte Chemoattractant Protein-1 (MCP-1) on Epithelial-Mesenchymal Transition in Human Peritoneal Mesothelial Cells / 대한신장학회지

PURPOSE: This study was undertaken to elucidate whether CC chemokine receptor 2 (CCR2) exists in human peritoneal mesothelial cells (HPMCs) and whether monocyte chemoattractant protein-1 (MCP-1) has direct effects on epithelial to mesenchymal transition (EMT) and fibronectin expression in HPMCs. METHODS: HPMCs were isolated from a piece of human omentum and were incubated with M199 media containing 5.6 mM glucose (LG), 5.6 mM glucose+94.4 mM mannitol (LG+M), LG+10 ng/mL recombinant human MCP-1 (LG+MCP-1), or 100 mM glucose (HG) with or without a specific inhibitor of CCR2, 1.0 micrometer RS102895, for 4 days. Levels of secreted MCP-1 in culture media were determined by ELISA. Western blot was performed to determine fibronectin, E-cadherin, alpha-smooth muscle actin (alpha-SMA) and CCR2 protein expression. RESULTS: MCP-1 protein levels were significantly increased in HG-conditioned media compared to LG media (p<0.05). CCR2 protein was expressed in HPMCs, but there was no difference between LGand HG-stimulated cells. alpha-SMA protein expressions in HG and LG+MCP-1 groups were significantly higher relative to LG cells, while E-cadherin protein expressions were decreased in HG and LG+ MCP-1 groups compared to LG cells (p<0.05). In addition, there were significant increases in fibronectin mRNA and protein expression in HG and LG+MCP-1 groups (p<0.05). These HG-induced changes were significantly abrogated upon pre-treatment with RS102895. CONCLUSION: HG and MCP-1 directly induce EMT and enhance fibronectin expression in HPMCs, and these HG-induced changes were attenuated by the inhibition of MCP-1/CCR2 system, suggesting that increased MCP-1 levels by HG may contribute to the development of peritoneal fibrosis.

The Effect of FR167653, p38 Mitogen-Activated Protein Kinase (MAPK) Inhibitor, on the Expression of Slit Diaphragm-Associated Proteins in Experimental Diabetic Nephropathy / 대한신장학회지

PURPOSE: This study was undertaken to investigate the effect of a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor, FR167653, on urinary albumin excretion and on the expression of slit diaphragm-associated proteins in diabetic rats. METHODS: Thirty-two Sprague-Dawley rats were injected with diluent [control (C), N=16] or streptozotocin intraperitoneally (DM, N=16). Eight rats from each group were treated with 5 mg/kg/day FR 167653 (C+FR, DM+FR) for 6 weeks. At the time of sacrifice, 24-hour urinary albumin excretion was determined by ELISA. Glomerular nephrin, P-cadherin, and ZO-1 mRNA and protein expression were determined by real-time PCR and Western blot, respectively, with sieved glomeruli. RESULTS: Urinary albumin excretion was significantly higher in DM compared to C rats, and this increase in albuminuria was significantly inhibited by the administration of FR167653 in DM rats. Glomerular phospho-p38 MAPK protein expression was significantly increased in DM rats compared to C rats, and FR167653 treatment significantly attenuated the increase in phospho-p38 MAPK expression in DM glomeruli. Nephrin mRNA and protein expression were higher in 6-week DM compared to C glomeruli, and these increases were significantly abrogated with FR167653 treatment in DM rats. In contrast, FR167653 had no effects on the decrease in P-cadherin expression and the increase in ZO-1 expression observed in DM glomeruli. CONCLUSION: These findings suggest that FR167653, a p38 MAPK inhibitor, reduce the amount of albuminuria in early diabetic nephropathy, and this anti-proteinuric effect seems to be related with the change of glomerular nephrin expression.

Factors associated with Endothelial Dysfunction in Hemodialysis Patients / 대한신장학회지

PURPOSE: Endothelial dysfunction is an event in the atherosclerotic process usually considered reversible at its early stage. Early detection, therefor, may improve the prognosis in the cardiovascular disease. The aim of this study was to investigate the vascular function in hemodialysis (HD) patients and to explore its relation to other various parameters with a specific emphasis on systemic inflammatory reaction (SIR), nutritional status and the presence of ischemic heart disease (IHD). METHODS: Flow-mediated endothelium-dependent vasodilatation (FMD) was measured, using Doppler sonogram, in 37 stable HD patients, 11 healthy people and 24 hypertensive controls. Nitroglycerine- induced endothelium-independent vasodilatation (EIV) and peak reaction time (PT) of each FMD and EIV were also measured. RESULTS: FMD in HD patients was decreased compared to healthy group whereas it was comparable in HD patients and hypertensive control. EIV in HD patients was significantly decreased compared to healthy and hypertensive controls. PT of each FMD and EIV was significantly delayed in HD patients. Each FMD and EIV showed a negative correlation with serum hsCRP level, but no significant correlations of FMD with other parameters were noted. Both FMD and EIV were further decreased in HD patients with IHD than non-IHD group. CONCLUSION: Our study confirmed a characteristic pattern of vascular dysfunction in HD patients: the impaired endothelial and smooth muscle function with a delayed reaction time. Importantly, SIR was one of the important factors determining vascular dysfunction in HD patients. Further studies will be necessary to define the causative role of SIR on endothelial dysfunction and the effect of inflammation- modulating therapy.

Analysis of Erroneous Overestimation of Blood Glucose in Patients on Continuous Ambulatory Peritoneal Dialysis with Icodextrin / 대한신장학회잡지

PURPOSE: Icodextrin in peritoneal cavity is absorbed via the lymphatics to the blood and metabolized to maltose and maltriose which may interfere with correct measurement of glucose. In an attempt to evaluate the effects of icodextrin on the erroneous results of blood glucose, we measured blood glucose by different methods. METHODS: Peripheral capillary blood and venous blood were obtained from 12 patients using icodextrin and from 12 patients not using icodextrin. Venous blood glucose was measured by using the laboratory technique (glucose oxidase method), and capillary blood glucose was measured by using a Surestep (glucose oxidase method) and an Acucheck (GDH-PQQ method). To estimate icodextrin and its metabolites indirectly, we calculated osmolal gap. We measured blood icodextrin and its metabolites with amyloglucosidase in icodextrin group. RESULTS: In icodextrin group, glucose was overestimated in the results of the GDH-PQQ method (delta= GDH-GOD=56.2+/-30 mg/dL [vein] 58+/-32 mg/dL [capillary]), but in the control group, there were no significant differences in the results between the glucose oxidase method and the GDH-PQQ method. There was a correlation between the osmolal gap and the differences in the results (delta=GDH-GOD) (r=0.741, p=.006 [vein], r=0.671, p=.017 [capillary]). Blood icodextrin and its metabolites were related with the differences in the results (delta=GDH-GOD) (p=.026, r=0.635), but there was no significant correlation between the osmolal gap and the icodextrin and its metabolites (p=0.086, r=0.515). CONCLUSION: Icodextrin and its metabolites may lead to erroneously high blood glucose levels when measured by GDH-PQQ method. It is necessary to be aware of this factor in order to prevent overlooking dangerous hypoglycemia.

Effect of Uric Acid (UA) on C-reactive Protein (CRP) Expression in Peripheral Blood Mononuclear Cells (PBMC) / 대한신장학회지

PURPOSE: Systemic inflammatory reaction (SIR) is an important determinant of cardiovascular (CV) mortality in CRF patients. UA is an end-product of purine metabolism, and recent studies have demonstrated that an elevated serum UA level is associated with an increased level of inflammatory mediators. Since hyperuricemia is one of the most prevalent complications in CRF and is linked to CV disease, we hypothesized hyperuricemia in CRF may play an important role in the development of CV disease by inducing SIR. METHODS: PBMCs were isolated by density gradient centrifugation in 21 CRF patients and age and sex-matched 20 healthy adults. CRP expression was evaluated by real time PCR and ELISA in PBMC stimulated with UA (0.3-12 mg/dL). RESULTS: There was no difference in constitutional CRP expression in PBMC from control and CRF patients. UA induced CRP mRNA (RT-PCR) and protein (ELISA) expression in PBMC, which was blocked by the organic anion transport inhibitor, probenecid (1 mM), suggesting entry of uric acid into cells was responsible for CRP expression. PBMC from CRF patients showed a significantly higher CRP production by UA compared to healthy control. There was no correlation between serum UA level and % increase in CRP production by UA. CONCLUSION: The exaggerated CRP expression by UA can be another mechanism of SIR and increased CV morbidity in CRF patients. Prospective studies with uric acid-lowering therapy are necessary to confirm clinical significance of these interesting in-vitro findings.

Effects of Short-Term Partial Correction of Anemia in End-Stage Renal Disease (ESRD) Patients on Maintenance Hemodialysis : Changes of Amino-Terminal Pro B-type Natriuretic Peptide (NT-pro BNP) and Echocardiographic Parameters / 대한신장학회잡지

BACKGROUND: Anemia is known to be one of the important risk factors in the development and the aggravation of cardiovascular diseases. This study was undertaken to evaluate the effect of anemia correction on blood NT-pro BNP level and echocardiographic parameters in ESRD patients on hemodialysis. METHODS: Recombinant human erythropoietin (rHuEPO) was administered in 20 hemodialysis patients (median age 51.5, M:F=2.3:1) with a target hemoglobin>12.0 g/dL for 3 months. All patients were subjected to a serial follow-up of hemoglobin, hematocrit, and NT-pro BNP. Echocardiographic examination was also performed before and after 3 months of therapy. RESULTS: Hemoglobin was increased at 3 months [12.3 g/dL (11.8-13.6)] compared with baseline [9.8 g/dL (9.1-10.4)] (p<0.01), and NT-pro BNP was significantly decreased at 3 months [3415 pg/mL (2717- 8160)] compared with baseline [6371 pg/mL (2338- 18269)] (p<0.05). Echocardiographic examination revealed no significant changes in left ventricular ejection fraction and left ventricular mass index. In Doppler imaging, however, there was significant decrease in E velocity [62.5 cm/sec (52.8-83.5) vs. 57.0 cm/sec (45.0-60.0), p<0.05], thereby decrement in E/E' [15.6 (13.4-25.7) vs. 14.3 (11.5-22.2), p<0.05]. CONCLUSION: Partial correction of anemia with rHuEPO in ESRD patients on hemodialysis results in the reduction of blood NT-pro BNP level and the decrease of E velocity and E/E'.

Effects of Short-Term Partial Correction of Anemia in End-Stage Renal Disease (ESRD) Patients on Maintenance Hemodialysis : Changes of Amino-Terminal Pro B-type Natriuretic Peptide (NT-pro BNP) and Echocardiographic Parameters / 대한신장학회잡지

BACKGROUND: Anemia is known to be one of the important risk factors in the development and the aggravation of cardiovascular diseases. This study was undertaken to evaluate the effect of anemia correction on blood NT-pro BNP level and echocardiographic parameters in ESRD patients on hemodialysis. METHODS: Recombinant human erythropoietin (rHuEPO) was administered in 20 hemodialysis patients (median age 51.5, M:F=2.3:1) with a target hemoglobin>12.0 g/dL for 3 months. All patients were subjected to a serial follow-up of hemoglobin, hematocrit, and NT-pro BNP. Echocardiographic examination was also performed before and after 3 months of therapy. RESULTS: Hemoglobin was increased at 3 months [12.3 g/dL (11.8-13.6)] compared with baseline [9.8 g/dL (9.1-10.4)] (p<0.01), and NT-pro BNP was significantly decreased at 3 months [3415 pg/mL (2717- 8160)] compared with baseline [6371 pg/mL (2338- 18269)] (p<0.05). Echocardiographic examination revealed no significant changes in left ventricular ejection fraction and left ventricular mass index. In Doppler imaging, however, there was significant decrease in E velocity [62.5 cm/sec (52.8-83.5) vs. 57.0 cm/sec (45.0-60.0), p<0.05], thereby decrement in E/E' [15.6 (13.4-25.7) vs. 14.3 (11.5-22.2), p<0.05]. CONCLUSION: Partial correction of anemia with rHuEPO in ESRD patients on hemodialysis results in the reduction of blood NT-pro BNP level and the decrease of E velocity and E/E'.

A case of acetaminophen induced anaphylaxis without aspirin sensitivity / 대한내과학회지

Acetaminophen is a world-wide used analgesic and anti-pyretic drug with less anti-in-flammatory effect, available without prescription in most countries. Allergic-like reactions to this drug, including urticaria, angioedema, and anaphylactic reactions have only rarely been reported. This report describes a systemic reaction to acetaminophen documented by oral provocation test in a 30-year-old female patient with a history of anaphylaxis associated with acetaminophen use, in a subject who tolerated aspirin. After an oral challenge with 108.3 mg of acetaminophen, the subject had itching sensation of tongue. With a dose of 162.5 mg (cumulative dose 270.8 mg) acetaminophen, systemic urticaria and rash developed. Also, hand and facial angioedema and chest tightness were noted. Significant change of FEV1 was not noted. But, this patient has bronchial hyperresponsiveness. A rare acute hypersensitivity reaction to acetaminophen without aspirin sensitivity is described in this study. The results of study suggest an other mechanism rather than inhibition of cyclooxygenase as responsible.