BACKGROUND/AIMS: Sirolimus (SRL) is a promising immunosuppressant replacingcalcineurin inhibitors (CNIs). This study was performed to evaluate the safetyand immunologic benefits of conversion to SRL in stable kidney transplant (KT)recipients exposed to CNIs for long periods. METHODS: Fourteen CNI-treated KT recipients with stable renal function for morethan 10 years were included. Either 2 or 3 mg per day of SRL was administeredwhile CNIs were reduced by half starting on day 1, and then stopped 2 weeks afterSRL introduction. The safety of SRL conversion was assessed considering thegraft function, acute rejection, and graft loss. Immunologic alterations were measuredvia serial changes of T cell and B cell subsets after SRL conversion. Adverseeffects of SRL conversion were also evaluated. RESULTS: Conversion to SRL was successful in nine patients (64.2%). Conversionto SRL preserved graft function as compared to the baseline value (p = 0.115). Noacute rejection or allograft loss was observed during the follow-up period. Immunemonitoring of T and B cells revealed a regulatory T cells increase after SRL conversion (p = 0.028). Most adverse events developed within 6 weeks after SRLconversion, and oral mucositis was the main cause of SRL withdrawal. CONCLUSIONS: Conversion to SRL can be safe and has immunologic benefits in KTrecipients with long-term CNI exposure. Close monitoring of mucocutaneous adverseevents is, however, required in the early period after SRL conversion.
Allografts ; B-Lymphocyte Subsets ; B-Lymphocytes ; Calcineurin* ; Follow-Up Studies ; Humans ; Kidney Transplantation ; Kidney* ; Sirolimus* ; Stomatitis ; T-Lymphocytes, Regulatory ; Transplantation* ; Transplants

BACKGROUND: Nephrotic syndrome (NS) and proteinuria are uncommon, often unrecognized manifestations of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Only a few isolated case reports and case series involving smaller number of patients who developed NS after HSCT have been published. METHODS: We reviewed the renal histopathological examination findings and clinical records of 15 patients who developed proteinuria after HSCT at Seoul and Yeouido St. Mary's Hospital (Seoul, Korea). We also measured the anti-PLA2 Rantibodies (M-type phospholipase A2 receptor) in the serum samples from the seven patients at the time of renal biopsy. RESULTS: All patients had GVHD. The most common indication for biopsy was proteinuria ( > 1 g/day), with nine patients having nephrotic range proteinuria. The most common histopathological finding was membranous nephropathy (MN; n = 12).Other findings were membranoproliferative glomerulonephritis, C1q nephropathy, and diabetic nephropathy. Eleven patients were treated with immunosuppressive agents, and three patients were treated only with angiotensin II receptor blocker. The overall response rate, including complete remission (urinary protein level < 0.3 g/day) and partial remission (urinary protein level = 0.31-3.4 g/day), was 73%. The mean follow-up period was 26 months, and none of the patients developed end-stage renal disease. All of the seven patients with MN had negative findings for anti-PLA2R antibodies, measured using an enzyme-linked immunosorbent assay kit. CONCLUSION: In this study the findings of 15 renal biopsies were analyzed and to our knowledge this is the largest clinicopathological study of GVHD-related biopsy-proven nephropathy. Approximately 80% of the patients were MN and 73% responded either partially or completely to immunosuppressive treatment. Currently, there is an increase in the incidence of GVHD-mediated renal disease, and therefore, renal biopsy is essential for diagnosing the nephropathy and preventing the progression of renal disease.
Antibodies ; Biopsy ; Diabetic Nephropathies ; Enzyme-Linked Immunosorbent Assay ; Follow-Up Studies ; Glomerulonephritis, Membranoproliferative ; Glomerulonephritis, Membranous ; Graft vs Host Disease* ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Immunosuppressive Agents ; Incidence ; Kidney Failure, Chronic ; Nephrotic Syndrome ; Phospholipases A2 ; Proteinuria ; Receptors, Angiotensin

Most of the previous studies on immune dysregulation in end-stage renal disease (ESRD) have focused on T cell immunity. We investigated B cell subpopulations in ESRD patients and the effect of hemodialysis (HD) on B cell-associated immune profiles in these patients. Forty-four ESRD [maintenance HD patients (n = 27) and pre-dialysis patients (n = 17)] and 27 healthy volunteers were included in this study. We determined the percentage of B cell subtypes, such as mature and immature B cells, memory B cells, and interleukin (IL)-10+ cells, as well as B cell-producing cytokines (IL-10, IL-4 and IL-21) by florescent activated cell sorting (FACS). B cell-associated gene expression was examined using real-time PCR and B cell producing cytokines (IL-10, IL-4 and IL-21) were determined using an enzyme-linked immunosorbent assay (ELISA). The percentage of total B cells and mature B cells did not differ significantly among the three groups. The percentages of memory B cells were significantly higher in the pre-dialysis group than in the HD group (P < 0.01), but the percentage of immature B cells was significantly lower in the pre-dialysis group than in the other groups. The percentages of IL-10-expressing cells that were CD19+ or immature B cells did not differ significantly (P > 0.05) between the two subgroups within the ESRD group, but the serum IL-10 concentration was significantly lower in the pre-dialysis group (P < 0.01). The results of this study demonstrate significantly altered B cell-associated immunity. Specifically, an imbalance of immature and memory B cells in ESRD patients was observed, with this finding predominating in pre-dialysis patients.
Adaptor Proteins, Signal Transducing/genetics ; Adult ; Antigens, CD19/metabolism ; B-Lymphocyte Subsets/immunology/metabolism ; B-Lymphocytes/*immunology/metabolism ; Cytokines/biosynthesis ; Female ; Humans ; Immunophenotyping ; Interleukin-10/metabolism ; Kidney Failure, Chronic/*immunology/metabolism ; Leukocytes, Mononuclear/metabolism ; Male ; Middle Aged ; Proto-Oncogene Proteins/genetics ; T-Lymphocytes, Regulatory/immunology/metabolism

B-lineage non-Hodgkin lymphoma may aberrantly coexpress T-cell markers. In general population, however, cases of diffuse large B-cell lymphomas with CD3 co-expression are rare because the CD3 marker is the most lineage specific T-cell antigen. We report a case of CD3 coexpressed diffuse large B-cell lymphoma in a 47-year-old male patient presented with dyspepsia who had transplanted a kidney 17 years ago. An esophagogastroduodenoscopy displayed an ulcerated mass in the gastric antrum. The pathology of the mass was monomorphic post-transplant lymphoproliferative disorder - specifically, CD20- and CD3-positive diffuse large B-cell lymphoma. Resection of the mass and postop chemotherapy were performed. A follow-up computerized tomography showed disapperance of tumor. No recurrence was observed until 7 month after treatment. Nevertheless, the patient's renal function gradually aggrevated and progressed to end stage renal disease. As far as we know, this is the first case of diffuse large B-cell lymphoma with CD3 coexpression after kidney transplant.
B-Lymphocytes ; Dyspepsia ; Endoscopy, Digestive System ; Follow-Up Studies ; Humans ; Kidney ; Kidney Failure, Chronic ; Lymphoma, B-Cell ; Lymphoma, Non-Hodgkin ; Lymphoproliferative Disorders ; Male ; Middle Aged ; Neoplasm Transplantation ; Pyloric Antrum ; Recurrence ; T-Lymphocytes ; Transplants ; Ulcer

The aim of this study was to evaluate whether the Th17 and Treg cell infiltration into allograft tissue is associated with the severity of allograft dysfunction and tissue injury in acute T cell-mediated rejection (ATCMR). Seventy-one allograft tissues with biopsy-proven ATCMR were included. The biopsy specimens were immunostained for FOXP3 and IL-17. The allograft function was assessed at biopsy by measuring serum creatinine (Scr) concentration, and by applying the modified diet in renal disease (MDRD) formula, which provides the estimated glomerular filtration rate (eGFR). The severity of allograft tissue injury was assessed by calculating tissue injury scores using the Banff classification. The average numbers of infiltrating Treg and Th17 cells were 11.6 +/- 12.2 cells/mm2 and 5.6 +/- 8.0 cells/mm2, respectively. The average Treg/Th17 ratio was 5.6 +/- 8.2. The Treg/Th17 ratio was significantly associated with allograft function (Scr and MDRD eGFR) and with the severity of interstitial injury and tubular injury (P < 0.05, all parameters). In separate analyses of the number of infiltrating Treg and Th17 cells, Th17 cell infiltration was significantly associated with allograft function and the severity of tissue injury. By contrast, Treg cell infiltration was not significantly associated with allograft dysfunction or the severity of tissue injury. The results of this study show that higher infiltration of Th17 cell compared with Treg cell is significantly associated with the severity of allograft dysfunction and tissue injury.
Acute Disease ; Creatinine/metabolism ; Forkhead Transcription Factors/metabolism ; Graft Rejection/*etiology/pathology ; Humans ; Immunoenzyme Techniques ; Interleukin-17/*metabolism ; Kidney Transplantation/*adverse effects ; Retrospective Studies ; T-Lymphocytes, Regulatory/*immunology/pathology ; Th17 Cells/*immunology/pathology ; Transplantation, Homologous

BACKGROUND AND OBJECTIVES: The second derivative of a photoplethysmogram (SDPTG) is a simple, convenient and non-invasive technique for pulse wave analysis. The SDPTG index correlates with age and other risk factors of atherosclerosis in the Japanese population, but has not yet been described in the Korean population. The purposes of this study were to analyze the age-related changes in the SDPTG of healthy subjects (study 1), and investigate the differences in the SDPTG of patients with hypertension, compared with those of normotensive subjects (study 2). We also compared the differences in the SDPTG between coronary artery disease (CAD) patients and normal subjects (study 3), to test the clinical usefulness of SDPTG in the evaluation of atherosclerosis. SUBJECTS AND METHODS: We consecutively studied 235 healthy adults, 40 with essential hypertension and 42 with CAD. Their SDPTG were recorded in the sitting position using a Fukuda FCP-3166. RESULTS: In study 1, the b/a ratio increased with age, whereas the c/a, d/a and e/a ratios decreased. The SDPTG aging index (AGI)(y) increased with age (x)(r=0.71, p=0.000;y=22.731x+54.571). In study 2, the patients with hypertension showed a lower average d/a ratio (-0.47+/-0.15 vs. -0.38+/-0.15, p=0.02) and higher average SDPTG AGI (-0.09+/-0.34 vs. -0.26+/-0.37, p=0.011) than the normotensive subjects. In study 3, the patients with CAD had higher average b/a ratio (-0.47+/-0.19 vs. -0.59+/-0.17, p=0.001) and SDPTG AGI (-0.01+/-0.41 vs. -0.23+/-0.40, p=0.004) than the normal subjects. In a logistic regression analysis, the SDPTG AGI was a significant determinant of CAD (p=0.046). CONCLUSION: The SDPTG aging index may be useful in the evaluation of vascular aging and damage due to hypertension and atherosclerosis.
Adult ; Aging ; Asian Continental Ancestry Group ; Atherosclerosis ; Coronary Artery Disease ; Humans ; Hypertension ; Logistic Models ; Photoplethysmography ; Pulse Wave Analysis ; Risk Factors

BACKGROUND AND OBJECTIVES: Ventricular premature beat (VPB) with a left bundle branch block morphology and an inferior axis usually originates from the right ventricular outflow tract (RVOT) and is a frequent clinical problem. Although some investigators have suggested that RVOT VPBs are associated with RVOT ventricular tachycardia, few data are available on patients with RVOT VPBs. The purpose of this study was to determine the clinical characteristics and prognosis of RVOT VPB. SUBJECTS AND METHODS: The study subjects were 161 consecutive patients with frequent RVOT VPBs on standard electrocardiography. All patients underwent clinical examinations, echocardiography and 24-hour ambulatory electrocardiography. Among these patients, 50 were followed up for a period averaging 28.5+/-18.1 months. RESULTS: No structural cardiac abnormalities were found in 149 (92.5%) of the 161 patients with frequent RVOT VPBs. The prevalence of complex VPBs was relatively high (101 of 161 patients: 62.7%) on initial 24-hour electrocardiography. In the case of the 50 follow-up patients, there was no significant difference in mean frequency of RVOT VPBs between baseline and follow-up study (636+/-482/hour vs. 569+/-502/hour, p=NS). Furthermore, VPBs tended to persist over the follow-up period in the majority (92%) of patients with frequent RVOT VPBs. Five patients (10%) developed nonsustained ventricular tachycardia, 2 (4%) sustained ventricular tachycardia and 1 (2%) died suddenly. Antiarrhythmic drugs are effective in decreasing the frequency of VPBs, and beta-blockers especially seem to be effective in decreasing the severity of VPBs. CONCLUSION: In the patients with frequent RVOT VPBs, sustained ventricular tachycardia or sudden death could develop. Therefore, careful observation is required in patients with frequent RVOT VPBs.
Anti-Arrhythmia Agents ; Axis, Cervical Vertebra ; Bundle-Branch Block ; Cardiac Complexes, Premature* ; Death, Sudden ; Echocardiography ; Electrocardiography ; Electrocardiography, Ambulatory ; Follow-Up Studies ; Humans ; Prevalence ; Prognosis ; Research Personnel ; Tachycardia, Ventricular ; Ventricular Premature Complexes

BACKGROUND AND OBJECTIVES: Large volume reduction after hemodialysis in patients with chronic renal failure alters the preload. We investigated the cardiac function by total ejection isovolume (TEI) index- a new simple, readily reproducible Doppler echocardiographic index combining systolic and diastolic function- before and after dialysis. MATERIALS AND METHOD: Thirty-one patients on maintenance hemodialysis including 6 diabetes and 13 hypertensives without known organic heart disease and with normal systolic function were enrolled. They were divided into two groups according to ultrafiltration volume at the study dialysis session, group 1 (2.5kg or less) and group 2 (more than 2.5 kg). They are 46+/-12 years old on average. We examined two-dimensional, M-mode, pulsed wave and tissue Doppler before and after dialysis immediately. TEI index was calculated by dividing the sum of the isovolumic relaxation time (IVRT) and isovolumic contraction time (ICT) by the ejection time. RESULTS: After dialysis, significant decrease of body weight was noted, but baseline heart rate, blood pressure, Left ventricular (LV) ejection fraction and LV mass index were not changed significantly. LV end-diastolic volume was decreased significantly after dialysis in all group, and end-systolic volume was decreased significantly in total and group 2. Peak early E velocity and ratio of E to the peak late (A) velocity (E/A) from mitral inflow signal were decreased significantly after dialysis in all group and deceleration time of early filling phase was prolonged in total and group 1, but A and IVRT did not change significantly. Of the septal mitral annulus motion, Ean velocity and Ean/Aan ratio was decreased, but no significant change was noted in the lateral annulus. The TEI index did not chage significantly after dialysis in all group. CONCLUSION: A new simple echocardiographic TEI index can be used to measure the global myocardial function in patients with chronic renal failure before and after dialysis, relatively independent of preload change.
Blood Pressure ; Body Weight ; Deceleration ; Dialysis ; Echocardiography ; Heart Diseases ; Heart Rate ; Humans ; Kidney Failure, Chronic ; Relaxation ; Renal Dialysis* ; Ultrafiltration

In the past 60 years the maternal mortality rate has declined rnarkedly. Nevertheless, death associated with childbirth is still a major public health problem. For women delivered of live infants, the leading causes of mortality are acute pulmonary embolism(mostly thromboembolic), pregnancy-induced hypertension, hemorrhage, and infection. Currently, the common cause of maternal rnortality are pulmonary embolisrn. Though acute pulmonary embolism is a potentially fatal disorder, when properly diagnosed and treated, clinically apparent pulmonary embolism was an uncommon cause of death. However, the diagnosis of acute pulmonary embolism is still a challenge for clinicians because of its nonspecific and variable clinical features. Pulmonary angiography, admittedly the 'gold standard' technique for this diagnosis, is costly, invasive, and not universally available. Noninvasive procedures such as lung scan has certainly simplified the diagnostic approach. However, lung scan is diagnostic in only 30 to 50% of patients, and many institutions lack nuclear medicine facilities. Thus, alternative imaging techniques are needed for the noninvasive diagnosis of pulmonary embolism. Echocradiography is rapid, practical and sensitive technique for the identification of right ventricular overload following acute pulmonary embolism. Echocardiographic identification of patients with right ventricular dysfunction is important because aggressive intervention with thrombolytics, certain inotropic and vasoactive agents, or embolectomy may improve outcome. We report herein two cases of acute pulmonary embolism after cesarean section. Certain clinical findings, hemodynamic values, and particularly, echocardiographic signs can indentify right ventricular dysfunction after pulmonary embolisrn. The patients was immediately treated mth intravenous heparin and inotropic support, which induced a rapid improvement of the clinical and hemodynamic parameters.
Angiography ; Cause of Death ; Cesarean Section* ; Diagnosis ; Echocardiography* ; Embolectomy ; Female ; Hemodynamics ; Hemorrhage ; Heparin ; Humans ; Hypertension, Pregnancy-Induced ; Infant ; Lung ; Maternal Mortality ; Mortality ; Nuclear Medicine ; Parturition ; Pregnancy ; Public Health ; Pulmonary Embolism* ; Ventricular Dysfunction, Right

BACKGROUND: The electrocardiogram may provide valuable information regarding the identity of the culprit coronary artery and the location of obstructing lesion within the artery, which may be of guidance in selecting the therapeutic modality. Previous studies have concluded that changes in lateral leads (I, aVL, V5, V6) are predictive of left circumflex coronary artery obstruction in inferior wall acute myocardial infarction. Elect-rocardiographic criteria for determining the location of the obstructing lesion, however, have not been well established. The purpose of this study is to investigate the patterns of ST segment depression in lateral leads in inferior wall acute myocardial infarction and the obstruction site of culprit artery according to ST segment depression in lateral leads. METHODS: We examined 78 patients with inferior wall acute myocardial infarction analizing their electrocardiogram and coronary angiography which performed during acute hospitalization. RESULTS: Of the fifty-five patients in which the culprit artery could be determined, 1)in 41 the culprit artery was the right coronary artery (19 proximal to the right ventricular branch and 22 distal), and in 14 the left circumflex coronary artery (7 proximal to the first obtuse marginal branch or involving a high first obtuse marginal branch, and 7 with distal obstruction). 2)Significant ST depression (ST< or =1 mm) in leads I and aVL was more common in right coronary artery obstruction (p<0.05 and p=0.01 respectively) than left circumflex artery. 3)It was difficult to define the location of obstruction with ST segment change of lateral precordial leads (V5, V6). CONCLUSIONS: In acute inferior wall myocardial infarction, ST segment depression in lateral limb leads (I, aVL) can be indicative of the right coronary artery obstruction and the ST segment depression pattern in lateral precordial leads was not indicative of the site of obstruction.
Arteries ; Coronary Angiography ; Coronary Vessels ; Depression* ; Electrocardiography ; Extremities ; Hospitalization ; Humans ; Inferior Wall Myocardial Infarction ; Myocardial Infarction*