From July 1988 to September 1992, we experienced 15 cases of thrombolysoangioplasty (TLA) at Chonnam University Hospital. Among 15 cases, 5 had claudication (Clinical stage II according to Modified Fontaine Classification), pain at rest (III), and gangrene(IV). Duration of symptoms was 1-7 months except patients of clinical stage IV unable to guess occlusion age. The occlusion length was 5-10cm in 8 cases, 10-20cm in 4 cases, and above 30cm in 2 cases. In all cases, thromolytic therapy was performed with intraarterial urokinase infusion. The total amount of urokinase ranged from 300,000 IU to 2,000,000 IU and infusion time ranged from 2 to 50 hours except three cases infused bolus dose only. Complete successful TLA was defined as technical (less than 50% of residual stenosis) and clinical success. Partial success was defined as technical success but clinical failure. Follow-up angiography could be performed in 8 cases. Overall initial success rate was 86.6% (13/15). Among them. Complete success was in 11 cases and partial success was in 2 cases. Recurrence of disease was not noted on all cases(n=8). Severe complications, such as hemorrhage, did not occurred. TLA was considered to be effective and safe way to recanalized chronic long artery occlusion in lower extremity.
Angiography ; Arteries ; Follow-Up Studies ; Hemorrhage ; Humans ; Jeollanam-do ; Lower Extremity ; Recurrence ; Urokinase-Type Plasminogen Activator

BACKGROUND:With the application of early reperfusion by thrombolysis after acute MI, the importance of nontransmural infarction is increasing. We evaluated 1) the changes of LV dimension, LV fibrosis and transforming growth factor-beta1 (TGF-beta1) mRNA expression in a rat model of nontransmural infarction and 2) effects of angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ATRB) treatment after nontransmural infarction. METHOD AND RESULTS: Female Sprague-Dawley rats were subjected to 45 minutes of coronary occlusion followed by reperfusion, and at 5 days after the operation, animals were randomized to untreated (MI-vehicle, n=19), captopril-treated (MI-captopril, n=15) and losartan-treated (MI-losartan, n=14) groups. LV dimension, measured by transthoracic echocardiography, was significantly increased at 26 days after MI, and both captopril and losartan treatment inhibited LV cavity dilatation (LV end-diastolic dimension (mm): MI-vehicle, MI-captopril, MI-losartan; 8.6 +/- 0.2, 7.8 +/- 0.2, 8.0 +/- 0.2, p<0.05 vs. MI-vehicle each). Interstitial fibrosis was reduced with both captopril and losartan treatment (p<0.05 vs. MI-vehicle). TGF-beta1 mRNA increased 2.6 fold at 10 days (p<0.05 vs. pre-MI), and normalized at 26 days after nontransmural MI. Captopril and losartan treatment blocked the induction of TGF-beta1 expression after nontransmural MI (p=S vs. pre-MI). CONCLUSION: After large nontransmural MI, ACEI and ATRB treatments attenuate LV remodeling and decrease interstitial fibrosis, at least partly by blocking the acute induction of TGF-beta1 mRNA expression.
Angiotensins* ; Animals ; Captopril ; Coronary Occlusion ; Dilatation ; Echocardiography ; Female ; Fibrosis ; Humans ; Infarction ; Losartan ; Models, Animal ; Peptidyl-Dipeptidase A* ; Rats, Sprague-Dawley ; Receptors, Angiotensin ; Reperfusion ; RNA, Messenger ; Transforming Growth Factor beta1 ; Transforming Growth Factors ; Ventricular Remodeling*

BACKGROUND: The bcr-abl gene rearrangement is a very important genetic marker in at least 95% of cases of chronic myeloid leukemia (CML). The technique that allows the detection of bcr-abl gene rearrangement seem to be the testing for the diagnoses and the detection of minimal residual disease (MRD) and may help in monitoring patients. Recent introduction of real-time quantitative PCR should eventually allow actual quantification of the target gene during amplification. In the present study, we investigated bcr-abl chimeric mRNA quantification in CML after bone marrow transplantation (BMT) by real-time RT-PCR and its clinical applicability to the decision of therapeutic intervention. METHODS: The subjects were a consecutive series of 9 CML patients with serial quantification of bcr-abl chimeric mRNA by real-time RT-PCR in peripheral blood or bone marrow aspirates. The sensitivity of real-time RT-PCR was compared to conventional RT-PCR and then the correlation with FISH results was analyzed. RESULTS: Seventeen bone marrow samples and 40 peripheral bloods were obtained from patients. The sensitivity of real-time RT-PCR was 10(-6) and positive signals were detected in negative cases by conventional RT-PCR. A significant correlation between the bcr-abl/G6PDH ratio by real-time RT-PCR and the proportion of positive cells for bcr-abl gene rearrangement by FISH was obtained (r=0.64). In the serial blood and bone marrow specimens, we found a progressive decrease in the bcr-abl/G6PDH ratio in all the patients. CONCLUSIONS: Our findings indicated that quantitative analysis of bcr-abl chimeric mRNA by real-time RT-PCR might be a useful tool for the monitoring of minimal residual disease in bcr-abl positive leukemic patients.
Bone Marrow ; Bone Marrow Transplantation* ; Diagnosis ; Gene Rearrangement ; Genetic Markers ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Neoplasm, Residual ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction* ; RNA, Messenger

BACKGROUND: AML with myelodysplasia related changes (AML MRC) is known to show a poor prognosis compared with de novo AML, but controversies exist about the prognostic impact of multilineage dysplasia (MLD) among MRC. We investigated the prognostic impact of MLD in AML MRC. METHODS: A total of 357 patients newly diagnosed as AML at Asan Medical Center from January 2001 to December 2005 were analyzed. They were diagnosed and classified as AML with recurrent genetic abnormalities, AML MRC, and AML not otherwise specified (AML NOS). Prognostic markers including overall survival (OS) and event free survival (EFS) were obtained through retrospective analysis of electronic medical records. RESULTS: AML MRC patients showed a lower complete remission (CR) rate (44.7% vs. 64.9%, P=0.002) and shorter OS (297 vs. 561 days, P=0.004) and EFS (229 vs. 374 days, P=0.004) than AML NOS patients. Patients with MLD among AML MRC also showed a lower CR rate (37.7%, P=0.001) and shorter OS (351 days, P=0.036) and EFS (242 days, P=0.076) than AML NOS patients. However, among AML MRC patients, there were no differences in OS, EFS and CR between patients with and without MLD. CONCLUSIONS: AML MRC patients showed a lower CR rate and shorter OS and EFS than AML NOS patients. AML MRC patients with MLD showed similar results and their prognosis was not different from those without MLD. MLD findings among AML MRC could be an independent poor prognostic factor in de novo AML.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cell Lineage ; Child ; Child, Preschool ; Data Interpretation, Statistical ; Disease-Free Survival ; Female ; Humans ; Infant ; Leukemia, Myeloid, Acute/complications/diagnosis/*mortality ; Male ; Middle Aged ; Myelodysplastic Syndromes/complications/*diagnosis ; Prognosis ; Retrospective Studies ; Survival Analysis

BACKGROUND: The CD34+ cell dose and infused number of committed progenitor cells in transplantation are important factors in hematologic engraftment. However, the relationship between expansion potential of progenitor cells and hematologic engraftment remains controversial. We evaluated whether expansion potential of progenitor cells is a predictive factor of post-transplantation hematologic engraftment. METHODS: Mononuclear cells isolated from mobilized peripheral blood and bone marrow were cultured with cytokine cocktail for 7 days. Progenitor cells and committed progenitors were analyzed using stem cell markers (CD34 and CD133) and lineage specific markers. Hematologic engraftment was defined as neutrophil counts over 500/microliter and platelet counts over 20,000/microliter without transfusion. Acute and chronic graft-versus-host disease (GVHD) were investigated. RESULTS: There was inverse tendency between the number and fold expansion of progenitor cells or committed (granulocytic or megakaryocytic) progenitors and time to engraftment. Especially, fold expansion of CD34(+)/CD33(+) cells was significantly correlated with time to neutrophil engraftment in bone marrow transplantation (r=-0.56, P=0.04). The infused number and fold expansion of lymphoid progenitors were not related to the occurrence of acute or chronic GVHD. CONCLUSIONS: We could not prove that expansion potential of progenitor cells and committed progenitor cells is correlated to hematologic engraftment although there is a correlation between CD34(+)/ CD33(+) cells and time to neutrophil engraftment. But, a further study on the value of expansion potential is required because there is an inverse tendency.
Bone Marrow ; Bone Marrow Transplantation ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Neutrophils ; Platelet Count ; Stem Cells

BACKGROUND: The Wilms' tumor gene (WT1) is located on chromosome 11p13. Several authors have shown that the expression of WT1 gene is associated with prognosis of acute leukemia. It was the aim of this study to investigate the relationship between WT1 positivity and the response to treatment in terms of rate of complete remissions (CR), and survival and to evaluate the prognostic value of WT1 expression in patients with acute leukemia. METHODS: We examined the presence of WT1 specific mRNA in bone marrow samples of 71 patients with acute leukemia at diagnosis (AML 39, ALL 32) by nested RT-PCR. The integrity and the amount of RNA were analyzed by amplification of the -actin gene as an internal control. The relative ratio of WT1 gene expression/ -actin was calculated and classified as not amplified (0), weakly amplified (1+), moderately amplified (2+), or strongly amplified (3+). RESULTS: Thirty-four (47.9%) of the patients with acute leukemia at diagnosis were WT1 PCR positive. Among the WT1 positive patients, 10 patients (14.1%) showed 1+, 20 patients (28.2%) 2+, and 4 patients (5.6%) 3+. The patients with WT1 mRNA expression were younger than those without it in AML. There was a tendency of a higher CR rates in WT1 negative patients than in WT1 positive ones (AML 61.9% vs. 50%, ALL 75.0% vs. 68.8%). The probability of 5 year survival was 62.2% for WT1 negative group and 44.1% for WT1 positive group in all patients. The median survival days accord-ing to levels of WT1 expression was 709 days for negative group, 310 days for 1+ or 2+ groups and 294 days for 3+ group. CONCLUSIONS: The present data suggest a clinical relevance of WT1 expression for the achieve-ment of CR and long term survival in acute leukemia. Analysis of WT1 expression with bone mar-row aspirates at the diagnosis of acute leukemia may be useful to predict prognosis.
Bone Marrow ; Diagnosis ; Gene Expression* ; Humans ; Leukemia* ; Polymerase Chain Reaction ; Prognosis ; RNA ; RNA, Messenger ; Wilms Tumor

BACKGROUND: The t(12;21)(p13;q22), which fuses the TEL gene on chromosome 12p13 and the AML1 gene on chromosome 21q22, is observed in approximately 20~25% of childhood B-lineage acute lymphoblastic leukemia (ALL) cases and is associated with a favorable outcome. A retrospective study was conducted to investigate the frequency of TEL/AML1 fusion in the patients diagnosed as childhood B-precursor ALL. METHODS: Because of the low detection rate by routine karyotypic analysis, we studied 54 children with B-lineage ALL using the fluorescence in situ hybridization (FISH) analysis. RESULTS: Results of this analysis demonstrated a 9.3% frequency of TEL/AML1 fusion, relatively lower than Japanese, Taiwanese and Caucasian children. All five patients with TEL/AML1 fusion showed CD10 positivity and predominance of male patients (4:1). Two cases of TEL/AML1 positive groups expressed the myeloid antigens, but no significance was noted (P>0.05). In TEL/AML1 positive groups, the leukemia was developed between 4 and 5 years old age (favorable age) and showed low initial leukocyte counts (<50,000/micro L). CONCLUSION: Although these findings combined with earlier reports indicate that TEL/ AML1 fusion was frequent genetic abnormality in childhood ALL, relatively low frequency in Korean patients suggested the existence of geographic or racial variations in the genotype of ALL.
Asian Continental Ancestry Group ; Child ; Child, Preschool ; Fluorescence ; Genotype ; Humans ; In Situ Hybridization ; Leukemia ; Leukocyte Count ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Retrospective Studies

BACKGROUND: The myelodysplastic syndromes (MDS) in childhood is considered to be very rare and the nature of this disease in childhood is very different from that in adults. We analyzed the hematologic findings of childhood myelodysplastic syndrome. METHODS: The retrospective study was performed with the confirmed patients who were admitted to the Department of Pediatrics, Asan Medical Center (AMC) from June 1989 till May 1999, to analyze the hematologic findings. Sixteen children with a primary myelodysplastic syndrome (MDS) were presented to AMC during a 10 year period. RESULTS: Morphological assessment of the peripheral blood and the bone marrow showed nine patients (56%) had refractory anemia (RA), two patients (13%) had RA with excess blasts (RAEB), five patients (31%) had RAEB in transformation (RAEB-t). Five children with juvenile chronic myelogenous leukemia were diagnosed over the same period. Age distribution showed the predilection between 6~10 years and male : female ratio was 1 : 1. Inperipheralblood, pancytopenia was found in seven cases (44%) and leukocytosis in four cases (25%). The bone marrow findings showed hypercellularity in 54%, hypocellularity in 8% and variable cellularity in 15% and myelofibrosis was observed in 23%. Various dyspoietic changes of erythrocytes, leuko- cytes and platelets in peripheral blood and three cell lines in bone marrow were observed and trilineage dysplasia was observed in 62% of MDS, and 56% of RA. The four cases (25%) of RAEB and RAEB-t have transformed to acute myelogenous leukemia. CONCLUSION: In our study, the MDS in childhood seemed to be characterized by higher incidence of RA. Compared with the adult MDS, trilineage dysplasia in RA was frequently seen, but, no significant differences of dyspoietic features between adults and childhood were observed.
Adult ; Age Distribution ; Anemia, Refractory ; Anemia, Refractory, with Excess of Blasts ; Bone Marrow ; Cell Line ; Child ; Chungcheongnam-do ; Erythrocytes ; Female ; Humans ; Incidence ; Leukemia, Myeloid, Acute ; Leukemia, Myelomonocytic, Juvenile ; Leukocytosis ; Male ; Myelodysplastic Syndromes* ; Pancytopenia ; Pediatrics ; Primary Myelofibrosis ; Retrospective Studies

Lineage switch from acute lymphoblastic leukemia (ALL) to acute myeloid leukemia (AML) is very rare. We report a case of a 9 yr-old ALL patient relapsed as acute myelomonocytic leukemia. At the initial diagnosis, the blast cell morphology and immunophenotype were consistent with the diagnosis of typical ALL (L1 subtype according to FAB classification). The BCR-ABL fusion gene was not found by reverse transcription-PCR. Complete remission (CR) was achieved after induction and consolidation chemotherapy (Children's Cancer Study Group 1891 protocol, CCG1891). Nine months, which is a very short time compared with other cases in the literatures, after the diagnosis of ALL, she relapsed with completely different blasts (typical AML, M4 according to FAB classification) in morphology, cytochemistry, and immunophenotyping. The karyotype has changed from 56,XY,+X,+Y,+Y,+4,+8,+10, +14,+17,-20,+21,+21,+21[6]/57,idem,+Y[19] to 46,XY,t(8;16)(p11.2;p13.1)[19]/46,XY[1], showing unrelated chromosomal abnormality to the karyotype at the initial diagnosis. Moreover, both findings were quite specific for each common cell ALL and acute myelomonocytic leukemia. These findings support that this case is completely different leukemic clones occurred at each leukemic expression. The treatment with AML 2000 protocol chemotherapy failed, and he underwent the chemotherapy with the combination of high dose cytarabine and mitoxantrone and has been in CR state for 21 months, until now.
*Cell Lineage ; Cell Transformation, Neoplastic ; Child ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute/*diagnosis/pathology ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/pathology

BACKGROUND: TEL (ETV6)/AML1 (RUNX1) rearrangement is observed in approximately 20-25% of childhood precursor B-ALL and is associated with a favorable outcome. Additional genetic changes, associated with TEL/AML1, are frequently found. We evaluated the prevalence and prognostic significance of TEL/AML1 rearrangement and additional genetic changes in the TEL and AML1 genes in Korean childhood precursor B-ALL. METHODS: We performed FISH using LSITEL/AML1 ES probe (Vysis, USA) in 123 children diagnosed as having precursor B-ALL and assessed clinical relevance of the TEL/AML1 rearrangement and additional genetic abnormalities. RESULTS: The frequency of TEL/AML1 was 17.1% (21/123) in patients with precursor B-ALL. TEL/ AML1-positive group showed male predominance (P=0.012) and younger age of onset than TEL/ AML1-negative group by 1.6 yr (P=0.013). The outcome of TEL/AML1-positive group tended to show lower incidences of relapse (1/21 vs 20/102), death (1/21 vs 17/102) and longer event free survival. Among TEL/AML1-positive patients, unrearranged TEL deletion, AML1 gain, and unrearranged TEL deletion combined with AML1 gain were detected in 61.9%, 23.8%, and 9.5%, respectively. There were no significant differences in the clinical features and outcome according to the presence or absence of additional genetic changes. CONCLUSIONS: The frequency of TEL/AML1 and additional genetic changes in TEL and AML1 is higher than previous studies in Korean children, and in close agreement with usually reported one, 20-25%. TEL/AML1-positive group showed a tendency toward better prognosis. Further study is needed to clarify the prognostic significance of additional changes in TEL and AML1 based on a large sample size.
Age Factors ; Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Core Binding Factor Alpha 2 Subunit/*genetics ; Disease-Free Survival ; Female ; Gene Deletion ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukocyte Count ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/mortality ; Prognosis ; Proto-Oncogene Proteins c-ets/*genetics ; Repressor Proteins/*genetics ; Republic of Korea ; Survival Rate ; *Translocation, Genetic