Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Objective: The aim of this study was to investigate differentially expressed genes and their functions in the hippocampus and striatum after heroin administration in cynomolgus macaques of different ages. Methods: Cynomolgus monkeys were divided by age as follows: 1 year (A1, n = 2); 3 to 4 years (A2, n = 2); 6 to 8 years (A3, n = 2); and older than 11 years (A4, n = 2). After heroin was injected intramuscularly into the monkeys (0.6 mg/kg), we performed large-scale transcriptome profiling in the hippocampus (H) and striatum (S) using RNA sequencing technology. Some genes were validated with real-time quantitative PCR. Results: In the hippocampus, the gene expression of A1H was similar to that of A4H, while the gene expression of A2H was similar to that of A3H. Genes associated with the mitogen-activated protein kinase signaling pathway (STMN1, FGF14, and MAPT) and -aminobutyric acid-ergic synapses (GABBR2 and GAD1) were differentially expressed among control and heroin-treated animals. Differential gene expression between A1S and A4S was the least significant, while differential gene expression between A3S and A2S was the most significant. Genes associated with the neurotrophin signaling pathway (NTRK1 and NGFR), autophagy (ATG5), and dopaminergic synapses (AKT1) in the striatum were differentially expressed among control and heroin-treated animals. Conclusion These results suggest that even a single heroin exposure can cause differential gene expression in the hippocampus and striatum of nonhuman primates at different ages.

PURPOSE: The treatment strategy for elderly patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) has not been established because of poor treatment tolerability and lack of data. MATERIALS AND METHODS: This multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcomes of patients older than 80 years who were diagnosed with DLBCL at 19 institutions in Korea between 2005 and 2016. RESULTS: A total of 194 patients were identified (median age, 83.3 years). Of these, 114 patients had an age-adjusted International Prognostic Index (aaIPI) score of 2-3 and 48 had a Charlson index score of 4 or more. R-CHOP was given in 124 cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in nine cases, and surgery alone in two cases. Twenty-nine patients did not undergo any treatment. The median number of chemotherapy cycles was three. Only 37 patients completed the planned treatment cycles. The overall response rate from 105 evaluable patients was 90.5% (complete response, 41.9%). Twentynine patients died due to treatment-related toxicities (TRT). Thirteen patients died due to TRT after the first cycle. Median overall survival was 14.0 months. The main causes of death were disease progression (30.8%) and TRT (27.1%). In multivariate analysis, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment. CONCLUSION: Age itself should not be a contraindication to treatment. However, since elderly patients show higher rates of TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents is needed.
Aged* ; B-Lymphocytes* ; Cause of Death ; Creatinine ; Disease Progression ; Drug Therapy ; Humans ; Hypoalbuminemia ; Korea ; Lymphoma, B-Cell* ; Multivariate Analysis ; Retrospective Studies*

Clostridium difficile is the most common nosocomial pathogen of the gastrointestinal tract. Pseudomembranous colitis occurs as a result of a severe inflammatory response to Clostridium difficile toxins. Pseudomembranous colitis is an increasingly frequent cause of morbidity and mortality among elderly hospitalized patients. Diarrhea is the most common manifestation. According to the literature, stools are almost never grossly bloody, and range from soft and unformed to watery or mucoid in consistency. We now report the cases of three patients with pseudomembranous colitis whose main clinical manifestation was hematochezia.
Aged ; Clostridium difficile ; Diarrhea ; Enterocolitis, Pseudomembranous ; Gastrointestinal Hemorrhage ; Gastrointestinal Tract ; Humans

PURPOSE: To demonstrate the presence of nerve fibers including nociceptive fibers in synovium of human knee joint using immunohistochemistry. MATERIALS AND METHODS: 10 Synovial membrane tissues of knee joint obtained from 5 cadavers were analyzed immunohistochemically using antibodies to protein gene product 9.5, betaIII-tubulin, substance P and calcitonin gene-related peptide (CGRP). RESULTS: Many nerve fibers immunoreactive for protein gene product 9.5 and betaIII-tubulin were demonstrated in synovial folds of human knee joints. Also, immunostaining showed the presence of free nerve ending fibers immunoreactive for substance P and calcitonin gene-related peptide in synovium. CONCLUSION: The presence of putative nerve fibers including nociceptive fibers in synovial folds supports a possible role for theses structures as source of knee joint pain.
Antibodies ; Cadaver ; Calcitonin Gene-Related Peptide ; Humans* ; Immunohistochemistry ; Knee Joint ; Knee* ; Nerve Endings ; Nerve Fibers* ; Substance P ; Synovial Membrane*

PURPOSE: We wanted to investigate the effects of Troglitazone (TRO) on the cellular growth in two human osteosarcoma cell lines (U2OS and HOS). MATERIALS AND METHODS: Cell viability was assessed by performing trypan blue exclusion assay. FACScan analysis was performed to study the cell cycle and apoptosis. Antibodies against PTEN, tAkt, pAKt, Bcl-2, Bax, pRB, p21(Cip1), and beta-actin were used in the Western blot analysis. RESULTS: TRO inhibited the growth of both the osteosarcoma cell lines. TRO induced G0/G1 arrest in the cell cycle progression for both osteosarcoma cell lines. TRO induced the apoptosis of HOS cells, but it decreased apoptosis of the U2OS cells. TRO induced Rb dephosphorylation and the increased expression of p21(Cip1). TRO increased the PTEN and Bcl-2 expressions and it decreased the level of pAkt, pRb and Bax. CONCLUSION: The present study suggested that TRO may be used as a chemotherapeutic agent for the treatment of human OS. Yet further study is required for uncovering the precise the mechanism of TRO.
Actins ; Antibodies ; Apoptosis ; Blotting, Western ; Cell Cycle ; Cell Line* ; Cell Survival ; Humans ; Osteosarcoma* ; Peroxisomes* ; Trypan Blue

BACKGROUND: To evaluate the efficacy of arterial switch operation for transposition of great arteries, serial echocardiographic studies were performed in 8 patients who underwent the surgery between 1989 and 1998 at Dept. of Thoracic & Cardiovascular Surgery, Yeungnam University Hospital in Daegu City, Korea. MATERIAL AND METHOD: Follow-up period ranged from 6 months to 11 years(average of 4.1 years). Body weight ranged from 2.6kg to 4.8kg, with average of 3.6kg. 5 of 8 patients were preoperatively diagnosed as TGA+VSD, and 3 as TGA+IVS. LV function was evaluated by the measurement of LV shortening fraction, LVSTI, and LVEF. RVSTI was also measured. Postoperative function of valve and growth of great vessels were analyzed by the measurement of PSPGV, valvular regurgitation, LA/AO ratio, root dimension of aorta and pulmonary artery, comparing with the age matched controls, respectively. RESULT: LVEF had an average of 65.0+/-9.03% which is tended to increase serially. LVAOPG had an average of 15.9mmHg. RVPAPG, 27.5mmHg. From the measurement of aortic root dimension of 6 patients at end-systole, aortic root growth was assumed to increase more than the mean value of normal growth. PA root dimension at end-systole showed a similar growth progress when compared with age matched normal controls. Postoperative pulmonic valve regurgitation was noted in 5 of total 8 patients, in which 1 patient who showed grade 2 and 4 showed below grade 1. AR, in 6 patients and all grade 1. Except 1 patient, all the valvular regurgitations were below grade 1, which was presumed to be clinically insignificant. CONCLUSION: LV function after arterial switch operation was maintained relatively well. Mild neoaortic stenosis was noted. Neopulmonary stenosis and regurgitation were less than moderate degree and surgical correction was not deemed to be necessary. Growth progress of aortic root was above normal than controls and PA root growth was similar to the normal controls, postoperatively. However, further change and refinement of surgical technique will decrease the incidence of neopulmonary stenosis and regurgitation.
Aorta ; Arteries* ; Body Weight ; Constriction, Pathologic ; Daegu ; Echocardiography* ; Follow-Up Studies* ; Humans ; Incidence ; Korea ; Pulmonary Artery ; Transposition of Great Vessels

Lemierre's syndrome is characterized by a rare fulminant condition resulting from primary oropharyngeal infection followed by secondary septic thrombophlebitis of the internal jugular vein and metastatic infection. A forty-year-old man who had been on ventilator due to severe chest trauma, showed severe reddish inflammatory swelling of the right cervical soft tissue and newly developed pneumonia. He went into in septic condition shortly thereafter. Thrombophlebitis with central abscess in the right internal jugular vein was identified by neck CT and MRA(magnetic resonance angiography). Right cervical swelling worsened in spite of clindamycin and heparin therapy. We performed immediate surgery for removal of septic thrombus and resection of internal jugular vein. Patient's septic condition, pneumonia, and local inflammatory reaction were improved within several days after surgery.
Abscess ; Clindamycin ; Heparin ; Jugular Veins ; Lemierre Syndrome* ; Neck ; Pneumonia ; Thorax ; Thrombophlebitis ; Thrombosis ; Ventilators, Mechanical

Aortic dissection after aortic valve replacement(AVR) is rare, but it is considered a definite disease entity. It's risk factors are a dilated ascending aorta(>or=50 mm) at the time of AVR, hypertension, and thin fragile aortic wall. We report the surgical treatment of a patient who had ascending aortic dissection 7 years after having undergone AVR due to aortic regurgitation associated with a dilated ascending aorta(50mm in outer diameter).
Aneurysm, Dissecting ; Aortic Valve Insufficiency ; Aortic Valve* ; Humans ; Hypertension ; Risk Factors

This experiment tried to elucidate the characteristics of senescence and differentiation in the reconstituted skin and the monolayer cultured human keratinocytes in vitro, respectively. While the keratinocytes were cultivated from undifferentiated state to completely senescent and differentiated, the monolayer cultured cells of every passage were doubly stained with SA-beta-gal initially, then keratins or involucrin. We also performed the SA-beta-gal enzyme staining and the immuno-reaction such as keratins or involucrin in the reconstituted skin. The results were as follows: Lack of reactivity against SA-beta-gal in the reconstituted skin indicated that there was no senescence occurred. The reconstituted skin showed decreased expression of K10 and preceded expression of involucrin compare to in vivo skin. Nevertheless, the reconstituted skin which did not express the K10 or involucrin in the basal cell maintained the differentiation system similar to that of in vivo skin. On the other hand, the monolayer cultured keratinocytes showed a thoroughly different pattern in the senescent and differentiating process. SA-beta-gal was colocalized with K10 or involucrin in the cells of high percentage ratio by the double staining method, and this indicated that the senescence and differentiation in the kratinocytes were simultaneously progressed. Reaching the nearer stage leading to the cell death, the cells choosed the one of senescence or differentiation pathway. It was supported by the fact that the percentage index of double staining together with SA-beta-gal and involucrin was lower at passage 5 than passage 1~4. The SA-beta-gal's reactivity was maximally reached at passage 4 and the involucrin maximally reached at passage 5. These trends suggested that the senescence was preceded by the differentiation. In conclusion, the reconstituted skin maintained only the differentiation system without the cell senescent process similar to the in vivo while the senescent and differentiating events were simultaneously processed in the monolayer cultured keratinocytes.
Aging ; Cell Aging* ; Cell Death ; Cells, Cultured ; Hand ; Humans* ; Keratinocytes* ; Skin*