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101.
Ahn YM Chang JS Kim Y Lee KY Kim JH Kim SC Maeng SJ Kim YS 《International clinical psychopharmacology》2005,20(3):157-161
The present study aimed to elucidate the effectiveness of clozapine treatment in reducing the disabling period of chronically ill schizophrenic patients by investigating their rehospitalization status. Of 232 schizophrenic patients with a history of clozapine use who were recruited from the clinic at Seoul National University Hospital, 117 were selected who had been followed up for more than 1 year with respect to rehospitalization. To obtain information about the period before the clozapine change, a chart review of these 117 patients was conducted. The number and length of hospitalizations of the patients significantly decreased after clozapine treatment compared to the same period before clozapine treatment. The hospital days per year of the patients were also decreased significantly after clozapine introduction. By analysing 38 patients who were followed up for more than 5 years, it was suggested that the decrease in the number and length of hospitalizations was substantially sustained for up to 5 years after clozapine treatment. This study showed that the number and length of hospitalizations are significantly decreased by long-term clozapine treatment and that this effect can positively affect the social outcome of schizophrenic patients. 相似文献
102.
Kim JS Jeung HK Cheong JW Maeng H Lee ST Hahn JS Ko YW Min YH 《British journal of haematology》2004,124(2):166-178
Apicidin, a histone deacetylase inhibitor, is a novel cyclic tetrapeptide with potent antiproliferative activity against various cancer cells. We examined whether apicidin potentiates the imatinib-induced apoptosis of Bcr-Abl-positive human leukaemia cells. In K562 cells, the co-administration of minimally toxic concentrations of imatinib and apicidin (imatinib/apicidin) for 48 h produced a marked increase in mitochondrial damage, processing of caspase cascades and apoptosis. Similar results were observed in leukaemic blasts obtained from patients with chronic myeloid leukaemia in blast crisis. Imatinib/apicidin co-treatment for 48 h resulted in a near complete loss of the full-length XIAP (X-linked inhibitor of apoptosis) protein, with a corresponding increase in the 29-kDa XIAP cleavage product. Both the degradation of XIAP and increased release of second mitochondria-derived activator of caspase/direct IAP-binding protein with low pI (Smac/DIABLO) into the cytosol were abrogated by pretreatment with the caspase-3 inhibitor DEVD-CHO. Imatinib/apicidin co-treatment for 48 h produced a prominent decrease in Bcr-Abl protein levels in a caspase-dependent manner. In summary, these data indicate that apicidin potentiates the imatinib-induced apoptosis of Bcr-Abl-positive leukaemia cells through the enhanced activation of the mitochondria-dependent caspase cascades, accompanied by caspase-dependent downregulation of Bcr-Abl and XIAP. These findings generate a rationale for further investigation of apicidin and imatinib as a potential therapeutic strategy in Bcr-Abl-positive leukaemias. 相似文献
103.
Maeng M Jensen LO Tilsted HH Kaltoft A Kelbaek H Abildgaard U Villadsen A Aarøe J Thayssen P Krusell LR Christiansen EH Bøtker HE Kristensen SD Ravkilde J Madsen M Sørensen HT Rasmussen K Thuesen L Lassen JF 《The American journal of cardiology》2011,(9):1232-1237
Diabetes is associated with an increased risk of major adverse cardiac events after percutaneous coronary intervention. We compared clinical outcomes in patients with and without diabetes mellitus treated with the second-generation Endeavor zotarolimus-eluting stent (ZES) or the first-generation Cypher Select+ sirolimus-eluting stent (SES). We randomized 2,332 patients to treatment with ZESs (n = 1,162, n = 169 diabetics) or SESs (n = 1,170, n = 168 diabetics) and followed them for 18 months. Randomization was stratified by presence/absence of diabetes. The primary end point was major adverse cardiac events defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Secondary end points included these individual end points plus all-cause mortality and target lesion revascularization. In diabetic patients, use of ZES compared to SES was associated with an increased risk of major adverse cardiac events (18.3% vs 4.8%, hazard ratio 4.05, 95% confidence interval 1.86 to 8.82), myocardial infarction (4.7% vs 0.6%, hazard ratio 8.09, 95% confidence interval 1.01 to 64.7), target vessel revascularization (14.2% vs 3.0%, hazard ratio 4.99, 95% confidence interval 1.90 to 13.1), and target lesion revascularization (12.4% vs 1.2%, hazard ratio 11.0, 95% confidence interval 2.59 to 47.1). In patients without diabetes differences in absolute risk decrease were smaller but similarly favored SES. In conclusion, implantation of ZESs compared to SESs is associated with a considerable increased risk of adverse events in patients with diabetes at 18-month follow-up. 相似文献
104.
105.
Daniel Ranch Martin YH Zhang Anthony A Portale Farzana Perwad 《Journal of bone and mineral research》2011,26(8):1883-1890
In X‐linked hypophosphatemia (XLH) and in its murine homologue, the Hyp mouse, increased circulating concentrations of fibroblast growth factor 23 (FGF‐23) are critical to the pathogenesis of disordered metabolism of phosphate (Pi) and 1,25‐dihydroxyvitamin D [1,25(OH)2D]. In this study, we hypothesized that in Hyp mice, FGF‐23‐mediated suppression of renal 1,25(OH)2D production and Pi reabsorption depends on activation of mitogen‐activated protein kinase (MAPK) signaling. Wild‐type and Hyp mice were administered either vehicle or the MEK inhibitor PD0325901 (12.5 mg/kg) orally daily for 4 days. At baseline, the renal abundance of early growth response 1 (egr1) mRNA was approximately 2‐fold greater in Hyp mice than in wild‐type mice. Treatment with PD0325901 greatly suppressed egr1 mRNA abundance in both wild‐type and Hyp mice. In Hyp mice, PD0325901 induced an 8‐fold increase in renal 1α‐hydroxylase mRNA expression and a 4‐fold increase in serum 1,25(OH)2D concentrations compared with vehicle‐treated Hyp mice. Serum Pi levels in Hyp mice increased significantly after treatment with PD0325901, and the increase was associated with increased renal Npt2a mRNA abundance and brush‐border membrane Npt2a protein expression. These findings provide evidence that in Hyp mice, MAPK signaling is constitutively activated in the kidney and support the hypothesis that the FGF‐23‐mediated suppression of renal 1,25(OH)2D production and Pi reabsorption depends on activation of MAPK signaling via MEK/ERK1/2. These findings demonstrate the physiologic importance of MAPK signaling in the actions of FGF‐23 in regulating renal 1,25(OH)2D and Pi metabolism. © 2011 American Society for Bone and Mineral Research 相似文献
106.
107.
Lee KR Maeng HJ Chae JB Chong S Kim DD Shim CK Chung SJ 《Drug metabolism and pharmacokinetics》2010,25(5):430-441
The objectives of this study were to evaluate the relative contribution of the direct pathway in overall brain transport for 17 model drugs with different physicochemical properties after nasal administrations and to identify factors that govern the fraction of the dose transported to the brain via the direct pathway (F(a, direct)). When the model drugs were nasally administered to rats, 5 of the 17 model drugs were delivered to a significant extent to the brain via the direct pathway. Multiple linear regression analyses showed that the correlation between various physicochemical properties and F(a, direct) was not statistically significant, indicative of a lack of primary physicochemical determinants in the direct transport pathway. Transporters such as rOAT3 and rOCT2 were expressed at significant levels in rat olfactory epithelia, and uptakes of standard substrates were significantly decreased in HEK293 cells expressing rOAT3 and rOCT2 in the presence of the five model drugs that were delivered to appreciable extents to the brain via the direct pathway. Therefore, these observations indicate that carrier-mediated transport may play a role in the brain delivery of drugs from the nose via the direct transport pathway. 相似文献
108.
Mun Ki Min Seok Ran Yeom Ji Ho Ryu Yong In Kim Maeng Real Park Sang Kyoon Han Seong Hwa Lee Suck Ju Cho 《Resuscitation》2013
Objectives
This study was designed to assess changes in cardiopulmonary resuscitation (CPR) quality and rescuer fatigue when rescuers are provided with a break during continuous chest compression CPR (CCC-CPR).Methods
The present prospective, randomized crossover study involved 63 emergency medical technician trainees. The subjects performed three different CCC-CPR methods on a manikin model. The first method was general CCC-CPR without a break (CCC), the second included a 10-s break after 200 chest compressions (10/200), and the third included a 10-s break after 100 chest compressions (10/100). All methods were performed for 10 min. We counted the total number of compressions and those with appropriate depth every 1 min during the 10 min and measured mean compression depth from the start of chest compressions to 10 min.Results
The 10/100 method showed the deepest compression depth, followed by the 10/200 and CCC methods. The mean compression depth showed a significant difference after 5 min had elapsed. The percentage of adequate compressions per min was calculated as the proportion of compressions with appropriate depth among total chest compressions. The percentage of adequate compressions declined over time for all methods. The 10/100 method showed the highest percentage of adequate compressions, followed by the 10/200 and CCC methods.Conclusion
When rescuers were provided a rest at a particular time during CCC-CPR, chest compression quality increased compared with CCC without rest. Therefore, we propose that a rescuer should be provided a rest during CCC-CPR, and specifically, we recommend a 10-s rest after 100 chest compressions. 相似文献109.
110.
Tim A Holt Tina D Hunter Candace Gunnarsson Nada Khan Paul Cload Gregory YH Lip 《The British journal of general practice》2012,62(603):e710-e717