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1.  Prostate cancer detection rate in patients with fluctuating prostate-specific antigen levels on the repeat prostate biopsy 
Prostate International  2014;2(1):26-30.
Purpose:
To evaluate whether the risk of prostate cancer was different according to the pattern of fluctuation in prostate-specific antigen (PSA) levels in patients undergoing repeat transrectal ultrasound-guided prostate biopsy (TRUS-Bx).
Methods:
From March 2003 to December 2012, 492 patients underwent repeat TRUS-Bx. The patients were stratified into 3 groups based on the PSA fluctuation pattern: group 1 (continuous elevation of PSA, n=169), group 2 (PSA fluctuation with PSA velocity [PSAV]≥1.0 ng/mL/yr, n=123), and group 3 (PSA fluctuation with PSAV<1.0 ng/mL/yr, n=200).
Results:
Prostate cancer was detected in 112 of 492 patients (22.8%) in the repeat biopsy set. According to the PSA fluctuation pattern, prostate cancer detection rates at repeat TRUS-Bx were 29.6% (50/169) for patients with continuously increasing PSA, 30.1% (37/123) for PSA fluctuation with PSAV ≥1.0 ng/mL/yr, and 12.5% (25/200) for PSA fluctuation with PSAV <1.0 ng/mL/yr. Multivariate analysis showed that PSA fluctuation pattern and high grade prostatic intraepithelial neoplasia at initial TRUS-Bx were the predictive parameters for positive repeat biopsies. Among the 96 patients (85.7%) who underwent radical prostatectomy, no significant differences in pathologic outcomes were found according to the PSA fluctuation pattern.
Conclusions:
The current study shows that the risk of prostate cancer at repeat TRUS-Bx was higher in men with a fluctuating PSA level and PSAV≥1.0 ng/mL/yr than in those with a fluctuating PSA level and PSAV<1.0 ng/mL/yr.
doi:10.12954/PI.13037
PMCID: PMC3970986
Prostate-specific antigen; Prostatic neoplasms; Biopsy; Needles
2.  A comprehensive review of neuroanatomy of the prostate 
Prostate International  2013;1(4):139-145.
Although oncologic efficacy is the primary goal of radical prostatectomy, preserving potency and continence is also important, given the indolent clinical course of most prostate cancers. In order to preserve and recover postoperative potency and continence after radical prostatectomy, a detailed understanding of the pelvic anatomy is necessary to recognize the optimal nerve-sparing plane and to minimize injury to the neurovascular bundles. Therefore, we reviewed the most recent findings from neuroanatomic studies of the prostate and adjacent tissues, some of which are contrary to the established consensus on pelvic anatomy. We also described the functional outcomes of radical prostatectomies following improved anatomical understanding and development of surgical techniques for preserving the neurovascular bundles.
doi:10.12954/PI.13020
PMCID: PMC3879050  PMID: 24392437
Prostatic neoplasms; Neurovascular bundle; Fascial anatomy; Penile erection; Urinary incontinence
3.  Prevalence and Clinical Features of Detrusor Underactivity among Elderly with Lower Urinary Tract Symptoms: A Comparison between Men and Women 
Korean Journal of Urology  2012;53(5):342-348.
Purpose
To identify the prevalence and clinical features of detrusor underactivity (DU) in elderly men and women presenting with lower urinary tract symptoms (LUTS).
Materials and Methods
We reviewed 1,179 patients aged over 65 years who had undergone a urodynamic study for LUTS with no neurological or anatomical conditions. DU was defined as a bladder contractility index <100 and a maximal flow rate (Qmax) ≤12 ml/s combined with a detrusor pressure at Qmax ≤10 cmH2O for men and women, respectively.
Results
Of the patients, 40.2% of men and 13.3% of women were classified as having DU (p<0.001). Types of clinical symptoms were not significantly different between patients with and without DU. In men, whereas the prevalence of bladder outlet obstruction (BOO) was constant across the age spectrum, the prevalence of DU and detrusor overactivity (DO) increased with age, and 46.5% of men with DU also had DO or BOO. In women, the prevalence of DU also increased with age, and the trend was more remarkable in women aged over 70 years. DU was accompanied by DO or urodynamic stress urinary incontinence (USUI) in 72.6% of the women with DU. Women with DU were found to have lower cystometric capacity and exhibited a greater incidence of reduced compliance than did women without DU.
Conclusions
DU was a common mechanism underlying LUTS in the elderly population, especially in men. One half of the men and three quarters of the women with DU also had other pathologies such as DO, BOO, or USUI.
doi:10.4111/kju.2012.53.5.342
PMCID: PMC3364474  PMID: 22670194
Aged; Prevalence; Urinary bladder; Urination disorders; Urodynamics
4.  Sunitinib Malate Synergistically Potentiates Anti-Tumor Effect of Gemcitabine in Human Bladder Cancer Cells 
Korean Journal of Urology  2011;52(1):55-63.
Purpose
Sunitinib malate (Sutent; Pfizer, New York, NY, USA) is a highly selective multi-targeted agent and has been reported to have potent anti-tumor effects against various tumors, including renal cell carcinoma and gastrointestinal stromal tumors. In this study, we explored in vitro the anti-tumor effect and related molecular mechanisms of sunitinib malate against human bladder cancer cell lines. We also determined the synergistic anti-tumor effect between sunitinib and conventional cytotoxic drugs, cisplatin and gemcitabine, in bladder cancer cells.
Materials and Methods
Six human cancer cell lines (HTB5, HTB9, T24, UMUC14, SW1710, and J82) were exposed to an escalating dose of sunitinib alone or in combination with cisplatin/gemcitabine, and the cytotoxic effect of the drugs was examined by CCK-8 assay. The synergistic effect between sunitinib and cisplatin/gemcitabine was determined by the combination index (CI) and clonogenic assay. Alterations in cell cycle (cyclin D, B1), survival (p-Akt, t-Akt), and apoptosis (Bax, Bad) regulator expression were analyzed by Western blotting.
Results
Like cisplatin and gemcitabine, sunitinib exerted a dose- and time-dependent anti-tumor effect in bladder cancer cells. However, sunitinib exhibited entirely different sensitivity profiles from cisplatin and gemcitabine. Sunitinib suppressed the expression of cyclin B1, p-Akt, and t-Akt while augmenting the expression of cyclin D and pro-apoptotic Bax and Bad in HTB5 cells. Analysis of the drug combination by the isobolic method and clonogenic assay revealed that sunitinib acts in synergy with gemcitabine in HTB5 cells.
Conclusions
These results indicate that sunitinib malate has a potent anti-tumor effect and may synergistically enhance the anti-tumor effect of gemcitabine in human bladder cancer cells.
doi:10.4111/kju.2011.52.1.55
PMCID: PMC3037508  PMID: 21344032
Carcinoma; Cisplatin; Gemcitabine; Sunitinib; Urinary bladder
5.  Regulation of Repair Choice 
DNA repair  2009;8(10):1235-1241.
Cell cycle plays a crucial role in regulating the pathway used to repair DNA double-strand breaks (DSBs). In Saccharomyces cerevisiae, homologous recombination is primarily limited to non-G1 cells as the formation of recombinogenic single-stranded DNA requires CDK1-dependent 5′ to 3′ resection of DNA ends. However, the effect of cell cycle on non-homologous end joining (NHEJ) is not yet clearly defined. Using an assay to quantitatively measure the contributions of each repair pathway to repair product formation and cellular survival after DSB induction, we found that NHEJ is most efficient at G1, and markedly repressed at G2. Repression of NHEJ at G2 is achieved by efficient end resection and by the reduced association of core NHEJ proteins with DNA breaks, both of which depend on the CDK1 activity. Importantly, repression of 5′ end resection by CDK1 inhibition at G2 alone did not fully restore either physical association of Ku/Dnl4-Lif1 with DSBs or NHEJ proficiency to the level at G1. Expression of excess Ku can partially offset the inhibition of end joining at G2. The results suggest that regulation of Ku/Dnl4-Lif1 affinity for DNA ends may contribute to the cell cycle-dependent modulation of NHEJ efficiency.
doi:10.1016/j.dnarep.2009.07.007
PMCID: PMC2748135  PMID: 19699692
Double strand break; End joining; Repair choice; Cell cycle
6.  Combination of clinical characteristics and transrectal ultrasound-guided biopsy to predict lobes without significant cancer: application in patient selection for hemiablative focal therapy 
Prostate International  2014;2(1):37-42.
Purpose:
A major limitation of performing hemiablative focal therapy (FT) for prostate cancer (PCa) is the possibility of accompanying significant cancer in the contralateral side of the prostate that is missed on prostate biopsy. We attempted to verify whether clinical and biopsy-related parameters can be used to predict the absence of significant cancer in the prostate lobe.
Methods:
We assumed that hemiablative FT could be performed in patients with low-risk PCa, with unilateral tumors as assessed by transrectal ultrasound-guided biopsy. We evaluated 214 patients who had undergone radical prostatectomy (RP) and fulfilled the eligibility criteria. Seemingly preserved lobes, defined by the absence of cancer on biopsy, were classified as lobes with no cancer (LNC), lobes with insignificant cancer (LIC), and lobes with significant cancer (LSC) according to RP pathology. Cases with an estimated tumor volume of <0.5 mL, a Gleason score of <7, and organ confinement without Gleason pattern 4 were classified as LIC. Univariate and multivariate logistic regression analyses were performed to identify predictors for LSC. Predictive accuracies of the multivariate models were assessed using receiver operating characteristic curve-derived areas under the curve.
Results:
Of 214 evaluated lobes, 45 (21.0%), 62, (29.0%), and 107 (50.0%) were classified as LNC, LIC, and LSC, respectively. Among the clinical and biopsy-related parameters, prostate-specific antigen density and prostate volume were identified as significant predictors for LSC in univariate regression analysis. However, multivariate analysis did not identify an independent predictor. Predictive accuracies of the multivariate models did not exceed 70.4%.
Conclusions:
Conventional parameters have limited value in predicting LSC in patients who are candidates for hemiablative FT.
doi:10.12954/PI.13031
PMCID: PMC3970988
Prostatic neoplasms; Tissue preservation; Patient selection
7.  Hand-Assisted Retroperitoneoscopic Nephroureterectomy without Hand-assisted Device 
Journal of Korean Medical Science  2005;20(5):901-903.
Various laparoscopic nephroureterectomy techniques for urothelial carcinoma of the upper urinary tract have been developed to minimize postoperative discomfort and the necessity for a lengthy convalescence. We performed hand-assisted retroperitoneoscopic nephroureterectomy without hand-assisted device in 3 male patients with urothelial carcinoma of the distal ureter. Average operative time and estimated blood loss were 251 min (range 235 to 280) and 250 mL (range 200 to 300), respectively. Complication did not occur and conversion to open surgery was not necessary in all cases. Postoperative analgesic requirements were moderate and the time to regular diet intake averaged 3 days (range 2 to 4). None of the patients had a positive margin on the final pathologic specimen. At the average follow-up of 8.1 months, no regional recurrence, port-site metastasis, bladder recurrence, or distant metastasis were noted in any patient. We described our initial experience with the described technique, which obviates the need for midprocedural patient repositioning.
doi:10.3346/jkms.2005.20.5.901
PMCID: PMC2779296  PMID: 16224173
Ureteral Neoplasms; Retroperitoneal Space; Laparoscopy
8.  Comparison of 30 mg and 40 mg of Mitomycin C Intravesical Instillation in Korean Superficial Bladder Cancer Patients: Prospective, Randomized Study 
Purpose
A prospective study was performed to compare the efficacy and safety of intravesical mitomycin C (MMC) instillation for the prophylaxis of bladder cancer at different concentrations (30 mg or 40 mg).
Materials and Methods
Ninety-seven patients that received complete transurethral resection for superficial bladder cancer were divided into two-randomized groups. One group (n=53) received 30 mg and the other group (n=44) received 40 mg dose of MMC weekly for 8 weeks, which was followed monthly for 10 months as maintenance therapy. The recurrence rates and side effects in both groups were recorded. The mean follow-up period was 32.4 months in the 30 mg group, and 32.0 months in the 40 mg group.
Results
The overall one and two year recurrence rates were 19% and 24% in the 30 mg group, and 12% and 22% in the 40 mg group, which was not significantly different (p>0.05). Most of the side effects were mild and transient. Moreover, the rates of the individual side effects were not statistically different in the two groups.
Conclusion
Our comparison of 30 mg and 40 mg intravesical MMC instillation showed no difference in either response or side effects. Thus, we tentatively conclude that we can use 30 mg instead of 40 mg as an intravesical MMC instillation dose.
doi:10.4143/crt.2005.37.1.44
PMCID: PMC2785421  PMID: 19956509
Bladder neoplasms; Mitomycin C; Instillation therapy
9.  Comparison of respiratory mechanics between sevoflurane and propofol-remifentanil anesthesia for laparoscopic colectomy 
Korean Journal of Anesthesiology  2014;66(2):131-135.
Background
The creation of pneumoperitoneum and Trendelenburg positioning during laparoscopic surgery are associated with respiratory changes. We aimed to compare respiratory mechanics while using intravenous propofol and remifentanil vs. sevoflurane during laparoscopic colectomy.
Methods
Sixty patients undergoing laparoscopic colectomy were randomly allocated to one of the two groups: group PR (propofol-remifentanil group; n = 30), and group S (sevoflurane group; n = 30). Peak inspiratory pressure (PIP), dynamic lung compliance (Cdyn), and respiratory resistance (Rrs) values at five different time points: 5 minutes after induction of anesthesia (supine position, T1), 3 minutes after pneumoperitoneum (lithotomy position, T2), 3 minutes after pneumoperitoneum while in the lithotomy-Trendelenburg position (T3), 30 minutes after pneumoperitoneum (T4), and 3 minutes after deflation of pneumoperitoneum (T5).
Results
In both groups, there were significant increases in PIP and Rrs while Cdyn decreased at times T2, T3, and T4 compared to T1 (P < 0.001). The Rrs of group PR for T2, T3, and T4 were significantly higher than those measured in group S for the corresponding time points (P < 0.05).
Conclusions
Respiratory mechanics can be adversely affected during laparoscopic colectomy. Respiratory resistance was significantly higher during propofol-remifentanil anesthesia than sevoflurane anesthesia.
doi:10.4097/kjae.2014.66.2.131
PMCID: PMC3948440  PMID: 24624271
Laparoscopy; Propofol; Remifentanil; Respiratory mechanics; Sevoflurane
10.  Molecular Characterization of Giardia duodenalis and Cryptosporidium parvum in Fecal Samples of Individuals in Mongolia 
The Giardia and Cryptosporidium species are widespread and frequent diarrhea-related parasites affecting humans and other mammalian species. The prevalence of these parasites in Mongolia is currently unknown. Therefore, we performed molecular analyses of G. duodenalis and C. parvum in stool samples from 138 patients hospitalized with diarrhea in Mongolia using nested polymerase chain reaction (PCR). A total of 5 (3.62%) and 7 (5.07%) fecal samples were positive for G. duodenalis and C. parvum, respectively. Giardia duodenalis and C. parvum infections were prevalent in children < 9 years of age. The assemblage-specific fragment patterns for the β-giardin gene of G. duodenalis revealed that all five samples testing positive belonged to Assemblage A by the PCR-restriction fragment polymorphism method. For sequencing and phylogenetic analysis of the 18S rDNA and HSP70 genes of all seven patients testing positive the genes were further identified to be of the C. parvum bovine genotype. This study is the first to report the prevalence of G. duodenalis and C. parvum and its molecular characterization of fecal samples from individuals with diarrhea in Mongolia.
doi:10.4269/ajtmh.13-0271
PMCID: PMC3886425  PMID: 24249428
11.  Development of a Rabbit Model for a Preclinical Comparison of Coronary Stent Types In-Vivo 
Korean Circulation Journal  2013;43(11):713-722.
Along with the development of innovative stent designs, preclinical trials in animal models are essential. Many animal models have been used and appear to yield comparable results to clinical trials despite substantial criticisms about their validity. Among the animal models, porcine coronary artery models have been the standard models for the preclinical evaluation of endovascular devices. However, rapid growth rate, high body weight potential, and the propensity to develop granulomatous inflammatory reactions are major limitations of the porcine coronary artery model. Compared with porcine coronary artery models, the comparative rabbit iliac artery model has the advantages of being small and easy to handle and relatively inexpensive. Furthermore, the rabbit model has been known to reliably reflect human restenosis histopathologically and have major advantages such as pairwise comparison, which makes each animal serve as its own control subject, therefore, maximizing its statistical power for comparative testing. However, despite the widespread use of this model, a systematic description of the procedure and harvest protocols has never been published. This article describes the surgical procedure, stent implantation procedure, method for tissue harvesting, and how measurements are performed. Although the results of animal models may not perfectly extrapolate to humans, the comparative rabbit iliac artery model may be a useful tool for assessing and comparing the efficacy of new coronary stents with conventional stent systems. This thorough description of the techniques required for vascular access, stent implantation, tissue preparation, and measurement, should aid investigators wishing to begin using the comparative rabbit iliac artery model.
doi:10.4070/kcj.2013.43.11.713
PMCID: PMC3866309  PMID: 24363745
Prosthesis and implants; Stents; Model, animal; NZW rabbits
12.  Comparison of Continence Recovery Between Robot-Assisted Laparoscopic Prostatectomy and Open Radical Retropubic Prostatectomy: A Single Surgeon Experience 
Korean Journal of Urology  2013;54(9):598-602.
Purpose
To evaluate the recovery of continence after robot-assisted laparoscopic prostatectomy (RALP) and open radical retropubic prostatectomy (RRP).
Materials and Methods
We identified 258 patients who underwent surgery by a single surgeon to treat localized prostate cancer. The patients were divided into two groups according to operative method. In group 1, 146 consecutive patients underwent RALP, and in group 2, 112 patients underwent RRP. To compare the interval until the return of urinary continence between the two groups, we used the Kaplan-Meier method and the log-rank test and Cox proportional hazard regression analyses.
Results
Differences between the two groups were found in mean estimated blood loss (EBL; p<0.001) and the rate of nerve sparing (p=0.004). When continence was defined as the use of 0 to 1 pad per day, 100% of group 1 and 98.2% of group 2 reported continence at 12 months (p=0.189). When continence was defined as no pad use, however, there was a significant difference between the two groups at 12 months: group 1, 95.7%, and group 2, 70.7% (p<0.001). The factors affecting time until no pad use in the univariate analysis with a Cox proportional hazards model were operation method, age, neurovascular bundle saving, membranous urethral length (MUL), EBL, and apical shape. In the multivariate analysis, only operation method, age, and MUL retained significance.
Conclusions
Our study suggests that RALP is an independent factor for the recovery of continence and that RALP has advantages for postoperative continence recovery and the quality of continence compared with RRP.
doi:10.4111/kju.2013.54.9.598
PMCID: PMC3773589  PMID: 24044093
Prostate neoplasms; Prostatectomy; Robotics; Urinary incontinence
13.  Rhox in mammalian reproduction and development 
Homeobox genes play essential roles in embryonic development and reproduction. Recently, a large cluster of homeobox genes, reproductive homeobox genes on the X chromosome (Rhox) genes, was discovered as three gene clusters, α, β, and γ in mice. It was found that Rhox genes were selectively expressed in reproduction-associated tissues, such as those of the testes, epididymis, ovaries, and placenta. Hence, it was proposed that Rhox genes are important for regulating various reproductive features, especially gametogenesis in male as well as in female mammals. It was first determined that 12 Rhox genes are clustered into α (Rhox1-4), β (Rhox5-9), and γ (Rhox10-12) subclusters, and recently Rhox13 has also been found. At present, 33 Rhox genes have been identified in the mouse genome, 11 in the rat, and three in the human. Rhox genes are also responsible for embryonic development, with considerable amounts of Rhox expression in trophoblasts, placenta tissue, embryonic stem cells, and primordial germ cells. In this article we summarized the current understanding of Rhox family genes involved in reproduction and embryonic development and elucidated a previously unreported cell-specific expression in ovarian cells.
doi:10.5653/cerm.2013.40.3.107
PMCID: PMC3811726  PMID: 24179867
Embryonic development; Gametogenesis; Homeobox gene; Reproduction; Rhox; Stem cells
14.  Prevalence of Toxoplasma gondii Infection in Household Cats in Korea and Risk Factors 
Several epidemiological surveys have reported the prevalence of Toxoplasma gondii infection in stray cats in Korea, but little information is available on T. gondii infection in household cats. The aim of the present study was to assess the prevalence and risk factors of T. gondii infection among household cats reared in Seoul, Korea. A total of 474 blood samples were collected from clinically healthy household cats. All samples were tested using ELISA and PCR. The risk factor analysis was based on a questionnaire filled out by the owners. The overall positive rate for ELISA and PCR assays was 2.2% (10/437) and 2.1% (10/474), respectively. With regard to the origin of cats, the positive rates among cats adopted from the animal shelter and veterinary clinic for stray cats were significantly different (P<0.05). Our study demonstrated that the positive rate of T. gondii infection in household cats was low and that this low prevalence was assumed to be associated with keeping the cats indoors and restriction of eating raw food and uncooked meat. Therefore, we suggest that the owners check the origin of the cats prior to adoption to prevent infection of other animals, including humans.
doi:10.3347/kjp.2013.51.3.357
PMCID: PMC3712112  PMID: 23864749
Toxoplasma gondii; risk factor; household cat; PCR; ELISA
16.  Acute Modulations in Stratum Corneum Permeability Barrier Function Affect Claudin Expression and Epidermal Tight Junction Function via Changes of Epidermal Calcium Gradient 
Yonsei Medical Journal  2013;54(2):523-528.
Tight junction (TJ) is recognized as a second barrier of the skin. Altered expression of TJ proteins in various skin diseases characterized by the abnormal permeability barrier such as psoriasis suggests that TJ could be affected by stratum corneum (SC) barrier status. However, the physiological relationship between SC and TJ barrier remains to be investigated. Therefore, we examined the effect of SC barrier disruption on the expression of TJ proteins, claudin (Cldn)-1 and Cldn-4, and TJ barrier function in hairless mouse skin. We also investigated whether the alterations in epidermal Ca2+ affected TJ proteins expression in vivo. Repeated tape-stripping induced a sequential change of the expression and function of TJ. As early as 15-30 minutes after tape-stripping, downregulation of Cldn-1 and Cldn-4 immunoreactivity and protein level without change in mRNA level was found. This was accompanied by the abnormal leakage of lanthanum. However, by 1 hour Cldn-1 and Cldn-4 immunolocalization recovered along with normalized lanthanum permeation pattern. Moreover, the mRNA and protein levels of Cldn-1 and Cldn-4 were increased by 1 to 6 hours after tape-stripping. Inhibition of calcium loss by immersion of barrier-disrupted skin into a high Ca2+ solution prevented the dislocation of Cldn-1 and Cldn-4. Occlusion of barrier-disrupted skin delayed the restoration of Cldn-1 and Cldn-4. Our results suggest that the alteration of epidermal Ca2+ gradient caused by SC barrier perturbation affects the TJ structure and function and the faster recovery of TJ as compared to the SC barrier may imply the protective homeostatic mechanism of skin barrier.
doi:10.3349/ymj.2013.54.2.523
PMCID: PMC3575975  PMID: 23364991
Tight junction; claudin-1; claudin-4; calcium gradient; stratum corneum permeability barrier
17.  Paraoxonase 1 Gene Polymorphism Does Not Affect Clopidogrel Response Variability but Is Associated with Clinical Outcome after PCI 
PLoS ONE  2013;8(2):e52779.
Background
Paraoxonase (PON) is a high-density-lipoprotein (HDL) associated enzyme with antioxidative and anti-atherogenic property. Its function is associated with coronary artery disease and its activity genetically controlled. We evaluated whether genetic variation of PON-1 is associated with clinical outcome in a large cohort of Korean patients with drug-eluting stents implantation.
Methods
A total of 1676 patients with drug-eluting stent implantation were enrolled in the prospective CROSS-VERIFY cohort from June 2006 to June 2010. We genotyped the PON1-Q192R gene, measured clopidogrel on-treatment platelet reactivity (OPR), and analyzed lipid profiles. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis at 12 months.
Results
PON-1 genotyping data were available in 1336 patients. Since the Q-allele is associated with decreased PON-activity, we analyzed the outcome between patients with QQ/QR (815 patients, 61%) and those with RR-genotype (521 patients, 39%). After adjustment for common cardiac risk factors, the QQ/QR-genotype was an independent predictor of the primary thrombotic endpoint with an 11-fold increased risk (HR 11.6, 95% CI: 1.55–87.0), but not repeat revascularization (HR 1.12, 95% CI: 0.78–1.61). The QQ/QR-genotype was not associated with OPR (QQ/QR: 231±86 PRU vs. RR 236±82 PRU, p = 0.342) but higher small-dense LDL levels (1.20±0.12 mg/dL vs. 0.76±0.15 mg/dL, p = 0.027). The increased risk of thrombotic outcomes was more profound in acute coronary syndrome (ACS) patients compared with non-ACS patients.
Conclusion
PON1 Q-allele is an independent predictor of worse cardiovascular outcome independent of platelet function and is associated with significantly higher levels of small dense LDL-C.
doi:10.1371/journal.pone.0052779
PMCID: PMC3572125  PMID: 23418418
18.  Efficacy and tolerability of combined medication of two different antimuscarinics for treatment of adults with idiopathic overactive bladder in whom a single agent antimuscarinic therapy failed 
Objective
Recent studies have investigated a combination of two antimuscarinics for adult neurogenic bladder managed with clean intermittent catheterization or pediatric refractory overactive bladder (OAB). We assessed the efficacy and tolerability of this strategy in adults with idiopathic OAB.
Methods:
We reviewed 49 patients with idiopathic OAB who received combined antimuscarinic medication. Patients had serially received different kinds of antimuscarinics as monotherapy, but wished to take combined medication due to a lack of sufficient subjective improvement in urgency, even with dosage escalation. Efficacy was measured by changes of episodes of urgency, daytime voiding, nocturia and mean voided volume before and after the addition of the second antimuscarinic.
Results:
The mean duration of combined medication was 9.3 months. After adding the second antimuscarinic, urgency per day decreased from 3.8 to 1.9 (p < 0.001) and daytime voiding decreased from 10.4 to 7.4 (p < 0.001). The number of nocturia episodes and the mean voided volume also improved, although there was no statistical significance. Efficacy did not differ between the 29 cases, with non-selective and non-selective drugs and 20 cases with non-selective and M3 selective drugs. Thirty-three (67.3%) patients reported to have benefited from combined medication. Maximal flow rate and post-void residual volume did not change in either of the sexes. Eleven (22.4%) patients discontinued the combination due to continued ineffectiveness and dry mouth.
Conclusion:
This retrospective study suggests that combined medication can help adults with refractory idiopathic OAB. Combined medication was tolerated in most of our patients.
doi:10.5489/cuaj.269
PMCID: PMC3650812  PMID: 23671514
19.  Serologic Survey of Toxoplasmosis in Seoul and Jeju-do, and a Brief Review of Its Seroprevalence in Korea 
Knowledge of the prevalence of human Toxoplasma gondii infection is required in the Republic of Korea. In this study, we surveyed the seroprevalence of T. gondii infection and analyzed the risk factors associated with seropositivity among residents in 2 administrative districts; Seoul and the island of Jeju-do, which have contrasting epidemiologic characteristics. Sera and blood collected from 2,150 residents (1,114 in Seoul and 1,036 in Jeju-do) were checked for IgG antibody titers using ELISA and for the T. gondii B1 gene using PCR. In addition, participants completed a questionnaire that solicited information on gender, age, occupation, eating habits, history of contact with animals, and travel abroad. The T. gondii B1 gene was not detected in all residents examined. However, ELISA showed 8.0% (89 of 1,114 sera) positive for IgG antibodies against T. gondii in Seoul and 11.3% (117 of 1,036 sera) in Jeju-do. In both districts, the positive rates were higher in males than in females, and those 40-79 years of age showed higher rates than other ages. In Seoul, residents older than 70 years of age showed the highest positive rate, 14.9%, whereas in Jeju-do the highest prevalence, 15.6%, was in those in their sixties. The higher seropositive rate in Jeju-do than in Seoul may be related to eating habits and occupations. The present results and a review of related literature are indicative of an increased seroprevalence of T. gondii in Korea in recent years.
doi:10.3347/kjp.2012.50.4.287
PMCID: PMC3514419  PMID: 23230325
Toxoplasma gondii; seroprevalence; B1 gene; resident; Seoul; Jeju-do; IgG; ELISA
20.  Larval Anisakid Infections in Marine Fish from Three Sea Areas of the Republic of Korea 
The present study was performed to determine the infection status of anisakid larvae in marine fish collected from 3 sea areas of the Republic of Korea. Total 86 marine fish (8 species) collected from the East Sea (Goseong-gun, Gangwon-do), 171 fish (10 species) from the South Sea (Sacheon-si, Gyeongsangnam-do), and 92 fish (7 species) from the Yellow Sea (Incheon Metropolitan City) were examined by both naked eyes and artificial digestion method. Among the total of 349 fish examined, 213 (61.0%) were infected with 8 species of anisakid larvae, i.e., Anisakis simplex, 6 types of Contracaecum spp., and Raphidascaris sp., and the mean larval density was 13.8 per infected fish. Anisakid larvae were detected in 45 fish (52.3%) from the East Sea, 131 fish (76.6%) from the South Sea, and 37 fish (40.2%) from the Yellow Sea. The average numbers of larvae detected were 4.0, 16.6, and 15.9, respectively. Anisakis simplex larvae were detected in 149 fish (42.7%), and the mean larval density was 9.0 per infected fish. They were found in 26 fish (30.2%) collected from the East Sea, 96 fish (56.1%) from the South Sea, and 27 fish (29.3%) from the Yellow Sea. The average numbers of larvae detected were 2.9, 10.3, and 10.5, respectively. Conclusively, the present study suggests that the infection rate and density of anisakid larvae are more or less higher in the fish from the South Sea than those from the East Sea or the Yellow Sea.
doi:10.3347/kjp.2012.50.4.295
PMCID: PMC3514420  PMID: 23230326
Anisakis simplex; anisakid larva; marine fish; the East Sea; the South Sea; the Yellow Sea
21.  Biochemical Recurrence in Gleason Score 7 Prostate Cancer in Korean Men: Significance of the Primary Gleason Grade 
Korean Journal of Urology  2012;53(12):826-829.
Purpose
To evaluate the impact of primary Gleason grade in Gleason score (GS) 7 prostate cancer on biochemical recurrence (BCR) after radical prostatectomy in Korean men.
Materials and Methods
We retrospectively reviewed records of 1,026 patients who underwent radical prostatectomy at Seoul National University Bundang Hospital between November 2003 and June 2009. We excluded patients who had received neoadjuvant therapy and had positive resection margins. Finally, 295 and 113 patients with GS 3+4 and GS 4+3, respectively, were included in this study. All patients were followed for at least 2 years.
Results
Of the 408 GS 7 patients, 295 (72.3%) were 3+4 and 113 (27.7%) were 4+3. Mean serum prostate specific antigen level in primary Gleason 3 was 8.99 ng/ml and primary Gleason 4 was 11.11 ng/ml. Patients with GS 4+3 were more likely to have extracapsular extension (30.1% vs. 17.6%, p<0.010) and lymphatic invasion (16.8% vs. 7.1%, p<0.005). After 2 years follow up BCR was detected in a total of 40 patients. In GS 7 with primary Gleason 3, BCR occurred in 15 (5.08%) patients while 20 (17.70%) showed BCR in GS 7 with primary Gleason 4.
Conclusions
In this study of a large, single center cohort of Korean men with GS 7 prostate cancer a noticeable difference in BCR was seen. Primary Gleason grade 4 have a higher risk of BCR compared to primary Gleason grade 3. This information may be useful when counseling patients on their prognosis and further management options.
doi:10.4111/kju.2012.53.12.826
PMCID: PMC3531634  PMID: 23301125
Biopsy; Prostate; Prostatectomy
22.  Faithful after break-up: suppression of chromosomal translocations 
Chromosome integrity in response to chemically or radiation-induced chromosome breaks and the perturbation of ongoing replication forks relies on multiple DNA repair mechanisms. However, repair of these lesions may lead to unwanted chromosome rearrangement if not properly executed or regulated. As these types of chromosomal alterations threaten the cell’s and the organism’s very own survival, multiple systems are developed to avoid or at least limit break-induced chromosomal rearrangements. In this review, we highlight cellular strategies for repressing DNA break-induced chromosomal translocations in multiple model systems including yeast, mouse, and human. These pathways select proper homologous templates or broken DNA ends for the faithful repair of DNA breaks to avoid undesirable chromosomal translocations.
doi:10.1007/s00018-009-0068-5
PMCID: PMC3501963  PMID: 19547915
Chromosomal translocation; Double strand break; DNA repair; Homologous recombination; End joining
23.  Microhomology Directs Diverse DNA Break Repair Pathways and Chromosomal Translocations 
PLoS Genetics  2012;8(11):e1003026.
Chromosomal structural change triggers carcinogenesis and the formation of other genetic diseases. The breakpoint junctions of these rearrangements often contain small overlapping sequences called “microhomology,” yet the genetic pathway(s) responsible have yet to be defined. We report a simple genetic system to detect microhomology-mediated repair (MHMR) events after a DNA double-strand break (DSB) in budding yeast cells. MHMR using >15 bp operates as a single-strand annealing variant, requiring the non-essential DNA polymerase subunit Pol32. MHMR is inhibited by sequence mismatches, but independent of extensive DNA synthesis like break-induced replication. However, MHMR using less than 14 bp is genetically distinct from that using longer microhomology and far less efficient for the repair of distant DSBs. MHMR catalyzes chromosomal translocation almost as efficiently as intra-chromosomal repair. The results suggest that the intrinsic annealing propensity between microhomology sequences efficiently leads to chromosomal rearrangements.
Author Summary
Cancer results from an accumulation of mutations that transform a normal cell into one that proliferates uncontrollably. DNA double-strand breaks (DSBs) can lead to genetic mutations and chromosome rearrangements, underscoring the importance of functional DNA DSB repair pathways in the maintenance of chromosome integrity and tumor suppression. Ample evidence suggests that cells possess multiple DSB repair mechanisms with distinct mutational potentials, and one or more of these pathways is likely responsible for the formation of chromosomal translocations. Importantly, at the junctions of many rearrangements, small (2–20 bp in length) overlapping sequences from each of the original sequences, termed “microhomology,” are found, and they may provide a clue as to how these rearrangements form. Here, we describe our genetic investigation into how flanking microhomology influences the type and frequency of DSB repair. We also show that microhomology-mediated repair (MHMR) efficiently induces chromosomal translocations. This research provides a basic understanding of the mechanisms that utilize microhomology for mutagenic repair.
doi:10.1371/journal.pgen.1003026
PMCID: PMC3493447  PMID: 23144625
24.  Prognostic Value of Body Mass Index in Korean Patients with Castration-Resistant Prostate Cancer 
Korean Journal of Urology  2012;53(11):761-765.
Purpose
We investigated the correlation between body mass index (BMI) and the prognosis of castration-resistant prostate cancer (CRPC) in patients who received docetaxel treatment.
Materials and Methods
A retrospective study was conducted of 55 patients who were diagnosed with CRPC and received docetaxel treatment between 2003 and 2009 at our institution. Patients with a normal or lower BMI (<23.0 kg/m2) were categorized as group I and patients with an overweight or greater BMI (≥23.0 kg/m2) were categorized as group II. Clinicopathological features and survival rates were evaluated by using the Kaplan-Meier method and Cox proportional hazards models.
Results
On the basis of BMI, 27 patients (49.1%) belonged to group I and 28 (50.9%) patients belonged to group II. Mean follow-up periods were 30 months and 34.2 months, respectively (p=0.381). There were no significant differences between the two groups in terms of age, prostate-specific antigen (PSA), Gleason score, Eastern Cooperative Oncology Group Performance Status, hemoglobin level, alkaline phosphatase level, distant metastasis, radiation treatments, or performance of radical prostatectomy (p>0.05). In the univariate analysis for predicting survival rates, BMI (p=0.005; hazard ratio [HR], 0.121), logPSA (p=0.044; HR, 2.878), and alkaline phosphatase level (p=0.039; HR, 8.582) were significant factors for prediction. In the multivariate analysis, BMI (p=0.005; HR, 0.55), logPSA (p=0.008; HR, 7.836), Gleason score (p=0.018; HR, 6.434), hemoglobin (p=0.006; HR, 0.096), alkaline phosphatase level (p=0.005; HR, 114.1), and metastasis to the internal organs (p=0.028; HR, 5.195) were significant factors for prediction.
Conclusions
Better effects on the cancer-specific survival rate were observed in cases with higher BMI.
doi:10.4111/kju.2012.53.11.761
PMCID: PMC3502734  PMID: 23185667
Cancer specific survival; Castration-resistant prostate cancer; Obesity
25.  Dermoscopy: A Useful Tool for the Diagnosis of Angiokeratoma 
Annals of Dermatology  2012;24(4):468-471.
Angiokeratoma is a rare vascular malformation of the upper dermis that presents clinically as deep red to blue-black in color and tends to take a diverse configuration without self-limiting. Here, we reported dermoscopic findings by two cases of angiokeratoma; solitary angiokeratoma and angiokeratoma circumscriptum. A 24-year-old male presented with a 2-months history of 5 mm sized black colored papule on the right buttock. A dermoscopic pattern characterized by red and dark lacunae, whitish veil covered with scale. A 26-year-old woman presented with multiple, 2~10 mm, dark colored papules on the anterior neck with zosteriform fashion since childhood. A dermoscopic pattern presented by red lacunae intermingled with whitish veil. As a previous report, our two cases was the most common dermoscopic pattern of angiokeratoma; red lacunae and whitish veil. Angiokeratoma is often diagnosed as melanocytic nevi, Spitz nevi, malignant melanomas, pigmented basal cell carcinomas, seborrheic keratoses, dermatofibromas and other vascular lesions including hemangiomas and pyogenic granulomas. However, in the dermoscopic view, these above lesions hardly show red lacunae with whitish veils. Therefore, the dermscopic view is a useful differential method of angiokeratoma.
doi:10.5021/ad.2012.24.4.468
PMCID: PMC3505781  PMID: 23197916
Angiokeratoma; Dermoscopy

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