The pathogenesis of lower urinary tract symptoms (LUTS) is uncertain. We investigated the potential role of inflammation in the development of LUTS, with the use of high-sensitivity C-reactive protein (hsCRP) as an inflammatory marker, in a population-based study of aging men in Korea.
Materials and Methods
Our study used a multistage stratified design to recruit a random sample of 1,510 men aged 45 years or older in Chuncheon, Korea, in 2003. Men with urologic or neurologic diseases that could cause voiding dysfunction were excluded. Also, men with medical conditions that could affect inflammation, such as infection or the use of nonsteroidal anti-inflammatory drugs, were excluded. LUTS were defined according to the International Prostate Symptom Score (IPSS). Various potential confounding factors were included in the analyses.
A total of 330 subjects were included in the final analyses. There were 155 (47.0%) with an IPSS<8 and 175 (53%) with an IPSS≥8. The mean age of all subjects was 69.2±8.4 years. The mean hsCRP level of all subjects was 2.30±3.27 (median, 1.19) mg/l. The hsCRP levels in subjects with an IPSS≥8 differed significantly from those in subjects with an IPSS<8. Also, IPSS, storage symptom, voiding symptom, and quality of life (QoL) scores increased as hsCRP levels increased, respectively. The hsCRP level remained an independent risk factor of LUTS (IPSS≥8, storage symptom score≥4, incomplete voiding, intermittency, and QoL) after adjustment for variable possible confounding factors.
Our results suggest that inflammatory processes may play an important role in the pathogenesis of LUTS and that hsCRP levels may indicate the severity of LUTS in aging men.
C-reactive protein; Inflammation; Lower urinary tract symptoms
With the improved surgical techniques and immunosuppression available today, conventional prognostic factors have taken on less significance. Accordingly, the native renal function of the donor is thought to be more important. Thus, we analyzed the prognostic significance of the donor's renal function as assessed by 24-hour urine creatinine clearance on kidney graft survival for 10 years after living kidney transplantation.
Materials and Methods
From January 1998 to July 2000, 71 living kidney transplantations were performed at a single institution. From among these, 68 recipients were followed for more than 6 months and were included in the present analysis. We analyzed kidney graft survival according to clinical parameters of the donor and the recipient.
Mean follow-up duration of recipients after living kidney transplantation was 115.0±39.4 months (range, 10 to 157 months), and 31 recipients (45.6%) experienced kidney graft loss during this time period. Estimated mean kidney graft survival time was 131.8±6.2 months, and 5-year and 10-year kidney graft survival rates were estimated as 88.2% and 61.0%, respectively. Donor's mean 24-hour urine creatinine clearance (Ccr) before kidney transplantation was 122.8±21.2 ml/min/1.73 m2 (range, 70.1 to 186.6 ml/min/1.73 m2). The 10-year kidney graft survival rates for cases stratified by a donor's Ccr lower and higher than 120 ml/min/1.73 m2 were 39.0% and 67.2%, respectively (p=0.005). In univariate and multivariate analysis, donor's Ccr was retained as an independent prognostic factor of kidney graft survival (p=0.001 and 0.005, respectively).
Donor's 24-hour urine Ccr before living kidney transplantation was an independent prognostic factor of kidney graft survival. Therefore, it should be considered before living kidney transplantation.
Creatinine; Kidney transplantation; Survival
The aim of the present study was to evaluate the effects of low-dose tamsulosin on sexual function in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia.
Materials and Methods
A total of 138 male LUTS patients aged more than 50 years with an International Prostate Symptom Score (IPSS) ≥8 were enrolled in this open-label, multicenter, prospective, noncomparative observational study. Clinical assessments included IPSS, quality of life (QoL) index, International Index of Erectile Function (IIEF), Danish Prostate Symptom Score (DAN-PSS), and an early morning erection questionnaire. The data were recorded at baseline and at 1 and 3 months after treatment with tamsulosin 0.2 mg/d. Adverse events were analyzed in all patients.
During the study period of 3 months, the IPSS and QoL index significantly improved from baseline by -11.40±9.40 and -1.11±1.36, respectively (p<0.001). However, there were no clinically relevant changes in total IIEF score (mean difference, 1.63±15.50; p=0.406) or the 5 subdomains (p>0.05). Furthermore, DAN-PSS weighted scores (A×B) showed no clinically relevant changes (mean difference on Q1, Q2, and Q3: -0.45±2.94, 0.27±2.50, and -1.27±2.27, p>0.05). In addition, there were no clinically significant changes in responses on the early morning erection questionnaire.
Tamsulosin at the dose of 0.2 mg significantly improved the IPSS and the QoL index compared with baseline. However, tamsulosin did not exhibit any significant impact on sexual function or any negative impact on ejaculatory function.
Ejaculation; Erectile dysfunction; Lower urinary tract symptoms; Prostatic hyperplasia; Tamsulosin
This study aimed at investigating sexual behavior patterns of elderly residents of urban areas in South Korea and their correlation with lower urinary tract symptoms.
Materials and Methods
From May, 2009 to October, 2009, 154 males and 299 females over 60 years old who visited senior welfare centers of Seoul were administered a questionnaire on sex life patterns and voiding symptoms.
Among the 154 males, 59 (38.3%) had sexual intercourse at least one time per month. The remaining 95 males (61.7%) did not have sexual intercourse, because of impotence for 52 males (52.6%), no sexual desire for 28 males (29.4%), and sex partner's problems for 15 males (15.7%). The higher International Prostate Symptom Score was, the lower International Index of Erectile Dysfunction-5 was (p=0.035). Among 299 females, 37 (12.4%) had sexual intercourse at least one time per month. The remaining 262 females (87.6%) did not have sexual intercourse, because of no spouse for 163 females (63.2%), no sexual desire for 48 females (18.6%), the spouse's impotence for 34 females (13.2%), and the spouse's bad health for 10 females (3.9%). It was found that self-diagnosis of overactive bladder affects sex life negatively.
The sexual behaviors of the elderly included varying activity. Sexual intercourse were significantly associated with lower urinary tract symptoms. Our results suggest that the counseling with the elderly about sexual health is as important as it is with non-elderly individuals.
Aged; Sexual behavior; Lower urinary tract symptoms
Insulin-like growth factors (IGFs) regulate a wide range of biological functions including cell proliferation, differentiation, and apoptosis through paracrine and autocrine mechanisms. Accordingly, the present study analyzed polymorphisms of IGF genes and their impact on the prognosis for patients with gastrointestinal stromal tumors (GISTs).
Two hundred-thirteen consecutive patients with GISTs who underwent curative surgery from 5 medical centers were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tumor tissue, and four IGF-1 (+2995C/A, +533C/T, IVS2-16540A/G, Ex4-177G/C) and one IGF-2 (IVS1+1280A/G) gene polymorphisms were determined using a Sequenom MassARRAY system.
With a median follow-up of 18.4 months, the estimated 5-year relapse-free survival and overall survival rates were 69.9% and 86.7%, respectively. In a multivariate analysis including age, gender, primary site of disease, pathology, and risk stratification, no significant association was observed between the polymorphism of the IGF-1 and IGF-2 genes and survival.
None of the five IGF-1 and IGF-2 gene polymorphisms investigated in this study was found to be an independent prognostic marker for Korean patients with surgically resected GIST. However, further studies on a larger scale are warranted to clarify the role of IGF-1 and IGF-2 gene polymorphisms as a prognostic biomarker for GIST patients.
Gastrointestinal stromal tumor; Insulin-like growth factor; Single nucleotide polymorphism; Prognosis
We report here on a rare case of primary malignant melanoma of the female urethra. A 69-year-old female presented at our hospital with a several month history of dysuria, poor stream, gross hematuria, intermittent blood spots, and a painful mass at the external urethral meatus. The physical examination revealed a soft, small, chestnut-sized lesion through the urethral orifice. The mass was tan colored, ulcerated, covered with necrotic tissue, and protruded from the external urethral meatus. The mass was removed by wide local excision under spinal anesthesia. The pathological diagnosis was malignant melanoma of the urethra. Computed tomography of the abdomen as well as a whole-body bone scan showed no evidence of metastasis. The patient has been free of disease for 6 months postoperatively. We discuss the clinicopathologic features and treatment of this tumor.
Female; Melanoma; Urethra
To investigate pathophysiological consequences and spontaneous recovery after cavernous nerve crush injury (CNCI) in a rat model.
Materials and Methods
Twenty 4-week-old male Sprague-Dawley rats were divided into the following groups: sham-operated group (n=10) and bilateral CNCI groups (n=10) for two different durations (12 and 24 weeks). At both time points, CN electrical stimulation was used to assess erectile function by measuring the intracavernous pressure. The expression of hypoxia inducible factor (HIF)-1α and sonic hedgehog (SHH) was examined in penile tissue. Immunohistochemical staining was performed for nerve growth factor (NGF), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and smooth muscle α-actin.
CNCI significantly decreased erectile function at 12 weeks (51.7% vs. 71.9%, mean ICP/BP ratio, p<0.05) and increased the expression of HIF-1α and decreased the expression of eNOS, nNOS, and SHH. At 24 weeks, erectile function in the CNCI group was improved with no significant difference versus the sham group (70.5% vs. 63.3%, mean ICP/BP ratio, p<0.05) or the CN group at 12 weeks (51.7% vs. 63.3%, mean ICP/BP ratio, p<0.05). By RT-PCR, the increase in HIF-1α and decrease in SHH mRNA was restored at 24 weeks. By immunohistochemistry, the expression of eNOS and nNOS was increased at 24 weeks.
CN injury induces significantly impaired erectile function and altered gene and protein expression, which suggests that local hypoxic and inflammatory processes may contribute to this change. Significant spontaneous recovery of erectile function was observed at 6 months after CN crush injury.
Erectile dysfunction; Hedgehog proteins; Nerve injury
Glioblastoma multiforme is one of the most common and aggressive tumors in central nervous system. It often possesses characteristic necrotic lesions with hemorrhages, which increase the chances of exposure to thrombin. Thrombin has been known as a regulator of MMP-9 expression and cancer cell migration. However, the effects of thrombin on glioma cells have not been clearly understood. In the present study, influences of thrombin on glioma cell migration were examined using Boyden chamber migration assay and thrombin-induced changes in MMP-9 expression were measured using zymography, semi-quantitative RT-PCR, and Western blotting. Furthermore, underlying signaling pathways by which thrombin induces MMP-9 expression were examined. Thrombin-induced migration and MMP-9 expression were significantly potentiated in the presence of wortmannin, a PI3K inhibitor, whereas MAPK inhibitors suppressed thrombin-induced migration and MMP-9 expression in C6 glioma cells. The present data strongly demonstrate that MAPK and PI3K pathways evidently regulate thrombin-induced migration and MMP-9 expression of C6 glioma cells. Therefore, the control of these pathways might be a beneficial therapeutic strategy for treatment of invasive glioblastoma multiforme.
Thrombin; MMP-9; C6 glioma cells; MAPK; PI3K
Although the incidence of bleeding complications during extracorporeal membrane oxygenator (ECMO) support has decreased in various trials, bleeding is still the most fatal complication. We investigated the ideal dosage and efficacy of nafamostat mesilate for use with ECMO in patients with acute cardiac or respiratory failure. We assessed 73 consecutive patients who received ECMO due to acute cardiac or respiratory failure between January 2006 and December 2009. To evaluate the efficacy of nafamostat mesilate, we divided the patients into 2 groups according to the anticoagulants used during ECMO support. All patients of nafamostat mesilate group were male with a mean age of 49.2 yr. Six, 3, 5, and 3 patients were diagnosed with acute myocardial infarction, cardiac arrest, septic shock, and acute respiratory distress syndrome, respectively. The mean dosage of nafamostat mesilate was 0.64 mg/kg/hr, and the mean duration of ECMO was 270.7 hr. The daily volume of transfused packed red blood cells, fresh frozen plasma, and cryoprecipitate and the number of complications related to hemorrhage and thrombosis was lower in the nafamostat mesilate group than in the heparin group. Nafamostat mesilate should be considered as an alternative anticoagulant to heparin to reduce bleeding complications during ECMO.
Extracorporeal Membrane Oxygenation; Anticoagulants; Heparin; Nafamostat; Complications; Intensive Care
The aim of this study was to evaluate the effect of desmopressin combined with anticholinergics on daytime frequency and urgency in female patients with overactive bladder (OAB).
Materials and Methods
We included 68 female patients with OAB. Patients were randomly assigned to receive 5 mg of solifenacin (group I) or 5 mg of solifenacin and 0.2 mg of desmopressin (group II) for 2 weeks. A pre/post-treatment 3-day voiding diary and the Urinary Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) were used to assess changes in voiding symptoms and quality of life (QoL); results were compared between the two groups.
Groups I and II included 31 and 37 patients, respectively. Time to first void was 12 min later in group II (105 min vs. 117 min), but this difference was not statistically significant. However, time to the second and third voids (203 min vs. 255 min, 312 min vs. 368 min) and the first urgency episode (212 min vs. 255 min) were significantly longer in group II. Compared with group I, patients in group II showed significant improvement in QoL scores. When improvement after treatment was defined as increase in time to first void of greater than 10% after 2 weeks of treatment, desmopressin with anticholinergics was more effective in patients over the age of 65 years and with more than 150 ml of voided volume.
Desmopressin combined with anticholinergics was more effective than anticholinergics only in the treatment of female patients with OAB.
Anticholinergics; Desmopressin; Overactive bladder
Neurofibrillary tangle (NFT) is a characteristic hallmark of Alzheimer's disease. GSK3β has been reported to play a major role in the NFT formation of tau. Dysfunction of autophagy might facilitate the aggregate formation of tau. The present study examined the role of GSK3β-mediated phosphorylation of tau species on their autophagic degradation. We transfected wild type tau (T4), caspase-3-cleaved tau at Asp421 (T4C3), or pseudophosphorylated tau at Ser396/Ser404 (T4-2EC) in the presence of active or enzyme-inactive GSK3β. Trehalose and 3-methyladenine (3-MA) were used to enhance or inhibit autophagic activity, respectively. All tau species showed increased accumulation with 3-MA treatment whereas reduced with trehalose, indicating that tau undergoes autophagic degradation. However, T4C3 and T4-2EC showed abundant formation of oligomers than T4. Active GSK3β in the presence of 3-MA resulted in significantly increased formation of insoluble tau aggregates. These results indicate that GSK3β-mediated phosphorylation and compromised autophagic activity significantly contribute to tau aggregation.
Tau; Autopahgy; Glycogen synthase kinase 3β; Trehalose; Neurofibrillary tangles
We investigated the functional outcomes regarding erectile function and urinary continence up to 5 years following radical prostatectomy (RP) in a cohort of Korean men. We retrospectively analyzed the clinicopathologic data of 85 Korean men who received open uni- or bilateral nerve-sparing RP for clinically localized prostate cancer and were followed up for at least 5 years postoperatively. From medical records, patients' status regarding urinary and erectile function at baseline and postoperative followups after RP was assessed. At 24 and 60 months after RP, proportions of subjects continent (no pads used) were 89.4% and 97.6%, respectively (P = 0.007). Excluding subjects (n = 24) who preoperatively reported having severe erectile dysfunction or lacked relevant informations, proportions of subjects capable of having vaginal intercourse regardless of erectile aid usage were 47.5% and 37.7% at 24 and 60 months from RP, respectively (P = 0.022). Patient's age at surgery (P = 0.047) and salvage radiation therapy (P = 0.026) were observed to be significant predictors of having erections sufficient for intercourse at 60 months from RP in multivariate analysis. Our results showed that while patients' postoperative status regarding urinary continence at 2 years from RP is generally maintained or improved at 5 year point, erectile function was observed to significantly declined from 2 years to 5 years following RP. Such decline in erectile function following RP may be more significant among men who were relatively older at surgery or those who received salvage therapy during postoperative follow-ups.
impotence; prostatectomy; prostatic neoplasm; urinary incontinence
The aim of this study was to investigate the relationship between lower urinary tract symptoms (LUTS) and risk factors for vascular diseases in a population-based cohort study, the Hallym Aging Study (HAS).
Materials and Methods
Among the 1,520 participants in HAS, 280 men aged more than 50 years, who underwent detailed health evaluations, including health-related questionnaires, evaluations of their medical history, and various life style factors, as well as clinical measurements, were included in the study. Vascular risk factors used in the present study including hypertension, diabetes mellitus, hyperlipidemia, and smoking and were assessed by medical history and clinical measurements. LUTS were assessed by validated questionnaires, the International Prostate Symptom Score (IPSS), and the relationship between LUTS and vascular risk factors was investigated.
Of the 280 men, 175 (62.5%) had moderate/severe LUTS (IPSS>7) and 260 (93%) had one or more vascular risk factors. The IPSS was similar in those with no (11.6±9.7) and one or two (11.5±8.5) vascular risk factors, but increased to 15.1±9.3 in those with 3 or more vascular risk factors (p<0.05). The multiple logistic regression analysis, controlling for age and body mass index (BMI) showed that men with 3 or more vascular risk factors were 3 times more likely to have moderate/severe LUTS than men without vascular risk factors (p<0.05).
Men with risk factors for vascular diseases are more likely to have LUTS and these findings suggest that vascular risk factors play a role in the development of LUTS.
Diagnosis; Risk factors; Urinary tract; Vascular diseases
Macintosh laryngoscopic intubation is a lifesaving procedure, but a difficult skill to learn. The Airtraq optical laryngoscope (AOL) is a novel intubation device with advantages over the direct laryngoscope for untrained personnel in a manikin study. We compared the effectiveness of AOL with Macintosh laryngoscope for tracheal intubation by novice personnel.
We selected 37 medical students with no prior tracheal intubation experience and educated them on using both laryngoscopes. Seventy-four patients were randomly divided into two groups (group A: AOL, group M: Macintosh laryngoscope). We recorded the tracheal intubation success rate, intubation time, number of attempts, intubation difficulty scale, and adverse effects.
The total success rate was similar in the two groups, but the success rate at first attempt was higher in group A (P < 0.01). Group A also showed reduced duration and attempts at intubation, as well as adverse effects such as oral cavity injury. Additionally, participant reports indicated that using the AOL was easier than the Macintosh laryngoscope (P < 0.01).
The AOL is a more effective instrument for tracheal intubation than Macintosh laryngoscope when used by novice personnel.
Airtraq optical laryngoscope; Intubation; Macintosh laryngoscope
We performed a comparative analysis of the plasma levels of antithrombin (AT) III, plasminogen, fibrinogen, and D-dimer among patients with and without clinically localized prostate cancer to investigate the clinical significance of the coagulation profile in prostate cancer.
Materials and Methods
A prospective study was performed in which plasma levels of AT III, plasminogen, fibrinogen, and D-dimer were assessed in patients before they underwent prostate biopsy. According to the results of the biopsy, the patients were categorized into the cancer group or the control group. Levels of the four coagulation factors were then compared between the cancer and control groups. Also, levels of the four coagulation factors were correlated with tumor stage and grade in the cancer group.
The cancer group had significantly lower levels of AT III activity and higher plasma D-dimer levels than did the control group (p=0.007 and p=0.018, respectively). Within the cancer group, no significant differences were observed in the levels of AT III, plasminogen, fibrinogen, or D-dimer between those with a pathological Gleason score of ≥7 and otherwise. Regarding pathologic stage of prostate cancer, the subjects with organ-confined disease and those with extraprostatic extension of a tumor demonstrated no significant differences in the preoperative levels of the four coagulation factors analyzed.
Our results suggest that plasma levels of AT III and D-dimer are altered in patients with prostate cancer. Further study is needed to elucidate the underlying mechanism and clinical significances of such a phenomenon among patients with clinically localized prostate cancer.
Prostatic neoplasms; Blood coagulation tests