A 50-year-old female who had undergone laparoscopic total hysterectomy at a local clinic owing to leiomyoma of the uterus was referred to our hospital after having dysuria, urgency, frequency, lower abdominal pain and right flank pain over several months. After routine examinations, cystoscopy, computed tomography and magnetic resonance imaging were performed, and non-ulcerative interstitial cystitis accompanied by postoperative fibrosis secondary to a previous surgery was suggested. Pentosan sulfuric polyester (Elmiron, Alza Pharmaceuticals, Mountain View, CA) reduced her severely debilitating symptoms and improved her quality of life. Both the hydronephrosis and the symptoms were relieved by ureteral stent insertion and percutaneous nephrostomy. However, a few days later, she presented with vaginal bleeding along with her previous symptoms, and punch biopsy of the vaginal stump resulted in a diagnosis of adenocarcinoma. Both ureterocutaneostomy with radical cystectomy and lower anterior resection for rectum invasion were conducted. After the slide review of the original specimen from the local clinic, she was diagnosed with recurrent cervical cancer of the vaginal stump.
Benign prostatic hyperplasia is often accompanied by age-related comorbidity, such as erectile dysfunction (ED). Recent data suggest an association between ED and lower urinary tract symptoms (LUTS), and increasing evidence indicates that the clinical use of phosphodiesterase type 5 (PDE5) inhibitors provides relief from LUTS. The aim of the present study was to investigate the effects of tadalafil (20 mg once every 3 days for 12 weeks, p.o.) in men with moderate-to-severe ED and LUTS and to investigate the duration of the effects of tadalafil beyond treatment cessation.
Materials and Methods
Men with an International Index of Erectile Function-5 (IIEF-5) score of less than 11 (representing "moderate-to-severe" ED status) and with an International Prostate Symptom Score (IPSS) of more than 8 (representing "moderate-to-severe" LUTS status) were enrolled. IPSS (total score, storage subscore, and voiding subscore) and IIEF-5 scores before treatment (baseline), during treatment (weeks 4 and 12 after treatment commencement), and after treatment (weeks 16 and 20after treatment commencement) were compared.
IPSS and IIEF-5 scores were significantly different between baseline and week 12 after treatment commencement. Furthermore, these scores were significantly different between baseline and week 20 after treatment commencement. However, except for IIEF-5 scores, no significant differences were observed between week 12 and week 20.
Treatment with 20 mg tadalafil (once every 3 days) had beneficial effects on LUTS and ED beyond treatment cessation in patients with moderate-to-severe ED and LUTS.
Tadalafil; Erectile dysfunction; Benign
Extracorporeal shock wave lithotripsy (ESWL) has revolutionized the management of urolithiasis since it was first introduced in 1980. ESWL is a well-established, safe and effective therapeutic alternative to surgical treatment for urolithiasis. Complications of ESWL do occur in a small number of patients, and when they do, they typically involve the kidney. We present a case of a young female patient who developed a huge hepatic subcapsular hematoma accompanied by hypovolemic shock after ESWL for a 9 mm stone in the right kidney. The hematoma measured 13×6 cm. Conservative care with no surgical intervention was chosen because there was no evidence of active bleeding on the computed tomography. After conservative therapy, the hematoma was gradually absorbed and the patient was discharged.
Lithotripsy; Hematoma; Complications
Prenatal environmental conditions affect the development of the fetus. In the present study, we investigated the effects of exposure to music and noise during pregnancy on neurogenesis and thickness in the motor and somatosensory cortex of rat pups.
The pregnant rats in the music-applied group were exposed to 65 dB of comfortable music for 1 hour, once per day, from the 15th day of pregnancy until delivery. The pregnant rats in the noise-applied group were exposed to 95 dB of sound from a supersonic sound machine for 1 hour, once per day, from the 15th day of pregnancy until delivery. After birth, the offspring were left undisturbed together with their mother. The rat pups were sacrificed at 21 days after birth.
Exposure to music during pregnancy increased neurogenesis in the motor and somatosensory cortex of rat pups. In contrast, rat pups exposed to noise during pregnancy showed decreased neurogenesis and thickness in the motor and somatosensory cortex.
Our study suggests that music and noise during the developmental period are important factors influencing brain development and urogenital disorders.
Music; Noise; Neurogenesis; Motor cortex; Somatosensory cortex
An overactive bladder (OAB) may be defined as urgency that is a sudden, compelling, difficult to defer desire to pass urine that is usually accompanied by frequency and nocturia and possibly by incontinence. Obesity and old age are two factors in various causes of OAB. Several epidemiologic studies have identified positive associations among obesity, old age, urinary incontinence, and OAB. However, although exercise has been known to improve obesity and reduce incontinent urine loss, little research has been done in elderly women. Therefore, we investigated the effects of exercise on obesity-related metabolic factors, blood lipid factors, and OAB symptoms in elderly Korean women.
Twenty-one women aged between 69 and 72 years were recruited from the Seoul senior towers in Korea. All subjects worked out on a motorized treadmill and stationary cycle for 40 minutes, respectively, and performed resistance exercise for 30 minutes once a day for 52 weeks. Body composition, blood pressure, blood lipids, OAB symptom score, and King's health questionnaire were investigated and analyzed.
Before performing physical exercise, all subjects showed increased OAB symptoms in association with enhanced body mass index (BMI), percentage fat, and blood lipid profiles. However, physical exercise for 52 weeks suppressed BMI, percentage fat, and blood lipid profiles and thus improved OAB symptoms.
We suggest that long-term physical exercise can be a valuable tool for remarkable improvement of OAB.
Overactive urinary bladder; Obesity; Exercise; Overactive bladder symptom score; King's health questionnaire
Recently, few studies were reported about the treatment of large, solitary, renal calculi between shockwave lithotripsy (SWL) and percutaneous nephrolithotomy (PNL). We assess the feasibility of SWL for managing solitary, lower calyceal stones over 1 cm by comparing the results of lower pole calculi treatment between patients that underwent SWL or PNL.
We retrospectively reviewed clinical data for patients who had undergone PNL or SWL due to lower calyceal stones over 1 cm. Group 1 consisted of patients who underwent SWL to treat lower pole renal calculi from 2010 to 2011. Group 2 included patients who underwent PNL to manage lower pole renal calculi from 2008 to 2009. We compared patient age, gender, stone size, comorbidities, postoperative complications, additional interventions and anatomical parameters between the two groups.
A total of 55 patients were enrolled in this study. The mean ages (±SD) of groups 1 (n = 33) and 2 (n = 22) were 55.1 (±13.0) and 50.0 (±10.6) years (p = 0.133) and mean stone sizes were 1.6 (±0.7) and 1.9 (±0.8) cm (p = 0.135), respectively. There were no significant differences in gender distribution, comorbidities or stone laterality between the two groups. No significant differences in various parameters were observed between patients with stones 1 to 2 cm and ones with stones 2 cm or larger.
Our results demonstrated that SWL is a safe, feasible treatment for solitary, lower calyceal stones over 1 cm.
Despite reports of persistent stress urinary incontinence (SUI) in patients after the midurethral sling (MUS) procedure, there is no widely accepted definition or cause of the condition. In many cases, the mesh implanted in the previous MUS procedure has been found to have migrated proximally. The aim of this study was to evaluate the efficacy of the modified distal urethral polypropylene sling, or canal transobturator tape (TOT), procedure for persistent SUI after a conventional MUS procedure on the assumption that persistent SUI after MUS is due to the location of the sling.
From January 2008 to April 2012, 31 female patients who underwent the canal TOT procedure presented with incontinence or lower urinary tract symptoms (LUTS) were included in this study. We identified patients who had been operated on by use of the conventional MUS procedure at other medical facilities, whose Valsalva leak pressure point was less than 120 cm-H2O by urodynamic study, and who were also diagnosed with persistent SUI. If vaginal or urethral mesh exposure was concomitant with persistent SUI, the mesh was removed completely or in part. Surgical procedures for canal TOT were identical to the original TOT procedures, except in the number and location of the vaginal incisions. Incontinence Impact Questionnaire-Short Form (IIQ-7) and Urogenital Distress Inventory-Short Form (UDI-6) scores were assessed preoperatively and at 3 months postoperatively.
There were no intraoperative or postoperative complications. Twenty-eight patients (90.3%) showed improvement in incontinence or other LUTS. Postoperative scores of the IIQ-7 (0.65±0.48) and UDI-6 (3.48±2.28) were significantly improved compared with preoperative scores (1.26±0.58 and 7.52±4.30, respectively; P<0.05).
Improper sling location is one of the major causes of persistent SUI after the conventional MUS procedure. Our results demonstrate that canal TOT may be an alternative method in the treatment of persistent SUI after the conventional MUS procedure.
Stress urinary incontinence; Suburethral slings; Recurrence
The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, α1-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats.
Adult female Sprague-Dawley rats, weighing 250±10 g (9 weeks old), were used in this study. The animals were divided into five groups (n=8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted.
Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment.
Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.
Overactive bladder; Cyclophosphamide; Tamsulosin; Rats
The involuntary dual control systems of the autonomic nervous system (ANS) in the bladder of awake spontaneously hypertensive rats (SHRs) were investigated through simultaneous registrations of intravesical and intraabdominal pressures to observe detrusor overactivity (DO) objectively as a core symptom of an overactive bladder. SHRs (n = 6) showed the features of overactive bladder syndrome during urodynamic study, especially DO during the filling phase. After injection of the nonselective sympathetic blocking agent labetalol, DO disappeared in 3 of 6 SHRs (50%). DO frequency decreased from 0.98 ± 0.22 min−1 to 0.28 ± 0.19 min−1 (p < 0.01), and DO pressure decreased from 3.82 ± 0.57 cm H2O to 1.90 ± 0.86 cm H2O (p < 0.05). This suggests that the DO originating from the overactive parasympathetic nervous system is attenuated by the nonselective blocking of the sympathetic nervous system. The detailed mechanism behind this result is still not known, but parasympathetic overactivity seems to require overactive sympathetic nervous system activity in a kind of balance between these two systems. These findings are consistent with recent clinical findings suggesting that patients with idiopathic overactive bladder may have ANS dysfunction, particularly a sympathetic dysfunction. The search for newer and better drugs than the current anticholinergic drugs as the mainstay for overactive bladder will be fueled by our research on these sympathetic mechanisms. Further studies of this principle are required.
autonomic nervous system; detrusor overactivity; labetalol
The second to fourth digit ratio (2D:4D) has been proposed as a putative biomarker for prenatal testosterone and covaries with the sensitivity of the androgen receptor (AR). Both prenatal testosterone and the AR play a central role in penile growth. In this study, we investigated the relationship between digit ratio and penile length. Korean men who were hospitalized for urological surgery at a single tertiary academic centre were examined in this study, and 144 men aged 20 years or older who gave informed consent were prospectively enrolled. Right-hand second- and fourth-digit lengths were measured by a single investigator prior to measurement of penile length. Under anaesthesia, flaccid and stretched penile lengths were measured by another investigator who did not measure nor have any the information regarding the digit lengths. Univariate and multivariate analysis using linear regression models showed that only height was a significant predictive factor for flaccid penile length (univariate analysis: r=0.185, P=0.026; multivariate analysis: r=0.172, P=0.038) and that only digit ratio was a significant predictive factor for stretched penile length (univariate analysis:r=−0.216, P=0.009; multivariate analysis: r=−0.201, P=0.024; stretched penile length=−9.201×digit ratio + 20.577). Based on this evidence, we suggest that the digit ratio can predict adult penile size and that the effects of prenatal testosterone may in part explain the differences in adult penile length.
digit ratio; flaccid penile length; stretched penile length
A 51-year-old diabetic woman was referred to our unit with a history of increasing pain in her right thigh and gait disturbance, 10 days following surgery for treatment of stress urinary incontinence with a transobturator tape. Examination elicited a tender right thigh associated with swelling and erythema. Inspection of the vagina revealed an exposed mesh through the vaginal erosion. Plain radiographs and magnetic resonance imaging revealed large thigh abscesses suggestive of gas gangrene from the pelvis to the calf. The mesh was completely removed; extensile incisions, as well as aggressive debridement of all necrotic tissue in the thigh and calf, were performed. A diagnosis of necrotizing fasciitis with gas extending to the lower leg level was confirmed. After mesh removal, abscess drainage and debridement, the patient recovered with antibiotics and daily wound care. Three months after the operation, the patient showed no recurrence of the infection.
Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In this review, we briefly introduce circadian clocks and their organization in mammals. We then summarize known daily or circadian variations in urinary function. Importantly, recent findings by others as well as results obtained by us suggest an active role of circadian clock genes in various urinary functions. Finally, we discuss possible research avenues for the circadian control of urinary function.
Circadian clocks; Urinary bladder; Urination; Urinary function
Stress urinary incontinence (SUI) commonly occurs in women, and it has an enormous impact on quality of life. Surgery, drugs, and exercise have been recommended for the treatment of this disease. Among these, exercise is known to be effective for the relief of symptoms of SUI; however, the efficacy and underlying mechanisms of the effect of exercise on SUI are poorly understood. We investigated the effect of swimming the symptom of SUI in relation to the expression of nerve growth factor (NGF) in rats.
Transabdominal urethrolysis was used to induce SUI, in Sprague-Dawley rats. The experimental groups were divided into the following three groups: sham-operation group, transabdominal urethrolysis-induced group, and transabdominal urethrolysis-induced and swimming group. The rats in the swimming group were forced to swim for 30 minutes once daily starting 2 weeks after SUI induction and continuing for 4 weeks. For this study, determination of abdominal leak point pressure and immunohistochemistry for NGF in the urethra and in the neuronal voiding centers (medial preoptic nucleus [MPA], ventrolateral periaqueductal gray [vlPAG], pontine micturition center [PMC], and spinal cord [L4-L5]) were performed.
Transabdominal urethrolysis significantly reduced the abdominal leak point pressure, thereby contributing to the induction of SUI. Abdominal leak point pressure, however, was significantly improved by swimming. The expression of NGF in the urethra and in the neuronal voiding centers (MPA, vlPAG, PMC, and L4-L5) relating to micturition was enhanced by the induction of SUI. Swimming, however, significantly suppressed SUI-induced NGF expression.
Swimming alleviated symptoms of transabdominal urethrolysis-induced SUI, as assessed by an increase in abdominal leak point pressure. The underlying mechanisms of these effects of swimming might be ascribed to the inhibitory effect of swimming on NGF expression.
Urinary incontinence; Swimming; Nerve growth factor; Rats
Oxytocin is associated with the ability to form normal social attachments. c-Fos is an immediate early gene whose expression is used as a marker for stimulus-induced changes in neurons. The effect of phosphodiesterase-5 (PDE-5) inhibitors on oxytocin activation in the brain without sexual stimuli has not yet been reported. In the present study, we investigated the effects of vardenafil on oxytocin and c-Fos expression in the paraventricular nucleus (PVN) of conscious rats.
Male Sprague-Dawley rats weighing 300±10 g were divided into 6 groups (n=5 in each group): the control group, the 1-day-0.5 mg/kg, the 1-day-1 mg/kg, the 1-day-2 mg/kg, the 3-day-1 mg/kg, and the 7-day-1 mg/kg vardenafil administration group. The experiment was conducted without sexual stimulation. Vardenafil was orally administered. The animals in the control group received an equivalent amount of distilled water orally. The expression of oxytocin and c-Fos in the PVN was detected by immunohistochemistry.
Oxytocin expression in the PVN was increased by 1 day administration of 2 mg/kg vardenafil, and this effect of vardenafil appeared in a duration-dependent manner. c-Fos in the oxytocin neurons of the PVN was increased by 1 day administration of 2 mg/kg vardenafil, and this effect of vardenafil also appeared in a duration-dependent manner. These results showed that vardenafil augments the expression of oxytocin with activation of oxytocin neurons in the PVN.
In this study, we showed that the PDE-5 inhibitor, vardenafil directly enhances oxytocin expression and also activates oxytocin neurons in the PVN, which indicates that vardenafil may exert positive effects on affiliation behavior and social interaction.
Vardenafil; Oxytocin; c-Fos; Paraventricular nucleus; Rats
Stress urinary incontinence (SUI) commonly occurs in women, and it causes enormous impact on quality of life. Surgery, drugs, and exercise have been recommended for the treatment of this disease. Among these exercise is also known to be effective for relieving thesymptoms of SUI, however, the efficacy and underlying mechanisms of exercise on SUI are poorly understood. In the present study, we investigated the effect of treadmill exercise on abdominal leak-point pressure and neuronal activity in the medial preoptic nucleus (MPA), ventrolateral periaqueductal gray (vlPAG), and pontine micturition center (PMC) following urethrolysis in rats.
Materials and Methods
Adult female Sprague-Dawley rats, weighing 250±10 g (9 weeks old), were used in this study. After having undergone transabdominal urethrolysis to induce SUI, the rats were divided into three groups (n=6 in each group): a sham operation group, an SUI-induced group, and an SUI-induced and treadmill exercise group. The rats in the exercise group performed treadmill running for 30 min once a day starting 2 weeks after the induction of SUI and continuing for 4 weeks after surgery. For this study, determination of abdominal leak point pressure and immunohistochemistry for c-Fos in the brain were performed.
Induction of transabdominal urethrolysis significantly reduced the abdominal leak point pressure, thereby contributing to the induction of SUI. In contrast, abdominal leak point pressure was significantly improved by treadmill exercise. The expression of c-Fosin the MPA, vlPAG, and PMC, the brain areas relating to micturition, was enhanced by the induction of SUI, whereas treadmill exercise significantly suppressed SUI-induced c-Fos expression, suggesting that neuronal activation in the micturition centers was suppressed by treadmill exercise.
The present results suggest that treadmill exercise may be an effective therapeutic modality for ameliorating the symptoms of SUI.
Urinary incontinence; Micturition; Treadmill test; c-Fos; Rats
Dendritic cell (DC)-based tumor vaccine is an attractive modality for the treatment of hormone-refractory prostate cancer (HRPC) because it has some efficacy and few side effects in patients with poor general conditions. The aim of this study was to establish which is the most effective DC vaccine for the treatment of HRPC. We compared DC vaccine sensitized with tumor lysate and a fusion vaccine of DCs and tumor cells.
Materials and Methods
The DU145 cancer cell line was purchased from the American Type Culture Collection. DCs were cultured from peripheral blood monocytes. Peripheral blood monocytes were cultured in RPMI 1640 medium supplemented with interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor, and 10% fetal calf serum. Tumor necrosis factor-alpha was added on day 7 to support maturation. Functional activity was measured in three groups: the DC single-culture group, the DC culture group with DC vaccine sensitized with tumor lysates, and the DC culture group prepared with tumor fusion vaccine made from irradiated tumor cells and monocyte-derived DCs by the polyethylene glycol method.
By FACS analysis, the rate of DC-tumor fusion vaccine was 20.3±3%. The IL-12 level produced by the DC-tumor fusion vaccine was significantly higher than that of DCs pulsed with tumor lysate (p<0.05). Also, the generation of interferon-γ by tumor-specific T cells in the DC-tumor fusion vaccine group was superior to that of DCs pulsed with tumor lysate (p<0.05). In addition, the T cells of the tumor lysate-pulsed DCs and tumor fusion vaccine had 1.6 and 2.5 times the functional activity, respectively, of the DC single-culture group in killing tumor cells in the cytotoxicity assay.
The DC-tumor fusion vaccine seems to be more effective than DC single-culture or DC-tumor lysate vaccine in the treatment of HRPC.
Prostatic neoplasms; Dendritic cells; Cancer vaccines