Extrauterine leiomyoma is a very rare clinical condition; we report a case of leiomyoma of the Retzius space in a 49-year-old women who suffered for two years from bladder voiding symptoms characterized by dysuria, feeling of incomplete emptying, and pelvic pain. Clinical evaluation and abdominal and transvaginal ultrasound suggested the presence of a voluminous (about 10 cm in diameter) fibromyoma of the anterior uterus surface. The urodynamic evaluation demonstrated the presence of bladder outlet obstruction (voiding pressure greater than 20 cm H2O and maximum flow rate less than 12 mL/s) with a postvoiding urine residual equal to 80 mL; moreover, the presence of cystocele and urethral stricture was ruled out performing clinical evaluation, cystography, and cystourethroscopy. The patient underwent laparotomy to remove the uterine fibromyoma. Intraoperatively, a voluminous soft mass arising from the Retzius space was found; it was firmly adhered to the uterus with obliteration of vesicouterine pouch owing to severe adhesion to the anterior surface of uterus. The tumour was isolated, enucleated from the prevesical space, and removed; moreover, the patient became asymptomatic after surgery. In conclusion, leiomyoma of the Retzius space is a very rare benign tumour that should be considered in the presence of severe bladder voiding symptoms.
In female patients with neuropathic bladder, the urethra is closed permanently in order to avoid urine leak. Then Benchekroun hydraulic ileal valve is attached to urinary bladder, thus providing a continent stoma for performing intermittent catheterisations.
We present a female patient with spina bifida who underwent Benchekroun continent vesicostomy in 1993. This patient developed severe stenosis of Benchekroun stoma and stones in urinary bladder. Dilatation of stoma and vesicolithotomy were carried out in 1995. Vesical calculi recurred; suprapubic cystolithotomy was performed in 1999. In March 2000, catheterisation of stoma was not possible and emergency suprapubic cystostomy was done. In April 2000, endoscopy was attempted through Benchekroun stoma. It was not possible to insert ureterorenoscope beyond two inches. The track was completely blocked. In November 2001, X-ray of abdomen showed several vesical calculi; suprapubic cystolithotomy was performed.
In March 2005, this patient developed pain in abdomen. X-ray of abdomen showed a large vesical calculus. In June 2005, suprapubic catheter was removed and a cystoscope was introduced in to the bladder. Then electrohydraulic lithotripsy was performed. In 2007, this patient was concerned about the increasing swelling in lower abdomen. Computed tomography of abdomen revealed midline, lower abdominal wall hernia, which contained several loops of small bowel and ileal cystoplasty. The large hernia was uncomfortable and tender on coughing, but did not cause obstructive bowel symptoms. Surgical repair of hernia was considered. But this patient would require alternative way of urinary diversion because the current location of suprapubic catheter would almost lead to infection of prosthetic material used in reconstruction of the anterior abdominal wall. After discussing risks of operative procedures with patient and her husband, it was decided not to proceed with surgery.
This case is a poignant reminder to spinal cord physicians that novel surgical techniques should be viewed cautiously, and patients should be informed of potential complications of surgical procedures some of which could be irreversible.
The urofacial syndrome is probably a subset of neurogenic bladder dysfunction syndromes characterized by detrusor-sphincter discoordination along with a characteristic inversion of facial expression with laughing. This characteristic facial expression can facilitate early detection of this disorder, which leads to poor bladder emptying with high residual urine, hydro-nephrosis with vesico-ureteral reflux and potentially renal failure if left untreated. The etiology of the urofacial syndrome is unknown. In our case, a 12-year-old boy of Middle-Eastern origin presented to the Outpatient Department of our hospital with left pyelonephritis, hydronephrosis and bladder dilatation. Voiding cystourethrography performed 15 days later revealed left vesicoureteral reflux. Cystoscopy revealed bladder trabeculation however an anatomic urethral obstruction was not noticed. Both, neurological examination and radiography of the lumbosacral spine were normal. Urodynamic evaluation revealed the typical findings of detrusor-sphincter discoordination.
Neurogenic bladder dysfunction; enuresis; recurrent urinary tract infections; residual urine
Postoperative voiding dysfunction is a bothersome complication after mid-urethral sling surgery. The current study presents multiple repeated postoperative voiding trials against a urine load of preoperative functional bladder capacity, as estimated by a preoperative frequency volume chart, to identify the relevance of preoperative and immediate factors to the outcome.
A total of 180 patients were enrolled from August 2008 to August 2011. Patients received mid-urethral sling surgery with a transobturator tape, with or without concomitant cystocele repair. Patients reported relevant medical histories and a 3-day frequency volume chart and underwent urodynamic studies. After surgery, patients were filled to their maximum bladder capacity as dictated by their frequency volume chart and performed the first voiding trial. Two subsequent voiding trials were performed after natural filling. Failure of any single voiding trial was considered failure. Patients who failed the final voiding trial received intermittent catheterization to follow-up. After screening for relevant factors with the use of univariate analyses, preoperative, surgical, and postoperative factors predicting outcome were estimated by logistic regression analysis.
The urine load at the voiding trial and the peak flow rate immediately preceding the voiding trial predicted voiding trial success in the multivariate analysis. Urine load and previous trial peak flow rate were relevant when tested against each individual voiding trial. Preoperative and surgical factors, such as age, parity, and concomitant cystocele repair, showed significance in the univariate analysis. Overall, 16.1% of patients who passed the first voiding trial failed on subsequent trials, whereas 36.8% of patients who failed the first voiding trial succeeded.
Postoperative voiding dysfunction is transient and is associated with the immediate voiding conditions following surgery. Close observation against urine overload in the bladder is important when weaning patients back to normal voiding conditions.
Suburethral slings; Urinary retention; Urinary incontinence
Normal voiding behavior in urethane-anesthetized rats includes contraction of the abdominal wall striated muscle, similar to the visceromotor response (VMR) to noxious bladder distension. Normal rat voiding requires pulsatile release of urine from a pressurized bladder. The abdominal wall contraction accompanying urine flow may provide a necessary pressure increment for normal efficient pulsatile voiding. This study aimed to evaluate the occurrence and necessity of the voiding-associated abdominal wall activity in urethane-anesthetized female rats
A free-voiding model was designed to allow assessment of abdominal wall activity during voiding resulting from physiologic bladder filling, in the absence of bladder or urethral instrumentation. Physiologic diuresis was promoted by rapid intravascular hydration. Intercontraction interval (ICI), voided volumes and EMG activity of the rectus abdominis were quantified. The contribution of abdominal wall contraction to voiding was eliminated in a second group of rats by injecting botulinum-A (BTX, 5 U) into each rectus abdominis to induce local paralysis. Uroflow parameters were compared between intact free-voiding and BTX-prepared animals.
Abdominal wall response is present in free voiding. BTX preparation eliminated the voiding-associated EMG activity. Average per-void volume decreased from 1.8 ml to 1.1 ml (p < 0.05), and reduced average flow from 0.17 ml/sec to 0.11 ml/sec (p < 0.05). Intercontraction interval (ICI) was not changed by BTX pretreatment.
The voiding-associated abdominal wall response is a necessary component of normal voiding in urethane anesthetized female rats. As the proximal urethra may be the origin of the afferent signaling which results in the abdominal wall response, the importance of the bladder pressure increment due to this response may be in maintaining a normal duration intermittent pulsatile high frequency oscillatory (IPHFO)/flow phase and thus efficient voiding. We propose the term Voiding-associated Abdominal Response (VAR) for the physiologic voiding-associated EMG/abdominal wall response, to distinguish it from the visceromotor response (VMR) to noxious bladder distension.
Bladder cancer is a significant healthcare problem in the United States of America with a high recurrence rate. Early detection of bladder cancer is essential for removing the tumor with preservation of the bladder, avoiding metastasis and hence improving prognosis and long-term survival. The objective of this study was to analyze the presence of DEK protein in voided urine of bladder cancer patients as a urine-based bladder cancer diagnostic test.
We examined the expression of DEK protein by western blot in 38 paired transitional cell carcinoma (TCC) bladder tumor tissues and adjacent normal tissue. The presence of DEK protein in voided urine was analyzed by western blot in 42 urine samples collected from patients with active TCC, other malignant urogenital disease and healthy individuals.
The DEK protein is expressed in 33 of 38 bladder tumor tissues with no expression in adjacent normal tissue. Based on our sample size, DEK protein is expressed in 100% of tumors of low malignant potential, 92% of tumors of low grade and in 71% of tumors of high grade. Next, we analyzed 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals for DEK protein expression by western blot analysis. We are the first to show that the DEK protein is present in the urine of bladder cancer patients. Approximately 84% of TCC patient urine specimens were positive for urine DEK.
Based on our pilot study of 38 bladder tumor tissue and 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals; DEK protein is expressed in bladder tumor tissue and voided urine of bladder cancer patients. The presence of DEK protein in voided urine is potentially a suitable biomarker for bladder cancer and that the screening for the presence of DEK protein in urine can be explored as a noninvasive diagnostic test for bladder cancer.
Objectives. Using a urethral device at the fossa navicularis, bladder pressure during voiding can be estimated by a minimal invasive technique. This study purposes a new diagnostic index for patients with lower urinary tract symptoms (LUTSs). Methods. Fifty one patients presenting with LUTSs were submitted to a conventional urodynamic and a minimal invasive study. The results obtained through the urethral device and invasive classic urodynamics were compared. The existing bladder outlet obstruction index (BOOI) equation that classifies men with LUTSs was modified to allow minimal invasive measurement of isovolumetric bladder pressure in place of detrusor pressure at maximum urine flow. Accuracy of the new equation for classifying obstruction was then tested in this group of men. Results. The modified equation identified men with obstruction with a positive predictive value of 68% and a negative predictive value of 70%, with an overall accuracy of 70%. Conclusions. The proposed equation can accurately classify over 70% of men without resorting to invasive pressure flow studies. We must now evaluate the usefulness of this classification for the surgical treatment of men with LUTSs.
to report our experience with 41 patients treated by early endoscopic realignment of complete post-traumatic rupture urethra.
Materials and Methods:
The study includes patients presented to our institute, between May 2004 and April 2009, with post-traumatic complete posterior urethral disruption. Preoperative retrograde urethrography, voiding cystourethrography and abdominopelvic CT were performed to evaluate the urethral defect length, the bladder neck competence, the prostate position, and the extent of the pelvic hematoma. Within the first week after trauma, antegrade and retrograde urethroscopy were performed to identify both urethral ends and insert urethral catheter. Patients were followed up by pericatheter retrograde urethrogram monthly postoperatively till catheter removal on disappearance of extravasation. Retrograde urethrography, voiding cystourethrography and urethroscopy were performed 1 month after the removal of the catheter. Follow-up abdominal ultrasound and uroflowmetry monthly till 6 months, bimonthly till 1 year, and every 3 months thereafter were encouraged. Urinary continence and postoperative erectile dysfunction were assessed by direct patient interview.
Forty one patients in the age group 17-61 years (mean 37.9) were treated. Patients were followed up for
Early endoscopic realignment for complete posterior urethral rupture is a feasible technique with no or minimal intraoperative complications. The technique is successful as the definitive line of therapy in reasonable number of patients and seems to render further future interventions for inevitable urethral stricture easier.
Early; endoscopic realignment; post-traumatic; posterior urethra; urethral rupture
The symptoms and diagnosis of the three most common female bladder-urethral dysfunctions (infection, stress incontinence, and irritable bladder syndrome) are examined so that the practitioner may better differentiate between these problems and some of their counterparts. Cystitis cystica, urethritis, and radiation cystitis are among the less common infections and are frequently missed. Other conditions can be mistaken for infections: urethral diverticulum, Hunner's ulcer, atrophic vaginitis, urethral stenosis. Stress urinary incontinence, arising from abnormal bladder-urethral unit physiology or from obesity, can benefit from Kegel's exercise to strengthen the external sphincter and pubococcygeus muscles. For irritable bladder syndrome, which is often misdiagnosed, a bladder drill with increasing voiding intervals is useful. Patient understanding of bladder function and the need for retraining is also important.
Although minimal evidence exists, bladder calculi in men with benign prostatic hyperplasia are thought to be secondary to bladder outlet obstruction induced urinary stasis. We performed a prospective, multi-institutional clinical trial to determine whether metabolic differences were present in men with and without bladder calculi undergoing surgical intervention for benign prostatic hyperplasia induced bladder outlet obstruction.
Materials and Methods
Men who elected surgery for bladder outlet obstruction secondary to benign prostatic hyperplasia with and without bladder calculi were assessed prospectively and compared. Men without bladder calculi retained more than 150 ml urine post-void residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic studies were compared.
Of the men 27 had bladder calculi and 30 did not. Bladder calculi were associated with previous renal stone disease in 36.7% of patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs 0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference in the history of other medical conditions or in serum electrolytes. Bladder calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p = 0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01).
In this comparative prospective analysis patients with bladder outlet obstruction and benign prostatic hyperplasia with bladder calculi were more likely to have a renal stone disease history, low urinary pH, low urinary magnesium and increased urinary uric acid supersaturation. These findings suggest that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder calculi is likely complex with multiple contributing lithogenic factors, including metabolic abnormalities and not just urinary stasis.
urinary bladder calculi; etiology; hematuria; urinary retention; prostatic hyperplasia
Aims—To investigate the expression of CD44 proteins in exfoliated urothelial cells and in tumour tissues from bladder cancer patients. A further objective was to evaluate the diagnostic potential of the changes observed in the expression of these proteins as a marker for non-invasive detection of bladder cancer.
Methods—Naturally voided urine specimens were collected from 47 patients with bladder cancer or severe urothelial dysplasia (n=3) and from a control group of 43 people with no evidence of neoplastic disease. Exfoliated urothelial cells floating in the urine were pelleted by centrifugation and lysed, and their constituent proteins extracted. The pattern of expression of CD44 proteins in each sample was examined by western blot analysis using a monoclonal antibody, Hermes 3, which recognises an epitope on the polypeptide backbone of the CD44 protein. Immunohistochemical studies were performed on neoplastic (n=10) and normal (n=4) bladder tissue specimens which were snap frozen in liquid nitrogen before examination with antibodies to CD44 gene products (CD44s and CD44v6).
Results—Western blot analysis revealed several high molecular weight CD44 isoforms > 160 kDa in urine cell lysates from 75% of patients with histologically confirmed bladder cancer and in two of the three patients with severe dysplasia. Such patterns were not detected in the urine cell pellets from any persons in the control group. Immunohistochemical studies of the tissue distribution of CD44s and CD44v6 showed that the differentiation and maturation of the epithelial cells in the normal bladder mucosa is accompanied by a decrease in CD44 protein expression. However, carcinoma cells overexpress standard and variant CD44 isoforms and continue to do so as they proceed through the thickened epithelial layer to the luminal surface and after they are shed into the urine.
Conclusions—The abnormal expression of CD44 proteins in exfoliated cancer cells may be a useful marker for the noninvasive diagnosis of bladder cancer.
Bladder cancer; exfoliated cancer cells; CD44 protein
Dysfunctional voiding (DV) is a voiding disorder characterized by dyssynergic striated sphincteric activity in the absence of a proven neurological etiology. It can present at any age with a spectrum of storage and voiding symptoms that may resemble florid neurogenic bladder. There is a striking lack of clarity regarding what this entity represents, the diagnostic methodology and treatment. The limitations of existing guideline documents are analyzed. Specifically, use of the term “habitual”, the assumption that bladder changes are secondary to the outlet, the emphasis on “staccato” voiding and the implication of striated urethral sphincter are discussed. Literature shows that DV may also present with continuous slow flow or normal flow. Dyssynergia may be at the level of the striated urethral sphincter, the pelvic floor or both, better termed “striated urethral sphincter-pelvic floor complex” (SUS-PFC).A diagnostic algorithm is provided so that patients are evaluated on merit rather than on the basis of different philosophies of individual centers. High-risk markers such as hydronephrosis, vesicoureteral reflux, renal failure or marked voiding difficulty should prompt a formal urodynamics evaluation and imaging for neurological etiology. Patients with predominantly storage symptoms with incidental staccato voiding can be managed initially, on the basis of non-invasive evaluation. Conservative urotherapy including biofeedback is appropriate initial management for patients without high risk factors. Treatment and evaluation should be escalated based on response. Patients with severe DV will need treatment similar to neurogenic bladder including clean intermittent catheterization and measures to control storage pressures.
Dysfunctional voiding; guidelines; International Children's Continence Society; International Continence Society; terminology; staccato voiding; urodynamics; uroflow
The aim of this study was to evaluate the effect of asymptomatic urethral caruncle (UC) on micturition in women suffering from urinary incontinence.
Materials and Methods
A total of 232 patients participated in the study. UC was diagnosed in 50 of 232 patients with urinary incontinence during a physical examination in our clinic. All cases were divided into 2 groups: UC combined with urinary incontinence (group 1) and urinary incontinence only (group 2). Urodynamic evaluations were performed according to the International Continence Society standards.
Both groups were similar in terms of voiding diary, pad test and residual urine volume. Urodynamic studies revealed no significant difference between group 1 and 2 (infravesical obstruction: 6% vs. 4.4%; overactive detrusor: 44% vs. 42.9% respectively). The rates of severe IPSS (37.8% vs. 20.9%) and severe cystocele (20.9% vs. 13.8%) were numerically higher in group 1 with no statistically significant difference.
Our results suggest that there is no effect of asymptomatic UC on lower urinary tract symptoms in women with urinary incontinence. Therefore, treating asymptomatic UC is unnecessary in these patients. However, during incontinence surgery, it is the surgeon's decision whether to treat asymptomatic UC.
Micturition; Urethra; Urodynamics
A patient with cholinergic dysautonomia and a patient with pandysautonomia have each been investigated for disturbances of bladder and urethral function. Both patients suffered from an inability to develop or sustain a detrusor contraction, while retaining normal bladder sensation. Biopsy specimens of bladder muscle stained for acetylcholinesterase revealed a significant reduction in cholinergic nerves compared with controls; however, the prominent cholinergic subepithelial plexus was strikingly preserved. These findings lend support to the view that acetylcholinesterase-containing nerves in the bladder muscle are motor fibres responsible for detrusor contraction, while those located in the subepithelium are sensory in function. Urethral sphincter electromyography revealed no abnormality of individual motor units, confirming that motor unit integrity in this muscle is dependent upon somatic rather than autonomic innervation. In the patient with pandysautonomia the proximal urethra was incompetent, while in the patient with cholinergic dysautonomia the bladder neck remained closed, as in controls. This suggests that sympathetic rather than parasympathetic efferent activity is necessary for the maintenance of proximal urethral competence.
We present our experience of comparison of endoscopic treatment of vesical calculus in bladder stone.
Materials and Methods:
This study included 67 patients of bladder stone treated in this hospital from between June 2006 to December 2009 who were randomly assigned in three groups—group 1 (transurethral removal using a nephroscope), group 2 (transurethral removal using a cystoscope), and group 3 (percutaneous removal using a nephroscope).
Statistical significant difference was observed in operating time—group 1 (32.1+ 8.5 mins), group 2 (69.2 +16.3), and group 3 (46 + 7.3). Statistically significant difference was also observed in the postoperative stay of the patient, which was highest for the group 3 patients. Complete clearance was achieved in all the patients. Group 1 had maximum number of urethral entries as compared to other two groups in consideration.
Transurethral stone removal using a nephroscope is safe and efficacious method of stone removal without increasing the morbidity of the patients.
Cystolithotripsy; percutaneous cystolitholapexy; transurethral cystolitholapexy; vesical calculus
The aim of this study was to assess the usefulness of PCR for diagnosis of Trichomonas vaginalis infection among male patients with chronic recurrent prostatitis and urethritis. Between June 2001 and December 2003, a total of 33 patients visited the Department of Urology, Hanyang University Guri Hospital and were examined for T. vaginalis infection by PCR and culture in TYM medium. For the PCR, we used primers based on a repetitive sequence cloned from T. vaginalis (TV-E650). Voided bladder urine (VB1 and VB3) was sampled from 33 men with symptoms of lower urinary tract infection (urethral charge, residual urine sensation, and frequency). Culture failed to detect any T. vaginalis infection whereas PCR identified 7 cases of trichomoniasis (21.2%). Five of the 7 cases had been diagnosed with prostatitis and 2 with urethritis. PCR for the 5 prostatitis cases yielded a positive 330 bp band from bothVB1 and VB3, whereas positive results were only obtained from VB1 for the 2 urethritis patients. We showed that the PCR method could detect T. vaginalis when there was only 1 T. vaginalis cell per PCR mixture. Our results strongly support the usefulness of PCR on urine samples for detecting T. vaginalis in chronic prostatitis and urethritis patients.
Trichomonas vaginalis; PCR; prostatitis; urethritis; urine
A 48-year-old man was hospitalized with the chief complaints of lower abdominal pain, pain during micturation and pollakuria. Plain radiography showed 2 giant bladder stone shadows: one as 6.0 × 5.0 cm and the other one 5.0 × 5.0 cm in size. Cystolithotomy was performed. The first stone weighed 400 g and measured 6.0 × 5.0 × 6.0 cm in size, and the other stone was fragmented to smaller particles with pneumatic lithotriptor. Although a bladder stone is not rare, this case is interesting for 2 huge bladder calculi that were completely obstructing the bladder outlet and observed several years following pelvic trauma. To the best of our knowledge, our patient represents one of the largest bladder stone cases reported to date.
Low compliance urinary bladder with posterior urethral valve is not uncommon. This report describes management with laparoscopic diverticulocystoplasty, ureteric reimplantation, and detrusorrhaphy.
Low compliance bladder with a posterior urethral valve is a common association. Augmentation cystoplasty is one of the management options. We present the case report of a 4-y-old boy who presented with low compliance bladder, bladder diverticulum, right obstructive megaureter, and left grade IV reflux, 6 mo following PUV fulguration. He was managed by laparoscopic diverticulocystoplasty with right ureteric reimplantation and left detrusorrhaphy. The patient showed subjective and urodynamic improvement at 12 mo follow-up. The use of diverticulum for augmentation is advantageous, as it abides by the principle of bladder augmentation with urothelium. This is the first case report of successful use of diverticulum for laparoscopic bladder augmentation in a child.
Low compliance bladder; Pediatric; Posterior urethral valve; Laparoscopy; Diverticulocystoplasty; Diverticulum
A 35-year-old gravida 7, para 1, and abortus 5 female with hypogastric pain and inability to void urine after 14 + 3 weeks of amenorrhea was examined in the emergency department. One year before, a uterine prolapse had been diagnosed in another hospital. Examination showed a uterine prolapse grade 2 with palpable bladder. The patient was unable to void urine. After a manual reduction of the uterine prolapse, the patient underwent an emergency catheterization for bladder drainage. A Hodge pessary (size 70) was placed, which led to spontaneous micturitions. Due to the persistence of the symptoms the following day, Hodge pessary was replaced by an Arabin cerclage pessary. Although the pessary could be removed from the beginning of the second trimester, due to the uterine prolapse as a predisposing factor in the patient and the uncomplicated progression of pregnancy, it was decided to maintain it in our patient. Therefore, Arabin cerclage pessary allowed a successful pregnancy outcome and was not associated with threatened preterm delivery or vaginal infection.
Human papillomaviruses (HPVs) are associated with proliferative lesions in a variety of human epithelial types. A 38-year-old female presented with a diagnosis of urethral condyloma acuminatum. She underwent transurethral resection of the urethral condyloma. At that time, multiple (five) bladder tumors were simultaneously found and also removed by transurethral resection. Four of the bladder tumors were diagnosed as squamous papilloma, and the other was urothelial inverted papilloma. Postoperative course was uneventful. Genomic DNA was extracted from 10 μm thick sections of each bladder tumor as well as urethral condyloma. Then, 16 types of HPV DNA sequences were assessed with the PapiPlex method using genomic DNA samples extracted from each bladder tumor as well as urethral condyloma. HPV-11 was detected in DNA extracted from the urethral condyloma, while no HPV DNA sequences were positive in any of the genomic DNA samples extracted from the bladder tumors.
A new animal model that can evaluate bladder function and nociceptive behavior concurrently was developed using freely moving, non-catheterized conscious rats to assess nociceptive behavior responses induced by intravesical instillation of RTx and its relationship with bladder dysfunction.
Materials and Methods
In female SD rats, RTx (0, 0.3 and 3μM) was instilled via a catheter temporarily inserted into the bladder through the urethra. Then, after removing the catheter, the incidence of nociceptive behavior (lower abdominal licking and freezing) was scored. Voided urine was collected continuously for the measurement of bladder capacity. In some animals, the pudendal nerves were transected bilaterally (PNT rats) in order to eliminate activation of urethral afferents by RTx.
Intravesical instillation of RTx induced decreased bladder capacity and increased nociceptive behaviors such as licking and freezing, which were blocked by BCTC, a TRPV1 antagonist. In PNT rats, the early phase of RTx-induced licking was decreased without affecting the RTx-induced reduction in bladder capacity and late-phase licking behavior, and RTx-induced late-phase licking in the water-unloaded group was observed to a lesser extent compared with the water-loaded diuresis group.
The intravesical instillation of RTx, which decreases bladder capacity, acts by at least three distinct mechanisms to induce licking behavior; (1) the immediate response mediated by activation of urethral afferents in the pudendal nerve, (2) a late occurring response evoked by direct stimulation of C-fiber afferents in the bladder and (3) gradual facilitation of the response elicited by bladder wall distension induced by rapid bladder filling.
rat; nociceptive behavior; urinary frequency; resiniferatoxin
OBJECTIVE: To review the clinical classification of childhood diurnal enuresis, to describe the evaluation process, and to discuss principles of management. QUALITY OF EVIDENCE: An extensive literature review was performed with a MEDLINE search. Articles were selected according to date of publication, clinical relevance, and availability. Recent articles, cohort studies of at least 50 patients, and randomized clinical trials were preferred. Recent editions of classic textbooks were consulted. Evaluation and management activities discussed in this article are supported by original and relevant literature. MAIN MESSAGE: Most causes of childhood diurnal enuresis can be determined by a thorough history coupled with a complete physical examination and urinalysis and culture. Supplementary investigations include ultrasonography of the kidneys and bladder to screen for neurogenic bladder and urethral obstruction. When obstruction, ectopic ureter, or bladder dysfunction is suspected, voiding cystourethrography and urodynamic studies are needed. Evaluation of neurogenic bladder includes magnetic resonance imaging of the spine. Treatment is aimed at correcting poor toilet habits, preventing or treating urinary tract infections, and using appropriate medication. CONCLUSIONS: In most instances, diurnal enuresis in childhood is a benign condition with an easily identifiable cause and an excellent prognosis with time and appropriate treatment.
Posterior urethral valves are the commonest cause of lower urinary tract outflow obstruction in male infants with an estimated incidence of 1:5000 male infants and 1:25,000 live births. Despite treatment with fulguration of the obstructing valves, bladder function is abnormal in up to 70% of older children and adolescents. Bladder dysfunction causes morbidity e.g. urinary incontinence and has been implicated in the late deterioration of renal function in this population. A poor understanding and inappropriate management of bladder dysfunction can result in unnecessary morbidity, which can handicap a child for life. Any method that measures function or dysfunction of the lower urinary tract constitutes a urodynamics investigation. Broadly, the investigations can be classified into simple or noninvasive urodynamics and invasive urodynamics. The objective of urodynamics assessments in children is to reproduce the patient's complaints or symptoms. Video urodynamics can provide additional information that may contribute to a further understanding of the problem under investigation. Urodynamics provides a useful tool to test the efficacy of treatment as well as determine any refinements necessary to improve the outcome of such treatment.
Children; posterior urethral valves; urodynamic evaluation
The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M3 subtype, with the M2 subtype providing a secondary backup role. Bladder relaxation, which is required for urine storage, is mediated by β-adrenoceptors, in most species involving a strong β3-component. An excessive stimulation of contraction or a reduced relaxation of the detrusor smooth muscle during the storage phase of the micturition cycle may contribute to bladder dysfunction known as the overactive bladder. Therefore, interference with the signal transduction of these receptors may be a viable approach to develop drugs for the treatment of overactive bladder. The prototypical signaling pathway of M3 receptors is activation of phospholipase C (PLC), and this pathway is also activated in the bladder. Nevertheless, PLC apparently contributes only in a very minor way to bladder contraction. Rather, muscarinic-receptor-mediated bladder contraction involves voltage-operated Ca2+ channels and Rho kinase. The prototypical signaling pathway of β-adrenoceptors is an activation of adenylyl cyclase with the subsequent formation of cAMP. Nevertheless, cAMP apparently contributes in a minor way only to β-adrenoceptor-mediated bladder relaxation. BKCa channels may play a greater role in β-adrenoceptor-mediated bladder relaxation. We conclude that apart from muscarinic receptor antagonists and β-adrenoceptor agonists, inhibitors of Rho kinase and activators of BKCa channels may have potential to treat an overactive bladder.
Bladder; Muscarinic receptor; β-adrenoceptor; Phospholipase C; cAMP; Rho kinase; BKCa channel; L-type Ca2+ channel
Bladder cancer is a significant cause of morbidity and mortality with a high recurrence rate. Early detection of bladder cancer is essential in order to remove the tumor, to preserve the organ and to avoid metastasis. The aim of this study was to analyze the differential expression of mitochondrial non-coding RNAs (sense and antisense) in cells isolated from voided urine of patients with bladder cancer as a noninvasive diagnostic assay.
The differential expression of the sense (SncmtRNA) and the antisense (ASncmtRNAs) transcripts in cells isolated from voided urine was determined by fluorescent in situ hybridization. The test uses a multiprobe mixture labeled with different fluorophores and takes about 1 hour to complete. We examined the expression of these transcripts in cells isolated from urine of 24 patients with bladder cancer and from 15 healthy donors.
This study indicates that the SncmtRNA and the ASncmtRNAs are stable in cells present in urine. The test reveals that the expression pattern of the mitochondrial transcripts can discriminate between normal and tumor cells. The analysis of 24 urine samples from patients with bladder cancer revealed expression of the SncmtRNA and down-regulation of the ASncmtRNAs. Exfoliated cells recovered from the urine of healthy donors do not express these mitochondrial transcripts. This is the first report showing that the differential expression of these mitochondrial transcripts can detect tumor cells in the urine of patients with low and high grade bladder cancer.
This pilot study indicates that fluorescent in situ hybridization of cells from urine of patients with different grades of bladder cancer confirmed the tumor origin of these cells. Samples from the 24 patients with bladder cancer contain cells that express the SncmtRNA and down-regulate the ASncmtRNAs. In contrast, the hybridization of the few exfoliated cells recovered from healthy donors revealed no expression of these mitochondrial transcripts. This assay can be explored as a non-invasive diagnostic tool for bladder cancer.