- Email: [email protected]
111Upregulation of both PDGF-bb and PDGF-BB receptor in human bladder fibroblasts in response to hydrostatic pressure in the physiologic range
109 W H I C H METHOD IS THE MOST RELIABLE IN DETERMINATION OF THE MAXIMUM BLADDER CAPACITY IN INCONTINENT CHILDREN WITH NON-NEUROPATHIC BLADDER DISORDERS: A COMPARISON OF 24 HOURS BLADDER DIARY, U R O F L O W M E T R Y AND CYSTOMETRY Rodoplu H., Ziylan O., Ineesu O., Oktar T., Ander H.
CAN ALPHA BLOCKER THERAPY BE AN ALTERNATIVE THERAPY TO BIOFEEDBACK IN DYSFUNCTIONAL VOIDING AND URINARY RETENTION: A PROSPECTIVE STUDY Yucel S. t, Akkaya E. 1, Guntekin E. 1, Kukul E. 1 Alcman S.2, Gur Guven A.2, Baykar~ ]¢i. tAkdeniz Univ. School of Med., Department of Urology, Antalya, Turkey, 2Akderiz Univ. School of Med., Department of Paediatric Nephrology, Antalya, Turkey
Istanbul University, Department of Urology, Paediatric Urology Section, Istanbul, Turkey INTRODUCTION & OBJECTIVES: The bladder capacity is an important parameter in the management of incontinent children with non-neuropathic bladder disorders. The traditional means of assessing bladder size has been urodynamics. We aimed to compare the findings of cystometric investigation with uroflowmetry and 24 hours bladder diary in a prospective design. MATERIAL & METHODS: Between January 2004-October 2004, total 41 cases (11 boys, 27 girls), who were addressed to the urodynamics laboratory, were included into the study. A bladder diary covered 5 days was obtained from each case. Subsequently, uroflowmetry included postvoiding residual urine measured by ultrasound and cystometric investigation were done at the same s6ance. The maximum bladder capacity at urodynamics and voided volume and residual urine volume at uroflowmetry were compared separately with the largest of the listed voided urinary volumes for each case using the paired, samples t-test. Incontinent cases due to neuropathic or anatomic causes were excluded from the study.
INTRODUCTION & OBJECTIVES: Traditional therapy for dysfunctional ,~oider (DV) children with urinary retention (UR) involves retraining the pelvic floor muscles using biofeedback (BF). Alpha blockers (AB) is reported to be also effective in children with UR and DV. We aimed to compare the efficacy of BF and AB in DV childre~ with UR. MATERIAL & METHODS: 28 patients with a mean age of 6.25 (range 4- 10) presented with symptoms of urinary incontinence, urgency and urinary tract infections without anatomic and neurogenic causes of UR. All patients had elevated post void residual urine (PVR) (mean: 59 ml, 32% of age expected capacity (AEC)). BF mm consisted of 16 patients (mean age: 6.5 years) with a mean of 54 ml PVR (30% of AEC) and AB arm consisted of 12 children (mean age: 5.9 years) with a mean of 64 ml (38% of AEC). Both groups were also instructed in timed voiding and constipation therapy. BF (median: 10, range: 6 16 sessions) and doxazosin (0.5-1 mg) was given and at the third month results of incontinence episodes, urinary tract infections, average and mean flow rates, PVR results and parental satisfaction grade (1- 10) are re-evalnated. 6 refractory cases were started on AB and BF and reevaluated after 4 weeks.
RESULTS: The mean age of the cases was 8.6±3.13 years (4-15 years). Overactive bladder syndrome was diagnosed in 33 cases. 8 cases had applied with monosymptomatic nocturnal enuresis complaint and overactive bladder existence was also defined in these cases. Estimated bladder capacities were 275.2±141.44 ml by bladder diary, 202.7--140.39 ml by uroflowmetry and 211.0-116B8 ml by cystometry. The bladder capacity estimated by bladder diary was higher than the bladder capacities estimated by uroflowmetry and cystometry (p<0.05). The difference between the capacities defned by uroflowmetry and cystometry was not significant statistically.
RESULTS: Mean PVR was 21 ml (12% of AEC) in BF arm (p<0.05) and 17 ml (10% ofAEC) (p<0.05) in AB arm. There was no statistical difference ofpost-tream:ent PVR between two arms (p>0.05). 4 (25%) children continued to have high PVR in BF arm and 2 (16%) did so in AB arm. 10 (62.5%) children of BF feedback had improved urge incontinence episodes while 7 (70%) children of AB group had improved urge incontinence episodes. In therapy responsive children, parental satisfaction was higher in AB arm (9.2 vs. 7.9) (p<0.05). Combined treatment of BF and AB helped 5 oul of 6 children with refractory high PVR. PVR decreased significantly after combinalion treatment of BF and AB (mean 80 m135% of AEC vs. mean 15 ml 7% of AEC). No drug related side-effect was reported in AB arm.
CONCLUSIONS: The bladder diary provides a reliable non-invasive estimate of bladder size in incontinent children with non-neuropathic bladder disorders. We conclude it should be an inherent part ofurodynamic investigation in this group of children.
CONCLUSIONS: AB therapy seems to be a viable alternative to BF in DV children with UR. Both types of treatment (BF and AB) can be additional therapies to each other in refractory cases.
111
112
UPREGULATION OF BOTH PDGF-BB AND PDGF-BB RECEPTOR IN H U M A N B L A D D E R FIBROBLASTS IN RESPONSE TO HYDROSTATIC PRESSURE IN THE PHYSIOLOGIC RANGE
C O L L A G E N PROLYL 4-HYDROXYLASE A C T I V I T Y IS UPREGULATED IN BLADDER OUTLET OBSTRUCTION Lee S.D., Miseeri R., Akbal C., Jung C., Kaefer M.
Akbal C., Lee S.D., Jung C., Rink R., Kaefer M. Indiana University School of Medicine, Paediatric Urology, Indianapolis, United States Indiana University School of Medicine, Paediatric Urology, Indianapolis, United States INTRODUCTION & OBJECTIVES: Bladder outlet obstruction can lead to the deposition of extracellular matrix and a resultant decrease in bladder wall compliance. Platelet derived growth factor (PDGF) is a potent mitogen for fibroblasts and can increase the deposition of extracellular matrix. We attempt to determine if the expression of PDGF-BB and its receptor are altered in human bladder fibroblasts and bladder smooth muscle cells when exposed to hydrostatic pressures in the physiologic range. MATERIAL & METHODS: Cultured human bladder fibroblasts and smooth muscle cells were evaluated in vitro by using a novel device that controls for hydrostatic pressure. Cells were exposed to pressures of 20 and 40 cm-H20 for up to 72 hours. Western blot analyses and reverse transcription polymerase chain reaction (RT-PCR) were performed to evaluate expression of both PDGF-BB and PDGF-BB Receptor (PDGF-BB R). RESULTS: Most notably, when human bladder fibroblasts were exposed to 40 cm-H20 sustained hydrostatic pressure, both PDGF-BB and its receptor increased up to 22 fold and 8 fold respectively, while at 20 cm-H20 the effect was minimal. RT-PCR for PDGF-BB R in human bladder fibroblasts revealed an increase when compared to control. Western blot analyses demonstrated that exposure of human bladder smooth muscle cells to a sustained hydrostatic pressure of 20 and 40 cm-H20 for up to 72 hours did not alter expression of either PDGF-BB or its receptor. CONCLUSIONS: Both PDGF-BB and PDGF-BB R for human bladder fbroblasts were up-regulated in a time and pressure dependent fashion after as little as 24 hours exposure to pressure of _< 40 cm-H20. Our results provide support for a potential role of both PDGF-BB and PDGF-BB R in bladder fibrosis secondary to increased intravesical pressure. Newer selective PDGF receptor antagonists may prove beneficial in preventing bladder wall fibrosis in patient with either anatomic or functional bladder outlet obstruction.
European Urology Supplements 4 (2005) No. 3, pp. 30
INTRODUCTION & OBJECTIVES: Bladder outlet obstruction with intravesical pressures exceeding 40 cm-H20 results in alterations in bladder physiology, including wall thickening, reduced compliance, and decreased capacity. From a biomechanical standpoint, compliance is primarily related to extracellular matrix depositSon. The collagen pmlyl 4-hydroxyalse (P 4-H) plays a critical role in the synthesis of the extracellular matrix. To study the alteration of P 4-H under the influence of variable hydrostatic pressures, we employed a novel pressure device to expose human bladder smooth muscle cells (HBSMC) and fibroblast to pressures in the physiologic range. Acute obstructed porcine bladder tissues were subsequently evaluated to see if these changes were also seen with in vivo. MATERIAL & METHODS: HBSMC and fibroblast were evaluated in vitro using a novel device that controls for hydrostatic pressure. Cells were exposed to pressures of 0, 20 and 40 cm-H20 for up to 72 hours. Expression of the P 4-H was studied using western blot. Acute bladder outlet obstruction was maintained in five male pigs for 24 hours. Six normal animals served as controls. Following sacrifice, tissues were snap frozen and the expression ofP 4-H evaluated in a similar fashion as for the isolated cells. Reverse transcription polymerase chain reaction (RT-PCR) was also performed to determine the altered expression of mRNA for P 4-H. RESULTS: Exposure of bladder fibroblasts to sustained hydrostatic pressure resulted in increased production of P 4-H protein in a time (up to 72 hours) and pressure (up to 40 cmH20) dependent manner. In contrast, no significant difference in the expression of P 4-H in HBSMC could be demonstrated relative to controls. In vivo, pigs were experienced a mean de~usor pressure of < 20 cm-HaO during the 24 hour period. P 4-Hprotein expression was significantly increased in the obstructed group when compared to those of controls. RT-PCR revealed similar changes in mRNA levels. CONCLUSIONS: Our results reveal that P 4-H in the human bladder is up-regulated in a time and pressure dependent fashion. This alteration of P 4-H may significantly influence the synthesis of extraceIlular matrix in vivo, leading to decreased compliance. Our results also support the concept that bladder outlet obstruction with resultant pressures of 40 cm. H20 or less result in molecular changes consistent with decreased compliance.
CAN ALPHA BLOCKER THERAPY BE AN ALTERNATIVE THERAPY TO BIOFEEDBACK IN DYSFUNCTIONAL VOIDING AND URINARY RETENTION: A PROSPECTIVE STUDY Yucel S. t, Akkaya E. 1, Guntekin E. 1, Kukul E. 1 Alcman S.2, Gur Guven A.2, Baykar~ ]¢i. tAkdeniz Univ. School of Med., Department of Urology, Antalya, Turkey, 2Akderiz Univ. School of Med., Department of Paediatric Nephrology, Antalya, Turkey
Istanbul University, Department of Urology, Paediatric Urology Section, Istanbul, Turkey INTRODUCTION & OBJECTIVES: The bladder capacity is an important parameter in the management of incontinent children with non-neuropathic bladder disorders. The traditional means of assessing bladder size has been urodynamics. We aimed to compare the findings of cystometric investigation with uroflowmetry and 24 hours bladder diary in a prospective design. MATERIAL & METHODS: Between January 2004-October 2004, total 41 cases (11 boys, 27 girls), who were addressed to the urodynamics laboratory, were included into the study. A bladder diary covered 5 days was obtained from each case. Subsequently, uroflowmetry included postvoiding residual urine measured by ultrasound and cystometric investigation were done at the same s6ance. The maximum bladder capacity at urodynamics and voided volume and residual urine volume at uroflowmetry were compared separately with the largest of the listed voided urinary volumes for each case using the paired, samples t-test. Incontinent cases due to neuropathic or anatomic causes were excluded from the study.
INTRODUCTION & OBJECTIVES: Traditional therapy for dysfunctional ,~oider (DV) children with urinary retention (UR) involves retraining the pelvic floor muscles using biofeedback (BF). Alpha blockers (AB) is reported to be also effective in children with UR and DV. We aimed to compare the efficacy of BF and AB in DV childre~ with UR. MATERIAL & METHODS: 28 patients with a mean age of 6.25 (range 4- 10) presented with symptoms of urinary incontinence, urgency and urinary tract infections without anatomic and neurogenic causes of UR. All patients had elevated post void residual urine (PVR) (mean: 59 ml, 32% of age expected capacity (AEC)). BF mm consisted of 16 patients (mean age: 6.5 years) with a mean of 54 ml PVR (30% of AEC) and AB arm consisted of 12 children (mean age: 5.9 years) with a mean of 64 ml (38% of AEC). Both groups were also instructed in timed voiding and constipation therapy. BF (median: 10, range: 6 16 sessions) and doxazosin (0.5-1 mg) was given and at the third month results of incontinence episodes, urinary tract infections, average and mean flow rates, PVR results and parental satisfaction grade (1- 10) are re-evalnated. 6 refractory cases were started on AB and BF and reevaluated after 4 weeks.
RESULTS: The mean age of the cases was 8.6±3.13 years (4-15 years). Overactive bladder syndrome was diagnosed in 33 cases. 8 cases had applied with monosymptomatic nocturnal enuresis complaint and overactive bladder existence was also defined in these cases. Estimated bladder capacities were 275.2±141.44 ml by bladder diary, 202.7--140.39 ml by uroflowmetry and 211.0-116B8 ml by cystometry. The bladder capacity estimated by bladder diary was higher than the bladder capacities estimated by uroflowmetry and cystometry (p<0.05). The difference between the capacities defned by uroflowmetry and cystometry was not significant statistically.
RESULTS: Mean PVR was 21 ml (12% of AEC) in BF arm (p<0.05) and 17 ml (10% ofAEC) (p<0.05) in AB arm. There was no statistical difference ofpost-tream:ent PVR between two arms (p>0.05). 4 (25%) children continued to have high PVR in BF arm and 2 (16%) did so in AB arm. 10 (62.5%) children of BF feedback had improved urge incontinence episodes while 7 (70%) children of AB group had improved urge incontinence episodes. In therapy responsive children, parental satisfaction was higher in AB arm (9.2 vs. 7.9) (p<0.05). Combined treatment of BF and AB helped 5 oul of 6 children with refractory high PVR. PVR decreased significantly after combinalion treatment of BF and AB (mean 80 m135% of AEC vs. mean 15 ml 7% of AEC). No drug related side-effect was reported in AB arm.
CONCLUSIONS: The bladder diary provides a reliable non-invasive estimate of bladder size in incontinent children with non-neuropathic bladder disorders. We conclude it should be an inherent part ofurodynamic investigation in this group of children.
CONCLUSIONS: AB therapy seems to be a viable alternative to BF in DV children with UR. Both types of treatment (BF and AB) can be additional therapies to each other in refractory cases.
111
112
UPREGULATION OF BOTH PDGF-BB AND PDGF-BB RECEPTOR IN H U M A N B L A D D E R FIBROBLASTS IN RESPONSE TO HYDROSTATIC PRESSURE IN THE PHYSIOLOGIC RANGE
C O L L A G E N PROLYL 4-HYDROXYLASE A C T I V I T Y IS UPREGULATED IN BLADDER OUTLET OBSTRUCTION Lee S.D., Miseeri R., Akbal C., Jung C., Kaefer M.
Akbal C., Lee S.D., Jung C., Rink R., Kaefer M. Indiana University School of Medicine, Paediatric Urology, Indianapolis, United States Indiana University School of Medicine, Paediatric Urology, Indianapolis, United States INTRODUCTION & OBJECTIVES: Bladder outlet obstruction can lead to the deposition of extracellular matrix and a resultant decrease in bladder wall compliance. Platelet derived growth factor (PDGF) is a potent mitogen for fibroblasts and can increase the deposition of extracellular matrix. We attempt to determine if the expression of PDGF-BB and its receptor are altered in human bladder fibroblasts and bladder smooth muscle cells when exposed to hydrostatic pressures in the physiologic range. MATERIAL & METHODS: Cultured human bladder fibroblasts and smooth muscle cells were evaluated in vitro by using a novel device that controls for hydrostatic pressure. Cells were exposed to pressures of 20 and 40 cm-H20 for up to 72 hours. Western blot analyses and reverse transcription polymerase chain reaction (RT-PCR) were performed to evaluate expression of both PDGF-BB and PDGF-BB Receptor (PDGF-BB R). RESULTS: Most notably, when human bladder fibroblasts were exposed to 40 cm-H20 sustained hydrostatic pressure, both PDGF-BB and its receptor increased up to 22 fold and 8 fold respectively, while at 20 cm-H20 the effect was minimal. RT-PCR for PDGF-BB R in human bladder fibroblasts revealed an increase when compared to control. Western blot analyses demonstrated that exposure of human bladder smooth muscle cells to a sustained hydrostatic pressure of 20 and 40 cm-H20 for up to 72 hours did not alter expression of either PDGF-BB or its receptor. CONCLUSIONS: Both PDGF-BB and PDGF-BB R for human bladder fbroblasts were up-regulated in a time and pressure dependent fashion after as little as 24 hours exposure to pressure of _< 40 cm-H20. Our results provide support for a potential role of both PDGF-BB and PDGF-BB R in bladder fibrosis secondary to increased intravesical pressure. Newer selective PDGF receptor antagonists may prove beneficial in preventing bladder wall fibrosis in patient with either anatomic or functional bladder outlet obstruction.
European Urology Supplements 4 (2005) No. 3, pp. 30
INTRODUCTION & OBJECTIVES: Bladder outlet obstruction with intravesical pressures exceeding 40 cm-H20 results in alterations in bladder physiology, including wall thickening, reduced compliance, and decreased capacity. From a biomechanical standpoint, compliance is primarily related to extracellular matrix depositSon. The collagen pmlyl 4-hydroxyalse (P 4-H) plays a critical role in the synthesis of the extracellular matrix. To study the alteration of P 4-H under the influence of variable hydrostatic pressures, we employed a novel pressure device to expose human bladder smooth muscle cells (HBSMC) and fibroblast to pressures in the physiologic range. Acute obstructed porcine bladder tissues were subsequently evaluated to see if these changes were also seen with in vivo. MATERIAL & METHODS: HBSMC and fibroblast were evaluated in vitro using a novel device that controls for hydrostatic pressure. Cells were exposed to pressures of 0, 20 and 40 cm-H20 for up to 72 hours. Expression of the P 4-H was studied using western blot. Acute bladder outlet obstruction was maintained in five male pigs for 24 hours. Six normal animals served as controls. Following sacrifice, tissues were snap frozen and the expression ofP 4-H evaluated in a similar fashion as for the isolated cells. Reverse transcription polymerase chain reaction (RT-PCR) was also performed to determine the altered expression of mRNA for P 4-H. RESULTS: Exposure of bladder fibroblasts to sustained hydrostatic pressure resulted in increased production of P 4-H protein in a time (up to 72 hours) and pressure (up to 40 cmH20) dependent manner. In contrast, no significant difference in the expression of P 4-H in HBSMC could be demonstrated relative to controls. In vivo, pigs were experienced a mean de~usor pressure of < 20 cm-HaO during the 24 hour period. P 4-Hprotein expression was significantly increased in the obstructed group when compared to those of controls. RT-PCR revealed similar changes in mRNA levels. CONCLUSIONS: Our results reveal that P 4-H in the human bladder is up-regulated in a time and pressure dependent fashion. This alteration of P 4-H may significantly influence the synthesis of extraceIlular matrix in vivo, leading to decreased compliance. Our results also support the concept that bladder outlet obstruction with resultant pressures of 40 cm. H20 or less result in molecular changes consistent with decreased compliance.