Interstitial cystitis (IC) is a disease defined by a constellation of signs and symptoms; its eti... more Interstitial cystitis (IC) is a disease defined by a constellation of signs and symptoms; its etiology is not well understood. There are multiple theories regarding the cause of IC; however, no one cause has been proven conclusively. In the meantime, physicians are trying to accurately diagnose a disease that has no identified definitive cause. There have been multiple tests designed to aid in the diagnosis of IC and there are new tests on the horizon that appear promising. However, the diagnosis of IC still is one of exclusion and based primarily on clinical findings. The most useful tests are described in this article, which may make diagnosis a more accurate, less arduous process.
ObjectivesTo assess the effects of intravesical injection of botulinum toxin type A (BTX) on a mo... more ObjectivesTo assess the effects of intravesical injection of botulinum toxin type A (BTX) on a model of detrusor overactivity induced by intravesical infusions of adenosine triphosphate (ATP) and capsaicin. BTX has recently been used clinically to treat overactive bladder syndromes without a precise knowledge of the mechanism of action.
Dr. Edward McGuire's academic career spans four decades. His impact in our field of female ur... more Dr. Edward McGuire's academic career spans four decades. His impact in our field of female urology and urodynamics is reflected by the many residents and fellows he has trained that are now academic leaders in our subspecialty. For this festschrift, my goals are to: (1) review the history of the surgical approaches to alleviate stress urinary incontinence (SUI) (2) discuss recent research in SUI and bladder storage symptoms and the influence of Dr. McGuire in these areas and (3) propose a paradigm shift in the understanding of the function of the bladder urothelium from providing barrier function to providing afferent input that affects bladder storage function. A literature review of the publications related to SUI and bladder storage symptoms was performed. Using Thompson Reuters ISI Web of Knowledge, the two most cited papers by Dr. McGuire are discussed. Dr. McGuire's two most cited publications are related to valsalva leak point pressure (VLPP) and the utility of the Am...
Scandinavian journal of urology and nephrology. Supplementum, 1996
Retrograde axonal tracers were used to assess the laterality of bladder innervation which is unkn... more Retrograde axonal tracers were used to assess the laterality of bladder innervation which is unknown. Fluoro-Gold and Fast Blue were injected into the left and right bladder walls, respectively of male Wistar rats. The major pelvic (MPG), pelvic accessory (PAG), and dorsal root (DRG) ganglia were then removed and analyzed. 59% and 33% of the total labelled MPG cells were found in the ipsilateral and contralateral MPG (efferents), respectively. 65% and 31% of the total labelled PAG cells were found in the ipsilateral and contralateral PAG (efferents) respectively. The L1/L2 and L6/S1 DRG each received similar amount of ipsilateral innervation (45-52%) based on total labelled cells at each DRG level. 8%, 4%, and 4% of labelled cells in the MPG, PAG and DRG, respectively, contained both Fluoro-Gold and Fast Blue consistent with bilateral input originating from a single neuron. Immunohistochemistry showed that 40% of retrogradely labelled PAG cells were positive for tyrosine hydroxylase...
A 42-year-old woman with an ileal loop urinary conduit that was placed 30 years ago was referred ... more A 42-year-old woman with an ileal loop urinary conduit that was placed 30 years ago was referred for cadaveric renal transplantation. The initial surgical plan was to perform a transplant ureteral reimplant directly into the ileal conduit with a concomitant left nephrectomy for angiomyolipoma. However, at surgery, a donor to native side-to-side ureteroureterostomy along with a simple left nephrectomy was performed. The cadaveric donor kidney was transplanted upside down to allow the donor ureter to reach the proximal native ureter. A follow-up loopogram performed 6 months after the operation revealed a widely patent anastomosis ). Serum creatinine was 0.8 mg/dL at 6 months after transplant.
To determine whether men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have uri... more To determine whether men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have urine markers previously described for patients with interstitial cystitis (IC; presence of antiproliferative factor [APF] activity, decreased levels of heparin-binding epidermal growth factor-like growth factor [HB-EGF], and increased levels of epidermal growth factor). Clean catch urine specimens were collected from 41 symptomatic patients with CP/CPPS, 36 asymptomatic men without bladder disease who served as the control group, and 24 men with IC. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and epidermal growth factor levels were determined by enzyme-linked immunosorbent assay. Men with CP/CPPS did not differ significantly from asymptomatic controls for any of the three markers tested (P >0.49). In contrast, APF activity was present significantly more often and HB-EGF levels were significantly lower in the urine specimens from men with IC than in the specimens from controls or patients with CP/CPPS (P <0.00001 for all four comparisons). Although the epidermal growth factor levels also tended to be higher in the urine from patients with IC than in the urine from controls, the difference did not reach statistical significance (P = 0.06). These findings indicate that at least two of the urine biomarkers previously identified in women with IC (presence of APF activity and decreased levels of HB-EGF) are also found in men with IC, but not in men with CP/CPPS. This finding suggests that IC and CP/CPPS may be two different disorders with distinct pathophysiologies. It also confirms the utility of the presence of APF activity and HB-EGF levels as markers for IC in men, as well as in women, with this disorder.
An Escherichia coli mutant (lpp-14-1), with an alteration of glycine to aspartic acid at the 14th... more An Escherichia coli mutant (lpp-14-1), with an alteration of glycine to aspartic acid at the 14th amino acid residue of the prolipoprotein signal sequence, has previously been shown to contain unmodified and unprocessed prolipoprotein in its cell envelope. Both the wild-type and the lpp-14-1 alleles of the lpp gene have been cloned onto a phage lambda vector. Two pseudorevertant alleles of lpp-14-1 (14R21 and 6a) have been isolated, cloned and sequenced. Amino acid sequences, deduced from the DNA sequences of the two revertant lipoprotein alleles, and biochemical characterization of the revertant lipoproteins, show that a conversion of the aspartic acid (residue 14) to asparagine completely restores the modification and processing of the 14R21 revertant prolipoprotein, while a change of the threonine-16 to isoleucine-16 partially enhances the modification and processing of the 6a prolipoprotein, which retains the aspartate-14 substitution. Secondary structure analysis of the reverta...
Aims: Urodynamic studies (UDS) are generally recommended prior to surgical treatment for stress u... more Aims: Urodynamic studies (UDS) are generally recommended prior to surgical treatment for stress urinary incontinence (SUI), despite insufficient evidence that it impacts treatment plans or outcomes in patients with uncomplicated SUI. This analysis aimed to calculate the cost incurred when UDS was performed as a supplement to a basic office evaluation and to extrapolate the potential savings of not doing UDS in this patient population on a national basis. Methods: This is a secondary analysis from the Value of Urodynamic Evaluation (ValUE) trial, a multicenter non-inferiority randomized trial to determine whether a basic office evaluation (OE) is non-inferior in terms of SUI surgery outcomes to office evaluation with addition of urodynamic studies (UDS). All participants underwent an OE; those patients who randomized to supplementary UDS underwent non-instrumented uroflowmetry, filling cystometry, and a pressure flow study. Costs associated with UDS were calculated using 2014 U.S. Medicare allowable fees. Models using various patient populations and payor mixes were created to obtain a range of potential costs of performing UDS in patients undergoing SUI surgery annually in the United States. Results: Six hundred thirty women were randomized to OE or OE plus UDS. There was no difference in surgical outcomes between the two groups. The per patient cost of UDS varied from site to site, and included complex cystometrogram $314-$343 (CPT codes 51728-51729) plus complex uroflowmetry $16 (CPT code 51741). Extrapolating these costs for US women similar to our study population, 13-33 million US dollars could be saved annually by not performing preoperative urodynamics. Conclusion: For women with uncomplicated SUI and a confirmatory preoperative basic office evaluation, tens of millions of dollars US could be saved annually by not performing urodynamic testing. In the management of such women, eliminating this preoperative test has a major economic benefit.
Understanding of the role of urothelium in regulating bladder function is continuing to evolve. W... more Understanding of the role of urothelium in regulating bladder function is continuing to evolve. While the urothelium is thought to function primarily as a barrier for preventing injurious substances and microorganisms from gaining access to bladder stroma and upper urinary tract, studies indicate it may also function in cell signaling events relating to voiding function. This review highlights urothelial abnormalities in bladder pain syndrome/interstitial cystitis (BPS/IC), feline interstitial cystitis (FIC), and nonneurogenic idiopathic overactive bladder (OAB). These bladder conditions are typified by lower urinary tract symptoms including urinary frequency, urgency, urgency incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and cells from affected clinical subjects and asymptomatic controls have been compared for expression of proteins and mRNA. Animal models have also been used to probe urothelial responses to injuries of the urothelium, urethra, or central nervous system, and transgenic techniques are being used to test specific urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to share some common pathophysiology including increased purinergic, TRPV1, and muscarinic signaling, increased urothelial permeability, and aberrant urothelial differentiation. One challenge is to determine which of several abnormally regulated signaling pathways is most important for mediating bladder dysfunction in these syndromes, with a goal of treating these conditions by targeting specific pathophysiology.
The differential diagnoses for anterior wall vaginal prolapse (AWVP) include cystocele, enterocel... more The differential diagnoses for anterior wall vaginal prolapse (AWVP) include cystocele, enterocele, urethral diverticulum, and Gartner duct cyst. We present a case of a patient with a known solitary right kidney (congenital absence of a left kidney) presenting with lower urinary tract symptoms, absence of urinary incontinence, and feeling of bulge in the vagina. Physical examination revealed grade II AWVP. Because congenital solitary kidney can be associated with other possible genitourinary abnormalities, a pelvic magnetic resonance imaging was obtained. Magnetic resonance imaging demonstrated a tubular structure spanning the left retroperitoneum to the region of the AWVP. Urodynamics revealed an obstructive voiding pattern during pressure-flow phase. The combination of transvaginal and transabdominal surgical excision of the tubular structure resolved the patient's lower urinary tract and prolapse symptoms. Anatomically, her AWVP was corrected. Histopathologic examination of t...
Objectives-The aim of this study is to identify urodynamic changes that correlate with successful... more Objectives-The aim of this study is to identify urodynamic changes that correlate with successful outcomes after stress urinary incontinence (SUI) surgery.
We previously determined that the urine of interstitial cystitis (IC) patients specifically conta... more We previously determined that the urine of interstitial cystitis (IC) patients specifically contains a factor (antiproliferative factor [APF]) that inhibits primary bladder epithelial cell proliferation, and that it has significantly decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and increased levels of epidermal growth factor (EGF) compared with urine from asymptomatic controls and patients with bacterial cystitis. We sought to confirm the specificity of these findings for IC using a larger patient population, including control patients with a variety of urogenital disorders. Clean catch urine specimens were collected from 219 symptomatic IC patients, 113 asymptomatic controls without bladder disease, and 211 patients with various urogenital diseases including acute bacterial cystitis, vulvovaginitis, chronic nonbacterial prostatitis, overactive bladder, hematuria, stress incontinence, neurogenic bladder, benign prostatic hyperplasia, bladder or pelvic pain without voiding symptoms, bladder cancer, prostate cancer, or miscellaneous diagnoses including anatomic disorders. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and EGF levels were determined by enzyme-linked immunosorbent assay. APF activity was present significantly more often in IC than control urine specimens (P <0.005 for IC vs any control group; sensitivity = 94%, specificity = 95%, P <10(-82) for IC vs all controls). HB-EGF levels were also significantly lower and EGF levels significantly higher in IC urine than in specimens from controls (P <10(-84) and P <10(-36), respectively). These findings confirm the utility of APF, HB-EGF, and EGF as markers for IC. Understanding the reasons for altered levels of these markers may lead to understanding the pathogenesis of this disorder.
A highly effective treatment for interstitial cystitis (IC) remains elusive. We determined whethe... more A highly effective treatment for interstitial cystitis (IC) remains elusive. We determined whether sacral third nerve root (S3) percutaneous neurostimulation (PNS) might be effective in relieving symptoms of IC, as well as in normalizing urinary factors that are specifically altered in IC. Six consecutive patients with symptoms and cystoscopic findings compatible with IC underwent 5 days of continuous S3 neurostimulation by way of leads placed percutaneously into the S3 foramen. Patients filled out voiding frequency diaries and pain and urgency questionnaires before PNS and at the end of PNS when the leads were removed. Urine specimens were collected at these two time points and measured for heparin-binding epidermal growth factor-like growth factor (HB-EGF) by enzyme-linked immunosorbent assay and for antiproliferative factor (APF) activity by (3)H-thymidine uptake by normal human bladder urothelial cells. S3 PNS significantly improved all measured parameters toward normal values. Voiding frequency decreased twofold from 23.1 +/- 4.6 to 10.6 +/- 4.0 voids daily during PNS (P = 0.0001). Pelvic pain on a scale of 1 to 10 decreased from 7.0 +/- 1.6 to 2.3 +/- 3.2 (P = 0.05). Urinary urgency on a scale of 1 to 10 decreased from 6.0 +/- 2.2 to 1.8 +/- 1.7 (P = 0. 02). Urinary HB-EGF concentration increased sevenfold from 1.5 +/- 2. 1 to 11.0 +/- 1.7 ng/mL (P <0.0001), and urinary APF activity decreased from -76.1% +/- 31% to -4.5% +/- 8.8% (P = 0.005). S3 PNS significantly decreased symptoms and normalized urinary HB-EGF and APF activity in patients with IC. These results suggest that permanent S3 PNS may be beneficial in treating IC.
We describe a reproducible and less invasive surgical approach to sacral neuromodulation (InterSt... more We describe a reproducible and less invasive surgical approach to sacral neuromodulation (InterStim Therapy) in the treatment of voiding dysfunction. Twenty patients underwent modified lead implantation (mean operative time 45 minutes) without any difficulties or complications, with a mean follow-up of 8 months (range 1 to 14).Technical Considerations. The highlights of these modifications include (a) fluoroscopy to localize the S3 foramen; (b) paramedian incision; (c) use of a cutoff S3 finder needle and a 14-gauge Angiocath to direct permanent lead into the S3 foramen without dissection; (d) use of lateral fluoroscopy to determine the depth of the Angiocath insertion; and (e) anchoring the lead to the lumbodorsal fascia (superficial to the sacral periosteum) using a moveable lead anchor system. These modifications simplify and minimize the invasiveness of this therapy without compromising the efficacy. Because of the simplicity of these modifications, we are currently using an implanted lead, rather than the temporary percutaneous lead, to assess patients' clinical response before implanting a pulse generator.
Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumor... more Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors. In this report, we demonstrated that ETK expression is progressively increased during bladder cancer progression. We found that downregulation of ETK in bladder cancer cells attenuated STAT3 and AKT activity whereas exogenous overexpression of ETK had opposite effects, suggesting that deregulation of ETK may attribute to the elevated activity of STAT3 and AKT frequently detected in bladder cancer. The survival, migration and invasion of bladder cancer cells were significantly compromised when ETK expression was knocked down by a specific shRNA. In addition, we showed that ETK localizes to mitochondria in bladder cancer cells through interacting with Bcl-XL and regulating ROS production and drug sensitivity.
Interstitial cystitis (IC) is a disease defined by a constellation of signs and symptoms; its eti... more Interstitial cystitis (IC) is a disease defined by a constellation of signs and symptoms; its etiology is not well understood. There are multiple theories regarding the cause of IC; however, no one cause has been proven conclusively. In the meantime, physicians are trying to accurately diagnose a disease that has no identified definitive cause. There have been multiple tests designed to aid in the diagnosis of IC and there are new tests on the horizon that appear promising. However, the diagnosis of IC still is one of exclusion and based primarily on clinical findings. The most useful tests are described in this article, which may make diagnosis a more accurate, less arduous process.
ObjectivesTo assess the effects of intravesical injection of botulinum toxin type A (BTX) on a mo... more ObjectivesTo assess the effects of intravesical injection of botulinum toxin type A (BTX) on a model of detrusor overactivity induced by intravesical infusions of adenosine triphosphate (ATP) and capsaicin. BTX has recently been used clinically to treat overactive bladder syndromes without a precise knowledge of the mechanism of action.
Dr. Edward McGuire's academic career spans four decades. His impact in our field of female ur... more Dr. Edward McGuire's academic career spans four decades. His impact in our field of female urology and urodynamics is reflected by the many residents and fellows he has trained that are now academic leaders in our subspecialty. For this festschrift, my goals are to: (1) review the history of the surgical approaches to alleviate stress urinary incontinence (SUI) (2) discuss recent research in SUI and bladder storage symptoms and the influence of Dr. McGuire in these areas and (3) propose a paradigm shift in the understanding of the function of the bladder urothelium from providing barrier function to providing afferent input that affects bladder storage function. A literature review of the publications related to SUI and bladder storage symptoms was performed. Using Thompson Reuters ISI Web of Knowledge, the two most cited papers by Dr. McGuire are discussed. Dr. McGuire's two most cited publications are related to valsalva leak point pressure (VLPP) and the utility of the Am...
Scandinavian journal of urology and nephrology. Supplementum, 1996
Retrograde axonal tracers were used to assess the laterality of bladder innervation which is unkn... more Retrograde axonal tracers were used to assess the laterality of bladder innervation which is unknown. Fluoro-Gold and Fast Blue were injected into the left and right bladder walls, respectively of male Wistar rats. The major pelvic (MPG), pelvic accessory (PAG), and dorsal root (DRG) ganglia were then removed and analyzed. 59% and 33% of the total labelled MPG cells were found in the ipsilateral and contralateral MPG (efferents), respectively. 65% and 31% of the total labelled PAG cells were found in the ipsilateral and contralateral PAG (efferents) respectively. The L1/L2 and L6/S1 DRG each received similar amount of ipsilateral innervation (45-52%) based on total labelled cells at each DRG level. 8%, 4%, and 4% of labelled cells in the MPG, PAG and DRG, respectively, contained both Fluoro-Gold and Fast Blue consistent with bilateral input originating from a single neuron. Immunohistochemistry showed that 40% of retrogradely labelled PAG cells were positive for tyrosine hydroxylase...
A 42-year-old woman with an ileal loop urinary conduit that was placed 30 years ago was referred ... more A 42-year-old woman with an ileal loop urinary conduit that was placed 30 years ago was referred for cadaveric renal transplantation. The initial surgical plan was to perform a transplant ureteral reimplant directly into the ileal conduit with a concomitant left nephrectomy for angiomyolipoma. However, at surgery, a donor to native side-to-side ureteroureterostomy along with a simple left nephrectomy was performed. The cadaveric donor kidney was transplanted upside down to allow the donor ureter to reach the proximal native ureter. A follow-up loopogram performed 6 months after the operation revealed a widely patent anastomosis ). Serum creatinine was 0.8 mg/dL at 6 months after transplant.
To determine whether men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have uri... more To determine whether men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have urine markers previously described for patients with interstitial cystitis (IC; presence of antiproliferative factor [APF] activity, decreased levels of heparin-binding epidermal growth factor-like growth factor [HB-EGF], and increased levels of epidermal growth factor). Clean catch urine specimens were collected from 41 symptomatic patients with CP/CPPS, 36 asymptomatic men without bladder disease who served as the control group, and 24 men with IC. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and epidermal growth factor levels were determined by enzyme-linked immunosorbent assay. Men with CP/CPPS did not differ significantly from asymptomatic controls for any of the three markers tested (P >0.49). In contrast, APF activity was present significantly more often and HB-EGF levels were significantly lower in the urine specimens from men with IC than in the specimens from controls or patients with CP/CPPS (P <0.00001 for all four comparisons). Although the epidermal growth factor levels also tended to be higher in the urine from patients with IC than in the urine from controls, the difference did not reach statistical significance (P = 0.06). These findings indicate that at least two of the urine biomarkers previously identified in women with IC (presence of APF activity and decreased levels of HB-EGF) are also found in men with IC, but not in men with CP/CPPS. This finding suggests that IC and CP/CPPS may be two different disorders with distinct pathophysiologies. It also confirms the utility of the presence of APF activity and HB-EGF levels as markers for IC in men, as well as in women, with this disorder.
An Escherichia coli mutant (lpp-14-1), with an alteration of glycine to aspartic acid at the 14th... more An Escherichia coli mutant (lpp-14-1), with an alteration of glycine to aspartic acid at the 14th amino acid residue of the prolipoprotein signal sequence, has previously been shown to contain unmodified and unprocessed prolipoprotein in its cell envelope. Both the wild-type and the lpp-14-1 alleles of the lpp gene have been cloned onto a phage lambda vector. Two pseudorevertant alleles of lpp-14-1 (14R21 and 6a) have been isolated, cloned and sequenced. Amino acid sequences, deduced from the DNA sequences of the two revertant lipoprotein alleles, and biochemical characterization of the revertant lipoproteins, show that a conversion of the aspartic acid (residue 14) to asparagine completely restores the modification and processing of the 14R21 revertant prolipoprotein, while a change of the threonine-16 to isoleucine-16 partially enhances the modification and processing of the 6a prolipoprotein, which retains the aspartate-14 substitution. Secondary structure analysis of the reverta...
Aims: Urodynamic studies (UDS) are generally recommended prior to surgical treatment for stress u... more Aims: Urodynamic studies (UDS) are generally recommended prior to surgical treatment for stress urinary incontinence (SUI), despite insufficient evidence that it impacts treatment plans or outcomes in patients with uncomplicated SUI. This analysis aimed to calculate the cost incurred when UDS was performed as a supplement to a basic office evaluation and to extrapolate the potential savings of not doing UDS in this patient population on a national basis. Methods: This is a secondary analysis from the Value of Urodynamic Evaluation (ValUE) trial, a multicenter non-inferiority randomized trial to determine whether a basic office evaluation (OE) is non-inferior in terms of SUI surgery outcomes to office evaluation with addition of urodynamic studies (UDS). All participants underwent an OE; those patients who randomized to supplementary UDS underwent non-instrumented uroflowmetry, filling cystometry, and a pressure flow study. Costs associated with UDS were calculated using 2014 U.S. Medicare allowable fees. Models using various patient populations and payor mixes were created to obtain a range of potential costs of performing UDS in patients undergoing SUI surgery annually in the United States. Results: Six hundred thirty women were randomized to OE or OE plus UDS. There was no difference in surgical outcomes between the two groups. The per patient cost of UDS varied from site to site, and included complex cystometrogram $314-$343 (CPT codes 51728-51729) plus complex uroflowmetry $16 (CPT code 51741). Extrapolating these costs for US women similar to our study population, 13-33 million US dollars could be saved annually by not performing preoperative urodynamics. Conclusion: For women with uncomplicated SUI and a confirmatory preoperative basic office evaluation, tens of millions of dollars US could be saved annually by not performing urodynamic testing. In the management of such women, eliminating this preoperative test has a major economic benefit.
Understanding of the role of urothelium in regulating bladder function is continuing to evolve. W... more Understanding of the role of urothelium in regulating bladder function is continuing to evolve. While the urothelium is thought to function primarily as a barrier for preventing injurious substances and microorganisms from gaining access to bladder stroma and upper urinary tract, studies indicate it may also function in cell signaling events relating to voiding function. This review highlights urothelial abnormalities in bladder pain syndrome/interstitial cystitis (BPS/IC), feline interstitial cystitis (FIC), and nonneurogenic idiopathic overactive bladder (OAB). These bladder conditions are typified by lower urinary tract symptoms including urinary frequency, urgency, urgency incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and cells from affected clinical subjects and asymptomatic controls have been compared for expression of proteins and mRNA. Animal models have also been used to probe urothelial responses to injuries of the urothelium, urethra, or central nervous system, and transgenic techniques are being used to test specific urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to share some common pathophysiology including increased purinergic, TRPV1, and muscarinic signaling, increased urothelial permeability, and aberrant urothelial differentiation. One challenge is to determine which of several abnormally regulated signaling pathways is most important for mediating bladder dysfunction in these syndromes, with a goal of treating these conditions by targeting specific pathophysiology.
The differential diagnoses for anterior wall vaginal prolapse (AWVP) include cystocele, enterocel... more The differential diagnoses for anterior wall vaginal prolapse (AWVP) include cystocele, enterocele, urethral diverticulum, and Gartner duct cyst. We present a case of a patient with a known solitary right kidney (congenital absence of a left kidney) presenting with lower urinary tract symptoms, absence of urinary incontinence, and feeling of bulge in the vagina. Physical examination revealed grade II AWVP. Because congenital solitary kidney can be associated with other possible genitourinary abnormalities, a pelvic magnetic resonance imaging was obtained. Magnetic resonance imaging demonstrated a tubular structure spanning the left retroperitoneum to the region of the AWVP. Urodynamics revealed an obstructive voiding pattern during pressure-flow phase. The combination of transvaginal and transabdominal surgical excision of the tubular structure resolved the patient's lower urinary tract and prolapse symptoms. Anatomically, her AWVP was corrected. Histopathologic examination of t...
Objectives-The aim of this study is to identify urodynamic changes that correlate with successful... more Objectives-The aim of this study is to identify urodynamic changes that correlate with successful outcomes after stress urinary incontinence (SUI) surgery.
We previously determined that the urine of interstitial cystitis (IC) patients specifically conta... more We previously determined that the urine of interstitial cystitis (IC) patients specifically contains a factor (antiproliferative factor [APF]) that inhibits primary bladder epithelial cell proliferation, and that it has significantly decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and increased levels of epidermal growth factor (EGF) compared with urine from asymptomatic controls and patients with bacterial cystitis. We sought to confirm the specificity of these findings for IC using a larger patient population, including control patients with a variety of urogenital disorders. Clean catch urine specimens were collected from 219 symptomatic IC patients, 113 asymptomatic controls without bladder disease, and 211 patients with various urogenital diseases including acute bacterial cystitis, vulvovaginitis, chronic nonbacterial prostatitis, overactive bladder, hematuria, stress incontinence, neurogenic bladder, benign prostatic hyperplasia, bladder or pelvic pain without voiding symptoms, bladder cancer, prostate cancer, or miscellaneous diagnoses including anatomic disorders. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and EGF levels were determined by enzyme-linked immunosorbent assay. APF activity was present significantly more often in IC than control urine specimens (P <0.005 for IC vs any control group; sensitivity = 94%, specificity = 95%, P <10(-82) for IC vs all controls). HB-EGF levels were also significantly lower and EGF levels significantly higher in IC urine than in specimens from controls (P <10(-84) and P <10(-36), respectively). These findings confirm the utility of APF, HB-EGF, and EGF as markers for IC. Understanding the reasons for altered levels of these markers may lead to understanding the pathogenesis of this disorder.
A highly effective treatment for interstitial cystitis (IC) remains elusive. We determined whethe... more A highly effective treatment for interstitial cystitis (IC) remains elusive. We determined whether sacral third nerve root (S3) percutaneous neurostimulation (PNS) might be effective in relieving symptoms of IC, as well as in normalizing urinary factors that are specifically altered in IC. Six consecutive patients with symptoms and cystoscopic findings compatible with IC underwent 5 days of continuous S3 neurostimulation by way of leads placed percutaneously into the S3 foramen. Patients filled out voiding frequency diaries and pain and urgency questionnaires before PNS and at the end of PNS when the leads were removed. Urine specimens were collected at these two time points and measured for heparin-binding epidermal growth factor-like growth factor (HB-EGF) by enzyme-linked immunosorbent assay and for antiproliferative factor (APF) activity by (3)H-thymidine uptake by normal human bladder urothelial cells. S3 PNS significantly improved all measured parameters toward normal values. Voiding frequency decreased twofold from 23.1 +/- 4.6 to 10.6 +/- 4.0 voids daily during PNS (P = 0.0001). Pelvic pain on a scale of 1 to 10 decreased from 7.0 +/- 1.6 to 2.3 +/- 3.2 (P = 0.05). Urinary urgency on a scale of 1 to 10 decreased from 6.0 +/- 2.2 to 1.8 +/- 1.7 (P = 0. 02). Urinary HB-EGF concentration increased sevenfold from 1.5 +/- 2. 1 to 11.0 +/- 1.7 ng/mL (P <0.0001), and urinary APF activity decreased from -76.1% +/- 31% to -4.5% +/- 8.8% (P = 0.005). S3 PNS significantly decreased symptoms and normalized urinary HB-EGF and APF activity in patients with IC. These results suggest that permanent S3 PNS may be beneficial in treating IC.
We describe a reproducible and less invasive surgical approach to sacral neuromodulation (InterSt... more We describe a reproducible and less invasive surgical approach to sacral neuromodulation (InterStim Therapy) in the treatment of voiding dysfunction. Twenty patients underwent modified lead implantation (mean operative time 45 minutes) without any difficulties or complications, with a mean follow-up of 8 months (range 1 to 14).Technical Considerations. The highlights of these modifications include (a) fluoroscopy to localize the S3 foramen; (b) paramedian incision; (c) use of a cutoff S3 finder needle and a 14-gauge Angiocath to direct permanent lead into the S3 foramen without dissection; (d) use of lateral fluoroscopy to determine the depth of the Angiocath insertion; and (e) anchoring the lead to the lumbodorsal fascia (superficial to the sacral periosteum) using a moveable lead anchor system. These modifications simplify and minimize the invasiveness of this therapy without compromising the efficacy. Because of the simplicity of these modifications, we are currently using an implanted lead, rather than the temporary percutaneous lead, to assess patients' clinical response before implanting a pulse generator.
Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumor... more Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors. In this report, we demonstrated that ETK expression is progressively increased during bladder cancer progression. We found that downregulation of ETK in bladder cancer cells attenuated STAT3 and AKT activity whereas exogenous overexpression of ETK had opposite effects, suggesting that deregulation of ETK may attribute to the elevated activity of STAT3 and AKT frequently detected in bladder cancer. The survival, migration and invasion of bladder cancer cells were significantly compromised when ETK expression was knocked down by a specific shRNA. In addition, we showed that ETK localizes to mitochondria in bladder cancer cells through interacting with Bcl-XL and regulating ROS production and drug sensitivity.
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Papers by Toby Chai