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J Christopher Austin

Publications and source records attributed to J Christopher Austin.

At least 19 recordsLinked to original sources
PubMed2006

Activation of the calcineurin pathway is associated with detrusor decompensation: a potential therapeutic target.

PURPOSE: We hypothesized that the calcineurin pathway mediated some of the complex remodeling process that allows a bladder subjected to partial outlet obstruction to adapt to its new workload. Atrial natriuretic factor mRNA expression served as a marker of calcineurin activation. MATERIALS AND METHODS: A total of 16 New Zealand White rabbits underwent surgical creation of partial outlet obstruction, followed by randomization to receive cyclosporin A (20 mg/kg intramuscularly twice daily) or no additional treatment for 14 days. Three animals underwent 2 weeks of partial bladder outlet obstruction followed by bladder biopsy and the reversal of obstruction. RESULTS: Atrial natriuretic factor expression was seen only in bladders with severe hypertrophy and it disappeared with the reversal of outlet obstruction. Cyclosporin A treatment resulted in a decrease in atrial natriuretic factor mRNA expression (p <0.05) and a marked shift in myosin heavy chain A-to-B ratios toward normal (p <0.01) and an increase in smooth muscle cross sectional area (p <0.05). Bladder mass decreased 40% but did not attain statistical significance (p = 0.08). CONCLUSIONS: The calcineurin pathway has a significant role in bladder wall hypertrophy following partial outlet obstruction. Bladder hypertrophy could not be fully prevented by cyclosporin A, suggesting that multiple signaling pathways are involved in this pathophysiology. The expression of myosin heavy chain AB isoforms is regulated in part by the calcineurin pathway.

Animals↗
PubMed2006

Calcification of glutaraldehyde cross-linked collagen in bladder neck injections in children with incontinence: a long-term complication.

PURPOSE: We report the incidence of calcifications developing at the bladder neck/urethra in pediatric patients treated with glutaraldehyde cross-linked collagen for urinary incontinence. MATERIALS AND METHODS: We reviewed charts of patients treated with glutaraldehyde cross-linked collagen injections for urinary incontinence between 1994 and 1999. Etiology of incontinence, pertinent medical history, operative details and postoperative imaging were examined. RESULTS: Of 31 patients 4 (13%) had development of submucosal calcifications in the bladder neck/urethra. All 4 patients had received multiple injections of glutaraldehyde cross-linked collagen for incontinence secondary to neurogenic bladder. The calcifications were confirmed surgically. Pathology reports available for 2 of 4 patients showed chronic inflammation without dysplasia or malignant changes. Mean followup was significantly different between calcified and noncalcified cases (10.3 vs 7.2 years, p = 0.009), as was total volume of collagen injected (21 vs 12 cc, p = 0.012). Mean time to diagnosis of calcifications was 8.8 years (range 7 to 11) after first injection. A total of 24 patients without calcification underwent bladder imaging at a mean of 6.8 years (+/-2.2) after glutaraldehyde cross-linked collagen injection, which was not significantly different than the time to diagnosis (p = 0.089). The number of injections was not significantly different between the 2 groups (p = 0.426). CONCLUSIONS: Of our patients 13% had development of calcifications at the site of prior glutaraldehyde cross-linked collagen injections for incontinence. These calcifications were surrounded by chronic inflammation. Patients who have undergone glutaraldehyde cross-linked collagen injections may benefit from long-term followup with bladder imaging to detect and follow calcifications at prior injection sites.

Adolescent↗
PubMed2006

Partial bladder outlet obstruction selectively abolishes protein kinase C induced contraction of rabbit detrusor smooth muscle.

PURPOSE: Despite the acute onset, partial bladder outlet obstruction in the rabbit induces detrusor remodeling similar to that in men with benign prostatic hyperplasia in terms of its impact on structural and functional alterations in smooth muscle. We determined if partial bladder outlet obstruction induced remodeling alters the protein kinase C signaling pathway that leads to contraction. MATERIALS AND METHODS: Smooth muscle from control animals and those subjected to 2 weeks of partial bladder outlet obstruction were mounted for isometric force recording, measurement of myosin light chain phosphorylation and levels of adducin phosphorylation. Bladder muscle strips were stimulated by phorbol dibutyrate or carbachol in the presence and absence of bisindolylmaleimide-1. RESULTS: Smooth muscle strips from animals subjected to partial bladder outlet obstruction showed little to no increase in stress in response to phorbol dibutyrate and no increase in myosin light chain phosphorylation levels. Muscle strips from control animals produced a robust contraction with concomitant increases in myosin light chain phosphorylation. Inhibition of protein kinase C by bisindolylmaleimide-1 significantly depressed carbachol induced contractions of muscle strips from control animals but it had no effect on carbachol induced contractions of muscle strips from outlet obstructed animals. Phorbol dibutyrate increased phospho-adducin levels in muscle strips from the 2 animal sources, suggesting that protein kinase C could be activated. CONCLUSIONS: We propose that partial bladder outlet obstruction does not alter protein kinase C activation, but rather abolishes or uncouples the pathway(s) downstream of protein kinase C, leading to contraction. Loss of this pathway may contribute to the loss of normal voiding behavior and the resultant decompensated state.

Animals↗
PubMed2006

Frequency of wetting is predictive of response to anticholinergic treatment in children with overactive bladder.

OBJECTIVES: To examine the variables relative to the response of oxybutynin treatment in children with daytime urinary incontinence. METHODS: The records of patients seen for voiding problems between 1999 and 2003 were reviewed. Patients taking oxybutynin for 3 months or longer were included in the study. Patients with structural or neurologic bladder abnormalities and those taking oxybutynin at the initial visit were excluded. Age, sex, uroflowmetry findings, postvoid residual urine volume, duration and severity of symptoms before oxybutynin, urinary tract infection history, constipation, and the duration, dosage, and adverse effects of oxybutynin treatment were evaluated. Data were analyzed using Fisher's exact test for categorical variables, the two-sample t test or Wilcoxon rank-sum test for continuous and ordinal variables, and the linear mixed model analysis for uroflow data. RESULTS: Eighty-one patients met the inclusion criteria. After an average follow-up of 1.2 years, 31 (38.3%) were dry, 25 (30.9%) had experienced significant improvement, 19 (23.5%) had experienced slight improvement, and 6 (7.4%) were unchanged. No significant differences were detected between those who became dry and those with little to no improvement with respect to age, sex, duration of symptoms, follow-up, uroflow pattern, postvoid residual urine volume, or bladder capacity. Those children presenting with decreased frequency of wetting episodes were significantly more likely to obtain daytime continence. The most common side effects were constipation (18.5%), dry mouth (17.3%), and flushing (13.6%). CONCLUSIONS: Children with daytime incontinence presenting with the lowest frequency of wetting were most likely to achieve continence. The frequency of wetting should be considered a significant prognostic variable when assessing the results of therapeutic intervention trials.

Adolescent↗
PubMed2006

Improved efficacy of extended release oxybutynin in children with persistent daytime urinary incontinence converted from regular oxybutynin.

OBJECTIVES: To examine the response to conversion from regular oxybutynin (Ditropan) to an extended-release form (Ditropan XL) in children with persistent daytime urinary incontinence. METHODS: A retrospective review of patients with daytime wetting who switched from Ditropan to Ditropan XL included patient age, sex, reason for the change in medication, uroflowmetry findings before and after the change, side effects, and duration and dosage of the medication. The data were analyzed using a paired, two-tailed t test, with P <0.05 considered significant. RESULTS: Twenty-seven patients were followed up for an average of 35.8 months. A lack of improvement (n = 11), convenience (n = 6), side effects (n = 2), and a dislike of the taste (n = 2) were identified as reasons for changing to the extended release form. The mean dosage of Ditropan and Ditropan XL did not differ significantly (0.40 and 0.38 mg/kg/day, respectively). After the change to Ditropan XL, 6 patients had a resolution of side effects and 7 developed new side effects. Of the 27 patients, 13 became dry or had significant improvement by the first visit after the change to Ditropan XL. Significant increases in voided volume (38% versus 53%; P <0.01) and total bladder capacity (55% versus 70%; P = 0.03), normalized for age-expected bladder capacity, occurred by the first clinic visit after beginning Ditropan XL. No significant changes in the postvoid residual urine volume occurred. CONCLUSIONS: The frequency of wetting decreased and the voided volume and bladder capacity increased after a change to Ditropan XL in children with persistent wetting when taking Ditropan.

Child↗
PubMed2006

Bladder volume at onset of reflux on initial cystogram predicts spontaneous resolution.

PURPOSE: Reflux grade is the factor most commonly used to predict spontaneous reflux resolution. We evaluated other potential predictive factors aside from reflux grade relative to spontaneous resolution. MATERIALS AND METHODS: We reviewed the records of 20 males and 98 females who were diagnosed with primary vesicoureteral reflux between ages 0 and 7 years between 1990 and 2000. Age, sex, height, weight, reflux grade, bladder volume at onset of reflux and laterality were recorded for the first, second and most recent voiding cystourethrogram or nuclear cystogram before spontaneous resolution or operative intervention. RESULTS: Of 118 patients 75 (64%) had spontaneous resolution, 27 (23%) underwent corrective surgery and 16 (13%) are still being followed. Average age at diagnosis was 2.3 years (range 1 day to 7.7 years) and average followup was 4.3 years (range 0.2 to 14). Average time to spontaneous resolution was 2.2 years (range 0.5 to 10.3) vs a time to operative treatment of 3.6 years (range 0.2 to 11.2). There was a significantly higher spontaneous resolution rate for lower reflux grades (p = 0.0004). Reflux occurring at greater than 75% of predicted bladder capacity had a significantly higher resolution rate (p = 0.0005). The initial height and weight percentile was not significant for predicting spontaneous resolution. Breakthrough urinary tract infections were negative predictors of spontaneous resolution (p <0.0001). CONCLUSIONS: In addition to grade, bladder volume relative to predicted bladder capacity at the onset of reflux appears to provide additional prognostic information regarding the likelihood of spontaneous resolution of primary vesicoureteral reflux.

Child↗
PubMed2005

Kidneys with reflux nephropathy maintain relative renal function after ureteral reimplantation.

PURPOSE: In children with severe unilateral reflux nephropathy and diminished relative renal function (RRF) a dilemma exists between the choice of treatment with ureteral reimplantation or nephrectomy. Limited followup data are available regarding relative renal function or postoperative complications after ureteral reimplantation in kidneys with significant unilateral reflux nephropathy. MATERIALS AND METHODS: We retrospectively reviewed the records of 460 patients who underwent ureteral reimplantation between 1980 and 2002, and identified children with primary vesicoureteral reflux and severe unilateral reflux nephropathy (RRF 30% or less on renal scintigraphy). The postoperative outcomes were assessed for relative renal function and complications including hypertension, pyelonephritis or persistent reflux. RESULTS: A total of 18 girls and 14 boys with a mean preoperative relative renal function of 20.1 +/- 7.8% (range 2% to 30%) met the inclusion criteria. Reflux grade in the poorly functioning kidney was II in 4 children (13%), III in 14 (44%), IV in 11 (34%) and V in 3 (9%). Reflux was unilateral in 15 children (47%) and bilateral in 17 (53%). Mean followup from surgery was 3.7 years (range 0.3 to 12.9). In 28 children with both preoperative and postoperative renal scans, mean preoperative RRF was 20.3 +/- 7.4% and mean postoperative RRF was 20.5 +/- 8.6% with a mean time between renal scans of 2.3 years. No statistically significant change was noted from preoperative to postoperative relative renal function with a mean change of +0.2 +/- 3.7% (range -6.5% to +10%, p=0.82). Postoperative complications occurred in 7 of the 32 children (22%), including hypertension (1), pyelonephritis (3) and persistent reflux (4). Pyelonephritis occurred in 1 child with persistent reflux. No statistically significant difference existed in mean preoperative relative renal function between those with and without complications (24.6 +/- 8.9% vs 18.8 +/- 7.2%, p = 0.09). CONCLUSIONS: Children who underwent ureteral reimplantation in association with unilateral reflux nephropathy maintained stable relative renal function.

Adolescent↗
PubMed2004

Vesicoureteral reflux: who benefits from surgery?

Increased recognition of the association between urinary tract infections and reflux, sibling screening, and the evaluation of antenatal hydronephrosis have resulted in an increase in the diagnosis of reflux early in life. Although many children would sustain no untoward affects of their condition if reflux were left untreated, the disease can be severe and even life threatening. Although antireflux operations have been refined and improved, it remains difficult to determine which individuals truly benefit from these operations. A large prospective randomized placebo-antibiotic-operation study with long-term follow-up is needed, as is the development of nomograms, to assess the individual child's risk of adverse outcomes.

Child↗
PubMed2004

Vesicoureteral reflux: surgical approaches.

The treatment of vesicoureteral reflux has evolved over the past half-century from primarily surgical to nonoperative treatments. Although the benefits of surgical correction versus medical management are debated, the surgical techniques that have evolved are highly effective in correcting vesicoureteral reflux. Recently, the US Food and Drug Administration has approved an injectable implant of dextranomer/hyaluronic acid copolymer for use in children, making the endoscopic treatment of reflux a potential alternative to open surgical correction. This article reviews the different surgical techniques,postoperative management, and complications, as well as the various implants used in the endoscopic correction of vesicoureteral reflux and their outcomes.

Animals↗
PubMed2004

Long-term outcome analysis of Starr plication for primary obstructive megaureters.

PURPOSE: The Starr technique of tapering megaureters was first reported in 1979. Although this method of ureteral plication is well known, to our knowledge there are no clinical studies regarding outcomes. We report the first long-term outcome results with the Starr technique for primary obstructive megaureters. MATERIALS AND METHODS: Three girls and 10 boys with a total of 16 primary obstructive megaureters (3 bilateral) underwent reimplantation with Starr plication between 1988 and 2000. Baseline and followup renal function (average followup 6.2 years) was determined with renal scan and/or 24-hour urinary creatinine clearance. Average age at operation was 5.6 years (range 2 months to 13 years). All ureters were plicated using the Starr technique with interrupted polydioxanone sutures performed by a single surgeon (CEH). Reimplantation methods were the Hendren technique in 7 and Politano-Leadbetter in 9. RESULTS: No ureter demonstrated obstruction postoperatively. One ureter refluxed, which resolved with subureteral collagen injection. Seven patients had mean preoperative and postoperative creatinine clearance +/- SD 72.9 +/- 14.8 and 102.1 +/- 10.9 cc per minute, respectively (p <0.05). Six patients underwent preoperative and postoperative renal scans. Average preoperative relative renal function on renal scan in the kidney with a megaureter was 53.0% +/- 6.7% (range 37% to 84%). Long-term followup (average 4.1 years) renal scan revealed a relative function of 53.3% +/- 9.2% (range 37% to 100%). CONCLUSIONS: Our data demonstrate that Starr plication is a safe procedure that provides long-term stabilization of renal function in the management of primary obstructive megaureter.

Adolescent↗
PubMed2004

A male murine model of partial bladder outlet obstruction reveals changes in detrusor morphology, contractility and Myosin isoform expression.

PURPOSE: Mice with gene deletion or targeted over expression are important for understanding the remodeling that follows partial bladder outlet obstruction (PBOO). This condition predominates in males. We produced PBOO in male mice and now report the physiological, histological and molecular consequences. MATERIALS AND METHODS: Male C57bl/6 mice were surgically obstructed or subjected to sham surgery and unoperated mice served as controls. Four weeks later the bladders were excised and their function was assessed with in vitro whole bladder cystometry. The optimum volume for pressure generation was determined and isometric pressures were measured for field stimulation and depolarization with KCl. Bladder hypertrophy was classified as severe-bladder mass greater than 50 mg or mild-bladder mass less than 50 mg. The percent muscle fraction was determined by histological analyses. The expression of C-terminal (SM1 and SM2) and N-terminal (SM-B and SM-A) isoforms of myosin heavy chain was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: Severely hypertrophied bladders had larger optimum volume (p >0.001) and generated less pressure in response to field stimulation (p >0.001) and KCl (p >0.01) with a slower rate of pressure generation than controls or sham operated mice. Increased SM1-to-SM2 and SM-A-to-SM-B ratios were noted in severely obstructed bladders relative to controls or sham operated mice (p <0.05). The muscle fraction decreased slightly in the severely hypertrophied group (p not significant). CONCLUSIONS: Our male mouse model of PBOO demonstrates an increase in bladder mass, larger capacity and significantly decreased pressure generation in the in vitro whole bladder model. Obstruction induced increases in the expression of C-terminal (SM1) and N-terminal (SM-A) myosin heavy chain isoforms.

Animals↗
PubMed2004

Improved uroflow parameters and post-void residual following biofeedback therapy in pediatric patients with dysfunctional voiding does not correspond to outcome.

PURPOSE: We evaluated pediatric patients who were treated with biofeedback for dysfunctional voiding with respect to clinical outcome and objective changes in uroflow parameters and post-void residual. MATERIALS AND METHODS: We retrospectively reviewed 81 patients treated for dysfunctional voiding and/or urinary tract infections with biofeedback. Conservative management had previously failed in all patients. Uroflow data and symptoms were reviewed, and clinical outcomes were recorded. For analysis, patients were stratified by symptoms of incontinence or presence of urinary tract infections. RESULTS: Of 73 patients with incontinence 22 (30%) became dry, 36 (49%) had improvement and 15 (21%) reported no change following biofeedback. In 39 (78%) of 50 patients with recurrent urinary tract infections resolved. Overall, there was a significant (p <0.002) increase in peak flow and average flow rate, and a significant decrease in post-void residual and post-void residual as a percent of predicted bladder capacity. There was no significant change in voided volume following biofeedback. Overall, there was no significant difference in uroflow parameters and post-void residual following biofeedback between patients with incontinence or infections, except for a higher maximum flow rate in patients who continued to have infections. CONCLUSIONS: Treatment of children with pelvic floor muscle biofeedback is associated with improved urinary continence and decreased urinary tract infections in the majority. It results in improvement in uroflow curves and parameters, and a decreased post-void residual. Posttreatment results of these parameters did not correlate with improvement in continence and urinary tract infections.

Adolescent↗
PubMed2004

Laparoscopic upper pole heminephrectomy for ectopic ureter: initial experience.

OBJECTIVES: To determine the feasibility, clinical outcomes, and complications of laparoscopic upper pole heminephrectomy for ectopic ureter. The standard treatment for a duplex kidney with a poorly functioning upper pole moiety is an upper pole heminephrectomy. We review our technique and experience with laparoscopic upper pole heminephrectomy. A brief review of the literature is provided. METHODS: A retrospective review of clinical records from three patients who underwent laparoscopic upper pole heminephrectomy was performed. Two of the three patients presented with lifelong urinary incontinence and were diagnosed with an ectopic ureter associated with a poorly functioning upper pole moiety. The third patient presented with recurrent episodes of pyelonephritis and was found to have a duplex kidney with a poorly functioning upper pole segment draining into a ureterocele. RESULTS: All three patients underwent laparoscopic upper pole heminephrectomy through the transperitoneal approach. Mean operative time, including ureteral stent insertion, was 198 minutes. Two of the three patients were discharged within 24 hours of surgery. The third patient had a urinary leak secondary to a small amount of residual upper pole parenchyma which resolved with superselective renal arterial embolization. All three patients are well at 5.3 months follow-up. CONCLUSIONS: Laparoscopic upper pole heminephrectomy for ectopic ureter is safe and reproducible and offers the patient the typical postoperative benefits of laparoscopic surgery.

Adolescent↗
PubMed2003

Laparoscopic upper-pole heminephrectomy for ectopic ureter: surgical technique.

A duplex kidney associated with a poorly functioning upper-pole segment is commonly associated with incontinence, voiding dysfunction, and urinary tract infections. A standard treatment option for this condition is upper-pole heminephrectomy. With the continued development of minimally invasive urology, this technique can now be safely performed laparoscopically. This report details step by step our technique of laparoscopic upper-pole heminephrectomy. Key points include placement of a catheter in the normal ureter at the start of the case, full mobilization of the upper-pole ureter away from the renal hilum, and precise identification of the vasculature supplying the upper pole. Laparoscopic upper-pole heminephrectomy for ectopic ureter is safe and reproducible and offers the patient the typical postoperative benefits of laparoscopic surgery.

Humans↗
PubMed2003

Comparison of viral vectors: gene transfer efficiency and tissue specificity in a bladder cancer model.

PURPOSE: Gene transfer efficiency and specific cell targeting of vectors is a major obstacle in preclinical studies of gene therapy for malignant disease. Previous attempts at gene transfer in bladder cancer models have resulted in variable urothelial and tumor transgene expression after intravesical administration of recombinant viral vectors. In the current study we compared the gene transfer efficiencies of different viral vectors. MATERIALS AND METHODS: We compared the gene transfer efficiencies of the viral vectors replication-deficient adenovirus, attenuated vaccinia virus (NYVAC) and canarypox virus (ALVAC) in vitro and in an orthotopic murine bladder cancer model. We used beta-galactosidase and firefly luciferase reporter gene expression to compare gene transfer efficiency. RESULTS: Significantly higher transgene expression was observed in vitro when these cells were infected with NYVAC or ALVAC compared with adenovirus vectors. Similarly the efficiency of adenovirus vectors to transfer genetic material into bladder urothelium and orthotopic bladder tumors was inferior to that of ALVAC and NYVAC vectors, which interestingly appeared to have a predilection to infect the orthotopic tumor. Analysis of the expression of coxsackie-adenovirus receptor using reverse transcriptase-polymerase chain reaction revealed the bladder tumor cell lines were lacking this adenovirus receptor. While adenovirus transferred genes poorly to normal bladder, coxsackie-adenovirus receptor expression was high in bladder tissue. CONCLUSIONS: The viral vectors examined in these experiments resulted in significantly different gene transfer in the orthotopic bladder cancer model, underscoring the importance of vector selection in gene therapy protocols.

Adenoviridae↗