Biomedical subjects

G Capolicchio

Publications and source records attributed to G Capolicchio.

13 recordsLinked to original sources

PubMed2001

Extracellular matrix gene responses in a novel ex vivo model of bladder stretch injury.

PURPOSE: Congenital bladder outlet obstruction from either mechanical or functional causes often results in clinical bladder fibrosis. We tested the hypothesis that early molecular changes relevant to fibrosis occur in response to stretch injury of the bladder wall and that specific extracellular matrix receptors mediate some of these responses. Furthermore, we introduce a novel ex vivo model of bladder injury which has advantages over previously described in vivo bladder outlet obstruction models by uniquely interrogating molecular responses to bladder distention. MATERIALS AND METHODS: The bladders of Sprague Dawley rats were hydrodistended transurethrally, the ureters and bladder neck were ligated, and the whole bladder was excised and incubated in culture medium in the distended state. At fixed time-points control and stretch bladders were snap frozen, RNA was extracted, and semiquantitative reverse transcription polymerase chain reaction for collagens I, III and XII, and RHAMM (receptor for hyaluronic acid) messenger (m) RNA was performed to establish trends in stretch related gene expression. Bladder specimens were also subjected to routine histological evaluation. RESULTS: An average 3-fold reduction in collagen I mRNA expression was seen with 8 hours of static stretch (p <0.05). Bladder stretch increased collagen III mRNA levels approximately 2.5-fold (p <0.05). Whole bladder collagen XII and RHAMM mRNA were elevated as much as 5-fold (p <0.05) with stretch. Blocking RHAMM function significantly attenuated these matrix gene responses (p = 0.01 to 0.005). CONCLUSIONS: The ex vivo model of whole bladder stretch is viable and easily reproducible for the study of molecular pathophysiological mechanisms contributing to maladaptive bladder disease. Furthermore, collagen gene transcription is revealed to be rapidly responsive to stretch injury of the bladder. Intact RHAMM receptor function is involved in these responses. Elucidation of the intermediate steps in this response to injury may allow for the development of novel therapeutic strategies which may prevent pathological matrix remodeling seen in clinical bladder disease.

Animals↗

PubMed2001

A population based analysis of continence outcomes and bladder exstrophy.

PURPOSE: Whereas the literature on bladder exstrophy is replete with outcomes of specific continence surgical procedures in highly select patients, there are no data on the outcomes related to continence for a complete exstrophy population, which is more comprehensive with respect to a variety of surgical procedures performed to achieve continence. To provide urologists and patients with an overview of potential continence outcomes devoid of any selection bias, we report on a comprehensive exstrophy population, focusing on the various procedures required for urinary continence. MATERIALS AND METHODS: We reviewed the charts of all patients with bladder and cloacal exstrophy who underwent a staged repair to achieve urinary continence at a single institution between 1988 and 1998. Urinary continence was then correlated to the types of surgical procedures, and subgroup analysis for predictors of urinary continence was performed. The type of bladder neck reconstruction allowed subgrouping cases into group 1-bladder neck reconstruction only, group 2-bladder neck reconstruction with augmentation and/or appendicovesicostomy and group 3-bladder neck closure. RESULTS: Of the 43 patients identified 26 were male, 4 had cloacal exstrophy and 3 had complex exstrophy variants with ectopic hindgut and spina bifida. Groups 1 to 3 comprised 9, 15 and 19 patients with urinary continence rates of 56%, 67% and 100%, respectively. The age at which patients became continent was delayed in groups 2 and 3 (8.2 and 8.7 years, respectively) compared to group 1 (4.8). Of all the potential variants measured gender was the strongest predictor of continence with 94% of females versus 69% of males achieving it. Of the males those with (57%) compared to those without (83%) a history of bladder neck stenosis or paraexstrophy flaps had worse continence. Repeat bladder neck reconstruction was only successful in 23% of patients. CONCLUSIONS: All patients can be rendered continent but many may achieve this successful outcome by other procedures following initial bladder neck reconstruction. When managing failed bladder neck reconstruction, the type of surgical repair chosen may need to address the need for enhanced bladder storage and the issue of potential bladder augmentation. The advances made in the treatment of the epispadiac urethra may now facilitate clean intermittent catheterization. Earlier recognition of the need for adjunctive storage procedures in addition to bladder neck reconstruction may facilitate the timing of providing enhanced continence, independence and self-esteem, and do so with fewer operative procedures. We speculate that the current complete urethral and bladder repair in newborns will add further to the storage functions of the native bladder tissues and improve the potential of achieving more effective bladder outlet control.

Bladder Exstrophy↗

PubMed2001

Collagen injection for treatment of urinary incontinence in children.

PURPOSE: We assess the success rate of periurethral collagen injection in children with neurogenic bladder dysfunction secondary to myelomeningocele. MATERIALS AND METHODS: From 1992 to 1998, 15 male and 5 female patients with spina bifida (age 13.3 +/- 3.8 years) underwent endoscopic collagen injection for the treatment of urinary incontinence secondary to sphincter deficiency. Mean followup was 4.2 years. Pretreatment urodynamic study showed a stable compliant bladder with an average leak point pressure of 52 cm. H2O (range 23 to 100). Concurrent medical management included anticholinergics in 15 cases, agonists in 3, and clean intermittent catheterization in 16. Five patients had undergone previous ileocystoplasty. RESULTS: Collagen injections were given with the patient under general anesthesia. The number of injections was 1 in 5 cases, 2 in 11, 3 in 3, and 4 in 1. Average collagen volume injected per treatment was 6.6 cc (range 2 to 13). All patients were evaluated on a subjective continence scale of no change (wet), improved or completely dry at the time of assessment. Of the 20 patients, 16 had no change, 3 showed improvement and 1 was dry. Initial improvement in the first 2 months after injection deteriorated thereafter in 16 cases. CONCLUSIONS: The previously reported high success rate of collagen injection is not supported by this study. With long-term followup collagen injection is rarely effective for treating urinary incontinence in children with neurogenic sphincter deficiency.

Adolescent↗

PubMed2001

Efficacy of endoscopic subureteral polydimethylsiloxane injection for treatment of vesicoureteral reflux in children: a North American clinical report.

PURPOSE: Subureteral injection of bulking agents is an accepted surgical treatment of vesicoureteral reflux in children. Polydimethylsiloxane, a silicone elastomer, is an ideal agent because of bulky consistency, lack of migration, minimal local inflammatory reaction and is safe in laboratory animals. We record our experience with endoscopic subureteral polydimethylsiloxane injection in children for vesicoureteral reflux. MATERIALS AND METHODS: During a 2-year period 16 boys and 58 girls, with an average age of 8 years, with 112 refluxing ureters underwent endoscopic subureteral polydimethylsiloxane injection to treat vesicoureteral reflux. Vesicoureteral reflux was grade I in 8, II in 43, III in 50, IV in 10 and V in 1 ureter. Operative indications were breakthrough urinary tract infection in 29 children, nonresolution of reflux 38 and high grade reflux 7. All procedures were on an outpatient basis and performed with patient under general anesthesia. All children had a postoperative ultrasound and voiding cystourethrogram at 12 weeks. Followup was from 6 to 24 months. RESULTS: Overall, reflux was corrected in 90 (81%) ureters and 56 (76%) children after a single injection. With repeat injection reflux was corrected in 101 (90%) ureters and 63 (85%) children. Correction by grade was 85%, 84%, 80%, 45% and 0% for grades I to V, respectively. With repeat injection correction was 100%, 92%, 90% and 55% for grades I to IV, respectively. There were no surgical complications. De novo contralateral reflux developed in 2 (3%) children. There were 3 (4%) children who required open ureteral reimplantation for failed injection. Detection of the polydimethylsiloxane implant by followup ultrasound was 89% sensitive and 86% specific for the correction of reflux. CONCLUSIONS: Endoscopic subureteral polydimethylsiloxane injection is an effective treatment of vesicoureteral reflux in children. The procedure is safe with low associated morbidity. The presence of the polydimethylsiloxane implant can be documented accurately by ultrasound, and there is a strong correlation between implant stability and correction of reflux.

Adolescent↗

PubMed2000

Outcomes of primary valve ablation versus urinary tract diversion in patients with posterior urethral valves.

OBJECTIVES: Although valve ablation is the treatment of choice for patients with posterior urethral valves, debate continues as to the role of urinary diversion. We sought to retrospectively compare the clinical and radiologic outcomes between valve ablation and urinary diversion for patients with posterior urethral valves. METHODS: We retrospectively reviewed the records of 50 consecutive patients with posterior urethral valves since January 1995. On the basis of the initial renal function and radiologic findings, patients were divided into three groups: group 1, normal renal function and radiologically normal upper tracts; group 2, normal renal function with hydronephrosis and/or reflux; and group 3, azotemia with hydronephrosis or reflux. RESULTS: All 22 patients in group 1 were treated with valve ablation. After a mean follow-up of 32 months, these children had normal renal function and no evidence of upper tract deterioration. All 13 patients in group 2 were also treated with valve ablation. The radiologic abnormalities (hydronephrosis, reflux) resolved in 50% of cases, with an average follow-up of 28 months. Of the 15 patients in group 3, 7 underwent valve ablation and 8 underwent urinary diversion. Urinary diversion was performed in patients with renal deterioration and severe hydronephrosis and/or high-grade reflux. Renal function returned to normal in all patients who underwent valve ablation except one; renal function returned to normal in only 3 of 8 patients who underwent urinary diversion. Radiologically, the severity of the hydronephrosis and reflux was downgraded in patients who underwent valve ablation but not in the diverted group. CONCLUSIONS: Valve ablation is the mainstay of treatment for patients with posterior urethral valves. Prenatal and postnatal factors, such as renal dysplasia and urinary tract infection, respectively, rather than the posterior valve treatment dictate the long-term renal and radiologic outcomes.

Adolescent↗

PubMed2000

Wilms' tumor. Surgical considerations and controversies.

Although the therapeutic objectives for Wilms' tumor are to maximize outcomes and minimize treatment morbidity, there are some controversial issues related to different therapeutic protocols. In this article, the authors address some of the issues such as the roles of tumor biopsy, preoperative chemotherapy, contralateral exploration, and partial nephrectomy.

Antineoplastic Agents↗

PubMed2000

The dysfunctional voiding scoring system: quantitative standardization of dysfunctional voiding symptoms in children.

PURPOSE: Academic research on pediatric nonneurogenic voiding dysfunction has long been hampered by the lack of a standardized reporting system for voiding symptoms. We evaluated the performance of a newly devised, objective instrument to quantify or grade the severity of abnormal voiding behaviors of children. MATERIALS AND METHODS: There were 10 voiding dysfunction parameters that were assigned scores of 0 to 3 according to prevalence, and possible total scores ranged from 0 to 30. The Dysfunctional Voiding Symptom Score was completed by 2 groups of patients. Group 1 consisted of patients 3 to 10 years old presenting to the pediatric urology clinic with a history of diurnal urinary incontinence, urinary tract infections or abnormal voiding habits. Group 2 consisted of an age matched cohort with no history of urological complaints presenting to hospital clinics outside of urology. Patients diagnosed with organic or anatomical disease, such as posterior urethral valves or meningomyelocele, were excluded from our analysis. RESULTS: Group 1 consisted of 104 patients (female-to-male ratio 4:1) with a median symptom score of 14 and group 2 consisted of 54 patients (female-to-male ratio 1.3:1) with a median score of 4. The dysfunctional voiding odds ratio was 2.93 for females compared to that of males. Using receiver operating characteristics the optimum cutoff score was 6.026 (sensitivity 92.77% and specificity 87.09%) for females and 9.02 (sensitivity of 80.95% and specificity of 91. 30%) for males. In addition, we found certain questions to be more reflective than others of dysfunctional voiding symptoms in our population. CONCLUSIONS: The Dysfunctional Voiding Symptom Score appears to provide accurate and objective, that is, numerical, grading of voiding behaviors of children. Comparative research studies of dysfunctional voiding diagnosis and response to therapy as well as objective measurements of treatment efficacy and outcomes analysis should be aided greatly by this system.

Child↗

PubMed2000

The natural history of neonatal vesicoureteral reflux associated with antenatal hydronephrosis.

PURPOSE: In an attempt to evaluate the natural history of neonatal vesicoureteral reflux, patients with antenatal history of hydronephrosis and documented reflux in the first 30 days of life were analyzed. MATERIALS AND METHODS: Between 1993 and 1998, 260 patients with a history of antenatal hydronephrosis were referred for evaluation. Of these patients 31 were diagnosed with unilateral or bilateral refluxing renal units (54 renal units). Patients were treated with a prospective plan of observational therapy and prophylactic antibiotics, and resolution rate was calculated in patients with adequate followup. Reflux grade was correlated with postnatal ultrasonographic findings, urinary tract infections and differential renal function. Outcome analysis of 34 high grade (III to V) refluxing renal units using the Kaplan-Meier survival curves was undertaken with the end point being complete resolution or improvement. Three patients with vesicostomy and 2 who underwent ureteral reimplantation were excluded from analysis. RESULTS: Reflux was grade I in 5% (33% males), II in 15% (62% males), III in 32% (71% males), IV in 18% (90% males) and V in 30% (100% males) of the patients. Postnatal ultrasound findings correlated poorly with the presence and degree of vesicoureteral reflux. Of 17 patients followed for at least 14 months (average followup 20) there was complete resolution in 60% with grade III, 50% with grade IV and 28% with grade V reflux. Using the Kaplan-Meier estimate there was a 50% chance of improvement (decrease in reflux grade by at least 2 grades) in high grade reflux by age 16 months. Urinary tract infections developed in 8 patients (26%) while on antibiotics. Of 46 renal units in 23 patients evaluated with a renal scan before urinary tract infection, 12 had less than 35% function. CONCLUSIONS: A normal postnatal ultrasound should not be a basis for excluding the use of cystography. Our Kaplan-Meier estimate shows that high grade reflux does improve and may resolve spontaneously. In addition, renal scarring may be seen with high and low grade reflux in the absence of urinary tract infection but high grade reflux is associated with a higher incidence of infection.

Female↗

PubMed1999

Prenatal diagnosis of hydronephrosis: impact on renal function and its recovery after pyeloplasty.

PURPOSE: We reviewed our experience with corrective surgery for congenital ureteropelvic junction obstruction to assess the impact of mode of presentation on renal function at diagnosis and on postoperative recovery of function. MATERIALS AND METHODS: We reviewed the records of consecutive children who underwent pyeloplasty or nephrectomy for ureteropelvic junction obstruction during a 5-year period at our hospitals. Patients were divided into those with and without a prenatal diagnosis of hydronephrosis. In each group we compared preoperative and postoperative differential renal function, as measured by nuclear renography. RESULTS: We identified 89 patients, of whom 51 (57%) and 38 (43%) presented with prenatal and postnatal hydronephrosis, respectively. Kidneys in which hydronephrosis was diagnosed prenatally had better average differential renal function than those in which the condition was detected postnatally (45 versus 37%). This difference was even more significant in kidneys with less than 40% initial function (31 versus 21%). Presentation with a palpable mass was associated with worst renal function (mean 23%). Postoperatively renal function did not recover significantly in either group. There was a minimal increase in postoperative differential renal function in the subgroup of patients in whom initial differential renal function was less than 40%, although there was no significant difference in the 2 groups (6.5 versus 4.8%). CONCLUSIONS: The early diagnosis of hydronephrosis provided by prenatal ultrasonography is associated with less obstructive nephropathy. Prolonged followup is necessary for studies of the natural history of hydronephrosis because relevant obstruction manifests clinically years later. Despite successful pyeloplasty function recovery is minimal in kidneys with poor function and hydronephrosis diagnosed prenatally. Our findings do not support previous observations that poor function markedly improves after obstruction is relieved.

Child, Preschool↗

PubMed1999

Supranormal renographic differential renal function in congenital hydronephrosis: fact, not artifact.

PURPOSE: Children with unilateral hydronephrosis, who had been prospectively examined with diethylenetriaminepentaacetic acid (DTPA) and dimercapto-succinic acid (DMSA) renography, were evaluated to determine whether supranormal renographic differential renal function exists. MATERIALS AND METHODS: A total of 54 children with congenital single system hydronephrosis underwent abdominal ultrasound, voiding cystourethrogram, and DTPA and DMSA renal scans. None had abnormalities of the bladder or contralateral kidney. Differential renal function greater than 55% was defined as supranormal. RESULTS: Of the 54 patients 15 (28%) with a median age of 4 months (range 0.5 to 66) were identified with supranormal renographic renal function on either DTPA or DMSA. Supranormal renographic renal function was detected by DMSA in 9 cases (mean 57+/-2%), DTPA in 8 (mean 58+/-2%) and both in 2 (mean 57+/-2%). Average function demonstrated in the 15 patients was 55+/-3% (range 51 to 62) with DMSA which was not different from that found with DTPA (mean 55+/-4%, range 46 to 61%). The kidneys with supranormal renographic renal function were significantly larger than hydronephrotic controls according to longitudinal parenchymal area on DMSA. Mean followup was 20 months for 13 patients, with 8 of 13 (62%) undergoing pyeloplasty. Followup DTPA renal scans available in 9 children revealed persistent supranormal function in 6, despite pyeloplasty in 3. CONCLUSIONS: Supranormal renographic differential renal function does exist in congenital hydronephrosis and when found the kidneys are consistently enlarged. The position of supranormal renographic renal function in the management algorithm of hydronephrosis remains to be elucidated as it does not appear to be a benign prognostic factor.

Child, Preschool↗

PubMed1998

The captopril renogram: a new tool for diagnosing and predicting obstruction in childhood hydronephrosis.

PURPOSE: We evaluated the difference in response patterns of captopril versus standard renography for assessing hydronephrosis due to suspected ureteropelvic and ureterovesical junction obstruction. This technique may identify hydronephrotic kidneys in which normal function is maintained by vasoactive compensatory mechanisms. Sustained obstruction may cause these mechanisms to fail, and expose the kidneys to permanent functional deterioration in the long term. MATERIAL AND METHODS: We prospectively studied 15 boys and 8 girls with a mean age of 3.5 years with grades III to IV/IV hydronephrosis. Evaluations included renal sonography, standard diuretic and captopril renography, glomerular filtration rate, voiding cystography, serum creatinine, blood pressure, and urinalysis with culture and sensitivity. Obstruction was suspected at the ureteropelvic junction in 19 kidneys and at the ureterovesical junction in 9. We compared differential function values obtained by standard diuretic and captopril renography. RESULTS: We observed certain patterns in response to captopril renography, including pattern 1--unilateral decrease in hydronephrotic kidney relative function in 5 of 23 cases, 2--bilateral decreased function in 2, 3--bilateral increased function in 4 and 4--no change in function in 12 on standard renography. When half-time was more than 20 minutes on standard diuretic renography in 8 cases, captopril renography showed an ipsilateral decrease and bilateral increase in glomerular filtration rate in 4 and 1, respectively, and no change in 3. In 12 of the 23 patients (52%) there was no difference in the results of captopril and diuretic renography as well as no change in differential function on standard diuretic renography during 1 1/2 years of observation. Surgical correction was performed in 4 patients in whom half-time was greater than 20 minutes and differential function was decreased on captopril renography. CONCLUSIONS: Our preliminary study reveals that there may be a role for captopril renography for detecting renin-angiotensin system mediated compensatory mechanisms in obstructive uropathy. When such compensatory mechanisms are activated, they may be unmasked by captopril, producing 1 of 4 patterns on renography and glomerular filtration rate. Patterns may indicate different degrees of impending renal function impairment and, thus, they may become useful for determining the progression of injury, when present, and the appropriate timing of surgical intervention.

Captopril↗

PubMed1998

Magnetic resonance imaging in children with voiding dysfunction: is it indicated?

PURPOSE: We evaluated the role of magnetic resonance imaging (MRI) of the lumbosacral spinal cord in children with complicated voiding dysfunction and normal neuro-orthopedic examination. MATERIALS AND METHODS: We reviewed the records of 32 consecutive children with complicated enuresis who were referred for neurosurgical evaluation, including those with a history of refractory voiding dysfunction or incontinence associated with persistent vesicoureteral reflux, encopresis, or associated leg or back pain. Nine patients were excluded from study because of urethral or anorectal anomalies, or failure to meet the inclusion criteria. Eligible for study inclusion were 23 children with a mean age of 8.9 years. Complete neurological and orthopedic examinations were normal in all patients except 1 with mild scoliosis and 1 with congenital facial palsy. RESULTS: Urodynamic studies revealed instability in 14 cases, hypertonia in 7, hyporeflexia in 2 and detrusor-sphincter dyssynergia in 4. Skeletal abnormalities, mostly spina bifida occulta, were detected in 16 of the 23 children (70%). Spinal MRI was normal in 21 patients (91.3%), including 1 with a tethered cord and lipoma associated with a complex skeletal abnormality, and 1 with a nonprogressive, nonsurgical T7 to T9 syrinx. Only the case of lipoma required neurosurgical intervention. CONCLUSIONS: The value of MRI is limited in children with voiding dysfunction and a normal neuro-orthopedic assessment. This study should be reserved for patients with associated neuroorthopedic findings or complex skeletal deformity on plain x-ray.

Adolescent↗

PubMed1997

Long-term results of percutaneous endopyelotomy in the treatment of children with failed open pyeloplasty.

PURPOSE: We reviewed our experience with the safety and long-term efficacy of percutaneous endopyelotomy in children with secondary ureteropelvic junction obstruction who previously underwent open pyeloplasty. MATERIALS AND METHODS: Nine patients a median of 7 years old underwent endopyelotomy between June 1985 and July 1995. Anderson-Hynes pyeloplasty had previously been performed in all children. Antegrade endopyelotomy was done with a cold knife in conjunction with balloon dilation in some cases. Postoperative stenting lasted 6 weeks. RESULTS: The median interval between pyeloplasty and endopyelotomy was 7.5 months. Mean operative time was 240 minutes. Percutaneous endopyelotomy was successful in 8 of the 9 patients. One patient who required repeat endopyelotomy after 4 years is presently well at 5 years of followup. Average followup was 5.6 years (range 2 to 10). There was a low morbidity rate, including 1 case of urinary tract infection, 1 of pneumonia and 1 that required blood transfusion. CONCLUSIONS: Percutaneous antegrade endopyelotomy is a safe, effective and durable alternative for children who previously underwent unsuccessful pyeloplasty.

Adolescent↗