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Biomedical subjects

Earl Y Cheng

Publications and source records attributed to Earl Y Cheng.

18 recordsLinked to original sources
PubMed2006

Branched peptide-amphiphiles as self-assembling coatings for tissue engineering scaffolds.

An important challenge in regenerative medicine is the design of suitable bioactive scaffold materials that can act as artificial extracellular matrices. We reported previously on a family of peptide-amphiphile (PA) molecules that self-assemble into high-aspect ratio nanofibers under physiological conditions, and can display bioactive peptide epitopes along each nanofiber's periphery. One type of PA displays its epitope at a branched site using a lysine dendron, a molecular feature that improves epitope availability on the nanofiber surface. In this work, we describe the application of these branched PA (b-PA) systems as self-assembling coatings for fiber-bonded poly(glycolic acid) scaffolds. b-PAs bearing variations of the RGDS adhesion epitope from fibronectin were shown by elemental analysis to coat repeatably onto fiber scaffolds. The retention of supramolecular organization after coating on the scaffold was demonstrated through spectroscopic identification of beta-sheet structures and the close association of hydrophobic tails in a model pyrene-containing PA system. Primary human bladder smooth muscle cells demonstrated greater initial adhesion to b-PA-functionalized scaffolds than to bare scaffolds or to those coated with linear PAs. This strategy of molecular design and coating may have potential application in bladder tissue regeneration.

Cells, Cultured↗
PubMed2006

Multi-institutional experience with PIC cystography--incidence of occult vesicoureteral reflux in children with febrile urinary tract infections.

OBJECTIVES: It has been reported that all children with febrile urinary tract infections (FUTIs) and normal voiding cystourethrogram (VCUG) findings show occult reflux (vesicoureteral reflux [VUR]) when examined by cystography performed with positioning of the instillation of contrast at the ureteral orifice (PIC cystography). In this study, we evaluated the reproducibility of this finding using a prospective multi-institutional collaborative examination to determine whether PIC-VUR is as common in such cases as previously shown. METHODS: From March 2002 to October 2003, four institutions performed PIC cystography consecutively and prospectively in pediatric cases of FUTI (greater than 101 degrees F) who had not shown VUR by conventional VCUG. We correlated the ureteral orifice (UO) configuration and position with the status of PIC-VUR. RESULTS: PIC cystography was performed in 39 children (31 girls and 8 boys; 75 FUTIs). We identified PIC-VUR in 32 (82%) of 39 children, involving 58 (74%) of 78 ureters. The likelihood of demonstrating PIC-VUR was increased 37-fold if the UO showed a patulous configuration and was increased 9-fold if the UO showed a lateral configuration. PIC-VUR was noted uniformly in UOs showing hydrodistension. CONCLUSIONS: This multi-institutional registry showed that the incidence of PIC-VUR (82%) in children with FUTI and normal standard VCUG findings is similar to that previously reported. We consider that PIC-VUR likely accounts for the FUTIs.

Administration, Intravesical↗
PubMed2006

Challenges in a larger bladder replacement with cell-seeded and unseeded small intestinal submucosa grafts in a subtotal cystectomy model.

OBJECTIVE: To evaluate small intestinal submucosa (SIS), unseeded or seeded, as a possible augmentation material in a canine model of subtotal cystectomy. MATERIALS AND METHODS: In all, 22 male dogs had a 90% partial cystectomy and were then divided into three groups. At 1 month after the initial cystectomy, dogs in group 1 (unseeded, six) and group 2 (seeded, six) received a bladder augmentation with a corresponding SIS graft. The dogs in group 3 (ten) received no further surgery and were considered the surgical control group. All dogs were evaluated before and after surgery with blood chemistry, urine culture, intravenous urography, cystograms and cystometrograms. After surgery (at 1, 5 and 9 months), the bladders were examined using routine histology and immunohistochemistry. RESULTS: All 22 dogs survived the subtotal cystectomy, and 18 survived their intended survival period. One dog, in group 2 (seeded), was killed at 1 month after augmentation due to bladder perforation caused by a large piece of incompletely absorbed SIS. Three other dogs (group 1, two; and group 2, one) were killed within 2 months after augmentation due to bladder obstruction by stones. Group 1 and group 2 SIS grafts had moderate to heavy adhesion, graft shrinkage, and some had bone and calcification at the graft site. Histologically, there was limited bladder regeneration in both groups. Interestingly, dogs in group 3 at 1 month after cystectomy (when group 1 and 2 received their augmentations) had severely shrunken bladders and histologically had severe inflammation, fibroblast infiltration and muscle hypertrophy. These results verify the subtotal cystectomy model. CONCLUSIONS: The use of seeded or unseeded SIS in a subtotal cystectomy model does not induce the same quality and quantity of bladder regeneration that is seen in the 40% non-inflammatory cystectomy model. This study provides important insights into the process of regeneration in a severely damaged bladder. The results led us to re-evaluate the critical elements required for a complete bladder replacement using tissue-engineering techniques.

Animals↗
PubMed2005

Primary lower urinary tract reconstruction for nonfunctioning renal moieties associated with obstructing ureteroceles.

PURPOSE: Upper pole heminephrectomy is the conventional treatment for severely compromised nonfunctioning renal units associated with ureteroceles due to the potential morbidity of leaving a nonfunctioning renal moiety in place. This approach often fails to address the pathological anatomical defect present at the bladder level, and during long-term followup the majority of patients require subsequent lower tract surgery due to persistent ureterocele, new or persistent vesicoureteral reflux, or recurrent infections. We determined the success of primary lower urinary tract reconstruction for nonfunctioning renal moieties and the morbidity associated with leaving nonfunctioning renal units in situ. MATERIALS AND METHODS: We present the collective experience of 2 institutions using definitive lower urinary tract reconstruction without upper tract ablative surgery in 16 patients with duplex collecting systems and an associated nonfunctioning renal moiety due to obstructing ureteroceles. RESULTS: At a mean followup of 62 months upper tract dilatation was decreased or completely resolved in all patients, no loss of renal function was present and 15 of 16 patients (94%) had no evidence of persistent reflux. Postoperative complications in the form of a urinary tract infection occurred in 2 of 16 patients (13%). No patient was febrile. No patient had development of hypertension, proteinuria or tumor during followup. CONCLUSIONS: We believe that primary, single stage, lower urinary tract reconstruction in children with severely compromised or nonfunctioning renal moieties damaged by ureteroceles is superior to upper urinary tract ablative surgery, successfully correcting the obstructive or refluxing pathology with minimal morbidity and risk during long-term followup.

Child↗
PubMed2005

Clean intermittent catheterization in genitally sensate children: patient experience and health related quality of life.

PURPOSE: Clean intermittent catheterization (CIC) has proven successful for bladder emptying in children without genital sensation with success rates of 94% to 100% in select groups. A subset of the pediatric population requires CIC for bladder dysfunction, yet has normal genital sensation. This study was designed to assess our experience with CIC in genitally sensate children and the health related (HR) quality of life (QOL) for them and their families. MATERIALS AND METHODS: A multimodality questionnaire on the usage, learning curve and degree of difficulty of CIC was developed. The PedsQLtrade mark 4.0 Generic Core Scales, a reliable, validated HRQOL survey developed for pediatric patients with chronic disease, was used to assess patient and parental QOL. Children in our practice with normal genital sensation and bladder dysfunction requiring CIC were contacted to complete these questionnaires. When possible, QOL data were collected from the patient (self-report) and one or both of the parents (parent-proxy report). RESULTS: Data for 12 males and 8 females were collected, including 30 QOL questionnaires (12 self, 18 proxy). Of the patients 80% were able to learn CIC technique in 1 clinic visit with the help of a nurse. On a 10-point scale (1-not difficult, 10-very difficult) the mean degree of difficulty for learning the CIC technique was 3.25 for males and 4.00 for females (3.55 overall). On a 10-point scale (1-uncomfortable, 10-very comfortable) mean comfort level with the CIC technique was 9.12 for females and 9.46 for males (9.33 overall). On the PedsQL 100-point scale mean QOL was 83.24 for the self-report compared to 81.78 for the parent proxy report. The QOL for normal children has previously been shown as 83 (self) to 87.61 (proxy). CONCLUSIONS: CIC was an easy technique for most sensate children to learn in 1 visit and master in a short time. Overall comfort with the technique was excellent and few problems were encountered. Their HRQOL was comparable to that of normal children.

Adolescent↗
PubMed2005

Bladder neck fistula after the complete primary repair of exstrophy: a multi-institutional experience.

PURPOSE: The major goals of complete primary repair of exstrophy (CPRE) are the re-creation of normal anatomy which allows bladder cycling and to reduce the number of future procedures necessary to achieve continence. It is unclear whether CPRE is associated with a higher bladder neck fistula rate than the traditional staged repair. We review a multi-institutional experience with the CPRE technique to evaluate the rate of bladder neck fistula. MATERIALS AND METHODS: A retrospective review of 18 boys and 4 girls who underwent CPRE at 4 tertiary pediatric urology referral centers during the last 6 years was performed. All pertinent technical aspects were reviewed, including timing of procedure, whether osteotomies were performed, and number of layers used to reconstruct the bladder neck and urethra. Complications were noted, especially that of bladder neck fistula. RESULTS: Mean followup was 22.6 months. Of the patients 14 (64%) underwent primary closure within the first 48 hours of life and only 1 required osteotomies. The remaining 8 patients underwent closure between 5 days and 3 months of age (mean 24.6 days) and all required osteotomies. Bladder neck fistula occurred postoperatively at the pubic junction in 9 males (41%). Four cases had a 2 layer closure that was covered with a single layer small intestinal submucosa onlay (Surgisis) and no patient had a fistula. Fistulas developed in 62.5% of patients with delayed closure vs 29% of those with immediate closure (p = 0.135). Two fistulas closed spontaneously and 7 required surgical closure at a mean of 7.5 months after the fistula occurred. CONCLUSIONS: This multi-institutional study demonstrates that bladder neck fistulas occur in almost half of patients following CPRE by experienced pediatric urologists. While spontaneous closure is possible, most will eventually require repair. The long-term implications of this finding with regard to continence and the need for additional bladder neck procedures remain to be seen. We are encouraged by the preliminary results of small intestinal submucosa coverage and will continue to evaluate its use at the time of primary exstrophy closure.

Bladder Exstrophy↗
PubMed2005

Role of basic fibroblast growth factor in the neuropathic bladder phenotype.

PURPOSE: The neuropathic bladder is characterized by increased muscle mass within the bladder wall and reduced functional capability. The exact cellular mechanisms that regulate these changes have yet to be elucidated. We determine the role of basic fibroblast growth factor (bFGF) in the increased smooth muscle cell (SMC) proliferation seen in the neuropathic bladder. MATERIALS AND METHODS: Primary human bladder SMC cultures were established from patients with either normal or neuropathic bladders (3 each). Expression of bFGF, smooth muscle markers and bFGF receptor-1 were quantified by immunohistochemistry and Western blot analysis. Cell proliferation was assayed by cell count after stimulation with recombinant bFGF in the presence and absence of a neutralizing anti-bFGF antibody. RESULTS: Neuropathic bladder SMC expressed higher levels of bFGF than normal bladder SMC. Functional studies using exogenous bFGF demonstrated a significant dose dependent increase in cell proliferation in normal and neuropathic bladder SMC. This stimulatory effect could be completely inhibited by simultaneous addition of anti-bFGF antibodies. Also, the higher rate of baseline cell proliferation in neuropathic bladder SMC could be brought down to normal levels after treatment with anti-bFGF antibodies. The addition of exogenous bFGF showed no effect on the expression of fibroblast growth factor receptor-1 or smooth muscle phenotypic markers, suggesting that bFGF induces cell proliferation in neuropathic bladders in an autocrine fashion. CONCLUSIONS: These novel findings support the hypothesis that bFGF is over expressed in the neuropathic bladder and directly influences an increase in SMC proliferation.

Blotting, Western↗
PubMed2004

Congenital midureteral stricture in children diagnosed with antenatal hydronephrosis.

OBJECTIVES: Antenatal hydronephrosis is the most common genitourinary pathologic finding during gestational ultrasonography. Congenital midureteral strictures are an unusual cause of prenatal hydronephrosis, with 13 total previously reported and only 1 diagnosed as a result of antenatal ultrasonography. METHODS: We present 4 cases of midureteral strictures as the cause of antenatal hydronephrosis and review the published data on congenital midureteral obstruction. RESULTS: All midureteral strictures in our series and in the published reports were treated surgically after varying periods of observation. Retrograde pyelography was diagnostic in all cases. CONCLUSIONS: This atypical cause of antenatal hydronephrosis may provide additional insight into the controversy regarding preoperative retrograde pyelography before surgical intervention for ureteropelvic junction obstruction. Given the typical misdiagnosis of ureteropelvic junction obstruction in the setting of midureteral stricture disease, we believe that the threshold for retrograde pyelography should be very low.

Child, Preschool↗
PubMed2004

Characterization of neuropathic bladder smooth muscle cells in culture.

PURPOSE: Clinically bladder cells used in tissue engineering techniques will come from neuropathic bladders and not normal bladders. We determined if neuropathic bladder smooth muscle (SM) cells (SMCs) retain functional differences when cultured in vitro. MATERIALS AND METHODS: Primary cultures of SMCs were established from patients with a neuropathic bladder (5) and a normal bladder (5). Expression of alpha-SM actin and SM myosin heavy chain was determined using immunocytochemical staining and Western blot analysis. Baseline cell proliferation and the mitogenic response to angiotensin II was assessed by cell counting and cell viability assays. Cell contractility was determined for normal and neuropathic SMCs using an in vitro collagen lattice assay. Cell adherence was measured assessed using partial and complete trypsinization assays. RESULTS: Normal and neuropathic SMCs showed similar morphology in culture, and similar patterns of alpha-SM actin and SM myosin expression. Following 10 days of plating under optimal growth conditions the number of neuropathic SMCs was 170% more than normal SMCs. In response to angiotensin II neuropathic SMCs reached 54% of maximal growth capacity as opposed to 30% for normal SMCs (p <0.01). Neuropathic SMCs contracted significantly less in 10% serum and calcium ionophore (p <0.05), as determined by in vitro contractility assays. Neuropathic SMCs had 19% and 30% less adherent cells than normal SMCs (p <0.01) following isotonic solution washes and trypsinization, respectively. CONCLUSIONS: These results demonstrate that cultured neuropathic bladder SMCs possess and maintain different characteristics than normal SMCs in vitro. The potential clinical implications of using these cells in conjunction with tissue engineering techniques for the promotion of bladder regeneration requires further investigation.

Cells, Cultured↗
PubMed2004

Reliable and reproducible bladder regeneration using unseeded distal small intestinal submucosa.

PURPOSE: Using the unseeded technique of tissue engineering, small intestinal submucosa (SIS) has been shown to promote bladder regeneration. Initial studies using hand-made SIS obtained from sows demonstrated consistent and reliable results but since then surgical regenerative results have been inconsistent. SIS has been obtained from various sources and processed in different ways, thereby making it difficult to determine the single most important factor in obtaining reliable and consistent bladder regeneration using the unseeded technique. We review some of the previously used SIS materials, and compare SIS material made from the proximal small bowel to SIS made from the distal ileum. MATERIALS AND METHODS: In a canine bladder augmentation model we directly compared SIS derived from proximal segments of jejunum to SIS derived from distal segments of ileum. All 6 animals underwent partial (40%) cystectomy and immediate augmentation with 1 of the 2 SIS materials. We assessed the harvested bladders for the amount of regeneration, SIS graft size and shrinkage 10 weeks after augmentation. RESULTS: Both SIS materials demonstrated some evidence of bladder regeneration but it appeared that only sow age greater than 3 years) distal ileum SIS produced consistent bladder regeneration without bone formation and severe shrinkage. CONCLUSIONS: After years of SIS bladder regeneration research, it appears that not all material, even if obtained from different segments of 1 sow's bowel, has the same regenerative results. Therefore, the acronym SIS should be considered generic. Before clinical bladder augmentation further investigation is needed to identify the regenerative potential of specific SIS segments.

Humans↗
PubMed2003

Proximal division of the urethral plate in staged hypospadias repair.

PURPOSE: We describe a new technique for staged hypospadias repair in which the urethral plate is divided proximally at the time of the first stage. MATERIALS AND METHODS: A total of 14 patients with proximal hypospadias associated with severe chordee were operated on using a new staged technique. At the time of the first stage the urethral plate was divided proximally at the level of the hypospadiac meatus. In 8 of 14 patients the intact plate was then incised and tubularized with the Snodgrass technique. In 6 patients the plate was tubularized at the time of the second stage. Correction of chordee was accomplished with dorsal plication and/or corporal body grafting. Byar's flaps were used to fill in the residual gap between the proximal hypospadiac meatus and the newly tubularized neourethra. The transposed flaps in the area of the urethral defect were then tubularized at the second stage. RESULTS: Followup ranged from 6 months to 3 years. Complications included a proximal pinpoint fistula and diverticulum in 1 case. An additional patient also had formation of a mild diverticulum that has not required surgical revision. No patients have had any evidence of distal urethral stricture formation. CONCLUSIONS: Proximal division of the urethral plate and application of the Snodgrass procedure to the staged repair of hypospadias have resulted in improved functional and cosmetic results. The major advantage of this new technique is preservation and use of the native urethral plate in the glans and subcoronal area. When complications occur with this technique, they are less severe compared to those of the traditional staged approach.

Follow-Up Studies↗
PubMed2002

Snodgrass hypospadias repair with vascularized dartos flap: the perfect repair for virgin cases of hypospadias?

PURPOSE: Since its introduction, the Snodgrass hypospadias repair has been applied to virtually all forms of hypospadias repair. However, fistula rates have still been reported to be as high as 5% from large center, multiple surgeon studies and 16% from smaller center studies. We report on the use of the Snodgrass repair in conjunction with routine use of a vascularized dartos flap and 2-layer closure of the neourethra from multiple institutions. MATERIALS AND METHODS: Records of patients who underwent a primary 1-stage hypospadias repair with the Snodgrass technique in conjunction with vascularized dartos flap coverage were reviewed. Nearly identical surgical technique was used by all 6 surgeons in each case, which included a 2-layer closure of the neourethra, preservation of the well vascularized periurethral tissue and routine use of vascularized dartos flap coverage. A total of 514 cases were identified, including 414 with distal and 100 with midshaft or proximal hypospadias. Stents were used in 292 of the 514 repairs. RESULTS: Of the 414 distal cases there were no fistulas and 1 case of meatal stenosis. Of the 100 proximal cases there were 3 fistulas and 1 case of meatal stenosis. The overall complication rate was less than 1% for all cases combined. CONCLUSIONS: This series represents the largest reported multi-institutional experience with the Snodgrass technique. When used in conjunction with vascularized dartos flap coverage, 2-layer closure of the neourethra and special attention to preservation of the periurethral vascular supply, this repair can be performed with a near 0 complication rate. We believe that this is the optimal repair for routine cases of hypospadias.

Humans↗
PubMed2002

The use of small intestinal submucosa as an off-the-shelf urethral sling material for pediatric urinary incontinence.

PURPOSE: Use of autologous rectus fascia for urethral slings in the pediatric population has produced reliable and predictable results. However, the potential morbidity and complications associated with harvesting the autologous rectus fascia have driven efforts to find a reliable off-the-shelf material for urethral slings. Small intestinal submucosa is a collagen based material that has been shown to promote tissue specific regeneration in a variety of organs. We report the clinical experience at 4 institutions with small intestinal submucosa for urethral slings. MATERIALS AND METHODS: A total of 20 patients 3 to 18 years old (mean age 8.7) received urethral slings using the commercially available form of small intestinal submucosa (STRATASIS, Cook Urologic Spencer, Indiana) via a sling suspension procedure from a suprapubic approach. RESULTS: The material was consistently uniform to work with and user-friendly. All 20 patients tolerated the procedure well with no intraoperative complications. Postoperative followup has ranged from 9 to 26 months (mean 13), and 14 (70%) patients are completely dry (85% in females and 43% in males). Of the 14 dry patients 13 are on intermittent catheterization and 1 female with epispadias voids spontaneously. CONCLUSIONS: This report is the largest and longest followup series using small intestinal submucosa as an "off the shelf" urethral sling material in children. These continence rates are equal to autologous fascia without additional morbidity of graft harvest.

Adolescent↗
PubMed2002

The practice of urethral dilation for voiding dysfunction among fellows of the Section on Urology of the American Academy of Pediatrics.

PURPOSE: Review of the literature reveals little scientific evidence to prove or disprove the efficacy of urethral dilation for children with dysfunctional voiding and recurrent urinary tract infections. We ascertain the current practice of urethral dilation among pediatric urologists. MATERIALS AND METHODS: An anonymous questionnaire regarding the practice of urethral dilation was mailed to all fellows in the Section on Urology of the American Academy of Pediatrics. The questionnaire contained 14 questions and included biographical information. RESULTS: The questionnaire response rate was 64%. When asked how one would treat a typical female child with classic voiding dysfunction, 87% responded with timed voiding and relaxation techniques with or without anticholinergics. Only 2.5% would proceed directly to cytoscopy and urethral dilation. For patients who did not respond to initial treatment, 67% would proceed with either urodynamics or biofeedback and only 10% would then perform urethral dilation. Of responders 61% do not practice urethral dilation under any circumstance, 36% will use it when all other means of therapy have failed, while only 2% use urethral dilation regularly and 2% find it helpful and will occasionally use it. Among physicians who perform urethral dilation 63% believed that less than half of the patients experienced long-term improvement. Overall, there was no consensus as to mechanism of action of urethral dilation. CONCLUSIONS: Urethral dilation is rarely used as primary treatment for pediatric voiding dysfunction, is usually reserved until all other treatments have failed and appears to have long-term efficacy in less than 50% of patients. To define better the need for this treatment modality and its efficacy, a randomized prospective trial is mandatory.

Attitude of Health Personnel↗
PubMed2002

Use of small intestinal submucosa for corporal body grafting in cases of severe penile curvature.

PURPOSE: Small intestinal submucosa is a unique biomaterial that has been found to promote tissue specific regeneration in the urinary tract. We present our experimental and clinical experience with small intestinal submucosa (SurgiSis, Cook Biotech, Spencer, Indiana) for pediatric corporal body reconstruction. MATERIAL AND METHODS: A total of 20 Fischer rats underwent implantation of a 7 x 3 mm. small intestinal submucosa graft following excision of an ellipse of tunica albuginea and 14 control animals underwent tunical excision with reimplantation of this autologous segment. The animals were euthanized, and the penis was sectioned and histologically studied at intervals of 1, 2, 4, 6, 16 and 24 weeks. In 15 pediatric patients small intestinal submucosa was used for corporal body grafting. The grafting procedure was performed along the ventral (hypospadias cases) or dorsal (epispadias cases) surface of the corporal bodies. The tunica albuginea was incised full thickness at the point of maximal curvature down to the cavernosal tissue and the defect was filled with a single layer of small intestinal submucosa. RESULTS: Measurements of the animal small intestinal submucosa grafts did not reveal significant graft contraction through 6 months. There was no graft expansion or ballooning after pharmacological induction of an artificial erection. Histologically, marked inflammation at 1 week precipitously decreased to a normal appearing tunica albuginea at 3 and 6 months. In all clinical cases small intestinal submucosa was found to be technically easy to handle. Mean followup is 14 months (range 5 to 26). All patients have a straight phallus as documented by observation of spontaneous erections or artificial erection at the time of stage 2 hypospadias repair. No complications occurred. CONCLUSIONS: Small intestinal submucosa demonstrates tissue specific regeneration properties in the rat and human tunica albuginea. It is an off-the-shelf material that is safe, technically easy to use and readily available.

Adolescent↗
PubMedDate not supplied

Bladder regeneration with cell-seeded small intestinal submucosa.

This study was performed to determine the regenerative properties of smooth muscle cells (SMCs) and urothelial cells (UCs) seeded on small intestinal submucosa (SIS), utilizing a nude mouse model. Human bladder SMCs and UCs were seeded on SIS in a layered coculture fashion. Cell-seeded SIS grafts (1 x 1 cm(2)) were maintained in a CO(2) incubator for 14 days and subsequently folded with the seeded cells facing the lumenal side and implanted subcutaneously into the flanks of nude mice (n = 20). Unseeded SIS grafts were implanted into the contralateral flanks of the mice to serve as controls. Grafts were harvested at 4, 8, and 12 weeks after implantation. By 12 weeks, layered urothelium with a central lumen was noted with early smooth muscle bundle formation peripherally. At each time point, the regenerated SMCs stained positive for alpha-smooth muscle actin, and the UCs stained positive for cytokeratin AE1/AE3. The control group demonstrated no evidence of organized bladder regeneration. This study demonstrates the potential for cell-seeded SIS to induce organized bladder regeneration in vivo. This also provides the basis for additional work utilizing seeded SIS grafts for bladder augmentation.

Animals↗