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Biomedical subjects

A Atala

Publications and source records attributed to A Atala.

At least 91 records · Page 5Linked to original sources

Human albumin solder supplemented with TGF-beta 1 accelerates healing following laser welded wound closure.

BACKGROUND AND OBJECTIVE: We examined the possibility that human albumin solder can be used as a vehicle for site specific delivery of growth factors for the purpose of accelerating tissue repair following laser welded wound closure. Certain human recombinant growth factors have been shown to accelerate wound healing in model systems. Pilot in vitro studies have established that several growth factors, including TGF-beta 1, maintain bioactivity following exposure to temperatures achieved during laser tissue welding. Using a temperature controlled laser delivery system (TCL) to precisely maintain welding temperatures, it is now possible to avoid thermal denaturation of exogenous bioactive molecules such as growth factors. STUDY DESIGN/MATERIALS AND METHODS: HB-EGF, bFGF, and TGF-beta 1 were tested in vitro for maintenance of bioactivity after exposure to 80 degrees C. In vivo experiments using porcine skin determined the efficacy of solders augmented with growth factors. Incisions were repaired using human albumin alone or supplemented with HB-EGF (2 micrograms), bFGF (10 micrograms), or TGF-beta 1 (1 microgram). Wounds were excised at 3, 5, and 7 days post-operatively. Tensile strength, total collagen content, and histology were performed. RESULTS: At 3 days, tensile strength (TS) of TGF-beta 1 wounds were 36% (P < 0.05) and 20% (n.s.) stronger than laser alone and suture closures, respectively. By 5 days the TS of the TGF-beta 1 group increased by 50% (P < 0.05) and 59% (P < 0.02) over laser alone and suture groups, respectively. At 7 days the TGF-beta 1 group was 50% (P < 0.05) and 79% (P < 0.01) stronger than laser solder alone or suture, respectively. The HB-EGF and bFGF groups were equivalent to the laser solder group at all time points. Total collagen TGF-beta 1 Accelerates Healing Following Laser Welding content at 7 days increased in the TGF-beta 1 group by 7% (n.s.) over the suture group and 21% (P < 0.05) in the laser group. CONCLUSION: Human albumin solder supplemented with TGF-beta 1 increases the early post-operative strength of laser welded wounds. This novel application of laser tissue soldering augmented with a growth factor has the potential to bring about immediate fluid tight seals while providing site specific delivery of biological modifiers. This may lead to an overall improvement in post-operative convalescence, wound infections, and hospital costs.

Albumins↗

Hydrocele of the spermatic cord: embryology and ultrasonographic appearance.

Five cases of hydrocele of the spermatic cord are presented. All five patients had a firm inguinal mass, and ultrasonography, performed to exclude adenopathy, incarcerated hernia, and paratesticular tumor, showed an avascular cystic mass superior to and separate from the testicle. A testicular hydrocele did not coexist. This typical appearance should lead to a confident diagnosis of this benign but rare anomaly. Elective surgery may prevent the development of an acquired indirect hernia.

Diagnosis, Differential↗

Ten-year experience with the artificial urinary sphincter in children.

PURPOSE: To assess the efficacy of the artificial urinary sphincter survival and continence were first evaluated 5 years ago. We now evaluated the effects of the artificial urinary sphincter more than a decade after implantation. MATERIALS AND METHODS: Before 1985 an artificial urinary sphincter was implanted in 22 male and 14 female consecutive patients 4 to 30 years old (median age 12). In addition, between 1985 and 1990, 18 other children underwent artificial urinary sphincter implantation. Results of both series were compared. RESULTS: Of the 25 sphincters in the original series that were functioning after 5 years 1 was removed and 2 patients were lost to followup, resulting in 22 functioning implants (61% of the patients). Mean survival time of the prostheses was 12.1 years and average followup for functioning sphincters was 13.7 years. There was no statistically significant difference in artificial urinary sphincter survival between the original group at 5 years and the second group treated after 1985. Of the patients in both groups with sphincters in place 32 of 39 (82%) were dry. Augmentation cystoplasty was performed in 9 of 18 patients (50%) in the second series (5 preoperatively and 4 postoperatively) compared to 10 of 36 (28%) in the original series at 5 years (3 preoperatively and 7 postoperatively). Renal failure developed in 6 patients from both series. CONCLUSIONS: The artificial urinary sphincter is a durable long-term solution for children with intractable incontinence. Long-term surveillance of the urinary tract is mandatory because of the potential for renal failure in patients who have bladder hypertonicity after placement of the device.

Adolescent↗

Progressive ureteral dilation for subsequent ureterocystoplasty.

PURPOSE: The complications associated with bladder augmentation using the gastrointestinal tract are well known. A bladder based ureteral flap is a viable alternative for augmentation. However, its use is limited to cases in which a dilated ureter is already present due to associated pathological conditions, such as reflux. We designed a system for performing progressive dilation in a normal ureter, which can subsequently be used for augmentation. MATERIALS AND METHODS: Ten rabbits underwent unilateral ureteral ligation at the ureterovesical junction and ipsilateral nephrectomy. A silicone catheter was threaded into the proximal ipsilateral ureter and connected to an injection port, which was secured subcutaneously. Ten days to 2 weeks after surgery a saline-antibiotic solution was injected subcutaneously daily into the injection port. Cystography and cystometrography were performed with an accurate measurement of bladder capacity. Ureterography was done initially and then weekly by injecting contrast medium into the ureter. After ureteral dilation ureterocystoplasty was performed in each animal. RESULTS: After 1 month of daily saline-antibiotic solution injections the ureteral units were dilated at least 10-fold, as measured by radiography. The dilated ureteral diameter exceeded that of adjacent colon in each instance. Augmentation cystoplasty was performed with the reconfigured dilated ureteral segment. Repeat cystography and cystometrography showed an average 260% increase in bladder capacity (range 190 to 380%). CONCLUSIONS: Ureteral dilation can be accomplished using our system. At least a 10-fold increase in ureteral size is possible. The dilated ureteral segment can be used effectively for bladder augmentation, avoiding the use of bowel segments.

Animals↗

Reconstructive options in genitourinary rhabdomyosarcoma.

PURPOSE: We attempted to develop a rational and consistent scheme for surgical reconstruction in patients with genitourinary rhabdomyosarcoma. MATERIALS AND METHODS: We reviewed the records of 35 patients with resectable genitourinary rhabdomyosarcoma treated from 1970 to 1993. RESULTS: Primary sites included bladder in 11 cases, prostate in 13, vagina/uterus in 9 and pelvic tumors of uncertain origin in 2. A total of 33 patients underwent surgery, including partial and radical cystectomy in 17 (bowel conduit diversion in 10, continent urinary diversion in 6 and ureterosigmoidostomy in 1). Overall 30 of the 33 surgical patients are free of disease 4 months to 24 years after diagnosis. CONCLUSIONS: A nonrefluxing colon conduit is appropriate at cystectomy. Continent diversion fashioned from the original conduit may be planned as the patient achieves a durable disease-free status.

Adolescent↗

Repair of the high vagina in girls with severely masculinized anatomy from the adrenogenital syndrome.

In the most severe form of congenital adrenal hyperplasia in females, the vagina is located above the level of the external urethral sphincter. Sixteen of these patients had reconstruction with a pull-through technique described previously. Nine are now adults; six have coitus and three do not. Five are young and sexually immature. Two have been lost to follow-up.

Adrenal Hyperplasia, Congenital↗

Comparative urodynamics of appendiceal and ureteral Mitrofanoff conduits in children.

We report the cystometric and conduit pressure profilometric findings of 20 children for whom the Mitrofanoff principle was applied to the construction of 21 continent catheterizable urinary conduits. Mitrofanoff conduits were fashioned from ureter in 10 cases, appendix in 8, ileum in 1, stomach in 1 and a combination appendix and ureter in 1. Conduit pressure profiles showed that functional profile length correlated strongly with the static profile maximal Mitrofanoff closure pressure (p = 0.04) and dynamic profile maximal Mitrofanoff closure pressure (p = 0.02). There was a statistically significant difference between clinical continence rates for children above and below the functional profile length threshold of 2.0 cm. (p = 0.05). The zone of continence corresponded to the region of the conduit intramural tunnel. Only 2 of 21 conduits were incontinent but both were constructed with ureters implanted into bowel reservoirs. Compared to appendiceal conduits, ureteral conduits had a lower functional profile length (p < 0.01) and static profile maximal Mitrofanoff closure pressure (p < 0.01), indicating a possible advantage to the use of the appendix.

Adolescent↗

The long-term urological response of neonates with myelodysplasia treated proactively with intermittent catheterization and anticholinergic therapy.

PURPOSE: Urinary tract management in children with myelodysplasia is controversial. Some advocate observation alone, while others believe that the prophylactic institution of intermittent catheterization and anticholinergic therapy may help to prevent deterioration. MATERIALS AND METHODS: A nonrandomized prospective study was instituted to compare the urological outcomes of a cohort of children who were at risk for urological deterioration on the basis of bladder-sphincter dyssynergia and/or high filling or voiding pressures. Those at risk were observed until deterioration occurred, or were placed on prophylactic intermittent catheterization with or without anticholinergic medication. RESULTS: Of 44 children at risk 35 followed by observation alone had urinary tract deterioration, whereas only 3 of 20 at risk treated with prophylactic intermittent catheterization had deterioration with time. CONCLUSIONS: Proactive bladder treatment significantly reduced the incidence of upper urinary tract deterioration and need for surgical intervention.

Cholinergic Antagonists↗

Meatal based hypospadias repair with the use of a dorsal subcutaneous flap to prevent urethrocutaneous fistula.

A technique using a dorsal dartos subcutaneous flap to wrap the neourethra after hypospadias repair is described. This method was used in a series of 204 meatal based repairs. Catheter drainage or diversion was not performed in any nontoilet trained child. The procedure was done on an ambulatory or 1-night hospitalization basis. No patient had a urethrocutaneous fistula. The additional covering of the neourethra with the dorsal subcutaneous flap appears to be excellent for avoiding the development of urethrocutaneous fistulas in patients with distal hypospadias.

Adolescent↗

Endoscopic treatment of vesicoureteral reflux with a chondrocyte-alginate suspension.

Injection of polytetrafluoroethylene (Teflon) or collagen has been used in the endoscopic treatment of vesicoureteral reflux. Although the principle of an endoscopic treatment is valid, there are concerns regarding the long-term safety and effectiveness of these substances. In search of a different injectable material we conducted experiments using chondrocytes in a biodegradable polymer solution for the treatment of vesicoureteral reflux in an animal model. Reflux was created in 4 mini-pigs and confirmed with a cystogram. Cartilage was obtained from the auricular surface of each animal. Chondrocytes were harvested and expanded in vitro. The cells were individually quantitated and concentrated to 40 million cells per cc. The cell suspensions were mixed with a sodium alginate and calcium sulfate solution. Each pig was injected unilaterally in the subureteral region with the autologous chondrocyte suspension. The opposite ureter served as an internal control in all animals. Cystograms showed resolution of reflux in the treated side and persistence of reflux in the opposite untreated side in each instance. Excretory urograms revealed no evidence of obstruction. Histological examination of the subureteral region demonstrated cartilage. Autologous chondrocytes can be readily harvested, expanded in vitro and injected cystoscopically. The cells survive and form a cartilage nidus that is nonantigenic. This system is able to correct reflux without any evidence of obstruction.

Alginates↗

Phenotypic and cytogenetic characterization of human bladder urothelia expanded in vitro.

A simple method for the harvest of bladder cell types from surgical specimens was used to generate strains of normal human urothelial cells that could be reproducibly cultivated, passaged and extensively expanded in serum-free medium. Immunostaining of the bladder epithelial cells with broadly reacting anti-cytokeratin antibodies and with an anti-cytokeratin antibody specific to cytokeratin 7, a transitional cell marker, indicated that they expressed a stable epithelial phenotype with serial passage. Low levels of immunostaining for E-cadherin and low levels of E-cadherin messenger ribonucleic acid, as determined by Northern blot analysis, and strongly positive immunostaining with an anti-vimentin antibody indicated collectively that the uroepithelial cells express a nonbarrier-forming phenotype under these culture conditions. However, when the urothelial cells were implanted subcutaneously into athymic mice on biodegradable synthetic polymers, they formed multilayered structures, suggesting that they retain the capability to differentiate in a living host. The urothelial cells proliferated in an epidermal growth factor independent manner and expressed high levels of transforming growth factor-alpha and amphiregulin messanger ribonucleic acids, suggesting the possibility of autocrine regulation of growth by epidermal growth factor-like factors. Cytogenetic analysis indicated that urothelial cells cultured for 6 passages possessed a normal chromosomal complement. These results demonstrate that primary cultures of autologous human bladder epithelial cells can be extensively expanded in vitro and, consequently, might be used in cell transplantation strategies for genitourinary reconstruction.

Amphiregulin↗

Management of severe hypospadias with a 2-stage repair.

From 1986 to 1993 we treated 1,437 children with hypospadias of whom 58 had scrotal or perineal hypospadias with severe chordee and a small phallus. These patients underwent a 2-stage surgical repair. The first stage of the procedure included correction of the chordee and advancement of preputial flaps ventrally and distally to the superior aspect of the glans. After 6 to 12 months the second stage of the procedure was performed using the previously transferred preputial skin to reconstruct the glans and urethra. A second layer of subcutaneous tissue or tunica vaginalis was used in several instances. A penile nerve block and a transparent biomembrane dressing (Tegaderm) allowed for early postoperative mobilization. Excellent functional and cosmetic results were achieved. There is a subset of patients with severe proximal hypospadias, chordee and a small phallus who may benefit best from a 2-stage procedure. In these children a 2-stage repair allows for a better cosmetic appearance and a lower complication rate than a 1-stage repair with a free or vascularized graft.

Child↗

Use of bowel for vaginal reconstruction.

There is a wide range of congenital vaginal abnormalities that can be reconstructed using bowel. From 1964 to 1993 we used bowel for vaginal reconstruction in 65 patients and all but 5 were treated since 1981. Patient age ranged from 9 months to 26 years. In 29 patients the bowel was used to extend a short vagina to the perineum, and in 36 the entire vagina was absent and required a substitute vagina. Indications for surgery included cloacal malformations in 34 cases, congenital absence of vagina in 12, cloacal exstrophy in 9 genetic male subjects, postoperative exenteration in 7, intersex in 2 and bladder exstrophy in 1. Rectum was used in 12 cases, sigmoid colon in 27 and small bowel in 26. Ten patients who are now adults have reported satisfactory coitus.

Adolescent↗

Detection of human androgen receptor mRNA expression abnormalities by competitive PCR.

A competitive polymerase chain reaction (PCR) method for analysis of androgen receptor (AR) mRNA expression is described. The technique involves the use of an in vitro-transcribed RNA (cRNA) corresponding to a region of the AR mRNA transcript as a competitor in reverse transcription and PCR (RT-PCR) using total cellular RNA. The competitor RNA contains a site-directed mutation that produces a restriction fragment length polymorphism after RT-PCR and endonuclease digestion. We demonstrate that incorporation of the competitor RNA into RT-PCR reactions allows rapid semiquantitative determination of relative AR mRNA levels without the necessity of following PCR product formation kinetically; reaction products are assessed at the conclusion of the reaction sequence and without the use of radioactive probes or other specialized detection systems. We have used competitive PCR to demonstrate low levels of AR mRNA in an androgen-unresponsive human prostate cell line (PC3). In addition, we have also used this method to confirm that genital fibroblasts obtained from a subject with penoscrotal hypospadias (a non-intersex masculinization defect) that exhibit low levels of high-affinity androgen binding also exhibit abnormally low AR mRNA levels. These last results suggest that some non-intersex malformations of the urogenital tract are associated with abnormalities in the expression of the androgen receptor.

Base Sequence↗

Extracorporeal shock-wave lithotripsy in transplanted kidney.

Urolithiasis is the least described urologic sequela of renal transplantation. We describe a renal transplant patient who presented with painless gross hematuria. An intravenous pyelogram demonstrated a 4 x 7-mm calculi in the region of the ureteropelvic junction, causing moderate hydronephrosis. The patient was treated successfully with extracorporeal shock-wave lithotripsy (ESWL). Serum creatinine and twenty-four-hour creatinine clearance were unchanged from levels prior to ESWL.

Adult↗

Implantation in vivo and retrieval of artificial structures consisting of rabbit and human urothelium and human bladder muscle.

The harvest of human bladder muscle and urothelial cells with subsequent growth may be useful for tissue replacement in genitourinary reconstruction. We previously reported the development of a system for the harvest, delivery and growth of rabbit urothelium in vivo using biodegradable polymers. We have now expanded and adapted this system for the harvest and in vivo implantation of human bladder urothelial and muscle cells. Synthetic polymer fibers of polyglycolic acid can serve as a scaffold and a delivery vehicle for the implantation of rabbit uroepithelial cells into athymic host animals. The polymers, which slowly degrade in vivo, allow the urothelial cells to survive at the implant site. We demonstrate that polyglycolic acid polymers support the proliferation of rabbit urothelial cells in situ and can serve as a maleable substrate for the creation of new urological structures that replace the degrading polymer fibers. We also show that human urothelial cells and bladder muscle cells, when implanted on polyglycolic acid fibers, from new urological structures in vivo composed of both cell types. The human cell-polymer xenografts can be recovered from host animals at extended times after implantation. These data suggest that feasibility of using polyglycolic acid polymers as substrates for the creation of human urothelial and muscle grafts for genitourinary reconstruction.

Animals↗