PubMed Health⌕ Search

Biomedical subjects

A Atala

Publications and source records attributed to A Atala.

At least 37 records · Page 2Linked to original sources
PubMed2000

Tissue-engineering applications for phallic reconstruction.

Pathologic penile conditions often require reconstructive surgery. Due to the limited amount of autologous tissues available for reconstruction, other tissue substitutes have been used. Phallic reconstruction using engineered autologous genital tissue, i.e., tissue derived from the patient's own cells, may be preferable. In this article we describe tissue-engineering approaches that may be applicable to genital reconstruction.

Biocompatible Materials↗
PubMed2000

Experimental and clinical experience using tissue regeneration for urethral reconstruction.

Various urethral conditions often require additional tissue for reconstruction. Although several innovative tissues have been proposed for possible use as free grafts for urethral repair, all have specific advantages and disadvantages. The use of these tissues may be associated with additional procedures for graft retrieval, prolonged hospitalization, and donor-site morbidity. For these reasons, alternate materials have been sought for urethral repair. Our laboratory has developed an acellular collagen matrix that has shown adequate urothelial-cell epithelialization and urethral-tissue regeneration both experimentally and clinically. After a 3-year follow-up period, all patients who have had their urethras reconstructed with the acellular matrix are doing well, showing no clinical change from their immediate postoperative results. Other acellular materials may soon be tried clinically. Long-term studies need to be conducted before any of these materials can be accepted for routine use in urethral reconstructive procedures.

Animals↗
PubMed2000

Renal therapy using tissue-engineered constructs and gene delivery.

Currently available renal replacement therapies are not optimal for most patients. In addition to the inherent shortage of transplant organs, significant complications are associated with renal transplantation and immunosuppressive therapy. Dialysis neglects the resorptive, homeostatic, metabolic, and endocrinologic functions of the kidney and only partially replaces its filtration properties, resulting in morbidity and mortality. Application of tissue-engineering techniques may improve many aspects of renal function replacement. Identification of the growth factors capable of directing tissue development and of the technique to be used for their delivery would aid in the engineering of human tissue. The combination of tissue-engineering strategies with gene therapy might allow the transfection of diseased tissues with designated cDNA to eliminate inherent or acquired defects. Devices that have been targeted at replacing a single aspect of renal function, in addition to three-dimensional renal units that are capable of excreting urine-like solutes, have been used experimentally. Combination of these strategies may allow the formation of tissue-engineered kidneys in the future.

Biocompatible Materials↗
PubMed2000

Controlled release of therapeutic agents: slow delivery and cell encapsulation.

Some of the most promising systems for the controlled release of bioactive agents, i.e., peptides or hormones, involve the encapsulation or entrapment of hormones or peptides in biocompatible polymeric devices that enable their continuous release over prolonged periods. In urology, two major pathologic conditions, androgen deficiency and prostate cancer, currently benefit from treatments based on controlled delivery. Leuprolide acetate depot (Lupron-depot) was one of the first controlled-delivery systems used for the treatment of prostate cancer. Clinical studies indicate that patients with prostate cancer who undergo therapy with leuprolide acetate depot can benefit from this treatment. Currently available androgen-replacement therapies include the oral administration of testosterone tablets or capsules, depot injections, sublingual treatment, and skin patches. However, side effects such as metabolic inactivation of testosterone on oral administration; fluctuations in levels of the hormone; and burning, rash, and skin necrosis during the use of skin patches may occur. These side effects may be avoided through the application of encapsulated Leydig cells, which produce testosterone. Studies in our laboratory have shown that Leydig cells encapsulated in alginate/poly-L-lysine/alginate microspheres are capable of secreting testosterone in culture and in vivo. Microencapsulated Leydig cells delivered intraperitoneally into castrated rats maintained a testosterone level of 0.51 ng/ml for more than 3 months without any human chorionic gonadotropin stimulation. Similar studies are also being conducted in our laboratory on encapsulation of ovarian cells for the secretion of progesterone and estrogen in culture and in vivo using microencapsulation techniques.

Animals↗
PubMed2000

Tissue engineering of artificial organs.

Tissue engineering efforts are currently being undertaken for every type of tissue and organ within the urinary system. Most of the effort expended to engineer genitourinary tissues has occurred within the last decade. Tissue engineering techniques require expertise in growth factor biology, a cell culture facility designed for human application, and personnel who have mastered the techniques of cell harvest, culture, and expansion. Polymer scaffold design and manufacturing resources are essential for the successful application of this technology. In order to apply these engineering techniques to humans, further studies need to be performed with many of the tissues described. The first human application of cell-based tissue engineering technology for urologic applications took place at our institution, with the injection of autologous cells for the correction of vesicoureteral reflux in children. The same technology has been expanded to treat adult patients with urinary incontinence. Trials of urethral tissue replacement with processed collagen matrices are in progress, and bladder replacement using tissue engineering techniques are currently being arranged. Recent progress suggests that engineered urologic tissues may have clinical applicability in the future.

Artificial Organs↗
PubMed2000

Ketorolac suppresses postoperative bladder spasms after pediatric ureteral reimplantation.

UNLABELLED: We evaluated the efficacy of ketorolac in suppressing postoperative bladder spasms after ureteroneocystostomy (ureteral reimplantation). Twenty-four pediatric patients undergoing intravesical ureteroneocystostomy were enrolled prospectively to receive either ketorolac or placebo via double-blinded randomization. Twelve patients in each group shared similar preoperative characteristics. All were maintained on an epidural infusion of bupivacaine (0.1%) with fentanyl (2 microg/mL) throughout the study. Patients were given either ketorolac (0.5 mg. kg(-1). dose(-1)) or placebo (equivalent volume saline) IV after surgery and every 6 h thereafter for 48 h. Parents were instructed to record bladder spasm episodes prospectively by using a standardized time-flow diary. Three patients (25%) in the ketorolac group experienced bladder spasms, compared with 10 patients (83%) in the placebo group (two-sided P < 0.05). The median severity score for the ketorolac group was 1.2 (mild = 1.0, severe = 3.0), compared with 2.6 for the placebo group (P = 0.003). We conclude that IV ketorolac reduces the frequency and severity of postoperative bladder spasms after intravesical ureteroneocystostomy. IMPLICATIONS: We studied the efficacy of ketorolac, a prostaglandin synthesis inhibitor, in the treatment of bladder spasm after ureteroneocystostomy (antireflux operation). Patients were randomized in a double-blinded manner to receive either ketorolac or placebo after the surgery. We demonstrate that ketorolac reduces the frequency and severity of postoperative bladder spasm.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Initial experience with the transurethral self-detachable balloon system for urinary incontinence in pediatric patients.

PURPOSE: A new endoscopic technique to treat urinary incontinence in children using a self-detachable balloon device was studied. MATERIALS AND METHODS: The study includes 11 patients with a mean age of 14.6 years and all of whom had intrinsic sphincter deficiency due to myelomeningocele in 9, spinal artery bleed in 1 and cloacal exstrophy in 1. All patients were on clean intermittent catheterization preoperatively and postoperatively. Endoscopic balloon treatment was performed on an outpatient basis. A mean of 5 balloons (range 2 to 8) were placed per patient. All patients underwent formal urodynamic study preoperatively and at 6 weeks and 6 months following balloon placement. RESULTS: Of the 9 patients without prior bladder neck surgery 7 had improvement in urodynamic parameters, including urethral pressure profile in all 7 and functional bladder capacity in 6, 4 were markedly improved clinically and 2 were dry. Two patients with prior bladder neck surgery were clinically unchanged following balloon placement, although 1 had urodynamic improvement. CONCLUSIONS: Our initial experience with the transurethral self-detachable balloon system as a minimally invasive outpatient procedure to treat urinary incontinence in children has been encouraging. To date this procedure appears most applicable to the patient who has not undergone surgery and has a neurogenic etiology for urinary incontinence.

Adolescent↗
PubMed2000

Defunctionalized bladders: effects before and after refunctionalization in an animal model.

PURPOSE: Bladder behavior after refunctionalization is usually unpredictable. We comparatively analyze various aspects of bladder defunctionalization and subsequent refunctionalization using an animal model. MATERIALS AND METHODS: A total of 18 rabbits were divided equally into 3 groups. Animals in group 1 underwent 2 successive surgical procedures, including bladder division and reattachment. Bladder division was performed by hemisecting the bladder from dome to trigone into a functioning and nonfunctioning chamber. Bladder reattachment was achieved by reanastomosing both hemibladders. Group 2 animals underwent sham operations, and group 3 animals were age matched normal controls. Serial urodynamic studies and fluoroscopic cystograms were performed in all animals. Gross, histochemical (hematoxylin and eosin, Masson's trichrome and Sirius red) and immunocytochemical (alpha-actin, collagen I and III) analyses, collagen content determination and organ bath studies were performed. RESULTS: The defunctionalized hemibladders demonstrated lower wet weight, capacity and compliance compared to the functional contralateral and normal control bladders. Refunctionalization of the bladders resulted in a progressive recovery of capacity and compliance with time. The bladder contractile response and connective tissue-to-muscle ratio were abnormal in the defunctionalized segments but normalized after bladder refunctionalization. CONCLUSIONS: Defunctionalization results in remarkable alterations in bladder growth, capacity, compliance and distribution of connective tissue. However, these bladders demonstrate an innate capacity to recover from these alterations following refunctionalization.

Animals↗
PubMed2000

Comparative assessment of pediatric testicular volume: orchidometer versus ultrasound.

PURPOSE: Testicular volume measurements obtained with the Prader and Rochester orchidometers were compared to those obtained using scrotal ultrasound. The ability of each orchidometer versus ultrasound in detecting volume differential between 2 testes and the accuracy of orchidometer measurement by a less experienced examiner to that of a urologist were compared. MATERIALS AND METHODS: A total of 65 males were examined by the attending urologist and urology nurse using the Prader and Rochester orchidometers, and scrotal ultrasound was subsequently performed by an attending radiologist. Statistical analysis of the results was performed to determine the correlation of orchidometer measurements between examiners, as well as with ultrasound, and sensitivity and specificity of orchidometer and ultrasound in detecting defined volume differentials between testes of 10%, 15%, 20% and 25%. RESULTS: There was a strong linear relationship between testicular volume measurements using either orchidometer and ultrasound. To detect a defined volume differential as determined by ultrasound orchidometer sensitivity was weak, whereas orchidometer specificity was better. There was a strong correlation between orchidometer measurements of the urology nurse and attending urologist. CONCLUSIONS: Although the orchidometer remains valuable in assessing size of the individual testis, it is too insensitive to volume differentials relative to ultrasound to be used routinely to determine growth impairment. For this reason observation of an adolescent with varicocele should include an annual ultrasound assessment of testicular volume.

Adolescent↗
PubMed2000

New methods of bladder augmentation.

Gastrointestinal segments are commonly used for bladder replacement or repair. However, when gastrointestinal tissue is in contact with the urinary tract, several complications may ensue. Recent surgical approaches have relied on native urological tissue for reconstruction. These are based on sound surgical principles, allowing for the exclusion of tissue that is not urological. De-epithelialized bowel segments, either alone or over native urothelium, have also been used. An experimental system of progressive dilatation for ureters and bladders has been proposed. This appears promising, although it has yet to be attempted clinically. There has been a resurgence of interest in the use of acellular collagen-based matrices as scaffolds for bladder regeneration; experimental work is currently underway. Recently, functional bladder tissue has been engineered using selective cell transplantation. This technique uses autologous cells, so avoiding rejection. Tissue is obtained from the host, the cells then dissociated and expanded in vitro, re-attached to a matrix and implanted into the same host. Clinical trials are currently being arranged. Even though the use of bowel for bladder tissue replacement was first proposed over 100 years ago, it remains the gold standard, despite its associated problems. It is evident that urothelial-urothelial anastomoses are preferable functionally. Experience is currently being gained with the recent clinical and experimental approaches to augmentation cystoplasty. It is hoped that this will result in more technologies and methods for bladder augmentation.

Animals↗
PubMed2000

Effect of chronic, low-pressure, sterile vesicoureteral reflux on renal growth and function in a porcine model: a radiologic and pathologic study.

PURPOSE: To study the effects of chronic, low-pressure, sterile vesicoureteral reflux (VUR) on renal growth and function in a porcine model. MATERIALS AND METHODS: Unilateral VUR was created in five pigs, with the contralateral kidney serving as a control. Preoperatively, and 1 year later, ultrasonography, technetium 99m-dimercaptosuccinic acid (DMSA) scintigraphy, contrast material-enhanced computed tomography (CT), and contrast-enhanced magnetic resonance (MR) imaging were performed. Morphologic abnormalities and relative uptake of (99m)Tc-DMSA were recorded. The postcontrast enhancement ratios for parenchymal regions of interest at CT and MR imaging were determined. Ruthenium 103-labeled microspheres were used to determine regional blood flow. After the pigs were sacrificed, the kidneys were excised, weighed, and analyzed pathologically. RESULTS: Two of five refluxing kidneys had less than 45% function at scintigraphy. One of these two kidneys was small at postmortem examination. There were no other imaging or gross pathologic abnormalities. There was no significant difference in regional blood flow between the refluxing and nonrefluxing kidneys. In all of the operated on kidneys, histologic examination showed focal chronic inflammation and fibrosis. CONCLUSION: Low-pressure sterile reflux into previously normal kidneys led to mild, focal, chronic interstitial inflammation and fibrosis after 1 year. Imaging findings were normal apart from a subtle decrease in tubular function in two refluxing kidneys.

Animals↗
PubMed2000

Sibling vesicoureteral reflux in multiple gestation births.

BACKGROUND: Vesicoureteral reflux (VUR) is the most commonly inherited disease of the genitourinary tract. Although the majority of evidence supports a genetic cause, the tendency for this condition to spontaneously improve over time has made it difficult to determine the actual mode of transmission. We report the incidence of VUR in siblings of multiple gestation births and for the first time compare the relative incidence of reflux between identical and fraternal twins. METHODS: A database consisting of all radionuclide cystograms and voiding cystourethrograms performed between the years 1986 and 1996 was searched for multiple gestation births. The medical records of each patient were evaluated for age at presentation, zygosity, reflux grade, and time to resolution. Children with secondary causes of VUR (eg, posterior urethral valves) were excluded. Triplets were treated as 2 pairs of twins for statistical analysis. RESULTS: Forty-six pairs met the inclusion criteria (31 dizygotic and 15 monozygotic). Overall, 23 (50%) of 46 siblings of index cases had demonstrable VUR. Comparison of VUR prevalence between identical and nonidentical twins was revealing with 80% (12/15) of identical twins and 35% (11/31) of fraternal twins having VUR. When only the youngest individuals in each group were considered, 100% (7/7) of the monozygotics and 50% (5/10) of the dizygotics demonstrated this trait. CONCLUSIONS: High concordance for VUR in identical twin siblings supports a genetic basis for the transmission of this disease. Results obtained from fraternal twin siblings provides convincing evidence that this trait is transmitted in an autosomal dominant fashion.

Child↗
PubMed2000

Tissue engineering applications in the genitourinary tract system.

The concept of cell transplantation using tissue engineering techniques has provided numerous possibilities in the area of urologic tissue reconstruction. Tissue engineering applications in the genitourinary tract system have been investigated in almost every tissue in order to improve, restore and replace existing tissue function. Although most reconstructive efforts still remain in the experimental stage, several technologies have been transferred to the bedside with satisfactory outcome. In this article, we describe tissue engineering approaches attempted in the genitourinary system for reconstruction.

Animals↗
PubMed1999

The incidence of intersexuality in children with cryptorchidism and hypospadias: stratification based on gonadal palpability and meatal position.

PURPOSE: The combined findings of cryptorchidism and hypospadias often indicate the existence of an intersex state. Testicular maldescent and incomplete tubularization of the urethral plate occur in a spectrum with the severity of the 2 processes likely dependent on the degree of pathophysiology in the androgenic hormonal axis. The incidence of intersexuality in children with undescended testes, hypospadias and otherwise nonambiguous male genitalia has been reported to be 27%. Although the likelihood of genotypic or gonadal ambiguity has previously been associated with meatal position in this population, to our knowledge our study is the first to evaluate the incidence of intersexuality relative to whether the undescended testis is palpable or nonpalpable. MATERIALS AND METHODS: The database at our hospital was searched for all cases of undescended testes (2,105) and hypospadias (1,057) between 1982 and 1996. Radiographic, histological and karyotypic data were compiled for all patients presenting with both diagnoses. Gonadal palpability (palpable versus nonpalpable) and meatal position (anterior versus mid versus posterior) were recorded and correlated with the likelihood of identifying an intersex condition. Ten boys with a diagnosis of undescended testes subsequent to inguinal hernial repair were excluded from study. Patients with congenital adrenal hyperplasia or complete testicular feminization were also excluded from study due to the clearly female appearance of the external genitalia. Statistical significance was assessed using Fisher's exact test. RESULTS: We identified 79 patients presenting with undescended testes, hypospadias and a phallus that was believed to be a possible penis. Intersex conditions were identified with nearly equal frequency in the 44 cases of unilateral (30%) and 35 of bilateral (32%) cryptorchidism. In the unilateral undescended testes group patients with a nonpalpable testis were at least 3-fold more likely to have an intersex condition than those with a palpable undescended testis (50 versus 15%, p = 0.02). In the bilateral group patients with 1 or more nonpalpable testes were also nearly 3-fold as likely to have an intersex condition than those with bilateral palpable undescended gonads (47 versus 16%, p = 0.07). Meatal position was graded as anterior in 33% of cases, mid in 25% and posterior in 41% with the more posterior location conferring a significantly greater likelihood of an intersex condition (anterior 2 of 26, mid 1 of 20 and posterior 21 of 33). CONCLUSIONS: Gonadal palpability is an important predictor of an intersex state in unilateral and bilateral cases of cryptorchidism with hypospadias. Patients with an undescended testis that cannot be palpated are significantly more likely to have an intersex condition than those in whom the undescended testis may be palpated on physical examination. The severity of hypospadias likewise has a strong positive correlation with an intersex state.

Child↗
PubMed1999

Reconstitution of human corporal smooth muscle and endothelial cells in vivo.

PURPOSE: The availability of autologous erectile tissue composed of corporal smooth muscle and endothelial cells would be beneficial in patients undergoing penile reconstruction. We previously showed that cultured cavernous cells seeded on polymer scaffolds form corporal muscle when implanted in vivo. However, to reconstruct corporal tissue endothelial and corporal muscle cells are necessary. In this study we investigated the possibility of developing tissue composed of corporal cells in vivo by combining smooth muscle and endothelial cells. MATERIALS AND METHODS: Human corporal smooth muscle and endothelial cells were seeded on biodegradable polyglycolic acid polymer scaffolds at concentrations of 20 x 10(6) and 10 x 10(6) cells per cm3, respectively. A total of 60 polymer scaffolds seeded with cells and 20 control polymers without cells were implanted in the subcutaneous space of 20 athymic mice. Mice were sacrificed 1, 3, 5, 7, 14, 21, 28 and 42 days, respectively, after implantation. Immunocytochemical and histochemical analyses were performed with antifactor VIII, antipancytokeratins and anti-alpha actin antibodies. RESULTS: Histologically the retrieved polymers seeded with corporal smooth muscle and endothelial cells showed the formation of multilayered smooth muscle strips adjacent to endothelial cells 7 days after implantation. Increased organization of the smooth muscle tissue and accumulation of endothelium lining the luminal structures were evident by 14 days. A well organized tissue construct was noted 28 and 42 days after implantation. There was no evidence of tissue formation in controls. Immunocytochemical analysis using antifactor VIII to identify native vasculature only and antipancytokeratins to identify ECV 304 endothelial cells only distinguished the origin of the vascular structures in each construct. Anti-alpha-actin confirmed the smooth muscle phenotype. CONCLUSIONS: Human corporal smooth muscle and endothelial cells seeded on biodegradable polymer scaffolds formed vascularized corpus cavernosum muscle when implanted in vivo. To our knowledge this is the first demonstration in tissue engineering in which capillary formation was facilitated by the addition of endothelial cells in composite tissue in vivo.

Animals↗
PubMed1999

Direct in vivo gene transfer to urological organs.

PURPOSE: Patients with urological disorders may benefit from gene based therapy. We investigated the feasibility of delivering exogenous genes into urological tissues in vivo using direct in vivo electrotransfection. MATERIALS AND METHODS: Gene transfer to rat kidneys, testes and bladders was accomplished via direct local injection of pGL3/luciferase and beta-galactosidase reporter gene constructs, followed by an electrical pulse ranging from 55 to 115 msec at 100 V. Direct injection of deoxyribonucleic acid without an electrical pulse served as the control. The transfected and nontransfected organs were retrieved and analyzed by luciferase activity assay, histochemical and immunocytochemical staining for beta-galactosidase, and reverse transcription polymerase chain reaction with primers specific for beta-galactosidase messenger ribonucleic acid. RESULTS: There was significant luciferase activity 1, 3 and 5 days after direct in vivo electrotransfection in kidneys and testes, and after 3, 5, 7 and 10 days in bladders. Positive beta-galactosidase enzyme activity and beta-galactosidase immunoreactivity were observed in the transfected renal tubular cells, testicular interstitial and germ cells, and uroepithelial bladder layer. Reverse transcription-polymerase chain reaction products of the transfected organs were noted, indicating the successful transcription of messenger ribonucleic acid. CONCLUSIONS: This study demonstrates that direct in vivo electrotransfection is a feasible method of transient gene delivery into intact urological organs. Its apparent safety and relative simplicity suggest that direct in vivo electrotransfection may be useful clinically.

Animals↗
PubMed1999

Autologous engineered cartilage rods for penile reconstruction.

PURPOSE: Conditions such as inadequate and ambiguous genitalia that are caused by rudimentary penis, severe hypospadias or traumatic injury require surgical intervention. Although silicone penile prostheses are an accepted treatment modality, biocompatibility issues may be a problem in select cases. We previously demonstrated that rods composed of cartilage could be created using chondrocytes seeded on biodegradable polymer scaffolds. We showed that the cartilage rods engineered ex situ were readily elastic and withstood high degrees of pressure. We investigated the feasibility of applying the engineered cartilage rods in situ in an animal model. MATERIALS AND METHODS: Autologous chondrocytes harvested from rabbit ears were grown and expanded in culture. Cells were seeded onto biodegradable poly-L-lactic acid coated polyglycolic acid polymer rods at a concentration of 50 x 10(6) chondrocytes per cm3. A total of 18 chondrocyte polymer scaffolds were implanted into the corporal spaces in 10 rabbits. As controls, 1 corpus in each of 2 rabbits was not implanted. The animals were sacrificed 1, 2, 3 or 6 months after implantation. Histological analysis was performed using hematoxylin and eosin, aldehyde fuschin-alcian blue and toluidine blue staining. RESULTS: All animals tolerated the implants for the duration of the study without any complications. Gross examination after retrieval at 1 month showed well formed, milky white cartilage structures within the corpora. All polymers were fully degraded by 2 months. There was no evidence of erosion or infection at any of the implant sites. Histological analysis using alcian blue and toluidine blue staining revealed mature and well formed chondrocytes in the retrieved implants. CONCLUSIONS: Autologous chondrocytes seeded on preformed biodegradable polymer structures form cartilage structures within the rabbit corpus cavernosum. This technology appears to be useful for creating autologous penile prostheses.

Animals↗