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Biomedical subjects

John P Gearhart

Publications and source records attributed to John P Gearhart.

At least 19 recordsLinked to original sources
PubMed2006

Anxiety disorders in children with epispadias-exstrophy.

OBJECTIVES: To evaluate the hypothesis that anxiety disorders are common comorbid conditions in children with the epispadias-exstrophy complex. METHODS: Twenty consecutive outpatient exstrophy subjects ranging in age from 5 to 22 years were assessed using a formalized semistructured psychiatric evaluation and were categorized according to the Diagnostic and Statistical Manual of Mental Disorders, version IV, criteria. Disorders were identified if subjects endured moderate to severe impairment in their home, academic, and social environments. RESULTS: All 20 subjects met the criteria for at least one anxiety disorder; 19 met criteria for more than one anxiety disorder. The adolescent subjects described a gradual waning of some specific symptoms some time after surgical correction of the physical conditions (eg, incontinence) but intensifying sexual anxiety with age. CONCLUSIONS: The epispadias-exstrophy complex appears to be associated with clinically significant vulnerabilities for anxiety disorders in children.

Adolescent↗
PubMed2006

Standing the test of time: long-term outcome of reconstruction of the exstrophy bladder.

The surgical management of classic bladder exstrophy has evolved over time. Different techniques are used to address the challenge of reconstructing these patients. We review the long-term outcomes of bladder exstrophy treatment from the published literature with regard to urinary continence, voiding and secondary complications. Continence now can be achieved in up to 80% of children in specialist centres. Whether such success can sustained into adult life is uncertain. About 40% of adults are dry in the best hands. Up to 84% of children can void, but there is some evidence that this function is lost with time in 70%. The need for bladder augmentation is widely variable between series, reported in 0-70% of children. This reduces the ability to void spontaneously to about 50% of children. It brings with it the later risk of metabolic disturbance and stone formation. Adults with exstrophy have a 694-fold increase in the risk of bladder cancer by the age of 40 years.

Adult↗
PubMed2006

An initial evaluation of pelvic floor function and quality of life of bladder exstrophy patients after ureterosigmoidostomy.

Classic bladder exstrophy is characterized by displaced pelvic floor musculature and significant skeletal and genitourinary defects. A paucity of data exist evaluating long-term pelvic floor function in exstrophy patients after ureterosigmoidostomy. This study is an initial attempt to evaluate the prevalence of urofecal incontinence, pelvic organ prolapse, and overall quality of life in patients who have had ureterosigmoidostomies. Fifty-two individuals who underwent ureterosigmoidostomy between 1937 and 1990 were identified through the Ureterosigmoidostomy Association and the Johns Hopkins bladder exstrophy database and mailed questionnaires approved by the Institutional Review Board (Johns Hopkins). Data were analyzed with SigmaStat 3.0 (SPSS, Inc., Chicago, IL). Eighty-three percent of the subjects responded, with a mean age of 44.4 years (range, 14-73 years) and mean of 40.9 years (range, 14-65 years) after ureterosigmoidostomy. Prevalence of daily urinary and fecal incontinence was 48% (n = 20) and 26% (n = 11), respectively, whereas the prevalence of weekly combined urofecal incontinence was 63% (n = 27). The incidence of pelvic organ prolapse in this cohort was 48% (n = 20). In these patients, a significant risk of urofecal incontinence and pelvic organ prolapse exists. Long-term follow-up studies are needed to understand the role of pelvic floor musculature in this complex birth defect.

Adolescent↗
PubMed2006

Repeat pelvic osteotomy in patients with failed closure of bladder exstrophy: applications and outcomes.

BACKGROUND/PURPOSE: In patients with failed primary or secondary closure of bladder exstrophy, repeat osteotomy is useful in facilitating reconstruction. The clinical consequences of repeated surgical disruption of the pelvic ring have not been carefully described, however. METHODS: We reviewed our experience with exstrophy patients who had undergone repeat pelvic osteotomy (RPO) and analyzed patient history, complications, and orthopedic outcomes. RESULTS: Fifty-six patients who underwent RPO were identified. All had previously failed at least one attempted bladder closure. The patients underwent RPO at a mean age of 23.2 months. The mean time from initial osteotomy to RPO was 20.5 months. Anterior innominate or combined iliac/innominate approaches comprised 80% of RPO procedures. Of the patients, 95% had a normal gait after RPO; all 3 patients with an abnormal gait had osteotomy site nonunion, which was treated with bone grafting. Five patients had local fixator pin site infections, which were managed with local care and oral antibiotics, and 1 patient had late osteomyelitis requiring incision and drainage. No patient had femoral or sciatic nerve palsy after RPO at our institution. CONCLUSIONS: Orthopedic complications after RPO are uncommon, and most patients have a normal gait postoperatively. Repeat pelvic osteotomy is useful in the complex reconstruction of failed exstrophy closures, and few cases fail reclosure when the reconstruction is combined with RPO.

Bladder Exstrophy↗
PubMed2006

Staged pelvic closure of extreme pubic diastasis in the exstrophy-epispadias complex.

PURPOSE: Staged pelvic closure has been shown to be beneficial in achieving pubic approximation in children with the exstrophy-epispadias complex. We have continued to use this procedure in children with extreme pelvic diastasis and have updated our experience. MATERIALS AND METHODS: We performed closure of the pelvis in 15 patients 12 months to 14 years old presenting with a pubic diastasis of at least 8 cm (range 8 to 16). Of the patients 14 had cloacal exstrophy and 1 had classic exstrophy. Two patients with cloacal exstrophy and the patient with classic exstrophy had prior complete dehiscence at primary closure, and 1 patient with cloacal exstrophy had partial dehiscence. The technique involved bilateral innominate and vertical iliac osteotomy, and placement of a bony fixator with interfragmentary pins. The fixator was gradually closed, and soft tissue and pelvic ring closure occurred 2 to 3 weeks later. In 9 of the 15 patients an interpubic stainless steel plate was used to keep the pubis in apposition at the time of bladder closure. RESULTS: At a mean followup of 5.5 years (range 6 months to 14 years) closure was successful in all 15 patients. One patient (age 12 months) had loosening of the pin between stages, which was salvaged with pin replacement. One patient had ureteral obstruction from hematoma after pin placement without direct pressure from the pins or bone. None of the patients had dehiscence or prolapse. CONCLUSIONS: This technique of staged pelvic closure can be used in the setting of primary or secondary pelvic reconstruction in patients presenting with extreme pelvic diastasis. The gradual reduction in diastasis allows gradual stretching of the soft tissues. It converts a major reconstruction challenge into 2 well tolerated components. However, the procedure is not recommended in children younger than 1 year due to the possibility of the pins loosening during diastasis reduction.

Adolescent↗
PubMed2006

Primary squamous cell carcinoma in unreconstructed exstrophic bladder.

Bladder exstrophy is associated with an increased incidence of primary adenocarcinoma of the bladder. We report a rare case of squamous cell carcinoma occurring in the unreconstructed, exstrophic bladder of a 53-year-old woman treated with radical cystectomy and radiochemotherapy. This case represents the oldest patient to present with squamous cell carcinoma of an unreconstructed exstrophic bladder. We discuss the potential mechanisms of carcinogenesis in this patient, noting how they may potentially differ from those in a patient with a reconstructed bladder.

Bladder Exstrophy↗
PubMed2006

Human embryoid body-derived stem cells in tissue engineering-enhanced migration in co-culture with bladder smooth muscle and urothelium.

OBJECTIVES: To evaluate the affinity between human stem cells and human bladder cells by analyzing their migration and proliferation patterns in co-culture. Human stem cells have great potential for tissue engineering purposes. Co-culture of stem cells with mature cells may promote differentiation. METHODS: Equal numbers of green fluorescent protein-labeled human embryonic germ cell derivates (SDECs) were plated, either alone or in the presence of red fluorescence-labeled (PKH 26) human bladder smooth muscle cells (SMCs) or urothelial cells (UROs). The co-cultures shared the same media (EGM2MV). The migration patterns of the different cell lines were measured daily, using an integrated grid, for 8 days with fluorescence microscopy. RESULTS: SDECs, grown alone, had a robust basal migration rate of between 0.3 and 0.7 mm/day compared with SMCs, which had a rate of 0.1 to 0.3 mm/day and UROs with a rate of 0.1 to 0.2 mm/day. Stem cell migration was enhanced in co-culture with SMCs or UROs to 0.5 to 1.0 mm/day. Migration of SDECs was more linear, directed toward SMCs or UROs, compared with the circumferential growth when plated alone. SMCs, more than UROs, migrated more rapidly in the presence of stem cells. CONCLUSIONS: Human stem cells showed improved migration in the presence of mature human bladder cells and were attracted to them, as shown by the altered direction of growth. Thus, co-culture of human stem cells with host SMCs can enhance seeding of matrices due to positive chemotaxis. Identifying the responsible factors may help to augment chemotaxis between desired cell types and optimize tissue regeneration.

Cell Movement↗
PubMed2005

Perinatal exposure to genistein alters reproductive development and aggressive behavior in male mice.

Exposure to endocrine disrupting chemicals adversely affects reproductive development and behavior in males. The goal of this study was to determine if exposure to genistein, an isoflavone found in soy, during early periods of sex differentiation alters reproductive development and behavior in male mice. Female C57BL/6 mice were fed a phytoestrogen-free diet supplemented with 0, 5 or 300 mg/kg of genistein throughout gestation and lactation. Anogenital distance (AGD) and body mass of male offspring was measured weekly from postnatal days 2-21, timing of preputial separation was assessed at puberty, and in adulthood, reproductive organ masses, sperm and testosterone production, and reproductive and aggressive behaviors were assessed. Exposure to genistein resulted in smaller AGD are reduced body mass, with the low-dose diet exerting a greater effect. Timing of preputial separation, adult reproductive behavior, sperm concentrations and testosterone production were not influenced by genistein treatment at either dose. Aggressive behaviors were decreased, whereas defensive behaviors were increased, in males that received the low-dose genistein diet. Exposure to genistein during critical periods of sex differentiation results in concurrent and persistent demasculinization in male mice. Phenotypic and behavioral abnormalities induced by genistein showed a non-monotonic response, where treatment with a low dose exerted a greater effect than treatment with a high dose of genistein. Given the popularity of soy infant formulas, the influence isoflavone exposure on reproductive and behavioral health in boys and men should be considered.

Administration, Oral↗
PubMed2005

Human embryoid body-derived stem cells in co-culture with bladder smooth muscle and urothelium.

OBJECTIVES: Human pluripotent stem cells have excellent regenerative abilities, making them attractive in bladder regeneration. Porcine small intestinal submucosa (SIS) is an established matrix well-suited to the urinary tract. We evaluated the ability of human embryonic germ (hEG) cell-derived stem cells to form a composite graft on SIS, grown alone or in combination with human bladder smooth muscle cells (SMCs) or urothelial (URO) cells. METHODS: The hEG cell-derived cell line SDEC had the best-fit profile for smooth muscle, as determined by its gene and protein expression. SDEC cells were seeded on SIS, either on its serosal or mucosal surface, and cultured for 7 or 14 days. Co-cultures of stem cells with URO cells or SMCs were also assessed under similar conditions. The grafts were analyzed by histologic examination for cell growth, morphology, and matrix penetration. RESULTS: SDEC cells grew in a monolayer on SIS, with a marked increase in three-dimensional growth when co-cultured with URO cells or SMCs. Penetration of the matrix was evident when seeded on the rough surface of the SIS, progressing with time. Stratification of the cell layers occurred on the smooth side of the SIS. CONCLUSIONS: This is the first description of hEG cell-derived stem cells in co-culture with bladder cells. hEG cell-derived stem cells grow well on SIS even when seeded at low concentrations in the presence of bladder cells (URO cells or SMCs). These composite grafts will be ideal to evaluate the in vivo functional characteristics of stem cells using an animal model of bladder regeneration.

Animals↗
PubMed2005

Human embryoid body-derived stem cells in bladder regeneration using rodent model.

OBJECTIVES: To evaluate the capability of a human embryonic germ (hEG) cell-derived cell line (SDEC), previously characterized in our laboratory, seeded on porcine small intestinal submucosa (SIS) to regenerate the injured rat bladder. METHODS: Fluorescent-labeled SDEC cells seeded on SIS for 8 days in vitro were used as bladder grafts in rats. A total of 30 congenitally athymic rats (six groups of 5 rats each), underwent partial cystectomy and replacement with plain SIS (groups 1 to 3) or cell-seeded SIS (groups 4 to 6). The rats were sacrificed after 7 (groups 1 and 4), 14 (groups 2 and 5), and 28 (groups 3 and 6) days. The bladders were analyzed by histopathologic examination and fluorescence microscopy. RESULTS: No graft rejection or diminution in bladder capacity occurred. Plain SIS implants had multiple calcareous deposits, not seen with the cell-seeded implants. Macroscopically, at 7 days, the grafts were healed with a cellular lining on the luminal aspect in groups 4 to 6. Microscopically, the rat bladder was completely regenerated 28 days after stem cell-seeded SIS implantation. Labeled stem cells were identified throughout the graft and contributed significantly to bladder regeneration. CONCLUSIONS: The results of this study have demonstrated the successful replacement of a bladder defect in a rat model using hEG cell-derived cells seeded on SIS grafts. Longer term analysis of these bladder grafts will allow evaluation of function, cell migration, and differentiation processes of human stem cells.

Animals↗
PubMed2005

Tissue expansion in management of failed phallic reconstruction: initial report of clinical series.

OBJECTIVES: To report the first significant experience with the use of tissue expanders in phallic reconstruction. Patients who have undergone multiple failed surgical procedures for repair of hypospadias or epispadias often have minimal residual skin available for additional reconstructive efforts. Although a variety of graft options exist, local skin expansion can provide pigment and texture-matched skin for reconstructive procedures. METHODS: We reviewed our experience with tissue expansion in patients after multiple failed phallic reconstructive efforts. A total of 18 males (mean age 13.2 years) with an underlying diagnosis of exstrophy/epispadias (n = 9), hypospadias (n = 7), partial androgen insensitivity syndrome (n = 1), and congenital adrenal hyperplasia (n = 1) had penile tissue expanders placed and inflated during a 6-week period. The expanders were removed at penile reconstruction. RESULTS: Tissue expanders were placed in 18 patients and successfully inflated in 17 patients. Good surgical results requiring no additional procedures were obtained in 8 (47%) of the 17 patients. Two patients subsequently underwent repeated tissue expansion; one of these patients had a good outcome after two expansions and supplemental pedicle graft, and the other had persistent fistulas and required a forearm graft. The implants were replaced because of extrusion in 3 patients and removed for malfunction, erosion, or infection in 1 patient each. CONCLUSIONS: The use of tissue expansion provides a useful option for reconstruction in patients with minimal or scarred skin after multiple failed prior phallic reconstructions and offers certain benefits over the transfer of free grafts. The availability of smaller tissue expanders makes this technique feasible even for young children.

Adolescent↗
PubMed2005

A reciprocal translocation 46,XY,t(8;9)(p11.2;q13) in a bladder exstrophy patient disrupts CNTNAP3 and presents evidence of a pericentromeric duplication on chromosome 9.

A patient with sporadic bladder exstrophy and de novo apparently balanced chromosomal translocation 46,XY,t(8;9)(p11.2;q13) was analyzed by fluorescence in situ hybridization (FISH) and molecular methods. We were able to map both translocation breakpoints to single genomic clones. The chromosome 8p11.2 breakpoint was mapped to BAC clone RP4-547J18, predicted to contain several hypothetical genes. Characterization of the chromosome 9q13 breakpoint indicated a disruption in the 5' region of CNTNAP3 within BAC RP11-292B8. This observation suggests possible involvement of CNTNAP3 in the etiology of bladder exstrophy. Additionally, FISH analysis identified several genomic copies of CNTNAP3 on both sides of the chromosome 9 centromere flanking the polymorphic heterochromatin. Northern blot analysis of lymphoblast and bladder RNA confirmed CNTNAP3 transcripts in these tissues and did not show abnormal CNTNAP3 expression in the proband and two unrelated patients with bladder exstrophy. The identification of multiple copies of three BAC clones in the proband, his parents, and unrelated controls suggests that duplications of CNTNAP3 and the surrounding genomic region have occurred as a result of repeated events of unequal crossing over and pericentric inversions during chromosome 9 evolution.

Base Sequence↗
PubMed2005

Variants of the exstrophy complex: a single institution experience.

PURPOSE: Variants of the bladder/cloacal exstrophy complex are rare. Different presentations and subsequent management and outcome are discussed. MATERIALS AND METHODS: We performed a retrospective review of our database of more than 815 patients with the exstrophy complex. Patients with variants of classic epispadias or bladder or cloacal exstrophy were identified. Anatomical presentation, surgical management, type of continence procedures and final outcome were evaluated. RESULTS: Of the 25 patients with variants 13 were treated primarily at our institution and 12 were referred. Time until primary bladder closure ranged from 1 day to 4 years. Followup after continence procedure ranged from 1 month to 39 years. Seven of the 25 patients are awaiting a continence procedure. Six patients are dry without a continence procedure, of whom 4 have superior vesical fistulas. A total of 11 patients underwent bladder neck reconstruction (BNR), of whom 3 are dry, 2 are dry during the day but are wet at night, 1 had a failed procedure and 5 are dry after continent diversion (CD). One additional patient underwent CD initially and is dry. Referred cases of epispadias with bladder prolapse were not recognized at birth and had delayed closure. Impaired bladder growth or failed BNR required CD in 4 patients, and 2 are awaiting a continence procedure. Skin covered and duplicate exstrophy had comparable outcomes to the classic presentations. Duplicated organs were used for reconstructive procedures. Of the 6 patients with cloacal variant 2 are continent of stool and 2 await a Pena procedure. One of these patients has an ileal stoma and 1 has a colostomy. CONCLUSIONS: The initial presentation of exstrophy variants can be confusing, often delaying initial treatment. Superior vesical fistulas permit continence without BNR due to an intact urinary sphincter. Variants such as epispadias with bladder prolapse and duplicate or skin covered exstrophy should be closed at birth with standardized techniques to promote bladder growth for later BNR. These cases are faced with the same long-term problems as the classic presentation. Cloacal variants can present with intact anal innervation, allowing a later Pena procedure.

Abnormalities, Multiple↗
PubMed2005

Surgical repair of bladder exstrophy in the modern era: contemporary practice patterns and the role of hospital case volume.

PURPOSE: Bladder exstrophy is a rare condition, and data are lacking regarding practice patterns in its surgical management. We used a large nationwide database to investigate practice patterns of bladder exstrophy repair. MATERIALS AND METHODS: We used the Nationwide Inpatient Sample (1988 to 2000) to identify patients who underwent surgical repair of bladder exstrophy (International Classification of Disease-9 code 578.6). We analyzed factors affecting practice patterns and outcomes. Hospital volume was based on caseload during the highest volume year of study participation (high volume 5 or more, mid volume 3 to 4 and low volume less than 3 cases). RESULTS: We identified 407 cases. Approximately half of the patients (53.2%) were hospitalized within 24 hours of birth, although 28% of patients were older than 1 year. Of the patients 54% were male. Exstrophy repair is extremely resource intensive. In this series mean length of hospital stay (LOS) was 24.6 +/- 22.8 days, and mean inflation adjusted hospital charges were 62,302 dollars (median 39,978 dollars). High volume hospitals (HVHs) had lower hospital charges (37,370 dollars) than mid volume (51,778 dollars) or low volume hospitals (LVHs, 50,474 dollars, p = 0.0095). On multivariate regression HVHs had lower charges even after controlling for other significant predictors, including LOS (p <0.0001). Patients at HVHs were more likely to undergo osteotomy (p = 0.007). Six patients died after exstrophy repair (1.5%), all of whom had been born prematurely (p <0.0001). Although death was more likely at LVHs, this was due to the fact that more patients at LVHs were born prematurely (4.2% at HVHs vs 5.9% at mid volume hospitals and 11.1% at LVHs, p = 0.027). CONCLUSIONS: Bladder exstrophy repair carries a high risk of morbidity and is resource intensive. Variations between high and low volume hospitals in practice patterns and case mix may contribute to observed differences in resource use, LOS and clinical outcomes.

Bladder Exstrophy↗
PubMed2005

The failed complete repair of bladder exstrophy: insights and outcomes.

PURPOSE: We describe the complications of complete repair and their management. MATERIALS AND METHODS: A total of 19 patients were referred after failed complete repair. Total dehiscence occurred in 6 males, major bladder prolapse in 3, minor prolapse in 3, pubic separation in 1, impassable stricture in 1, and total hemiglans and corporal loss in 2. Overall, partial glans loss was seen in 7 patients, urethral loss in 5 and penile skin loss in 3. One female had complete dehiscence and 1 had major prolapse, both losing the urethrovaginal septum. One female had an impassable stricture. RESULTS: Six males with dehiscence underwent re-closure with osteotomy. Urethral replacement was performed with full thickness skin graft (FTSG) in 3 and with buccal mucosa in 3. Five patients underwent a modified Cantwell-Ransley (C-R) epispadias repair after placement of skin expanders, and 1 awaits repair. The 3 patients with major prolapse underwent re-closure with osteotomy. A urethral buccal graft was used in 1 patient, FTSG was used in 2 at a later operation and all 3 underwent C-R epispadias repair. Of the 3 patients with minor prolapse 2 underwent re-closure with osteotomy using urethral buccal graft or FTSG followed later with a C-R repair. The final patient with minor prolapse underwent re-closure with osteotomy and C-R repair after testosterone stimulation. One patient with pubic separation and urethral and skin loss underwent re-closure with osteotomy, C-R repair after skin expanders and later bladder neck repair. In 1 case a ureteral graft replaced a posterior urethral stricture. Of the 2 patients with hemiglans and corporal loss 1 underwent penile torsion repair and later hypospadias repair, while the other is being observed. Two females underwent re-closure with osteotomy and urethral replacement with tubularized bladder. The case of stricture was managed endoscopically. CONCLUSIONS: Complications of complete repair are similar to those of other repairs but more serious if soft tissue loss occurs. Because of these increased risks, this procedure and its formidable complications are best managed by experienced exstrophy surgeons.

Bladder Exstrophy↗
PubMed2005

Ambiguous genitalia and intersex.

Intersex disorders are rare congenital malformations with over 80% being diagnosed with congenital adrenal hyperplasia (CAH). It can be challenging to determine the correct gender at birth and a detailed understanding of the embryology and anatomy is crucial. The birth of a child with intersex is a true emergency situation and an immediate transfer to a medical center familiar with the diagnosis and management of intersex conditions should occur. In children with palpable gonads the presence of a Y chromosome is almost certain, since ovotestes or ovaries usually do not descend. Almost all those patients with male pseudohermaphroditism lack Mullerian structures due to MIS production from the Sertoli cells, but the insufficient testosterone stimulation leads to an inadequate male phenotype. The clinical manifestation of all CAH forms is characterized by the virilization of the outer genitalia. Surgical correction techniques have been developed and can provide satisfactory cosmetic and functional results. The discussion of the management of patients with intersex disorders continues. Current data challenge the past practice of sex reassignment. Further data are necessary to formulate guidelines and recommendations fitting for the individual situation of each patient. Until then the parents have to be supplied with the current data and outcome studies to make the correct choice for their child.

Diagnosis, Differential↗