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Biomedical subjects

Mark P Cain

Publications and source records attributed to Mark P Cain.

30 records · Page 2Linked to original sources
PubMed2003

Two bladders and two vaginas in two planes: one urogenital sinus.

We report 2 cases of persistent urogenital sinus (UGS) with duplication of the bladder and vagina in different planes. Cystoscopy and vaginoscopy were used to diagnose persistent UGS with bladder and vaginal duplication in 2 infants with recurrent urinary tract infection. Surgical repair was done by way of a midline abdominal and perineal approach using tubularized UGS to reconstruct the urethra. Persistent UGS represents a major anomaly; these patients had the added complexity of duplication of the bladder and vagina. In these complex patients, the true anatomy may only become apparent during the surgical reconstruction, necessitating a flexible, individual approach.

Abnormalities, Multiple↗
PubMed2003

The Indiana experience with artificial urinary sphincters in children and young adults.

PURPOSE: We reviewed a 22-year single institutional experience with the artificial urinary sphincter in children and adolescents. To our knowledge this report represents the largest series in the world in children. MATERIALS AND METHODS: Between 1980 and 2002, 142 patients underwent implantation of an artificial urinary sphincter, of whom 93 males and 41 females with a median age of 10 years (range 3 to 39) were available for analysis. A total of 59 patients initially received an AMS 742/792 (American Medical Systems, Inc., Minnetonka, Minnesota) artificial urinary sphincter, of whom 33 were subsequently changed to an AMS 800, while 75 initially received an AMS 800 model. Sphincter followup was terminated at device removal or at the last documented contact. The etiology of incontinence was neuropathic bladder in 107 cases (80%), the exstrophy/epispadias complex in 21 (16%) and other in 6 (4%). Outcome measures included continence, mechanical complications (leakage, tube kink and pump malfunction), functioning sphincter revisions (change in cuff size, pump repositioning and bulbar cuff placement), surgical complications (erosion, infection and misplacement) and associated surgical procedures. Mean followup of the pre-800 and 800 models was 6.9 (range 0.2 to 21.5) and 7.5 years (range 0.1 to 17.1), respectively. Fisher's exact test, Kaplan-Meier life analysis and the chi-square test were used for statistical analysis. RESULTS: After artificial urinary sphincter placement in the 134 patients continence was achieved in 86%, improved in 4% and not achieved in 10%. Of those with a sphincter in place 92% were continent. In terms of bladder emptying after artificial urinary sphincter insertion 22% of patients voided, 11% voided combined with clean intermittent catheterization, 48% performed clean intermittent catheterization only via the urethra, 16% performed it via a catherizable channel and 3% used urinary diversion. A mechanical complication developed in 38 of the 59 patients (64%) with pre-800 model compared with 33 of the 109 (30%) with the 800 model (p <0.0001). A mechanical complication occurred every 7.6 versus 16 patient-years for the pre-800 versus 800 models (p = 0.0001). Revision was required in 15 of the 59 patients (25%) with a pre-800 model versus 17 of the 109 (16%) with the 800 model (p = 0.103). Revision was performed every 22.7 versus 44.3 patient-years for the pre-800 versus the 800 model (p = 0.023). The artificial urinary sphincter eroded in 11 of the 59 patients (19%) with the pre-800 versus 17 of the 109 (16%) with the 800 model (p = 0.52). Ten patients experienced a total of 12 perforations of the augmented bladder after artificial urinary sphincter implantation. A total of 164 secondary surgical procedures were performed, including 38 of 134 bladder augmentations (28%). A total of 30 sphincters were permanently removed. CONCLUSIONS: The artificial urinary sphincter is the only bladder neck procedure that allows spontaneous voiding in the neuropathic population, obviates the need for clean intermittent catheterization and yet is compatible with it when necessary. It is also equally versatile in the 2 genders. Mechanical complications occur but they were dramatically decreased by the modifications of the AMS 800 model. In addition, secondary bladder augmentation was required in 28% of our patients. Lifelong followup is mandatory in all patients with an artificial urinary sphincter.

Adolescent↗
PubMed2003

Lipopolysaccharide and inflammatory cytokines cause an inducible nitric oxide synthase-dependent bladder smooth muscle fibrotic response.

PURPOSE: Bladder wall fibrosis is a sequela of recurrent urinary tract infection (UTI). Inducible nitric oxide synthase (iNOS) has been shown to mediate the fibrotic response to inflammation in other tissues. We determined if iNOS could be involved in the fibrotic response to recurrent UTI. MATERIALS AND METHODS: Human bladder smooth muscle cells (SMC) were treated with bacterial lipopolysaccharides (LPS) and a mixture of inflammatory cytokines. The level of collagen type III, and the levels of iNOS mRNA, protein and activity were determined. The effect of the iNOS inhibitor aminoguanidine on collagen type III expression was then assessed. RESULTS: Expression of collagen type III, iNOS mRNA and iNOS protein as well as iNOS activity were increased in bladder SMC treated with the combination of LPS and cytokines. The increase in collagen type III expression was inhibited by pretreatment of cells with aminoguanidine. CONCLUSIONS: LPS and inflammatory cytokines induce collagen type III expression in an iNOS dependent manner in human bladder SMC. This finding suggests that iNOS may be a critical mediator of the bladder wall fibrotic response to chronic UTI and iNOS inhibitors may be of therapeutic value in patients with chronic UTI.

Cells, Cultured↗
PubMed2003

Complications of small intestinal submucosa for corporal body grafting for proximal hypospadias.

PURPOSE: Small intestinal submucosa (SIS) has been described for corporal body grafting in cases of severe penile curvature. We reviewed our experience with a 2-stage repair using corporal body grafting with SIS for proximal hypospadias and severe chordee. MATERIALS AND METHODS: A retrospective chart review was performed on 12 patients with penoscrotal hypospadias and severe chordee. Corporal grafting was performed with a 4-layer SIS graft (STRATASIS, Cook Biotech, Spencer, Indiana). Patients were evaluated postoperatively with clinic visits after both stages of repair to assess results. RESULTS: Corporal body grafting with SIS was performed in 12 patients between June and December 2001. Average patient age at the time of stage 1 repair was 9 months. Of the 12 patients 8 (66%) had no complications and 10 (83%) have a straight phallus following stage 2 repair. Complications occurred in 4 patients (33%), 2 of which were minor and did not require surgical correction. There were 2 major complications related to the SIS graft, 1 of which required excision of the graft and replacement with a tunica albuginea flap, and the other required 3 dorsal plications to correct residual chordee. CONCLUSIONS: Our experience using the 4-layer SIS resulted in 2 major complications requiring surgical correction during stage 2 repair. This rate exceeds the complications reported with either dermal or tunica vaginalis grafts. Currently we have stopped using SIS for corporal grafting.

Adolescent↗
PubMed2003

Long-term outcome of the surgical treatment of concealed penis.

PURPOSE: The term concealed penis describes a spectrum of disorders ranging from penoscrotal webbing to a completely buried penis. A number of surgical procedures have been described to correct this condition but little has been written about long-term results. We report our long-term results of the surgical correction of concealed penis based on a survey of parents. MATERIALS AND METHODS: A retrospective review of patients treated from 1995 to 1999 identified 18 males with a minimum of 21 months of followup whose parents were available for evaluation via telephone interview. The parents were questioned about the initial problems that they associated with concealed penis, such as appearance and accessibility of the penis, ease of hygiene, severity of concealment and negative feelings about the appearance of the penis. Parents were also questioned about the results of surgery and how the surgical result improved or failed to improve their concerns. Specifically, they were questioned about whether the surgery helped to alleviate negative concerns, improve hygiene and make the penis more assessable. RESULTS: Of the 18 patients 14 were infants/toddlers (group 1) and 4 were adolescents (group 2). Group 1 patients with a mean age of 2 years were evaluated at a mean of 41.7 (range 21 to 76) months and group 2 patients with a mean age of 12 years were evaluated at a mean of 38.8 (25 to 63) months after surgery. Before surgery 57% of patients in group 1 and 50% in group 2 complained of difficulty with hygiene. Of the parents 64% of group 1 and 75% of group 2 described their child as having a completely hidden penis. On the other hand, only 57% of parents in group 1 expressed negative feelings about the appearance of the penis compared to all parents in group 2. Following surgery group 1 patients fared better reporting improvements in hygiene (87%), accessibility (86%) and improved appearance of the penis (100%). Results from surgical intervention were less successful in group 2, with improved hygiene in 50%, improved penile accessibility in 75% and improved appearance in 50% of patients. Interestingly, all group 2 parents would still recommend the same surgery to a friend with the same problem despite less than perfect results compared to 79% of group 1 parents who would recommend surgery to others. CONCLUSIONS: Our long-term outcome survey data demonstrate that surgical correction of concealed penis addresses an array of presenting complaints. According to the parents of patients surgery is almost uniformly successful in toddlers and less often successful in adolescents. However, despite its limited success in older patients, most parents thought that surgery was a positive intervention and would recommend it to a friend with a similar condition.

Adolescent↗
PubMed2003

Alpha blocker therapy for children with dysfunctional voiding and urinary retention.

PURPOSE: Alpha blocker therapy has been successfully used to decrease residual urine in children with complex neuropathic and nonneuropathic voiding dysfunction. We evaluated the safety and efficacy of using selective alpha blocker therapy for children with uncomplicated voiding dysfunction and underlying poor bladder emptying. MATERIALS AND METHODS: A total of 55 patients with a mean age of 7.9 years presented with symptoms of urinary incontinence, urgency and urinary tract infection. All patients had increased post-void residual (PVR) on bladder ultrasound, with a mean residual volume of 65 ml (22% of age expected capacity). All patients were treated with doxazosin, a selective alpha-1 adrenergic antagonist, at dosages of 0.5 mg to 2.0 mg daily. Of the patients 38 were treated at presentation with a regimen of anticholinergics, timed voiding and antibiotic prophylaxis before initiating alpha blocker therapy. Patients were reevaluated with post-void ultrasound of the bladder 6 weeks after initiating alpha blocker therapy. RESULTS: After starting doxazosin average PVR decreased to 8 ml (p <0.0001), representing an 88% reduction in residual urine (or reduction to only 2.7% of age expected bladder capacity). Medication was discontinued in 2 patients due to minor side effects. CONCLUSIONS: Selective alpha blocker therapy appears to be effective for improving bladder emptying in children with an overactive bladder, wetting, recurrent infection and increased PVR urine. This therapy may be used as either a replacement or in addition to biofeedback in patients with urinary retention. Further investigation, including a prospective randomized trial of alpha blocker therapy in children with urinary tract dysfunction, is warranted based on the findings of our study.

Adolescent↗
PubMed2002

Long-term followup and outcome of continent catheterizable vesicocstomy using the Rink modification.

PURPOSE: Multiple techniques have been described to create a Mitrofanoff channel in the pediatric population. A small subset of patients only requires creation of a catheterizable channel without bladder augmentation. These patients are ideal candidates for a procedure that avoids the use of intestine, especially in the absence of a suitable appendix. We used a modification of the Casale vesicostomy, as described by Rink, to create a continent vesicostomy in these children. We report our long-term experience with this technique. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients who underwent continent vesicostomy at our institution between 1992 and 2000. Patient diagnosis, stomal site, associated bladder procedures, stomal continence, followup and complications associated with continent vesicostomy were documented. RESULTS: Of the 31 patients who underwent continent vesicostomy, as described by Rink, 14 were female and 17 were male. Average age was 9 years (range 2.5 to 22). Primary diagnosis included neuropathic bladder in 15 cases, the prune-belly syndrome in 6, cloacal exstrophy/anomaly in 5 and other in 5. The stoma was placed in the lower abdomen in 17 patients, in the umbilicus in 7 and in a neoumbilicus in 7. Simultaneous procedures included ureteral reimplantation in 8 cases, bladder augmentation in 5, bladder neck surgery in 4 and reduction cystoplasty in 2. Mean followup was 41 months. All patients achieved excellent stomal continence. Complications included stomal stenosis requiring revision in 14 cases (45%). Stenosis developed in 60% of the patients with neuropathic bladder and in 86% with an umbilical stoma. Eventually 6 patients underwent conversion to an alternative catheterizable channel. CONCLUSIONS: Continent vesicostomy can be performed successfully when there is any underlying bladder pathology with 100% stomal continence. Despite the higher rate of stomal problems with this type of Mitrofanoff channel we think that continent vesicostomy is a reasonable alternative in patients with a large bladder requiring only catheterizable channel creation. Because of the excellent results reported with the Monti-Yang technique, we would currently recommend this procedure over continent vesicostomy when bowel is used for bladder reconstruction.

Adolescent↗
PubMed2002

Alterations in the molecular determinants of bladder compliance at hydrostatic pressures less than 40 cm. H2O.

PURPOSE: Bladder outlet obstruction with intravesical pressures exceeding 40 cm. H2O often results in irreversible renal damage. Bladder outlet obstruction also results in alterations in bladder physiology, including wall thickening, reduced compliance and decreased capacity. If unchecked these changes may lead to the subsequent need for bladder augmentation. From a biomechanical standpoint, compliance is primarily related to extracellular matrix deposition, which in turn is dependent on the balanced activity of proteolytic enzymes (that is matrix metalloproteinases [MMPs]) and their endogenous inhibitors (that is tissue inhibitors of metalloproteinases [TIMPs]). To date, the threshold pressure above which alterations in these key determinants of bladder compliance occur has not been determined. Therefore, using a novel device of our own design, we applied hydrostatic pressures in the physiological range to human bladder smooth muscle cells to determine the effect on MMPs, TIMP-1 and transcription of the major structural collagens (types I and III). MATERIALS AND METHODS: Human bladder smooth muscle cells (staining positive for alpha-smooth muscle actin) were plated at a density of 100,000 cells per 10 cm.2 and cultured for 2 days in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum. Cells were subsequently exposed to pressures of 0.3, 20 and 40 cm. H2O for 1, 3, 7 and 24 hours in serum-free DMEM. A computer interface maintained pressure levels for the duration of the experiments and collected pressure data. MMP-1 and 3, and TIMP-1 immunoassay and zymography for MMP-2 and 9 were performed. Polymerase chain reaction for human collagen types I and III was performed following reverse transcription of total purified mRNA. All experiments were repeated 3 times and statistical analysis was performed using a 2-tailed Student t test. RESULTS: Exposure of bladder smooth muscle cells to a sustained hydrostatic pressure of 20 cm. H2O for 7 hours in serum-free DMEM resulted in a time dependent decrease in MMP-1, 2 and 9 activity (15%, 37% and 25%) compared to controls maintained at atmospheric pressure (p <0.01). TIMP-1 levels increased an average of 10% after exposure to 20 cm. H2O. These changes became statistically significant when the cells were exposed to 40 cm. H2O pressure for 3, 7 and 24 hours (+14%, +21% and +50%, respectively). No statistically significant differences in MMP-3 and collagen type I or III mRNA levels were observed. CONCLUSIONS: Our results reveal that MMP-1, 2 and 9 are significantly down-regulated in a time and pressure dependent fashion following exposure of bladder smooth muscle cells to 20 cm. H2O for as little as 7 hours. TIMP-1 levels increased under similar conditions. These alterations in MMPs and TIMP-1 favor accumulation of extracellular matrix, structural components associated with bladder wall thickness and decreased compliance. These results are consistent with previous data from animal models of complete outlet obstruction. Our results support the concept that pressures 40 cm. H2O or less contribute to molecular changes consistent with decreased compliance associated with bladder dysfunction.

Collagen Type I↗
PubMed2002

Percutaneous cystolithotomy in the pediatric augmented bladder.

PURPOSE: Bladder stones are a common problem following augmentation cystoplasty. With the addition of Mitrofanoff channels for intermittent catheterization and more aggressive bladder neck tightening procedures, the incidence of stones has increased and endoscopic access to the bladder has become more complicated. We present our results of percutaneous endoscopic cystolithotomy in children with bladder augmentation. MATERIALS AND METHODS: We performed percutaneous extraction of bladder calculi in 13 children with bladder augmentation. All patients performed catheterization either via a Mitrofanoff channel, artificial urinary sphincter or plicated ileal limb of an ileocecal reservoir. The prior suprapubic tube site was dilated with an Amplatz set for access, and stones were removed intact or fragmented by laser or electrohydraulic lithotripsy. RESULTS: Percutaneous extraction was successful in 12 of the 13 patients (92%). The remaining patient had a small posterior bladder perforation and open cystolithotomy was performed. All patients were discharged home in 24 to 36 hours, and there have been no stone recurrences with a mean followup of 24 months. CONCLUSIONS: Percutaneous stone removal using the previous suprapubic tract is a simple, effective and minimally invasive option for removing stones in an augmented bladder. This technique avoids potential injury to the continence mechanism of the reconstructed bladder neck or Mitrofanoff channel. Percutaneous stone removal has become our procedure of choice for managing calculi in the augmented bladder.

Adolescent↗
PubMed2002

The relationship between müllerian inhibiting substance and androgens in boys with hypospadias.

PURPOSE: The etiology of hypospadias is probably multifactorial and disruption of androgen production may have a role. Müllerian inhibiting substance (MIS), a hormone produced by Sertoli cells, has been shown to suppress androgen biosynthesis in Leydig cells by inhibiting cytochrome P450c17 hydroxylase/lyase (CYP17) gene expression. We investigated the relationship between serum MIS and androgens in boys with isolated hypospadias compared with normal boys. MATERIALS AND METHODS: Serum levels of MIS, testosterone and androstenedione were measured in 29 boys with distal hypospadias (midshaft or less) and 21 normal boys undergoing circumcision. The subjects were stratified according to age 12 months or younger (group 1) and 13 to 24 months old (group 2). Statistical evaluation was performed by Student's t test. RESULTS: Mean age plus or minus standard error of mean of normal boys and their respective age matched groups with hypospadias were not significantly different. Within each respective age group serum müllerian inhibiting substance levels in boys with hypospadias were significantly higher compared with those of normal boys (129.6 +/- 1.8 and 96.1 +/- 1.8, p <0.03 for group 1 and 143.2 +/- 2.0 and 77.2 +/- 2.3, p <0.005 for group 2). Serum MIS levels were not statistically different when normal boys or boys with hypospadias were compared across age groups. In group 1 serum testosterone levels in boys with hypospadias were not significantly different from those of normal boys (0.36 +/- 0.20 and 0.56 +/- 0.32 pg./ml., respectively). In group 2 normal boys serum testosterone levels were higher than these in boys with hypospadias (2.36 +/- 0.47 and 0.35 +/- 0.23 pg./ml., p <0.01). Serum androstenedione levels in group 1 boys with hypospadias were significantly lower compared with those of normal boys of similar age (0.29 +/- 0.1 and 0.64 +/- 0.16 ng./ml., respectively, p <0.003). Androstenedione levels among older boys were not different (0.49 +/- 0.25 and 0.32 +/- 0.11 ng./ml., respectively. CONCLUSIONS: The association between elevated serum MIS levels and lower testosterone concentrations in boys with hypospadias suggests that MIS may have some role in the development of hypospadias, possibly mediated by MIS inhibition of CYP17 gene expression.

Androstenedione↗
PubMed2002

Use of a Monti channel for administration of antegrade continence enemas.

PURPOSE: Success with Malone antegrade continence enemas (MACE) requires reliable access to the colon and a customized enema regimen. Use of the appendix in situ provides a natural and well-vascularized conduit. When the appendix is absent or inadequate, alternative techniques are required. We report our experience using Monti channels to administer antegrade continence enemas. MATERIALS AND METHODS: Of the 106 MACE procedures performed in 53 months a Monti-MACE was created in 13. Indications for use of ileum, technique, ease of catheterization and incidence of complications were reviewed. RESULTS: Mean followup was 21.7 months. Two patients had transient difficulty advancing the catheter into the cecum. Stoma revisions were required for critical stenosis in 2 patients (15.4%). Stoma leakage occurred in 1 patient after multiple stoma revisions. CONCLUSIONS: The Monti-MACE provides continent access to the colon for antegrade enemas. The rate of stomal revision is only slightly higher than that reported for appendicocecostomy. While use of the appendix in situ remains our preference, reconfigured ileum is a reliable substitute in patients without a suitable appendix.

Adolescent↗