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P Merguerian

Publications and source records attributed to P Merguerian.

12 recordsLinked to original sources
PubMed2001

Organ and species specificity in the stimulation of transitional epithelial cell growth by fibroblasts.

OBJECTIVES: Culture of transitional epithelium for urinary tract reconstruction has been problematic due, in part, to the dependence of urothelial cells on a basal layer of bladder fibroblasts for growth. In vitro studies on the effect of bladder, ureter, and intestinal fibroblast cocultures and conditioned media upon urothelial cell growth were conducted to better characterize the dependence of urothelial cells of fibroblasts. METHODS: Primary cultures of human and porcine bladder, ureter, and intestinal fibroblasts and bladder and ureter urothelial cells were established. The urothelial cells were incubated with fibroblasts in a coculture system and growth compared to that of individual fibroblast and urothelial cultures. Urothelium-specific medium was exposed to the fibroblast cultures for 6, 12, and 24 h. Urothelial cell growth in each of the fibroblast-conditioned media was evaluated. RESULTS: Coculture of human urothelial cells with human bladder and ureter fibroblasts yielded increased cell growth when compared to the cells in individual culture. This improvement was greatest for the bladder fibroblasts in coculture with bladder epithelial cells. The media exposed to bladder and ureter fibroblasts for 24 h significantly increased bladder and ureter urothelial growth compared to fresh medium. Coculture with intestinal fibroblasts and exposure to intestinal fibroblast conditioned media did not significantly stimulate urothelial cell growth. Similarly, coculture and conditioned media studies of porcine urothelial cells with porcine bladder and ureter fibroblasts (but not intestinal fibroblasts) yielded increased cell growth when compared to the cells in individual culture, particularly with bladder fibroblasts. However, human urothelial cells were not stimulated by porcine bladder and ureter fibroblast conditioned media, nor were porcine urothelial cells stimulated by human bladder and ureter fibroblast conditioned media. CONCLUSIONS: The ability of urinary fibroblasts to stimulate urothelial cell proliferation resides in an unidentified soluble factor secreted into the medium, independent of the presence of the fibroblasts. This factor is relatively organ and species-specific.

Animals↗
PubMed2001

A prospective randomized clinical trial to evaluate methods of postoperative care of hypospadias.

PURPOSE: Hypospadias repair is a common operation performed by pediatric urologists. Perhaps the greatest variable and source of controversy of postoperative care is the surgical dressing. We hypothesized that using no dressing would achieve surgically comparable results to those traditionally achieved by a postoperative dressing and it would also simplify postoperative parent delivered home care. Accordingly we designed a prospective randomized clinical trial to compare surgical outcome and postoperative care after hypospadias repair in boys with no dressing and those who received 1 of the 2 most common types of dressing. MATERIALS AND METHODS: In a 12-month period 120 boys with an average age of 2.2 years underwent primary 1-stage hypospadias repair at a single center with 4 participating surgeons. Repair was performed in 60 boys with proximal and 60 with distal hypospadias on an outpatient basis. Ethics and Internal Review Board approval, and informed consent were obtained. Boys were then prospectively randomized to receive no dressing, an adhesive biomembrane dressing or a compressive wrap dressing. Comprehensive instructions on postoperative care were distributed to all families and a questionnaire was distributed to the parents at the initial followup. Surgical outcome was evaluated and questionnaire responses were analyzed. Fisher's exact test was done to test the significance of differences in surgical outcomes and questionnaire responses. RESULTS: A total of 117 boys completed the prospective randomized trial. Surgical staff withdrew 3 cases from randomized selection to place a dressing for postoperative hemostasis. We obtained 101 questionnaires for response analysis. The type or absence of the dressing did not correlate with the need for repeat procedures, urethrocutaneous fistula, or meatal stenosis or regression. Analysis revealed less narcotic use in the no dressing group and fewer telephone calls to the urology nurse, or on-call resident and/or fellow. These findings were statistically significant. In addition, there were more unscheduled visits to the urology clinic, emergency room or primary physician office by boys with than without a dressing. Furthermore, 29% of the parents were not psychologically prepared to remove the dressing and 12% were so reluctant that the dressing was removed at the urology outpatient clinic. CONCLUSIONS: The surgical outcome and rate of adverse events or complications were not compromised without a postoperative dressing. An absent dressing simplified postoperative ambulatory parent delivered home care. We recommend that dressings should be omitted from routine use after hypospadias repair.

Bandages↗
PubMed2001

High resolution ultrasound characterization of early allograft hemodynamics in pediatric living related renal transplantation.

PURPOSE: Allograft vascular thrombosis occurs in 5% to 10% of pediatric renal transplants. The hemodynamics of renal allograft immediately after implantation is unclear. High resolution Doppler ultrasound of the renal allograft performed in the operating room after incision closure is an effective and objective method to advance our understanding of baseline renal allograft hemodynamics, and identify unsuspected vascular complications early enough to ensure prompt surgical repair. MATERIALS AND METHODS: Between September 1998 and July 2000 high resolution, color power Doppler ultrasound was prospectively performed on 21 living related renal transplants in the operating room immediately after incision closure. Each ultrasound described allograft anastomotic blood flow, direction of diastolic flow, parenchymal perfusion and resistive indexes. RESULTS: There were 20 (95%) allografts with good power Doppler perfusion that had satisfactory immediate function with no vascular complications at 9 to 26-month followup. Initially, anastomotic turbulence was described in 15 (71%) allografts, and resistive indexes were abnormal in 8 (38%). Turbulence and abnormal resistive index normalized in all allografts by 1-month followup. Ultrasound of 1 allograft identified unsuspected poor perfusion and reversal of diastolic flow in the operating room after incision closure. In another allograft in which a 4-hour post-transplant ultrasound was compared with the baseline study in the operating room an unsuspected thrombosis of the right common iliac vein was confirmed. CONCLUSIONS: Good parenchymal perfusion and forward diastolic flow after renal reperfusion correlated well with immediate graft function. Initial turbulence and abnormal resistive index in the presence of favorable perfusion are misleading and not independent predictors of graft function. Ultrasound performed in the operating room identified 2 unsuspected major vascular complications facilitating prompt surgical correction.

Adolescent↗
PubMed2000

Murine xenogeneic immune responses to the human testis: a presumed immune-privileged tissue.

INTRODUCTION: Immune privilege provides a natural paradigm for potentially down-regulating allogeneic and xenogeneic inflammatory immune responses. Fas ligand has been suggested as a general underlying mechanism of immune privilege; the human Fas ligand has been shown to ligate murine Fas in vitro. METHODS: In this study, we examined whether the human testicular xenograft, a presumed immune-privileged tissue would have prolonged survival in mice. In addition, in vitro and in vivo murine xenogeneic immune responses to the human testicular xenografts were characterized using MHC class I, MHC class II, CD4, CD8, CD4/8 knockout mice. RESULTS: Unlike in rodent testis, Fas ligand mRNA is not expressed and Fas is highly expressed in human testis. Human testicular xenografts are immunogenic, and do not induce any preferential pattern of recipient systemic Th1 or Th2 cytokine bias. Interestingly, an indefinite survival of the human testicular xenografts is observed in murine MHC class II knockout mice, whereas the human skin xenografts were rejected without a delay. In vivo murine immune responses to human testicular xenografts require a recipient MHC class II-dependent CD4 T cell-mediated process that appears to depend on B7-1/B7-2 costimulatory signals. CONCLUSIONS: Our results demonstrate that the concept of immune privilege, as defined by the expression of Fas ligand and prolonged survival after transplantation, cannot be extended to human testis. The stringent restriction of murine xenogeneic immune responses to discordant human testicular xenografts to the indirect MHC class II-dependent CD4 T cell-mediated pathway suggests a potential venue for immune modulation to induce tolerance across a discordant species barrier.

Animals↗
PubMed2000

The natural history of neonatal vesicoureteral reflux associated with antenatal hydronephrosis.

PURPOSE: In an attempt to evaluate the natural history of neonatal vesicoureteral reflux, patients with antenatal history of hydronephrosis and documented reflux in the first 30 days of life were analyzed. MATERIALS AND METHODS: Between 1993 and 1998, 260 patients with a history of antenatal hydronephrosis were referred for evaluation. Of these patients 31 were diagnosed with unilateral or bilateral refluxing renal units (54 renal units). Patients were treated with a prospective plan of observational therapy and prophylactic antibiotics, and resolution rate was calculated in patients with adequate followup. Reflux grade was correlated with postnatal ultrasonographic findings, urinary tract infections and differential renal function. Outcome analysis of 34 high grade (III to V) refluxing renal units using the Kaplan-Meier survival curves was undertaken with the end point being complete resolution or improvement. Three patients with vesicostomy and 2 who underwent ureteral reimplantation were excluded from analysis. RESULTS: Reflux was grade I in 5% (33% males), II in 15% (62% males), III in 32% (71% males), IV in 18% (90% males) and V in 30% (100% males) of the patients. Postnatal ultrasound findings correlated poorly with the presence and degree of vesicoureteral reflux. Of 17 patients followed for at least 14 months (average followup 20) there was complete resolution in 60% with grade III, 50% with grade IV and 28% with grade V reflux. Using the Kaplan-Meier estimate there was a 50% chance of improvement (decrease in reflux grade by at least 2 grades) in high grade reflux by age 16 months. Urinary tract infections developed in 8 patients (26%) while on antibiotics. Of 46 renal units in 23 patients evaluated with a renal scan before urinary tract infection, 12 had less than 35% function. CONCLUSIONS: A normal postnatal ultrasound should not be a basis for excluding the use of cystography. Our Kaplan-Meier estimate shows that high grade reflux does improve and may resolve spontaneously. In addition, renal scarring may be seen with high and low grade reflux in the absence of urinary tract infection but high grade reflux is associated with a higher incidence of infection.

Female↗
PubMed1999

Concomitant modified bladder neck closure and Mitrofanoff urinary diversion.

PURPOSE: We describe a modification of bladder neck closure for managing urinary incontinence in children. MATERIALS AND METHODS: In 11 patients with intractable urinary incontinence that persisted after multiple failed surgical procedures we performed modified bladder neck closure with construction of a catheterizable continent conduit. RESULTS: Mean followup is 3 years. All patients were continent after the procedure and none had a fistula or urinary leakage. One patient required stomal and conduit revision, and bladder stones in 3 necessitated endoscopic removal. CONCLUSIONS: We recommend this modified technique of bladder neck closure as an option for managing urinary incontinence in a complex group of children because it allows the achievement of continence with minimal morbidity.

Adolescent↗
PubMed1994

Grafting of cultured uroepithelium and bladder mucosa into de-epithelialized segments of colon in rabbits.

Urinary tract reconstruction using bowel can result in acid-base and electrolyte abnormalities. We tested the feasibility of grafting bladder mucosa and urothelial cells grown on a biodegradable polyglactin 910 scaffold onto de-epithelialized segments of bowel in the rabbit. A segment of de-epithelialized colon was either grafted with cultured urothelium on a collagen mesh scaffold (12 rabbits) or with free bladder mucosa (11 rabbits). In 10 rabbits that served as a control group another segment of bowel was isolated and de-epithelialized. No urothelial or bowel epithelial growth was present 4 weeks later in 10 of the isolated de-epithelialized colonic segments grafted with the cultured urothelium. In 2 segments a minute focus of epithelium staining positively for anticytokeratin antibodies AE1 and AE3 was seen but this could not be histologically differentiated as either urothelium or native colonic epithelium. All 7 surviving animals that underwent a bladder mucosal graft had viable urothelium at sacrifice 30 days postoperatively. In 2 of the 7 rabbits microscopic nests of colonic epithelium were also found underneath the urothelial layer. Of the 7 internal controls 6 had no evidence of bowel epithelial regrowth 4 weeks after de-epithelialization. This study demonstrated that a confluent layer of urothelial cells could be grown in culture using a scaffold of biodegradable mesh and rat tail collagen. We also showed that bladder mucosal grafts can be grown on de-epithelialized bowel segments. We were unable to graft successfully cultured urothelial cells onto a de-epithelialized bowel segment. Further improvement in understanding the role of the submucosal matrix in cell growth may lead to future success in covering large segments of de-epithelialized bowel with autologous urothelium.

Animals↗
PubMed1985

Animal model for the study of internal anal sphincter activity.

This paper describes a simple and reliable model for studying the internal anal sphincter (IAS) in the rat. The activity of the sphincter was recorded by a two-balloon system. The compliance of the balloon allowed measurements of pressure changes lower than 0.1 cm H2O. The anatomical and physiological characteristics of the rat IAS were found to be in many aspects similar to those found in the human. The rectoanal reflex in the rat consists of relaxation followed by contraction. The threshold for this response is 0.4-0.6 ml of air. The response of the IAS to prolonged rectal distension showed adaptation in 50% of the animals. Intraarterial application of drugs produced rapid, dose-dependent and reproducible effects on the IAS. The results described in this work show that the rat is a useful and convenient model for studying anal function. It may be used to investigate both the physiology and pharmacology of the IAS activity.

Adaptation, Physiological↗
PubMed1984

Physiological and pharmacological studies of the internal anal sphincter in the rat.

The rectoanal reflex in the rat consists of relaxation followed by contraction of the internal anal sphincter (IAS). Beta-adrenergic drugs produce prolonged relaxation of the IAS, where alpha-agonists cause brief relaxation followed by contraction. Muscarinic cholinergic drugs contract the IAS. ATP and related purines produce relaxation which is blocked by theophylline. The reflex persists during adregeneric, cholinergic, and purinergic block. The potassium-blocker apamin prevents the relaxation induced by rectal distension. This suggests that the reflex is not mediated by adrenergic, cholinergic, or purinergic transmitters. Blocking potassium conductance was apparently the only way to eliminate this reflex.

Acetylcholine↗
PubMed1984

An experimental model of a submucosally tunnelled valve for the replacement of the ileo-cecal valve.

An enteric valve to prevent colonic content reflux and to prolong small bowel transit time was created by passing small bowel through a submucosal tunnel in the colon. Barium enema, Gl tract series, and iso- and antiperistaltic pressure measurements showed the valve to be of competence equal to the ileo-cecal valve. Late pathological examination revealed a patent valve with minimal scar formation. The optimal submucosal tunnel length was between 4 and 6 cm. This valve can, theoretically, increase the absorptive capacity in short bowel syndrome and may serve as a substitute for the critically important ileo-cecal valve.

Animals↗