Search PubMed⌕ Search

Biomedical subjects

Craig A Peters

Publications and source records attributed to Craig A Peters.

31 records · Page 2Linked to original sources
PubMed2004

Laparoscopy in pediatric urology.

PURPOSE OF REVIEW: Laparoscopic surgery in pediatric urology is beginning to accelerate in its application and this has been reflected in increasing series of progressively more complex procedures. To review these, and assess the character of this evolution, articles dealing with diagnostic and operative laparoscopic surgery from mid 2002 to late 2003 have been reviewed. RECENT FINDINGS: Several important trends can be seen, including the emergence of increasing numbers of multi-center studies, comparative assessments between properly matched open procedures, as well as comparisons between various laparoscopic techniques. The role of diagnostic laparoscopy in cryptorchidism seems well established, although attempts at being more selective in its application have been published. Operative procedures are being performed to include not only simple removal of tissues, but also reconstructive procedures such as pyeloplasty in more than anecdotal numbers. A strong emphasis has been placed on retroperitoneal access, which is inherently more attractive, but the challenges of this technique are evident. Ultimately it should become more efficient with experience. SUMMARY: There has been a steady and progressively more widespread application of laparoscopic techniques in pediatric urology, which has been somewhat slow to develop compared with adult laparoscopy. It seems likely that this progression will continue to accelerate.

Child↗
PubMed2004

Caveolae are negative regulators of transforming growth factor-beta1 signaling in ureteral smooth muscle cells.

PURPOSE: The mechanisms underlying ureteral cell regulation are largely unknown. Previous studies have identified lipid rafts/caveolae as regulators of growth stimulatory signals in ureteral smooth muscle cells (USMCs). In this study we determined whether growth inhibitory signaling by transforming growth factor-beta1 (TGF-beta1) is also regulated by caveolae in USMC. MATERIALS AND METHODS: Expression of components of the TGF-beta1 signaling axis in USMCs was determined by immunoblot and mRNA analyses. Growth regulatory activity of TGF-beta1 was assessed by H-thymidine incorporation. In select experiments caveolae were disrupted reversibly by cholesterol depletion and replenishment prior to TGF-beta1 treatment. TGF-beta1-responsive gene expression was evaluated using the TGF-beta1 responsive promoter-reporter construct 3TP-Lux. RESULTS: USMCs expressed TGF-beta1, types I and II TGF-beta1 receptors, and the effector Smad-2. TGF-beta1 potently inhibited DNA synthesis in USMCs (IC50 60 pM). TGF-beta1 mediated DNA synthesis inhibition was potentiated following the disruption of caveolae by cholesterol depletion. This effect was reversible with membrane cholesterol restoration. TGF-beta1 stimulated gene activity was augmented by caveolae disruption, while caveolae reformation returned promoter activity to baseline levels. CONCLUSIONS: TGF-beta1 is a potent growth inhibitor of USMCs and its activity can be enhanced by caveolae ablation. These findings suggest a role for TGF-beta1 in the growth regulation of normal ureteral cells and implicate caveolar membrane domains in the negative regulation of TGF-beta1 signaling. These studies may be relevant to ureteral pathologies that are characterized by smooth muscle dysplasia.

Animals↗
PubMed2004

Is adolescent varicocele a progressive disease process?

PURPOSE: We determined whether there was evidence of progression in either varicocele grade or testicular volume differentials over time in our adolescent varicocele population. MATERIALS AND METHODS: A total of 41 boys 7.3 to 19 years old (mean age 13.7, SD 2.5) were seen at sequential visits. At each visit varicocele grade was determined by the attending urologist and ultrasound calculated testicular volume differential was determined by an attending ultrasonographer. A senior staff statistician performed statistical analysis of the sequential data. RESULTS: The varicocele grade data were analyzed using the nonparametric Wilcoxon test and no significant evidence of progression on sequential visits was demonstrated. Similarly, the serial volume differential data were assessed using the paired t test and no significant evidence for progression of testicular volume differentials was demonstrated. CONCLUSIONS: In our study population neither varicocele grade nor change in testicular volume differentials increased over time in a statistically significant manner. These results argue against the concept that adolescent varicocele is a progressive disease process.

Adolescent↗
PubMed2003

Platelet derived growth factor-BB is a potent mitogen for rat ureteral and human bladder smooth muscle cells: dependence on lipid rafts for cell signaling.

PURPOSE: Fibromuscular tissues of the detrusor/bladder body (B), trigone (T) and ureter (U) display distinct patterns of tissue remodeling in pathologic contexts, however the mechanisms underlying these observations are unknown. In this study we asked whether B, T and U smooth muscle cells (SMC) respond to several SMC growth factors and explored the role of caveolae/lipid raft membrane microdomains in signaling by one of these factors, PDGF-BB. MATERIALS AND METHODS: SMC were isolated and cultured from B, T and U from newborn rats and from human bladder detrusor. Responses to growth factors were assessed by cell proliferation, DNA synthesis, and immunoblot methods. Cholesterol was depleted from cell membranes in select experiments using cyclodextrin and the cholesterol synthesis inhibitor lovastatin. High-affinity PDGF receptor (PDGFR) sites were measured by 125I-PDGF-BB binding assay. RESULTS: PDGF-BB increased DNA synthesis rate in U and T SMC, with U SMC being highly responsive; in contrast, B SMC did not respond to this growth factor. Two other mitogens, HB-EGF and FGF-2, marginally stimulated DNA synthesis in all lineages. Human detrusor (hD) SMC were also highly responsive to PDGF-BB. Differences in responses to PDGF-BB correlated with translocation of PDGFRs into the caveolae/lipid raft membrane fraction following stimulation, but not with the number of high affinity PDGF binding sites. Cholesterol depletion from cell membranes reduced the response of U and hD SMC to PDGF-BB. CONCLUSIONS: These findings indicate that 1) PDGF-BB is likely to be a physiologically relevant stimulator of mitogenic signaling in certain types of urinary tract SMC, 2) there are significant and unanticipated regional differences in the ability of urinary tract SMC to respond to muscle mitogens, and 3) lipid raft membrane microdomains mediate, in part, the ability of urinary tract SMC to respond to PDGF-mediated signals.

Animals↗
PubMed2003

Ureteral function is modulated by a local renin-angiotensin system.

PURPOSE: Although many aspects of ureteral physiology are well characterized, the exact mechanism of ureteral smooth muscle modulation has not been fully established. In other smooth muscle contractility is modulated by angiotensin II (AngII). We determined the presence of a local ureteral renin-angiotensin system and characterized the functional role of AngII in ureteral smooth muscle. MATERIALS AND METHODS: Reverse transcriptase-polymerase chain reaction was performed to determine the expression of angiotensinogen, renin, angiotensin-converting enzyme and angiotensin receptor subtype 1 mRNA. The presence of AngII in ureteral tissue was determined by immunohistochemistry. Human and pig ureteral smooth muscle strips were suspended in tissue baths to determine the effect of the AngII receptor antagonist losartan on the frequency and amplitude of spontaneous ureteral contractions. Electrical field stimulation was performed before and after exposure to losartan. RESULTS: Angiotensinogen, renin, angiotensin-converting enzyme and angiotensin receptor subtype 1 mRNA expression was detected in human ureter. Immunoreactivity for AngII was demonstrated in smooth muscle bundles and blood vessels of the ureter. Losartan decreased the amplitude and frequency of spontaneous ureteral contractions as well as the contractile response to electrical field stimulation in a dose dependent manner. CONCLUSIONS: Gene expression of AngII precursors and receptor, and localization of AngII in the ureter suggest the presence of a local renin-angiotensin system in the ureter. The effect of AngII receptor antagonist on contractile responses suggests that AngII modulates ureteral smooth muscle contractile function. Therefore, a local renin-angiotensin system may have an important role in ureteral function under physiological and pathological conditions.

Adult↗
PubMed2003

Signaling through PI3K/Akt mediates stretch and PDGF-BB-dependent DNA synthesis in bladder smooth muscle cells.

PURPOSE: Smooth muscle cells (SMC) of the bladder undergo hypertrophy and hyperplasia following exposure to sustained mechanical overload. Although superficial similarities in the response of the heart and bladder to hypertrophic stimuli suggest that similar molecular mechanisms may be involved, this remains to be demonstrated. In this study we compared signal transduction pathway activation in primary culture bladder SMC and cardiac myofibroblasts in response to cyclic stretch. The effects of growth factor stimulation on pathway activation in bladder SMC were also investigated. MATERIALS AND METHODS: Primary culture rodent bladder SMC or cardiac myofibroblasts were subjected to cyclic stretch-relaxation in the absence or presence of pharmacologic inhibitors of the phosphoinositide-3-kinase, (PI3K)/Akt, extracellular signal-regulated kinase-mitogen activated protein kinase (Erk-MAPK) or the p38 stress-activated protein kinase-2 (SAPK2) pathways. In parallel experiments human bladder SMC were treated with platelet-derived growth factor-BB (PDGF-BB), heparin-binding EGF-like growth factor (HB-EGF) or fibroblast growth factor-2 (FGF-2). In each case the extent of DNA synthesis was determined by uptake of tritiated thymidine, and activation of specific signaling intermediates was determined by immunoblot analysis using antibodies to the non-phosphorylated and phosphorylated (activated) forms of Akt, p38 and Erk1/2. RESULTS: Akt and p38 were rapidly phosphorylated in stretched bladder SMC and cardiac myofibroblasts, and stretch-induced DNA synthesis in these cells was ablated with inhibitors of PI3K or p38 but not Erk-MAPK. Similarly, PDGF-BB up-regulated DNA synthesis in bladder SMC in a p38 and Akt-dependent manner. CONCLUSIONS: We conclude that distinct stimuli, such as mechanical stretch and PDGF-BB, promote DNA synthesis in bladder SMC through shared downstream signaling pathways. Furthermore, phenotypically similar cells from the bladder and heart show comparable pathway activation in response to stretch. These findings suggest that similar molecular mechanisms underlie the altered growth responses of the bladder and heart to mechanical overload. This study also provides the first report of Akt activation in bladder SMC and suggests that Akt, consistent with its pivotal role in cardiac hypertrophy, may also be a key regulator of remodeling in the SMC compartment of the bladder exposed to hypertrophic/hyperplastic stimuli in vivo.

Animals↗
PubMed2003

Dynamic renal scintigraphy in children with vesicoureteral reflux and suspected coexisting ureteropelvic junction obstruction.

PURPOSE: We evaluated whether findings on voiding cystourethrography suggesting ureteropelvic junction (UPJ) obstruction coexists with vesicoureteral reflux (VUR) are associated with parameters on dynamic renal scintigraphy that support significant obstruction. MATERIALS AND METHODS: We reviewed records of 44 patients referred for scintigraphy after voiding cystourethrography performed at age 1 day to 9.4 years (mean 7 months, median 1.7 months) showed VUR and findings suggestive of UPJ obstruction (blockage of contrast material at the UPJ, contrast dilution in the renal pelvis, slow renal pelvic drainage). Results were correlated with Society for Fetal Urology hydronephrosis grade and ureteral morphology. RESULTS: Halftime was in the obstructive range (20 minutes or greater) for 7 of 47 kidneys (15%). The prevalence of a post-furosemide pelvicaliceal drainage halftime in the obstructive range increased with hydronephrosis grade (0% grade 1, 17% grade 2, 50% grade 3 to 4, p = 0.002) but did not vary with ureteral morphology (p = 0.08). In 12 of 38 cases (31%) where suspected UPJ obstruction was unilateral and a contralateral kidney was present differential uptake of the affected kidney was less than 45%. The prevalence of differential uptake less than 45% was higher in patients with than without ureteral dilatation (48% vs 12%, p = 0.02) but did not vary with hydronephrosis grade (p = 0.93). CONCLUSIONS: In children with VUR and suspected coexisting UPJ obstruction dynamic renal scintigraphy may support significant obstruction when hydronephrosis is at least moderate in degree or ureteral dilatation is present but is unlikely to do so if neither is observed.

Child↗
PubMed2002

Rate and predictors of spontaneous resolution of prenatally diagnosed primary nonrefluxing megaureter.

PURPOSE: We assessed clinical and ultrasound predictors of the spontaneous resolution of prenatally diagnosed, primary nonrefluxing megaureter. MATERIALS AND METHODS: Primary nonrefluxing megaureter was prenatally diagnosed in 54 neonates from 1993 to 1998, including 15 in whom it was bilateral (69 megaureters). Median followup period from birth to the last radiology examination was 25.8 months (range 2.3 to 72). RESULTS: Of the patients 10 underwent surgical repair for severe hydroureteronephrosis, including decreasing renal function on diuretic renography in 1, and an episode of bilateral obstruction and acute renal failure in 1. Hydroureteronephrosis resolved in 39 cases (72%) and persisted in 5 at 30 to 72 months of followup. Laterality, gender and retrovesical ureteral diameter had no significant effect on the resolution rate (p >0.05). Mean initial ureteral diameter in patients with resolution was less than in those without resolution and in those who underwent surgery (0.8 versus 1.15 and 1.32 cm., respectively). Presenting hydronephrosis grade was a significant predictor of the resolution rate (p = 0.03). Grades 1 to 3 hydronephrosis resolved at a median age of 12.9, 23.9 and 34.6 months, respectively (range 4.1 to 66). In patients in whom grades 4 and 5 hydronephrosis resolved the median age at resolution was 48.5 months. CONCLUSIONS: Most cases of prenatally diagnosed, primary nonrefluxing megaureter resolve spontaneously. Grades 1 to 3 hydronephrosis tend to resolve between ages 12 and 36 months. For these grades followup intervals may be progressively elongated after a pattern of improving hydronephrosis has been established. In children with grade 4 or 5 hydronephrosis, or a retrovesical ureteral diameter of greater than 1 cm. the condition may resolve slowly and require surgery.

Child↗
PubMed2002

The decision to undergo DNA or protein synthesis is determined by the degree of mechanical deformation in human bladder muscle cells.

OBJECTIVES: To investigate the effect of varying levels of mechanical deformation (cyclic stretch-relaxation) on protein and DNA synthesis rates in human bladder smooth muscle cells (SMCs). Cells in the bladder wall respond to outlet obstruction by increasing rates of protein synthesis ("hypertrophy") and/or DNA synthesis ("hyperplasia"); however, it is not established how these distinct processes are initiated. METHODS: Primary cultures of human bladder SMCs were generated and maintained according to published methods. Cells were plated on type I collagen-coated elastomer-bottomed plates and subjected to cyclical stretch-relaxation (0.1 Hz) at 6%, 12%, and 20% elongation using a computer-controlled stretch-inducing device. DNA and protein synthesis rates were determined by uptake of radiolabeled thymidine and leucine, respectively. Nonstretched cells served as controls. RESULTS: Mechanical stretch stimulated DNA synthesis in a dose and time-dependent manner with marked upregulation (4.5-fold) in response to 20% elongation. Mechanical deformation also elicited changes in protein synthesis in bladder SMCs. However, in contrast to the DNA synthesis pattern, leucine uptake over time was stimulated at 6% and 12% elongation, and no protein synthesis response was seen at 20% elongation. CONCLUSIONS: Our findings suggest that stretch, in isolation from other potential mediators such as pressure or hypoxia, can induce either a hyperplastic or hypertrophic response in bladder SMCs and that the cells' response is dependent on the intensity of the stretch stimulus. These observations may be relevant to the process of in vivo tissue remodeling stimulated by bladder distension or contractile dysfunction.

Cells, Cultured↗
PubMedDate not supplied

Intravesical robotically assisted bilateral ureteral reimplantation.

An efficient laparoendoscopic technique for bilateral intravesical ureteral reimplantation would offer the certainty of cure provided by open surgery with the reduced morbidity of laparoscopy. We have assessed the clinical utility of robotically assisted intravesical bilateral ureteral reimplantation in children. Ports are placed in the dome of the bladder, and the procedure is performed in a fashion identical to that used for open transtrigonal reimplantation. A catheter is left in place for 1 or 2 days. With modifications in port placement using the VersaStep radially dilating sheath system, we have not had any port-site leakage. One patient has unilateral persisting low-grade reflux. This technique may be a useful option for antireflux surgery and should be further refined.

Child, Preschool↗