Outcome of fetuses with lower urinary tract obstruction and normal amniotic fluid volume in second trimester of pregnancy.

OBJECTIVE: Congenital lower urinary tract obstruction (LUTO) is a rare condition with high perinatal mortality and morbidity when associated with severe oligohydramnios or anhydramnios in the second trimester of pregnancy. Severe pulmonary hypoplasia and end-stage renal disease are the underlying causes of poor neonatal outcome in these cases. However, little is known about the subset of fetal LUTO that is associated with a normal volume of amniotic fluid at midgestation. The objective of the current study was to describe the natural history, underlying causes, survival and postnatal renal function outcomes in pregnancies with fetal LUTO and normal amniotic fluid volume during the second trimester of pregnancy. METHODS: This was a retrospective study of all pregnancies with fetal LUTO and normal amniotic fluid volume in the second trimester that received prenatal and postnatal care at our quaternary care institution between 2013 and 2017. Data on demographic characteristics, fetal interventions, perinatal survival, need for neonatal respiratory support, postnatal renal function and need for dialysis at the age of 1 and 24 months were analyzed. RESULTS: Of the 18 fetuses that met the study criteria, 17 (94.4%) survived the perinatal period. Eleven (61.1%) pregnancies developed oligohydramnios in the third trimester, six of which were eligible for and underwent fetal intervention with vesicoamniotic shunt placement, which was performed successfully in all six cases. Two (11.1%) neonates required respiratory support owing to pulmonary hypoplasia. At the age of 2 years, 14 children had follow-up information available, two (14.3%) of whom had normal renal function, eight (57.1%) had developed some degree of chronic kidney disease (Stage 1-4) and four (28.6%) had developed end-stage renal disease (ESRD), including two who had already manifested ESRD in the neonatal period. CONCLUSIONS: Most fetuses diagnosed prenatally with LUTO that is associated with a normal volume of amniotic fluid at midgestation will have a favorable outcome in terms of perinatal survival and few will need long-term respiratory support. However, these children are still at increased risk for chronic renal disease, ESRD and need for renal replacement therapy. Larger multicenter studies are needed to characterize the prenatal factors associated with postnatal renal function, and to investigate the role of fetal intervention in the group of fetuses that present with late-onset oligohydramnios and evidence of preserved fetal renal function. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Fetal lower urinary tract obstruction: proposal for standardized multidisciplinary prenatal management based on disease severity.

OBJECTIVE: To present a single center experience of a standardized prenatal multidisciplinary management protocol for fetal lower urinary tract obstruction (LUTO) and to propose a classification of fetal LUTO based on disease severity. METHODS: This was a retrospective cohort study of 25 consecutive fetal patients with prenatal diagnosis of primary LUTO. Fetal intervention was offered after evaluation by a multidisciplinary team. Analyses were conducted using Bayesian methodology to determine predictors of survival at 6 months postpartum. Odds ratios (ORs) with 95% credibility intervals are reported. RESULTS: Fifteen (60.0%) of the 25 patients referred for assessment survived to postnatal evaluation. Fetal vesicoamniotic shunt was placed in 14 (56.0%) patients with 12 survivors. Multivariable analysis suggested that fetal intervention (OR, 6.97 (0.88-70.16), Pr(OR > 1) = 96.7%), anhydramnios (OR, 0.12 (0.04-0.35), Pr(OR < 1) = 99.9%), favorable fetal urine analysis (OR, 3.98 (0.63-25.15), Pr(OR > 1) = 92.7%) and absence of renal cortical cysts (OR, 3.9 (0.66-24.2), Pr(OR > 1) = 93.3%) were predictors of survival. CONCLUSIONS: Fetal intervention and fetal renal function were independently associated with postnatal survival of fetuses with LUTO. A classification based on the severity of disease is proposed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Urological fistulas after fetal cystoscopic laser ablation of posterior urethral valves: surgical technical aspects.

OBJECTIVE: To describe the surgical technical aspects associated with the development of urological fistulas after fetal antegrade cystoscopic laser fulguration of the posterior urethral valves (PUV). METHODS: The perioperative data for all fetal cystoscopies performed between January 2004 and August 2013 at three institutions in the USA, France and Brazil were reviewed, with particular emphasis on surgical technical aspects of the procedure and the complications encountered. RESULTS: A total of 40 fetal cystoscopies were performed at the three institutions. Laser fulguration of the PUV was performed in 23 of these cases, with a survival rate of 60.9% (14/23) and normal renal function in 85.7% (12/14) of these infants. Urological fistulas were diagnosed postnatally in four (10%) newborns. The presence of fistulas was associated with a higher gestational age at diagnosis of PUV (P < 0.01) and with the use of semi-curved rather than curved sheaths (P < 0.01), the use of a diode laser (P < 0.01) and the use of higher laser power and energy (P < 0.01 and P < 0.01, respectively), as well as with less operator experience (P < 0.01) and with absence of fetal anesthesia/immobilization (P = 0.02). CONCLUSION: Urological fistulas are a severe complication of fetal cystoscopic laser fulguration of PUV and are associated with type, energy and power settings of the laser and instrumentation. The use of appropriate technique and proper training of the operator are necessary to perform this fetal intervention safely.

Safety of oral robenacoxib in the cat.

The safety of robenacoxib, a nonsteroidal anti-inflammatory drug with high selectivity for inhibition of the cyclooxygenase (COX)-2 isoform of COX, was investigated in the cat in two randomized, blinded, placebo-controlled, parallel-group studies. Robenacoxib was administered orally to healthy young domestic short-hair cats at dosages of 0 (placebo), 5 and 10 mg/kg once daily for 28 days (study 1) and at 0 (placebo), 2, 6 and 10 mg/kg twice daily for 42 days (study 2). The recommended minimum dosage for robenacoxib tablets in cats is 1 mg/kg once daily (range 1-2.4 mg/kg). Relative to placebo treatment, no toxicologically significant effects of robenacoxib were recorded in either study, based on general observations of health, haematological and clinical chemistry variables and urinalyses in life, and by post mortem organ weight, gross pathology and histopathology assessments. Pharmacokinetic-pharmacodynamic simulations indicated that all dosages of robenacoxib were associated with marked inhibition of COX-2 at peak effect (median I(max) 97.8-99.4% inhibition) with lesser inhibition of COX-1 (median I(max) 26.8-58.3% inhibition). Inhibition of the COXs was short lasting, with >10% median inhibition persisting for 4.0 h for COX-2 and 1.5 h for COX-1. These levels of inhibition of COX-1 and COX-2 twice daily with robenacoxib were not associated with any detectable toxicity, suggesting that, as previously described in dogs, the high safety index of robenacoxib in cats may be related to a combination of its high COX-2 selectivity and short residence time in the central compartment.

The changing gender landscape of pediatric urology fellowship: results from a survey of fellows and recent graduates.

INTRODUCTION: Women are entering the subspecialty of pediatric urology at an accelerated rate. Gender differences affecting fellowship and job selection have been identified in other fields of medicine. OBJECTIVE: The objective of this study was to understand gender differences in pediatric urology fellowship and job selection and how they may affect the workforce. STUDY DESIGN: A 47-question electronic survey consisting of questions regarding demographics, residency training, and factors influencing fellowship and job selection was distributed to current fellows and recent graduates in pediatric urology in May 2017. RESULTS: A total of 111 recent and current fellows were contacted, and 72% completed the survey (55% female [F] and 45% male [M]; 61% current fellows and 39% recent fellows). Respondents rated factors important in choosing pediatric urology on a scale of 1-5 (1, not important and 5, extremely important), and the top three for both genders were 1-working with children, 2-influential mentors, and 3-bread and butter cases such as inguinal orchiopexy. During residency, 93% of respondents reported having influential mentors in pediatric urology. However, mentorship was more important in fellowship choice for males than females (3.6 F, 4.1 M; P-value = 0.048), and 45% reported having only male mentors. Rating factors important in job choice on a scale of 1-5, respondents reported the top factors as 1-rapport with partners/mentorship (4.5), 2-geography/family preferences (4.3), and 3-participation in mentoring/teaching (3.8). Although most job selection criteria were rated similarly between genders, females rated call schedule higher than males (3.5 F, 2.9 M, P-value = 0.009). Although most females and males (79% of F, 78% of M, P-value = 0.868) sought primarily academic positions, a smaller proportion of females accepted academic positions (52% of F, 72% of M, P-value 0.26), and females reported lower satisfaction regarding the availability of jobs on a scale of 1-5 (1, very dissatisfied and 5, very satisfied; 3.1 F, 3.7 M; P-value = 0.034), particularly in academic positions (3.1 F, 3.7 M; P-value = 0.06). This difference was more pronounced in current fellows than recent graduates and may represent a worsening trend. CONCLUSION: Although significant gender differences in fellowship and job selection may exist in other fields, we found that women and men choose pediatric urology fellowships and jobs using similar criteria, which include work-life balance. Gender differences exist in the influence of mentors, indicating a need for more female mentors. While men and women sought similar types of jobs, women were less satisfied with the availability of jobs, particularly academic jobs, than men, which warrants further investigation.

Do pediatricians routinely perform genitourinary examinations during well-child visits? A review from a large tertiary pediatric hospital.

BACKGROUND: The male genital examination is a common source of discomfort for the patient and medical provider. Performance of male genital examination is imperative; however, as many treatable diagnoses can be made. Undescended testicles (UDTs), hernias, testicular tumors, and urethral abnormalities are all potentially concerning findings which can be discovered on routine examination. OBJECTIVE: The objectives of this study are to determine the rate at which general pediatricians perform routine genitourinary (GU) examinations in the pediatric population and to determine the rate at which UDT are diagnosed or documented in the patient's history. The authors hypothesize the rate of pediatric GU examination during routine well-child visits to be in line with the previously reported rates in the adult literature. STUDY DESIGN: Nine hundred ninety-six consecutive male well-child visits conducted by general pediatricians at the study institution were reviewed. These visits were evaluated for documentation of a detailed GU examination as well as the presence of UDT from these examinations. In addition, past medical and surgical histories were reviewed to determine if a diagnosis of UDT was noted. RESULTS: Pediatricians at the study institution documented GU examinations 99.1% of the time during male well-child visits. Only 1.1% of the cohort had a documentation of UDT at any time point. Of the 11 patients with UDT, 6 boys (54.5%) had spontaneous descent with no referral to urology, whereas 5 (45.5%) required orchidopexy. DISCUSSION: Prior reports suggest 70-75% of routine office visits include a genital examination. None of these reports reviewed the pediatric population, thus making this review novel in this respect. In addition, the results are vastly different from these prior studies as the authors demonstrated over 99% of male well-child examinations included documentation of a thorough genital examination. A limitation of the study is its retrospective nature, which creates a lack of standardization across the data set. In addition, without being physically present in the examination room, one cannot discern whether an examination is simply being documented without actual performance because of the template format of the electronic medical record (EMR). Furthermore, the study was not designed to best evaluate the true rate of UDTs; therefore, the reported rate of 1.1% cannot be accurately associated with a particular age at diagnosis. CONCLUSIONS: Pediatricians do, in fact, document GU examinations on a routine basis. This finding cannot be taken with complete certainty as verification of actual examination performance is impractical. While the data demonstrated a lower than expected rate of UDT, depending upon age at diagnosis, this could indicate that although examinations are being documented, their accuracy may be diminished because of various factors at play in the healthcare system as a whole, including improper exam performance and EMR templates. Follow-up studies are required to verify these potentially changing rates of UDT and to determine if there is discordance between documentation and performance of GU examinations.

Birth prevalence of hypospadias and hypospadias risk factors in newborn males in the United States from 1997 to 2012.

BACKGROUND: Hypospadias is a common genitourinary malformation and there are conflicting data on whether its prevalence is increasing. Previous studies have described associations with risk factors including small for gestational age (SGA), multiple gestation birth, environmental influences, and maternal factors. OBJECTIVE: The objective of this study was to examine birth prevalence of hypospadias and hypospadias risk factors in a large national dataset and to evaluate for changes from 1997 to 2012. We hypothesized that any increase in the birth prevalence of hypospadias would be associated with an increase in risk factors such as SGA, prematurity, or multiple gestation birth. STUDY DESIGN: The Kids' Inpatient Database was used to generate national estimates for prevalence of males born with hypospadias, SGA, prematurity, or to a multiple gestation and then prevalences were evaluated for association with time. Multivariable logistic regression was used to evaluate whether birth prevalence of hypospadias was associated with increasing year, SGA, prematurity, and multiple gestation birth. RESULTS: The estimated birth prevalence of hypospadias increased from 6.1 per 1000 births (95% confidence interval [CI] 5.9 to 6.3) to 6.8 per 1000 births (95% CI 6.7 to 7.0), an 11.5% increase from 1997-2012 (P = 0.014). Among male births, the prevalence of SGA increased 74%, multiple gestation increased 25%, and prematurity increased 20% (P < 0.001 for all) (Summary Figure). A risk factor was seen in around 20% of males born with hypospadias. Hypospadias birth prevalence also increased in males without risk factors but was not statistically significant (9.1% increase, P = 0.5). On multivariable logistic regression, being born SGA (odds ratio [OR] = 3.3), to a multiple gestation (OR = 1.1), or premature (OR 1.9) were associated with increased odds of hypospadias (P < 0.01 for all), whereas increasing year was not (P = 0.3). CONCLUSIONS: The estimated birth prevalence of hypospadias in the United States increased from 6.1 to 6.8 per 1000 births from 1997 to 2012. Known hypospadias risk factors of SGA birth, multiple gestation birth, and premature birth also increased over this time to a higher degree. About 20% of males born with hypospadias had one of these risk factors. The birth prevalence of hypospadias in males without any studied risk factors also increased, but this was not statistically significant. More studies are needed to evaluate whether this increase in hypospadias prevalence is due to increases in known hypospadias risk factors, new environmental exposures, improved diagnosis at birth, some combination, or unrelated causes.

Comparing treatment modalities for transplant kidney vesicoureteral reflux in the pediatric population.

INTRODUCTION: Non-refluxing ureteral reimplantation is favored in pediatric renal transplantation to prevent complications, such as vesicoureteral reflux (VUR) in the transplant ureter. VUR resulting in febrile urinary tract infections remains a problem in this population, leading to repeated hospitalizations and increased morbidity. Revision of the vesicoureteral anastomosis can be a surgical challenge due to scar tissue and tenuous vascularity of the transplant ureter. Therefore, alternative options such as endoscopic injection of Deflux at the neo-orifice and surveillance with prophylactic antibiotics have emerged as potential treatment modalities for transplant ureter VUR. OBJECTIVE: The authors reviewed their experience of the management of VUR in the transplant ureter, comparing outcomes of various modalities. STUDY DESIGN: With Institutional Review Board approval, a retrospective chart review of all renal transplant patients from January 2002 to January 2017 was conducted. All patients with VUR on voiding cystourethrogram (VCUG) after surgery were identified. Indications for end-stage renal disease, urologic comorbidities, pretransplant VCUG, and operative details were recorded. After transplantation, febrile urinary tract infections, ultrasound findings, and any further interventions-surveillance, subureteral endoscopic injection of Deflux, or ureteral reimplantation-were documented along with their outcomes. RESULTS: Overall, VUR was identified in 35/285 (12.3%) transplant patients after a non-refluxing ureteroneocystostomy. VUR was managed with surveillance in 17/35 (49%), intravesical Deflux injection in 11/35 (31%), and immediate redo ureteral reimplantation in 7/35 (20%). Ten out of 11 patients undergoing Deflux injection had a postoperative VCUG. All patients developed VUR recurrence; the majority showed immediate failure and only 1/10 showed late recurrence. Of the immediate failures, 3/9 patients were maintained on prophylactic antibiotics, and 6/9 patients underwent ureteral reimplantation. In these six patients undergoing reimplantation after failed Deflux, 3/6 (50%) patients required additional surgeries: One patient developed recurrence of reflux and two patients developed ureterovesical junction obstruction. In contrast, no complications were seen in patients undergoing primary ureteral reimplantation. DISCUSSION: The study is limited by low numbers and a retrospective design. However, the results of this study differ significantly from the published Deflux series showing a success rate of more than 50% in the treatment of transplant kidney VUR. In fact, post-Deflux redo ureteral reimplantation was associated with an increased risk of postoperative complication. CONCLUSION: The use of Deflux in the post-transplant setting has poor results. In the study series, 11/11 patients demonstrated clinical and radiographic failure. Therefore, as an institution the authors do not recommend Deflux as first-line treatment of VUR in the transplant patient.

Design and evaluation of immunotoxicity studies.

The evaluation of potential adverse effects of pharmaceuticals on the immune system is part of the standard drug development procedures and needs to be available prior to the start of phase III clinical trials. Although the histopathological assessment of lymphoid organs/tissues is considered fundamental for the identification and characterization of immunotoxic reactions, additional investigations are now recommended by the European guidelines for repeated-dose toxicity testing of medicinal products in order to achieve an accurate assessment of immune system functionality with regard to immunomodulation. In the present paper, we describe and discuss a study design which permits the investigation of the immune function in a 4-week study in rats following immunization by subcutaneous administration of the T-dependent antigen Keyhole Limpet Hemocynin (KLH). This includes assessment of hematology parameters, titration of KLH-specific antibodies in serum, lymphocyte immunophenotyping in blood, thymus, spleen and lymph nodes, macroscopic pathology and histopathological evaluation of the lymphatic organs/tissues and of the injection sites.

Imaging characteristics associated with failure of nonoperative management in high-grade pediatric blunt renal trauma.

INTRODUCTION: Some children who sustain high-grade blunt renal injury may require operative intervention. In the present study, it was hypothesized that there are computed tomography (CT) characteristics that can identify which of these children are most likely to need operative intervention. MATERIALS AND METHODS: A retrospective review was performed of all pediatric blunt renal trauma patients at a single level-I trauma center from 1990 to 2015. Inclusion criteria were: children with American Association for the Surgery of Trauma (AAST) Grade-IV or V renal injuries, aged ≤18 years, and having available CT images with delayed cuts. The CTs were regraded according to the revised AAST grading system proposed by Buckley and McAninch in 2011. Radiographic characteristics of renal injury were correlated with the primary outcome of any operative intervention: ureteral stent, angiography, nephrectomy/renorrhaphy, and percutaneous nephrostomy/drain. RESULTS: One patient had a Grade-V injury and 26 patients had Grade-IV injuries. Nine patients (33.3%) underwent operative interventions. Patients in the operative intervention cohort were more likely to manifest a collecting system filling defect (P = 0.040) (Fig. A) and lacked ureteral opacification (P = 0.010). The CT characteristics, including percentage of devascularized parenchyma, medial contrast extravasation, intravascular contrast extravasation, perirenal hematoma distance and laceration location, were not statistically significant. Of the 21 patients who had a collecting system injury, eight (38.1%) needed ureteral stents. Renorrhaphy was necessary for one patient. Although the first operative intervention occurred at a median of hospital day 1 (range 0.5-2.5), additional operative interventions occurred from day 4-16. Thus, it is prudent to closely follow-up these patients for the first month after injury. Two patients with complex renal injuries had an accessory renal artery resulting in well-perfused upper and lower pole fragments, and were managed nonoperatively without readmission (Fig. B). CONCLUSIONS: Collecting system defects and lack of ureteral opacification were significantly associated with failure of nonoperative management. A multicenter trial is needed to confirm these findings and whether nonsignificant CT findings are associated with operative intervention. In the month after renal injury, these patients should be mindful of any changes in symptoms, and maintain a low index of suspicion for an emergency room visit. For the physician, close follow-up and appropriate counseling of these high-risk patients is advised.

Fc receptor expression, concanavalin A capping, and enzyme content of bovine neonatal neutrophils: a comparative study with adult cattle.

The increased susceptibility of newborns to infection may in part be related to impaired in vitro functions of neonatal polymorphonuclear neutrophils (PMNs). To evaluate early steps in the activation cycle of bovine PMNs we determined the expression of Fc receptors (FcRs) with an erythrocyte rosetting assay utilizing bovine anti-sheep immunoglobulin G2 IgG2 and the accumulation of ligand receptor complexes or "caps" with fluorochrome-coupled concanavalin A (Con A caps) on neutrophils from adult (A-PMN) and newborn (N-PMN) bovines. In addition, the levels of myeloperoxidase (MPO) and alkaline phosphatase (AP) were determined. FcR expression is reduced in N-PMNs (P less than .001), in contrast to results observed with human N-PMNs. Basal capping of Con A binding sites is reduced (P less than .05) in N-PMNs but is enhanced (P less than .001) upon pretreatment with colchicine (0.5, 5.0, and 50.0 microns). These findings are again contrary to results observed with human N-PMNs. Consistent with findings in human neonates, however, are reduced levels of cellular MPO (P less than .05) and elevated cellular AP (P less than .001) in the neonate. The functional significance of elevated AP levels and altered Con A capping in N-PMNs is unclear. However, diminished expression of FcR could potentially contribute to impaired adherence and phagocytosis of bacteria, and reduced activity of neutrophil MPO could indicate weaker microbicidal capacity of neonatal cells. The demonstrated impairment of N-PMN functions could potentially contribute to reducing the effectiveness of the cellular host defense system in neonatal calves.

Current indications for cutaneous ureterostomy.

OBJECTIVE: To assess the current indications for cutaneous ureterostomy in children. METHOD: A total of 32 children underwent cutaneous ureterostomy at Texas Children's Hospital from 1975 to 1990. Medical records were reviewed to determine the urologic diagnosis, the indication for urinary diversion, the type of ureterostomy performed, and the outcome for each patient. RESULTS: Twenty patients underwent loop cutaneous ureterostomy (LCU) or pyelostomy and 12 patients underwent end cutaneous ureterostomy (ECU). The main indication for LCU was obstructive uropathy unresponsive to lower urinary tract drainage, and the most common cause was posterior urethral valves. Other indications for LCU included obstruction requiring delayed surgical correction, high-grade reflux into a solitary kidney, and obstruction with infection. The children who required ECU were an older, more diverse group than those who underwent LCU. The main indication for ECU was poor bladder function secondary to a variety of congenital anomalies, including prune-belly syndrome, posterior urethral valves, bladder exstrophy, and urogenital sinus defect. CONCLUSION: LCU is easy to perform and is an excellent method for achieving temporary upper urinary tract drainage. ECU is suited for long-term or permanent urinary diversion in children with at least one dilated ureter, and can provide a socially acceptable stoma when delayed reconstruction is necessary. Many children who were "permanently" diverted by ECU may be undiverted using newer reconstructive techniques.

Pediatric pyeloplasty: outcome analysis based on patient age and surgical technique.

OBJECTIVES: To analyze our experience with open pyeloplasty, with specific emphasis on procedural outcome on the basis of patient age, surgical technique, complication rate, and complication management. METHODS: All patients from 1974 to 1994 who underwent pyeloplasty at our institution were included in our review. Charts were analyzed for age at presentation, presenting signs and symptoms, type of surgical reconstruction, complications and treatment, and final outcome. RESULTS: From 1974 to 1994, 234 pyeloplasties were performed in 227 patients (108 less than 1 year old, 119 more than 1 year old). The percentage of children less than 1 year old increased throughout: 24% for 1975 to 1980, 37% for 1981 to 1990, and 69% for 1991 to 1994. Presenting signs and symptoms varied according to the age of the child at pyeloplasty. For children less than 1 year old, these were prenatal ultrasound in 86 (79%), urinary tract infection (UTI) in 9 (8%), and abdominal mass in 5 (4.6%). For children more than 1 year old, these were pain in 57 (48%), UTI in 29 (24%), hematuria in 12 (10%), and prenatal ultrasound in 3 (2.5%). Reconstruction was a dismembered pyeloplasty in all cases. The majority of patients in both age groups underwent a nonintubated repair (less than 1 year old, 99 of 114; more than 1 year old, 102 of 120). Postoperative results were evaluated by ultrasound or intravenous urography, with improvement or stable results in 95% of children less than 1 year old and in 96% of children more than 1 year old. Complications included UTI in 18 patients (7.7%), recurrent obstruction in 5 (2.1%), and persistent leak in 4 (1.7%). The complication rate was not related to age. CONCLUSIONS: The nonintubated, dismembered pyeloplasty is an excellent technique for all age groups and has a low complication rate.

In vitro model of the inner parts of a vessel wall with cultured human vascular cells.

BACKGROUND: Transfilter culture systems with enzymatically isolated human vascular cells were established to imitate the morphologic situation of the inner parts of a vessel wall. METHODS: In transfilter cultures, only smooth muscle cells were seeded on one side of the filter, whereas in transfilter cocultures, smooth muscle cells were cultivated in the presence of confluent or nonconfluent (injured) endothelial cells on the other side of the filter. The filter mimics the porous internal elastic lamina. Fourteen days after seeding, cultures were fixed, embedded in Araldite (Serva, Heidelberg, Germany), and prepared for histologic examination (light microscopy, indirect immunofluorescence staining of von Willebrand factor- and alpha-smooth muscle actin-antigen). RESULTS: In transfilter cultures, smooth muscle cells migrated through the pores to the opposite side of the filter, replicated there, and formed fibromuscular proliferates (two to four layers of smooth muscle cells). The proliferation rates of the smooth muscle cells were similar on both sides of the filter and showed an optimum rate on day 4 in culture as determined by 5-bromo-2'-deoxyuridine labeling. By cocultivating a confluent endothelial cell layer on one side of the filter, migratory activity of smooth muscle cells was inhibited. However, when smooth muscle cells were cultivated together with proliferating endothelial cells (injured state), proliferation of smooth muscle cells was massively stimulated (up to 12 layers of smooth muscle cells). CONCLUSIONS: The results indicate that the confluency of the endothelial cells and their proliferation rate influence the migratory and proliferative behavior of smooth muscle cells. The transfilter system may be a suitable model for prescreening of potential antiproliferative and antiarteriosclerotic drugs.

Chemotactic competence of neutrophils from neonatal calves. Functional comparison with neutrophils from adult cattle.

Neonates demonstrate an increased susceptibility to infection. Defects in locomotory functions of newborn neutrophils may play a crucial role in this context. We therefore compared the migratory response of newborn (N-PMN) and adult (A-PMN) bovine neutrophils in a microwell filter assay. Stimulation with four different endotoxins (E. coli O128B:4 and O55B:5; S. abortus equi; S. typhimurium), with zymosan-activated plasma (ZAP) and with C5a induced dose-dependent migration of A-PMNs and N-PMNs. Migration of unstimulated cells and of cells stimulated with diluted ZAP or C5a was higher (P less than 0.05) in N-PMNs. Migration of A- and N-PMNs towards C5a was inhibited (P less than 0.001) by preincubation with either a steroidal (122 microM flumethasone) or nonsteroidal (3.3 microM phenylbutazone) antiinflammatory drug. Migratory responses of N-PMNs were inhibited less by SAIDs than were responses of A-PMNs (P less than 0.05); indeed dexamethasone slightly enhanced N-PMN responses towards C5a, and 510 microM flunixin meglumine enhanced C5a-induced migration in both age groups. Endotoxins from E. coli O55:B4, S. abortus equi, and S. typhimurium induced a higher rate of migration (P less than 0.05) in N-PMNs. In contrast to the above findings, measurement of the maximal distance of migration by the leading-front method did not reveal age-related differences. Migration speed of PMNs was lower after stimulation with C5a than with ZAP, but could be restored partly by adding human vitamin D-binding protein (Gc-globulin). The demonstrated hyperirritability of bovine N-PMNs represents a major functional difference to neonatal neutrophils from other species, including man. It may additionally be related to altered PMN functions and neonatal disease susceptibility.

In vitro aggregation of bovine neonatal neutrophils. A comparative study with adult cattle.

Deficient in vitro functions of neonatal neutrophils have been reported in various species. They may be functionally related to the well-known susceptibility of newborn individuals to microbial infections. To evaluate an early step in the sequence of neutrophil activation, neutrophils from adult cows (A-PMN) and newborn calves (N-PMN) were stimulated with zymosan-activated plasma (ZAP) or with the lipid mediator platelet-activating factor (PAF): Aggregation was recorded kinetically in a standard aggregometer and measured quantitatively as the area under the aggregation curve (AUAC). The mean +/- SEM of the AUAC of the first 2.5 min of the reaction induced with ZAP was similar in N-PMN and A-PMN. However, N-PMN deaggregated only partially, whereas A-PMN deaggregated almost completely (P less than 0.05). This may indicate a mechanism of microvascular sequestration in vivo with the potential to inhibit chemotaxis. PAF (10(-5)-10(-10) M) aggregated N- and A-PMNs similarly and dose-dependently with a maximal reaction at 10(-6) M. Inhibition of aggregation induced by 10(-6) M PAF was evaluated by preincubation with four antiinflammatory drugs: dexamethasone (Dex: 5.1, 51.0, 510.0 microM), flumethasone (Flu: 12.2 and 122.0 microM), phenylbutazone (PB: 0.33 and 3.3 mM), and flunixin meglumine (Flxin: 51 and 510 microM). Dex and Flu each inhibited (P less than 0.05) PAF-induced N-PMN aggregation at the highest dose, and A-PMN aggregation at the two higher doses. PB and Flxin each inhibited aggregation of N- and A-PMNs at all doses used. We compared the inhibition rate in both age groups and could demonstrate that Dex, Flu, and Flxin each at the highest dose, and PB at all doses used, inhibited PAF-induced aggregation less (P less than 0.05) in N-PMNs than in A-PMNs. These functional differences indicate hyperirritability of N-PMNs, and they need further elucidation to help understand mechanisms of increased neonatal susceptibility.

Management of the penile shaft skin in hypospadias repair: alternative to Byars' flaps.

Two variations for resurfacing the penile shaft skin after repair of hypospadias defects are described. These techniques have been used in an effort to prevent some of the skin tags, tension at the penoscrotal angle, and oblique suture lines that may occur with the traditional Byars' flaps.

Neutron production from polyethylene and common spacecraft materials.

We report experimental measurements of neutron production from collisions of neutron beams with polyethylene blocks simulating tissue at the Los Alamos National Laboratory Neutron Science Center and 1 GeV/amu iron nuclei with spacecraft shielding materials at the Brookhaven National Laboratory AGS.

Distal hypospadias repair with meatal-based flaps on an outpatient basis.

We report the results of primary repairs that were performed on 52 consecutive patients with distal hypospadias as an outpatient procedure. A modified Mathieu repair with meatal-based vascularized flap was performed under 2.5 optical magnification using Scottring retractors, traction sutures, micro instruments and fine suture material. A total of 3 patients had complications that required reoperation (5.8%). One of these 3 complications was a urethrocutaneous fistula (1.9%). We found that the repair of distal hypospadias was successful with meatal-based flap using contemporary finer approaches and equipment.