Biomedical subjects
Publications and source records attributed to P H McKenna.
Most patients with significant posterior urethral valves are identified antenatally. However, even with a normal antenatal ultrasound scan, posterior urethral valves may be detected after birth. We present a patient with significant upper urinary tract involvement identified 2 days after birth, despite a normal third-trimester antenatal ultrasound scan.
PURPOSE: Little data are available on the appropriate followup protocols for patients treated medically or surgically for vesicoureteral reflux. We surveyed urologists who primarily practice pediatric urology to determine current practice patterns for following patients treated for vesicoureteral reflux. MATERIALS AND METHODS: A 1-page survey was mailed to the 225 members of the American Academy of Pediatrics, Section on Urology. The mailing roster and labels were provided by the American Academy of Pediatrics. The survey included questions on the followup of patients with low and high grade reflux treated medically or surgically. Returned surveys were blindly tabulated by 2 independent reviewers (F. A. F. and P. H. M.). RESULTS: Of the 225 surveys 155 were returned and analyzed for an overall response rate of approximately 61%. Urine culture is routinely performed by 64% and 71% of respondents to follow children with uncorrected low grade reflux and those with high grade reflux undergoing medical treatment, respectively, generally at 3 to 6-month intervals. To follow patients with reflux voiding cystourethrography or radionuclide scan is performed yearly by 99% of study participants, while 77% perform ultrasound. Renal scan and excretory urography are done infrequently. The timing of the surgical correction of unresolved asymptomatic reflux and/or when to discontinue antibiotics in these cases varied significantly among survey respondents. After antireflux surgery 92% and 91% of respondents perform voiding cystourethrography and ultrasound, respectively. Recommended followup after ureteroneocystotomy varied greatly among survey participants. CONCLUSIONS: The overwhelming majority of practitioners agree on the timing and type of radiographic studies to be used to follow children treated for reflux and the majority routinely perform urine culture. Opinion on the continuation of antibiotics and timing of surgical intervention for asymptomatic unresolved reflux is divided. Wide variation exists on the recommended followup after reimplantation.
PURPOSE: Conservative estimates indicate that up to 54% of patients who present with vesicoureteral reflux have dysfunction voiding. Children with voiding dysfunction and vesicoureteral reflux historically have a high breakthrough infection rate of 34% to 43%. Breakthrough infection represents significant morbidity and it is the most common indication for surgical intervention for vesicoureteral reflux. Voiding dysfunction is present in 79% of patients who proceed to reflux surgery. We evaluated the impact of pelvic floor muscle retraining combined with a medical program in patients with voiding dysfunction and vesicoureteral reflux. MATERIALS AND METHODS: Children with a history consistent with voiding dysfunction and vesicoureteral reflux were screened by uroflowmetry/electromyography, bladder scan for post-void residual urine, renal ultrasound and voiding cystourethrography. Confirmed cases of voiding dysfunction and vesicoureteral reflux were prospectively enrolled in this study. Children participated in an interactive, computer assisted, pelvic floor muscle retraining program that involved a conservative medical regimen and pelvic floor muscle retraining. All patients received prophylactic antibiotics. We evaluated the rate of breakthrough urinary tract infection, reflux outcome and surgical intervention. A literature review with the key words vesicoureteral reflux, voiding dysfunction and urinary tract infection was performed to identify historical control cases for comparison. RESULTS: Study enrollment criteria were fulfilled by 49 girls and 4 boys 4 to 13 years old (average age 8.8), representing 72 units with low grades I to II (48) and high grades III to V (24) reflux. Mean followup was 24 months. Initial uroflowmetry/electromyography and bladder scan revealed a staccato flow pattern and normal post-void residual urine in 11% of cases, staccato flow pattern and elevated post-void residual urine in 10%, flattened flow pattern and normal post-void residual urine in 28%, and flattened flow pattern and elevated post-void residual urine in 51%. Breakthrough infection developed in 5 patients (10%), including 1 in whom reflux had resolved and 1 with grade I reflux who underwent observation. The parents of 2 patients elected to complete biofeedback without surgical intervention and these patients did not have a repeat infection. Reimplantation was performed in 1 case (2%). There was resolution in 18 low and 7 high grade refluxing units, including 2 older patients with a long history of high grade bilateral disease. Average time to resolution was 7.8 months. We noted elevated post-void residual urine in 88% of the patients with high grade reflux. Average age at resolution was 9.2 years. During a 24-month period one of us (P. H. M.) noted a greater than 90% decrease in surgical intervention. CONCLUSIONS: A combined conservative medical and computer game assisted pelvic floor muscle retraining program appears to have decreased the incidence of breakthrough urinary tract infections and facilitated reflux resolution in children with voiding dysfunction and vesicoureteral reflux. Patients with high grade reflux and voiding dysfunction commonly present with elevated post-void residual urine, contraindicating the indiscriminate administration of anticholinergics. Decreasing the rate of urinary tract infections may have a dramatic impact on the need for surgical intervention and enable the reflux resolution rate to approximate that in patients without voiding dysfunction. Prospective controlled trials are needed to determine whether pelvic floor muscle retraining combined with a conservative medical regimen alters the natural history of vesicoureteral reflux in patients with voiding dysfunction.
PURPOSE: We reviewed our experience with a conservative medical program and computer game assisted pelvic floor muscle retraining in patients with voiding dysfunction to substantiate our previous findings that demonstrated improvement and/or cure in a majority of patients, and identify factors that may be associated with unsuccessful treatment. MATERIALS AND METHODS: All patients presenting with symptoms of dysfunctional voiding enrolled in our pelvic floor muscle retraining were examined. Cases were subjectively evaluated for improvement of nocturnal enuresis, diurnal enuresis, constipation, encopresis and incidence of break through urinary tract infection. Patients in whom our initial conservative approach that included our biofeedback program failed were further treated with medication, and outcomes were reviewed as well. Fisher's exact test was used for statistical analysis to identify factors that may predict failure with our program. RESULTS: During the last 2 years 134 girls and 34 boys were enrolled in the pelvic floor muscle retraining program. Of the patients 160 (95%) were compliant with the program. Mean patient age was 7.6 years (range 4 to 18). The average number of hourly treatment sessions was 4.9 (range 2 to 13). Uroflowmetry and electromyography demonstrated a flattened flow pattern with increased post-void residual volume in 32% of patients, flattened flow pattern with normal post-void residual 47%, staccato flow pattern with increased post-void residual 11% and staccato flow pattern with normal post-void residual 10%. Subjective improvement was demonstrated in 87% (146) of patients, while 13% (22) had no improvement. Statistically significant predictors of failure included bladder capacity less than 60% of predicted volume (p <0.03) and patient noncompliance (p <0.04). Twelve patients who had no improvement with biofeedback were treated with medication and 10 (83%) improved. Multichannel urodynamics or spinal magnetic resonance imaging (MRI) was obtained in only 7 (4%) of our patients with no neurological lesion identified by spinal MRI. CONCLUSIONS: A conservative program combined with computer game assisted pelvic floor muscle retraining improves symptoms in most patients with voiding dysfunction. A majority of patients can be treated without medication. However, in a select population of patients with a small capacity bladder in whom biofeedback fails, anticholinergic medication appears to alleviate symptoms. In our experience almost all patients presenting with symptoms of voiding dysfunction can be treated without multichannel urodynamics, spinal MRI or medication.
We present what is to our knowledge the first antenatal detection of a proximal ureteral diverticulum, an extremely rare urologic abnormality, that was successfully reconstructed in the early postnatal period and should henceforth be included in the differential diagnosis of the antenatally detected cystic mass.
PURPOSE: Studies have demonstrated that the pro-angiogenic cytokine interleukin-8 (IL-8) and the IL-8 receptors likely have a role in the growth and metastasis of various solid tumors. We hypothesized that in vivo neuroblastoma expresses IL-8 and the IL-8 receptors A and B, and that factors known to regulate IL-8 expression are present and active in the neuroblastoma microenvironment. MATERIALS AND METHODS: To confirm the presence of IL-8/IL-8 receptors in neuroblastoma, immunohistochemical analysis for IL-8 and its receptors was performed on 10 archival specimens, including benign adrenal and well to poorly differentiated neuroblastoma samples. Immunohistochemical analysis was also performed for interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha. Cultured neuroblastoma cells SK-N-MC and SK-N-SH were stimulated with 10 ng./ml. IL-1beta or tumor necrosis factor-alpha and control media (15 each). Cell culture supernatants were analyzed with enzyme-linked immunosorbant assay for IL-8 levels at 24 and 48 hours. RESULTS: Minimal expression of IL-8 was noted in benign adrenal tissue but expression for IL-8 was present in all neuroblastoma specimens. Microvessel staining was present in 30% of the specimens. All tumor specimens expressed IL-8 receptor B, and both receptors were expressed in the tumor microvasculature. Immunohistochemical analysis confirmed the presence of IL-1beta and tumor necrosis factor in the neuroblastoma microenvironment. In vitro studies demonstrated that SK-N-MC and SK-N-SH cells express low levels of IL-8 under normal conditions and that IL-1beta and tumor necrosis factor-alpha significantly increased expression of IL-8 at 24 and 48 hours. CONCLUSIONS: Our results indicate that IL-8 and its receptors are expressed in neuroblastoma tumor specimens. In addition, the fact that IL-1beta and tumor necrosis factor-alpha are expressed in the neuroblastoma microenvironment combined with our in vitro results suggests that these cytokines may be involved in in vivo regulation of IL-8 in human neuroblastoma. Understanding the angiogenic factors and regulatory cascade promoting angiogensis in neuroblastoma may lead to the development of effective anti-angiogenic strategies.
PURPOSE: The incidence of an antenatally detected genitourinary abnormality is 0.5% of all pregnancies assessed, and rarely is antenatal intervention indicated. A survey of pediatric urologists was undertaken to evaluate current practice patterns and recommendations regarding the need to intervene in the antenatal period. MATERIALS AND METHODS: A survey instrument was mailed to all members of the Society for Fetal Urology. There were 7 case scenarios that addressed critical decision points in patients with antenatally detected genitourinary abnormalities. RESULTS: A total of 112 of 188 Society for Fetal Urology members (60%) completed the survey. Observation with serial ultrasound was recommended for a 32-week fetus with ureteropelvic junction obstruction. For a 36-week fetus with suspected posterior urethral valves without oligohydramnios most respondents elected no intervention with a minority favoring early delivery. For a 23-week fetus with suspected posterior urethral valves and oligohydramnios with normal bladder electrolytes most respondents agreed with a vesicoamniotic shunt. There was no clear consensus for a 20-week fetus with suspected posterior urethral valves, oligohydramnios and a nonfunctioning right kidney. Most respondents recommended serial ultrasound to follow an 18-week fetus with suspected posterior urethral valves and normal amniotic fluid. Antenatal intervention was not recommended for a 20-week fetus with bilateral renal cystic disease, and most respondents elected no intervention for a 28-week fetus with a solitary kidney with suspected ureteropelvic junction obstruction and normal amniotic fluid. CONCLUSIONS: Situations that warrant antenatal intervention for a genitourinary abnormality are exceedingly low and may include cases of oligohydramnios, suspected favorable renal function and the absence of life threatening congenital abnormalities. In cases with normal amniotic fluid antenatal intervention is not recommended regardless of the detected abnormality. There is an emerging trend toward early delivery of fetuses with severe genitourinary abnormalities, normal amniotic fluid and confirmed lung maturity.
Over the last several decades voiding dysfunction in children has primarily been associated with incontinence and thought to be secondary to bladder instability from delayed brain maturation. Full urodynamic evaluation became the standard recommendation and treatment centred on early institution of anticholinergics. Recently, this strategy has been questioned as medical programs including pelvic floor muscle treatments have shown tremendous success in curing incontinence, decreasing surgical rates for vesicoureteral reflux, and decreasing recurrent urinary tract infections.
PURPOSE: We evaluated a new noninvasive outpatient method of pelvic muscle retraining in children using computer game assisted biofeedback. MATERIALS AND METHODS: All patients in whom voiding dysfunction was confirmed by history, uroflowmetry-electromyography and voiding cystourethrography were enrolled in a pelvic floor muscle retraining program. Patients received a pretreatment, mid treatment and posttreatment survey instrument documenting subjective improvement, including the frequency of diurnal enuresis, nocturnal enuresis, constipation and encopresis. Pretreatment and posttreatment simultaneous uroflowmetry surface electrode electromyography was performed and post-void residual urine volume was determined in all patients. RESULTS: A total of 8 boys and 33 girls 5 to 11 years old (mean age 7.2) completed therapy and were available for evaluation. These patients completed 2 to 11 (average 6) hourly treatment sessions. Followup was 3 to 15 months (average 7). At the midterm evaluation improvement in nocturnal enuresis was reported by 57% of the patients, diurnal enuresis by 84%, constipation by 83% and encopresis by 91%. End treatment evaluation revealed improvement in nocturnal enuresis by 90% of patients, diurnal enuresis by 89%, constipation by 100% and encopresis by 100%. Uroflowmetry-electromyography patterns improved in 42% of the patients and post-void residual urine decreased in 57%. Comparison of initial to end recorded millivoltage pelvic floor muscle values demonstrated that 56% of the patients had lower resting tone at the beginning of the session after completing therapy and 78% had improved contracting tone after performing Kegel exercises, as proved by increased microvoltage values. Initial uroflowmetry-electromyography revealed certain categories of cases, including a flattened voiding curve with a hyperactive pelvic floor and low post-void residual urine in 40%, a flattened voiding curve with a hyperactive pelvic floor and high post-void residual urine in 40%, a staccato voiding curve with a hyperactive pelvic floor and low post-void residual urine in 3%, and a staccato voiding curve with a hyperactive pelvic floor and high post-void residual urine in 17%. Of the girls 91% presented with the classic spinning top deformity on voiding cystourethrography. A total of 22 patients presented with a significant history of recurrent urinary tract infections, and infection developed in 3 during treatment and followup. Vesicoureteral reflux in 14 patients resolved during treatment in 3, reimplantation was performed in 1 and 10 are still being observed. CONCLUSIONS: A program of conservative medical management with computer game assisted pelvic floor muscle retraining resulted in significant subjective improvement in continence, constipation and encopresis as well as objective improvement in uroflowmetry-electromyography, post-void residual urine volume and the microvoltage value of pelvic floor muscles in the majority of patients with dysfunctional voiding.
PURPOSE: Approximately 10 to 30% of prenatal cases of hydronephrosis result in the postnatal diagnosis of vesicoureteral reflux. Using a new generic prenatal-postnatal data sheet developed by the Society for Fetal Urology the characteristics, natural history and outcome of prenatal hydronephrosis confirmed postnatally to be vesicoureteral reflux were documented at 3 centers. MATERIALS AND METHODS: We performed a retrospective multicenter review of Society for Fetal Urology data sheets completed for each patient in whom prenatal hydronephrosis was proved to be postnatal vesicoureteral reflux from 1993 to 1998. RESULTS: In 56 male and 15 female patients with prenatal hydronephrosis a total of 116 refluxing renal units were confirmed postnatally. Of the 116 renal units 112 were hydronephrotic prenatally. During gestation increased hydronephrosis was noted with voiding in 4 cases. Of the 112 hydronephrotic renal units only 26 ureters in 15 patients were seen prenatally. The obstetrician considered the diagnosis of vesicoureteral reflux in only 24% of the cases. Postnatally 116 refluxing renal units were identified. Initial postnatal ultrasound was normal in 25% of the cases. Bilateral reflux was present in 36 male and 9 female patients. In 10 of the 19 uncircumcised patients (53%) urinary tract infection developed despite antibiotic prophylaxis. In 15 of the 74 renal units with grades III to V reflux the condition resolved at an average patient age of 0.9 and 2.1 years in boys and girls, respectively. A total of 27 refluxing renal units were reimplanted. CONCLUSIONS: The majority of prenatal reflux occurs in boys, and it is high grade and bilateral. The data sheets designed by the Society for Fetal Urology are useful data collection instruments. The presentation and natural history of vesicoureteral reflux are different in male and female individuals. In a significant number of renal units high grade reflux resolves spontaneously. Early circumcision may decrease the incidence of breakthrough urinary tract infection in this subpopulation. In addition, the effective management of prenatally detected reflux depends on multispecialty communication.
The postnatal management of the antenatally detected ureteropelvic junction obstruction relies on several factors, including the degree of hydronephrosis detected postnatally, the renogram washout curve, and the degree of renal function. It is imperative for the urologist to review all renal scans because of the inherent pitfalls in performing and interpreting these studies. A select population demonstrating severe pyelocaliectasis and poor function exists in which an intraoperative renal biopsy may be a better predictor of future renal function when compared with the preoperative renal scan. We present a patient with poor renal function that normalized with early surgical intervention.
One percent of all pregnancies are found to have an antenatal abnormality; of these, 20% involve the genitourinary system. Today, controversy still exists regarding the postnatal management of some antenatal abnormalities detected by ultrasound. We present a case in which antenatal hydronephrosis initially detected by ultrasound appeared to resolve in utero. Postnatally, the child developed Citrobacter diversus urosepsis, meningitis, and cerebral abscess. Voiding cystourethrogram obtained after resolution of sepsis revealed grade IV reflux. This case underscores the importance of a full postnatal evaluation for all children with antenatal hydronephrosis and alerts clinicians to a virulent pathogen not commonly associated with urinary tract infection.
OBJECTIVE: We present the experience at Connecticut Children's Medical Center (CCMC) with single-system bilateral ectopic ureters (SSBUE), a rare clinical entity which continues to challenge the pediatric urologist. Innovative diagnostic and reconstructive techniques are utilized in an effort to preserve renal function and develop urinary continence in a select group of patients. METHODS: A review of the English language literature was performed to identify all female patients with SSBUE and evaluate their treatment and outcomes. In addition, we present our experience with three cases of SSBUE at CCMC and describe the recent advances in the management of such patients. RESULTS: From 1937 to 1999, 25 articles described 54 female patients with SSBUE. Patients were treated with a variety of reconstructive procedures that resulted in a low overall continence rate of 20% (eight of 39 reported outcomes). We evaluated three patients with SSBUE at CCMC. Our first patient had undergone three previous operations prior to her successful procedure at CCMC utilizing a new technique to achieve urinary continence in which a portion of the anterior bladder wall is used for bladder neck reconstruction. Our last patient was identified antenatally by the maternal-fetal obstetrician, evaluated postnatally by the pediatric urologist, and underwent formal urodynamics and proximal urinary diversion for an obstructed upper collecting system. No previous reports focus on antenatal identification, accurate postnatal diagnosis, urodynamic assessment and early intervention including upper urinary tract diversion, and staged Pippi Salle bladder neck reconstruction. CONCLUSION: The CCMC experience with SSBUE demonstrates the recent achievements in complex urinary tract reconstruction that have taken place in pediatric urology. We describe diagnostic studies such as formal urodynamics and the growing trend to identify urologic problems antenatally. A team approach involving the obstetrician, pediatric urologist, neonatologist, and the pediatrician has been beneficial. As pediatric urology moves into the new millennium there are prospects for even more innovative diagnostic and therapeutic options for children with urologic problems.
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PURPOSE: We evaluated practice patterns among urologists managing vesicoureteral reflux, and identified areas of consensus and controversy requiring further research. MATERIALS AND METHODS: A 1-page questionnaire addressing various aspects of reflux management, including screening, diagnosis, treatment and followup, was mailed to a cohort of 225 practicing urologists identified by the membership roster of the American Academy of Pediatrics, Section on Pediatric Urology. Coded returned mailers were blindly analyzed and tabulated by 2 reviewers. Questionnaires were subdivided using a coding system by decade (1970s or earlier, 1980s and so forth) of participant membership in the American Urological Association. Select questions were analyzed to determine whether time of training affected the response. RESULTS: Of 225 surveys 155 were returned and usable (overall 60.8% response rate). General agreement exists regarding several important points in the management of vesicoureteral reflux, including evaluation of patients at the initial urinary tract infection (78.1% of respondents), use of voiding cystourethrography and ultrasound at the initial evaluation (99.4 and 96.8%, respectively), and evaluation of sibling reflux (83.2%). Certain absolute and relative indications for surgical intervention require further clarification. Various reimplantation techniques are used today, stents are not placed by the majority of practitioners and significant variations exist in the duration of postoperative hospital stay. CONCLUSIONS: Today there is substantial consensus among urologists on many issues regarding vesicoureteral reflux management. However, the areas of controversy will only be clarified by further scientific and clinical outcomes based research.
PURPOSE: The XX male syndrome presents with a spectrum of clinical appearances from phenotypic male individuals to true hermaphrodites. Previous reports established the sex determining region of the Y chromosome (SRY) gene as the testis determining factor. However, a subset of XX sex reversed male individuals exists without a translocation of SRY deoxyribonucleic acid (DNA) material to the X chromosome. In addition to clinical or endocrinological criteria, Y DNA probe studies, and radiological and surgical evaluation as indicated are necessary for an accurate diagnosis. MATERIALS AND METHODS: We evaluated 5 XX sex reversed patients (2 true hermaphrodites and 3 male individuals) by physical examination, pedigree analysis, endocrinological testing, molecular analysis of Y DNA, radiological studies and surgery (exploration and/or biopsy). RESULTS: All patients were SRY gene negative. Two patients were siblings. Complete endocrinological testing was negative in all cases. Two patients had a normal male phenotype. Radiological findings confirmed by cystoscopy or laparoscopy revealed a utricle, vesicoureteral reflux, and cervix and uterus in various patients. Gonadal biopsy showed ovotestes or ovary and testis in the 2 true hermaphrodites. The 3 XX male individuals had normal immature testes on biopsy. CONCLUSIONS: Categories of XX sex reversal include classic XX male individuals with normal phenotypes, nonclassic XX male individuals with sexual ambiguity and XX true hermaphrodites. Simple translocation of the SRY gene to the X chromosome does not always account for testicular differentiation and a male phenotype. The masculinization of our patients in the absence of SRY suggests an alteration of 1 or more downstream Y, X or autosomal testis determining genes. We present another theory for male sex determination, including a downstream gene on the X chromosome in which expression is influenced by X inactivation. Y DNA genomic analysis, radiological studies and laparoscopic evaluation with gonadal biopsy as appropriate are recommended for complete assessment and treatment of these intersex patients.
PURPOSE: Our aim was to evaluate the effect of current Wilms tumor chemotherapy on renal growth and function after unilateral nephrectomy. MATERIALS AND METHODS: Yorkshire piglets were enrolled in 2 study groups: group 1--6 underwent unilateral nephrectomy and placebo infusion, and group 2--10 underwent nephrectomy, and infusion of 7.5 mcg/kg. actinomycin D and 0.75 mcg/m2 vincristine according to the National Wilms Tumor Study 4 protocol. Weekly measurements of renal size by ultrasound and gross specimens at sacrifice at age 11 weeks were examined and weekly laboratory studies were recorded. Growth rates of renal length and volume were evaluated by linear regression analysis. Terminal renal length and volume were compared between groups. RESULTS: Mean slope plus or minus standard deviation of the rate of growth in length in the control and chemotherapy groups was 0.067 +/- 0.004 and 0.074 +/- 0.011, respectively (p < or = 0.148, not statistically significant). Mean slope of growth in volume was 1.401 +/- 0.240 versus 1.642 +/- 0.456 (p < or = 0.252), average terminal renal length was 10.71 +/- 1.02 versus 11.58 +/- 1.03 cm (p < or = 0.13, not significant) and mean final volume was 128.67 +/- 32.41 versus 137 +/- 32.52 cc (p < or = 0.65). No differences in final serum creatinine levels were noted. CONCLUSIONS: Chemotherapy for Wilms tumor did not adversely affect contralateral renal growth or function in a nephrectomized piglet model.
PURPOSE: We attempted to evaluate the accuracy of renal ultrasound measurements for determining actual kidney size in a growing renal unit. MATERIALS AND METHODS: We evaluated 18 renal units in growing piglets weekly for 11 weeks on ultrasound. Measured parameters included length, transverse and anteroposterior dimensions, and volume. At 11 weeks final ultrasound measurements were obtained, animals were sacrificed and gross specimen measurements were made. Final ultrasound dimensions and serial measurements were correlated with actual size. Growth charts were constructed to evaluate variability between observations. RESULTS: Mean difference between final ultrasound renal length and actual size was 3.8 mm. (correlation coefficient 0.74). Serial length measurements were not more accurate than isolated measurements for predicting final length (correlation coefficient 0.34). Volume measurement was not more accurate than renal length. Analysis of individual growth charts revealed a significant week-to-week variation. CONCLUSIONS: Error in ultrasound measured kidney length can equal 1 or more years of growth in a child. Our results show that caution should be used when incorporating ultrasound measurements into surgical decision making.